Carbon-hydrogen Spin-spin Coupling Constants

Progress m .V.UR Sprrrrorcopy. 1981. Vol. 14. pp. 175-296 @ Pergamoo Press Ltd. Printed in Great Britain

CARBON-HYDROGEN SPIN-SPIN COUPLING CONSTANTS

POULERIKHANSEN

Institut 1. Life Sciences and Chemistry, Roskilde University Center, P.O. Box 260.4000 Roskilde, Denmark

(Receioed 9 Nocember 1980)

CONTENTS

Introduction Nomenclature Techniques 3.1. Single Frequency Spectra 3.2. Selective Population Transfer Techniques 3.3. Gated Decoupling Techniques without Population Transfer 3.4. 2D Spectroscopy 3.5. Polarization Transfer 3.6. Tailored Excitation 3.7. Satellite Methods 3.8. Sign Determination 3.9. Off-Resonance Decoupled Spectra 3.10. Other Techniques 3.11. J(CD) 3.12. Summary Assignments

5. Solvent Etlects 6. Secondary Isotope Effects 7. Temperature EITects 8. One-Bond Coupling Constants

8.1. Hybridization 8.2. Bond Angle EITects

8.2.1. Ring Strain 8.2.2. Steric ENects

8.3. Substituent EITects 8.3.1. Additivity 8.3.2. Electronegativity 8.3.3. Lone-Pair Effects 8.3.4. Electric Field Effects

8.4. Correlations 8.4.1. Correlations with Reactivity Parameters

8.5. Other Aspects 8.6. Theoretical Calculations 8.7. Summary

9. Two-Bond Coupling Constants 9.1. ‘J(C,C=X,H)X =OorN 9.2. *J(C, C, H)

9.2.1. Substituent Effects 9.2.2. Electronegativity

9.3. Bond Length Dependence 9.4. Bond Angle Dependence 9.5. Correlations 9.6. Summary

IO. Three-Bond Coupling Constants 10.1.

10.2.

10.3. 10.4.

JPNMRS ,.:, _ *

Karplus Equation 10.1.1. sp’ Hybridized Terminal Carbon 10.1.2. s$ Hybridized Terminal Carbon 10.1.3. SD Hvbridized Terminal Carbon Substituknt Effects 10.2.1. Theoretical Approach 10.2.2. Electronegativity 10.2.3. Additivity of Substituent EtTects 10.2.4. Correlations Bond Order or Bond Length Dependence Summary

175

178 178 178 179 179 181 182 183 184 184 185 185 185 185 186 186 187 188 189 189 189 189 189 190 190 190 190 190 193 193 194 194 194 195 195 195 197 197 I97 208 209 209 210 210 210 210 211 211 211 211 212 213 214 214 214

176 POUL Eatr HANSM

11. Couplings over Four or More Bonds 11.1. Aromatic Compounds 11.2. “J(C-Arom, H-x) 11.3. Other Couplings in Aromatic Systems 11.4. Couplings over Heteroatoms 11.5. Summary

12. Couplings to Side-Chain Protons 12.1. ‘J(C,C, H,)

12.1.1. ‘J(C,C,C,H,)(n=Zor3) 12.1.2. ‘J(C, C, C=O, H,)

12.2 Theoretical Calculations 13. Coupling Through Heteroatoms

13.1. Coupling Through Oxygen 13.1.1. “J(C ,..., O,H)(n=2,3or4) 13.1.2. Couplings of C, 0, C, H Type

13.1.2.1. 3J(C,0,C,H) 13.1.2.2. ‘J(C=O,O,C,H)

13.1.3. Applications 13.1.4. Summary

13.2. Coupling Through Nitrogen 13.2.1. *J(CO,N, H) 13.2.2. *J(C, N, H) and ‘J(C, C,N, H)

13.2.2.1. *J(C,N,H) 13.2.2.2. *J(C,C,N,H) 13.2.2.3. *J(C,CO,N, H) 13.2.2.4. *J(CO,C, N, H)

13.2.3. ‘J(C.N.C.H) 13.2.3.1. Nucleosides and nucleotides 13.2.3.2. Amides and peptides 13.2.3.3. 3J(C,N,C,H)

13.2.4. Others 13.25. Summary

13.3. Coupling through Heteroatoms other than Oxygen and Nitt 14. Comparison of Different Types of Coupling Constants

14.1. Comparisons between “J(C, H) and “J(H, H) 14.1.1. ‘J(C, H) vs. *J(H, H) 14.1.2. “J(C,H)vs.“J(H,H) 14.1.3. Summary

f4.2. Comparison of”J(C, H) and “J(C,C) 14.3. Comparison of”J(C,C,. . . , C, H) and “J(C, X,. . . , H) 14.4. Summary

15. Spectra in Nematic Phase 15.1. Technique 15.2. Anisotropy 15.3. Correction for Vibrational Motion 15.4. Indirect Couplings 15.5. Results 15.6. Summary

16. Aliphatic Compounds 16.1. Cyclic Compounds 16.2. Acyclic Compounds 16.3. Polyhalogenated Compounds 16.4. Acids, Acid Derivatives, Amino Acids and Peptides

17. Carbohydrates 17.1. ‘J(C,H) 17.2. *J(C,C,H)

17.2.1. Summary 17.3. )J(C, H) 17.4. Summary

18. Olefins 18.1. ‘J(C,H)

18.1.1. Strain 18.1.2. Cyclic Compounds 18.1.3. Substituent Effects 18.1.4. Complexation 18.1.5. Allenes 18.1.6. Quinones 18.1.7. Theoretical Calculations

214 214 214 215 215 216 216 216 216 216 216 216 216 216 219 219 222 222 223 223 224 224 224 226 226 226 226 226 229 229 229 230 230 231 231 232 232 232 232 232 232 233 233 233 233 233 233 234 234 248 248 248 248 249 249 251 252 253 253 253 253 253 255 255 256 256 256 256 256 18.2. ‘J(C, H)

258

18.4.

18.5.

Carbon-hydrogen spin-spin coupling constants

)J(C, C=C, H) 18.4.1. ‘J(C(sp’), H) 18.4.2. ‘J(C0, H) 18.4.3. ‘J(C(sp*), C=C, H) 18.4.4. Dependence upon Bond Angle Other Couplings

19. Acetylenes 20. Aromatic Compounds

20.1. ‘J(C,H) 20.2. *J(C, H)

20.2.1. Alternant 20.2.2. Non-Alternant 20.2.3. Other Data

20.3. ‘J(C, H) 20.4. 4J(C, H) and ‘J(C, H) 20.5. Coupling with Side-Chain Carbons 20.6. Applications 20.7, Summary

21. Aromatic Heterocycles 21.1. Six-Membered Rings

21.1.1. Pyridines 21.1.2. Pyridine-N-Oxides 21.1.3. Ouinoline and Isoouinolines

21.2.

21.3. 21.4.

21.1.4. C&her Heteroatoms than Nitrogen 21.15. Six-Membered Rings with two Nitrogens 21.1.6. Triazine 21.1.7. Protonation of Nitrogen Heterocycles 21.1.8. Coumarins 21.1.9. Miscellaneous Five-Membered Rings 21.2.1. Furanes 21.2.2. Thiophenes 21.2.3. Pyrroles 21.2.4. Di-, Tri- and Tetrazoles 21.25. Oxazoles and Thiazoles 21.2.6. Miscellaneous Deprotonation Summary

22. Non-Aromatic Heterocycles 22.1. Three-Membered Rings 22.2. Four-Membered Rings 22.3. Five-Membered Rings 22.4. Six-Membered Rings

23. Ions 23.1. Carbocations

24.

25.

231.1. Alkylcarbocations 23.1.2. Cations of Aromatic Compounds 23.1.3. Aromatic Cations 23.1.4. Cyclic Non-Aromatic Cations of Non-Aromatic Origin 23.1.5. Ions of Metalorganic Compounds

23.2. Anions 23.3. Other Ionic Species

23.3.1. Halonium Ions 23.3.2. Other Ions

23.4. Summary Metal Organic Compounds 24.1. Metaltricarbonyl Complexes

24.1.1. Iron and Ruthenium Carbonyl Complexes 24.1.2. Chromium Complexes

24.2. Metal Organic Complexes 24.2.1. Group 111 24.2.2. Group IV 24.2.3. Group VI 24.2.4. Group IIB 24.2.5. Group VHIB

Short Summary of some Recent Papers

References

Note Added in Proof

References Added in Proof

177

259 259 261 261 262 262 263 268 268 268 268 270 270 270 270 270 270 270 270 270 270 272 272 272 272 272 273 273 273 274 274 274 274 274 275 275 276 276 276 276 276 276 276 277 277 277 278 278 279 279 279 280 280 280 280 280 280 280 281 281 281 281 281 281 281 281

282

294

295

POUL ERIK HANSEN 178

AISEFT

CNDO cw 1D DMSO FID FP f.0.a. FT GASP DSPI HMPA INDO INEPT LMO MIND0 NOE ORND RF SFORD SLMO SPI SPT

& T2

GLOSSARY OF ABBREVIATIOSS

Abundant Isotope Signals elimination by FT NMR Complete neglect of differential overlap Continuous wave Two dimensional Dimethylsulphoxide Free induction decay Finite perturbation First order analysis Fourier transform Gated spin tickling DifTerence selective population inversion Hexamethylphosphotriamide Intermediate neglect of differential overlap Insensitive nuclei enhanced polarization transfer Localized molecular orbitals Minimization of energy + INDO Nuclear Overhauser elfect Off-resonance noise decoupling Radio frequency Single frequency off-resonance decoupling Strictly localized molecular orbitals Selective population inversion Selective population transfer Spin-lattice relaxation time Spin-spin relaxation time

I. INTRODUCTION

The development and interest in carbon-hydrogen coupling constants may be illustrated by the number of papers published. In a very early (1965) account of J(CH), Emsley, Feeney and Sutcliffe”) included 36 papers. In 1971 Stothers”) referred to approximately 150 papers while in 1980 there were more than 900 papers dealing with this type of coupling constant. Several textbooks”-” treat carbon-hydrogen coup-

ling constants as do numerous review papers.‘5-8’ Most of these will be referred to in the appropriate sections.

The great interest in carbon-hydrogen coupling

constants is clearly spurred on by the great appli- cability of these coupling constants. They are used

extensively for assignment purposes, in structure elucidation, in stereochemical studies, rotamer population studies, substituent effect studies and studies to gauge steric strain. They are applied in the study of the structure and equilibration of carbonium ions. In addition they have been used to study the preferred positions of lithiation, to monitor tautomerism, to predict acidity, to demonstrate the existence of hydrogen bonds and to determine bond orders. They were also used in biosynthetic studies, before the method was superceded by studies of carbon-carbon coupling constants.

The huge amount of information available has made a selection necessary. In the present study I am going to concentrate upon recent work, but of course with references to original background papers. The many aspects and different connections in which carbon-hydrogen couplings occur, furthermore, demand that special emphasis is given to

applications. One area of special interest is that of

conformational studies as both one-, two- and three- bond coupling constants have proven useful in such

studies. To describe coupling constants a ZD-method of

presentation would be very useful. Having the different coupling constants on one axis and using the different classes of compounds as spreading parameter on the other. a very detailed and well composed picture could be produced. However in this review the two axes are placed one after the other. The coupling constants and their general features are treated first. while the classes of compounds are taken last with special emphasis upon their application. Techniques to obtain magnitudes and signs of coupling constants are also treated in some detail and so is the analysis of single frequency spectra. Other areas such as assignment of 13C spectra and spectra of molecules in

nematic phases are presented in a more cursory way. The groups of compounds include aliphatic, olefinic, acetylenic, aromatic and heterocyclic compounds as well as carbenium, carbonium and carbanions, complexes and organometallic compounds. Theoretical calculations have recently been reviewed by Kowalewski.(g’ The basic theories were extensively reviewed and new developments are few, so this article concentrates on the applications of theoretical calculations and they are included in the relevant sections.

2. NOMENCLATURE

Abbreviations are listed. “J(C, H) is a general way of describing a carbon-hydrogen coupling across II bonds. In more specific cases the intervening atoms

are mentioned, e.g. 3J(C,N,C,H). Couplings across two and three bonds are called

two-bond and three-bond coupling constants rather than geminal and vicinal.

Single frequency spectra refer to spectra containing all the coupling information while others have used

the term undecoupled. cis and tram are used in many contexts instead of

periplanar and antiperiplanar. References without letters refer to all references

under that number, whereas references with letters on refer to that specific one.

3. TECHNIQUES

Many of the existing data are of less than prime quality as they were obtained from a first order analysis of second order spectra. A tendency to give splittings rather than coupling constants from a complete iterative analysis, under the pretext that this type of parameter should be more useful for organic chemists, must be strongly dissuaded. Too many totally erroneous conclusions have been reached based on results from such shortcuts. The access to and use of iterative programmes for analysis of NMR spectra is nowadays so easy and chemists using

Carbon-hydrogen spin-spin coupling constants 179

coupling constants for assignment and structure elucidation will profit from using the correct procedures in the analysis of spectra.

The techniques available to obtain the values of coupling constants are many. The use of *H “C satellite spectra are extensively treated by Goldstein er ~1.‘~’ and will only be mentioned briefly in a couple of special cases. Single frequency spectra are treated in some detail. Although the excellent results obtained in this field are not of recent date, they form the basis for judgement of the quality of data from new techniques.

Most of the recent advances make extensive use of computers. The 2D technique originally suggested by Jeener”” and generalized by Ernst et al.” *) is the basis for several techniques. These techniques are very demanding on computer memory and hardware modifications are usually also necessary.

3.1. Single Frequency Spectra

Gated decoupling(12-14’ is the universally accepted technique for recording 13C single frequency FT spectra (Fig. 1A). The analysis of single frequency spectra is described in a very enlightening manner in papers by Jakobsen et al. (16-1s) The spectra observed are the X part of e.g. ABX, ABCX, etc. spin systems. From the analysis vx, JAB, JAX and J~x may be obtained as well as in some cases isotope effects upon the proton chemical shifts!‘6-L8’ For a general description of the analysis of NMR spectra see Refs. I and 15. To analyse the spectra computer simulations are necessary. In order to get good results very accurate line positions should be obtained.“” This is secured by recording spectra of samples in sealed degassed tubes using non-viscous solvents and good digital resolution is achieved by observing small spectral windows. Jakobsen”” has claimed that a spectral resolution of + 0.03 Hz is necessary. Further requirements are a good S/N ratio, so that the less intense combination lines may be obtained. IH chemical shifts and coupling constants should be recorded on the same sample.(16J It is essential to assign as many lines as possible and to obtain as low a rms error as possible. Several solutions may give very similar rms errors. (*’ It has been debated whether the rms error alone is a sufficient means of distinguishing the different solutions. (“) It is sufficient provided that the line positions are determined with great accuracy and many combination lines are included. Complementary evidence may be obtained from ‘H i3C satellite spectra’20*26’ as well as from a comparison with coupling constants in similar systems or environments.“”

Selective decoupling or SPT experiments may also be very useful in differentiating between the different energy level diagrams associated with each set.“9*29) A detailed analysis has been described in several cases:benzene,“8~23~toluene,“8’fluorobenzenes,’21~22’ monosubstituted benzenes!“’ pyridine,“@ furane,“” pyrrole,‘25’ thiophene,(z6’ cyclopentadiene,(24’ spiro-

heptadiene,“‘j’ butadieneiron tricarbonyl’19) and biphenylene.“*’

The very good resolution and the well-known ‘H chemical shifts may not always be available in complex situations. Errors involved in the analysis of the X part of an ABX spin system as though it was part of an AMX spin system (first order analysis) are discussed by Cyr et al. ‘29’ A graphical method is devised to estimate the probable errors involved. Attempts to extend such an approach to more complex spin systems turned out to be unfeasible. Jones et a1.‘3oJ emphasized that in AB.. . X spin systems a non-first order appearance is observed when ‘J(CH), 2 = 66, where A6 is the ‘H chemical shift separation between two closely coupled protons. Under this condition one wing of the 13C satellite overlaps the resonance of the other strongly coupled proton leading to a mixing of their wave functions.

3.2. Selectitie Population Transfer Techniques

In CW mode NMR, transitory selective irradiation leads to population transfer’31’ and hence to intensity variations of the perturbed transitions. Similarly INDOR experiments are based upon spin transfer. As INDOR is confined to CW experiments an alternative method was devised for FT NMR spectroscopy.‘32*33’

SPT (selective population transfer) and SPI (selective population inversion) are abbreviations for two identical techniques. SPT has the advantage of being the most accurate as a complete inversion is not always possible, whereas SPI has the virtue of being an acronym. The most important point, however, is the equivalence of the two (SPT = SPI). A weak irradiation field H, (e.g. yuH,/Zn = 0.1-0.3 Hz) is selectively applied to one of the ‘H transitions in the 13C-lH satellite spectrum, for T set fulfilling the condition yu x H, x K = 7c (n-pulse), prior to excitation of the 13C resonance by a strong non-selective rf pulse (see Fig. IB). Provided that r is chosen so that T -=ZZ T,, where T, is the shortest spin-lattice relaxation time for any of the connected 13C, ‘H transitions, the SPT n-pulse causes complete inversion of the corresponding energy level populations.

The SPT method leads to a substantial increase in sensitivity!33’ In molecules with degenerate ‘H transitions as in e.g. AX, spin systems, extremely large intensity changes may be obtained in the 13C spectrum.(34’

The SPT technique is also very useful in determining relative signs of coupling constants of weakly coupled spin systems.‘32*3s’ Difference selective population inversion (DSPI) spectra have also been applied to eliminate all lines not affected by the n-pulse!36’ A slightly different timing sequence (see Fig. 1C and D) was utilized by Bundgilrd and Jakobsenf3” to observe hidden lines in 13C NMR spectra. An illustration was also given in the analysis of methyltetrolate.‘38’

Application of the SPT technique has one inherent difficulty if it is applied to closely spaced lines. To

180 POUL ERIK HANSEX

(A)

Ol-4 NS NS NS

Off

n ! n AT i PD AT ’ PD

(B)

Oil ri r-l

Off I- T I-

Noise

Selective pulse

(C)

Otl m

Off T Selective pulse

n I AT’ PD AT ’

l-l ; AT ’

+ f Sign in memory

(D) n n Selective pulse

T T

l-l ; n ; ‘r !

n I

+ + Sign in memory

(El

t , Selective continuous

n j n I n :

IFI

,

NS NS NS Noise

A Selective continuous

(G)

Selective

FIG. 1. Upper trace gives behaviour of the B, decoupling field. Lower trace the B, field. + and - signs refer to the way FID are stored in the memory. A. Gated decoupling.“3~‘4’ B. SPT,‘3L1 SPI,‘33) or GASP.“‘@ C. DSPL’)@ D. DSPT.‘3’b E. Continuous selective irradiation!39*401 F. Ob servation of coupling constants

without intensity changes.‘56) G. Tickling experiment.“9’


avoid perturbing the close lying transition a weak field must be utilized, but this requires longer r times in order to get a n-pulse and because of the longer T the system may relax during the application of the pulse.

An alternative method avoiding this problem has been proposed by Koole et CI!.‘~~*‘~’ (See Fig. 1E.) In this method they irradiate the satellite lines con- tinuously. In their study of methyl isocyanide they conclude that the continuous method is superior to the SPT method for this type of molecule, because of the short T, values of the 13C-14N transitions which would cause relaxation during the pulse. This proposal has been refuted by Jakobsen and Bilds$e(41) on grounds of experimental and computer simulated’4L) SPT experiments. Intensity variations in experiments using continuous irradiation have also been observed by McDonald and Mazurek.‘43-46)

mation. In systems with degenerate transitions a better sensitivity is observed.(“) Likewise an improvement in sensitivity is possible if progressive saturation can be exploited.‘4’-49) The SPT/SPI method has also proven to be very useful in sign determination of coupling constants in weakly coupled systems where considerable sensitivity improvements may be obtained. The central idea of the method is the use of a selective n-pulse. However, this requirement of selectivity constitutes a time consuming problem. If the power becomes too large, selectivity is lost and neighbouring lines will be affected. If the duration of the pulse is too long, relaxation processes and secondary population transfer within the system will diminish the gain in sensitivity. A suitable compromise has to be determined for each new case. The SPT/SPI technique has been used in a number of other caSeS (19.24.50-55)

A technique called GASP (gated spin tickling) which is very similar to SPT has also been described.‘46) The only difference lies in the strength of the decoupling field.

3.3. Gated Decoupling Techniques without Population Transfer

The increased sensitivity provided by SPT experi- Within the framework of gated decoupling several ments is given by the ratio yH/yX to a first approxi- experiments have been described. Spin-tickling(39)

(a)

I NS I 9d I

1 I I I

;

‘I I ‘2 I

Rep. I Evolution 1 Detection I

(b)

‘H

I3 C

‘H

(cl

;I fl I f2

FIG. 2. Some pulse sequences used in 2D spectroscopy.“‘*‘”

182 POUL ERIK HANSEN

may be accomplished by irradiation of the satellite lines during acquisition of the free-induction decay (FID) using an appropriate amplitude of the decoupling field (Fig. 1G). By providing a long delay time significant intensity changes are prevented. Intensity changes (both positive and negative) may cause problems in spectra of complicated molecules. To avoid these effects selective proton decoupling has been combined with gated noise decoupling (Fig. IF). (56) No intensity changes are observed but the full NOE effect is retained.

3.4. 2D Spectroscopy

The idea of Jeener (t°) of applying two consecutive Fourier transformations has led to two major types of techniques: the 2D spectra and the 2D spin- echo spectra. The theory for the former has been described by Ernst et al} 11.57) and by Kumar} 59) No attempt will be made here to go into theory, but rather to describe the experimental conditions and the results, that may be relevant for the studies of carbon-hydrogen coupling constants. The schematic sequences are described in Fig. 2A-C. Three time intervals are considered, a preparation period, an evolution period of length tl and a detection period of length t2"

In experiment A at time t = 0 transverse magnetization is created by means of a 90" pulse. During 0 < t < t~, the magnetization is allowed to precess freely. At time t~ broad band decoupling is started. The experiment is repeated for various values of t r After 2D Fourier transformation, the two frequency

axes represent the undecoupled spectrum and the fully decoupled spectrum. The achievement of 2D spectroscopy is observation of each muhiplet without overlap with other signals. The ordinary spectrum has been spread in a second dimension according to the chemical shifts. The price to be paid is a reduction in sensitivity of approximately a factor 3 compared to 1D spectra and the need for large storage space in the computer. By the use of disks this last requirement is easily met. One further advantage is that by cutting ID cross sections through a 2D spectrum obtained in an inhomogeneous (but stable) magnetic field high resolution spectra with coupling constants information may be obtained} t ~ Other schemes are suggested as shown in Figs. 2B and C and filtering may be used to selectively observe one particular carbon site.

2D spin-echo spectroscopy is an extension of "J-spectra", (6°'6t) combined with the 2D technique. Normally heteronuclear spin-spin couplings do not modulate spin-echoes. (6°'6~) Two different schemes have been devised to restore the modulation and thereby gain information about the C - - H coup- lings3 ~s'62"63) The pulse sequences are shown in Figs. 3A and B. As seen, proton noise decoupling is employed in both the "gated decoupling" and the "proton flip" methods in the preparative period in order to establish a NOE effect of the carbon-13 signal. The echo modulation as a function of t t is Fourier transformed into the frequency domain giving the J-spectrum. The half echo may be treated as a FID and its component may be separated by Fourier transformation as a function of t 2. The axis in the 2D

(a)

1 NS 'H NS I

90* 180"

n n ~'O TR

~3 C

( b )

NS [-7 NS ~H

n I I

1 r, t2

~3 C

90" 180" Acquisition

FiG. 3. Pulse sequences used for J-spectroscopy. A. Gated decoupler technique. B. Proton flip tech- nique3 ~s.62.63~ Upper trace, pattern of proton irradiation, lower trace, spin echo sequence applied to the

tac spins. 30 defocusing period. ~R refocusing period.


spectrum is now the chemical shift axis and the J-spectrum shows the carbon-hydrogen coupling. When spin echo methods are used excellent resolution is obtained, even for non-spinning samples. Line- widths as narrow as 0.1 Hz have been reported.‘66’ In the “gated decoupler” method the echoes are modulated at a frequency of J/4, whereas in the “proton flip” method the modulation frequency is J/2. Slightly better resolution is thus obtained in the latter method.

Spurious responses often appear in these 2D spectra, known as “phantoms” or “ghosts”. They come out differently in the two methods.‘s8’ They may be eliminated using a four-step pulse sequence.‘64’ The “gated decoupler” and the “proton flip” method applied to systems with strong H-H coupling give different responses.‘65*66) The former is similar to a 1D spectrum whereas the latter produces a J-spectrum containing more lines and possesses an apparent mirror symmetry.@’ Negative intensities may also be observed. A modified LAOCOON programme was used to analyse this particular type of spectrum. Both techniques were applied to the analysis of the “C spectrum of pyridine and results similar to those of Hansen and Jakobsen(‘@ were obtained. The method has also been applied to cholesterol.‘67’ The outer lines of the methyl quartets were weak. This was believed to arise from the effect of an imperfect proton flip pulse caused by inhomogeneity of the RF-field. 2D spectra are often plotted in the absolute mode in order to avoid the complications of the “phase twist”

(A)

which appear in the phase-sensitive displays. For accurate measurement the latter method is preferred because of the narrower linewidths. Furthermore as some intensities are negative, this approach is less desirable. Schemes to avoid phase twist have been devised.‘68*69)

A modification using off-resonance decoupling instead of noise-decoupling has been proposed by Miiller(70~ (Figs. 4A and B). In this manner the various heteronuclear coupling constants may be assigned.

The spin-echo method has so far been the most popular 2D method for observation of high-resolution spectra. Excellent resolution may be obtained on magnets with modest homogeneity if the magnetic field is stable. Large samples may thus be studied with advantage. The few disadvantages are the large amounts of data produced and the poorer sensitivity than that of ID spectroscopy. Many different schemes have been proposed and more are likely to appear to explore this new and rich field for the determination of carbon-hydrogen coupling constants.

3.5. Polarization Tratlsfer

Magnetization of one nuclear species can be enhanced by transfer of polarization from a second species having a larger magnetogyric ratio (the nucleus is typically ‘H). The abundant spins are usually called, I, and the dilute ones, S. Cross- polarization has been used extensively in solid state

1 Off - resanance ‘H

(B) PY

Off - resonance ‘H

(Cl

: IH

: ‘3c I I tl f2

FIG. 4. A and B. Off-resonance J-spectra.““’ C. Indirect detection.“”

184 POUL ERIK HANSES

NMR.“‘.“’ Cross-polarization in liquids was demonstrated by Bertrand er a/.(73-75’ The method was called JCP as spin-spin coupling is responsible for the magnetization transfer. The proposed method was very sensitive to a mismatch of the Hartman-Hahn condition.‘76’ An improved method, RJCP, has recently been given, 175) but the method is less suitable for high resolution studies.

An indirect detection method was devised by Maudsley and Ernst. (“I The method relies on a coherent transfer of transverse magnetization to nuclei of high gyromagnetic ratio. A coupling between the two nuclei is a prerequisite. The pulse sequence is shown in Fig. 4C. The precessing I spin magnetization is measured as a function of t, for various evolution times t,. A 2D Fourier transformation leads to the desired 2D spectrum. The observed intensities did not correspond to the theoretically predicted ones. These anomalies are likely to be due to relaxation effects and to insufficient field strengths of the carbon-13 RF pulse. The sensitivity of indirect observation of 13C resonances theoretically should be almost an order of magnitude more sensitive than that of direct observation due to the larger gyromagnetic ratio of the observed protons. A related scheme was put forward by Morris and Freeman. “*) (These authors use an opposite convention for I and S.‘27)) Their pulse sequence is closely related to that used in heteronuclear 2D spectroscopy (see Section 4), but relies on the excitation of spin echoes and employs a fixed delay 51 equal to 1/4JIs (see Fig. 5). When proton- coupled spectra are measured the intensities are as follows: doublets - l:l, triplets - 1:O:l and - 1: - 1: 1: I for quartets. The method is best suited for carbons bearing hydrogens (otherwise very long r must be employed) and an improvement in sensitivity of a factor 5 - 6 vs. the normal single frequency spectrum is obtained. The acronym INEPT (insensitive nuclei enhanced by polarization transfer) has been adopted for this technique. A double transfer of polarization leading to observation of the high y nuclei has been proposed by Bodenhausen and Ruben,“” but this method has so far only been applied to “N.

Finally, Miiller (so) has correlated the single quantum transitions of the I species to the forbidden heteronuclear multiple quantum transitions of the S species. In this way an indirect detection of the single quantum transitions of the S species is accomplished. The sensitivity is completely independent of the ‘/ of S. An alternative to conventional cross-correlation spectroscopy described in Reference 77 was also given.

90x BOX 9OY

n l-l n S-spans ‘H

I-spins 13C T ! ’ r

FIG. 5. INEPT experiment.“” 7 = l;(1Jlsl s.

NS

I I I I I I I I

T 1

FIG. 6. DANTE pulse sequences.‘“”

3.6. Tniloreti Excitariort

Tailored excitation was first described by Tomlinson and Hill.‘*l) A train of radio-frequency pulses is used to control the range of resonance frequencies to be excited. The method was originally proposed to eliminate strong solvent signals and for homodecoupling purposes in general. Applied to the decoupling field, selective double and triple experiments could easily be performed. Ernst’s7’ and Freeman(82**3’ have suggested a modification of the technique which includes gated decoupling. One line in the decoupled spectrum is excited, but the proton decoupler is switched off before acquisition of the FID. The result is an undecoupled sub-spectrum of the 13C resonance excited and a.considerable and very important simplification has been obtained. A very detailed description of tailored excitation has been given elsewhere. (83) One of the drawbacks of the Tomlinson-Hill method is that a considerable part of the computer memory is occupied with information concerning the tailoring pulse sequence. A much simpler pulse sequence, DANTE, has been described by Morris and Freeman.‘83’ The selective pulse sequence consists of a regular train of identical, short, strong RF pulses, flip angle <c n/2 radians, spacing T set apart. This is equal to a set of sidebands l/r Hz apart in the frequency domain. By selecting l/5 correctly only one sideband falls inside the spectrum of interest (see Fig. 6). The price to be paid for the separation of the individual multiplets is of course that a series of sub-spectra must be collected, one for each 13C chemical shift. Rebate may be gained in favourable cases in which non-overlapping shifts may be excited simultaneously’s4’ or, in cases where long pulse-delays are necessary, other nuclei may be excited during the delay period.@*’ Tailored excitation and 2D spectroscopy may also be combined.‘63’ Practical uses of tailored excitation are also described in References 8.5 and 86.

3.7. Satellite Methods

One satellite technique, AISEFT,‘87-*9’ will be mentioned. In this technique which is similar to DSPTt3’) and DSPI,‘36) the abundant isotope signals are eliminated by FT. AISEFT is useful for the observation of satellites from low abundance nuclei (e.g. 13C) in ‘H NMR spectra, all other lines being sup- pressed in principle.

Two free induction decays are subtracted (one obtained under normal conditions, one with irradiation at the rare spin frequency) see Fig. 7.

Carbon-hydrogen spin-spin couplmg constants 185

I NS NS "C

+ + FIG. 7. Pulse sequences used in the AISEFT technique.“” + and - refer to the sign that the FID is given in the

computer memory.

3.8. Sign Determination

Sign determination of coupling constants using selective spin-decoupling and spin-tickling in the CW mode has been treated in great detail.“‘) Signs may be obtained by the above-mentioned methods, by analysis of second order spectra (Section 3.1) by means of the SPT/SPI technique (most suitable for use in first order spectra) (Section 3.2) or by the INDORt9” technique. An off-resonance method involving a quaternary carbon has also been described.“”

Triple resonance experiments in which both ‘H and ‘ON are irradiated have recently been used in the analysis of NMR spectra of amides.‘92*93J

3.9. OfJ-Resonance Decoupled Spectra

The analysis of SFORD spectra of the AA’X systems has been dealt with in various disguises by several authors. Newark and Hi11(94) observed a complex pattern in the off-resonance spectrum of fumaric acid (AA’X spin system) and ascribed this to virtual coupling. Grutzner (95) took the same effect as evidence for the presence of two neighbouring carbons bearing hydrogen. Fritz and Sautertg6) and PrangC and Lallemand(97r treated the AA’X spin system and showed that this system because of different Bloch- Siegert shifts of nuclei A and A’ can be analysed as an ABX system. By varying the decoupler power and regarding the behaviour in the X-part of the two lines separated by JAx+JA’x the relative signs of the two-bond couplings may be determined. A more practically oriented approach was taken by Hagaman.(98) A thorough theoretical treatment of the ABX spin-system was also presented.‘99) A general discussion is also given in Reference 3. Two factors must be considered in the analysis of ABX systems, namely, the reduction in J and the Block-Siegert shift. A graphical presentation is presented by Radeglia. (loo*‘ol) A related analysis using off- resonance noise decoupling (ORND) was made by Roth.“02’

Reduced coupling constants obtained from off- resonance decoupled spectra have been cited in a number of cases.~103-108)

3.10. Other Techniques

Deuteriation has been used to simplify the analysis of complicated spectra. (‘09) Massive deuteriation (all hydrogens but one exchanged) combined with ‘H broadband decoupling result in some very simple

spectrat1’0-112’ from which the numerical magnitude of “.J(C, H) may be obtained. Partial deuteriation has been applied in the analysis of carbohydrates. Both OH and CH hydrogens may be exchanged.““’ The possible influence of secondary isotope effects are discussed in Section 6. Selective enrichment with “C results in much simpler 13C spectra and the carbon- hydrogen coupling constants may also be obtained from the ‘H spectrum. This technique has been used especially in the analysis of carbohydrates (tide infra).“13*’ 14) Tailored excitation or 21) techniques should be able to provide the same information, but many more transients are needed of course.

3.11. J(C, D)

Substitution of a hydrogen by a deuterium has a marked effect on the r3C spectrum. Not only are triplets observed in the proton decoupled 13C spectrum but also isotope effects on chemical shifts may be observed. Deuterium substitution is thus a useful tool in the assignment of carbon spectra. As deuterium has spin 1, the C, D couplings will appear as triplets with a theoretical splitting of .~&u x J(C,H). Early repOrtS(23’115-122) showed that this expectation was fulfilled, so that ‘J(C,D) could be observed easily, whereas 2J(C, D) and ‘J(C, D) would usually not be resolved on the poorly resolved broad signals. (23.25.49.115.116.120,121,123-125) Measurement

of “J(C, D), which can be made in proton decoupled spectra, is thus a possible way of obtaining carbon- proton coupling constants. However, the work of Colli et a/.“‘*) and Breitmaier et a1.(126) points towards a possible primary isotope effect on ‘J(C, H). The difference yn/ynJ(C,D)-J(C,H) was in most cases negative. Unfortunately the uncertainty in the measurement of J(C,D) was too large to make any firm conclusions, but a trend was present. A tabulation of recent data including uncertainties is given in Table 1. As may be seen from this table none of the A(yn/yc”.J(C, D) -“J(C, H)) with exception of 35 in benzene and ‘J in chloroform falls outside the experimental uncertainty, but it is conspicuous that the negative signs are clearly dominant, as pointed out by Colli et a1.(“*) More accurate studies are, however, necessary before any conclusion can be drawn.

Because of the uncertainties in measuring J(C,D) and because the measured couplings are multiplied by approximately six times, the obtained J(C,H) couplings are not so precise. Furthermore, line broadenings or reductions of the couplings because of rapid relaxation of a deuterium connected to a carbon may cause further problems. These effects depend upon “J(C, D) and T,(‘H), as described by Pople.(r2’) They are unlikely to play a role in the case of one bond couplings, but may well affect the smaller two- and three-bond couplings. A few cases have been reported.‘49*121r

isotope effects on ‘J(C, H) coupling constants have been treated theoretically by Sergeev and Solkan.“2*’


TABLE 1. A comparison of “J(C. D) and “J(C, H) coupling constantsa (Hz)

” "J(C. D) ;.n,$nJ(C. D) J(C. H) A Refs.

Methane-d, 1 19.3 kO.3 Methane-d, 1 19.2 20.2 Methane-d, I 19.1 io.1 Benzene- 1,3. S-d, I 24.23 k 0.06

1 24.2 kO.1 3 1.12 kO.03

Chloroform I 31.9 +0.1 I 31.98 +0.14

Acetonitrile I 20.78 kO.13 Acetophenone 1 19.25 50.32 Diethyl malonate I 20. I5 &- 0.32 Sodium acetate 1 19.51 +0.12 Cyclobutene I 25.82 kO.05

1 21.08 50.05 2 0.95 kO.05 2 0.75 kO.05 2 0.64 kO.05 3 1.07 +0.05 3 2.00 + 0.05

Pyrrole 2 0.6 iO.1 3 I.05 kO.05

Pyridine 1 25.0c +0.2 1 27.3 +0.2 I 25.2” kO.2

125.73 * 1.9 125.08 * 1.3 124.42 kO.7 157.84 kO.39 157.65 +0.65

7.30 f 0.20 207.81 kO.65

208.33 +0.91 135.37 kO.85 125.40 k 2.08 131.27 k2.08

127.10 kO.78 168.20 kO.33 137.32 f 0.33

6.18 kO.33 4.89 & 0.33 4.17 +0.33 6.97 +0.33

13.03 IO.53 3.91 kO.65 6.84 f 0.33

162.86 f 1.3 177.84 f 1.3 164.16 f 1.3

125.3 to.4 124.9 kO.3 124.5 +0.2 157.65 f 0.09b 157.65 +0.09b

7.63 k0.09b 208.8 to.2 209. I2 i 0.05 136.20 + 0.02 1’7.34 +0.02 132.28 +0.04 127.12 50.05 168.58 50.05 137.16 kO.05 - 6.63 + 0.05

5.03 +0.05 - 4.40 f 0.05 + 7.34 + 0.05

+ 13.18 +0.05 + 3.80 +0.03 +7.11 kO.03 162.41 kO.03 177.63 k 0.03 163.04 f 0.03

+ 0.43 f 2.3 -0.18 k 1.6

0.08 +0.9 + 0.19 * 0.48

0.00 +0.74 -0.33 +0.29 - 0.99 + 0.85 -0.79 -10.96 -0.83 kO.87 - 1.94 f 2.30 - 1.01 k2.12 -0.02 kO.83 -0.38 kO.38 +0.16 kO.38 -0.45 kO.38 -0.14 50.38 -0.23 kO.38 -0.37 kO.38 -0.15 kO.38 +O.ll +0.68 -0.27 +0.36 +0.45 + 1.33 +0.21 + 1.33 + 1.12 + 1.33

130 130

130 110.123 118 110,123 129

129 129 129 129

I25

25

18,118

a. More data are given in References 23, 115-I 17, 119-122, 124, 126, 131-139 and 824. b. Obtained from perdeuterated benzene. Coupling constants not corrected for second order isotope effects. c. May be interchanged. as the numbering is unclear in the original reference. The order of coupling constants is given in

Reference 137 as ‘J(C-z, D) = 26.9 +0.5 Hz, ‘J(C-/j. D) = 25.0 +0.5 Hz and ‘J(C-;, D) = 24.7 kO.5 Hz.

INDO FP calculations showed that ‘J(C,H) varies with the bond length. Assuming that the isotope effects are due to changes in the molecular geometry

it was established that ‘A.7 would be around - 1 Hz. Other examples of ‘J(C, D) are found in References 128-139.

Couplings to tritium may be treated in a similar way. Al-Rawi et al. (*29) observed a very good agree-

ment between J(C,H) and yu/;‘rJ(C,T).

3.12. Smmary

The view advocated in leading scientific

journals (140-142) that simple line separations can be used instead of computed coupling constants and that such splittings should be sufficiently good to mirror major trends, must be strongly disputed.

A very large number of techniques are now available for obtaining both the magnitudes and signs of coupling constants and within the last couple of years new techniques to improve S/N and resolution have helped to make assignment and analysis easier.

The new techniques represent a shift towards more emphasis on computer memory, fast background storage and on new software.

4. ASSIGNXIESTS

Assignment techniques have been treated in many papers and textbooks. (2-J~‘J3-146’ Many techniques are based upon the observation or the existence of a

carbon-hydrogen coupling in some form. As will be

seen from the discussion of the different types of coupling constants the ranges for most couplings are known in some detail, thereby helping assignment based upon observation of carbon-proton coupling constants (both one-bond and long-range). The use of long-range coupling constants has increased since 1972 when Grutzner(145) reviewed 13C-‘H coupling and did not report any uses of long-range coupling in assignments. Correlation of carbon and hydrogen chemical shifts, deuterium substitution, disappearance of long-range coupling and coupling constant patterns are other means of assignment.

Coherent off-resonance decoupling may be used to correlate ‘H and 13C NMR chemical shifts. A very useful graphical method was devised by Birdsall and Feeney!“” This method has been widely used and has the advantage that it may be automated.

Splitting patterns in single frequency spectra, primarily due to one-bond coupling constants, have been used extensively for assignment purposes. Often extensive overlap occurs in single frequency spectra. To minimize this, coherent off-resonance decoupling (SFORD) may be used. A theoretical analysistlsO’ predicted that the normal binomial intensity distribution should be retained, provided that the irradiation field was strong enough. In practice peak-height distortions within the spin-multiplets often occur leading to misassignments of a triplet for a singlet or a quartet as a singlet. Grutzner et n[.” 50) have shown that these intensity distortions are caused by spatial inhomogeneity of the decoupler field leading to a


preferential broadening of the outer lines of, for example, a quartet. Methods of circumventing this problem have been suggested! “O)

Recently a new technique called J-scaling has been proposed by Freeman and Morris.“5” J-scaling allows proton-c&bon splittings to be scaled down by any desired factor and the spectra are not significantly affected by inhomogeneity of the decoupling field. Two different schemes have been suggested. Strong proton-proton coupling may complicate spectra obtained by method B.

A simpler multipulse approach avoiding the time- consuming 2D technique has been suggested by Aue and Ernst.“s3’ The two different pulse sequences are given. The appearance is quite similar to off-resonance decoupled spectra.

“Spin-Rip” decoupling”s4J (application of a sequence of 180’ pulse in the centre of intervals between sampling operation) may lead to complete decoupling, but by displacing the 180° pulse in an alternating manner also to J-scaling.

Correlation of ‘% and ‘H chemical shifts may be done by off-resonance decoupling experiments as just described. It may also be achieved by the cross- correlation technique described by Maudsley and Ernst”” for detection of nuclei with small y values. This technique(‘s5*‘56J can be utilized for any pair of nuclei as long as they are coupled. No net transfer of magnetization occurs and complete decoupling leads to no signal. Two schemes to avoid this by a net transfer of magnetization have been described!‘57J The observation of long-range carbon-proton coupling may be used in the assignment of quaternary carbons.(3*‘s8J Likewise the removal of these can also be useful. Takeuchi”59-‘62J demonstrated how selective decoupling of long range C-H coupling could be used for assignments. Couplings to hydroxyl protons have attracted much interest recently. In those cases in which such couplings can be observed their identity may be ascertained by removal either by addition of D,0”6’J or by heating”64J and carbons in ortho and/or ipso position may be assigned in this way (see Section 13.1.1).

Coupling patterns have been shown to be useful for assignment purposes in highly symmetric systems.(‘6s*‘66J

5. SOLVENT EFFECTS

Solvent effects on the coupling constants result from changes in the electronic distribution induced by the solvent molecules. Studies are limited to rigid molecules to exclude effects caused by solvent induced conformational changes. Solvent effects on ‘J(C, H) have been reviewed extensively by Barfield and Johnston”67J and by Smith.“68J The latter presented a large body of experimental data. Some new evidence has been gathered since 1972.

The Fermi mechanism dominates ‘J(C, H). A change in the magnitude of the coupling constant

must involve a change in the charge density at either the carbon or the hydrogen atom or both. The firm basis for theoretical treatment of spin-spin couplings has led to a number of theoretical treatments of solvent effects.

Electrostatic effects between solute and solvent molecules have often been considered the cause of solvent dependent coupling because of the observed changes often correlate with some function of the dielectric constant of the medium. However, the problem is more complicated than this because of the possible contribution from other types of intermolecular interactions such as specific association effects, especially hydrogen bonding.‘169*‘70’ Raynes et a1.(‘7’*L72J and Cox and Smith”73J have estimated solvent effects on the basis of polarization of the C-H bond caused by electric fields from neighbouring solvent molecules. Barfield and Johnston’16” in their review pointed out that explanations based on electric field effects failed, because they do not take into account the transportation of charge out of the C-H region. Barfield and Johnstont*67J performed FP INDO MO calculations taking into account the solvent effect through the Onsager reaction field model,(L74J a cubic closest packed cluster model or a point dipole model with rotational averaging. The experimental trends for ‘J(C,H) in all these cases were well reproduced. It was also pointed out that because of the high concentrations used self- association may play a role.

Kondo et ~1.“‘~’ adopted the Klopman solvation theory~L76*L77J to estimate the solvent effect in the MINDO/Z MO approximation. Experimental data for acrylonitrile, dichloromethane and chloroform in various solvents were given. Tetrachloromethane was used as reference solvent. The largest experimental variation of acrylonitrile was + 2.6 Hz observed in DMSO. Dichloromethane diluted with N-methylacetamide gave an increase of + 2.7 Hz at a volume fraction of 0.2. Likewise chloroform gave an increase of +6.3 Hz. All the calculated values of ‘J(C, H) were larger than the observed data but the tendency that ‘J(C,H) increases with increasing E (dielectric constant) is reproduced. The observed data fell approximately on a straight line if plotted against (E - 1 )/E

(5.1)

The magnitude of o provides a measure of the solvent dependence of ‘J. An increase in the number of halogen atoms in methane leads to an increase in the solvent effect. In other words C-H bonds near polar substituents are expected to show larger solvent effects according to this theory.

Another study including aprotic dipolar solvents was performed by Meille et al.‘178J They investigated the complex between chloroform and HMPT (hexamethylphosphoric triamide). The mole fraction of complexed molecules was measured from the ‘H chemical shifts. The measurements were per-


formed both for a mixture of CHCI, and HMPT and the same mixture diluted with CS,. A linear regression led to J(free) = 207.6 + 0.3 Hz and J(complex) = 222.3 k 1 Hz (CS,) and J(free) = 209.5 &- 0.25 Hz and J(complex) = 221.65 + 0.8 Hz (HMPT). The difference in J(free) was ascribed to self-association of the CHCl, molecules. The higher value of the J(complex) was ascribed “to small angle changes in CHCI,“. It was mentioned, however, that the increase could also be caused by bond length or electronic density charge variations.

Looking at the number of data presented since 1972 it is obvious that solvent effects upon ‘J(C, H) cannot be interpreted in simple terms. Some results supporting the ideas of Kondo(175’ were given by Meillet’78’ (as just described) and by Elgamal~‘7g~ for bergapten (a furanoncoumarin). C-2, the carbon next to the furan oxygen gave ‘J(C-2’,H-2’) 204.3Hz in CDCI, and 207.5 Hz in DMSO. Shapiro(150) found that the ‘J(C, H) of monofluoro- and l,l-difluoroacetone were essentially solvent independent. Hammel et n1.“s’) recorded spectra of acetylacetones in several solvents and at different concentrations; with one exception the coupling constants changed by less than 1.2Hz. Thorpe et n[.usza) found small effects in imidazole of the order of 1 Hz in ‘J(CH) in going from CDCI, to DMSO. However, ‘J(C-2, H-2) increased whereas ‘J(C-4,H-4) decreased. The effects observed on the long-range coupling were smaller than the experimental uncertainty. ‘J(C,H) of cis- and trans-di-t- butylethylenes showed variations of l-l.5 Hz in going from the neat liquid to chloroform.(“zb) The “J of pyridine showed changes of up to 6% in going from deuteroacetone to D,0.(65)

Bock and Pedersent183) investigated solvent effects on ‘J(C,H) in carbohydrates. As differences in ‘J(C-l,H-1) are used extensively to predict the anomeric configuration (see Section 17) it was of great interest to establish that this difference was maintained in various solvents. The coupling constants were smaller in DMSO than in water, but larger in chloroform than in DMSO. A similar trend was observed for methanol as solute. The difference between ‘J(C-l,H-1 eq) and ‘J(C-l,H-1 ax) was roughly conserved (Table 21). Schaefer et ~1.t’~~’ showed that the one-bond carbon-hydrogen coupling constant involving the olefinic carbon in 1,3-dioxole increased by 0.65 Hz in going from benzene to acetone solution, whereas the coupling involving the methylene carbon increased only 0.25 Hz. INDO MO calculations showing that the olefinic hydrogens carry less negative charge than do the methylene hydrogens. The authors concluded that the specific interactions with the acetone molecules were largest at the olefinic site. Evans(‘69) aired the view that a C-H bond close to a polar group was already considerably polarized, so that the reaction field due to the dielectric medium would be less effective in changing ‘J(C,H). This argument is opposite to that of Kondo et ,1.““’ However, the haloforms were shown to be a

special caset169’ so that the generality of the conclusion reached by Kondot”” is questionable.

Studying p-substituted phenyltrimethylsilanes, Brouant et ~l.~‘~‘) plotted ‘J(C.H) vs. the Hammet (T values and found different slopes for the two solvents Ccl, and CH,Cl,. They attributed this difference to the ability of CH,Cl, to interact with the para- substituent either through a chlorine or a hydrogen, whereas the Ccl, only had the former possibility.

Wasylishen et c11.“~~) concluded that the limited number of data for 2-chloropropane suggested that the effect of solvents on the two- and three-bond carbon proton couplings were not large. Likewise Inamoto ec n1.t”” observed variations less than 3 % on ‘J(C, CO, H) in aldehydes in the three solvents Ccl,, CHCI, and acetone. Species or solvents containing OH groups do not follow a simple dependence of solvent dielectric constants as already pointed out by Watts and Goldstein’170’ and more studies including compounds or solvents in which specific interactions may occur are clearly needed. Solvent effects on ‘J of some organometallic compounds are mentioned in Section 24.2.

Solvent effects are small. For ‘.I maximally 7 % and for long-range couplings even smaller. The practical consequences of solvent effects on carbon-hydrogen coupling constants is thus limited, but still constitutes an interesting and challenging theoretical problem and may give very useful information about solute- solvent interactions.

6. SECONDARY ISOTOPE EFFECTS

Alei and Wageman (t30) investigated ‘J(C, H) in CH,, CH,D, CH,D,, and CHD, and ‘J(C,D) in CH,D, CH,D,, CHD, and CD,. Both ‘J(C, H) and ‘J(C, D) remained essentially constant although a trend towards slightly smaller values with increasing deuterium substitution may be indicated. Murray(‘*s) concluded after a remeasurement of ‘J(CH3) = 126.0 f 0.2Hz and ‘J(CDHs) = 125.41 + 0.2Hz in toluene and toluene-x-d that the secondary isotope effect resulted in a barely significant reduction. This is in agreement with the observation of Alei and Wageman. u 30) A comparison of ‘J observed in penta- deuterobenzene” lo) (157.65 rt 0.09 Hz) and benzene (158.43 f 0.04 Hz)“*) could suggest, however, the existence of a secondary isotope effect. A theoretical study by Sergeev and Solkan”**) indicated that the secondary isotope effects were not likely to be observable with a resolution of 0.1 Hz. Secondary isotope effects caused by the presence of 13C rather than ‘*C have been claimed in case of carbon-carbon coupling constants.“8g’ No such effect has been observed with J(C,H) and from a very precise study of J(H,H) in propene no difference was found between the C-12 and the C-13 molecules.~190)

No significant differences in ‘J(CH,) were observed for dimethylcadmium in the three different isotopes ’ 'ICd, ‘“Cd and 113Cd,“9”


In general it can be concluded that secondary isotope effects are very small.

7. l-EE.\IPERATURE EFFECT5

Liittke et al.“gZ’ observed no changes of ‘J(C, H) of octadeuteriobicyclopropyl over the temperature range -65°C to + 70°C. Some of the two-bond couplings involving formyl protons in aldehydes increased slightly as the temperature increased!‘g3) Two different explanations were forwarded. One was based upon the finding of Smith and COX”~~) that ‘J(H, H) should become more negative in solvents with higher dielectric constant. Assuming that ‘J(C, H) behaves similarly, ‘J(C,H) should decrease as an increase in temperature decreases the dielectric constant. The alternative assumed an intermolecular hydrogen bond between the aldehyde molecules. Hydrogen bonding decreases the 2J. Increasing the temperature reduces the intermolecular bonding.

8. ONE-BOND COUPLING CONSTANTS

Much of the early interest in one-bond carbon- hydrogen coupling constants has centred around theoretical models to explain their dependence upon hybridization,“g5*‘g6’ the average excitation energy, effective nuclear charge”g8) or the fact that ‘J(C, H) values were related to the fractional s-character. Other aspects of one-bond coupling constants include effects of steric strain and the angle distortions often associated with steric interactions as well as the possible rehybridization. Substituent effects may be related both to electronegativity, lone-pairs on neighbouring substituents or to other features such as electron density. ‘J(C,H) may also be related to other NMR observables such as 13C chemical shifts, hydrogen- hydrogen or hydrogen-fluorine coupling constants or to entities calculated in MO calculations.

8.1. H$ridizafiot’

The relationship originally proposed by Miiller and Pritchard”“) and by Shoolery:“g6)

‘J(C, H) = 5OOp,, (8.1)

(PCH is the fractional s-character of the carbon orbital used in the bond) has been used extensively. Its limitations have been discussed in some of the previously mentioned work,“‘7.‘98’ and it has been critically reviewed.“gg*200’

Only the most recent results are included here. Weigert er nl. (201’ have stated that in the absence of an electronegative substituent there seemed to be a correlation of s-character with the carbon-hydrogen coupling constant. Olah and Comissarov’202’ found that the relationship was also valid in the case of positively charged carbon-atoms.

Among the uses of equation (8.1) can be mentioned that an sp2 hybridization of the ylidic carbons in phosphorous ylides has been deduced from the

changes in ‘J upon deprotonation of the cation (13.5 Hz to 153 Hz).‘*O~*~O” The results of Albright er a1.“05’ are from salt adducts according to Reference 206. In methylene-triphenylarzorane no rehybridization took place.“06’

The increase in ’ J(C-xc, H-Z) of cr-lithiothiacyclo- hexane l-oxide compared with the parent compound was taken as evidence for a hybridization change, as the increase in the negative charge would lead to a decrease in coupling constant.‘207) Based on a comparison with trimethylenephosphorane’203.20” it was furthermore predicted that C-r configuration was planar or nearly planar. Coupling constants of carbonium and carbanions are treated further in Section 23.

Other correlations dealing with hybridizations have been proposed.“08*209) A relationship

‘J(C, H) = 1079&/(1 +s&)-54.9 (8.2)

where scH is the bond overlap. A similar relationship was derived for ‘J(C, C). Equation (8.2) was shown to have advantages over the simpler equation (8.1) and was believed to be useful for hydrocarbons in spite of the drastic approximations involved. The origin of the constants was discussed by Gil and Geraldes.““’ The equation was applied to unsaturated hydrocarbons where it also gave an improved result.

Hybridization in small ring systems has attracted some interest. Simultaneous monitoring of ‘J(C,C) may be of help in such studies.“07*2’o-2’4’ Nair”“’ used the same approach in azirines. The need to restrict correlations to homogeneous groups and to use a rigorous mathematical procedure were stressed by Iordache.” 16)

8.2. Bond Angle Effects

Changes in bond angles and bond lengths are physically observables contrary to variations in hybridizations but the two parameters are closely related. Bond angles different from those found at atoms with tetrahedral, trigonal or linear geometry may be caused by incorporation into ring systems or by steric interaction with neighbouring groups.

8.2.1. Rirlg Strc’ir’. Small ring systems have been investigated and equation (8.2) used to estimate bond hybridization. Wiberg et a1.‘2’7’ pointed out difficulties in applying this correlation to couplings in strained ring systems. Gopinathan and Narasimhan’2’6’ used the SCF MO (CNDO/Z) FPT formalism to calculate ‘J in three-membered rings and found a satisfactory agreement with experimental data. For a given type of wave function, the calculated J(C,H) appeared to be roughly proportional to the square of the “bond order”. Figeys et a1.‘2’g’ used LMO’s to arrive at the following equation:

J(CH) = 6.93(%s)-51.06

(standard deviation 4.98 Hz) (8.3)

190 POUL ERM HANSEN

The bicyclo[l.l.OJbutanes have already been mentioned”“-2’3’ and older references are given in Ref- erences 2 and 5. More recent studies deal with substituted cyclobutanes’“” and l&disubstituted-la,2,7,7a- tetrahydro-1.2,7-metheno-lH-cycle-propa-[b] naph-

thalene.‘“” Benzocycloalkenes”“‘-“5’ have also been investigated. In these compounds both the methylene and the aromatic C-H bonds give interesting coupling constants

(CH, 1, (C&h

1 2.

For it = 1 (Structures 1 and 2) ‘J(C-a,H-a) of the methylene is large _ ~~OHZ,‘~~~*~~~~**” but falls sharply off and reaches with n = 3 a value close to that observed in cyclohexane.“22’ Bond angle variations were suggested as the cause of the small ‘J(C-3, H-3) in I-carbomethoxy-2,2,4,4_tetramethyl- bicyclo[ l.l.0]butane.‘2131

In cyclic olefins ‘J(C, H) depends clearly upon the ring size. ‘**s’ In the non-alternant aromatics, azulenes, differences between ‘J in different rings are observed!22g-23” The change in ‘J(C,H) between benzene and the tropylium ion can also partly be explained by an angle change.‘23” Tokita et n1.‘233’ correlated ‘J(C,H) with strain energy calculated by the force-field method :

‘J(C, H) = 0.42Es + 124.8

(s.d. 0.2 Hz and C.C. 0.99) (8.4)

The main weakness of this correlation is that the data only encompass ring sizes from three to six. The relation between one-bond couplings of bridgehead protons in [2.2.1]-systems and the total strain energy showed no correlation.‘1g6*23J’ Joela’235’ calculated coupling constants using mutual and self- atom polarizabilities with no other semi-empirical parameters than Slater exponents. The results for norbonene, norbornane, 2-endo-methyl- and 2-exo- methyl-5-norbornene were very good except for the C-H coupling of the 7-sJn-position. However, slight changes in the coordinates give substantial changes in the coupling constants.

82.2. Steric Effects. These have been discussed by Servis er ~1.“~~’ for trimethylsilyl-substituted methanes. rManatt er nl.““’ used equation (8.2) to estimate the changes in coupling constants that can result from angular changes caused by steric compression or ring strain. The examples were confined to aromatic and olefinic systems and they will be discussed later in the context of one-bond couplings of olefinic compounds (Section 18.1.1). Alkyl substitution orrho to the carbon in question leads to a decrease in ‘J(C,H). Such a decrease was observed in methyl-naphthalene,‘2’7.2Z8’ but even more so with isopropyl- or t-butyl substituents!‘3” In case of isopropyl- and r-butyl groups

the effect is most likely steric and possibly caused by angular distortions. The variations in ‘JlC. H) for a C-H bond next to an atom having lone pairs have been explained by Gorenstein er ‘r1.““” in terms of a bond-angle distortion. Bond-angle changes were rationalized on the basis of equation ~82). In a tetrahedral atom, hybridization arguments required that the distortion of one-bond angle must lead to distortion in one or more other angles. Confining the changes to two bond angles gave changes as seen in Table 2. The distortions were estimated by means of CNDO/Z calculations!“‘.“” Several comments can be made. Equation (8.2) is only applicable to hydrocarbons according to MacsiE er ‘il.“o8’ Further- more the examples given are very few and the exact geometries are not known. In cyclohexane ‘J(C, H),, > ‘J(C.H),,. which may or may not be explained depending upon the magnitude of the distortions and thus the model is without any predictive value. Finally the predicted changes are different from

those predicted in olefins and aromatic hydrocarbons (Table 2).

8.3. Strbstifuent Effects

Substituents may perturb one-bond couplings in different ways according to their electronegativity, overlap with lone pairs, electric fields (due to the substituent), angle changes caused by steric interaction, or bond-length changes.

8.3.1. Additi~Q. Substituent effects have been shown to be additive in substituted alkanes,‘ZJ3)

in halobenzenes,‘21Jr and in polysubstituted pyridines.‘2’5’ Additivity has also been shown in diketo- piperazines based upon data from amino acids,“‘6’

and in fl-1,2,3,4,5,6-hexachlorocyclohexane.’*”~

8.3.2. Electroneyrrtkity. In Me,.Y derivatives

(X = Si, Ge, Sn, Pb, H, C, I, S, Br, N, Cl, 0. and F) ‘J(C, Hj have been tabulated’24”’ against Pauling”” or Muller’250’ electronegativity and results similar to those obtained by DouglasfZ5” and Yue”“’ were found.

One-bond couplings in fluoroalkylsilanes are related to 13C chemical shifts”53’ although some serious deviations were found. As charge densities can success- fully be related to ‘H and 13C chemical shifts, in some cases, correlation of charge densities with one-bond coupling constants have also been attempted.‘25” It was found that a linear correlation was restricted to substituents of the same row of the periodic system. In a-bromo- and r-iodobutyraldehyde the iJ(CO, H) did not vary with the electronegativity of the sc-substituent.‘2s5’

8.3.3. Low-Pair Effects. Lone-pair electrons were originally observed to affect two-bond proton- proton@ and proton-nitrogen”63J coupling constants. Studies of oximes and aziridines”56-‘60’


TABLE 2. Calculated changes in ‘J(C. H) as a function of changes in the bond angles

DeformatiotP

AJb.C

(aromatic) AP

(olefinic) Deformation’ AP’

(aliphatic)

Cl2 + 10

+8 +6 +4 +2

0 1

54 -6 -8

-10 -12

- 28.4 - 19.5 - 12.3

-6.9 -3.0 -0.8

0 -0.8 - 3.0 - 6.9

- 12.3 - 19.5 - 28.4

-44.6 - 32.5 - 22.4 +6 - 6.0 - 14.2 +4 +0.3 -7.8 k2 + 5.5 -3.1 k1 + 6.6

0 0 0 + 1.5 + I.5

0.0 -3.1 - 7.8

- 14.2

a. In degrees. b. C-C-C angle 120’. c. Start parameters O,, = 122.0” and f3?, = 116’

showed that lone-pairs also affect ‘J(C,H) in such a way that the larger coupling in which the C-H bond is cis to the nitrogen lone-pair rather than trans. This finding was substantiated by theoretical calculations!25’-‘5g*z61r Studies of other systems have since been performed’262*263’ and lone-pair effects have been used to explain the difference in carbon- hydrogen coupling constants in methylene groups next to an atom having lone-pair electrons. Many examples occur for carbohydrates (Section 17.1). In these compounds the effect has been used to determine the stereochemistry of the anomeric a-carbon. Many of the studies of lone-pair effects have been performed in six-membered rings (such as for carbohydrates). In cyclohexane ‘J(C, H),, > ‘J(C, H),, the difference being 4Hz. In trimethylene sulphites Albriktsen’26J’ observed ‘J(C-4. H-4),, = 155 Hz and ‘J(C-4,H-4),, = 147Hz. The effect of the S=O group was expected to be small in this compound. (Structure 3.)

51

H eq -Y 0

** 0, \ S

%X II 0

Y 0

O I-&

Y H ax

Similar effects were observed by Bock and Wiebe(265) in 2-substituted 1,3-dioxanes. The difference between ‘J(C, H)eq and ‘J(C,H),,, 166Hz vs. 158 Hz, was smaller than expected from the presence of two oxygens. The coupling constants in cyclohexane are *J(C,H),, = 126.6Hz and ‘J(C, H),, = 122.6 Hz’l12.266.‘67’

van Binst and Tourwe’268) measured the ‘J(C. H) of the angular C-H bond next to a nitrogen in reserpine and yohimbine (both of known geometry) and found that in the latter where the lone-pair electrons are cis to the C-H bond the coupling JPNMRS ,,:4 - B

d. Reference 237. e. AIIcA = A&. f. Reference 240.

constant is 6-9Hz larger than in the former. This lone-pair effect was used to determine the configuration of benzo- and indoloquinalizines as well as the preferred position of the N-H bond in (runs- decahydroquinoline. The very low ‘J(C, H) = 123 Hz in quinolizidine itself (Structure 5) compared with

H

&

9r

N

5

125 Hz in trans-decalin is in agreement with the trans- orientation of the nitrogen lone-pair and the C-9a, H bond and it stresses the fact that a rrans-relationship has little effect upon ‘J(C,H). Takeuchi et 01.‘~~~’ observed similar effects in hexahydro-3H-oxazolo- [3,4C]pyridines. The difference is 10 Hz in this case and they concluded that this stereochemical dependence is a powerful tool for the investigation of non- aromatic heterocycles.

Egli et c~l.“‘~’ measured ‘J(C,H) in a number of simple open chain model peptides as well as for cyclosarcosyls. The latter have the advantage of containing two C-a methylene hydrogens. In cyclotetra- sarcosyls a difference of 12.5 Hz (137.5 and 150.0 Hz) was observed and the effects were discussed in terms of the lone-pair electrons. For conformational averaged system ‘J(C-a, H-z) values in the range 140.0-142.5 Hz were observed. For amino acids and peptides the ionization state may also play a role in determining ‘J values.

In 5-thioglucopyranoside a difference of only 3 Hz is found in ‘J(C,H) between the a- and g-isomer. The small difference was ascribed to an anomalously small ‘J value for the a-anomer. In other words, ‘J(C, H,,) is enhanced less in case of sulphur than with oxygen!270i In theoretical calculations (de infm) attention was drawn to the fact that the energy


difference between the p and s type lone-pairs may be important. The difference between ‘J(C,H)cis and ‘J(C,H)rrans or between ‘J(C,H)gauche and ‘J(C,H)trans can be summarized for different compounds as follows: oximes 14Hz, aziridines 10 Hz, oxaziridines 5-7 Hz, carbohydrates w 10 Hz, imidazolidines 10 Hz, peptides 12.5 Hz (a maximum of 15-20Hz was predicted). Theoretically Gil and Geraldes~zOO~ predicted a difference of 20Hz in the fragment shown in Structure 6. Sulphur gives a

H’\ P ,c=x

H’ 2

6

smaller difference than oxygen or nitrogen. The effect of heteroatoms at the r-carbon has thus been proven convincingly and its sterochemical properties may be used to full advantage.

A point of interest is whether substituents further away from the C-H bond in question may influence ‘J(C, H). In 2- and 6-halogeno-4-terr-butyl-cyclo- hexanone it was observed that 1J(C-2,H-2),9 > *J(C-2, H-2),,. The difference decreases in the order Br > Cl > F.t2’la) Egli et a1.“o6) have discussed the possible influence of the CO group in peptides on’J(C-cc, H-u). In 2-methyl-2-t-butyl-4,6-dioxo-1,3- dioxanes ‘J(C-5,H-5) is different for the axial and the equatorial proton (129.0 and 138.3 Hz respectively).(27’b’ Theoretical calculations on acetaldehyde showed that the orientation of the C=O group has only little effect. A variation of +0.3 Hz was found in varying the dihedral angle (between C-O and C-H) from 0 to 90°.(27’c)

Werstiuk et a1.(234’ observed that the one-bond coupling of the bridgehead proton G( to the carbonyl group in bicyclic and tricyclic carbonyl compounds showed an increase compared with that in the parent compounds, whereas acyclic or monocyclic ketones give almost the same values as in the hydrocarbons.(272) Whether or not the carbonyl groups play a role has not been definitely decided. Albriktsen(264) has discussed the possible effect of the SO group in trimethylene sulphite. This effect was judged to be small. In contrast ‘J(C-5,H-cc),, < ‘J(C-5,H-5),, which is an effect two bonds away from the nearest oxygen (Structure 3). In 2,4,6- trimethyl-1,3-dioxane a similar effect was observed.(240)

Carbonyl groups in N-methyl amides were shown both experimentally and theoretically not to influence the one-bond coupling of the N-methyl group.(273’

The theoretical treatments of ‘J(C,H) in general have shed some light upon lone-pair effects. Gil and Teixeira-Dias(Z58’showed that a negative contribution to ‘J(C, H) is to be expected if the lone-pair orbital on a neighbouring atom and the C-H bond are antiperiplanar, whereas a positive contribution will result

if they are “cis”. They also predicted a form of additivity if more lone-pairs are present.

AugC: and David ‘271) have performed ab initio STO- 3G MO calculations on 2-chlorotetrahydropyrane (model compound) in its two possible chair conformations in order to investigate the cause of the difference of ‘J(C-l,H-l,,) and ‘J(C-l,H-l,,), e.g. in carbohydrates. The calculations predicted that the equatorial C-H bonds next to the ring oxygen had a higher “s-character” than the axial ones, while all other C-H bonds had practically the same s- character. Assuming a direct proportionality between “s-character” and ‘J(C, H) the experimentally observed differences are qualitatively explained. The difference in s-character is considered a consequence of an interaction of the oxygen Zp-type lone-pair with the anti-bonding orbital cc- of the axial C-H bond. The calculations also showed that the anomeric effect is proportional to the energy difference between the p and s type oxygen lone-pairs. Calculations on a model ring system are thus able to predict that ‘J(C-1, Heq) > ‘J(C-l,H,,) and that there is no significant effect on ‘J(C-n, H) if C-n is not a neigh- bour to the ring oxygen. However, calculations performed on methanol rotamers, an acylic system, did not reveal any significant differences in the s-characters of the various C-H bonds. However, it is difficult, on the basis of this paper to draw general conclusions as the authors use both s-type and p-type lone-pairs (supposedly using atomic orbitals) and at the same time talk about s-characters (hybridization picture). ‘J(C, H) in methanol was calculated by Cyr et a1.c275) (CNDO/Z approx.), who found that ‘J increased as the lone-pair electrons approached the C-H bond (Table 3). Aminova and Samitov’276’ used both methanol(276) and methylamine(276) as models, but the results are not in agreement with the experimental findings. Similar disagreement between observed and calculated values are found for methyl- phosphine.(277’ Samitov et a1.(27s) have calculated ‘J(C, H) in CH,POCl,, (CH,),PO(OH), (CH,),PO,

TABLE 3. Theoretical calculations of ‘J(C, H) in methanol

ea ‘J(C-l,H-l)b ‘J(C-1, H-l)

0 162.3 30” 79.05 60” 165.0 78.49

1200 169.5 76.45 180 171.3 75.22 240 77.58 270 76.45 300 78.49 330 79.05

H

<H-l a.

@ b. From Cyr et a1.‘275’ c. From Aminova and Samitov.‘2’6’


CH,PH,, (CHj),P, (CH,),PH. In the tetra-coordinated compounds and for CH,POCl, the orientation of the P-O bond was considered, whereas for the tricoordinated compounds the orientation of the “lone pairs” was considered. For all three types it is clear that the ‘J(C, H) coupling constant is sensitive to the spatial orientation of the surrounding atoms.

Lone-pair effects are now well established and their effects for different atoms have to some extent been mapped. Theoretical calculations on these give very variable results. Effects of lone-pairs further away are clearly demonstrated, but need much more attention.

8.3.4. Electric Field Eflects. Since the original paper of Buckingham(279) on electric field effects a few papers have discussed this type of substituent efiect upon carbon-hydrogen coupling constants. Miiller’2*0”’ has examined ‘J(C,H,) in a number of halogenated toluenes to determine whether a halogen could create field effects, which would lower the “average triplet excitation energy”. No significant effects were observed. According to Pople and Santry(2Wb’ (equation (8.5)) ‘J(C,H) depends on the product of the s-electron density at both the carbon (s:(o)) and at the hydrogen (s;(o)) nuclei and on the atom-atom polarizability (n~sc). Raynes and Sutherly”‘*’ attributed the electric field dependence of ‘J(C,H) to variations in n,,,and evaluated the electric fields at the bond centres. Hammel and Smith(28’*282) criticized this neglect of changes in s;(o) and s;(o) and attempted to take into account the electric field gradients along the C-H bonds. Neglecting second order terms in E (the field along the C-H bond) they arrived at the following equations

J = ~~‘~rCr”s~(o)si%0) (8.5)

For methine protons:

AJ(C,H) = J(C.H)-J,(C,H)

= ackHE,(H) x aHk,E=(C) (8Sa)

For methyl protons:

AJ(C,H) = 0.33E,(H)-O.O14E,,(C)( x 10-4) (8.5.b)

/3-Diketones yielded ackH =0.52x 10s4 and aHkc = 0.018 x 10e4. Equation (8.5b) is an improved version of that presented in Reference 181. The coefficients show that the important effects occur at hydrogen atoms rather than at carbon.

Reynolds er af.‘2*3i have investigated r-methyl and cr-t-butyl-4-substituted styrenes (Structure 7). The angle of twist between the benzene ring and the plane of C-cc. C-8. H-8, H-9 is different in the cc-methyl and the a-t-butyl-derivatives. Additionally the C-b, H-8

/

X-Qp.. /y--H9

HIi 7

bond is almost perpendicular to the field due to the polar substituent and the C-/?,H-9 bond is almost parallel. The effects of the electric field are reflected in the behaviour of ‘J(C-&H-9) and ‘J(C-B,H-8). The former is more sensitive to substituent effects. To exclude stereospecific effects through bonds calculations were performed for CH,X - CzH4 pairs with a geometry identical to that of 4-substituted styrenes. Since there is no intervening aromatic system, these calculations should reflect only the electric field effect. The calculated effects are consistent with a through- space field effect. Field effects may also be estimated by correlation with the Swain-Lupton’Z84) parameters, F (field) and R (resonance). In both cases, the correlation revealed that ‘J(C-p, H-9) is more sensitive to field effects than ‘J(C-/?, H-8). For other correlations with reactivity parameters see Section 8.4.1. Electric field e!Tects have also been discussed in conjunction with solvent effects” 7‘-‘73) (Section 5).

8.4. Correlations

One-bond couplings have been related to other physical observables such as chemical shifts. Pekh et ~l.‘~~~~correlated ‘J(C-X, H-X) with the substituent at C-X by replacing the hydrogen with a methyl group. The examples were norbornane, norbornene, bicyclo[3.2.l]octane, adamantane and the corresponding l-methyl derivatives. Other relationships with chemical shifts are found in substituted compounds in which the first atom is not a carbon (uide i&z).

Morishima ef .l.‘286) related 13C contact shifts (obtained when the di-tert-butyl nitroxide radical (DBNO) was added) to ‘J(C, H). They explained the correlation in terms of a finite perturbation of the spin density at the carbon resulting from a transfer of spin density from the DBNO molecule to the H of the C-H bond. Jankowski(287-2*9J proposed a semi- empirical way of improving the Karplus equation dealing with ‘J(H, H)‘290)

‘J(H-i, H-j) = Aces* B+BZ’J(C-i, H-i)

+ ‘J(C-j, H-j) (8.7) A = 8.79 and B = 0.004

The idea being that ‘J(C, H) reflects both changes in the hybridization and the electronic structure of the involved bonds. The equation was tested using a compound with fixed geometry and known angles and a slightly better agreement than with a simple Karplus equation was obtained. However, A and B values different from those of equation (8.7) were obtained from L-proline.‘289’ In cycle-alkanes ‘J(C,H) and ‘J(C, F) may be correlated (107c) but it was pointed out that coupling mechanisms other than the Fermi contact term may contribute to ‘J(C,F).‘29*~292) In Me,X derivatives * J(C, H) and *J(H, C, H) correlated quite well, but the correlation could not be extended beyond this simple series.(24*1

19-l POUL ERIK HANSEN

Newton et al.““’ have correlated experimental stituents showed that a distinct correlation exists for one-bond couplings and theoretically calculated %s the two types of substituents. The two plots are characters to obtain: parallel.““”

J(C.H) = 5.70(‘l,r)- 18.4Hz (8.8)

(s.d. 5.7 Hz)

On basis of this equation ‘J(C, H) of Dewar benzene and benzvalene was predicted.

Mamatyuk and Koptuyg@g” have concluded from studies of cations and anions of anthracenes that

‘J(C,H) values depend mainly on the variation of charge at the hydrogen. Based upon electron densities calculated in theCND0/2 approximation they arrived at the following empirical equation:

J(C.H)= t61+1939H+27qc

(I” = -$,(o) and 9c = 1 -s;(o)

(8.9)

where s$(o) and s;(o) are the electron densities of the hydrogen and carbon s-orbitals. This equation predicts the opposite trend to equation (8.5).

8.4.1. Correlariotl with RencriGty Pnrometers. Yoder er 01.“g6’ have reported a linear relationship between ‘J(C. H3) and Hammett a-constants in substituted

toluenes, t-butyl NJ-dimethyl anilines and anisoles. These investigations have been extended to substituted phenylsilanes, phenylmethylsilanes. and phenyl- dimethylsilanes.““’ Freeburger and Spialter”‘“’ examined 25 substituted phenyltrimethylsilanes and

found that ‘J(C, H) did correlate with 0,. o,,, and up. but that no general o could be used as in the preceding paper. Hess et ~I/.(‘~~’ have investigated

substituted aryltrimethylsilanes and also aryltri- methylgermanes, aryldimethylphosphines and arsines

and arylmethylsulfides and supported the finding that ‘J(C,H,) values in the aryltrimethylsilanes do not correlate with Q. Poor correlation was also obtained for the germanes and arsenes. In substituted benzyl- dimethylsilanes and phenyltetramethylsilanes a good correlation was obtained for the benzyl protons in the former and also in substituted toluenes.(‘OO’ Excellent correlation of Hammett G and o+ (donor substituents) \vith ‘J(C. H,) in N-methylpyridinium salts was obtained.““’ p and G from tnrtn and ptrrrc-substituted toluenes, anisoles, and aldehydes were used to obtain o. for ortho-substituted ones.(30’) One-bond coupling constants involving imidoyl protons in 4- and 4’- substituted N-benzylidineanilines fitted the Hammett relationship using o constants.‘30J-30b’ ‘J was correlated with cl and up in monosubstituted benzenes by Ernst er n/.“”

Parameters in orrho-substituted aromatic compounds cannot in general be analysed with the Hammett equation. Yoder et al.c30sr have applied the Taft approach’309’ using the substituent constants 6, and o$ to analyse ‘J(CH,) of ortho-substituted NJ-dimethyl-. acetyl-. thioanisoles and chloro- methylbenzenes. In general the correlations were good. The use of F and R values of Swain and Lupton improved the correlation slightly in some cases, but yielded slightly poorer results in others. The effect of hydrogen bonding was shown to be important in cases of anisoles and acetophenones, which showed improved correlation when amino derivatives were left out. Other parameters such as V, the van der Waal’s radius. Q/3’o’ or (E*) were added to the regression equation, but none of these seemed to be of

any significance. ‘J(C, H,) and 2J(C-2, H-2) of para- substituted toluenes were found to vary systematically and correlated well with F and R.(311a’ ‘J(C,H)

of substituted Buorobenzenes correlated best with I (31 ICI

A Hammett relation has also been referred to in Sections 5 and 9.1.

Use of carbon-hydrogen coupling constants not only provides an alternative way of determining the Hammett 0 and p constants, but it also provides valuable information about the way of transmission of substituent effects.

8.5. Other Aspects

‘J(C, H,) of 2,6_substituted dimethylanilines, di- ethylanilines and methylanilines were studied in order to evaluate the effects of steric hindrance.‘3”b’ 2,6-Dimethyl substitution in toluene, anisole and

N-methylaniline produced a small decrease of 0.5 Hz, whereas in the dialkylaniline a decrease of at least I.5 Hz resulted, which was taken as evidence for steric inhibition of resonance in &lo-substituted toluenes, anisoles and aldehydes.

8.6. Theoretica! Colcdarions

A correlation with the Swain-Lupton parameters, F and R. has been observed in 4-substituted-2,6- dinitroanisoles.‘30J’ ‘J of 2- and 3-substituted furanes, thiophenes and selenophenes have been correlated with different types of reactivity parameters. The greatest success was obtained when the reactivity constants, F and R. of Swain and Lupton were used.““’ A plot ofJ(C. H) vs. the F values for a series of substituted methanes with either -I’ or I- sub-

Recent papers on theoretical calculations of coupling constants have dealt with two important aspects. development of simple methods and estimation of contributions other than the Fermi contact one. Dewar et al.(3”’ used the MIND0/3 method and finite perturbation theory. The coupling constants obtained are somewhat inferior to those using the INDO method. Lee and Schulman’3’3’ have calculated ~b irlitio values for the orbital contributions to carbon-hydrogen coupling constants. For one bond couplings this term is negligible, whereas for ‘J(HNC) it may be dominant.

Andrt et 01.‘~‘~) have calculated the Fermi contact contribution by standard extended Hiickel. CNDO/Z


and STO-3G LCAO-MO procedures. Rather pessi- mistically they concluded that none of the methods was able to reproduce satisfactorily the magnitudes of the coupling constants and they proposed ways to improve the results.

Strictly localized molecular orbitals (SLMO) were used by MiertuS et u/.‘~‘~’ to derive the following equation for halomethanes:

‘J(C,H) = -2.436-361.144~C(2s)‘H(l~)’ (8.10)

standard deviation 5.88 Hz, E in eV, E is the ground orbital energy of the SLMO. C(2s) and H(ls) are the s-characters. BoEat3’@ has used a modified PCILO method. Other approaches have already been mentioned.‘274-278’

Runge ‘317) has related ‘J(C,H) in substituted allenes to the carbon 2s and hydrogen Is overlap populations (QsCsH):

‘J(C, H) = 1064.9Q,,,, - 142.0 (8.11)

r = 0.93

using ob initio STO-36 orbitals. Equation (8.11) worked well with substituents bonded via first row atoms (CO) as well as second row atoms (Si, S, Cl). The relationships of coupling constants with a6 initio overlap populations seemed to be superior to correlations with squares of semi-empirical bond orders, irrespective of the fact that there is no direct quantum mechanical justification of the first type.(317)

A pseudo atom MO approach has been developed by Maciel and Summerhayst3’BJ and applied to substituted methanes.

Jacobsen et ~1.‘~‘~’ have calculated ‘J(C, H) in diazomethane. The best agreement was obtained using the SOS INDO CI approach.

8.1. Summary

The general situation must be said to be that substituent effects on one-bond carbon-hydrogen coupling constants are understood in such detail that qualitative judgements can be made, but quantitative predictions based upon theoretical or physically observed parameters are seldom general enough to be used in a broad context.

9. TWO-BOND COUPLING COXSTANTS

Two-bond coupling constants are characterized by their change of sign from positive in acetylenes to negative in some aliphatic compounds. As the coupling constants often are small (with the exception of couplings across carbonyl groups or along triple bonds) and as substituents are expected to have a profound effect upon *J, it is imperative to determine their signs.

Two-bond coupling constants in general including carbon-hydrogen ones were discussed by Ewing.‘*’ Attempts will be made in this section to develop further the generalization of substituent effects. Two-

bond coupling constants are therefore tabulated extensively in Tables 4, 5, 7, 16. 19, 22-25, 29. 30, 33. Their uses in stereochemical applications are stressed. Qualitative theoretical treatments are of importance in the understanding of two-bond coupling constants, whereas quantitative theoretical calculations hdve

shown very little promise and they will only be mentioned in a few cases.

9.1. ‘J(C, C=X,H) X = 0 or N

Large positive two-bond coupling constants are observed along triple bonds (Section 19 and Table 29) and for two-bond coupling *J(C,C=X,H), X being 0 or N (Table 4). Couplings in aldehydes are three times as large as in oximes or o-methyl oximes.(320’ Those of Schiff’s bases fall in between.t3*” Similar trends have been found in the case of hydrogen- hydrogent322a) and of carbon-carbon couplings constants.(3z2b) Yamamoto et a1.(‘93’ estimated that the main contribution to the large coupling constant came from delocalization of the lone-pair electrons of the carbonyl oxygen and the low excitation energy of these electrons and the situation is very similar to that for 2J(H, C=O, H) as treated by Pople and Bothner- By &?*a)

Ortho-substituted aldehydes have smaller two-bond coupling constants than metn- and para-derivatives. Hydrogen bonding decrease *J(C, CO, H) slightly as judged from the value in o-hydroxyaldehyde compared with that of o-methoxybenzaldehyde.“93’ Similar conclusions can be made from a series of gossypols (o-hydroxybenzaldehydes)t32’a) and from pyridoxal S’-phosphate. (32~c) In the latter case a slight dependence upon pH was observed, possibly caused by the change of ionization state of the nearby phosphate group.

Bernassau et oI.“‘~~’ observed that *J(C,C=O, H) varies linearly with the free activation energy of the formyl group rotation barrier for a series of p-substituted benzaldehydes. Inamoto and Masuda(‘*‘) found that ‘J(C,CO,H) of m- and p-substituted benzaldehydes correlates well with the Hammett o,,, and cp constants, respectively. Ewingt”” found a decrease in ‘J(C,CO, H) of 2-halogeno-butyralde- hydes with increasing electronegativity of the halogen although Sackmann and Dreeskampt3’3b’ had observed a marked increase with increasing number of halogens at C-2 in acetaldehyde. The increase for a single chlorine is also much higher in the latter case (Table 4). These differences were explained in terms of different rotamer populations. Two effects were supposed to influence ‘J: inductive withdrawal will be largely from the symmetric orbitals and result in a positive change, and back-donation of the halogen lone-pair electrons into the asymmetric orbitals will also give a positive contribution. The latter effect depends upon their stereochemistry and were assumed to be most effective when the halogen and the hydrogen are antiperiplanar.


TABLE 4. ‘AC. C = X. H) X = 0 or N

C-i, H ‘J(C-i, CO, H) Refs.

Butyraldehyde 2-Chlorobutyraldehyde 2-Bromobutyraldehyde 2-Iodobutyraldehyde Acetaldehyde 2Chloroacetaldehyde

2,2’-Dichloroacetaldehyde Trichloracetaldehyde Tribromoacetaldehyde 3,6-OO-Dimethylversiconal acetate Benzaldehyde

2-Methylbenzaldehyde 2-Hydroxybenzaldehyde 2-Methoxybenzaldehyde

2Chlorobenzaldehyde

2-Nitrobenzaldehyde 3-Methylbenzaldehyde 3-Methoxybenzaldehyde 3Chlorobenzaldehyde 3-Bromobenzaldehyde 3-Nitrobenzaldehyde 4-Methylbenzaldehyde 4-Methoxybenzaldehyde 4-Hydroxybenzaldehyde 4Chlorobenzaldehyde

4-Bromobenzaldehyde 4Cyanobenzaldehyde CNitrobenzaldehyde Hemigossypolone Hemigossypolone-7-methylether Hemigossypol 7-Methoxyhemigossypol Gossypol C-25 terpenoids

1,2-Benzenedicarbaldehyde I, 3-Benzenedicarbaldehyde 1,4_Benzenedicarbaldehyde o-Hydroxy-m-methoxybenzaldehyde o-Methoxy-m-methoxybenzaldehyde o-Methoxy-p-methoxybenzaldehyde m-Methoxy-p-methoxybenzaldehyde Vanilline 1-Naphthaldehyde Acrolein trons-Crotonaldehyde Pyridine 2carbaldehyde Pyridine 3-carbaldehyde Pyridine 4-carbaldehyde

Pyridoxal5’-phosphate

Polyoxin N Benzaldehyde oxime 4Chlorobenzaldehyde oxime 2-Chlorobenzaldehyde oxime Pyridine ecarbaldehyde oxime ZlMethoxybenzaldehyde o-methyloxime a-Aminolentic acid pyridoxal Schiffs base

C-2, H C-2, H C-2, H C-2, H C-2, H C-2, H

C-2, H C-2, H C-2, H C-l’, H C-1,H

C-l, H C-1,H C-1,H

C-l, H

C-1,H C-1,H C-l, H C-1,H C-1,H C-1,H C-1,H C-I,H C-I,H C-I,H

C-1,H C-1,H C-I,H C-5, H C-5, H C-5, H C-5, H C-5, H C-5, H C-5, H C-5, H C-l, H C-1,H C-I,H C-I,H C-1,H C-l, H C-l,H C-l,H C-1,H C-2, H C-2, H C-2, H C-3, H C-4, H

c-4

C-3, H C-1,H C-l,H C-I,H C-4, H C-I,H C-4, H

24.8 26.5 27.6 28.9 26.6 32.5 31 35.8 46.3 51.6 24 23.8 24.11 24. I 24.08 23.1 20.13 22.1 22.6 23.3 21.4 25.2 23.7 24.3 25.0 24.8 26.0 23.8 23.9 23.9 24.6 24.4 24.7 25.2 25.3 20.3 19.6 17.8 18.2 17.9 20.0 19.8 19.8 24.85 24.94 24.70 19.8 23.2 22.3 24.4 24.9 24.1 26.6

+ 26.3 22.7 24.3 25.3 25.4 19.2c 21.4d 31.3 8.2 6.6 8.2 7.3 6.9 7.2

255 255 255 255 323b 809 807 323b 323b 323b 597 320 382 187a 27

187’ 395 187a 320 187a 320 187p 187’ 187’ 187a 187’ 187* 187* 187’ 187b 187a 320 187a 187’ 187% 323a 323a 323a 323a 323a 323a 323a 323a 323 323 323 193 193 193 193 825 193 804 807 193 193 320 193 323~

433 320 320 320 320 320 321

a. Solvent CDCI,; values for neat solution, Ccl, and (CD,),CO solvents were also given. b. Solvent (CD,),CO. c. pH 6.8. d. pH 8.7.


8

A similar situation to that observed in oximes is found for ‘J(C-3, H-2) in pyridine and other heterocycles. Gunther er al. ‘324) found that N-protonation decreases the two-bond coupling in the fragment of Structure 8 and this finding can be rationalized using the arguments provided by the Pople and Bothner-By MO theory.(322a)

9.2. 2J(c, c, H)

As mentioned before two-bond coupling across carbons of sp, or sp, hybridization are usually small (one exception is the coupling across a carbonyl group as described in Section 9.1). (See Table 5.)

9.2.1. Substituenr eficts. These effects were surveyed by Jameson and Damascor32s’ and also by Ewing.‘*’ The former considered effects at C-/3 and C-a as well as the effects of stereochemistry. Increasing the s-character of the bonds to hydrogen and C-/I make ‘J(C, H) more positive. Likewise, electronegative substituents at C-p make ‘5 more positive. Increasing the s-character at C-a increases the absolute magnitude

H\ /x =c

; Q

9

of ‘J. Electronegative substituents at C-a likewise make 12JI greater. The consequences of the direction of the substituents at C-a relative to the C-j, H bond was first realized in olefins. Weigert and Robertst3261 found that a substituent cis to C-/I, H gives a negative contribution, whereas a substituent trans gives a positive contribution. Furthermore, substituent effects in polysubstituted olefins are additive. Jameson and Damasco(32s’ discussed this orientational effect in terms of exchange integrals. That the direction of the

H\C=C B U’X

10

substituted plays a role has been confirmed in many other systems. Schaefer et a1.“84’ performed theoretical calculations in order to explain the positive 2J(C-3, H-3’) value of 1,3-dioxolyl and found a large positive sign, when one oxygen was tram and one gauche, whereas if both oxygens are gauche the couplings are smaller implying that a trans substituent in aliphatic systems also gives a positive contribution. Similar calculations for alcohols showed the same trend!327) That 2J in aliphatic compounds depends upon the orientation of the hydroxyl group and other oxygens has been used extensively in conformational studies of carbohydrates (Section 17). The differ-

ences between 2J(C-l, H-2) in n-propylhalides and 2J(C-2, H-2) in n-propylhalides and ‘J(C-2. H-l) in isopropylhalides have been explained by Spoormaker and de Bie(32*J as originating from different rotamer populations. The insensitivity to the electronegativity of the substituent of ‘J(C-2, H-l) in isopropyl derivatives may seem to contradict such a proposal, but this insensitivity is most likely the result of a cancellation of effects which indicates that ‘J(s- t) - 2 x ‘J(s-c).

Theoretical calculations using the Dirac Vector model and Penney-Dirac bond orders indicate that two-bond coupling constants in amino acids depend upon the dihedral angle 0, C, C-a, H-a (Structure 11). Both the c- and the n-contribution were evaluated. The former is negative, large and constant, whereas the latter gives identical results for 6 = 0” and 180°.(329’ These findings are opposite to the findings of Jameson and Damasco(32s’ as well as to data for 2J(C=0,C).(330’

The dependence of the direction of the carbonyl group was used by Vogeli et al.““’ to determine the direction of the carbonyl group in olefinic aldehydes. Pihlaja and ROSSI ‘t332) claimed to observe different 2J(CH3, H,,) and 2J(CH3, H,,) in 4,5-dimethyl-2- oxo-1,3-dioxolanes. However, the first-order analysis seems inadequate in this case. Because the substituent, a ring oxygen, is in the middle of the coupling path, no directional effects are expected (oide infia).

9.2.2. Elecrronegaticity. Substitution at C-8 with electronegative substituents leads to more positive coupling constants. This is demonstrated in olefins (Table 6), and also in 2-substituted carboxylic acids (Tables 7 and 8). Substitution at C-a has different effects dependent on whether the substituent is cis or tram to the C-/&H bond (Structures 9 and 10). Such a dependence on electronegativity has been observed. In the latter case the coupling becomes more negative with increasing electronegativity of the substituent, in the former it becomes more positive with increasing electronegativity. This feature has been demonstrated in olefins (Section 18.3), but the first case may also be observed in benzene derivatives (Section 20.2).

Tarpley and Goldstein showed that 2J(C-1,H-2) and 2J(C-3, H-2) correlate approximately with electronegativity for chloro-, bromo- and iodobenzene(244’ and within halouracils.r333’ The values in a more extensive series of compounds including fluoro- benzene(22’ have been correlated with electronegativity!27’ Good correlations were found only for 2J(C-3,H-2). Thus in most cases through bond

198 P O U L ERIK H A N S E N

TABLE 5. Two-bond carbon-hydrogen coupling constants, 2J(C, C, H) a'b

2j zjc Re~

Ethane Ethyl fluoride

Ethyl chloride

Ethyl bromide

Ethyl iodide

Ethanol

Ethyl acetate Ethyl ether Triethylamine Ethyl nitrate Propionic acid Propionitrile Ethyl trichlorosilane Trifluoroethanol Propane

Propyl fluoride

Propyl chloride

Propyl bromide

Propyl iodide

Isopropyl fluoride lsopropyl chloride

Isopropyl bromide

Isopropyl iodide

Isopropanol Diisopropyl ether Isopropyl acetate lsopropyl nitrite lsopropyl nitrate Diisopropyl disulfide Isopropylamine Benzylisopropylamine 2-Nitro-2-met hylethane. lsopropylmethylketone Isopropylphenylketone 2-Methylbutanoyl chloride 2-Phenylpropane Isopropylcyanide lsopropylmagnesium chloride 1, 1, 1, 4, 4, 4-Hexafluorobutane 1, 1, 1, 3, 3-Pentafluorobutane

2-Chloro- 1,4-dibromo 1,2, 2-trifluorobutane endo- 1, 2, 3, 4, 5, 7, 7-heptachloronorbornene

l-Chlorocyclopropane

Cyclohexane

C-1, H-2 -4 .8 C-2, H-1 -4 .8 548 C-I, H-2 -4.58 C-2, H-1 - 1.86 328

-4.53 - 1.66 819 C-I, H-2 -4.48 C-2, H-I -2.85 328

4.2 2.6 826 -4.47 -2.87 459

C- 1, H-2 - 4.60 C-2, H- 1 - 2.65 328 4.0 2.1 826

- 4.70 - 2.68 459 C-I ,H-2 -4.85 C-2, H-I -2 .8 328

- 5.0 826 -5 .04 -2.75 459

C- 1, H-2 - 4.64 C-2. H- 1 - 2.26 459 -3 .3 -2 .2 807

C- l, H-2 - 4.43 C-2, H- 1 - 2.61 459 C-I ,H-2 -4 .56 C-2, H-I -2.57 459 C-l, H-2 -4 .40 C-2, H- 1 - 2.83 459 C- I, H-2 - 4.73 C-2, H- 1 - 3.54 459 C-l, H-2 -4.61 C-2, H-I -4.56 459 C- 1, H-2 - 4.66 C-2, H- 1 - 5.43 459 C-I, H-2 -4.18 C-2, H-I - 5.06 459

C-2, H- 1 - 3.8 807 C-I,H-2 C-2, H-I -4 .3 328

-4.25 820 C- 1, H-2 - 1.70 328 C-2, H-3 C-3 H-2 C-I H-2 C-2 H-3 C-3 H-2 C-I H-2 C-2 H-3 C-3 H-2 C-I H-2 C-2 H-3 C-3 H-2 C-2, H-I C-2, H-I

-4 .4 - 4.39 -4 .8 C-2, H-I - 4.50 -4 .6 -4 .2 C-2, H-I -4 .4 -4 .3 -4 .3 C-2, H-I -4 .4 -4 .3 -4.1 C-2, H-1 -4 .2 -3 .8 -4.36 C-I,H-2 - 4.29 C- 1, H-2

C-2, H-I -4.38 C-I,H-2

C-2, H-I -4.64 C-I, H-2

C-2, H-I -4.35 C-2, H-I -4.18 C-2, H-1 -4 .3 C-2, H-1 -4 .4 C-2, H-1 -4 .1 C-2, H-I -4 .2 C-2, H-I -4 .3

C-2, H-1 -4 .3

C-2, H-1 -4 .0 C-2, H-I -4 .2

C-2, H-I -4.1

C-2, H-3 h - 5.02 C-I,H-2 h 7.2 C-3, H-2 h 5.2 C-3, H-4 h 5.2 C-I,H-3 - 3 C-5, H-6 -6.1 a

< 2.0 e C-I ,H-2 - 1.15 d C- 1, H-2 - 5.05 c C- 1, H-2 c - 3.69 C- 1, H-2 a - 3.94

C-I,H-2 C-I,H-2 C-I,H-2 C-I H-2 C-1 H-2 C-1 H-2 C-1 H-2 C-I H-2 C-I H-2 C-I H-2 C-I H-2 C-I H-2 C-I H-2 C-I H-2 C-1 H-2

C-2, H-I

-2 .8 328

-2 .6 328

- 2.65 328

0.0 - 1.88 - 1 . 9 5

- 1 . 7 4

- - 1.88 -2.05 - 2.06 -0 .76 -0.85 - 1.5

0.3 - 1.6 -2 .6 - 1.4

• - 1.6 -2 .8 -4 .8 -4 .4 -4 .7 -4 .0 -4 .9 -5 .0

- 4

328 328 186 328 186 328 186 186 186 186 186 186 186 186 186 186 186 186 186 186 186 186 496 495

497 494

8

112


TABLE 5 (contd.)

25

199

Ref.

Adamantane-d,

/I-1,2.3,4,5.6-Hexachlorocyclohexane 2,2-Dichloropropane 2,2-Dibromopropane Si, Si’-Dimethylsilacyclobutane I-Phenyl-I, 2-dibromo-2nitroethane

Ethylene oxide Ethylene sulphide 2,2.4.4-Tetramethylbicyclo[ I.l.O]butane rratw2.5-Dimethyl-2-rerr-butyl-4,6-dioxo-I, 3-

dioxane cis-2-Phenyl-5-methyl-4.6dioxo-I, 3-dioxane trc1ns-3.6-Dimethyl-2-oxo-1,4-dioxane cis-3,6-Dimethyl-2-oxo-l.4-dioxane tro~w-5,6-Dimethyl-4-oxo-l,3-dioxane

3.4-Dihydro-cis-2.3,4-trimethyl-ZH-I, 3. benzoxazine

3,4-Dihydro-trans-2,3.4-trimethyl-2H-I, 3- benzoxazine

rrans-5,6-Dimethyl-2-oxo-1,4-dioxane

cis-2,5,5.6-Tetramethyl-l-oxo- t,3-dioxane

Tetrahydro-2,3-dimethyl-I, 3-oxazine 2-Methyl-l. 3-dioxane 2-Methyl-l, 3-dioxalane 4-Methyl-2-oxo-l,3-dioxolane

craw4,5-dimethyl-2-oxo-I, 3-dioxolane

cis-4,5-dimethyl-2-oxo-1,3-dioxolane

5-Ethyl-5-phenylbarbituric acid I. 1.2,2-Tetraphenylethane Trimethylene sulphite

5-Methyltrimethylene sulphite

S-t-Butyltrimethylene sulphite 5-Phenyltrimethylene sulphite 4-Methyltrimethylene sulphite

C-2, H- 1 (- )3.32’ C-l, H-2 (- )3.34’ C-l. H-2 -5.12 C-2, H-I -4.3 C-2, H- 1 -4.6 C-2, H-3 4.1 C-2, H- 1 h -9.9 C-l. H-Zh et C-2, H-Is - 2.38 C-2,H-Is - 1.50 C-1, H-3 - 2.02

124

241 369 369 793

35

471 477 213

C-5, CH, -6.2 341 C-5, CH, - 5.4 341 C-3,CH, -4.3 341 C-3, CH, -4.2 341 C-S,CH, - 4.6 341 C-6,CH, - 1.3 341

C-4, CH, c-2, CA,

-4.6 < 1.5

341 341

C-4, CH, C-2,CH, C-5, CH, C-6, CH, C-6,CH, C-2, CH, C-2, CH, C-2, CH, C-2,CH, C-4, CH, C-4, H-5 C-5, H-4 C-4, CH, C-4, H-5 C-4, CH, C-4, H-5 C-5, H-I’ C-l, H-Zh C-4, H-5

-4.1 <1.5 - 2.3 - 1.6 -2.4 +2.3 co.5 + 1.6 + 6.0

4.4 3.9 5.5 3.9 4.4 1.95 4.4 4.3

-5.4 1.5 1.3 2.6

341 341 341 341 341 341 341 341 341 332

332

332

c-5, H-6

C-4, H-5 CH,. H-5 C-4, H-5 C-4, H-5 C-4, H-5 C-6, H-5 C-6, H-5 CH,. H-4

1.4 7.3 3.9 6.2 5.1 5.9 5.6 1.3 2.9

821 822 264 264 264 264 264 264 264 264 264 264 264 264

a. If the sign is not given, it has not been determined. but is usually assumed negative. b. The coupling is through sp3 hybridized carbons. C. The carbon in the middle of the coupling path is substituted. d. C-Cl5 and H are warts to one another. e. C-Cl, and H are cis to one another. f. Calculated from C-D coupling constants. g. The dual path nature of this coupling should not be overlooked. h. More than one substituent.

inductive effects were not the only mechanism influ- fluorides and chlorides, but the bromides and iodides encing the coupling constant. Field effects and, show values more negative than expected. This devi- in aromatic systems, mesomeric interactions and ation was suggested to originate in the participation n-inductive effects are likely to be active!“’ of occupied d-orbitals.t328’ In general 2J(C-a, H-/I) is

In ethyl and isopropyl halides ‘J(C-a, H-P) shows a very insensitive to substitution as shown in a large slight increase with decreasing electronegativity for series of isopropyl derivatives.rLE6)

TA

BLE

6.

One

- an

d tw

o-bo

nd

coup

ling

cons

tant

s in

ole

fins

R4?

4)

/ R

I(H

I)

‘ccc

. /2

‘\

R3i

H3)

.R

2(H

2)

R,

RI

R,

R4

Y

X

‘J(C

-X,H

-Y)

X

Y

*J(C

-X,H

-Y)

Ref

s.

H

H

H

H

I

Mon

osub

stitu

ted

F H

H

H

I 2 2

Cl

H

H

H

1 2 2

Br

H

H

H

1 2 2

1 2 3 4 2 3 4 2 3 4 2 3 4

156.

4 I

156.

2

200.

18

162.

16

159.

18

194.

86

I 16

0.89

1

162.

64

2 I I 2 1 19

6.58

19

6.1

1 16

0.26

15

9.6

1 16

3.63

16

3.8

2 1 1 2 19

0.X

.5

I 15

9.20

1

164.

09

2

3 -

2.4

3 +

7.5

4 -

1.9

2 +

6.9

3 +7

.1

4 -

8.3

2 +6

.8

3 +6

.75

3 +

1.5

*0.5

4 -

8.5

+0.5

2 +

5.8

f0.2

4.

0 3

6.6

4 9.

1 -

8.2

2 +

6.25

3 +4

.15

4 -7

.8

2 +

4.0

548

834

835

835

804

835

804

835

804

326

804

835

808

865

808

835

808

826

826

826

804

804

835

804

835

804

835

804

CN

H

H

H

2 17

6.74

17

6.65

16

5.43

16

5.37

16

3.20

16

3.01

18

2’

166’

14

0.28

13

9.8

156.

13

3 +

0.29

81

0 83

6 -

4.42

81

0 83

6 -

3.61

81

0 83

6 7*

1 56

0h

560h

2 3

2

WW

, H

H

1 2 H

836

837

2 83

6 80

4 83

6 80

4

- 7.

0

-2.5

-

0.8

2 2

4 15

6.45

Si

Cl 3

H

CH

O

H

CO

OH

H

H

H

H

I 2 1 -

6.85

+

1.8

2 16

2.3

3 16

2.3

4 15

6.6

804

-3.4

1

2 +

0.25

+

1.55

80

4 33

1 80

4 80

4

- 0.

2 -4

.55

-0.6

-0

.4

1 2 2

4 2 2 C

OO

Me

CO

CH

,

804

1 2

170

560h

1

3 16

2’

560h

2

-0.3

5 80

4 -0

.25

331

2 16

2 +l

161

f I

159*

1 16

5.0

838

331

1 3

- I.

1 83

8 4

-3.2

-0.3

-

3.1

8.8

- 1.

15

- 2.

60

331

838

-C=CH

H

CH

, H

H

H

H

H

3 58

2 2 2

160.

7 16

0.5

152.

0 15

1.90

15

7.0

157.

00

153.

1 15

3.50

15

1.92

1 2 4 2 3 4

549

2 2 4

2 +0

.35

- I.

04

- 2.

63

190

2

RI

R*

R,

R,

TA

BL

E 6

(co

ntd.

) E

X

Y

‘J(C

-X,H

- Y

) X

Y

*J

(C-X

,H-Y

) R

ek.

H

H

H

I 2 2

2 17

2 f

1.0

3 16

3 f

I.0

4 16

3 +

1.0

1 3

813

1 4

-7kl

.O

2 2

-4

+ 1.

0 1

3 1.

0 kO

.3

567

1 4

2.9

f 0.

2 54

3

CFC

F,B

r

CH

,Br

H

(CH

AC

H

CH

=CtI

,

H

CH

CI,

C

HC

I,CH

, C

HC

l,CH

,

ccl,

CH

,CH

,CC

I,

OC

OM

e

OC

,H,

OC

,H,

H

S&H

, H

NH

CO

Me

Z-P

yrol

iden

e H

H

Sn(C

,H,h

H

H

H

H

H

1 2

150.

04

2 3

157.

2 1

2 4

153.

29

2 3

159.

21

2 4

154.

9 1

1 1

156

1 2

159

2 4

155

1 2

172

2 3

163

1 2

166

2 3

160

1 2

169

2 3

162

1 2

156

2 3

158

2 2

- 0.

05

550

551

H

CH

,-CH

=CH

,

H

H

554

554

554

554

1 3

+ 7.

6 1

4 -

7.9

2 2

+9.6

5 2

2 +9

.75

556,

X04

80

4 80

4 80

4 x3

x H

H

2

182

+I

3 16

5 *I

4

159

+-1

H

1 3

1 4

2 2

(+

)5.3

( -

)5.

3 ( +

)9.7

X04

H

H

2 17

1 &

l 3

163*

1 4

159

+1

2 17

2 &

I 3

162

*I

4 15

4 *1

2

157

*1

3 16

0 +l

4

162+

1

83X

H

1 3

+ 3.

5 55

b x3

x H

H

H

H

x39

H

H

Dis

ubst

itute

d

CH

, (C

H,)

,C

H

CH

, H

1

2 H

(C

H,)

,C

H

I 2

148.

7 14

8.0

147.

56

149.

4 14

7.38

14

9.38

15

3.5

237

182

543

237

543

807

331

807

825

825

844

825

804

845 96

33

1

331

331

W&

C

H

CH

, H

CH

,

CH

O

H

H

1 2 1

2 4 2 1

4 -1

.9

-0.8

- 1.

5 -I

-

3.5

- 3.

3 1

- 2.

77

4.4

-2.8

-

1.7

-0.5

-

5.9

- 5.

9 ( -

)3.

5 ( +

)8.0

(+

)lo.

o 0.8

0.3 1.8

2.0

- 0.

4 -

1.4

( - )

6.2

t+)6

.2

- 6.

I ( +

)3.8

-6

.8

( - )

6.2

( + )5

.7

160

146.

1 15

1.3

160.

3

CH

,OH

CO

OC

,H,

H

H

Ph

Ph

H

H

1 2 1

4 2 4

2 I 4 2

154.

4 16

8.6

2 1 2 4

CO

OC

,H,

H

CO

OC

,H,

H

CO

OH

CN

OC

H,

CH

,

CN

CO

CH

,

OG

H,

Cl

OC

H,

Cl

331

845

658

320

842

826

326

846

331

2 19

9.1

198

4

Br

I Cl

Cl

Cl

Br

Br I CH

,

CO

OH

CO

NFH

,),

CH

,

2 20

4 1

4

331

331

331

TA

BLE

6 (

con

td.)

R,

R,

R,

R,

X

Y

‘J(C

-X.H

- Y

) X

Y

*J

(C-X

,H-

Y)

Ref

s.

H

CO

OH

H

H

C

OO

H

H

H

H

CH

, H

H

(C

HW

I 4

( - )6

.4

1

4

- 5.9

2

2

t+)o

.9

331

331

237

182

543

231

543

331

560h

331

804

845

804

99

554

554

554

331

331

658

842

326

845

826

326

846

554

331

554

Br

I CH

, (C

H,),C

(CH

W

CN

CN

C

OO

H

CO

OH

C

OO

C2H

,

CO

OC

H,

CH

,CI

CH

,CI

CH

,NC

IH,

OC

H,

OC

zH5

Cl

Br

I Cl

Cl

1 I 1 2 I 1 1

I 2 I 2 1

2 I I I 2 I 2

153.4

149.5

148.3

3

150.4

149.9

5

152.2

4

2

2

2 3

2

2 2

2

3 2

3

2 3 2

2

2

3

2

3

H

t1

H

H

H

H

H

H

H

H

H

H

H

H

H

CH

,

CH

,

CN

C

H,

CO

OH

C

OO

C,H

,

CO

OC

H,

CH

QI,

CH

,

CH

,CC

I,-

CH

,CH

,CI

CH

2C

CI,

- C

H,

C=C

H

1 3

2

2

1

3

1

3

2

2

1

3

1

3

+3.3

-

2.4

7&

l +0

.2

-0.5

+

3.3

6

1.5

+

3.0

7

H

H

184

H

H

H

167.6

168

157

163

160

157

150

154

1 3

- I.1

H

H

H

( + )

3.7

(+

)12.0

( +

)8.9

16.0

16.5

15.4

15.7

IS

.0

14.7

+ll.

O

H

H

H

CH

, C

l 197.3

198.3

200

H

H

H

H

Br

3

3

H

H

I CH

, 193

159

I 2

3 2

(+

)lO.S

( +

)7.4

H

H

C

H,C

I 194

162

Cl

Br

Br

H

H

H

H

CO

OH

W

CO

OH

I 2

3 2 3

( + )

7.7

(+)6

.6

(+ )

10.8

(+

)6.8

(+

)7.3

(+

)6.2

( +

IS.

4 (+

H.l

(+)I

.3

+ 3.

8 -6

.3

(+ )

3.7

tsg

(-&

3 ( +

)7.

0 ( -

)7

.0

(+ )

2.7

( -

p.9

( + J

7.0

(-,::

Y

(-;::

(-,:I

( +

j3.

9 ( -

)6

.3

(+w

0.3

1.3

-0.9

-6.3

+

5.6

331

331

331

331

2 2 3

H

2 I 2

2 3 2 3 3 4 3 4 3 4 3 4 3 4 3 3 4 3 4 3 4 3 4 3 3

I H

Bf

Cl

Cl

CO

OH

H

H

H

Br

CN

CO

OH

(2-b

CH

,

CO

OH

826

331

331

331

Cl Cl

Bf

H

H

H

H

H

331

331

331

331

1

W

CH

,

CH

,

CH

,

CN

CH

, C

l

H

H

H

H

I

CO

OH

CHO

H

H

H

H

331

331

OA

c

OA

c

Cl

H

H

H

H

H H

331

331

326

842

841

826

568

557

Br

GH

,

PC

I,

Br

H

H

Cl

H

H

167

167.

6 16

0.8

165.

5 16

3.3

4

Cl

H

H

TA

BL

E 6

(co

ntd.

)

R,

R2

R3

R4

X

Y

‘J(C

-X,H

-Y)

X

Y

‘J(C

-X,H

-Y)

Ref

s.

Tri

subs

titut

ed

H

H

Br

Cl

H

Cl

H

(CH

AC

H

N(C

H,)

, C

H,

N(C

H,)

, C

H,

N(C

H,)

, C

H,

N(C

H,)

, C

H,

N(C

HA

C

,H,

H

CO

OC

zHs

CO

R

H

CO

R

H

H

CH

, H

C

(CH

,),

Cl

Cl

Br

F Cl

CH

, X

C

CO

CH

, X

C

X’

X’

RN

H

CH

,NH

C

H,N

H

Cl

Er

Cl

F CH

, H

H

H

H

CH

H

CH

:

CH

, C

H,

C(C

Ha)

J

I I 2 2 2 2 2 1 1 1 I 1

2 2 14

8.01

4

I50.

3-

150.

9 4

150.

2 4

152.

6 4

151.

9 4

152.

3 I

166.

1 2

163.

5 2

160.

2 I

148.

4 I

143.

3

200

2 I

8.4

+0.2

X

.46

rt 0

.04

8.5

f 0.

5 8.

9 2

I 7.

8 8.

0 2

2 5.

1 +0

.2

2 2

11.0

io.2

I 4

d

840

841

842

326

326

826

843

843

543

576

576

576

576

576

811

811

811

542

542

a.

Not

co

rrec

ted.

b.

So

lven

t de

pend

ence

ha

s be

en

inve

stig

ated

.

c.

X e

qual

to

R

, an

d R

, ei

ther

H

or

CH

,.

d.

Not

ob

serv

able

. N

N

e.

X e

qual

to

1

2 N

N

f.

X e

qual

to

n‘

,h,,

3

A

N

N

g.

X e

qual

to

A

NA

,,

3

h.

‘J(C

H)

has

also

be

en

inve

stig

ated

in

nic

kel

com

plex

es.

i. B

ased

on

fi

rst

orde

r an

alys

is.

j. L

ine

split

tings

ar

e ci

ted

in R

efer

ence

14

0b.


TABLE 7. ‘J(COOH. C-x) and ‘J(COOH. C.C. H-B) in amino acids’

PD ‘J(C0. H) ‘J(C0. HI ‘&CO. H) Refs.

z-Corho.yd Grolrp Alanine

Valine

2-Aminobutyric acid

Leucine

Homoserine

Phenylalanine Glutamic acid 7-methylester Aspartic acid

L-Histidine

N-Methylhistidine

N, N-Dimethylhistidine

N, N. N-Trimethylhistidine

Tryptophan S-Methyl-L-Cysteine

Hexamethylcysteine

Cysteic acid Serine

Threonine

Allothreonine

N-Acetylalanine

A-Acetylvaline N-Acetylphenylalanine N-Acetylaspartic acid

N-Acetylhistidine

N-Benzoylphenylalanine N-Acetyl-L-alanine N-acetamide Ala-Phe-Gly-Ala-Ala Pyridoxal Phenylalanine SchiAs base L-Prolylglycine Glycyl-L-proline Cycle-(glycyl-L-prolyl) Cycle-(glycyl-L-prolyl-glycyl)L (Glycyl-L-prolyl),

-0.5 5.7

12.0 -0.5

5.7 I I.9 0.5 5.7

11.7 +c OC

-c

I.1 6.0

CO 4.2 0.3 - 2-

11.0 2+c

+< OC

_c

2+c OC

_c

2+c +c OC

2-l-= 0’

+= DC

_c

2+c 0’

2-c 0.5

10.2 0. I 5.1 0’

II.1 0.6 5.8

Il.2 11.1 d d

2.5 10.3 + 0

-

d e

f f

f

5.1 5.0 4.2 6.2

- 4.9 5.0 6.0 5.0 4.7

6.0 5.3 6.0 5.2 7.1 5.3 5.0 5.0 6.4 5.3 5.7 4.5 4.9 3.5 3.7 5.5 4.7 4.4 6.0 5.6

6.3 5.7 5.0 5.6 4.6 5.8

- 6.3 - 5.4

6.2 5.3

5.5 6.0 5.4 5.7 4.8 5.0 6.3

7.0 6.6 6.8 6.0 5.1

4.9 5.0

5.05 4.65-4.85 5.9 5.0 4.0

4.2 4.2

4.1 4.2 3.1 2.3 4.3 3.8 4.0 6.32b 4.06 3.75 3.8 4.2

3.9b 3.5b 4.0b 3.3b 2.gb 2.5Sb 4.3b 3.6b 3.4b 3.2b 4.9b 4.0b

3.7b 5.5b 4.7b 4.4b 5.4b 4.gb 2.45 3.5b 3.4” 3.4b 3.4 3.2 3.1 1.9 3.2b 2.0 2.0 1.9 2.1

3.8 2.0 2.0 4.2 4.2 2.3 4.7b 3.5b 3.3b 3.0 2.9 2.1 3.2b 3.6

2.4

357 357 357 357 357 357 357 357 357 505

2.36 505 2.92 505

357 2.7 357

357 357 357 358 358 358 358 358 358 358 358 358 358 358 358 358 358 358 506 358 358 358

7.9 358 6.8 358 I.8 358 6.2 357

357 357 357 357 357 357 357 357 357 357 357 508 357 357 358 358 358 508 508 402

2.4 321 503 503 503 503 503

208

PD

POUL ERM HANSEN

TABLE 7 (contd.)

‘&CO. H) ‘JICO. H) ‘J(C0. H) Refs.

[Leu5]-enkephalin d

Valinomycin m n 0

P

m n 0

P

Glycylhistidine

CJ&-(L-threoninyl-L-histidine) Glutatione, oxidized Diaminoethane Pd(ll)complex of histidine /I-Alanine

/SCarboxy Group Aspartic acid

N-Acetylaspartic acid

cycle-(Asp-Pro)

m n 0

P

m n 0

i.7 2+c

OC -c

4.1 2+

+ 0

0.3 _c 2-c

11.0 2.5

10.3

_P

4.3h 3.8’ 6.2’ 4.8k 4.6q 6.1“ 7.2s 6.1q 4.8q 6.5’

2.7

3.lb 2.6

- 1.9 7.3’ < 1.0 3.0’

- 2.2 5.8’ 5.7’ 2.9 5.6‘ < 1.0 6.4’ 5.5s 2.7 4.7’ 4.3’ 1.8 6.0’ < 1.0 3.5’ 4.0’ 2.4 5.0 3.2b 6.8 3.5b 4.7 3.5b 4.4 3.lb

2.lU 4.0h

6.8 2.6b 5.2 2.8b 6.7 5.1

c 7.2 _ 7.4 6. I 6.1 6.1 4.0 5.8 3.7

_ 6.7 6.7 _ 5.8 * 5.8

6.0 5.8 5.7

1.0 421 421 421 421

2.6 4’1 412 412 412 412 412 412 412 412 412 412 412 412 412 412 412 412 412 412 412 412 357 358 358 358 359 146 358

357

357 358 358 357 357 357 507

a. Coupling constants to side chain acid groups are also given. b. Averaged coupling constants. j. Phe4 residue. c. Refer to charge rather than to pD. k. LeuS residue. d. Solvent, DMSO-d,. 1. Solvent, cyclohexane-d,,. e. Solvent, methanol-d,. m. Solvent, CDCI,. f. pD not given. n. Solvent, CCIJDMSO-d, (3: 1). g. Tyrosine residue. o. Solvent, methanol-d, + 2 7; H,O. h. City’ residue. p. K + complex. Solvent, CDCI,. i. Gly’ residue.

9. r. S.

t. U.

V.

X.

D-Valine residue. L-Lac residue. L-Val residue. D-Hui residue. His residue. COOH state of pcarbon COO- stateof y-carbon.

The influence of a nitrogen has also been studied in constants in unsaturated five-membered carbocyclic heterocycles. ‘J(C-2, H-3) is markedly different from rings are predominantly dependent on the C-C bond ‘J(C-3, H-2) in pyridine’rbJ and so are 2J(C-3, H-4) and ‘J(C-4, H-3) in isoquinoline(334) and ‘J(C-7, H-6) HP and ‘J(C-6,H-7) in 5-azaazulene.‘335) The effects of N-protonation have already been mentioned (Section 9.1). c\/c*

9.3. Bond Length Dependence Ia X

Braun et a1.(335*336’ showed that two-bond coupling 12


TABLE 8. ‘J(COOH. C, H) and ‘J(COOH. C, C, H) in compounds other than ammo acids

‘J Refs.

Phenylsuccinic acid

2-Phenyl-3-methyl-butanedioic acid 2-Methyl-3-isoptopylbutanedioic acid 3-Methylbutanoic acid 2-Bromo-3-methylbutanoic acid 2-Hydroxy-3-methylbutanoic acid Propanoic acid

4-Cyano-3,4,5-triphenylheptane-dioic acid

Cytidine S’-monophospho-N- acetylneuraminic acidk

Neuraminic acid methylester /3-methylglycoside Neuraminic acid methylester a-methylglycoside Neuraminic acid a-methyl glycoside /I-Neuraminic acid

4.3p 355 2.51 4.3b 2.Q l..Y 3.IC 7.5* 3.2* 7.55 3.0e

C- 1, H-2 6.4 C-l. H-3 1.6 362 C-4, H-3 _ 5.8 C-4, H-t 1.t 362 CO, H-2 - 6.80 CO, H-3 + 2.90 381 CO, H-2 -4.38 CO, H-3 + 2.57 381 CO, H-2 ( - )3.6 CO, H-3 2.3 CO, H-2 6.9 CO, H-3 5.8 454

7.0’ 5.5’ 357 5.9s 5.1s

CO, H-2 -5h CO, H-3 -2h 511

CO, H-3’ <l 504 CO, H-3) <l CO, H-3’ 61 504 co, H-3) Cl CO, H-3’ 5.9 504 co, H-3) Gl CO, H-3’ 5.4 504 co, H-3j <I CO, H-3’ <I 504 co, H-3j <I

a. Solvent D,O, pH = 6. b. Solvent D,O, pH = 9. c. Solvent, pyridine-d,. d. Solvent, acetone-d,.

e. Solvent, acetic acid-d,. f. Solvent D,O, pD = 0.5. g. Solvent D,O, pD = 11.5. h. Solvent D,O, pD = 9.

i. Axial. j. Equatorial. k. Turned out to be a /?-D-neuraminic acid.

length. A quantitative linear relationship was found:

‘J(C,H)= 24.15xrcc-29.09

(13 points, r = 0.91, stdev. 0.6 Hz) (9.1)

The low correlation coefficient suggested to the authors that the bond length is not the only factor influencing ‘J(C, H). Aydin et a1.‘337’ observed likewise an increase in ‘J with increasing bond length in aromatic compounds. However, different values for ‘J(C-2, H-l) and ‘J(C-1, H-2) of naphthalene were attributed to different bond angles.

9.4. Bond Angle Dependence

Marshall et ,1.(338’ observed a decrease in the numerical magnitude of 2J(C0,H-l) in l+cyclohexadienes with decreasing C, C, H angle. The same trend was observed for the ‘J(H-4, H-4’). Braun and Kinkeldei’339i found *J(CH) coupling constants in azulenes of 4-5 Hz in the five-membered ring, but couplings of < 1 Hz, in the seven-membered ring (Table 33). Vogeli et al.‘33” also found a dependence upon the ring size in five- and six-membered rings, whereas Hansen and LedtLzs’ in their study of cyclobutene observed a *J(C-1, H-2) value very similar to that observed in 2-methylbutene.

Denis and Malrieu’340i calculated spin-spin coupling constants to the fourth order by a double perturbation development starting from a fully localized determinant in the PCILO-CNDO method. They showed that the calculated ZJ(C,H) values depend both on bond lengths and bond angles.

9.5. Correlations

~yrr&‘341’ correlated *J(CH,,H) in cyclic compounds (five- and six-membered rings) with the corresponding *J(H, H) coupling constants to give the following relationship:

‘J(CH,, H) = 0.55 x *J(H, H)+4.93 (9.2)

For a methyl group attached to a sp* hybridized carbon the following equation was formulated:

*J(CH3,H) = 0.58 x ‘J(H,H)+2.86 (9.3)

Equation (9.2) is not suitable for acyclic compounds. Ayrfs and Partanen(34zi used the same equation to predict ‘J(H,H) in a seven-membered ring system. Schaefer(343) has correlated *J(H, H) and 2J(C, H) in planar molecules with Ax = -x~~+&+x~~) where ,y is the magnetic susceptibility. Flygare’344’ has related this parameter to the extent of electron


delocalization in planar ring sys&ems and it can thus be used as a measure of aromaticity. A plot of ‘J( ‘%=C-H) vs. AI gives two distinct lines (as with ‘J(H, H)). with those compounds which are normally considered to be aromatic on one and those being non-aromatic on the other.

No correlation of two-bond couplings of allenes with the squares of the bond order obtained from the CNDO/Z scheme could be observed. However, if plotted vs. the corresponding STO-3G overlap populations they show a fair correlation.‘3’7’

‘J = 63.35Q,$,,, - 78.61

r = -0.93 (9.4)

9.6. Summar}

The influence of substituents on two-bond coupling constants has now been thoroughly investigated and two-bond coupling constants could become an important tool in stereochemical studies. However, it should not be overlooked that although substituents play an important role, changes in bond angles and bond length may modify two-bond coupling constants considerably. Furthermore, the importance of determining signs of two-bond coupling constants should not be neglected, if several substituents are present.

IO. THREE-BOND COUPLING CONSTANTS

Three-bond coupling constants have been used extensively in stereochemical studies in conjunction with a Karplus-type relationship. Consequently, much effort has been invested in the establishing of Karplus equations. More recently substituent effects have also been studied in great detail, but as seen in Structure I3 the number of parameters (substituent effects, hybridization effects, bond-order changes and angle changes) is very large indeed. The situation is less complex for carboxylic acid derivatives, in which A, B, and C are fixed, than in aliphatic compounds.

H\ T A

Three-bond carbon-hydrogen coupling constants have been used widely in the study of side-chain conformations of amino acids. Besides stereochemical studies three-bond coupling constants have attracted much use in assignment problem because of their usually large magnitudes and constant sign (positive).

10.1. Knrph Eqwh3r1

10.1.1. Sp3Hybridked Termind Carbon. Construc-

tion of a Karplus curve’290*3’5) (equations 10.1 or 10.2)

3J = ,-tcosZ8+B (10.1) or

35 = ‘4cos”t)+BcosfI+C (10.2)

have been attempted both theoretically and experimentally. For hydrocarbons, Wasylishen and Schaefer’316.317’ obtained from theoretical calculations

3J = 3.56 cos 20 - 1.00 cos 8 +4.26 (10.3)

3J = 7.12cos’6,- 1.00c0s8+0.70 (10.4)

The equation (10.3) has been rewritten in the form of cosz 0 to make comparisons easier. Experimentally Chertkov and Sergeev (l*‘) found that the expression

3J = 8.1~0~~0 (10.5)

fitted the experimental data obtained from cyclohexane. Aydin and Giinther(34s) established an equation (10.6) based upon data from norbornanes (C-D coupling constants were measured).

3J = 7.89 cos* 0 - 1.23 cos 0 - 0.63 (10.6)

In substituted compounds slightly different equations are obtained. de Marcos and Llinas’349’ derived their equation from coupling constants of ornithines in alumichrome. The couplings were related to known crystallographic dihedral angles.

‘J = (10.2f0.9)cos’O-(1.3+1.2)c0sO

+(0.2&0.2) (10.7)

A Karplus relation was established in a hydroxy sub- situated fragment (Structure 14) by Spoormaker and de Bie.t350’

‘J = 2.57 cos 2(0 - 5.53) - 0.38 cos (0 - 5.53) + 3.09 (10.8)

H\ n /“”

7-c;, H ‘$H3

14

The phase shift was the result of the orientation of the hydroxy group with respect to the C-H bond.‘3501 This was also supported by theoretical calculations!“” For torsional angles of 30-60’ a very small substituent effect is observed, because the C-X bond is almost perpendicular to the C-H bond in question. t3*” Schwarz and Perlin(35L) constructed a curve based upon both ‘J(C-l,H-3) and 3J(C-1.0.H-5) of carbohydrates. As seen later in Table 22 the ‘J(C-I, H-3) couplings cited do not form a better Karplus curve, than the couplings through nitrogen as used by Lemieux et ~1.‘~~‘) (See Section 13.2.3.1 or the ones just cited.) Despite the fact that only ‘J(C,C,C, H) coupling constants are included, a considerable scatter is still present. 3J(600) values


vary over a range of O-3.3 Hz, whereas 3J(1800) vary from 4 to 5.5 Hz. The disposition of the oxygen atoms on the coupling path seems to play a role!351*3531 ‘J(gauche) and ‘J(trans) and ‘J(av) may be obtained from the equations (10.1-10.12) and applied in the analysis of flexible systems. 3Jg and ‘Jtr for the different systems are as follows:

3Jg = 0.75 Hz ‘Jtr = 8.58 Hz hydrocarbon’34*’

‘Jg = 2.02 Hz ‘Jtr = 11.7 Hz ornithines(349’

‘Jg = 1.99 Hz 3Jtr = 5.98 Hz hydroxy substituents(3s0)

For carbohydrates Schwarz and Perlin’35’) estimated a 3Jg _ 2Hz and a ‘Jtr > 8Hz. It is obvious that substituents modify ‘Jg and ‘Jtr as well as the entire Karplus curve.

Three-bond coupling constants through heteroatoms may also be used to construct a Karplus curve as shown previously by Lemieux et a/.(352’ (Section 13.2.3.1). No major differences are expected between 3J(C, C, C, H) and ‘J(C, N, C, H) according to theoretical calculations!347’

10.1.2. Sp2 Hybridized Terminal Carbon. In the case of sp2 hybridized carbons in carbonyl groups much less work has been done in attempting to establish Karplus curves. Experience with carbon-carbon coupling constants’3s4’ tells us that these couplings will not necessarily behave in the same way as in compounds with sp3 hybridized carbons. The main work dealing with sp’ hybridized carbons has been performed with amino acids in which ‘J(COOH, H)g and ‘J(COOH,H),, have been obtained from an analysis of rotamer distributions gained from three- bond hydrogen-hydrogen coupling constants. In carboxylic acids Rennekamp and Kingsbury’335’ have utilized ‘J(CO, H) of “C enriched phenylsuccinic acid to determine the most populated rotamer assuming ‘Jtr > ‘Jg. A ‘Jtr _ 11 Hz and a 3Jg _ 2Hz were estimated. In amino acids Hansen, Roberts and Feeney (356*357) determined ‘Jg and ‘Jtr for aspartic acid(357’ and serine(357) making use of the ‘Jav observed in alanine. The group of amino acids was extended by Espersen and Martin’35s’ to include acylated histidines and cysteine derivatives (Section 16.4) Ptak et aL’359’ used values derived from equation (13.2).

‘Jg = 0.8 Hz 3Jtr = 11.0 Hz aspartic acid(357)

‘Jg = 1.5Hz ‘J tr = 7.6 Hz serine’357’

‘Jg = 1.3kO.3 Hz ‘Jtr = 9.8kO.3 Hz cysteines’358)

‘Jg = 0.4fO.SHz 3Jtr = 11.9fO.SHz average of values(357)

It is obvious from the above shown values of ‘Jg and ‘Jtr that substituents influence 3Jg and ‘Jtr. Furthermore, as discussed in Section 10.1.1 the dependence may be complex.

Martin(360) has evaluated the relative merits of a two parameter (3Jtr and 3Jg) and a six parameter

(3J,-3J,) approach. In the latter all possible three- bond coupling constants were assumed to be different. Using both ‘J(H.H) and 3J(C0,H) coupling constants the author concluded that a six parameter aproach yielded no better a fit than the two parameter approach and suggested the following two coupling constants ‘Jg = 1.2Hz and 3Jtr = lO.OHz. London et a1.‘36” calculated ‘J(C0.H) in aspartic and glutamic acid using MO INDO-FPT calculations. A minimum was observed at 0 = 90”. 3Jg was equal to 1.26, 2.67 Hz, 1.61 and 2.35 Hz, respectively and ‘Jtr was equal to 8.17 Hz and 8.76 Hz for the two different ,G-hydrogens again underlining that differentiation among jJg and among 3Jtr values should possibly be used.

INDO-FPT calculations on methylbenzoate(347) showed that ‘J(C0, H-2) are larger than ‘J(C0, H-6). INDO-SOS calculations on benzaldehyde and benzoic acid gave the same trend and showed additionally somewhat smaller couplings for a twist angle of 90’ in the former case, but not in the latter. Methylsubsti- tution at the 2-position has only minor emects.‘330’

10.1.3. Sp Hybridized Terminal Carbon. Wang and Kingsbury’362’ estimated a ‘J(C-N, H)g value equal to 2-3 Hz and a 3J(C-N, H)tr equal to 9-9.5 Hz for nitriles.

10.2. Substituent Effects

Substituent effects may be investigated both experimentally and theoretically to shed light on some of the factors controlling three-bond coupling constants. Effects to be treated are dependence on electronegativity of substituents, position along the coupling path and the orientation of the substituent relative to the bonds between the atoms of the coupling path.

10.2.1. Theoretical Approach. Molecular orbital calculations (INDO) of coupling constants over three- bonds have generally shown good agreement with experimental findings (see for example Reference 9). Wasylishen and Schaefer’347’ compared theoretical calculations of propane equation (10.3) 2-fluoropropane, 2,2-difluoropropane and propyllithium. In the case of 1-fluoropropane with the C-F bond trans to the methyl group the difference is given by equation (10.9)

-AJ = l.O6cos20-0.78cosO+ 1.08. (10.9)

With the substituent in a gauche position no substantial substituent effects are found. If the C-F bond is perpendicular to the C-C-C plane, then the value of AJ/J never becomes very large, irrespective of the orientation of the C-H, bond. In 2-fluoropropane a more complex relationship was found (10.10)

3J = 3.69- 1.16cos~+3.1Ocos20

-0.19sinB+0.70sin20 (10.10)

Furthermore, ‘J also depends upon the mutual orientation of the C-F and the C-H, bonds. The substituent effect is small when the C-F bond is

POUL ERIK HANSEN

3Hc\c/c\, 15

perpendicular to the C-H, bond. For propyllithium the following equation (10.11) gave a good fit to the data:

‘J = 2.O4cos2e+0.93cose+2.25 (10.11)

At a given angle the magnitude of J is smaller than in propane. Schwarz and Perlin’35*) found in carbohydrates that ‘J is 2-3Hz smaller when an oxygen containing substituent is in the C-C-H plane (Structure 16b) rather than being out of the plane (Structure 16a). This finding was supported by theoretical calculations with a simple model (1,2- propanediol).‘353)

H OH

(a) @I

16

One of the most difficult parameters to obtain experimentally is the y-effect due to the effects of such a substituent on the rotamer distribution (for an experimental determination see Section 10.2.2). The y-effects of methyl groups were first discussed in relation to carbon-carbon coupling constants.‘363) The principle of impinging rear lobes (IRL)‘363’ was later questioned.‘364-366) The model compounds used in these studies(364) made it difficult to say whether the effect was a p- or a y-substituent effect. INDO-FPT results for a number of hydrocarbons(365) showed that p-effects were small in comparison to y-methyl effects for carbon-hydrogen coupling constants. The calculations gave a y-effect of 1.2-1.4Hz for a methyl group, whereas experimental data (although very few) indicate that the real effect may well be twice as large. Studies on 2-d-adamantane support this view.(iz4)

A modification of the INDO-FPT procedure in which elements of the Fock matrices associated with orbitals centred on various atom pairs were set equal to zero in each SCF cycle permitted a qualified guess as to which coupling paths are important. Interactions involving the hydrogen atom at C-l and the methyl hydrogens of the g-methyl group give a negative contribution, which is partially cancelled by an interaction between the orbitals at C-l and the y-methyl hydrogen (see Structure 17). This technique has been used to

great advantage in disentangling all the possible coupling paths and effects that may be important.(366*367)

In a propane fragment a positive contribution to 3J (180’) is obtained from the hydrogen at the y-carbon. The disappearance of such overlap by substitution will give a negative contribution to the substituent effect.‘366’ Dimethyl substitution at C-l or C-2 has very little effect. This is also the case for dimethyl substitution at the C-3 carbon for dihedral angles of less than 120”. In contrast 3J (180’) is 1.7 Hz less than the value for propane as just mentioned. Thus methyl groups at C-3(C-g) make negative contributions. Other substituents at C-3 likewise make negative contributions even if the substituents do not carry hydrogens. For ethyl substituents a small increment is observed, which was ascribed to a B-effect. Hydroxy- substitution gives the smallest couplings if the OH hydrogen points towards C-l as shown in Structure 18.

H.

‘0 I

S\c/C\H 18 -

Barfield(366) concluded from these calculations that the non-bonded interactions dominated three-bond coupling constants and as a consequence it is not possible to obtain a satisfactory representation by a simple trigonometric relationship as given by (3.1 or 3.2).

Another non-bonded interaction of importance may be that between bridgeheads. Bridgehead interactions were estimatedo6*) in bicycloalkanes using the approach of leaving out matrix elements as just described. The non-bonded bridgehead interactions give negative contributions and these may become quite large in compounds with short distances between the bridgehead carbons (_ - 30 Hz for a separation of 0.184nm). In the case of carbon-carbon coupling constants bridgehead interactions were judged to be part of the reason why additivity of coupling constants is not observed.

10.2.2. Electronegafioity. Spoormaker and de Bie(328) have investigated ‘J(C, H) in isopropyl halides. In- creasing the electronegativity of the substituent at an intervening carbon atom (8) decreases the coupling

constants whereas substitution with an electronegativity substituent at the cc-carbon augments the coupling. A similar result was found by Karabatsos

H L

17


and Orzech.‘369’ Substitution at the y-carbon does not necessarily lead to T-substituent effects as the measured coupling constant depends upon the rotamer distribution as seen in Structure 21. If the rotamer populations are assumed identical in n-propyl fluoride and chloride an extrapolation vs. Pauling electronegativity shows a slight decrease of ‘J(C,H) with increasing electronegativity. However, using the 3J(H, F) coupling constants in the case of the fluoride values of 3Jg equal to 3.2 Hz and ‘Jtr equal to 6.57 Hz can be estimated (see also Section 10.2). The y-effect may be usefully studied in neopentyl derivatives(370) as the rotamer distributions around the C-j?, C-7 bond

are identical. The measured coupling constants need to be corrected for p-substituent eITects. The /?-methyl substituent effect was set equal to -0.57 Hz. The three-bond couplings when plotted vs. E, fit a straight line:

3J = -0.3&+5.6 (10.12)

The couplings should be equal to those observed in n-propyl compounds if pr = prl = pII in the latter. However, the experimental data for n-propyl compounds deviate significantly from the straight line. Y-Methyl effects are discussed in Section 10.2.1.

10.2.3. Additivity ojSttbstittrent Effects. In order to generalize substituent effects a study of additivity was undertaken by Spoormaker and de Bie.‘37” They found that 3J(C,H) is proportional to ‘J(C,H) for monosubstituted propanes with first row substituents. As substituent effects on one-bond coupling constants for these substituents have been shown to be additive (Section 8.3.1) it was expected that the substituent

TABLE 9. Three-bond coupling constants. ‘J(C, C. C, H),’ in aliphatic compounds

‘J Dihedral angle Refs.

2-endo-Methyl-2-borneol

rrans-Cterr-butyl-I-methylcyclohexan-l-01

Borneo1

Bornylamine 2-Methyl-2-butanol L-Ascorbic acid Menthone Menthol

SEthyl-S-phenylbarbituric acid

Neopentylamine Neopentyl alcohol Neopentyl chloride Neopentyl bromide Neopentyl iodide Propylamine Propyl alcohol Propyl fluoride Propyl chloride

Propyl bromide Propyl iodide r-Butyl fluoride r-Butyl chloride t-Butyl bromide t-Butyl iodide I, 3-Diaminopropane 3-Amino-I-propanol

I, 3-Dihydroxypropane 3-Chloro-I-propanol

I, 3-Dichloropropane I, I-Dichloropropane

CH3, H-3cndo CH,, H-3,,, C-IO, H-2,,d, CH,, H-2 CH,, H-2 C- IO, H-2,,, C-IO, H-6,,, C-IO, H-2,,, C-l, H-3 c-4, H-6 CH,, I-I

CH,, H

CH,, H

C-4, CH, C-5, CH, CH,, I-I

CH,, H

CH,, H

CH,, H

CH,, H

CH,, H

CH,, H

CH,, H

CH,, H

CH,, H

CH,, H

CH,, H

CH,, H

CH3.H

CH,, H

C-l. H-3 C-l, H-3 C-3, H-l C-l, H-3 C-3, H-l C-l. H-3 C-l, H-3 C-3, H-l

5.25 1.63 0.6 f 0.2 2.90 5.50 2.8 2.8 2.7 3.0 + 0.2 2.4 2.5 5.Ob 2.5’ 4.93 5.2 3.59 3.50 3.54 3.62 3.72 4.3 4.4 4.6 4.5 4.4 4.5 4.1 3.81 4.08 4.22 4.45 4.2 4.3 4.6 4.5 5.6 4.4 5.7 4.2

0 350 120

-79 49 350

167 350

350 454 408

84 84

821

370 370 310 370 370 370 370 370 370

370 370 370 370 370 370 371 371

371 371

371 371

a. All carbons sp’ hybridized. b. Preferentially trans. c. Preferentially gauche.

214 POUL EIUK HANSES

effects at ‘J(C-r, H) would also be additive. The increments for methyl, chloro, amino and hydroxy substitution at both I- and /?-positions were estimated. The y-substituent effect was determined from neopentane derivatives as just described (Section 10.2.2). The increments determined in aliphatic compounds were also transferred to acid derivatives!“l’ whether or not such a procedure is strictly valid has yet to be shown.

10.2.4. Correlations. Forrest and Sukumar’372’compared 3J(CH3,H) in t-butyl halides with ‘J(H, H) in isopropyl halides and found a good correlation between the two types of coupling constant (10.13)

3J(C, H) = 1.2 3J(H, H) - 3.5 (10.13)

Carbon-hydrogen coupling constants are thus slightly more sensitive to substituent effects. The coupling constant values (Table 9) also show a decrease with increasing electronegativity. The same trend is shown for p-substitution in isopropyl derivatives (oitie infm). The authors caution against using the relationship in other compounds with substituents in different positions.

10.3. Bond Order or Bond Len&h Dependence

Seel er 01.‘~‘~’ found that 3J(C,H) in aromatic hydrocarbons depends upon HMO-x-bond order P,,.,, or the CC bond length of the central bond (R,,,,) according to equations (10.14) and (10.15).

3J = 13.73P,,- 1.66 (10.14)

3J = -31.45R,,+51.52 (10.15)

R in nm.

Braun and Kinkeldei’37J1 have studied ‘J(CH,, H) values in methyl substituted five and seven-membered non-benzenoid polycyclic aromatic hydrocarbons. For seven-membered rings without steric interactions (0 = G’ = 115.7’) the following equation (10.16) was estimated:

3J(CH3,H) = -25.69 x Rccf41.43 (10.16)

r = 0.990 s.d. 0.12 HZ

For other cases the magnitudes are largely determined by the CCH bond angles 0 and 0’. In methyl substituted cyclohexadienes Vligeli and von Philipsborn’375’ observed a n-bond order dependence of 3J(CH3,H). Such a n-bond order effect was also observed in aromatic systems such as methyl substituted benzenes and naphthalenes.

Bond angle distortions may perturb (decrease) this type of coupling considerably.

10.4. Summary

The realization that non-bonded interactions play such a dominant role in the transmission of three- bond coupling constants has diminished the hope that

general Karplus curves may be obtained. If Karplus equations are to be used, very similar compounds with similar substituents must be studied. The use of Jg and Jtr for rotamer population studies is not affected to the same extent, as they refer to specific geometries, but it must also be realized that in this case additional substituents may cause unexpected non-bonded interactions. The work of Marco and LlinBs’3’g1 reveal that three-bond couplings can also be observed in macromolecules, a finding that may encourage further investigations in this field.

II. COUPLliVGS OVER FOUR OR MORE BOSDS

Couplings over four or more bonds are most often observed in highly conjugated systems although spatially close nuclei may also couple even when there are a large number of bonds separating the nuclei.

Marshall et ,1.‘338) found similarities between five-bond carbon-hydrogen and hydrogen-hydrogen couplings. The theoretical and practical results obtained by Barfield et d.(376.377’ on hydrogen- hydrogen coupling constants may probably be transferred to carbon-hydrogen couplings.

In aliphatic compounds 4J or ‘J couplings are usually not observed. In cyclohexane-d,, Chertkov and Sergeev (“” found from a comparison of high and low temperature spectra that all ‘J values have the same signs. Correlation with ‘J(H,H) favours a negative sign for 4J(C,H). In the olefinic systems. 1,4-dihydrocyclohexadienes,couplingsover five bonds were observed and used to describe the puckering of these compounds. ‘338) In crotonic and isocrotonic acid a negative ‘J(CO,CH,) of approximately 1 Hz(~‘~.~“) was found.

1 1.1. Aromntic Compounds

Four-bond coupling constants in benzenes, 4J(C- arom,H-arom) are always negative (Table 30) and they fall in the range -0.74 to - 1.88 Hz. Poor correlation between ‘J and E, were found, although Tarpley and Goldstein (244) found a good correlation with 4J(C-3,H-6) in the more limited series of halobenzenes. However “J(C-3, H-6) correlates well with 4J(H,H)tratls in 2-substituted 1,3-butadienes. A positive four-bond coupling across a W-path was observed between C-4 and H-2 in pyrene.~‘2’~3s” Recently. long-range couplings have been measured in a number of thienopyridines.‘382’ It was concluded from these experiments that couplings having a W-path are positive, whereas other four-bond couplings are negative. 5J(C-4,H-l) in pyrene’381) are positive and so are most five-bond couplings in the thienopyridines.‘3*2’

11.2. “J(C-arom, H-r)

Theoretical calculations indicate that both 4J(C-3, H-r) and 5J(C-4, H-z) of benzaldehyde should depend upon the orientation and twist angle of the aldehyde group.“”


The four-bond coupling was calculated to be most positive in case of the zig-zag coupling path. The five-bond coupling seems to be dominated by a n-electron mechanism, as they are rather small when H-r lies in the plane of the benzene ring and reach a maximum when the C--HZ bond is orthogonal to the aromatic plane. ‘J in benzaldehyde is +0.49 Hz.‘~~~) However, in salicylaldehydes’3s3’ 4J(C-3. H) > ‘J(C-5.H) (Table 10). In gossypols where the aldehyde also is hydrogen-bonded O’Brien and Stipanovic”““’ observed that ‘J is between 2.4 and 2.9Hz for a W- path. In contrast, Bernausseau et .1.‘323d) (Table-30) observed in dialdehydes that 4J(C-3, H-r) are around 0.5 Hz and that these couplings do not depend in any systematic way on the conformation of the formyl group. In view of the results from the hydrogen- bonded aldehydes it seems likely that the aldehyde groups in the dialdehydes show a conformational average. Similarly, theoretical calculations showed a

dependence of ‘J(C-3,CH,) and 5J(C-4,CH3) in toluene!“’ Hansen and Jacobsen”*’ determined the latter to be positive and numerically larger than the four-bond coupling.

11.3. Other Couplings in Aromatic Systems

Four- and five-bond coupling constants between C-z and aromatic hydrogens are also observed.(‘8*380*38Z~ Both four- and five-bond coupling constants are positive.

A couple of four-bond couplings between two side chain nuclei have also been reported!330’

11.4. Couplings over Heteroatoms

Four-bond couplings over oxygen are observed in hydrogen-bonded phenols. Only the W-shaped path gives observable couplings.““**‘9” (Table 10.)

TABLE 10. Coupling constants over four or more bondsa

i,j, k, lb Refs.

2-Methylacetophenone 2-Methylpivalophenone Crotonic acid lsocrotonic acid Trans-crotonaldehyde Methylbenzoate

Toluene

l,4-Dihydrobenzoic acid 1.4-Dihydro-I-naphthoic acid 9. IO-Dihydro-9-anthroic acid Benzaldehyde

Toluene

Hemigossypolone Hemigossypolone-7-methylether Hemigossypol Gossypol C-25 Terpenoids Salicylaldehyde

CO, CH, CO.CH, CO, CH, CO, CH, CO,CH, CO, H-3 CO, H-4 CH,, H-3 CH,. H-4 CO, H-4 CO, H-4 CO, H-IO CO, H-3 CO, H-4 C-3, H-r C-4. H-a C-3, H-a C-4, H-a C-7, H-a C-7, H-LX C-7, H-z C-7, H-a C-7, H-2 C-3, H-z C-5, H-a C-4, H C-3. OH c-4,6-OH C-4,2-OH C-4, &OH

2.2.2.3 2,2,2.3 2,2,2.3 2.2,2,3 2.2,2,3 2.2,2,2 2,2,2,2,2 3,2,2,2 3,2,2,2.2 2,3*2.2,3 2v3.2.2.3 2,3,2,2,3 2,2,2,2 2,2,2.2,2 2,2,2,2 2,2,2,2.2 2,2,2.3 2,2,2.3 2,2,2,2 2.2.2.2 2.2.2.2 2.2,2,2 2.2,2,2 2,2,2,2 2,2,2,2 292, N, 3 2,2,2.0 2,2,2.0 2,z 70 2,2,2,0

0.50 0.40

-0.85 - 1.28

(+,;::I ( + JO.48

f0.54 +0.65

4.65 2.86 0.7

+ 0.49 +0.12 +0.48 +0.12 -0.39 +0.84

2.7 2.5 2.9 2.9 2.4 2.11

-0 2.6 1.8 I.2 1.2 1.5

Polyoxin N

Norlichexanthone I-Butyrylphloroglucinol-2-monomethylether I-Butyrylphloroglucinol-3,6-dimethylether I-Butyrylphloroglucinol-2,4-dimethylether 2-Chloro-3-cyano-4-methoxy-6-methylpyridine C-3. CH, 2,2,0,3 0.9 Methyltetrolate CO, CH, 2, 1, 1.3 - 1.48 Methyl nonynate C-l, H-4 2,L 1.3 w I.8 Butadiene C-l. H-5 2,2.2,2 -1.115

C-l, H-5 2,2,2,2 0.03 I-Buten-3-yne C-l, H-4 2,2,1,I + 2.8

C-4, H-l L&2,2 <I C-4, H-2 k&2,2 Cl

Cyanopropyne C-l,H-4 3,L I, I -3

354 354 378 378 574

380

18

338 338 338 381

18

323a 323a 323a 323a 323a 383

433 164 394

394 394

55b 53

815 550

582

477b

a. Four-bond couplings in aromatic compounds involving aromatic carbons and hydrogens are given in Table 30 and in Reference 27. For four bond couplings to hydroxy hydrogens, see also Table I I.

b. Numbers refer to hybridization of the carbons in the coupling path. Capital letters indicate the nature of the heteroatom.

216 Pour ERIK HANSES

The present material supports the assumption that long-range carbon-hydrogen couplings behave in

many respects like hydrogen-hydrogen couplings. Four-bond couplings with a It’-path are the largest and most likely to be observed.

12. COL’PLINGS TO SIDE-CHAIN PROTOSS

Two- and three-bond couplings to r-protons in side-chains (Structure 22) are treated in this section (four- or five-bond couplings were treated in

C2C /

0 I= 22

Section 11). Coupling constants to side-chain protons have been mainly used for assignment purposes,““”

but they may possibly be used in conformational studies of side-chains.

12.1. 2J(C,C,H,)

The two-bond coupling was shown to be - 5.97 Hz

in toluene!‘“’ In methylpyridines’3”S’ and methyl- quinolines ’38s*386J it is also close to 6 Hz and slightly more negative in 2- and 3-methylthiophene and 2-methylfurane. tLoJJ In methylsubstituted benzimi-

dazoles ‘.I varies from 6.5 to 8 Hz’~~” and in methyl- coumarines from 5.5 to 6.5 Hz.‘.‘~~’

12.1.1. ‘J(C’, C, C, C&I = 2 or 3. Three-bond couplings between orrho-carbons and methyl protons fall in the range 4-6 Hz.(~~~“’ In methylazulenes

the range is 4-5 Hz. ‘33y’ In 4-methylthiaazole the

larger ‘J(C-5, CH,) compared with ‘J(C-3, CH,) was attributed to a larger n-bond order. As well as a-bond order, the orientation of the C-H methyl bonds will

also be important in determining the magnitude of 3J(C,CH3).‘347*38y’ A d ependence upon bond-order,

the number of s-hydrogens and their orientation was observed in I- and 2-methylnaphthalene. I-hydroxy- methylnaphthalene and acenaphthenone.‘3”” Rabaron Ed 01.t~~~’ observed different couplings to protons in a methyl group than to the methylene protons of a benzyl group in 3-methyl and 3-benzyl-4- hydroxycoumarines.

Huneck and HiiRet3y’J has reported some ususually small coupling constants to methyl group protons in 2,6-dichloro-1,3,6-tri-O-methylnorlichexanthon.

12.1.2. 3J(C, C, C=O, H,). The three-bond coupling of benzaldehyde is +2.11 Hz’~‘*~~*’ In salicylaldehyde, in which the aldehyde group is hydrogen bonded. a very marked difference between “J(C-2. H)

and ‘J(C-6,H) was observed with the former being the largest. ‘383’ Similarly couplings between 4.2 and 5.2 Hz were reported in the hydrogen bonded gossy-

p01s.‘~‘~” Thus the rrcrns geometry leads to a much larger coupling constant.

Bernausseau et al.‘“‘““’ found three-bond couplings very close to 2 Hz in I.?. 1,3- and 1,4-

dialdehydes.

12.2. Theoreticnl Cnlcrrlations

Calculations by Ernst et aL’27’ and by Wasylishen and Schaeferc3”‘J confirmed these findings. Ernst er o/.t2” performed theoretical calculations on toluene and benzaldehyde which showed that ‘J(C-l,CH,) and “J(C-1,H) depend vaguely upon the dihedral

angle 0, whereas 3J(C-2, CH,) and 3J(C-2, H) depend strongly upon U. Also the four-bond couplings show a sensitivity to the twist angle (see Section 11). Calcu- lations by Wasylishen and Schaefer’347’ on toluene and propene show a quite dissimilar behaviour except for dihedral angles of 0” and 180’. The results were taken as evidence for a theory that x-electrons interactions are not significant for these two 0 angles, but mostly for angles between 0 and 90”.

13. COUPLING THROUGH HETEROATOiMS

This section is divided in three parts. Coupling through oxygen, nitrogen and nuclei other than oxygen and nitrogen.

13.1. Coupling throuyh Oxygen

Two different kinds of coupling constants are

encountered, “J(C,. . . , 0,H) and “J(C,O ,..., C,H). The latter type has been most thoroughly investi-

gated and it is still too early to tell whether they have different coupling properties. Experimentally they differ in the sense that “J(C,....O, H) is often

difficult to observe because of exchange.

13.1.1. “J(C,. . . ,O, H) (17 = 2, 3 or 4). These couplings were first observed by Wehrli.‘163’ “J(C,. . . , 0,H) may be used for assignment purposes (the presence of such a coupling is easily proven as it disappears on addition of D,O) and to monitor the presence of intramolecular hydrogen bonds.

(a) W

23

Fast exchange averages out “J(C,C,O, H). Inter- mediate exchange leads to broadened signals.‘55b’


TABLE Il. ‘J(C, 0, H) and ‘J(C, C, 0, H)’ coupling constants

217

‘J Dihedral angle Solvent Refs.

Methanol C-l Ethanol C-l

2-Propanol C-l t-Butanol C-l 2.3 : 5,6-Di-O-isopropylidene-z-D-

mannofuranose a-D-Glucopyranose Salicylaldehyde C-l

Methyl salicylate c-2

C-l Salicylaldoxime 2-Methoxyphenole 4, S-Dibromo-2-methoxyphenole C-l

2-Chlorophenol C-l 2-Nitrophenol 4,6-Dibromo-2-nitrophenol 2-Acetylphenol

2-Hydroxy-I-naphthaldehyde C-2 2,2’-Dihydroxybenzophenone 2-Amino-3-carboxy-4-hydroxy-6-

methylpyrone C-4, OH 3-Ethylcarboxy-4-hydroxy-6-

methylpyridone c-4 3-Carbamido-4-hydroxy-6-

methylpyridone c-4 Morin c-5 Naringenin c-5

2-Carbethoxy-5,7-dihydroxy-4’- methoxyisoflavone C-5

Methoxyhemigossypol c-4 Derivative of 7-methoxyhemi-

gossypolone C-6 I-Butyrylphloroglucinol

2-methylether c-4

3-Methyl-1-butyrylphloroglucinol C-4

3-Methyl I-(2-methylpropionyl) phloroglucinol2-methylether C-4

I-Butyrylphloroglucinol 2,4-dimethylether C-6

Norlichexanthone C-l

Chartreusin Juglone Dihydrogranaticine methylester C-8 Stellatin C-8 3-Hydroxycoumarin c-3 4-Hydroxycoumarin c-4 6, ‘I-Dihydroxycoumarin C-6 7, I-Dihydroxycoumarin C-8 6,7-Dihydroxy-4-methylcoumarin C-6

c-7

- 3.00 - 2.67

- 2.44 -2.12

4.75

2.5

3.lh

3.8

5.0

4.0

-30

5.2 3.7 4.0

4.9

4.4

4.2

5.0

4.7

4.5

5.0

4.9

2.5 4 4 2.5 3.5 1.5 4 3.5

c-2

c-2 c-2

2.93 3.1 3.13 2.57

C-2b C-lC c-2 C-6

C-6

C-3 C-6 c-2 C-6 C-6 C-6

::; C-6 c-3 c-3

9.2 2.0 4.2 7.37

;:: 4.4 4.0 8.3 7.5 5.4 7.4h 3.4h 8.0b 8.0’ 7.2

-9 3.5 7.5 7.5 7.5k

0 180 180 180

0 0

180 180 180 180

0 180 180 180 18oi

0 180 180 180

C-6

C-4a

7.3 180 6.4 180 4.7 0 4.6 0

C-6 7.0 180 C-4a 4.3 0 c-5 4.2 0

C-5 5.2 0

C-l 5.5 0 C-5 6.8 180 C-l 5.7 0 c-3 6.6 180

C-l 5.7s 0 C-5 6.7s 180

C-l 5.7 0 c-5 7.0 180 c-2 6.1 180 C-8a 4.9 0 C-4a 6.9 180 c-2 7.6 180 c-7 5 0

DMSO

CDCI,

DMSO ether CDCI, CDCI, DMSO CDCI, CDCI,

CDCI,

CDCI, CDCI, CDCI, CDCI,

CDCI, CDCI,

DMSO

DMSO

DMSO DMSO’ acetone DMSO

CDCI,

acetone

CDCI,

CDCI,

392,393

323a

acetone

323a

394’

acetone 394

acetone 394

acetone 394

DMSO 164

DMSO CDCI, CDCI,

I;)MSO DMSO DMSO DMSO DMSO

604 140a 823 398 530 530 530 530 530

383 383 382 383 383

396 512a 383d

392 392 392 140a 392 140a 320 140a 140a

140a 140a 140a 140a 140a 140a 140a

55b

55b

55b 393 393


TABLE 11 (contd.)


7,8-Dihydroxy-4-methylcoumarin C-7 2 DSISO 530 6-/I-D-Glucosyl-7-

hydroxycoumarin C-6 3.5 c-7 3.5 DSISO 530

Ascochitine C-6 3 C-6 6 397 C-16 4

lsophomazin C-1Oa 4 399 C-8a 4

a. “J(COH) are given in the footnotes. b. C-2,O,H-I. c. C-l, 0. H-2. d. 4J(C-5, OH) = 1.49 Hz.

4J(C0, OH) = -0.69 Hz. e. The smaller value in ether is ascribed to slow exchange. 1. Dry DMSO. g. Showed only couplings to OH at low concentrations

c 5 % (W/V j.

h. Observed at - 10°C. i. Difficult to reproduce. j. Temperature - 28°C. k. Observed with difficulty at low temperature. I. ‘I(C-4, OH) = 1.2 Hz. m. ‘J(C-4. OH) = 1.5 Hz. n. 4J(C-3, OH) _ 0.5 Hz. o. Line broadening due to exchange. p. Not given.

This type of coupling is best observed in dry solvents, and in DMSO. Lowering the temperature also improves the situation.“g’ Couplings are mostly observed in intramolecularly hydrogen-bonded species. No couplings have been observed in phenol itself but are seen in structures such as Structures 23A-C. Several such couplings are given in Table 11. Chang et LI~.‘~‘~’ observed stereospecific couplings in structures like 23A where 3J(C-2,C-l, 0. H) - 7.5-8.3 ([runs geometry) and 3J(C-8a,C-l, 0, H) - 4.4 Hz (cisgeometry). ‘J(C-1,0, H) - 3.7 Hz. As seen in Table 11 ‘J(C, 0, H) varies between 2.5 and 5.0 Hz. The magnitude of ‘J(C, 0, H) is not linked to the magnitude of ‘J. 3J(C,C,0,H) s-cis varies between 3.4 and 5.7 Hz. The high values are obtained in the phloroglucinoles (uitle inl;o). A typical value in Structure 23A is 4.5 Hz. ‘J(C, C, 0, H) s-tr falls between 8.3 and 5.4Hz. Slow exchange is supposed to influence the values as observed in salicylaldehyde in DMSO and in ether’392’ and so is the concen- tration.‘3Y4’ The solvent plays an essential role in the observation of couplings to OH-protons. Chang et d.(320*3g2~393~ have reported that depending upon the water content of DMSO hydrogen-bonded phenols may show two sets of carbon signals, one belonging to a hydrogen-bonded species and the other to a free species. In very dry DMSO only one species was observed, the one with an intramolecular hydrogen-bond and in this couplings to OH may be observed. On basis of these results the original report”63’ of 3J(C, C, 0, H) in 5-hydroxyflavones was questioned.

possibly influence the coupling, is a twist of the carbonyl group due to steric hindrance. Coupling across four bonds has been observed in the phloroglucinols and a W-path was suggested to be optimal.‘394’

.‘J(C, C, 0, H) was used to demonstrate the planar- ity of the hydrogen bond in Schiff’s bases of pyridoxal.““’

Ayris et al. (3*3) have compared experimental values (obtained from a complete analysis of salicylaldehyde) with theoretical values (INDO MO-calculations) and found a fair agreement with the numerical values. Couplings to non-phenolic hydroxy protons have also been observed.

*J(C, 0, H) values in simple alcohols are negative and between 2 and 3 Hz in magnitude.‘383’ ‘J(C, 0, H) are most likely positive but vary from 2Hz in a-D-glucose (C-l, 0, H-2)(395’ to 9.2 Hz in 2,3 :5,6- di-O-isopropylidene-cc-D-mannofuranose, 3J(C-2, 0, H-l).(3g6) The small values in the former are believed to indicate that the anti-rotamer is unimportant. On the other hand an antiperiplanar arrangement of OH-l and C-2 is highly likely in the latter.

From observation of ‘H and 13C contact shifts for protic substances like alcohols in the presence of di-t- butylnitroxide radical (DBNO) Morishima et aL(*s6)

were able to predict the relative signs and magnitudes of H-H vs. C-H coupling constants. For methanol they predicted ‘J(C, 0, H) = + 7.8 Hz. Unfortunately the predicted sign is not in agreement with the experimentally determined one. Aminova and Samitov’*‘@ calculated a 2J(C, 0, H) - 8 Hz.

The couplings in phloroglucinols as reported by Colombo et a1.‘397’ observed a three-bond coupling AyrCs and Widen’3p4) show much less difference of 4Hz to the acid proton of a hydrogen-bonded between ‘J(C, C, 0, H) s-c and ‘J(C, C, 0, H) s-tr (5.6 carboxylic acid. and 6.7 Hz, respectively). 3J(s-rr) is smaller than most, Sopchick et al. WM investigated a number of deriva- but not especially small, whereas ‘J(s-c) is much tives of the C-type with X = NO,, R-C = 0, Cl, larger than the typical values. It is not known if this S-R, etc. and they discussed the observation of can be ascribed to a substituent effect caused by the a 3J(C,0, H) coupling as a possible criterion for methoxy group in position 3. Another factor that may differentiation between weak and strong hydrogen


bonding. The discussion was based upon a comparison with other evidence such as IR data and “C chemical shifts of the CO carbons. Good agreement was not found which could be due to lack of sensitivity of 3J(COH) to the geometry of the hydrogen bond. Broadenings of the signals in dicoumarol, that dis- appeared upon addition of D?O. was taken as evidence for intramolecular hydrogen-bonding between the two parts of the molecule.‘JOO’

Chang et a1.‘3Lo’ used 3J(C,0, H) to distinguish between an enol-imin and a keto-enamine form.

Simpson et a/.‘39**399’ used “J(C.. . . .O,H) for assignment purposes.

13.1.2. Couplings of C, 0, C, H type. The shortest possible coupling path for this type of coupling is three bonds and no problems with exchange have been encountered.

13.1.2.1. 3J(C,0,C, H). The richest source of three- bond couplings of this kind is found in carbohydrates (Table 12). As with ‘J(C,C,C,H) the dependence upon the dihedral angle is of interest. A comparison with 3J(C,C,C, H) is made in Section 14.3. Schwarz and Perlin”“’ plotted both ‘J(C, C, C, H) and 3J(C, 0, C, H) vs. the dihedral angle on the same curve and found a Karplus-shaped curve, but with a considerable scatter. Hamer et (11.“~~’ plotted

3J(C,0,C, H) against the C,O,C, H dihedral angle and found, that the Karplus shape was evident. Few experimental data for the 0 range from 0” to 60” were given due to the difficulty of finding relevant model compounds. From the curve the following average coupling constants may be abstracted. 3J(Oo) = 5.2 Hz, 3J(600) = )Jg = 2.0 Hz, 3.J(900) = z 0 Hz, ‘J( 120°) = 1.2 Hz and 3J(1800) = ‘Jtr = 6.2 Hz. The curve shows less scatter than the similar ‘J(C,C,C, H) curve (Section 10.1.1) presumably because the coupling path of 3J(C-1, 0, C-5, H-S) is quite similar in all the compounds (the only variation is around C-l). This Karplus curve is especially well suited to the determination of the inter-residue dihedral angles 4 and II/ of di- and polysaccharides (Section 10.1). Dorman er dcro” studied O-methyl ethers (Structures 24, 2.5).

The coupling in dimethylether can be considered to be equal to

35 = 1/3(3Jt + 2 JJg) (13.1)

The tram form is supposed to become more favour-

TABLE 12. ‘J(C, 0. C, H) coupling constants in carbohydrates’

‘W, 0. C, i-i) Dihedral angle Refs.

/I-D-Glucose C-5. H-I -0 60 351 /?-D-Glucose-d, C-l. H-5 2.2 109 Methyl-2,3,4,6-tetra-O-acetyl a-D-glucopyranoside C-l, H-5 2 II4 Methyl-2.3,4,6-tetra-O-acetyl/3-D-glucopyranoside C-l, H-S 2.5 II4

1,2,3,4,6-Penta-O-acetyl-z-D-glucopyranose C-l, H-5 2.5 60 351 1,2-0-Isopropylidene-3.5.6-tri-O-ortho-

formyl-z-D-glucofuranose C-6, H 4.6 160 351 1,2-O-lsopropylidene-z-D-glucofuranose C-l. H-5 -0 II0 351

I, 2: 5.6-Di-0-Isopropylidene-z-D-glucofuranose C-l, H-S -0 I10 351

I, 2-O-Isopropylidene-r-D-glucofurano-6,3-lactone C-6, H-3 -0 100 351 I, 2-0-lsopropylidene+L-iodofuranurono-6,3-

lactone C-6, H-3 -0 100 351 D-Mannono-l.Clactone C-l,H-5 -0 110 351 Methyl-x-D-galactopyranoside C-5, H-l +6.0 539 1,6-Anhydro#-D-galactopyranose C-I, H-6b +3.7 120 539

C-6, H-I + 5.2 160 2,2’-Anhydro-I-fi-D-arabinofuranosyluracil C-2, H-2 2.0 II2 402

2,5’-Anhydro-2’. 3’-isopropylideneneuridine C-2, H-5 8.7 I58 402 C-2’, H-5” 2.0 38

l.6-Anhydro-/I-D-galactopyranoside C-l. H-5 +6.1 170 539 C-5, H- 1 +5 180

Methyl /kellobioside-d, C-l. H-5 2.2 109 Methyl /I-cellobioside-&, heptaacetate C-l, H-5 3.0 I09

Cyclohexaamylose-d, C-5, H-I 6.2 109 Methyl P-a//o aldohexofuranoside C-l. H-4 -4 523c Methyl /3-ribo aldopentofuranoside C-l, H-4 4.0 523d Methyl fi-arabbm aldopentofuranoside C-l,H-4 3.0 523d

a. Glycosidic bonds are given in Table 15. b. H-6 endo.

c. In the z-gluco, I-gluco, z-allo. z-manno, ,V-manno, z-galacto, and a-galacto derivatives no coupling could be observed. d. In the z-xylo, j-xylo, z-ribo. z-1~x0, and z-arabino derivatives no coupling could be observed.


TABLE 13. “J(C, 0, C. H) coupling constants. C-H bond in a freely rotating part of the moleculea

X,Y 'J&Z-x, H-y) Refs.

Dimethyl ether Methyl propyl ether

Methyl butyl ether

Methyl isobutyl ether

Methyl neopentyl ether

Methyl isopropyl ether

Methyl set-butyl ether

Methyl tert-butyl ether Diethyl ether Dimethoxymethane

1,2_Dimethoxyethane

Methoxyallene 2-Chloro-3-cyano-4-methoxy-6-methylpyridine Cairnlomycin Cairnlomycinonitrile D monoacetate I-Methoxy-4-t-butylcyclohexane

Methyl-2-deoxy-a-D-arabino-hexopyranoside Methyl-a-D-glucopyranoside Methyl-B-D-glucopyranoside Methyl-a-D-mannopyranoside Methyl-P-D-mannopyranoside Methyl-2-deoxy+D-arabino-hexapyranoside Methyl formate

Ethyl formate

Propyl formate Butyl formate Isobutyl formate Neopentyl formate

Isopropyl formate

set-Butyl formate tert-Butyl formate Methyl acetate

Ethyl acetate

Benzyl acetate Neopentyl acetate Isopropyl acetate

2,2,4,4-Tetramethyl-3-pentylacetate Thiazolindinones Dihydrothiazinones /?-D-Glucopyranosepentaacetate

Ethyl-a-D-glucopyranoside Isopropyl-x-D-glucopyranoside Methyl-fl-D-glucopyranoside

Ethyl-b-D-glucopyranoside CH,. I Isopropyl+?-D-glucopyranoside t-B;tyl&&glu~opy&noside

CH, 1 C, 1

Methyl-2-deoxy-r-D-arabino-hexapyranoside CH,, 1 p-Dioxene c-2, H-6

CH,. H CH,. CH, CH,. CH, CH,,CHL CH,, CH, CH,, CH, CH?. CH, CH,.CH, CH,, CH, CH,, CH CH, CH, CH,.CH, CH,.CH, CH,, CH,

CH,, CH,

CHz, CH,

CH,, CH2 CH,. CH, CH,,CH, CH,, CH 4,CH,

3,CH, 3,CH3

CH,. 1

‘X3.1 CH,, 1 CH,. 1

CH,, 1

CH,, 1 CH,. I CH,, CH CO, CH, CH,, CH CO, CH2 CO, CH, CO, CH2 CO, CHL CH,, CH CO, CH, CH, CH CO,CH CO,CH CH,, CH CO, CH,

CO, CH,

CO, CH, CO, CH, CO, CH

CO, CH CO, CH, CO, CH, co, 1 co, 2 co, 4 CO,6 CO,6 CH,. 1 CH, 1 CH,, 1

+ 5.7 3.2 5.2 3.1 5.25 3.05 5.2 2.65 5.3 3.85 5.0 4.2 4.8 4.0 3.1 4.4 6.6 5.15 1.65

t7.5 4.2 5.9 6.0 3.8b 3.1C 3.2d 3.8 4.5d 3.v 4.3 4.2 4.27 4.00 4.14 3.32 3.15 3.15 3.10 4.20 2.80 4.25 3.22 3.45 0.99 3.83 3.95 3.20 3.25 3.40 2.70 3.00 2.90 4.60 3.1-3.9= 3.9-4.2’ 3.6 3.6 3.6 2.5 3.2 3.8 3.8 4.5 4.6 4.6 4.6 4.2 3.2 4.53

827 40la. b 4Ola 40la. b -1Ola -tOla, b 401a 40la. b 401a 4Ola

401a

401a 401a

56

401a

413 55b

403 403 402

402 402 402 402 402 402 401a

401a

401a 401a JOla 401a

401a

401a 401a 401a 404 401a 404 404 404 401a 404 404 423 423 402

414 414 402 410 414 414 414 414 480


TABLE I3 (contd. I

I(. .r ‘AC-x, H-J) Refs.

Methyl-2-deoxy+D-glucopyranoside CH,. I 2.7 410 Methyl-2-deoxy-z-D-glucopyranoside CH,. I 4.4 410 1.4-Oxathiane 2.6 4.8 409 rrtr~rs-2,6-Dichloro- I. J-oxathiane 2.6 4.8 409 ris-2.6-Dichloro-l.4-oxathiane 2.6 2.8 409 I-Methoxycoumarin 4.CH, 4 530 7-Methoxycoumarin 7.CH, 4 530 Valinomycin C;C,-Hz 2.8-3.6’ 412 Chloroformicacid methylester CO,CH, +4.50 407 Minimycin CO. 6 9.5 405 4-Methyl-2-oxo-I. 3-dioxolane co.4 2.9 332 rroris-4, S-dimethyl-_ T-oxo-1,3-dioxolane co. 4 2.4 332 cis-4.Sdimethyl-2-oxo-l.3-dioxolane co.4 2.4 332

Coupling constants in rigid molecules and carbohydrates are given in Tables 14, 15 and 22. OCH, equatorial. OCH, axial. Solvent effects were studied. but no effects found. Several derivatives studied. More data are given in this reference. Varies with solvent and counter ion.

TARLE 14. Carbon-proton couplings ‘J(C. 0. C. H) in compounds of fixed geometry

Vinylene carbonateC I, 3-Dioxole

Bis- I, 3-dioxolyl Methylene dioxobenzene S-Methyl methylenedioxobenzene p-Dioxene

I, 4-Dioxane I, 3.5-Trioxane 1, SDioxolane 2-Phenyl-5-methyl- I, 3-dioxane

Ascorbic acid a-D-Glucopyranose 3,4,6-triacetate I. 2-

(methylorthoacetate)

2.2’-Anhydro-I-D-w&iw-furanosyluracil 2,5’-Anhydro-2’. 3’-isopropylidenecyclouridine

(.LJ)

2.4 2.4 4,2 2.4 1.7 1.7 2.6 5.3 296 2.6 4.5 2.4 2.4 co.4

co, I co, 2 2.2 2.5

‘J(C-x, H-y)

9.26 6.7 I

+ 2.43 6.75 2.05 f 0.05 2.05 kO.05 3.17a 4.53b 4.23 5.65

+ 3.55 I 7.9 2.0

0 0 2.0 8.7 2.0

Dihedral angle

180 180 120 180 120 I20

60 180 60

90 90

I20 -158

-38

Refs.

184.406,441 184

I84 184 184 480

401a 401a 401a 402

408

352

352,426 352.426

a. ‘J(C-2, H-6) + ‘J(C-2. H-5). b. ‘J(C-5, H-3) +4J(C-5. H-2). c. More correctly called I, 3-Dioxole-2-one.

able with increasing bulkiness of R leading to a decrease of ‘.I. Indeed a decrease was observed experimentally. With R equal to t-butyl the smallest coupling constant was observed and this was set equal to 3J(600). Inserting a ‘Jg of 2.7 Hz into equation (13.1) leads to a 3Jtr of II.8 Hz. The coupling constants are somewhat larger than those predicted from carbohydrates (ok/e suprrr). Lemieux““” predicted a 3Jtr in the region of 9Hz from the study of dimethoxy methane. Substituent efTects were also discussed for the ethers. The larger coupling observed in dimethylether compared with “J(C, 0, CH,) in the other ethers (Tables I3 and 14) was ascribed to a substituent effect.

The large difference between 3J(CH3,0,CH) in 2-dimethoxyethane and dimethylether may also be ascribed to a substituent effect. The fact that 3J(CH,0,CH3) is similar to that of dimethyl ether is probably due to a ditTerence in substituent effects as discussed in Section 10.2.2. The small difference between ‘.I in 1,4-dioxane and 1,3,5-trioxane was also ascribed to substituent effects.

Results with model compounds. “C enriched alkyl pyranosides, showed that 3J(C’, 0, H-l) is different in r- and /I-anomers and that a slight change occurs in the /I-anomer when the size of the aglycon increases. This change was ascribed to unfavourable nonbonded

777 ___ POUL ERIK HAMEN

interactions. On the basis of these results it was concluded that the 4 angle is between 0 and 60°.‘402)

A typical value for aromatic ethers ‘J(C-arom. 0, CH,) is 6 Hz.““’

13.1.3.2. -‘J(C=O.O.C, H). From the very early investigations by Karabatsos et (I/.“‘+) on acetates it was concluded that 3Jg < 2.3 Hz and 3Jtr > 7.4 Hz.

26

From the study of Structure 26 a -‘J(g) value of 4.6Hz could be inferred. Dorman et ~1.‘~~‘) later pointed out that microwave studies show that the molecules are not in perfectly staggered conformations. 3Jg and ‘Jtr may also be obtained from compounds with a fixed geometry. In minimycin’405’ 3J(C0, 0, C, H)tr = 9.5 Hz was observed. Similarly vinylene carbonate gave a ‘J value of 9.3 Hz’4061 Three effects may make the latter result different from ‘Jtr. (i) A four-bond coupling may give a small negative contribution, (ii) the small angle in the five- membered ring may possibly influence ‘J, (iii) the substituent effect of oxygen at the carbonyl carbon may play a role. From a comparison of formates and acetates Dorman et a1.t4”’ concluded that carbon substitution at the carbonyl carbon has only a very small effect. The effect of an electronegative substituent (chlorine) may be obtained from a comparison of methyl acetatefJoJ’ and methylchloroformate’407’ (Table 13). The effect is small, but not negligible. 3Jg may be obtained from l-ascorbic acid.‘40”’ ‘J(C-I, 0, C-4, H-4) = 2.0 Hz. Theoretical calculations by Wasylishen and Schaefer’347’ gave ‘Jtr = 5.38 Hz and ‘Jg = 0.75 Hz for methylbenzoic acid. A very firm dependence on dihedral angle has thus been established. However, Pihlaja and Rossi’332’ showed that 3J (CO, 0. C, H) in methyl-2-oxo- 1,3-dioxolanes does not depend upon the dihedral angle.

13.1.3. AppIicariorrs. Spoormaker and de Biec409’ determined the isomer ratio of cis-2.6-dichloro-l.4- oxathiane. However, if a 95 : 5 ratio is assumed as obtained from two-bond coupling (Section 16.2) and if the influence of the chlorines is neglected a 3J( 180”) - 7Hz is obtained. Lemieux et 01.‘402*4’o’ used -‘J(CH,,O,C,H-1) to estimate the rotamer population around the C-l, 0, CH, bond. It is found

1 II III

27

that both methyl r-D-glucose and its 2-deoxy derivative display smaller couplings than the corresponding p-derivatives (see Table 12). This points towards a higher population of Structure 27, I and II in the r-derivatives relative to the b-derivatives. This is in accordance with the exo-anomeric effect as discussed by Lemieux et 01.‘~~~’

Likewise ‘J may be used to investigate acylated compounds as shown by Lemieux.““” In /I-glucose- pentaacetate is 3J(C0,0,C. H) close to 3.6 Hz for C-l, C-2 and C-4. Two different couplings are observed for C-6. In valinomycin ‘J(C-3’,C-4. H-4) fall between 2.5 and 3.6 Hz depending on solvent and counter ion and ‘J(C-l’,C-3,H-r) between 2.5 and 3.7 Hz, The value of 2.5 Hz for the K’ complex was used to deduce a 4 angle of -94&6” for the L-lactic acid residue.““’

Runge and Kosbahn’““’ observed a ‘J(CH,.O. C0.H) value of 7.5 Hz, which they interpreted as evidence for a preferential syn form (Structure 28).

0

II H/c\o/eH3

28

This is in agreement with electron diffraction evidence. A fine structure of C-4’ and C-S due to coupling through oxygen was found in pyridoxal, which is locked into a hemiacetal form.(321aV

The regularity of ‘J(C, 0, C, H) as discussed above may be used to determine the two inter-residue dihedral angles, 4 and J/, as shown in Structure 29.

Ci(n +I) CL;1

V

CF(fl-1) O-5

Y

c-2 c- 1

C-‘*\ HI-n

CI-n &\

H-1

(a) (b)

(c)

29

The relative orientation of the two residues in disaccharides should be reflected in the three-bond coupling across the glucoside linkage. This possibility was demonstrated by Lemieux er ~1.‘~~” and by Dormant40’a) in 1973. For a review on glycosides see References 270 and 414. However. these inter-residue couplings are usually measured from ‘H coupled spectra which frequently suffer seriously from signal overlap and second-order effects. Extensive C-deuteriation may simplify the spectra.‘109.“‘5’The use of 13C enriched species also simplifies the analysis as ‘.I may then be determined from ‘H satellite spectra.~“3~“4’ Couplings are given in Table 14.


The Karplus curve set up by Hamer et al.‘to9’ is not well defined in the area between 00 and 60”. which is rather unfortunate as many 6 and rl/ angles fall in this region. Furthermore. as only one three-bond carbon- hydrogen coupling can be determined, one cannot distinguish a 0 angle of x from those 180” -x, 180’ +x or 3600-.K. Another difficulty is the distinction between freely rotating and fixed conformations. In order to be able to solve these problems coupling constants such as ‘J(C,O,C) and 3J(C.0,C,C) in addition to 3J (C, 0, C, H) should also be determined. The dihedral angles obtained can be compared with those determined by X-ray crystallography. For maltose good agreement between the solid and the liquid state is observed. For cyclohexa-amylose. I++ is somewhat larger in solution than in the solid state. Thus the X-ray data cannot be used to construct a Karplus curve. t4r5) Some preliminary results were given, 096’ but the poor resolution made conclusions difficult. A comparison of coupling constants of methyl cellobioside in H,O and of methyl cellobioside hepta-acetate in CDCI, shows that ‘J(C-l,H-4’) increases + 1 Hz whereas 3J(C-4’, H-l) remains constant. On the basis of these results the 4 angle may be suggested to be 10-20” larger in the hepta-acetate in CDCI,. This parallels the results of a comparison of the conformations of methyl /I-maltoside and its

hepta-acetate (Table 15). The couplings obtained in B-laminarabiose octa-acetate point towards angles close to O”, whereas the coupling in z-cellobioseocta- acetate is compatible with angles 10’. 50” or ~350~~113.11”

13.1.4. Scrmmar~. Coupling constants through oxygen have been shown to be very useful for conformational analysis, e.g. of carbohydrates. These couplings through oxygen shall of course be compared with the very similar couplings through sulphur or nitrogen.

13.2 Coupling through Nitrogen

The couplings through nitrogen may be divided into two groups like couplings through oxygen, “J(C,.... N, H) and “J (C, N, . . . , C, H). The former type is best characterized in amides and only a few amine cases have been reported. The latter type occur in several different kinds of compounds, nucleosides and nucleotides, both intra- and inter-ring couplings, in amides and in peptides. ‘J(C0. N. H), JJ(C. N, C, H) and )J(CO, N, C, H) may all be used in stereochemical studies. ‘J(CO,N,H) can be used to determine the w angle of the peptide backbone (Structure 30) and this angle may also be obtained from 3J(C-z.C0,

TABLE 15. ‘J(C.0.C H’) across glycosidic bonds’

‘AC, 0, C H) Refs.

Maltose C-l,H-4

z-Maltose hepta-acetate /?-Maltose peracetate z-Maltose octa-acetate Methyl /I-maltoside Methyl /I-maltoside peracetate Phenyl /I-maltoside peracetate Maltosan Maltosan peracetate z-Cellobiose z-Cellobiose octa-acetate Methyl /I-cellobiose-d,’

C-l. H-4’ C-l. H-4 C-l’. H-4 C-l. H-4 C-l.H-4 C-l. H-4 C-l. H-4 C-l. H-4 C-l. H-4 C-I’, H-4 C-l. H-4

Methyl /I-cellobioside-d, hepta-acetate

/?-Gentiobiose octa-acetate

/I-Laminarabiose octa-acetate /I-Nigerose octa-acetate Cyclohexa-amylose-d,.C

Cyclohexa-amylose peracetate’ I. z-Trehalose

C-4’. H-I

C-l. H-4 C-6, H-l’ C-l’, H-6

C-I’, H-3 C-l’, H-3 C-l. H-4

C-4, H-l’ C-l, H-4 C-l.H-4

-3.4 c3.5d

4.04 3.5d 3.8

-5.2 _ 4.0d - 4.0d

4.5J 4.0d

_ 1-2 5.5 4.3 4.0 4.2

5.2 3.8 2b 4c 5.5 3.1 4.8 3.5 5.2

<4.5d 2.5d

396 415 415 415 113,114 4Olb 415 415 415 415 396 113, I14 109 270 109

109 113

113. II4 113. I14 270 415

270 415

a. For a definition see Structure 29. b. pro-S. c. pro-R. d. Given as AI*“‘. e. tj rt 100 and 4 + 100 obtained for cyclohexa-amylose. f. JI 25” and 4 - 38” determined by X-ray crystallography.

,lPNMRS ,4:4 - D


N’. I-i’), 4 may be gained by use of ‘J(CO, C-a, N, H) and 3J(C”0. NH, C-X H-r). $ may be obtained from ‘J(CO,C-r. H-2) (Section 9.2.1). In nucleosides. the

$ angle may be determined by means of ‘J(C, N. C-l’. H-l’) (Structure 31). The sterochemical properties of nucleosides and nucleotides have been reviewed by Davies.‘4’6’

OH OH

H-l’ H

(a) ON

31. (a) Uridine. The predominant conformation shown (nnri). 0 = 45”.“*“’ (b) Adenosine. The predominant confor-

mation shown (outi). 0 = 40“.@““’

13.2.1. ‘J(CO,N,H). These couplings were first reported by Dorman and Boveyt4’ ‘) in simple amides.

In N-methyl amides, two types are observable, one

“\\ iH (s-c) /c-N\H (s-l)

32

involving the carbonyl carbon and the other the N-methyl carbon. The nomenclature for the first- mentioned type is given in Structure 32. This choice underlines the single-bonded nature of the C-N bond and stresses the importance of the direction of the carbonyl group. Values are given in Table 16.

Two problems are associated with measuring ‘J(C0, N, H). The first one is broadening due to 14N and the other is the chance of proton exchange. Barboui and Petrescu’93’ and Jakobsen et ,1.‘92’ have shown that 14N decoupling improves the line-widths

considerably. In two cases 15N enriched material has been used.(*‘8.4’9t B ecause of line broadening Dorman and Boveyc41 ‘) quote their results as being approximate. Formamide is a key compound in the assess- ment of the possibility of using ‘J(CO.N, H) for conformational studies as it contains two protons

“\ /Hs +*.9 Hz

/C-N\H, -5.2 Hz

33

syt~ and arlti to the carbonyl group. Barboui and Petrescu(93’ determined the relative signs of ‘J. They

did, however, notice that different assignments of HA and Hs (Structure 33) are given in the literature and recent investigations point to the fact that HA and H, should be interchanged. The signs are then parallel to two-bond carbon-carbon, ‘J(CO,N,C), couplings.‘4’0) The *J(CO, N, H) coupling is clearly dependent upon the orientation of the carbonyl group although the opposite view has recently been

put forward. (4’9’ However, sign determinations are

necessary before these couplings can be used in this way. ‘J(C0, N. H) thus provides a potential tool for determining the o-angle of peptide backbones. Only two examples are presently known, [Leu’]-enke-

phalin’J2” and N-acetyl-L-alanine-N-acetamide’“73’ (Table 15). It should be considered, that 2J(C0,N, H) will most likely be small compared with the linewidth in normal peptides. In alumichrome couplings to the NH protons cannot be detected and in enterobactin *J(CO, N. H) is found to be considerably smaller than

‘J(C0, C, H-z),‘~“~’ which is around 5 Hz. A theoretical calculation of ‘J(C0,N.H) by

Gavrilov rr a!.‘“*‘) neither gave the correct sign nor

showed a clearcut difference between 2J(C0, N, H) s-c and ‘J(C0, N, H)s-t.

13.2.2. ‘J(C, N, H) ad 3J(C, C,N, H). These types of coupling constants are most easily studied in alkyl- amides, in anilides and in lactams, where there is only slow exchange of the amide protons. None of these couplings has a carbonyl group in the coupling path.

Couplings to amino protons have been reported in o&o-substituted compounds (mostly benzene derivatives).‘14’)

13.2.2.1. ‘f(C, N, H). Such couplings not involving

the carbonyl group may be found in alkyl or aryl amides or in lactams. Dorman et al.““’ have reported couplings of 2.8 and 2.7 Hz in N-methylformamide and N-methylacetamide. Fronza er &‘42’) observed a coupling of the order of 6Hz in A3-pyrrolin-2-one. In anilides a two-bond coupling of 3tSSbJ has been reported, whereas Sopchich and Kingsbury’14o’ have reported that they most likely were close to zero.

Only one example of a two-bond coupling to an amino proton has been so far reported. namely that of


TUILE 16. Carbon-Proton couplings through a nitrogen. “J(C,. . . , N, H)

‘J GeometryC ‘J Dihedral angle Refs.

Formamideb

N-Methylformamide

Acetamide

N-Methylacetamided

N-Acetyl-L-alanine N-acetamide

Acetanilide A’-Pyrrolin-2-one

CO, H CH,, H

CO, H C-a, H CH,, H CO,H C-5, NH

2-Chloro-acetanilide

2-Nitro-acetanilide

2Carbomethoxyacetanilide

2-Methylsulphinylacetanilide

2,4,6-Tribromoformanilide

2-Nitroaniline 4,6-Dibromo-2nitroaniline 2,4,6-Tribromoaniline

2-Chloro-N-ethylaniline 3-Amino-l, 2,Ctriazine 2-Acetamino-3-carboxy-4-

C-3, NH,

hydroxy-6-methylpyrylium salt C-2, NH 2-Amino-3-carboxy-4-hydroxy-6-

methylpyridylium salt 3-Carboxamide-3-hydroxy-6-

methyl-2-pyridone

CO, H CO,H CO, H

CH,, H

CO, H

[Leu5]enkephalin

Valinomycin

CO, He 2.6 CO, H’ 3.9

Alanine’ /I-Neuraminic acid Neuraminic acid methylester

,Y-methylglucoside Neuraminic acid methylester

a-methylglucoside Neuraminic acid

a-methylglucoside

CO, H 6.1

CO, H 5.9

CO, H 6.2

CO, H 6.2

- 5.2’ + 2.9’ c. 3.1

3.94 2.8 2.19 2.65 2.5 2.65 2.5 3.7 2.7

3.8 4.6 2.5 2.5 5.6

1.5

3

s-t s-c s-t

s-c CH,, I-I s-t s-c s-t s-t

C-h I-I 1.9 273

C-2'. H Cl

C-3, NH C-4, NH C-6, NH C-2, NH C-6, NH C-2, NH C-6, NH C-2, NH C-6, NH C-2, NH C-6, NH C-2, NH C-6, NH, C-6, NH, C-6,NH, C-2, NH, C-6, NH,

6.0 5.0

_ 4.5’ -2.5

4.9 m 5.4 2.6 3.7

?a 2.8 6.8 6.4 6.1 6.1 6m

180 0

180

180 0

180

la0 0

a50 428

140a

140a

140a

140a

140a

140a 140a 140a

l40a 424

55b

55b

55b

C-3, NH, -2

C-3, NH C-3, NH, C-5, NH CH,, NH CO, Hg CO, Hh C-8, H- 1

-5” -5” -4

2.5 1.5 0.8 3.0’ 1.d 2.7h 2.6 2.8

CO, NH; CO, H-5

CO, H-5

CO, H-5

CO, H-5

< 0.4 0 7.1 180

180 0

I.8

2.2

2.4

93

417 418 417 418 417 419 417 419 417

421

412

357 504

504

504

504

ments, see text. b. Reference gives values of 2.4 and 5.6 Hz. c. For a definition see Structure 32. d. Data for dominant conformer. e. Gly*. f. Gly3. g. Phe4. h. Let?.

a. The authors suggest a possible reversal of the assign- i. Solvent, CDCI,. j. Solvent, CCIJDMSO-d, (3: 1). k. K+ complex. Solvent, CDCI,, KCNS. I. Recorded at - 28” in CDCI,. m. Recorded at - 30’ in CDCI,. Gave a similar coupling

constant in DMSO-d, at room temperature. n. Broadening due to exchange. o. In concentrated HCI.

2’6 POUL ERIK HANSES

‘J(C-3. N. H) in 3-amino-1,2,4-triazine”“’ (Table 15).

Aminova and Samitov”‘@ calculated ‘J(C, N, H) 1 - 5.5 Hz in methylamine and Lee and Schulman”i3’ found from a6 ir~irio calculations a ‘J(C, N, H) value of 4.8 Hz in HNC.

13.2.2.2. ‘J(C, C. N, H). Sopchich and Kings- bury”*’ showed in ortho-substituted anilides that

‘J(C-3,C-1. N. H) = 3J(L800) is larger than ‘J(C-6. C-l,N,H) = ‘J(P). A great deal of scatter in 3J(C-6, C- 1. N, H) is observed although this coupling is not expected to be inhuenced by the substituents at position 2. The scatter in 3J limits the usefulness of this coupling as an indicator ofgeometry.

In a pyrylium salt 3J(O”) is as small as 1.5 Hz.“‘~) In a 6-methyl lactam a difference was observed between ‘J(CH,, C. N, H) and 3J(C-5, C, N, H)tSSbJ (Table 16).

A theoretical calculation gave the following equation:(“s’

‘J(C,C.N,H) = 5.7cosZO-2.7cos0+0.1 (13.2)

Experimentally, an example from peptides, 3J(C-p, C-g,N, H) was determined in valinomycin in two different solvents and with different counter ions.‘4’2J This coupling constant may give information about the $ angle.

Coupling constants to amino protons of orfho- substituted compounds show that ‘J(C-6,C-l,NH,) are identical for the two amine protons. An N-ethylaniline shows the same coupling as in primary amines, so the limited data presently available do not suggest a geometric dependence for this type of coupling. In Structure 34 3J(C-1,C-2, N, H) was 7.8 Hz.‘4231 Again may hydrogen bonding to the ester group reduce the exchange rate.

0 ax 1; O: i c

,H

ti I COOCH,

34

13.2.2.3. ‘J(C,CO,N,H). These can be measured in amides larger than formamides. N-alkyl acetamide gives a very small three-bond coupling - 1 Hz. The

geometry of the coupling path is supposed to be cis. In acetamide the mm coupling is 7.1 Hz”“‘) and in A3-pyrrohn-2-one 3J(C,C0, N, H) is equal to 6 Hz,‘~‘~’ whereas in other compounds there are equal couplings to both amide protons.tsSbl Theoretical calculations predict the large difference between ‘J trnns and ‘J cis well.‘273’

13.2.2.4. ‘J(CO, C, N, H). These coupling constants may be observed in peptides and give information about the 4 angle. 3J(C0,C-r,N, H) values were

observed in enkephalin and they were small, 0.8- 1 5 Hz”*l’ A theoretical calculation gives equation

(;3.3)+s’

‘J(C0,C.N.H)=4.7cos20-1.5cos~fO.l (13.3)

With the 4 angle held constant to 180’ the I(/ angle was varied, but the variation in ‘J is not more than 0.12 Hz.““’

In concentrated hydrochloric acid the exchange of the amino-protons of alanine is sufficiently slow to permit observation of ‘J(COOH. C, NH,)‘357i (Table 16).

13.2.3. 3J(C, N, C, H). This type ofcoupiingis found

in nucleosides, nucleotides and peptides. In this section nucleosides and peptides will be dealt with separately although they have much in common.

13.2.3.1. Nucleosides and nucleotides. One im-

portant conformational parameter is the torsional angle, x, relating the relative positions of base and sugar moieties about the glycosidic bond. (Structure 31).

The use of 3J(C-2,N,C’,H-l’) (see Structure 31) for stereochemical purposes was first advanced by Lemieux et a1.‘352.402’ It was stated that ‘J(C,H)

is more sensitive to structural parameters (such as electronegativity, heteroatom, carbon hybridization) than hydrogen-hydrogen coupling constants. The approach of Lemieux et rr1.‘356.426’ was to prepare

H-6

0

HO’ b-2

(a)

0

(W

35

specifically i3C-enriched compounds with a fixed geometry (Structure 35a,b). They used both ‘J(C,N, C, H) and ‘J(C, 0, C, H) coupling constants to construct their Karplus curve. ‘332*426) It must be pointed


out that for 3J(C, N, C, H) substituent effects were not idines and purines. A similar approach was used by taken into account.

Davies’4’6*“27’ showed that not only 3J(C-2, N, Utawa and Uramoto.‘428’ The predominant conformation is the anti one.

C-l’, H- 1’) but also ‘J(C-6, N, C- l’, H- 1’) can be used Schweizer and Kreishman”“9*430’ compared to predict the predominant conformation of pyrim- 3J(C-2. N.C’, H-l’) in cytidine and 6-methylcytidine

TABLE 17. ‘J(C. N, C. H’) in purine and pyrimidine nucleosides and nucleotides


Cytidine 6-Methylcytidine Cytidine 2’-monophosphate

Cytidine 3’-monophosphate

Cytidine 5’-monophosphate

C-2. H-l’ C-2. H-l’ C-2. H-l’ C-6. H-I’ C-2.H-1’ C-6, H-I’ C-2, H-I’

C-6, H-l’

3-N-Phenylcytidine-5’-monophosphate C-2, H-l’ C-6, H-I’ CH,.CH,

Methylcytidine 5’-monophosphate C-2, H-l’ C-6, H-I’

Methyl 3-N-methylcytidine 5’-monophosphate C-2, H-I’

Uridine 5’-monophosphate C-2.CH, C-2, H-l’ C-6, H-I’

3-N-Methyluridine 5’-monophosphate C-2, H-l’ C-6, H-l’ C-2, CH,

Methyl uridine 5’-monophosphate C-2, H-l’ C-6, H-l’

Methyl 3-N-methyluridine 5’-monophosphate C-6, H-l’ Uridine C-2, H-I’

C-2, H-I’ C-2. H-l’ C-6, H-I’

5Hydroxyuridine C-2, H-l’ C-6, H-l’

6-Azauridine C-2, H-l’ Uracil polyoxine C C-2, H-I’

C-6, H-I’ Polyoxin C C-2, H-I’

C-6, H-I’ 2,2’-Anhydro-I-/I-D-arabino-furanosyluracil C-2, H-I’ 2,5’-Anhydro-2’,3’-isopropylidenecyclouridine C-2, H-I’ 2’. 3’-0-Isopropylidene uridine C-2. H-I’ 5’-Deoxy-5’-iodo-2’. 3’-0-isopropylidene uridine C-2, H-l’ 5’-Deoxy-5’-iodo-uridine C-2, H-l’ S-Bromouridine C-2, H-l’

C-6, H-l’ S-Bromodeoxyuridine C-6, H-l’ Deoxyuridine C-2. H-l’

/I, /I, /I-Trichloroethyl 5’-amino-5’- deoxythymidine-5’-phosphate

Adenosine

Allopurinol riboside Tubercidine

Guanosine

AICA Riboside

Polyoxin N Minimycin Anhydrooctose uranic acid nucleoside

C-6; H-I’

C-2, H-l’ C-4. H-I’ C-8, H-l’ C-4, H-l’ C-4, H-I’ C-8, H-l’ C-4. H-I’ C-8, H-l’ C-5. H-I’ C-2, H-l’ C-5, H-l’ C-4. H- 1’ C-2, H-l’

3+1 6kl 2.4 3.9 2.3 3.5 1.3 1.8 3.7 3.0

_ 2.0 3.6

_ 2.0 1.5 3.7

-2.0 2.0 1.8 3.4 1.8 3.7 2.4 1.8 3.7 3.7 2.4 2.4 2.1 3.7 2.9 4.2

-1 3.9 4.4 3.4 3.5 3.6 6.6 2.4 5.0 2.9 2.4 3.6 3.7 2.1 3.7

2 2.9 3.8 1.5 2.9 4.4 2.2 3.7 2.4 3.4 3.9 3.7 3

DMSO 429 DMSO 429 D,O 422

DzO

DrO

422

422 431 422 431 431

‘A0 DrO

DzO

DzO

DzO

D,O

D,O 431

D,O D,O

-45 D,O DrO

D,O

431 427 352 428 428 428

D,O 428 D,O 428

‘30 428

-134 DMSO -175 CDCI,

CDCI; CDCI, D,O:acetone D,O

352.402.426 352,402,426 352 352 352 427

D20 427 DzO 427

D,O 40

‘W D,O

DzO

D,O

D,O 433 DzO 405 D,O 162

431

431

431

431

431 428

428 428

428

428

228 POUL Eanc HANSEN

TABLE 18. Carbon-Proton couplings through nitrogen, “J(C,N,C, H)

‘J Geometry Refs.

N-Methylacetamide CO, CH, N-Methylacetamide-d, CO, CH, N-Acetyl-L-alanine-N-acetamide C-1, C-Hx N-Methylformamide-d,(trans) CO,CH,

N-Methylformamide-d,(cis) N, N-Dimethylformamide

l-Naphthalene-N,N-dimethyl- carboxamide

N-Acetylalanine N-Acetylalanineamide Alanine sodium carbonate Alanineamide sodium carbamate H,N-Ala-Phe-Gly-Ala-Ala-COOH N-Ethyl carbaminate N-Isopropyl carbaminate N-Acetyl-L-tryptophan Glycine sodium carbamate Glycineamide sodium carbamate Phenylglycylglycine sodium carbamate Phenylglycylalanine sodium carbamate Cycfo-Disarcosyl

Cycle-tetrasarcosyl

C-2, CH, Bis(dimethylaluminium)-N, N’-

dimethyloxamide CO, CH,

Uracil c-2, H-6 Uridine c-2, H-6 Cytocine c-2, H-6 Cytidine c-2, H-6 L-Thiazolidine-4carboxylic acid CS, Ha

N-Acetyl-L-thiazolidine-4-carboxylic acid C-b, H-a

Thyrotropin releasing factor CO, H-ak Valinomycin CO, H-as

[Leus]-enkephalin

Gly-Pro-Leu-Gly

CO, H-a’ CO, H-a’ CO, H-z”

AZ-Cephalosporin C-8, H-4 Penicillins C-7, H-3 Anhydro-octose uranic acid nucleoside c-2, H-6

CH,,CH

CO, CH, CO, CH, CO,CH,

CO, CH, CO, CH, ‘CO, H-a ‘CO, H-a “CO, H-a “CO, H-a aCO, H-a CO, H CO, H CO. H CO, H CO, H CO, H CO,H CH,, H-a C-a, CH, CH,, Hs-a C-5, CH, CH,, H,-a

CO, H-a’

3.9 3.5 2.5 3.1 3.81 5.1 5.17

-4.3 +4.34 +2.72

3.42b 2.85b 2.4 2.2 1.9 2.2 2.2 3.3 2.6

::: 4.3 4.0 2.4

co.5 3.3 4.0 3.0 6.3’ 1.6* 3.0

5.5e 4.5’ 8.0 8.0 9+1 9+1 3.4h 2.7’ 1.5)

4.52y 3.4ry

-2 3.0’ 2.3m 2.9” 2.4’ 0.6P

co.51 1.7m 3.4” 2.50

<0.5p 1.7 1.7 2.8”

-0” 5.0 5.0 6

273 417 273 -l17 418 417 -118 417

s-t 92 s-c

s-t s-c

322b

402 402 402 402 402 402 402 437 402 402 402 402 106

106

180 180 180 180

136s

352 352 429 429 698

699

439c 412

421

439c

750 750

180 162


in DMSO and demonstrated a large change (Table 17) in agreement with the expected change in conformation from a predominant anti to a syn conformation. Lee and Char&‘311 studied methyl substituted uridine- and cytidine monophosphates. As seen from Table 17 methylation at N-3 or at the phosphate moiety does not lead to any major changes in ‘J. The dihedral angle around the glycosidic bond was estimated to be about 45”. Nottoli er n/.‘JJZ’ studied ,&,X/&trichloroethyl 5’-amino-5’-deoxythymidine-S- phosphate and deduced a predominantly arm conformation as found for the natural nucleosides.

Uramoto et ~1.‘~~~) observed 3J(C-5, C-l’, H-l’) in polyoxim N in which the base is a pyrazole ring.

Studies of S-bromo-1-methyluracil, I-methylcyto- sine and 1,3-dimethyluracil showed that

‘J(C-6, N, CH,) > 3J(C-2, N, CH,),

probably due to the effect of the keto group at C-2. The difference is about 0.6 Hz in uracils and -0.9 Hz in cytosine. For methylpurines 3J(C-8, N, CH,) > ‘J(C-4,N, CH,) the difference is _ 1.2 Hz.‘~“)

13.2.3.2. Amides and peptides. ‘J(CO, N, C, H) may be studied in alkylsubstituted amides. Values for simple amides show, that coupling to a methyl group syn to the carbonyl group is smaller than to that anti to the carbonyl group.‘92*417*4’8) The assignment given in Reference 330 should be reversed as indicated in Reference 420.

The use of 3J(C0, N, C, H) has been reviewed by Bystrov’435’ and this coupling has been the subject of several theoretical treatments.

Bystrov et a1.‘412*436) constructed a Karplus curve (equation (13.4)) based upon the average value from N-methyl acetamide, the value for N-acetyl-L- trypthophan bound to 6-chymotrypsin’437i and N- acetyl-l-alanyl-N-methyl amide.‘273’

‘J(CO,N,C-cc,H)=9.0cos2f7-4.4~0~0-0.8 (13.4)

This equation may be compared with theoretical equations (13.5 and 13.6)

‘J (CO, N, C-u, H)

= 3.3cos2tl-l.3cos6)-1.2sin2t)‘442) (13.5)

3J(C0,N,C-a,H)=4.5cos2~-1.3cos~-1.2 (13.6)

The influence of the relative arrangement of the car- bony1 group and the /?-carbon. as a rule. does not ex- ceed 0.2 Hz.““’ Mohanakrishnan and Easwaran’43S)

used a Dirac vector model to calculate ‘J(C0.N. C-r,H) in peptides. The results show an angular dependence, which can be expressed in the form

‘J(CO, N. C-a, H)

= 7.55cos’0-0.44Bcosf7-2.34Hz (13.7)

(0 is related to the torsional angle 4 of the backbone).

They predicted a negative three-bond coupling for dihedral angles around 900. Both the K- and the u-contribution were evaluated and it was emphasised that the Ir-contribution depends upon the core polarization, which again may depend upon the environment.

The 3J(C0,N,C, H) tells about the 4 angle of peptides and they have been reported in a number of peptides as shown in Table 18.

Toma et u~.‘~‘~~~ observed significantly different 3J(C0, C, C, H) of Gly-’ 3C-Pro-Leu-Gly in DMSO and in water, indicating that the conformation of the backbone is solvent dependent. These values were used to elucidate the backbone structures of thyrotropin-releasing factor,‘439ac) [Leu’]-enkepha- line,‘42’J and valinomycin. ‘412*440s) N-acetyl derivatives and carbonates have been studied as model compounds for peptides. It was unexpectedly found that 3J is larger for alanine than for glycine derivatives.‘402i Rodgers and Roberts’437’ studied the binding of N-acetyl- ‘3CO-L-trypthophan to chymotrypsin and found by extrapolation a ‘J of -0.78kO.8 Hz in the bound state.

13.2.3.3. 3J(C, N, C, H). Examples of such coupling in molecules with none of the carbons being a carbonyl carbon is reported in cyclo-sarcosyls.‘106i Two types of coupling constants, ‘J(CH,, N, C-a, H) and ‘J(C-r, N, C, H ‘), are encountered. The former type is fairly constant (Table 18), whereas the latter depends strongly on the conformation.‘108) Strictly speaking ‘J(C-6, N, C-l’, H-l’) of nucleosides and nucleotides belong also to this category. (Table 17.)

13.2.4. Others. In salicylaldehyde oxime a )J(C’, N, 0, H) of 5.3 Hz was reported.“*” In methyl isocyanide, ‘J(C=, N, C, H3) is 2.72 Hz.‘~~~~‘) A similar coupling was observed in a series of Schilf’s bases in which 3J 5 6.3 +0.5 Hz (pD = 8.2) and 8.6f0.5 Hz (pD = 12.3) suggesting that their conformations at constant pH are the same. ‘32’i A coupling constant around

a. Carbonyl group ofacetyl or carbamate part or carbonyl group of the glycine residue. b. Assignments reversed from those given in Reference 422a as shown in Reference 354. c. H’. k. CO of the pyroglutamic residue, H-a of d. Ho.

q. CO of D-Hui, H-a of D-Val. the histidine residue. r. CO of L-Lac, H-a of L-Val.

e. CO, N-CH, rrans. I. Solvent, cyclohexane. s. f. CO, N-CH, cis.

CO of Gly, H-a of Gly. m. Solvent, chloroform. t. CO of Gly, H-a of Phe.

g. More values given in this reference. h. pH 1.3.

n. Solvent, carbontetrachloride/DMSO-d, u. CO of Pro, H-a of Leu. (3:l).

i. pH 6.1. v. Solvent, DMSO-I,.

j. pH 8.3. o. Solvent, ethanol + 2 oA water. x. Solvent, D,O. Zwitterion state. p. K’ complex. Solvent, chloroform, KCNS. y. pD = 5.7.


TABLE 19. Coupling constants “J(C. X. H) and ‘J(C. X. C, H) in which X is not oxygen or nitrogen

Heteroarom “J(C. H) n Refs.

2-Chloro-3-cyano-4-ethio-6-methyl-pyridine S C-4. S. CH, 1,3-Dithiole-2-thione S CS. S. C. H 1.3-Dithiole-2-one S CO, S, C, H L-Thiazolidine--I-carbonylic acid S C. S. C. H”

N-Acetyl-L-thiazolidine-4-carboxylic acid S C. S. C. H”

1.4-Oxathiane S C-3, S, C, H trc~rts-2.6-Dichloro-1.4-oxathiane S C-3. S. C, H cis-2.6-Dichloro- 1,4-oxathiane S C-3, S, C, H

2-Nitrothiophenol 2Carboxymethylthiophenol

(CH,),Si

S S S Si

C-6. C, S. H C-6, C. S. H C-2, C, S, H C. Si. C. H

(CH,),SiCI (CH,),SiCI, (CH,l,(CICHZ)Si (CH,J,(CICH,)SiCI (CH,)L(CI,CH)SiCI Dichlorodimethyl silane (CH,),SIOCH,CH, (CH,)2SiO(CH2CH,), (CH,),SiSCH, ((CH,),W,N (CHJ,Ge (CH,I,Sn (CH,).,Pb (CH,),Hg (CH,),Se (CH,),Te I.5C,B,H, Bis(dimethyl aluminium)-N. N’-

dimethyloxamide Bis(diethylgallium)-N, N’-dimethyloxamide

;; Si Si Si Si si Si Si Si Ge Sn Pb

Hg Se Te B

C. Si. C, H C, Si, C, H C, Si. C, H C, Si. C. H C, Si. C, H C, Si, H C. Si. C, H C. Si, C. H C, Si, C. H C, Si, C. H C. Ge, C. H C. Sn, C. H C, Pb, C, H C. Hg. C, H C, Se. C. H C, Te, C. H C,B,C.H

Phenylphosphine

Al Ga Ga P P P P Fe Fe Fe

CH,, Al. CH, CH,.Ga.CH, CH,.Ga.CH, C-l,P,H C-2. P, H C-3, P. H C-4, P, H C-4, Fe. Hx C-4, Fe. Hx C-2, Fe. Hx

Protonated butadiene iron tricarbonyl Protonated cyclobutadiene iron tricarbonyl Protonated norbornadiene iron tricarbonyl

S

S

C.S.C.Hr

C.S.C.He

3 3 3 3

3

3

3

3 3 3

3 3 3 3

3 3 3 3 3 2 3 3 3 3 3 3 3 3 3 3 3

3 3 3 2 3 4 5 2 2 2

4.0 8.1 kO.02

10.42 f 0.02 2.5” 2.7b 3.0’ 3.3” 2.7b 1.1’ 3.5” 3.4” 1.3” 2.0” 3.1 3.3 2.6h 4.0’ 5 7. I’ 3.5”

+ 2.0 2.1

(+)(.sj (+)l.lj ( + )2.6i (fjl.5’

0.5 kO.2 15.0 2.5 1.0 I.9 2.0 1.9 1.3 I .05 1.74

+ 4.0 + 3. I 19.7k

4.5 5.8 5.8 2”’ 5m Orn Irn

73.7 81.2 37.8’

55b 441 441 698

699

409 409 409

140a I40a

828 201 445 445 445 445 445 443 446 446 447 447 201 201 201 201 444 444 448

136 136

442

451 453 451,453

a. pH in solution 1.3. f. s-t. k. Multiplecoupling paths. b. pH in solution 6.1. g. s-c. I. Average value. c. pH in solution 8.3. h. Axial. m. Estimated values. d. The carbonyl and the hydrogen syn. i. Equatorial. n. H-/I’. e. The carbonyl and the hydrogen cmri. j. Sign assumed. o. H-B’.

5 Hz was observed in pyridoxylidene-l-valine.‘3”a’ Comparisons with couplings through oxygen is made ‘J(CO, N=, C, H) was observed in 4-benzyliden-2- in Section 14.3. phenyl(methyl)-A2-oxazolin-5-ones.~HobJ

13.25. Srrmnrary. Whether or not such an extensive 13.3. Coupling through Heteroatoms other than Oxygetl

subdivision of three-bond coupling constants through and Nitrogen

nitrogen is really necessary has still to be proven. Spoormaker and de Biec409’ have observed three- Theoretical calculations have indicated that the orien- bond 3J(C, S, C, H) couplings in 1,Coxathianes. An tation of, for example, C=O groups play little role. average value of 3.1 Hz was observed in the parent


compound, whereas 3J(C-3. S, C, H) 180” = 4.0f0.4 and ‘J(C-3,S.C H) 60” = 2.6kO.4 were observed in the cis-2,6-dichloro derivative (at least 957; of the molecules are in the form in which the two chlorines are in equatorial positions). Furthermore for 3J in the trans-2.6-dichloro derivative is the mean value of the couplings observed in the cis-derivatives (50:50 distribution between its two isomers was observed) it was tempting to suggest that substituents play only a small role in these couplings.

A difference between ‘J(C0, S, C, H) and the similar 3J(CS.S.C,H) couplings of 1.7Hz (Table 19) was ascribed to differences in the effective nuclear charge in the radical part of the 2s orbital at the coupled carbon.“J” Very few 3J(C, C, S, H) couplings have been observed, but the few known values (Table 19) seem quite similar to 3J(C,C,0, H). A difference between the s-c and the s-t form is clearly observed.“40’

Tentative values “J(C, P. H) have been obtained in phenylphosphine and these have been compared with theoretical values (INDO MO). The INDO calculations overestimated *J, but 3J was in reasonable agreement with experiment. The four-bond coupling is predicted to be close to zero at low values of 0 and the angular dependence of the five-bond coupling suggested it is dominated by a n-mechanism.‘442) A theoretical approach was also made by Samitov et c11.“‘~

Two- and three-bond couplings through silicon have been reported l*J(C,Si, H)l = 15.0,‘443) with a much larger size than the corresponding *J(C, C, H) couplings. ‘J(C,Si,C, H) has been shown to be positive’4’J*‘45’ in a number of cases. The magnitudes vary from 0.5 to 2.6Hz probably caused by electronegative substituents (see Table 19). Three-bond coupling constants through silicon were also observed by Harris et LI~.‘~~~-‘*‘) in silanes.

Onak and Wan”“@observed a three-bond coupling constant, 3J(C, B.C. H) in r3C enriched IS-dicarba- close-pentaborane. The cage structure of the molecule

provides three equivalent coupling paths (Structure 36). Couplings ‘J(C,Al,C,H) and ‘J(C.Ga,C.H) have also been reported. “36) (Table 19.) Whitesides and Maglio t449) observed large two-bond couplings of the type C-metal-H in cyanide hydride complexes of

irridium, rhodium and platinum and a stereochemical dependence was observed. The coupling constants in the carbonyl hydrides of manganese, tungsten and molybdenum complexes were smaller than in the above mentioned compounds. No stereochemical dependence was observed. Carbonyl hydrides of iron, ruthenium. osmium. rhenium and osmium were also reported. (uO’ Treatment of butadiene tricarbonyl with an excess of fluorosulphonic acid in sulphur dioxide at -60’ leads to pronation of the iron and subsequent observation of *J(C. Fe, H) equal to 73.7 Hz!“‘) A similar treatment of norbornadieneiron tricarbonyl resulted in both C-2 and C-6 being coupled with the hydrido proton with a coupling of 38Hz’*“’ (only half the magnitude of that observed in butadiene tricarbonyl complex). Cyclobutadieneiron”53’ also gives a stable complex with ‘J(C.Fe.H) = 81.2Hz __

1 5 H Fe-H

(CO),

37

and it was concluded that a (T-A complex had been formed (Structure 37). The norbornadieneiron tricar- bony] compound was assumed to exist as two rapidly equilibrating compounds.‘452’

Weigert et crl.‘*O1’ correlated 3J(C, X, C, H) with ‘J(H, X, C, H), but observed that the former are larger than expected.

14. COMPARISON OF DIFFERENT TYPES OF COUPLING CONSTANTS

Comparison of coupling constants is made mainly for two purposes, (i) to establish a common coupling mechanism and (ii) to establish that it is valid to transfer knowledge from a well-known or easily accessible type of coupling constant to a less common one. The early interest in comparison of carbon- hydrogen with hydrogen-hydrogen coupling constants probably originated from the many examples known of the latter type. However, at present carbon- hydrogen coupling constants are so well-documented that they form the major entity for comparisons.

Within carbon-hydrogen coupling constant it is also of interest to compare the different types of coupling constants especially those passing only through carbons with these also passing through heteroatoms. In the first thirteen sections a distinction between these types of coupling constants has been made and correlations between coupling constants have also been mentioned.

14.1. Comparisons between “J(C, H) and”J(H, H)

Marshall et a1.“’ reviewed this subject up to 1974 and the early results will not be included here


except to say that the original idea goes back to

Karabatsos et a1.‘454’ who suggested that the ratio “J(C. H)i”J(H. H) should depend upon l/(A x B x C) in which A is the ratio between mean excitation

energies. ~3 the gyromagnetic ratios and C the ratio of the electron densities at the carbon and hydrogen. For sp3 hybridized carbon I/(A x B x C) is equal to 0.30. for sp2 equal to 0.40 and for sp equal to 0.60.

This very simple picture has been confirmed experimentally in only a very few cases.

14.1.1. ‘J(C,H) cs. ‘J(H,H). Marshall et ~1.“’ found in their review paper that 2J(C0,H) of carboxylic acids behaved irregularly and it was pointed out that the orientation of the carboxyl group relative to the geminal proton was not the same in all the compounds studied. In olefins ‘J(CH,, H) vs. 2J(H, H) gives a ratio between + 1.44 and + 1.64. Differences in bond angles and bond lengths were considered and it was suggested that the latter factor may be responsible.“‘” Ayrls’3J” correlated ‘J(CH3, H) and “J(H, H) in cyclic compounds in which the intervening carbon is sp3 hybridized. A very substantial intercept

was observed. The reason for this has not been established.

14.1.2. “J(C, H) L'S. "J(H, H). Carbon-hydrogen coupling constants in benzene derivatives are usually very time-consuming to obtain. Some effort has been put into finding appropriate model compounds such as substituted olefins from which hydrogen-hydrogen coupling constants could be obtained and then used to predict the carbon-hydrogen couplings of benzenes.“8*‘7*JSS’ Ernst et aLc2” correlated *J(C-3, H-2) with 2J(H,H) in monosubstituted ethylenes and in 2-substituted 1,3-butadienes and found a good correlation. The same concept was transferred to heterocycles!’ 6*456’

Another useful comparison was made between "J(CH,, H) and “J(H, H) in both aromatic and olefinic systems. A fairly consistent ratio of -0.6 has been found.‘375*386’ The range of compounds studied by Vijgeli and von Philipsborn’375) was extended by

Douglas,“s7’ who found a greater spread in the ratios

when increasing the range of electronegativities of the

substituents. ;iyr%‘45n’ correlated 3J(CH3, H) with 3J(H, H) in trans-3-substituted-2-propenes and in the corresponding ethylenes and found

3J(C, H) = 0.46( kO.04)

x ‘J(H,H)+ 1.58(f0.52) (14.1)

with a correlation coefficient r = 0.956. Braun and Kinkeldei’374) dealt with methylsub-

stituted azulenes (Section 10.3) and found a good correlation between ‘J(CH,,H) and 3J(H,H) for sterically non-hindered methyl groups.

A ratio close to 0.6 is also obtained in dihydro- aromatic carboxylic acids.(328’ Van de Ven and de Haan”“’ found that comparable carbon-hydrogen

and hydrogen-hydrogen coupling constants are similar in the cyclopentadiene part of Spiro [Z.l]heptadiene- 4,6. Forrest and Sukumar’37Z) correlated ‘J(CH,, H)

in rert-butyl derivatives with ‘J(H. H) of isopropyl derivatives and arrived at equation (10.13). Spoormaker and de Bie’350’ on their side compared 3J(C. H) in the fragment CH,CR’(OH)CR”HH with ‘J(H. H) in HCR’(OH)CR”HH. The ratios range from 0.72 to 0.42. In a study of isopropylhalides the same

authors also compared ‘J(C, H) and 3J(H. H) of the same compound and found

‘J(C,H) = 0.71 x 3J(H,H)+0.16 (14.2)

Chertkov and Sergeev (‘5g) found that ethyl derivatives

have 3J(C.H) proportional to 2J(H,H) of methane derivatives (proportionality factor 0.4kO.l).

14.1.3. Swnmary. From what has been said above it is difficult to compare ranges of ratios with equations correlating the two parameters and the former type should be abandoned as no simple relationship between ‘J(C, H) and 3J(H, H) has been established.

14.2. Comparison of”J(C, H) and "J(C, C)

Early results were discussed by Marshall et ~1.“) and some more recent results are given by Hansen!354*460’ Carbon-carbon, carbon-hydrogen and hydrogen- hydrogen coupling constants representing different coupling types and magnitudes were compared and similar signs found.‘32’bJ The theoretical treatment by

Barfield et aI.(3b5*36b) also reveals a close correspondence between carbon-hydrogen and carbon-carbon coupling constants.

Investigations of two-bond coupling constants of carbohydrates also show a close correspondence. (Section 17.2.)

14.3. Comparisonof”J(C,C ,..., C,H)and"J(C,X ,..., H)

Theoretical calculations show that replacement of the central carbon atom in propane by a heteroatom does not radically alter the computed coupling.‘347)

The experimental evidence that no major changes are observed by separating e.g. 3J(C, N, C, H), 3J(C,0, C, H) and 3J(C, C, C, H) confirms this prediction as do the equations (10.4), (10.6), (10.7), (10.8), (13.4), (13.5) and (13.6) which are very similar both in numerical values and certainly in structure.

When it comes to heteroatoms other than first row elements the picture may well be very different. Weigert et al. (‘01) found that ‘J(C, Me,C, H) are

much larger than expected as judged from ‘J(H, Me, C, H). Very few data are as yet available to warrant a more thorough discussion of this subject.

14.4. Sumrm-y

Comparisons of J(C, H) with "J(C, X,C,H) or possibly also with “J (C.. . , X. H) may well turn out to


be very fruitful as very similar trends have been established. Quantitative expressions are however still lacking.

15. SPECTRA IN NEMATIC PHASE

Dissolving compounds in liquid crystals, either thermotropic or lyotropic, leads to a partial orientation. In this case the coupling constants both direct (dipole-dipole), D, and indirect (through bonds). J, determine the appearance of the spectrum. The method has been reviewed by Diehl and Khetrapal’461’ who concentrated on ‘H spectra and hydrogen- hydrogen coupling constants and also by Emsley and Lindon,t462a) Lunazzir46zb’ and Khetrapal and Kunwart462C) and by Kelker and Hatz.t462d’ From the direct coupling constants, ratios of bond lengths and henceamolecularstructuremay bededuced.In thecase of carbon-hydrogen dipole-dipole coupling constants information of relative carbon-hydrogen bond distances may also be found.

15.1. Technique

Both ‘H-l% satellite spectra and i3C single frequency spectra have been recorded. The AISEFT technique is very useful in the first case.t88-90) The introduction of two low viscoscity solvents, Merck ZLI 1167, which orients with the optic axis perpendicular to the magnetic field and hence allows sample rotation in iron magnets and Merck ZLI 1132 which orients parallel to the magnetic field and hence allows sample rotation in superconducting magnets, has led to linewidths smaller than one Hz.(~~~) In analysing spectraseveralproblemsmust becopedwithsuchasthe large number oflines to beassigned and the great chance of overlapping lines, but also of fundamental importance is the fact that line positions are sensitive only to thesumZD(CH)+J(CH)+ kAJ(CH).Thelattertermis due to anisotropy of the indirect coupling constant. Usually the J(CH) values are taken from studies of the compound in isotropic media (for possible solvent effects see Section 5). In the final analysis two questions must be answered, (i) does anisotropy play an important role for J(CH)?, (ii)should the derived bond lengths be corrected for vibrational motion?

15.2. Anisotropy

The work of Englert et a1.‘464) on [13C]benzene in a nematic phase showed that it is unnecessary to include a large anisotropic contribution to the indirect i3C-H coupling constants. Furthermore, Bhattacharyya and Dailey’465*“b”’ concluded that neglecting the anisotropy in the indirect 13C-H coupling tensor is justified as very good agreement was obtained with microwave data without taking anisotropy into account. On the other hand, Price and Schumann(467) concluded from an investigation of 1,3,5trichlorobenzene, that the geometrical data were not in agreement with the assumption that there

is no influence of isotope substitution on the orientation and no anisotropy in the indirect coupling. However this conclusion could be misleading since the effects of vibrations were neglected.

15.3. Correctionfor Vibrational Motion

Corrections for molecular vibrations have been discussed by Diehl et al. (46*J In case of pyrazine’469’ the corrections were calculated on the basis of a force-field of p-dichlorobenzene. In a study of thiophene and furane r4’O) the r,-structure (corrected for harmonic vibrat;ons) of thiophene and furane were determined from ‘H-“C-satellite spectra. This study demon- strates the importance of vibrational corrections for the observed internuclear distance ratios, particularly those involving carbon-hydrogen bond lengths. Cor- rections as large as 4-5 y0 were determined. This effect is due to large wagging motions of the C-H bond, which reduce the dipolar coupling.(47” The C-H bond lengths without correction were much too large (0.1 t 3-0.114nm). but they agree with microwave data after the correction had been performed. r2- structures of benzene,t463’m-dichlorobenzene,‘472’ and 1,2,3-trichlorobenzene’473i and other aromatic molecules have also been reported.

15.4. Indirect Couplings

By studying spectra of samples with different degrees of orientatic-r the need to know “J(C,H) coupling constants may be lessened. The D values are proportional to the orientation and the J values are constant, and hence both can be determined as demonstrated by Burnell et a1!474*4751 The degree of orientation may be altered by changing the temperature(46s*466’ and the signs of J(CH) may be determined.t466’ Signs of J(CH) may also be obtained in some cases from a comparison of the calculated bond lengths in the two cases and then selecting the best result.

15.5. Rest&s

s-TriazinewasstudiedusingtheAISEFTmethod.’s9) Good agreement with results from Raman spectra in the gas phase, but not with the X-ray data was found. Besides the molecules already mentioned methanol,‘465’ methyl chloride,‘466) methyl bromide,‘466) methyl iodide, (466) benzonitrile, t4’~’ ethylenoxide,‘477’ ethylene sulphide,‘477i N-methylformamide,‘4’*’ benzenechromium tricarbonyl,‘47r” dimethylmercury,‘479’ and methylmercuric halides,‘479i have been studied in nematic liquid crystalline phases.

The data obtained by NMR are compared with other types of data, X-ray, microwave and neutron dif- faction. As discussed by Diehl and Niederberger’471’ these techniques may lead to different structures. However, an internuclear distance can always be expressed as the sum of the equilibrium distance, r. and the vibrational contribution, Ar.


r’ -=$+z(l+~-g (15.1) r I,

This means that the relative distances measured by NMR are quite close to the equilibrium values. if the relative vibrational contributions to the other two respective distances are close to each other.

The effects of nematic solvents on internuclear distance ratios have also been studied and found to be of the order of 1 0,‘.(4b3) / 0

p-Dioxene’4s0’ was studied in two lyotropic meso- phases based on decyl sulphate or potassium laurate. At room temperature the flipping motion is sufficiently rapid to average the environments of the axial and equatorial protons. The complete structure could not be determined with the available data. However, the conformational twist angle. r, which could be reliably determined. is the most interesting feature of the molecule.

Only compounds having simple NMR spectra may be investigated in the liquid crystalline phase as the analysis otherwise becomes too complex and the

amount of overlap of lines too serious as shown from the very symmetrical molecules studied so far.

The differing results reported by various authors may be understood in the light of the large corrections necessary to correct for the vibrational motions. Relative H. H distances seem to be well calculated from partially orientated ‘H NMR spectra, whereas the t3C-H distances must be corrected for vibrational motion. As this is done only in a few cases Jacobsen and Schaumburg’47b’ concluded that the use of NMR spectroscopy of molecules in liquid crystalline solvents is a useful method in determining relative H.H distances. while it is questionable for

determination of relative C, H distances unless a very careful correction for vibrational motion is done.

16. ALIPHATIC COMPOUNDS

This section covers the characteristics of coupling constants in aliphatic compounds including amino acids but not carbohydrates. Aliphatics may be divided in many different ways and into different classes and as much of the material has already been presented, the text will be very brief and mostly in tabular form.

TAIILF: 20. Three-bond carbon-hydrogen coupling constants, ‘J(C. C. C. H)” in hydrocarbons

‘J Dihedral angle Refs.

Propane

Cyclohcxaneh

Adamantane-tl,s Adamantane-tl,

2-Methylbutane

2-Methylpropane

C-l. H-3

C-l, H-3eq C-l, H-3ax C-l. H-3” C-3,H-1“ C-4, H-2 C-4. H-2 C-4, H-2 C-2, H-4

CH,. H

Butane

2.2-Dimethylpropane

C-l. H-3 C-2, H-4 C-l,H-3

Bicycle [2.2.2] octane-d, Bicycle [2.2. I] heptane

C-3, H-I C-3, H-l

C-4, H-l

2,2.4.4-Tetramethylbicyclo [ 1.1.01

butane C-I,CH,(exo) C-I.CH,(endo)

I-Deuteriobicyclo [2.2.2] octane C-3, H-l I-Deuteriobicyclo [2.2.l] heptane C-3. H-l

C-4, H-I

5.7 +0.2 C 820 5.86 328 8.12 I80 112 2.12 60 5.33 180 365 5.57 I80 124

<3 60 7.17 I80 3.74 C 371 4.1 5.21 C 372 5.25 371 4.04 371

5.4 4.65 C 372 4.62 4.66 371 7.0 368 7.0c 368 6.76 829 8.7’ 368 8.75 829

4.60 213 5.20 7.0 367 7.0 367 6. I5 830 8.7 361 8.54 830

a. For ‘J in substituted compounds see Table 9. b. Low temperatureexperiment. c. Free rotation. d. Identical coupling paths. e. Obtained from ‘J(C. D).

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Met

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te

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I, 2

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2-

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se

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a 16

0 a

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7 a

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5

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170

160.

5

Met

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ide

160

170

I51

I53

146

140

I43

145

I53

I49

I52

I50

I50

144

I45

I45

140

143

146

I45

146

143

I45

150

I43

I50

142

146

146

146

146

I41

146

I41

I57

142

I53

146

144

147

145

I45

I54

148

148

156

I51

146

148

146

146

I45

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148

I45

I45

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147

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147.

5

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148

- I4

5 -_

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143

141’

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144

148

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150

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51

6 14

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7 I4

8 51

6 51

6 14

8 51

6 53

0 53

0 53

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516

516

537

515

516

515,

517

516

516

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522b

53

7 51

5,51

6 51

5-51

7 51

6 51

6 51

6 51

7 51

6 51

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5

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517

517

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651

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Position ot-H

-lb C

-l, H

-l C

-2, H

-2 C

-3, H

-3 C

-4, H-4

C-S, H

-S C

-6, H

-6 R

efs.

Methyl-2-dcoxy-a-D

-hesopyranosidc 170

Methyl-2-dcoxy-/l-D

-hrsopyranosidc 161

2-Deoxy-a-D

-knopyranosc tctra-acetate

17s

2-Deoxy-fi-D

-ltrxopyranose tetra-acetate

165

SECTIO

N 3

Methyl

4,6-O-benzylidene-2-deoxy-a-D

-r&j.

hexopyranoside

Methyl

4.6~O-benzylidene-3-deoxy-a-D

-riho- hexopyranoside

Methyl

3,4-dideoxy-a-D-er~rhru-hcxopyran.oside

165 168.5 167.5 169 169 173 17s 17s 176 175 174 175 175

Methyl

3,4-dideoxy-a-D-rr~rhro-hexopyranoside

peracetate

1,6-Anhydro-/I-D

-pyranose trho

I, 6-Anhydro+D

-pyranose ido

I, 6-Anhydro-/I-D

-pyranose gulo

I, 6-Anhydro-/J-D

-pyranose m

/o I, 6-A

nhydro-/t-D-pyranose

gcrlucro 1,6-A

nhydro-/j-D-pyranose

n~utmo

1,6-Anhydro-/j-D

-pyranose o/lo

I, 6-Anhydro+D

-pyranose plnco

I, 6-Anhydro-2,3-O

-isopropylidene-/~-D-m

annopyranose M

ethyl 6-deoxy-a-L

-mannoside

Methyl

6-deoxy-/l-L-m

annoside Propyl6-deoxy-a-L

-mannoside

Propyl6-dcoxy-/I-L-m

annoside Isopropyl

6-dcoxy-a-L-m

annosidc Isopropyl

6-deoxy-/l-L-m

annoside

kZT

lON

4

Methyl

tri-O-acetyl-2.3,

S-z-D-xylofuranoside

Methyl

tri-O-acetyl-2,3,

S-/j-D-xylohtranoside

2, S-Dim

ethoxy-2, S-dihydrofuran”

2, S-Dim

ethoxy-2, S-dihydrofuran

187 171

168 158 166 152 166 154

176.25 522a

172.50 522a

176.0’ 522a

172.5” 522a

130 130 130 134 132

130.5ax 127.5eq

140 143 143 148 148

J3 g 145 145 150 151 150 144 143.7 149 150 150.6

145 146

144 145

144 150

150 148

132 132

I: 6

g 8

g R

132.5

129 132.5

128.5

R

g R

R

144

148 145

149 146

146 136

142 150

143 152

144 150.6

148.0 149

145 147

147 156.1

-145

144 144

516 142

143 516

150 149

516

143 148

516

274

274

140 140

I x3’ 143

143 In)“.’

143 143

183” 144

148 183’

143 148

183” 155

150 183”

157 153

522bh 160

IS4 521

159 154

521 160

IS2 521

158 157

521 158

153 521

161 152

521

158 152

160 152

521 521 522b 517” 517” 517r 517” 517s 517r

I, 2-

O-l

sop

rop

ylid

enc-

3..5

.6-t

ri-O

-ort

ho

form

yl-o

l-D

- g

luco

lura

no

se

I, 2-

O-l

sop

rop

ylid

cnc-

a-D

-glu

colu

ran

ose

I, 2-

O-I

sop

rop

ylid

cne-

/I-L

-id

ofu

ran

osc

M

eth

yl

a-g

llrco

-ru

ran

osi

de

Met

hyl

/j-

gb

rco

-lu

ran

osi

de

Met

hyl

a-

trllo

-lu

ran

osi

de

Met

hyl

/I-

n/lo

-fu

ran

osi

de

Met

hyl

a-

t)l(

t111

1o-l

urB

no

sid

e M

eth

yl

/I-,,t

crrl

rto

-Tu

ran

osi

de

Met

hyl

a-

go

lncr

o-r

ura

no

sid

e M

eth

yl

/I-yr

rln

cro

-Tu

ran

osi

de

Met

hyl

a-

.sy/

o-l

ura

no

sid

e M

eth

yl

/kq

&h

tran

osi

de

Met

hyl

a-

rih

o-l

ura

no

sid

e M

eth

yl

/kib

o-l

ura

no

sid

e M

eth

yl

a-ly

xo-f

ura

no

sid

e M

eth

yl

/ku

rub

itw

-fu

ran

osi

de

Met

hyl

a-

urt

rhiw

-htr

ano

sid

e a-

Ery

rbo

-lu

ran

ose

b

-Ery

rbo

-lu

ran

ose

a-

Tb

reo

-lu

ran

ose

&

Tb

rro

-lu

ran

ose

G

lyco

lald

ehyd

e,

hyd

rate

G

lyce

rald

ehyd

e,

hyd

rate

E

ryth

rose

h

ydra

te

Th

reo

se

hyd

rate

G

lyce

rald

chyd

e-3-

ph

osp

hat

e,

hyd

rate

E

ryth

rosc

-4-p

ho

sph

ate,

h

ydra

te

Th

reo

sc-4

-ph

osp

hat

e,

hyd

rate

a-

Ara

bir

w-l

ura

no

se-S

-ph

osp

hat

e /&

tru

bin

o-l

ura

no

se-S

ph

osp

hat

e a-

Rib

o-f

ura

no

se-S

ph

osp

hat

e /&

Rih

o-h

tran

ose

-S-p

ho

sph

ate

a-X

ylo

-hrr

ano

se-S

ph

osp

hat

e /l-

Xyl

o-f

ura

no

se-S

ph

osp

hat

e a-

Lyx

o-l

ura

no

se-5

-ph

osp

hat

e j%

Lyx

o-f

ura

no

se-5

-ph

osp

hat

e I,

2:5,

6-D

i-0-

iso

pro

pyl

iden

e-a-

D-g

luco

fura

no

se

SIC

TIO

N

5 I-

Th

iom

eth

yl

tctr

a-0-

acet

yl-/

t-D

-glu

cop

yran

osi

de

I-T

hio

elh

yl-l

etra

-O-a

cety

l+D

-glu

cop

yran

osi

de

Tet

ra-0

-ace

tyl-

a-D

-glu

cop

yran

osy

l fl

uo

rid

e

I86

174.

0 17

2.5

174.

5 17

4.0

172.

4 17

5.0

174.

0 17

2.0

173.

0 17

4.0

173.

0 17

4.0

171.

0 17

4.0

173.

0 17

2.3

150.

3 17

2.3

150.

3 17

2.3

152.

5 17

3.8

151.

8 16

3.9

162.

1 16

4.2

162.

8 15

9.8

163.

9 16

2.6

172.

3 17

4.9

173.

6 17

3.0

173.

4 17

1.6

171.

9 17

4.5

186

e a I5

6 51

6 a

I53

516

e 18

6 51

6

143.

3 14

1.5

141.

5

149.

6 14

7.4

152.

9 15

3.6

150.

7 15

3.6

145.

2 14

7.4

154.

0 15

2.1

152.

8 15

2.8

145.

9 14

5.0

148’

35

1

I54

143’

35

1 14

3 14

3’

143

351

523

523

523

523

523

523

523

523

523

523

523

523

523

523

523

832

832

832

832

832

832

832

832

524

524

524

524

524

524

524

524

524

524

524

149’

35

1 14

9

TA

DL

E 2

1 (c

ontd

.)

Posi

tion

olH

-lb

C-l

. H

-l

C-2

. H

-2

C-3

, H

-3

C-4

, H

-4

C-S

. H

-S

C-6

, H

-6

pers

.

Tet

ra-0

-acc

tyl-

,%D

-glu

copy

rano

syl

fluo

ride

T

etra

-0-a

cety

l-a-

D-g

luco

pyra

nosy

l ch

lori

de

Tet

ra-0

-ace

tyl-

/1-D

-glu

copy

rano

syl

chlo

ride

T

etra

-0-a

cety

l-a-

D-g

luco

pyra

nosy

l br

omid

e I-

N-P

hcny

l a-

D-g

luco

pyra

nosi

de

tetr

a-ac

etat

e I-

N-P

heny

l P-

D-g

tuco

pyra

nosi

de

tetr

a-ac

etat

e I-

N-p

-Nitr

ophe

nyl-

fi-D

-glu

copy

rano

side

te

tra-

acet

ate

P-D

-Glu

copy

rano

side

az

ide

tetr

a-ac

etat

e T

eIra

-O-a

cely

l-a-

D-g

iuco

pyra

nosy

l py

ridi

nium

br

omid

e C

ytid

ine

5’-m

onop

hosp

hate

3-

N-M

ethy

lcyt

idin

e 5’

.mon

opho

spha

te

Met

hylc

ytid

ine

5’-m

onop

hosp

hate

M

ethy

l 3-

N-m

ethy

lcyt

idin

e 5’

-mon

opho

spha

te

Uri

dine

5’

-mon

opho

spha

te

/I-N

-Met

hylu

ridi

ne

S-m

onop

hosp

hate

M

ethy

luri

dine

5’

-mon

opho

spha

te

Met

hyl

3-N

-met

hylu

ridi

ne

5’-m

onop

hosp

hate

2-

Am

ino-

2-de

oxy-

a-D

-glu

copy

rano

se

2-A

min

o-2-

deox

y-a-

D-g

luco

pyra

nose

D

C1

2-A

min

o-2-

deox

y-a-

D-g

luco

pyra

nose

te

tra-

acel

ate

2-A

min

o-2-

deox

y-/j-

D-g

luco

pyra

rnos

e 2-

Am

ino-

2-de

oxy-

/i-D

-ght

copy

rano

se

DC

I 2-

Ace

tam

ido-

2-de

oxy-

a-D

-glu

copy

rano

se

2-A

ceta

mid

o-2-

deox

y+D

-glu

copy

rano

se

a-D

-Glu

copy

ranu

roni

c ac

id

sodi

um

salt

/I-D

-Ghr

copy

ranu

roni

c ac

id

sodi

um

salt

S-T

hio-

a-D

-glu

copy

rano

se

tetr

a-ac

etat

e 5-

Thi

o-/l-

D-g

luco

pyra

nose

te

tra-

acet

ate

Met

hyl-

S-th

io-a

-D-g

luco

pyra

nosi

de

tetr

a-ac

etat

e M

ethy

l-W

hio-

/l-D

-glu

copy

rano

side

te

tra-

acet

ate

SE

CT

ION

6 Su

cros

e

Mal

tose

Met

hyl

/I-m

alto

side

a e a e e a a a ax

e e a a a e a e a e a e a e

I78

184

I71

I85

I65

I55

160

160

163

170.

3 17

3.3

170.

9 17

3.3

170.

3 17

1.5

170.

3 17

0.9

171

170

177

163

I61

172.

8 16

0 17

0.4

161.

6 16

0 I5

7 16

0 15

7

169.

0’

168.

5 17

2.5

172

171.

5”

172”

16

2.5”

16

0”

173.

0

140

150

I45

I45

152.

3 15

0.8

148.

9 14

5.8

153.

8 15

0.9

148.

0 14

5.1

153.

2 15

2.0

149.

5 14

5.6

153.

8 14

9.4

149.

7 14

5.3

151.

4 15

3.2

150.

1 14

7.1

152.

6 15

0.2

150.

2 14

7.1

152.

0 15

1.7

150.

5 14

7.6

152.

8 15

0.9

150.

4 14

8.4

-140

145.

0 14

5.0”

516

516

516

516

516

516

516

I45

516

516

431

431

431

431

431

431

431

431

516

538

516

516

53g

532

532

532

532

230

230

230

230

415

515

415

515

415

515

415

515

415


I I ! I I

TABLE 21 (

con

td.)

Po

siti

on

o

f H

-lb

C

-l,

H-l

C

-2,

H-2

C

-3,

H-3

C

-4,

H-4

C

-5,

H-5

C

-6,

H-6

R

eh.

/I-M

eth

yl

myc

aro

sid

e /I-

Fo

rom

ysin

e a-

Fo

rom

ysin

c cc

-Met

hyl

myc

aro

sid

e O

cto

syla

cid

A

C

ho

nd

roit

in

A r

esid

ues

Ch

on

dro

itin

B

rrs

idu

cs

Ch

on

dro

icin

C

rrs

idu

es

Hep

arin

rc

sid

urs

SE

CT

lON

-/

Dim

eth

yl

(4,6

-di-

O-a

cety

l-2,

3-d

ides

oxy

-a-D

-rg

~fh

ro-

hex

apyr

ano

syl)

p

ho

sph

on

ate

Dim

eth

yl

(4,5

-di-

O-a

cety

l-2,

3-d

ides

oxy

-/~-

D-r

~~r/

~r~-

h

exap

yran

osy

l)

ph

osp

ho

nat

e

Dim

eth

yl

(4,6

-di-

0-ac

etyl

-2,3

-did

eso

xy-a

-D-r

/tw

o-

hex

op

yran

osy

l)

ph

osp

ho

nat

c

Dim

eth

yl

(4-O

-ace

tyl-

2,3-

did

eso

xy-/

l-D

-g/y

cero

- p

enta

pyr

ano

syl)

p

ho

sph

on

ate

Dim

eth

yl-(

6-O

-ace

tyl-

2,3,

4-tr

ides

oxy

-a-L

-y/~

~~er

a-

hex

op

yran

osy

l)

ph

osp

ho

nat

e

Dim

eth

yl-(

6-O

-ace

tyl-

2,3.

4-tr

ides

oxy

-/~-

L-g

l.ww

~~-

hex

op

yran

osy

l)

ph

osp

ho

nat

e

(2R

)-D

imct

hyl

-tct

rah

ydro

pyr

an-p

ho

sph

om

ne

Dim

eth

yl-(

4,6-

di-

O-a

cety

l-2.

3-d

ides

oxy

-a-D

-q~f

/rro

- h

ex-2

-en

op

yran

osy

l)

ph

osp

ho

nat

e

Dim

eth

yl-(

4,6-

di-

O-a

cety

l-2,

3-d

ides

oxy

-/b

D-e

r~rl

nw

- h

ex-2

-en

op

yran

osy

l)

ph

osp

ho

nat

e

161.

9 I5

7.7

165.

1 16

8.1

161

162

162

168

I61

160

170

172

535

535

535

535

533’

53

2

532

532

532

e'

144.

0 13

3.5

133.

0 14

8.0

148.

0 14

6.0

518,

519

a’

138.

5 13

1.0

131.

5 14

9.0

148.

0 14

7.5

518,

519

e 14

5.3

129.

0 13

1.0

149.

0 14

3.0

148.

0 51

8,51

9

a’

131.

5 13

3.0

132.

0 14

4.0

143.

0 51

8,51

9

e’

147.

0 13

0.0

130.

0 13

0.0

147.

0 14

6.0

518,

519

a’

142.

0 12

8.0

128.

0 13

0.0

143.

5

142.

0 13

0.0

132.

0 13

0.0

144.

0

150.

0

_.

518,

519

518,

519

ey

148.

1

ay

142.

0

168.

0

168.

0

168.

0 15

2.3

149.

5 14

8.8’

14

8.8

518,

520

167.

0 15

1.0

146.

0 14

8.0’

14

8.0

518,

520

160”

14

3’

Dim

ethy

l-(4

,6-d

i-C

J-ac

etyl

-2,3

-did

esox

y-a-

D-r

lrrr

o-

hex-

2-en

opyr

anos

yl)

phos

phon

ate

Dim

ethy

l-(4

,6-d

i-O

-ace

tyl-

2,3-

dide

soxy

-/L

D-r

/trro

- he

x-2-

enop

yran

osyl

) ph

osph

onat

e

Dim

ethy

l-(4

-0-a

cety

l-2,

3-di

deso

xy-a

-D-g

/yce

ro-

pent

-2-e

no-p

yran

osyl

) ph

osph

onat

e

Dim

ethy

l-(4

-0-a

cety

l-2.

3-di

deso

xy-/

I-D

-gly

cero

- pe

nt-2

-eno

-pyr

anos

yl)

phos

phon

ate

148.

0 16

9.0

169.

0 15

1.0

145.

0 14

8.0’

51

8,52

0 14

8.0

142.

3 17

1.0

166.

5 15

0.0

142.

5 14

9.6’

51

8,52

0 14

9.6

143.

5 16

8.0

166.

5 14

3.0

143.

0’

518,

520

149.

0

147.

0 16

9.0

166.

5 14

9.0

148.

0’

518,

520

148.

0

a.

b.

:. e.

f. g.

h.

i. j. k.

I.

m.

n.

0.

;I r. s.

1.

u.

V.

X. Y.

Mo

st

cou

plin

g

con

stan

ts

are

mea

sure

d

as f

irst

o

rder

sp

litti

ng

s an

d

are

qu

ote

d

as

f I

Hz.

In

cas

es

whe

re

solv

ent

effe

cts

have

be

en

inve

stig

ated

so

lven

ts

are

give

n,

othe

rwis

e no

t. a

= ax

ial,

e =

equa

tori

al.

Ove

rlap

ping

re

sona

nce.

So

lven

t, de

uter

ochl

orof

orm

. So

lven

t, ac

eton

e-d,

. So

lven

t, di

met

hyls

ulph

oxid

e-dI

,. O

ther

gl

ycos

ides

ar

e al

so

repo

rted

in

thi

s pa

per

and

fall

insi

de

the

rang

e in

dica

ted.

So

lven

t, he

avy

wat

er.

Ass

ignm

ent

usua

lly

not

mad

e.

The

ph

enyl

boro

nate

ad

opts

a

‘C,

conf

orm

atio

n.

Not

ice

the

smal

l di

lTer

ence

in

cou

plin

g co

nsta

nts

betw

een

the

a- a

nd

/I-a

nom

ers.

A

mix

ture

of

‘C

, an

d “C

, co

nfor

mer

s ex

ist.

Has

be

en

reas

sign

ed

(see

Ref

eren

ce

5 17

).

C-l

’. C

-4’.

C-S

. C

-2’.

C-3

’. C

-7’.

H-7

’=

146

Hz.

Ir

clrl

s.

cis.

In

clud

ed

t’or

com

para

tive

reas

ons.

‘C

, co

nfor

mat

ion.

e

and

a de

note

in

the

se

case

s qu

asi-

equa

tori

al

and

quas

r-ax

ial.

TA

IILI

; 22

. T

wo-

an

d th

ree-

bond

ca

rbon

-hyd

roge

n co

uplin

g co

nsta

nts

in c

arbo

hydr

ateP

h”

25

‘J

Dih

edra

l an

gle

Rch

.

a-D

-Glu

copy

rano

se

a-D

-Glu

copy

rano

se-5

,6,6

-d,

Met

hyl-

a-D

-glu

copy

rano

side

a-D

-Glu

copy

rano

se

pent

a-ac

etat

e

/I-D

-Glu

copy

rano

se

j-D

-Glu

copy

rano

se-5

,6,6

-t/s

Met

hyl-

/j-D

-glu

copy

rano

side

-d,

/I-D

-Glu

copy

rano

se

pent

a-ac

etat

e

a-D

-Gal

acto

pyra

nose

M

ethy

l a-

D-g

alac

topy

rano

side

P-D

-Gal

acto

pyra

nose

C-l

, H

-2

C-2

, H

-3

C-3

, H

-4

C-l

, H

-2

C-2

, H

-3

C-3

, H

-2

C-3

, H

-4

C-6

, H

-5

C-l

, H

-2

C-2

, H

-3

C-6

, H

-5

C-l

, H

-2

C-l

, H

-2

C-2

, H

-3

C-l

, H

-2

C-2

, H

-3

C-3

, H

-2

C-2

, H

-4

C-4

. H

-5

C-l

,H-2

C

-6,

H-5

C

-2,

H-3

C

-l,

H-2

C

-2,

H-l

C

-2,

H-3

C

-3,

H-2

C

-3,

H-4

C

-6,

H-5

C

-l,H

-2

C-2

, H

-3

C-3

, H

-2

C-3

. H

-4

($0

( -

)5.0

-0

5.5

5.5

5.5

0 4.1

*I

5.9

-0 5.

5 -

5.1

(-T

;

5:s

5.0

5.0

- 3.

0e

- 2.

v 5.

0 0 6.

0 -0

( -$.

o ( -

)5

.0

( -

)5.0

( -

)5

.0

C-l

, H

-3

C-2

, H

-4

C-3

, H

-l

C-6

, H

-4

C-6

, H

-4

2.8

C-2

, H

-4

0 C

-3,

H-

1 0

C-l

,H-3

0

C-6

, H

-4

2

C-2

, H

-4

C-3

, H

-I

0 0 5.5

3.3

+ 5.

0

+ 5.

0

351

327b

32

7b

327a

I80 60

60

351

531

327b

35

1 53

7 35

1 32

7b

327a

327a

60

60

351

327b

53

-l

539

537

327b

Met

hyl

/j-D

-gal

acto

pyra

nosi

de

I, 6

-Anh

ydro

-/f-

gala

ctop

yran

ose

1,6-

Anh

ydro

-/I-

D-g

alac

topy

rano

se

lria

ccla

te

a-D

-Man

nopy

rano

se

a-D

-Man

nopy

rano

se

pent

a-ac

etat

e

Met

hyl

a-D

-man

nopy

rano

side

,9

-D-M

anno

se

Met

hyl

I-D

-man

nopy

rano

side

Met

hyl

6-de

soxy

-a-D

-man

nose

tr

iace

tate

M

ethy

l 6-

deso

xy-/

l-D

-man

nose

tr

iace

tate

M

ethy

l /k

ello

bios

ide-

d,

Met

hyl

/kel

lobi

osid

e-d,

he

ptaa

ceta

te

Cyc

lohe

xa-a

myl

osc-

cl,

a-D

-Allo

pyra

nose

j?

-D-A

llopy

rano

se

I,6-A

nhyd

ro-/

I-D

-allo

pyra

nose

1.6A

nhyd

ro+D

-allo

pyra

nose

tr

iace

tate

Met

hyl

/-D

-gul

opyr

anos

ide

1,6-

Anh

ydro

+-D

-gul

opyr

anos

e 1.

6Anh

ydro

-j?-

D-g

ulop

yran

ose

tria

ceta

te

Met

hyl

2,3-

di-0

-ace

tyl-

4,6-

O-b

enzy

liden

e-a-

D-

altr

opyr

anos

ide

2,7-

Anh

ydro

-/I-

D-g

luco

hepl

ulop

yran

osc

C-3

, H

-4

C-2

, H

-l

C-2

, H

-3

c-3,

H

-2

C-4

, H

-S

C-4

, H

-3

C-5

, H

-4

c-5,

H

-6(e

x0)

C-6

, H

-5

(-::

: (-

-WI

;r;‘;

(3

3'

(-)3

(-

WS

;rg ( - )

2:8

C-5

, H

-4

C-l

, H

-2

C-3

, H

-2

C-4

, H

-3

C-3

, H

-4

C-3

, H

-2

C-2

, H

-3

C-l

, H

-2

C-2

, H

-I

C-2

, H

-3

C-2

, H

-I

C-2

, H

-l

C-2

, H

- 1

C-4

’. H

-S

C-5

’. H

-4

C-4

’. H

-5

C-s

’, H

-4

C-4

, H

-S

C-5

, H

-4

C-l

,H-2

C

-l.

H-2

C

-3,

H-2

C

-3,

H-4

C

-3,

H-2

C

-3,

H-4

C

-3,

H-4

-0

-0

(-+

)2

;I$:

;

;I;::

-0

- 1.

6

(+)8

-0

(+)7

-0

+

9.0

-3.0

-3

.5

- 3.

0 -3

.0

-3.5

-2

.9

-0

- 5.

0 ( -

)5

.0

( - )

5.0

( - )

5.0

( - p

.0

( - )

3.6

C-2

, H

-3

(-J4

.5

C-4

, H

-3

(-Ft

.4

C-4

, H

-5

(-k4

.4

C-l

, H

-3

+ 3.

7 17

0 32

7b

539

C-3

, H

-I

C-3

, H

-5

C-4

, H

-2

C-4

, H

-6(e

xo)

C-5

, H

-3

C-6

, H

-4

+ 4.

6 $4

.6

+4

+3

+4.5

+

5.2

180

180

I80

170

I80

I80

327b

53

9

327b

53

9

327h

53

7 32

7h

327h

327b

53

7 32

7b

327h

539

539

IO9

IO9

IO9

327a

32

7a

327h

327b

327b

32

7b

327h

327b

32

7b

TA

BLE

22

(c

onld

.)

Dih

edra

l z.

I ‘J

an

gle

Rcf

s.

2,7-

Anh

ydro

+D-m

anno

hept

ulop

yran

ose

I, 2

-O-l

sopr

opyl

iden

e-3,

5.6-

tri-

0-or

thof

orm

yl-a

-D-

gluc

olur

anos

e I,

2-O

-lso

prop

ylid

cne-

a-D

-glu

cofu

rano

se

I, 2

-O-l

sopr

opyl

iden

e-/I

-L-i

dofu

rano

sc

I, 2

: 5,

6-D

i-0-

isop

ropy

lidcn

c-a-

D-g

luco

fura

nose

C-4

, H

-3

C-6

, H

-5

C-6

, H

-5

C-l

,H-2

C

-6,

H-5

C

-6,

H-5

C

-6,

H-5

C-2

, H

- 1

C-l

, H

-2

3-O

-Ace

tyl-

I,

2: 5,

6-di

-O-is

opro

pylid

enc-

a-D

- gl

ucof

uran

ose

C-l

, H

-2

C-2

, H

-l

C-3

. H

-4

C-2

, H

-3

I, 2

-0-l

sopr

opyl

iden

e-a-

D-g

luco

fura

nuro

no-6

,3-l

acto

ne

C-6

, H

-5

I, 2

-0-1

sopr

opyl

iden

e-/~

-L-i

dofu

ranu

rono

-6,3

-lac

tone

C

-6,

H-5

D

-Man

nono

-1.4

~lac

lone

C

-l,

H-2

C

ytid

ine

5’-m

onop

hosp

hate

M

ethy

lcyt

idin

e S-

mon

opho

spha

te

Met

hylu

ridi

ne

5’-m

onop

hosp

hate

2-

Am

ino-

2-de

oxy-

a-D

-glu

copy

rano

se

DC

I C

-I,

H-2

2-

Am

ino-

2-de

oxy-

/I-D

-glu

copy

rano

se

DC

I C

-I,H

-2

2-A

min

o-2-

deox

y-a-

D-m

anno

se

DC

I C

-l,

H-2

2-

Am

ino-

2-de

oxy-

/l-D

-man

nose

D

CI

C-l

, H

-2

3-0-

Ace

tyl-

I, 2:

5,6-

di-0

-iso

prop

ylid

cne-

a-D

-allo

fura

nose

M

ethy

l a-

!l/lc

co-h

cxor

uurt

luos

idc

C-l

.H-2

C

-2.

H-I

C

-2,

H-3

M

ethy

l /~

-ylr

rco-

Ilcx

oTur

nllo

sidc

C

-l,

H-2

C

-2,

H-l

C

-2,

H-3

M

ethy

l a-

[r//o

-hsx

ortlr

;lrlo

sitlc

C

-I,

I#-2

M

ethy

l /~

-lr/

lollc

xohl

r;ln

osid

c C

-l,H

-2

C-2

. H

-I

C-2

, H

-3

Met

hyl

a-nw

rrrr

o-he

xofu

rano

side

C

-l.

H-2

C

-2.

H-l

C

-2.

H-3

-0

-0 0 5.

5 <2

0 0

+ 5.

6 +5

.5

( + ,s

.; ( +

)5.5

(-)4

.0

( -

)2.8

4.

1 0 4.

8

-2.6

-6

.9

-3.1

-

3.0

0 4.0

4.0

0 0 3.0

0 0 0 0 -3

0 0

C-6

, H

-4

0

C-I

,H-3

5.

5 C

-6,

H-4

2.

4 C

-6,

H-4

0

C-6

, H

-4

2.7

C-l

, H

-3

5.5

C-l

, H

-3

-t4.

6 14

0 53

9

C-6

, H

-4

9.1

C-6

, H

-4

6.6

C-l

.H-3

8.

9 C

-2’.

H-4

2.

8 C

-2’,

H-4

2.

4 C

-2’,

H-4

2.

4

C-l

. H

-3

-0

C-1

.1-1

-3

4.0

C-2

, H

-4

0

C-I

,H-3

4.

5 C

-2.

H-4

0

C-1

.11-

3 4.

5 C

-I,

H-3

0

C-2

. H

-4

0

C-l

,H-3

0

523

C-2

. H

-4

0 52

3

327b

70

I40

140

351

351

351

351

327b

32

7a

140

351

351

140

351

431

431

431

538

538

538

538

loo

539

523

523

523

523

523

523

523

523

523

Met

hyl

/I-r

rrcn

r/ro

-hcx

ofur

snos

ide

Met

hyl

a-gc

tltr~

ro-h

cxof

uran

osid

e

Met

hyl

B-g

trltr

clo-

hexo

fura

nosi

de

Met

hyl

a-sy

fo-f

urln

osid

e

Met

hyl

/ -.v

y/o-

fura

nosi

de

Met

hyl

cc-r

-iho

-fur

anos

ide

Met

hyl

/I-r

&o-

fura

nosi

de

Met

hyl

a-/y

.uo-

fura

nosi

de

Met

hyl

/I-o

rabi

no-f

uran

osid

e

Met

hyl

a-tr

robi

rro-

fura

nosi

de

Thr

eose

hy

drat

e a-

Thr

ro-f

uran

ose

/~-E

ryrk

ro-f

uran

ose

/J-T

llreo

-fur

anos

e T

hreo

se-C

phos

phat

e,

hydr

ate

a-R

iho-

fura

nose

-Sph

osph

ate

/I-L

yxo-

fura

nose

-S-p

hosp

hate

C-I

, H

-2

0 C

-2,

H-l

0

C-2

, H

-3

0 C

-I,

H-2

3.

0’

C-2

, H

-l

0 C

-2,

H-3

4.

5 C

-l,

H-2

0

C-2

, H

-I

0 C

-2,

H-3

4.

0 C

-l,

H-2

0

C-2

,H

1 >3

C

-2,

H-3

>3

C

-l,

H-2

0

C-2

, H

- 1

0 C

-2,

H-3

3.

5 C

-l,

H-2

0

C-l

, H

-2

0 C

-2,

H-l

0

C-2

, H

-3

0 C

-l,

H-2

0

C-2

, H

-l

0 C

-3,

H-2

0

C-l

,H-2

3.

0’

C-2

, H

-l

0 C

-2,

H-3

>4

C

-l,H

-2

0 C

-2,

H-I

0

C-2

, H

-3

3.5

C-l

, H

-2

4.4

C-l

, H

-2

- 1.

9 C

-l,H

-2

_ 3.

4 C

-l,

H-2

4.

4 C

-l,

H-2

3.

5”

C-l

, H

-2

1.6

C-l

, H

-2

4.8

a.

Cou

plin

gs

thro

ugh

oxyg

en

(‘J(

C-I

. H

-5)

and

3J(C

-S,

H-l

))

are

give

n in

Tab

le

12.

b.

If t

he s

igns

of

the

cou

plin

g co

nsta

nts

have

be

en

dete

rmin

ed

thes

e ar

e in

dica

ted.

Si

gns

in b

rack

ets

are

assu

med

fr

om

com

pari

son

with

si

mila

r co

uplin

gs.

c.

A z

ero

mea

ns

that

a

coup

ling

has

not

been

ob

serv

ed

and

that

it

is m

ost

likel

y <

1 H

z.

d.

Solv

ent,

pyri

dine

-d,:h

eavy

w

ater

(7

:3).

c.

So

lvcn

l. ch

loro

form

. f.

May

be

int

erch

ange

d.

g.

pH

= 2.

1.

C-l

, H

-3

C-2

, H

-4

C-l

,H-3

C

-2,

H-4

C-l

,H-3

C

-2,

H-4

C-l

,H-3

C

-2,

H-4

C-l

.H-3

C

-2,

H-4

C-l

, H

-3

C-l

,H-3

C

-2,

H-4

C-l

,H-3

C

-2,

H-4

C-l

, H

-3

C-2

, H

-4

C-l

, H

-3

C-2

, H

-4

4 0 0’

0 0 0 0 0 4.0

0 4.0

0 0 4.0

0 0’

0 0 0

523

523

523

523

523

523

523

523

523

523

523

523

523

523

523

523

523

523

523

523

523

523

523

523

523

523

523

523

x32

832

832

524

524

-

‘X3 POUL ERM HASSES

The effects of ring size upon ‘J were discussed in

Section 82.1. Very large one-bond coupling constants were found in bicyclobutane.“‘“‘.“Y” but also in the substituted ones.‘2”.“3.‘*” In cvclopropanes ‘J falls around 160 Hz.““” Similarly ‘j values of 170.26 Hz and 175.33 Hz were observed in ethylene sulphide and ethylene oxide. ““’ In cyclopentane and cyclo- pentanone values of 128.22 Hz and 131.39 Hz were found.““s’ Qclohexane has been analysed at a sufficiently low temperature to freeze out the confor-

mations and to allow the two one-bond coupling constants (126.44 and 122.44Hz) to be observed.““’ The one involving the equatorial hydrogen is the larger.

Among the bi- and tricyclic compounds, adamantane is of special interest because of the low ring strain. ‘J(C-l.H) is 131.21 Hz and ‘J(C-2.H) is 175 86 Hz.“~” The coupling constants were obtained - . from the corresponding carbon-deuterium coupling constants (see Section 3.1 I J. Slightly different coupling constants were measured in off-resonance decoupled spectra.“07” Other cyclic compounds investigated are bicyclo[n. l.0]hydrocarbons.‘J”4’ One-bond coupling has been shown to be a good indicator of strain in the ~rltlo-er’clo-bridged bicyclo[ I. 1 .O] butanes.‘487’ Pinancs,““’ norbornenols,@” norbornanols.““” benzonorbornene,‘.‘“” benzonorbornadiene.‘4Hs’ di- methylenenorbornane, ‘4yo’ 2,3-dimethylene-7-oxid- norbornane.“go’ and 2.3.5,6-tetramethylene-7-oxa-

norbornane”‘“’ have also been investigated. Dicls- Alder adducts of furan have three-membered rings with large ‘J(C.H) values.(“““J In bicyclic diones it

was found that the ‘J at the bridgehead z to the carbonyl group is larger than in similar acyclic and monocyclic ketones. In connection with chemical reactions nortricyclenes”07b’ and 4-chloro-3-methoxy- bicyclo[2.2.0]hexane-I-carboxylic acid’48y’ have been investigated.

16.2. Acyclic Cornpowds

One-bond coupling constants have not yet proved

useful in this type of compound except for assignment purposes as they depend only approximately on the electronegativity of the substituent.‘“‘“’

However. Witherup and Abott’3’3F’ have observed in pyridoxal-5’-phosphate and in pyridoxamine-S’- phosphate that the one-bond coupling for methylene carbon atoms is about 25 Hz less than those reported for the methylene groups of organic phosphates. The authors ascribed this to an interaction of the aromatic ring with the phosphorylated methylene group. Two- bond coupling constants are given in Tables 4, 5, 7, 8. Ail two-bond coupling constants for which signs have been determined are negative, but the magnitude varies considerably with the number, the position. and the nature of the substituents as discussed in Section Y.3.1. As ‘J depends upon the orientation of the

substituent on the /?-carbon relative to the C-H bond. rotamer populations may in principle be determined using two-bond coupling constants. This possibility has been used in the case ofcis-2,6-dichloro- l.4-oxathiane.“og’ As the difference between ‘J(s-y)

and ‘J(s-rr) most likely will be largest for very electronegative substituents. the method is most useful if such substituents are present. A few examples of differences between ‘J(s-tr) and ‘J&y) are found in Table 5. That cumulative substitueJt effects may become large is demonstrated in I-phenyl-1,2-dibromo-2-nitroethane.“j’

Acid catalysed rearrangements of “C-labelled ketones have been studied by means of two- and three- bond carbon-hydrogen coupling constants.‘Jy’b’

Three-bond coupling constants have already been

discussed at some length in Section 10. Couplings in hydrocarbons are given in Table 20 and those of substituted aliphatic compounds in Table 9. Values from carbohydrates are given in Tables 21 and 22.

Polychlorinated cpmpounds are of industrial

interest and are furthermore easy to analyse by means of carbon-hydrogen coupling constants. b-1,2,3,4,5,6- Hexachlorocyclohexane’247’ gave both ‘J, ‘J, and ‘5. A large number of chlorinated compounds was recorded by Hawkes et ,1.“‘*’ and by Velicho ef ~11.‘~‘~’ who summarized one-bond coupling constants. Two- bond coupling constants were reported by Cain and Roberts”” m 1,2.3,4,X7,7-heptachloronorbornene (Table 5). but the sign and magnitude of the two coupling constants are not in agreement with the rules in Section 9.2.1.

Polyfluorinated compounds do not give simple 13C

spectra and a full analysis is needed. Conformational analyses have been done in several instances dealing with l,l-difluoroacetone,~L80’ pentafluorobutane,‘4y5’ l.1,1,4.4.4-hexafluorobutane,‘496’ 3-chloro- and 2- chloro-l,4-dibromo-1,2.2-trifluorobutane.’497’

16.4. Acitls, Acid Derkatices, AnGo Acids and Peptirles

Long-range coupling constants of amino acids and peptides have recently been reviewed by Bystrov.‘4’5J Conformational aspects have also been treated by Deslaurier and Smith.‘500.50”

As there are no protons attached directly to the

carbon in a carboxylic acid group, the long-range coupling constants become most important. One- bond coupling constants of carbons next to a carboxylic acid group are not different from those for other methylene groups. In amino acids ‘J(C-1, H-r) vary with pH, but the variation is too small (- 6 Hz for the pH range of 1-13) to be very useful.‘49y) ‘J in amino acids are given in References 246 and 349. Two-bond coupling constants in acids are given in Table 8 and those of amino acids in Table 7. The latter are seen to vary with the ionization state of the carboxylic acid group.““’ From theoretical consider-


ations it was suggested that the direction of the carboxyl group(329) plays a role. Experimental results from carbon-carbon coupling constants clearly show that such a dependence may well be correct.‘330*35” Varying the amino acids of cyclic peptides containing glycyl residues revealed some variation of ‘J(CO, H-z) in the glycyl residue. 029’ Three-bond coupling constants are intimately related to conformational studies of acids”” and amino acids’356.357’ and peptides(l~6,35’.J”.“L, but they may also be used for assignment purposes. “J6*356*501’ They can be used both to identify carbonyl-carbons”‘6) and to distinguish between the /3-protons of the side chain!356’ However, the conformational aspect is by far the most important. The theory for this is discussed in Section 10.1.2. Conformations of carboxylic acid groups were studied in phenyl succinic acid.‘355’ methyl a-D- neuraminic acid(371.50J’ and acyclic diacids.062’ The number of amino acids and peptides investigated is much larger and the results are reported in Table 7. Amino acids are reported in References 146, 356, 357, 360, 503 and 504, peptides in 357, 359. 421 and 505, acyl derivatives in 357 and 506 and of pyridoxal Schiffs bases in 321. Differential line broadenings were observed in the carbonyl carbons of the ornithines of alumichrome.‘349)

the anomeric configuration in pyranoses. This effect, its potential and limitations have been thoroughly investigated by Bock and Pedersen,‘183*5’5-517’ by Thiem et a1.‘518-520) and by Paulsen et nI.c521’ It is now firmly established that

‘J(C-1. H-eq) > *J(C-l.H-ax)

with an approximate difference of 10Hz. ‘J(C, H-eq) is usually around 170 Hz and ‘J(C, H-ax) around 160Hz in carbohydrates. Slightly higher values are observed in methylglycosides. An unusually high value was reported in 1,6-anhydro-/?-D-allo-pyranose (187 Hz).(~‘~’ Peracetylation leads to somewhat higher values than in the unsubstituted carbohydrates (Table 21), but the difference between anomers is usually maintained at 10 Hz.

According to Bock and PederserQSL6’ the absolute value of ‘J(C-1, H- 1) depends upon, (i) the orientation of the carbon-hydrogen bond relative to the lone pairs of the ring oxygen, (ii) the electronegativity of the substituent at C-l, (iii) the nature and the total number of electronegative substituents attached to the rest of the molecule. The influence of bond angle variations has since been investigated by Adiwidjaja et ul!520J

Line broadenings due to unresolved three-bond couplings were also used to determine the stereochemistry of the products from Bucherer-Bergs and the Strecker reactions.‘509.510J

Conformation of cyclic cyanides was also determined using 3J(CN, H J. (5’ ‘) Acyclic dinitriles have also been investigated!362’

17. CARBOHYDRATES

Structure elucidation is a very important part of carbohydrate chemistry and this prompted early attempts to correlate 3J(C.H) with dihedral angles.‘35’*352’ The promising early results encour- aged further investigations and use of this parameter in carbohydrates. One-bond coupling constants were also found to be of great use in distinguishing between anomers(’ 14e5 15) of pyranose derivatives. These coupling constants have been investigated very thoroughly as seen in Tables 21 and 22 and they have also been used extensively in polysaccharides. Sub- stituent effects, solvent effects and angle dependence have all been investigated. Two-bond coupling constants have also become of importance in structural investigations (Section 9.2.1) of carbohydrates.

The origin of the difference between ‘J(C, H-eq) and ‘J(C,H-ax) was studied in 1,3-dioxanes(265’ and it was found that ‘J(C, H) depends upon the orientation of the protons relative to the ring oxygens. This finding is consistent with other observations’257~258*262.263’ and theoretical calculations (de irlfra) that ‘J(C. H) is increased when neighbouring lone pairs are present close to the proton (see also Section 8.3.3). The difference was observed to be between 7 and 8 Hz, which is somewhat less than in methylglycosides. Taking into account that C-2 lies between two oxygens a larger effect might have been expected if the O-1 oxygen in carbohydrates plays as important a role as the ring oxygen. From a comparison of glycosides of various sorts no differences have been observed. This was explained by Bock and Pedersenc516’ by assuming that the -0-H and the O-R bond would have the same orientation (Structure 38). This assumption

Carbon-hydrogen coupling constants have been treated by Perlin’z70~5’zJ in reviews dealing more generally with carbohydrates and 13C NMR spectroscopy.

38. Looking along the 0-l,C-I bond (oxygen in front). All three possible rotamers.

17.1. ‘J(C, H)

is supported by Lemieux’41” who has shown the existence of an exo-anomeric effect (the R-group is in both X- and P-anomers antiperiplanar to C, in Structure 38).

A difference in ‘J(C-1,H) between the a- and the Exchanging O-l with a more electronegative /I-anomer was observed by Perlin and Casu.“5”J This element such as chlorine or fluorine increases difference can be used with advantage to determine ‘J(C-1, H), a 10 Hz difference usually being observed

30 POUL ERIK HANSEN

as seen in Table 21. Thioglucosides give smaller absolute values for ‘J(C-1, H) than 0-glucosides.‘Z70’ Phosphonates’s”.s’” are reported to give a difference of about g Hz (the actual values measured from mixtures of conformers are 5-6Hz as seen in Table 21). Nitrogen substitution maintains a difference of 10 Hz. Changes in the substituent at C-2 do not affect the ‘J(C-1, H-l) appreciably as seen from a comparison of glucopyranoside and 2-deoxy, L- deoxy-‘-amino and 2-O-methyl derivatives.‘5’6’ A comparison of methyl 2,3,5-D-xylofuranoside-triacetate and 2,5-dimethoxy-2,5-dihydrofurane showed again that substituents at C-2 play a very small role ‘(??a1

The changes in ‘J(C-I. H) thus arise from a fairly localized effect. It may be noticed though that peracetylation leads to higher coupling constants and that solvent change also perturbs ‘J(C-1.H) (see Section 5 and Table 2 I ).

CH,OH

HO

OH OH

OH

HO

‘=4

CH,OH OH

4Ct ‘c, 39

Hexopyranoses are supposed to exist in the ‘C, form (Structure 39). Studies of ‘J in compounds with ‘C, geometry may be carried out in 1.6-anhydro- hcxopyranoses.‘5”.s”bj

Not all pentopyranoses give a single conformer in solution. This is reflected in the ‘J(C-l,H-1)of methyl y-D-ribopyranoside tetra-acetate and of r-D-ribo- pyranose tetra-acetate (Table 21.4). However, by investigating other pentoses Bock, Lundt and Pedersen’5’7)showed that

*J(C-l,H-eq) > ‘J(C-I,H-ax).

Having firmly established the range of ‘J(C-1, H-eq) and ‘J(C-I,H-ax) in pentoses these coupling constants may be used to give qualitative estimates of the two conformers ‘C, and ‘C, of pentoses. Confor- mational equilibria often depend upon solvent, but in this case solvent effects should be studied before drawing conclusions based on coupling constants measured in a different solvent (cirle irfra).

Recently. carbon-hydrogen coupling constants of furanosides have been discussed in some detail. Cyr and Periin’5’3’ investigated aldohexo- and pento-

furanosides, whereas Serianni er .l.‘5”.832’ looked at z and p erphro and threo furanoses as well as pento- furano-j-phosphates. For the tetroses little difference was found between ‘J(C- 1, H- 1) values. Values ranging from 172 to 174 Hz were obtained for the cyclic forms. and from 162 to 164Hz for the acyclic hydrates. A similar difference between cyclic and open forms was observed in the case of *J(C-2,H-2). Similar effects were also observed in the tetrosephosphates. One- bond couplings may thus be useful for di+in<uishing between these two forms.‘5’“.s3” ‘.I((‘-!. I I- I j values in the furanose forms of cyclic tetroses and of pentose 5phosphates were compared and it was shown that the cis-1,2 anomers have a slightly larger coupling than the corresponding rrcrr~s-1.2 anomers (difierence 1.5-2.6 Hz). Structure 40. A similar spread in coupling

cis-I,2 lrans - I,2

40

constants was observed in methyl furanosides’523’ (Table 21).

Adiwidjaja et al. ‘520’ have extended the investigation to include 2,3-didesoxy-hex-2-enopyranosyl- phosphates. They found that t.J(C-1, H-I-eq) > ‘J(C-l,H-l-ax), but the difference is around 6 Hz. This is supposed to be due to the smaller dihedral angle between the C-H bond and the lone pair orbitals as the quasi-equatorial and quasi-axial positions found in these compounds lead to deviations of 10-15’ from normal axial and equatorial positions. A similar finding was made by Taravel and Vottero’s2’s’ for a xylofuranoside and in dihydrofurane.

Friebolin er ,/.‘525’ have observed in the u-anomers of polysaccharides ‘J(C-1, H) values ranging from 168.5-171.5 Hz and in /I-anomers from 151-163 Hz. The /I-anomers included compounds such as tri-O- methylcellulose, -mannan, -lichenan and pustulan. The authors drew attention to the great spread and suggested a connection with the different glycosidic bonds such as 1 + 4,l ---t 3 and 1 -+ 6.

The difference between ‘J(C, H-eq) and J(C, H-ax) was used to determine the anomer configurations of carbohydrate residues of disaccharides such as cellobiose.“‘3’ laminarabiose.“‘31 gentiobiose” 13’ nigerose” 13) and of polysaccharides such as D- mannopyranosides,‘5z6’ L-rhamnopyranosides,‘526’ maltose and related compounds.“‘51 alginates from Laminaria digitata and hyperborea,““’ and Klepsiella capsular polysaccharides.‘52s’ Sugar moieties of nucleosides and nucleotides have also been investigated. /?$,/I-Trichloroethyl 5’-amino-S-deoxythymidine-5’-phosphate.‘13” pyridinium ribonucleo- tides’“31’ and ezomycin’5”g’ are some examples given in Table 21.6. Other compounds investigated are


glycosyl coumarin,‘530’ chromomycin A,.““’ chon- droitin sulphates A, B, and C,‘53” octosyl acid A(s33’ and the macrolide antibiotics, pumaricin’53” and spiramycin III.

So far only coupling constants involving carbon adjacent to the ring oxygen have been treated. As seen in Table 21 many other couplings have been measured (with varying precision due to the often severe overlap problems), but no pattern has yet been recognized and at present these couplings are of no use for conformational studies.

However. in pentopyranoses differences between ‘J(C-5, H-5(R)) and ‘J(C-5, H-S(S)) should be observable, as the geometry is the same as that around C-l (see Structure 41). This assumption is supported

;JH ;,.

cs Cl

I II

41. I: Looking along the C-1.0-5 bond (oxygen in front). II: Looking along the C-5,0-5 bond (oxygen in front).

by theoretical calculations (uide infra), but in practice the analysis of the C-5 signal is often very difficult because of the small chemical shift-difference between H-.5(R) and H-5(S). However, some values have been cited and in most cases a difference has been observed. Bock and PedersetG5”) assumed that ‘J(C-5, H-eq) was the largest by analogy with the ‘J(C-l,H-eq) values.

Solvent effects have been investigated by Bock and Pedersen,“*3’ who found a difference of 2-4Hz between coupling constants measured on samples dissolved in D,O and DMSO, the coupling constants were smaller in the latter solvent. The rather limited solubility of most carbohydrates in non-polar solvents has prevented a more general investigation. In the few cases in which measurements on samples in CDCI, solution have been performed the values seem fairly irregular. The authorscall for caution and recommend that comparisons must be made of coupling constants obtained in the same solvent (Section 5).

Relations similar to those observed for ‘J(C,H) have been found in the case of phosphorus or fluorine substituents at C-l. In the former case ‘J(C-I, P-eq) is 19-23 Hz larger than ‘J(C-1, P-ax). These values are calculated based on the measured values, which are averaged values, because of the existence of mixtures of 4C, and ‘C, conformers.(s20) In the latter case ‘J(C,F) is negative, but numerically ‘J(C-l,F-eq) is larger than J(C-l,F-ax) by 10-l 1 Hz.‘5361

17.2. 2J(C,C,H)

The two-bond carbon-hydrogen coupling constants observed in pyranoses range from -5.7 to

+9 Hz. Two-bond coupling constants are very sensitive to substituent effects, so signs should be determined. As seen in Table 22 some signs have been determined. The fact that ‘JIG-l,H-2) values are so different in Z- and p-glucose points towards their possible use in stereochemical studies.‘J5L’

A very simple-minded analysis of two-bond coupling constants in substituted compounds led to a set of thumb rules to assess the substituent effects (Section 9.2.1) (i) substitution at the carbon in the middle of the coupling path (Ca) gives a positive contribution, (ii) substitution at the carbon in question (CA) gives a substituent effect that depends upon the orientation of the C-X bond relative to the C-H bond. If C-X and C-H are gal&e (Structure 42a). a negative contribution is expected, whereas a positive contribution is expected if they are antiperiplanar (WWIS) (Structure 42b). In carbohydrates both situations are

H\C_C; H\C_C

B A B \ A X

(a)

42

(b)

usually present as is multiple substitution at one of the carbons as well. Several approaches have been made to rationalize ‘J of carbohydrates.

Perlin et ~1.“~‘*‘~~) observed that an oxygen orui to the proton appears to make a positive contribution to ‘5 and an oxygen gauche, a negative one. Looking at ‘J(C-1, H-2) Perlin et ~1.‘~“’ suggested that the two oxygens at C-l add up vectorially (Structure 43, l-3).

0

(1) (2) (3)

(4) (5) (6)

43

Theoretical calculations, using ethanol and 1,1- ethanediol as model compounds are in accordance with these experimental observations. Cyr. Hamer and Perlin’327bJ concluded from a very large body of material ‘5 values ranged from - 6 to 0 Hz, whereas a range from 0 to +8 Hz is found when Ca has two oxygen atoms. If Ca has one and CA two oxygens ‘J varies from - 6 to + 6 Hz. From representative two-

252 Pour ERIK HANSEN

bond couplihgs also including ‘J(C-2, H-3). *J(C-3. H-2). ‘J(C-3. H-4). ‘J(C-4. H-3). ‘J(C-4. H-5). ‘J(C-5. H-4) and ‘J(C-6, H-5) it was shown that conformers give almost identical values of 5 Hz. whereas the coupling in Structure 43.4 is much smaller _ 0 Hz due to the nrlri disposition in that case. Bock and Pedersen’j3” concluded that the two-bond couplings have values which are determined by the orientation of the oxygens directly connected to the coupling path and they had some success in relating a projection of the C-O bonds onto an axis rrans to the Ca-H bond (if the HO--C,\ bond is antiperiplanar with Ca-H the projection is equal to + I). Structure 44. A

-

1

H

J+

C

OH +

44

projection of + 2 corresponds to a ‘J(C, C, H) value of + 9.0 Hz. A projection of + 0.5 to -0.5 corrsponds to a value around 0 Hz. A projection of + 1.5 corresponds to a coupling of + 5.5 Hz. However, in cases where only two oxygens are bonded to the coupling path the approach of Perlin er a/.‘327~35’1 is sufficient. Using the approach of Perlin er o/.(327*35” one cannot explain why ‘J(C-1, H-2) in /I-D-mannose is 1.6 Hz, while those of a-D-glucose and r-D-mannose are close to zero although all three compounds have the same orientation of C-O-5 and C-OH1 relative to C-H-2.(537’ Structure 45.

Walker er o/.(537) compared values obtained in carbohydrates and in inositols”““’ and suggested that a ring carbon and a ring oxygen have the same effect. As electronegativity seems to play an important role this seems less likely and more (and better) data are needed before such a conclusion can be reached.

Trends similar to those described above have also been observed for ‘J(C-1, H-2) in 2-amino-2-desoxy- sugars.(5’*’ The values of 2-amino-2-desoxy-glucose are quite similar to those observed in glucose (Table 22). Substitution with electronegative groups at Ca leads to a more positive two-bond coupling. The effects of a hydroxy or an ether oxygen may be estimated from a comparison of ethane. ethanol and

ethyl ether. The substituent is in the first case +2.5 Hz and in the latter + 2.2 Hz. They are thus very similar and also similar to that of an amino group (+LOHz).

So far mostly dihedral angles of 60” (gcrltche) and 180“ (arlri) have been investigated. An example of an angle close to 90” was described in 1.2:5,6-di-O-isopropylidene-r-D-glucofuranose!3’-’ Unusual values caused by distorted angles were also hinted at to explain ‘J(C-2. H-l ) in 1.6-anhydro-/?-D-galactopyranose.(53g’ Theoretical calculations indicate a smooth increase with increasing dihedral angle.‘32”

Most of the data discussed so far are from pyranoses. Furanoses have also been studied recently, but due to the uncertainty of their conformation they have so far not been analysed in terms of substituent orientations!5’3.52J.“j”

Two-bond carbon-carbon coupling constants have also been investigated in carbohydrates and other similar compounds and the trends are very much like those of carbon-hydrogen couplings.“5”.537’ Com- parison should be very useful and the concept used to explain two-bond couplings should cover both types, although a slightly more complex situation is found in the case of ‘J(C. C).

17.2. I. Smtmnry. The two-bond couplings are usually difficult to measure and the necessity of knowing the signs limits their practical use. The carbohydrates may otherwise form a useful group of compounds for studies of two-bond couplings. so that a better theoretical understanding of these couplings may be achieved. ~

It is likely that an approach similar to that of Perlin er 01.(~*‘*~~~’ in which substituents at the carbon in the middle of the coupling path are giving a positive contribution (most likely independent of their orientation) and those at the carbon in question, depending upon the orientation will explain the broad features, although it must be admitted that such a simple approach will not be able to predict the finer details. More sophisticated theories taking into account the mutual orientation of the hydroxyl groups will probably have to be developed to account fully for all the experimental data. As shown by Barfield et 01.‘~~~~~~~) (Section IO. 1.1) 3J depends strongly upon non-bonded interactions and so does ‘J most likely. In addition, possible angle deformations have to be considered.

OH OH

(a) (‘4 (d

45. (a) x-D-glucopyranose. (b) fi-D-mannopyranose (c) r-D-mannopyranose.


17.3. ‘J(C. H)

Three-bond coupling ‘J(C. C, C. H) has been treated in Section 10, and ‘J(C. 0. C. H) was treated in Section 13.1. Examples of the former type are given in Table 9 and of the latter in Tables 13 and 14. 3J(C. H) of carbohydrates are shown in Table 12. As many of the data used to construct Karplus curves were taken from carbohydrates and as glycosidic bonds have already been considered a very brief discussion will suffice here.

Cyr and Perlin’523’ pointed out that only three- bond couplings > 2-2.5 Hz were directly observable in single frequency 13C spectra. Furthermore in stereochemical studies of the rings, coupling to C-l and C-2 can be advantageously studied as their signals are affected only by protons of the ring. whereas C-3 and C-4 can couple with exocyclic protons.

Five-membered rings of pentoses are puckered and there may be several pseudorotating envelopes and twist conformations. Cyr and Perlin(sz3J have excluded unlikely conformations based upon consideration of 3J(C, H) and ‘J(H, H) couplings. However, more than one likely conformation was usually given for each compound.

‘J(C-I, H-l) is very useful in the determination of anomer configuration. Future use will probably concentrate around polysaccharides and to some extent around qualitative prediction of the predominant conformation of pyranoses in cases where mixtures of conformations (often solvent dependent) are present.

2J(C. C. H) is useful to determine the configuration around C-2 to C-S, where ‘J(C, H) is of little help. A positive feature is the progressive increase in magnitude as the angle between C-OH and C-H increases. This feature has so far only been predicted theoretically.

‘J(C,C, C, H) is not proving to be as useful as once hoped.

‘J(C, 0, C, H) has shown promise in the determination of dihedral angles between sugar moieties.

18. OLEFIXS

The rigidity of the double bond combined with fairly simple spin systems (at least in substituted ethylenes) has made investigations of coupling constants in olefins very useful and attractive. A number of features have been studied with success in olefins such as substituent effects on ‘J and ‘J, the additivity of these and their orientational dependence, the effect of bond angle variations caused by steric strain or by strain from ring systems.

18.1. ‘J(C,H)

18. I. I. Stroirl. One-bond couplings in crowded

olefins may tell us something about the effects of steric compression and consequently about the effects of angle changes upon carbon-hydrogen couplings. ‘J(H.H) increases with decreasing < HCC angle.“?8.5’O’ and one would expect ‘J(C. H) to be similarly perturbed. In fact the magnitudes of *J(C. H) in sterically strained olefins compared with ethene suggest that steric strain and thus possibly angle changes play a role in determining the magnitude of * J(C. H) (see Table 6).

For cyclic olefins the main effect causing the increase of ‘J(C. H) in the smaller rings is not a steric effect but rehybridization. “‘a’ Based on the formula (8.2) suggested by Maksic”“” (see Section 8.2.2). Manatt et CI/.‘~~” calculated (Table 2) the effect of a change in the C=C-H angle (holding the C=C-C angle constant) on the values of ‘J(C. H) in olefins (and in benzenes). An increase in O,, (Structure 46) decreased ‘J whereas a decrease acted the

C2C/H 813

‘H

46

opposite way if the angle change is larger than six degrees. These findings agree quite well with those of Summerhays and Maciel!sJ” who estimated a decrease of 0.9 Hz per degree decrease in 0 (Structure 46). A quantitative relationship has not yet been determined, but qualitatively the predictions and the experimental values agree.

In heavily crowded alkyl olefins a cis steric effect results in a decrease in ‘J!5J’-5J2’ In tmns-di-r-butylethylene the strain leads to an increase in the p-character of the C-H bond, which fits the small ‘J(C, H) observed.“2”) A comparison of t-butyl and di-t-butylethylenes revealed that inclusion of one t-butyl group has a major effect on the rJ(C.H,,,), but much smaller effects upon ‘J(C. H,,,) and ‘J(C, H,,,,,). The values of rrrrns-di-r-butylethylene can be predicted reasonably well from the values of I-r-butylethylene. but this is not the case for cis-1,2-di- t-butylethylene.‘5J3’ Garrat and TidwelltLsZb’ call for great caution in the use of ‘J(C,H) to determine in-plane and out of plane deformations.

Strain is also encountered in cyclic olefins. Laszlo and von SchleyerfSua) observed larger values of ‘J(C. H) in three and four-membered rings than in six and seven-membered rings (Table 23). This effect was ascribed to rehybridization.“‘* More examples of cyclic compounds are given in Section 8.2. I.

The methylenecycloalkenes have large differences in angle strain, but significant variations in coupling constants were not observed.‘5’12) Likewise ‘J(C. H) in bicyclo[3.3.l]non-I-ene is 156.2 Hzt5”‘) compared with 148.8 Hz for ‘J(C, H) of trimethylethylene. The double bond of the former is highly strained. but there is no steric compression of the olefinic hydrogens.‘5421


TABLE 23. One- and two-bond coupling constants across double bonds in cyclic compounds”

'J 'J Refs.

A’-Pyrrolin-2-one

N-Acetyl-A’-pyrrolin-2-one

N-Methyl-A’-pyrrolin-2-one

A’-Pyrrolin-2-one

N-Methyl-A’-pyrrolin-2-one

p-Dioxene Vinylene carbonate I, 3-Dithiole-2-thione I. 3-Dithiole-2-one 1. 3-Dioxoleb I. 3-Dioxalec Bis- I. 3-dioxolyl Cyclobutene Thiete-I. I-dioxided

Cyclopentene C-l

Cyclohexene C-l

Cycloheptene Cycle-octene Methylenecyclobutane Methylenecyclopentane Methylenecyclohexane Methylenecycloheptane 4-Phenylcyclopentene Pentafulvene

C-l C-l C-l C-l C-l C-l C-l C-l c-2 c-4 C-l c-2 c-3 c-4 C-6 C-l C-l c-2 c-3 c-4 C-6 C-l c-2 C-l

6-f-Butylfulvene

Bicycle [3.3. I] non- I -ene 6-Acetoxyfulvene

6,6-Tetramethylene fulvene

6.6-Diphenylfulvene

6.6-Dimethylfulvene

6.6-Dicyclopropylfulvene

6.6-bis-N, N-dimethylaminofulvene

Spiro [2.4] heptadiene-4.6

c-3 c-4 c-3 c-4 c-3 c-4 c-4 C-5 c-4 C-5 c-2 C-l C-l C-l C-I C-l C-l C-l c-2

c-3

C-l

C-l

C-l

c-4 C-5

175.4 174.2 178.5 176.0 176.0 175.0 179.5 185.0 180.0 180 191.99 kO.01 220. I5 189.5 kO.03 190.73 kO.03 205.82 205. I7 207.66 168.58 198.5’ 200.2 186.5’ 186.2 161.6 160 158.4 156.48 156.2 156.0 154.9 154.2 153.5 153.4 160 170 166 160 172 166 167 170 I50 156.2 170 167 170 170 I91 169 167 171.66

167.9

168.8

161.19

168.9 164.53

C-3. H-4 3.0 C-4. H-3 4.0 C-3. H-4 3.5 C-4, H-3 2.5

C-2. H-3 C-l. H-2 C-l. H-2 C-l. H-2 C-l. H-2 C-l. H-2 C-l. H-2 C-l. H-2 C-2, H-3

C-3, H-2

15.63 +0.02 . 17.47

4.66 f 0.02 3.97 + 0.02

20.04 19.97 19.97

+ 1.22 +6.5

7.2 + 1.8

C-l, H-2 +0.3

C-l. H-2 3.96 C-5, H-l 7.15 C-l, H-2 3.78 C-2. H-I 3.82 C-2. H-3 5.8 I C-5. H-I 7.23 C-l, H-2 3.90 C-2. H-I 3.67 C-2. H-3 5.79 C-5, H-I 7.24 C-l, H-2 5.02 C-2, H-l 4.15 C-2, H-3 5.61 C-5, H-l 6.05 C-4, H-5 + 3.22 C-5, H-4 f4.19 c-5. H-6 + 5.90

422

422

422

422

422

480 441.406 441 441 184 184 184 I25 122 555 122 555 228 544a 228 269 228 228 542 542 542 542 545 546

546

544b 546

546

336

336

336

336

20


T^SLE 23 (contd.)

255

tg 2j Re~.

Spiro 14.4] nonadiene-1, 3

Cyclopentadiene

1, 3, 5, 5-Tetramethyl-3-phenyl-cyclohex-6-ene 1, 3, 5, 5-Tetramethyl-3-(l-naphthyl)-cyclohex-

6-ene 1, 3, 5, 5-Tet ramethyl-3-phenyl-cyclohex- l-ene 1, 3, 5, 5-Tetramethyl-1, 3-cyclohexadiene

I-Trimethylsilyloxycyclobutene 1 -Trimet hylsilyloxycyclopent ene l-Trimethylsilyloxycyclohexene 1 -Trimet hylsilyloxycycloheptene 1 -Trimet hylsilyloxycyclooctene 1 -Trimet hylsilyloxycyclononene 1 -Trimet hylsilyloxy-E-cyclodecene 1-Trimethylsilyloxy-E-cyclo-undecene l-Trimethylsilyloxy-Z-cyclo-undecene l-Trimethylsilyloxy-E-cyclododecene 1 -Trimet hylsilyloxy-Z-cyclododecene Methyl-i-sila-cyclopent-2-ene

Bromomethyl-l-sila-cyclopent-2-ene

Phenyl- l-sila-cyclopent-2-ene

Diphenyl- l-sila-cyclopent-2-ene

Diphenyl-l-germa-cyclopent-2-ene

Cyclopent-2-enone

Cyclohex-2-enone

Protonated cyclopent-2-enone

Protonated cyclohex-2-enone

a-Pyrone

2-Keto-2, 4-dihydrofurane

Maleic anhydride

C-I 165.70 C-2 163.97

C-I 169.11 C-2 163.86

C-6 155.8

C-6 159.7 C-2 159.8

C-2 171.2 C-2 162.3 C-2 151.8 C-2 149.1 C-2 147.7 C-2 149.0 C-2 149.4 C-2 149.0 C-2 152.6 C-2 150.4 C-2 153.6 C-2 142 C-3 154 C-2 141 C-3 165 C-2 155 C-3 155 C-2 160 C-3 ~ 162 C-2 165 C-3 ~ 165 C-2 170.4 C-3 166.2 C-2 162.3 C-3 157.5 C-2 180.7 C-3 173.7 C-2 174.0 C-3 164.8

C-I,H-2 +2.81 C-2, H-3 + 6.42 C-2, H-I +4.63 C-l, H-2 3.56 C-2, H-3 6.73 C-2, H- 1 4.66

C-3, H-4 ~< 1.0 C-I, H-3 ~< 1.0

C-3 H-7 C-2 H-8 C-3 H-7 C-2 H-8 C-3 H-7 C-2 H-8 C-3 H-7 C-2 H-8 C-I H-2 C-2 H-I C-I H-2 C-2 H-I C-2 H-3

4.4 4.5 0.3 0.3 2.5 2.4 0.4 0.4

+0.9 0.3

( + )3.6 (+)4.5

3.6

20

24

817

817 817 331

547 547 547 547 547 547 547 547 547 547 547 556

556

556

556

556

331,569

331,569

569

569

55a

331

96

a. For some early references see Reference 540. b. Solvent, acetone-d 6. c. Solvent, benzene-d 6. d. Solvent, acetone-d 6. Also reported in CDCI 3. e. Values from = 3C spectrum. Data from satellite spectrum slightly different.

18.1.2. Cyclic Compounds. Precise values for cyclobutene, "251 cyclopentadiene 122~ and cyclohexene t267j are now available (Table 23). Other five-membered rings which have been studied include 4-phenylcyclopentene, t545~ spiro[2.4]heptadiene-4,6: 2°~ spiro- [4.4]nonadiene-l,3, c2°~ and some substituted fulvenes.{336,5.,6}

Some trimethylsilyloxy substituted cycloalkenes with the substituent at the double bond have been compared with the corresponding unsubstituted compounds. For cyclobutene and cyclopentene good agreement between ~J(C,H) values for substituted J P N & A R S 1 4 : 4 . [=

and unsubstituted compounds was found. For cyclohexene, heptene and octene the coupling constant of the substituted compounds are 7 H z smaller. This difference is possibly due to differences in the conformation of the trimethyisilyl group3547~

18.1.3. Substituent Effects. In order to discuss substituent effects it is necessary to know the basic parameters of the hydrocarbons. Ethylene ~548} and propene have been studied in great detail "9°.549} and so has butadiene t5 so} and 1,4-pentadiene ts s t} (Table 6).

Ewing ~552~ observed an approximate correlation of


‘J(C-1, H-2) (called ‘J,,,) with the electronegativity Ex as would be expected on the basis of the Bent mode1.‘553) However, a plot of A’J,,,, against cr,, gives an excellent linear fit with exception of the substituents CHO, COCH, and CN, i.e. substituents in conjugation with the double bond. The value for the SiR, substituent is also off the line, which according to Ewing may be caused by conjugation of the d-orbitals with the double bond. Excluding the above mentioned compounds the rest of the data obey the following equation:

‘J,,,(X)- ‘J,,,,,(H) = 80.00,-0.6 r = 0.997 (18.1)

iJ(C-2,H-3) and ‘J(C-2,H-4) were also treated in a similar manner and Ewingt5s2) found that the effects of substituents are five times smaller than those on ‘J(C-1, H-2). Opposite trends are found for iJ(C-2,H-3) and ‘J(C-2,H-4) with the former increasing with 6,. ‘J(C-2, H-4) will generally decrease with increasing electronegativity, but the halogens behave anomalously. Values of *J(C, H) substituted ethylenes are given in Table 6. The effect on ‘J(C, H) of a methyl group substitution in propene was estimated.‘54*’ AiJ gem = -4.5 Hz, A’Jlronr = 0.6 Hz and A’J,, = -2.9 Hz. The effect of a t-butyl group has already been discussed (Section 8.2.2).

The effects of halogens in side chains have been described. A CH,CI or even a CH,CCI,R group may lead to a 7-9 Hz increase of ‘J(C-1, H-l) compared with the corresponding CH, or the CH,CH,R compounds.‘5’4’

Substituent effects on ‘J(C, H) may also be studied for heterocychc ring compounds. A comparison of ‘J in cyclobutenet’25J and thiete sulphone(‘23*555’ revealed substituent effects not only upon ‘J(C-1, H-l) but also upon ‘J(C-2,H-2). The latter is increased by almost 20Hz. (125) A similar situation is found for dimethyl-l-sila-cyclopent-Zene and even more marked in the vinyl group of the methyl vinyl derivative. It was suggested that the decrease in the coupling constant is associated with the presence of a positive charge as shown in Structure 47.‘5561

/H +/ H

M/c=c\H - M-_-C-_-C

‘H

41

‘J(C,H) in olefins shows a distinct dependence upon substitution. ‘J(C-l,H-2) (see Structure 48) is changed most, whereas ‘J(C-2, H-3) and iJ(C-2, H-4) are changed less, but differently. The stereospecific differences may be used for stereochemical studies. An example was given by Sheer,‘557) who determined the structure of (chlorovinyl) dichlorophosphine.

18.1.4. Complexation. Howell and Trahanowskyts5*’ compared ‘J(C, H) in benzonorbornadiene, in syn-

($-benzonorbornadiene)tricarbonylchromium and in ($-benzonorbornadiene)dicarbonylchromium. Large changes in ‘J of iJ(C-l,H-1) and ‘J(C-5,H-5) were observed in going from the first to the last. Rhodium complexes of cycle-octa-1.5diene. ethylene and norbornadiene give rise to only slight changes in ‘J(C, H).‘559J [Bis(tri-0-tolyl phosphite)] nickel complexes have also been measured, but the inadequate analysis does not really permit any conclusions to be drawn.‘560J

18.1.5. AIlenes. The analysis of single frequency spectra of allenes is complex. The inadequacy of a first-order analysis may be shown by comparison of References 39 and 561. Values are given in Table 24. As can be seen, ‘J(C-1, H-l) values are closely related to the corresponding couplings in ethylenes. ‘J in allenes are larger by 12 Hz. Couplings in the non- substituted end are hardly perturbed.

‘J(C, H) of N-isopropylphenylketinimine is comparable with that of allene!562’

18.1.6. Quinones. The analysis of the satellite spectra of p-benzoquinone in different solvents give different values.t563*564) The analysis of the 13C spectrum of di- deutero p-benzoquinones has also been reported.t133’

18.1.7. Theoretical Cnhlntions. Steiger et ~1.‘~~~’ have calculated the dependence of ‘J(C-l.H-2) of acrolein and methylvinyl ether upon the C=C bond length. A correlation between experimental and theoretical values was also produced.‘566) The best results were obtained using the CND0/2 approximation with a sp-basis set and constant Coulomb integrals. Including 3d orbitals with substituents of third row elements did not improve the results. The optimum equation is:

‘J(C-l,H-2)(exp.) = 3.08’J(C-l,H-2)- 13.38 (18.2)

r = 0.886

Runget3”’ has calculated ‘J in allenes (see Sec- tion 8.6). Calculations by the maximum overlap method’209) are also mentioned in Section 8.6.

18.2. *J(C, H)

Two-bond couplings in olefins have been treated in reviews(5*s’ and also very thoroughly by Vogeli, Herz and von Philipsborn.‘33”

The subjects of interest are the stereospecificity and the additivity. c3*@ The stereospecificity is seen in Table 23. *J(C-l,H-3), in which the substituent and the hydrogen are tram (Structure 48) to one another.

Hs’ “Hz

48

TA

BL

E 2

4. C

oupl

ing

cons

tant

s in

alle

nes’

H’\

/H

’ c=

c=c

H

/’

* ‘\

x 1

Subs

titue

nt

H

C2h

H,C

=CH

H

,C=C

HC

H,

C,H

s C

OO

CH

, C

N

(CH

Mi

CH

,O

CH

,S

Cl

Br I

‘J(C

-l,H

-1)

‘J(C

-3,

H-2

) ‘J

(C-2

, H

-l)

‘J(C

-2,

H-2

) ‘J

(C-I

, H

-2)

‘J(C

-3,

H-l

) R

ek.

167.

8 16

7.8

- 3.

9 -3

.9

+ 7.

7 +7

.7

39

168.

2 16

8.2

561

158.

0 16

4.0

+ 6.

0 56

1 16

8 16

8 56

1 16

8 16

7 81

4b

159.

9 16

3.0

+4.2

+4

.2

+ 8.

3 56

1 17

2.5

171.

6 0

0 +1

27

+ 8.

8 56

1 18

0.0

167.

1 -4

.4

- 4.

4 +7

.5

+6.5

56

1 18

5.8

171.

0 -5

.7

-4.2

7.

6 6.

4 39

14

8.0

169.

0 -7

.5

-7.5

+8

.1

+7.5

56

1 15

2.5

166.

9 -8

.5

-3.4

+6

.7

+ 8.

4 39

19

1.4

167.

5 +9

.0

+4.5

+7

.5

561

1921

16

7.5

+ 8.

0 -4

.4

8.1

6.2

39

181.

3 16

5.2

+ 5.

5 +

5.5

+5.0

56

1 18

0.9

168.

9 +

1.3

-4.4

8.

8 +

6.8

39

206.

9 17

0.1

+6.3

-4

.5

f9.3

+6

.5

39

+ 4.

9 +

4.9

+ 4.

9 +

4.0

561

209.

3 17

0.4

+6.2

-4

.4

+9.8

+

7.0

39

+4.3

+4

.3

+ 8.

7 +

7.7

561

204.

8 17

0.1

+ 4.

0 +

4.0

+ 7.

2 56

1

a.

The

co

uplin

gs

give

n in

Ref

eren

ce

561

wer

e ob

tain

ed

from

a

firs

t or

der

spec

tral

an

alys

is.

b.

In R

efer

ence

81

4 on

e bo

nd

coup

ling

cons

tant

s of

disu

bstit

uted

al

lene

s ar

e al

so

give

n,

but

they

ar

e no

t si

gnif

ican

tly

diff

eren

t fr

om

thos

e sh

own

here

.


is increased by electronegative substituents. However, a trichlorosilyl group has little effect. *J(C-1, H-4), in which the substituent and the hydrogen are cis to one another (Structure 48). decreases upon substitution. An exception is the trichloromethyl group, and also for the bromomethyl group an increase has been reported’567J although the methyl-substituted compound shows little effect.

*J(C-1, H-2) depends upon the electronegativity of the substituent, but the C-N and C-C substituents seem to be exceptions. The magnitude of the latter has, however, been questioned.‘331’ The two-bond coupling constants fall in the following ranges: ‘J(C-l,H-3) varies between -2.5 and +7.6Hz, ‘J(C-1, H-4) varies between (-9.7) -8.5 and -0.8 (+2.9) whereas *J(C-2, H-2) varies from -7.0 to + 6.9 Hz.

Substituent effects of monosubstituted vinyl compounds have been derived and used to calculate coupling constants in di- and trisubstituted vinyl compounds.‘326~33’*54s*568’ Very good agreement was obtained for trans-1,2-disubstituted ethylenes (average deviations 0.4 Hz), whereas the deviations for &-I,2 and yem-l,l-disubstituted compounds were larger.‘331i Knowing that the substituent effects are additive investigation of disubstituted compounds provides a double check on both magnitudes and signs of the substituent effects. Ambiguities in the analysis of acrylic acid and acrolein have been -solved this way ‘331)

Two-bond coupling constants may be used for configurational assignments of di- and trisubstituted ethylenes.‘331) Two-bond couplings may depend upon the C-C-H angle in a similar way to *J(H,H) (Section 9.4). Cyclic compounds are very suitable for studying this aspect. Two-bond coupling constants in five and six-membered rings have been studied in detail and for all compounds it is seen (Table 23) that *J(C, H) of the five-membered rings are much larger than in the six-membered ring cyclopent-Zenone vs. cyclohex-2-enone,‘33’*569i a-pyrone vs. l-keto-l,Cdi- hydrofuran,‘31 ‘) cyclopentadiene’**) or fulvene’336’ vs. cyclohexene. ‘2671 However, for cyclobutene’125) a coupling very close to that expected in 2-butene is observed. An extrapolation to very small angles is thus not possible. Large two-bond carbon-carbon coupling constants in five-membered rings are also known.‘354*460) Substituent effects may also be studied in heterocyclic compounds. Very large two-bond couplings were observed in 1,3-dioxole”84’ and in 1,3-dioxole-2-one.‘184~406’ In 1,3-dithiole-2-thione’441i and 1,3-dithiole-2-one’4411 the couplings are much smaller, reflecting the lower electronegativity of the sulphur. A comparison between cyclobutene”25’ and Thiete 1,1-dioxide”**) revealed the substituent effects of a sulphone substituent not investigated otherwise. The different behaviour of *J(C-3, H-2) in Thiete l,l- dioxide and *J(C-2,H-1) in vinyl bromide (although bromine and an SO group have the same electronegativity) was ascribed to the possible effect of the

different dipole moments relative to the C-H bond.‘122i

The comparison of analogous coupling constants in viny1 compounds and in pyridones, pyrones and pyrylium salts showed that qualitatively the same type of correlation with substituent electronegativity holds for the vinyl compounds as for six-membered heterocycles.‘ssb’

A good linear relationship was found between *J(C-2, H-1 ) in allenes and in ethylenes. The differences in the hybridization of the C-2 atom seem to have little effect. *J in allenes is about 1 Hz smaller than those in the ethylenes.“”

Couplings between side-chain carbons and geminal protons have attracted some interest recently especially if the carbon is part of a carbonyl group.‘J31i The carbon may also be part of a conjugated system such as butadiene,‘549) cyc10pentadiene’24i or cyclobutene.‘lZ5) Coupling constants for the latter type are given in Table 23. The situation in which the carbon is an alkyl group has been studied in detail by jiyrgs’34” and the couplings compared with *J(H, H) Section 9.5. Other values are given in Reference 331.

o\\5_c/x B’H

49

*J(CO, H) and *J(CH,, H) show the same dependence upon b-substitution (Structure 49) as the analogous *J(H, H). (Table 25.) Furthermore *J(CO, H) depends upon the orientation of the CO group as demonstrated in cyclohex-2-enone and 2-methylpent-Zene-4-one. In the former a cis arrangement gives a small coupling, whereas in the latter a trans arrangement leads to a large coupling constant.‘331i This observation parallels those made for *J(C, C).‘330*354) The analogy with carbon-carbon couplings can be taken even further as *J(CO,C),., for acids are larger than *J(CO,C),,. This feature is also found for *J(CO, H) as the coupling in a-pyrone (s-c geometry Structure 50) is large and positive.

0 H

2-C

0’ ‘H

50

Acrylic and crotonic acids have similar geometries leading to almost the same coupling constant. How-


/H TABLE 25. ‘J(CO, H) in derivatives of C=C

\ type

co

s’

‘J(C0. H) Refs.

Acrylic acid rrans-2-Chloroacrylic acid rrans-2-Bromoacrylic acid trans-Crotonic acid cis-2-Chloroacrylic acid cis-2-Bromoacrylic acid cis-2-Iodoacrylic acid cis-Crotonic acid a-Pyrone 2-Keto-2,Cdihydrofurane Ethylferulate Diethylmalonate 2-Methylmaleic acidb Maleic anhydride 2-Methylmaleic anhydride Dimethyl 2-dimethylaminomaleate Diethylfumarate Ethylfumarate potassium salt

2-Methylfumaric acidb Acrolein Methylvinylketone

Cyclopent-2-enonea

Cyclohex-2-enone’

trans-Crotonaldehyde

cis-Crotonaldehyde 2-Methylpent-2-ene-4-one

CO. H-2 CO, H-2 CO, H-2 CO, H-2 CO, H-2 CO, H-2 CO, H-2 CO, H-2 CO, H-3 CO, H-3 CO, H-b CO, H-2 CO, H-3 CO, H-2 CO, CH3 CO, H-3 CO, H-2 CO, H-2 CO, H-3 CO, H-2 CO, H-2 CO. H-2

CO, H-7

CO, H-7

CO, H-2 CO, H-2 CO, H-3

+ 4. I 804 (+)I.9 331 (C)1.9 331 ( + )3.9 331

( + )0.9 331

( + )0.7 331

(C)LO 331

(+ )3.6 331 +4.7 331

(+ )9.7 331 6.8 or 4.0 825

+ 2.6 570 + 2.2 570 + 7.4 570 + 7.5 570

0 570 >2.5 570

3.1 570 2.9 570 2.0 570

+2.2 804 +2.8 804

2.98 569 5.65 569 5.7 331 0.5 569

kO.6 331 ( + )2.3 331 (+)I.3 331 ( + )5.3 331

a. Coupling constants for the protonated species are given in Reference 569. b. Similar compounds with more complicated substituents at position 2 give similar

values.

ever, Braun(570’ observed much smaller couplings in both maleic acid and fumaric acid derivatives. Only maleic anhydride has a large coupling, again showing that a s-c geometry may lead to a large coupling and also that two-bond couplings in five-membered rings are unusually large.

The explanation for the discrepancy between the couplings in acrylic acid and crotonic acid on one side and fumaric acid and maleic acid on the other is not clear. It cannot be ascribed to conformational difference and the substituent effect of a COOH group is most likely very small.

*J(CO,H-2) is small and unobservable in p- quinone(‘331 and in hemigossypolone in agreement with the finding for cyclohex-2-enone,r33’J6gJ but observable in 2-oxyderivatives of 1,4-naphthoquin- one (5711

18.4. 3J(C, C=C, H)

The situations most thoroughly investigated are those in which the hybridizations of the external

carbon is sp’ (usually a methyl group) or sp’ (either a

system).

18.4.1. ‘J(C(sp’), H). Compounds with sp3 hybridized carbons were investigated by Anderssonr572J and by Vogeli and von Philipsborn’375’ who found that

3J(C, H ),,a, > 3J(C, H),is in parallel with ‘J(H,H). 3J(C, H) and 3J(H, H) were also compared’375~457*458’ (Section 10.2.4). Couplings are shown in Table 26. Substitution at C-2 changes the ratio between ‘J(C. H),i,, and ‘J(C. H),,,,,_. Electronegative substituents make ‘J(r)13J(c) larger than in the hydrocarbons. Substitution at the sp’ hybridized carbon

R\C LH SC’ \

;Hj

H’ H F

=c

H =R

51


TABLE 26. Three-bond couplings across double bonds’

cl /H RI, ,R,

c=c c=c

’ ‘H R’ ‘R .l 9

R, R2 R3 R4 Geometry Refs.

CH,

CH,

CH,

CH,

CH,

CH,

-3

CH,

CH,

CH,

CH,

CH,

W

CH,

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

-3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

-3

CH3

H

CH,CI

Ph

CH,

Br

CHKH,),

CH,Ph

&H.&H,

C H CAm’

6 4 (Pi &H&H,

(m) CEC

CN

CH,OH

Cl

COOH

CH,OC,H,

H H H H H

H

H H H

H H COOH

NKH,),

;s3

COOH CH,OH

CH3

CH3

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H H H H H

H

H Br Cl

Ph CN COOH COCH, COCH, COCH,

CH3

CH3 Ph

CHKH,),

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

CN CHO COOH COOEt COCH,

Cl

Br H H

H H H H H H H H H

H

‘X3, H

CH,, H

‘X3, H

CH,, H

CH,, H

‘X3, H

CH,, H

CH,, H

CH,, H

CH,, H

CH,, H

CJ53, H

CH,, H

CH,. I-J

CH,. H

CH3.H

CH,,H

CH,. H

CH,, H CH,, H CH,, H

CH,,H

CH,, H

CH,, H

CH,, I-I

CH,, H

CH,, H

CH,, H

CH,, H

CH,, I-I

CH,, H

CH,, H

CH,, I-I

CH,, I-I

CH,, H

12.65 1.55

10.4c 10.3 6.0’ 5.9

1 1.3c 11.1 6.9’ 6.7

12.4’ 5.2 8.9c 8.9 4.5 4.6

11.3 6.9

10.7 6.6

11.1 6.6

11.2 6.8

11.3 6.7

10.2 6.4

10.2 6.4

11.2 6.4 8.7 4.1

10.1 5.7

10.7 6.0 6.4 5.9 6.3 6.3 6.6 6.6 4.oc 5.6 4.7c 7.oc 7.2= 8.1 7.9 9.3 7.1 6.5 8.0 7.8 7.1 8.2 8.4 1.4 8.4 7.5

tr cis tr

cis

tr

CiS

tr cis tr

cis

tr cis tr cis tr cis tr cis tr cis tr cis tr cis tr cis tr cis tr cis tr cis CiS

cis cis cis cis

cis

cis tr tr

tr tr tr tr tr tr tr tr tr cis tr cis

549

572 375 572 375 572 315 512 375 512

572 375 572 375 375

375

375

375

315

375

458

315

375

375

375

458 572 458 458 458 510 572 458 512 512 572 458 458 458 510 510 570 570 375 375 375

315


TABLE 26 (contd.)

RI RI R, R, Geometry Refs.

CH, GH, CH, CzH, CH, CH,OH CH,

FoH CH, CH, CH, CH, COOH CH, coo* CH,OH CH,

CH,OH CH, CH,OH CH, CH,CI CH,

CH,Br H

CH,OC,H, CH,

CH, H H H H H H H H

CH, H H

H

H

H CH, CH, CH, COCH, COCH, COOH co* H

H CH, H

H

H

CH,. H CH,, H CH,. H CH,, H CH,. H CH,, H CH,. H CH,. H CH,. H

CH,, B CH,, H CH,, H

CH,, H

CH,, H

8.6 7.4 7.0 6.9 7.0 7.0 6.7 2.6

10.8 6.2 9.3 7.6

13.9c 13.8 7.5= 7.6

15.5 9.1

11.4 6.4

tr cis cis cis cis cis cis cis tr cis tr cis tr

cis

tr cis tr cis

375 375 375 375 570 570 570 570 375

375 375 572

572

375

375

a. Line splittings for a great number of olefins are given in Reference 140b.

WCH,), c. Determined from a first-order analysis. d. Anhydride.

increases both ‘J(t) and ‘J(c), but the increase is not related directly to electronegativity.‘37sr Steric interactions may also perturb ‘J(CH,,H) and the steric interaction may be either with the CH, group or the =C-H bond (Structure Sl).The former situation was ascribed to a polarization of the CH, bond analogous to that described for y-effects upon chemical shifts,‘573’ as the decrease in the ratio ‘J(t)/‘J(c) can be correlated with the difference in ‘“C chemical shifts of the methyl group trans or cis to the perturbing substituent kI(CH,),,,,,, -6(CH,),,,I and also because the effect is only large for carbons bearing a hydrogen. However, a change in ‘J(C, H,) was not observed, as would have been expected. Very small differences between 3J(c) and 3J(t) are also found for 3-pentene-2- ones and in methyl substituted butenedioic acids!570’

‘J(C-3,H-1) of cyc10butene~‘25~ is very similar to 3J(CH3, H-l) of propene,‘s4g’ whereas 3J(CH3, H) of 2-methyl-maleic anhydride has a very small value.‘s70’

184.2. ‘J(C0, H). Examples of this type of coupling are given in Table 27. ‘J(C0, H),,,, of aldehydes are strongly perturbed by space-filling substituents at the fl-olefinic carbon,“75’ whereas ‘J(CO, H),,,,, of carboxylic are fairly constant. Schreurs et aL(56g) pointed out that the effects of methyl substitution at a and P-carbons are additive, which indicates an electronegativity effect. They also discussed 3J(C0,H) for methylvinylketone, cyclopent-Zenone and cyclohex- 2-enone. 3J(C0,H) is larger for the five-membered ring, whereas 3J of acrylic acid”“’ and maleic anhydride(570’ are identical.

The steric effects have so far been discussed on the basis of angle changes or polarization of C-H bonds. Although the aldehyde group is small a reorientation of the carbonyl group may be a possibility. 3J(C0, C) depends to some extent upon the orientation of the carbonyl group’330’ and this may also be the case for 3J(C0, H)

‘C /

=c /I 2=5\

X

52

‘J of this kind are also reported for quinones.“33*s71’ The coupling is decreased by about 3Hz upon hydroxy substitution at the a-carbon.

These coupling constants have been used extensively for configurational studies.(140b~375*378J33*S70*574) Other couplings of this type were reported for c&Cc,/?‘- unsaturated ketones.(s7s’

18.4.3. 3J(C(spz)C=C, H). Three-bond couplings have also been studied for conjugated systems. The coupling ‘J(C-l,H-4) in butadiene is small.‘ssO~ In cyclopentadiene ‘J(C, H),, is linearly correlated to the HMO-n-bond order of the central C-C bond(22’ (see Section 10.2.4). 3J in five-membered rings are also reported for fulvenes(336’ and spirocyc10pentadienes.‘20’ Braun et ~1.(!‘~’ found that ‘J(C-&H-7) in a (2-di- methylamino-1-propenyl)triazine is identical to that of butadiene.

262 POUL ERM HANSEN

TABLE 27. Couplings across double bonds, “J(C0, C, C, H)”

R,, ,COX

c=c R’ ‘R 2 I

X R, R, R, ‘J ‘J b Refs.

OH

OH

::: OH OH OH

O&H,

O&H, OCH,

OCH, OCH, OH

O&H,

$

OCH, OK

OGH, OH H

H

CH,

CH, CH, CH, H H

CH,

H C,H,OCHJ

RC R

CH, H H

F$H,), H H

CH, H

CH,

CH, CH, H H

CH, CH, CH, CH,

H

H

H

CH, H H

CH, H

H C,H,CH2-

CH,CO,CH, H COOCH, H H H H H COOC,H, COOK COOH H

H

H CH, H CH, H Rr H R’

H

H

CH, H RC

CH, H H

COOC,H, H

COOCH, H COOH COOC,H, cod cod COOCH, H H H H

H

CH, H

CH, H R’ H Rh H

14.1 7.6

12.8 6.5

13.2 7.4

13.1 14.5 6.78

12.6 6.5

13.55 7.0

1.5-2.2 11.8-12.2 2.5 6.8 2.2 11.9 2.6 13.4 7.4 14.6 7.5 13.7 0 9.8 3.1 6.0 2.9 6.7 2.0 7.2

15.9 10.1 15.2 9.4

11.0 9.7

11.7 8.9

10.9 9.7

11.0 9.7

t C

t

c

t C

t

t

C

t

c

t

C

t

C

t

t

t

t

t

C

C

C

t

C

t

C

t

C

t

C

t

C

t

C

375

375

375 375 375 375 375 375

375 375

570 570 570 570 570 570 570 570 570 570 375

375

375 375 375 375 375 375 375 375

a. Coupling constants of some cyclic compounds are given in Reference 375. b. c and t refer to cis and trans geometry.

d. Anhydride.

- k H

c. R= - NCH,),

e. Compound, a,-gluttiferin. f. Compound, morellin. g. Compound, isomorellin. h. Compound, moreollin. i. Compound, isomoreollin.

Victor and RingeP”) used ‘J(C-3,H-1) to determine the preferred orientation of substituent at C-l in butatriene-bis-tricarbonyl iron complexes.

‘J(C-I, H-2) in monosubstituted allenes increases with increasing electronegativity of the substituent, whereas ‘J(C-3, H-l) decreases!39)

18.4.4. Dependence upon Bond Angle. By analogy with 3J(H, H) the value of 3J(C, H) should also depend upon the angles 0, and e2 (Structure 53). Cooper and

53 3J(C,C0,C, H) is useful in the conformational

Mannatt’540) showed that 3J(H,H)ci, for olefins increases with decreasing 0, and 0,. By analogy with results on ‘J(H,H) Marshall and Seiwell(37s’ suggested that 3J(C,H) should decrease 0.2 Hz per degree increase in 0, or t&. The results from z- substituted crotonic acids, cyclopent-2-enone and cyclohex-2-enone are not in agreement with this prediction.‘s69’ For aromatic compounds 3J(CH,, H) values depend upon the bond order of the central bond (Section 10.3). However the dependence upon

both 0, and e2 makes it difficult to reach a unique solution to this problem.

18.5. Other Couplings


TABLE 28. ‘J(C, CO, C, H) in z, p-unsaturated ketones

263

‘J Refs.

H

c5 0 (+)3.1

CH, \

R c=o \ /

c=c 2.1

’ ‘H CH,

CH, \

H c=o \ /

c=c 2.1

/ ‘H CH,

CH, \

H c=o \ /

c=c

’ ‘If CH,O

CH, \

H c=o \ /

-c=c.

(WhN’ ‘H

2.0

3.1

331

570

570

570

570

d /H a. R=

c\ NCH,),

b. Is supposed to be an equal mixture of the two rotamers.

analysis of a$-unsaturated ketones.““’ Structure 54. The largest coupling is expected in Structure 54b in which a trans situation is present. Some variation is

‘H - ‘H - 54

observed in 3J(t) (from 2.0 to 3.1 Hz). ‘J(c) is always close to zero (Table 28). Whether the variation in 3J(t) is caused by substituents attached to the other olefinic carbon or by variations in the rotamer populations has not been clarified. 3J in cyclohex-tenone, which has a tram geometry, is identical to the predicted upper limit. An average conformation was predicted

‘I Refs.

CH, \

H\ iC=Ob c=c

H’ ‘H

0 II

W \ 7\

C=C CH,=

R’ ‘H

0 II

CH, \ 7\

C=C CH,

’ ‘H CH3

0 II

H\ 7\ c=c

/ \ CH3 KHAN H

(+)1.4 331,570

0 570

0 570

0 570

0 II

CH, \ 7\

C=C CH, / \

CH; H

(+P.2 331

in methylvinylketone and in this compound ‘.I is + 1.4 H12.0~”

19. ACETYLENES

The number of acetylenes studied is naturally quite limited. The magnitudes of ‘J and ‘5 have been known for a long time as they both can be obtained from ‘H satellite spectra. ‘J range from 275.5 to 236H.z and ‘5 from +65.5 to +41 Hz (Table 29). Lunazzi et ~11.‘~‘s) found a linear dependence between ‘J(C, H) or ‘J(C, C, H) and Pauling electronegativity:

tJ = 208.4( f 4.7) + 17.4( f 1.8)E, (19.1)

Simonnin(s79r correlated I.7 with ‘H chemical shifts. An improved equation was suggested by Rosenberg and Drenth,(Sso) who corrected the ‘H chemical shifts


TABLE 29. One- and two-bond carbon-proton couplings in acetylenes

H-C3C--X

x ‘J 2J Refs.

H

F Cl Br

CH,” CH,CI CH,Br CH,OCH,

C(CH,),OH CH,CN CH=CHzb

/

COOH CHO CH,OOCCH, C,H,OCOOCH,

C,Hs

CECH 259 CCC-rC,H, 257

Si(CH,), 236

Si(C,HA 239

Ge(C,Hs), 236

Sn(C&), 238 N(C,H,)CH, 258

N(C.sHA 259 P(CsH,), 244

PUGH,), 246

P(sC,H,), 246

P(C,H,), 247 P(sC,H,) (C=CH) 243 P(C=CH), 250 P(0) (GH,) 252 P(0) (tC,H,) (CECH) 250

P(S)(GH,), 250

t&H, 263

OC,Hs 269

S&H, 253

S&H, 256

SO,(nC,H,) 266

P-N(C,H,), 248 P(OW, 245

P(O) (C,H,), 252.7

P(O)(NMeA 249

P(O) @Et), 253

248.4 248.7 249 248.91 +O.l 275.5 270.0 261.0 255.0 248 252 252 253 253 251 251.7

251

49.4 kO.2 49.7

49.62 k 0. I 65.5 60.5 56.0 51.5 50.8 50 50 49

50.2

548 834 847 805 578 578 578 578 580,581,848 580 580 580

1 580 582

49.2 396

50.2 47.9 50.0 * 0.2 49.9 +0.2 50 49.8 +0.5 49.9 49.6

52 42 42.5 42 41 52.5 55.5 45

46 45.8 45 48 49

46

61

51.6

45 43.5 45.7 24.6’

840 849 828 828 580 579 844 840

1 580 579 579 579 579 579 579 580 580 580 579 580 580 580 580 580 580 579 580 579 580 806 806 806 806 806

a. ‘J(C-3. H-l) = 3.6 Hz. b. ‘J(C-4. H-2) = +4.0 Hz. ‘J(C-2. H-4) = +4.8 Hz. 4J(C-1, H-4) = f 2.8 Hz. c. Should probably be 42.6.

TA

BL

E 3

0. C

oupl

ing

cons

tant

s in

dis

ubst

itute

d be

nzen

esL

*b

i ‘J

(C-i

, H

-i)

Lj

*J(C

-i,

H-j

) kj

‘J

(C-i

, H

-j)

Lj

*J(C

-i,

H-j

) R

ek.

1,2-

Dif

luor

oben

zene

3

163.

75

1.6

- 5.

50

4 16

3.89

3.

4 1.

52

1,2-

Ben

zene

dica

rbal

dehy

de

3 16

3.03

4

163.

83

Salic

ylal

dehy

de

4,3

- 1.

05

4-5

0.98

136

0.38

3,4

1.61

4,3

0.85

4,5

1.47

2,3

-2.5

5

3 4

162.

39

162.

7 15

9.68

16

1.0

5 16

4.26

16

5.5

3,4

1.04

1.

6

4.3

0.31

4.5

1.82

5.

4 0.

80

6 5.

6 0.

1

6,5

1.79

1.

0 1,

2-D

imet

hylb

enze

ne

1,3-

Ditl

uoro

benz

ene

159.

26

159.

8 15

4.8

160.

5 16

5.45

16

5.26

16

3.63

I,2

- 6.

02

1.5

13.0

2 19

6 -4

.60

2,4

4.58

4.

5 0.

84

4,2

4.03

5.

4 -0

.21

4.6

7.94

193

7.53

135

11.5

5

395

9.28

4,6

9.25

1.3

6.43

1.5

6.93

3.5

7.71

436

7.55

1.3

4.98

1.5

7.67

t: 10

.00

7.61

3,5

7.45

7.

5

4,6

8.91

8.

7

5.3

7.89

7.

9

6.4

8.63

8.

8

1.4

-1.8

7 3.

6 -

1.32

21

b

1,4

- 1.

07

3,6

-0.8

9 32

3d

1.4

- 1.

27

275

- 1.

39

383

383

383

383

383

392

383

392

383

383

392

383

383

392

227

376

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for the diamagnetic anisotropy contribution:

tJ(C,H) = 6.69"6(H)corr + 235 Hz (19.2)

Couplings over three or four bonds have been reported in only a few cases. In propynenitrile ~J(C-3.CH~) is +5.1 Hz. 1~77b~ in propyne 3j(C-3. H) is +3 .6Hz tsst~ and in l-buten-3-yne 3J(C-4, H-3) is 4.0Hz and aJ(C-2, H-4) equal to 4.8 Hz. tSa'~ Four- bond couplings are given in Table 10.

20. AROMATIC COMPOUNDS

This section concentrates upon benzene derivatives as polycyclic aromatic hydrocarbons have been reviewed recently, t*s3~ Heteroaromatic compounds are treated in the following section.

The analysis of single frequency taC spectra of benzene derivatives is a time-consuming affair (Section 3.1). The use of other techniques such as extensive deuteration and measurement of tJ(C, D) has already been evaluated (Sections 3.10 and 3.11). Some of the aspects studied in benzene derivatives have been correlated with *J(H, H) of ethylenes and butadienes, with electronegativity E~ or with two parameters such as ~r and p or R and F. Additivity effects have also been studied.

20.1. IJ(C,H)

One-bond coupling constants in benzene derivatives for monosubstituted ones are given in References 18. 21, 23, 27, 121, 311b and 584a--c, for disubstituted ones in Table 30 and three-, four- and five-substituted derivatives are mentioned in References 584d-h. One- bond coupling constants of naphthalenes are given in Table 31 and of other polycyclic aromatic hydrocarbons in Table 32.

1J in benzene is close to 158 Hz although some minor variations have been reported3t a.23.~ ~ t~ One- bond coupling constants in alternant polycyclic hydrocarbons vary between 154.6-160 Hz (Table 32). The lower limit was observed in the case of ~J(C-4,H-4) in phenanthrene, os4i~ In non-alternant hydrocarbons a larger difference is observed. In five-membered rings t j values vary from 165.4 to 168.3 (171-+4)Hz in azulene, 12a°'23~ pyracylene, tsss~ dihydropyrazu- lene t5851 and aceheptylene, t335~ In the six-membered rings ~J values are quite similar to those observed in the alternant polycyclic aromatic hydrocarbons whereas the couplings in the seven-membered rings fall between 152.4 and 159.1 Hz. (230"23t'335"339) In the alternant hydrocarbon, 1,2,3,4-dibenzocycloocta- tetraene, the one-bond couplings constant in the eight- membered ring are 158 and 161 Hz. tSsail In biphenylene IJ(C-1, H-I) is as large as 163.33 Hz. (2a~

xJ in mono-substituted benzenes does not correlate with electronegativity Ex, but with the two parameters a~ and tTp. (27) Correlation with Hammett a constants has also been attempted, c3°5.586~

1J(C-2,H-2) values vary ~12Hz, tj(C-3, H-3) is 8.9 Hz, but tJ(C-4, H-4) is only 4.6 Hz. ~zT~

The ortho-effect of alkyl-substituents of o-di-t-butyl benzene, ~227~ 2,7-di-t-butyl pyrene ~58a~ and isopropyl pyrene ~239~ cause a reduction in t j . However, the ortho-effect of a three or four-membered ring causes an increase in 1ji222-227~ (see Section 8.2.1L Five- membered rings have little effect as judged from studies on fluorene. The steric effects just mentioned may explain the large coupling in biphenylene or the small coupling tj(C-4, H-4) in phenanthrene.

The polycyclic compounds also permit the study of substituent effects such as peri-effects (Structure 55)

H X

55

upon tJ(C<t,H-ct). Nitro, hydroxy, methoxy and aldehyde groups in a peri-position cause an increase, bromine has little effect, whereas amino and methyl groups lead to a decrease (see Table 31 ).

The study of substituted naphthalenes ~Ssa~ revealed also that a hydroxy or methoxy group in the 2-position may have different effects upon t J(C- l, H 1 ) and ~J(C-3, H-3), whereas an acetoxy group increase both.~Sag~

One-bond coupling in anions and cations is treated in Section 23. Couplings in naphthalene," 19.373) monosubstituted naphthalenes, tSssj disubstituted naphthalene, ~5sa'59°~ trisubstituted naphthalenes, ~59t's92~ i j in phenalenones t593.~94~ and in 3-fluorodibenzo- I'a,i]pyrene. t59s~ have also been reported. Anthra- quino- and naphthoquinoid structures are found in many biomolecules. ~597-6°2~ 1j in a 9,9'-bianthracene has also been reported. ~6°a~ 1j in other bimolecules are found in References 604 and 605. Couplings of methyl substituted aceheptylene and azulene are given in Reference 335 and of other azulenes in Reference 596.

20.2. 2J(C, H)

20.2.1. Alternant. Two-bond couplings in the alternant hydrocarbons are small and they can have either sign, Table 33.

Aydin et al. t3371 found that 2,] in benzene and naphthalene correlate approximately with the C,C bond length.

2j of monosubstituted benzenes have been compared with 2 j (H,H) of vinyl or 2-substituted butadienes. A good correlation exists between 2j(C-1, H-2) in benzene and vinyl derivatives. 2J(C-I,H-2) may also be correlated with the average 3j(H, H) of vinyl derivatives. Correlation with the electronegativity E~, is only satisfactory for 2j(C-3, H-2). Better correlations

TA

BL

E 33

. L

ong-

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nts

of p

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yclic

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ocar

bons

Nap

htha

lene

a Py

rene

b Fl

uora

nthe

ned

Bip

heny

lene

’ A

zule

ne’

‘J(C

-l,H

-2)

1.10

*J

(C-I

, H

-2)

+ 1

.19

C-l

,H-2

2.

5 C

-2, H

-I

I .38

C

-l,

H-3

8.

1 ‘J

(C-2

, H

- I )

0.

64

‘J(C

-3,

H-2

) *J

(C-2

, H

-l)

+0.

85

C-3

, H-2

3.

7 C

-3, H

-l

8.77

C

-l,

H-8

4.

7 1.

56

‘J(C

-4,

H-5

) +

0.8

c-7,

H-8

-4

.6

C-l

, H

-2

1.53

C

-4, H

-3

3.0

*J(C

-9,

H-I

)

1.83

C

-l,

H-3

8.

1 1.

44

10.9

‘J

(C-3

, H

-l)

C-3

, H-2

c-

4, H

-6

8.43

‘J

(C-I

, H

-3)

+7.

81

C-3

, H-l

6.

5 C

-4, H

-2

+6.

16

‘J(C

-8,

H-l

) C

-5, H

-7

10.5

4.

86

‘J(C

-lO

,H-1

) +

5.3

C

-8, H

-IO

6.

9 C

-4, H

-l

- 1.

34

C-6

, H-4

10

.8

‘J(C

-IO

,H-I

) 5.

86

‘J(C

-I,

H-I

O)

+ 5

.05

‘J(C

-9,

H-2

) 8.

06

4J(C

-4,

H-l

) t-

p.64

4J

(C-l

, H

-9)

-0.6

5 4J

(C-I

0, H

-2)

(-)I

.10

4J(C

-10,

H-2

) +

0.4

=

‘J(C

-IO

, H

-3)

-0.9

e

a. T

aken

fro

m R

efer

ence

373

. b.

Tak

en f

rom

Ref

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121

and

239.

c.

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ppro

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ate

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d. T

aken

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eler

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30.

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35.


are obtained if CT~ and u1 are used.“‘) The following equations were derived:

‘J(C-l,H-2) = 1.846+4.278a,-12.371~~ (20.1)

‘J(C-3, H-2) = 1.305 + 1.341a,- 3.404~~ (20.2)

*J(C-3, H-4) = 1.201-0.702~~ + l.l28a, (20.3)

‘J(C-4,H-3) = 1.167+0.517a,,-0.745~~ (20.4)

A correlation was not found for the case of 2J(C-2, H-3). (“’ Very few long range couplings have been accurately determined in substituted polycyclic aromatic hydrocarbons, but the trend for couplings within the substituted ring is the same.

20.2.2. Non-alternant. ‘J(C-2,H-1) and *J(C-l,H-2) values of azulene are 4.7-4.8 Hz and *J(C-2. H-l ) of acenepthylene is 4.1 Hz.‘~~~’ In dihydropyracylene *J(C-1, H-2) is either 3.2 or 5.1 Hz.‘~“‘~ Large’couplings in five-membered rings have also been observed in other cyclic compounds (Section 9.4).

20.2.3. Other Data. Two-bond couplings not given in the Tables are observed in phenalenonersg3’ and in diacetoxynaphthalenes.‘5sg*sg0i

20.3. ‘J(C, H)

Three-bond coupling constants are large, 4-12 Hz (see Tables 30 and 33).

3J(t) of naphthalene and benzene correlate with n-bond order or bond length of the central carbon- carbon bond.‘373i CNDO calculations predict three- bond coupling constants that are between 0.31 and 0.34 times too small,‘2’g~606i whereas FP-INDO calculations gave coupling constants which are slightly too large. (6071 3J(C-2, H-6) of monosubstituted benzenes correlate well with ‘J(H, H),,,, of vinyl derivatives.‘*” The correlation with E, is very poor for ‘J(C-1, H-3) and 3J(C-4, H-2), but fairly good in the case of ‘J(C-2, H-4), ‘J(C-2, H-6) and ‘J(C-3, H-S). Using the two parameters up and u1 only ‘J(C-4, H-2) did not show good correlations.‘*”

In polycyclic hydrocarbons inter-ring three-bond couplings are also observed. These are usually smaller than those within the same ring probably because of the cis geometry. Examples in the hydrocarbons, naphthalene and pyrene show that ‘J(t) 5 8 Hz, whereas 3J(c) - 5 Hz. The fact that 3J(c) < 3J(t) may be used for assignment purposes.(603)

Other polycyclic aromatics with three-bond couplings not mentioned in the Tables are: disubstituted naphthalenes,‘s82~5*g*5g01 trisubstituted naphtha- Ienes(SgL~S92’ phenalenone.“g3i azulenealdehyde.‘s82’ 9,9’-bianthracene.‘b”3’ First-order couplings of methylated benzenes and benzoic acids have also been presented’60*i and three-bond couplings are also given in Reference 584a-h.

20.4. 4J(C, H) and ‘J(C, If)

Four-bond couplings in benzene derivatives are

all negative and 5 1 Hz in magnitude. For other geometries of the coupling path 4./ may also be positive.r5”3’ Very few examples of ‘J are known.““’

20.5. Coupliny with Side-Chain Carbons

Not many benzene derivatives containing information of this type have been investigated: examples are toluenej’si methylbenzoate’3s0i and benzaldehyde. t’s*i The magnitudes are similar in the three compounds. Both 45 and 5J are positive. ‘J(CH,, H) were compared with 3J(H, H)‘335*374*375.45*’ (Section 14.1.2).

20.6. Applications

Pederse#“i used one-bond couplings to identify the reactive positions of aromatic systems in lithiation reactions.

20.7. Summary

Coupling constants in aromatic systems have been used mostly for assignment purposes. The dependence upon electronegativity, electric field and mesomeric effects have been investigated. Steric effects have been discussed in a few cases, and the peri geometry of some polycyclic aromatic compounds offers a suitable situation for such studies.

21. AROMATIC HETEROCYCLES

The analyses of the 13C single frequency spectra of heterocycles is in some respects easier than that of the corresponding hydrocarbons as the heteroatoms bring about a spread in both the ‘H and the i3C chemical shifts.

The heterocycles provide several interesting features such as (i) coupling through heteroatoms, (ii) a comparison of protonated and non-protonated heterocycles and (iii) the determination of the predominant tautomeric forms.

The discussion of heterocycles will be concentrated around the smaller and simpler members such as furanes, thiophenes, pyrroles and pyridines. Other results will be given more briefly.

The heterocycles may conveniently be divided into two groups, those in which the heterocyclic ring is aromatic and those in which it is not. No attempt will be made to discuss where the borderline is as this is not very important in the present context.

21.1 Six-Membered Rings

21.1.1. Pyridines. The analysis of the single frequency 13C spectrum of pyridine by Hansen and Jakobsen(16’ has set a standard for the analysis ofcom- plicated spectra and has since been used as a test for the capability of new methods.‘65*7B*40g) Apart from


a.92 H

+11.16 H 177.63

r 6.9

n.,.

H 6.4 H

H

H 6.12

-1.~4 H H 4.16

4.10 H H 187.42

H 2.0

-1.4 H H 6.5

H 1.32.~

-1.5 H H 10.4

9.8 H H 182.7

H 10.1

0.0 H

IO.) H 202.7

9.1 H H 207. I

1.3 H

H 8.0

+ 6.56 + 163.04

I .65 +a.47

H n.r.

7.20 H H 171.95

“.r. H H s.13

H 1.~1

H 0.0

5.2 H H 169.9

H 6.7

H 162.8

I

* 162.41

r6.34

H H n’r’

H H &I0 H

H 1699.58

H 9.5

166.2 H

H 9.1 9.5 H H 1.9

186.0 7.5 9.~ H 2.0

9.0

H y.___H

H 187.5 H

y..H

‘N’

(d)

(0

(e)

(h)

56. (a) From Reference 16. (b) From Reference 324. (c) From Reference 619. (d) From Reference 456. (e) From Reference 456. (f) From Reference 456. (g) From Reference 629. (h) From References 90 and 629.

n.r. means not resolved. Dot indicates the position ol “C.

‘J(C-2, H-3), ‘J(C-3, H-2) and ‘J(C-2, H-6) the long- used as it is much smaller in pyridones than in range coupling constants in pyridine are similar to the oxypyridines. w’*’ A N-hydroxy-2-pyridone is found in corresponding couplings in benzene. The two-bond tenellin.‘61 5’ 2-Aminopyridine has been compared with couplings ‘J(C-2, H-3) and *J(C-3, H-2) are larger in the 2-oxypyridines.‘6’1’ One-bond couplings in methyl- magnitude than *J in benzene, and thus show the pyridines.‘3*‘*J55’ cyanopyridines,@16 chloropyri- same variation to substituent electronegativity as the dines’*‘51 as well as in polysubstituted pyri- corresponding monosubstituted ethylenes. The three- dinesosb~“” are also given. Pyridine moieties are also bond coupling ‘J(C-2, H-6) across a nitrogen shows present in some biomolecules, caerulomycin B, Ct617’ an increase of the order of 3.6Hz as compared with and Dt403’ and in isophomazin099’ for which approxi- three-bond couplings in benzene and pyridine.“@ See mate values of ‘J are reported. Structure 56.

A number of substituted pyridines have also been 21.1.2. Pyridine-N-Oxide. One-bond couplings in investigated, but only in a few cases(16.32*36’ are the pyridine-N-oxides are from 6 to 10 Hz larger than in quality of the data of the high standard set by the pyridine.‘6’8’ Theoretical calculations indicate that pyridine study. orbital and spin-dipolar terms should contribute to

Bis-annelated pyridines have been studied by ‘J(C, H).‘6’8’ Long-range couplings are also given in Thummel and Kohli.‘6’0*6’1’ 2,3:5,6-Di(cyclohexa)- Reference 619. 3J(C-2, N, C-6, H-6) is diminished pyridine has a ‘J(C-4, H-4) similar to 2,3,5,6-tetra- dramatically (see Structure 56). Some resemblance to methylpyridine. As the size of the fused rings decreases protonated pyridine is also noticed. the ’ J(C-4, H-4) increases. Increasing the steric strain, the electron density at the bridge-head is decreased 21.1.3. Quinoline nrrn Isoquinoline. Coupling con- while that at the carbon ortho to the bridge-head (in stants in quinoline,‘620’ isoquinoline@*” and methyl- this case at C-4) is increased. H-4 is deshielded and the quinolines’3*6,620’ are similar to those observed in polarization of the C-4, H-4 bond is reflected in ‘J. benzene and pyridine. ‘16’ Coupling constants in iso- The trend is similar to that observed with annelated quinoline alkaloids are also reported.t6*” benzenes (Section 8.2). Streitwieser et ~1.‘~‘~) have claimed that for the bridge-head carbon the atomic 21.1.4. Other Heteroatoms than Nitrogen. Only a orbitals used to construct a fused strained ring have first order spectral analysis giving *J(CH) of phos- higher p-character, hence the remaining orbital has a phabenzene, arzabenzene, exist!6L2’ Couplings in higher s-character. For the series of annelated pyri- phospha- and arzabenzene fall between 156 and dines the effects are apparent both in ‘J(C-4,H-4) 161 Hz, not very different from that of benzeneJ6**’ values and in their basicities (in Structure 57 pK, Thus for elements more electropositive than carbon a

values are given). The linearity observed initially in decrease, comparable to the increase observed in II-IV~bl” is not conserved if 1 is taken into account. pyridine, is not observed.

21.1.5. Six-membered Rings with two Nitrogens.

033 Pyridazine, pyrimidine and pyrazine show the same

0

trends as pyridine, but enhanced in those cases where the two nitrogens act together.‘45b’ In 4- and T-sub-

N stituted pyrimidines none of the carbon-proton coup- 4.40 6.42 lings correlates with electronegativity.‘623’ Additivity

I I1 of one-bond couplings in 4,5-dimethyl, 4,6-dimethyl and 4,5,6-trimethylpyrimidine’624’ was demonstrated based upon data from monosubstituted pyrimidines.

H 155.2 H 132.2

I The pyrimidines have attracted most attention as they

060 appear in biological substances. However, the predominant tautomeric form of uracil and thymine make this relationship only a formal one. The COUP-

lings across nitrogen are given in Table 17. Spectral 7.30 8.09 parameters of 2( I H) pyrazinones have been character-

III IV ized’625’ and so have those of pyridopyrimidines.@*@

57 In purine ‘J through nitrogen does not correlate with bond-order.‘627’ Couplings of 2,6 and 2,6_disubstituted

The hydroxypyridines exist in the cases of 2- and purines show that ‘J(C-2,H-2) have a mean value

4-hydropyridines as the keto forms whereas the of 203.9 f3.8 Hz. iJ(C-6. H-6) is 185.1 + 3.4 Hz and 3-hydroxypyridines are in the hydroxy form. A com- ‘J(C-8, H-8) 211.1+ 1.2 Hz.@*” parison with the corresponding methoxypyridines shows considerable differences of ‘J(C-3, H-3).1613’ 21.1.6. Triazine. Coupling constants in 1,2,4- and One-bond couplings may thus be used to determine l,3,5-triazine@9*629’ methyl derivatives’629’ and 3- the tautomeric equilibria. ‘J(C-5.H-6) can also be amino-l 2 4-triazine’414’ have been reported. A com- 7 3



7.01 11.03 10.03 7.60 10.0 7.0 +7.45 +8.69

6.88 201.79 5.02 185.29 3.5 189 +6.63 I +183.28

H

4.12 114.67 3.83 166.99 f

)--& -yJ; :jr-J: +yj:

6.08 13.79 9.82 4.64 10.4 4.5 +7.43 +8.34

(a) (b) (d (4

58. (a) From Reference 17. (b) From Reference 26. (c) From References 454 and 655. (d) From Reference 25.

parison between couplings in benzene, pyridine, the diazines and the triazines has been made.‘629’ For two-bond couplings additivity is not found (Structure 58). The three-bond coupling across nitrogen is much larger in pyridine than the three-bond coupling in benzene, whereas it decreases again in the di- and triazines.

21.1.7. Protondon of Nirroyen Heterocycles. Pro- tonation of pyridine leads to (i) an increase of ‘J(C, H), (ii) an increase of ‘J(C-2, H-3) and (iii) a decrease of ‘J(C-3, H-2) and of 3J(C-2, H-6)f32J1 (see Structure 56). One-bond couplings in 2-methylpyridine, in both the protonated and non-protonated forms have been given by Riand et al., (630’ who also reported one- bond coupling and long-range protonation effects in 4-methylpyrimidine. A similar trend is observed in quinoline, in 4-ch10roquinoline(623J and in pyridinium betaines.‘630) The effects of protonation may be used to determine the sites of protonation in biologically important molecules. Examples are pteridines,‘324*63Lp632) isocytosine>631’ desamino-isocytosine,‘63’) AMP(324) and 2,4-dimethoxy-pyrimidine.‘321’ Pyridoxine and pyridoxamine’32’aJ show two-bond coupling ‘J(C-5, H-6) y 2-3Hz, which is much smaller than the corresponding coupling in pyridine(‘@ or in 2- methyl-3-hydroxypyridine-4,5-dicarboxylic acid.(32’“J The predominant form of pyridoxine is one with the pyridinium nitrogen protonated where the magnitude of the coupling is closer to that observed in pyridinium ions.321a)

Coupling constants in pyridoxal, pyridoxal-5’-phosphate. pyridoxamine-Y-phosphate are given by Witherup and Abott, 023c) who for pyridoxine reported a ‘J(C-5, H-6) = 4.9 Hz at pH 2.7, but gave no values at high pH (IO-1 1).

21.1.8. Coumarins. The observation of long-range carbon-proton coupling constants has proved very

valuable in the assignment of coumarins.(3*s*635) A comparison of coumarin and methylcoumarins shows that a meta methyl group lowers ‘J(C,H) by about 3 Hz. A methyl group at an ortho or para-position has little effect except when C-8 is substituted.‘38*’ Of the long-range couplings observed ‘J(C-4, H-5) are typically about 5 Hz. Data for halosubstituted coumarins are given in References 635 and 636. 3-Substituted-4-hydroxy coumarins are treated by Rabaron et n1.,‘390’ and a variety of substitution patterns by C-j. Chang et a1.‘637’ Couplings (“J) are reported for furo-coumarins.(‘79’ Methoxy substi-’ tution at C-5 increases ‘J(C-4, HI-4) and ‘J(C-8, H-8). but not ‘J(C-3, H-3). Dicoumarols(638’ exhibit an interesting coupling to the bridge methine proton. Flavonoid compounds represent a large class of natural products. The coupling constants have mostly been used for assignment purposes.(‘64*39’~393~60’*639-642) ‘J(C-2, H-2) is large - 196Hz and it is diminished 2-3Hz upon methyl or phenyl substitution at C-3 (642'

21.1.9. Miscellaneous. Pyrylium perchlorate yields one-bond couplings, ‘J(C-2, H-2) which are unusually large, 2 18 Hz(643) and the 2,4,6 substituted ions also give )J(C-3, H-5).(644) A pyrylium-like structure also exists in the xanthylium ions.‘645’ ‘J(C, H) values para to oxygen are 166.2 and 165.8 Hz which are much less than the ‘J(C-4, H-4) = 180 Hz’~~~’ reported for the pyrylium ion. Spectra of 4-pyrone derivatives give a ‘J(C-2, H-2) value close to 200 Hz, whereas ‘J(C-3, H-3) is close to 168Hz. The three-bond coupling through oxygen 3J(C-2, H-6) _ 8 Hz is slightly larger than the similar coupling in furane. 3J(C-4,H-6) is only -6Hz. which is somewhat smaller than in c&unsaturated carbonyl compounds(646’ (Section 18.4.2). Long range couplings of 4-pyrone(“47J were obtained from satellite spectra and the coupling constants are similar to the substituted compounds,


but substitution at C-2 seems to reduce “J(C-3, H-3) slightly.‘6’6’ Both signs and magnitudes of the long- range couplings of 2-pyrone are given.“” 2J and ‘J are positive and *J negative. ‘J(C-2,H-6) is similar to that observed in the 4-pyrones. Couplings involving C-2, C-3, C-4, H-3 and H-4 are very similar to those of acrylic acid.‘s3’

Coupling constants of 5,10-dimethyl-S.lO-dihydro- phenono-phosphazine and its oxide show only small differences.‘648’

The single frequency “C spectrum of 2-amino- pyrimidine hydrobromide is very complex. Couplings to NH are not observed.‘649’

The spectra of phenoxathiins and azaphenoxathiins have been scrutinized by Martin et n1.,‘8s*86.650’ who also discussed the effects of N-oxidation of I-aza- phenoxathiin.“j”’ N-oxidation leads to an increase in ‘J(C-2,H-2) and ‘J(C-4,H-4) and influences the couplings involving C-r and C-j. The effects are quite similar to those observed with pyridine (Section 21.1.2). It was suggested that the effects of N-oxidation may be used for assignment purposes of complex heteroaromatic molecules.

2 1.2. Fire-Membered Rhys

21.2.1. Furanes. The original analysis of the single frequency “C spectrum of furane (4s5) has since been questioned.“7*“6’ Wrong assignments for ‘J(C-2. H-3) and ‘J(C-2,H-4) are also given in Reference 653. The complete analysis including signs is now known (Structure 58). In addition a number of derivatives have been investigated. An extensive number of 2-substituted furanes were investigated by Gronowitz et trl. (307) 2- and 3-substituted ones by Kiewiet et ,I.,‘ks” Runsink et a/.“@ and by Fringuelli et d.‘6ss’

A reassignment of 2-methylfurane has been presented.“46’

Furane like structures are also found in dibenzo- furane”3’*6s6’ and in aflatoxin B,.‘s98)

2 I .2.2. Thiopher~es. A complete iterative analysis of the spectrum of thiophene has provided the most accurate results’26’ although the spectrum is very nearly first order (‘s4.6s2) (Structure 58). The signs of the coupling constants are all positive. 2- and 3-substituted thiophenes have been treated by Gronowitz et a!.(657) and by Roberts and Weigert.‘4s5’The assignments of 2-methylthiophene by the latter authors have since been changed based on assignments involving specifically deuterated compounds.‘6s7’ In most 3-substituted thiophenes -‘J(C-5, H-2) < ‘J(C-5, H-4). Sign determinations ofcoupling constants in 2-bromo- thiophene,‘6s8’ 2,3-dibromothiophene’32.36’ and tri(3- bromo-2-thienyl)phosphine’9”alsogive positivesigns. Couplings of bromothiophenes,“39”~658~65Y1 methyl- thiophenes(‘04) are also reported as well as the ‘J value in cephalontin’660’ and in some anti- histamines.‘66” Thiophene-like structures are also found in dibenzothiophenes for which one-bond couplings have been obtained.“3’.656’

Long-range coupling constants in selenophenes are given by Weigert and Roberts.“‘ss’ and substituted selenophenes have been investigated by Gronowitz et a1.‘6ss~662’ and by Garreau et al. m3’

21.2.3. Pw-ales. The 13C spectrum of “N and 15N pyrrole has been analysed!‘5~Js’.66” but some dis- crepancies in the magnitudes of the long-range coupling constants exist. The “C ‘H satellite spectrum’664’ and the 13C single frequency spectrum of ‘5N-pyrrole give almost identical results.‘25’ Excep- tions are for the ‘J value and for the couplings to H-l. The latter finding could be a result of the different solvents used (acetone-d,,“” neat,‘664’). ‘J(C, H) values have been obtained for methyl-, nitro- and dinitropyrroles. ’66s’ The pyrrole moiety constitutes a building block for biologically important molecules such as porphyrins. Coupling constants for the di-cation were calculated using the Pople- Beveridge CNDO/Z approach.‘666’ The one-bond couplings of the above mentioned cations together with those of methane, ethylene, benzene, pyrrole and acethylene give the following expression ‘JF# = J$ + 26.91 Hz. The calculated two- and . three- bond couplings in pyrrole are systematically too low (by a factor 2-3), as has also been observed in polycyclic aromatic hydrocarbons (Section 20.3). Un- decylprodigiosin also contains pyrroles. In a perdeuterated species ‘J(C-4,H-4)A = 172.8 and ‘J(C-4, H-4), = 171.OHz were determined.‘668’ Coupling constants of cyclononyl and butylcycloheptylpro- digine were used for assignment purposes.‘669’ The satellite spectrum of pyrrolnitrin, ld,3-“C displays two long-range couplings, 2J(C-3,H-2) equal to 5.3 Hz and 3J(C-3, H-5) equal to 9.0 Hz.@“’

Indoles are likewise part of many biomolecules. One-bond couplings have been reported for sporides- mi#“’ and cochiodinal.‘67’)

Fringuelli et a/.(6ss’ compared coupling constants in furanes, thiophenes, selenophenes and tellurophene and found good correlations between the electronegativity of the heteroatom and the magnitude of ‘J(C-a, H-r) and ‘J(C-/?, H-/l), respectively. Good correlations between the 13C chemical shifts of C-r VS.

‘J(C-cr,H-r) and C-p vs. ‘J(C-fl, H-p) were also obtained. Correlations between A’J and F with 2-and 3-substituted furanes, thiophenes and selenophenes were also attempted and 10 out of 18 correlations have a correlation coefficient better than 0.95. Some of the long-range couplings also show a correlation with the electronegativity of the heteroatom.‘.“”

2 1.2.4. Di-, Tri and Tetmzoles. In aqueous solutions at pH values greater than the pK, of imidazole, imidazole may exist in two different tautomeric forms (Structure 59). Average couplings are given in Reference 182 for four different solvents and also in Reference 673. Wasylishen and Tomlinson’674’ used one-bond coupling constants to monitor the state of ionization of the imidazole ring. A method of deter-


mining the relative amount of I and 11 based upon 3J was also developed.‘67” ‘J(C-5, H-2) and ‘J(C-4, H-2) were measured in I-methylimidazole (the tautomeric form is II) and the couplings were corrected for the methyl group substituent effect. Because of the large difference between 3J(C-5, H-2) and ‘J(C-4, H-2) (4.3 and 10.4 Hz in imidazole II), the relative populations of II may be determined from equation (21.1).

X,, = 1.705-0.164~3J(C-5,H-2),b, (21.1)

The method was applied to a number of imidazoles and histidines.‘673’ Hunkapiller et uL(~“’ measured *.I(C-2, H-2) in the histidine residue of ol-lytic protease (a serine protease). By comparison with one-bond couplings from model compounds they found that over the pH range 4-6.7 the catalytic triad consists of a neutral aspartic acid and a neutral histidine residue. At pH below 4 the histidine becomes protonated and three different species are observed, one neutral (‘J = 208 Hz) and two protonated (‘J = 222 and 218 Hz).

All coupling constants including signs were determined for N-acetylimidazole using the SPI technique. la9) All the couplings are positive. 3J(C-5, H-2) = +2.7 Hz, whereas ‘J(C-4, H-2) = + 11.7 Hz. The larger coupling is that across a nitrogen as in pyridine.

Pyrazole in DMSO shows slow exchange for the NH protons and separate signals of C-3 and C-5 are observed.‘676’ Begtrup’677.678’ used ‘J to estimate the tautomeric equilibrium of 1,2,3_triazole, l,2,4- triazole’678’ and tetrazole. ‘678) The coupling constants of the parent compounds (in which several tautomers are in equilibrium) were compared with analogous coupling constants of N-methylated derivatives with fixed structures representing each of the single tautomers. The method using ‘J is clearly much less sensitive than that using ‘J. Two-bond couplings have also been reported!67*’

Azoles, except pyrrole, form adducts with ketonic solvents at low temperature. The ‘J couplings of a pyrazole:acetone adduct are similar to those of I-methylpyrazole. Furthermore, the average of the two coupling constants measured for the adduct is equal to the average value measured in pyrazole. The same feature was found for two-bond couplings, whereas the average of the three-bond coupling -‘J(C-3,H-5) and 3J(C-5,H-3) do not agree with the value for pyrazole. The tetrazole adduct has a coupling similar to that of I-methyltetrazole. thereby defining the structure of the adduct.‘678’ Coupling constants

obtained from a first order analysis of the indazole spectrum have been reported.“s2a’ The spectra of tetrazoles have also been examined by Kiinnecke et LI~.‘~‘~-“~” 1-N-phenyl and 2-N-phenyl as well as tetrazole were dissolved in sulphuric acid and ‘J(C-5. H-5) compared with the ‘J(C-5, H-5) value observed in phenylethyltetrazole tetrafluoraborates of known structure. The position of protonation was determined unambiguously.‘6s0’ ‘J(C-5, H-5) in l- substituted tetrazoles correlates quite well with u,. The relationship was used to establish the structure of a N’-Sn(Bu), derivative.‘681’

‘J of indazoles have been reported by Elguero et uI.‘~~~’ and ‘J of thio- and seleno-di and triazole were reported by Svanholm.‘683’ Imidazo[1,5-a]- pyranes yield coupling constants comparable to those of the component parent molecules.‘“84’ Tetramethyl- ene-3,3’-di-l,2,4-triazole”‘85J also yields one-bond coupling constants.

21.2.5. Oxazoles and thiazoles. “J of oxazoles showed that the coupling constants were only slightly affected by substituents.(686a’ Isooxazoles are also analysed.‘686bJ Oxazoles, thizzoles and isothiazoles have been studied in detail by Faure et aL(686b) and by Wasylishen and Hutton.@“’ The coupling constants were obtained by first-order analysis. Some differences were observed (the spectra were recorded in two different solvents in the two studies).

Coupling constants of thiazole, 2-bromo- and 2-aminothiazole have been obtained by Bojesen et a/.‘688’ from studies on l3 C enriched compounds. All couplings are positive. Improved resolution was achieved by examining the compounds at low temperature. Theoretically calculated coupling constants (CNDO/Z) are too small, but the relative magnitudes are correct. Coupling constants in a variety of acyl- thiazoles’68gJ and one-bond couplings in phenyl- thiazoles(690’ have also been reported.

21.2.6. Miscellaneous. The structure of l,6.6ai.4- trithiapentalene’6y’*byz’ has been discussed and it was concluded that the most likely structure is a symmetric naphthalene-like IOn-electron system. Structure 60. The most striking observation is that

g-s-y Q&

60

‘J(C-2, H-3) = -4.6 Hz. We*’ This is the only negative two-bond coupling constant so far reported for sulphur heterocycles.

Polyoxin N contains a 4-hydroxypyrazole ring for which coupling constants have been given(433) and this is also the case for some analogues of indolizine.(693J


21.3. Deprotonation

Deprotonation has been discussed for pterin (mono- anion), xanthopterin and isoxanthopterin (di-anions). The latter compounds exist predominantly in the amide form in the neutral molecule. Both one-bond and long-range couplings are reported.(631’

21.4. Summary

The investigations of heterocyclic compounds show that couplings involving nuclei close to or across the heteronuclei are markedly different from those of benzene, whereas those involving nuclei remote from the heteroatom are of comparable magnitude. One and two-bond couplings involving carbons or hydrogens next to the heteroatom show a behaviour similar to that of monosubstituted ethylenes. Couplings across the heteroatoms are much larger in the case of nitrogen than in the case of oxygen or sulphur. These couplings are especially perturbed by protonation. ‘J(C, H) is related to the electronegativity of the heteroatom in five-membered but not in six-membered rings. Whether this reflects a difference between five and six-membered rings or the fact that the heteroatoms of the former are group six elements whereas the latter are from group five is unknown.

22. NON-AROIMATK HETEROCYCLES

The non-aromatic heterocycles form a very mixed assembly with few related compounds in each group and will be divided here according to ring size. Coup- lings through the heteroatoms are observed in these types of compounds and some three-bond coupling constants are given in Tables 14, 16-19.

22.1. Three-Membered Rings

This group includes compounds such as epoxides, thiirane and aziridines. One-bond couplings in the latter category have already been discussed in the section dealing with lone-pair effects. Considerable ring strain is present and large one-bond coupling constants are observed.

Kingsbury er al. (6g4) found that 3J(C,H) values in methyl substituted derivatives decrease in compounds with heteroatoms 0, N, S, C in the mentioned order and that 3J(C,H) roughly parallels 3J(H, H) in its dependence on electronegativity (increases with decreasing electronegativity) and the bond length of the C, C bond.

One-bond couplings were observed in ethylene episulphone.‘6g5)

the magnitudes and signs of the couplings have been reported.t6g6’

22.3. Fice-Membered Rings

Satellite spectra give the coupling constants of 2,5- dihydrofurane. A rJ(C-3, H-3) value of 168.0 Hz is of similar magnitude to that observed in cyclobutene.‘697’ The ‘J(C-d, H-6) and ‘J(C-6, H-6’) of L-thiazolidine- 4-carboxylic acid ([S]-proline) are very similar (Structure 61). Changes in ‘J with pH suggested that

61

important conformational changes of the ring take place particularly during the ionization of the amine group.‘6g*) 3J(C0, H-P’) is larger than 3J(C0, H-/T) both in the cis and trans isomer of the anionic form of N-acetyl [S]-proline supporting a puckered form of the five-membered ring.‘6gg) Coupling constants in penicillins and cephalosporins have been compared(700) and it was noticed that 3J(C-7,H-3) of penicillins and ‘J(C-8, H-4) of A’-cephalosporin are similar in magnitude (Table 18) although the nitrogen in the coupling path is pyrimidal in the former and planar in the latter. t700’ Structures 62 and 63.

RHN S

y+

. 1 N 3 g

0 COONa

62

63

‘J and 2J have been determined for some imidazolidines!701’ The stereochemistry of the isoxaziline ring has been determined by means of ‘J(C, H).““’

lJ(C-2, H-2) values of ring annelated 1,3-dioxolanes depend slightly on the ring-size of the annelated ring. (‘03) Couplings of some heterocyclic spiropyranes give couplings in agreement with those in analogous non-cyclic compounds.‘704)

One-bond couplings of biotin and its derivatives have been used for assignment purposes.“‘”

22.2. Four-Membered Rings 22.4. Six-Membered Rings

Thiete sulphone (122.555) has already been discussed The couplings through oxygen in 2-oxo-1,3-dioxo- (Section 18.1.3). Both the spectra of trimethylene lanet332) and the one-bond couplings of 4,6-dioxo-1,3- oxide and sulphide have been analysed in detail and dioxanes’27’b1 have been discussed (Section 13.1.2.1).


A first-order analysis of the spectra of morpholine, N-methylmorpholine and 1-methyl-4-piperidone have been given(706) as well as for deglucopterocercine’706’ which also contains a six-membered nitrogen substituted ring.

23. IONS

Carbon-hydrogen coupling constants are observed both in carbocations and in carbanions. The use of “super acids”(707) has given the former type an enor- mous boost. However, usually only one-bond couplings are reported. A review of carbocations includes “J(C, H) up to 1974. (‘O*) Brown(709’ has discussed the “nonclassical ion” problem.

No attempts will be made here to go into this standing discussion, as coupling constants provide only one piece of evidence among many. ‘J(C, H) can be used to show the existence of equilibrating species. ‘J(C,H) has traditionally been correlated with s- character and this aspect is discussed. ‘J may also be used to distinguish between trivalent (classical carbenium ions) and “non-classical carbonium ions”.

23.1. Carbocations

The carbocations are divided into three broad groups in this section, alkyl, aromatic and ions involving metals.

tJ(C,H) is dependent upon the effective nuclear charge, but it depends also upon bond length, s-character, mean excitation energy and bond polarization.““’ ‘J(C, H) can thus not in any simple way be correlated to s-character. Furthermore, theoretical calculations show that variations in bond angles cause a change of ‘J(C-1, H-4), but not in Pfis,.(710)

23.1.1. Alkylcarbocations. Values of static carbenium ions are given for a long row of alkylcarbenium ions.‘71’*7’2’ ‘J(CH,, H) of a methyl group adjacent to a positive charged carbon is fairly constant (131.4-132.5 H.z).“~~*‘~*) Kelly et a1.(713’ showed that ‘J(C,H) values are dependent upon the dihedral angle between the C-H bond and the unoccupied p-orbital of the cationic carbon. The difference between ‘J(C, H) of the cation and neutral model compounds (ketones) can be expressed as:

AJ = 22.5 - 33.1 x cos* 0 (23.1)

(A) (B)

A gives the maximum inductive enhancement and B gives the maximum hyper-configurative diminution. Theoretical calculations confirmed this finding giving an equation(*‘tc):

AJ(C, H) = 5.51- 18.4 x cos* 0 + 7.08 cos4 0 (23.2)

In this case ‘J of the ethyl ion was compared with ‘J of ethane. A classical carbenium ion was found in 2-phenyl-2-bicyclo[l.l.l]pentyl cation giving ‘J of

the bridge-head carbon of 164.0 Hz”t4) which is very similar to that of the parent hydrocarbon.‘715’

Coupling constants of equilibrating carbonium ions were first described for the dimethylisopropyl carbonium ion. “l t’ The average coupling constant was reported as 64Hz and since has been given as 67.5 Hz.“‘*) Butylcarbonium ion has a lJ(C, H) of 66.7 Hz for this coupling.“‘*’ 2,3-Dimethyl-2-norbornyl cation has an average coupling of 58.5 Hz. This was compared with ‘J in model cations such as the 1,2-dimethylcyclohexyl cation and the 1,2-dimethyl- cyclopentyl cation. (‘r6) A rapidly equilibrating ion (1,thydrogen shift between bridge-heads) was also detected in bicyclo[4.4.0]decyl, bicyclo[4.3.0]nonyl and bicyclo[3.3.0]octyl cations ( 1 J(C, H) = 50.8, 55.3 and 57.3 Hz, respectively).““’

A non-classical carbonium structure of ‘I-norbornenyl cations has been established.(718*719’ A “bishomocyclopropenyl” structure was suggested.” 19’ This structure involves three-centre bonds (Structure 64a).“*O’

(a) (W

The fast 6,2 hydrogen shift of 2-norbornyl cations can be frozen out.“* *.‘**) Based on chemical shift and coupling constant evidence, it was argued that the frozen out form is the non-classical ion with a penta- coordinated bridging carbon atom (Structure 64b) with the C-6 carbon of tetrahedral nature and carrying little charge.“**) The ‘J(C-l.H-1) = ‘J(C-2,H-2) of 184.5 Hz was compared with estimates of the magnitude of an equilibrating Wagner-Meerwein classical ion. The difference of almost 20Hz points again to a frozen structure.“**) 1,2-diphenyl-2-norbornyl~723~ and 1,2-dimethyl-2-norbornyl cations(724’ were shown to be rapidly equilibrating ions having low energy barriers for 1,2-Wagner-Meerwein shifts. (W-M in Structure 65). The 2-methyl-2-norbornyl cation is a

65

tertiary carbenium ion stabilized by partial u delocalization (‘J(C-1, H-l) = 169.5) whereas in 2-phenyl-2- norbornyl cation much less u delocalization is present (‘J(C-1, H-l) = 158.4 Hz).“*)) The 1,ZdimethyL2- benzonorbornyl cation also undergoes rapid 1,2-M-W shift (‘J(C-l,H-1) = 180.4H~)(~*~)verysimilar to that

278 POUL ERIK HASSEN

of 1,2-dimethyl- and 1,2-diphenyl-2-norbornyl cation some of the cations, but so far these have not attracted (tide supra). much attention (711~713~726~727~7~1~

The 2-bicyclo[Z.l.l]hexyI cation is best represented as a mixture of exchanging carbenium ion intermediates (‘J(C-1. H-l) = 184.5 Hz) although the equilibration involves u-bridged carbonium ions.““’

Other non-classical ions were observed in the trishomocyclopropenyi cation.~7L8~729’ In this compound ‘J(C-1, H-l) = 195.4 Hz.“~~’ A similar coupling constant was observed in the 9-penta- cyclo[4.3.0.0.2~10.3~s0.5~7]nonyl cation (‘J(C-6, H-6) = 204H~).“~~) Hart and Willer’730’ have measured ‘J(C, H) involving the apical carbon atom of a (CH); cation. The large value (220Hz) is consistent with a pyramidal structure, which was said to correspond approximately to sp hybridization. In any case the very high value is indicative of a non-classical ion as judged by ‘J(C, H) values in model compounds such as bicyclo[2.1.0]pentane’731’ and trishomocyclopro- penyl cation (tide supra).

23.1.2. Cations of Aromatic Compounds. The arenium ions act as intermediates in electrophilic substitution reactions and also in many isomerizations and trans-alkylation reactions. The benzenonium ion shows an averaged coupling of 26 Hz.““.“~’ Theor- etical calculations of coupling constants of dillerent types of C,Ht ions do not predict any major differences and ‘.I was thus concluded to be less useful for structure determination in these types of compound.‘744J

An average coupling ‘J(C-8,H-8) in l-methylnaphthalene cation was reported to be 167.1 Hz.“~~’

The anthracenium ion gives the coupling constants

162.1 168.1

H H

H 168.0

The nature of the cyclopropyl carbinyl cation has been much debated.1723*733’ a-Bridged compounds such as Structures 67 and 68 have been proposed. H 168.8

66 67 68

Kelly and Brown’733’ argued that for such structures ‘J of the apical carbon is not as large as expected and that the coupling constants are in better agreement with equilibrating classical cations. However, Olah and Liang(734) pointed out that the magnitude of the apical ‘J(C,H) is not critical, but that the large magnitude of ‘J of the methylene carbon is indicative of increased strain due to the formation of the 0 bridge. Comparisons were made with similar ions such as 8,9-dihydro-2-adamantyl/737’ 2,4-dihydro-5- homoadamantyl-,‘736’ 3-nortricyclyl’737’ and 3-homo- nortricyclyl cations. (734) Olah and Liang’734) stressed that ‘J is not a very useful parameter for distinguishing between classical and non-classical ions.

shown in Structure 69.‘746’ Koptyug et a1.(747) observed one-bond couplings of 127.5 Hz and 163.2 Hz for the two meso carbons in anthracenium hepta- chlorodialuminate and concluded that the addition had taken place at one of the meso carbons.

The frozen out one-bond coupling constants of the ethylene benzenium ion, and 4-methoxy benzenium ion’748) have coupling constants of 168.3-174.6 Hz. The ipso carbon of the latter has a coupling of 125.9 Hz. The coupling constant is similar to that of the styryl ion.

Studies of related compounds comprise those of I-methylcyclopropyl carbinyl cation’739’ and 3-nortricyclyl cations”3s’ as well as a number of different cyclopropyl carbinyl cations.‘738’ Staral and Roberts’740) observed a new species in the treatment of cyclopropylcarbinol with SbF,-SO&IF-SO,F, solution at -12Y, namely the 0-protonated cyclo- butanol.

Forsyth and Olah’749’ reported one-bond coupling constants between 168 and 185Hz for di-cations of pyrene, anthracene and pentacene. The couplings of the pyrene di-cations are 13-26 Hz larger than in the neutral molecule. Mamatyuk and Koptyug’294’ found that for such ions ‘J(C,H) depends mainly on the variation of charge on the hydrogen atoms equation (8.9).

23.1.3. Aromatic Cations. In this section aromatic cations are described. They are often generated from non-aromatic precursors.

The increase of ‘J(C, H) of the tropylium ion compared with the isoelectronic benzene molecules has been related to the effective nuclear charge.‘1’1*337)

Kirchen et aI.“*‘) observed an unusually small ‘J The 1,tdimethyl benzocyclobutadiene di-cation in the cyclodecyl cation. The one-bond coupling con- has couplings of the six-membered ring of 172.4 and stant of only 32 + 5 Hz was assigned to the high-field 182.8 Hz,“~” and also that 1.2,3,4-tetra- and 1,2- “jc-hydrido” proton. The non-bridging bridge-head diphenylcyclobutadiene cation have been investi- proton shows a coupling of 158 Hz. gated. (75 I) The ‘J(C-3, H-3) value in the cyclobutane

Long-range coupling constants are observed in ring is as large as 209.6Hz, and those of the phenyl

128.9 168.0

69


rings are between 160.2 and 174.2Hz. In the 1,2- difluoro-2,4-diphenylcyclobutadiene di-cation a non- equivalence of the ortho protons gives rise to quite different coupling constants (174.2 and 166.3 Hz). ‘J(C, If,) of the tetramethylcyclobutadiene di-cation is 137.3 Hz quite similar to that observed in the 1,2- dimethylbenzocyclobutadienedi-cation.’750JDibenzo- cyclobutadiene cation (generated from biphenylene) has couplings of 190.4 Hz and 186.9 Hz.“~~’

The 1,4,5,8-tetramethyldibenzocyclobutadiene di- cation has ‘J(C-2. H-2) = 187.8 Hz. Diprotonation of benzocyclobutenedione gives the structure shown in Structure 70. The NMR data was said to show that

I II

70

Structure 70.11 predominated.(752’ The l,Cdimethyl- cyclooctatetraene di-cation has a 6n-electron system. ‘J(C-2, H-2) = 167.2 Hz, J(C-5, H-5) = 168.0Hz and ‘J(C-6,H-6) = 166.8 Hz which are not very different from that observed in the tropylium ion (‘J = 166.79 Hz).““’ The 1,3,5,7-tetramethylcyclo- octatetraene di-cation gives a coupling of 166.2 Hz.““’ The homotropylium ion gives ‘J’ values ranging from 155.8-175.8 Hz.“~”

23.1.4. Cyclic Non-Aromutic Cations of Non- Aromatic Origin. Halogen substituted cyclobutenyl cations have one-bond couplings involving the carbon not bearing halogen of 207.3 and 208.5 Hz.““’

BicycloU. 1.01 hexenyl cations were considered as cyclopentyl-like cations with charge delocalization into the cyclopropane ring. All couplings are larger than 180H~.(‘~“’

23.1.5. Ions of’hfetalorganic Compounds. a-Ions of alkylsubstituted ferrocenes have been studied in some detail.‘756-762’ However, the results for a-ions of methyl, ethyl, isopropyl, benzyl and 2-methyl propyl vary from author to author. The magnitudes of the ‘J(C,H) values of the cyclopentadienyl rings (178.2-190.0Hz) are different from those observed in diphenylcarbenium ions. (757J Tricarbonyl iron cations of butadiene,““’ pentadiene(452’ and cyclobutadiene”53’ have already been mentioned (Section 13.3) because of the large 2J(C0, Fe,H) couplings observed in the complex. The nature of the protonated diene-iron complex depends on the acidity of the media. The complex of o-type is observed only with excess of fluorosulphuric acid. Typical one-bond couplings in these complexes are shown in Structure 71. The one-bond couplings in 1,3-butadiene iron tricarbonyl in less acid media are smalIer.(451’ Similar

182.9 170.3

l-i H 191.2

H

+&; ‘02’:+H 191.4

H<Co), H-Fe (CO),

(3

181.4

HFc(CO)~

(W

HFe (CO),

(cl

71. (a) Taken from Reference 451. (b) Taken from Reference 453. (c)Taken from Reference 452.

couplings were reported in hexadienyl tricarbonyl iron cations.(763’

23.2. Anions

As discussed in Section 8.1 ‘J(C, H) values of anions would decrease compared with the values in the neutral species if the charge is the only determining factor. Waack has studied many lithium compounds (for references see 707 and 761). Marquet et a1!207*764~765’ have studied sulphur-stabilized carbanions. ‘J(C,H) was shown to be a good probe of the geometry of anionic carbons. In both z-lithio- sulphoxides and sulphones larger coupling constants than those in the starting compounds were observed indicating a change in hybridization. The effects of different solvents and counterions were also studied as well as addition of a cryptand. Change of solvent and counterion cause changes of-up to 12 Hz varying from sulphide, to sulphone and sulphoxide, whereas addition of cryptand has only a small effect on the sulphide and the sulphone but a dramatic effect upon the sulphoxide. ‘764’ Coupling constants observed in di- alkyl sulphonium phenylacylides point towards an essentially sp2 hybridized ylide carbon.(766’

One-bond couplings of phosphorus ylides have been discussed in Section 8.1. Further values are given for some phenyl phosphorus ylides.(767’ In cases with no further substituent ‘J for the ylide carbon is close to 150 Hz.

Mono- and di-anions were generated by using the dimsyi anion and ‘J(C. H) was given!768’

Coupling constants of delocalized anions such as the butadienyl anion and the 3-vinylpentadienenyl anion showed magnitudes from 137-156 Hz.“~”

‘J of 1,3,5,7-cycle-nonatetraene is 20Hz less than the value for the corresponding anion.‘770’ This was explained as a hybridization change in going from the

280 POIJL ERIK HANSEN

puckered to the planar ion. A similar change was observed in the aza analogue.‘770’

The cyclopentadienyl lithium salt has the following coupling constants ‘J(C, H) = 159.1 Hz, ‘J(C, H) = 5.65 Hz and 3J(C, H) = 8.20 Hz. The hyperfine structure in the spectra of the sodium and potassium salts are superimposable upon that of the lithium salt indicating a common structure.““) The one-bond coupling should be compared with that of ferrocene (174.8 Hz).

van Dongen et ~1.“‘~’ reported one-bond couplings of phenyl-lithium, benzyl-lithium, diphenylmethyl- lithium and trityl-lithium and found that the coupling constants involving the aromatic ring carbons are smaller than those in benzene, but there is no correlation between the magnitude of ‘J and the n-electron density of the carbon atoms.

The di-anions of 1,2,3,4-dibenzocyclo-octatetraene again show a decrease compared with the parent compound, and the decrease varies from 4.6 to 17.8 Hz.‘~~~”

23.3. Other Ionic Species

23.3.1. Halonium Ions. Halonium ions have been reviewed by 01ah.‘773’ One-bond couplings of dimethylhalonium fluoroantimonates(774J show an increase of 3-10 Hz compared with their precursors. Increases of lo-15 Hz have been reported for ‘J(C, H) in cyclic five-membered haionium ions.““’ The larger increase in the values of the ethylene bromonium ion was ascribed to the formation of a three-membered ring”‘@ (Structure 72). The couplings ofchloromethyl

72

and bis(chloromethyl)halonium ions were found to be uniformly 30 Hz larger than in the dimethylhalonium ions.““’ Coupling constants of cyclopropylhalonium ions have also been given!“s’

23.3.2. Other Ions. $-C,H,(CO),FeCH C6Hl has been prepared and shown to have couplings involving the cyclopentadiene ring carbons of ‘J(C,H) = 185 HZ and ‘J(C, H) = 7 Hz.“‘~)

Tropyliumchromium tricarbonyl ion shows an increase of iJ compared to that in the tropylium ion of +8.8Hz, whereas the effects at ‘J, 3J and 4J are < I Hz.t3-“) The effect of complexation is discussed further in Section 24.

23.4. Summary

One-bond couplings of classical carbenium and non-classical carbonium ions follow approximately the same trends as described for non-ionic species. Long-range couplings have not been used to any significant extent. One-bond couplings in anions may be useful in monitoring hybridization changes on

going to the ionized state although counter ions and solvents also seem to play a very important role. Some characteristic coupling constants are shown on Structure 73.

(a)

CH3\ /

‘=I

-c-c +

Cc)

f&l-

: H 182.8

W

w (0 (B)

73. (a) ‘J(C, H) of a methyl group next to a carbenium ion. (b) Classical carbenium ion. (c) Equilibrating ion. (d) Classical carbenium ion stabilized by cyclopropane ring. (e) Non- classical carbonium ion. (I) Non-classical carbonium ion.

(g) Pyrimidal ion.

24. METAL ORGANIC COMPOUNDS

This section is divided into two parts, one containing metalcarbonyl complexes and the other metalorganic compounds. These types of compound have been reviewed by Mann.“sO’

24.1. Metaltricarbonyl Complexes

24.1.1. Iron and Ruthenium Carbonyl Complexes. A detailed analysis of butadiene iron tricarbonylt”) gave ‘J values which when compared with the one-bond couplings of butadiene show a large increase of ‘J(C-2,H-c) = + 11.1 Hz and ‘J(C-l,H-a) = +6.6Hz and a small decrease of ‘J(C-1, H-b) = - 1.2Hz. A more approximate analysis has also been published for both cyclohexadiene- and butadieneiron tricarbonyl”*ti (Structure 74). A similar change has

H-b

74

also been observed in cyclopentadienyl and arene ligands’782*783i It was speculated that the large increase of ‘J(C-2, H-c) could be the result of an increase in the effective nuclear charge caused by electron donation from the ligand to the metal. Very similar


results were observed in butadiene ruthenium tricarbonyl. ‘784) Oxa- and aza[4.4.3]propellanes tricar- bonyliron complexes also give similar results.(785’ In complexes of 2,3_dimethylindene compounds the difference between ‘J(C-I, H-a) and ‘J(C-1, H-b) increases similar to the effect already described for the butadiene compIex.‘786J

silicon.‘793’ Coupling constants in 2,5,.5_tris(trimethylsilyl)cyclopentadiene’7q”’ have also been reported.

The couplings of the 4H-indeneiron pentacarbonyl complex were compared with the couplings of the azulene complex. ““’ In both cases the couplings of the five-membered ring are close to 180 Hz, which has also been found in cyclopentadienyl systems n-bonded to transition metals.(788a)

For aryltrimethyltin derivatives the ‘J(C. H,) values are insensitive to substituents at the aromatic ring.‘795’

One-bond couplings. ‘J(C, H,) for derivatives of (CH,),Pb(acac), in strong acids or coordinating solvents have a variation from 146.1 to 153.6 Hz. The largest coupling was observed for HMPT. For (CH,),SnO. ‘J(C,H3) could be correlated with

G(Sn-CH3).‘7q6’

Hydroxymethyl-, a-hydroxyethyl- and cc-hydroxy- benzylcyclobutadieneiron tricarbonyl show large one-bond couplings (188--190H~).~‘*~~~

‘J(C,H,) in (CH,),Pb(acac), is larger than the coupling in (CH3)aPb. The reason was ascribed to an accumulation of positive charge on the central lead atom. Solvent effects show that ‘J(C, H,) is larger in HMPT than in CHCI,, CH,OH and DMS0.‘7q6bJ

24.2.3. Group VI. For the compounds 24.1.2. Chromium Complexes. Bodner and Todd”“)

reported ‘J(C,H) values for Cr(CO), complexes of benzene and anisole and explained the increase compared with the parent molecules as a withdrawal of electron density from the framework of the arene ring also leading to an increase of the effective nuclear charge. Their argument is different from that of Emanuel and Randall(782’ who suggested a donation of n-electron density.

Me,_,M(SeMe),(M = Si,Ge or Sn) ‘J(C, H,)

is constant.(797a’ The one-bond coupling in the addition product of tolueneselenyl chloride to ethylene shows that the product is not an episelenurane.‘797bL

24.2.4. Group IIB. The fact that ‘J(C, H) in dimethyl cadmium does not show cadmium isotope elects was mentioned in Section 6.1’qo)

The increase of ‘J(C,H) in r-benzenechromium tricarbonyl compared to benzene was connected to an increase in bond order of the C-H bond as judged from ab initio calculations. However, backbonding from the metal to the ligand was also predicted and this will result in an appreciable negative charge in the ring, which should lead to a reduction in the coupling constant (Section 8). The authors point out that an interpretation of the results is difficult because of the multifactorial dependence.““’

‘J(C, H,) of CH,HgNO, in strong acids correlates with S(Hg-CH,), as is also found in the case of (CH,),SnO (tide supra). ‘J(C, H,) also correlates with ‘J(Hg-H) and v,,~,,,(C-H).(‘~~’

24.2.5. Group MllB. Ferrocenes have been investigated both as neutral’7”2*799,800’ and as ionic ~p~~~~~~757~758~761~762)

Coupling constants in

Chromium and rhodium complexes were also discussed in Section 18.1.

[Rh(C,Me,)(benZene)][PF&

24.2. Metal Organic Complexes

The range of organometalorganic compounds is very large and because only a limited number of carbon-hydrogen coupling constants are available the information is scattered. The following section is a very short summary of this data.

and the corresponding iridium complex have been reported. The coupling constants for the benzene rings (184 and 188 Hz) are much larger than ‘J of benzene itself. This observation is analogous to that for benzenechromium tricarbonyl (ode supra) and the larger couplings have been connected with the di-cationic nature.‘801)

24.2.1. Group III. One bond couplings in l-methyl- and 2-methyl groups of a close-pentaborane have been discussed in terms of %s character.(791) ‘J(C, H) values in some simple boranes R,_,BX, (R = CH,, X = N(SH,), OCH, or SCH,, n = 0,1,2,3) have also been reported.‘792’

The ‘J(C, H) values in norbornenyl palladium(H) or platinum(H) provide clear evidence for a n-homo- allyllic bonding scheme. (*02) Studies of seven neutral cis-dimethylplatinum(I1) derivatives of type cis- (CH3)2PtL, show that *J(C, H,) (- 124 Hz) is essentially insensitive to variations in the remaining ligands.‘803’

25. SHORT SUMMARY OF SOlME RECENT PAPERS

24.2.2. Group IV. Organic silicon compounds have already been mentioned in connexion with “J(C,X,H).

A very high ‘J(C,H) value involving the methine

‘J(C,H,) is approximately constant in the series of carbon of the orthoformamide C,H,,N3 compared

(CH,),SiH,_,. Fordimethylsilacyclobutane ‘J(C,H,) with C9HlsN3 has been ascribed to lone-pair effects.@52) Spoormaker and de Biets5’) showed that

involving the carbon next to the silicon is much smalIer than ‘f(C, H,) for the carbon away from the

the equation for the effects of substituent on synclinal proton-proton coupling constants can be modified to


yield values for synclinal carbon-proton coupling constants. The same authors’*s”1 also investigated ‘J(C, H) values and concluded that methyl substituent effects at the P-carbon are not constant. “J(C, H) for dimethylacetylene has also been determined!*55’

The conformation of tartaric acids has been determined by means of ‘J(COOH, H).‘856*857’ Fischman et nl. discussed 3J(C0, H-8) of oxytocin.

Serianni and Barker@58’ have determined ‘J(C, H) and ‘J(C, D) in threose, erythrose, ribose 5-phosphate and glyceraldehyde )-phosphate. In no cases was AJ larger than the experimental uncertainty.

The configuration of the anomeric carbons and the inter-residue angle of rhamnobiose were studied by meansof’J(C-1,H-l)and3J(C-l,H-1’).~*5g~Similarly ‘J(C-1, H-A) has been reported for someoligosacchar- ides related to blood group determinants.‘860’

Coupling constants of nicotine metabolites(861’ and of colchicine@62’ have been reported.

3J(C, N, C, H) of S-carbomethoxymethyl-uracil and uridine indicate anti conformations.‘863)

* J(C, H) values have allowed the determination of the type of ring junction as well as the predominant tautomeric form for s-triazol-as-triazinones.(86”

Natakul et &‘865) have determined ‘J(C,H) for tricyclobutabenzene. Large ‘J(C, H) values were observed in LnMCH, derivatives.‘*66)

Jaouen et ~1.‘~~‘) reported “J(C,H) of bis(tricarbonylchromium) diphenylmethyl carbanion. The value of ‘J(C-r, H-a) suggests a less delocalized negative charge than in (C,H,),CHLi. ‘J(C,H) for stabilized and unstabilized sulphonium ylides indicate that the ylidic carbon is more flattened than in the corresponding salts.‘868’

Both ‘J(C,H)and 2J(C,C,H)of((C,H5),N),PX3-~ (X = Cl or C,H,) compounds have been determined, and both ‘J(C-a.H-a) and *J(C-p,H-8) are affected by the number of chlorines at the phosphorus.‘86g’

The satellite spectrum of benzaldehyde oriented in a liquid crystal solvent has been analysed!870)

Acli,lor~/edyetnents-l.am indebted to Mrs. Anne-Lise Roed and Miss Birthe Hother Nielsen for the typing of the manuscript. I wish 10 acknowledge the helpfulc&m&ts of K. Bock, J. P. Jacobsen and S. Braun.

1.

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H. STAAB and IM. HAENEL, Chem. Ber. 103, 1095 (1970). G. R. WEISMAN. V. JOHNXIN and R. E. FIALA, Tetrahedron Left. 3635 I1 9X0).

T. SP~~RMAKER and M. J. A. DE BIE. Recrtil. 99. 154 (1980).

T. SP~~RMAKER and M. J. A. DE BIE. Reclril, 99, 194 (1980). K. HAYAMIZU and 0. YAMAMOTO. Org. Mayn. Reson. 13,460 ( 1980). J. ASCENSO and V. IM. S. GIL, Canad. J. Chem. 58, 1376 (1980). A. J. FISCHMAN. D. H. LIVE. H. R. WYSSBROD, W. C. AGOSTA and D. COWBURN. J. Am. Chem. SOC. 102,2533 (1980). A. S. SERIANNI and R. BARKER, Canad. J. Chem. 57,3 I60

(1979).

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863.

864.

865.

866. 867.

868.

869.

870.

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NOTE ADDED IN PROOF

r,-structures of 1,2.4-trichlorobenzene.‘87L’ 1,2,4,5- and 1,2,3,4-tetrachlorobenzene@“’ and of seleno- phene@73) from 13C satellites are also reported. Pachler and Wessels(*74J have described how selective population inversion can lead to coupling constants even when no splittings are observed. Second order effects in ABX systems have been described”“) (see Ref. 30). ZD-spectroscopy has been used to determine couplings in oligosaccharides.@76’ Theoretical calculations using neglect of diatomic differential overlap approximation in the FP method gave better results than the INDO approximation when applied to benzene and cyclopentadiene.(“‘) The INDO approximation in the SOS method has been applied to carbonium ions.‘878) Isotope effects on ‘J(C,H) have been calculated for methane, ethylene and acetylene.(879)

High resolution ‘“C-{ 14N} spectra of pyridinium tetrafluoroborate dissolved in CD,CN gave values of

both one-bond and long range coupling constants somewhat different from those reported in Ref. 324 and shown in Structure 56.““’ One-bond and three- bond couplings of I-(substituted phenyl) pyridinium salts have been reported.““)

Coupling constants of the pyridinium ion have been

calculated and the ionization effects discussed.‘882’ Coupling constants of methyl- and aminopyrimidines have been reported. ‘883’ Further studies of phen-

oxythiins have used “j(C, H) for assignment

purposes.(884) (See also Refs. 85,86 and 650). Long range coupling constants have been used

for assignment purposes in chaetochromin.(885) ‘J(CH,, N, C, H) shows a Karplus like dependence in N-methylated peptides. (8861 Exchange of bromine

with lithium lead to a decrease of 1J(C,H).(887) The data of Refs. 691 and 692 have recently been questioned.““) Wells et a1.‘889) reported slightly different coupling constants for azulene compared to


Refs. 230 and 231. This discrepancy suggests that a complete analysis of the single frequency spectrum of this molecule is required. ‘J(C,D) of cis- and truns-I-ethyl-4-methylcyclohexane. d3 have been reported.““’ Conformations of malic and thiomalic acids have been compared using 3J(C0, H)‘*“) and the conformation of 5,6,7,&tetrahydrofolic acid and related pterins have been studied!8g2’ Diacetylenes showed couplings over one to three bonds.‘*g3*8g41 One-bond coupling constants of some cage compounds have been related to hybridization.@g5’ Couplings in tetracycloheptanes and octanes showed large bridgehead one-bond coupling constants.“‘@ ‘J of a pentacyclododecane@g7) and of l-chlortriquin- acene’8g8t have also been reported. ‘J of phosphon- ium, arsonium, sulphonium and pyrimidinium keto- stabilized salts and their ylides have been compared!8qq’ ‘J was also used to monitor the geometry of the C- 1 carbon in carbanionic species formed from phosphonates.‘qOO) ‘.I of alkyl halides mixed with antimony or arsenic pentafluoride showed variations with the solvent.(“” The cyclohexadienyl anion showed a ‘J(C-6, H-6) typical of a sp3 hybridized carbon.‘q02) A large and temperature dependent isotope effect upon ‘J(C,H3) of different hydrogen bonded species of HOs3(CO),,CH20 has been ascribed to*a shift in the equilibrium.~g03’ Bisneo- pentylidene complexes of niobium and tantalum showed very small one-bond couplings.‘q04.q05) Coupling constants of silatranes,‘906) nitrothio- phenes,c9”’ methylsubstituted piperidinesJqo8’ nitro- enamines’90q’ and of dimethylsulphoxide, -sulphide and -ether’gLo’ have also been reported.

REFERENCES ADDED IN PROOF

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872. P. DIEHL, G. DOMBI and H. BI%IGER, Org. Mugn. Reson. 14, 281 (1980).

873. G. CHIDICHIMO, F. LELJ, M. LONGERI, N. Russo and C. A. VERACINI, J. Mngn. Reson. 41.35 (1980).

874. R. PACHLER and P. L. WESSELS, Org. Magn. Reson. 14, 374 (1980).

875. A. W. DOUGLAS and M. SHAPIRO, Org. Magn. Reson. 14, 38 (1980).

876. L. D. HALL and G. A. MORRIS, Carbohydr. Res. 82, 175 (1980).

877. V. N. SOLKAN and N. B. LEONIDOV, Zhur. Struk Khim. 20, 1104 (1979).

878. A. A. CHERESIMIN and P: V. SCHASTNEV, Org. Magn. Reson. 14.327 (1980).

879. Kh. ORAZBERDIEV, V. M. MA~~AEV and N. M. SERGEEV in Mngn. Reson. Reiat. Phenom. Proc. Congr. Amperh 20th. Springer, Berlin (1979).

880.

881.

882.

883.

884.

885.

886.

887.

888.

889.

890.

891. 892.

893.

894.

895.

896.

897.

898.

899.

900.

901.

902.

903.

904.

905.

906.

907.

908.

909.

910.

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Carbon-hydrogen Spin-spin Coupling Constants

Documents

h type

couplings of c

bond coupling constants

bond length dependence

summary assignments

summary io

summary f4

bond angle dependence