Bpo c Chapter 22

7/29/2019 Bpo c Chapter 22

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ARENES. ELECTROPHAROMAT C SUBST

B nzene and other aromatic hydrocarbons usually have such strikinglydifferent properties from typical open-chain conjugated polyenes, such as1,3,5-hexatriene, that it is convenient to consider them as a separate class ofcom pounds called arenes. In this cha pter w e shall outline the essential featuresof the chemistry of arenes, particularly their reactions with electrophilic re-agents which result in the substitution of a ring hydrogen with ot he r functiona lgroups. So m e of the impo rtant prope rties of benz ene were discussed in Chap-ter 21 in connection with the valence-bond and molecular-orbital theories,which rationalize the bonding in benzene and account for the remarkable sta-bility and low reac tivity of ben zen e (Section 21-3A ). T hi s cha pte r is especiallyconcerned with chemical properties of benzene and its derivatives as well asrelated ring systems.

22-1 NOMENCLATUREThe naming of benzene derivatives was considered in Section 3-5 and is rela-tively straightforward. However, many benzene derivatives have acquired


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22-1 Nomenclature 4 025t r iv ia l names, and we draw your a t ten t ion to a few of these below. The ac-cep ted name for the C,H,- group a s a subst i tuen t is phenyl.

benzenol sodium benzenamine methoxybenzene(phenol) benzenolate (aniline) methyl phenyl ether(sodium phenoxide) (anisole)

C H = C H , C H O

ethenylbenzene benzenecarbaldehyde benzenecarboxylicacid(phenylethene, (benzaldehyde) (benzoic acid)styrene)

T h e m ore com plex r ing sys tem s having two o r mo re fused benzene r ings havenonsystemat ic name s a nd i llogical number ing sys tems. They are descr ibed a spolynuclear aromat ic hydrocarbons , th e th re e m ost im por tan t examples beingnaphthalene, an thracene, a nd phenanthrene. In an thracene the r ings are con-nected in a linear manner , whereas in phenanthrene they are connectedangularly:

benzene naphthalene anthracene phenanthrene

The accepted number ing sys tem for these hydrocarbons i s as shown in thes t ructures . The 1- and 2-posi tions of the naphthalene r ing som et imes aredes igna ted a s a a nd P , but w e prefer no t to u se these des ignations. S om e illus-trat ive subst i tut ion products are:

I-methylnaphthalene 2-methylnaphthalene 1-methy anthracene 9-methylphenanthrene


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22 Arenes. Electrophi l ic Aroma t ic Subs t i tut ionThe names tha t have been given to these and other more e labora tetypes of polynuclear arom atic hydrocarb ons ar e for the m ost p art distressinglyuninformative with respect to their structures. '

Exercise 22-1 How many structurally different monomethyl derivatives are possiblefor each of the fol lowing com pounds? Name each.a. naphthalene b. anthracene c. phenanthreneExercise 22-2 How many isomeric p roducts co uld each of the dimethyl benzenesgive on introduction of a third substituent? Name each isomer, using chlorine as thethird substituent.

Exercise 22-3 Nam e each of the fol lowing com pounds by the IUPAC system:

22-2 PHYSICAL PROPERTIES OF ARENEST h e pleasant o dors of the derivatives of many are nes is the origin of the nam earomatic hydrocarbons. The arenes themselves general ly are qui te toxic;som e ar e carcinogenic and inhalat ion of their vapors should be avoided. T h evolatile arenes are highly flammable and burn with a luminous sooty flame,in contrast to alkanes and alkenes, which usually burn with a bluish flameleaving li t tle carbo n residu e.

T h e mo re c omm on arenes and their physical propert ies a re given inTable 22-1. They are less dense than water and are highly insoluble. BoilingIA thorough summary of names and numbering systems has been published by A. M .Patterson, L. T. Capell , and D. F. Walker , Ring Index , 2nd ed. , American ChemicalSociety , 1960. Le ss co mp lete but useful sum maries are given in various handb ooksof chemistry.


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22-2 Phys ical Properties of ArenesTable 22-1Physical P ropert ies of Arenes

CompoundMP , BP, Density,"C "C dd20

benzenemethy l benze ne (toluene)ethyl benze nepropy l benzeneisopropyl benzene [ ( I methylethyl) benzene]tert-butyl benzene [(2,2-dimethylethyl)benzene]1,2-dimethyl benzene (ortho-xylene)1,3-dimethylbenzene (meta-xylene)1,4-dimethylbenzene (para-xylene)1,3,5-trimethylbenzene (me si ty lene)1,2,4,5-tetramethyl ben zen e (d ure ne)naphthaleneanthracenephenanthrene

points increase fairly regularly with increasing molecular weight, but there islittle correlatio n betw een melting point a nd m olecular weight. Th e meltingpoint is highly depende nt on the sym metry of the comp ound; thus benzenemelts 100" higher than m ethylbenzene, an d the m ore sym metrical 1,4-dimethyl-benzene (para-x ylen e) has a higher melting point than either the 1,2- o r the1,3-isomer. This latter fact is utilized in the separation by fractional crys-tall ization of 1,4-dimethylbenzene from m ixtures of isomers produced frompetroleum.

22-3 SPECTRAL PROPERTIES OF ARENES22-3A Infrared Spe ctraT h e presence of a phenyl group in a com pound can be ascer ta ined with a fa irdegree of certainty from its infrared spectrum. For example, in Figure 22-1w e se e the infrared spec tra of methylbenz ene, an d of 1,2- 1,3- , and 1,4-di-methylbenzene. That each spectrum is of a benzene der ivat ive is apparentf rom cer ta in comm on features . Th e two bands near 1600 cm-I and 1500 cm-l,although of variable intensity, have been correlated with the stretching vibra-tions of the carbon-carbon bond s of the arom atic r ing; also, the sha rp ban dsnea r 3030 cm-l ar e characterist ic of aromatic C-I3 bonds. Othe r bands in the


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22 Arenes. Elec trophil ic Aromatic Substitution

"I Lr 00 0.-+ r.-"I Pg 5u 0r 5-02 gE ."3 .tic m0 g .

0 2* 5 gg z 5N a 12$ 7 '0$ 5 .&5 0 %a m + - -E Z ~-~ 2 ;w- 7' E 12 00a s&"o7- cu -- c a.;." ."- 0 %a, g 75r"gu -2 & g2 -gg$ 2 2C Q 0; 2 - :h . Z u5 czm a *E . y% 3 2g 22;+" a, 0g gu K TU % E$ 2 0LCc Q g

0 a5-50c;r a"" .& 7e ~ 6g 2 0.- a, 0LLUcO


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22-3 Spectral Properties of Arenes 1029

Figure 22-2 Infrared spectra of two isomeric compounds of formulaC7H7CI see Exercise 22-4)

spectra, especially those between 1650 cm-I and 2000 cm-l, between 1225cm-I and 950 cm-l, and below 900 cm-l, have been correlated with the num-ber and positions of ring substituents. Although we shall not document allthese various bands in detail, each of the spectra in Figure 22-1 is marked toshow some of the correlations that have been made.

Exercise 22-4 Identi fy the two compounds with molecular formula C,H,CI from theinfrared spectra shown in Figure 22-2.


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1038 22 Arenes. Electrophil ic Aromatic Substitut ion22-3B Electronic Ab sorpt ion Spe ctraCompared to s traight-chain conjugated polyenes, aromatic compounds haverelatively complex absorption spectra with several bands in the ultravioletregion. Benzene and the alkylbenzenes show two bands in which we shall beprimarily interested, one near 200 nm and the oth er near 260 nm. Th e 200-nmband is of fairly high intensity and corresponds to excitation of a v electronof the conjugated system to a v* orbital (i.e., a v- * transition). Theexcited state has significant contributions from dipolar structures such as 1

Th is is analogous to the absorption ba nds of conjugated dienes (Section 9-9B)except that the wavelength of absorption of benzene is shorter. In fact, the200-nm absorptions of ben zen e and the alkylbenzenes are just beyon d therange of most comm ercial quartz spectrometers . Ho we ver , these absorptions(which w e say arise from th e ben zene clhromophore2) are intensified an dshifted to longer wavelengths when the conjugated system is extended byreplacement of the ring hydrogens by unsaturated groups (e.g., -CH=CH,,-C =C H , -C I3 =0 , and -C =N ; see Table 22-2). T he delocalized v-elec-tron system of the absorbing chromophore now includes the electrons of theunsaturated substituent as well as those of the ring. In the specific case ofethenylbenzene the excited state is a hybrid structure composite of 2a and 2band other related dipolar structures:

H\CHCH2 K c/C H ~ ~ \C//CH,6 . 0 etc .

0 /ethenyl benze ne 0(styrene) 221 2b

Similar effects are observed for benzene derivatives in which the sub-stituent has unshared electron pairs that can be conjugated with the benzenering (e.g., -NH ,, -OH, -cl :) . A n unshared electron pair is to some extentdelocalized to become a part of the aromatic v-electron system in both theground and excited states, but more importantly in the excited state. This is2A chromophore is a grouping of atoms in an organic molecule that gives rise to color,or has the potential of doing so when other groups called auxochromes are present(also see Section 28-4).


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22-3B Electronic Absorption SpectraTable 22-2Effect of Conjugation on Electronic Absorption by the Benzene Chromophore

Compound hmaxr nma Ernax

aln ethanol

illustrated for benzenamine (aniline) by the following structures, whichcontribute to t he hybrid structure:

benzenamine 0(aniline)T he data of Table 22-3 show the effect on the benzene chromophore of thistype of substituent- he substituent often being called an auxochr~me.~h isterm means that, although the substituent itself is not responsible for theabsorption band, it shifts the absorption of the chromophoric group, in thiscase the benzene ring, toward longer wavelengths. The auxochromic groupsusually increase the intensity of the absorption also.Exercise 22-5 Predict the effect on the ultraviolet spectrum of a water solution ofbenzenamine when hydrochloric acid is added. Explain why a solution of sodiumbenzenoxide abso rbs at longer wavelengths than a so lution of benzenol (see Table22-3) .


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22 Arenes. Electrophilic Aromatic SubstitutionTable 22-3Effect of Auxochromic Substituents on Electronic Absorpt ion by the BenzeneChromophore

Compound Amax , nma Emax- --- - - ...- - --

"In ethanol or water

The benzene chromophore itself gives rise to a second band at longerwavelengths. This band, shown for benzene in Figure 22-3, is of relativelylow intensity and is found under high resolution to be a composite of severalnarrow peaks. It appears t o be characteristic of aromatic hydrocarbons becau seno analogous band is found in the spectra of conjugated acyclic polyenes. Forthis reason it often is called the benzenoid band. T h e position and intensity ofthis band, like the one at shorter wavelengths, is affected by the nature of thering substituents, particularly by those that exten d the conjugated system, asmay be seen from the data in Table 22-4.

wavelength, nm------,Figure 22-3 Ultraviolet absorption spectrum of benzene (in cyclo-hexane) showing the "benzenoid" band


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22-38 Electronic Absorption SpectraTable 22-4Effects of Structure on Electronic Absorption Corresponding to the Benzenoid Band

Compound Am a x ! nma Ernax

(naphthacene)

(pentacene)- - - - - -

"Mostly In ethanol solution

The benzenoid band corresponds to a low-energy n --+ n* transition of thebenzene molecules. The absorption intensity is weak because the n* stateinvolved has the same electronic symmetry as the ground state of benzene,and transitions between symmetrical states usually are forbidden. The transi-tions are observed in this case only because the vibrations of the ring cause itto be slightly distorted at given instants. In the valence-bond treatment thisexcited state of benzene is an antibonding state of the n electrons.The electronic spectra of polynuclear aromatic hydrocarbons such asnaphthalene and anthracene, in which aromatic rings are fused together in al inear manner, resemble the spectrum of benzene except that the bands areshifted to longer wavelengths. In fact, with the four linearly connected ringsof naph thacene , th e benzenoid band is shifted far enough to longer wavelengths


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1034 22 Arenes. Electrophil ic Aromatic Substitutionto be in the visible region of the spectrum (see Table 22-4). Accordingly,naphthacene is yellow. Th e next higher mem ber, pentacene, is blue.Com poun ds such as phenanthrene, chrysen e, and pyrene, in which thearomatic rings are fused in an angular manner, have complex electronic spectrawith considerable fine structure. Th e A values normally are at sh orter wave-lengths than those of their linear isomers.

phenanthrene chrysene pyrene

22-3C Nuclear M agne tic Resonance SpectraThe chemical shifts of arene protons (6.5 ppm to 8.0 ppm) characteristicallyare toward lower magnetic fields than those of protons attached to ordinarydouble bonds (4.6 ppm to 6.9 ppm). T h e difference of about 2 ppm canno t beeasily explained because the hydrogens in both types of systems are bondedto carbon through sp% bonds (Sections 6-4C and 6-5A).

At least part of the chemical-shift difference between arene protons and alkeneprotons is the result of the special property of n- electrons in aromatic systemsof circulating freely above and below the plane of the carbon nuclei, as shownin Figure 22-4. When a molecule such as benzene is subjected to a magneticfield that has a component perpendicular to the plane of the ring, the electronscirculate around the ring in such a way as to produce a local magnetic dipolein the direction oppos i te to the applied field. This diam agnetic shielding effectacts to reduce the applied field in the center of the ring. Therefore, if a protoncould be located in the center of the ring, the applied field would have to behigher than normal to counteract the local diamagnetic field and bring the protoninto resonance. A proton outside the ring is affected in the opposite way (par a -ma gnet ic desh ie ld ing effect) because, as can be seen from the diagram, suchprotons are located in the return path of the lines of force associated with thelocal field and thus are in a field greater than that arising from the externalmagnet alone. When the plane of the molecule is oriented parallel to the field,the diamagnetic circulation is cut off. As a result, as the molecules tumble overand over in the liquid the component of magnetization perpendicular to the planeof the ring varies rapidly. Nonetheless, a substantial n e t paramagnetic effect isexperienced by the ring hydrogens. The resonance line positions therefore areshifted to lower magnetic fields.


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22-3C Nuclear Magnetic Resonance Spectra

induceddipo le magnet ic

Figure 22-4 Diagram representing the circulation of the 7 ~ . lectrons ofan aromatic ring under the influence of an applied magnetic f ield, H,.This diagram corresponds to the same kind of effect as that shown inFigure 9-26. The strength of the induced magnetic f ield, or dipole, isproportional to the applied f ield.

Strong evidence in confirmation of the above explanation of the chemicalshifts of aromatic hydrogens is provided by a study of the cyclic conjugatedpolyene [181annulene, which has hydrogens both "inside" and "outside"the r ing:

T h e inside hydrogens are strongly shielded, coming at 1.9 ppm upfield f romtetramethylsi lane, while the outs ide hydrogens are desh ie lded and come a t8.8 ppm downfield f rom T M S . A s w e shal l see , the r ing cur ren t e f fec t i s qu i tegeneral and co nsti tute s a widely used test for aromatic characte r in conjugatedpolyene r ing systems.


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22-4 Electrophilic Aromatic Substitution 4837conjunction with integrated line intensities and approximate values of thecoupling constants betwe en the ring hydrogens, as shown below:

Exercise 22-7 Establish the structures of the following benzene derivatives on thebasis of their empirical formulas and nmr spectra shown in Figure 22-6. R e r r ~ m b e rthat equivalent protons normally do not split each other's resonances.a. C,H,, b. C,H,OCI c. C,H,,O, d. C,H,,

22-4 ELECTROPHILIC AROMATIC SUBSTITUTION22-44 Scope and MechanismIn this section we shall be mainly interested in the reactions of arenes that in-volve attack on the c arbon ato m s of the arom atic ring. We shall not elaboratenow on the reactions of substituent groups arou nd the ring.The principal types of reactions involving aromatic rings are substitu-tion, addition, and oxidation. Of these, the most comm on ty pe is electrophilicsubstitution. A summ ary of the m ore important substitution reactions of ben-zene is given in Figure 22-7. M an y of the reagents used to achieve these sub-stitutions will be familiar to you in connection with electrophilic additionreactions to alkenes (e.g., Cl,, Br,, H 2 S 0 4 , and HO C1; Section 10-3). Elec-trophilic addition to alkenes and electrophilic aromatic substitution are bothpolar, stepwise proc esses, and t he key step for each is attac k of an electrophileat ca rbon to form a cationic intermediate. We may represent this type of reac-tion by th e following general equ atio ns, in which the attac king reagent isreprese nted either formally as a cation, XO, or a s a neutral but polarized mole-

6 0 60cule, X----Y:electrophilic aromatic substitirtion (first step)

electrophilic addition to alkenes (first step)so 8 0 0H,C==X@ (o r X- - - - - - -Y)--+ H,C-CH2X (+ Y O )


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Figure 22-6 Proton nmr spectra of some benzene derivatives at 60 MHzwi th reference to TMS at 0 ppm (see Exercise 22-7)


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1040 22 Arenes. Electrophi l ic A romatic S ubst i tut ionmay be formulated in terms of the following contributing structures, whichare assumed to contribute essentially equally:

The importance of writing the hybrid structure with the partial charges at thesethree positions will become evident later. This kind of ion is referred to as a(T complex or a benzenium ion.

The aromatic ring is regenerated from this cationic intermediate by lossof a proton from the sp3-hybridized carbon. The electron pair of this C-Hbond then becomes part of the aromatic n-electron system and a substitutionproduct of benzene, C,H,X, is formed.

electrophilic aromatic substitution (second step)X

The gain in stabilization attendant on regeneration of the aromatic ring issufficiently advantageous that this, rather than combination of the cation withYe , normally is the favored course of reaction. Herein lies the differencebetween aromatic substitution and alkene addition. In the case of alkenes thereusually is no substantial resonance energy to be gained by loss of a proton fromthe intermediate, which tends therefore to react by combination with a nucleo-philic reagent.electrophilic addition to alkenes (second step)0CH2-CH2X +Y@ ---+YCH2--CH2X

Exercise 22-8 Calculate from appropriate bond-energy and stabi lization-energytables (4-3 and 21-1) the heats of reaction of chlorine with benzene to give (a) chloro-benzene and (b) 5,6-dichloro-l,3-cycloh exad iene. Your answer shou ld indica te thatsubstitution is energetically more favorable than addition.


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22-4B Nature of the Substituting Agent 1041Exercise 22-9 Devise an experimental test to determine whether the followingaddit ion-elimination mechanism for bromination of benzene actually takes place.

22-4B Nature of the Substituting AgentIt is important to realize that in aromatic substitution the actual electrophilic0 60 60substituting agent, X or X-U, is not necessarily the reagent that is added tothe reaction mixture. For example, nitration in mixtures of nitric and sulfuricacids is not brought about by attack of the nitric acid molecule on the aromaticcompound, but by attack of a more electrophilic species, the nitronium ion,[email protected] ion is formed from nitric acid and sulfuric acid according to thefollowing equation:

The nitronium ion attacks the aromatic ring to give first a nitrobenzenium ionand then an aromatic nitro compound:

0 No2@-+ n trobenzeneIn general, the function of a catalyst (which is so often necessary to

promote aromatic substitution) is to generate an electrophilic substitutingagent from the given reagents. Thus it is necessary to consider carefully foreach substitution reaction what the actual substituting agent may be. Thisproblem does not arise to the same degree in electrophilic additions to alkenes,because alkenes are so much more reactive than arenes that the reagentsemployed (e.g., Br,, Cl,, HBr, HCl, HOCl, HOBr, H,OO) themselves aresufficiently electrophilic to react with alkenes without the aid of a catalyst. Infact, conditions that lead to substitution of arenes, such as nitration in mixturesof nitric and sulfuric acid, often will degrade the carbon skeleton of alkenes.

Now we shall consider the individual substitution reactions listed inFigure 22-1 with regard to the nature of the substituting agent and the utilityfor synthesis of various classes of aromatic compounds.


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1042 22 Arenes. Elec troph i l ic Aroma tic Subst i tut ion22-4C NitrationThe nitronium ion, NO2@,s the active nitrating agent in nitric acid-sulfuricacid mixtures. The nitration of methylbenzene (toluene) is a typical exampleof a nitration that proceeds well using nitric acid in a 1:2 mixture with sulfuricacid. The nitration product is a mixture of 2-, 3-, and 4-nitromethylbenzenes:

The presence of appreciable amounts of water in the reaction mixture isdeleterious because water tends to reverse the reaction by which nitroniumion is formed:

For this reason the potency of a nitric-sulfuric acid mixture can be consider-ably increased by using fuming nitric and fuming sulfuric acids. With suchmixtures nitration of relatively unreactive compounds can be achieved. Forexample, 4-nitromethylbenzene is far less reactive than methylbenzene, butwhen heated with an excess of nitric acid in fuming sulfuric acid, it can beconverted successively to 2,4-dinitromethylbenzene and to 2,4,6-trinitro-methylbenzene (TNT):

HNO,, 120" qNo2NO,, 120"SO37 H2SO4 ' SO,, H~SO,NO24-nitromethyl benzen e NO22,4-dinitromethyl benzen e7 H 3

NO22,4,6-trinitromethyl be nzen e (TNT)

There are several interesting features about the nitration reactions thusfar discussed. For instance, the conditions required for nitration of 4-nitro-


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22-4C Nitrat ion 11043methylbenzene would rapidly oxidize an alkene by cleavage of the double bond:

Also the mononitration of methylbenzene does not lead to equal amounts ofthe three possible products. The methyl substituent apparently orients theentering substituent preferentially to the 2 and 4 positions. This aspect ofaromatic substitution will be discussed in Section 22-5 in conjunction with theeffect of substituents on the reactivity of aromatic compounds.

Some compounds are sufficiently reactive that they can be nitrated withnitric acid in ethanoic acid. Pertinent examples are 1,3,5-trimethylbenzeneand naphthalene:

I1Other convenient nitrating reagents are benzoyl nitrate, C,H,CONO,,II

and ethanoyl nitrate, CH,CONO,. These reagents provide a source of NO,@and have some advantage over I-INO,.H,SO, mixtures in that they are solublein organic solvents such as ethanenitrile or nitromethane. Having homogeneoussolutions is especially important for kinetic studies of nitration. The reagentsusually are prepared in solution as required from the corresponding acylchloride and silver nitrate or from the acid anhydride and nitric acid. Suchreagents are hazardous materials and must be handled with care.

C6H5COCl + AgN0, ICH3CN > C6H5C0N02 + AgCl(s)benzenecarbonyl chlor ide benzenecarbonyl nitrate(benzoyl chlor ide) (benzo yl nitrate)0I(CH,CO),O + I-INO, --+ CH3C-O-N@ + CH:,CO,H

ethanoic anhy dride ethanoyl nitrate


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22 Arenes. Electrophil ic Aromatic SubstitutionNitronium salts of the type NO ,@ X G arevery pow erful nitrating agen ts.The counter ion, X@,must be non-nucleophilic and usually is Auoroborate,

BF,@ o r S b F G G :

Exercise 22-10 Why is ni trat ion with ethanoyl ni trate accelerated by added f luoro-boric ac id, HBF,, but retarded by added hydrochlor ic ac id ?Exercise 22-11 Why do fair ly reactive arenes, such as benzene, methylbenzene, andethylbenzene, react with excess nitric acid in nitromethane solution at a rate that isindepen dent o f the conce ntration of the arene (i .e.,zero order in arene conce ntration)?Does this lack of dep en den ce on arene concentration mean that ni trat ion of an equi-molar m ixture of benzene a nd methyl benzene would necessarily give an equimolarmixture of nitrobenzene and nitromethyl benzen es? Why or why not?

22-4-D HalogenationT o som e degree w e h ave oversimplified electrophilic substitution by neglectingthe possible role of the 1 :1 charge-transfer com plexes that m ost electrophilesform with arene s (see Section 10-3C for discussion of analogous com plexes ofalkenes):

charge-transfer CT comp lexor orn com plex benzenium ion

With halogens, especially iodine, complex formation is visually evident fromthe color of solutions of the halogen in arenes. Although complex formationmay assist substitution by bringing the halogen and arene in close proximity,substitution does not necessarily occur. A catalyst usually is required, andthe catalysts most frequently used are metal halides that are capable of ac-cepting electrons (i.e., Lewis acids such as FeBr,, AlCl,, and ZnC1,). Their


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3046 22 Arenes. Electrophil ic Arom atic SubstitutionWith co mb inations of this kind good yields of iodination pro duc ts are obtained:

2- iodomethyl benzene 4- iodomethyl benzene(ortho-iodotoluene) (para-iodotoluene)

Halog en subs ti tu tion reac t ions wi th chlor ine or bromine mu s t be car-ried out with adequate protection from strong l ight . If such precautions arenot taken, an a lkylbenzene will react rapidly with halogen by a photochemicalproc ess to substi tute a hydrogen of the alkyl grou p rather tha n of the aromaticring. T h e reaction has a l ight-induced, radical-chain mech anism of the kind dis-cussed for the chlor ina t ion of propen e (Sect ion 14-3A). Th us m ethylbenzenereacts with brom ine w hen i l luminated to give phenylm ethyl brom ide; but whenlight is excluded and a Lewis acid catalyst is present , substi tut ion occurs togive principally the 2- and 4-bromomethylbenzenes . Much less of the 3-bromomethyl benzen e is formed:

phenylmethyl bromide(benzyl bromide)

Brbromomethyl benzenes

Benzene i tself can be induced to add halogens on s trong irradiat ion to givepolyhalocyclohexanes (see Sections 2 1-3A and 22-9C).

Exercise 22-12 Reagents, besides the mo lecular halog ens, that effect haloge nsubstitution inclu de hypo chlorous and hypobromous a cids . They are m ost effect ivewhen a strong a cid is present and care is taken to exclu de formation of halide ions.Account for the catalytic effect of acid and the anticatalytic effect of halide ions.


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22-4E Alkylat ion 1047Exercise 22-13 Arrange the following bromine-containing species in order of theirexpe cted reactivity in ach ieving ele ctro ph il ic aromatic brom ination: HO Br, Br,, Br@,BrG, HB r, H,OBr@, BrCI.Exercise 22-14 Aluminum chloride is a much more powerful catalyst than ferr icbrom ide for bromination 'of benz ene. W ould yo u exp ect the com bination of aluminumchlorid e and bromine to give m uch chlorobenzene in reaction with benzene? Explain.Exercise 22-15 a. The bromination of benzene is catalyzed by small amounts ofiodine. Devise a po ssib le explanation for this ca talytic effect.b. The kinetic expression for the bromination of naphthalene in ethanoic acid in-volves a term that is first order in napthalene and second order in bromine. How cantwo m olecules of bromine and one of naphthalene be involved in the rate-determiningstep of bromination? Explain why the kinetic expression simplifies to first order innaphthalene and first order in bromine in 50% aqueous ethanoic acid.

22-4E Al kylationAn important method of synthesis of alkylbenzenes utilizes an alkyl halideas the alkylating agent and a metal halide, usually aluminum chloride, ascatalyst:

+ HBrbenzene ethyl brom ide ethyl benzene( large excess) 83%

This class of reaction is called Friedel-Crafts alkylation in honor of itsdiscoverers, C. Friedel (a French chemist) and J . M. Crafts (an Americanchemist). The metal-halide catalyst functions much as it does in halogenationreactions to provide a source of a positive substituting agent, which in thiscase is a carbocation:

(Imethylethyl )benzene(isopropyl benzene, cu men e)+ AlCl, + HCl


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f 048 22 Arenes. Electrophi l ic Aromatic Substi tutionAlkylation is not restricted to alkyl halides; alcohols and alkenes may

be used to advantage in the presence of acidic catalysts such as H3P04,H2S04,HE;, BF,, or HF-BF,. Ethylbenzene is made commercially from benzene andethene using phosphoric acid as the catalyst. Isopropylbenzene is madesimilarly from benzene and propene:

Under these conditions the carbocation, which is the active substituting agent,is generated by protonation of the alkene:

With alcohols the electrophile can be formed by initial protonation by theacid catalyst and subsequent cleavage to a carbocation:

CH3\ CH3CHOH + H2S04t-.CH3/ CH3

Exercise 22-16 Write a mechanism for the alkylation of benzene with 2-propanolcatalyzed by boron tr if luoride.


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22-4E Alkylat ionLimitations of Al kylation ReactionsPolysubsti tutionThere are several factors that limit the usefulness of alkylation reactions. First,it may be difficult to limit reaction to monosubstitution because introductionof one alkyl substituent tends to activate the ring towards a second substitu-tion (see Section 22-5). Therefore, to obtain reasonable yields of a monoalkyl-benzene, it usually is necessary to use a large excess of benzene relative tothe alkylating agent:

ethyl benzen eC,H5Br CH,CH,\ ( limited )

benzene quantitiesAIC1, CH3CH2 CHzCH,1,3,5-tr iethylbenzene

Rearrangement of the alkylating agentA second limitation is the penchant for the alkylating reagent to give rearrange-ment products. As an example, the alkylation of benzene with 1-chloropropaneleads to a mixture of propylbenzene and isopropylbenzene. We may write thereaction as first involving formation of a propyl cation, which is a primarycarbocation:

This ion either can alkylate benzene to give propylbenzene,

or it can rearrange to a more stable secondary ion by the transfer of a hydrogenfrom a neighboring carbon together with its bonding electron pair (i.e., 1,2-hydride shift). The positive charge is thereby transferred from C1 to C2:


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1050 22 Arenes. Electrophi l ic Aromatic Substi tutionAlkylation of benzene with the isopropyl cation then produces isopropyl-benzene:

Rearrangements of this type involving carbocation intermediates often occurin Friedel-Crafts alkylations with primary and secon dary alkyl groups largerthan C, and C,. Related carbocation rearrangements a re discussed in Sec-tions 8-9B and 15-5E.Rearrangement of productsFurth er complications ar ise from the fact that the alkylation reactions some-times a re und er equilibrium control rather than kinetic control. Products oftenisomerize and disproportionate, particularly in the pres ence of large am ountsof catalyst. T hu s 1,2- and 1,4-dimethylbenzenes (ortho- and para-xylene s)are conv erted by large am ounts of Friedel-Crafts catalys ts into 1,3-dimethyl-benzene (meta-xylene):

Ethylbenzene disproportionates under the influence of excess HF-BF,to benzene and 1,3-diethylbenzene:

Exercise 22-17 Ex plain how it is pos sib le that the ratio of prod ucts iso lated fromequil ibration of 1,2-, 1,3-, and l ,4-dim ethy lbenz ene s is 18:58 :24 in the prese nce of asm all am ount of HF-BF,, but is ess en tially 0:100 :0 in the pre sen ce of exce ss HF-BF,.No tice that HBF, is an extremely strong ac id.Exercise 22-1 8 Acco unt for the fol lowing observations:a. 3-Methyl-2-butanol alkylate s benzene in HF to give (1,1 dimethy lpropyl)benz ene.


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22-4F Acylationb. 1-Chloronorbornane will not alkylate benzene in the presence of AICI,.

c. 1-Methylcyclopentyl cat ion is formed from each of the compounds shown belowunder the indic ated con dit ions at low temperatures (-70").

SbF -SOchlorocyclohexaneAH F-S bF5-SO2cyclohexene

cyclohexanol FS03H-S bF5

22-4F AcylationAcylation and alkylation of arenes are closely related. Both reactions weredeveloped as the result of the collaboration between Friedel and Crafts, in

I1877. The acylation reaction introduces an acyl group, R-C=O, into anaromatic ring and the product is an aryl ketone:

The acylating reagents commonly used are carboxylic acid halides, RCOCI,anhydrides, (RCO),O, or the acid itself, RCO,H. A strong proton or otherLewis-acid catalyst is essential. The catalyst functions to generate the acylcation:


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1052 22 Arenes. Electroph i l ic Arom atic Substi tutionThe catalyst most commonly used with acyl halides and anhydrides is alumi-num chloride:

phenylethanone(acetophenone)

Acylation differs from alkylation in that the reaction usually is carriedout in a solvent, commonly carbon disulfide, CS,, or nitrobenzene. Further-more, acylation requires more catalyst than alkylation, because much of thecatalyst is tied up and inactivated by complex formation with the productketone:

CH,1 : I comp lex

Unlike alkylation, acylation is controlled easily to give monosubstitu-tion, because once an acyl group is attached to a benzene ring, it is not possibleto introduce a second acyl group into the same ring. Because of this, a con-venient synthesis of alkylbenzenes starts with acylation, followed by reductionof the carbonyl group with zinc and hydrochloric acid (Section 16-6). Forexample, propylbenzene is prepared best by this two-step route because,as we have noted, the direct alkylation of benzene with propyl chlorideproduces considerable amounts of isopropylbenzene and polysubstitutionproducts:

propanoyl chlor ide propy l benzene


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22-4F Acylation "1053In the acylation of alkylbenzene the product almost always is the para

isomer. The synthesis of (4-tert-butylpheny1)ethanone illustrates this as well asthe sequential use of alkylation and acylation reactions:

Al-Hg CH,COClor AlC13-nitrobenzene >

AlCl, tert-butyl benze ne

COCH,(4-tert-butylpheny1)ethanone

Chemists are inclined to give names to reactions that associate them either withtheir discoverers or with the products they give. This practice can be confusingbecause many named reactions (or "name reactions") which once were thoughtto be quite unrelated, have turned out to have very similar mechanisms. Thuswe have two very closely related acylation reactions: one is the Friedel-Crafts

0ketone synthesis, in which the electrophile is R-C=O; and the other is the0Gattermann-Koch aldehyde synthesis, in which the electrophile is H -C=O:

The latter reaction utilizes carbon monoxide and HC1 under pressure in thepresence of aluminum chloride. The electrophile may be considered to beformed as follows:

Two reactions related to Friedel-Crafts reactions are illustrated in Exercises22-21 and 22-22.


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4054 22 Arenes. Electrophil ic A romatic Substi tut ion

Exercise 22-19 Anthraquinone can be synthesized from phthal ic anhydride andbenzene in two steps. The first step is ca talyze d by AICI,, the sec ond by fuming sul-fur ic acid. Write mechanisms for both reactions and suggest why fuming sulfur ic isrequired in the seco nd step but not in the f irst.

phthalic anhydride orfho- enzoyl benzoic acid

0anthraquinone

Exercise 22-20 Suggest possible routes for the synthesis of the following com-pounds:a. diphenylmethane from benzoic acid and benzeneb. 1-ethyl-4-methyl benzene from methyl benzeneExercise 22-21 a. Su bstitution of a chlorom ethyl grou p, -CH,CI, on an arom aticr ing is cal led c hloro m ethy lat ion and is accomp l ished using methanal, HCI, and ame tal-halide catalyst (ZnCI,). Write reas ona ble me cha nistic steps that co uld be in-volved in this reaction:

ZnClC6H6+ C H 2 0+ HCI ----A6H5CH2CI+ H 2 0b. Phenylmethyl chloride can be formed from benzene and chloromethyl methylether, CICH,OCH,, in the pres en ce of stan nic chlo ride, SnCI,. W rite reason able mecha -nistic steps, aga in s upp orted by an alogy , for this reaction. No tice that SnCI, is aLewis ac id .Exercise 22-22 The Ga tterm ann rea ctio n (not to be confused with the Gattermann-Koch aldehyde synthesis) introduces the H-C=O function into reac tive aromaticcom pou nds such as 2-naphthalenol. The necessary reagents are H CN , HCI, and ame tal-halide catalyst (ZnCI, or AICI,), and the initial p rodu ct must be treated with


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22-4G Sulfonation 1055water. Write a mechanism for this react ion that is supported by analogy to otherreact ions discussed in this chapter.

22-4G SulfonationSub stitutio n of the sulfonic acid (-S0,I-T) gro up fo r a hydroge n of an arom atichydrocarbon can be carried out by heating the hydrocarbon with a s l ightexcess of concentrated or fuming sulfuric acid :

H2:2?$3:3 ,0 enzenesulfon~c cia

The actual sulfonating agent normally is th e SO, molecule, which, a l thoughneutral, has a powerfully electrophil ic sulfur atom :

Sulfonation is revers ib le and the -S 0 3 H group can be removed by hydrolysisa t 180":0I/O H HO-S-OH

0I10


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1056 22 Arenes. Electrophilic Aromatic SubstitutionA useful alternative prep aration of sulfonyl derivatives is possible withchlorosulfonic acid:

benzenesulfonylch lor ide

Th is proced ure has an advantage ov er direct sulfonation in that sulfo nj~ l hlo-rides usually are soluble in organic solvents and may be easily separated fromthe reaction mixture. Also, the sulfonyl chloride is a more useful intermediatethan the sulfonic acid , bu t ca n be converted to the acid by hydro lysis if desired:

Sulfonation is important in the commercial production of an important class ofdetergents - he sodium alkylbenzenesulfonates:

sodium alkylbenzenesulfonatesurfactant (detergent)

The synthesis illustrates several important types of reactions that we havediscussed in this and previous chapters. First, the alkyl group R usually is aC,, group derived from the straight-chain hydrocarbon, dodecane, which onphotochlorination gives a mixture of chlorododecanes:

hvCI2H2,+ C12 --+ C12H25Cl+ HC1dodecane chlorododecanes(pr imary and secondary)This mixture of chlorododecanes is used to alkylate benzene, thereby giving amixture of isomeric dodecylbenzenes, called detergent alkylate:

0 C12H2&1 l 3 + HCIdodecy l benzene(detergent alkylate)


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22-4H Hydrogen Exchange 4 05'7Sulfonation of the detergent alkylate gives exclusively the 4-dodecylbenzene-sulfonic acids, which with sodium hydroxide form water-soluble dodecylben-zenesulfonates:

In many countries it is prohibited by law to market detergents of this type,which have highly branched alkyl groups. The reason is that quaternary car-bons and, to a lesser extent, tertiary carbons are not degraded readily by bac-teria in sewage treatment plants:

-CH2--C-CH2- quaternary carbon is not easi ly biodegradableI ZC/ \

Exercise 22-23 Show ex plic itly how an al kyl s ide cha in of al kyl benzenesulfonatescould be formed with a quaternary carbon, i f the C12alkane used at the start of thesynthesis contained any branched-cha in C12 somers.

22-4H Hydrogen ExchangeIt is possible to replace the ring hydrogens of many aromatic compounds byexchange with strong acids. When an isotopically labeled acid such as D,SO,is used, this reaction is an easy way to introduce deuterium. The mechanism isanalogous to other electrophilic substitutions:

0.'2.0. + DSO, t-lPerdeuteriobenzene3 can be made from benzene in good yield if a sufficientlylarge excess of deuteriosulfuric acid is used. Deuteration might appear to becompetitive with sulfonation, but deuteration actually occurs under muchmilder conditions.

T h e prefix per, as in perdeuterio- or perfluoro-, means that all the hydrogens have beenreplaced with the named substituent, D or F. Perhydro means saturated or fullyhydrogenated.


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1058 22 Arenes. Electrophilic Aromatic Substitution22-41 Aromatic Substitution by Electrophilic eta la ti on

Because metals are electropositive elements they can be considered potentialelectrophiles. Their reactions with arenes have been investigated most thor-oughly for mercury. Benzene can be substituted with HgX@derived from amercuric salt, HgX,, in the presence of an acid catalyst. The salt most com-

0Imonly used is mercuric ethanoate, Hg(OCCH,),. The catalyst is considered tofunction by assisting the generation of the active electrophile, HgX? Othermetals that may be introduced directly into an aromatic ring in this mannerinclude thallium and lead.

22-5 EFFECT OF SUBSTITUENTS ON REACTIVITY ANDORIENTATION IN ELECTROPHILIC AROMATICSUBSTITUTION

In planning syntheses based on substitution reactions of substituted benzenes,it is imperative to be able to pr edict in advan ce which of the available positionsof the ring are likely to be most reactive. This is now possible with a ratherhigh degree of certainty, thanks to the w ork of m any chem ists during the past100 years. F ew , if any other , problem s in organic chemistry have received somuch attention over so many years, and there are now sufficient data on theorientatio n and reactivity effects of ring sub stituents in electrophilic su bstitu-tion to permit the formulation of some very valuable generalizations.Basically, three experimen tal problems are involved in the substitutionreactions of arom atic com pounds: (1) proof of structu re of the isomers thatar e form ed; (2) determination of the percentage of each isomer formed, if theproduct is a mixture; and (3 ) m easurem ent of the reactivity of the com poundbeing su bstituted relative to som e standard substance, usually ben zene.


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22-5 Effect of Substitutents on Reactivity and Orientation in Electrophilic Aromatic Substitution 1059For benzenoid compounds, structures can be established by thehistorically important substitution method (Section 1 1F) or with the aid ofcorrelations between spectroscopic properties and positions of substitution,as we indicated in Section 22-3. Also, it is often possible to identify theisomers by converting them to compounds of known structure. For example,trifluoromethylbenzene on nitration gives only one product, which has beenshown to be the 3-nitro derivative by conversion to the known 3-nitrobenzoicacid by concentrated sulfuric acid:

T he ratios of isomers formed in substitution reactions can be determinedby spectroscopic means o r by the analytical separation methods discussed inSection 9-2. We mainly are concerned in this chapter with the reactivity andorientation observed in arom atic substitution.

22-5A The Pattern of Orientation in Arom atic SubstitutionThe reaction most studied in connection with the orientation problem isnitration, but the principles established also apply for the most part to therelated rea ctions of halogenation, sulfonation, alkylation, and acylation . Som eillustrative data for the nitration of a number of mono-substituted benzenederivatives are given in Table 22-5. Th e table includes the percentage of ortho,me ta, and pa ra isome rs form ed, along with their reactivities relative to benzen e.We s ee tha t the re is a wide range of reactivity according to the n atu re of the sub-stituent, and that the ortho , meta, and p ara positions a re not equally reactive.Although these substituent effects may appear complex, they are relatedclosely to the effects controlling the pattern of orientation in electrophilicaddition to substituted alkene s (Section 10-4), as will be explained in thefollowing section.

22-513 Electronic EffectsIt is helpful to c ons truc t an en ergy diagram for substitution by an electrophileX@ f a benzene derivative, CBH5Y,n which Y is a sub stituent group (Figure22-8). Th e ra te of substitution at a ny one position (w e have arbitrarily chosenin Figure 22-8 to compare the 3 and 4 positions) will depend on the height ofthe energy barrier between the reactants and the transition state. Effects thatact to lower the heights of the barriers increase the rates of substitution.Because the transition state and the positively charged intermediate for


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1060 22 Arenes. Electrophil ic Aromatic Substitut ionTable 22-5Orientation and Rate Data for Nitration of SomeMonosubstituted Benzene Derivativesa

OrientationRelative

Substituent, Y % ortho % meta % para reactivity

aThe data are representative but wil l vary to som e extent with the rea ctioncondit ions and nature of the substitut ing agent.

aromatic substitution have much the same energy, any effect that stabilizesthis intermediate is likely also to lower the energy of the transition state andincrease the rate of substitution. Thus under conditions of kinetic control thepreferred arene substitution prod uct, as in alkene addition, will be that derivedfrom the most stable of the possible intermediates. Therefore the problem ofpredicting relative rates and orientation in aromatic substitution becomes oneof deciding what factors are likely to stabilize or destabilize the variouspossible intermediates relative to on e another and t o the ground state.W e now can examine the structures of the three substitution intermedi-ates with a view to deciding how the substituent might affect their stability.According to the valence-bond me thod, the positive charge in the ring is dis-persed m ainly on alternate carbon s, as sh ow below.ortho scrbstitution


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22-5B Electronic Effects

reaction coordinateFigure 22-8 Energy diagram for the substitution of a compound C,H,Yin the 3 and 4 positions. It is assumed here that the relative rates aredetermined by differences in AH$ and not in AS*. Because AHf is lessthan AH;, substitution to give the 4-isomer is "kinetically preferred."

para substitution

me ta substitutionY Y

T h e subst ituen t Y should (and do es) exer t its electronic influence morestrongly from the ortho and para posit ions than from the meta posit ion be-cause Y in the o rtho and the p ara positions is close to a positively charged ringcarbon. This electronic influence will be stabilizing if I7 has a net electron-donating effect, and destabilizing if Y is electron withdrawing. A group canwithdraw electrons relative to hydrogen if it is more electronegative thanhydrogen and this is called the electron-withdrawing inductive effect (also


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$062 22 Arenes. Electrophilic Aromatic SubstitutionTable 22-6Orientation and Reactivity Effects of Ring Substituents

ortho-para-Orientation, ortho-para-Orientation, meta-Orientation,with activation with deactivation with deactivation

-NR2-NHCOCH3-alkyl (e.g., CH,)-aryl (e.g., C6H5)

see Section 18-2B). A group also can withdraw electrons by the resonanceeffect:

electron-withdrawinginductive effect electron-withdrawingresonance effect

Accordingly, substituents fall into one of the following categories.

Meta-d rect ing substi tuentsA ring substituent Y that is electron withdrawing relative to hydrogen and hasno capacity to donate electrons by a resonance effect will decrease the re-activity of C,H,Y, especially at the ortho and para positions. The result is asluggish reaction (deactivation) with substitution occurring preferentially atthe meta position. Substituents in this category are -NO,, --CF,, -CO,R,0-NR,, and so on (also see Tables 22-5 and 22-6). No groups are known thatdirect the electrophile to the meta position and, at the same time, make thephenyl derivative more reactive relative to benzene.


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22-5B Electronic EffectsOrtho-para d irectin g su bstituents

1. A ring substituent, -Y, that has an electron pair on the atom adja-cent to the ring gives ortho-para substitution in preference to meta substitution.The reason is that the intermediate can be stabilized by an electron-donatingresonance effect from Y that is effective from the ortho and para positions only:

This effect is made clear in the valence-bond structures for the ortho-parasubstitution intermediates from benzenol (phenol):

para substitution

Substituents of the type -Y include -OH, -OR, -SR, -NH,, andhalogens. Most of these groups also are electron withdrawing by an inductiveeffect that opposes their resonance effect. However, as we saw in the case ofalkene additions (Section 10-4C), even when -Y is an electronegative group,stabilization of the intermediate cation by donation of unshared electrons ofY : to the adjacent positive carbon more than compensates for the polar elec-tron-withdrawing properties of Y. Electron donation thus controls the orienta-tion. If, however, the group is strongly electron withdrawing (e.g., -Y =- , -C1, - r, -I), the reactivity of the compound C,H,Y may be reduced.Groups of this kind are ortho-para directing with deactivation.

But if the polar effect is not pronounced, then substitution can be power-fully assisted by the substituent. This is ortho-para direction with activationand is provided by groups such as -OH, -OR, -SR, and -NH,. A morecomprehensive list of substituents and their orientation effects is provided inTable 22-6.

2. When no important T-electron effect is possible, as with alkyl groups,the orientation effect of a substituent is controlled by its polar effect and thedegree to which it polarizes the bonding electrons of the ring. Alkyl groups


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4 064 22 Arenes. Electrophil ic Aromatic Substi tut ionactually are electron donating and therefore are ortho-para directing withactivation.

soSOB electron-donating polar or polarizabi l i ty effect3---, for Y less electron-att ract ing than carbo n/polar ized Y-C bond /C=

22-56 Steric EffectsT hu s far we h ave m ade no d istinction betwe en the reactivities of the ortho andthe para positions, yet they clearly are not equal. If they were equal, theortho:para ratio would be 2:P, thereby reflecting the fact that there are twoorth o positions but only on e pa ra position in monosubstituted benzenes. M ostsubstitution reactions favor the para product, sometimes by a considerableamount (see Table 22-5). A reasonable explanation is that ortho substitutionis subject to steric hindrance between the substituent and the entering group.tert-Butylbenzene, for example, gives much less ortho n itration than methyl-benzene (Table 22-5), thereby suggesting that the size of the substituent isimportant. Also, tert-butylbenzene gives no ortho alkylation with tert-butylchloride, suggesting that the size of the entering group is also important:

Exercise 22-24 Draw the structures of the intermediate cation s for nitration of nitro-benzene in the 2 , 3, and 4 posit ions. Use the structures to explain why the nitro groupis meta-orient ing with deactivat ion. Use the same kind of arguments to explain theorientation ob se rve d with -CF,, -CHO, -CH2CI, and -NH2 groups in electroph i l icaromatic substitution (Table 22-6) .


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22 Arenes. Electrophilic Aromatic Substitutionbecause of the deactivating effect of a nitro grqup. Also, the most likely positionof substitution should be, and is, ortho to the methyl group and meta to thenitro group:

When the two substituents have opposed orientation effects, it is not alwayseasy to predict what products will be obtained. For example, N-(2-methoxy-pheny1)ethanamide has two powerful o,p-directing substituents, -OCH, andNHCOCH,. Nitration of this compound gives mainly the 4-nitro derivative,which indicates that the -NHCOCH, exerts a stronger influence than-OCH,:

YHCOCH, NHCOCH,

Seemingly anomalous effects of substituents are known, but such effectsmay be due to equilibrium control. One example is the alumjnum chloride-catalyzed alkylation of benzene, which leads to the formation of a 1,3,5-trialkylbenzene in preference to the expected 1,2,4-isomer (see Section 22-4E).The preferred reaction occurs particularly readily because alkylation is revers-ible and because alkylation is one of the least selective of the electrophilicaromatic substitutions (considerable meta isomer is formed even under condi-tions where kinetic control is dominant). Equilibrium control, which favors the1,3,5-product rather than the less stable 1,2,4-product, becomes most evidentwhen the reaction time, the reaction temperature, and aluminum chlorideconcentration are increased. Another source of anomalous substituent effectsis discussed in the next section.

Exercise 22-29 Predict the favored position(s) of substitution in the nitration of thefollowing compounds:a. 4-nitro-1-phenyl benzene d. 1,3-dibromobenzeneb. 4-methyl benzenecarboxyl ic acid e. I - f luoro-3-methoxybenzenec. 3-methyl benzenecarboxyl ic acid f . 1,3-dimethylbenzene

22-7 IPS0 SUBSTITUTIONFor all practical purposes, electrophilic aromatic substitution is confined to thesubstitution of a ring hydrogen. Does this mean that an electrophile such as


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22-7 IP S0 S ubsti tut ion

NO,@ only attacks hydrogen-bearing carbons? What about substituted ringcarbons?

Electrophilic attack at methyl-bearing carbons, particularly in ortho- andpara-dimethylbenzenes, would appear quite reasonable because the electron-donating character of the other methyl group should activate the ring bystabilizing the intermediate ion:

CH, CH,Attaclc at the substituted (ipso) carbon evidently does occur, but it does notlead directly to substitution products because demethylation, unlike deprotona-tion, does not occur:

NO,

Instead, the nitro group changes positions to the neighboring ring carbon, whichthen can eliminate a proton to form a substitution product:

Because the product obtained indirectly (by ips0 substitution) is indistinguish-able from that expected by direct electrophilic attack at C2, it is not possible tosay how much, if any, product is formed by the ipso route in this reaction.

In general, orientation effects in the substitution of alkylbenzenes are compli-cated by ipso attack. For example, in the nitration of 4-methylisopropylbenzene(para-cymene) about 10% of the nitration product is 4-nitromethylbenzene:

(22-1)NO2

CH/ \ CH/ \ CH/ \CH, CH, CH, CH, CH, CH,para-cymene (10%) 3 (82%) 4 8%)


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22 Arenes. Electrophil ic Aromatic SubstitutionThe 4-nitromethylbenzene arises from ips0 attack of NO,@at the isopropyl-

substituted ring carbon. Unlike methyl, the isopropyl group is eliminatedrapidly a s propene. Can we say that the other products, 3 and 4, arise by directsubstitution? Evidently not, because nitration at 0" gives two other products,5 and 6, which must be formed by i p so attack at the ~nethyl-bearing arbon. Atlow temperatures, intermediate ion 7 is attacked by the weakly nucleophilicethanoate ion to give 5 and 6. Both of these adducts solvolyze rapidly in 78%sulfuric acid to give 3 only:

Exercise 22-30* a. In the nitration of para-cymene by ethanoyl nitrate in ethanoicanhydride, the observed product com posit ion at 0" is 41 % 5 and 6, 41 % 3, 8%4, and10% of 4-nitromethylbenzene. Use these results to determine the relative reac-t iv i t ies of the para-cymene ring carbons towards NO,? Give your answer relative toC3 as unity (C3 is the carbo n next to the isop ropyl gro up). Determine the relative re-activ i t ies based on the data obtained in Equation 22-1. How does neglect of ipsosubstitution affect calculation of relative reactivities of the ring carbons?b. Write a mechanism for the solvolytic conversion of 5 and 6 to 3.


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22-8 Subst itution React ions of Polynuclear Aromat ic H ydrocarbons22-8 SUBSTITUTION REACTIONS OF POLYNUCLEARAROMATIC HYDROCARBONSAlthough naphthalene, phenanthrene, and anthracene resemble benzene inmany respects, they are more reactive than benzene in both substitution andaddition reactions. This increased reactivity is expected on theoretical groundsbecause quantum-mechanical calculations show that the net loss in stabiliza-tion energy for the first step in electrophilic substitution or addition decreasesprogressively from benzene to anthracene; therefore the reactivity in sub-stitution and addition reactions should increase from benzene to anthracene.In considering the properties of the polynuclear hydrocarbons relativeto benzene, it is important to recognize that we neither expect nor find that allthe carbon-carbon bonds in polynuclear hydrocarbons are alike or correspondto benzene bonds in being halfway between single and double bonds.

ml naphthaleneanthracene

10

The 1,2 bonds in both napthalene and anthracene are in fact shorter than theother ring bonds, whereas the 9,10 bond in phenanthrene closely resemblesan alkene double bond in both its length and chemical reactivity.

Exercise 22-31 Draw the Kekule-type valence-bond structures for napthalene,anthracene, and phenanthrene. Est imate the percentage of double-bond characterfor the 9,10 bond of phenanthrene, assuming that each of the valenc e-bond structurescontributes equa lly to the h ybr id structure.


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4090 22 Arenes. Electrophil ic Aromatic Substitution22-8A Napthalene

Orientation in the substitution of naphthalene can be complex, although the1 posit ion is the most reactive. So m e examples follow.

\ 1-naphthalenesulfonic acid2-naphthalenesulfonic acid

Sometimes, small changes in the reagents and condit ions change the patternof orientation. One example is sulfonation, in which the orientation changeswith reaction tem perature. An oth er example is Friedel-Crafts acylation; incarbon disulf ide the major product is the 1-isomer, whereas in nitrobenzenethe m ajor product is the 2-isomer.Substitution usually occurs more readily at the 1 position than at the 2 posi-t ion because the intermediate for 1-substi tut ion is more s table than that for2-substi tut ion. The reason is that the most favorable resonance s tructures forei ther in termediate are thos e that have one f ~ i l l yaromatic r ing. We c an see that


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22-8A,B Naphthalene and Phenanthrene1-substitution is more favorable because the positive charge in the 1-substitu-tion intermediate can be distributed over two positions, leaving one aromaticring unchanged. Only one resonance structure is possible for the 2-substitutionintermediate that retains a benzenoid-bond arrangement for one of the rings.

less importantresonance structure

less importantmx resonance structureExercise 22-32 Devise an experiment that would establish whether the acylation ofnaphthalene in the 2 position in nitrobenzene solution is the result of thermodynamiccontrol of the orientation.Exercise 22-33 Predict the orientation in the following reactions:a. I-methylnaphthalene + Br, c. 2-naphthalenecarboxylic acid + HNO,b. 2-methylnaphthalene + HNO,

22-8B PhenanthreneThe reactions of the higher hydrocarbons with electrophilic reagents are morecomplex than of naphthalene. For example, phenanthrene can be nitrated andsulfonated, and the products are mixtures of 1- , 2-, 3-, 4-, and 9-substitutedphenanthrenes:

K positions of substitution of phenanthrene

However, the 9,10 bond in phenanthrene is quite reactive; in fact it is almost asreactive as an alkene double bond. Addition therefore occurs fairly readily;


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22 Arenes. Electrophil ic Aromatic Substi tut ionhalogenation can give both 9,lO-addition and 9-substitution products by thefollowing scheme:

22-8C AnthraceneAnthracene is even more reactive than phenanthrene and has a greater ten-dency to add at the 9,10 positions than to substitute. However, the additionproducts of nitration and halogenation readily undergo elimination to form the9-substitution products:

Exercise 22-34 Show how one can predict quali tat ively the character of the 1 ,2bond in acenaphthylene.

22-9 ADDITION REACTIONS OF ARENES22-9A Catalytic HydrogenationBenzenoid compounds are not readily converted to cyclohexane derivatives.Nevertheless, several addition reactions are carried out on an industrial scale.


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22-9 Addition Reactions of ArenesMen tion was m ade previously of the hydrogenation of benz ene to cycloh exanein the presence of a nickel catalyst:

Ni, 10 atmo+3H2500 '0The reaction is very important because cyclohexane is used widely as a sol-vent a nd also is oxidized to cyclohexanone, a n important intermediate in thesynthesis of hexanedioic (adipic) and azacycloheptan-2-one (caprolactam),which are used in the preparation of nylon (Section 24-3C).Other cyclohexyl compounds are obtained by catalytic hydrogenationof the corresponding benzene derivatives. Th us cyclohexanol is obtained frombenzenol, and cyclohexanam ine is obtained from benzenam ine (aniline):

H,, Pt, 20"0 H l C 0 2 H , H,O , H I 0benzenol cyclohexanol benzenamine(phenol) (aniline) cyclohexanamine(cyclohexylamine)

Naphthalene can be reduced more easily than benzene. With sodiumin alcohol, 1,4-dihydronaphthalene is formed. Catalytic hydrogenation givestetralin (1,2,3,4-tetrahydronaphthalene). urther reduction to give perhydro-naphthalene (decalin) can be achieved on prolonged catalytic hydrogenationat relatively high temp eratures and p ressures:

H 2 , N i140- 160"30 atm

H Z ,N i200, 100-300 atm >1,2,3,4-tetrahydronaphthalene(tetralin) bicyclo[4.4.0] decane(perhydronaphthalene, decalin)


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1074 22 Arenes. Electrophilic Aromatic SubstitutionPhenanthrene and anthracene are reduced readily to the dihydro level

by addition to the 9,10 positions. Further reduction of the terminal benzenerings is relatively difficult:

Na, C2H50H ocHoCH222-9B Reduction of Arenes w ith M etalsCatalytic hydrogenation of benzene cannot be stopped at cyclohexene orcyclohexadiene; it proceeds to cyclohexane. This is because the rate of thefirst addition step is much slower than of the subsequent steps:

0 >[o(fast),[o]fast)>0(slow)

(not isolated) (not isolated)

However, benzene and its derivatives can be reduced to cyclohexa-dienes by solutions of metals such as Li, Na, K, Zn, and Hg in a weakly acidicsolvent, such as liquid ammonia, amines, or ether-alcohol mixtures. Thisgeneral type of reaction is known as the Birch reduction after the Australianchemist, A. J. Birch. With benzene, reduction with metals leads to l,4-cyclo-hexadiene:


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22-9B Reduction of Arenes with MetalsThe initial step of the Birch reduction is an electron transfer to the lowestunoccupied molecular orbital of the benzene n- system (see Figure 21-5) toform a radical anion:

Subsequent steps include a sequence of proton- and electron-transfer stepsas follows:

Substi tuent effects observed for this reaction are entirely consistent with thosedescribed for electrophilic substitution and addition-only reversed. That is,the reactivity of an arene in metal reductions is increased by electron-with-drawing groups and decreased by electron-donating groups. Substituents thatcan stabilize the anion-radical intermediate facilitate the reduction (see Exer-cise 22-35).Reduction with metals in weakly acidic solvents is not restricted to

arenes. A useful related reaction reduces alkynes to trans-alkenes, and pro-vides a useful alternative to catalytic hydrogenation, which favors formationof cis-alkenes (Section 11-2A):

\H2, Pd, Pb, \ 1?="\H H

trans

cis


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4 076 22 Arenes. Electrophilic Aromatic Substitution

Exercise 22-35* Explain why sodium in l iquid ammonia reduces methoxybenzene(anisole) to 1 me thoxy -l,4-cyclohe xadien e, w hereas it reduces sodium benzoate tosodium 25-cy clohe xad ienecaTboxylate:

Exercise 22-36 Predict the Birch reduction products of the following reactions:Naa. anthracene-2 H 5 0 H Na, C2H 50Hc.* methyl benzene-H3(/)Nab. naphthalene-H3(/)Exercise 22-37* A side reaction when re ducing benzene derivatives to 1,4-cyclo-hexadienes with l ithium or sodium in l iquid ammonia is over-reduction to give cy-clohexenes. Addition of ethanol greatly reduces the importance of this side reaction.Explain what role ethanol plays in preventing over-reduction.

22-9C Halogen AdditionBenzene will add chlorine on irradiation with light to give the fully saturatedhexachlorocyclobexane as a mixture of stereoisomers:

T h e reaction is comm ercially important beca use one of the isomers is a potentinsecticide. Th e product is marketed as a m ixture of isomers in which the activeisomer (y) is optimally about 40% by weight. It has a variety of trade nam es:Fortified, BH C, Lindane, Gam me xane , Hexachlor .

active y isomer


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22-90 Cycloaddi t ion22-9D Cy cloadd t ionIn Chapter 13 we encountered the Diels-Alder reaction, which involves addi-tion of a reactive alkene (dienophile) to the 1,4 positions of a conjugated diene.Neither benzene nor naphthalene reacts significantly with dienophiles onsimple heating, but anthracene does react. Gycloaddition occurs between the9,10 positions:

cis-butenedioicanhydr ide(maleic anhydr ide)

Exercise 22-38 Neglect ing steric-hindrance effects use the stabil izat ion energiesin Table 21-1 (p. 985) to explain why cis-butenedioic anhydride adds more readilyto anthracene than to benzene and adds across the 9,10 posit ions but not the 1,4positions of anthracene.

Reactions in which the transition state has a smnllev volume than the reactantsare speeded up by an increase in pressure. This is the case with napthalene andcis-butenedioic anhydride. An 80% yield of adduct is obtained at 100" at15,000 atmospheres pressure, whereas at one atmosphere and 100, the yi ~ ldis only 10%.

100, 1 atm10%80%100, 15,000 atm

22-10 OXIDATION REACTIONSThe reagents usually employed for the oxidation of alkenes (e.g., CrO,,KMnO,, H202,Os04) normally do not attack benzene. At high temperatures,benzene can be oxidized to cis-butenedioic (maleic) anhydride by air with a


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1078 22 Arenes. Electrophilic Aromatic Substitutionvanadium pentoxide catalyst. Naphthalene can be similarly oxidized to1,2-benzenedioic (phthalic) anhydride:

cis-butenedioic anhydride(maleic anhydride)0

01,2-benzenedioic anhydr ide(phthalic anhydride)

Both anhydrides are prepared in this manner on a large scale for use in theproduction of ester polymers (Section 29-5A). Phthalic anhydride also is pre-pared by the oxidation of 1 ,2-dimethylbenzene:

Phthalic anhydride is used to make anthraquinone (Exercise 22-19) and tomake esters of phthalic acid, which are used widely to plasticize polymers.Ozonization of aroma tic hydrocarbo ns is possible. Benzene itself givesethane dial (glyoxal) :


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22-1 1 Sources and Uses of Aromatic Hydrocarbons 1079The double-bond character of the 9,10 bond in phenanthrene is particularlyevident in ozonization. This bond is attacked preferentially, which leads to theformation of a dialdehyde when the ozonide is reduced with iodide ion:

Exercise 22-39 What pro ducts would you expe ct to be formed in the ozonization ofthe fol lowing substances? Consider carefully which bonds are l ikely to be mostreactive.a. 1,2-dimethylbenzeneb. naphthalenec. acenap hthylene (see E xercise 22-43)

22-11 SOURCES AND USES OF AROMATICHYDROCARBONSBenzene and many of its derivatives are manufactured on a large scale for usein high-octane gasolines and in the production of polymers, insecticides, de-tergents, dyes, and many miscellaneous chemicals. Prior to World War 11,coal was the only important source of aromatic hydrocarbons, but during thewar and thereafter, the demand for benzene, methylbenzene, and the dimethyl-benzenes rose so sharply that other sources had to be found. Today, most ofthe benzene and almost all of the methylbenzene and the dimethylbenzenesproduced in the United States are derived from petroleum.

Coal tar, which is a distillate obtained in the coking of coal (Section 4-2), isa source of an amazing number of aromatic compounds. Some of these are listedin Table 22-7, which includes nitrogen, oxygen, and sulfur compounds, as wellas hydrocarbons. Although petroleum from some locations contains fairly sub-stantial amounts of aromatic hydrocarbons, it is not a principal source for suchcompounds. Rather, aromatic compounds are synthesized from the C,-C,,gasoline fraction from petroleum refining by a process referred to in the pe-troleum industry as catalytic re-forming or hydroforming.This involves heatinga C,-C,, fraction with hydrogen in the presence of a catalyst to modify themolecular structure of its components. Some amazing transformations take


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6080 22 Arenes. Electrophil ic Aromatic Substi tut ionTable 22-7P r i n c i p a l C o m p o u n d s O b t a i n e d f r o m C o a l Ta ra pb

naphthalene

fluorene

chrysene

1 methyl-naphthalene 2-methyl-naphthalene

anthracene

pyrene

acenaphthene

phenanthrene

fluoranthene

Ni t rogen compounds

azabenzene 2-methylazabenzene 3-methylazabenzene 4-methylazabenzene(pyr id ne) (a-pico l ne) (p-pico l ne) (Y-picol ine)

I -azanaphthalene(quinol ine)

H9-azaf luorene(carbazole)

9-azaanthracene(acr idine)


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22-11 Sources and U ses of Aromatic H ydroca rbonsOxygen and su lfur compoun ds

OHbenzenol 2-methy l benzenol 3-methy l benzenol 4-methy l benzenol(phenol) (ortho-cresol) (meta-cresol) (para-cresol)

CH32,5-dimethy l benzenol thiacyc lop enta- 1-naphthalenol 2-naphthalenol(para-xy lenol) diene (Inaphthol) (2-naphthol)

(and other xy lenols) ( thiophene)

"Com piled from Chem istry of Coal Uti l ization, National Research Cou ncil Comm ittee, H. H. Lowry(Ed.), John W iley and Sons, Inc., 1945.bNone of the comp ound s l isted are very abundant in coal tar. Even naphthalene, which is presentin the largest amount, constitutes only 10-1 1% of coa l tar."Benzene and the mono- and d imethy lbenzenes are present in very smal l amount (0.3% total)in coal tar.

place, and the C,-C, alkanes can be converted to cycloalkanes which, in turn,are converted to arenes. Benzene, methylbenzene (toluene), and the dimethyl-benzenes (xylenes) are produced primarily in this way:

rnethylcyclopentane cyclohexane benzene

rnethylcyclohexane methyl benzene(toluene)


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cyclohexane cyclohexanone cyclohexanoneI oximeCzH,6-hexanediamine, nylon 66hexanedioic acid(ad ip ic ac id)1 chlorobenzene phenol cyclohexanol

BENZENE benzenesulfonic bis-phenol A --+ epoxy, phenoxy resinsacid (paints, adhesives)T

I - al kyl benzenes~ R = c H ~ c H ~ ~0 - olystyrene and co polymers

/ (fi lms, m olded articles, syn-thetic rubbers, adhesives)ethenyl benze ne(styrene)

- lasticizers, pla stics (fi lms, mold ed articles)cis-butenedioic anhydride(maleic anhydride)


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22-1 1 Sources and Uses o f Aromatic Hydro carbo ns

I benzenemedicinals

polyurethanes(foams, mo ldedarticles)

NC O

METHYLBENZENE(toluene)

1,3-dicarbonylamino-4-methyl benzene(2,4-toluenediisocyanate)

benzoic acid> solvent

C H ~ CO, H1,4-DIMETHYLBENZENE 1,4-benzene-(para-xylene) dicarb oxyl c ac id(terephthal c acid)

Ic3 ac> > phth alic estersCH3 C (plasticizers),I polymers (resins and0 coatings)

1,2-DIMETHYLBENZENE 1,2-benzenedicarboxylic(ortho-xyl ene) anhy dride(phthalic anhydride)

Figure 22-10 lmportant chemicals derived from methyl-substitutedbenzenes

Much of the aromatic product obtained by catalytic re-forming is blendedwith other fractions from petroleum refining to give high-octane gasoline. Therest is separated into its component hydrocarbons, which then are utilized bythe chemical industry for the production of chemicals derived from benzene,methylbenzene, and the dimethylbenzenes, as summarized in Figures 22-9and 22- 10.

4 igure 22-9 lmportant chem icals deriv ed from benzene


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4084 22 Arenes. Electrophil ic Aromatic Substitution22-12 SOME CONJUGATED CYCLIC POLYENES22-1 2A AzuleneTh ere are several compo unds that possess som e measure of aroma tic charac-ter typical of benzene, but do not possess a benzenoid ring. Appropriately,they have (4n -t 2) n electrons and are classified as nonbenzenoid aromaticcom poun ds (se e Section 21-9). An example is azulene, which is isomeric withnaphthalene an d has a five- and a seven-mem bered ring fused through adjacentcarbons:

A s th e nam e implies, it is deep blue. I t is less stable than naphthalene, to whichit isomerizes quantitatively on heating abov e 350" in the absence of air:

Azulene has a significant polarity, with the five-membered ring negative andthe seven-membered ring positive. The structure can be represented as a hybridof neutral and ionic structures:

The polarization that has the five-membered ring negative and the seven-membered ring positive corresponds to ionic structures that have six (i.e.,4 n + 2) electrons in both the five- and seven-membered rings (Section 21-9B).

In keeping with its aromatic character and unsymmetrical charge distribution,azulene undergoes certain typical electrophilic substitution reactions at theI and 3 positions. Thus Friedel-Crafts acylation leads to a mixture of 1 -ethanoylazulene and 1,3-diethanoylazulene:

COCH, COCH,


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22-1 2 Some Conjugated Cyclic Polyenes 8 085Furthermore, in the presence of strong acids the 1 position is protonated togive a derivative of the relatively stable cycloheptatrienyl (tropylium) ion(Section 2 1-9B):

azulene(blue) azulenium ion(orange-yellow)

22-128 Cyclooctatetraene1,3,4,7-Cyclooctatetraene (or simply cyclooctatetraene) is a bright-yellow,nonplanar, nonaromatic compound (Section 21-9A). Apparently the resonanceenergy of a planar structure is insufficient to overcome the unfavorable anglestrain the planar structure would have with its C-C-C bond angles of 135".Cyclooctatetraene normally assumes a "tub" structure with alternating singleand double bonds:

planarThere is, however, nmr evidence that indicates that the tub form is in rapidequilibrium with a very small amount of the planar form at room temperature.There is about a 15-ltcal mole-l energy difference between the two forms. Thedication, C8Hg2@,nd the dianion of cyclooctatetraene, C8Hg2@, hich have(4n+2)n electrons, appear to exist in planar conformations (see Exercise 2 1-16,p. 996).

Cyclooctatetraene can be prepared readily by polymerization of ethyne inthe presence of nickel cyanide:

It could be manufactured on a large scale, but no large-scale commercial usesof the substance have yet been developed.The chemistry of cyclooctatetraene is interesting and unusual. Particularly

noteworthy is the way in which it undergoes addition reactions to form productsthat appear to be derived from the bicyclic isomer, bicyclo[4.2.0]2,4,7-octa-triene, 8. In fact, there is an electrocyclic equilibrium between cyclooctate-traene and 8 (Section 2 1- 1OD) and, although the position of equilibrium lies


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22 Arenes. Electrophil ic Aromatic Substitut ionfar on the side of cyclooctatetraene, 8 is more reactive and leads to the ob-served addition products:

1 [4 + 21 cycloadditioncis-butenedioic(maleic) anhydrideTreatment of the bridged dichloride with strong bases causes elimination ofhydrogen chloride and formation of chlorocyclooctatetraene:

The diverse ways in which cyclooctatetraene can react with a given reagentunder different conditions is well illustrated by the variety of products ob-tained on oxidation with mercuric ethanoate in ethanoic acid, methanol, andwater:

Efforts to prepare "pentalene," a bridged analog of cyclooctatetraene, havenot been very successful so far. A substance that appears to be a methylpenta-


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22-1 2C Annulenes 4087lene has been characterized at -180" by its spectral properties. On warmingto -1 05" it forms a dimer.

Exercise 22-40* The rate of the Diels-Alder addit ion between cyclooctatetraeneand tetracyanoethene is proportional to the tetracyanoethene concentration, [C,(CN),], at low conce ntrations of the ad de nd s but be co m es ind ep en de nt of [C,(CN),]at high concentrations. Write a me chan ism that acc ounts for this behavior.

Exercise 22-41" Write reasonable me chan isms for the different oxid ation reactionsof cyclooctatetraene with mercuric ethanoate in ethanoic acid, methanol, and watersolutions. No tice that com poun ds of the type Hg(OR), appe ar to a ct in some casesas @ OR -donat ing agents and also that the ox ide produ ced f rom cyclooctatetraeneand peroxyacids (Section 15-1 1C) rearranges readily in the presence of acids tophenylethanal.Exercise 22-42* The dianion C,HE2@,which corresponds to pentalene, has beenprepared and appears to be reasonably stable. Why may the dianion be more stablethan pen talen e itself? (See Se ction 21 -9B.)

22-126 AnnulenesCyclooctatetraene is nonplanar. One reason is that the angle strain is severe inthe planar form. Is it possible that larger-ring conjugated polyalkenes may havestrainless planar structures? Models show that a strainless structure can beachieved with two or more of the double bonds only in trans configurations,and then only with a large enough ring that the "inside" hydrogens do not inter-fere with one another.

In discussing compounds of this type, it will be convenient to use the name[nlanizulene to designate the simple conjugated cyclic polyalkenes, with nreferring to the number of carbons in the ring-benzene being [6]annulene.The simplest conjugated cyclic polyolefin that could have a strainless planarring containing trans double bonds, except for interferences between the in-side hydrogens, is [101annulene:


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22 Arenes. Electrophilic Aroma tic Substitut ionInside-hydrogen interferences are likely to be of some importance in allannulenes up to [30]annulene. Many annulenes have been synthesized byF. Sondheimer.

We have mentioned already (Section 22-3C) the large differences in nmrchemical shifts between the inside and outside hydrogens of [ 181annulene-substance which with 18 n- electrons should be aromatic by the 4n + 2 rule.These differences are observed only at low temperatures. The proton nmr spec-trum of [18]annulene at room temperature is a single resonance, which indi-cates that the inside (Ha) and outside (H,) hydrogens are equilibrating rapidly.This can take place only if cis-trans interconversion occurs about the doublebonds (marked c and t):

ande thersimilar

structures

At low temperatures, this equilibration is slow enough that separate groups ofresonances for the inside and outside hydrogens can be discerned in an nmrexperiment (see Sections 9-10C and 27-2).

A theoretical prediction that has been borne out by experiment is that anannulene with 4n n electrons should have a paramagnetic circulation of elec-trons- that is, opposite in direction to that shown in Figure 22-4 for benzene.For example, [16]annulene, which has 4n electrons, is not very stable andexists as a very rapidly interconverting mixture of two configurational isomers:

At very low temperatures (-155"), the proton nmr spectrum shows the innerhydrogens at 612.9-10.5 and the outer hydrogens at 65.7-6.4, which is inexactly the opposite order to the shifts observed with [18]annulene and theother known [4n + 21 n-electron annulenes.

The annulenes generally are not stable compounds, but the [4n +2 annulenesclearly show typical aromatic reactions. For instance [18] annulene has beenconverted to the nitro, ethanoyl, bromo, and carbaldehyde derivatives byelectrophilic substitution reactions.


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22-13 Fluxional Compounds 4089

Exercise 22-43* Predict which of the fol lowing com pound s may have some aromaticcharacter. Give your reasons.

acepl ieadylene

22-13 FLUXIONAL COMPOUNDSA number of compounds are known to rearrange from one structure to anentirely equivalent structure, sometimes with extraordinary facility. Such com-pounds are said to be fluxional to distinguish them from tautomers (whichusually involve rearrangements between nonequivalent structures). Simpleexamples are the Cope rearrangement of 1,5-hexadiene,

and the electrocyclic rearrangement of bicyclo [5.1 O] -2,5-octadiene,

If the two methylenes of 9 are bridged with two double-bonded carbons, weget the remarkable structure 10 , called "bullvalene," which rapidly intercon-verts amongst equivalent structures:

etc.

Equilibration of fluxional molecules must not be confused with resonance.In each electrocyclic reaction, the nuclei alter their positions as bond lengthsand angles change. Interconversion of fluxional molecules also must not be


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Supplementary Exercisesd. C,H,(NO,),, whic h ca n gi ve only two the oreti ca lly pos si bl e diffe rent ring mono -bromosu bstitution produ cts.22-46 Pred ict the most favora ble pos ition for mono nitration for each of the followingsubstances. Indicate whether the rate is greater, or less, than for the nitration of ben-zene. Give your reasoning in each case.a, fluorobenzene f. 4-bromo-1 -methoxyben zeneb. tr ifluoromethyl benze ne g. phenylsulf inyl benzene, C6H5SOC6H5c. phenylethanone h. I- tert-butyl-4-methyl benzened. phenylmethyldimethylamine oxide, 00

0 i. dip hen yliod on ium nitrate, (C6H5),I NO,C,H,CH,N(CH,),O @ j. 1,3-diphenylbenzene (meta-terphenyl)e. d iphenylmethane k. N-(4-phenylpheny1)ethanamide22-47 Ex plain why the brom ination of benzenamine (anil ine) gives 2,4,6-tribromo-benzenamine (2,4,6-tribromoaniline), whereas the nitration with mixed acids gives3-nitrobenzenamine (meta-nitroanil ine).22-48 Ex plain how co mp arison of the followin g reson ance structures for para sub-stitution with the corres pon ding ones for meta substitution may (or may not) lead tothe expectation that ortho-para orientation would be favored for the nitro, cyano, and-CH=CHNO, groups.

22-49 Starting with benzene, show how the fol low ing compou nds c ou ld be prepared.Specify the requ ired reagents and catalysts.a. 1-bromo-4-nitrobenzeneb. 4-isopropyl-3-nitrobenzenesulfonic ac idc. 4-tert- butyl ben zene carb aldeh yded. C,H5COCH2CH2C02He. 1,2,4,5-tetrachlorocyclohexane22-50 Offer a suitable ex plana tion of eac h of the following facts:a. Nitration of arenes in c oncentrated nitr ic ac id is retarded by added nitrate ions andstrongly accelerated by small amounts of sulfuric acid.b. Nitrobenzene is a suitable solvent to use in Friedel-Crafts acyla tion of benzenederivatives.c. Benzene an d other arenes usua l ly do not react with nuc leoph i les by either addit ionor substitution.


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4 092 22 Arenes. Electrophilic Aromatic Substitutiond. Pyridine is almos t inert to nitration with mix ed n itr ic a nd sulfur ic acids, a reactionthat proceeds read i ly with benzene.22-51 Indicate the structures of the major product(s) expected in the followingreactions:

a. (CH,),CH -0)t H, + CH,COCI AICI,cs2 >HCI

Ie. CH,CONH H~(CCH3)2 ,HCIO,

(T is ,H, or tritium)

AICI,g (-\>CH2CH,CH2COCl C S 2 r

22-52 Draw the structures of the products A, B, C , D in the stepwise reaction se-quences shown.

NHCOCH,1HNO, aq. H 2 S0 4H2SO4 ' heat >


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Supplementary Exercises

22-53 The pest icide DDT is made commercial ly by the react ion of chlorobenzenewith tr ichloroethanal (chloral) in the presenc e of an ac id catalyst (H2S 04).Show thesteps that are likely to be involved in this reaction:

(as hydrate) DDT

22-54 Hexachlorophene, the controversial germicide, is prepared from 2,4,5-tri-ch lorobenzenol (2 moles) and methanal (1 mole) in the presence of concentratedsulfuric ac id. Show the steps involv ed and the ex pec ted orientation of the substituentsin the f inal product.

I22-55 Trifluoroperoxyethanoic ac id, CF3-C-OOH reacts with methoxy benzene togive 2- and 4-methoxybenzenols:

Ex plain the nature of this reaction. What is likely to b e the subs tituting agent? Whatproducts w ould you expect from tri fluoroperoxyethanoic ac id and f luorobenzene?Would fluorobenzene be more, or less, reactive than methoxybenzene?22-56 Ethanoic anhydride reacts with concentrated nitric acid to yield the ratheruns table ethanoyl nitrate (acetyl nitrate), wh ich is a useful nitrating agent. Withmixtures of benzene and methylbenzene , ethanoyl nitrate produce s a mixture of nitro-benzene and 2- and 4-nitromethylbenzenes. When nitrated separately, each com-pound reacts at the same overall rate, but when mixed together, 25 times morenitromethylbenzene is formed than nitrobenzene.a. Write equations for the formation of ethanoyl nitrate and its use in nitration ofbenzene derivat ives.b. Cons ider p oss ible mec hanism s for nitrations with ethanoyl nitrate and show howthe abo ve observat ions w ith benzene and methylbenzene alone or in mixtures can berationalized by proper choice of the rate-determining step.


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1094 22 Arenes. Electrophil ic Aromatic Substitution22-57 4-Nitrome thyl benzen e-2,6-D2 ,s nitrated by a mixture of nitric an d sulfuric a cid sat the same rate as ordinary 4-nitromethylbenzene under conditions in which the rateof nitration v is g iven by v = k[nitrome thylbenz ene] [N O2 @ ]. Review Section 15-6B.)a. Explain what conclusion may be drawn from this result as to the mechanism ofnitration under these co

Bpo c Chapter 22

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