correlation between them The cations that are more readily hydrolysed show lower pH
values while the cations that hydrolyse with difficulty gave higher pH values This correlation
Cu(OTf)2 464 4 753 Y(OTf)3 445 6 770 Difficult to hydrolyse Er(OTf)3 559 0 790 La(OTf)3 564 8 850 Zn(OTf)2 540 2 896
The idea of invoking the hydrolysis constants may be useful but poses some problems if
applied in a simplistic fashion To simply write a pKh value for a given metal ion is to ignore
the potential effects of the counterion of that cation on the pKh value of that given metal
entity The pKh values cited in Table 46 are derived from previous work and were calculated
for a variety of metal salts including those of sulphates nitrates and chlorides These
constants would be useful for the particular metal with the particular counterions but not
As a case in point salts of Zn+2 (if we accept that pKh values hold for all salts of a given
metal) are difficult to hydrolyse since they present with a pKh value of 896 This would
equally hold true of salts of Li+ which have a pKh value of 1364 (It should be remembered
at this stage that the pKh values were determined primarily from sulphates nitrates and
chloride salts of these metals) No chemist with any experience of organozinc or
organolithium compounds would support the view that such compounds are difficult to
hydrolyse Indeed the opposite view would be held
The converse would be true of certain compounds of tin(IV) SnCl4 is correctly held to
hydrolyse rapidly In contrast Bu3SnOH used as an anti-foulant in paints for marine
structures including ships is sufficiently long-lived to be a marine pollutant that disrupts the
reproductive cycles of many marine organisms26 These simple examples exemplify the
stance that pKh values should be used judiciously in the interpretation of other chemical data
In the present work the readerrsquos attention is drawn to the entries for In+3 and Sc+3 In(OTf)3
and InCl3 give pH values of 28 and 43 while leading to hydrolysis of the silyl enol ether to
the extent of 59 and 6 respectively Exactly the opposite result is obtained for Sc+3 ScCl3
gives a pH of 25 and hydrolysis of the enol ether of 41 while ScCl3 gives a pH of 28 but
shows hydrolysis of the enol ether of only 6 These results taken together with the
arguments above clearly indicate the situation to be more complex than a simple reliance
upon a single parameter purports There is an equally strong if not stronger correlation
between pH and the extent of hydrolysis of the enol ether than there is when using the pKh
values but even here there are some results that are difficult to rationalise (see for example
the entry for Ca(OTf)2 in Table 46) where even at high pH values some hydrolysis takes
place In this instance it is quite possible that the use of a combination of Broslashnsted-driven and
metal-driven mechanisms is the best approach to rationalising the outcomes
433 The possible role of water in the Mukaiyama aldol reaction
In this study and others still to be reported many metal triflates are not only tolerant to water
but at least in some cases require the presence of water to operate efficiently Kobayashi
although never expressed in this way has alluded to the importance of water in the catalytic
activity of metal triflates and has specifically ascribed the effect to the water exchange
phenomenon While not in disagreement with this view the results of the present
152
investigation suggest a more complex situation with regard to the referred to water exchange
rate constant
Kobayashi2427a indicated that metal triflates that are good Lewis acid catalysts in aqueous
media have fast WERC (water exchange rate constants) In a mixture of THFwater the metal
will preferentially bind to the water molecules present and that these will rapidly exchange
on the metal with other water molecules This phenomenon is said by Kobayashi not to occur
or to occur to a much slower extent with coordinating solvents such as THF Due to the rapid
exchange of the water molecule on the metal there is a chance for an aldehyde to bind to and
be activated by the metal and for the aldol reaction to occur
Against this background Kobayashi ascribed the lack of reactivity in dry THF to the slow
exchange between the THF coordinated metal and the aldehyde This suggestion cannot go
unchallenged in view of the fact that other metal coordinating species less likely to participate
in ligand exchange on metal cations (eg diamines27b and crown ethers) do not suppress the
catalytic activity of metal triflates27c Furthermore it has been demonstrated that in aqueous
solutions of Eu(OTf)3 the Eu3+ ion remains fully or nearly full coordinated to water even with
less than 5 water in THF27d The effect of low water concentration could well be associated
with the incomplete dissociation of Eu(OTf)3 the same situation should apply to other metal
triflates However an alternative explanation is tentatively afforded namely that the water is
an essential reagent to drive the reaction to completion by removing the silyl group of the
immediate product (Scheme 411)
OSiMe3
O
R R
M
+
H2O
OSiMe3
RR
OM
O O
M
RR
O OHR
R
+ H+
Scheme 411 Mukaiyama aldol reaction showing silyl ether removed by water
In the absence of water the poorly nucleophilic triflate will have to act as a nucleophile to
remove the silyl protecting group but in the process TMSOTf will be generated However
this is a very active silylating agent In this case the reaction would be at best reversible It is
therefore suggested that water (or possibly metal bound water as M-OH or M-OH2) plays the
role of the Cl- ion in the well known TiCl4ndashcatalysed or related Mukaiyama reactions
(Scheme 412) In this regard it is of interest to note that the majority of metal triflate
153
catalysed reactions which appear to be significantly enhanced by the presence of water
involves reactions of enol ether silyl enol ethers in particular1
OSiMe3
MePh
Ph
PhCHO TiCl4 CH2Cl2
OMe
Ph Ph
SiMe
MeMe
O
H Ph
TiCl3Cl -Me3SiCl
Me PhPhPh
O OTi
ClCl Cl
H2O
Me PhPhPh
O OH
+
Scheme 412 The Mukaiyama aldol reaction
Even if the role of water is not directly involved in the immediate aldol reaction it must still
play a role in the hydrolysis of the metalated aldol product in order to return the metal to the
catalytic cycle
In order to further investigate the role of water THF was dried in the present study by
passing it over a column of activated alumina (see chapter 3 for details) The water content
was determined by Karl Fischer analysis and found to be 8 ppm The Lewis acids were dried
under vacuum at elevated temperature to remove water The aldol reactions were repeated
using the same conditions as before and to ensure that there was no influence from external
water the reactions were carried out in a glove box The results both in the presence and
absence of water are summarised in Table 47
Table 47 Yield () aldol reactions in dry THF
Lewis acid Yield () Aldol
THF H2O (91)
Yield () Aldol in dry
THF
La(OTf)3 92 35 Y(OTf)3 89 83
InCl3 89 44 Zn(OTf)2 77 0 Sc(OTf)3 96 0a Cu(OTf)2 94 35
a Sc(OTf)3 polymerised the THF No desired reaction was detected
154
The question immediately arises whether this dramatic decrease in yield may be due to poor
solubility in dry THF Kobayashi made no comment in this regard In the present study it was
found that the effect could not be ascribed to low solubility since the metal triflates in
question displayed sufficient solubility in THF
(It is interesting to note that many metal triflates promote polymerisation of THF and that
such solutions cannot be kept for long periods of time This fact was included in the design of
these experiments and fresh solutions were always prepared)
Dichloromethane is a non-coordinating solvent and therefore even in the absence of water
this solvent should leave the metal open to the aldehyde for coordination and activation
(polarisation) for the aldol reaction to take place This would be in contrast to Kobayashirsquos
comments relating to the THF inhibiting such coordination in dry THF To determine if the
WERC was the only critical factor in these reactions the DCM was dried by passing it over a
column of alumina and Karl Fischer titration determined the water content to be only 2 ppm
The aldol reactions in this solvent were carried out in a glove box to prevent the ingress of
atmospheric water (Table 48)
Table 48 Yield () aldol reactions carried out in dry DCM
Lewis acid Yield () Aldol
La(OTf)3 lt1 Sc(OTf)3 lt1
InCl3 lt1 Cu(OTf)2 lt1 Zn(OTf)2 lt1
The virtual total unreactivity in this medium could not be ascribed solely to the insolubility of
the triflates in the DCM It is true that most metal triflates have limited solubility in this
solvent but it has been used successfully in related reactions28 where lower solubility resulted
in lower reactivity but not in the cessation of reactivity
From these results it is clear that it is not only the WERC that is playing a role in these
reactions although this concept canrsquot be altogether discounted as being partly determinative
of the success of the reaction at this stage When these reactions are carried out in a dry non
binding solvent DCM which for all intents and purposes contains no water the aldehyde
155
should be free to bind to the metal of the triflate However the reaction does not proceed It
would appear that water plays an important and possibly different role from that implied by
invoking the WERC concept in these reactions It has already been indicated earlier in this
thesis that it may be an essential ingredient in the reaction medium In order to ensure the
success of the reaction
To ensure that the binding of the aldehyde takes place in DCM (a prerequisite for the aldol
reaction to take place) NMR experiments were carried out The chemical shifts of
benzaldehyde were determined in CD2Cl2 (Figure 44) The respective metal triflates and
chlorides were then added to the benzaldehyde DCM mixture Any change in the chemical
shift of the signals in the spectra provides an indication of coordination The NMR samples
were made up in the glove box using dry CD2Cl2 (dried by passage over activated alumina)
and the Lewis acids were pre-dried under vacuum at elevated temperature to remove water
H
O
1001
788764755
Figure 44 Benzaldehyde showing 1H chemical shifts in CD2Cl2
Table 49 Change in chemical shift of benzaldehyde on complexation of metal triflate
Lewis Acid
Δδ H aldehyde
Δδ Ortho
protons
Δδ Para
protons
Δδ Meta
protons 1001 788 764 755
Sc(OTf)3 -0033a 0109 0108 0044
ScCl3 0054 0093 009 0029
In(OTf)3 -0015a 016 016 007
InCl3 0507 012 012 0064 aNegative values indicate an upfield shift
The results from the 1H NMR data (Table 49) not only provide direct evidence of metal
triflate solubility but also indicate that the aldehyde does in fact bind the metals in DCM In
all cases we see a shift in the 1H NMR spectra when the metal triflate or chloride is added to
the benzaldehydeDCM mixture indicating complexation of the metal This complexation
should in turn activate the aldehyde towards nucleophilic attack and the aldol reaction should
proceed (Figure45)
156
R1
CHR2
OSiMe3
H
O
M(OTf)3
δ
δ
Figure 45 Activation of benzaldehyde by metal triflate
It is of interest to note that on the addition of the metal salts to the aldehyde a single sharp
aldehyde peak (shifted from its original position as shown in Figure 46) is observed rather
than two peaks representing the complexed and uncomplexed aldehyde respectively (Figure
47)29 This situation points to the presence of only a single type of species in solution
(bound aldehyde) but may also represent the presence of rapid exchange of bound and free
aldehyde as shown pictorially in Figure 48 Low temperature NMR may have resolved this
question but was not pursued due to solubility problems (See chapter 5 for further discussions
on NMR) Any reduction in reaction rate in this solvent is unlikely to be due to exchange
phenomena
Figure 46 1H NMR of benzaldehyde complexed to ScCl3
157
Figure 47 NMR peaks showing the difference between fast intermediate and slow exchange
of ligands
Also noteworthy is the effect of the different Lewis acids on the aldehyde proton Both of the
metal triflates shift the aldehyde proton downfield the change in the shift is small Contrary
to this the metal chlorides shift the aldehyde peak upfield and the change in shift is much
greater this is possibly due to the chlorine atom interacting with the aldehyde proton this
would not occur with the oxygen atom of the triflate as it is electron deficient
44 A perspective of metal triflates in organic solvents
At this stage of the discussion it is important to give consideration to the manner in which
ionic compounds dissolve in organic solvents which vary widely in terms of polarity
dielectric constants and co-ordination abilities to metals
158
441 On solvation of the metal triflates in dry organic solvents
Judging by their high melting points and ease of dissolution in water it is reasonable to
assume that most metal triflates are ionic compounds The heat of solvation (qmx) of such
compounds in water will be given by equation 4130
qmx = umx ndash (wm ndash wx) eq 41
Where
umx = the energy required to convert the ionic lattice into separate ions
wm = the energy released on solvation of the cation
wx = the energy released on solvation of the anion
The lattice energy of umx of metal salts of the type MX2 is extremely high (in the region of
500ndash700 KCalmol-1 range) This will ensure relatively low solubility in organic solvents with
low polarity (and therefore low dielectric constants) Even here ion associations rather than
free ion pairs will be obsereved30 which decreases the potential energy of ions in solution31
In fact association between cations and anions in solution (close ion cluster formation) has
been shown to be magnitudes higher in solvents with intermediate to low dielectric constants
such as acetone (22 є) than in solvents with high dielectric constants such as
dimethylsulfoxide (472 є) (Table 410)
159
Table 410 Dielectric constants of several organic solvents
Solvent Dielectric constant (є)31
Water 79
Dimethyl sulphoxide 472
Acetonitrile 375
Methanol 315
Ethanol 242
Acetone 22
Chlorobenzene 56
Tetrahydrofuran 76
Ether 45
Benzene 23
Pentane 18
The clusters will (because of lower potential energy) have considerably less polarising ability
(compare I and II Figure 48) for activating ligands (aldehydes) than the corresponding fully
charged metal species (irrespective of which solvent molecules are associated with the cluster
or free metal cation respectively) Furthermore the metal in the cluster is shielded from the
ligand by the close association of anions30
OH
OH
M3+M OTfTfO
I Cluster (close ion pair) II Free ion
OTf M OTf M OTF
Quadruplet
3+
OTf M OTfTriplet
-
Examples of close ion pairs
Figure 48 Possible cluster formations versus free ion formation of metal triflate in organic
solvents
Even solvents with some coordinating properties (eg nitromethane and acetonitrile
preferred solvents for metal triflate catalysis) are poor solvents for most ionic compounds In
these cases there will remain a tendency to form clusters of close ion pairs (eg -+- +-+ +-+
+-+- +-+- etc)32
160
Furthermore solvents with a low dielectric constant have a low capacity for supporting
charge separation which is a necessary consequence of polarisation This is the reason for the
exceedingly large differences in rates of some SN2 reactions (Scheme 413) between neutral
species in different solvents31 This will also apply to the polarisation of aldehydes and the
likes thereof by Lewis acids
Et3N + CH3Iδ δ
Et3NMe IEt3N Me I Scheme 413 Typical SN2 reaction
Table 411 Rate of SN2 reaction in Scheme 413 in different solvents
Solvent Dielectric
constant (є) Rate (Ks )
Hexane 20 1
Chlorobenzene 56 1200
Acetonitrile 375 12000
In summation then the activation (polarisation) of aldehydes or related compounds by Lewis
acids in solvents of low dielectric constants and low coordinating ability can be expected to
be limited Secondly through the shielding effect of the counter ions of the clusters the rate
of exchange of the ligands (such as aldehydes) in the bulk solvent and the inner metal of the
clusters where interaction with the metals can take place will be slower
MSn OH
+ MSn-1
O
H
+ S eq 42
MnXm
P
OH
+
ClusterP = net charge
MnXm
PO
H
MnXm-1
P+1O
H
+ x-1
Aldehyde inbulk solvent eq 43
Scheme 414 Activation of the aldehyde by the Lewis acid in dry organic solvent
161
Thus according to Kobayashi the slow exchange seen in equation 42 (Scheme 414) accounts
for his results and the slow exchange seen in equation 43 (Scheme 414) would account for
the results seen in the present investigation However as is clear from the foregoing poorly
catalysed reactions are not necessarily due to slow exchange between the ligand and the
solvated metal The decrease in the reaction rate may not be due to a simple solvent
exchange but may in contrast be rationalised on the basis of solvent-induced cluster or tight
ion-pair formation
442 The possible role of water in organic solvents
One now has to consider the effects of the small amounts of water in the organic solutions of
the metal triflates Due to its high dielectric constant and significant coordinating ability to
metal ions it is expected that water would have a dramatic effect on the properties of the
solutions It will quickly result in the solution of the metal ions and dissociation of the
lsquoclustersrsquo into smaller units eventually to close ion pairs and then eventually to free solvated
ions
Kobayashirsquos results26 suggest that this occurs with the rare earth metal triflates at around 50
equivalents of water This assertion is based on the assumption that optimal catalytic activity
will be reached at the maximum degree of dissociation of the solute (triflate)
Along the way the Lewis acid capability of the metals is increased provided that rapid
exchange between the free aldehyde and the solvated metal can occur It is reasonable to
suggest that this rapid exchange will be possible with metals that can change their
coordination number over a wide range as is the case with the rare earth metals which have
coordination spheres of up to 12 ligands
One aspect of metal triflates which has to be addressed now is its possible source of Broslashnsted
acidity in protic solvents It is known that many higher valent metal species associate with
water or other protic solvents to generate Broslashnsted acids of varying acid strength (Scheme
415)34
162
M+n + H2O M(H2O)x
+n
M(H2O)x-1OH+n-1
+ H+
Broslashnsted acid
Kh
Scheme 415 Formation of Broslashnsted acidity through polarisation of water by a Lewis acid
These can be differentiated by different Kh values24 In a case where the Kh value is high the
question arises to what extent the metal salt will act as a Lewis acid and to what extent does
Broslashnsted acidity play a role (As has already been argued however one must exercise
caution when using an hydrolysis constant since amongst others the counter ion on the
metal plays an important role in the rate of hydrolysis) Other workers1112 claim that it is
possible to distinguish between these possibly by ascertaining the effect of an added hindered
base on the reaction rate
This attempt at rationalisation was aimed at indicating that Lewis acid acidity and catalytic
activity are complex phenomena that depend on many factors the presence of water in
particular
45 The case for 26-di-tert-butyl-4-methyl-pyridine From the results discussed earlier it is unlikely that the Mukaiyama aldol reaction is mainly
Broslashnsted acid catalysed since Broslashnsted acids so readily hydrolyse the enol ethers However
if the hindered base is added to the reaction medium one can expect that the Broslashnsted
acidityactivity will be suppressed allowing the reaction to proceed under Lewis acid
conditions
Therefore addition of the base to the reaction medium should have one of two effects 1) no
effect on the reaction where Lewis acids are almost exclusively present and 2) allow the aldol
reaction to proceed where previously the silyl ether was destroyed by Broslashnsted acidity
The Mukaiyama aldol reactions were therefore carried out in the presence of 26-di-tert-
butyl-4-methylpyridine (Table 412) Surprisingly the addition of the base generally resulted
in a rapid reduction of the reaction rate
163
Table 412 Yield () aldol reactions carried out in the presence of DTBMP
Lewis acid
Without
DTBMP
Yield ()
Aldol
15 eq
DTBMP
Yield ()
Aldol
50 eq
DTBMP
Yield ()
Aldol
La(OTf)3 92 0 0
Sc(OTf)3 96 79 50
InCl3 89 99 0
Cu(OTf)2 94 65 0
Clearly the effect of the hindered base cannot be ascribed simply to the action of a proton
scavenger As stated earlier other authors also neglected to take into account the possible
interaction of the base with the protic solvent (Scheme 416) The base (nucleophile)
generated in this equilibrium will undoubtedly deactivate the Lewis acid present
N+ ROH
NH
+ RO
Scheme 416 Interaction of DTBMP with protic solvent to form nucleophile
Solutions of THFH2O (91) and metal triflates (in the same ratio as was used in the aldol
reactions) were made up and the pH measurements taken after which 15 equivalents of the
hindered base DTBMP were added to and the pH measurements were again recorded The
results are summarised in Table 413 The aqueous solutions of THF and triflate exhibit
higher pH values when large excesses of the base are added (15 equivalents)
Table 413 pH measurements of Lewis acids in THFH2O with and without DTBMP
Lewis acid pH in
THFH2O (91)
pH in THFH2O
(91) and 15 eq
DTBMP
La(OTf)3 629 678 Al(OTf)3 294 357 Sc(OTf)3 212 327 Cu(OTf)2 443 506
164
These results (Table 413) indicate that because of the lower basicity of this sterically
hindered base (see Figure 41) it is difficult to suppress the Broslashnsted acidity completely using
15 equivalents thereof This apparently explains why Barrett and others were required to use
such large excesses of the base (up to 1000 equivalents in some cases) However the
possibility at these large excesses of base that the solution will become alkaline particularly
in the case of metals with low Kh values was not considered
46 Summary
So far the investigation strongly suggested that some of the metal triflates formed a type of
Broslashnsted acidity in the presence of water in organic solvents These triflates cannot be used in
the aldol reaction because of their rapid destruction of the silyl ether Other metal triflates
with relatively low Kh values however effectively catalyse the aldol reaction On the other
hand these metal triflates are not only water tolerant but are particularly water dependent for
their successful catalysis Specifically the present study on the Mukaiyama aldol reaction
showed that without a certain amount of water present which has been shown to form an
amount of Broslashnsted acid the reactions do not proceed in both coordinating (THF) and non-
coordinating (DCM) solvents
47 Carbocation formation
471 Carbocation formation in wet and dry solvents
The formation of retinylic carbocations in a number of solvents was studied by Blatz and
Pippert35 By using low temperatures (between -35 degC and -50 degC) and rapid handling they
were able to detect the carbocations of retinyl acetate and retinol in a number of solvent-
Broslashnsted acid systems Treatment of retinyl acetate or retinol with a Broslashnsted acid results in a
carbocation being formed this carbocation is a characteristic blue colour and can be easily
measured using UVVis spectrophotometry (Scheme 417) They found the λmax of the cation
to be solvent dependent
165
Retinyl acetate
O
O
H+O
OH
CH2+ HO
O
Acetic acidCarbocation
Scheme 417 Carbocation formation using retinyl acetate
Barrett et al12 then used the same protocol in his study of resorcinarenes In their study they
used retinol as the probe and found that [Yb(H2O)9(OTf)3] produced carbocations in THF
when AcOH and PhCO2H were added but not when resorcinol was added TfOH gave
carbocations and surprisingly so did [Yb(H2O)9(OTf)3] in MeNO2 in the absence of any
additives The conclusion drawn from the study was that the action of [Yb(H2O)9(OTf)3] on
the resorcinarene was the result of Broslashnsted acidity
To further investigate the role of water in metal triflate catalysed reactions and the possible
formation of Broslashnsted type acidity in the present study the reaction of retinyl acetate and
acid was explored This reaction was used in order to determine if solutions of the metal
triflates in organic solvents form a type of Broslashnsted acidity in the presence of water
In order to establish a working protocol experiments were initially carried out using Broslashnsted
acids A 22 x 10-5 M solution of retinyl acetate in ether was prepared and cooled to -50 degC in
an acetone dry ice bath to mimic Blatz and Pippertrsquos conditions35 The reactions are
performed at this temperature in order to prolong the lifetime of the carbocations35 At room
temperature the lifespan of the carbocation is so fleeting that spectrophotometric
measurements would be impossible35 In the present instance nitrogen was continuously
flushed across the optics of the spectrophotometer and the cells to eliminate condensation
The retinyl acetate was added first to the quartz cuvette and then the acid under investigation
was added A UVVis spectrum of the untreated solution of retinyl acetate shows its
characteristic absorption peak at around 289 nm (Figure 49) The Broslashnsted acids were then
added to fresh retinyl acetate solutions and their spectra were recorded The UVVis scans
were run over a period of time to ensure that the whole life-span of the carbocation was
166
recorded Carbocations were successfully formed using methanesulfonic acid triflic acid and
p-toluenesulfonic acid (Table 414)
Figure 49 UVVis scan of retinyl acetate and its corresponding carbocation showing the
typical wavelengths and colours of the solutions
Table 414 Variation of λmax and absorptivity of the retinyl carbocation
Acida Solvent λ max Absorption
Methanesulfonic acid Ether 604 0205
Triflic acid Ether 600 0491
p-Toluenesulfonic acid Ether 599 0151 a 50 uL of the acid were added to the 3 mL of retinyl acetate solution
The results show the characteristic wavelength of the retinylic carbocation which absorbs at
around 600 nm (Figure 411) Blatz35 showed the wavelength of the maximum absorption
(λmax) to be a slight function of the solvent it did not deviate more than a few nm to either
side of this wavelength
To determine if the metal triflates would yield carbocations on addition of the retinyl acetate
they had to be dissolved in a non protic solvent in order to eliminate any proton source The
metal triflates were found to be relatively soluble in nitrobenzene This was established after
much trial and error involving a large number of solvents
167
As a visual test Al(OTf)3 dissolved in nitrobenzene was added to a solution of retinyl acetate
which immediately turned blue Interestingly the carbocation was sustainable at room
temperature for several minutes This was in contrast to previous work which indicated that
low temperatures are imperative to the longevity of the carbocation This is possibly due to
the cation being stabilised by the solvating effects of the nitro groups (Figure 410)
N
NO
O
O
O
Figure 410 Solvation of carbocation by nitrobenzene
Encouraged by these results the same visual tests were carried out using In(OTf)3 Hf(OTf)4
Yb(OTf)3 and Sc(OTf)3 All of these metal triflates tested formed sustainable carbocations in
nitrobenzene from retinyl acetate at room temperature
In order to carry out the investigation in a more quantitative manner Al(OTf)3 was chosen
because of previous successes that had been realised in the present study with this metal
triflate
Karl Fischer titration showed that the nitrobenzene used thus far from the bottle (Aldrich
product) contained 352 ppm of water The aim of the experiments was to determine whether
Al(OTf)3 formed the carbocation through the formation of Broslashnsted acidity The experiments
were to be repeated in the presence of the sterically hindered base DTBMP as a test for
Broslashnsted acidity Additionally the solvent would be dried as much as possible in an attempt
to prevent the formation of water promoted Broslashnsted-type acidity by the presence of water
Stock solutions of the retinyl acetate Al(OTf)3 DTBMP and triflic acid were made up in
nitrobenzene 15 mL of the retinyl acetate solution were added to the quartz cuvette To this
was added the solution either of the Lewis acid or Broslashnsted acid (Table 415)
168
Table 415 Results of carbocation formation in nitrobenzene
Solution Additive C+ formation Absorption
Retinyl acetatea Al(OTf)3d Positive 0314
Retinyl acetateb TfOHe Positive 0810
Retinyl acetate +
DTBMPc TfOH Negative 0
Retinyl acetate +
DTBMPc Al(OTf)3 Negative 0
a Retinyl acetate solution 10 M b Retinyl acetate solution 0001 M c DTBMP solution 3 molar equivalents per acid added
dAl(OTf)3 solution 01M e TfOH solution 001 M
Carbocations were formed when the Al(OTf)3 or the triflic acid solutions were added to the
retinyl acetate stock solutions (Table 415) The intensity of the carbocation formed with the
triflic acid was much greater than that formed with Al(OTf)3 especially considering that the
solutions used for the triflic acid experiments are far more dilute than those used in the
Al(OTf)3 experiments (0001M versus 10 M retinyl acetate respectively) This is to be
expected if the formation of the carbocation from the Al(OTf)3 is due to Broslashnsted acidity by
hydrolysis
In the next series of experiments the sterically hindered base was added to the reaction and
mixtures no carbocations are formed with either the triflic acid or the Al(OTf)3 This strongly
suggests that the metal triflate is forming a Broslashnsted-type acid in the presence of water
Pleasingly unlike previous work that had been carried out using this hindered base12 only
three equivalents of DTBMP had to be added before the reaction was quenched
However to be absolutely sure that the carbocations were being formed due to Broslashnsted
acidity the next step was to remove the water and thus the source of the protons from the
solvent The nitrobenzene was dried by passing it through a column of activated alumina and
the water content was determined by Karl Fischer titration to be 3 ppm The stock solution of
retinyl acetate was made up to the same dilutions as before However it was found that the
Al(OTf)3 was now insoluble in the dried nitrobenzene Even after vigorous stirring and mild
heating the Al(OTf)3 powder remained at the bottom of the volumetric flask This was not the
only instance of solubility problems with metal triflates in non-polar in particular in dry
non- polar solvents
169
Little information could be found on the solubilising effect of small amounts of water on
metal triflates in non-polar organic solvents It is reasonable to assume in view of earlier
discussions on the solvation of ionic compounds in organic solvents that small amounts of
water through solvation of ions will increase the solubility significantly In this regard it
may be of importance to note that the following general observation was made in all of the
relevant experiments in this study addition of the functionalised substrate such as the
aldehyde to the non-polar organic solvents resulted in the dramatic increase in the solubility
of the metal triflates It is suggested that the solvationligation of ions (cations in particular)
by functionalised substrates may be responsible for this phenomenon
A series of other dry non protic solvents was evaluated for the purpose of carrying out this
reaction with Al(OTf)3 The metal triflate has a very limited solubility in non-coordinating
solvents making the choice of solvent very difficult However ionic liquids with a non-
coordinating counter ion were considered to be a potential solution to this problem For this
1-butyl-3-methylimidazolium triflate ([bmim][OTf]) was prepared (Figure 411)
N+ N
-OTf416
Figure 411 1-butyl-3-methylimidazolium triflate ([bmim][OTf])
The ionic liquid was prepared in the following way 1-chlorobutane and N-methylimidazole
were heated at 80 degC for 48 hours The resultant ionic liquid was then washed with ethyl
acetate to remove any unreacted starting material (the ionic liquid is immiscible with ethyl
acetate) The residual solvent in the ionic liquid was then removed under vacuum to yield 1-
butyl-3-methylimidazolium chloride ([bmim][Cl]) an ionic liquid An excess of LiOTf was
then added to this ionic liquid of [bmim][Cl] in water and the solution was allowed to stir for
24 hours in order for an ion exchange reaction to take place between the -Cl and the -OTf The
mixture was extracted with ethyl acetate and the residual solvent was removed under vacuum
Water and an excess of NaOTf was then added resulting in a biphasic system namely the
ionic liquid [bmim][OTf] and an aqueous solution of NaCl and excess NaOTf After 12
hours the aqueous layer was separated from the ionic liquid which was then dried under
vacuum at 80 degC for 72 hours
170
Karl Fischer titration of the [bmim][OTf] determined the water content to be 845 ppm water
The Al(OTf)3 readily dissolved in the ionic liquid However unexpectedly all attempts to
form carbocations in the ionic liquid failed The failure to generate Broslashnsted acidity in this
wet solvent may be due to the common ion effect in this case the triflate counter ions of the
ionic liquid (Scheme 418) which may suppress Broslashnsted acid formation by competing with
water molecules for coordination
Al(OTf)3 + H2O Al(OTf)2(OH) + OTf- + H+
BA OTf-
Al(OTf)3
BA =Al(OTf)3K
OTf-
α1
OTf-
K =
Scheme 418 Common ion effect on Al(OTf)3 in [bmim][OTf]
Al(OTf)3 was found to have some solubility in DCM A mixture of DCM and Al(OTf)3 was
allowed to stir at 35 degC overnight to generate a saturated solution after which it was allowed
to cool and the undissolved triflate settled to the bottom of the volumetric flask An aliquot of
the supernatant (5 mL) was measured out and the solvent removed under vacuum The
Al(OTf)3 that remained was weighed and it was found that 25 mg of Al(OTf)3 was soluble in
5 mL of DCM
Using this information stock solutions of Al(OTf)3 retinyl acetate DTBMP and triflic acid
were made up in DCM Karl Fischer titration determined the water content of the DCM from
the bottle to be 24 ppm UVVis spectrophotometry experiments were carried out as before
(Table 416)
171
Table 416 Results of carbocation formation in DCM
Solution Additive C+ Formation Absorption
Retinyl acetatea Al(OTf)3d Positive 174
Retinyl acetateb TfOHe Positive 317
Retinyl acetate +
DTBMPc TfOH Negative 0
Retinyl acetate +
DTBMPc Al(OTf)3 Negative 0
a Retinyl acetate solution 001 M b Retinyl acetate solution 0001 M c DTBMP solution 3 molar equivalents as per acid
added d Al(OTf)3 solution 001M e TfOH solution 0001 M
Carbocations were formed when Al(OTf)3 or triflic acid were added to the retinyl acetate
solutions As was the case with the nitrobenzene solutions the intensity of the cation formed
with the triflic acid was greater than that formed with the Al(OTf)3 (Figure 412) When
DTBMP was added to the solutions no carbocation formation is seen in either case
The DCM was dried by passing it over a column of alumina that had been activated in an
oven at 250 degC for 24 hours Karl Fischer titration was then carried out on the DCM and the
water content was found to be 2 ppm The corresponding stock solutions as previously were
made up To ensure that no atmospheric water found its way into the samples all work was
carried out in the glove box
172
Figure 412 UVVis scan showing the different intensities of carbocation formation with
triflic acid and Al(OTf)3 in DCM
The interesting shifts that can be seen in the λmax of the above UVVis scans may be the result
of the different counter ions formed in the reactions ie -OTf and Al(OTf)4-
Carbocations were formed at a similar intensity as before when the experiments are carried
out using triflic acid in the dry DCM When attempts were made to form carbocations in dry
DCM with Al(OTf)3 the solution turned a very faint blue a slight absorption peak can be
seen on the UVVis spectrum (Figure 413)
Figure 413 UVVis scan of Al(OTf)3 and retinyl acetate in dry DCM
173
At such a low concentration of water this result was unexpected as most of the water and
therefore also the source of Broslashnsted acidity had been removed from the system However a
DSC (differential scanning calorimetry) analysis of the Al(OTf)3 showed that the salt
contains a relatively large amount of water (Figure 414) The sample of Al(OTf)3 for that
analysis was made up in an inert atmosphere (glove box) and the scan was conducted under a
blanket of nitrogen The results of the scan showed one endotherm peak at a temperature of
170 degC and another at 260 degC (Figure 414) The lower temperature peak was assumed to
belong to lsquoloosely boundrsquo water and the higher temperature peak to that of water bound
directly to the metal centre
Figure 414 DSC scan of standard Al(OTf)3
This water along with the small amount of water left in the DCM may have been the source
of the Broslashnsted acidity that was promoting the weak carbocation formation that was seen in
the previous experiments A sample of the same Al(OTf)3 was then dried under reduced
pressure at 120 degC for 48 hours and the DSC scan was repeated Both of the endotherm
peaks had disappeared (Figure 415)
174
Figure 415 DSC scan of dried Al(OTf)3
To determine if it was in fact water that had been removed from the Al(OTf)3 sample and not
residual TfOH a small portion of the dried Al(OTf)3 powder was exposed to the atmosphere
for 15 minutes A DSC scan of this sample was then recorded The endotherm peaks reappear
at both 170 degC and 260 degC This strongly suggests that the endotherm peaks are as a result of
water bound to the Al(OTf)3
The carbocation formation experiment was repeated using the dried Al(OTf)3 in dried DCM
Stock solutions were made up in the glove box As before solubility was a problem and the
solution had to be heated to 35 degC before the Al(OTf)3 became completely soluble in the
solvent When the Al(OTf)3 solution was added to the retinyl acetate solution the solution did
not turn blue Nevertheless after some time Al(OTf)3 could be seen accumulating slowly on
the bottom of the cuvette Around the fine powder a blue colour could be seen forming on the
interface of the powder and the solvent
A possible explanation of this phenomenon is the irreversible hydrolysis on the crystal faces
of the Al(OTf)3 that occurs on exposure to moisture to yield amphoteric patches of
aluminium oxide on the surface33 This observation has been made for certain types of
alumina surfaces and may account for the present phenomena
175
472 The proton and the sterically hindered base ndash X-ray crystallography
In(OTf)3 and DTBMP were dissolved in DCM The DCM was then allowed to evaporate
slowly allowing crystals to form The crystals were then analysed using X-ray
crystallography (Figure 416)
Figure 416 Crystal structure of protonated DTBMP with OTf- counterion (417)
Table 417 Crystal data of protonated 26-di-tertbutyl-4-methyl pyridine
C20H20F3N2O3S Dx = 1607 Mg mminus3
Mr = 42544 F000 = 884
Orthorhombic Pna21 Mo Kα radiation λ = 071073 Aring
a = 228420 (16) Aring Cell parameters from 3551 reflections
b = 90680 (6) Aring θ = 24ndash280deg
c = 84873 (6) Aring micro = 024 mmminus1
V = 17580 (2) Aring3 T = 296 (2) K
Z = 4 041 times 022 times 019 mm
The crystal structure shows a pyridium ion with no metal found in the crystal structure and
presumably In(OTf)2(OH) is formed in the process This is consistent with a previous finding
176
of this investigation (see section 45 The case for 26-di-tert-butyl-4-methyl-pyridine) The
crystals formed in the presence of In(OTf)3 are identical to those formed when the same
experiment is carried out using triflic acid The latter experiment also generated crystals
identical to those described in Figure 416 and Table 417 above
48 Friedel-Crafts alkenylation reactions of arenes
481 Optimising the reaction
So far in the investigation it has been established that the metal triflates can form Broslashnsted
type acidity to varying degrees in the presence of water in organic solvents In the case of the
Mukaiyama aldol reaction this results in the hydrolysis of the silyl enol ether Furthermore
Broslashnsted acidity has been shown to be causative in the formation of carbocations using
retinyl acetate and a metal triflate An X-ray structure determination on crystals formed upon
the reaction of In(OTf)3 with the sterically hindered base DTBMP showed that a proton binds
to the base and that triflate is the counter ion
Since a metal triflate may exhibit both kinds of activity (Lewis and Broslashnsted acidity) it needs
to be established whether the Broslashnsted acid or the Lewis acid drives the reaction or whether it
is a combination of the two Alternatively the question may be asked as whether such a metal
triflate can act purely as a Lewis acid in the absence of water or protic solvent The Friedel-
Crafts alkenylation (Scheme 418) reaction of arenes was chosen for this part of the
investigation as it is a proton-neutral reaction Once the water is removed from the reaction
there is no other source of protons available for the generation of Broslashnsted acidity In this
way the extent of Lewis acid catalysis can possibly be determined
The reaction between p-xylene and phenylacetylene (Scheme 419) is known to be catalysed
by In Sc and Zr triflates36 This served as a starting point for the current investigation Using
the same experimental procedure set out in the 2000 communication36 a range of metal
triflates (20 mol) was used in the reaction between p-xylene and phenylacetylene
177
Ph HM(OTf)n 20 mol85 oC
Ph
H
H
+ +
Ph H
H
418 419 420 Scheme 419 Friedel-Crafts reaction of p-xylene with phenylacetylene
The reactions were carried out at 85 degC for 24 hours after which the yields were determined
by 1H NMR spectroscopy (Table 418) This was done by integration of the remaining
acetylene proton signal against the signal of the vinylic hydrogen in the product The yields
of the products were mostly poor many of the metal triflates failed to catalyse the reaction at
all (Table 418) but this may be due to solubility problems in the non-polar reaction medium
The problem was somewhat overcome by the addition of nitromethane to the p-xylene The
reactions were then repeated in this solvent mixture Several of the reactions were repeated
(Table 418) The yields of the products were generally if sometimes only slightly so
improved from the previous run In an attempt to try to further optimise the reactions those
metal triflates that had performed best were used in reactions where the amount of p-xylene
was systematically reduced (Table 419)
Table 418 Yield () of Friedel-Crafts alkenylation reactions catalysed by various M(OTf)x
Lewis acid
Reaction Yield ()a
Reactions +200 uL
nitromethaneYield ()a
Zr(OTf)4 53 58 Al(OTf)3 50 86 Cu(OTf)2 0 - Ca(OTf)2 0 - Hf(OTf)4 63 64 Zn(OTf)2 0 0 La(OTf)3 0 - Sc(OTf)3 68 100 Sm(OTf)3 0 0 Y(OTf)3 0 0
ScCl3 0 21 InCl3 50 53 TfOH 31 31
a Yields determined by 1H NMR spectroscopy
178
By decreasing the volume of p-xylene used in the reaction mixture the yields of the product
were greatly improved The results are summarised in Table 419
Table 419 Yield () of Friedel-Crafts alkenylation reactions in various amounts of
p-xylenea
Metal triflate
Yield ()b 8 mL p-xylene
Yield ()b
4 mL p-xylene
Yield ()b
2 mL p-xylene
Zr(OTf)4 53 68 100 Al(OTf)3 100 100 100 Sc(OTf)3 100 100 100 Hf(OTf)4 76 100 100
a p-xylene phenylacetylene (100 uL) nitromethane (200 uL) 20 mol M(OTf)x b Yield determined by 1H NMR
spectroscopy
The application of metal triflates in the Friedel-Crafts alkenylation reaction is expected to
have a wide application For example the study also showed that phenyl acetylene could be
successfully reacted with a wide range of aromatic systems including toluene anisole etc
using the same metal triflates (Table 420)
Table 420 Yield () of Friedel-Crafts alkenylation reactions with alternative aromatic
systemsa
Lewis Acid 10 mol
Yield ()b
Cumene 16 mL 48 h
Yield ()b
Anisole 16 mL 24 h
Yield ()b
Toluene 16 mL 48 h
Zr(OTf)4 71 gt 95 66 Al(OTf)3 47 gt95 77
a p-xylene phenylacetylene (100 uL) nitromethane (200 uL) 20 mol M(OTf)x b Yields determined by 1H NMR
spectroscopy products not isolated
482 Reactions in dry solvent
Once the optimal reaction conditions had been established the p-xylene and nitromethane
were dried Karl Fischer titration was carried out on the solvents to determine their water
content before and after drying Nitromethane from the bottle was found to contain 325 ppm
water Working in the glove box the solvent was passed through a column of activated
179
alumina and the dry nitromethane was found to contain 22 ppm water The p-xylene was
dried for 24 hours over 3Aring molecular sieves that had been activated in an oven at 250 degC The
dried p-xylene was found to contain 1 ppm water When the solvents were mixed in the same
ratio as they were used in the previous reaction mixture the Karl Fischer titration was
repeated on the solvent mixture and the water content was found to be 5 ppm This mixture
was then used for the reactions
The metal triflates were dried under high vacuum at 120 degC for 48 hours to remove all traces
of water DSC scans were carried out to ensure and confirm that the all of the metal triflates
were dry Additionally all preparation work took place in a glove box The scans showed no
endotherm peaks that are characteristic of the presence of water
The Friedel-Crafts alkenylation reactions were then repeated (Table 421) using the dry
solvents in order to determine to what extent Broslashnsted acidity plays a role in these reactions
Since for all intents and purposes the water had been removed from these reactions the
possibility of generating Broslashnsted acidity had also been eliminated
Table 421 Friedel-Crafts alkenylation reaction in dry solventa
Metal Triflate
Yield ()b Solvent from
bottle
Yield ()b Dry solvent
Zr(OTf)4 68 24 Al(OTf)3 100 100 Sc(OTf)3 100 74 Hf(OTf)4 100 35
TfOH 31 21 a 4 mL p-xylene 20 mol M(OTf)x 85 degC 24 h b Yields determined by 1H NMR spectroscopy
Table 421 shows that yield of the reactions decreases moderately to significantly when they
were carried out in dry medium except in the case of Al(OTf)3 The results indicate that the
reactions can be sustained in a thoroughly dried solvent and are in this case very probably
Lewis acid promoted However the higher activity in slightly wetter solvents could be due to
several effects including increased solubility andor solvation of ions resulting in improved
ionic dissociation and exchange of the metal triflates (solvation effects) 1H and 13C NMR
spectroscopy of phenyl acetylene in deuterated DCM suggests that Al(OTf)3 does bind to the
triple bond of the phenyl acetylene Complexation results in a clear downfield shift of the
180
acetylic hydrogen and triple bond carbons (from 531 ppm to 528 ppm in the proton
spectrum and from 838 ppm to 839 ppm in the 13C spectrum) The possibility of increased
activity due to the formation of a protic acid from water binding to the metal triflate is a
realistic possibility The phenomenon of increased catalytic activity of metal triflates in the
presence of water has been observed throughout this investigation
It is clear that Al(OTf)3 is a very active catalyst for the Friedel-Crafts alkenylation reaction
under investigation Reactions were performed under dry conditions using smaller amounts of
catalyst Only at a catalyst loading of 5 mol was a decrease in reactivity observed (ie 10
mol catalyst led to quantitative conversion to product) In this case the yield of the reaction
was 60
Despite the generally lower yields obtained in the Friedel-Crafts alkenylation reaction in dry
organic medium it appears as if this particular reaction is indeed primarily Lewis acid
catalysed in the case of Al(OTf)3 (and possibly for the other metal triflates used in this study-
although a large contribution from a Broslashnsted-acid catalysed mechanism may be the force
with those metal triflates that were severely affected by the drying ie Zr(OTf)4 and
Hf(OTf)4)
The effect of the lower water content on the triflic acid can be explained in terms of
diminished dissociation in a solvent with lower dielectric constant and poor solvating
properties There seems to be no simplistic trend with regards to water on the metal triflates
This may be due to the dual mechanism and the unpredictable reactivities and quantities of
the given Lewis acid and Broslashnsted acid that forms
In cases where metal triflates were not completely soluble in the reaction medium but some
portion remained as solid particles the contribution of a heterogeneous component to the
reaction cannot be excluded This possibility has not been investigated but should command
attention
181
49 Conclusions
Summation of results described in publications and new results outlined in this investigation
led to the conclusion that the presence of water (or other protic molecules) in organic solvents
can affect the catalytic activity of the metal triflates in different ways Not only can it
increase solubility but catalytic activity can be increased by solvation water complexation
while results in the formation of Broslashnsted acid activity The effect of water and other protic
solvents will generally not be easy to determine to predict or be ascribed to a specific factor
The dramatic effect of small amounts of water on the catalytic ability of metal triflates raises
the question of the effect of water on Lewis acid activity in general and as to the nature of the
nature of the active catalyst In the minds of most practising chemists Lewis acid catalysis
appears to play out as the simple activation of a substrate by a metal centre This study has
amply demonstrated that this is not the case Instead the reality appears to be one in which
water plays a critical if sometimes determinative role in the successful outcome of the
reaction In all likelihood many (if not most) reactions that are held to be purely Lewis acid
catalysed are either Broslashnsted acid catalysed (by complex Broslashnsted acids of the type MXnmdash
OH2) or co-catalysed by Broslashnsted-Lewis synergism in which hydrogen bonding and metal
bonding where a MmdashOH2 moiety lead to favourable transition states
Throughout all of the work of the present study water has shown to play a critical role In
only one case was this not so The study clearly points to the complexity faced when
considering Lewis acid catalysis at a fundamental level as has been done here It is quite
likely given the manifold reactions investigated here and the complex interplay between
Lewis and Broslashnsted acidity (the latter being almost ubiquitous in the presence of Lewis
acids) that the fundamental way in which chemists think of such activators should be
modified
Comparing the catalytic activity of metal triflates becomes particularly problematic when
water (or a protic solvent) is a potential reagent (eg in the Mukaiyama aldol reaction) Such
comparisons should preferably be carried out with model reactions that are inert to water
The results described suggest that metal triflates in water-containing solvents often catalyse
reactions by a dual mechanism (Lewis andor Broslashnsted acid mediated) and that the relative
182
importance of these two mechanisms differ from metal to metal The results further indicate
that the interpretation of the effect of the addition of the sterically hindered base to a reaction
medium should be interpreted with caution particularly where large excesses of the base are
added
An observation of particular importance is that some metal triflates are not only tolerant to
water but require water for their catalytic activity The sometimes dramatic effect of drying
the organic solvent on the metal triflate catalytic activity highlights the role of small amounts
of water in organic reactions in general
In turn this point focuses attention as to what is meant by using what organic chemists usually
term dry solvents The previous chapter highlighted the difficulties in drying organic solvents
and serves as a relief for the present work
183
410 References
1 Kobayashi S Sugiura M Kitagawa H Lam W W L Chem Rev 2002 102
2227
2 Scifinder Scholar search of ldquoMetal Triflate Catalysisrdquo 2002-2009 ndash 307 hits
3 a) Kobayashi S Synlett 1994 9 689 b) Kobayashi S Chem Lett 1991 12 2187
c) Kobayashi S Ogawa C Chem Eur J 2006 12 5954 d) Keller E Feringa B
L Tetrahedron Lett 1996 37 1879
4 Williams D B G Lawton M Org Biomol Chem 2005 3 3269
5 Bizier P N Atkins S R Helland L C Colvin S F Twitchell J R Cloninger
M J Carb Res 2008 343 2814
6 Noji M Ohno T Fuji K Futaba N Tajima H Ishii K J Org Chem 2003
68 9340
7 Ollevier T Lavie-Compin G Tetrahedron Lett 2004 45 49
8 Brown H C Kanner B J Am Chem Soc 1966 88 986
9 Ollevier T Nadeau E Guay-Beacutegin A-A Tetrahedron Lett 2006 47 5351
10 Dumeunier R Markoacute I E Tetrahedron Lett 2004 45 825
11 Bizier P N Atkins S R Helland L C Colvin S F Twitchell J R Cloninger
M J Carb Res 2008 343 2814
12 Barrett A G M Braddock D C Henschke J P Walker E R J Chem Soc
Perkin Trans 1999 873
13 Curtis A D M Tetrahedron Lett 1997 38 4295
14 Pieroni O L Rodriquez N M Vuano B M Cabaleiro M C J Chem Res (S)
1994 188
15 Waller F J Barrett A G M Braddock D C Ramprasad D Tetrahedron Lett
1998 39 1641
16 Waller F J Barrett A G M Braddock D C Ramprasad D Chem Commun
1997 613
17 Barrett A G M Braddock D C Chem Commun 1997 351
18 Claydon J Greeves N Warren S Wothers P Organic Chemistry Oxford
University Press New York 2001
19 Smith M B March J Advanced Organic Chemistry Reactions Mechanisms and
Structure 5th ed Wiley New York 2001
20 Mukaiyama T Pure Appl Chem 1983 55 1749
184
185
21 Loh T-P Pei J Cao G-Q Chem Commun 1996 1819
22 Van de weghe P Collin J Tetrahedron Lett 1993 34 3881
23 Hollis T K Bosnich B J Am Chem Soc 1995 117
24 Kobayashi S Nagayama S Busujima T J Am Chem Soc 1998 120 8287
25 Baes C F Jr Mesmer R The Hydrolysis of Cations Wiley New York 1976
26 Hagger J A Depledge M H Galloway T S Marine Pollution Bulletin 2005 51
811
27 a) Kobayashi S Synlett 1994 9 689 b) Ding R Katebzadeh K Roman L
Bergquist K E Lindstrm U M J Org Chem 2006 71 352 c) Kobayashi S
Manabe K Acc Chem Res 2002 35 209 d) Dissanayake P Allen M J J Am
Chem Soc 2008 131 6342
28 Chaminade X Chiba Shunsuke C Narasaka K Duntildeach E Tetrahedron Lett
2008 49 2384
29 Drago R S Physical Methods in Chemistry Saunders 1976
30 Gould E S Mechanism and Structure in Organic Chemistry Holt Reinhart and
Winston 1959
31 Purcell K F Kotz J C Inorganic Chemistry Sauders 1977
32 Gladstone S Textbook of Physical Chemistry Macmillen 1953
33 Isaacs N S Physical Organic Chemistry Longman 1987
34 Smith M B Organic Synthesis McGraw-Hill Singapore 1994
35 Blatz P E Pippert D L J Am Chem Soc 1967 90 1296
36 Tsuchimoto T Maeda T Shirakawa E Kawakami Y Chem Commun 2000
1573
37 Carruthers W Coldham I Modern Methods Inorganic Synthesis Cambridge
University Press UK 2004
Chapter 5
Ranking of Lewis acids
51 Introduction
The final aim of this investigation was to rank the metal triflates according to their Lewis
acid strength using spectroscopic methods This type of ranking had proved marginally
successful for other more traditional types of Lewis acids such as the metal halogens
However to our knowledge a study like this has not been undertaken for the metal
triflates
Despite attempts by many researchers the quantitative measurements of Lewis acid
strength across a broad range does not exist The quantitative measurement of Lewis
acidity appears to be one of the persistent problems of the acid-base theory Lewis
himself pointed out that relative acidity (or basicity) would depend on the choice of
reference base (or acid)
The most reliable method for determining the strength of a Lewis acid would be the
determination of the enthalpy change accompanying the formation of the acid-base
adduct in the gas phase1 This method also has its drawbacks it is not available to a wide
range of compounds and although it tells us the acidity in the gas phase the question
arises as to whether the data could be extrapolated to the solvent phase
The hard-soft acid-base (HSAB) concept was introduced in 1963 by Pearson2 and can
explain affinities between acids and bases that do not depend on electronegativity and
other related properties3 According to this principle hard acids prefer to bond to hard
bases and soft acids prefer to bond to soft bases Electrostatic interaction is presumed to
be the dominant source of stabilisation in the hard acid-hard base complex In the case of
soft acid-soft base complexes electron delocalisation between the frontier orbitals has
been thought to be the principal interaction4
186
The HSAB principles give us a good qualitative indication upon which to work
However we are unable to determine anything about the inherent strength of the acid or
base
Nevertheless there have been many successes in correlating relative Lewis acid strength
using an array of techniques (for a full review see Chapter 1) Childs carried out a study
using NMR spectroscopy by examining the shifts of complexed bases versus the
uncomplexed bases4 He was able to determine the Lewis acidity of a variety of acids
Other studies have been carried out using UVVis spectrophotometry to determine Lewis
acidity eg by the difference in the wavelength of complexed and uncomplexed carbonyl
groups Often spectroscopic information is applied in calculating equilibrium constants
which then forms the basis for ranking of the Lewis acids
The aim of the present investigation was to establish a ranking for a variety of metal
triflates with respect to Lewis acidity using NMR IR and UVVis spectroscopy and to
determine if the ranking found by these methods correlated with each other
52 Lewis acidity from NMR resonance shifts
Crotonaldehyde
The ranking of Lewis acids by NMR spectroscopy is based on the assumption that when
the Lewis acid (electron acceptor) binds to the electron donor (Lewis base) there is a
reduction of electron density on the Lewis base This reduction of electron density results
in a downfield shift in the NMR signals of the basic compound The stronger the Lewis
acid the more dramatic the shift on the NMR spectra These shifts can then be compared
to one another and a ranking obtained
One of the most comprehensive investigations carried out on the ranking of Lewis acids
using NMR spectroscopy was done by Childs et al4 In this investigation metal halides
were used as the Lewis acids The most successful probe (base) used in the investigation
187
was crotonaldehyde although others were also employed (this study is outlined more fully
in Chapter 1 section 132 of this thesis)
Childsrsquos study formed the starting point of the current investigation While investigating
the role of water in metal triflate catalysis (Chapter 4) it was found that the triflates had
some solubility in DCM and that this solubility increased when an aldehyde or other
functionalised organic compound was added to the mixture In light of these findings the
current NMR investigation was carried in deuterated DCM using (asymp 01 M)
crotonaldehyde (for numbering see Figures 51 and 53) as the probe An excess of 12
equivalents (with respect to the aldehyde) of the Lewis acid was used to ensure that all of
the aldehyde was coordinated to the metal The 1H and 13C NMR spectra in all instances
showed only one set of signals indicating complete (within the limits of NMR sensitivity)
coordination to the metal The 1H and 13C NMR results with respect to several Lewis
acids are recorded in Table 51 and 52 respectively
H
H3C
OH
H3
12
Figure 51 Proton numbering used on crotonaldehyde
Table 51 1H NMR chemical shift differences (Δδ) of crotonaldehyde on complexation
with various Lewis acids
NMR
signala
Croton
aldehyde
δ
Δ δ on
addition
of
Al(OTf)3
Δ δ on
addition
of
AlCl3
Δ δ on
addition
of
Sc(OTf)3
Δ δ on
addition
of
ScCl3
Δ δ on
addition
of
In(OTf)3
Δ δ on
addition
of
InCl3
H-1 947 -026 -016 -025 003 -006 -007
H-2 610 054 013 044 045 030 027
H-3 687 093 023 093 071 050 043
CH3 201 029 012 028 021 016 013 a Negative values indicate an upfield shift
188
The results show significant shifts for both H-3 and H-2 resonance in all cases (Table
51) Furthermore Al(OTf)3 and Sc(OTf)3 effect the greatest of these shifts particularly
with regard to H-3 The same trend is seen by the CH3 group However the shifts are of
smaller magnitude In every case the shifts are mutually consistent and can readily be
interpreted in terms of the relative Lewis acidity of the metals The following ranking is
therefore suggested Al(OTf)3 gt Sc(OTf)3 gt In(OTf)3 And for the chloride series ScCl3 gt
InCl3 gt AlCl3 (H-1 shifts did not correlate with the above suggested Lewis acid ranking
this may be due to anisotropic shielding induced by the oxygen-metal bond on the nearby
H-1 hydrogen) The order found for the chloride series appears to be anomalous with
respect to AlCl3 Other workers have found that AlCl3 gt InCl356 However probes
(bases) used in these studies were different In one case ethyl acetate was used5 and in
the other 9-fluorenone6 which could be a possible reason for the difference in the
rankings Childs4 did not use AlCl3 or InCl3 in his study
Figure 52 1H NMR chemical shift differences of crotonaldehyde versus the various
Lewis acids
189
H
O
3
12
4 Figure 53 Carbon numbering used on crotonaldehyde
Table 52 13C NMR chemical shift differences (Δδ) of crotonaldehyde on complexation
with various Lewis acids
NMR
signala
Croton
aldehyde
δ
Δ δ on
addition
of
Al(OTf)3
Δ δ on
addition
of
AlCl3
Δ δ on
addition
of
Sc(OTf)3
Δ δ on
addition
of
ScCl3
Δ δ on
addition
of
In(OTf)3
Δ δ on
addition
of
InCl3
C-1 1941 111 04 116 175 04 29
C-2 1348 -20 05 -14 -15 03 -02
C-3 1544 219 02 221 1752 04 45
C-4 187 26 06 27 24 05 09 a Negative values indicate an upfield shift
The significant shifts seen in C-1 and C-3 following the same reasoning as before these
shifts appear to support Lewis acid acidity ranking Al(OTf)3 asymp Sc(OTf)3 gt In(OTf)3 The
chloride series remains the same as before
The measure of consistency found in this method strongly suggests that this may be a
valuable method for the ranking of Lewis acids particularly since the large number of
aldehydes available that will allow a great measure of fine tuning This is a subject of an
ongoing study in our laboratory
190
Figure 54 13C chemical shift differences of crotonaldehyde versus the various Lewis
acids
Ionic liquids as a solvent for NMR spectroscopy
Work carried out previously in this investigation showed that the metal triflates were
soluble in ionic liquids in particular [bmim][OTf] (Chapter 4) In order to extend the
current study on the ranking of the metal triflates using NMR spectroscopy it was
decided to employ the use of ionic liquids as the solvent To do this a 10 mm NMR tube
was used in which the ionic liquid along with the aldehyde and the metal triflate was
placed A coaxial tube filled with deuterated benzene was then inserted into the 10 mm
NMR tube containing the ionic liquid (deuterated benzene was used due to its high
deuterium content when other deuterated solvents were used for these experiments for
example CDCl3 or CD3OD a lock could not be obtained on the NMR spectrometer)
Trans-cinnamaldehyde was used as the probe in these experiments (Figure 55 and Table
53)
191
C3C2 C1
H1
OH3
H2 Figure 55 Atom numbering on trans-cinnamaldehyde
Table 53 1H and13C chemical shift differences (Δδ) of trans-cinnamaldehyde in
[bmim][OTf] on complexation with various metal triflates
NMR signala
Trans-
cinnamaldehyde
δ ppm
H-1
969
H-2
669
C-1
1948
C-2
1291
C-3
1537
Lewis acid Δδ H-1 Δδ H-2 Δδ C-1 Δδ C-2 Δδ C-3
Hf(OTf)4 003 005 13 -02 12
Sc(OTf)3 -016 -002 24 01 25
In(OTf)3 -0171 0047 17 00 16
Ca(OTf)2 -0074 0014 04 -04 02
Zn(OTf)2 -005 0038 29 03 26
Y(OTf)3 -0048 0145 31 03 33
Zr(OTf)4 -0107 004 23 -07 24
Al(OTf)3 -0076 0032 09 00 09
LiOTf -0017 0055 10 01 07 a Negative values indicate an upfield shift
The outcomes of these experiments show a strong correlation between the shifts in the
resonance of C-1 and C-3 (Figure 56) The shifts observed for C-2 appear to be random
There is no relationship between the data obtained for H-1 and H-2 and the results could
also not be linked to the resonance shifts observed in the carbon spectra No shifts were
seen for H-3 Due to the lack of correlations any ranking obtained from this method
would be inconclusive at best
192
Figure 56 13C chemical shift differences of trans-cinnamaldehyde versus the various
Lewis acids
Phosphorus NMR
Methoxycarbonylation reactions using phosphorus ligands are one of the focuses of
work in our laboratories Recently it was discovered that a metal triflate can co-catalyse
these reactions where previously they had been exclusively Broslashnsted acid catalysed6 In
light of these findings and in order to find out more about how the metal triflates worked
in these reactions phosphorus probes were used in an NMR study in an attempt to rank
the Lewis acidity of the metal triflates
Spencer et al7 conducted a study into the ranking of Lewis acids using 31P NMR
spectroscopy in which triphenylphosphine oxide was used as the probe along with
calorimetric techniques to determine the enthalpy changes and the equilibrium constants
The Lewis acids under investigation were trimethylchlorosilane -germane and -stannane
193
The workers found little correlation between the 31P shifts recorded and the
thermodynamic data
In the current study the NMR experiments were initially carried out by a colleague using
deuterated methanol This solvent was chosen as it mimics the reaction conditions of the
methoxycarbonylation reaction which was the reaction under investigation The probe
used was triphenylphosphine and a variety of metal triflates were used 8
The results showed that there was no shift in the 31P NMR chemical shifts on addition of
any of the Lewis acids which may be due to two factors Firstly the metal triflates are
relatively hard Lewis acids and the probe being used ie triphenylphosphine is a
comparatively soft Lewis base which would account for the absence of interaction
between the two Secondly the deuterated solvent is methanol which is itself a
coordinating solvent The metal ions of the triflate salts may preferentially coordinate to
the harder oxygen atom of the alcohol over the softer phosphorus atom
To establish if any coordination with phosphorus was possible the 31P NMR experiments
were repeated with several of the metal triflates in deuterated DCM a non-coordinating
solvent The phosphorus probes were also extended to include triphenylphosphine oxide
and diphenylphosphinobenzaldehyde The results are summarised in Table 54
Table 54 31P NMR chemical shift differences (Δδ) of phosphorus compounds on
complexation with various metal triflates
Phosphorus compound
δ uncomplexeda
Δ δ on addition
of Al(OTf)3
Δ δ on addition
of Sc(OTf)3
Δ δ on addition
of In(OTf)3
Triphenyl phosphine -511 071 1072 1006
Triphenyl phosphine oxide 2778 1195 1939 1749
Diphenylphosphino benzaldehyde -1044 4399 4399 4398
a Referenced to 85 phosphoric acid in water using a coaxial tube insert
194
Gratifyingly complexation of the metal triflates to the phosphorus centre was seen in each
case causing large downfield shifts in the resonance of the 31P signals A linear
relationship exists between the shifts found for triphenylphosphine and those of
triphenylphosphine oxide ie Sc(OTf)3 gt In(OTf)3 gt Al(OTf)3 The order of this series
differs from the order found with crotonaldehyde
Interestingly when diphenylphosphinobenzaldehyde is used as the probe the change seen
in the resonance of the 31P NMR signals are identical for the three metal triflates used
(ie 439 ppm) No precedence for these phenomena could be found in the literature
However a possible explanation could be the formation of a chelate (Figure 57) between
the phosphorus atom and the oxygen atom on the aldehyde to the metal of the triflate
This chelate would form a stable six membered ring and in so doing the phosphorus
would take on a formal positive charge Presumably the primary binding in the structure
is between the harder oxygen atom and the hard metal centres The secondary binding to
the phosphorus atom is rendered advantageous by virtue of the chelate structure and
leads to the observed similarities This would account for the fact that all of the metal
triflates used in the study appear to withdraw electrons at the same rate from this Lewis
base The strong downfield chemical shift is typical of metal bound P (III) atoms
P H
O
(OTf)3M
Figure 57 Diphenylphosphinobenzaldehyde chelated to a metal triflate
What this work highlights is the need to exercise caution when using this method of
ranking It should be recommended that this method leads to relative ranking of the
Lewis acids that is relative to the probe (base) being used at the time rather than an
absolute method of ranking This is because each base has its own unique electronic
characteristics and will be affected by the Lewis acid in different ways This is unlike the
scale used for Broslashnsted acidity which uses proton acidity as a common feature
195
Equilibrium constants by NMR
NMR spectroscopy has been applied to determine the equilibrium constants (Keq) of
Lewis acid-base adducts and from this information a ranking of Lewis acidities should be
possible A 11 stoichiometry of the acid-base is generally assumed1 This method can of
course only be applied when there is slow exchange between the bound and unbound
ligand In this case it is assumed that the resonance shifts on the 1H NMR spectra of
unbound-base versus bound-base can be integrated and the respective concentrations
determined Here Keq = [acid-base complex][acid][base] This method assumes that the 1H NMR integral for the signal of a CH proton of a complexed molecule of the base in
question is directly proportional to the mole fraction of that species and may be related as
a proportional mole fraction to the integral on the same CH signal of the free base A
successful study of this kind was carried out by Branch et al1 where 9-fluorenone was
used as the probe and it was found that the ranking obtained from the NMR study could
be correlated to some other thermodynamic data obtained
In the current study crotonaldehyde was used as a probe in deuterated DCM Mixtures of
a 11 ratio of the aldehyde to metal triflate were carefully weighed out on a five decimal
balance Each solution for NMR was made up in 08 mL of deuterated DCM The
mixtures were stirred for 30 minutes at room temperature before the NMR spectra was
taken All spectra were recorded at 25 degC several metal triflates were investigates giving
comparable results therefore Table 56 contains results of only two of these triflates
namely Sc(OTf)3 and In(OTf)3
The results (Table 55) of the 11 12 14 etc ratio of metal to ligand were surprising in
that none of the spectra showed unbound crotonaldehyde Therefore clearly rapid
equilibrium between the bound and unbound aldehyde is established resulting in
weighted averaging of the signals9
In this case the following equation applies
δiave = (1-Nc) δic + Nc x δif
196
Where
δiave = observed signal for nucleus i in NMR spectrum
δif = signal of nucleus i of free base (ligand)
δic = signal of nucleus i of complexed base (ligand)
Nc = mol fraction of complexed base (ligand)
Table 55 1H chemical shift differences (Δδ) of crotonaldehyde on complexation with
various metal triflates
NMR signal
Croton aldehyde
δ
Δ δ on addition
of Sc(OTf)3
11
Δ δ on addition
of Sc(OTf)3
12
Δ δ on addition
of Sc(OTf)3
14
Δ δ on addition
of Sc(OTf)3
18 aH-1 947 -027 -022 -015 -008
H-2 687 045 014 026 014
H-3 610 100 083 057 024
CH3 201 028 023 014 005
NMR signal
Croton aldehyde
δ
Δ δ on addition
of In(OTf)3
11
Δ δ on addition
of In(OTf)3
12
Δ δ on addition
of In(OTf)3
14
Δ δ on addition
of InOTf)3
18 aH-1 947 -009 -008 -007 -006
H-2 687 027 019 010 008
H-3 610 049 037 021 017
CH3 201 014 007 004 003 a negative values indicate an upfield shift
In this case in principle the equilibrium constants should still be obtainable by calculation
provided that the equilibrium is not so for to the right ie to the complex that the amount
of free metal and of ligand cannot be accurately measured The linear relationship
between the signals H3 and CH3 of the complexed crotonaldehyde strongly suggest
almost quantitative complexation of both Sc(OTf)3 and In(OTf)3 in all cases The similar
results with other triflates therefore does not allow the ranking of the Lewis acidity in
197
this solvent A ranking using the NMR method would require the use of a more polar and
coordinating solvent to decrease the affinity of the ligand for the metal but then again the
ranking will be critically dependent on the chose of the solvent and will change from
solvent to solvent
Equilibrium constants UVVis
The calculation of equilibrium constants of acid-base adducts has been carried out using
data obtained by UVVis measurements10 In spectroscopic methods concentration is
directly proportional to absorptivity according to Beerrsquos law (Equation 1)
A = εbc 1
Where A = absorbance
ε = molar absorptivity
b = cell length (cm)
c = concentration (molL)
It has been found that the addition of the Lewis acid to specific types of Lewis bases
leads to a decreases in intensity of the absorption band of the free base and a new band
characteristic of the adduct usually appearing at a wavelength longer than that of the base
(Figure 58)9
198
Figure 58 UVVis spectrum of adduct formation between Lewis base and Lewis acid
Thus by using known concentrations of base and adding known concentrations of the
Lewis acid it is possible to determine the strength of a Lewis acid This is done by
calculating the Keq in the following way Keq = [acid-base complex][acid][base] The
concentrations are calculated from the absorptivity taken from the UVVis spectra9
In an attempt to rank metal triflates using this method a dilute solution (10-5 M) of 4-
methyl-3-nitroaniline was prepared in DCM and solutions of metal triflates of equal
molarity were also prepared The UVVis absorption profile of the free base was recorded
(Figure 59)
The absorption maximum of the base is seen at 424 nm When the solution of Al(OTf)3
was added no new absorption band was seen in fact no change in the spectrum was seen
at all (Figure 59) This behaviour was also observed when Sc(OTf)3 and In(OTf)3
solutions were added to the probe
199
Figure 59 UVVis spectrum of 4-methyl-3-aniline in DCM
Dilute solutions of 2-nitrodiphenylamine and 4-nitrodiphenylamine in DCM were
investigated as alternative probes The UVVis scans were carried out as before
However no complexation of the Lewis acid to the probe could be detected The lack of
coordination seen in these experiments may be due to the metal triflates forming close ion
pairs in the DCM and thus not been available to bind to the nitrogen This would be
particularly true due to the very low concentration of the probe (low in order to record a
UVVis spectrum of this chromophore) which would favour dissociation of a weak
complex
In an attempt to circumvent this problem dilute solutions of the same probes and the
metal triflates were made up in THF This solvent has better solvating capabilities than
DCM which may make metal ions more available for coordination to the nitrogen The
UVVis scans were then repeated These experiments showed a slight attenuation of the
original band (Figure 510 and Figure 511) when the Lewis acid solutions were added to
the probes
Satchell and Wardell10 observed the same phenomena in their work where on addition of
the Lewis acid the absorption band attributed to the base was simply reduced and no new
band characteristic of an acid-base adduct appeared According to these authors this was
200
ascribed to protonation of the aniline and the resultant anilinium ion absorbing at a much
shorter wavelength (bathochromic shift end absorption) than the parent base11
In the current study many other probes were evaluated (Table 56) and similar results
were obtained in each case ie attenuation of the original band
Figure 510 UVVis spectrum of Figure 511 UVVis spectrum of 4-
4-nitrodiphenylaniline in THF nitrodiphenylaniline coordinated to
Lewis Acid
Table 56 Δλ of probe on addition of a Lewis acid
Lewis base used Solvent Result
Pyridine THF Attenuation of original peak
2-Bromoanline THF Attenuation of original peak
4-Chloroaniline Ether No observable result
Diphenylaniline THF Attenuation of original peak
4-Nitroacetophenone Ether Attenuation of original peak
As a result equilibrium constants could not be calculated The possibility of using the
extent of attenuation of Lewis acid acidity is presently under investigation in our
laboratory
201
53 Infrared Spectroscopy (IR)
Given that only marginal success was found using NMR-based and UVVis approaches
to the ranking of the metal triflates according to equilibrium constants altogether another
method was sought
The ranking of Lewis acidity using IR spectroscopy has been reported5 When a Lewis
acid binds to a Lewis base such as the oxygen of the carbonyl group perturbation of this
bond occurs The strength of the donor-acceptor bond is reflected in the extent of the
weakening of the C=O bond This can be measured by the change in the bond stretching
frequency (Δν) on IR Lappert5 carried out a study in which ethyl acetate was used as a
probe and boron halides as the Lewis acids He found good correlation of his results with
other studies (as described in detail in Chapter 1 section 132)
Pyridine was used as an infrared probe by Yang and Kou11 to determine the Lewis acidity
of ionic liquids According to the study the presence of a band near 1450 cm-1 indicates
Lewis acidity whilst a band near 1540 cm-1 is indicative of Broslashnsted acidity With respect
to the current investigation this approach may have a two-fold advantage The metal
triflates are soluble in ionic liquids which should enable an IR study to be carried out
aimed at a possible ranking of the metal triflates In addition further information
regarding the induced Broslashnsted acidity arising due to the presence of the metal triflates
may be obtained
Yang and Kou studied CuCl2 FeCl3 and ZnCl2 in [bmim][Cl] In our study [bmim][OTf]
was the ionic liquid and the corresponding metal triflates were used We also repeated
Yangrsquos study of the chlorides in [bmim][OTf] and obtained the same ranking namely
ZnCl2 gt FeCl3 gt CuCl2 The reason behind the use of ndashOTf counter ion is so that the
ionic liquid would provide the same counter ions as the those provided by the metal
triflates guaranteeing the integrity of those species
202
In the current investigation metal triflates (11 equivalents) were added to pyridine in 03
mL of [bmim][OTf] The mixture was stirred at room temperature until complete
dissolution of the metal triflate was obtained Infrared spectra were taken of the
complexes using KBr pellets The results of the experiments are summarised in Table 57
The results indicate that the Lewis acids form a complex with the pyridine this can be
seen by a shift in the peak at around 1440 cm-1 which according to Yang11 indicates
Lewis acidity Closer inspection of Table 57 shows clear difference between the mono
and divalent metals on the one hand and the trivalent metals on the other
Table 57 Δν (cm-1) of pyridine on complexation with various Lewis acids in
[bmim][OTf]
Lewis acid cm-1 Δν (cm-1)Broslashnsted
acid coordination
Pyridine (original peaks) 14400 15893 NaOTf 14410 10 -a
LiOTf 14422 22 -a
Ca(OTf)2 14424 24 -a
Zn(OTf)2 14520 120 -a
Cu(OTf)2 14530 130 -a
Ba(OTf)2 14610 210 -a
LiCl 14860 460 -a
ScCl3 14870 470 -a
In(OTf)3 14880 480 15417 Al(OTf)3 14880 480 15412 Sc(OTf)3 14890 490 15403 Hf(OTf)4 14890 490 15412 Y(OTf)3 14890 490 15403 Er(OTf)4 14890 490 15396 Zr(OTf)4 14890 490 15431 Nd(OTf)3 14890 490 15415 Sm(OTf)3 14890 490 15461 La(OTf)3 14890 490 15439
InCl3 14890 490 -a
GaCl3 14890 490 15437 a ndash indicates no Broslashnsted acid coordination observed
203
With regard to the former and assuming that the extent of the shift in pyridine peak at
1440 cm-1 is indicative of Lewis acid acidity the following ranking of the Lewis acids
can be deduced LiCl gt Ba(OTf)3 gt Cu(OTf)2 gt Zn(OTf)2 gt Ca(OTf)2 gt LiOTf gt NaOTf
Interestingly pyridine seems to have a limit as a probe It would appear that it is only
effective for the softer Lewis acids where we see a range of shifts When we move to the
harder Lewis acids we see a maximum in the shift no matter which Lewis acid is added
These observations are similar to those observed in the 31P NMR study when
diphenylphosphinobenzaldehyde was used as a probe
It is therefore suggested that the interaction between pyridine and the Lewis acid results
in quantitative bond formation and placing a full positive charge on the nitrogen The
bond orders in all of these complexes are essentially the same resulting in similar
absorption frequencies and therefore a lack of discrimination between the different
metals This was not observed by Yang et al because they used a limited number of
metal salts
According to Yang11 a peak in the region of 1540 cm-1 indicates Broslashnsted acidity The
results of the current study (Table 57) indicate that a number of the metal triflates form a
type of Broslashnsted acidity in the ionic liquid These finding are in line with those found in
chapter 4 in which it was found that the metal triflates form Broslashnsted acidity in organic
solvents in the presence of water It should be noted here that although the [bmim][OTF]
was left under high vacuum at high temperature such organic liquids are notoriously
difficult to dry because of the ionic environment The remaining water in the ionic liquid
is most likely the cause of the Broslashnsted acidity seen in this study A noteworthy point
here is that none of the softer Lewis acids used in this study showed Broslashnsted acid
activity
In a further attempt to find a probe that could be used to rank the harder Lewis acids it
was thought that by making the probe more electron poor binding through the lone pair
204
on the nitrogen would be inhibited and in this way the probe may differentiate between
the harder Lewis acids
For the purpose of this aspect of the study several of the harder metal triflates were used
namely Al(OTf)3 Sc(OTf)3 and In(OTf)3 in order to determine if these probes could
discriminate between their electron withdrawing abilities The results are summarised in
Table 58
Table 58 Δν (cm-1) of electron-poor pyridine derivatives on complexation with various
Lewis acids in [bmim][OTf]
Probe and Peak of interest (cm-1)
ν (cm-1) on addition of Al(OTf)3
ν (cm-1) on addition of Sc(OTf)3
ν (cm-1) on addition of In(OTf)3
2 ndash Chloro ndash 6 ndash Methoxypyridine
14694 14694 14694 14694
2 ndash Chloro ndash 5 ndash Nitropyridine
144428 14463 14463 14463
26 - Difluoropyridine 14484 14484 14484 14484 25 ndash Dichloropyridine 14439 14439 14439 14439
From the outcome of these experiments is appears that by withdrawing electron density
from the nitrogen of the pyridine ring it the nitrogen has become a softer base by virtue of
electron density delocalisation and thus will no longer bond with the triflates which on
the whole are hard Lewis acids possibly accounting for the lack of complexation by the
metal triflates seen in the above results (Table 58)
The next logical step in the study was to add electron density onto the ring in an attempt
to make the nitrogen of the pyridine moiety harder and in this way it may discriminate
between the harder Lewis acids Infrared experiments were carried out in the same way
using pyridine derivatives that bearing electron donating moieties using three metal
triflates as before (Table 59)
205
Table 59 Δν (cm-1) of electron rich pyridine derivatives on complexation with various
Lewis acids in [bmim]][OTf]
Probe and Peak of interest (cm-1)
ν (cm-1) on addition of Al(OTf)3
ν (cm-1) on addition of Sc(OTf)3
ν (cm-1) on addition of In(OTf)3
246-Trimethylpyridine 16112 16400 16400 16400
23-Lutidine 15880 Suppression of signal
Suppression of signal
Suppression of signal
23-Lutidine 15581 Suppression of signal
Suppression of signal
Suppression of signal
22rsquo-Dipyridine 14557 14834 14801 14791
The results show that the metal triflates do in fact bind to the electron rich pyridine
derivatives The signals of 23-lutidine and 23- lutidine are suppressed on the addition of
the Lewis acid and no conclusive results could be drawn from the spectra At best it
would appear that the 22rsquo-dipyridine base shows a ranking of the metal triflates of
Al(OTf)3 gt Sc(OTf)3 gt In(OTf)3 However the probe is not sufficiently sensitive to
distinguish Lewis acidity with ease
Numerous other probes for the infrared were also evaluated in this study but are not
discussed exhaustively Various compounds containing carbonyl groups were used but it
was found that instead of seeing a shift in the peak of interest the intensity of the peak
diminished on complexation of the metal triflate Phosphines such as triphenyl phosphine
and triphenylphosphine oxide were also studied little discrimination was seen between
the Lewis acids
It is possible that the use of harder bases possibility even anions is called for For
example it may be that sodium aryl amides (NaNRRrsquo) would be useful or even
phenoxides Due to time constraints these aspects could not be pursued but are put
forward as a possibility for future study in this area
206
55 Conclusions
What the above discussion highlights is that the acidity of Lewis acids should be looked
at in relative terms This stems from the fact that the measurements be it by NMR
spectroscopy IR etc not only measure the extent to which the acid accepts the electrons
from the base but also the extent to which the base is donating the electrons As was seen
in the NMR study different rankings can be obtained when different Lewis bases are
used Ideally one base should be used to rank all Lewis acids But as was shown in the
infrared study the softer Lewis acids could be ranked using pyridine but this probe was
unable to discriminate between the harder Lewis acids
As was mentioned in the beginning of this chapter the quantitative measurements of
Lewis acids is a perennial problem of the Lewis acid-base theory and becomes more
complicated when carried out with metal triflates Amongst others their solubility is
limited to very few solvents making spectroscopic studies difficult
In cases where Lewis acids form strong 11 complexes with ligands induced chemical
shifts appear to be a valuable method for ranking of Lewis acid acidity
207
208
References
1 Branch C S Bott S G Barron A R J Organomet Chem 2003 666 23
2 Pearson RG J Am Chem Soc 1963 85 3533
3 Corma A Garcia H Chem Rev 2003 103 4307
4 Childs R F Mulholland D L Nixon A J Can Chem 1982 60 801
5 Lappert M F J Chem Soc 1962 103 542
6 Williams D B G Shaw M L Green M J Holzapfel C W Angew Chem
Int Ed 2008 47 560
7 Spencer J N Barton S C Cader B M Corsico C D Harrison L E
Mankuta M E Yoder C H Organometallics 1985 4 394
8 Shaw M L Unpublished data University of Johannesburg 2009
9 Drago R S Physical Methods in Chemistry Saunders 1976
10 Satchell D P N Wardell J L J Chem Soc 1964 4134
11 Yang Y Kou Y Chem Commun 2004 226
Summary of conclusions and suggested future research
Main conclusions
The application of Al(OTf)3 and other metal triflates as Lewis acid catalysts for organic
transformations has now been expanded to include reactions not previously investigated
with this compound as facilitator While the mechanism of activation in extremely dry
solvents may be through Lewis acidity (coordination of functionalised substrates to metal
cations) a dual mechanism (ie including Broslashnsted acidity) appears to be operative in
aqueous systems The relative importance of the two mechanisms differs from metal to
metal
The role of water in all systems is yet to be established with certainty and may include
increasing the solubility of metal triflates solvation of metal cations or a source of
Broslashnsted acidity (through activation of water by coordination to metal cations) A starting
point for such investigation requires the availability of extremely dry organic solvents A
very successful method for the rapid drying of several organic solvents has been
identified
With respect to the identification of the Broslashnsted acid component of a possible dual
mechanism the formation of cations from retinyl acetate appears to be a proton specific
reaction However the assumed discrimination between Lewis and Broslashnsted acidity on
the basis of the effect of an added hindered pyridine should be interpreted with caution
particularly in cases where the base is added in a large excess
Comparing the catalytic activity is particularly problematic when water (or a protic
solvent) is a (potential) reagent (eg Mukaiyama aldol reaction) Such comparisons
should preferably be carried out with model reactions which are inert to water
The observation that some metal triflates are not only tolerant of water but require water
for their catalytic activity poses the question of the role of small amounts of water in
209
organic reactions in general This question is particularly relevant in light of the
difficulties experienced in drying organic solvents
Several methods which have been suggested for the comparison of Lewis acidity were
evaluated with respect to metal triflates While none of the methods proved to be ideal
with the view to establishing ranking of Lewis acidity induced NMR chemical shifts of
selected probes appeared to hold the most promise
Future research
There is a real need to establish and compare the solubility of metal triflates in different
organic solvents and to use this information to evaluate their catalytic activities on a
comparative molar basis Too many reactions in the literature proceed in low yield
without mention of whether activity was possibly precluded due to insolubility of the
metal triflates which was identified in the present study as particularly problematic in dry
solvents or when larger amounts of metal triflates are to be dissolved in given solvents
The effects of small amounts of water on metal triflate catalysed reactions in organic
solvents would constitute a useful area of research Similarly there is merit in studies
directed in establishing the role of water in metal triflate catalysed reactions carried out in
water In this regard model reactions should be selected that are completely inert to water
or at least such that water should not be a potential participant in the reaction (as is the
case for the hydrolysis of one of the reactants in the Mukaiyama aldol reaction)
A need exists for obtaining more information on the exact mode of activation of
substrates by metal triflates in non-polar non-coordinating organic solvents eg the
nature of exchange phenomena operating in these situations where non solvated partly
dissociated metal triflates are involved as against dissociated and solvated species in
aqueous or other protic media
210
211
The role of the counterion should be studied in more detail not only with a view to
obtaining better understanding but to suggest cheaper alternatives to the relatively
expensive triflates
In view of its green credentials the application of metal triflates Al(OTf)3 in particular
the identification of new opportunities in synthesis offers real rewards It will be
particularly useful to find applications where the more traditional catalysts fail due either
to a lack of (selective) activity or due to extreme sensitivity of the substrate eg the
extreme sensitivity of pyrroles and indoles to protic acids
Chapter 6
Experimental data and characterisation
61 Standard experimental techniques
611 Chromatography
Thin-layer chromatography (TLC) was conducted on Merck GF254 pre-coated silica
gel aluminium backed plates (025 mm layer) Various solvent mixtures were used to
elute the chromatograms with a mixture of hexane and EtOAc usually being the
eluent of choice Compounds were visualised either by their fluorescence under UV
light (254 nm) or after spraying the TLC plate with a chromic acid solution and then
heating it over an open flame
Flash column chromatography (FCC) refers to column chromatography under
nitrogen pressure (ca 50 kPa) The columns were loaded with Merck Kieselgel 60
(230-400 mesh) and eluted with the appropriate solvent mixtures
612 Anhydrous solvents and reagents
Toluene was dried by passing it over activated alumina under nitrogen pressure (ca
50 kPa) The toluene was then heated over sodium-benzophenone under a nitrogen
atmosphere until the solution turned a deep blue colour The solvent was freshly
distilled before use Dichloromethane dichloroethane and 12-dimethoxyethane were
respectively heated over CaH2 under N2 with subsequent distillation Ethyl acetate
was distilled from K2CO3 using a Vigreux distillation column Hexanes were distilled
prior to use
62 Spectroscopical and spectrometrical methods
621 Nuclear Magnetic Resonance Spectroscopy (NMR)
NMR spectra were recorded using a Varian Gemini 2000 300 MHz spectrometer
The samples were made up in CDCl3 unless otherwise indicated The 1H NMR data
212
are listed in order chemical shift (δ reported in ppm and referenced to the residual
solvent peak of CDCl3 [δ = 724 ppm] or in the case of aromatic compounds to TMS
[δ = 000 ppm]) the multiplicity (s = singlet d = doublet q = quartet br s = broad
singlet dd = doublet of doublets dt = doublet of triplets dq = doublet of quartetsddd
= doublet of doublets od doublets ddt = doublet of doublets of triplets p = pentet sx
= sextet sp = septet) the number of integrated protons the coupling constant J
expressed in Hz and finally the specific hydrogen allocation Spin decoupling
experiments assisted with the determination of the coupling constants and hydrogen
allocation 13C NMR data are listed in the order chemical shift (δ reported in ppm
and referenced to the residual solvent peak of CDCl3 [δ = 770 ppm] and the specific
carbon atom allocation In some cases HSQC HMBC and COSY spectroscopy were
used to assist in the allocation of the spectra
622 Mass spectroscopy (mz)
Mass spectrometry was performed on the Thermo Double Focusing sector High
Resolution mass spectrometer Techniques included EIMS and CIMS
623 Infrared spectroscopy (IR)
A Tensor 27 spectrophotometer was used to record IR spectra using an ATR fitting
The data are listed with characteristic peaks indicated in wavenumber (cm-1)
63 Melting Points
Melting points were determined using a Gallencamp oil immersion apparatus and are
uncorrected
213
64 Chemical methods
Chapter 2
Metal triflates in protection group chemistry
641 General procedure for acetal formation
The aldehyde or ketone (125 mmol) was added to a mixture of the anhydrous alcohol
and 1 mol (0059 g) of the Al(OTf)3 The orthoester (273 mL 25 mmol) was slowly
added to the mixture and the reaction was stirred at room temperature for one hour
The reactions were quenched by passing the reaction mixture through a plug of
neutral alumina to remove the Al(OTf)3 The volatiles were then removed under
vacuum If further purification was necessary bulb-to-bulb vacuum distillation was
used
1-(Dimethoxymethyl)-4-methoxy benzene1 (11)
H
MeO OMe
H3CO
Yield 97 yellow oil
IR νmax (ATR diamond crystal neat) 1464 1301 1246 1049 785 cm-1 1H NMR (300 MHz CDCl3) δH 734 (d 2H J = 87 Hz H2 and H6) 686 (d
2H J = 90 Hz H3 and H5) 532 (s 1H acetal) 377 (s 3H OCH3)
328 (s 6H 2x OCH3) 13C NMR (75 MHz CDCl3) δC 1596 (C4) 1303 (C1) 1278 (C2 and C6) 1134
(C3 and C4) 1030 (acetal) 551 (OCH3) 525 (2 x OCH3)
HRMS (mz) Calculated [M ndash OMe]+ C9H11O2 = 1510765
Obtained = 1510753
214
1-(diethoxymethyl)-4-methoxy benzene2 (12)
H
EtO OEt
H3CO
Yield 90 yellow oil
IR νmax (ATR diamond crystal neat) 2974 1511 1246 1034 772cm-1 1H NMR (300 MHz CDCl3) δH 736 (d 2H J = 93 and J= 06 Hz H2 H6)
685 (d 2H J = 87 Hz H3 H5) 543 (s 1H acetal) 376 (s 3H
OCH3) 376 ndash 345 (m 4H 2 x OCH2) 120 ( t 6H J = 71 Hz CH3) 13C NMR (75 MHz CDCl3) δC 19063 (COC3H) 1318 (ipso) 1280 (ortho)
1133 (meta) 1013 (acetal) 607 (2 x OCH2) 150 (2 x CH3)
HRMS (mz) Calculated [M ndash OEt]+ C10H13O2 = 165091
Obtained = 1650910
1-Chloro-4-(dimethoxymethyl) benzene3 (13)
MeO
H
OMe
Cl
Yield gt98 colourless oil
IR νmax (ATR diamond crystal neat) 2937 2830 1088 1052 808 cm-1 1H NMR (300 MHz CDCl3) δH 736 (d 2H J = 75 Hz H2 H6) 731 (d J =
66 Hz H3 H5) 535 (s 1H acetal) 329 (s 6H 2 x OCH3) 13C NMR (75 MHz CDCl3) δC 1366 (ipso) 1342 (para) 1283 (meta) 1283
(ortho) 1022 (acetal) 525 (2 x OCH3)
HRMS (mz) Calculated [M ndash OMe]+ C9H11ClO = 1560258
Obtained = 1569867
215
1-chloro-4-(diethoxymethyl)benzene2 (14)
EtO
H
OEt
Cl
Yield gt98 colourless oil
IR νmax (ATR diamond crystal neat) 2975 2881 1087 1051 1015 cm-1 1H NMR (300 MHz CDCl3) δH 729 (d 2H J = 51 Hz H2 H6) 729 (d 2H J
= 75 Hz H3 H5) 545 (s 1H acetal) 360ndash356 (m 4H 2 x
CH2CH3) 120 (t 6H J = 71 Hz 2 x CH2CH3) 13C NMR (75 MHz CDCl3) δC 1376 (ipso) 1339 (para) 1282 (meta) 1230
(ortho) 1006 (acetal) 608 (2 x CH2CH3) 150 (2 x CH2CH3)
HRMS (mz) Calculated [M ndash OEt]+ C9H10ClO = 1690415
Obtained = 1690416
4-Nitroacetophenone dimethyl acetal (15)
MeO OMe
O2N
Yield 97 yellow solid
mp 612 ndash 634 degC
IR νmax (ATR diamond crystal neat) 2945 1520 1350 1086 1034 cm-1 1H NMR (300 MHz CDCl3) δH 818 (d 2H J = 87 Hz H2 and H6) 765 (d
2H J = 93 Hz H3 H5) 317 (s 6H 2 x OCH3) 151 (s 3H CH3) 13C NMR (75 MHz CDCl3) δC (1501 (CNO2) 1475 (ipso) 1274 (meta) 1234
(ortho) 491 (2 x OCH3) 258 (CH3)
HRMS (mz) Calculated [M ndash CH3]+ C9H10NO4 = 1960604
Obtained = 1960593
216
4-Nitroacetophenone dimethyl acetal (16)
EtO OEt
O2N
Yield 92 yellow oil
IR νmax (ATR diamond crystal neat) 12976 1520 1347 1045 857 cm- 1H NMR (300 MHz CDCl3) δH 810 (d 2H J = 78 Hz H2 and H6) 762 (d
2H J = 78 Hz H3 H5) 345 ndash 338 (m 2H CH2ACH3) 330 ndash 320
(m 2H CH2BCH3) 147 (s 3H CH3) 14 (t J = 63 Hz 6H 2 x
OCH2CH3) 13C NMR (75 MHz CDCl3) δC (1511 (ipso NO2) 1473 (ipso acetal) 1272 (C3
and C5) 1232 (C2 and C6) 1006 (Cα) 569 (2 x OCH2CH3) 268
(CH3) 151 (OCH3)
HRMS (mz) Calculated [M ndash OEt]+ C9H10NO4 = 1940812
Obtained = 1940811
o-Nitrobenzaldehyde dimethyl acetal4 (17)
H
MeO OMe
NO2
Yield 95 light yellow oil
IR νmax (ATR diamond crystal neat) 2937 1529 1359 1108 1055 cm-1 1H NMR (300 MHz CDCl3) δH 777 (d 2H J = 66 and 12 Hz H3 H6) 774
(d 1H J = 63 and 15 Hz H4) 756 (t 1H J = 78 and 11 Hz H5)
589 (s 1H acetal) 336 (s 6H 2 x OCH3) 13C NMR (75 MHz CDCl3) δC 148 (CNO2) 1325 (ipso) 1325 (C6) 1293
(C3) 1280 (C5) 1241 (C4) 997 (acetal) 544 (2 x OCH3)
HRMS (mz) Calculated [M ndash OMe]+ C8H8NO3 = 1660499
Obtained = 1660498
217
o-Nitrobenzaldehyde diethyl acetal4 (18)
H
EtO OEt
NO2
Yield gt98 light yellow oil
IR νmax (ATR diamond crystal neat) 2977 1529 1360 1108 1055 cm-1 1H NMR (300 MHz CDCl3) δH782 (d 1H J = 63 Hz H3) 777 (d 1H J =
78 Hz H6) 757 (dt 1H J = 60 and 13 Hz H5) 743 (dt 1H J = 78
and 15 Hz H4) 371 ndash 361 (m 2H 2 x OCH2ACH3) 360 ndash 350(m
2H 2 x OCH2BCH3) 122 (t 6H J = 72 Hz CH2CH3) 13C NMR (75 MHz CDCl3) δC 1336 (CNO2) 1324 (C6) 1291 (C3) 1280
1241 (C4) 983 (acetal) 634 (2 x OCH2) 150 (2 x CH3)
HRMS (mz) Calculated [M ndash OEt]+ C9H10NO4 = 1800666
Obtained = 1800655
(33-Dimethoxy-1-propen-1-yl)-benzene3 (19)
Ph OMe
OMe
Yield gt98 yellow oil
IR νmax (ATR diamond crystal neat) 2932 1449 1190 1049 772cm-1 1H NMR (300 MHz CDCl3) δH 744 ndash 736 (m 2H ortho) 735 -726 (m 3H
meta para) 674 (d 1H J = 159 Hz PhCH=CH) 617 (dd 1H J =
161 and 50 Hz PhCH=CH) 497 (d 1H J = 11 and 45 Hz acetal)
338 (s 6H OCH3) 13C NMR (75 MHz CDCl3) δC 1360 (ipso) 1335 (para) 1285 (meta) 1280
(PhCH=CH) 1266 (para) 1256 (PhCH=CH) 1028 (acetal) 526 (2
x OCH3)
HRMS (mz) Calculated [M ndash OMe]+ C10H11O = 1470804
Obtained = 1470805
218
(33-Diethoxy-1-propen-1-yl)-benzene (110)
Ph OEt
OEt
Yield gt98 light yellow oil
IR νmax (ATR diamond crystal neat) 2975 1679 1120 1049 969 cm-1 1H NMR (300 MHz CDCl3) δH 740 (d 2H J = 78 Hz ortho) 730 ndash 723 (m
3H meta para) 670 (d 1H J = 162 Hz PhCH=CH) 620 (dd 1H J
= 162 and 51 Hz PhCH=CH) 372 ndash 367 (m 2H OCH2ACH3) 361
ndash 350 (m 2H OCH2BCH3) 124 (t 6H J = 70 Hz 2 x CH2CH3) 13C NMR (75 MHz CDCl3) δC 1361 (ipso) 1329 (PhCH=CH) 1285 (meta)
1280 (para) 1267 (ortho) 1266 (PhCH=CH) 1014 (acetal) 610 (2
x OCH2CH3) 152 (2 x OCH2CH3)
HRMS (mz) Calculated [M ndash OEt]+ C11H13O = 1610961
Obtained = 1610960
11rsquo-Dimethoxy-decane5 (111)
MeO
OMe
H
Yield gt98 colourless oil
IR νmax (ATR diamond crystal neat) 2923 1219 1122 1055 769cm-1 1H NMR (300 MHz CDCl3) δH 430 (t 1H J = 59 Hz acetal) 325 (s 3H 2 x
OCH3) 152 (m 2H CH2CH3) 123 ndash 121 (m 14H CH3(CH2)7CH2)
082 (t 3H J = 65 Hz CH2CH3) 13C NMR (75 MHz CDCl3) δC 1045 (CH) 524 (OCH3) 324 (CH2CH) 318
(CH3CH2CH2) 295 ndash 293 (CHCH2(CH2)5) 246 (CH3CH2) 226
(CH2CH2CH) 140 (CH3)
HRMS (mz) Calculated [M ndash OMe]+ C11H23O = 1711743
Obtained = 1711741
219
11rsquo-Diethoxy-decane5 (112)
EtO
OEt
H
Yield gt98 colourless oil
IR νmax (CHCl3) 2943 1222 1234 1064 765 cm-1 1H NMR (300 MHz CDCl3) δH 444 (t 3H J = 47 Hz acetal) 360 (m 2H
CH2A) 346 (m 2H CH2B) 155 (m 2H CH2CH) 124ndash198 (m
12H CH3CH2(CH2)6CH2) 175 (t 6H J = 75 Hz 2 x OCH3) 084 (t
3H J = 66 Hz CH3) 13C NMR (75 MHz CDCl3) δC 1030 (acetal) 607 (2 x OCH2CH3) 336
(CH2CH) 318 (CH3CH2CH2) 294ndash293 (CHCH2(CH2)5) 247
(CH3CH2) 226 (CHCH2CH2) 153 (2 x OCH2CH3) 141 (CH3)
HRMS (mz) Calculated [M ndash OEt]+ C12H25O = 1851900
Obtained = 1851902
Dimethoxymethyl-cyclohexane (113)
OMe
OMe
Yield gt98 colourless oil
IR νmax (ATR diamond crystal neat) 2929 1215 1083 1048 754 cm-1 1H NMR (300 MHz CDCl3) δH 395 (d 1H J = 69 Hz acetal) 330 (s 6H 2 x
OCH3) 175ndash167 (m 4H H2A H3A H5A H6A) 163ndash150 (m 2H
H4) 121ndash110 (m 2H H2B H6B) 107ndash091 (m 2H H3B H5B) 13C NMR (75 MHz CDCl3) δC 1085 (acetal) 534 (2 x OCH3) 400 (C1) 280
(C3 and C5) 263 (C4) 257 (C4 and C6)
HRMS (mz) Calculated [M ndash OMe]+ C8H15O = 1271117
Obtained = 1271099
220
Diethoxymethyl cyclohexane (214)
OEt
OEt
Yield gt98 light yellow oil
IR νmax (ATR diamond crystal neat) 2925 2853 1130 1080 1056 cm-1 1H NMR (300 MHz CDCl3) δH 408 (d 1H J = 72 Hz acetal) 365 ndash 358 (m
2H OCH2ACH3) 355 ndash 340 (m 2H OCH2BCH3) 177 -167 (m 4H
H2A H3A H5A H6A) 162 -119 (m 2H H4) 114 (t 6H J = 72 Hz
CH2CH3) 106 ndash 087 (m 4H H2B H3B H5B H6B) 13C NMR (75 MHz CDCl3) δC 1067 (acetal) 615 (2 x OCH2) 407 (C1) 281
(C3 and C5) 264 (C4) 258 (C2 and C6) 153 (2 x OCH2CH3) 1HRMS (mz) Calculated [M ndash OEt]+ C8H15O = 1411274
Obtained = 1411275
55-dimethyl-2-phenyl-13-dioxane (215)
O
O
Yield 98White solid
mp 443 ndash 474 degC
IR νmax (ATR diamond crystal neat) 2960 1456 1392 1106 770 cm-1 1H NMR (300 MHz CDCl3) δH 751ndash748 (m 2H ortho) 738ndash734 (m 3H
meta para) 538 (s 1H acetal) 373 (d 2H J = 111 Hz OCH2A)
370 (d 2H J = 111 Hz OCH2B) 129 (s 3H CH3) 078 (s 3H CH3) 13C NMR (75 MHz CDCl3) δC 1384 (ipso) 1288 (para) 1283 (meta) 1261
(ortho) 1018 (acetal) 776 (2 x OCH2) 230 (CH3) 219 (CH3)
HRMS (mz) Calculated [M]+ C12H16O2 = 1921150
Obtained = 1921147
221
Dimethoxymethyl-benzene3 (216)
H
MeO OMe
Yield 98 light yellow oil
IR νmax (ATR diamond crystal neat) 2975 1338 1094 1050 700 cm-1 1H NMR (300 MHz CDCl3) δH 745 - 750 (m 2H H-aromatic) 732 - 7393
(m 3H H-aromatic) 541 (s 1H CH(OCH3)2) 333 (s 6H 2 x CH3) 13C NMR (75 MHz CDCl3) δC 1381 (ipso) 1284 (para) 1282 (meta) 1267
(ortho) 1031 (CH) 526 (OCH3)
HRMS (mz) Calculated [M ndash OMe]+ C8H9O = 1210648
Obtained = 1210445
Dimethoxymethyl-benzene2 (217)
H
EtO OEt
Yield 92 dark yellow oil
IR νmax (ATR diamond crystal neat) 2963 1324 1089 1047 745 cm-1
H NMR (300 MHz CDCl3) δH 750ndash752 (m 2H H-aromatic) 730ndash740 (m
3H H-aromatic) 553 (s 1H CH(OCH3)2) 350ndash366(m 4H 2 x
OCH2) 126 (t 6H J = 705 Hz 2 x CH3) 13C NMR (75 MHz CDCl3) δC 1389 (ipso) 1280 (para) 1280 (meta) 1264
(ortho) 1013 (CH) 607 (OCH2) 150 (CH2CH3) 1HRMS (mz) Calculated [M ndash OEt]+ C9H11O = 1350804
Obtained = 1350807
222
(11-Dimethoxyethyl)-benzene4 (218)
MeO OMe
Yield gt98 light yellow oil
IR νmax (ATR diamond crystal neat) 2929 1215 1083 1048 754 cm-1 1H NMR (300 MHz CDCl3) δH 753 (d 2H J = 75 Hz ortho) 740 ndash 728 (m
3H meta para) 320 (s 6H 2 x OCH3) 160 (s 3H CH3) 13C NMR (75 MHz CDCl3) δC 1420 (ipso) 1280 (ortho) 1274 (para) 1261
(meta) 1016 (acetal) 488 (2 x OCH3) 260 (CH3)
HRMS (mz) Calculated [M ndash CH3]+ C9H11O2 = 1510754
Obtained = 1510755
(11-Diethoxyethyl)-benzene4 (219)
EtO OEt
Yield 82 light yellow oil
IR νmax (ATR diamond crystal neat) 2974 1219 1119 1049 772cm-1 1H NMR (300 MHz CDCl3) δH 756 (d 2H J = 156 Hz ortho) 740 ndash 726 (m
3H meta para) 355 ndash 345 (m 2H CH2ACH3) 343 ndash 333 (m 2H
CH2BCH3) 160 (s 3H CH3) 123 (t 6H J = 71 Hz 2 x CH2CH3) 13C NMR (75 MHz CDCl3) δC 1438 (ipso) 1280 (ortho) 1272 (para) 1272
(para) 1261 (meta) 1011 (acetal) 566 (2 x OCH2CH3) 271
(OCH2CH3)
HRMS (mz) Calculated [M ndash OEt]+ C11H15O2 = 1791067
Obtained = 1791067
223
11-Dimethoxy cyclohexane (220) MeO OMe
Yield gt98 dark yellow oil
IR νmax (ATR diamond crystal neat) 2937 1701 1102 1050 908cm-1 1H NMR (300 MHz CDCl3) δH 314 (s 6H 2 x OCH3) 161ndash157 (m 4H H2
H6) 150ndash142 (m 4H H3 H5) 138ndash135 (m 2H H4) 13C NMR (75 MHz CDCl3) δC 1000 (Cα) 473 (2 x OCH3) 326 (C2 C6) 254
(C4) 228 (C3 C5)
HRMS (mz) Calculated [M ndash OMe]+ C7H13O = 1130961
Obtained = 1130967
11-Diethoxy cyclohexane (221) EtO OEt
Yield 93 dark yellow oil
IR νmax (ATR diamond crystal neat) 2933 1714 1115 1090 1053 cm-1
H NMR (300 MHz CDCl3) δH 343 (q 4H J = 71 Hz 2 x CH2CH3) 162 (m
2H H2 H6) 147 (m 2H H3 H5) 137 (m 1H H4) 115 (t 6H J =
71 Hz 2 x CH2CH3) 13C NMR (75 MHz CDCl3) δC 1000 (Cα) 547 (2 x OCH2) 338 (C2 C6) 256
(C4) 230 (C3 C5) 156 (2 x CH2CH3)
HRMS (mz) Calculated [M ndash OEt]+ C8H16O = 1281196
Obtained = 1281196
224