Cleavage of ethers in an ionic liquid. Enhancement, selectivity and potential application

Article abstract of DOI:10.1039/c7ob01096f

The cleavage of a series of ethers was examined in an ionic liquid containing hydrogen bromide. Reactions that did not proceed in either water or DMSO were found to proceed readily in this system, with notable selectivity between the cleavage of the different ether types examined herein. Increasing the proportion of water in the reaction mixture dramatically decreased the rate constant of ether cleavage; this could, in part, be attributed to a decrease in the solvent stabilisation of the transition state. Through analysis of the electronic requirements of the reaction (using substrates containing substituents with different Hammett parameters) and observation of rate enhancements for an ortho substituted system, the importance of the extent of protonation of the ether prior to nucleophilic attack was demonstrated.

Full text of DOI:10.1039/c7ob01096f

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ISSN 1477-0520
COMMUNICATION
Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
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Cleavage of ethers in an ionic liquid. Enhancement, selectivity
and potential application†
William E. S. Hart,a Leigh Aldous a,b and Jason B. Harper a,*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
The cleavage of a series of ethers was examined in an ionic liquid containing hydrogen bromide. Reactions that did not
proceed in either water or DMSO were found to proceed readily in this system, with notable selectivity between the
cleavage of the different ether types examined herein. Increasing the proportion of water in the reaction mixture
dramatically decreased the rate constant of ether cleavage; this could, in part, be attributed to a decrease in the solvent
stabilisation of the transition state. Through analysis of the electronic requirements of the reaction (using substrates
containing substituents with different Hammett parameters) and observation of rate enhancements for an ortho
substituted system, the importance of the extent of protonation of the ether prior to nucleophilic attack was
demonstrated.
www.rsc.org/
Conditions examined for this cleavage include dealkylation
under Brønsted acidic conditions,16-18 hydrolysis in acidic ionic
liquids,19-21 oxidation,22 and cleavage in ionic liquids catalysed
Introduction
The cleavage of ethers usually requires relatively harsh
conditions due to the inherent stability of this bond.1 As a
result of this stability, they find use as protecting groups in
organic synthesis.2 Ethers are also a very common functional
group found in nature, with more than 50% of the linkages
between the phenolic monomers comprising lignin being
ethers.3 Given how common ether linkages are, significant
efforts have been made to make the cleavage of ethers more
efficient and selective.2, 4, 5 One such avenue of exploration is
in the use of ionic liquids to both enhance the reactivity as well
as improve the selectivity of reactions involving ethers.5-8
Ionic liquids are arbitrarily defined as salts with a melting
point below 100◦C.9 Given that they consist of essentially
unsolvated anions and cations,10 they affect reactions
differently than molecular solvents.11-14 These solvents are also
capable of dissolving a wide range of molecules that are
otherwise insoluble or sparingly soluble in conventional
solvents.15
by the presence of metals.23 Although mechanisms have been
proposed, the microscopic origin of why ionic liquids enable
these reactions has not yet been determined; if these origins
were known, it might be possible to develop new ionic liquids
in order to control the rate of reaction and/or the selectivity of
a process in a rational fashion. Achieving reaction selectivity is
particularly desired as ether cleavage reactions in ionic liquids
are known to rapidly undergo a range of side reactions.17 As
such, the work described herein aims to develop an
understanding of how ionic liquids affect the cleavage of
ethers towards developing a selective method for the
breakdown of compounds containing a large range of
structurally similar ethers, such as lignin in biomass.
Results and discussion
The initial reaction considered, the cleavage of anisole 1, is
shown in Scheme 1. The reaction mixture was generated
through combining the ionic liquid N-butylpyridinium triflate
([Bpyr][OTf], compound 3 in Scheme 1), N-butylpyridinium
bromide ([Bpyr][Br]) and triflic acid. This reaction likely
proceeds through protonation of the ether oxygen, then
nucleophilic attack of the bromide onto the methyl group.24
The relative pKa values of the species present suggest that
hydrogen bromide is generated in situ and that the anisole 1 is
protonated (at least to some extent) under the reaction
conditions used.* It is important to note however, that
reported pKa values are in water and that some variation
would be expected when the solvent system is changed to the
ionic liquid used here. Subsequent nucleophilic attack by
bromide results in the loss of methyl bromide from the system.
Ionic liquids have been examined for their ability to
facilitate the cleavage of a range of ethers; predominately
those that can be related to the ether linkages in lignin.
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The change in observed reactivity could be due to one (or
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DOI: 10.1039/C7OB01096F
more) of a series of reasons. One possibility is that when the
solvent is changed from an ionic liquid to a molecular solvent,
the position of the protonation equilibrium changes, altering
the concentration of reactive protonated form of the anisole
and hence changing the rate accordingly. An additional
contribution could be that there are significant changes to the
solvation environment of either the transition state or the
starting materials (or both) resulting an increase in the
reaction rate in the ionic liquid; rate enhancements as a result
of each of these types of interactions have been previously
described.12
In order to further investigate possible microscopic origins
of the rate changes, temperature dependent kinetic studies
(over the temperature range 318 K to 348 K) were also
undertaken at both a high and a low water content. This
allowed construction of an Eyring plot (see ESI) for each set of
conditions and determination of the activation parameters in
each case (Table 1). When the water content of the reaction
mixture increased, there was an increase seen in both the
enthalpy (ΔH‡) and entropy (ΔS‡) of activation.¥ The change in
enthalpy of activation is more significant than the change in
entropy, corresponding to the observed rate constant
decrease on increasing the amount of water.
Scheme 1. The reaction of anisole 1 in ionic liquid 3 containing hydrogen bromide.
The ionic liquid 3 was chosen for this analysis because it
has been shown previously that this salt is a good solvent for a
range of solutes, including complex structures containing
different ether functionalities such as lignin.25 Hydrogen
bromide was chosen as the reagent for the compounds used
here as it is readily produced in situ and previous studies have
demonstrated ether cleavage under similar conditions.5
Conversion of the anisole 1 to phenol 2 was monitored
1
using H NMR spectroscopy and was found to proceed in this
ionic liquid mixture with a half life of ca. 40 min at 342.6 K.£
Under equivalent conditions (343 K, 0.5 M hydrogen bromide)
no reaction was observed in either aqueous solution or in
dimethylsulfoxide solution after 72 h. That is, the ionic liquid
facilitates a reaction that is otherwise not possible in these
solvents.
Given the lack of reaction in water and the fact that triflate
ionic liquids are generally hygroscopic,26 the reaction was
performed in mixtures containing a range of different water
contents from 4-25 mol%.€ A clear decrease in the rate
constant was noted with increasing proportion of water in the
reaction mixture (Figure 1). At ca. 24% by mole water in the
reaction mixture, which corresponds to ca. 2% water by mass,
while progress of the reaction was still able to be monitored,
the rate constant was 25-fold less than that observed in the
driest mixture considered. This observation demonstrates that
small amounts of water (by mass) can significantly affect the
reaction and that even when ionic liquid 3 is the predominant
species, the reaction is effectively halted.
Table 1 Activation parameters for the reaction of anisole 1 in the ionic liquid 3
containing hydrogen bromide (Scheme 1).
Water Content / mol% a ΔH‡ / kJ mol-1 b
ΔS‡ / J K-1 mol-1 b
-185.0 ± 4.1
13.4 ± 1.9
24.3 ± 2.8
67.1 ± 1.4
99.5 ± 3.0
-111.6 ± 9.1
a
Uncertainties quoted are the standard deviation of at least six samples
b
measured in duplicate. Uncertainties quoted are from the fit of the linear
regression.
The activation parameters determined incorporate some
component from the initial equilibrium (see ESI). Whilst the
enthalpy of activation can be determined unequivocally, the
entropy of activation cannot. However, it is not anticipated
that the change in entropy of activation noted can be
accounted for by the change in the position of the initial
equilibrium alone (see ESI for full details).
The increase in the enthalpy of activation indicates that
there is either a more stabilised starting material or a less
stabilised transition state when the proportion of water in the
ionic liquid increases. So either (i) the water solvates the
anisolium and bromide ions (the 'starting materials' for the
rate determining step) more effectively than the ionic liquid 3
and this solvation is more significant than that of the transition
state or (ii) the water solvates the transition state less
effectively than the ionic liquid and this solvation is more
significant than that of the starting material. The
accompanying increase in the entropy of activation is
consistent with either (i) an increased interaction between the
solvent mixture and the anisolium cation relative to the
transition state, or (ii) a reduction in the extent of interaction
between the solvent mixture and the transition state (relative
to the starting material).
Figure 1. The rate constants of the reaction of anisole 1 in mixtures containing
hydrogen bromide in [Bpyr][OTf] 3 with varying water content. The reaction was
carried out with ca. 15 equivalents of hydrogen bromide at 342.6 K. Uncertainties in
water content are half the range of duplicate measurements. Uncertainties in the rate
constants come from the fit of the data to the kinetic equation and are negligible
compared to the variation between samples; values lie within the size of the marker
used.
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Given the charged nature of the ionic liquid 3 and of the
anisolium cation, it seems unlikely that the predominate
variation in microscopic interactions is an increase in starting
material solvation when the charged ionic liquid solvent is
replaced with neutral water; this would support option (ii)
above. If, however, the water is more capable of stabilising
the charged anisolium (perhaps due to size and more effective
solvation), option (i) would be the most likely explanation.
Kamlet-Taft solvent parameters might also provide insight
into the differences observed between the two solvent
compositions, particularly the ability to solvate the anisolium
ion. Whilst not reported for the exact ionic liquid here, the
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DOI: 10.1039/C7OB01096F
related
N-octylpyridinium
triflate,
N-methyl-4-
methylpyridinium triflate and three isomeric N-octylpicolinium
triflates all exhibit α values of between 0.48 and 0.51, and β
values between 0.29 and 0.33; polarity π* values are also over
a similarly narrow range (0.95-0.99).28 Even changing the
cation to the 1-butyl-3-methylimidazolium system only
increases the values of α and β to 0.50 and 0.57, respectively.27
These values are substantially different to water, which has
Kamlet-Taft solvent parameters of 1.12 (α) and 0.14 (β),28
indicating that it is a stronger hydrogen bond donor and a
weaker hydrogen bond acceptor than the ionic liquid 3. Given
the anisolium cation would be expected to be a hydrogen
bond donor, this gives greater evidence in support of option
(ii) above. Irrespective, enthalpic effects dominate the rate
changes observed in these cases.
In order to examine if the ionic liquid effects upon the
reaction of ethers extend to more complex systems, both
phenethoxybenzene 4 and 1-methoxy-2-phenethoxybenzene 5
were considered. These compounds were examined because
they contain phenethyl phenyl ethers, the most common ether
linkage present in lignin;15 if selective ether cleavage could
occur between different ether types (such as in species 5)
there is the potential for selective degradation of lignin to
generate feedstock chemicals.
Figure 2. The rate constants of the reaction of the phenyl ether 4 in mixtures
containing hydrogen bromide in [Bpyr][OTf] 3 with varying water content. The reaction
was carried out with ca. 15 equivalents of hydrogen bromide at 342.6 K. Uncertainties
in water content are half the range of duplicate measurements. Uncertainties in the
rate constants come from the fit of the data to the kinetic equation and are negligible
compared to the variation between samples; values lie within the size of the marker
used.
There are two key things to note from this plot. The first point
relates to the relative rate of reaction of the two species 1 and
4; when the methyl group from anisole is replaced with a
phenethyl group to give compound 4, the rate constant of
ether cleavage decreases by as much as a factor of 20 for
comparable water contents. This difference is likely due to the
increased steric bulk of the second aromatic ring, hindering
nucleophilic attack of the bromide onto the oxonium ion. The
second point of note is that the trend is consistent with the
results seen for the reaction for compound 1; i.e. as the water
content of the solvent mixture increases, the rate constant of
reaction also decreases. Given this trend (Figure 2), it is
reasonable to assume that a similar microscopic effect is
causing the decrease in rate constant in the case of ether 4 as
was seen with compound 1, though no studies were
undertaken to confirm this.
Given the large change in the rate constants for the ether
cleavage between the reactions of anisole 1 and compound 4,
methoxy-2-phenethoxybenzene 5 was synthesised (for details,
see ESI) to allow direct competition studies. Once again, the
rate constant of the reaction for each of the ethers was
monitored across a range of different water contents using 1H
NMR spectroscopy. It should be noted that the reaction at the
methyl ether site was significantly faster than the phenyl ether
site (ca. 30-50 times faster for reaction at the methyl ether,
depending on the water content), simplifying the kinetic
analysis dramatically; the reaction at the methyl ether was
effectively completed before significant reaction of the phenyl
ether was noted. The demethylation reaction was conclusively
observed using NMR spectroscopy (cf. as observed for
compound 1); representative spectra are displayed in Figure
S7. This can be seen in Scheme 2 where the reaction proceeds
almost entirely through pathway a.
Initially, the ether 4 (prepared as outlined in the ESI) was
studied in a manner analogous to that for the anisole 1 in
order to examine if the more sterically hindered ether would
react in the same manner. Under the same conditions as the
initial studies, the reaction of the ether 4 proceeded more
slowly (with a half life of ca. 12 h). As was observed for the
methyl ether 1, no reaction was noted in either water or
dimethylsulfoxide under the same conditions. Once again, the
effect of the water concentration on the rate constant of the
process was examined, and the variation of such with water
content is shown in Figure 2.
The change in the rate constant of the reaction of the
phenyl ether 4 with the water content of the mixture follows a
similar trend to the reaction of anisole 1; as the water content
in the ionic liquid increases, the rate of reaction decreases.
Figure 3 illustrates the change in rate constant for reaction
at each site in the species 5 on changing the water content of
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the reaction mixture. The first point to note is that the general the case of the partially degraded starting materiVaile)w. ATrhticeleeOxntlirnae
DOI: 10.1039/C7OB01096F
trend seen previously, namely decrease in each of the rate oxygen containing functional group, however, might be
constants with increasing water concentration was again expected to stabilise the protonated form of the anisole 3; the
noted here, implying that similar microscopic interactions are result would be a more stable starting material for the rate
once again important.
limiting step, which would be expected to cause a decrease in
the rate of reaction. Similarly, it is unlikely that steric effects
would cause a rate increase. This suggests that perhaps
enhanced protonation of the ether functionalities in
compound 5, perhaps through a bifurcated hydrogen bond
(Figure 4), is responsible for these observations.
O
O
5
a
b
O
OH
O
Br
R
O
OH
H+
O
R
OH
OH
Br
+
Figure 4. The proposed structure for the bifurcated hydrogen bond that causes the rate
acceleration seen in the ortho substituted compound 5.
Scheme 2. The two potential paths for reaction of the ether 5 in mixtures
containing hydrogen bromide. Due to the large difference in the rate of reaction
between the methyl and phenethyl ethers, the reaction proceeds almost entirely via
pathway a.
After observing the increase in the rate constants for ether
cleavage in the ortho substituted case 5, both the meta
(compound 6) and the para (compound 7) substituted
substrates were synthesised (for details, see ESI) to further
examine the contributions of electronic effects to the reaction
and any importance of the sites being adjacent (i.e. the extent
to which a bifurcated hydrogen bond is significant). The
reactions were carried out under the same conditions as
previously and, once more, the progress of the processes
followed using 1H NMR spectroscopy to obtain the rate
constants shown in Table 2. Once again, kinetic analyses were
straightforward given the large differences in the observed
rate constants for the two processes. Also included in Table 2
are the relative rates of reaction at the different sites in
diethers 5-7.
Figure 3. The rate constants of the reaction of the diether 5 in mixtures containing
hydrogen bromide in [Bpyr][OTf] 3 with varying water content. Rate constants for
reaction at the methyl ether site are illustrated in blue and refer to the left axis while
rate constants for the phenyl ether is shown in red and uses the right axis. The reaction
was carried out with ca. 15 equivalents of hydrogen bromide at 342.6 K. Uncertainties
in water content are half the range of duplicate measurements. Uncertainties in the
rate constants come from the fit of the data to the kinetic equation and are negligible
compared to the variation between samples; values lie within the size of the marker
used.
Table 2 The rate of constants reaction between one of the ethers 5-7 and hydrogen
bromide dissolved in [Bpyr][OTf] 3 with ca. 5% by mole water at the sites specified,
along with ratio of these rate constants. The reaction was carried out with ca. 15
equivalents of hydrogen bromide at 342.6 K.
Substrate
k2 phenethyl
ether reaction
/ x 10-4 M-1 s-1 a
-
0.233 ± 0.056
0.679 ± 0.016
0.230 ± 0.002
0.775 ± 0.010
k2 methyl ether
k2 methyl ether
/ x 10-4 M-1 s-1 a
/ k2 phenethyl ether b
A significant difference between the diether case 5 and
each of the monoethers 1 and 4, however, is that the rate
constants for each of the reactions are larger when the two
functional groups are combined in the same compound; this is
seen across the full range of water contents examined. The
rate constants for ether cleavage in compound 5 are between
2- and 6-fold larger across the range of water contents
considered when compared to compounds 1 and 4, where
cleavage of each ether type was considered individually.
1
4
5
6
7
4.66 ± 0.12
-
24.06 ± 0.15
4.76 ± 0.13
13.69 ± 0.28
-
-
34.6 ± 0.8
20.5 ± 0.6
17.4 ± 0.4
aUncertainties quoted are the standard deviation of three replicate experiments.
bUncertainties quoted are compounded from the relative errors of the rate
constants used.
When considering these data, it is important to highlight
the different electronic effects of oxygen functionalities
depending on their position on the aromatic ring. In the para
One possible explanation of this rate enhancement might
be the electronic effects of an additional ether (or alcohol, in
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position, resonance electron donating effects dominate, whilst
in the meta position inductive electron withdrawing effects
dominate.29 Typically substituents at the ortho position are
not considered in such analyses because their position
adjacent to the site of substitution leads to steric and through-
space electronic interactions (field effects) which vary with the
nature of the process being considered.30 However, in the
ortho position oxygen containing functionalities might be
expected to be net electron donating, similar to if they were in
the para position.
Immediately apparent from these data is that the rate
constants for the meta substituted diether 6 are almost the
same as for the monoether cases 1 and 4. This suggests that
any electronic effects of the oxygenated substituent in this
position are negligible. The para case 7 is of interest as rate
enhancements relative to the monoether cases are again
noted. This observation suggests some component of the rate
enhancement in the ortho case is due to the electron donating
nature of the substituent; while the greater rate enhancement
in the ortho case compared to the para case is consistent with
the formation of the bifurcated hydrogen bond (Figure 4)
proposed earlier. Of interest though is the relative rate
enhancement, which can be seen in the final column of Table
2.
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It should be noted that due to the presence of both
through space electronic (field) and steric effects, Hammett σ
values are typically not reported for ortho substituents. In the
case of Figure 5, potential σ values for compounds 5 and 10
were calculated using the procedure outlined by Fujita and
Nishioka30 (For further details about the calculations used see
ESI). The implications of using these data will be discussed
further below.
Considering initially only the data for the species with
well defined Hammett σ values,₦ it can see seen that there is a
correlation with the electronic nature of the substituent on the
reagents 4, 6-9. Notable here is that the Hammett
susceptibility constant (the gradient of the plot) is -1.31 ± 0.16.
The fact that the magnitude is greater than one is consistent
with a larger effect of the substituent on the rate constant
than for the dissociation of benzoic acid from which the
reference σ values are obtained.31 However, the sign of
The increase in the rate constant for the methyl ether
cleavage relative to the phenethyl ether case is substantially
higher for the ortho substituted case 5 than for either of the
other diethers 6 and 7. It might be reasonably assumed that
any electronic effects on each process, including increasing the
extent of protonation through bifurcated hydrogen bond
formation, would be similar so it does not seem likely that the
cleavage of the methyl ether is enhanced relative to that of the
phenyl ether. Rather, these data suggest that another factor is
reducing the rate constant of the phenethyl ether cleavage.
One explanation could be reduction in the extent of
protonation through subsequent reaction of the hydroxy
substituent. However none of the expected notable changes in
the aromatic region of the 1H NMR spectra were seen.
Alternatively, the reaction at the phenethyl ether might simply
be more susceptible to steric effects of an ortho substituent
than the methyl ether.
In an effort to further examine electronic effects on the
rate of reaction at the phenethyl ether site, compounds 8-10
were also synthesised (for details, see ESI). These compounds
were chosen to examine the rate of phenethyl ether cleavage
in systems with substituents of differing electronic character.
Compound 10 was particularly included to examine if
substitution at the ortho position would cause the same rate
constant increase in a system without the possibility for a
bifurcated hydrogen bond.
Figure 5. A Hammett plot for the reaction between hydrogen bromide and each of a
series of substituted phenethyl ethers 4-10. Uncertainties in rate are from triplicate
experiments compounded by division while uncertainties in the σ value for compounds
5 and 10 are the ranges generated during calculation of the ortho σ parameter using
the chosen model reaction.
the gradient is key; the negative value of the substituent
constant shows that the process is favoured by electron
donating groups and disfavoured by electron withdrawing
groups. As was argued above, this is inconsistent with the key
effect being on the rate determining step, where electron
donating groups which would be expected to stabilise the
protonated starting material and result in a decrease in the
rate constant.§
An alternative explanation for the negative susceptibility
constant for this process relates to the position of the
equilibrium between the starting ethers and their protonated
forms (see ESI for illustration of this equilibrium). While an
Data for the rate of reaction for compounds 8-10 were
obtained in the same manner as the other compounds studied
here and graphs similar to Figures 1-3 were obtained (see ESI
for more details). Rate data for each of the compounds 4-10 at
approximately the same water content were used to construct
a Hammett plot (Figure 5) in order to examine if a trend could
be seen in respect to the electronic nature of the substituent.
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electron donating group would be expected to stabilise the Activation parameters were calculated using the bimolecular
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protonated intermediate, slowing down the nucleophilic attack form of the Eyring equation37 (for further information see ESI).
DOI: 10.1039/C7OB01096F
of the bromide, it would also shift the position of the initial
For kinetic measurements with half lives shorter than 3 h,
equilibrium towards the product.¶ The Hammett correlation the reaction was maintained at a constant temperature inside
suggests that this second effect dominates, though the the NMR spectrometer used; temperature calibration was
magnitude being 'only' 1.31 ± 0.16 (cf. 2-3.5 for equilibria with verified using a temperature probe suspended in ethylene
negative charge development on an oxygen centre32,$) implies glycol prior to beginning the reactions. For kinetic
that effects on the rate determining step also contribute.
measurements with half lives longer than 3 h, reactions were
1
Irrespective, an important outcome here is that the extent kept at the desired temperature in a water bath and their H
of protonation of the ether moiety is key in determining the NMR spectra were obtained periodically, enabling at least 10
change in observed rate constant. This extent of protonation measurements over at least three half-lives of the reaction in
is demonstrated in terms of electronic effects and also likely question. For reactions of compounds 5-7, a mixture of both
contributes to the effect of the ionic liquid on the reaction. techniques was used; the rate of reaction was measured for
Considering this protonation also leads into a brief final the cleavage of the methyl ether with the sample in the
discussion of the effect of ortho substituents.
spectrometer prior to the rate of reaction for the phenethyl
As mentioned above, Hammett values for ortho ether cleavage being measured using the water bath
substituents are typically not used given that it is difficult to technique described above.
take into account field and steric effects. The values used to
present the data in Figure 5 are calculated based on reported
data for a similar reaction (in this case the acid dissociation of
Conclusions
an aryl ammonium cation, see ESI for other assessed model
reactions and discussion about the differences between them).
Immediately apparent is that the methyl substituted case 10
has a smaller rate of reaction than might be expected based on
the correlation of the other data, whilst the methoxy case 4¢
has a rate constant that is larger. The former effect is
consistent with a negative steric effect of the methyl group; if
this is taken into account and the Hammett σ value adjusted,
the rate constant enhancement in the methoxy case 4
becomes even more marked (the Hammett σ value for
methoxy becomes less negative). This clearly supports the
argument above that there is another effect of the ortho
methoxy group, with formation of a bridged protonated
species most likely.
This work has examined the reaction of a range of different,
but structurally similar, ethers in an ionic liquid 3. The reaction
between these ethers was not seen to progress in the
molecular solvents considered under these conditions but the
presence of the ionic liquid has enabled this reaction to
progress in an efficient manner. It was seen that the
microscopic origin of the rate enhancement seen here was a
decrease in the degree of stabilisation between the ionic liquid
and the transition state with increasing water content noting
also the possibility of affecting the extent to which the ether
was protonated. Irrespective, the ionic liquid facilitates the
ether cleavage process.
The reaction of the different ether types is significantly
affected by steric effects, as was shown by the 20-fold rate
constant difference between compounds 1 and 4. This
difference immediately introduces the possibility of exploiting
this kinetic selectivity in such systems. Examination of the
Experimental
Anisole 1 was commercially available and was purified electronic effects suggested that affecting the position of the
immediately prior to use according to literature procedure.33 initial protonation equilibrium was key; this was supported by
Triflic
acid
was
purchased
from results with ortho substituted phenyl ethers where the
Sigma-Aldrich and used without further purification. The ionic formation of a proton bridged complex can accelerate this
liquid 3 was prepared from its bromide precursor, which itself reaction further.
Both these steric and electronic
was prepared through alkylation of the parent heterocycle.34 characteristics offer the potential to build in selectivity to a
The substrates 4-10 were prepared based on literature process through kinetic resolution.
methods.35, 36 For details of all synthetic preparations, see ESI.
A combination of the features above – namely the
For each of the kinetic analyses, samples were prepared selectivity and the enhanced rates relative to molecular
that contained the reagent compound (one of species 1, 4-10, solvents – along with the demonstrated solubility of complex
ca. 15 mM) and [Bpyr][Br] (>10 equivalents) in [Bpyr][OTf] 3. materials in such ionic liquids leads to further opportunity.
Where applicable, water was also added to the mixture to get There is the potential to consider more complex ethers such as
the desired mole fraction. Triflic acid was then added (one lignin and their degradation in a controlled fashion.
equivalent relative to [Bpyr][Br]) to initiate the reaction.
Pseudo first order rate constants were obtained through
Acknowledgements
WESH acknowledges the support of the Australian government
through the receipt of an Australian Postgraduate Award. This
work was supported by the Australian Research Council
monitoring the aliphatic signals of the reagents and products
1
using H NMR spectroscopy (see ESI for the signals that were
used in each case). These rate constants were then converted
to the corresponding bimolecular rate constants using the
concentration of the bromide for subsequent analysis.
6 | J. Name., 2012, 00, 1-3
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Organic & Biomolecular Chemistry
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3. A. Brandt, J. Grasvik, J. P. Hallett and T. Welton,VGiewreAernticlCehOenmlin.e,
through Projects DE130100770 (awarded to LA) and
DP130102331 (awarded to JBH), along with the University of
New South Wales Faculty of Science Research Grant
Programme (awarded to JBH). The authors would also like to
acknowledge the NMR facility within the Mark Wainwright
Analytical Centre at the University of New South Wales for
NMR support.
DOI: 10.1039/C7OB01096F
2013, 15, 550-583.
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Notes and references
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in the nature of the transition state39,40).
§ For an example of a closely related reaction (involving substrates
positively charged adjacent to
a benzene ring undergoing
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$ The authors are unaware of any reported data involving Hammett
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¢ It should be noted that the substituent present when the 30. T. Fujita and T. Nishioka, in Progress in Physical Organic
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