Kinetic and mechanistic investigations of the Baylis-Hillman reaction in ionic liquids

Article abstract of DOI:10.1039/c4ra14764b

We report here a quantitative study of the kinetics and mechanism of the Baylis-Hillman reaction in the presence of ionic liquids as solvent media. Apparently, a simple Baylis-Hillman reaction can occur by two different exclusive mechanisms in ionic liquids. The delicate balance of these mechanisms is maintained by the ionic environment employed. The main features of the possible mechanism have been described here along with interesting kinetic consequences. The measurement of rate constants and activation energy parameters demonstrate that as the medium becomes basic, the order of the reaction changes from 1 to 2. An unexpected change in the mechanism of the reaction is observed with a change in the nature of the ionic liquid. The Linear Solvation Energy Relationship has also been used as an investigating tool to delineate the respective contributions of the cation and anion of the ionic liquid. The observation strongly dictates the dependency of the mechanism of the Baylis-Hillman reaction on the nature of the anion of the ionic liquids undertaken for this study.

Full text of DOI:10.1039/c4ra14764b

RSC Advances
View Article Online
View Journal | View Issue
PAPER
Kinetic and mechanistic investigations of the
Baylis–Hillman reaction in ionic liquids†
Cite this: RSC Adv., 2015, 5, 2994
*
Anshu Singh and Anil Kumar
We report here a quantitative study of the kinetics and mechanism of the Baylis–Hillman reaction in the
presence of ionic liquids as solvent media. Apparently, a simple Baylis–Hillman reaction can occur by
two different exclusive mechanisms in ionic liquids. The delicate balance of these mechanisms is
maintained by the ionic environment employed. The main features of the possible mechanism have
been described here along with interesting kinetic consequences. The measurement of rate constants
and activation energy parameters demonstrate that as the medium becomes basic, the order of the
reaction changes from 1 to 2. An unexpected change in the mechanism of the reaction is observed with
a change in the nature of the ionic liquid. The Linear Solvation Energy Relationship has also been used as
an investigating tool to delineate the respective contributions of the cation and anion of the ionic liquid.
The observation strongly dictates the dependency of the mechanism of the Baylis–Hillman reaction on
the nature of the anion of the ionic liquids undertaken for this study.
Received 30th September 2014
Accepted 28th November 2014
DOI: 10.1039/c4ra14764b
www.rsc.org/advances
Baylis–Hillman reaction in the imidazolium based ionic
liquid.19 However, it was later shown that the imidazolium salts,
Introduction
with hydrogen at C-2 position, are deprotonated under mildly
basic conditions, forming corresponding carbenes with unde-
sirable side reactions.20 This undesired deprotonation was
partly overcome by the application of C-2 substituted imidazo-
lium salts for carrying out Baylis–Hillman reaction.21 Efficient
catalysis with good yield and reduced reaction times were
reported for pyridinium based ionic liquids too.22 However, the
need of application of efficient ionic liquids for carrying out
Baylis–Hillman reaction still stimulates a continuous research
effort. In spite of several attempts made in the past, the
mechanism of Baylis–Hillman reaction is still an issue of
debate. In 1986, Hill and Isaacs have proposed a mechanism
based on pressure dependence, rate and kinetic isotope effect.23
They proposed that a-proton cleavage was not taking place in
the rate determining step of the reaction. A kinetic study of the
reaction between acetaldehyde and acrylonitrile was followed
and the rates observed depended linearly on the rst power of
each concentration, conrming the empirical rate
expression as:
The Baylis–Hillman reaction offers a potential strategy to
construct highly functionalized products with a new stereo-
centre.1 The Baylis–Hillman reaction is essentially a three-
component reaction involving coupling of the a-position of
the activated alkene with carbon electrophiles under the cata-
lytic inuence of a tertiary amine, providing a simple and
convenient methodology for synthesis of densely functionalised
molecules. In fact, the ease of selectivity simplies the process
of assembling a carbon framework, which involves creativity
and is thus categorized as an important research topic in
science.2–10 Several articles have appeared in the literature
elaborating the basic mechanistic aspects and applications of
the synthesized products.11–13 More recently, ionic liquids have
been employed as solvent media for catalyzing many important
organic reactions.14–17 Ionic liquids possess many interesting
properties such as wide temperature window, very low vapour
pressure, recyclability etc. which make them different from
other conventional solvents and facilitate attributes which are
of fundamental interests to chemists. An ionic liquid is made
up of cation and anion, either of which or both may interact
with the reactants and affect the course of the reaction. Baylis–
Hillman reaction has also been carried out in ionic liquids.18
There are reports describing acceleration of DABCO-catalysed
rate ¼ k3[MeCHO][ACN][DABCO]
Based upon these studies they proposed the mechanism of
the Baylis–Hillman reaction to be proceeding in three impor-
tant steps as (a) Michael addition, involving attack of a base on
an activated alkene, forming an enolate (b) nucleophilic attack
of the enolate on an aldehyde and (c) proton transfer and the
National Chemical Laboratory, Physical Chemistry, NCL, Pune, Maharashtra, India.
E-mail: a.kumar@ncl.res.in
† Electronic supplementary information (ESI) available: This section includes
procedure for synthesis of ionic liquids, GC parameters, general procedure of
reaction, GC chromatogram, NMRs of product and ionic liquids. See DOI:
10.1039/c4ra14764b
2994 | RSC Adv., 2015, 5, 2994–3004
This journal is © The Royal Society of Chemistry 2015

View Article Online
Paper
RSC Advances
elimination of base resulting into product formation Methyl acrylate was distilled prior to use. 1-Morpholine, 1-bro-
(Scheme 1). mobutane, pyrrolidine, piperidine, 1-methylimidazole, pyri-
Later, Bode and Kaye, using acrylates also supported Hill and dine, Lithium bis(triuoromethane)sulfonimide >99% purity
Isaacs mechanism.24 A signicant contribution was made by was used as obtained from M/S Sigma-Aldrich company.
McQuade and co-workers who discovered a new pathway of the
reaction.25 Surprisingly, they observed that when the reaction
Synthesis of the ionic liquids
was carried out in polar aprotic solvent as DMSO, a new
All ionic liquids were synthesized as per the procedure given in
mechanism was operating based on hemiacetal intermediate.
literature. Detailed synthesis of the ionic liquids is given in the
The reaction showed second order dependence on aldehyde
ESI.† The water content of all ionic liquids was measured by
concentration. Although the report was quite intriguing, the
Karl-Fischer coulometer and was found to be less than 50 ppm.
mechanistic investigation of the reaction in a varied range of
solvents is still less studied. This report encouraged us to
determine the kinetic aspects of this reaction in a variety of
Kinetic measurements
ionic liquids.26 In this report from our lab we reported that the The reaction was initiated by the addition of methyl acrylate
rate determining step is second order in aldehyde, while rst 0.9028 ml (1 M) to the stirred solution of p-nitrobenzaldehyde
order in acrylate and DABCO when carried out in ethylsulfate and 1 ml of DABCO (1 M) in a given solvent. The temperature
based ionic liquids. These results were in contrast to the was maintained by Julabo constant temperature bath main-
observation made in organic solvents. From the earlier studies tained at 25 ꢀC with an accuracy of ꢁ0.01 K. The progress of the
the role of cations of ionic liquids in catalysing the reaction is reaction was monitored by withdrawing 1 ml of reaction
still in the state of infancy. In order to investigate the role of mixture in ether at appropriate time intervals. Chlorobenzene
cations and anions, Linear Solvation Energy Relationship was used as an internal standard. The extracted sample was
(LSER) has been employed here as a part of our investigating injected for GC analysis using a Varian CP-3800 gas chromato-
tool. To the best of our knowledge the inuence of various ionic gram. All reactions were monitored before 15% conversion. The
liquids on the reactivity of Baylis–Hillman reaction by LSER has k2 values were obtained from the integration of the peak area of
not been systematically reported earlier. As a part of our the product with respect to internal standard at different
investigation of various organic reactions in environment intervals of time. Slope of x/a(a ꢂ x) versus time plot and of
benign media.27–29 we herein investigate Baylis–Hillman reac- ln(a/a ꢂ x) versus time plot gave the value of pseudo second
tion in a variety of solvents with differing cations and anions. order and of rst order rate constant respectively. Relative peak
The roles of anions and cations have been further delineated by area was at prior calibrated with respect to the pure product of
LSER.
Baylis–Hillman reaction. No byproducts were observed during
entire reaction. Order plots were made by plotting rate versus
concentration of p-nitrobenzaldehyde. Linear dependence of
the rate of reaction on p-nitrobenzaldehyde concentration
exhibited reaction to be of rst order and nonlinear dependence
was an indication of second order. The rate constants measured
were reproducible to ꢁ3%.
Experimental section
1,4-Diazabicyclo [2.2.2]octane [DABCO] with (>99% purity) and
p-nitrobenzaldehyde, (>98% purity) were obtained from M/S
Sigma-Aldrich company and were used without further puri-
cation. Methanol, dichloromethane, toluene, dimethylsulfate,
ethyl acetate were used as obtained from Merck Germany.
Determination of activation parameters
Temperature dependent rate constants k2 was determined in
different ionic liquids at 5 different temperatures. Required
temperature was maintained by Julabo constant temperature
bath with an accuracy of ꢁ0.01 K. The reaction was started by
the addition of methyl acrylate, 0.9028 ml (1 M) to a stirred
solution of p-nitrobenzaldehyde (0.04 M) and DABCO (1 M) in
1 ml of solvent. The progress of the reaction was followed by GC.
1 ml of aliquot was withdrawn from the reaction mixture at
appropriate time interval and was further diluted and extracted
in ether. The extracted sample was then injected for GC
Scheme 1 Mechanism of Baylis–Hillman reaction as proposed by Hill
and Isaacs.
Scheme 2 The investigated Baylis–Hillman reaction.
RSC Adv., 2015, 5, 2994–3004 | 2995
This journal is © The Royal Society of Chemistry 2015

View Article Online
RSC Advances
Paper
analysis. Chlorobenzene was used as an internal standard. out in [Opyr][HSO4] and [Opy][HSO4], the reaction the reaction
Calculation of k2 has already been explained in the kinetic showed an order of 2. In order to ascertain the role of sulfate
measurement section. Arrhenius and Eyring equation were based ionic liquids, reaction was also carried out in [Py][HSO4],
used for the calculation of activation parameters. Each experi- [Opip][HSO4] and [MeMo][MeSO4]. The plot of (vc/vt) versus
ment was carried out in triplicate and the standard error in concentration for these ionic liquids also exhibited second
measurement was ꢁ6% [Pyr][HSO4], ꢁ8% [Opy][HSO4] and 10% order dependence on p-nitrobenzaldehyde concentration. The
for [Opyr][HSO4].
rate plots are given in Fig. 2. An order of two suggested
involvement of two equivalents of aldehyde in the rate deter-
mining step of the reaction. This observation suggested that
probably there was a change in the mechanism of the reaction
with the change in the structure of ionic liquid. The yield
obtained in case of [Pyr][HSO4] (with an order of 2) and [Pyr]
[HCOO] (with an order of 1) ionic liquids were 70% and 68%,
respectively. The possibility of acid–base equilibria between
DABCO and the ionic liquid cationic component was thwarted
since the moieties chosen as cationic component was suffi-
ciently basic as compared to that of DABCO. This eliminated the
possibility of the proton exchange between the catalyst taken
and the ionic liquids. Henceforth, any possibility of side reac-
tion can be neglected in the present study.30 Further, to inves-
tigate the role of cations in the kinetic and mechanistic aspect
of reaction, a number of ionic liquids with same anion and
different cations were synthesized. No change was however
observed in the order of the reaction upon changing the cation
of ionic liquids. This was quiet intriguing as it indicated the
nominal role played by the cations of ionic liquids in inu-
encing the mechanism of the reaction. [Opyr][HSO4] ionic
liquid was solid at room temperature and the kinetic study was
performed at higher temperatures (55 ꢀC). Higher rate
constants observed in [Opyr][HSO4] can be explained by the
inuence of higher temperature employed for carrying out the
experiments. [Pyr][HSO4], [MeMo][MeSO4] and [Opip][HSO4]
showed higher k2 values due to high value of solvatochromic
parameter, b, 0.966. b parameter is a measure of the basicity or
electron accepting tendency of the anions of ionic liquids.
Higher value of b indicates presence of higher electron density
on the anions of ionic liquids, which can probably greatly affect
the kinetics of the reaction by interacting strongly with the
zwitterionic species formed during the course of the reaction.
Other anions based on HCOOꢂ, NTf2ꢂ, CF3COOꢂ, CH3COOꢂ,
Results and discussion
As shown in Scheme 2, we have investigated the reaction
between p-nitrobenzaldehyde, 1 methyl acrylate, 2 and DABCO
as a catalyst in the presence of different ionic liquids used as
solvents. Investigation of the reaction in other electron rich
aldehydes such as benzaldehyde and anisaldehyde was thwar-
ted since the reaction was sluggish and took considerable
longer reaction time for its completion.7a The nature of the
solvent is an important determinant of the solute–solvent
interactions and resultant kinetic parameters. As ionic liquids
have the potential to act as solvent media, different from that
offered by any other solvent, it is expected that ionic liquids may
inuence the kinetics of the Baylis–Hillman reaction. In order
to discern the role of cations of ionic liquids on Baylis–Hillman
reaction, we present in the current investigation the mecha-
nistic aspects in the presence of ionic liquids. The ionic liquids
synthesized and used in the reaction were [Opy][HSO4], [Opyr]
[HSO4], [Opip][HSO4], [MeMo][MeSO4], [Pyr][HSO4], [Pyr]
[CH3COO], [Pyr][HCOO], [Mbpyr][NTf2], [Pyr][NO3], [Bmim][Br],
[Pyr][CF3COO] and [Opipe][HSO4]. Amino acids and imidazo-
lium based ionic liquids cannot be used due to the involvement
of side reactions.20
The kinetic results in these ionic liquids together with their
acronyms and names are given in Table 1. The plot of (vc/vt)
versus concentration for [Pyr][NO3], [Pyr][CH3COO], [Pyr]
[HCOO], [Mbpyr][NTf2], [Pyr][CF3COO] showed linear depen-
dence of rate of the reaction on p-nitrobenzaldehyde concen-
tration. Interestingly, an order of one indicated the involvement
of one equivalent of p-nitrobenzaldehyde in the rate deter-
mining step of reaction. Rate plots are given in Fig. 1 for illus-
tration. However, interestingly when the reaction was carried
Table 1 Kinetic data for the reaction of p-nitrobenzaldehyde 1 and methyl acrylate 2 with DABCO in different ionic liquids
Acronyms
Names of ionic liquids
Aldehyde order, n
k2 (pseudo rate constant)
[Opyr][HSO4]
[Opy][HSO4]
[Opip][HSO4]
[Pyr][HSO4]
[MeMo][MeSO4]
[Pyr][NO3]
[Pyr][CH3COO]
[Pyr][HCOO]
[MbPyr][NTf2]
[Pyr][CF3COO]
[Bmim][Br]
1-Octylpyrrolidinium hydrogensulfate
1-Octylpyridinium hydrogensulfate
1-Octylpiperidinium hydrogensulfate
Pyrrolidinium hydrogensulfate
1-Methylmorpholinium methylsulfate
Pyrrolidinium nitrate
Pyrrolidinium acetate
Pyrrolidinium formate
1-Butyl-3-methylpyrrolidinium bis(triuoromethanesulfonyl)imide
Pyrrolidinium triuoroacetate
1-Butyl-3-methylimidazolium bromide
1-Octylpiperazinium hydrogensulfate
2
2
2
2
2
1
1
1
1.18 ꢃ 10ꢂ3 Mꢂ1 ꢂ1
s
s
7.35 ꢃ 10ꢂ4 Mꢂ1 ꢂ1
1.22 ꢃ 10ꢂ3 Mꢂ1 ꢂ1
s
s
1.35 ꢃ 10ꢂ3 Mꢂ1 ꢂ1
1.13 ꢃ 10ꢂ3 Mꢂ1 sꢂ1
3.46 ꢃ 10ꢂ5 sꢂ1
3.33 ꢃ 10ꢂ5 sꢂ1
4.15 ꢃ 10ꢂ5 sꢂ1
4.00 ꢃ 10ꢂ5 sꢂ1
1.94 ꢃ 10ꢂ5 sꢂ1
—
1
1
Too fast
[Opipe][HSO4]
Solid < 90 ꢀ
C
—
2996 | RSC Adv., 2015, 5, 2994–3004
This journal is © The Royal Society of Chemistry 2015

View Article Online
Paper
RSC Advances
Fig. 1 The plots of the rate, (vc/vt) versus concentration of 1 for the reaction of 1 with 2 in presence of DABCO in (a) [Mbpyr][NTf2], correlation
coefficient, r ¼ 0.0.982, (b) [Pyr][CH3COO], r ¼ 0.958, (c) [Pyr][NO3], r ¼ 0.994, (d) [Pyr][CF3COO], r ¼ 0.980, (e) [Pyr][HCOO], r ¼ 0.987.
ꢂ
NO3 had comparatively lower rate constants of the reaction interval of 5 ꢀC. The plots of ln(k/T) versus 1/T are given in Fig. 3
due to the lower b values.31
and of ln k versus 1/T are given in Fig. 4. DsH, DsS and
Esa values were calculated from the slope and intercept of the
graphs. The values are reported in Table 2. The observed
magnitude of entropy for the reaction undertaken can credibly
be associated with a process in which two successive bond
formations occurred in conjunction with development of full
charges. Esa for [Pyr][HSO4] is minimum which is in accordance
of observation of higher rate constants of the reaction.
Esa 'observed for [Opy][HSO4] was comparatively higher. This
Eyring activation parameters
In order to obtain greater insight into the mechanism of the
reaction activation parameters, DsH and DsS were both
determined using Eyring equation. Esa was calculated from
Arrhenius equation. The reaction in [Pyr][HSO4] and [Opy]
[HSO4] was carried out at 25, 35, 45, 55 and 65 ꢀC. However for
ꢀ
[Opyr][HSO4] the reaction was carried out at 50 to 70 C at an
This journal is © The Royal Society of Chemistry 2015
RSC Adv., 2015, 5, 2994–3004 | 2997

View Article Online
RSC Advances
Paper
Fig. 2 The plots of the rate, (vc/vt) versus concentration of 1 for the reaction of 1 with 2 in presence of DABCO in (a) [Opip][HSO4], correlation
coefficient, r ¼ 0.997, (b) [Opy][HSO4], r ¼ 0.952, (c) [MeMo][MeSO4], r ¼ 0.999, (d) [Pyr][HSO4], r ¼ 0.985 (e) [Opyr][HSO4], r ¼ 0.961.
can be a determinant factor in the observed slow pace of the to elucidate the effect of longer alkyl chain length on the
reaction as reported in Table 1. Higher enthalpy of activation kinetics and mechanism of the reaction, [Opyr][HSO4] and [Opy]
observed for [Opyr][HSO4] can be explained by a noticeable [HSO4] ionic liquids were also deeply scrutinized. Results indi-
change of the reaction from being exergonic to endergonic. This cate that there is an increase in the Esa energy upon moving
can provide a rationalization of the fact that the reaction cannot from [Pyr][HSO4] to [Opyr][HSO4] suggesting that increase in the
be performed at elevated temperatures. Higher entropy for alkyl chain length of the cation can have detrimental effect on
reaction in [Opyr][HSO4] suggests that bond formation becomes the rate of the reaction. Irrespective of increased activation
comparatively difficult at elevated temperatures.32 Inspite of energy barrier, the observed order of the reaction in [Pyr][HSO4],
unfavourable DsS the reaction carried out in [Opyr][HSO4] [Opyr][HSO4] and [Opy][HSO4] remains 2. This is a very impor-
possess k2 of the order of 1.18 ꢃ 10ꢂ3 Mꢂ1 sꢂ1. This can be tant nding that the mechanism of the reaction is independent
explained by very high b value of the sulfate based ionic liquids. of the alkyl chain length of the cation. The reaction follows the
Interestingly, presence of sulfate based anions makes thermo- same pathway in the investigated ionic liquids. Long alkyl chain
dynamically unfavorable reaction, kinetically favorable. In order length of the cation is acting as a determinant to slow down the
2998 | RSC Adv., 2015, 5, 2994–3004
This journal is © The Royal Society of Chemistry 2015

View Article Online
Paper
RSC Advances
Fig. 3 Eyring plots (ln(k/T) vs. 1/T) for the reaction of p-nitrobenzaldehyde, 1 and methyl acrylate, 2 with DABCO in (a) [OPy][HSO4] (b) [OPyr]
[HSO4] (c) [Pyr][HSO4].
reaction velocity as shown in Table 1. The interaction of the effect. Latter is further divisible into hydrogen bond accepting
cation of ionic liquid with the reactants is comparatively weaker tendency (b) and hydrogen bond donar tendency (a). A variety of
as compared to that of the anions. This may be due to the higher interactions varying from intermolecular specic and non
charge density on the sulfate based anions as compared to that specic solute–solvent interactions can be described by a
of the cations. Electron rich anion can inuence the reaction concept of LSER given by:
mechanism, containing charged species, in a more rational way
as compared to that of cation.
(XYZ) ¼ (XYZ)0 + aA + bB + cC
where (XYZ)0 represents property in a nonpolar medium, a, b,
Solvent-reactivity relationship
and c are coefficients which shows the dependence of physical
One of the most comprehensive and widely used solvent scales
and chemical properties (XYZ) in a particular solvent on various
for understanding and interpreting solvent behaviour in reac-
parameters of the solvent. The origin of the equation is from
tion dynamics is linear solvation energy relationship (LSER).
The use of solvatochromic probes for the characterization of
molecular environment of reactants by LSER is well docu-
mented in the literature. The interaction of solvatochromic dyes
with pure solvents or mixtures are a combination of many
effects. The basic premise of linear solvation energy relation-
ship is that attractive solute–solvent interaction can be repre-
sented as a linear combination of nonspecic dipolarity/
polarizability (p*) and specic hydrogen bond formation
Kamlet–Ta equation which has been veried many times in
the literature. It is one of the most successful quantitative
methods for describing solvent effect with a multiparameter
equation. The most established multivariate of LSER is that of
Kamlet and Ta given by:33
(XYZ) ¼ (XYZ)0 + aa + bb + cp*
This journal is © The Royal Society of Chemistry 2015
RSC Adv., 2015, 5, 2994–3004 | 2999

View Article Online
RSC Advances
Paper
Fig. 4 Arrhenius plots (ln k versus 1/T) for the reaction of p-nitrobenzaldehyde, 1 and methyl acrylate, 2 with DABCO in ionic liquids in (a) [OPy]
[HSO4] (b) [OPyr][HSO4] and (c) [Pyr][HSO4].
where a is the hydrogen bond donation, b is hydrogen bond also separately tted with the individual a, b and p* parameters.
accepting tendency (basicity) and p* is the dipolarity/ The plots are given in Fig. 5(a)–(c). The correlation coefficient
polarizability tendency. In the case of reactions the equation very clearly exhibited the dependency of k2 on b value. Appli-
can be written as:
cation of the monoparametric equation does not offer satis-
factory results. The resulting correlation, obtained by multiple
regression, is signicant although with some scatter gave the
coefficient values as follows:
log kobs ¼ log k0 + aa + bb + cp* + other parameters
log k2cal ¼ ꢂ8.581 + 1.069 ꢃ a + 6.022 ꢃ b ꢂ 0.325p* (r2 ¼ 0.997)
We have made attempts to correlate reaction rate constants
with solvatochromic parameters. At rst linear regression was
done followed by multiple regressions. The rate constants were
All the parameters appear to be important here. However
contribution of a and p* is comparatively negligible as shown
by regression values. Interestingly the contribution of b is
dominant in affecting the rate of the reaction. The magnitude of
coefficient of b indicates a good degree of interaction between
the anions of ionic liquids and the substrate. Upon plotting the
log k2 values calculated from equation and experimental k2
values, solvation pattern as shown in Fig. 5(d) is obtained. The
correlation thus obtained between log k2exp and log k2cal is fairly
satisfactory, where k2exp and k2cal are the experimental and
calculated k2 values.
Table
2 Activation parameters for the reaction of p-nitro-
benzaldehyde, 1 and methyl acrylate, 2 with DABCO in ionic liquids
Eas
D
sH
D
sS
S. no.
Ionic liquids
(kJ molꢂ1
)
(kJ molꢂ1
)
(J molꢂ1 Kꢂ1
)
1
2
3
[Pyr][HSO4]
[Opyr][HSO4]
[Opy][HSO4]
16.30
129.51
69.95
13.70
126.74
67.31
ꢂ256.20
92.11
ꢂ80.76
3000 | RSC Adv., 2015, 5, 2994–3004
This journal is © The Royal Society of Chemistry 2015

View Article Online
Paper
RSC Advances
Fig. 5 The plots of log k2 versus (a) a, correlation coefficient ¼ 0.774 (b) b, correlation coefficient ¼ 0.876 and (c) p*, correlation coefficient ¼
ꢂ0.248 (d) correlation of the log of calculated and experimental k2 values for the reaction of p-nitrobenzaldehyde, 1 and methyl acrylate, 2 with
DABCO in ionic liquids.
and rate law equations. Based upon the experimental observa-
tions presented here we also propose a similar mechanism in
ionic liquids which is exclusively ‘anion dependent’. The steps
involved are (a) the reversible Michael addition, involving the
attack of DABCO on activated alkene to form an enolate which is
a zwitterionic species (b) the attack of enolate on the rst equiv.
of aldehyde in order to give second zwitterionic species (c)
attack of second zwitterionic species on another equiv. of
aldehyde leading to the formation of a hemiacetal intermediate
(d) transfer of a proton from the a-position of C–H bond to the
alkoxide (RDS) and (e) elimination of base with the formation of
Mechanism of the reaction
The above studies show the predominance of the role of the
anion of ionic liquids in catalysing the Baylis–Hillman reaction.
A minor role is played by a whereas p* plays insignicant role.
Biparametric equation itself contributes signicantly to the rate
constants with b playing an important role Increase in the alkyl
chain length only increases the activation energy of the reac-
tion. It has no appreciable effect on the order of the reaction.
ꢂ
However, the presence of HSO4 as anion does affect the
mechanism of the reaction. As HSO4 ion has a high b value,34
ꢂ
henceforth it can considerably affect the mechanism and
kinetics of the Baylis–Hillman reaction. In 2005, McQuade and
co-workers have reported second order dependence of rate of
Baylis–Hillman reaction on aldehyde concentration. Solvent
like DMSO which has a high b value (0.743) was very effective in
driving the reaction to a new pathway which was different to the
one proposed by Hill and Isaacs. There results were in complete
agreement based upon competitive experiments, kinetic study
ꢂ
product. The electron rich species such as DMSO and HSO4
ion when present in the reaction medium can destabilize the
negative charge present on the alkoxide oxygen. These species
solvate only cation making negative charge highly reactive and
bare for attack. The developed negative charge tries to satisfy
itself by proton transfer from a-carbon. Unfortunately, this
transfer leads to an unstable 4-membered transition state. Such
proton transfer is geometrically unfavourable too. The presence
This journal is © The Royal Society of Chemistry 2015
RSC Adv., 2015, 5, 2994–3004 | 3001

View Article Online
RSC Advances
Paper
Scheme 3 Mechanism of Baylis–Hillman reaction proposed by McQuade and co-workers.
of high charge density on DMSO and HSO4ꢂ ion further makes the Kamlet–Ta based LSER approach. It has been found that
the 4-membered transition state unstable. The species then the choice of the best parameter for every type of interaction is
attacks another equivalent of p-nitrobenzaldehyde to form a very crucial because of the complexity of the reaction medium
highly stable 6-membered transition state. The proton transfer and also because of their susceptibility towards more than one
from a-carbon to alkoxide ion is now energetically favourable. facets of the undergoing reaction. Kamlet–Ta based LSER
This attack generates hemiacetal intermediate. Rest of the step approach also show that Baylis–Hillman reaction exhibits anion
is the same as elimination of base and product formation. The dependency. The correlations are best explained by the high
results give a insight into the mechanistic pathway of the basicity of the anions of ionic liquids involved. It has been
ꢂ
reactioꢂn and quite interestingly suggests that HSO4 and shown that both rate constant and mechanism of Baylis–Hill-
MeSO4 based anion follows McQuade pathway with two man reaction shows dependency on more basic anions. In
equivalents of aldehyde in the rate determining step of reaction short, it has been demonstrated here that the ionic liquids with
(Scheme 3) and other anion based ionic liquids follows Hill and more basic anions follow McQuade mechanism and ionic
Isaacs pathway with only one equivalents of aldehyde present in liquids with less basic ones follow Hill and Isaacs mechanism.
the rate determining step of the reaction.
Acknowledgements
Conclusion
AS is thankful to UGC, New Delhi for an award of a Senior
In conclusion, we have used kinetic experiments to demonstrate
that the mechanism of the Baylis–Hillman reaction is not
unique for all ionic liquids. The nature of the anion of ionic
liquids and its basicity can be a very important determinant
factor in deciding the pathway of the reaction. The sulfate based
ionic liquids are very peculiar in their behaviour since they are
the only anions which have two equivalents of p-nitro-
benzaldehyde participating in the rate determining step of the
reaction. Other anions based ionic liquids, when employed have
only one equivalent of p-nitrobenzaldehyde participating in the
rate determining step of the reaction. The valid mechanism in
ionic liquids, under investigation, can be a function of the b
value of the anion of ionic liquid. The role of the solvent in the
kinetics and the rate of reaction has been further conrmed by
Research Fellowship to her. AK is grateful to Department of
Science & Technology, New Delhi for awarding him a J. C. Bose
National Fellowship (SR/S2/JCB-26/2009).
Notes and references
1 A. B. Baylis and M. E. D. Hillman, German Patent 2155113,
1972, Chem. Abstr., 1972, 77, 34174q.
2 P. V. Ramachandran, S. Madhi, L. Bland-Berry,
M. V. R. Reddy and M. J. O'Donnell, J. Am. Chem. Soc.,
2005, 127, 13450–13451.
3 G. W. Kabalka, B. Venkataiah and G. Dong, J. Org. Chem.,
2004, 69, 5807–5809.
3002 | RSC Adv., 2015, 5, 2994–3004
This journal is © The Royal Society of Chemistry 2015

View Article Online
Paper
RSC Advances
4 H. S. Lee, J. M. Kim and J. N. Kim, Tetrahedron Lett., 2007, 48,
4119–4122 and ref. cited therein.
5 B. M. Trost, M. R. Machacek and H. C. Tsui, J. Am. Chem. Soc.,
2005, 127, 7014–7024.
6 L. A. Paquette, G. D. Bennett, M. B. Isaac and A. Chhatriwalla,
J. Org. Chem., 1998, 63, 1836–1845.
7 (a) V. K. Aggarwal, A. Mereu, G. J. Tarver and R. McCague, J.
Org. Chem., 1998, 63, 7183–7189 and ref. cited therein; (b)
V. K. Aggarwal, D. K. Dean, A. Mereu and R. Williams, J.
Org. Chem., 2002, 67, 510–514; (c) V. K. Aggarwal, I. Emme
and S. Y. Fulford, J. Org. Chem., 2003, 68, 692–700; (d)
S. Y. Fulford and G. C. Lloyd-Jones, Angew. Chem., Int. Ed.,
2005, 44, 1706–1708; (h) S. E. Drewes, N. D. Emslie,
N. Karodia and A. A. Khan, Chem. Ber., 1990, 123, 1447–
1448; (i) R. Oda, T. Kawabata and S. Tanimoto, Tetrahedron
Lett., 1964, 5, 1653–1657.
13 (a) D. Roy and R. B. Sunoj, Chem.–Eur. J., 2008, 14, 10530–
10534; (b) D. Roy and R. B. Sunoj, Org. Lett., 2007, 9, 4873–
4876; (c) C. Patel and R. B. Sunoj, J. Org. Chem., 2010, 75,
359–367; (d) D. Roy, C. Patel and R. B. Sunoj, J. Org. Chem.,
2009, 74, 6936–6943; (e) P. Verma, P. Verma and
R. B. Sunoj, Org. Biomol. Chem., 2014, 12, 2176–2179.
V. K. Aggarwal, A. M. M. Castro, A. Mereu and H. Adams, 14 M. J. Earle and K. R. Seddon, Pure Appl. Chem., 2000, 72,
Tetrahedron Lett., 2002, 43, 1577–1581; (e) E. L. Myers, 1391–1398.
J. G. de Vries and V. K. Aggarwal, Angew. Chem., Int. Ed., 15 T. Welton, Chem. Rev., 1999, 99, 2071–2083.
2007, 46, 1893–1896; (f) V. K. Aggarwal, A. Patin and 16 J. Dupont, R. F. de Souza and P. A. Z. Suarez, Chem. Rev.,
S. Tisserand, Org. Lett., 2005, 7, 2555–2557; (g) E. L. Myers,
C. P. Butts and V. K. Aggarwal, Chem. Commun., 2006, 17 J. K. D. Surette, L. Green and R. D. Singer, Chem. Commun.,
4434–4436. 1996, 2753–2754.
8 J.-N. Tan, M. Ahmar and Y. Queneau, RSC Adv., 2013, 3, 18 (a) X. Mi, S. Luo, H. Xu, L. Zhang and J.-P. Cheng,
2002, 102, 3667–3692.
17649–17653.
Tetrahedron, 2006, 62, 2537–2554; (b) C. L. Johnson,
R. E. Donkor, W. Nawaz and N. Karodia, Tetrahedron Lett.,
2004, 45, 7359–7361; (c) C. A. M. Afonso, L. C. Branco,
N. R. Candeias, P. M. P. Gois, N. M. T. Lourenco,
N. M. M. Mateus and J. N. Rosa, Chem. Commun., 2007,
2669–2679; (d) L. S. Santos, B. A. D. Neto, C. S. Consorti,
C. H. Pavam, W. P. Almeida, F. Coelho, J. Dupont and
M. N. Eberlin, J. Phys. Org. Chem., 2006, 19, 731–736; (e)
L. S. Santos, C. H. Pavam, W. P. Almeida, F. Coelho and
M. N. Eberlin, Angew. Chem., Int. Ed., 2004, 43, 4330–4333;
(f) E. J. Kim, S. Y. Ko and C. E. Song, Helv. Chim. Acta,
2003, 86, 894–899; (g) H. Gong, C.-q. Cai, N.-f. Yang,
L.-w. Yang, J. Zhang and Q.-h. Fan, J. Mol. Catal. A: Chem.,
2006, 249, 236–239; (h) S. Zhao, E. Zhao, P. Shen, M. Zhao
and J. Sun, Ultrason. Sonochem., 2008, 15, 955–959; (i)
K. Jeong and J. S. Ryu, J. Org. Chem., 2010, 75, 4183–4189;
9 Z. Duan, Z. Zhang, P. Qian, J. Han and Y. Pan, RSC Adv., 2013,
3, 10127–10130.
10 D. Basavaiah, G. Veeraraghavaiah and S. S. Badsara, Org.
Biomol. Chem., 2014, 12, 1551–1555.
11 (a) M. V. Pilipecz, P. Scheiber, Z. Vincze, T. R. Varga, G. Toth
and P. Nemes, Tetrahedron, 2014, 64, 4355–4360; (b)
D. C. Babu, Ch. B. Rao, K. Venkatesham, J. J. P. Selvam
and Y. Venkateswarlu, Carbohydr. Res., 2014, 388, 130–137;
(c) H. Mandai, K. Shimowaki, S. Keita, K. Mitsudo and
S. Suga, Asian J. Org. Chem., 2014, 3, 437–441; (d)
J. A. F. Ramos, T. J. Nagem and J. G. Taylor, Lett. Org.
Chem., 2014, 11, 194; (e) Y. Matsuda, M. Kato,
T. Kawaguchi, T. Koyama, Y. Saikawa and M. Nakata,
Tetrahedron, 2014, 70, 1154–1168; (f) A. Latorre, J. A. Saez,
S. Rodriguez and F. V. Gonzalez, Tetrahedron, 2014, 70, 97–
102; (g) T. M. Rodrigues, M. S. Santos, H. Santos and
F. Coelho, Tetrahedron Lett., 2014, 55, 180–183; (h) L.-F.
R. Kristerson, J. P. S. Scaramal, J. A. L. C. Resende,
C. F. Tormena, F. Claudia, F. L. Oliveira, R. Aparicio and
˜
´
(j) E. J. Lenardao, J. O. Feijo, S. Thurow, G. Perin,
R. G. Jacob and C. C. Silveira, Tetrahedron Lett., 2009, 50,
5215–5217; (k) X. Mi, S. Luo and J.-P. Cheng, J. Org. Chem.,
2005, 70, 2338–2341.
F. Coelho, Tetrahedron, 2014, 70, 3319–3326; (i) S. Kotani, 19 J. N. Rosa, C. A. M. Afonso and A. Santos, Tetrahedron, 2001,
M. Ito, H. Nozaki, M. Sugiura, M. Ogasawara and 57, 4189–4193.
M. Nakajima, Tetrahedron Lett., 2013, 54, 6430–6433; (j) 20 V. K. Aggarwal, I. Emme and A. Mereu, Chem. Commun.,
B. A. Shairgojray, A. A. Dar and B. B. Ahmad, Tetrahedron 2002, 1612–1613.
Lett., 2013, 54, 2391–2394; (k) D. Basavaiah, B. S. Reddy 21 J.-C. Hsu, Y.-H. Yen and Y.-H. Chu, Tetrahedron Lett., 2004,
and S. S. Badsara, Chem. Rev., 2010, 110, 5447–5674 and
ref. cited therein.
12 (a) H. M. R. Hoffmann and J. Rabe, Angew. Chem., Int. Ed.
45, 4673–4676.
22 S.-H. Zhao, H.-R. Zhang, L.-H. Feng and Z.-B. Chen, J. Mol.
Catal. A: Chem., 2006, 258, 251–256.
Engl., 1983, 22, 795–796; (b) L. J. Brzezinski, S. Rafel and 23 J. S. Hill and N. S. Isaacs, J. Phys. Org. Chem., 1990, 3, 285–
J. W. Leahy, J. Am. Chem. Soc., 1997, 119, 4317–4318; (c) 288.
Y. Iwabuchi, M. Nakatani, N. Yokoyama and 24 M. L. Bode and P. T. Kaye, Tetrahedron Lett., 1991, 32, 5611–
S. Hatakeyama, J. Am. Chem. Soc., 1999, 121, 10219–10220; 5614.
(d) D. Basavaiah, D. S. Sharada, N. Kumaragurubaran and 25 K. E. Price, S. J. Broadwater, H. M. Jung and D. T. McQuade,
R. M. Reddy, J. Org. Chem., 2002, 67, 7135–7137; (e) Org. Lett., 2005, 7, 147–150.
M. E. Kra, T. F. N. Haxell, K. A. Seibert and 26 A. Singh and A. Kumar, J. Org. Chem., 2012, 77, 8775–8779.
K. A. Abboud, J. Am. Chem. Soc., 2006, 128, 4174–4175; (f) 27 S. Tiwari and A. Kumar, Angew. Chem., Int. Ed., 2006, 45,
R. Robiette, V. K. Aggarwal and J. N. Harvey, J. Am. Chem.
Soc., 2007, 129, 15513–15525; (g) V. K. Aggarwal,
4824–4825.
This journal is © The Royal Society of Chemistry 2015
RSC Adv., 2015, 5, 2994–3004 | 3003

View Article Online
RSC Advances
Paper
28 S. Tiwari, N. Khupse and A. Kumar, J. Org. Chem., 2008, 73, 32 D. Cantillo and C. O. Kappe, J. Org. Chem., 2010, 75, 8615–
9075–9083. 8626.
29 A. Kumar and S. S. Pawar, J. Mol. Catal. A: Chem., 2004, 211, 33 (a) J. L. M. Abboud, M. J. Kamlet and R. W. Ta, Prog. Phys.
43–47 and ref. cited therein.
Org. Chem., 1981, 13, 485–630; (b) R. W. Ta, J.-L.
M. Abboud, M. J. Kamlet and M. H. Abraham, J. Solution
Chem., 1985, 14, 153–186.
30 P. M. Dewick, in Essentials of Organic Chemistry: For Students
of Pharmacy, Medicinal Chemistry and Biological Chemistry,
Wiley, New York, 2006, pp. 1–710.
31 C. Chiappe, C. S. Pomelli and S. Rajamani, J. Phys. Chem. B,
2011, 115, 9653–9661.
34 S. K. Shukla, N. D. Khupse and A. Kumar, Phys. Chem. Chem.
Phys., 2012, 14, 2754–2760.
3004 | RSC Adv., 2015, 5, 2994–3004
This journal is © The Royal Society of Chemistry 2015