Impact of sulfur heteroatoms on the activity of quaternary ammonium salts as phase transfer catalysts for nucleophilic displacement reactions

Article abstract of DOI:10.1016/j.molcata.2014.12.006

The application of a new class of alkylammonium salts as phase-transfer catalysts was investigated. These salts are tetra(4-thiaalkyl) ammonium bromides, and the key questions of the study focus on how the incorporation of a sulfur atom in the alkyl chains affects the efficacy of the salts as phase-transfer catalysts. Employing the nucleophilic substitution of cyanide for bromide on 1-bromopentane as a model reaction, reaction rate constants and activation energies are evaluated. The kinetic parameters obtained using the tetrathiaalkylammonium salts are compared to those obtained using their tetraalkylammonium analogs. The general trend is that the presence of sulfur in the alkyl chains reduces the reaction rates and increases activation energies. This trend is analyzed both in terms of computational modeling and experimental distribution coefficients to determine the cause of the slower reaction rates. Thiaquats are shown to distribute more into the aqueous phase than traditional quat salts of similar chain length, resulting in lower organic phase concentrations. Quantum calculations indicate stronger ion pairing for the thiaquats, increasing activation energies and slowing reaction rates. Thus, differences in rate enhancements are attributable both to phase distribution and ion pairing effects.

Full text of DOI:10.1016/j.molcata.2014.12.006

Journal of Molecular Catalysis A: Chemical 398 (2015) 282–288
Contents lists available at ScienceDirect
Journal of Molecular Catalysis A: Chemical
journal homepage: www.elsevier.com/locate/molcata
Impact of sulfur heteroatoms on the activity of quaternary
ammonium salts as phase transfer catalysts for nucleophilic
displacement reactions
a,∗
b
b
a
Christy Wheeler West , Richard A. O’Brien , E. Alan Salter , Brian E. Hollingsworth ,
a
a
a
b
Thai L. Huynh , Rachel E. Sweat , Nathan J. Griffin , Andrzej Wierzbicki ,
James H. Davis Jrb
a
Department of Chemical and Biomolecular Engineering, University of South Alabama, Mobile, AL 36688, USA
Department of Chemistry, University of South Alabama, Mobile, AL 36688, USA
b
a r t i c l e i n f o
a b s t r a c t
Article history:
The application of a new class of alkylammonium salts as phase-transfer catalysts was investigated. These
salts are tetra(4-thiaalkyl) ammonium bromides, and the key questions of the study focus on how the
incorporation of a sulfur atom in the alkyl chains affects the efficacy of the salts as phase-transfer catalysts.
Employing the nucleophilic substitution of cyanide for bromide on 1-bromopentane as a model reaction,
reaction rate constants and activation energies are evaluated. The kinetic parameters obtained using the
tetrathiaalkylammonium salts are compared to those obtained using their tetraalkylammonium analogs.
The general trend is that the presence of sulfur in the alkyl chains reduces the reaction rates and increases
activation energies. This trend is analyzed both in terms of computational modeling and experimental
distribution coefficients to determine the cause of the slower reaction rates. Thiaquats are shown to
distribute more into the aqueous phase than traditional quat salts of similar chain length, resulting in
lower organic phase concentrations. Quantum calculations indicate stronger ion pairing for the thiaquats,
increasing activation energies and slowing reaction rates. Thus, differences in rate enhancements are
attributable both to phase distribution and ion pairing effects.
Received 5 September 2014
Received in revised form 5 December 2014
Accepted 6 December 2014
Available online 20 December 2014
Keywords:
Quaternary ammonium salts
Phase-transfer catalysis
Nucleophilic substitution
©
2014 Elsevier B.V. All rights reserved.
+
−
1
. Introduction
this case is represented by Q X , and the desired intrinsic reaction
is the one that takes place in the organic phase. For more com-
plex interfacial reactions, an alternate mechanism was proposed by
Makosza [3]. Whether a transfer or interfacial mechanism predom-
inates depends on numerous factors, including the organophilicity
of the catalyst and the degree of hydration of ionic reactants.
Due to their ionic yet lipophilic nature, the most common classes
of phase-transfer catalysts are the quaternary tetraalkylammonium
or tetraalkylphosphonium salts, called “quat salts” [4]. In these, the
alkyl chains in the cations promote solubility in organic solvents.
The anion for reaction is exchanged between the reactant cation
and the catalyst cation either in the aqueous phase or at the inter-
face between the phases, and carried into the organic phase for
reaction as part of an ion pair with the quaternary cation. Most of
the literature on PTC argues that not only does the phase-transfer
catalyst act to bring the anion into contact with the organic reagent,
but also that the anion is activated for reaction, having stronger
nucleophilicity as a result of looser pairing with the quaternary
cation than with its original cation, often Na+ or K . Evidence for
this argument has been found in the trends with respect to alkyl
A common challenge encountered in organic synthesis is the
need to bring about reaction between two reagents that are present
in immiscible phases. For example, a reaction might require an
anion that is available in a water-soluble salt to displace a leaving
group on a compound present in an organic solvent. One means of
addressing this issue is the use a phase-transfer agent that acts to
bring one reactant across a phase boundary and into contact with
the other reactant. As the reaction takes place, the phase-transfer
agent is regenerated and available for another cycle. Because of
this regeneration, the phase-transfer agents are necessary only in
catalytic amounts, and thus the process is termed phase-transfer
catalysis (PTC) [1].
The simplest case of a phase-transfer catalytic mechanism is the
Starks’ transfer mechanism, depicted in Fig. 1 [2]. The catalyst in
+
∗ Corresponding author. Tel.: +1 251 460 6160.
E-mail address: cwwest@southalabama.edu (C.W. West).
http://dx.doi.org/10.1016/j.molcata.2014.12.006
1
381-1169/© 2014 Elsevier B.V. All rights reserved.

C.W. West et al. / Journal of Molecular Catalysis A: Chemical 398 (2015) 282–288
283
bromide (99% purity), both purchased from Aldrich Chemical Com-
pany and used without further purification.
Reactants for the phase-transfer reactions were obtained from
Acros Organics. The 1-bromopentane was obtained in 99% purity
and used as received. The potassium cyanide was purchased from
Fisher Scientific and used as received.
2
.2. Catalyst synthesis
Fig. 1. Starks’ transfer mechanism for a phase-transfer catalyzed nucleophilic sub-
stitution reaction: R − X + M Y → R − Y + M X . M = metal cation, Q+ = quaternary
+
−
+
−
+
The synthesis methods for the tetra(4-thiaalkyl) ammonium
+
−
ammonium ion. Q X is the phase-transfer catalyst.
bromides employed as phase-transfer catalysts in this study are
as described in a recent paper [8]. For these particular salts,
the thiols used were ethanethiol, 1-propanethiol, 2-propanethiol,
and octanethiol, resulting in the compounds tetra(4-thiahexyl)
ammonium bromide, tetra(4-thiaheptyl) ammonium bromide,
tetra(3-methyl-4-thiahexyl) ammonium bromide and tetra(4-
thiadodecyl) ammonium bromide, respectively.
2.3. Phase transfer catalytic reactions
Experiments were conducted to evaluate the reaction kinetics
Fig. 2. A tetra(4-thiaalkyl) ammonium salt. The structure may be varied by altering
the nature of the R- group. Traditional quat salts have a methylene group in place
of the sulfur atoms.
parameters using both the tetra(4-thiaalkyl) ammonium bromide
catalysts and the tetraalkylammonium bromides of analogous
chain lengths. These reactions were carried out in a 50 mL round-
bottom flask with stirring and temperature control. The organic
phase was initially 10.0 mL of 0.200 M 1-bromopentane in toluene,
and the aqueous phase was 2.0 mL of a saturated solution of potas-
sium cyanide. The amount of potassium cyanide initially present
was 20 times the stoichiometric amount, and solid was visible
throughout the experiment. Catalyst amounts in all experiments
were 5.0% of the molar amount of 1-bromopentane.
chain lengths: looser pairing is associated with longer chains, which
yield faster reaction rates [5,6]. This idea was challenged in a recent
paper which argued that the effect was solely due to distribution
between the phases, with longer chains resulting in higher catalyst
complex concentrations in the organic phase [7].
Recent work in our group has addressed the synthesis of a novel
class of quaternary ammonium salts, tetra(4-thiaalkyl) ammonium
salts, represented in Fig. 2 [8]. These salts have a sulfur atom replac-
ing the fourth methylene group from the nitrogen center on each
chain. The sulfur in the chain is an artifact of a new versatile synthe-
sis method employing thiol-ene click chemistry to synthesize these
salts with a variety of functional groups beyond the sulfur [9]. This
study investigates the use of these novel “thiaquat” salts as phase-
transfer catalysts. As a model reaction, we have chosen one that
has a well-characterized mechanism, the cyanide displacement on
an alkyl halide. This irreversible, second-order nucleophilic sub-
stitution reaction is commonly used to evaluate the behavior of
novel phase-transfer catalysts [10–18]. In this case, the substrate is
◦
◦
◦
◦
Reactions were conducted at 40 C, 50 C, 60 C, and 80 C. In
each case, the catalyst was first dissolved in the organic reactant
solution, and both solutions were brought to temperature before
being combined. Samples of 1 ␮L of the organic phase were taken
periodically throughout the reaction time and analyzed using a
gas chromatograph (Agilent 7820A) equipped with a thermal con-
ductivity detector. Stirring was maintained at 1400 rpm for all
experiments.
2.4. Distribution ratios
1
-bromopentane:
The distribution of the quaternary salts between toluene and
water was evaluated gravimetrically. A sample of the salt was first
dissolved in toluene, and an equal volume of water was added. The
flask was placed in a temperature-controlled bath and its contents
were stirred slowly over a 24 h period (“slow-stir” method) [19].
The stirring was stopped, and the phases were allowed to sepa-
rate completely, still at the desired temperature. Several samples
of known volume were drawn from each phase. Sample volumes
ranged from 1.000 mL to 4.000 mL. After complete evaporation of
the solvent, the mass of salt remaining was measured, and the rel-
ative amounts from organic and aqueous phase samples were used
to evaluate distribution ratios.
+
−
Br
Q
C5H11Br + KCN → C5H11CN + KBr
By using an already well-understood reaction system, we are
able to use PTC as a tool to elucidate information about the behavior
of these compounds. Additionally, we are investigating the effi-
cacy of these salts as phase-transfer catalysts and exploring their
potential for industrial applications of PTC.
2
. Experimental
2.1. Materials
2.5. Quantum-based computational modeling
For the catalysts syntheses, all of the starting organic thi-
ols employed for our studies were commercially available in
high purity and used without further purification. Octanethiol
Preliminary optimizations and post-generation of electrostatic
potential energy maps were performed using Spartan ’08 (Wave-
function, Inc., Irvine, CA). The isolated cations and cation/bromide
complexes were optimized in the gas phase using the B3LYP density
functional method [20–23] and the 6-31G(d,p)** basis set [24–26].
All structures were reoptimized and confirmed as stable by com-
puting analytic vibrational frequencies using Gaussian 09 [27].
(
>98.5% purity), ethanethiol (97% purity) and 2,2-dimethoxy-2-
phenylacetophenone (99% purity, photoinitiator) were purchased
from Aldrich Chemical Company. 1-Propanethiol (98% purity) and
2
-propanethiol (isopropylthiol, 98% purity) were purchased from
Acros Organics. Each salt was synthesized using tetraallylammo-
nium bromide prepared from triallylamine (99% purity) and allyl

2
84
C.W. West et al. / Journal of Molecular Catalysis A: Chemical 398 (2015) 282–288
Fig. 4. Pseudo-first-order integrated rate expression for reaction of 1-
◦
bromopentane to hexanenitrile at 60 C using analogous tetraalkylammonium and
tetra(4-thiaalkylammonium) bromides as phase-transfer catalysts. The legend is
the same as in Fig. 3.
◦
Fig. 3. Fractional conversion of 1-bromopentane to hexanenitrile at 60 C using
analogous tetraalkylammonium and tetra(4-thiaalkylammonium) bromides as
phase-transfer catalysts. ᭹ TDAB, ꢀ SC8, ꢀ THAB, ♦ S(n-C3).
+
−
−
under these conditions. The regenerated Q Br is able to partition
between phases and undergo exchange for CN more rapidly than
3
. Results and discussion
the intrinsic reaction occurs in the organic phase, and thus equilib-
+
−
rium levels of the Q CN are maintained in the organic phase.
Reaction data analysis for experiments with all of the other
catalysts evaluated in this study also indicates pseudo-first-order
kinetics. This consistency points to analogous mechanisms with the
same rate determining step for all catalysts studied. Upon compar-
ing the data in Figs. 3 and 4 with all of the later reaction systems
described, we see no indication that there are differing reaction
mechanisms occurring. Rate constants for all reactions described
in this paper are included in Table 1, along with the abbreviations
used for each salt. The abbreviated naming system used to distin-
guish between the thiaquat salts is based on the identification of
the alkyl groups attached to the sulfur.
3.1. Comparison of alkyl and thiaalkyl catalyst activities
To evaluate the influence that the presence of a sulfur atom
in the alkyl chains has on the effectiveness of a tetraalkyl-
ammonium salt as a phase-transfer catalyst, we compared
tetraalkylammonium and tetra(4-thiaalkylammonium) bromides
having chain lengths of twelve units and seven units. These salts
are tetradodecylammonium bromide (TDAB) and tetraheptylam-
monium bromide (THAB) and their respective thiaquat analogs
tetra(4-thiadodecylammonium) and (SC ) and tetra(4-thiaheptyl)
ammonium bromide (S(n-C )). Results of these reactions at 60 C
8
◦
3
are shown in Fig. 3, which shows the conversion of 1-bromopentane
to hexanenitrile over time for catalysts of both classes and chain
lengths. The two tetraalkylammonium catalysts result in similar
reaction rates, with slower rates for the sulfur-containing catalysts.
Based on the molecularity of a rate-limiting elementary step
taking place in the organic phase:
For the reactions represented in Fig. 3, rate constants for TDAB
and THAB are equal, but those for SC8 and S(n-C ) are lower.
3
The similarity of the rates for the two reactions with traditional
catalysts despite different chain lengths is consistent with other
Table 1
C5H11Br + CN− → C5H11Br + Br−
Pseudo-first order rate constants for reaction of 1-bromopentane to hexanenitrile
using various quaternary ammonium salts as phase-transfer catalysts. In all cases,
aqueous phase is saturated KCN solution, and catalyst concentration is 0.010 M
unless otherwise noted.
second-order kinetics are implied, but the concentration of the cat-
alyst complex is assumed constant, giving the rate law
Quaternary cation in catalystsa
Abbreviation
Temperature Rate constant,
ꢁ
r = k [C5H 1Br]org
(1)
1
◦
ꢁ
6
−1
)
(
C)
k × 10 (s
where
Tetradodecylammonium
TDAB
40
22.0
50.1
95.4
261
6.54
17.8
38.5
142
50
ꢁ
+
−
k = k[Q CN ]org
(2)
60
80
Integration of the rate law yields the pseudo-first-order integrated
rate expression:
Tetra(4-thiadodecyl) ammonium SC8
40
50
60
1
− X
) = kꢁt
80
60
40
ln(
(3)
1
62.2b
20.0
44.7
92.8
3.18
9.60
20.7
7.57
9.48
21.6
47.9
Tetraheptylammonium
THAB
where X is conversion of 1-bromopentane. The data from Fig. 3 are
plotted according to this expression in Fig. 4.
50
60
40
The linearity of the data in Fig. 4 suggests that the reaction
kinetics are indeed pseudo-first-order with respect to the concen-
tration of 1-bromopentane, and the slopes of the lines represent the
rate constants. This kinetic behavior is consistent with a constant
amount of the reactive complex between the quaternary cation in
the phase-transfer catalyst and the cyanide ion in the organic phase.
The apparently constant concentration of the catalyst complex indi-
cates that the reaction is rate-limited rather than transfer-limited
Tetra(4-thiaheptyl) ammonium
S(n-C3)
5
6
0
0
Tetra(4-thiahexyl) ammonium
Tetra(4-thia-5-methylhexyl)
ammonium
SC2
S(i-C3)
60
40
50
60
a
Anion is bromide in each case.
b
Amount of catalyst used is doubled.

C.W. West et al. / Journal of Molecular Catalysis A: Chemical 398 (2015) 282–288
285
Fig. 5. Effect of chain length in tetra(4-thiaalkyl) ammonium bromide catalysts on
Fig. 6. Effect of S-substituent branching in tetra(4-thiaalkyl) ammonium bromide
catalysts on the rate of conversion of 1-bromopentane to hexanenitrile at 60 C. ꢂ
S(i-C3), ᭹ S(n-C3).
◦
the rate of conversion of 1-bromopentane to hexanenitrile at 60 C. ꢁ SC8, ꢂ S(n-C3),
◦
᭹
SC2.
studies. The slower reaction rates for the thiaquat catalysts indi-
cate additional factors introduced by the incorporation of sulfur
in the chains. One interpretation of this result is that the sulfur
atoms cause conformational and electronic changes in the chains
that allow for tighter ion pairing with the cyanide ions, reducing
their nucleophilicity and thus the rate of the substitution reac-
tion. This explanation implies smaller intrinsic rate constant (k)
for the thiaquat-catalyzed reactions. Another possible explanation
is that the sulfurs affect the partitioning of the catalyst between the
organic and the aqueous phases. In this analysis, the apparent rate
ꢁ
+
−
constant k is lowered by a reduction in [Q CN ]org. Both of these
possibilities will be addressed later in this paper.
3.2. Effect of chain length for thiaalkyl catalysts
In addition to the twelve- and seven-unit chains used for com-
parison to traditional catalysts, a six-unit salt, tetra(4-thiahexyl)
Fig. 7. Arrhenius plot for evaluation of activation energies for phase-transfer cat-
alyzed reaction of 1-bromopentane to hexanenitrile with various catalysts. ᭹ TDAB,
ꢀ SC , ꢀ THAB, ♦ S(n-C ), ꢀ S(i-C ).
ammonium bromide (SC ), was employed. Results for all three
2
8
3
3
straight-chain thiaquat salts are shown in Fig. 5. The data indicate
that increasing the length of the carbon chain beyond the sulfur
atom increases the rate of reaction. At these total chain lengths,
the overall chain length did not affect rates for traditional quats, as
noted previously. This is consistent with the interpretation that the
sulfur atoms have induced alterations in the geometry and electron
density in the chains that result in a tighter association between the
catalyst cation and nucleophilic anion. Shorter chains beyond the
sulfur augment its effects by making the region around the sulfur
more accessible to the anions.
3
.4. Effect of temperature
The effect of temperature on the rates of reaction using lin-
ear catalysts with 7- and 12-unit chains both with and without
sulfur was evaluated by performing reactions at 40, 50, 60, and
8
◦
0 C. The branched thiaquat, S(i-C ) is also shown. As expected,
3
the rate of reaction increased with temperature in all cases. Using
rate constants obtained by plotting pseudo-first-order integrated
expressions, the Arrhenius plots shown in Fig. 7 were constructed.
Activation energies were calculated using the slopes from linear fits
of the data in Fig. 7, and are reported in Table 2.
For the traditional quat salts, the activation energy for the
quat with the longer chains is lower. This can be explained in
that the longer chains make the positive center less accessible to
3.3. Effect of branching for thiaalkyl catalysts
To explore the hypothesis that a more accessible region adjacent
to the sulfur slows the rate of reaction, we investigated the effect
of branching on the alkyl chain beyond the sulfur. Using isopropyl
chains beyond the sulfur rather than ethyl or n-propyl chains, reac-
tion rates were again evaluated, and results are compared in Fig. 6.
The rate with the isopropyl group is markedly faster than that with
the straight chains, and is in fact the fastest rate measured with thi-
aquat catalysts. Like the effect of chain length discussed above, this
observation supports the explanation that reaction rates are low-
ered as a result of stronger ion association when the sulfur is present
and the adjacent methylene units are accessible to the nucleophilic
anion.
Table 2
Activation energies for phase-transfer catalyzed substitution of cyanide on 1-
bromopentane.
Catalyst
EA (kJ/mol)
TDAB
THAB
SC8
S(n-C3)
S(i-C3)
56
66
70
81
70

2
86
C.W. West et al. / Journal of Molecular Catalysis A: Chemical 398 (2015) 282–288
Table 3
that hydration of the cyanide ions will cause an increase in aque-
+
−
◦
Experimental distribution ratios of Q Br between toluene and water at 60 C, and
the percent of the total catalyst amount that is present in the organic phase.
ous phase concentrations for the cyanide salts over the bromide
salts measured. However, while the values are for the bromide salts,
the trends for the cyanide salts should be similar. Another notable
difference between these values and those in the actual reacting
system may result from the ionic strength of the solution in the
reaction experiments. Here we have no added salt, and the aque-
ous phase during reaction is saturated with KCN. While the degree
to which this will affect distribution is not quantified, its effect on
the hydration and distribution of the two thiaquat salts with termi-
nal propyl groups should be similar. We predict that the increased
ionic strength in the aqueous phase will increase the amount of cat-
alyst complex in the organic phase. In summary, while the values
in Table 3 do not represent the distribution ratios for the specific
reactive complex in this study, the trend in values should be similar
for our reactive system.
Salt
˛
%Q+org
2
2
1
−
TDAB
THAB
SC8
S(n-C3)
S(i-C3)
1.1 × 10
1.0 × 10
4.0 × 10
1.1 × 10
99%
99%
98%
1.1%
1.8%
2
2
1.8 × 10−
the anion, thus weakening the ion pairing and making the ion a
stronger nucleophile. The activation energies for the thiaquat salts
are higher than those for their analogous alkyl quats. The higher
activation energy for the sulfur-containing salts is consistent with
our interpretation that the thiaalkylammonium cations associate
more strongly with the reactant anions, as more energy is neces-
sary to weaken that association for reaction to occur. The data for
the branched thiaquat supports this reasoning, showing that with
hindered access to the sulfur region, the activation energy is similar
to that with a longer chain. This effect is discussed further below in
terms of computational results.
Also included in Table 3 are values for the percent of the total
quat salt in the system that is present in the organic phase. Based
on those distribution ratios and the relative volumes of the toluene
and aqueous phases, this percent was calculated:
−
1
+
%
Q
= (1 + 1
)
× 100%
(5)
o r g
˛
3.5. Effect of catalyst amount
If the difference in apparent rate constants is solely due to the
difference in distribution between the phases, then the ratios of the
rate constants using two different catalysts should be equal to the
ratio of the percent of total catalyst present in the organic phase:
The effect of changing the amount of catalyst in the system was
◦
investigated by doubling the amount of SC for a reaction at 60 C.
8
As can be seen in the data in Table 1, the increase in the apparent
rate constant is less than a factor of 2. One possible explanation for
this behavior is that the solubility of the catalyst in toluene was
+
%
Q
k1
org,1
=
(6)
+
+
−
k2
%Q
exceeded in this case. If so, then [Q CN ] in Eq. (2) is not actually
doubled as intended, resulting in a lessened rate enhancement. An
additional possibility for consideration is that the rate of reaction at
the higher catalyst concentration is sufficiently fast that mass trans-
fer limitations at the phase boundary begin to affect the apparent
rate.
org,2
This relationship is based upon the assumption that the rate limit-
ing step is the second-order elementary step in the organic phase,
shown in Fig. 1.
Comparing the thiaalkyl salts in Table 3 to the TDAB and THAB,
the relationship between the rate constants shown in Eq. (6) does
not appear to hold true. For the longer salts, TDAB and SC , there is
8
3
.6. Mass-transfer limitations
not a significant difference in organic phase concentration, but the
◦
rate constant for SC is less than half of that for TDAB at 60 C. For
8
Based on the activation energies shown in Table 2, we conclude
the smaller salts, the rate constants are of the same order of mag-
nitude, while the distribution ratios differ by almost four orders
of magnitude. If the difference in rates resulted from distribution
only, the rate constant for the thiaalkyl salts should be approxi-
mately 50 times smaller than that for the THAB. The fact that the
thiaquat rates are much faster than predicted by the distribution
ratio may indicate significant reaction occurring at the interface
with the thiaquat catalysts.
The difference in reaction rates resulting from reactions using
each of the two 7-unit thiaalkyl quats also does not appear
attributable to distribution alone. The distribution ratios are sim-
ilar, while the rate constant for the salt with the isopropyl group
attached to the sulfur is more than twice that for the one with the
n-propyl group. Even more significant, the rate for the branched
that the stirring rate of 1400 rpm is sufficiently high that the rate
of mass transfer does not limit the rate of reaction for most of the
experiments performed. Temperature dependence would be sig-
nificantly reduced if mass transfer were the rate-limiting step. The
one case where that may present an exception is the reaction with
doubled catalyst amount, addressed above.
3.7. Distribution ratios
The measured distribution ratios, defined:
+
−
[
Q Br ]
org
˛
=
(4)
+
−
aq
[
Q Br ]
thiaquat S(i-C ) is greater than that for the longer-chain thiaquat
SC , despite the much greater concentration of the SC8 complex
8
for selected quaternary ammonium salts between toluene and
water at 60 C are displayed in Table 3.
3
◦
in the organic phase. A likely explanation for this behavior is that
in addition to distribution effects, the strength of ion pairing has a
critical effect on reaction rates. This is further explored below using
molecular modeling.
A pronounced difference is observed between the behavior of
the traditional quats and the thiaquats, indicating a significant
increase in hydrophilicity resulting from the presence of the sulfurs.
This can be attributed to interaction between the lone pairs on the
sulfur atoms and the hydrogens in the water molecules. Further evi-
dence supporting this explanation can be found in comparing the
distribution ratios for the three thiaquats in the table. The salt with
the octyl chain beyond this sulfur favors the organic phase, while
both salts with terminal propyl groups favor the aqueous phase.
Note that these values were measured using a bromide anion
rather than the cyanide anion in the reacting complex. It is possible
3.8. Quantum-based modeling
Computational molecular models were generated for the set of
seven-unit-chain quat salts, which includes the linear traditional
and thiaquat analogs and one branched thiaquat. The lowest-
energy conformations of these model cations and their cyanide

C.W. West et al. / Journal of Molecular Catalysis A: Chemical 398 (2015) 282–288
287
Fig. 8. Optimized structures of cations (top) and cyanide complexes (bottom) using B3LYP/6-31G(d,p) model: (a) Tetraheptylammonium cyanide (b) Tetra(4-thiaheptyl)
ammonium cyanide (S(n-C3)) (c) Tetra(5-methyl-4-thiahexyl) ammonium cyanide. (S(i-C3)) Common elstat scale for cations: +98.0 (red) to +418.0 (blue). Common elstat
scale for complexes: −292.3 (red) to +162.0 (blue). Elstat units are kJ/mol. (For interpretation of the references to colour in this figure legend, the reader is referred to the
web version of this article.)
complexes are shown in Fig. 8. At the left side of Fig. 8 are the tetra-
heptylammonium cation (top) and its cyanide complex (bottom).
In the center and are the tetra(4-thiaheptyl) ammonium cation
and its cyanide complex. This cation has a terminal n-propyl chain
beyond the sulfur atom. On the right, the thiaquat terminating in
an isopropyl group attached to the sulfur is shown.
the quat cation by 10.5 kJ/mol. These trends are consistent with the
qualitative appearance of the elstat maps illustrated in Fig. 8. They
also follow the trend in reaction rates, with lower cyanide bind-
ing energies resulting in faster reactions. The agreement between
these trends leads to the conclusion that stronger ion pairing for
the thiaquat salts compared to tradition salts does in fact play a
role in the reducing the nucleophilicity of the cyanide ions, thus
decreasing reaction rates.
The depictions of the isolated cations at the top of Fig. 8 show
a quasi-tetrahedral arrangement of the chains about the nitrogen
center. All three possess S symmetry. As expected, there is a grad-
4
ual falling off of positive charge along the heptyl chains of the alkyl
quat cation. In contrast, the electronegative sulfur atom of the 4-
thiaheptyl chains causes the C3 and C5 methylene regions to be far
more positive than their alkyl counterparts. This effect is some-
what less pronounced in the branched cation, likely due to the
electron-donating inductive effect of the additional methyl group
on C5.
As a result of the greater positive potential distributed down
the thiaalkyl chains and the low barrier to rotation about the C S
bonds, comparatively stronger binding with greater delocalization
of the anion’s charge is achieved in the thiaquat-anion complexes.
As can be seen at the bottom of Fig. 8, all three complexes have
chains in partial contact with cyanide ion (red/orange). Some C C
bonds adopt gauche conformations to maximize anion–cation con-
tacts. The behavior of the salts is in agreement with our findings
reported previously [8]. The maximum negative elstat magnitudes
in the cyanide complexes follow the trend: alkyl quat > branched
thiaquat > linear thiaquat. This trend is consistent with the trend
in reaction rates for the series, indicating that stronger ion pairing
between the cation and cyanide results in a reduced nucleophilicity
of the cyanide, slowing the intrinsic reaction rate.
4. Conclusions
We have demonstrated that tetra(4-thiaalkyl) ammonium bro-
mide salts are effective as phase-transfer catalysts for nucleophilic
substitution reactions. While the sulfur atoms in the chain do
reduce the activity as a PTC compared to analogous tetraalkylam-
monium salts, the reduction in rate can be overcome by a slight
increase in temperature. Furthermore, branching on the catalyst
chains beyond the sulfur atom reduces the effect of the sulfur,
thus enhancing the reaction rate. Thus, opportunities exist to take
advantage of the straightforward, versatile, and inexpensive cat-
alyst synthesis method to prepare catalysts that are tailored for
specific applications.
In addition to informing potential applications for the thiaquat
catalysts, we have used these catalysts to show the effects of both
phase distribution and ion pairing on rate enhancement under PTC
conditions. Both factors were shown to have effects on rates, with
increased partitioning in the organic phase and weaker ion pairing
both resulting in faster reactions.
Acknowledgments
To quantify this effect, we have evaluated the difference in bind-
ing energies by computing ꢀE for cyanide ion exchange between
the cations. The question of interest is whether the difference in
binding energy accounts for the difference in rates for the reac-
tions with the three catalysts. For the linear quat cation and linear
This work was possible in part by a grant of high performance
computing resources and technical support from the Alabama
Supercomputer Authority.
thiaquat S(n-C ), our computational model shows that cyanide
3
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