Mechanistic change in the reactivity of substituted phenyl acetates over phenyl thiolacetates toward imidazole in aqueous phase

Article abstract of DOI:10.1002/kin.20074

The kinetics of aminolysis of several substituted phenyl acetates by imidazole is studied in aqueous medium at 20°C and an ionic strength of 0.1 M (KCl). By following the leaving groups spectrophotometrically (λ _max = 272-401 nm), under excess free imidazole, pseudo-first-order rate constants (κ_obs) are obtained. For the esters with good nucleofuges, the reaction follows clean second-order kinetics and the plots of (κ_obs - κ_H) against free imidazole concentration are linear at constant pH. The macroscopic nucleophilic substitution rate constants (κ_N) are obtained as the slopes of these plots and found to be pH independent. For the esters with poor nucleofuges, a rate dependence on more than first power of the free imidazole and a linear dependence of κ′₂ on free imidazole is observed. Accordingly, the microscopic rate constants for the assisted paths viz. κ_ga and κ_gb have been disseminated besides for simple bimolecular attack. The Broensted-type plots and Hammett plots were constructed whose slope values are consistent with a stepwise mechanism through a bipolar tetrahedral addition intermediate whose formation or breakdown being rate determining for various paths. Comparison of this reaction of oxyesters with the earlier reported works on similar reaction of analogue thiolesters under identical reaction conditions showed remarkable mechanistic differences which are discussed in detail. The discussion is extended to include the details on previously studied ammonolysis of these two types of esters wherein thiolesters showed differed reactivity than that reported in the present study.

Full text of DOI:10.1002/kin.20074

Mechanistic Change in the
Reactivity of Substituted
Phenyl Acetates over Phenyl
Thiolacetates Toward
Imidazole in Aqueous Phase
D. RAJARATHNAM,1 T. JEYAKUMAR,2 P. ANANTHAKRISHNA NADAR2
1Department of Chemical and Biomolecular Engineering, The National University of Singapore,
4 Engineering Drive 4, Singapore 117576
2Department of Chemistry, Annamalai University, Annamalai Nagar 608 002, Tamilnadu, India
Received 25 August 2004; accepted 22 November 2004
DOI 10.1002/kin.20074
Published online in Wiley InterScience (www.interscience.wiley.com).
ABSTRACT: The kinetics of aminolysis of several substituted phenyl acetates by imidazole is
studied in aqueous medium at 20◦C and an ionic strength of 0.1 M (KCl). By following the leav-
ing groups spectrophotometrically (λmax = 272–401 nm), under excess free imidazole, pseudo-
first-order rate constants (kobs) are obtained. For the esters with good nucleofuges, the reaction
follows clean second-order kinetics and the plots of (kobs − kH) against free imidazole concen-
tration are linear at constant pH. The macroscopic nucleophilic substitution rate constants (kN)
are obtained as the slopes of these plots and found to be pH independent. For the esters with
poor nucleofuges, a rate dependence on more than first power of the free imidazole and a linear
dependence of k2ꢀ on free imidazole is observed. Accordingly, the microscopic rate constants
for the assisted paths viz. kga and kgb have been disseminated besides for simple bimolecu-
¨
lar attack. The Bronsted-type plots and Hammett plots were constructed whose slope values
are consistent with a stepwise mechanism through a bipolar tetrahedral addition intermedi-
ate whose formation or breakdown being rate determining for various paths. Comparison of
this reaction of oxyesters with the earlier reported works on similar reaction of analogue thi-
olesters under identical reaction conditions showed remarkable mechanistic differences which
are discussed in detail. The discussion is extended to include the details on previously studied
ammonolysis of these two types of esters wherein thiolesters showed differed reactivity than
that reported in the present study. ꢁ 2005 Wiley Periodicals, Inc. Int J Chem Kinet 37: 211–221,
C
2005
INTRODUCTION
The nucleophilic substitution reactions of esters in
aqueousmediumhavealwaysbeenthesubjectofexten-
sivekineticstudiesandthemechanisticdetailsofwhich
Correspondence to: D. Rajarathnam; e-mail: chedr@nus.edu.sg.
2005 Wiley Periodicals, Inc.
c
ꢁ

212
RAJARATHNAM, JEYAKUMAR, AND NADAR
have greater implications in elucidating the enzyme-
catalyzed acyl transfer reactions of biochemical sys-
tems [1–3]. The mechanism of these reactions has been
well established through structure-reactivity correla-
tions in which a zwitterionic tetrahedral intermediate
(T ) in the reaction path has always been predicted
[4,5], whose stability and the rate-determining step
have been found to be dependent on the presence of
proton acceptor/donor agents and on the basicity of the
leaving group (Scheme 1). In this mechanism, the rate-
determining step is first order in amine concentration
for nucleofuges from more reactive esters and leads
to the rate-determining breakdown of T to products
phase include such as the aminolysis of phenyl- and
4-nitrophenyl thiolacetates [6], 2,4-dinitrophenyl- and
2,4,6-trinitrophenyl thiolacetates [7], phenyl dithioac-
etate [8], 4-nitrophenyl dithioacetate [9], and of the
aminolysis of thionoesters too [10,11].
Our earlier studies on the imidazolysis [12] and
ammonolysis [13] of several substituted phenyl thio-
lacetates in aqueous phase showed contradictory re-
sults; the reactions of which for the former proceeding
through a general-acid assisted path (kga), while the
latter through simple bi-molecular nucleophilic attack
(kN) lacking any such assisted paths. Further, a com-
parison of ammonolysis of thiol esters with substituted
phenyl acetates showed a mechanistic change with en-
hanced reactivity [13]. In a similar pattern, keeping in
view of the catalytic cycle of the cysteine proteases—
a large group of proteolytic enzymes containing cys-
teine thiol and histidine imidazole units at their active
sites, which is known to proceed through acyl-thiol
intermediate [14–21], it is of special interest to inves-
tigate further and reevaluate the available data to shed
light on the mechanism of imidazolysis of phenyl thi-
olacetates. Hence, the aminolysis of a comprehensive
series of analogue oxyesters is studied in the present
work employing imidazole as nucleophile under identi-
cal reaction conditions observed for thiol esters, though
(k2 step) with k ꢂ k2. For poor nucleofuges, T is
−1
less unstable and catalyzed pathways become kineti-
cally evident leading to a change in mechanism, and
the reaction proceeds either through T − by general-
base assistance (kgb, k3 step) with k3[>NH] ꢂ k2 or
through T + by general-acid assistance (kga, k4 step)
with k4[>NH+2 ] ꢂ k2 with subsequent rapid break-
down of respective intermediates into products.
Although considerable amount of mechanistic de-
tails available for the aminolysis of phenyl acetates in
aqueous medium, less is known for their thiol ana-
logues and the catalysis involved therein. Some re-
ports on similar reactions on the latter in aqueous
Scheme 1

MECHANISTIC CHANGE IN THE REACTIVITY OF SUBSTITUTED PHENYL ACETATES
213
imidazole-catalyzed hydrolysis of phenyl acetates has
been studied earlier in aqueous medium [22–26] and
in partly aqueous medium [27] with limited number
of substituents. The results are interpreted in terms of
structure-reactivity relationships with subsequent pro-
posal of a plausible mechanism and compared to that of
the previously reported ones for thiol esters [12]. The
difference in reactivity is discussed besides the rea-
son for the mechanistic change in the reactions of thiol
esters toward imidazole and ammonia under identical
conditions is also presented.
of the corresponding phenolate ions at regular inter-
vals of time. The wavelengths of maximum absorption,
λmax (nm), for the substituted phenolate ions are as fol-
lows: H, 275; 3-CH3, 288; 4-CH3, 280; 3-Br, 290; 4-Br,
296; 3-Cl, 291; 4-Cl, 285; 4-F, 272; 4-NO2, 401. The
initial ester concentration was (5–6) × 10−5 M, and
that of free imidazole concentration was kept at several
fold excess over the substrate. For each compound, the
aminolysis was studied at five different [Im]F in buffers
of fixed pH at each of the four different pH values. The
pH values of the kinetic solutions were determined us-
ing an ITL digital pHmeter both prior to and at the
completion of reactions. The glass electrode was cali-
brated using standard procedures [30].
All the reactions in the present work fitted good
pseudo-first-order kinetics up to greater than 90% of
the total reaction. Pseudo-first-order rate coefficients
(kobs) were found throughout by means of the Guggen-
heim method employing least-squares technique [31].
The correlation coefficients of the linear regression
were always ≥0.999. The experimental conditions
of imidazolysis and the rate coefficients are given
in Table I.
In order to evaluate the results, the alkaline hydrol-
ysis of phenyl acetates was also followed spectropho-
tometrically using known concentrations of potassium
hydroxide at 20.0 0.01◦C and ionic strength 0.1 M
(KCl). The second-order rate coefficients, khyd (where
khyd = kobs/[OH−]), for the substrate with various sub-
stituents are H = 1.36 0.08, 3-CH3 = 1.16 0.02,
4-CH3 = 1.27 0.04, 3-Br = 1.98 0.07, 4-Br =
1.73 0.03, 3-Cl = 2.28 0.06, 4-Cl = 1.80 0.03,
4-F = 2.46 0.07, and 4-NO2 = 5.01 0.09.
EXPERIMENTAL
Materials
All the 3- and 4-substituted phenyl acetates were pre-
pared from corresponding phenols, respectively, by
procedures from the literature [28]. Reagent grade
imidazole (Fluka) was recrystallized shortly before
use and potassium chloride (Merck) was used as
such. Water was double distilled. The imidazole was
employed as buffer to maintain constant pH. The
imidazole–imidazolium buffer was prepared shortly
before the kinetic run, by the addition of calcu-
lated amounts of standardized hydrochloric acid so-
lution to aqueous solutions of known imidazole-free
base. At any fixed pH, the concentration of free im-
idazole ([Im]F) in the buffer was evaluated using
Eq. (1)
[Im]T · Ka
[Im]F =
(1)
+
Ka + aH
Product Studies
where, [Im]T is the total concentration of imidazole
buffer ([Im]F + [ImH+]), Ka is the dissociation con-
stant of the conjugate acid of the imidazole (ImH+),
The product studies were carried out according to the
procedure already reported [32], based on the method
of Katz et al. [33]. The aminolysis of the ester was al-
lowed to go to completion, and the amide formed was
determined by conversion to acetylhydroxamic acid-
ferric ion complex. The absorbance of the complex was
determined spectrophotometrically at λmax = 540 nm
and the concentration of acetamide was determined
from a calibration plot obtained through the standard
solutions of acetamide, which showed in all the cases
at least 90% of the formation of amide product under
the experimental conditions.
+
and aH is the hydrogen ion activity. The pKa of
imidazolium ion (7.21) under identical conditions to
that of the kinetic measurements was determined from
measurement of the pH by half-neutralization method
[29].
Kinetic Measurements
These measurements were carried out in aqueous so-
lution, ionic strength 0.1 M (KCl), using a JASCO
UVIDEC 340 UV-VIS spectrophotometer equipped
with a themostated cell holder. The reactions were
initiated by adding a solution of 30 ꢀL of the ester
stock solution (in dioxan) to 3 mL of thermally equili-
brated (20.0 0.01◦C) imidazole–imidazolium buffer.
The reactions were followed by monitoring the release
RESULTS AND DISCUSSION
The pseudo-first-order rate constants (kobs) calculated
for the aminolysis of phenyl acetates are converted to

214
RAJARATHNAM, JEYAKUMAR, AND NADAR
Table I Summary of Experimental Conditions and Rate Constants for the Imidazolysis of Substituted Phenyl
Acetatesa
b
Substituents
H
pH
[Im]F (M)
kobs − kH (10−3 s−1
)
k2ꢀ (10−2 s−1 M−1
)
6.97
7.41
7.72
8.07
6.97
7.40
7.71
8.05
6.95
7.41
7.70
8.01
7.21
7.49
7.72
8.02
7.21
7.50
7.72
8.02
7.21
7.52
7.75
8.02
7.22
7.50
7.76
8.10
7.21
7.41
7.62
7.80
7.23
7.49
7.75
8.02
0.11–0.24
0.18–0.41
0.25–0.53
0.29–0.61
0.12–0.25
0.20–0.42
0.25–0.53
0.29–0.60
0.12–0.25
0.20–0.43
0.25–0.52
0.28–0.59
0.04–0.12
0.05–0.16
0.06–0.19
0.07–0.21
0.06–0.18
0.08–0.24
0.09–0.28
0.10–0.31
0.04–0.12
0.05–0.16
0.06–0.19
0.07–0.21
0.04–0.12
1.79–4.63
3.02–7.76
4.16–10.30
4.82–11.70
1.54–3.66
2.57–6.14
3.25–7.69
3.76–8.90
1.02–2.56
1.79–4.44
2.25–5.45
2.63–6.39
3.60–11.10
4.76–14.70
5.60–17.30
6.41–19.80
2.67–8.47
3.54–11.10
4.11–13.00
4.67–14.80
3.08–9.52
4.17–12.80
4.87–15.00
5.49–16.90
2.11–6.72
2.89–9.08
3.47–10.90
4.02–12.60
1.06–3.17
1.23–3.77
1.60–4.61
1.82–4.89
1.86–9.61
2.64–13.50
3.57–17.30
4.17–20.30
1.61–1.89
1.63–1.90
1.64–1.91
1.66–1.93
1.26–1.43
1.27–1.45
1.29–1.46
1.30–1.47
0.86–1.03
0.88–1.04
0.90–1.05
0.92–1.08
8.71–8.98
8.82–9.08
8.93–9.19
9.04–9.29
4.38–4.62
4.40–4.63
4.43–4.68
4.45–4.70
7.47–7.68
7.56–7.76
7.65–7.85
7.75–7.96
5.19–5.42
5.31–5.56
5.42–5.68
5.54–5.78
1.73 0.06
1.67 0.02
1.81 0.02
1.82 0.07
169.8 1.9
168.1 1.4
171.6 1.1
170.5 1.6
3-CH3
4-CH3
3-Cl
4-Cl
3-Br
4-Br
0.05–0.16
0.06–0.19
0.07–0.22
4-F
0.0606–0.1820
0.0741–0.2225
0.0868–0.2606
0.0958–0.2875
0.00126–0.00632
0.00165–0.00826
0.00195–0.00975
0.00217–0.01080
4-NO2
a In aqueous solution at 20 0.1◦C, ionic strength 0.1 M (KCl). At least five runs were carried out at each pH. The errors shown are standard
deviations.
b Concentration of free imidazole.
the apparent second-order rate constants, k2ꢀ , where
buffer concentrations indicating the order of the reac-
tion is more than one with respect to free imidazole.
The plots of log(kobs − kH) against log[Im]F for these
esters are linear with slope values more than 1. A rep-
resentative plot of phenyl acetate is shown in Fig. 1.
Further, a linear dependence is observed in the plots
of k2ꢀ against [Im]F suggesting that the aminolysis may
involve assisted pathways by an additional molecule of
imidazole.
k2ꢀ = (kobs − kH)/[Im]F, kH being the product of khyd
,
the second-order rate constant for the alkaline hydroly-
sis of phenyl acetates, and the concentration of hydrox-
ide ion present in the system for aminolysis, calculated
from aOH− and the activity of hydroxide ion [23]. In the
aminolysis, k2ꢀ values calculated for all the esters ex-
cept 4-fluoro- and 4-nitrophenyl acetates vary with pH
and increase with increase in the concentration of free
imidazole in the buffers (Table I). The kobs values for
these esters increase more rapidly than the first power
of free imidazole concentration in a series of imidazole
The reactions for phenyl acetates that show higher
order dependency on free imidazole concentration are
governed by the kinetic law under the experimental

MECHANISTIC CHANGE IN THE REACTIVITY OF SUBSTITUTED PHENYL ACETATES
215
Figure 1 Plot of log(kobs − kH) against log[Im]F for phenyl acetate at pH 6.97.
conditions given by Eqs. (2) and (3),
The values of k0 and kN were obtained as the intercept
and slope, respectively, of linear plots of (kobs − kH)
against [Im]F at constant pH. For the reactions by these
esters, the value of k0, the rate constant comprising
d[ArO−]
= (kobs − kH) [Ester]
(2)
dt
2
(kobs − kH) = kN[Im]F + kgb[Im]F + kga[Im]F[ImH+]
(3)
+
Table II Values of Slopes (kgb + kga · aH /Ka) and
Intercepts (kN) of the Plots of (kobs − kH)/[Im]F Against
Dividing Eq. (3) throughout by [Im]F with subse-
[Im]F
quent re-arrangement gives Eq. (4) (since [ImH+] =
Substituents aH /Ka Slope (10−2
)
Intercept (10−2
)
+
+
[Im]F · aH /Ka),
H
1.69
0.62
0.30
0.13
1.69
0.63
0.31
0.14
1.78
0.74
0.54
0.50
0.97
0.51
0.30
0.15
0.97
0.50
0.30
0.15
0.97
0.50
0.28
0.15
0.97
0.50
0.27
0.13
2.12
1.22
0.98
0.86
1.29
0.81
0.63
0.54
1.33
0.74
0.54
0.50
3.29
2.37
2.10
1.72
1.99
1.44
1.35
1.22
2.56
1.85
1.55
1.52
2.75
2.31
2.06
1.59
1.37
1.40
1.42
1.45
1.10
1.11
1.13
1.15
0.70
0.72
0.76
0.79
8.58
8.70
8.80
9.00
4.26
4.28
4.30
4.34
7.37
7.46
7.55
7.65
5.08
5.19
5.29
5.43
(kobs − kH)
+
= kN + (kgb + kga · aH /Ka)[Im]F (4)
[Im]F
where, kN, kgb, kga, and Ka are the rate constants for
simple nucleophilic attack of imidazole, general base
assisted attack of imidazole, the general acid assisted
attack of imidazole, and the dissociation constant of
imidazolium ion respectively. The values of kN and
3-CH3
4-CH3
3-Cl
4-Cl
3-Br
4-Br
+
(kgb + kga · aH /Ka) are obtained as the intercepts and
slopesfromtheplotsof(kobs − kH)/[Im]F against[Im]F
for each pH of the medium (Table II). Further plot of
+
these slope values against aH /Ka should give kgb and
kga astheinterceptandslope, respectively. Theratecon-
stants kN, kgb, and kga thus derived are given in Table III.
For 4-fluoro- and 4-nitrophenyl acetates k2ꢀ values
are almost constant within a given pH and indepen-
dent of free imidazole concentration (Table I). The
plots of log(kobs − kH) against log[Im]F for these es-
ters are linear with unit slope. A representative plot of
4-fluorophenyl acetate is shown in Fig. 2. Thus, the
aminolysis of these esters depends only upon the first
power of free imidazole concentration and the reaction
proceeds through simple nucleophilic attack on ester
which is governed by Eq. (5),
(kobs − kH) = k0 + kN[Im]F
(5)

216
RAJARATHNAM, JEYAKUMAR, AND NADAR
Table III Rate Constants Pertained to Various Paths for the Aminolysis of Substituted Phenyl Acetates by Imidazole
Substituents
kga (10−3 s−1 M−2
)
kgb (10−3 s−1 M−2
)
kN (10−2 s−1 M−1
)
H
7.41
4.80
5.18
18.70
9.43
13.30
12.60
–
8.26
4.85
4.04
14.70
10.50
12.40
15.80
–
1.41 0.03
1.12 0.02
0.74 0.04
8.77 0.18
4.30 0.03
7.51 0.12
5.25 0.15
1.70 0.06
171.2 1.7
3-CH3
4-CH3
3-Cl
4-Cl
3-Br
4-Br
4-F
4-NO2
–
–
assisted paths, was negligible compared to the aminol-
ysis term in Eq. (5) and kN values obtained were pH
independent. These plots are exemplified for the case
of fluoroester at various pH values in Fig. 3. The mean
kN values are given in Table III along with the rate
constants of other esters.
46] for simple unassisted nucleophilic attack and a low
magnitude to rate-determining formation of T [5–7,
29,40,45–54] for assisted nucleophilic attack whereby
T
is stabilized by a second molecule of nucleophile
either in free form or in protonated form and proceeds
through rapid formation of anionic tetrahedral interme-
diate (T −) and cationic tetrahedral intermediate (T +)
respectively to products.
The Hammett plots appropriate to various paths of
aminolysis against σ values of the substituents [31]
are shown in Figs. 4–6 with slope values of 0.96
(r = 0.940), 0.98 (r = 0.863), and 1.69 (r = 0.992)
respectively for general acid assisted, general base as-
sisted, and simple bimolecular nucleophilic attack by
imidazole. In a similar fashion, Bro¨nsted-type plots are
drawn for various rate constants against pKa of leav-
ing phenols [34]. The plots are shown in Figs. 7–9 with
slope values of −0.46 (r = 0.977), −0.47 (r = 0.880),
and −0.77 (r = 0.982) respectively. The values of
these slopes are consistent with a stepwise mechanism,
where a zwitterionic tetrahedral addition intermediate
(T ) is found on the reaction pathway. Generally, for
most of the reactions of acyl compounds, a high magni-
tude in ρ and β values has always been attributed to the
rate-determining breakdown of T to products [10,35–
The observed results are also in line with ρ val-
ues obtained in the imidazole-catalyzed hydrolysis of
substituted phenyl acetates where a larger value (1.8–
1.9) was obtained for simple unassisted hydrolysis and
a lower value (0.5) for assisted hydrolysis [25a,25c].
Similarly, larger β values (0.8–1.5) were observed in
the aminolysis of 4-nitrophenyl acetate by substituted
imidazoles [25a,25b] and in the aminolysis of phenyl
acetate, 4-nitrophenyl acetate, and 2,4-dinitrophenyl
acetate by structurally related amino nucleophiles [24],
which have been attributed to simple unassisted nucle-
ophilic attack.
Based on the above information, a common mech-
anism for the imidazolysis of phenyl acetates, which
includes various pathways leading to the products, can
Figure 2 Plot of log(kobs − kH) against log[Im]F for 4-fluorophenyl acetate at pH 7.21.

MECHANISTIC CHANGE IN THE REACTIVITY OF SUBSTITUTED PHENYL ACETATES
217
Figure 3 Plots of (kobs − kH) against [Im]F for 4-fluorophenyl acetate at various pH values.
be presumed to operate as given in Scheme 1. By apply-
ing the steady state approximation to the intermediates
T , T −, and T +, a general expression (Eq. (6)) can be
written,
from which the rate expressions for simple nucle-
ophilic, general-base and general-acid assisted paths
can be given as (kobs − kH) = k1k2[Im]F/k−1, (kobs
−
2
kH) = k1k3[Im]F /(k−1 + k3[Im]F), and (kobs − kH) =
k1k4[Im]F[Im · H+]/(k−1 + k4[ImH+]), respectively.
Thus in the imidazolysis of phenyl acetates with
poor nucleofuges, the dissemination of various path-
ways leading to product is possible whereas for phenyl
thiolacetates with poor nucleofuges for similar reaction
k1(k2 + k3[Im]F + k4[ImH+])[Im]F
(kobs − kH) =
k
−1 + k2 + k3[Im]F + k4[ImH+]
(6)
Figure 4 Hammett plot obtained in the general-acid assisted imidazolysis of substituted phenyl acetates in aqueous medium,
20◦C, ionic strength 0.1 M (KCl).

218
RAJARATHNAM, JEYAKUMAR, AND NADAR
Figure 5 Hammett plot obtained in the general-base assisted imidazolysis of substituted phenyl acetates in aqueous medium,
20◦C, ionic strength 0.1 M (KCl).
Figure 6 Hammett plot obtained in the simple nucleophilic imidazolysis of substituted phenyl acetates in aqueous medium,
20◦C, ionic strength 0.1 M (KCl).
Figure 7 Bro¨nsted-type plot obtained in the general-acid assisted imidazolysis of substituted phenyl acetates in aqueous
medium, 20◦C, ionic strength 0.1 M (KCl).

MECHANISTIC CHANGE IN THE REACTIVITY OF SUBSTITUTED PHENYL ACETATES
219
Figure 8 Bro¨nsted-type plot obtained in the general-base assisted imidazolysis of substituted phenyl acetates in aqueous
medium, 20◦C, ionic strength 0.1 M (KCl).
kN and kga were prominent with no kinetic significance
of kgb [12]. This observation is again in contradic-
tion that the ammonolysis of phenyl thiolacetates in
aqueous medium irrespective of the nature of the sub-
stituents proceeds only through the simple bimolecular
nucleophilic substitution path with assisted paths as has
been kinetically evident for analogue oxyesters [13].
In acyl transfer reactions, the rate-determining step
for the breakdown of a dipolar tetrahedral addition in-
termediate is determined by the relative rates of ex-
pulsion of the amine and aryloxide (or alkoxide) leav-
ing groups. Though these rates are determined largely
by the intrinsic properties of each group, but also
governed by the driving force exerted mutually on
each other. With basic nucleophile and reactive es-
ters (with good leaving groups), there will be a lev-
eling off of reaction rate which reflects in a decrease
in the overall sensitivity of the reaction rate with the
expulsion of amine and aryloxy groups from the in-
termediate being competitive. This has been amply
demonstrated and reported by Jencks and Gilchrist for
the reaction of basic amines with highly reactive acyl
compounds such as 1-acetoxy-4-methoxypyridinium
cation [24], N-acetylpyridinium cations [44], aryl
chloroformates and carbonate esters [45], and N,O-
trimethylenephthalimidium cations [55].
Figure 9 Bro¨nsted-type plot obtained in the simple nucleophilic imidazolysis of substituted phenyl acetates in aqueous medium,
20◦C, ionic strength 0.1 M (KCl).

220
RAJARATHNAM, JEYAKUMAR, AND NADAR
ity coefficient of SO32− in deuterium oxide (2.59 fold)
compared to water is also attributed to the influence
of lone pair electrons of sulfur atom [57,60]. Thus, for
phenyl thiolacetates, the polarization induced by sul-
fur in conjunction with the resonance interaction from
the initial attack of imidazole may increase the basicity
of the carbonyl oxygen leading to easy proton donation
from an imidazolium ion resulting in predominant gen-
eral acid assistance through k4 step in Scheme 1 with
a transition state of which may resemble to that shown
in Structure 2.
Imidazole has an increased nucleophilic reactivity
than ammonia due to resonance stabilization of the
transition state involving electron donation from the
second nitrogen atom to carbonyl group and possibly to
the leaving group as shown in Structure 1 [55]. For the
reactions of imidazole with reactive acyl compounds
such as 1-acetoxy-4-methoxy-pyridinium perchlorate
[24] and acetic anhydride [44], it has been predicted
that the transition state as shown in Structure 1 reached
earlier so that less bond formation and resonance sta-
bilization are developed and the enhanced reactivity of
imidazole disappears. Similar effect can be considered
operative with thiolesters toward imidazole resulting in
catalyzed path for the expulsion of thiol anions from
stabilized T .
Structure 2
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