Effect of nucleophile on the activation parameters of transesterification of 4-nitrophenyl benzoates

Article abstract of DOI:10.1134/S1070428010030048

Activation parameters of the reaction of 4-nitrophenyl benzoates with benzenethiol in the presence of potassium carbonate in dimethylformamide were determined. The entropies of activation for the reactions of unsubstituted 4-nitrophenyl benzoate and 4-nit

Full text of DOI:10.1134/S1070428010030048

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 3, pp. 326–330. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © I.A. Os’kina, V.M. Vlasov, 2010, published in Zhurnal Organicheskoi Khimii, 2010, Vol. 46, No. 3, pp. 334–338.
Effect of Nucleophile on the Activation Parameters
of Transesterification of 4-Nitrophenyl Benzoates
I. A. Os’kina and V. M. Vlasov
Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division, Russian Academy of Sciences,
pr. Akademika Lavrent’eva 9, Novosibirsk, 630090 Russia
e-mail: oi@nioch.nsc.ru
Received June 2, 2009
Abstract—Activation parameters of the reaction of 4-nitrophenyl benzoates with benzenethiol in the presence
of potassium carbonate in dimethylformamide were determined. The entropies of activation for the reactions of
unsubstituted 4-nitrophenyl benzoate and 4-nitrophenyl benzoates having donor substituents are positive. The
relative contributions of the enthalpy and entropy of activation to the Gibbs energy of activation are discussed.
Variation of the activation parameters upon replacement of benzenethiol by 4-chlorophenol is analyzed.
DOI: 10.1134/S1070428010030048
Acyl group transfer reactions of esters are the
subject of extensive theoretical and experimental
studies due to their important role in biological proc-
esses [1–3] and broad spectrum of practical applica-
tions [4–7]. Data on variations of the enthalpy of ac-
The goal of the present work was to analyze varia-
tions in the activation parameters of transesterification
of 4-nitrophenyl benzoates, depending on the nucleo-
phile nature.
We estimated the apparent rate constants for the
reactions of 4-nitrophenyl benzoate (III) with benzene-
thiol (VII) in the presence of potassium carbonate in
DMF at different temperatures. Using the log(k/T)–1/T
dependence (Fig. 1) we calculated by the Eyring equa-
≠
≠
tivation (∆H ), entropy of activation (∆S ), and Gibbs
≠
energy of activation (∆G ), depending on the reactant
nature, are very important for understanding the mech-
anism of transesterification process. Activation param-
eters for reactions at a carbonyl carbon atom were
reviewed in [8]; however, published data on activation
parameters for transesterification reactions are very
few in number [9].
≠
≠
≠
tion [15] the activation parameters ∆H , ∆S , and ∆G
for the reaction of III with benzenethiol in the pres-
ence of K CO in DMF, which reflected variation of
2
3
the reactivity in energy units (Table 1). On the basis of
these values and the data of [11] we determined the
≠
≠
≠
We previously [10] estimated ∆H , ∆S , and ∆G
values for the reactions of 4-nitrophenyl benzoates
with 4-chlorophenol in dimethylformamide in the pres-
ence of potassium carbonate. It was shown that the
ratio of the enthalpy and entropy contributions to the
energy barrier in the examined transesterification proc-
ess depends on the substituent nature in 4-nitrophenyl
benzoates. As shown in [11, 12], the nature of nucleo-
phile also affects the rate of transesterification. The
observed differences in the reactivity of oxygen- and
sulfur-centered nucleophiles are consistent with the
Scheme 1.
O
OAr
R
+
PhSH
I–VI
VII
O
K CO , DMF, 15–36°C
SPh
2
3
R
+ ArOK
difference in the nucleophile basicities (the pK values
a
of benzenethiol and 4-chlorophenol in DMF are 10.8
and 16.4, respectively [13]); they could also be deter-
mined by different polarizabilities of the nucleophilic
center [14].
VIII–XIII
I, VIII, R = 4-MeO; II, IX, R = 4-Me; III, X, R = H; IV,
XI, R = 4-Br; V, XII, R = 3-Br; VI, XIII; R = 4-F C; Ar =
4-O NC
3
2
6 4
H .
3
26

EFFECT OF NUCLEOPHILE ON THE ACTIVATION PARAMETERS
327
log(kap/T)
activation parameters for the reactions of I, II, and IV–
VI with benzenethiol (VII) in DMF in the presence of
potassium carbonate.
As in the reactions of 4-nitrophenyl benzoates with
–
–
3.5
4.0
4
-chlorophenol in the presence of K CO in DMF [10],
2 3
≠
≠
the parameters ∆H and ∆S found in the present work
showed high sensitivity to the substituent in the acid
fragment of 4-nitrophenyl benzoates, and these param-
eters changed over quite broad ranges, though the
≠
range of variation of ∆G remained typical of reactions
of carbonyl compounds with nucleophiles [8]. The
reactions with compounds having electron-donating
groups are characterized by large enthalpies of activa-
tion and large entropies of activation. Increase in the
electron-acceptor power of the substituent in 4-nitro-
phenyl benzoates leads to considerable reduction of the
contributions of both enthalpy and entropy factors to
the energy barrier.
–4.5
.00320 0.00325 0.00330 0.00335 0.00340 0.00345
0
–
1
1
/T, K
Fig. 1. Plot of log(k/T) versus reciprocal temperature for the
reaction of 4-nitrophenyl benzoate (III) with benzenethiol in
–
1
the presence of K
2
CO
3
in DMF: log(kap/T) = –4857.7T
+
Comparison of the activation parameters for the
reactions of substituted 4-nitrophenyl benzoates with
benzenethiol and 4-chlorophenol in the presence of
K CO in DMF (Table 1) revealed the following linear
1
2.5; r = 0.998, s = 0.05, n = 3.
stituent constants σ [16, 17]. Table 2 contains the
slopes (in absolute values) of the dependences of ac-
tivation parameters for transesterification of 4-nitro-
phenyl benzoates with benzenethiol and 4-chloro-
phenol upon substituent constants σ. It is seen (Fig. 2)
that these slopes are fairly large, indicating high sensi-
tivity of the activation parameters to substituent effect.
2
3
≠
≠
O
relations: ∆H = 1.4∆H + 25 (r = 0.984, s = 6.9,
n = 5); ∆S = 1.6∆S + 198 (r = 0.976, s = 26, n = 5),
G = 0.5∆G + 40 (r = 0.979, s = 0.7, n = 5). These
S
≠
S
≠
O
≠
≠
∆
S O
relations indicate that the activation parameters for the
reaction of 4-nitrophenyl benzoates with benzenethiol
≠
≠
≠
(
∆H , ∆S , ∆G ) are higher than those for the reaction
≠
S
S
S
The absolute values of the slopes of the ∆H —σ and
≠
of the same substrate with 4-chlorophenol (∆H ,
S , ∆G ).
O O
≠
O
∆
S —σ dependences are larger for the reaction of
≠
≠
∆
4
-nitrophenyl benzoates with benzenethiol than for the
≠
It is known that substituent effect on activation
parameters may be estimated by the slope of the
dependence of the corresponding parameter upon sub-
reaction with 4-chlorophenol (∆H —σ: |ρ| = 108.5 and
76.4, respectively; ∆S —σ: |ρ| = 332 and 192, respec-
≠
tively), while the sensitivity of the Gibbs activation
Table 1. Activation parameters for the reactions of 4-nitrophenyl benzoates I–VI with benzenethiol in the presence of
a
K
2 3
CO in DMF
≠
≠
–1
–1
≠
≠
Compound no.
∆H , kJ/mol
∆S , J mol K
T∆S , kJ/mol
∆G , kJ/mol
I
112.1±9.5 (61.2)
106.5±8.5 (55.6)
093.0±6.5 (54.8)
067.6±8.0 (25.6)
040.4±4.6
0–92.0±8.3 (–71.4)
0–80.6±3.6 (–80.5)
0–42.1±0.8 (–76.1)
0–35.9±6.5 (–158.2)
–125.3±18.8
–27.5 (–21.2)
–24.1 (–23.9)
–12.6 (–22.6)
–10.7 (–47.0)
–37.5
84.6 (82.4)
82.4 (79.5)
80.4 (77.4)
78.3 (72.6)
77.9 (00.0)
76.8 (68.1)
II
b
III
IV
V
VI
028.3±3.5 (4.9)
–162.1±27.5 (–212.9)
–48.5 (–63.2)
a
≠
≠
≠
The activation parameters ∆H , ∆S , and ∆G were determined from the activation parameters for the reaction with 4-nitrophenyl
≠
≠
≠
≠
≠
≠
≠
≠
benzoate (III) and differences in the activation parameters ∆∆H = ∆H (R) – ∆H (H), ∆∆S = ∆S (R) – ∆S (H), and ∆∆G = ∆G (R) –
G (H), calculated from the data in [11]. In parentheses are given the activation parameters for the reactions of esters I–III, V, and VI
≠
∆
≠
≠
2 3
with 4-chlorophenol in the presence of K CO in DMF according to [10]. The T∆S and ∆G values were calculated at 24 and 26°C.
b
≠
≠
≠
The activation parameters ∆H , ∆S , and ∆G for compound III were calculated by the Eyring equation [15] from the log(k/T)—1/T
dependence.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 3 2010

3
28
OS’KINA, VLASOV
Table 2. Slopes (absolute values |ρ|) of the dependences of
activation parameters (a) upon substituent constants σ for
transesterification of 4-nitrophenyl benzoates, a = ρσ + c
compounds with nucleophiles are usually assumed to
be characterized by negative entropies of activation
a
[19], positive entropies of activation were found for
some bimolecular nucleophilic reactions [16, 20].
Positive entropies of activation in the reactions of sub-
stituted 4-nitrophenyl benzoates I–III with benzene-
thiol in the presence of K CO in DMF suggest that
solvation of the initial compounds is stronger than
solvation of the transition state. Presumably, the transi-
tion state formed with participation of benzenethiol is
less polarizable than the initial nucleophilic complex
Activation
parameter
4-Chloro-
phenol
Benzenethiol
b
≠
∆H
108.5 (c = 87.7, r = 0.992, s = 5.0,
n = 6)
076.4
192.0
060.0
016.3
2
3
≠
∆S
332 (c = 21.8, r = 0.987, s = 19,
n = 6)
≠
T∆S
99.4 (c = 6.5, r = 0.987, s = 5.8,
n = 6)
(
PhSH·K CO ), so that nonspecific solvation of the
2 3
≠
∆G
9 (c = 81.1, r = 0.970, s = 0.8,
n = 6)
transition state derived from 4-nitrophenyl benzoates
with electron-donating groups weakens. The presence
of electron-withdrawing substituents in compounds
IV–VI creates additional capabilities for charge delo-
calization in the transition state, which increases its
nonspecific solvation and leads to negative entropy of
activation. Eventually, large energy consumption for
bond rupture and formation in the reactions of com-
pounds with electron-donor groups is compensated by
desolvation, whereas reduced energy consumption for
bond rupture and formation in the reactions of com-
pounds with electron-withdrawing groups us supple-
mented by enhanced solvation of the transition state.
a
Substituent constants σ were taken from [18].
Data of [11].
b
energy to the substituent nature is higher for the reac-
tion with 4-chlorophenol (∆G —σ: |ρ| = 9 and 16.3,
respectively).
≠
The enthalpy component provides the main contri-
bution to the Gibbs energy of activation in the reac-
tions of substituted 4-nitrophenyl benzoates I–V with
benzenethiol in the presence of K CO in DMF. The
entropy contribution was found to predominate in the
reaction of 4-nitrophenyl 4-trifluoromethylbenzoate
2
3
The observed increase in the enthalpy of activation
for the reactions of substituted 4-nitrophenyl benzoates
with benzenethiol in the presence of K CO in DMF,
(
VI) with benzenethiol (K CO , DMF). It should be
2 3
emphasized that the entropies of activation for 4-nitro-
phenyl benzoate (III) and its analogs with donor sub-
stituents are positive. Although reactions of carbonyl
2
3
as compared to 4-chlorophenol (Table 1, Fig. 2), may
be rationalized in terms of increase in energy con-
sumption for bond rupture and formation, which
reduces the electrophilicity of the carbonyl carbon
atom toward benzenethiol. Increase in the entropy of
activation in the reactions of substituted 4-nitrophenyl
benzoates in going from 4-chlorophenol as nucleophile
to benzenethiol (Table 1, Fig. 2) is very consistent with
the assumption that the reactions of substituted 4-ni-
trophenyl benzoates with benzenethiol involve forma-
≠
≠
≠
∆
G , T∆S , ∆H , kJ/mol
1
20
8
4
0
0
0
1
2
3
4
tion of acyclic transition state (TS ) [11] and that the
S
transition state in their reactions with 4-chlorophenol
≠
≠
K
O
O
K
O
O
–
40
80
5
6
O
O
δ+
K
δ–K
–
δ–
O
O
H
δ–
H
–
0.4
–0.2
0.0
0.2
0.4
0.6 σ
S δ–
O
≠
≠
Fig. 2. Plots of activation parameters (1, 2) ∆G , (3, 4) T∆S ,
and (5, 6) ∆H versus substituent constants σ for the reac-
Ph
Ar'
OAr
OAr
≠
tions of substituted 4-nitrophenyl benzoates with (1, 3, 5) ben-
zenethiol and (2, 4, 6) 4-chlorophenol in the presence of
R
R
K
2
CO
3
in DMF.
TSS
TSO
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 3 2010

EFFECT OF NUCLEOPHILE ON THE ACTIVATION PARAMETERS
329
in DMF in the presence of K CO has cyclic structure
Determination of the apparent rate constants for
the reaction of 4-nitrophenyl benzoate (III) with
benzenethiol in the presence of potassium carbo-
nate in dimethylformamide. The procedure was
analogous to that reported in [10]. A flask was flushed
with argon and charged with K CO (grain size
2
3
(
TS ) [12].
O
Increase of the enthalpy and entropy contributions
leads to increase in the Gibbs energy of activation
Table 1, Fig. 2) and reduction in the reactivity of
(
2
3
substituted 4-nitrophenyl benzoates in transesterifica-
tion reaction upon replacement of 4-chlorophenol as
nucleophile by benzenethiol [10–12].
d ≤ 0.5 mm) and a solution of benzenethiol in 2 ml of
DMF, the K CO –PhSH ratio being 1.4:1 or higher.
2
3
The mixture was stirred for 30 min using a magnetic
Thus the reactions of substituted 4-nitrophenyl ben-
zoates with benzenethiol in the presence of potassium
carbonate in dimethylformamide are characterized by
higher activation parameters than those found for their
reactions with 4-chlorophenol, which is likely to be
determined by change of the transition state structure.
stirrer (n ≥ 750 rpm) at 15, 26, or 36°C. The initial
–2
reactant concentrations were (2–6)×10 M. A solution
of 4-nitrophenyl benzoate (III) in 2 ml of DMF,
adjusted to the same temperature, was added, and the
mixture was stirred. A sample was withdrawn and
added to a mixture of chloroform with 10% hydro-
chloric acid, and the organic phase was separated,
dried, and analyzed. The product concentration was
determined by GLC, and the rate constant was calcu-
lated using second-order equation:
EXPERIMENTAL
The reaction mixtures were analyzed by GLC on
an LKhM-72 chromatograph equipped with a thermal
conductivity detector; SKTFT-803 column packed with
k = {2.303/[τ(a – b)]}log{[b(a – x)]/[a(b – x)]},
1
5% of VS-1 on Chromaton W; carrier gas helium,
where a and b are the initial reactant concentrations
flow rate 60 ml/min; linear oven temperature pro-
gramming from 50 to 270°C at a rate of 10 deg/min.
The components were quantitated by the internal
normalization technique using hexamethylbenzene as
standard. The products were identified by addition of
authentic samples. Commercial dimethylformamide
was distilled under reduced pressure first over calcium
hydride and then over molecular sieves and was stored
over molecular sieves under argon. Commercial potas-
sium carbonate was ground, bolted through a 0.5-mm
sieve, calcined in a muffle furnace, and again ground
and bolted through a 0.5-mm sieve. Commercial ben-
zenethiol was purified by standard procedures. 4-Ni-
trophenyl benzoates were synthesized according to the
procedures described in [10, 11], and their physical
constants were consistent with published data.
(
M), x is the product concentration (M), and τ is the
reaction time (s). The apparent rate constants calculat-
ed from the results of at least three parallel runs were
as follows, l mol s : 15°C, k = (1.3 ±0.2)×10 ;
–1 –1
–2
–2
–1
2
6°C, k = (4.9±0.7)×10 ; 36°C, k = (2.0±0.04)×10 .
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