Kinetics of glycine arenesulfonylation in the water-propan-2-ol system

Article abstract of DOI:10.1134/S1070363207060151

The kinetics of the glycine N-acylation with 3-nitrobenzenesulfonyl chloride in the water-propan-2-ol mixture containing 40-80 wt% water was studied at 298 K. In going from the mixture containing 40% water to that containing 80% water, the arenesulfonylat

Full text of DOI:10.1134/S1070363207060151

ISSN 1070-3632, Russian Journal of General Chemistry, 2007, Vol. 77, No. 6, pp. 1040 1043.
Pleiades Publishing, Ltd., 2007.
Original Russian Text T.P. Kustova, L.B. Kochetova, N.V. Kalinina, 2007, published in Zhurnal Obshchei Khimii, 2007, Vol. 77, No. 6, pp. 951 954.
Kinetics of Glycine Arenesulfonylation
in the Water Propan-2-ol System
T. P. Kustova, L. B. Kochetova, and N. V. Kalinina
Ivanovo State University,
ul. Ermaka 39, Ivanovo, 153025 Russia
fax: (4932)346600
e-mail: kustova_t@mail.ru
Received December 21, 2006
Abstract The kinetics of the glycine N-acylation with 3-nitrobenzenesulfonyl chloride in the water pro-
pan-2-ol mixture containing 40 80 wt % water was studied at 298 K. In going from the mixture containing
4
0% water to that containing 80% water, the arenesulfonylation rate constant increases by a factor of 40.
Glycine is considerably more reactive in the arenesulfonylation than aminobenzoic acids.
DOI: 10.1134/S1070363207060151
Numerous functional derivatives of arenesulfonic
acids form an important class of biologically active
compounds [1, 2]. More than 50 substances contain-
ing NH SO2 group (according to the Merck Index
lists [3]) are widely used in the clinical practice for
the medical treatment and prophylaxis of bacterial
infections. Furthermore, this class of compounds ex-
hibits the diuretic, hypoglycemic, antihypertensive,
and some other properties [4].
rate of hydrolysis of sulfonyl chloride; and some other
factors.
Our kinetic study of the glycine arenelsulfonylation
with 3-nitrobenzenesulfonyl chloride was performed
at 298 K in water propan-2-ol mixtures with the water
content varying from 40 to 80% wt %.
As known, glycine and all the other -amino acids
exist in water organic solvent mixtures as a set of
nonionized and ionized species (Scheme 1) depending
on pH.
Some of arenesulfonic acid derivatives are enzyme
inhibitors [5]. In view of the proteinic nature of
enzymes, it is of particular interest to study the reac-
tivity of their structural units, -amino acids, in the
arenesulfonylation. No precision kinetic data on this
subject have been reported, due to problems con-
sidered below.
Scheme 1.
+
NH CH COO
3
2
II
K1
K3
+
H+
+
H+
Here we report on a kinetic study of the glycine
arenesulfonylation with 3-nitrobenzenesulfonyl chlo-
ride in the water propan-2-ol system. A wide range of
compositions of the binary solvent was examined. We
have studied previously [6] the reactivity of amino-
benzoic acids in the arenesulfonylation with 3- and
+
NH3CH2COOH
KD NH2CH2COO
I
IV
H+
H+
K2
K4
4-nitrobenzenesulfonyl chlorides in water propan-2-ol
NH2CH2COOH
mixtures. The kinetics of the reaction of -amino
acids with arenesulfonyl chlorides was not studied up
to now. The factors complicating such studies are as
follows: lack of reliable data on the thermodynamics
of dissociation of -amino acids in water propan-2-ol
mixtures, necessary for evaluating the contributions of
the active forms of the amino acids in arenesulfonyla-
tion; need in exact control of pH in the solutions
under investigation, as pH affects not only the ratio
of the ionic species of the amino acids, but also the
III
Here K and K are the acid dissociation constants of
the cationic form of glycine, K is that of the zwitter-
ionic form, and K , that of the uncharged form; KD
characterizes the equilibrium II III. It was found
previously [7] that in water and aqueous-organic
mixtures with the organic component content of up to
90 wt % the relative content of the -amino acid
zwitterions exceeds that of the uncharged molecules
1
2
3
4
1040

KINETICS OF GLYCINE ARENESULFONYLATION IN THE WATER PROPAN-2-OL SYSTEM
1041
4
5
by a factor of 10 10 . Therefore, the acid dissocia-
tion of -amino acids follows the pathway I II
IV. Hence, the experimentally evaluated thermo-
dynamic constants of the acid dissociation of glycine
in acidic and basic solutions, K and K , can be refer-
3-Nitrobenzenesulfonyl chloride can react only
with the neutral (III) and anionic (IV) forms of
glycine containing the nonprotonated amino group;
therefore, the arenesulfonation can occur along two
pathways (Schemes 2, 3).
aI
aII
red to the equilibria I II and II IV, respectively.
Scheme 2.
SO Cl
NH CH COOH +
SO NHCH COOH + HCl
2 2
2
2
2
NO2
NO2
Scheme 3.
SO Cl
NH CH COO +
SO NHCH COO + HCl
2 2
2
2
2
NO2
NO2
The acylation of glycine in a water propan-2-ol
mixture is accompanied by hydrolysis (Scheme 4) and
alcoholysis of the sulfonyl chloride.
tities were used for calculating the relative content of
ionic species of -amino acids in solution at different
pH values. The data obtained show that, under the
conditions of our experiment (pH 5 6), the fraction
of the anionic form of glycine in water propan-2-ol
mixtures with the water content exceeding 40 wt %
exceeds the fraction of the molecular form by a factor
of 10 100. As we showed in [10, 11], in the reaction
of glycine with benzoyl chloride the neutral form does
not significantly contribute to the observed reaction
rate. Based on these data, it can be assumed that in
the reaction under study k0 0 << k , and Eq. (1) can
be transformed into (2).
Scheme 4.
SO Cl + H O
SO H + HCl
3
2
2
NO2
NO2
According to Schemes 2 and 3, the rate of a de-
crease in the concentration of sulfonyl chloride at the
2
3
glycine acid chloride ratio C /C 10 10 is deter-
g
s
mined by the following equation:
dC /d = [kh + (k )C ]C .
(2)
s
g
s
dC /d = [kh + (k0 0 + k )C ]C = k C , (1)
s
g
s
ob s
Here kob = k + (k )Cg.
h
where kob = k + (k
order rate constant evaluated in the kinetic experiment;
kh is the rate constant of the acid chloride hydrolysis;
+ k )C is the observed first-
g
h
0
0
The fraction of the anionic form
by Eq. (3).
is determined
k0 and k are the second-order rate constants of the
KaII
(
3)
=
.
nonionized and anionic forms of glycine;
and
0
CH + KaII
+
are the fractions of these forms in solution. The al-
coholysis of 3-nitrobenzenesulfonyl chloride was
neglected because it was shown previously that the
contribution of methanolysis competing with acylation
does not exceed 2 3%, and in the case of other al-
cohols it is still lower.
For glycine, KaII is 10 10 [2], and under the condi-
6
tions of the kinetic experiment CH
+
10 M. There-
fore, the term KaII in the denominator of Eq. (3) can
be neglected. Then,
KaII
=
,
+
(4)
(5)
CH
k K Cg
The thermodynamic dissociation constants of a
series of -amino acids in water propan-2-ol mixtures
aII
k = k +
.
o
h
C
H+
(
KaI and K ) were evaluated in [8, 9]. These quan-
aII
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 77 No. 6 2007

1042
KUSTOVA et al.
Kinetic characteristics of the reaction of glycine with 3-nitrobenzenesulfonyl chloride in water propan-2-ol mixtures,
2
98 K
,
wt%
106 CH
+
, M
pKaII
a
104 k , s 1
10 kapp 1 , s 1
C
H
+
10 3 k , l mol 1 s 1
H O
h
2
3
5
6
7
8
9.80
0.10
0.17
0.12
0.15
2.29
2.47
3.22
4.79
6.31
10.01
9.98
9.91
9.92
9.91
5.62 0.55
6.47 1.27
7.50 1.16
12.90 1.40
20.00 2.10
0.34 0.08
1.18 0.22
1.86 0.19
3.10 0.22
6.31 0.34
0.80 0.19
2.78 0.52
4.87 0.50
12.37 0.88
32.37 1.74
a
Data from [7].
It follows from Eq. (5) that, when CH
+
is constant,
glycine and aminobenzoic acids in the water dioxane
3
4
the dependence of k on C is linear with a slope of
k K (CH ) . Similar dependences with the correla-
tion coefficients of 0.960 0.998 were obtained for all
the water propan-2-ol mixtures under study (see
figure).
system (10 10 ) were found in [10]. In going from
40 to 70% water propan-2-ol solution, k for the re-
action under consideration increases by a factor of 15,
whereas for aminobenzoic acids the increase is
somewhat less pronounced (by a factor of 3 7). This
means that the solvation effects are stronger in the
arenesulfonylation of glycine.
ob
g
1
+
aII
The quantity k KaII can be regarded as apparent rate
constant of glycine N-acylation.
EXPERIMENTAL
kapp = k KaII.
(6)
The rate constants of the acid chloride hydrolysis
kh, apparent rate constants kapp, and rate constants of
arenesulfonylation of the anionic form of glycine k
are listed in the table.
Glycine (pure grade) was dried at 150 C and used
without additional purification. 3-Nitrobenzenesul-
fonyl chloride (pure grade) was recrystallized from
hexane. Propan-2-ol (chemically pure grade) was
dried with anhydrous copper(II) sulfate and distilled
on a column at atmospheric pressure. Sodium acetate
The data presented show that glycine is more active
in arenesulfonylation than the previously studied
aminobenzoic acids [6]. For all the compositions of
water propan-2-ol mixtures, the rate constants differ
(analytically pure grade) was recrystallized from
water. Acetic acid (analytically pure grade) was used
without additional purification. All the water-contain-
ing solutions were prepared with double-distilled
water. The physicochemical constants (mp, bp) of the
reagents after the purification were in agreement with
the reference data [12].
4
5
by a factor of 10 10 . Similar ratios of the rate
constants of the reactions of benzoyl chloride with
kob 10 , s 1
3
1
The glycine N-acylation rate was monitored by
measuring the sulfonyl chloride concentration with an
SF-46 spectrophotometer at 242 nm using an Shch
8
1
312 digital voltmeter. The working glycine solution
2
in the water propan-2-ol mixture containing acetate
buffer (0.05 M CH COOH and 0.008 M CH COONa)
4
3
3
3
was prepared just before the kinetic experiment. The
working solution was placed in a cell (l = 1 cm) lo-
cated in the temperature-controlled block of the spec-
trophotometer. After reaching the required tempera-
ture, a solution of 3-nitrobenzenesulfonyl chloride in
propan-2-ol was added into the cell in an amount
providing the 3-nitrobenzenesulfonyl chloride con-
centration in the reaction mixture of 5 10 3 M. The
pH measurements of the working solutions were car-
ried out with an I-160M pH meter equipped with an
ES-10603 glass electrode and an ESr-10103 reference
4
5
0
0
0.5
1
0
2
C
10 , M
g
Observed rate constant of the reaction of glycine with
-nitrobenzenesulfonyl chloride at 298 K as a function
of the initial glycine concentration. Solvent water prop-
an-2-ol; (1) 80.15, (2) 70.12, (3) 60.17, (4) 50.10,
and (5) 39.80 wt % water.
3
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 77 No. 6 2007

KINETICS OF GLYCINE ARENESULFONYLATION IN THE WATER PROPAN-2-OL SYSTEM
1043
electrode. The H function of the glass electrode,
logCH = a + bpH, was determined for each solution
3. Merck Index, Budavari, S., Ed., Rahway: Merck, 1989,
+
11th ed., p. 1416.
composition by calibration with perchloric acid. The
a and b values for the water propan-2-ol mixtures
4
. The Pharmacological Basis of Theraupeutics, Good-
man, L.S., Rall, T.W., Murad, F., and Macmillan, F.,
Eds., New York, 1985, 7th ed.
studied are presented below:
.30 0.10, b = 0.995 0.029, r = 0.999;
0.10 wt %, a = 0.26 0.41, b = 0.999 0.118, r =
.995; = 60.17 wt %, a = 0.24 0.18, b =
.997 0.051, r = 0.999;
.14 0.05, b = 0.978 0.015, r = 0.999;
= 39.80 wt %, a =
H O
2
0
=
H O
2
5. Scozzafava, A. and Supuran, C.T., Bioorg. Med.
Chem., 2000, vol. 8, no. 3, p. 637.
5
0
H O
2
6
. Kustova, T.P., Kuritsyn, L.V., and Khripkova, L.N.,
Zh. Obshch. Khim., 2001, vol. 71, no. 4, p. 668.
0
= 70.12 wt %, a =
H O
2
0
=
H O
2
7
. Kuritsyn, L.V., Kustova, T.P., Sadovnikov, A.I., Ka-
linina, N.V., and Klyuev, M.V., Kinetika reaktsii
atsil’nogo perenosa (Kinetics of Acyl Transfer Reac-
tions), Kuritsyn, L.V., Ed., Ivanovo: Ivanov. Gos.
Univ., 2006.
8
0
0.15 wt %, a = 0.08 0.07, b = 0.978 0.022, r =
.999.
ACKNOWLEDGMENTS
8
9
. Kuritsyn, L.V., Kalinina, N.V., and Khripkova, L.N.,
Zh. Fiz. Khim., 2000, vol. 74, no. 9, p. 1721.
The study was performed within the framework of
the RNP 2.2.1.1.7181 project of the Ministry of
Education and Science of the Russian Federation.
. Kuritsyn, L.V., Kalinina, N.V., and Khripkova, L.N.,
Zh. Fiz. Khim., 1998, vol. 72, no. 12, p. 2264.
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