Synthesis and kinetic study of hydrolysis of Di-2-chloroaniline phosphate ester in acidic medium

Article abstract of DOI:10.1002/kin.20460

The kinetics and mechanism of the acid-catalyzed hydrolysis of di-2-chloroaniline phosphate ester were studied in 0.5-7.0 mol dm^-3 hydrochloric acid at 80°C in 20/80 (v/v) dioxane-water medium. The log rate profile shows rate maximum at 4.0 mol dm^-3 hydrochloric acid. The results show that di-2-chloroaniline phosphate is reactive mainly via conjugate acid species. Ionic strength data show a positive salt effect. The effect of different parameters such as temperature, solvent, and substrate concentration on the rate of hydrolysis was studied. Molecularity and order of the reaction have been supported, by Arrhenius parameters, the Zucker-Hammett hypothesis. The rate values shown by experimental and theoretical computational hold good agreements in the entire acid range.

Full text of DOI:10.1002/kin.20460

Synthesis and Kinetic Study
of Hydrolysis of Di-2-
chloroaniline Phosphate
Ester in Acidic Medium
NITIN CHOURE, S. A. BHOITE
School of Studies in Chemistry, Pt. Ravishankar Shukla University, Raipur, Chattisgarh 492 010, India
Received 20 May 2009; revised 15 July 2009, 28 August 2009; accepted 30 August 2009
DOI 10.1002/kin.20460
Published online in Wiley InterScience (www.interscience.wiley.com).
ABSTRACT: The kinetics and mechanism of the acid-catalyzed hydrolysis of di-2-chloroaniline
phosphate ester were studied in 0.5–7.0 mol dm−3 hydrochloric acid at 80◦C in 20/80 (v/v)
dioxane–water medium. The log rate profile shows rate maximum at 4.0 mol dm−3 hydrochlo-
ric acid. The results show that di-2-chloroaniline phosphate is reactive mainly via conjugate
acid species. Ionic strength data show a positive salt effect. The effect of different parameters
such as temperature, solvent, and substrate concentration on the rate of hydrolysis was stud-
ied. Molecularity and order of the reaction have been supported by Arrhenius parameters, the
Zucker–Hammett hypothesis. The rate values shown by experimental and theoretical computa-
tional hold good agreements in the entire acid range. ꢀ 2009 Wiley Periodicals, Inc. Int J Chem
C
Kinet 42: 126–131, 2010
fast detoxification and decontamination method [5].
Organophosphorous compounds are widely used as
pesticides, insecticides, and chemical warfare agents
[6–8], as fire retardants [9], and in smoke genera-
tion [10]. Cyclic amine phosphate in combination with
phosphoramidic acid media and sulfa drugs are very
important for their pharmaceutical and medicinal value
[11] and as cancer chemotherapeutic agents [12].
INTRODUCTION
Phosphate ester hydrolysis plays a very important role
in energy metabolism and in various cellular signal
transduction pathways in biological systems [1]. Phos-
phate mono- and diesters are relatively stable and play
a key role in biochemical reactions [2]. Phosphate mo-
noesters are intermediates in a variety of metabolic
pathways, and phosphate diesters are the essential com-
ponents of DNA and RNA [3]. Phosphate triesters are
more reactive than the corresponding mono- and di-
esters and do not participate in living organisms as
metabolites [3,4]. The widespread use of toxic phos-
phates and phosphonates as insecticides, and their use
as chemical weapons, has led to investigation of the
EXPERIMENTAL
Materials
Di-2-chloroaniline phosphate was synthesized by the
literature method in our laboratory [13].
The method involves the reaction of 2-chloroaniline
and phosphorous oxychloride in 2:1 mole ratio to
give crude diester as a solid. The crude product so
Correspondence to: S. A. Bhoite; e-mail: sa.bhoite10@
gmail.com.
2009 Wiley Periodicals, Inc.
c
ꢀ

SYNTHESIS AND KINETIC STUDY OF HYDROLYSIS OF DI-2-CHLOROANILINE PHOSPHATE ESTER
127
obtained was recrystallized by ammonia solution and
1.8
hydrochloric acid to get a pure sample. The melting
1.6
point of diester noted is 197◦C. All the chemicals used
1.4
were of AR grade, and all solutions were prepared in
1.2
triply distilled water.
1
0.8
0.6
Kinetics
0.4
Hydrolysis of di-2-chloroaniline phosphate ester was
0.2
carried out at 80◦C employing a 5.0 × 10−4 mol dm−3
0
solution in 20/80 (v/v) dioxane–water medium. The
0
2
4
6
8
progress of the kinetic study was carried out by Allen’s
modified method [14], using spectrophotometer at
735 nm. The constant ionic strengths were maintained
by using mixtures of HCl and NaCl. Pseudo-first-order
rate constants (ke) were derived from the first-order
rate equation.
HCl (mol dm–3
)
Figure 1 Plot of 3 + log ke versus HCl mol dm−3 for acidic
hydrolysis of di-2-chloroaniline phosphate ester.
attributed to complete conversion of the substrate into
its conjugate acid species as described in Scheme 1:
a. formation of conjugate acid species by fast pre-
equilibrium proton transfer;
RESULTS AND DISCUSSION
b. bimolecular nucleophilic attack of water on phos-
phorous via conjugate acid species SN2 (P).
Hydrolysis via Conjugate Acid Species
The kinetics of the hydrolysis of di-2-chloroaniline
phosphate ester (I) was studied in 0.5–7.0 mol dm−3
hydrochloric acid at 80◦C. The diphosphate esters
are not soluble in water; a 20/80 (v/v) dioxane-water
medium was used. Dioxane was inert under our exper-
imental conditions and permitted rate measurement for
long periods of time. Pseudo-first-order rate constants
were obtained at several hydrochloric acid concentra-
tions. These are summarized in Table I and illustrated
in Fig. 1. From the results, it may be seen that the
rate of hydrolysis increases with the increase in acid
molarity up to 4.0 mol dm−3 hydrochloric acid. The
maximum rate at 4.0 mol dm−3 hydrochloric acid was
O
H
OH
N
P
Cl
N
H
Cl
I
The decrease in the rate after 4.0 mol dm−3 hy-
drochloric acid was attributed to the lowering of con-
centration of attacking nucleophile taking part in the
reaction, i.e., due to variation in water activity.
Table I Kinetic Rate Data for the Acidic Hydrolysis of
Di-2-chloroaniline Phosphate Ester
HCl
(mol dm−3
ke × 103
Effect of Ionic Strength
)
pH
(min−1
)
3 + log ke
The kinetic salt effect was studied at different ionic
strengths, 1.0, 2.0, and 3.0 μ, using an appropriate
mixture of sodium chloride and hydrochloric acid. The
rate constants are summarized in Table II and illus-
trated in Fig. 2. Hydrolysis at each ionic strength is de-
noted by linear curves that make a positive slope with
the acid axis; hydrolysis is subjected to acid-catalysis
at each ionic strength. The slope of straight lines in-
creases with the increase in the ionic strength. Hence,
acid-catalyzed hydrolysis is attributed to the positive
salt effect. These lines meet at one point on the rate
axis, indicating the participation of neutral species as
described in Scheme 1.
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
5.0
6.0
7.0
0.30
0.00
5.71
9.57
13.0
19.1
25.3
31.0
39.0
48.9
32.7
22.5
10.7
0.76
0.98
1.11
1.28
1.40
1.49
1.59
1.69
1.51
1.35
1.03
−0.18
−0.30
−0.40
−0.48
−0.54
−0.60
−0.70
−0.78
−0.84
Conditions: Temperature = 80◦C, [substrate] = 5.0 × 10−4 mol
dm−3
.
International Journal of Chemical Kinetics DOI 10.1002/kin

128
CHOURE AND BHOITE
O
P
O
H
N
H
N
H
Fast
OH
OH
H
+ H
P
N
Cl
N
H
Cl
Cl
Cl
Neutral species
Conjugate acid species
Scheme 1
Table II Kinetic Rate Data for the Acidic Hydrolysis of Di-2-chloroaniline Phosphate at Constant Ionic Strength
Composition
Ionic Strength (mol dm−3
)
HCl (mol dm−3
)
NaCl (mol dm−3
)
ke × 103 (b) (min−1
)
1.0
1.0
1.0
1.0
2.0
2.0
2.0
2.0
3.0
3.0
3.0
3.0
0.20
0.50
0.60
0.80
0.40
0.80
1.20
1.60
0.80
1.00
1.50
2.00
0.80
0.50
0.40
0.20
1.60
1.20
0.80
0.40
2.20
2.00
1.50
1.00
1.68
3.91
5.05
6.12
4.10
8.15
10.9
13.9
10.2
12.9
17.3
23.4
Temperature = 80◦C, [substrate] = 5.0 × 10−4 mol dm−3
.
Three linear plots show the acid-catalyzed hydrol-
ysis of di-2-chloroaniline phosphate at three different
ionic strengths by the following rate equation:
ionic effect indicates that di-2-chloroaniline phosphate
ester undergoes acid-catalyzed hydrolysis with posi-
tive effect of the ionic strength. The corresponding
slope values at constant ionic strengths 1.0, 2.0, and
3.0 μ are 7.56 × 10−3, 8.04 × 10−3, and 10.7 ×
10−3 mol dm−3 min−1, respectively.
Figure 3 shows the specific acid-catalyzed rates
with their logarithmic values at that ionic strength.
The slope of the line represents a constant bHꢁ + , where
+
+
ke = kH CH
(1)
+
+
where, ke, kH , and CH are experimental rate coeffi-
cients, specific acid-catalyzed rate, and concentration
of hydrogen ion [H+], respectively. The accelerating
3μ
25
1.5
20
15
10
5
2μ
1μ
Slope = 0.07
e
1
k
e
0.5
0
k
0
0
1
2
3
4
0
0.5
1
1.5
2
2.5
HCl (mol dm–3
)
Ionic strength
Figure 2 Plot of ke × 103 min−1 versus HCl mol dm−3 for
Figure 3 Plot of 3 + log ke versus ionic strength for acidic
the acidic hydrolysis of di-2-chloroaniline phosphate ester.
hydrolysis of di-2-chloroaniline phosphate ester.
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SYNTHESIS AND KINETIC STUDY OF HYDROLYSIS OF DI-2-CHLOROANILINE PHOSPHATE ESTER
129
Table III Theoretical and Experimental Rate Data for the Acidic Hydrolysis of Di-2-chloroaniline Phosphate Ester
b
HCl (mol dm−3
)
kH CH × 103
kN × 103
ke × 103
log(aH O
)
ke × 103a
ke × 103 (min−1
)
+
+
2
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
5.0
6.0
7.0
3.34
7.24
11.8
17.0
23.1
30.0
37.9
47.0
69.0
97.3
133.4
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
4.34
8.24
12.8
18.0
24.1
31.0
38.9
48.0
70.0
98.3
134.4
–
–
–
–
–
–
–
4.34
8.24
12.8
18.0
24.1
31.0
38.9
48.0
33.1
22.4
10.2
5.71
9.57
13.0
19.1
25.3
31.0
39.0
48.9
32.7
22.5
10.7
–
(0.16)2
(0.22)3
(0.28)4
a Theoretical rate.
b Experimental rate.
bꢁ = b/2.303, and intercepts on the rate axis represent
kN = kNo exp bNꢁ μ
(6)
(7)
+
the specific acid-catalyzed rates (log kH ). The linear-
log kN = log kNo + bNꢁ μ
ity of the curve (Fig. 3) shows the following relation of
the rate constant with ionic strength. This presents an
empirical form of the Debye–Huckel equation [15]:
where kN is neutral rate and bNꢁ = bN/2.303.
Equations (5) and (7) may be used for the acid-
catalyzed and the neutral rates, respectively, at each
experimental rate.
k = ke exp bHꢁ + · μ
(2)
The specific acid-catalyzed rate may be shown as
+
+
ke = kH CH + kN
(8)
ꢁ
+
+
kH = kHo exp bH+ · μ
(3)
Table III summarizes both the observed and theoretical
rates of the hydrolysis in the acid region from 0.5 to
4.0 mol dm−3 hydrochloric acid. The lowering in rates
at 5.0, 6.0, and 7.0 mol dm−3 hydrochloric acid may
be attributed to the lowering in the concentration and
participation of water molecules.
ꢁ
+
+
where kH , kHo , bH+ , and μ are specific acid-catalyzed
rate at that ionic strength, specific acid-catalyzed rate
at zero ionic strength, a constant, and ionic strength,
respectively.
Specific acid-catalyzed rates can be converted into
acid-catalyzed rates,
The rate beyond 4.0 mol dm−3 HCl was calculated
employing the Brønsted–Bjerrum equation [16].
n
kH · CH = kHo · CH · exp ·bHꢁ + · μ
(4)
ke = kH CH (aH O)n + kN(aH O
)
(9)
+
+
+
+
+
+
2
2
log kH · CH = log kHo + log CH + bHꢁ + · μ (5)
kH CH = kHoCH exp bH+ μ (a
)
(10)
ꢁ
n
+
+
+
+
+
+
+
H2O
Table IV Zucker–Hammett, Hammett, Bunnett, and Bunnett–Olsen Plot Data for the Hydrolysis of Di-2-chloroaniline
Phosphate Ester
HCl
(mol dm−3
ke × 103
3 + log ke−
(min−1
)
3 + log ke bꢁμ −Ho log CH
log(aH O
)
3 + log ke+ Ho − log CH
(− log CH + Ho)
+
+
+
)
2
1.0
1.5
2.0
2.5
3.0
3.5
4.0
5.0
6.0
7.0
9.57
13.0
19.0
25.3
31.0
39.0
48.9
32.7
22.5
10.7
0.98
1.11
1.28
1.40
1.49
1.59
1.69
1.51
1.35
1.03
0.07 0.20
0.11 0.47
0.14 0.69
0.18 0.87
0.21 1.05
0.25 1.23
0.28 1.40
0.35 1.76
0.42 2.12
0.49 2.53
0.00
0.18
0.30
0.40
0.48
0.54
0.60
0.70
0.78
0.84
0.02
0.03
0.04
0.05
0.07
0.09
0.11
0.16
0.21
0.28
0.78
0.64
0.59
0.53
0.44
0.36
0.29
−0.25
−0.77
−1.50
0.98
0.93
0.98
1.00
1.01
1.05
1.09
0.81
0.57
0.19
0.20
0.29
0.39
0.47
0.57
0.69
0.80
1.06
1.34
1.69
International Journal of Chemical Kinetics DOI 10.1002/kin

130
CHOURE AND BHOITE
H
O
H
O
P
H
H
δ
O
H
H
N
H
O
P
OH
NP
H
Slow
OH
H
N
H
Cl
Cl
N
Cl
Cl
Transitition state
Fast
OH2
OH
O
O
P
-H
NH2
+
OH
P
HO
Cl
N
N
H
H
δ
O
H
Cl
Cl
H
Slow
NH
O
O
P
Cl
Fast
+
OH
+
HO
OH
HO
H
P
OH
δ
O
H
H
H
NH2
+
NH
Cl
Parent compound
Cl
Scheme 2
+
+
+
+
log kH · CH = log kHo + log CH
the reactions that give a linear plot of log rate constants
against the acidity function (−Ho) did not involve wa-
ter molecules in the rate-determining step. The slope
value 0.60 ( 0.01) (figure not shown) of the plot is
far from unity, indicating the absence of unimolecular
hydrolysis.
+ bHꢁ μ + n log(aH O
)
2
The neutral rate at higher concentration is as follows:
kN = kNo exp bNꢁ μ(aH O
)
(11)
n
2
The second part of the hypothesis deals with a plot
between the log rate constant and the log acid mo-
larity. A unit or approximately unit slope of this plot
was used as a criterion to predict the probable mech-
anism to be bimolecular, i.e., the reaction involves
the participation of water molecule in the transition
state (Scheme 2). The slope value 1.19 ( 0.06) (figure
not shown) clearly indicates the bimolecularity of the
reaction.
where n is an integer and aH O is water activity. The
2
revised estimated rates agree well with the experi-
mentally observed rates (Table III). It is clear from
the above results that hydrolysis of di-2-chloroaniline
phosphate ester in acid solution occurs via both con-
jugate acid and neutral species and their rates are sub-
jected to ionic strength or water activity.
The slope values of ω = 8.44( 0.46), ω∗ =
2.84( 0.55), and ꢀ = 1.28( 0.07) for Bunnett [19]
and Bunnett–Olsen [20] parameters (figure not shown)
for di-2-chloroaniline phosphate ester also indicate a
Molecularity of Reaction
The Zucker–Hammett [17] hypothesis is made up of
two parts. In the first part, Hammett [18] postulated that
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SYNTHESIS AND KINETIC STUDY OF HYDROLYSIS OF DI-2-CHLOROANILINE PHOSPHATE ESTER
131
Table V Solvent Effect Rate Data for the Hydrolysis of
Di-2-chloroaniline Phosphate Ester
subjected to the positive effect of the ionic strength.
The bimolecular nature of hydrolysis was supported
by different parameters such as Hammett, Zucker–
Hammett, Bunnett, Bunnett—Olsen, and Arrhenius.
The bimolecular hydrolysis with P–N bond fission of
the conjugate acid species was proposed. The SN (P)
mechanism was suggested for the hydrolysis via con-
jugate acid species.
HCl
(mol dm−3
% of dioxane
(v/v)
ke × 103
)
(min−1
)
3 + log ke
2.0
2.0
2.0
20.0
30.0
40.0
19.0
21.5
24.3
1.28
1.33
1.38
2
The authors are thankful to Prof. (Mrs.) Rama Pande, Head,
School of Studies in Chemistry, Pt. Ravishankar Shukla
University, Raipur, India, for providing research facilities.
slow proton transfer with a nucleophilic attack of the
water molecule. See Table IV.
Effect of Temperature
BIBLIOGRAPHY
Arrhenius parameters [21] (figure not shown) deter-
mined for the hydrolysis at 3.0 mol dm−3 HCl are
activation energy (Ea) = 13.7 kcal mol−1, frequency
factor (A) = 1.63 × 10−5 s−1, and entropy (−ꢁS=) =
28.9 e.u. These values indicate the bimolecular nature
of the hydrolytic reaction.
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Effect of Solvent
Table V shows that the rate constant values gradually
increases with the gradual addition of dioxane. Diox-
ane is regarded as a polar aprotic solvent. The effect of
solvent on the rate of hydrolysis indicates the transition
state in which charge is dispersed. This is in accordance
with Chanley’s observation [22].
A comparative kinetic study of the acid-catalyzed
hydrolysis of di-2-chloroaniline phosphate ester with
other diesters, which also give a linear relation between
rates and hydrogen ion (H+) concentration in moder-
ately acid solution and resemble simple esters in be-
havior, helps in presuming a bimolecular nucleophilic
attack of water involving P–N bond fission (data not
shown). Thus, the acid-catalyzed hydrolysis of di-2-
chloroaniline phosphate ester involves the bimolecu-
lar attack of water on phosphorous of conjugate acid
species formed by fast preequilibrium proton transfer.
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CONCLUSION
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80, 2686.
Di-2-chloroaniline phosphate ester in 0.5–7.0 mol
dm−3 HCl was found to hydrolyze via neutral and con-
jugate acid species. The acid-catalyzed hydrolysis is
International Journal of Chemical Kinetics DOI 10.1002/kin