Unexpected rate enhancement in the intramolecular carboxylic Acid-catalyzed cleavage of o-carboxybenzohydroxamic acid

Article abstract of DOI:10.1002/(sici)1099-1395(199803)11:3<216::aid-poc992>3.0.co;2-9

Phthalic anhydride was detected spectrophotometrically in the hydrolysis of o-carboxybenzohydroxamic acid (OCBA) in CH₃CN-H₂O solvent containing 0.03 mol dm^-3 HCl. Pseudo-first-order rate constants (K₁) for hydrolysis of OCBA are almost independent of the change in CH₃CN content from 10 to 80% (v/v) in mixed aqueous solvents. The rate constants k₁ are more than 10-fold larger than the corresponding rate constants for hydrolysis of phthalamic acid. These observations are explained in terms of a mechanism slightly different from the mechanism for hydrolysis of phthalamic acid. The activation parameters, ΔH * and ΔS *, are not affected appreciably by an increase in CH₃CN content from 10 to 80% in mixed aqueous solvents.

Full text of DOI:10.1002/(sici)1099-1395(199803)11:3<216::aid-poc992>3.0.co;2-9

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, VOL. 11, 216–222 (1998)
Unexpected rate enhancement in the intramolecular
carboxylic Acid-catalyzed cleavage of o-carboxybenzo-
hydroxamic acid
M. Niyaz Khan*
Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia
Received 22 June 1997; revised 27 July 1997; accepted 4 September 1997
ABSTRACT: Phthalic anhydride was detected spectrophotometrically in the hydrolysis of o-carboxybenzo-
hydroxamic acid (OCBA) in CH3CN–H2O solvent containing 0.03 mol dmꢀ3 HCl. Pseudo-first-order rate constants
(k1) for hydrolysis of OCBA are almost independent of the change in CH3CN content from 10 to 80% (v/v) in mixed
aqueous solvents. The rate constants k1 are more than 10-fold larger than the corresponding rate constants for
hydrolysis of phthalamic acid. These observations are explained in terms of a mechanism slightly different from the
mechanism for hydrolysis of phthalamic acid. The activation parameters, DH* and DS*, are not affected appreciably
by an increase in CH3CN content from 10 to 80% in mixed aqueous solvents. 1998 John Wiley & Sons, Ltd.
KEYWORDS: o-carboxybenzohydroxamic acid; phthalic anhydride; phthalic acid; hydrolysis; intramolecular acid
catalysis; kinetics; activation parameters
INTRODUCTION
phthalic anhydride.12 The present study was initiated
with the aim of exploring the effect of the OH group (in
the leaving group) on the rate of uncatalyzed hydrolysis
of o-carboxybenzohydroxamic acid.
The mechanistic details of intramolecular carboxylic acid
participation in amide hydrolysis have been explored by
several workers.1–11 Most of these intramolecular reac-
tions involve uncatalyzed, external general acid (GA)-
and external general base (GB)-catalyzed hydrolysis. The
general mechanism suggested and supported in these
‡
reactions is shown in Scheme 1, where B and BH
represent GB catalyst and GA catalyst, respectively. In
almost all of these studies,6–9 the rate constants (k) for
uncatalyzed hydrolysis showed negative reaction con-
stants (r or r*). It is interesting that the leaving groups
(—NHR) in all these mechanistically well studied
reactions contain only one basic site (i.e. the nitrogen
atom) where internal proton transfer can occur.
o-Carboxybenzohydroxamic acid contains two basic
sites (N and O) in the leaving group (—NHOH), although
these two basic sites are not of equal basicity, where
internal proton transfer can occur. Hydrolysis of o-
carboxybenzohydroxamic acid has been shown to
involve nucleophilic catalysis by the neighboring car-
boxylate group (o-CO2ꢀ) and intermediate formation of
*Correspondence to: M. N. Khan, Department of Chemistry, Faculty
of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Contract/grant sponsor: Universiti Malaya; contract grant number:
F408/96.
Scheme 1
Contract/grant sponsor: IRPA; contract grant number: 09-02-03-003.
1998 John Wiley & Sons, Ltd.
CCC 0894–3230/98/030216–07 $17.50

ACID-CATALYZED CLEAVAGE OF o-CARBOXYBENZOHYDROXAMIC ACID
217
Figure 1. Plot of absorbance at 310 nm against time for a mixed aqueous solution
of o-carboxybenzohydroxamic acid (2 Â 10ꢀ3 mol dmꢀ3) in 80% CH3CN and
0.037 mol dmꢀ3 HCl at 35°C
rates of formation and decay of PAn in the hydrolysis of
o-carboxybenzohydroxamic acid in an acidic medium
were studied spectrophotometrically at 310 nm in water–
acetonitrile solvents.
EXPERIMENTAL
Materials. All chemicals were of reagent grade and were
obtained from Fluka, Aldrich and Merck. Distilled water
was used throughout and stock solutions of N-hydroxy-
phthalimide were prepared frequently in acetonitrile.
In a typical kinetic run with a total volume of 4.8 cm3
of the reaction mixture containing 0.5 cm3 of 0.02 mol
dmꢀ3 N-hydroxyphthalimide (in acetonitrile solvent),
0.2 cm3 of 0.25 mol dmꢀ3 NaOH, 3.5 cm3 of CH3CN and
0.6 cm3 of H2O, the reaction was allowed to complete a
period of more than 30 half-lives (i.e. nearly 900 s) at
35°C. The hydrolysis of the hydrolytic product of N-
hydroxyphthalimide (NHPH), i.e. hydrolysis of o-car-
boxybenzohydroxamic acid (OCBA), was then initiated
by adding 0.2 cm3 of 1.18 mol dmꢀ3 HCl to the reaction
mixture. The resulting reaction mixture, having a total
volume of 5.0 cm3, contained 2 Â 10ꢀ4 mol dmꢀ3
OCBA, 0.037 mol dmꢀ3 HCl and 80% CH3CN. The
change in absorbance (AU) at 310 nm was monitored as a
function of time (t) using a diode-array spectrophoto-
meter. The observed data (for a typical kinetic run) are
shown in Fig. 1.
Kinetic measurements. The formation of phthalic
anhydride (PAn) as an intermediate in the hydrolysis of
phthalamic acid and its N-substituted derivatives has
been unequivocally ascertained.1,8,11 Phthalic anhydride
absorbs significantly whereas phthalamic and N-substi-
tuted phthalamic acids do not absorb to a detectable
extent at 310 nm. If the rate of hydrolysis of PAn is
slower than that of phthalamic acid or N-substituted
phthalamic acid, then the rate of hydrolysis of phthalamic
acid or N-substituted phthalamic acid can easily be
studied spectrophotometrically at 310 nm. Blackburn et
al.8 studied the rate of hydrolysis of phthalamic acid and
a few N-arylphthalamic acids by monitoring the change
in [PAn] spectrophotometrically at 310 nm in the
presence of high concentrations of sodium perchlorate,
where the rate of hydrolysis of PAn was greatly
retarded.13 The rate of hydrolysis of N,N-dimethylphthal-
amic acid in acidic medium was found to be almost
independent of increasing acetonitrile content [from 10 to
80% (v/v) (all percentage concentrations are by volume
in this paper)] in mixed aqueous solvents.11 However, the
rate of hydrolysis of PAn in acidic medium decreased
nearly 200-fold with increase in acetonitrile content from
2 to 80% in mixed aqueous solvents.14 These results
show that the presence of PAn in the hydrolysis of
phthalamic acid or its N-substituted derivatives can be
easily detected spectrophotometrically by using water–
acetonitrile or water–aprotic organic solvents. Hence, the
In an earlier report,15 product analysis of the alkaline
hydrolysis of N-hydroxyphthalimide in an aqueous sol-
vent containing 2% CH3CN revealed a 100% conversion
of reactant (N-hydroxyphthalimide) into the expected
product, OCBA. An extremely slow rate of hydrolysis of
the product (OCBA) was observed at pH 11.4 (only ca
<20% hydrolysis occurred within a period of 7 days at
ambient temperature15).
Kinetic data analysis. A monotonic increase in AU in the
initial phase of the reaction (hydrolysis of OCBA)
followed by a monotonic decrease in AU in the final
phase of the reaction (Fig. 1) indicates the involvement of
a stable intermediate in the hydrolysis of OCBA. The
1998 John Wiley & Sons, Ltd.
JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, VOL. 11, 216–222 (1998)

Table 1. Values of k1, k2, eapp and AU0 calculated from equations (2) and (3) for hydrolysis of o-carboxybenzohydroxamic acid and phthalic anhydride in an acidic mediuma
[MeCN]
(%, v/v)
Temperature
b
b
c
d
(°C)
103k1 (sꢀ1
)
103k1caled (sꢀ1
)
104k2 (sꢀ1
)
104k2caled (sꢀ1
)
eapp
AU0
AUmax
te (s)
104kobsf (sꢀ1
)
10
20
30
40
50
60
35
1.47 Æ 0.16g
1.88
103 Æ 10g
118
720 Æ 101g
0.055
0.208
1800
103
(688)h
40
45
50
35
2.92 Æ 0.16
4.75 Æ 0.34
6.12 Æ 0.60
2.26 Æ 0.10
2.86
4.28
6.34
2.39
157 Æ 1
187 Æ 15
206 Æ 24
70.2 Æ 3.1
145
177
214
64.7
754 Æ 62
729 Æ 72
787 Æ 106
631 Æ 35
(606)
741 Æ 62
621 Æ 78
779 Æ 56
688 Æ 63
(514)
697 Æ 115
613 Æ 12
812 Æ 188
489 Æ 100
(379)
577 Æ 146
595 Æ 36
650 Æ 46
506 Æ 19
(308)
0.090
0.050
0.035
0.065
0.286
0.290
0.331
0.307
1260
900
600
2403
63.7
32.8
16.2
9.05
3.88
40
45
50
35
3.50 Æ 0.22
6.71 Æ 0.73
9.37 Æ 0.54
2.31 Æ 0.18
3.85
6.11
9.58
2.70
94.9 Æ 6.8
102 Æ 12
170 Æ 11
44.5 Æ 3.5
88.7
120
162
0.060
0.065
0.090
0.050
0.372
0.436
0.500
0.409
1563
1038
738
39.1
2223
40
45i
50
35
3.70 Æ 0.54
7.21 Æ 0.09
8.63 Æ 1.83
2.68 Æ 0.59
4.10
6.31
9.06
2.85
55.4 Æ 8.4
72.1 Æ 0.9
115 Æ 25
56.0
79.4
111
0.060
0.046 Æ 0.006
0.052
0.489
0.509
0.582
0.445
2363
1142
690
20.1 Æ 4.4
22.1
0.018
3200
40
45
50
35
4.00 Æ 1.07
7.18 Æ 0.54
9.38 Æ 0.83
2.41 Æ 0.11
4.33
6.50
9.64
2.28
31.9 Æ 8.6
36.4 Æ 2.6
48.0 Æ 4.0
11.8 Æ 0.5
28.9
37.4
48.1
13.1
0.040
0.045
0.050
0.035
0.526
0.648
0.716
0.554
2200
1338
903
3147
40
45
50
35
3.32 Æ 0.25
6.28 Æ 0.43
9.29 Æ 0.69
2.45 Æ 0.41
3.71
5.94
9.38
2.65
18.5 Æ 1.4
24.0 Æ 1.6
29.8 Æ 2.4
5.96 Æ 0.09
17.5
23.2
30.4
6.33
535 Æ 35
507 Æ 26
518 Æ 28
398 Æ 4
(254)
0.040
0.030
0.050
0.030
0.569
0.605
0.672
0.540
4383
1980
1460
3663
40
45
50
35
35
4.12 Æ 0.12
5.45 Æ 0.20
7.86 Æ 0.30
2.84 Æ 0.02
2.29 Æ 0.09
3.85
5.53
7.86
8.59 Æ 0.29
10.8 Æ 0.4
13.5 Æ 0.5
3.59 Æ 0.03
2.86 Æ 0.17
8.25
10.7
13.6
378 Æ 8
465 Æ 11
476 Æ 11
329 Æ 1
320 Æ 8
(217)
357 Æ 3
363 Æ 2
383 Æ 5
296 Æ 1
(171)
0.040
0.020
0.050
0.020
0.000
0.542
0.666
0.735
0.486
0.475
5400
2223
2058
3600
3200
67.3j
70
2.60
2.67
1.63
0.61
40
45
50
35
3.85 Æ 0.07
6.00 Æ 0.05
7.81 Æ 0.16
2.27 Æ 0.02
3.83
5.57
8.01
3.30 Æ 0.05
4.93 Æ 0.04
6.35 Æ 0.20
0.954 Æ 0.010
3.60
4.80
6.36
0.020
0.070
0.070
0.050
0.592
0.654
0.691
0.563
6463
5373
1218
8943
80k
40
4.40 Æ 0.03
1.22 Æ 0.01
261 Æ 1
0.040
0.507
7200
a
[OCBA]0Á = 2 Â 10ꢀ3 mol dmꢀ3, [HCl] = 0.027 mol dmꢀ3, mixed H2O–MeCN solvent, ꢀ = 310 nm.
b Calculated from the Eyring equation [equation (4)] using the activation parameters listed in Table 2.
c
Units are dm3 molꢀ1 cmꢀ1
.
d Observed maximum absorbance at 310 nm.
e
Maximum reaction time attained in the kinetic run.
f Pseudo-first-order rate constants, kobs, for hydrolysis of phthalic anhydride at 0.005 mol dmꢀ3 HCl, and 30°C14 (it should be noted that pseudo first-order rate constants, kobs, were found to be almost unchanged with
change in [HCl] from 0.005 to 1.0 mol dmꢀ3 in aqueous solvents containing 2% CH3CN14).
g Error limits are standard deviations.
h Values in parentheses were obtained from the hydrolysis of phthalic anhydride at 0.005 mol dmꢀ3 HCl and 30°C.14
i k1 = k2.
j [OCBA]0 = 1.92 Â 10ꢀ3 mol dmꢀ3; [HCl] = 0.072 mol dmꢀ3
.
k [OCBA]0 = 2 Â 10ꢀ3 mol dmꢀ3; [HCl] = 0.037 mol dmꢀ3
.

ACID-CATALYZED CLEAVAGE OF o-CARBOXYBENZOHYDROXAMIC ACID
219
reaction scheme for hydrolysis of OCBA may be
expressed as
change in AU with reaction time (t), under the reaction
conditions when k1 = k2 = k, is given by
AU ˆ kt‰XŠ0"app expꢁꢀkt† ‡ AU0
The non-linear least-squares technique was used to
calculate k, eapp and AU0, which are given in Table 1.
ꢁ3†
k1
k2
ꢀ!
ꢀ!
OCBA
PAn
phthalic acid
ꢁ1†
H2O;
ꢀNH2OH
H2O
where k1 and k2 represent pseudo first-order rate con-
stants for hydrolysis of OCBA and PAn, respectively.
The change in AU due to the change in [PAn] during
the course of reaction is given by
RESULTS AND DISCUSSION
Several kinetic runs were carried out within the
temperature range 35–50°C at 0.027 mol dmꢀ3 HCl
and 10% CH3CN in mixed aqueous solvents. Similar
observations were made with 20, 30, 40, 50, 60 and 70%
CH3CN. These kinetic data were used to calculate k1, k2,
‰XŠ0"appk1
AU ˆ
‰expꢁꢀk1t† ꢀ expꢁꢀk2t†Š ‡ AU0 ꢁ2†
k2 ꢀ k1
where [X]0 is the concentration of OCBA at reaction time
t = 0. The value of [X]0 is taken as the initial concentra-
tion of N-hydroxyphthalimide ([NHPH]0). It may be
noted that any error in [X]0 introduced by assuming that
[X]0 = [NHPH]0 will affect only the magnitude of eapp
(apparent molar absorptivity) and it will not affect the
magnitudes of k1 and k2. In equation (2), eapp = ePAnꢀe,
eapp and AU0 from equations (2) and (3), as summarized
in Table 1. The values of k1, k2, eapp and AU0 were also
obtained at 35 and 40°C in mixed H2O–CH3CN solvents
containing 80% CH3CN (Table 1).
The rate constants k1, and k2, obtained within the
temperature range 35–50°C at a constant content of
CH3CN in mixed aqueous solvent, obeyed the Eyring
equation:
and AU0 = e[X]0 with e = eOCBA ꢂ ePA, where eOCBA
,
e
PAn, and ePA are the molar absorptivities of OCBA, PAn
and phthalic acid, respectively. The assumption that
eOCBA ꢂ ePA at 310 nm is supported by the spectra of
phthalamic acid and phthalic acid.8
k ˆ ꢁKBT=h† expꢁÁSÃ=R† expꢁꢀÁHÃ=RT† ꢁ4†
where k = k1 or k2 and all other symbols have their usual
meanings. The activation parameters, DH* and DS*, were
calculated from equation (4) using the non-linear least-
squares method. The calculated values of DH* and DS* at
different contents of CH3CN are summarized in Table 2.
The fitting of the observed data to equation (4) is evident
from the calculated values of the rate constants, as shown
in Table 1 and from the standard deviations associated
with DH* and DS* (Table 2).
The detailed kinetic studies on phthalamic, N-sub-
stituted phthalamic7,8 and related compounds6,9 support
the mechanism shown as route A in Scheme 2. A similar
mechanism (route A) was also proposed by Bender et
al.1b in their classical paper on the hydrolysis of
phthalamic acid. An alternative mechanism, shown as
The values of k1, k2, eapp and AU0 were determined as
follows. The values of k1, k2, eapp and least squares (Ædi2,
where di = AUi ꢀ AUcalcdi with AUi and AUcalcdi repre-
senting the ith observed and calculated absorbance in a
single kinetic run) were calculated from equation (2) at a
presumed value of AU0 using the non-linear least-squares
technique. Similar calculations were carried out at
several presumed values of AU0. The best value of AU0
was considered to be that for which Ædi2 turned out to be
minimum. The calculated values of k1, k2 and eapp at the
statistically best values of AU0 under different experi-
mental conditions are summarized in Table 1.
It was found that under certain experimental condi-
tions, k1 = k2. Equation (2) is valid only when k1 ≠ k2. The
Table 2. Values of DH* and DS* for hydrolysis of o-carboxybenzohydroxamic acid (OCBA) and phthalic anhydride (PAn) in acidic
medium at different contents of MeCN in mixed aqueous solventsa
OCBAb
PAnc
[MeCN] (%, v/v)
DH* (kcal molꢀ1
)
ꢀDS* (cal Kꢀ1 molꢀ1
)
DH* (kcal molꢀ1
)
ꢀDS* (cal Kꢀ1 molꢀ1
)
10
20
30
40
50
60
70
15.40 Æ 2.56d
17.68 Æ 2.06
15.30 Æ 3.47
15.43 Æ 2.07
18.01 Æ 1.57
13.71 Æ 1.00
14.19 Æ 1.64
21.0 Æ 8.0d
13.1 Æ 6.4
20.6 Æ 10.8
20.1 Æ 6.5
12.2 Æ 4.9
25.9 Æ 3.1
24.3 Æ 5.1
7.27 Æ 1.88d
11.45 Æ 2.77
13.16 Æ 1.96
9.60 Æ 1.49
10.44 Æ 1.26
9.49 Æ 0.76
10.80 Æ 1.18
43.8 Æ 5.9d
31.4 Æ 8.7
26.9 Æ 6.1
39.5 Æ 4.7
37.8 Æ 3.9
42.4 Æ 2.4
39.9 Æ 3.7
a
Conditions as given in Table 1.
b The activation parameters refer to k1.
c
The activation parameters refer to k2.
d Error limits are standard deviations.
1998 John Wiley & Sons, Ltd.
JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, VOL. 11, 216–222 (1998)

220
M. N. KHAN
Scheme 2
route B in Scheme 2, cannot be completely ruled out. In
Scheme 2, the k3 step presumably involves transition
state TS1. The introduction of substituents in R (Scheme
k1 = 18 sꢀ1 at 35°C and 60% CH3CN16 and 105 k1 = 24
sꢀ1 at 47°C and within the pH range 1.3–1.8 in pure
water as solvent1). These observations are considered to
be unusual or unexpected because in terms of reported
negative r and r* values for the related reactions,6–9 the
k1 values for OCBA must be smaller than the correspond-
ing values for phthalamic acid because ꢁ*OH > ꢁ*H.17
The strong electron-withdrawing effect of OH compared
with H is evident from the ionization constants (Ka) of
2
‡
‡NH4 (pKa = 9.21)18 and NH3OH (pKa = 5.97).18 The
values of k1 shown in Table 1 predict a positive r* value
for the hydrolysis of OCBA. These observations cannot
be explained in terms of the reaction mechanisms shown
in Scheme 2. The most probable mechanism for the
hydrolysis of OCBA is shown in Scheme 3, where the
formation of 1 involves the transition state TS2.
2) resulted in a negative reaction constant (r or r*).6–9
These results predict that electron-withdrawing substi-
tuents (i.e. substituents with positive substituent con-
stants, ꢁ or ꢁ*) must decrease whereas electron-donating
substituents (i.e. substituents with negative substituent
constants, ꢁ or ꢁ*) must increase the rate of hydrolysis. A
nearly 2.5-fold lower rate of hydrolysis of N-(o-carboxy-
benzoyl)glycine (105 k1 = 7.0 sꢀ1 at 35°C) compared
with that of phthalamic acid (105 k1 = 20 sꢀ1 at 35°C) in
CH3CN–H2O solvents containing 70% CH3CN16 re-
vealed a negative r* for the reaction because ꢁ*
COOH > ꢁ*H.17
The rate constants, k1, for the hydrolysis of OCBA at
different contents of CH3CN and temperatures (Table 1)
are more than 10-fold larger than the corresponding rate
constants for the hydrolysis of phthalamic acid (105
One might argue that the transition state TS2 seems
Scheme 3
1998 John Wiley & Sons, Ltd.
JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, VOL. 11, 216–222 (1998)

ACID-CATALYZED CLEAVAGE OF o-CARBOXYBENZOHYDROXAMIC ACID
221
unlikely to be at lower energy than that involving prior
protonation on the carbonyl oxygen (i.e. Scheme 2, route
A). Perhaps the species involving protonation on the
carbonyl oxygen is present in greater concentration than
otherwise due to stabilization by hydrogen bond forma-
tion between the hydrogen on the carbonyl oxygen and
the oxygen of the OH group involving a five-membered
ring. If this suggested mechanistic explanation for the
unusual rate enhancement is considered to be more
plausible, then it is difficult to explain the observed
nearly 2.5-fold lower rate of acid hydrolysis of N-(o-
carboxybenzoyl)glycine (NCG) compared with that of
phthalamic acid under similar experimental conditions.16
In the acid hydrolysis of NCG, the species involving
protonation on the carbonyl oxygen is expected to be
stabilized by hydrogen bond formation between the
hydrogen on the carbonyl oxygen and the carbonyl
oxygen of carboxyl group of the glycine moiety
involving a seven-membered ring. Furthermore, the
strength of such internal hydrogen bonding is expected
to increase with decrease in the dielectric constant of the
medium and consequently the rate constants, k1, should
show an increase with decrease in the dielectric constant
of the reaction medium. The rate constants, k1, for acid
hydrolysis of N,N-dimethylphthalamic acid were almost
unaffected by an increase in the content of CH3CN from
10 to 80% in mixed aqueous solvents.11 Similarly, a
change in CH3CN content from 60 to 70% produced
essentially no effect on k1 for acid hydrolysis of
phthalamic acid.16
The rate constants, k1, for hydrolysis of OCBA are
almost independent of CH3CN content within the range
10–80% (Table 1). The rate constants, k1 for hydrolysis
of N,N-dimethylphthalamic acid showed an increase of
nearly twofold with increase in the content of CH3CN up
to ca 60%, after which they showed a decrease of ca
twofold with increase in CH3CN content from 60 to
90%.11 It is interesting that changes in the dielectric
constant and in the solvating properties of the reaction
medium do not affect greatly the rate of intramolecular
reactions involving neutral reacting sites. Hence it seems
that the belief that one of the main factors responsible for
the unusually high catalytic efficiency of enzymes is the
changes in the dielectric constant and in the solvating
properties of the micro reaction environment of active
sites of enzymes compared with the macro solvent
environment needs careful review.
amic acid16 and N,N-dimethylphthalamic acid.11 These
results and the results reported by Blackburn et al.8
demonstrate that the intermediate which absorbs at
310 nm in these reactions is phthalic anhydride. An
increase in CH3CN content from 10 to 80% decreased k2
from 103 Â 10ꢀ4 to 0.95 Â 10ꢀ4 sꢀ1 at 35°C (Table 1).
The mechanistic explanations of the effects of mixed
aqueous–organic solvents on k2 are described else-
where.14
A change in the CH3CN content from 10 to 70% in
mixed aqueous solvents appears to have no appreciable
effect on the activation parameters, DH* and DS*, for the
hydrolysis of OCBA (Table 2). These activation par-
ameters are comparable to those obtained in various
intramolecular nucleophilic reactions.1a,19 It seems that
an increase in CH3CN content from 10 to 30% increases
both DH* and DS* for the hydrolysis of PAn. A further
increase in CH3CN content beyond 30% does not affect
appreciably either DH* or DS* (Table 2). The signifi-
cantly large negative values of DS* for the hydrolysis of
PAn (Table 2) indicate the involvement of several solvent
molecules in the transition state. This is in agreement
with the proposed mechanism for the hydrolysis of
PAn.14
Acknowledgments
The author thanks the Universiti Malaya (Vote F408/96)
andd IRPA (Grant No. 09–02–03–0003) for financial
support of this work.
REFERENCES
1. (a) M. L. Bender. J. Am. Chem. Soc. 79, 1258 (1957); (b) M. L.
Bender, Y.-L. Chow and F. Chloupek. J. Am. Chem. Soc. 80, 5380
(1958).
2. H. Morawetz and J. A. Shafer. J. Am. Chem. Soc. 84, 3783 (1962).
3. J. Brown, S. C. K. Su and J. A. Shafer. J. Am. Chem. Soc. 88, 4468
(1966).
4. (a) T. Higuchi, T. Miki, A. C. Shah and A. K. Herd. J. Am. Chem.
Soc. 85, 3655 (1963), (b) T. Higuchi, L. Eberson and A. K. Herd. J.
Am. Chem. Soc. 88, 3805 (1966).
5. G. Dahlgren and N. L. Simmerman. J. Phys. Chem. 89, 3626
(1965).
6. (a) M. F. Aldersley, A. J. Kirby and P. W. Lancaster. J. Chem. Soc.,
Chem. Commun. 570 (1972); (b) A. J. Kirby and P. V. Lancaster. J.
Chem. Soc., Perkin Trans. 2 1206 (1972); (c) A. J. Kirby, R. S.
McDonald and C. R. Smith. J. Chem. Soc., Perkin Trans. 2 1495
(1974); (d) M. F. Aldersley, A. J. Kirby, P. W. Lancaster, R. S.
McDonald and C. R. Smith. J. Chem. Soc., Perkin Trans. 2 1487
(1974).
7. M. D. Hawkins. J. Chem. Soc., Perkin Trans. 2 642 (1976).
8. R. A. M. Blackburn, B. Capon and A. C. McRitchie. Bioorg. Chem.
6, 71 (1977).
9. R. Kluger and C.-H. Lam. J. Am. Chem. Soc. 97, 5536 (1975); 100,
2191 (1978).
10. F. M. Menger and M. Ladika. J. Am. Chem. Soc. 110, 6794 (1988).
11. M. N. Khan. Indian J. Chem. 32A, 387 (1993).
12. A. Ahmad, K. Karel and V. Miroslav. Sb. Ved. Pr., Vys. Sk.
Chemickotechnol., Pardubice 30, 203 (1973); Chem. Abstr. 82,
97399 (1975).
The rate constants, k2, shown in Table 1 are com-
parable to the pseudo first-order rate constants for
hydrolysis of authentic PAn obtained under similar
experimental conditions14 (Table 1). Similarly, the values
of eapp at different contents of CH3CN in mixed aqueous
solvents are not significantly different from the corre-
sponding eapp obtained for hydrolysis of authentic PAn
under essentially similar experimental conditions (Table
1).14 Similar comparable results were obtained in the acid
hydrolysis of N-(o-carboxybenzoyl)glycine,16 phthal-
1998 John Wiley & Sons, Ltd.
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222
M. N. KHAN
13. C. A. Bunton, J. H. Fendler, N. A. Fuller, S. Perry and J. Rocek. J.
Chem. Soc. 5361 (1963).
14. M. N. Khan. Indian J. Chem. 32A, 395 (1993).
15. M. N. Khan. Int. J. Chem. Kinet. 23, 567 (1991).
16. M. N. Khan. J. Org. Chem. 61, 8063 (1996).
17. J. Hine. Structural Effects on Equilibria in Organic Chemistry,
p. 91. Wiley, New York (1975).
18. M. N. Khan. J. Chem. Soc., Perkin Trans. 2 199 (1989).
19. (a) T. Graafland, J. B. F. N. Engberts and A. J. Kirby. J. Org. Chem.
42, 2462 (1977); (b) T. H. Fife, J. E. C. Hutchins and M. S. Wang.
J. Am. Chem. Soc. 97, 5878 (1975).
1998 John Wiley & Sons, Ltd.
JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, VOL. 11, 216–222 (1998)