Kinetic evidence for the occurrence of general acid-base catalysis in N-methylhydroxylaminolysis of N-ethoxycarbonylphthalimide (NCPH)

Article abstract of DOI:10.1002/(SICI)1097-4601(1997)29:9<647::AID-KIN1>3.0.CO;2-U

Pseudo-first-order rate constants (k_{1 obs}) for the reaction of MeNHOH with NCPH obey the relationship: k_{1 obs} = k_b' [MeNHOH]_T² where [MeNHOH]_T represents total concentration of N-methylhydroxylamine buffer. The rate constants, k_{1 obs} obtained at different total concentration of acetate buffer ([Buf]_T] in the presence of 0.004 mol dm^-3 MeNHOH follow the relationship: k_{1 obs} = k_b[Buf]_T. The values of acetate buffer-catalyzed rate constant (k_b) at different pH reveal the occurrence of both general base- and general acid- or general base-specific acid-catalysis in the reaction of MeNHOH with NCPH.

Full text of DOI:10.1002/(SICI)1097-4601(1997)29:9<647::AID-KIN1>3.0.CO;2-U

Kinetic Evidence for the
Occurrence of General
Acid-Base Catalysis in
N-Methylhydroxylaminolysis of
N-Ethoxycarbonylphthalimide
(
NCPH)
M. NIYAZ KHAN
Department of Chemistry, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
Received 14 October 1996; accepted 9 December 1996
ABSTRACT: Pseudo-first-order rate constants (k1 obs) for the reaction of MeNHOH with NCPH
2
obey the relationship: k1 obs ϭ kЈ[MeNHOH]T where [MeNHOH] represents total concentra-
b
T
tion of N-methylhydroxylamine buffer. The rate constants, k1 obs obtained at different total
Ϫ3
concentration of acetate buffer ([Buf] ) in the presence of 0.004 mol dm MeNHOH follow
T
the relationship: k1 obs ϭ k [Buf] . The values of acetate buffer-catalyzed rate constant (k ) at
b
T
b
different pH reveal the occurrence of both general base- and general acid- or general base-
specific acid-catalysis in the reaction of MeNHOH with NCPH. © 1997 John Wiley & Sons, Inc. Int
J Chem Kinet 29: 647–654, 1997.
INTRODUCTION
have been understood, many features of these cataly-
ses are still mysterious. For example, certain amines
exhibit GA or GB catalysis while other amines of the
same class do not show such catalysis towards a par-
ticular reacting system.
We have been studying the kinetics and mecha-
nism of aminolysis of imides where the leaving
groups are not free to rotate around the bond being
cleaved during the course of reaction. In the aminoly-
sis of maleimide, primary amines [3] did not show
GA–GB catalysis while secondary [4] and tertiary
General acid-base (GA-GB) catalysis appears to be
the ubiquitous feature of many enzyme-catalyzed
reactions [1]. Since the awareness of this fact, a huge
amount of kinetic work has been carried out
on enzyme model reactions to understand the
mechanism(s) of these catalyses [2]. Although many
fine details of the mechanism(s) of these catalyses
Correspondence to: M. N. Khan
Contract grant Sponsor: Universiti Malaya Research Vote
F408/96
[5] amines showed GA–GB and GA catalysis, re-
spectively. Such a selective reactivity of primary, sec-
ondary, and tertiary amines could not be detected in
©
1997 John Wiley & Sons, Inc.
CCC 0538-8066/97/090647-08

6
48
KHAN
the aminolysis of phthalimide [6], NCPH [7], and
N-hydroxyphthalimide [8]. General base catalysis has
been observed in the reactions of hydroxylamine
with NCPH [7], N-hydroxyphthalimide [9], and
in the reaction of N-methylhydroxylamine with N-hy-
droxyphthalimide [10]. Nucleophilic reactivity of N-
methylhydroxylamine is only slightly lower (ca.
nium chloride were obtained from Aldrich. All other
chemicals used were also commercial products of
reagent grade. Standard solution of NCPH was pre-
pared in acetonitrile. All the buffer solutions of de-
sired pH were freshly prepared just before the start of
the kinetic runs.
2
4%) than that of hydroxylamine towards ionized
Kinetic Measurements
Ϫ
phenyl salicylate (PS ) [11]. The nucleophilic reac-
tivity towards PS of hydroxylamine is similar to that
N-Ethoxycarbonylphthalimide (NCPH) absorbs
strongly while the immediate product of the reaction
of N-methoxyhydroxylamine with NCPH, ethyl N-[o-
Ϫ
of morpholine [11]. But nucleophilic reactivity to-
wards NCPH of morpholine is nearly 75-fold smaller
than that of hydroxylamine [7]. These observations
prompted us to carry out the rate study on the reac-
tion of N-methylhydroxylamine with NCPH. The re-
sults and their probable explanation(s) are described
in this article.
(
(
N-methyl-N-hydroxycarbamoyl)benzoyl]carbamate
EBC) does not absorb to a detectable extent at
3
00 nm. Thus, the rate of N-methylhydroxylaminoly-
sis of NCPH should be conveniently studied by moni-
toring the decrease in absorbance (Aobs) due to disap-
pearance of NCPH at 300 nm.
In a typical kinetic run, the reaction mixture con-
taining all the reaction components except NCPH re-
quired for an appropriate experimental condition was
EXPERIMENTAL
Materials
3
prepared in a total volume of 24.65 cm of water as
the solvent and was then placed in a thermostatic wa-
ter bath for equilibration at 30°C. After about 10 min
equilibration, the reaction was initiated by adding
Reagent grade chemicals such as N-ethoxycar-
bonylphthalimide (NCPH), N-methylhydroxylammo-
Figure 1 Variation of observed absorbance (A ) vs. reaction time (t) for a typical kinetic
obs
Ϫ4
Ϫ3
Ϫ3
run where
[NCPH] ϵ [X] ϭ 2.8 ϫ 10
mol dm
,
[MeNHOH] ϭ 0.004 mol dm
,
0
0
T
Ϫ3
Ϫ3
[
Buf] ϭ 0.15 mol dm , pH 5.66, 30°C, ionic strength 1.0 mol dm (by KCl), and the aqueous
T
reaction mixture contained 1.4%, v/v MeCN. Solid line is drawn through the calculated points us-
3
Ϫ1
ing kinetic equation: Aobs
ϭ
Ϫ1
␧app[X] exp(Ϫk1 obst) ϩ Aϱ with 10 k
ϭ 2.49 Ϯ 0.02 s ,
0
1 obs
3
Ϫ1
␧app ϭ 2230 Ϯ 6 dm mol cm , and A ϭ 0.040 Ϯ 0.001 where observed data within the reac-
ϱ
tion period of 20–190
s were used and the last data point was assigned as at
t ϭ 7200 s, Aobs ϭ 0.040.

OCCURRENCE OF GENERAL ACID-BASE CATALYSIS
649
3
Ϫ3
0
.35 cm of 0.02 mol dm NCPH solution (prepared
The observed absorbance (Aobs) at different reac-
tion time is the sum of absorbance due to NCPH and
C. The Aobs values in the initial phase of the reaction
only (until reaction time, t Ͻ 1 halflife) were consid-
in acetonitrile) to the equilibrated reaction mixture.
An aliquot of nearly 2.5 cm was quickly withdrawn
from the reaction mixture and transferred to 3 cm
3
3
quartz cuvette kept in the thermostated cell compart-
ment of the spectrophotometer. The change in the ab-
sorbance with time was monitored at 300 nm by the
use of a digital display of the Beckman Model 35
spectrophotometer. The constant temperature (30°C)
of the cell compartment was controlled electronically
by the use of the temperature control unit of the spec-
trophotometer. The pH values of the reaction mix-
tures were determined with Philips digital pH meter
Model PW 9409 and the pH for each kinetic run was
found to be constant during the course of the reac-
tion.
ered in the calculation of k . In the absence of the for-
1
mation of C, the value of Aobs must be ca. 0.04 at
t ϭ ϱ . Thus, an arbitrary value of Aobs of 0.04 at
t ϭ ϱ was considered in each kinetic run. The reac-
tion time (t) for the period of Ͼ10 halflives (t ) was
1
/2
considered as t (i.e., time at t ϭ ϱ). For a typical ki-
ϱ
netic run (Fig. 1), the Aobs values in the initial phase
of the reaction were considered within the reaction
time (t) range of 20–190 s and Aobs ϭ 0.04 at
t ϭ 7200 s (ϭ t
). These observed data were treated
ϱ
with eq. (2)
The observed data for a typical kinetic run is
shown in Figure 1. These observed data indicate a de-
crease followed by an increase and then decrease
again in Aobs with increase in the reaction time (t).
This shows that the immediate product of N-methyl-
hydroxylaminolysis of NCPH, EBC, converts to an-
other product, C, which absorbs significantly at
A
obs ϭ ␧app[X]
0
exp(Ϫk1 obst) ϩ A
ϱ
(2)
where [X] is the initial concentration of NCPH.
Pseudo-first-order rate constant (k1 obs) apparent mo-
lar absorption coefficient (␧app) and absorbance at
0
t ϭ ϱ (A ) were calculated from eq. (2) using the
ϱ
nonlinear least-squares technique. The values of these
calculated parameters are shown in the caption of
Figure 1. The fitting of the observed data to eq. (2) is
evident from the solid line drawn through the Acalcd
values as shown in Figure 1. The change in the value
of t from 2600 s (t1/2 ϭ 9) to 10800 s (t1/2 ϭ 36) did
not bring any change in the value of k1 obs while at
t ϭ 1800 s (t1/2 ϭ 6.4), the value of k1 obs reduced by
only 1.6%. These calculations indicate that at any ar-
3
00 nm and C further converts to product D which
does not absorb at 300 nm. Thus, the cleavage of
NCPH in the presence of MeNHOH may be repre-
sented by the reaction scheme as shown by eq. (1).
Ferric hydroxamic acid assay [9] of the end reac-
tion product (D) revealed D as o-carboxy(N-
methyl)benzohydroxamic acid. Although the struc-
tural characterization of C could not be done, similar
cyclized products were observed in the reactions
ϱ
ϱ
bitrary assigned value of t at Ն10 halflives will not
affect the calculated value of k1 obs .
ϱ
of N-hydroxyphthalimide with NH OH [9] and
2
MeNHOH [10].
CO
CONHCO CH CH
2
2
3
k1
NCO CH CH ϩ CH NHOH
2
2
3
3
CO
CON(CH )OH
3
NCPH
EBC
ϪNH CO CH CH k2
2
2
2
3
(1)
O
C
COOH
O
k3
H O
2
NCH3
CON(CH )OH
C
3
O
D
C

6
50
KHAN
RESULTS AND DISCUSSION
Reaction of MeNHOH with NCPH in
MeNHOH Buffers
A few kinetic runs were carried out on N-methylhy-
droxylaminolysis of NCPH within the total MeN-
HOH buffer concentration ([MeNHOH] ) range of
T
Ϫ3
0
3
.010 to 0.022 mol dm at pH 5.53 Ϯ 0.02 and
0°C. The ionic strength of the reaction mixture was
Ϫ3
kept constant at 1.0 mol dm by KCl. Pseudo-first-
order rate constants (k1 obs) as shown in Table I were
tried to fit to the kinetic eq. (3).
2
k1 obs Ϫ k ϭ k [MeNHOH] ϩ kЈ[MeNHOH]
T
(3)
w
n
T
b
The value of buffer-independent rate constant for hy-
Ϫ4 Ϫ1
drolysis (k ) of 2.6 ϫ 10
s
was obtained from an
w
earlier report [7]. The nucleophilic second-order (kn)
and buffer-catalyzed apparent third-order (kЈ) rate
b
constants were calculated from eq. (3) using the least-
squares technique and the respective values obtained
Ϫ3
3
Ϫ1 Ϫ1
are (Ϫ13.3 Ϯ 8.4) ϫ 10 dm mol
0
s
and 4.14 Ϯ
6
Ϫ2 Ϫ1
.45 dm mol s . The negative value of k with
n
high standard deviation merely indicates that the con-
Figure 2 Plots showing the dependence of kobscor upon
tribution of k [MeNHOH] is insignificant compared
[Buf] for the reaction of NCPH with MeNHOH under the
n
T
T
2
with kЈ[MeNHOH] under the experimental condi-
presence of acetate buffer (Buf ) at pH 5.20 (O), 5.67 (⌬),
and 5.97 (᭞). The solid lines are drawn through the least-
squares calculated points as described in the text.
b
T
tions imposed. The more reliable value of kЈ of
b
6
Ϫ2 Ϫ1
3
.32 Ϯ 0.28 dm mol
s
was obtained from eq. (3)
with k ϭ 0.
n
ure 2. Observed pseudo-first-order rate constant
cor
(
k1 obs) is related to k
through the relationship:
1 obs
Reaction of MeNHOH with NCPH Under
the Presence of Acetate Buffers
cor
1 obs
k1 obs Ϫ k ϭ k
where k ϭ k ϩ k f [Buf ] .
0
0 w B B T
The rate constants, k and k represent first- and sec-
w
B
In order to discover the effects of acetate buffers on
the rate of the reaction of MeNHOH with NCPH,
several kinetic runs were carried out at a constant
concentration (= 0.004 mol dm ) of MeNHOH and
at different total acetate buffer concentrations
ond-order rate constants for uncatalyzed and general
base-catalyzed hydrolysis of NCPH and fB ϭ
A
A
A
K /(a ϩ K ) where K is the ionization constant
a
H
a
a
Ϫ3
Ϫ4 Ϫ1
of acetic acid. The values of k (ϭ 2.6 ϫ 10 s )
w
Ϫ3
3
Ϫ1 Ϫ1
and k (ϭ 1.23 ϫ (10 dm mol s ) were ob-
B
(
[Buf] ) of desired pH. Corrected pseudo-first-order
tained by carrying out the experiments in the absence
of amine nucleophile [7]. Corrected pseudo-first-or-
T
cor
rate constants (k1 obs ) are shown graphically in Fig-
a
Table I Pseudo-First-Order Rate Constants for the Reaction of MeNHOH with NCPH at pH 5.53 Ϯ 0.02 and 30°C
b
Ϫ3
103k /sϪ1
103k cor c/sϪ1
103k
cor d/sϪ1
l calcd
[
MeNHOH] /mol dm
T
l obs
l obs
0.010
0.013
0.016
0.019
0.022
0.613 Ϯ 0.020e
0.775 Ϯ 0.040
1.03 Ϯ 0.04
1.50 Ϯ 0.01
2.00 Ϯ 0.05
0.353
0.515
0.770
1.24
0.332
0.562
0.851
1.20
1.74
1.61
a
Ϫ4
mol dmϪ3, ionic strength 1.0 mol dmϪ3 (by KCl), and aqueous reaction mixture contained 1.4%,
Conditions: [NCPH] ϭ 2.8 ϫ 10
0
(
v/v) MeCN.
b
Total concentration of MeNHOH buffer.
c
d
e
k1 obscor ϭ k1 obs Ϫ kw where kw ϭ 2.6 ϫ 10Ϫ4sϪ1
.
Calculated from eq. (2) with kn ϭ 0, and k ' ϭ 3.32 dm mol sϪ1
6
Ϫ2
.
b
Error limits are standard deviations.

OCCURRENCE OF GENERAL ACID-BASE CATALYSIS
651
a
Table II The Values of Calculated Parameters (k and k ) from Eq. (4)
b
4
Ϫ1
10 k /dm molϪ1sϪ1
3
3
b
Ϫ3
pH
10 k/s
1.60 Ϯ 0.68c
[Buf] range /mol dm
# of runs
7
b
T
5
5
5
.20 Ϯ 0.00c
9.48 Ϯ 0.23c
10.2 Ϯ 0.3
14.8 Ϯ 0.4
14.3 Ϯ 0.3
15.5 Ϯ 0.4
14.8 Ϯ 0.6
0.1–0.5
0.1–0.5
0.1–0.5
0
.0
Ϫ1.1 Ϯ 0.4
.0
Ϫ1.5 Ϯ 1.1
.0
.67 Ϯ 0.01
.97 Ϯ 0.02
7
7
0
0
a Conditions: [NCPH] ϭ 2.8 ϫ 10 mol dmϪ3, [MeNHOH] ϭ 0.004 mol dm , 30°C, ionic strength 1.0 mol dmϪ3 and aqueous reac-
Ϫ4
Ϫ3
0
tion mixture contained 1.4%, (v/v) MeCN.
b
Total acetate buffer concentration.
Error limits are standard deviations.
c
der rate constants (k1 obscor) revealed a linear increase
values of k at different pH were also calculated from
b
with increase in [Buf] (Fig. 2). The rate constants,
k1 obs were tried to fit to eq. (4)
eq. (4) with k ϭ 0 (Table II). The fitting of the ob-
served data to eq. (4) is evident from the plots of Fig-
ure 2 where the solid lines are drawn through the
least-squares calculated points.
T
cor
k1 obscor ϭ k ϩ k [Buf]
(4)
b
T
The general rate law for the cleavage of NCPH in
the presence of MeNHOH and external acetate buffer
where k and kb represent buffer-independent and
buffer-dependent apparent first- and second-order rate
constants for the reaction of MeNHOH with NCPH.
Linear least-squares technique was used to calculate k
(
Buf) may be given as
2
rate ϭ {k ϩ k f [Buf] ϩ kЈ [MeNHOH]
w
B
B
T
gb
and k from eq. (4) and the values of these calculated
b
ϩ kgb[MeNHOH][B]
rate constants at different pH are summarized in
Table II. The calculated values of k are either negative
or positive with considerably high standard devia-
tions. These values of k indicate the insignificant con-
tribution of k compared with k [Buf] in eq. (4). The
ϩ
ϩ k [MeNHOH][BH ]}[NCPH] (5)
ga
where [B] represents the concentration of general
base form of external buffer (i.e., acetate ion). In
eq. (5), k and k represent third-order rate constants
b
T
gb
ga
Figure 3 Plot showing the dependence of k /( f f [MeNHOH] ) upon a for the buffer-cat-
b
Am
B
T
H
alyzed N-methylhydroxylaminolysis of NCPH at 30°C. The solid line is drawn through the least-
6
Ϫ2 Ϫ1
A
squares calculated points using eq. (8) with k ϭ 6.20 Ϯ 1.21 dm mol
s
and k /Ka ϭ
ga
gb
6
9
Ϫ3 Ϫ1
(5.32 Ϯ 0.31) ϫ 10 dm mol
s .

6
52
KHAN
ϩ
for general base (B) and general acid (BH )-
experimental conditions. Observed rate law:
catalyzed N-methylhydroxylaminolysis of NCPH,
rate ϭ k1 obs[NCPH] and eq. (5) can lead to eq. (6)
respectively.
The
kinetic
term
such
as
kn[MeNHOH][NCPH] is not included in eq. (5)
k1 obs ϭ k ϩ k f [Buf] ϩ kЈ fAm2[MeNHOH]T2
w
B
B
T
gb
because the contribution of such a term turned
ϩ (k f ϩ k f )f [MeNHOH] [Buf] (6)
gb B ga BHϩ Am T T
out
to
be
insignificant
compared
with
2
ϩ
kЈ[MeNHOH] [NCPH] {eq. (3)} under the present
where [MeNHOH] ϭ [MeNHOH] ϩ [MeNH OH ]
b
T
T
2
O
C
O
C
k11
kϪ1
NCO CH CH ϩ CH NHOH
NCO CH CH
2 2 3
2
2
3
3
1
C
O
C
ϩ
OϪ H CNHOH
3
Ϯ
T
NCPH
1
3
ϩ
ϩ
1
k (BH ) ϪBH
ϪB k (B)
2
B ϭ CH NHOH
O
3
Ϫ
2
ϭ CH CH
3
CNHCO CH CH
2
2
3
CN(CH )OH
3
O
EBC
Scheme I
CO
NCO CH CH
2
2
3
C
ϩ
Ϫ
O
H CNOH
3
B
H
TS1
ϩ
CO
C
H9B
NCO CH CH
3
2
2
ϩ
Ϫ
O
O
H CNOH
3
H
TS2
ϩ
CO
H
NCO CH CH
3
2
2
C
ϩ
Ϫ
H CNOH
3
B
H
TS3

OCCURRENCE OF GENERAL ACID-BASE CATALYSIS
653
Ϫ
and
[Buf] ϭ [CH COOH] ϩ [CH COO ],
ports on the occurrence of stepwise GB and specific
acid catalyses in the aminolysis of imides [4,7]. In
view of conventional belief that a termolecular colli-
sion is much less probable than a bimolecular colli-
T
3
3
fAm ϭ KaAm/(a ϩ K ),
AM
Ka ϭ a [MeNHOH]/
ϭ a /(a ϩ K ). For the ki-
netic runs carried out at a constant [MeNHOH] , pH,
Am
H
a
H
ϩ
A
[MeNH OH ], and f
2
BHϩ
H
H
a
T
and at different [Buf] , eqs. (4) and (6) revealed that
sion, we prefer the occurrence of TS rather than
T
2
A
TS3 .
The
calculated
value
of
k /K
ga a
k ϭ kgЈb fAm2[MeNHOH]T2
(7)
6
9
Ϫ3 Ϫ1
{ϭ (5.32 Ϯ 0.31) ϫ 10 dm mol s } gave k as
ga
6
Ϫ2 Ϫ1
A
1
11 Ϯ 7 dm mol
s
(where pKa ϭ 4.68).
and
ADDENDUM
A
kb ϭ (kgb ϩ k a /K )f fB[MeNHOH]T (8)
ga
H
a
Am
The value of nucleophilic second-order rate constant
kn) for the reaction of MeNHOH with NCPH could
not be obtained while under similar experimental
Similarly, for the kinetic runs carried out at a constant
(
pH and at different [MeNHOH] with [Buf] ϭ 0,
T
T
eqs. (3) and (6) revealed that
conditions, the value of k for the reaction of HN-
n
3
Ϫ1 Ϫ1
HOH with NCPH turned out to be 6.4 dm mol
s
2
kЈ ϭ kЈ f
(9)
b
gb Am
[
7]. This shows that k for MeNHOH is much smaller
n
than that for HNHOH although MeNHOH is slightly
stronger base than HNHOH. The mechanism for the
reaction of MeNHOH with NCPH in the presence of
acetate buffers appeared to be different from the
mechanism for the reaction of HNHOH with NCPH
under almost similar experimental conditions. These
characteristic differences in the reactivity of MeN-
HOH and HNHOH towards NCPH are difficult to ex-
The calculated value of kЈ (ϭ 3.32 Ϯ 0.28
b
6
Ϫ2 Ϫ1
dm mol s ) at pH 5.53 yielded k Ј as 125 Ϯ
gb
6
Ϫ2 Ϫ1
Am
1
1 dm mol
s
with pK ϭ 6.24 [11]. Although
the value of kЈ (125 dm mol s ) is not very reli-
a
6
Ϫ2 Ϫ1
gb
able because it has been determined from kinetic data
at a single pH, it may be used to demonstrate the in-
significant contribution of k compared with k [Buf]
b
T
in eq. (4). The calculated values of k from eq. (7) are
plain in terms of pK , structural features, and intrin-
Ϫ5 Ϫ1
Ϫ5 Ϫ1
Ϫ5 Ϫ1
a
1
.4 ϫ 10 s , 9.0 ϫ 10 s , and 24.4 ϫ 10
s
sic nucleophilicity of these amines.
at pH 5.20, 5.67, and 5.97, respectively. These calcu-
lated values of k are smaller than the lowest observed
cor
Ϫ3
k1 obs obtained at 0.1 mol dm [Buf] by the factor
T
This investigation was financed partly by Universiti Malaya
Research Vote F408/96.
of Ն 6. This analysis shows that the maximum contri-
bution of k is Ͻ14% in eq. (4).
The values of k at 3 different pH were found to fit
b
to eq. (8). The plot of k /( f f [MeNHOH] ) vs. a
b
Am
B
T
H
BIBLIOGRAPHY
turned out to be linear as shown in Figure 3. The
A
least-squares calculated values of k and k /K are
gb
ga
a
6
Ϫ2 Ϫ1
1. (a)A. R. Fersht, Enzyme Structure and Mechanism,
Freeman, New York, 1977; (b) W. P. Jencks, Adv. Enzy-
mol., 43, 219 (1975); (c) W. P. Jencks, Catalysis in
Chemistry and Enzymology, McGraw-Hill, New York,
6
1
.20 Ϯ 1.21 dm mol
0 dm mol s , respectively.
s
and (5.32 Ϯ 0.31) ϫ
6
9
Ϫ3 Ϫ1
The simplest mechanism that is consistent with
the observed data may be shown in Scheme I. The
probable transition states involved in the rate-deter-
1
969.
2
. (a) W. P. Jencks, Acc. Chem. Res., 9, 425 (1976); 13,
161 (1980); Chem. Soc. Rev., 10, 345 (1981); Chem.
Rev., 85, 511 (1985); (b) L. D. Kershner and R. L.
Schowen, J. Am. Chem. Soc., 93, 2014 (1971); (c) K.
N. Dalby, A. J. Kirby, and F. Hollfelder, Pure Appl.
Chem., 66, 687 (1994).
1
1
mining k - and k -steps may be shown as TS and
2
3
1
TS2 , respectively. It is noteworthy that
ϩ
k [MeNHOH][BH ][NCPH] is kinetically indistin-
ga
guishable from k [MeNHOH][B]a [NCPH] (where
gba
H
A
ϩ
kgba ϭ k /K and BH represents general acid,
ga
a
3
. M. N. Khan, J. Chem. Soc. Perkin Trans 2, 1977
acetic acid). The most likely transition state involved
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(1985).
4
5
. M. N. Khan, J. Chem. Soc. Perkin Trans. 2, 819 (1987).
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TS . Generally GA–GB-catalyzed reactions involve
3
either GA or GB catalysis [12–17]. Simultaneous oc-
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(1985).
6
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