Proximity effect on the general base catalysed hydrolysis of amide linkage: The role of cationic surfactant, CTABr

Article abstract of DOI:10.1007/s12039-011-0084-5

The bis phenoxide forms of (1,2) bis(2-hydroxybenzamido) ethane(I) , (1,5) bis(2-hydroxybenzamido) 3-azapentane(II) , (1,3) bis(2-hydroxybenzamido) propane(III) , and (1,8) bis(2-hydroxybenzamido) 3,6- diazaoctane(IV) undergo facile hydrolysis of one of the amide groups (0.02 ≤ [OH?]T (mol dm? ³) ≤ 0.5, 10% MeOH (v/v) + H₂O medium) without exhibiting [OH?] dependence. The reactivity trend follows I ～ II >> III ～ IV with low activation enthalpy {25.7±2.8 ≤ δH≠ (kJ mol?¹) ≤ 64.8±7.0}. The high negative and comparable values of activation entropy{?234 ±8 ≤ δS≠ (J K?1 mol? ¹) ≤ ?127 ± 20} are consistent with closely similar, and ordered transition states which can be assembled by favourably oriented phenoxide groups. The solvent kinetic isotope effect for I, κ ^H2O/κ ^D2O+^H2O ～ 1 (20 and 50 volume% D₂O) , indicates that proton transfer is not involved as a part of the rate controlling process. The observed slowing down of the rate of this reaction for I in the micellar pseudo phase of CTABr also supports the proposed mechanism. Under premicellar conditions, however, rate acceleration is observed, a consequence believed to be associated with the capping effect of the hydrophobic tail of the surfactant cation forming the reactive ion-pair, CTA+, (I-2H) ²? exclusively in the aqueous pseudo phase. Indian Academy of Sciences.

Full text of DOI:10.1007/s12039-011-0084-5

c
J. Chem. Sci. Vol. 123, No. 4, July 2011, pp. 497–507. ꢀ Indian Academy of Sciences.
Proximity effect on the general base catalysed hydrolysis of amide
linkage: The role of cationic surfactant, CTABr
SARAT C DASH and ANADI C DASH∗
Department of Chemistry, Utkal University, Bhubaneswar 751 004, India
e-mail: acdash1@rediffmail.com
MS received 18 August 2010; accepted 28 February 2011
Abstract. The bis phenoxide forms of (1,2)bis(2-hydroxybenzamido)ethane(I), (1,5)bis(2-hydroxybenz-
amido)3-azapentane(II), (1,3)bis(2-hydroxybenzamido)propane(III), and (1,8)bis(2-hydroxybenzamido)3,6-
diazaoctane(IV) undergo facile hydrolysis of one of the amide groups (0.02 ≤ [OH−]T (mol dm−3) ≤ 0.5,
10% MeOH (v/v) + H2O medium) without exhibiting [OH−] dependence. The reactivity trend follows I ∼
II >> III ∼ IV with low activation enthalpy {25.7 2.8 ≤ ꢀH= (kJ mol−1) ≤ 64.8 7.0}. The high negative
and comparable values of activation entropy{−234 8 ≤ ꢀS= (J K−1 mol−1) ≤ −127 20} are consistent
with closely similar, and ordered transition states which can be assembled by favourably oriented phenoxide
groups. The solvent kinetic isotope effect for I, kH2O/kD2O+H2O ∼ 1 (20 and 50 volume% D2O), indicates that
proton transfer is not involved as a part of the rate controlling process. The observed slowing down of the rate
of this reaction for I in the micellar pseudo phase of CTABr also supports the proposed mechanism. Under pre-
micellar conditions, however, rate acceleration is observed, a consequence believed to be associated with the
capping effect of the hydrophobic tail of the surfactant cation forming the reactive ion-pair, CTA+, (I-2H)2−
exclusively in the aqueous pseudo phase.
Keywords. 2-Hydroxybenzamides; kinetics; micellar effect.
1. Introduction
with a view to understand the mechanism of binary and
ternary complex formation and electron transfer pro-
cesses.7 As a part of this program we felt it worthwhile
to investigate the kinetics of acid and base hydrolysis of
such polydentate amide ligands.
The amide moiety is a fundamental unit in biological
chemistry. Its remarkable resistance to hydrolysis is a
key feature of the stability of complex protein struc-
tures. However, the amide unit in a molecule can suf-
fer slow hydrolytic splitting under the catalytic action
of acids and bases. Brown et al.1 reviewed this aspect
in 1992 and discussed the influence of stereo-electronic
effects of the functional groups attached to the amide
N-site. Subsequent to this Bowden et al.2 reported
the intra molecular catalysis by neighbouring carbonyl
group in the alkaline hydrolysis of 2-formyl acetanilide
and related amides. In the recent years considerable
emphasis has been attached to the polydentate ligands
endowed with phenol–amide functionalities. Several
transition metal complexes of such ligands have been
synthesized, structurally characterized,3,4 and their cat-
alytic applications in organic synthesis in limited cases
have been demonstrated.5,6 We have been working on
the solution state kinetics and equilibria involving poly-
dentate phenol–amide ligands and transition metal ions
We
have
chosen
(1,2)bis(2-hydroxybenz-
amido)ethane(I),(1,5)bis(2-hydroxybenzamido)3-aza-
pentane(II),(1,3)bis(2-hydroxybenzamido)propane(III),
and (1,8)bis(2-hydroxybenzamido)3,6-diazaoctane(IV)
in order to examine the intramolecular participation
of the phenol (phenoxide), if any, on the hydrolysis
of the amide function. The relevant literature survey
showed to the best of our knowledge that it has not
been reported earlier. However, data are available for
salicylamide and related systems1,8 for comparison.
H
O
O
H
H
O
O
H
H
H
N
O
O
O
N
O
H
NH
H
N
N
NH
NH
H
H
H
H
O
O
O
O
O
O
O
O
N
N
N
N
H
H
H
H
∗For correspondence
I
II
III
IV
497

498
Sarat C Dash and Anadi C Dash
with glass - Ag/AgCl, NaCl (3 mol dm−3) combined
2. Experimental
2.1 Materials
electrode CL51 was used for pH measurements.
The amines, (1,2)diaminoethane, (1,3)diaminopropane,
(1,5)diamino 3- azapentane, and (1,8)diamino 3,5-diaza-
octane (BDH), methyl salicylate (Siscochem/Merck,
India) were used as received. The bis (2-hydroxy-
benzamides) of the multidentate amines (I–IV) were
synthesized by condensing the respective amines with
methyl salicylate in 1:2 mol ratio at 70◦C and purified
by re-crystallization from 50% (v/v) methanol water
mixture.9–12 The samples were air dried and stored over
silica gel in a desiccator for further drying. The puri-
ties of the samples (I–IV) were further checked by ele-
mental analyses which were in good agreement with
the calculated values. The IR spectra displayed strong
band at 1630–1646 cm−1 characteristic of νstr.(C=O) as
reported earlier.9–11 The Uv-Vis spectral data for the
samples are as follows: λmax, nm (ε, dm3 mol−1 cm−1):
297.0 (6089) [I], 298.0 (6971) [II], 298.5(6306) [III],
298.0 (7925) [IV].
2.3 Kinetic measurements
The rate measurements were made under pseudo first
order conditions at 29.5 ≤ t(◦C) ≤ 70.0. The reac-
tion mixture containing the desired amounts of all
components except the amide was equilibrated in a
measuring flask (25 cm3) at the desired temperature
in a thermostatic bath. After thermal equilibrium was
reached a known volume (2.5 cm3) of methanolic solu-
tion of the substrate was quickly transferred to the reac-
tion mixture which was shaken well and transferred
to one of the 10 mm quartz cells housed in the ther-
mostatted cell compartment of the spectrophotometer.
The progress of the reaction was monitored by the
decrease of absorbance at 329 nm measured against
solvent blank. The concentrations of the amides were
∼ (4–5) × 10−5 mol dm−3 and that of NaOH was varied
in the range of 0.02–0.5 mol dm−3.
A constant value of absorbance could not be achieved
even after 3 days. However, independent measurements
(by mixing the corresponding amines, salicylic acid and
NaOH, I = 0.5 mol dm−3) showed that a reaction mix-
ture for the complete hydrolysis of the amides (I–IV) to
the corresponding amines and salicylate had very small
absorbance at the experimental wave length (329 nm).
This indicated that the base hydrolysis occurred in two
phases, the second one being extremely slow. We, there-
fore, investigated the first phase of the reaction in which
only one amide bond was hydrolysed resulting in the
formation of one mole of salicylate per mole of the
amides (I–IV) hydrolysed. The absorbance time data
Cetyltrimethylammonium
bromide
(CTABr)
(Aldrich, 99%) was used as received. All other chemi-
cals used in the kinetic study were of analytical grade.
Methanol was GR grade (Merck, purity 99.8%). Water
was doubly distilled, the second distillation being made
from alkaline KMnO4 in an all glass distillation appa-
ratus. All reactions were studied in 10% (v/v) MeOH +
H2O medium unless otherwise mentioned (see text).
Ionic strength (I) was adjusted with NaClO4.
The stock solution of NaClO4 was prepared by mix-
ing standardized solution of NaOH with the standard-
ized solution of HClO4. The pH of stock NaClO4 was
adjusted to 6. The concentration of NaClO4 was fur-
ther checked by alkalimetry after exchanging a known
volume of its dilute solution with Dowex 50W X-8
(H+ form) resin and titrating the liberated acid against
standard alkali. D2O was received from Bhaba Atomic
Research Centre, India.
H
H
H
H
N
N
N
O
N
O
C
H
k1
C
O
C
O
O
O
C
H
-
k-1
O
H
-O
-
O
H
-O
2.2 Instrumentation
k2
UV-visible absorption spectra and kinetics were mon-
itored with a Cecil spectrophotometer model CE 7200
(U.K.). The cell block was thermostatted to the desired
temperature by a thermostatic controller model CE
2024. A pair of 10 mm matched quartz cells was used.
The IR spectra were run on a Perkin Elmer 1760X
FTIR as KBr pellet. 1H and 13C NMR were recorded on
Bruker 400 and 100 MHz NMR spectrometers respec-
tively at IIT Madras. A Systronics pH meter model 335
H
H
N
O
N
H
O
H
C
O
C
-
O
+
-O
Scheme 1. Intra molecular general base catalysed hydrol-
ysis of I.

Intra molecular general base catalysed hydrolysis of amide
499
(a)
(b)
Figure 1. (a) 1H NMR spectrum of (1,2)bis(2-hydroxyenzamide)ethane (I) in
1
(CD3)2SO, (b) H NMR spectrum of the hydrolysis product of (I) in CDCl3, (c)
13C NMR spectrum of (I) in (CD3)2SO, (d) 13C NMR spectrum of the hydrolysis
product of (I) in (CD3)2SO.

500
Sarat C Dash and Anadi C Dash
(d)
Figure 1. (continued.)
were treated by Guggenheim method13 (see equation 1) were fitted to equation (1) by a nonlinear least squares
as the infinity absorbance for the first phase of the program keeping ꢀ close to ca. t1/2. The representative
reaction was uncertain.
absorbance-time plots are shown in figure S1.
At − At+ꢀ = C exp (−kobst) .
(1)
2.4 Product analysis
In equation (1), C = (A0–A ){1–exp(–kobsꢀ)}, ꢀ = a
∞
constant time interval and At is absorbance at time t.
C and kobs were varied and the absorbance-time data
In a typical experiment an aqueous methanolic solu-
tion of I (0.153 g) was treated with excess of NaOH

Intra molecular general base catalysed hydrolysis of amide
501
thus ascribed to the primary amine function generated
during hydrolysis of one of the amide groups; the pres-
ence of the other amide group is indicated by the signal
at 8.603 ppm corresponding to the same at 8.511 ppm
for I, a down field shift of 0.092 ppm may be a con-
sequence of the hydrogen bonding of the amide proton
with the primary amine site (see Structure V).
KM
2-
2-
IM
Dn
IW
+
H2O
kM
kW
H2O
H
O
O
N
H
PRODUCTS
N
H
H
H2O
kWIP
V
Further the aliphatic proton signals (3.65–3.66 pp)
for I are considerably shifted up field (2.602–
2.611 ppm) and the spectra become more complex in
the aromatic region (7.34–7.754 ppm) upon hydrolysis
of one of the amide functions. The 13C NMR spectra
(figures 1c, d) also display small shifts of 13C signals
on hydrolysis of I, the most significant being that of the
phenol (C–OH) and amide (C=O) functions (160.72,
170.48 ppm for I; 160.24 and 169.95 for the hydrolysed
product).
KIP
2-
IW + CTA+
-
IPW
Scheme 2. Hydrolysis of I in the presence of CTABr; IW2−
and I2M− denote (I-2H)2− in aqueous and micellar pseudo
phases respectively.
(0.05 mol dm−3) and the mixture was left for 24 h (ca.
∼ 9t1/2) at room temperature (30◦C). The mixture was
then acidified with HClO4 to pH 1 and extracted with
CHCl3 at least thrice. All the CHCl3 extracts were
combined and evaporated to dryness. A white solid was
obtained which was dissolved in 0.1 mol dm−3 NaOH.
After proper dilution in 0.1 mol dm−3 alkali the UV
spectrum of the solution was recorded and matched
with that of salicylic acid under similar condition.
Agreement was excellent indicating that the product
was salicylic acid. Using a calibration curve of the ab-
sorbance of salicylic acid in 0.1 mol dm−3 NaOH (λ =
3. Results
3.1 Preliminary observations
The repetitive spectral scans for I-IV in acidic medium
([HClO4] = 0.05 mol dm−3, 40◦C) did not show any
change over an extended period thus indicating that the
substrates were very stable to acid catalysed hydrolysis.
However, they underwent slow base catalysed hydroly-
sis; clean isosbestic points were observed at 308 nm and
265 nm for I and II respectively (see figure 2 and inset)
during the early phase of the reaction corresponding to
the hydrolysis of one amide function.
For III and IV the isosbestic points appearing around
260, 305 nm and 258, 342 nm respectively were not so
well defined during the period of measurement (figure
S2 and inset) presumably due to slowness of the reac-
tion. The rate data are collected in table 1. A compari-
son of the rate and activation parameters is presented in
table 2.
300 nm) it was found that 99
1% of one of the
–CO–NH-groups in I was hydrolysed yielding sali-
cylic acid. The acidified aqueous extract containing the
intermediate displayed characteristic UV spectrum {λ,
nm(shoulder) = 300, λmax, nm = 329) thus confirming
that one of the salicylate moiety is present in the inter-
mediate. Similar observations were made for II–IV.
In another set of experiment I was hydrolysed
at 40◦C in alkaline medium as described above for
4 h (ca. ∼ 4t1/2), the reaction mixture was then neu-
tralised with dilute HClO4 and extracted repeatedly
with CHCl3. The solid obtained by evaporation of the
CHCl3 extract was analysed by H and 13C NMR; the
1
3.2 Effect of of cetyltrimethylammonium bromide
(CTABr)
1H and 13C NMR spectra of I are also presented for
comparison (see figures 1a–d).
The product displays a 1H peak (broad) at 6.136 ppm Rate measurements were made in the presence of the
which does not appear in the H spectrum of I and is surfactant CTABr for I as a representative case to shed
1

502
Sarat C Dash and Anadi C Dash
Figure 2. Repetitive spectral scans for the hydrolysis of I and II (inset)
in alkaline medium.10% MeOH + H2O (v/v), [NaOH]T = 0.05, I
=
0.5 mol dm−3; 40◦C:. 105 [I]T([II]T) = 4.80 (6.98) mol dm−3, ꢀt = 15 min
(1–8), and 48 h (9); absorbance decreased with time at 329 nm.
light on the mechanism of the reaction (see later). The reaction was, however, observed (figure S3) when the
relevant rate data are collected in table 3. It is interesting proportion of D2O was raised to 99% (1% MeOH,
to note that there is a substantial retarding effect of the [OH−]T = 0.02 mol dm−3, 40◦C) which was attributed
surfactant. The variation of [OH−] in the presence of to the incomplete ionization of the phenol groups under
the surfactant had practically no effect on kobs.
this condition.
3.3 Effect of ionic strength
4. Discussion
The effect of ionic strength on kobs at a constant
[OH−]T (= 0.035 mol dm−3) was investigated for the
representative amide, I. We obtained 104kobs(s−1) as
For all the di-amides (I–IV) the second step of hydrol-
ysis was significantly slower than the first one. The rate
constant (kobs) for the first step was also virtually inde-
pendent of [OH−] (see table 1) once both the phenol
groups are completely deprotonated to the phenoxide
form. Our earlier data (pKO H1 and pKO H2) of these
diphenol diamides showed that these will exist in the
bis phenoxide form at [OH−] ≥ 0.02 mol dm−3).9,10,14,15
The zero time uv-vis spectral data for I at [OH−]T =
0.02 − 0.5 mol dm−3 (29◦C, I = 0.5 mol dm−3,
10% MeOH + H2O) was also independent of [OH−]
0.89
0.06, 0.84
0.02, 0.86
0.02 and 0.88
0.04 at ionic strengths, I = 0.05, 0.10, 0.20 and
0.50 mol dm−3 (30.5◦C) respectively. Thus the observed
rate constant is insensitive to the ionic strength
variation.
3.4 Solvent isotope effect
The solvent kinetic isotope effect (SKIE) was inves- thus supporting that ionization of the phenol groups
tigated for I in 20%D2O + 79% H2O + 1% MeOH were complete and further ionization of the amide func-
(v/v) and 50% D2O + 49% H2O + 1% MeOH (v/v) tion(s) of the bis phenoxide species did not occur to
([OH−]T = 0.035 mol dm−3, 40◦C) and we obtained a measurable extent. The lack of [OH−], and ionic
(D2O+H2O)
H2O
obs
k
/kobs
as 0.90 0.07 and 1.06 0.02 respec- strength dependence of kobs clearly discounts the possi-
tively. As against this substantial slowing down of the bility of the reaction of the bis-phenoxide species with

Intra molecular general base catalysed hydrolysis of amide
503
Table 1. Rate constants for the first step of hydrolysis of the phenol–amide compounds, I–IV.a
[NaOH]
(mol dm−3
104kobs(s−1 b
)
)
29.5◦
35.0◦
40.0◦
45.0◦
50.0◦C
I
0.01
0.02
0.03
0.035
0.04
0.05
0.10
0.20
0.30
0.50
-
-
-
3.20 0.30
1.77 0.06d
1.83 0.17d
-
0.55 0.07
1.02 0.04
0.89 0.17c
-
1.50 0.03
1.77 0.04
-
-
0.72 0.06
0.74 0.09d
-
-
-
-
-
1.30 0.02
1.51 0.02
-
1.26 0.09
1.45 0.03
1.92 0.03
1.60 0.15d
-
2.20 0.06
1.72 0.04
-
0.81 0.10d
-
1.63 0.21c
1.61 0.30c
2.03 0.03
0.70 0.08
2.43 0.06c
II
0.01
0.02
0.03
0.05
0.10
0.20
0.30
0.40
0.50
-
-
2.49 0.12
2.92 0.16
2.63 0.04
2.36 0.10
2.39 0.16
1.96 0.37d
2.88 0.12
2.84 0.31d
1.46 0.03
-
-
-
-
-
-
-
-
-
-
-
-
-
-
2.30 0.03
2.75 0.03
1.78 0.04
2.68 0.03
2.59 0.06
-
2.40 0.08
3.02 0.05
2.75 0.03
2.81 0.04
3.13 0.05
-
a10% MeOH + H2O (v/v), Ionic strength (I) = 0.5 mol dm−3
.
bweighted average of 104kobs (s−1): 0.87 0.05(60.0◦C),1.10
0.35 (65.0◦C), 1.68
0.24 (70◦C) for III, and 1.29
0.31(60.0◦C), 1.56 0.09 (65.0◦C), 2.25 0.06 (70.0◦C) for IV at [NaOH]T = 0.05 and 0.5 mol dm−3; w = 1/[σ(kobs)]2.
c,d weighted average of triplicate (c) or duplicate (d) runs. All other kobs (and σ(kobs)) are from a single run at each [NaOH].
OH−. In contrast to these observations Ahmad et al.8 repulsion between OH− and the di- negative reactants
showed that the phenoxide form of salicylamide under- which does not favour approach of OH− to the reactive
went base hydrolysis exclusively via [OH−] dependent HN–C=O centre. The value of kobs at 45◦C, [OH−]T =
path; the ionization of the amide group of the phenoxide 0.7 mol dm−3 (I = 3.0 mol dm−3) for salicylamide as
form of salicylamide was detected by them kinetically calculated from the activation parameter data reported
at an elevated temperature and much higher [OH−]T by Ahmad et al.8 turned out 2.5 × 10−6 s−1. Disre-
(= 0.5 − 3 mol dm−3, 95◦C). In our case deprotona- garding the ionic strength effect it turns out that the
tion of the amides is insignificant and also the reactivity bis phenoxide form of I reacts 80 times faster than the
of the bis- phenoxide moieties with OH− is negligible phenoxide form of salicylamide (koIbs/kosablsicylamide = 80)
which may be ascribed at least partly to the coulombic at the same temperature without being further assisted
Table 2. Comparison of the rate constants and activation parameters.
Compound
104k(25◦C)/s−1a,b
ꢀH=/kJ mol−1
ꢀS=/J K−1 mol−1
I
II
III
IV
0.58
1.17
0.064
0.063
49.9 11.1
25.7 2.7
58.8 3.8
64.8 7.0
−(1.58 0.36) × 102
−(2.34 0.08) × 102
−(1.47 0.11) × 102
−(1.27 0.20) × 102
acalcd: k = (kbT/h)× exp (−ꢀH=/RT + ꢀS=/R).
bValues of 104k/s−1: 0.69 0.042 (29.5◦), 1.37 0.067 (35.0◦), 1.72 0.083 (40.0◦),
2.00 0.10 (45.0◦C) [for I]; 1.99 0.20 (40.0◦), 2.46 0.17 (45.0◦), 2.84 0.09
(50.0◦C) [for II]; these are the weighted averages of kobs at different [NaOH] (see
table 1). For III and IV, see foot note b of table 1.

504
Sarat C Dash and Anadi C Dash
Figure 3. Plot of log kW (25◦C) versus pK1OH + pK2OH for I(1), II(2), III(3) and IV (4).
H
N
H
H
N
N
H
O
H
C
N
N
O
O
C
O
H
-
C
O
H
-O
O
C
O
H
-
O
H
-O
(I-2H)2-
Figure 4. Phenoxide promoted hydration of the amide function.
(II-2H)2-
by [OH−]. This is clearly an indication of the intra therefore, clearly delineates the proximity effect on the
molecular general base catalysis of the phenoxide func- intra molecular base catalysed hydrolysis of the amide
tions on the hydrolysis of the amide bond. However, function, a basic unit of considerable importance in
the reactivity sequence I ∼ II > III ∼ IV (see table 2 macromolecules of biological significance.
and figure 3) further suggests that favourable orienta-
A general scheme for the phenoxide catalysed
tion of the phenoxide moieties with respect to the amide hydrolysis reaction consistent with our observations is
carbonyl function is important for their general base presented for I in scheme 1. However, the relatively
catalytic effect in the attack of H2O at the –C=O–NH lower reactivities for III and IV is reconciled with inef-
function. When we constructed molecular models of the ficient catalysis of the phenoxide groups due to their
bis phenoxide forms of I-IV we found that only for I larger distance of separation from the reactive HN–
and II the two phenoxide groups can be brought close C=O centre and also possible involvement of more than
to each other and also proximate to one of the amide one water molecules bridging the phenoxide groups,
carbonyl with a bridging H2O molecule (see figure 4).
For the other two (III, IV) the two phenoxide moi-
eties are disposed around the reactive amide function
at a longer distance. As such the bridging of the two
phenoxide groups through hydrogen bonding neces-
sitates involvement of more water molecules. Con-
sequently the phenoxide promoted hydration of the
reactive carbon centre becomes less efficient in the lat-
ter case which results in a weaker catalysis. This work,
one of them being an attacking nucleophile.
Consistent with this scheme kobs is given by
kobs = k1k2/ (k−1 + k2) .
(2)
Interestingly the observed solvent kinetic isotope effect
(D2O+H2O)
H2O
(SKIE) for I, (k /kobs
∼ 1, see above) is com-
obs
parable in magnitude to the SKIE for the second
order base catalysed hydrolysis of N,N dimethyl benza-
mide (0.90 0.18) and N,N (ethyl)(1,1,1 trifluroethyl)

Intra molecular general base catalysed hydrolysis of amide
505
disposed around the reaction centre and directing a
molecule of water to the amide C=O centre.
Figure 5 further depicts that there is a catalytic effect
of CTABr at <0.001 mol dm−3. This, we believe, is due
to the influence of a pre-micellar aggregate. Consider-
ing the coulombic interaction between CTA+ and the
reactant, (I-2H)2−, the pre-micellar aggregate may be
an ion-pair.
On the basis of the pseudo phase (PP) model19 and
including reactive ion-pair formation in the aqueous
pseudo phase, scheme 2 is proposed.
Accordingly, the observed rate constant is given by
equation (3).
kW + kWIP KIP[CTA+] + kM KM[Dn]
kobs
=
.
(3)
1 + KIP[CT A+] + KM[Dn]
Figure 5. 104kobs(s−1) versus 102[CTABr](mol dm−3) plot
at 29.5◦C. The curve is drawn through 104kcal(s−1) (see table
3) as against the experimental points.
Using [CTA+] = c.m.c., [Dn] = [CTABr]T − c.m.c.,
KMꢂ
=
KM/(1 + KIP[CTA+]), kWꢂ
=
(kW
+
kWIP KIP[CTA+])/(1+KIP[CTA+]), equation (3) is recast
as equation (4).
ꢀ
ꢁ ꢀ
ꢁ
kobs = kWꢂ + kM KMꢂ [Dn] / 1 + KMꢂ [Dn] .
(4)
benzamide(1.05 0.04) involving rate limiting nucle-
ophilic addition of OH− at the amide carbonyl cen-
tre.1,16 This leads us to believe that proton transfer is
not involved in the rate limiting step. The rate determin-
ing process essentially involves the nucleophilic attack
of H2O at the amide C=O centre (see scheme 1) so that
A weighted least squares20 fit to the linearized form of
equation (4), using 1.45 ≤ 104kWꢂ (s−1) ≤ 1.70, and
0.3 ≤ 104 c. m. c. ≤ 4.0 {(kWꢂ − kobs)−1 versus [Dn]−1
plot}, yielded the first approximate values of kM KMꢂ and
KMꢂ ; the best fit values (corr. coeff. = 0.9802) of KMꢂ and
104kM were 121 21 dm3 mol−1 and 0.29 0.14 s−1
kobs ≈ k1 (k2 > k ). This is also in conformity with
−1
the recent theoretical calculations on the base hydroly-
sis of amides in water in which the nucleophilic attack
of OH− at the amide carbonyl function is shown to be
the rate determining step.17
Table 3. Effect of CTABr on hydrolysis of I.a
[OH−]T
[CTABr]T
(mol dm−3
104kobs
(s−1
104 kcal
c
The large negative values of ꢀS= (see table 2) are
consistent with an ordered structure of the transition
state as demanded in the k1 path. However, a rela-
tively larger values of ꢀH= for III and IV are in tune
with the energy involved in assembling a number of
water molecules and bridging the phenoxide moieties
for favourably directing the nucleophile to the C=O
centres for these substrates.
(mol dm−3
)
)
)
(s−1
)
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.01
0.02
0.03
0.04
0.0010
0.0020
0.0050
0.010
0.030
0.050
0.060
0.100
0.020
0.020
0.020
0.020
1.43 0.03
1.39 0.04
1.13 0.07
0.85 0.01
0.66 0.04
0.84 0.11b
0.65 0.05
0.36 0.11b
0.77 0.02
0.84 0.04
0.57 0.02
0.57 0.02
1.46
1.32
1.05
0.84
0.60
0.54
0.52
0.48
0.67
0.67
0.67
0.67
Khan and Azri18 recently reported that the
hydrolysis of the phenoxide form of N-(2ꢂ-
hydroxyphenyl)phthalimide is retarded by the cationic
micelle of CTABr; in this case the reaction involves
phenoxide promoted H2O addition to the –N–C=O
moiety (intramolecular general base mechanism). Our
observation is similar to that of Khan et al.18 Thus
the observed inhibitory effect of CTABr (see figure 5)
on the rate of hydrolysis of the dianion of I, (I-2H)2−
is consistent with the absence of the OH− dependent
path, the reaction being mediated by the general base
catalytic effect of the phenoxide groups favourably
a29.5
0.1◦C; [I]T: (2.8–5.5)
×
10−5 mol dm−3
;
10%(v/v)MeOH + H2O medium.
bAverage of duplicate runs; all other kobs( σkobs) values are
from a single run for a given condition.
cSee equation (4): 104 kWꢂ
=
1.66
0.16 s−1
−1, KMꢂ
[(kcal − kobs)/ σkobs] =
,
104 kM KMꢂ
=
79.1
56.0 dm3 mol−1
s
=
ꢂ
(1.90 0.87) × 102 dm3 mol−1
,
2
118.7, c. m. c. = 1.0 × 10−4 mol dm−3
.

506
Sarat C Dash and Anadi C Dash
respectively with 104kWꢂ (s−1) = 1.50 and 104 c. m. c. = ion-pair formation constant for 2−, +1 charge type
1.0 mol dm−3. The value of c. m. c. was then held fixed interaction in aqueous medium is predicated from the
at 1.0 × 10−4 mol dm−3, the kobs data were refitted to coulombic concept to be <10 dm3 mol−1 for the hard
equation (4) by a weighted nonlinear least squares com- sphere ions.22 In this particular case it is hard to believe
puter program using the first approximate values of kWꢂ , that KIP value will exceed 103. The value of KMꢂ negates
kM KMꢂ and KMꢂ . We obtained 104kWꢂ (−1) = 1.66 0.16, such a possibility also. Hence we prefer the former
104kM KMꢂ (dm3 mol−1 s−1) = 79.1 56.0 and 10−2 KMꢂ interpretation. A relatively high value of KIP (∼103) for
(dm3 mol−1) = 1.90 0.87 which gave 104kM (s−1) as the interaction between CTA+ and (I–2H)2− in aqueous
0.42 0.35 (see foot note c of table 3). It is thus evident environment is likely to be due to both coulombic and
that the micellar binding of (I-2H)2− reduces its reactiv- hydrophobic effects (see figure 6), the latter possibly
ity (104kw(s−1) = 0.69 0.04) despite the fact that the squeezes the reactive anion favourably due to coiling of
residence site of this reactive dianion is predominantly the tail of the surfactant ion and accelerates the water
the water-rich region of the micellar pseudo phase. Our addition at the C=O function.
result is consistent with the earlier observations that the
The rate acceleration due to this kind of capping
decreased availability of water in the micellar pseudo effect was earlier observed by us in the intra molecu-
phase as also its lower polarity than bulk water, slow lar isomerization of O-bonded sulphite to its S-bonded
down the water addition reactions.19(a), 21
form in the case of (tetren)Co-OSO+2 when the reac-
Now turning to the value of kWꢂ a reasonable assess- tion was carried out in the presence of sodium dodecyl
ment of the reactivity of the IP can be made as follows. sulphate (SDS).23
If it is assumed that KIP [CTA+] ([CTA+] = c. m. c.)
<< 1 and KIP < 103 dm3 mol−1 then kWIP {=(kWꢂ
−
kW)/[CTA+], [CTA+] = 1.0 × 10−4 mol dm−3} assumes
a value >(1.0 0.2) × 10−3 s−1 (29.5◦C, using kw =
0.69 0.045 × 10−4 s−1, see foot note c of table 2).
5. Conclusion
The present work demonstrates that the bis phenox-
ide species of (1,2)bis(2-hydroxybenzamido)ethane
(I), (1,5)bis(2-hydroxybenzamido)3-azapentane (II),
A substantial catalytic effect of the ion-pair(kWIP/kW
>
14 3) in the aqueous pseudo-phase is envisaged. On
the other hand, if KIP ∼ 105 dm3 mol−1 then kWIP turns
out 1.6 0.2 × 10−4 s−1; the ion-pair only nominally
(1,3)bis(2-hydroxybenzamido)propane
(III),
and
(1,8)bis(2-hydroxybenzamido)3,6-diazaoctane
(IV)
catalyses the reaction (kWIP /kw = 2.3
0.3). The
undergo exclusively phenoxide promoted hydrolysis
H3C
H3C
H3C
N
H
H
N+
H3C
O-
HN
C
O
H3C
H3C
kWIP
+
H3C
H
H
N
N+
O-
N
O
H3C
C
O
C
-
O
H
CO2
-
O
H
-O
+(I-2H )2-
CTA
,
Figure 6. Tentative structure of the ion-pair, CTA+,(I-2H)2− and its reaction.

Intra molecular general base catalysed hydrolysis of amide
(general base catalysis) of one of the amide bonds. The References
507
observed reactivity trend: I ∼ II >> III ∼ IV depicts
the proximity effect of the two phenoxide moieties
in the same molecule in the rate limiting hydration
of the amide carbonyl function. This is supported by
the low values of the activation enthalpy {ꢀH= (kJ
1. Brown R S, Bennet A J and Slebocka-Tilk H 1992
Acc. Chem. Res. 25 481
2. Bowden K, Hiscocks S P and Reddy M K 1997 J. Chem.
Soc. Perkin Trans. 2 1133
3. Sunatsuki Y, Nakamura M, Matsumoto N and Kai F
1997 Bull. Chem. Soc. Jpn. 70 1851
mol−1): 49.9
11.1 (I), 25.7
2.8 (II), 58.8
3.8
4. Stassinopoulos A, Schulte G, Papaefthymiou G C and
Caradonna J P 1991 J. Am. Chem. Soc. 113 8686
5. Stassinopoulos A and Caradonna J P 1990 J. Am. Chem.
Soc. 112 7071
6. Nguyen C, Guarjardo R J and Mascharak P K 1996
Inorg. Chem. 35 6273
7. Nayak S, Dash A C and Lahiri G K 2008 Transit. Met.
Chem. 33 39 and references cited therein
8. Ahmad R, Khan M N and Khan A A 1976 Ind. J. Chem.
14A 807
9. Dash A C and Mishra A N 1998 Ind. J. Chem. 37A
961
(III), and 64.8
7.0 (IV)}. The substantially low
values of ꢀS= {−158 36 (I), −234 8 (II), −147
11 (III) and −127 20 (IV) J K−1 mol −1} are also
consistent with closely similar, and ordered transition
states which can be assembled by favourably oriented
phenoxide groups. The solvent kinetic isotope effect
(SKIE), kH2O/kD2O+H2O ∼ 1 (20 and 50 volume % D2O)
for I indicates that proton transfer is not involved as
a part of the rate controlling process. The observed
slowing down of the rate of this reaction for I in the
micellar pseudo phase of CTABr also supports the
proposed mechanism. Under pre-micellar conditions,
however, rate acceleration is observed due to the ion-
pair catalysis, a consequence believed to be associated
with the capping effect of the hydrophobic tail of the
surfactant cation, forming the ion-pair, CTA+,(I-2H)2−
exclusively in the aqueous pseudo phase.
10. Nayak S and Dash A C 2003 Ind. J. Chem. 42A
2427
11. Dash A C and Rath R K 2004 Ind. J. Chem. 43A 310
12. Chandra S K and Chakravorty A 1992 Inorg. Chem.
31 760
13. Frost A A and Pearson R G 1961 Kinetics and mecha-
nism, 2nd edn (New York: Wiley) p 49
14. Nayak S, Dash A C, Nayak P K and Das D 2005 Transit.
Met. Chem. 30 917
15. Nayak S and Dash A C 2006 Transit. Met. Chem. 31
813
Acknowledgements
16. Slebocka-Tilk H, Bennet A J, Keillor J W, Brown R S,
Guthrie J P and Jodhan A J 1990 J. Am. Chem. Soc. 112
8507; (b) Slebocka-Tilk H., Bennet A J, Hogg A J and
Brown R S 1991 J. Am. Chem. Soc. 113 1288
17. Galabov B, Cheshmedzhieva D, Ilieva S and Hadjieva B
2004 J. Phys. Chem. A108 1147
18. Khan N and Azri H R 2010 J. Phys. Chem. B 114 8089
19. Al-Lohedan H, Bunton C A and Mhala M M 1982 J.
Am. Chem. Soc. 104 6654; (b) Dash A C, Dash B ad
SCD is thankful to the University Grants commission,
India for the award of a teacher fellowship, to the
Principal and Governing Council of Nimapara College,
Nimapara, Orissa, India for granting study leave and
to the Head of the Department of Chemistry, Utkal
University for extending infrastructural facilities.
Panda D 1985 J. Org. Chem. 50 2905
20. For Y = (kWꢂ −kobs
)
−1, σ(Y) = σ(kobs)×(kWꢂ −kobs
)
,
−2
Supplementary material
and w(Y) = [σ(Y)]−2
21. Menger F M, Yoshinaga H, Venkatasubban K S ad
Das A R 1981 J. Org. Chem. 46 415
Figure S1 showing the absorbance versus time plots
for I–IV, Figures S2 (for II, III) and S3 (for I) show-
ing the repetitive spectral scans for the hydrolysis in
H2O + MeOH, and D2O (90% v/v) are submitted as
supplementary material (see www.ias.in/chemsci).
22. Fuoss R 1958 J. Am. Chem. Soc. 80 5059; Eigen M 1954
Z. Physik. Chem. (Frankfurt) 1 176
23. Dash A C and Patnaik A K 1995 J. Chem. Res. (S) 230
(M) 1529