Conversion of imidazoles to imidazolones with chloramine-B: kinetic and mechanistic study

Article abstract of DOI:10.1007/s00706-016-1663-4

Oxidative conversion of 1H-imidazole (IzlH) and 2-substituted imidazoles viz., 2-ethyl-1H-imidazole (2-EtIzlH), 2-methyl-1H-imidazole (2-MeIzlH), 1H-imidazole-2-ester (2-EsIzlH), and 1H-imidazole-2-carbaldehyde (2-CaIzlH) to the corresponding imidazolones with sodium N-chlorobenzenesulfonamide or chloramine-B (CAB) were established. This reaction was kinetically investigated at 303?K in HClO₄ medium. Under comparable experimental conditions, the oxidation reactions followed identical kinetics for all the five imidazoles with a first-order dependence of rate on [CAB]_o and fractional-order dependence each on [imidazole]_o and [H⁺]. Effects of added benzenesulfonamide, halide ions, NaClO₄, and MeOH on the rate of reaction have been studied. Reaction products were identified and characterized by GC–MS and NMR spectral analysis. The rates are measured at different temperatures and the composite activation parameters have been computed from the Arrhenius plots. Isokinetic temperature (β) was found to be 449?K which is higher than the experimental temperature (303?K), indicating that the rate has been under enthalpy control. Relative reactivity of these imidazoles is in the order: 2-EtIzlH?>?2-MeIzlH?>?IzlH?>?2-EsIzlH?>?2-CaIzlH. H₂O⁺Cl have been postulated as the reactive oxidizing species. The reaction mechanism and the derived rate law are in good agreement with the observed experimental results. Spectroscopic studies have been made for an intermediate complex formation between CAB and imidazole. Advantages of the present method include: mild reaction conditions, cost-effectiveness, short reaction time, ease of isolation of products, and the use of eco-friendly reagents. Hence, the methodology developed could be adopted for the facile oxidative conversion of imidazoles to imidazolones and can be scaled up to industrial operation with suitable modification. Graphical abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s00706-016-1663-4

Monatsh Chem
DOI 10.1007/s00706-016-1663-4
ORIGINAL PAPER
Conversion of imidazoles to imidazolones with chloramine-B:
kinetic and mechanistic study
A. S. Manjunatha1 Puttaswamy1
•
Received: 24 July 2015 / Accepted: 10 January 2016
Ó Springer-Verlag Wien 2016
Abstract Oxidative conversion of 1H-imidazole (IzlH)
and 2-substituted imidazoles viz., 2-ethyl-1H-imidazole (2-
EtIzlH), 2-methyl-1H-imidazole (2-MeIzlH), 1H-imida-
zole-2-ester (2-EsIzlH), and 1H-imidazole-2-carbaldehyde
(2-CaIzlH) to the corresponding imidazolones with sodium
N-chlorobenzenesulfonamide or chloramine-B (CAB) were
established. This reaction was kinetically investigated at
303 K in HClO4 medium. Under comparable experimental
conditions, the oxidation reactions followed identical
kinetics for all the five imidazoles with a first-order
dependence of rate on [CAB]o and fractional-order
dependence each on [imidazole]o and [H?]. Effects of
added benzenesulfonamide, halide ions, NaClO4, and
MeOH on the rate of reaction have been studied. Reaction
products were identified and characterized by GC–MS and
NMR spectral analysis. The rates are measured at different
temperatures and the composite activation parameters have
been computed from the Arrhenius plots. Isokinetic tem-
perature (b) was found to be 449 K which is higher than
the experimental temperature (303 K), indicating that the
rate has been under enthalpy control. Relative reactivity of
these imidazoles is in the order: 2-EtIzlH [ 2-MeI-
zlH [ IzlH [ 2-EsIzlH [ 2-CaIzlH. H2O?Cl have been
postulated as the reactive oxidizing species. The reaction
mechanism and the derived rate law are in good agreement
with the observed experimental results. Spectroscopic
studies have been made for an intermediate complex for-
mation between CAB and imidazole. Advantages of the
present method include: mild reaction conditions, cost-ef-
fectiveness, short reaction time, ease of isolation of
products, and the use of eco-friendly reagents. Hence, the
methodology developed could be adopted for the facile
oxidative conversion of imidazoles to imidazolones and
can be scaled up to industrial operation with
suitable modification.
Graphical abstract
N
N
O
R
R
N
H
N
H
Imidazole
Imidazolone
HClO4/H2O
30 °C
+
+
O
S
O
Cl
+
-
+
NH2
+
Cl
Na
N
S
Na
O
O
Benzenesulfonamide
Chloramine-B
,
,
R = -H, -CH3 -C2H5 -CHO, -COOEt
Keywords Imidazole Á Chloramine-B Á
Oxidation kinetics Á Mechanism Á Activation parameters Á
Structure reactivity
Introduction
Electronic supplementary material The online version of this
article (doi:10.1007/s00706-016-1663-4) contains supplementary
material, which is available to authorized users.
Oxidation of organic compounds with high selectivity is a
foremost transformation in organic synthesis and important
in mechanistic chemistry. Chemical kinetics deals with the
study of the rates of chemical reactions and with the
description of the mechanism by which they proceed. Hence,
oxidation-kinetic study is the significant area of research in
chemistry to suit the optimum conditions and to unfold the
& Puttaswamy
pswamy_chem@yahoo.com
1
Department of Chemistry, Bangalore University, Central
College Campus, Bangalore 560 001, India
123

A. S. Manjunatha, Puttaswamy
mechanistic chemistry of a particular reaction [1, 2]. Imi-
dazole is a five-membered planar ring and it exists in two
equivalent tautomeric forms. Imidazoles show amphoteric
properties. Imidazole is incorporated into many important
biological molecules and the most pervasive is histidine.
Imidazoles are common components of a large number of
natural products and pharmaceutically active molecules.
Imidazole and its derivatives possess a number of versatile
properties and pharmaceutical applications include anti-
cancer, antiinflammatory, antibacterial, antifungal, antiviral,
antitubercular, antidiabetic, and antimalarial ones [3]. Sub-
stituted imidazoles are important moieties constituted in
pharmaceuticals, pesticides, and bioactive compounds [4].
Many imidazoles with a single heterocyclic substituent in the
2-position serve as key intermediates in the synthesis of
pharmaceutically active compounds. Mild oxidation of
imidazoles to imidazolones find importance in synthetic
organic chemistry and considerable work has been carried
out in this direction [5]. Further, various kinds of imida-
zolones are biologically and pharmaceutically very
important, since many of them possess antihypertensive,
antidiabetic, and antiinflammatory force [6]. In spite of
extensive medicinal applications of imidazoles and imida-
zolones, no information is available on the oxidative
conversion of imidazoles to imidazolones from the kinetic
and mechanistic point of view. Therefore, the mechanistic
picture and rate law for these redox systems were obscure.
Hence, it is very essential to know the kinetic and mecha-
nistic basis for the redox chemistry of these systems. This
kind of research knowledge would be very beneficial to
synthetic chemists and also kineticists who are working on
the mechanistic chemistry of imidazoles in biological sys-
tems. For these reasons, in the present research, conversion
of imidazoles and 2-imidazoles to the corresponding imi-
dazolones have been developed for our oxidation-kinetic and
mechanistic study.
chlorobenzenesulfonamide or chloramine-B (CAB) is the
benzene analogue of CAT, which can be easily prepared
from the reaction of benzenesulfonamide and chlorine in
basic solutions. Chloramine-B is a stable compound with
slightly higher active chlorine content than CAT. There are
but few reports on the synthetic and mechanistic chemistry
of CAB [8, 12, 14–16].
Our initial experiments began with the examination of
oxidation of the selected imidazoles with CAT in acid
medium. These redox systems at different experimental
conditions were too sluggish to be measured kinetically.
Then we thought of using CAB as an oxidant and we were
delighted to see that the reactions proceeded smoothly.
Hence, CAB is an excellent oxidant in effectively con-
trolled conversion of 2-imidazoles to corresponding
imidazolones. Consequently, in the course of this research,
optimum conditions for the facile oxidation of 2-imida-
zoles to 2-imidazolones with CAB in acid medium were
established. The present paper reports the oxidation-ki-
netics of the imidazoles and substituted imidazoles viz.,
2-ethyl-1H-imidazole (2-EtIzlH), 2-methyl-1H-imidazole
(2-MeIzlH), 1H-imidazole(IzlH), 1H-imidazole-2-ester (2-
EsIzlH), and 1H-imidazole-2-carbaldehyde (2-CaIzlH)
with CAB in acid medium at 303 K. Additionally, these
synthesized imidazolones are useful as intermediates for
polymers, agrochemicals, and pharmaceutical compounds.
Objectives of the present research are to: (a) establish
optimum conditions for the facile oxidation of 2-imida-
zoles to 2-imidazolones; (b) deduce all the possible kinetic
data; (c) elucidate the possible reaction mechanism
(scheme); (d) put forward kinetic rate law; (e) identify the
stoichiometry and oxidation products; (f) ascertain the
reactive species; (g) establish the isokinetic relationship
through activation parameters; and (h) asses the relative
reactivity of imidazoles.
Organic sulfonyl-N-haloamines (N-haloamines) are mild
oxidizing/halogenating/analytical reagents containing a
strongly polarized N-bonded halogen in its ?1 oxidation
state [7]. Kinetics and mechanism of oxidation by these
reagents have attracted the attention of chemists due to
their diverse properties to act as halonium cations, hypo-
halites and N-anions [7]. They interact with a wide range of
functional groups in aqueous, partially aqueous and non-
aqueous media in the presence of an acid or a base. As a
result, these reagents have been used as mild and selective
oxidizing agents in synthetic organic and mechanistic
chemistry [7–12]. The prominent member of this group of
compounds is sodium-N-chloro-p-toluenesulfonamide,
commonly known as chloramine-T (CAT), it is a well-
known oxidizing/halogenating/analytical agent and the
kinetic and mechanistic aspects of many of its reactions
have been well documented [7–13]. Sodium-N-
Results and discussion
Reaction stoichiometry
Varying ratios of CAB to imidazoles in the presence of
5.0 9 10-4 mol dm-3 HClO4 were equilibrated at 303 K
for 48 h. Determination of the unreacted CAB showed that
one mole of the imidazole consumed one mole of CAB in
all the cases. Accordingly, the stoichiometric Eq. (1) can
be formulated (Scheme 1).
Representative oxidation procedure
for the conversion of imidazoles to imidazolones
A mixture of 0.68 g of imidazole, 2.13 g of oxidant
(chloramine-B) in presence of 2.5 cm3 (0.01 mol dm-3) of
123

Conversion of imidazoles to imidazolones with chloramine-B: kinetic and mechanistic study
was investigated at several initial concentrations of the
Scheme 1
N
N
reactants in the presence of HClO4 at 303 K. Similar oxi-
dation-kinetic behavior was observed for all five
imidazoles studied under identical experimental conditions.
O
R
R
N
H
N
H
Imidazole
Imidazolone
HClO4/H2O
30 °C
(1)
+
+
O
S
O
Effect of varying reactant concentrations
on the reaction rate
Cl
+
-
+
NH2
+
Cl
Na
N
S
Na
O
O
Benzenesulfonamide
-COOEt
Chloramine-B
The reactions performed in the presence of HClO4, under
pseudo-first-order conditions of [imidazole]o ꢀ [CAB]o,
gave linear plots of log [CAB] vs. time (R2 [ 0.9884). The
linearity of these plots, together with the constancy of the
slopes for various [CAB]o, indicating a first-order depen-
dence of the rate on [CAB]o. The pseudo-first-order rate
constants (k0/s-1) obtained are listed in Table 2. Under the
same experimental conditions, an increase in [imidazole]o
increased the k0 values (Table 2). Plots of log k0 vs. log
[imidazole] were linear (R2 [ 0.9900) with fractional
slopes (0.27–0.51), showing a fractional-order dependence
of the rate on [imidazole]o. Further, plots of k0 vs. [imi-
dazole] were linear (R2 [ 0.9900) with a y-intercept,
confirming a fractional-order dependence of rate on [imi-
dazole]o. The rate increased with increase in [HClO4]
(Table 2) and plots of log k0 vs. log [HClO4] were linear
(R2 [ 0.9707) with fractional slopes (0.26–0.54), thus
illustrating a fractional-order dependence of rate on [H?].
Further, plots of k0 vs. [H?] were linear (R2 [ 0.9900) with
a y-intercept corresponding to a rate law of the type:
rate = a ? b [H?] and confirming the order to be less than
unity with respect to [H?].
=
R
-CH -C H
, ,
-CHO,
3
2 5
-H,
aqueous perchloric acid was stirred at 303 K for 8–10 h.
After completion of the reaction (monitored by TLC), the
reaction products were neutralized with alkali and extrac-
ted with ether. The organic products were subjected to spot
tests and chromatographic analysis (TLC technique). Fur-
ther, the reaction mixture was extracted with ethyl acetate
and dried over sodium sulfate. The solvent was evaporated
under reduced pressure to obtain crude products. The crude
products were purified on silica gel column by using pet-
roleum ether and ethyl acetate as solvents to get the pure
products. Above analyses revealed the formation of cor-
responding imidazolones as the oxidation products of
imidazoles. 3,5-Dihydroimidazol-4-one, 2-methyl-3,5-di-
hydroimidazol-4-one, 2-ethyl-3,5-dihydroimidazol-4-one,
3,5-dihydro-4-oxoimidazol-2-carbaldehyde, and 3,5-dihy-
dro-4-oxoimidazol-2-ester are the oxidation products of
1H-imidazole, 2-methyl-1H-imidazole, 2-ethyl-1H-imida-
zole, 1H-imidazole-2-carbaldehyde, and 1H-imidazole-2-
ester, respectively. The mass spectra showed a molecular
ion peak at m/z = 84 amu (Fig. 1), 99 amu (M ? 1,
Fig. 2), and 112 amu (Fig. 3), clearly confirming 3,5-di-
Effect of varying benzenesulfonamide (BSA)
on the reaction rate
hydroimidazol-4-one,
2-methyl-3,5-dihydroimidazol-4-
Addition of benzenesulfonamide (BSA) to the reaction
mixture retards the rate (Table 3) while keeping other
experimental conditions constant. Plots of log k0 vs. log
[BSA] were linear (R2 [ 0.9924) with negative fractional
slopes (0.10–0.42), indicating the involvement of BSA
with oxidant in a pre-equilibrium step prior to the rate-
limiting step (rls).
one, and 2-ethyl-3,5-dihydroimidazol-4-one as oxidation
products of 1H-imidazole, 2-methyl-1H-imidazole, and
2-ethyl-1H-imidazole, respectively. Further these products
were confirmed by NMR data (supplementary material,
Figs. 1s–3s). Furthermore, we have succeeded in estimat-
ing the products, imidazolones, in case of all the five
imidazoles. In some typical experiments, the weight of
imidazolones and their percentage yield obtained are
recorded in Table 1. The recovery of imidazolones was
87–93 % yields. Further no reaction was noticed between
oxidation products and CAB under prevailing experimental
conditions.
Effect of varying ionic strength of the medium
on the reaction rate
The effect of ionic strength of the medium on the reaction
rate was carried with 0.2 mol dm-3 NaClO4 solution by
keeping other experimental conditions constant. It was
found that ionic strength had negligible effect on the
reaction rate indicating that non-ionic species are involved
in the rls. Subsequently, the ionic strength of the reaction
mixture was not kept constant for kinetic runs.
Kinetic orders
The kinetics of oxidation of imidazole and 2-substituted
imidazoles (henceforth abbreviated as imidazole) by CAB
123

A. S. Manjunatha, Puttaswamy
Fig. 1 Mass spectrum of 3,5-
dihydroimidazol-4-one with its
parent molecular ion peak at
m/z = 84 amu
Arrhenius plots of log k0 vs. 1/T (R2 [ 0.9988), values of
activation parameters (Ea, DH=, DS=, DG=, and log A) for
the composite reactions were calculated. These data are
tabulated in Table 5.
Effect of varying dielectric constant of the medium
on the reaction rate
The dielectric constant (D) of the medium was varied using
different proportions of MeOH and H2O (0–15 %, v/v),
keeping other experimental conditions constant. The reaction
rateincreasedwithincreaseinmethanolcontent (Table 4) and
plots of log k0 vs. 1/D were found to be linear (R2 [ 0.9933)
with positive slopes. Values of dielectric constant of MeOH-
H2O reported in the literature [17] were employed. Blank
experiments performed showed that MeOH was not oxidized
by CAB under the prevailing experimental conditions.
Effect of Cl2 ion on the reaction rate
The effect of Cl- ion on the rate of the reaction was studied
using 0.2 M NaCl. There was no significant effect of Cl-
on the rate, suggesting no interhalogen or free chlorine was
formed during the reaction sequence.
Polymerization study
Effect of varying temperature on the reaction rate
Addition of acrylamide solution to the reaction mixture did
not initiate polymerization, showing the absence of free
radical species. This clearly ruled out the possibility of free
radical mechanism.
To calculate the activation parameter, the reaction was
studied over a range of temperatures (288–323 K), keeping
other experimental conditions constant. From the linear
123

Conversion of imidazoles to imidazolones with chloramine-B: kinetic and mechanistic study
Fig. 2 Mass spectrum of
2-methyl-3,5-dihydroimidazol-
4-one with its parent molecular
ion peak at m/z = 99 amu
(M ? 1)
Oxidizing species of CAB
parent amide. Dichloramine-T and the free acid undergo
hydrolysis according to reactions (5) and (6). PhSO2NHCl
further protonates to give diprotonated species as shown in
reaction (7). This diprotonated species hydrolyzed to yield
PhSO2NH2 and H2O?Cl species, reaction (8). Finally
hypochlorous acid ionizes according to reaction (9).
Therefore, the possible oxidizing species in acidified CAB
solutions are PhSO2NHCl, PhSO2NCl2, HOCl, and
H2O?Cl.
Chloramine-B, (PhSO2NClNa) like chloramine-T, is a mild
and effective oxidizing agent in both acidic and alkaline
media due to its versatile behavior [7]. In general, CAB
undergoes a two electron change in its reactions forming
the reduction products BSA and NaCl [18]. The redox
potential of CAB/BSA is pH dependent and decreases with
increases in pH of the medium.
Chloramine-B behaves as a strong electrolyte [19] in
aqueous solutions and depending upon the pH of the
medium it furnishes following types of reactive species in
solutions [19–21] (Scheme 2).
Chloramine-B dissociates to give an anion PhSO2NCl-
as shown in reaction (2). The anion picks up a proton in
acid medium to give the free acid PhSO2NHCl according
to reaction (3). This free acid undergoes disproportionation
[20] via reaction (4) giving rise to dichloramine-B and the
If PhSO2NCl2 were to be the reactive species, then the
rate law predicts a second-order dependence of rate on
[CAB]o, see Eq. (4) but experimentally clear first-order
plots were obtained for the disappearance of CAB. Soper
[22] reported that [HOCl] is very small in acidified CAB
solution and is independent of the [CAB]. On the basis of
the above facts, the role of PhSO2NCl2 and HOCl in the
present case can be ignored. Further, Swain and Crist [23]
have pointed out in their studies that hypochlorite ion
123

A. S. Manjunatha, Puttaswamy
Fig. 3 Mass spectrum of
2-ethyl-3,5-dihydroimidazol-4-
one with its parent molecular
ion peak at m/z = 112 amu
formed in a prior equilibrium before the rate-limiting step
is a better electrophile than HOCl. Formation of the species
of the type PhSO2N?H2Cl has been reported with CAB in
acid medium (Eq. (7)). In the present investigations, the
rate of the reaction increases with increase in [H?] but it is
retarded by the added BSA (PhSO2NH2). This indicates
that Eqs. (7) and (8) play a dominant role in the present
case. Furthermore, CAB contains a polar N-Cl bond as the
source of positive chlorine Cl? species, which forms the
conjugate acid, PhSO2NHCl in acidic solutions. The con-
jugate acid with N-Cl bond in fact interacts with the
hydronium ion (H3O?), to form the reactive oxidant spe-
cies H2O?Cl and the BSA (PhSO2NH2) [24]. Hence, the
most reactive oxidizing species in the present case is
H2O?Cl.
shift of 4 nm from 220 to 216 nm of CAB was observed.
This can be probably attributed to complexation between
CAB and imidazole.
In the light of these considerations, a mechanism
(Scheme 3) is formulated for the oxidation of imidazole
and 2-substituted imidazoles with CAB in acid medium to
substantiate the observed experimental results.
A detailed mechanistic interpretation for the Scheme 3
has been worked out in Scheme 4. In Scheme 4, an initial
equilibrium step involves protonation of CAB forming an
active oxidizing species, H2O?Cl with the elimination of
PhSO2NH2 as shown in step (i). In the next pre-equilibrium
fast step (ii) an electrophilic attack of the positive chlorine
of the oxidizing species H2O?Cl at the 5-position of the
imidazole followed by the elimination of a proton and
addition of a proton at the 4-position may give chloro
substituted intermediate complex. In the next slow and rls
step the intermediate complex undergoes a nucleophilic
attack at the iminium carbon by H2O followed by loss of a
Spectroscopic measurements were made for imidazole,
CAB, and a mixture of both. Absorption maxima of 214,
220, and 216 nm for imidazole, CAB and a mixture of both
were noticed in acidic solutions (Fig. 4). A hypsochromic
123

Conversion of imidazoles to imidazolones with chloramine-B: kinetic and mechanistic study
Table 1 Percentage yield of imidazolones obtained from the oxidation of imidazoles with CAB in acid medium
Weight of imidazolone Weight of imidazolone
Yield of
imidazoles / %
Imidazoles
Imidazolones
/ g (found)
/ g (expected)
N
N
O
N
1.20
1.23
89.4
N
H
N
H
N
CH3
N
CH3
O
1.10
1.12
0.98
1.03
1.20
1.19
1.11
1.16
91.6
93.6
87.8
88.8
N
H
H
N
N
H5
H5
C2
C2
O
N
H
N
N
H
N
COOEt
CHO
COOEt
CHO
O
N
N
H
H
N
N
O
N
N
H
H
Experimental conditions: equimolar quantities of CAB and imidazoles were taken to calculate the percentage yield of imidazolones
K1K2k3½CABŠt½ImidazoleŠ½H3OþŠ
molecule of HCl to give the final product imidazolone as
Rate ¼
[PhSO2NH2] + K1[H3Oþ] + K1K2[Imidazole][H3Oþ]
shown in step (iii).
ð15Þ
Deduction of rate law
Rate law (15) is in accordance all observed kinetic data, in
which a first-order dependence of rate on [CAB]o, frac-
tional-order dependence each on [imidazole]o and [H?],
and an inverse-fractional-order on [PhSO2NH2] was
noticed.
From the slow and rate-limiting step (iii) of Scheme 3,
Rate ¼ k3½ComplexŠ
ð10Þ
The value of the complex can be determined as follows: the
total concentration of CAB is given as
Evaluation of reaction constants
[CAB]t ¼ [PhSO2NHCl] þ [H2OþCl] þ [Complex] ð11Þ
From steps (i) and (ii) of Scheme 3,
Since rate = k0 [CAB]t, under pseudo-first-order conditions
of [CAB]o ꢁ\ [imidazole]o, Eq. (15) can be transformed
as:
½PhSO2NH2Š½ComplexŠ
½PhSO2NHCl] =
ð12Þ
ð13Þ
K1K2½H30þŠ½Imidazole]
K1K2k3½ImidazoleŠ½H3OþŠ
k0¼
½PhSO2NH2Š þ K1½H3OþŠ þ K1K2½Imidazole][H3OþŠ
½ComplexŠ
[H2OþCl] ¼
ð16Þ
K2[Imidazole]
By substituting for [PhSO2NHCl] and [H2O?Cl] from
Eqs. (12) and (13) into Eq. (11) and solving for [Complex],
we get
1
½PhSO2NH2Š
1
1
¼
þ
þ
k0 K1K2k3½Imidazole][H3OþŠ K2k3½Imidazole] k3
ð17Þ
ð18Þ
ꢀ
ꢁ
K1K2½CABŠt½ImidazoleŠ½H3OþŠ
1
k0
1
½PhSO2NH2Š
1
1
¼
þ
þ
[Complex] ¼
½Imidazole] K1K2k3½H3OþŠ K2k3
k3
[PhSO2NH2] + K1[H3Oþ] + K1K2[Imidazole][H3Oþ]
ð14Þ
In order to deduce equilibrium and decomposition con-
stants, according to Eqs. (17) and (18), the reaction was
4.0 9 10-4
Upon substituting for [Complex] from Eq. (14) into
Eq. (10), one obtains
studied
at
constant
mol dm-3
123

A. S. Manjunatha, Puttaswamy
Table 2 Effect of varying CAB and imidazole concentrations of the reaction rate at 303 K
k0 9 104/s-1
[CAB]o 9
104/mol dm-3
[imidazole] 9
103/mol dm-3
[HClO4] 9
104/mol dm-3
[BSA] 9
104/mol dm-3
2-EtIzlH
2-MeIzH
IzlH
2-EsIzlH
2-CaIzlH
0.20
0.50
1.00
2.00
4.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
0.10
0.50
1.00
2.00
4.00
1.00
1.00
1.00
1.00
1.00
5.00
5.00
5.00
5.00
5.00
5.00
5.00
5.00
5.00
5.00
1.00
3.00
5.00
10.0
15.0
–
9.15
6.35
5.32
4.93
2.63
–
9.20
6.41
5.30
4.89
2.62
–
9.21
6.39
5.35
4.96
2.65
–
9.25
6.41
5.29
4.94
2.71
–
9.23
6.38
5.38
4.95
2.68
4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
1.96 (1.85)
5.50 (4.70)
9.21 (7.93)
13.4 (11.8)
18.9 (13.2)
2.81 (2.87)
5.56 (5.05)
9.21 (7.93)
11.2 (10.9)
13.4 (13.0)
1.60 (1.55)
4.25 (3.74)
6.39 (4.72)
8.67 (6.02)
14.5 (8.74)
2.06 (2.42)
4.25 (3.92)
6.39 (4.72)
9.38 (5.75)
12.3 (6.89)
1.45 (1.30)
3.35 (2.84)
5.35 (3.74)
6.81 (5.12)
8.67 (6.05)
1.86 (2.05)
3.07 (3.49)
5.35 (3.74)
6.20 (4.56)
7.98 (4.92)
1.32 (1.15)
3.05 (2.31)
4.96 (2.75)
5.90 (3.31)
8.32 (4.01)
1.95 (1.65)
2.80 (2.41)
4.96 (2.75)
5.75 (3.15)
7.42 (3.55)
1.20 (1.02)
2.00 (1.47)
2.65 (1.59)
3.90 (1.75)
5.87 (1.85)
1.72 (1.05)
2.37 (1.29)
2.65 (1.59)
3.62 (2.33)
4.19 (2.89)
Values in parentheses refer to the effect of [imidazole] and [HClO4] in presence of 4.0 9 10-4 mol dm-3 BSA
From the slopes and intercepts of the above plots, the
values of equilibrium constants K1 and K2, and the
decomposition constant k3 were evaluated for all the
imidazoles. These values are recorded in Table 6. The
proposed mechanism and the derived rate law are
supported by the experimental findings given below.
The proposed reaction mechanism is also evinced by the
observed zero effect of ionic strength on the rate of the
reaction. This can be justified by Brønsted and Bjerrum
theory of salt effects [25]. According to this concept, the
effect of ionic strength (l) on the rate for a reaction
involving two ions A and B is given by the relationship:
Table 3 Effect of varying benzenesulfonamide concentration on the
reaction rate at 303 K
[BSA] 9 104/mol dm-3 k0 9 104/s-1
2-
EtIzlH MeIzlH
2-
IzlH 2- 2-
EsIzlH CaIzlH
0
9.21
8.73
7.93
7.29
6.39
5.24
4.72
3.83
5.35 4.96
2.65
2.02
1.59
1.15
2.0
4.0
8.0
4.68 3.62
3.74 2.75
3.09 2.02
[CAB]o = 1.0 9 10-4
mol dm-3
,
[imidazole]o = 1.0 9 10-3
mol dm-3, [HClO4] = 5.0 9 10-4 mol dm-3
log k0 ¼ log k0 þ 1:018ZAZBl1=2
ð19Þ
benzenesulfonamide by varying concentrations of imida-
zole and HClO4 in the concentration range given in
Table 2.
From Eq. (17), plots of 1/k0 vs. 1/[H?] at constant [im-
idazole] and [PhSO2NH2] were linear (Fig. 5;
R2 [ 0.9900) with
Here, ZA and ZB are the values of the ions A and B, and k0
and k0 are the rate constants in the presence and in the
absence of the added electrolyte, respectively. Above
equation shows that a plot of log k0 vs. l1/2 should be linear
with a slope of 1.018 ZAZB and an intercept of log ko. As
the slope of the line depends on ZAZB, i.e., charges of the
reacting ions, three special cases may rise: (a) if A and B
have similar signs, then ZAZB will be positive and the rate
constant k0 increases with Hl; (b) if A and B have dis-
similar charges, then ZAZB will be negative and the rate
constant k0 decreases with Hl; and (c) if either A or B is
uncharged or neutral then ZAZB is equal to zero and k0 is
independent of the ionic strength of the solution. In the
present case, variation of ionic strength of the medium does
not alter the rate of reaction, this clearly signifies that one
½PhSO2NH2Š
Slope ¼
K1K2k3½Imidazole]
1
1
and Intercept ¼
þ
K3k3½Imidazole]
k3
From Eq. (18), plots of 1/k0 vs. 1/[imidazole] at constant
[H?] and [PhSO2NH2] were linear (Fig. 6; R2 = 0.9905)
with
½PhSO2NH2Š
1
1
Slope ¼
þ
and Intercept ¼
K1K2k3[H3Oþ] K2k3
k3
123

Conversion of imidazoles to imidazolones with chloramine-B: kinetic and mechanistic study
Table 4 Effect of varying dielectric constant of the medium on the reaction rate at 303 K
% MeOH (v/v)
D
k0 9 104/s-1
2-EtIzlH
2-MeIzlH
IzlH
2-EsIzlH
2-CaIzlH
0
76.73
74.50
72.37
69.75
9.21
13.1
18.2
25.8
6.39
9.31
12.9
18.4
5.35
8.42
11.1
16.4
4.96
6.29
9.24
12.8
2.65
3.40
5.36
7.22
5
10
15
[CAB]o = 1.0 9 10-4 mol dm-3, [imidazole]o = 1.0 9 10-3 mol dm-3, [HClO4] = 5.0 9 10-4 mol dm-3
Table 5 Effect of varying temperature on the reaction rate and activation parameters for the oxidation of imidazoles by CAB in acid medium
Temperature/K
k0 9 104/s-1
2-EtIzlH
2-MeIzlH
IzlH
2-EsIzlH
2-CaIzlH
288
3.09
4.60
6.34
9.21
13.5
18.5
26.5
34.5
49.8
48.0
89.6
-140
10.0
2.32
3.19
4.68
6.39
9.69
13.2
18.9
25.8
52.6
50.1
92.9
-135
9.77
1.89
2.57
3.87
5.35
7.92
11.0
15.7
21.9
54.7
52.2
93.5
-131
9.61
1.75
2.48
3.58
4.96
6.95
10.1
14.2
21.4
57.6
55.1
93.7
-126
10.0
1.01
1.31
1.89
2.65
3.80
5.32
7.94
10.5
64.3
58.2
95.1
-120
10.3
293
298
303
308
313
318
323
Ea/kJ mol-1
DH=/kJ mol-1
DG=/kJ mol-1
DS=/J K-1 mol-1
Log A
[CAB]o = 1.0 9 10-4 mol dm-3, [imidazole]o = 1.0 9 10-3 mol dm-3, [HClO4] = 5.0 9 10-4 mol dm-3
Scheme 2
Na+
PhSO2NCl-
PhSO2NHCl
+
PhSO2NClNa
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
3.0
2.5
2.0
1.5
1.0
0.5
0.0
H+
C
PhSO2NCl-
+
B
A = Imidazole
B = CAB
+
2 PhSO2NHCl
A
NH2
NH2
PhSO2
PhSO2NCl2
+
+
HOCl
H
C = Imidazole + CAB Mixture
2O
PhSO2
PhSO2NHCl
PhSO2NCl2
+
+
H
2O
PhSO2NHCl HOCl
+
H+
PhSO2 2Cl
NH
+
PhSO2NHCl
+
PhSO2 2Cl
2O+Cl
+
+
H
H
NH2
PhSO2
NH
2O
H+
-
+
HOCl
OCl
of the reactant species is a neutral molecule as seen in
slow/rls of Scheme 4. Hence, the observed ionic strength
effect is in agreement with the above theory.
200
250
300
350
400
Wavelength/nm
The effect of changing solvent composition on the rate
of reaction has been described in detail in various
Fig. 4 UV-Vis spectra of (A) imidazole, (B) CAB, and (C) a mixture
of both in an acid medium
123

A. S. Manjunatha, Puttaswamy
ꢂ
ꢃ
NZAZBe2
monographs [26–30]. The dependence of the rate constant
on the dielectric constant of the medium is given by the
following relationship:
ln k0 ¼ ln k00
ð20Þ
DRTr#
0
In this equation, ko is the rate constant in a medium of
infinite dielectric constant, ZAe and ZBe are the total
charges on the ions A and B, r# is the radius of the acti-
vated complex, R, T, and N have their usual meanings. The
equation predicts a linear plot of log k0 vs. 1/D with a
negative slope if the charges on the ions are of the same
sign and a positive slope if they are opposite sign. The
positive dielectric effect observed in the present study
(Table 4) clearly supports the involvement of dissimilar
charges in the rate-limiting step (Scheme 4).
Scheme 3
K1
3O+
Imidazole
Complex
+
+
NH2
PhSO2
2O+Cl
H
H
PhSO2NHCl
fast
(i)
K2
k3
2O+Cl
+
H
fast
Complex
Products
(ii)
(iii)
slow & rls
Scheme 4
O
S
O
Cl
(i)
K1
(fast)
3O+
N
+
+
NH2
S
H
H
2O+Cl
Na
O
O
Benzenesulfonamide
Chloramine-B
N
N
N
K2
(ii)
2O+Cl
+ H
-H+
-H2
O
(fast)
Cl
Cl
R
R
R
N
H
N
N
H
H
H
+H+
N
Imidazole
R
Cl
N
H
Intermediate
(iii)
Cl
N
N
N
k3
and
-H+
Cl
(slow
rds)
Cl
H
R
R
N
R
N
H
N
H
H
O
..
O
H
2O
H
H
Intermediate
-HCl
N
O
R
N
H
Imidazolone
123

Conversion of imidazoles to imidazolones with chloramine-B: kinetic and mechanistic study
10000
2-EtIzlH in comparison with 2-MeIzlH can be endorsed
2-EtIzlH
2-MeIzlH
IzlH
2-EsIzlH
2-CaIzlH
due to the differences in the electron donating effect of the
-C2H5 and -CH3 groups and also through the positive
inductive effect, thereby enhancing the electron density by
imidazolium ring make the reaction very fast. Furthermore,
2-CaIzlH have least reactive assessment with 2-EsIzlH
because the attached electron withdrawing group in
2-CaIzlH rapidly decreases the nucleophilicity on the aro-
matic ring than electron withdrawing group present in
2-EsIzlH.
8000
6000
4000
2000
0
Isokinetic relationship
The rate constants and activation energies in Table 5 reveal
that activation energy is highest for the slowest reaction
and vice versa as expected indicating that the reaction is
under enthalpy control. This is verified by calculating the
isokinetic temperature (b) from the slope of the linear plot
of DH= vs. DS= (Fig. 7; R2 = 0.9987). The value b found
is 453 K, which is higher than the experimental tempera-
ture (303 K) employed in the present work. The genuine
nature of isokinetic relationship was a0lso tested through the
Exner criterion [31] by plotting log k (303K) vs. log k0(293K)
(Fig. 7; R2 = 0.9993). The isokinetic temperature b can be
evaluated from the expression: b = T1T2(q - 1)/
(qT2 - T1) where q is the slope of the Exner plot; b was
found to be 449 K. The proposed mechanism is also sup-
ported by the moderate values of energy of activation and
other activation parameters. The fairly high negative DS=
values reflect a greater degree of ordering in the transition
state than the initial state, due to an increase in solvation
during the solvation process. The near constancy of DG=
values indicates that the same types of reaction mechanism
could be operative for all the five imidazoles studied.
0
2000
4000
6000
1/[H+]
8000
10000
Fig. 5 Plots of log 1/k‘vs. 1/[H?] at constant [BSA]
2- EtIzlH
2- MeIzlH
IzlH
2- EsIzlH
2- CaIzlH
10000
8000
6000
4000
2000
0
0
2000
4000
6000
8000
10000
1/[Imidazole]
Fig. 6 Plots of log 1/k‘vs. 1/[imidazole] at constant [BSA]
Table 6 Values of equilibrium and decomposition constants
Conclusion
Substrate
K1 9 102
K2 9 103
k3 9 104
In the course of this research, optimum conditions for the
facile oxidative conversion of imidazole (IzlH) and 2-
substituited imidazoles viz., 2-ethyl-1H-imidazole (2-EtI-
zlH), 2-methyl-1H-imidazole (2-MeIzlH), 1H-imidazole-2-
ester (2-EsIzlH), and 1H-imidazole-2-carbaldehyde (2-
CaIzlH) to the corresponding imidazolones with chlo-
ramine-B have been developed in acid medium. These
reactions follow identical kinetics with a rate law:
y
/dm-3mol-1
/s-1
2-EtIzlH
2-MeIzlH
IzlH
25.0
14.5
14.8
50.8
41.7
2.66
6.50
3.50
25.0
14.2
12.5
7.70
7.14
3.84
1.69
2-EsIzlH
2-CaIzlH
x
Àz
Àd½CABŠ=dt ¼ k½CABŠ ½imidazoleŠ ½HþŠ ½BSAŠ
o
o
It can be seen from the Table 5 that the rate of oxidation
of imidazoles by CAB in presence of HClO4 increases in
the order: 2-EtIzlH [ 2-MeIzlH [ IzlH [ 2-EsIzlH [ 2-
CaIzlH. This trend due to combined effect of the electronic
and steric factors of the substitutents attached to the 2-
position of imidazole ring. The higher reactivity of
where x, y, and z \ 1; BSA is benzenesulfonamide. Acti-
vation parameters and reaction constants have been
deduced. The isokinetic temperature was evaluated.
The rate of oxidation of imidazoles follows the order:
2-EtIzlH [ 2-MeIzlH [ IzlH [ 2-EsIzlH [ 2-CaIzlH.
A
123

A. S. Manjunatha, Puttaswamy
Fig. 7 Isokinetic plots of0
(a) log k‘0(303K) vs. log k‘ (293K)
(b) DH= vs. DS=
1.0
0.9
0.8
0.7
0.6
0.5
0.4
58
56
54
52
50
48
(a)
(b)
(a)
0.1
120
0.2
0.3
0.4
130
0.5
0.6
0.7
140
4+log k'(293K)
(b) -ΔS#
125
135
suitable reaction scheme is proposed and an appropriate
rate law is deduced to account for the observed experi-
mental results. The present method offers many advantages
including high yield, simplicity, short reaction times, cost-
effectivity and involvement of non-toxic reagents which
make the reaction process is simple, smooth, and envi-
ronmentally benign. Hence, this redox system can be
scaled up to industrial process with suitable modification.
[oxidant]o in acid medium at 303 K. The progress of the
reaction was monitored by the iodometric method. The
experimental procedure we followed here was identical to
that reported earlier [15]. The course of the reaction was
studied for at least two half-lives. The pseudo-first-order rate
constants (k0/s-1) calculated from the linear plots of log
[CAB] vs. time. All the kinetic runs were carried out twice to
check the reproducibility. The values are found to be
reproducible within 3–6 % error. Regression coefficient
(R2) were calculated using fx - 100 W scientific calculator.
Experimental
Acknowledgments The authors are thankful to Prof. M. A. Pasha of
this Department for his valuable suggestions on the proposed reaction
scheme.
Sigma make chloramine-B was purified by the method of
Morris et al. [20]. An aqueous solution of CAB was prepared
and standardized by iodometric method. 2-Ethyl-1H-imi-
dazole and 1H-imidazole-2-carbaldehyde (Sigma),
2-methyl-1H-imidazole (SRL Pvt. Ltd., India), 1H-imida-
zole (SD Fine Chem. Ltd., India) and 1H-imidazole-2-ester
(Avra Synthesis Pvt. Ltd., India) were of acceptable grades
of purity and were used as received. Aqueous solutions of the
compounds were used for kinetic studies. Reagent grade
chemicals and doubly distilled water were used throughout
the experiment. SL 159 Elico UV–Vis spectrophotometer
was used for studying the formation of intermediate com-
plex. GC–MS data were obtained on a 17A Shimadzu gas
chromatograph with a QP-5050A Shimadzu mass spec-
trometer. NMR spectra were obtained on a Bruker WH
400-MHz nuclear magnetic resonance spectrometer.
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