Kinetic and mechanistic investigations and thermodynamic quantities for different steps involved in the mechanism of oxidation of procainamide by hexacyanoferrate(III) in aqueous alkaline medium: a spectrophotometric study

Article abstract of DOI:10.1007/s00706-015-1410-2

The kinetics of oxidation of procainamide by alkaline hexacyanoferrate(III) at a constant ionic strength of 1.10 mol dm^-3 has been studied spectrophotometrically at 25°C. The stoichiometric analysis indicates that one mole of procainamide requires two moles of hexacyanoferrate(III). The reaction products are identified and confirmed by IR, NMR, and GC-MS spectral studies. The reaction is first order with respect to oxidant, Fe(CN) ₆ ^3- and less than unit order with respect to procainamide and alkali concentrations. Increasing ionic strength and decreasing dielectric constant of the medium increases the rate of reaction. The added products did not have any significant effect on the rate of reaction. Based on the experimental results, a suitable mechanism is proposed and the following rate law is derived and verified. Activation parameters are evaluated with respect to the slow step of the mechanism and thermodynamic quantities are also calculated. Voltammetric behavior of procainamide is also made.

Full text of DOI:10.1007/s00706-015-1410-2

Monatsh Chem
DOI 10.1007/s00706-015-1410-2
ORIGINAL PAPER
Kinetic and mechanistic investigations and thermodynamic
quantities for different steps involved in the mechanism
of oxidation of procainamide by hexacyanoferrate(III) in aqueous
alkaline medium: a spectrophotometric study
M. D. Meti
S. T. Nandibewoor
•
M. H. Lamani
•
•
A. G. Naikar
•
S. S. Sutar
•
S. A. Chimatadar
Received: 20 May 2014 / Accepted: 2 January 2015
Ó Springer-Verlag Wien 2015
Abstract The kinetics of oxidation of procainamide by
alkaline hexacyanoferrate(III) at a constant ionic strength
Graphical abstract
-
3
of 1.10 mol dm has been studied spectrophotometrically
at 25 °C. The stoichiometric analysis indicates that one
mole of procainamide requires two moles of hexacyano-
ferrate(III). The reaction products are identified and
confirmed by IR, NMR, and GC–MS spectral studies. The
O
N
N
H
3
-
+
2 [Fe(CN)6
]
+
3 H2
O
H
2
N
O
H
2
N
H
H
]4-
+
2 OH-
OH
+
+
2 C
2
H
6
+
2
[Fe(CN)
6
3
-
reaction is first order with respect to oxidant, Fe(CN) and
NH2
6
H
2
N
less than unit order with respect to procainamide and alkali
concentrations. Increasing ionic strength and decreasing
dielectric constant of the medium increases the rate of
reaction. The added products did not have any significant
effect on the rate of reaction. Based on the experimental
results, a suitable mechanism is proposed and the following
rate law is derived and verified. Activation parameters are
evaluated with respect to the slow step of the mechanism
and thermodynamic quantities are also calculated. Vol-
tammetric behavior of procainamide is also made.
4
-Aminobenzoic acid
(E)-Ethene-1,2-diamine
Keywords Hexacyanoferrate(III) ꢀ Procainamide ꢀ
Kinetics ꢀ Oxidation ꢀ Thermodynamic parameters
Introduction
Procainamide is a pharmaceutical antiarrhythmic agent
used for the medical treatment of cardiac arrhythmias and
also used for both supraventricular and ventricular
arrhythmias indicated in the treatment of premature ven-
tricular contractions, ventricular tachycardia, atrial
fibrillation, and paroxysmal atrial tachycardia [1]. Pro-
cainamide’s
major
active
metabolite
is
N-
acetylprocainamide (NAPA), which is approximately
equipotent with the parent drug as an antiarrhythmic agent
[
2]. NAPA has an elimination half-life about twice that of
Electronic supplementary material The online version of this
article (doi:10.1007/s00706-015-1410-2) contains supplementary
material, which is available to authorized users.
procainamide, and it can reach somewhat higher plasma
levels during chronic procainamide administration [3].
Procainamide measurement in plasma is advocated as a
useful, if not mandatory, guide to therapy. The accepted
therapeutic concentration range for procainamide hydro-
M. D. Meti ꢀ M. H. Lamani ꢀ A. G. Naikar ꢀ
S. S. Sutar ꢀ S. T. Nandibewoor ꢀ S. A. Chimatadar (&)
P. G. Department of Studies in Chemistry, Karnatak University,
Pavate Nagar, Dharwad 580003, India
3
chloride (PAH) is 4–8 mg/dm , but its major metabolite, N-
e-mail: schimatadar@gmail.com
acetylprocainamide, which also has an antiarrhythmic
123

M. D. Meti et al.
effect in humans, is found in similar concentrations in the
plasma of patients who are undergoing therapy with pro-
cainamide. Therefore, therapy can be optimal only if both
procainamide and N-acetylprocainamide are considered
(1) accumulate the kinetic data, (2) intermediate detection
and product analysis, (3) concentration determination of all
species present, (4) deciding on a method of following the
rate, (5) kinetic analysis, (6) determination of the mecha-
nism, (7) design kinetic rate laws, (8) deduce
thermodynamic parameters, and (9) characterize the pro-
ducts. We have also studied the electrooxidation of
procainamide by glassy carbon electrode.
[
4]. The chemical structure of procainamide hydrochloride
is shown in Fig. 1.
Hexacyanoferrate(III) has been widely used to oxidize
numerous organic and inorganic compounds in alkaline and
acidic media. Literature survey reveals [5, 6] that alkaline
hexacyanoferrate(III) ion simply acts as an electron
abstracting reagent in redox reactions. However, [7] have
suggested different paths of oxidation of aldehydes, ketones,
and nitroparaffins by hexacyanoferrate(III). While [8, 9]
discussing the oxidation of formaldehyde, acetone, and ethyl
methyl ketone by hexacyanoferrate(III), they have suggested
that the oxidation takes place via an electron transfer process
resulting in the formation of a free radical intermediate. In
alkaline medium, the redox potential [10] of the couple
Results and discussion
Stoichiometry and product analysis
Different sets of reaction mixtures containing varying ratios
of hexacyanoferrate(III) to PAH in the presence of constant
-
amount of OH , KNO and at constant ionic strength of
3
-
3
1.10 mol dm were allowed to react for about 5 h at 25 °C
under nitrogen atmosphere in a closed vessel. The remaining
concentration of hexacyanoferrate(III) was assayed by
measuring the absorbance at 420 nm. The results indicated
that two moles of hexacyanoferrate(III) reacted with one
mole of procainamide as given in Scheme 1.
3
6
ꢁ
4ꢁ
FeðCNÞ = FeðCNÞ6 is þ 0:450 V:
Thus, the study of PAH becomes important because of
its biological significance and selectivity towards the oxi-
dants. In view of the lack of literature on the oxidation of
PAH by hexacyanoferrate(III), and to explore the mecha-
nistic aspects of hexacyanoferrate(III) oxidation in alkaline
medium, we have studied the title reaction. The main
important objectives of the present kinetic investigation are
After the completion of the reaction, the reaction mix-
ture was acidified, concentrated, and extracted with ether.
The major products were identified as 4-aminobenzoic acid
and (E)-ethene-1,2-diamine, which was separated by col-
umn chromatography using hexane: ethyl acetate as eluent.
The IR spectrum of 4-aminobenzoic acid showed a sharp
O
.
HCl
-1
band at 1,672 cm which corresponds to carbonyl group
N
-1
stretching. The bands at 3,366 and 3,465 cm are due to
N
H
symmetric and asymmetric stretching of -NH group (suppl.
2
1
Fig. 1). The H NMR spectral analysis of 4-aminobenzoic
H N
2
acid exhibited a doublet at 6.54 ppm due to aromatic protons.
One more doublet of aromatic protons resonated at 7.59 ppm
Fig. 1 The chemical structure of procainamide hydrochloride
Scheme 1
O
N
N
H
+
2 [Fe(CN)6]3 + 3 H O
-
2
H N
2
O
H N
H
2
+ 2 C H + 2 [Fe(CN)6]4- + 2 OH-
2
6
OH
+
H
NH2
H N
2
4
-Aminobenzoic acid
(E)-Ethene-1,2-diamine
.
1
23

Kinetic and mechanistic investigations
Fig. 2 GC-MS spectrum of the product 4-aminobenzoic acid showed base peak at 120 amu and molecular ion peak at 137 amu
1
suppl. Fig. 2). The C NMR spectral analysis of 4-amino-
3
(
Table 1 Effect of variation of hexacyanoferrate(III), procainamide,
-
and OH on the oxidation of procainamide by hexacyanoferrate(III)
at 25 °C and I = 1.10 mol dm
benzoic acid exhibited a peak 167 ppm due to carboxylic
acid carbon. A signal at 153 ppm is attributed to aromatic
-
3
3
-
4
] 9 10 /
3
[PAH] 9 10 /
-3
mol dm
-
[OH ]/
mol dm
3
carbon adjacent to –NH carbon a peak at 131 ppm is due to
2
[Fe(CN)
mol dm
6
3
kobs 9 10 /
-
-3
-1
s
aromatic carbons, one more peak at 116.854 ppm is attrib-
uted to aromatic carbon adjacent to carboxylic group and
remaining two aromatic carbons resonated at 112.52 ppm
0
1
2
3
5
2
2
2
2
2
2
2
2
2
2
.50
.0
.0
.0
.0
.0
.0
.0
.0
.0
.0
.0
.0
.0
.0.
2.0
2.0
2.0
2.0
2.0
0.50
1.0
2.0
3.0
5.0
2.0
2.0
2.0
2.0
2.0
0.5
1.40
1.43
1.49
1.41
1.37
0.55
0.81
1.49
1.91
2.85
0.59
1.05
1.49
2.02
3.47
0.5
(
suppl. Fig. 3). The GC–MS analysis of 4-aminobenzoic acid
showed a base peak at 120 amu and molecular ion peak at
37 amu (Fig. 2). Another product (E)-ethene-1,2-diamine
0.5
0.5
1
0.5
was confirmed by its GC–MS spectrum, which showed a
molecular ion peak at 58 amu (suppl. Fig. 4).
0.5
0.5
0.5
Reaction order
0.5
0.5
The reaction orders were determined from the slope of the
plots of log kobs vs. log(concentration) by varying the
concentrations of procainamide and alkali in turn while
keeping all other concentrations and conditions constant.
0.10
0.30
0.50
0.70
1.00
Effect of [hexacyanoferrate(III)]
At constant concentration of procainamide, alkali and at
reaction. This also indicates first order with respect to
hexacyanoferrate(III).
-
3
constant ionic strength, I = 1.10 mol dm , the hexa-
-
4
cyanoferrate(III) concentration varied from 0.5 9 10
-3
(Table 1). The order with
-
to 5.0 9 10 mol dm
4
Effect of [procainamide]
respect to hexacyanoferrate(III) concentration was found
to be unity, since the rate constant kobs was constant at
different hexacyanoferrate(III) concentrations. The
pseudo-first order plots under these conditions were
almost parallel and linear over 70 % completion of the
The substrate, procainamide concentration was varied in
-3
-
the concentration range of 0.5 9 10 –5.0 9 10
3
-
3
mol dm at 25 °C (Table 1), keeping all other conditions
constant. The rate constant, kobs, increased with increase in
123

M. D. Meti et al.
the concentration of procainamide. From the slope of the
plot of log kobs vs. log [PAH], the order with respect to
procainamide concentration was found to be less than unity
where u
1
and u are volume fractions; and D and D are
2 1 2
dielectric constants of water and t-butyl alcohol as 78.5 and
10.9 at 298 K, respectively. For example, at u (t-butyl
alcohol) = 10 %
(
0.72).
D ¼ ð78:5 ꢂ 90Þ=100 þ ð10:9 ꢂ 10Þ=100 ¼ 71:74:
Effect of [alkali]
In the same way, the values of D were calculated at the
other percentage of t-butyl alcohol. The solvent did not
react with the oxidant under the experimental conditions.
The solvent composition, t-butyl alcohol/water of the
The effect of alkali concentration on the reaction was
-
3
studied in the range 0.1–1.0 mol dm (Table 1) at con-
stant concentrations of procainamide, hexacyanoferrate(III)
-
3
reaction mixture was varied up to
u
(t-butyl
and at constant ionic strength of 1.10 mol dm at 25 °C.
The rate constant increased with increase in the alkali
concentration. The order was found to be less than unity
alcohol) = 30 %. On decreasing the dielectric constant of
the reaction medium, an increase in the rate was observed,
and the plot of log kobs vs. 1/D was linear with a positive
slope (Fig. 3).
(
0.79).
Effect of ionic strength and dielectric constant
Effect of added products
At constant concentration of reactants and keeping other
conditions constant as well, the ionic strength was var-
ied by varying the concentration of potassium nitrate
The effect of initially added products, hexacyanoferrate(II)
and p-aminobenzoic acid did not have any significant effect
on the rate of reaction.
-
3
between 0.50 and 1.40 mol dm and the rate was found
to increase with increasing ionic strength. A plot of log
kobs vs. HI is linear with positive slope (Fig. 3). The
effect of dielectric constant was studied by varying the
t-butanol/water volume fraction u in the reaction mix-
ture with all other conditions being maintained constant.
Since dielectric constants of aqueous t-butanol mixtures
are not available in literature, they were computed from
the values of pure liquids [11]. The dielectric constants
of the reaction medium at various composition of t-butyl
alcohol/water were calculated using the following
equation:
Test for free radicals (polymerization study)
The intervention of free radicals in the reaction was exam-
ined as follows: The reaction mixture, to which a known
quantity of acrylonitrile scavenger had been initially added,
was kept for 5 h in a nitrogen atmosphere. On diluting the
reaction mixture with methanol, no precipitate resulted,
indicating the absence of free radicals in the reaction.
Effect of temperature
D ¼ u D1 þ u D2;
1
2
The rate of reaction was measured at different temperatures
1
5, 25, 35, and 45 °C under varying alkali and procain-
1
/D x 10–2
amide concentrations. The rate was found to increase with
the increasing temperature. The rate constant, k, of slow
step, K , the value of first equilibrium step and K , the
1
.0
1.4
1.8
0
0
0
0
.8
.6
.4
.2
1
1
0
0
.5
.1
.7
.3
1
2
value of second equilibrium step of Scheme 1 were
obtained from the slopes and intercepts of the plots of 1/
-
kobs vs. 1/[PAH] and 1/kobs vs. 1/[OH ] at four different
temperatures and are given in Table 2. The data were
subjected to least square analysis. The enthalpy of activa-
#
#
tion, DH and entropy of activation, DS were obtained by
Eyring equation in both cases [12]
ꢀ
ꢁ
kBT
6
kBT
6
6¼
ðꢁDG =RTÞ
ꢁ DH þ TDS =RT
k ¼
exp
¼
exp
;
h
h
ð1Þ
where k is the rate constant, k is Boltzmann’s constant,
0.0
0.6
0.8
1.0
1.2
1.4
1.6
B
√I
h is Planck’s constant, R is the gas constant, T is the
#
absolute temperature and DG is the Gibbs energy of
activation. The linear form of Eq. (1) is
Fig. 3 Effect of ionic strength and dielectric constant on the
oxidation of procainamide by alkaline hexacyanoferrate(III)
1
23

Kinetic and mechanistic investigations
Table 2 Activation parameters and thermodynamic quantities for the oxidation of procainamide by hexacynaoferrate(III) in alkaline medium
with respect to the slow step of Scheme 3
(
A) Effect of temperature and activation parameters
3
k 9 10 /s
-1
Temperature/K
Parameters
Values
59 ± 2
-
1
288
298
308
318
1.19
3.70
5.78
13.4
a
E /kJ mol
#
-1
DH /kJ mol
56 ± 6.3
-123 ± 21
93 ± 0.52
8 ± 0.2
#
-1
-1
DS /J K mol
#
-1
DG /kJ mol
log A
(
B) Effect of temperature on first and second equilibrium step of Scheme 3
3
/dm mol
-1
-3
3
-1
Temperature/K
K
1
2
K 9 10 /dm mol
2
2
3
3
88
98
08
18
0.18
0.28
0.49
0.74
and K
4.48
3.37
2.30
1.66
(
C) Thermodynamic quantities with respect to K
1
2
Thermodynamic quantities
Values from K
1
Values from K
2
-
1
DH/kJ mol
37
113
3.2
-26
-19
-20
-1
-1
DS/J K mol
DG298/kJ mol
-
1
6
¼
6
first cycle was generally recorded. However, no peak was
observed in the reverse scan, suggesting that the oxidation
process is an irreversible one. In Fig. 4, (a) is bare electrode
and (b) is oxidation of PAH with buffer (pH 7.0).
k
DH
RT
DS
kB
ln ¼ ꢁ
þ þ ln h
:
ð2Þ
T
R
The slope of the plot of log k/T vs. 1/T gives the value of
#
enthalpy of activation, DH . By using this value of DH ,
and the rate constant at a particular temperature T, the
#
The variation of the concentrations of the oxidant, sub-
strate, and alkali, while keeping other conditions constant,
showed that the reaction is first order in oxidant, less than
unit order in substrate and alkali concentrations. The reac-
tion between procainamide and hexacyanoferrate(III) has a
stoichiometry of 1:2. Based on the experimental results, a
mechanism is proposed for which all the observed orders in
#
value of entropy of activation, DS was obtained by simple
rearrangement of Eq. (1). Using these values of DH and
DS , the free energy of activation DG was obtained and
values are given in Table 2. A van’t Hoff plot was drawn
for the variation of K and K with temperature, i.e., (log
#
#
#
1
2
K vs. 1/T and log K vs. 1/T). The values of enthalpy of
1
-
each constituent such as [oxidant], [reductant], and [OH ]
reaction DH, entropy of reaction DS, and free energy of
reaction DG, were calculated, and these values are given in
Table 2. A comparison of these values obtained for the
slow step shows that the reaction before the rate
determining step is fairly fast as it involves low
activation energy.
may be well accommodated. Oxidation of procainamide by
hexacyanoferrate(III) in alkaline media is a non-comple-
mentary reaction with two moles of oxidant reacts with one
mole of substrate. Based on the experimental rate law, the
kinetic model is presented as Scheme 2.
The mechanism (Scheme 3) involves combination of
alkali with procainamide to give the anionic form of pro-
cainamide in a prior equilibrium step, which is also
Cyclic voltammetric behavior of procainamide
-
supported by the observed fractional order in [OH ] and
The electrochemical behavior of PAH at glassy carbon
electrode was investigated using cyclic voltammetry (CV) at
physiological pH 7.0. The cyclic voltammograms obtained
[PAH]. Hexacyanoferrate(III) then reacts with anionic form
of procainamide to give a complex (C). This complex
(C) undergoes decomposition in a slow step to give 4-ami-
-4
-1
4-
1
1
for 1.0 9 10 mol dm PAH solution at a scan rate of
0 mV/s exhibit a well-defined irreversible anodic peak at
nobenzoic acid, [Fe(CN)6 ] and intermediate of N ,N -
5
diethylethane-1,2-diamine. In a subsequent fast step this
1
1
about 0.9139 V at glassy carbon electrode. The results are
shown in Fig. 4. The voltammograms corresponding to the
intermediate of N ,N -diethylethane-1,2-diamine decom-
poses to give (E)-ethene-1,2-diamine with elimination of
123

M. D. Meti et al.
h
From Eqs. (3) and (4), we have
i
ethane as a by-product. All these results were proposed in a
detailed mechanistic as shown in Scheme 3.
3ꢁ
6
½
Cꢃ ¼ K2 Anionic form of PAHꢃ ½FEðCNÞ
:
Since Scheme 3 is in accordance with the generally
well-accepted principle of non-complementary oxidations
taking place in sequence of one-electron steps. Spectro-
scopic evidence for the complex formation between
oxidant and substrate was obtained from UV–Vis spectra of
h
From the first step of Scheme 3, we have
ꢁi
3
6
Rate ¼ kK Anionic form of PAHꢃ ½FEðCNÞ
:
ð5Þ
2
-
4
-3
hexacyanoferrate(III) (2.0 9 10 mol dm ) and PAH
-
2.0 9 10 mol dm ) a mixture of both (suppl. Fig. 5).
3
-3
½Anionic form of PAHꢃ
K ¼
(
1
ꢁ
½
PAHꢃ ½OH ꢃ
A hypsochromic shift of about 10 nm from 275 to 265 nm
ꢁ
in the spectra of procainamide to mixture of hexacyano-
½Anionic form of PAHꢃ ¼ K ½PAHꢃ ½OH ꢃ:
ð6Þ
ð7Þ
1
ferrate(III) and PAH was observed.
Substituting Eq. (6) in Eq. (5),
From Scheme 3, the rate [Eq. (13)] can be derived as
follows:
ꢁ
3ꢁ
Rate ¼ k K1K2 ½PAHꢃ ½OH ꢃ ½FeðCNÞ ꢃf :
3-
f
f
6
3
ꢁ
Rate ¼
¼ k½Complexꢃ:
ð3Þ
ð4Þ
The total concentration of [Fe(CN)
6
] is given by
dt
3
6
ꢁꢃT ¼ ½FeðCNÞ3ꢁ
½
FeðCNÞ
ꢃf þ C
From the second step of Scheme 3, we have
6
3ꢁ
ꢁ
3ꢁ
¼
½FeðCNÞ ꢃ þ K1K2 ½PAHꢃ ½OH ꢃ ½FeðCNÞ ꢃf
6
f
f
f
6
½
Cꢃ
K2 ¼
3ꢁ
ꢁ
f
Anionic form of PAHꢃ½FEðCNÞ ꢁꢃ
3
6
¼ ½FeðCNÞ6 ꢃ þ ð1 þ K K ½PAHꢃ ½OH ꢃ Þ;
f
1
2
f
½
3
6
-
where [Fe(CN) ]f and [Fe(CN)6 ]T refer to free and total
3-
3
[
[
Fe(CN) ] concentration, respectively. Therefore, free
6
-
Fe(CN) ]f is given by
3
6
3
6
ꢁ
T
½
FeðCNÞ
ꢃ
FeðCNÞ ꢁꢃf ¼
3
6
:
ð8Þ
½
ꢁ
ð1 þ K1K2½Sꢃ ½OH ꢃ
Similarly,
ꢁ
ꢁ
½
½
OH ꢃ ¼ ½OH ꢃ þ ½Anionic form of PAHꢃ ½Cꢃ
T
f
OHꢁꢃ ¼ ½OH ꢃ þ K ½PAHꢃ ½OH ꢃ
ꢁ
ꢁ
T
f
1
ꢁ
3ꢁ
þ K1K2½PAHꢃ ½OH ꢃ½FEðCNÞ
ꢃ
6
ꢁ
½
OH ꢃ
ꢁ
T
½
OH ꢃ ¼
:
f
ꢁ
ꢁ
3ꢁ
1
þ K1½PAHꢃ ½OH ꢃ þ K1K2½PAHꢃ ½OH ꢃ½FEðCNÞ
ꢃ
6
3
6
-
In view of low concentration of [PAH] and [Fe(CN)
3
]
Fig. 4 Cyclic voltammograms at the glassy carbon electrode in
phosphate buffer solution (pH 7): a in the presence bare pH 7; b in the
-
used, the terms K [PAH] and K K [PAH] [Fe(CN) ] are
1
1
2
6
-
4
-1
presence of procainamide (1.0 9 10 M) at the scan rate 0.05 V s
neglected compared to unity. Therefore,
Scheme 2
PAH + OH-
Anionic form of PAH + H O
2
Anionic form of PAH + [Fe(CN)6]3-
Complex (C)
Complex (C) + 2 H O
Product + Intermediate + [Fe(CN)6]4-
Final Products + [Fe(CN)6]4-
2
Intermediate + [Fe(CN)6]3-
.
1
23

Kinetic and mechanistic investigations
Scheme 3
O
O
N
N
N
H
K
1
N
+ OH-
+ H O
2
H N
H N
2
2
O
N
N
K2
+
[Fe(CN)
6
]3-
(Complex)4-
H N
2
O
k
OH
Complex)4-
+
2 H O
+ [Fe(CN)6]4- + OH-
+
N
(
2
H N
slow
2
H N
2
1
1
4
-Aminobenzoic acid
N ,N -Diethylethane-1,2-diamine
H N
H
2
fast
+ [Fe(CN)6]3- + 2 H O
+ 2 C H6 + [Fe(CN)6]4- + 2 OH-
N
2
2
H N
2
H
NH2
1
1
N ,N -Diethylethane-1,2-diamine
(E)-Ethene-1,2-diamine
.
ꢁ
3ꢁ
ꢁ
ꢁ
kK K ½PAHꢃ ½OH ꢃ ½FeðCNÞ
ꢃ
1
2
T
T
6
T
½
OH ꢃ ¼ ½OH ꢃ :
ð9Þ
f
T
Rate ¼
1
ꢁ
ꢁ
2
ꢁ 2
þ K1K2½PAHꢃ ½OH ꢃÞ þ K1½OH ꢃ þ ðK K2 ½OH ꢃ ½PAHꢃ
1
In the similar way, [PAH] was also calculated as
f
ð11Þ
In view of low concentration of [PAH] used, the terms
-
K K [OH ] [PAH] are neglected. Therefore,
follows:
½
PAHꢃ ¼ ½PAHꢃf þ ½Anionic form of PAHꢃ þ ½Cꢃ
T
2
1
2
ꢁ
¼
½PAHꢃ þ K1 ½PAHꢃ½OH ꢃ þ K2 ½Anionic form of PAHꢃ
f
ꢁ
3ꢁ
kK1K2½PAHꢃ ½OH ꢃ ½FeðCNÞ
ꢃ
3
ꢁ
T
T
6
T
ꢂ ½FeðCNÞ
ꢃ
Rate ¼
:
6
ꢁ
ꢁ
2
1
ꢁ 2
ð1 þ K1K2½PAHꢃ ½OH ꢃÞ þ K1½OH ꢃ þ ðK K2 ½OH ꢃ ½PAHꢃÞ
ꢁ
ꢁ
¼
½PAHꢃ þ K1 ½PAHꢃ½OH ꢃ þ K1K2½PAHꢃ½OH ꢃ
f
ð12Þ
3
ꢁ
ꢂ ½FeðCNÞ
ꢃ
6
Or
½
PAHꢃT
ꢁ
T
Rate
½Fe(CNÞ 36 ꢁ
kK K ½PAHꢃ ½OH ꢃ
1
2
ꢁ
½
PAHꢃ ¼
:
T
f
3ꢁ
kobs
¼
¼
:
ꢁ
ꢁ
1
þ K1 ½OH ꢃ þ K1K2½OH ꢃ ½FeðCNÞ
ꢃ
In view of low concentration of [Fe(CN) ] used, the
ꢁ
6
ꢃ
1 þ K1½OH ꢃ þ K1K2 ½PAHꢃ½OH ꢃ
3
-
ð12Þ
6
-
terms K K [OH ] [Fe(CN) ] are neglected. Therefore,
3-
6
1
2
Further Eq. (12) can be rearranged to Eq. (13), which is
suitable for verification.
½
PAHꢃT
½
PAHꢃ ¼
:
ð10Þ
f
ꢁ
1
þ K1 ½OH ꢃ
Substituting Eqs. (8)–(10) in Eq. (7) and omitting
1
1
1
1
¼
þ
þ k
:
ð13Þ
kobs
k K1 K2½PAHꢃ ½OHꢁꢃ
k K2½PAHꢃ
subscripts ‘T’ and ‘f’, we have
The effect of ionic strength and dielectric constant of
medium on the rate explains qualitatively the reaction
between ions having the same charge, as seen in
ꢁ
3ꢁ
kK K ½PAHꢃ ½OH ꢃ ½FeðCNÞ
ꢃ
1
2
T
T
6
T
Rate ¼
ꢁ
ꢁ
ð1 þ K1 ½OH ꢃÞ ð1 þ K1K2½PAH] ½OH ꢃ
123

M. D. Meti et al.
–
3
–1
1
/[OH ]/dm mol
1.5 2.0
Experimental
0
.0
0.5
1.0
2.5
3.0
3
2
2
1
1
0
0
.0
.5
.0
.5
.0
.5
.0
2.0
Reagent grade chemicals and double distilled water were
used throughout the work. The stock solution of the oxidant
hexacyanoferrate(III) was prepared by dissolving potas-
sium hexacyanoferrate(III) (SISCO-CHEM) in water and
the concentration was ascertained by iodometric titration
1
.5
-
3
[
15]. A stock solution of substrate 0.01 mol dm pro-
1.0
cainamide (Sigma Aldrich) was prepared by dissolving
PAH in distilled water. Potassium hydroxide (s. d. fine-
-
Chem Ltd.), was used as the source of OH to vary the
0
.5
alkali concentration in the reaction media. The potassium
nitrate solution was prepared by dissolving potassium
nitrate in double distilled water and was used to maintain
the ionic strength in the reaction medium.
0.0
0
.0
2.0
4.0
6.0
8.0
10.0
12.0
3
3
–1
1
/[PAH] x 10 /dm mol
Equipments and spectral measurements
Fig. 5 Verification of rate law [Eq. (12)] in the form of Eq. (13)
For kinetic measurements, a Peltier Accessory (tempera-
ture control) attached Varian CARY 50 Bio UV–vis.
spectrophotometer (Varian, Victoria-3170, Australia) was
used. For product analysis, the QP-2010S Shimadzu gas
chromatograph mass spectrometer, Nicolet 5700-FT-IR
Scheme 3. The thermodynamic quantities for the
different equilibrium steps in Scheme 3 can be
-
evaluated as follows. The [PAH], [OH ] were varied
1
at four different temperatures. According to Eq. (13),
spectrometer (Thermo, U.S.A) were used; H NMR spectra
other conditions being constant, plots of 1/k
vs.
were recorded on a 300 MHz spectrometer (Bruker, Swit-
13
obs
-
/[PAH] and 1/kobs vs. 1/[OH ] should be linear and
1
zerland).
C NMR was recorded on a 400 MHz
are found to be so (Fig. 5). From the slopes and
spectrometer (Bruker, Switzerland) in DMSO-d with TMS
6
intercepts, the values of K , K , and k were calculated
1
as an internal standard.
2
at different temperatures (Table 2). van’t Hoff plot was
Electrochemical measurements were carried out on a
CHI 630D electrochemical analyzer (CH Instruments Inc.,
USA). The voltammetric measurements were carried out in
made for the variation of K and K . For example at 25°
1
2
C (log K vs. 1/T and log K vs. 1/T), the values of
1
2
3
enthalpy of reaction DH, entropy of reaction DS, and
free energy of reaction DG were calculated for the first
and second equilibrium steps of Scheme 3. These values
are given in Table 2. A comparison of the DH value
a 10 cm single compartment three-electrode glass cell
with Ag/AgCl as a reference electrode, a platinum wire as
counter electrode, and a 2 mm diameter glassy carbon
electrode as a working electrode (part no. CHI101). For pH
measurements, an Elico pH meter model LI120 was used.
-
1
#
(
37 kJ mol ) from K1 of first step with that of DH
56 kJ mol ) obtained for rate determining step shows
-
1
(
that the reaction before the rate determining step is fairly
fast as it involves low activation energy [13]. A high
Kinetic measurements
#
-1
-1
negative value of DS (-102 J K mol ) suggests that
intermediate complex (C) is more ordered than the
reactants [14].
Kinetic measurement was carried out at 25 ± 0.1 °C and at
-
3
constant ionic strength, I = 1.10 mol dm . Reactions
were initiated by mixing previously thermostated solutions
of hexacyanoferrate(III) and procainamide which also
contained the required amount of potassium hydroxide and
potassium nitrate. The kinetics was followed under pseudo-
first order conditions with PAH in excess. Progress of
reaction was followed by measuring the absorbance of
hexacyanoferrate(III) in the reaction mixture at 420 nm in
a 1 cm cell placed in the thermostated compartment of a
Varian carry 50 Bio UV–Vis spectrophotometer. At this
wavelength, all other materials concerned have negligible
absorbance. Application of Beer’s law under reaction
Conclusion
Spectroscopic investigation and oxidation of procainamide
by hexacyanoferrate(III) in aqueous alkaline media have
been studied. Rate constant of slow step and other equi-
librium constants involved in the mechanism are evaluated
and activation parameters with respect to slow step of
reaction were computed. The mechanism described here
are consistent with all experimental results.
-
4
conditions had been verified between 1.0 9 10
and
1
23

Kinetic and mechanistic investigations
0
0
0
0
0
0
0
.30
.25
.20
.15
.10
.05
.00
polishing, the electrode was rinsed thoroughly with milli-
pore water. After this mechanical treatment, the GCE was
placed in buffer solution and various voltammograms were
recorded until a steady state baseline voltammogram was
obtained. The GCE was first activated in phosphate buffer
(pH 7.0) by cyclic voltammetric sweeps between 0.2 and
(
a)
(
a)
1
.6 V until stable cyclic voltammograms were obtained.
3
Then, the electrodes were transferred into another 10 cm
of phosphate buffer (pH 7.0) containing proper amount of
PAH and cyclic voltammograms were recorded between
(
j)
(
j)
-
1
0.2 and 1.6 V, with a scan rate of 50 mV s
.
320
350
380
410
440
470
500
Wavelength/nm
References
Fig. 6 UV-Vis spectral changes during oxidation of procainamide by
3
-
-4
] = 2.0 9 10 , [PAH] =
hexacyanoferrate(III) at 25 °C; [Fe(CN)
6
-
.0 9 10 , [OH ] = 0.5 mol dm , and I = 1.10 mol dm with
3
-
-3
-3
1
2
. Stearns FM, Trevose PA (1981) Clin Chem 27:2064
. Dutcher JS, Strong JM, Lucas SV, Lee WK, Atkinson AJ (1977)
Clin Pharmacol Ther 22:447
2
scanning time interval of 1.0 min
3
. Drayer DE, Reidenberg MM, Sevy RW (1974) Proc Soc Exp Biol
Med 146:358
-
0.0 9 10 mol dm of hexacyanoferrate(III) at 420 nm
4
-3
1
and the extinction coefficient was found to be
-1
4. Dutcher JS, Strong JM (1977) Clin Chem 23:1318
5. Day MC, Selbin J (1964) Theoretical inorganic chemistry.
Reinhold Publishing Corporation, New York, p 226
3
-1
e = 1,075 ± 10 dm mol cm
The kinetics was followed for more than 85 % com-
.
6
7
. Kelson EP, Ericson PP (2000) Int J Chem Kinet 32:760
. Vovk AI, Muraaveva IV, Kukhar VP (2000) Russ J Gen Chem
70:1108
pletion of the reaction and good first order kinetics was
observed. The first order rate constant, k were obtained
obs
3
-
from the plot of log(Fe(CN) ) vs. time. The first order
8. Speakman PT, Waters WA (1955) J Chem Soc 40
. Singh VN, Singh MP, Saxena BL, Singh MP (1969) Can J Chem
7:1051
0. Singh VN, Singh MP, Saxena BL (1970) Indian J Chem 8:529
6
9
plots were linear over 75 % completion of the reaction.
The first order rate constants were reproducible within
4
1
±
5 % and are the average of at least three independent
11. Lide DR (ed) (1992) CRC Handbook of Chemistry and Physics,
73rd edn. CRC Press, London, p 8
kinetic runs. Spectral changes during the chemical reaction
for standard condition at 25 °C are shown in Fig. 6. It is
evident from the figure that the concentration of hexacya-
noferrate(III) decreases at 420 nm.
1
1
1
2. Byadagi KS, Naik DV, Savanur AP, Nandibewoor ST, Chi-
matadar SA (2010) React Kinet Mech Catal 99:53
3. Bilehal DC, Kulkarni RM, Nandibewoor ST (2001) Can J Chem
79:1926
4. Weissberger A, Lewis ES (eds) (1974) Investigations of Rates
and Mechanism of Reactions in Techniques of Chemistry, vol 4.
Wiley, New York, p 421
Cyclic voltammetric measurements
1
5. Jeffery GH, Bassett J, Mendham J, Denny RC (1996) Vogel’s
textbook of quantitative chemical analysis, 5th edn. ELBS
Longman, Essex, p 339
The GCE was carefully polished using 0.3 micron Al O
2
3
slurry on a polishing cloth before each experiment. After
123