Monatsh Chem (2015) 146:14851493

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 M. H. Lamani A. G. Naikar S. S. Sutar

S. T. Nandibewoor S. A. Chimatadar

Received: 20 May 2014 / Accepted: 2 January 2015 / Published online: 31 January 2015
Springer-Verlag Wien 2015

Abstract The kinetics of oxidation of procainamide by Graphical abstract

alkaline hexacyanoferrate(III) at a constant ionic strength
of 1.10 mol dm-3 has been studied spectrophotometrically O
N
at 25 C. The stoichiometric analysis indicates that one N
H + 2 [Fe(CN)6]3- + 3 H2O

mole of procainamide requires two moles of hexacyano- H 2N

ferrate(III). The reaction products are identified and

O
confirmed by IR, NMR, and GCMS spectral studies. The H 2N H
OH + + 2 C2H6 + 2 [Fe(CN)6]4- + 2 OH-
reaction is first order with respect to oxidant, Fe(CN)3-
6 and H NH2
H 2N
less than unit order with respect to procainamide and alkali 4-Aminobenzoic acid (E)-Ethene-1,2-diamine

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.
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.
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
e-mail: schimatadar@gmail.com
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-
cainamides 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
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-
chloride (PAH) is 48 mg/dm3, but its major metabolite, N-
acetylprocainamide, which also has an antiarrhythmic

123
1486
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
[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
FeCN3 4
6 = FeCN6 is 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
O .
HCl
N
N stretching. The bands at 3,366 and 3,465 cm-1 are due to
H symmetric and asymmetric stretching of -NH2 group (suppl.
H2N
Fig. 1 The chemical structure of procainamide hydrochloride
Scheme 1
O
N
H + 2 [Fe(CN)6]3- + 3 H2O
H 2N
O
OH
H 2N
4-Aminobenzoic acid
123
M. D. Meti et al.
(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.
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-, KNO3 and at constant ionic strength of
1.10 mol dm-3 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.
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
band at 1,672 cm-1 which corresponds to carbonyl group
Fig. 1). The 1H NMR spectral analysis of 4-aminobenzoic
acid exhibited a doublet at 6.54 ppm due to aromatic protons.
One more doublet of aromatic protons resonated at 7.59 ppm
N
H 2N H
+ + 2 C2H6 + 2 [Fe(CN)6]4- + 2 OH-
H NH2
(E)-Ethene-1,2-diamine
Kinetic and mechanistic investigations 1487

Fig. 2 GC-MS spectrum of the product 4-aminobenzoic acid showed base peak at 120 amu and molecular ion peak at 137 amu

(suppl. Fig. 2). The 13C NMR spectral analysis of 4-amino- Table 1 Effect of variation of hexacyanoferrate(III), procainamide,
benzoic acid exhibited a peak 167 ppm due to carboxylic and OH- on the oxidation of procainamide by hexacyanoferrate(III)
at 25 C and I = 1.10 mol dm-3
acid carbon. A signal at 153 ppm is attributed to aromatic
carbon adjacent to NH2 carbon a peak at 131 ppm is due to [Fe(CN)3- 4
6 ] 9 10 / [PAH] 9 103/ [OH-]/ kobs 9 103/
aromatic carbons, one more peak at 116.854 ppm is attrib- mol dm-3 mol dm-3 mol dm-3 s-1
uted to aromatic carbon adjacent to carboxylic group and 0.50 2.0 0.5 1.40
remaining two aromatic carbons resonated at 112.52 ppm 1.0 2.0 0.5 1.43
(suppl. Fig. 3). The GCMS analysis of 4-aminobenzoic acid 2.0 2.0 0.5 1.49
showed a base peak at 120 amu and molecular ion peak at 3.0 2.0 0.5 1.41
137 amu (Fig. 2). Another product (E)-ethene-1,2-diamine 5.0 2.0 0.5 1.37
was confirmed by its GCMS spectrum, which showed a 2.0 0.50 0.5 0.55
molecular ion peak at 58 amu (suppl. Fig. 4). 2.0 1.0 0.5 0.81
2.0 2.0 0.5 1.49
Reaction order
2.0 3.0 0.5 1.91
2.0 5.0 0.5 2.85
The reaction orders were determined from the slope of the
2.0 2.0 0.10 0.59
plots of log kobs vs. log(concentration) by varying the
2.0 2.0 0.30 1.05
concentrations of procainamide and alkali in turn while
2.0 2.0 0.50 1.49
keeping all other concentrations and conditions constant.
2.0 2.0 0.70 2.02
2.0. 2.0 1.00 3.47
Effect of [hexacyanoferrate(III)]

At constant concentration of procainamide, alkali and at
constant ionic strength, I = 1.10 mol dm-3, the hexa-
cyanoferrate(III) concentration varied from 0.5 9 10-4
to 5.0 9 10-4 mol dm-3 (Table 1). The order with
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
reaction. This also indicates first order with respect to
hexacyanoferrate(III).
Effect of [procainamide]
The substrate, procainamide concentration was varied in
the concentration range of 0.5 9 10-35.0 9 10-3
mol dm-3 at 25 C (Table 1), keeping all other conditions
constant. The rate constant, kobs, increased with increase in

123
1488
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
(0.72).
Effect of [alkali]
The effect of alkali concentration on the reaction was
studied in the range 0.11.0 mol dm-3 (Table 1) at con-
stant concentrations of procainamide, hexacyanoferrate(III)
and at constant ionic strength of 1.10 mol dm-3 at 25 C.
The rate constant increased with increase in the alkali
concentration. The order was found to be less than unity
(0.79).
Effect of ionic strength and dielectric constant
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
between 0.50 and 1.40 mol dm-3 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:
D u1 D1 u2 D2 ;
1/D x 10 2
1.0 1.4 1.8
1.5
1.1
1+log kobs
0.7
0.3
0.6 0.8 1.0 1.2 1.4
I
Fig. 3 Effect of ionic strength and dielectric constant on the
oxidation of procainamide by alkaline hexacyanoferrate(III)
123
M. D. Meti et al.
where u1 and u2 are volume fractions; and D1 and D2 are
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 %
D 78:5  90=100 10:9  10=100 71:74:
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
reaction mixture was varied up to u (t-butyl
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).
Effect of added products
The effect of initially added products, hexacyanoferrate(II)
and p-aminobenzoic acid did not have any significant effect
on the rate of reaction.
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
The rate of reaction was measured at different temperatures
15, 25, 35, and 45 C under varying alkali and procain-
amide concentrations. The rate was found to increase with
0.8 the increasing temperature. The rate constant, k, of slow
step, K1, the value of first equilibrium step and K2, the
value of second equilibrium step of Scheme 1 were
0.6 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
3+log kobs
0.4 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]
0.2  6 
kB T kB T 6
expDG =RT exp DH TDS =RT ;
6
k
h h
1
0.0
1.6
where k is the rate constant, kB is Boltzmanns constant,
h is Plancks 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
Kinetic and mechanistic investigations 1489

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
Temperature/K k 9 103/s-1 Parameters Values

288 1.19 Ea/kJ mol-1 59 2

298 3.70 DH#/kJ mol-1 56 6.3
308 5.78 DS#/J K-1 mol-1 -123 21
318 13.4 DG#/kJ mol-1 93 0.52
log A 8 0.2
(B) Effect of temperature on first and second equilibrium step of Scheme 3
Temperature/K K1/dm3 mol-1 K2 9 10-3/dm3 mol-1

288 0.18 4.48

298 0.28 3.37
308 0.49 2.30
318 0.74 1.66
(C) Thermodynamic quantities with respect to K1 and K2
Thermodynamic quantities Values from K1 Values from K2

DH/kJ mol-1 37 -26

DS/J K-1 mol-1 113 -19
DG298/kJ mol-1 3.2 -20

k DH 6 DS6 kB first cycle was generally recorded. However, no peak was

ln  ln :
T RT R h
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
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 vant Hoff plot was drawn
for the variation of K1 and K2 with temperature, i.e., (log
K1 vs. 1/T and log K2 vs. 1/T). The values of enthalpy of
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.
Cyclic voltammetric behavior of procainamide
The electrochemical behavior of PAH at glassy carbon
electrode was investigated using cyclic voltammetry (CV) at
physiological pH 7.0. The cyclic voltammograms obtained
for 1.0 9 10-4 mol dm-1 PAH solution at a scan rate of
2 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).
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
each constituent such as [oxidant], [reductant], and [OH-]
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
supported by the observed fractional order in [OH-] and
[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-
nobenzoic acid, [Fe(CN)4- 6 ] and intermediate of N ,N -
1 1

50 mV/s exhibit a well-defined irreversible anodic peak at diethylethane-1,2-diamine. In a subsequent fast step this
about 0.9139 V at glassy carbon electrode. The results are intermediate of N1,N1-diethylethane-1,2-diamine decom-
shown in Fig. 4. The voltammograms corresponding to the poses to give (E)-ethene-1,2-diamine with elimination of

123
1490 M. D. Meti et al.

h i
ethane as a by-product. All these results were proposed in a
C K2 Anionic form of PAH FECN3
6 :
detailed mechanistic as shown in Scheme 3.
Since Scheme 3 is in accordance with the generally From Eqs. (3) and (4), we have
well-accepted principle of non-complementary oxidations h i
taking place in sequence of one-electron steps. Spectro- Rate kK2 Anionic form of PAH FECN3
6 : 5
scopic evidence for the complex formation between
oxidant and substrate was obtained from UVVis spectra of From the first step of Scheme 3, we have
hexacyanoferrate(III) (2.0 9 10-4 mol dm-3) and PAH
Anionic form of PAH
(2.0 9 10-3 mol dm-3) a mixture of both (suppl. Fig. 5). K1
A hypsochromic shift of about 10 nm from 275 to 265 nm PAH OH 
in the spectra of procainamide to mixture of hexacyano- Anionic form of PAH K1 PAH OH : 6
ferrate(III) and PAH was observed.
Substituting Eq. (6) in Eq. (5),
From Scheme 3, the rate [Eq. (13)] can be derived as
follows: Rate k K1 K2 PAHf OH f FeCN3
6 f : 7
dFeCN3
6 
Rate kComplex: 3 The total concentration of [Fe(CN)3-
6 ] is given by
dt
From the second step of Scheme 3, we have FeCN3 3
6 T FeCN6 f C

C FeCN3  3
6 f K1 K2 PAHf OH f FeCN6 f
K2 4 FeCN3 
Anionic form of PAHFECN3 6 f 1 K1 K2 PAHf OH f ;
6 

where [Fe(CN)3- 3-
6 ]f and [Fe(CN)6 ]T refer to free and total
3
[Fe(CN)6] concentration, respectively. Therefore, free
[Fe(CN)3-
6 ]f is given by

FeCN36 T
FeCN3
6 f : 8
1 K1 K2 S OH 
Similarly,
OH T OH f Anionic form of PAH C

OH T OH f K1 PAH OH 

K1 K2 PAH OH FECN3
6 

OH T
OH f :
1 K1 PAH OH  K1 K2 PAH OH FECN3

6 

In view of low concentration of [PAH] and [Fe(CN)3-

6 ]
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 K1[PAH] and K1K2[PAH] [Fe(CN)3- 6 ] are
presence of procainamide (1.0 9 10-4 M) at the scan rate 0.05 V s-1 neglected compared to unity. Therefore,

Scheme 2
PAH + OH- Anionic form of PAH + H2O

Anionic form of PAH + [Fe(CN)6]3- Complex (C)

Complex (C) + 2 H2O Product + Intermediate + [Fe(CN)6]4-

Intermediate + [Fe(CN)6]3- Final Products + [Fe(CN)6]4-

123
Kinetic and mechanistic investigations 1491

Scheme 3
O O
N N
N K1 N
+ OH -
H + H 2O

H2N H 2N

O
N
N K2
3-
+ [Fe(CN)6] (Complex)4-
H 2N

k OH
(Complex)4- + 2 H2O + N + [Fe(CN)6]4- + OH-
slow H 2N
H2 N
4-Aminobenzoic acid N1,N1-Diethylethane-1,2-diamine

H 2N H
fast
N + [Fe(CN)6]3- + 2 H2O + 2 C2H6 + [Fe(CN)6]4- + 2 OH-
H2N
H NH2
1 1
N ,N -Diethylethane-1,2-diamine (E)-Ethene-1,2-diamine

OH f OH T : 9 kK1 K2 PAHT OH T FeCN3

6 T
Rate
1 K1 K2 PAH OH  K1 OH  K12 K2 OH 2 PAH
In the similar way, [PAH]f was also calculated as 11
follows:
In view of low concentration of [PAH] used, the terms
PAHT PAHf Anionic form of PAH C
K21K2 [OH-] [PAH] are neglected. Therefore,
PAHf K1 PAHOH  K2 Anionic form of PAH
kK1 K2 PAHT OH T FeCN3
6 T
 FeCN3
6 
Rate :
1 K1 K2 PAH OH  K1 OH  K12 K2 OH 2 PAH
PAHf K1 PAHOH  K1 K2 PAHOH 
12
 FeCN3
6 
Or
PAHT Rate kK1 K2 PAHT OH T
PAHf : kobs :

1 K1 OH  K1 K2 OH  
FeCN3
6  Fe(CN3 1 K1 OH  K1 K2 PAHOH 
6 
In view of low concentration of [Fe(CN)3-
6 ] used, the 12
terms K1K2[OH-] [Fe(CN)3-6 ] are neglected. Therefore,
Further Eq. (12) can be rearranged to Eq. (13), which is
PAHT suitable for verification.
PAHf : 10
1 K1 OH  1 1 1 1
: 13
Substituting Eqs. (8)(10) in Eq. (7) and omitting kobs k K1 K2 PAH OH  k K2 PAH k
subscripts T and f, we have
The effect of ionic strength and dielectric constant of
kK1 K2 PAHT OH T FeCN3
6 T medium on the rate explains qualitatively the reaction
Rate
1 K1 OH  1 K1 K2 PAH] OH  between ions having the same charge, as seen in

123
1492
1/[OH ]/dm3 mol1
0.0 0.5 1.0 1.5 2.0
3.0
2.5
2.0
1/kobs 103 /s
1.5
1.0
0.5
0.0
0.0 2.0 4.0 6.0 8.0
1/[PAH] x 103/dm3 mol1
Fig. 5 Verification of rate law [Eq. (12)] in the form of Eq. (13)
Scheme 3. The thermodynamic quantities for the
different equilibrium steps in Scheme 3 can be
evaluated as follows. The [PAH], [OH-] were varied
at four different temperatures. According to Eq. (13),
other conditions being constant, plots of 1/kobs vs.
1/[PAH] and 1/kobs vs. 1/[OH-] should be linear and
are found to be so (Fig. 5). From the slopes and
intercepts, the values of K1, K2, and k were calculated
at different temperatures (Table 2). vant Hoff plot was
made for the variation of K1 and K2. For example at 25
C (log K1 vs. 1/T and log K2 vs. 1/T), the values of
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
(37 kJ mol-1) from K1 of first step with that of DH#
(56 kJ mol-1) obtained for rate determining step shows
that the reaction before the rate determining step is fairly
fast as it involves low activation energy [13]. A high
negative value of DS# (-102 J K-1 mol-1) suggests that
intermediate complex (C) is more ordered than the
reactants [14].
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.
123
M. D. Meti et al.
Experimental
2.5 3.0
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-
1.5
sium hexacyanoferrate(III) (SISCO-CHEM) in water and
the concentration was ascertained by iodometric titration
1/kobs 103/s
[15]. A stock solution of substrate 0.01 mol dm-3 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
0.0
10.0 12.0
the ionic strength in the reaction medium.
Equipments and spectral measurements
For kinetic measurements, a Peltier Accessory (tempera-
ture control) attached Varian CARY 50 Bio UVvis.
spectrophotometer (Varian, Victoria-3170, Australia) was
used. For product analysis, the QP-2010S Shimadzu gas
chromatograph mass spectrometer, Nicolet 5700-FT-IR
spectrometer (Thermo, U.S.A) were used; 1H NMR spectra
were recorded on a 300 MHz spectrometer (Bruker, Swit-
zerland). 13C NMR was recorded on a 400 MHz
spectrometer (Bruker, Switzerland) in DMSO-d6 with TMS
as an internal standard.
Electrochemical measurements were carried out on a
CHI 630D electrochemical analyzer (CH Instruments Inc.,
USA). The voltammetric measurements were carried out in
a 10 cm3 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.
Kinetic measurements
Kinetic measurement was carried out at 25 0.1 C and at
constant ionic strength, I = 1.10 mol dm-3. 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 UVVis spectrophotometer. At this
wavelength, all other materials concerned have negligible
absorbance. Application of Beers law under reaction
conditions had been verified between 1.0 9 10-4 and
Kinetic and mechanistic investigations 1493

0.30 polishing, the electrode was rinsed thoroughly with milli-

pore water. After this mechanical treatment, the GCE was
0.25
placed in buffer solution and various voltammograms were
0.20 recorded until a steady state baseline voltammogram was
Absorbance

(a) obtained. The GCE was first activated in phosphate buffer

(a)
0.15 (pH 7.0) by cyclic voltammetric sweeps between 0.2 and
1.6 V until stable cyclic voltammograms were obtained.
0.10
Then, the electrodes were transferred into another 10 cm3
(j) of phosphate buffer (pH 7.0) containing proper amount of
0.05
(j) PAH and cyclic voltammograms were recorded between
0.00 0.2 and 1.6 V, with a scan rate of 50 mV s-1.
320 350 380 410 440 470 500
Wavelength/nm

Fig. 6 UV-Vis spectral changes during oxidation of procainamide by

hexacyanoferrate(III) at 25 C; [Fe(CN)3- -4
6 ] = 2.0 9 10 , [PAH] =
2.0 9 10-3, [OH-] = 0.5 mol dm-3, and I = 1.10 mol dm-3 with
scanning time interval of 1.0 min
10.0 9 10-4 mol dm-3 of hexacyanoferrate(III) at 420 nm
and the extinction coefficient was found to be
e = 1,075 10 dm3 mol-1 cm-1.
The kinetics was followed for more than 85 % com-
pletion of the reaction and good first order kinetics was
observed. The first order rate constant, kobs were obtained
from the plot of log(Fe(CN)3- 6 ) vs. time. The first order
plots were linear over 75 % completion of the reaction.
The first order rate constants were reproducible within
5 % and are the average of at least three independent
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.
Cyclic voltammetric measurements
The GCE was carefully polished using 0.3 micron Al2O3
slurry on a polishing cloth before each experiment. After
References
1. Stearns FM, Trevose PA (1981) Clin Chem 27:2064
2. Dutcher JS, Strong JM, Lucas SV, Lee WK, Atkinson AJ (1977)
Clin Pharmacol Ther 22:447
3. Drayer DE, Reidenberg MM, Sevy RW (1974) Proc Soc Exp Biol
Med 146:358
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
6. Kelson EP, Ericson PP (2000) Int J Chem Kinet 32:760
7. Vovk AI, Muraaveva IV, Kukhar VP (2000) Russ J Gen Chem
70:1108
8. Speakman PT, Waters WA (1955) J Chem Soc 40
9. Singh VN, Singh MP, Saxena BL, Singh MP (1969) Can J Chem
47:1051
10. Singh VN, Singh MP, Saxena BL (1970) Indian J Chem 8:529
11. Lide DR (ed) (1992) CRC Handbook of Chemistry and Physics,
73rd edn. CRC Press, London, p 8
12. Byadagi KS, Naik DV, Savanur AP, Nandibewoor ST, Chi-
matadar SA (2010) React Kinet Mech Catal 99:53
13. Bilehal DC, Kulkarni RM, Nandibewoor ST (2001) Can J Chem
79:1926
14. Weissberger A, Lewis ES (eds) (1974) Investigations of Rates
and Mechanism of Reactions in Techniques of Chemistry, vol 4.
Wiley, New York, p 421
15. Jeffery GH, Bassett J, Mendham J, Denny RC (1996) Vogels
textbook of quantitative chemical analysis, 5th edn. ELBS
Longman, Essex, p 339

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