Kinetics and mechanism of oxidation of aspirin by bromamine-T, N-bromosuccinimide, and N-bromophthalimide

Article abstract of DOI:10.1002/(SICI)1097-4601(1998)30:6<407::AID-KIN2>3.0.CO;2-W

The kinetics of the oxidation of aspirin (ASP) by bromamine-T (BAT), N-bromo-succinimide (NBS), and N-bromophthalimide (NBP) has been studied in aqueous perchloric acid at 303 K. The oxidation reaction follows identical kinetics with first-order in [oxidant], fractional-order in [ASP], and inverse fractional-order in [H⁺]. Under identical experimental conditions the extent of oxidation with different oxidizing agents is in the order: NBS > BAT > NBP, The rate decreased with decreasing dielectric constant of the medium. The variation of ionic strength and the addition of the reaction products and halide ions had no significant effect on the reaction rate. The solvent isotope effect was studied using D₂O. Kinetic parameters were evaluated by studying the reaction at different temperatures. The reaction products were identified by GC-MS. The proposed reaction mechanism and the derived rate law are consistent with the observed kinetic data. Formation and decomposition constants for ASP-oxidant complexes have been evaluated. Decarboxylation, bromination, and loss of acetic acid gave 2,4,6-tribromophenol.

Full text of DOI:10.1002/(SICI)1097-4601(1998)30:6<407::AID-KIN2>3.0.CO;2-W

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Kinetics and Mechanism of
Oxidation of Aspirin by
Bromamine-T, N-
Bromosuccinimide, and N-
Bromophthalimide
R. RAMACHANDRAPPA,1 PUTTASWAMY,1 S. M. MAYANNA,1 N. M. MADE GOWDA2
1Department of Post-Graduate Studies in Chemistry, Central College, Bangalore University, Bangalore–560 001, India
2Department of Chemistry, Western Illinois University, 1 University Circle, Macomb, Illinois 61455
Received 6 March 1997; accepted 10 October 1997
ABSTRACT: The kinetics of the oxidation of aspirin (ASP) by bromamine-T (BAT), N-bromo-
succinimide (NBS), and N-bromophthalimide (NBP) has been studied in aqueous perchloric
acid at 303 K. The oxidation reaction follows identical kinetics with first-order in [oxidant],
fractional-order in [ASP], and inverse fractional-order in [Hϩ]. Under identical experimental
conditions the extent of oxidation with different oxidizing agents is in the order: NBS Ͼ
BAT Ͼ NBP. The rate decreased with decreasing dielectric constant of the medium. The vari-
ation of ionic strength and the addition of the reaction products and halide ions had no
significant effect on the reaction rate. The solvent isotope effect was studied using D2O. Kinetic
parameters were evaluated by studying the reaction at different temperatures. The reaction
products were identified by GC–MS. The proposed reaction mechanism and the derived rate
law are consistent with the observed kinetic data. Formation and decomposition constants
for ASP-oxidant complexes have been evaluated. Decarboxylation, bromination, and loss of
acetic acid gave 2,4,6-tribromophenol. ᭧ 1998 John Wiley & Sons, Inc. Int J Chem Kinet: 30: 407–414, 1998
number of organic and inorganic substrates using bro-
mamine-T (BAT), N-bromosuccinimide (NBS), and
N-bromophthalimide (NBP) have been studied exten-
sively [6–12]. The present article reports our study on
the kinetics and mechanism of oxidation of aspirin
(ASP) by BAT, NBS, and NBP in perchloric acid me-
dium.
INTRODUCTION
Aspirin (acetylsalicylic acid) is a nonsteroidal anal-
gesic, anti-inflammatory, and antipyretic agent. It is
used in acute conditions such as headache, arthralgia,
myalgia, and other cases requiring mild analgesia. As-
pirin is widely studied in medicine and several meth-
ods are suggested in the literature for its determination
[1,2]. Very few kinetics of aspirin hydrolysis are re-
ported in the literature [3,5]. It is therefore of interest
to investigate the kinetics of its reaction with oxidizing
agents. The kinetics and mechanism of oxidation of a
EXPERIMENTAL
Bromamine-T was obtained by partial debromination
of dibromamine-T (DBT) in 4 M NaOH [13]. The pu-
rity of BAT obtained was checked iodometrically and
Correspondence to: N. M. Made Gowda and Puttaswamy
᭧ 1998 John Wiley & Sons, Inc.
CCC 0538-8066/98/060407-08

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408
RAMACHANDRAPPA ET AL.
Figure 1 Mass spectrum of p-toluenesulfonamide with its parent molecular ion peak at mass/charge 171.
through its mass, UV, IR, and 1H and 13C NMR data.
An aqueous solution of BAT was prepared, standard-
ized by the iodometric method, and preserved in
brown bottles. N-Bromosuccinimide, from Loba,
Bombay, India, was used without further purification.
The purity was checked iodometrically and by its IR
spectrum. N-Bromophthalimide was prepared by the
reported method [14]. The purity was checked iodom-
etrically and by its IR spectrum. Aqueous solutions of
NBS and NBP were always prepared afresh, standard-
ized, and used.
Aspirin (Merck) was used without further purifi-
cation. A solution of the compound was prepared in
acetic acid-water [10:90] mixture. All solutions were
prepared using AR chemicals and double distilled wa-
ter. A constant ionic strength of the medium was main-
tained using a concentrated solution of sodium per-
chlorate.
Kinetic Measurement
The reaction was carried out in glass-stoppered Pyrex
boiling tubes whose outer surface was coated black to
eliminate photochemical effects. Requisite amounts of
the solutions of ASP and NaClO4, HClO4, and water
(to keep the total volume constant for all runs) were
taken in the tube and thermostated at
for ther-
303 K
mal equilibrium. A measured amount of the oxidant
solution, also thermostated at the same temperature,
was rapidly added to the mixture with stirring in the
boiling tube. The progress of the reaction was moni-
tored by iodometric determination of the unreacted ox-
idant in measured aliquots of the reaction mixture
withdrawn at different intervals of time. The course of
the reaction was studied for two half-lives. The
pseudo-first-order rate constants (kЈ) calculated were
reproducible (Ϯ3%).
Figure 2 Mass spectrum of 2,4,6-tribromophenol with its parent molecular ion peak at mass/charge 331.

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OXIDATION OF ASPIRIN BY BROMAMINE-T
409
Table I Effect of Varying Reactant Concentrations on
the Reaction Ratea
Stoichiometry and Product Analysis
Various ratios of ASP and the oxidant were equili-
brated in the presence of HClO4 for 24h (303 K) under
the condition [oxidant]o ϾϾ [aspirin]o. Determination
of the unreacted oxidant in the reaction mixtures
showed that one mole of ASP consumed 3 moles of
oxidant, conforming to the following stoichiometry:
Ϫ
1
kЈ ϫ 104/s
104 [Oxidant]/M 103 [ASP]O/M NBS BAT NBP
8.0
9.0
8.0
8.0
8.0
8.0
8.0
2.0
4.0
6.0
8.0
5.70
5.80
5.78
5.84
5.90
1.92
3.24
4.50
5.78
6.60
7.67
8.80
4.85
4.80
4.90
4.98
4.70
1.90
3.20
4.05
4.90
5.70
6.40
7.75
1.88
1.95
1.97
1.85
1.90
0.63
0.92
1.42
1.97
2.45
2.82
3.38
10.0
11.0
12.0
10.0
10.0
10.0
10.0
10.0
10.0
10.0
ϩ
ϩ H O !:
2
C9H8O4 3 R9NHBr
(ASP) (BAT)
C6H3OBr3 ϩ 3 R9NH2 ϩ CO2 (1)
ϩ
ϩ H O !:
2
C9H8O4 3 RЈ"NBr
(ASP) (NBS/NBP)
C6H3OBr3 ϩ 3 RЈ"NH ϩ CO2 (2)
10.0
12.0
14.0
a [HClO4] ϭ 2.00 ϫ 10Ϫ3 M; ␮ ϭ 0.50 M; and Temp. ϭ
303 K.
where R ϭ CH3
SO2 for BAT and RЈ ϭ
O
O
C
C
Table II Effect of Perchloric Acid Concentration on
the Reaction Ratea
for NBS or
for NBP.
C
C
O
Ϫ1
kЈ ϫ 104/s
103 [HClO4]/M
NBS
BAT
NBP
O
1.0
2.0
4.0
6.0
8.0
10.0
12.0
14.0
7.40
5.78
4.43
3.90
3.54
3.24
3.08
2.92
5.70
4.90
4.58
3.98
3.60
3.29
2.95
2.70
2.5
The reduction product of BAT, p-toluenesulfonamide
(PTS), was identified by paper chromatography using
benzyl alcohol saturated with water as the solvent sys-
tem with ascending irrigation and using 0.5% vanillin
in 1% HCl in EtOH as the spray reagent (Rf ϭ
0.905). The GC–MS data were obtained on a 17A
Shimadzu gas chromatograph with a QP-5000 Shi-
madzu mass spectrometer. The GC had a capillary col-
umn with 250ЊC oven temperature, 200ЊC interface
temperature, and approximately 150ЊC column tem-
perature. The mass data were obtained using the elec-
tron impact method. The mass spectrum showing an
Mϩ parent ion peak at 171 amu clearly confirms PTS
(Fig. 1). Succinimide and phthalimide were detected
by methods reported elsewhere [9–12]. The oxidation
product of ASP, 2,4,5-tribromophenol, was confirmed
by IR and MS spectral studies (Fig. 2).
1.97
1.45
1.22
1.10
1.02
0.92
0.80
a [Oxidant]O ϭ 1.00 ϫ 10Ϫ3 M; [ASP]O ϭ 8.00 ϫ 10Ϫ3 M; ␮
ϭ 0.50 M; and Temp. ϭ 303 K.
Table III Effect of Dielectric Constant (D) of the
Medium on the Rate of Reaction
kЈ ϫ 104/s
Ϫ1
% MeOH
(v/v)
Da
NBS
BAT
NBP
0.0
10
20
30
40
76.73
72.37
67.48
62.71
58.06
5.78
4.30
2.52
1.45
0.85
4.90
3.50
2.35
1.65
1.05
1.97
1.65
1.21
0.72
0.50
RESULTS
The kinetics of oxidation of ASP by BAT, NBS, and
NBP was investigated at several initial concentrations
of the reactants in HClO4 medium. The same oxidation
behavior was observed for all the three oxidants (OX).
[Oxidant]O ϭ 1.00 ϫ 10Ϫ3 M;
[ASP]O ϭ 8.00 ϫ 10Ϫ3 M;
[HClO4] ϭ 2.00 ϫ 10Ϫ3 M; ␮ ϭ 0.50 M; and Temp. 303 K.
a Values of D are from the literature, ref. [15].

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410
RAMACHANDRAPPA ET AL.
Figure 3 Plots of log kЈ vs. 1/D at 303 K.
Figure 4 Arrhenius plots of log kЈ vs. 1/T.
At constant acid concentration with the substrate in
excess, plots of log [OX]o/[OX] vs. time were linear
indicating a first-order dependence of the rate on [OX].
The pseudo-first-order rate constants (kЈ) obtained are
given in Table I.
The rate increased with increasing [ASP]o (Table
I). Plots of log kЈ vs. log [ASP]o were linear with
slopes (ca. 0.6) with all the three oxidants, thus indi-
cating a fractional-order dependence on the substrate
concentration. The rate of reaction decreased with in-
crease in [HClO4] (Table II). Plots of log kЈ vs. log
[HClO4] were linear with negative fractional slopes
indicating a negative fractional order (ca. Ϫ0.3) in
[Hϩ].
10Ϫ2 M), in the form of NaCl or NaBr, had no signif-
icant effect on the rate. The reaction was also studied
in aqueous MeOH of different compositions (0–40%
v/v). It was observed that an increase in MeOH content
retarded the rate of reaction (Table III). The values of
the dielectric constant (D) of water-MeOH mixtures
of different compositions are available in the literature
[15]. Plots of log kЈ vs. 1/D were linear (Fig. 3) with
negative slopes supporting a rate-limiting step with
charge dispersal. Blank experiments performed
The variation of the ionic strength (␮ ϭ 0.10 Ϫ
0.60 M) of the medium using sodium perchlorate or
the addition of the reaction products (p-toluenesulfon-
2
amide or succinimide or phthalimide) (1.0 ϫ 10Ϫ
Ϫ
4.0 ϫ 10Ϫ2 M) had no effect on the reaction rate. The
addition of ClϪ or BrϪ ions (1.0 ϫ 10Ϫ Ϫ 4.0 ϫ
2
Table IV Effect of Temperature on the Rate of
Reaction
Ϫ1
kЈ ϫ 104/s
Temperature
(K)
NBS
BAT
NBP
297
303
310
318
3.38
5.78
7.67
1.82
4.90
9.00
17.0
1.05
1.97
3.15
7.02
11.04
[Oxidant]O ϭ 1.00 ϫ 10Ϫ3 M;
[ASP]O ϭ 8.00 ϫ 10Ϫ3 M;
[HClO4] ϭ 2.0 ϫ 10Ϫ3 M; and ␮ ϭ 0.50 M.
Figure 5 Eyring plots of log (kЈ/T) vs. 1/T.