Kinetic Study and Mechanism Hydrolysis of 4-Bromo-3,5 dimethylphenyl?N-methylcarbamate in Aqueous Media

Article abstract of DOI:10.1002/kin.21113

Degradation via hydrolysis is among the main transformation pathways and particularly for N-methylcarbamates. Carbamate pesticide hydrolysis is known to proceed through alkaline catalysis, with reaction of the hydroxide ion with the carbonyl function or with abstraction of hydrogen in the α position with respect to the carbonyl. This reaction leads to the formation of methylamine and corresponding phenol. In this respect, the reaction kinetics of 4-bromo-3,5-dimethylphenyl?N-methylcarbamate (BDMC) hydrolysis have been investigated in alkaline solution using a spectrophotometric technique and reversed phase liquid chromatography. The kinetic constants were determined following a proposed pseudo–first-order kinetic model. The positive activation entropy ΔS^≠ = +35.73 J mol^?1 K^?1 and the absence of general base catalysis indicated an unimolecular elimination conjugate base (E1cB) hydrolytic mechanism involving the formation of methyl isocyanate. This result was confirmed by the fact that BDMC fits well into br?nsted and Hammett lines, obtained for a series of substituted N-methylcarbamate whose decomposition in aqueous media was established to follow an E1cB mechanism.

Full text of DOI:10.1002/kin.21113

Kinetic Study and
Mechanism Hydrolysis of
4-Bromo-3,5
dimethylphenyl N-
methylcarbamate in
Aqueous Media
1
1
2
1
`
´
JIHENE BEN ATTIG, RANDA OUERTANI, ADEL MEGRICHE, NEJIB BEN HAMIDA,
LATIFA LATROUS EL ATRACHE1,3
1Laboratoire de Chimie Analytique et Electrochimie, Faculte´ des Sciences de Tunis, Universite´ de Tunis El Manar, Campus
universitaire El Manar II, 2092 Tunis, Tunisie
2Laboratoire de Chimie Mine´rale applique´e, Faculte´ des Sciences de Tunis, Universite´ de Tunis El Manar, Campus
universitaire El Manar II, 2092 Tunis, Tunisie
3Institut Pre´paratoire aux Etudes d’Inge´nieurs d’El Manar, Universite´ de Tunis El Manar, B.P.244 El Manar II,
2092 Tunis, Tunisie
Received 21 April 2017; revised 17 July 2017; accepted 24 July 2017
DOI 10.1002/kin.21113
Published online in Wiley Online Library (wileyonlinelibrary.com).
ABSTRACT: Degradation via hydrolysis is among the main transformation pathways and partic-
ularly for N-methylcarbamates. Carbamate pesticide hydrolysis is known to proceed through
alkaline catalysis, with reaction of the hydroxide ion with the carbonyl function or with ab-
straction of hydrogen in the α position with respect to the carbonyl. This reaction leads to the
formation of methylamine and corresponding phenol. In this respect, the reaction kinetics of
4-bromo-3,5-dimethylphenyl N-methylcarbamate (BDMC) hydrolysis have been investigated
in alkaline solution using a spectrophotometric technique and reversed phase liquid chro-
matography. The kinetic constants were determined following a proposed pseudo–first-order
ࣔ
kinetic model. The positive activation entropy ꢀS = +35.73 J mol−1 K−1 and the absence of
general base catalysis indicated an unimolecular elimination conjugate base (E1cB) hydrolytic
mechanism involving the formation of methyl isocyanate. This result was confirmed by the fact
Correspondence to: Latifa Latrous El Atrache; e-mail: latifa.
latrous@ipeiem.rnu.tn.
ꢀC
2017 Wiley Periodicals, Inc.

2
ATTIG ET AL.
that BDMC fits well into bro¨nsted and Hammett lines, obtained for a series of substituted N-
methylcarbamate whose decomposition in aqueous media was established to follow an E1cB
ꢀC
mechanism.
2017 Wiley Periodicals, Inc. Int J Chem Kinet 1–9, 2017
EXPERIMENTAL
INTRODUCTION
Materials
Phenyl-N-methylcarbamate (PNMCs) pesticides are
aryl esters of phenyl-N-methyl substituted carbamic
acids [1]. The substituents on the phenyl ring can
change the characteristic nature of the parent com-
pound in hydrophobic, electronic, and hydrogen bond-
ing and can thus affect the ability of complexa-
tion with acethylcholinesterase, a determining factor
for its cholinesterase inhibition activity [2]. Most of
PNMCs are degraded into their metabolites shortly
after application. In alkaline media, PNMCs can be
easily hydrolyzed to form methylamine and substi-
tuted phenols. The corresponding mechanism involves
either an addition of OH− into the carbonyl with a
further elimination of the RO− leaving group or an
abstraction of the hydrogen of the methylcarbamate
moiety again evolving with the elimination of the RO−
group. Consequently, we have undertaken in our lab-
oratory a study of the determination of both the ki-
netic and mechanistic aspects of the hydrolysis reac-
tion of carbaryl [3], carbofuran [4], methiocarb [5],
bendiocarb [6], zectran [7], aminocarb [8], landrin [9],
ethiofencarb [10], carzol [11], isoprocarb [12], and pir-
imicarb [13]. We showed that hydrolysis of PNMCs ex-
hibited pseudo–first-order kinetics with respect to sub-
strate in aqueous media. The positive activation entropy
obtained and the fact that each N-methylcarbamate
(NMC) fits well onto a bro¨nsted and Hammett plots,
obtained for a series of substituted N-methylcarbamate
supports an unimolecular elimination conjugate base
(E1cB) reaction scheme for the hydrolysis of
PNMCs.
A SCINCO S-3100 spectrophotometer fitted with a
thermostated multiple cell compartment was used for
all spectroscopic measurements. The analysis and stor-
age of data were carried out by means of software
LabProꢀR Plus S W.
The liquid chromatography diode array detection
(LC-DAD) system consists of a gradient model pump
from Varian ProStar model 240, a rheodyne manual
sample injector valve model 7725 i with a 20-µL loop.
A model Varian ProStar 330 diode array detector was
connected to a computer station. Separations were per-
formed using a Symmetry C18, 150 × 4.6 mm i.d,
5-µm particulate size analytical column.
The mobile phase was acetonitrile–water (70:30,
v/v). It was set at a flow rate of 1 mL min−1. The
measured wavelength was 200 nm.
Reagents and Solvents
BDMC and 4-bromo-3,5-dimethylphenol were ob-
tained from Supelco (Saint-Quentin Fallavier, France).
Methanol, acetonitrile, and water were of HPLC grade.
HydrochloricacidHCl (35–38%), Borax(Na2B4O7, 10
H2O), sodium hydroxide (NaOH), potassium dihydro-
gen phosphate (KH2PO4), sodium hydrogen phosphate
(Na2HPO4), and potassium chloride (KCl) were pur-
chased from Fluka (Saint-Quentin Fallavier, France).
Preparation of Solutions
In this respect, this paper is an extension of
such studies to the degradation scheme of 4-bromo-
3,5dimethylphenyl N-methylcarbamate (BDMC) to
yield 4-bromo-3,5-dimethylphenol in aqueous media.
As part of our continuing interest in degradation of
NMCs in aqueous matrices, kinetic and mechanistic as-
pects of the hydrolysis of BDMC were carried out. Our
aims in this work were as follows: (1) to identify the
major transformation product of BDMC by means of
spectrophotometric UV and liquid chromatography, (2)
to investigate the hydrolysis of BDMC in Milli-Q water
under different pH and temperature values, and (3) to
investigate the degradation of BDMC in environmental
water.
The standard stock solution of BDMC of
1000 µg·mL−1 was prepared by dissolving
20 mg in 20 mL of methanol. The different
aqueous solutions were prepared at different pH by the
dilution of standard stock solution at a concentration
of 10 µg·mL−1 in the appropriate buffer. The ionic
strength (I) of these solutions was kept constant equal
to the unity by addition of KCl.
Determination of the Rate Constant kobs of
the Hydrolysis Reaction of BDMC
Spectrophotometric Method. The kinetics of the hy-
drolysis reaction of the BDMC was followed by
International Journal of Chemical Kinetics DOI 10.1002/kin.21113

HYDROLYSIS OF 4-BROMO-3,5 DIMETHYLPHENYL N-METHYLCARBAMATE IN AQUEOUS MEDIA
t=0min
3
1,6
t=30s
t=1min
t=1min30s
t=2min
t=2min30s
t=3min
t=4min
t=5min
t=6min
t=7min
t=9min
t=11min
t=13min
t=16min
t=21min
t=31min
t=41min
1,4
1,2
1,0
0,8
0,6
0,4
0,2
0,0
200
250
wavelength (nm)
300
350
Figure 1 UV spectra versus time of the hydrolysis reaction of BDMC (10 µg·mL−1) in phosphate buffer solution at pH 11.12,
T = 21°C, and I = 1.00 M. [Color figure can be viewed at wileyonlinelibrary.com]
measuring the variation in absorbance versus time cor-
responding to the disappearance of the substrate or to
the appearance of the hydrolysis product. The pres-
ence of two isobestic points at (λ = 218 nm and
229 nm) on the ultraviolet BDMC spectra recorded
versus time indicates that there is no intermediate ac-
cumulation and that the reaction exhibited pseudo–first
order with respect to the carbamate (Fig. 1). The ob-
served rate constant kobs was determined graphically
from the slope of the following linear equation:
equation:
ꢀ
ꢁ
e KB
h
Ea
T
ꢀS= = 2.3 R log kobs − log
− log T
+
(2)
where h and KB are the Planck and Boltzmann
constants, respectively, and R is the gas constant
log(e K ) = 10.753.
B
h
ln (A∞ − At ) = −kobst + ln (A∞ − A0)
(1)
where A0, Aꢀ, and At are, respectively, the absorbance
at initial, infinity, and at time t.
pKa Measurement
The pKa of 4-bromo-3,5-dimethylphenol was deter-
mined experimentally by plotting:
Liquid Chromatographic Method. The recording of
the chromatographic evolution versus time during the
hydrolysis reaction of the BDMC is shown in Fig. 2.
kobs were obtained by plotting ln (A∞ − At ) versus
time, where Aꢀ, and At are the peak area at infinity and
at time t, respectively. (Eq. (1)).
A − AAH
log
= f (pH)
−
AA − A
−
where AA , AAH, and A are, respectively, the ab-
sorbances of the phenolate ion in 1 M NaOH, of the
nonionized carbamate in 1 M HCl, and of the mixture of
the two species in buffer solutions ranging from pH 8.7
to 11.5. The pKa value of 4-bromo-3,5-dimethylphenol
was obtained from the intercept of the graph and is 9.95
(T = 21°C, I = 1.00, KCl).
Entropy Activation
The activation energy was determined from the slope
of the straight line of the Arrhenius plot. The en-
tropy activation ꢀS= was obtained from the following
International Journal of Chemical Kinetics DOI 10.1002/kin.21113

4
ATTIG ET AL.
Figure 2 Chromatogram versus time of the hydrolysis of BDMC at pH 8.76, T = 28°C, and I = 1 M. [BDMC] = 10 µg·mL−1
;
Column: INERTSIL ODS-4 C-18 (15 cm × 4.6 mm ID), dp: 5 µm; mobile phase: acetonitrile-water (70:30, v / v); Flow rate:
1 mL·min−1; at λ = 200 nm; Inj: 20 µL. [Color figure can be viewed at wileyonlinelibrary.com]
RESULTS AND DISCUSSION
1,6
a
b
c
1,4
Determination of
4-Bromo-3,5-dimethylphenol as a
1,2
Hydrolysis Product
1,0
The good superposition of the UV spectrum of the
hydrolysis product (Fig. 3, spectrum c) with that of
a 4-bromo-3,5-dimethylphenol (Fig. 3, spectrum b)
confirmed that the BDMC hydrolyzes quantatively in
4-bromo-3,5-dimethylphenol. Furthermore, the chro-
matogram resulting from the hydrolysis reaction of the
BDMC shows the presence of two peaks at the re-
tention times tR = 4.05 and 3.81 min corresponding,
respectively, to the BDMC and its degradation prod-
uct. The identification of the latter is carried out by
comparing its retention time with an authentic sample
(Fig. 4).
0,8
0,6
0,4
0,2
0,0
200
250
300
350
400
wavelength (nm)
Figure 3 UV absorption spectra of BDMC (a) of 4-bromo-
3,5-dimethylphenol (b) and of the hydrolysis product (c) at
pH 10.33; T = 21°C and I = 1M, [BDMC] = [4-bromo-3,5-
dimethylphenol] = 10 µg·mL−1. [Color figure can be viewed
at wileyonlinelibrary.com]
Effect of pH
The pseudo–first-order rate constants of the hydrolysis
reaction of BDMC in aqueous media at 21°C and for
an ionic strength I = 1.00 M were determined in pH
buffer solutions ranging from 7.6 to 12 by measuring
the variation in absorbance versus time correspond-
ing to the appearance of its degradation product at
λ = 242 nm.
The logarithmic variation of the rate constant kobs
of the BDMC hydrolysis reaction as a function of pH
is a straight line of slope one (log kobs = 0.9014 pH −
10.858; R2 = 0.999) (Fig. 5) of Eqs. (3) and (4). This
International Journal of Chemical Kinetics DOI 10.1002/kin.21113

HYDROLYSIS OF 4-BROMO-3,5 DIMETHYLPHENYL N-METHYLCARBAMATE IN AQUEOUS MEDIA
5
These equations corresponding respectively to the
two mechanisms E1cB and a bimolecular addition
conjugated base (BAc2) proposed for the hydrolysis
reaction of the BDMC (Scheme 1) [14,15]. Both
mechanisms E1cB and BAc2 differ mainly by the
formation of a methyl isocyanate intermediate. The
detection of this intermediate in the reaction medium
is very difficult because of the extreme fugacity of this
compound. In fact, the methyl isocyanate reacts rapidly
with the hydroxyl ion to form N-methylcarbamic
acid, which, by decarboxylation, leads to
methylamine [16].
3,81
3,84
4,05
(a)
(b)
Possibility of Mechanism E2: Research for
General Base Catalysis
Time (min)
A bimolecular elimination mechanism E2 may be
proposed for the hydrolysis reaction of BDMC. It
is in accordance with the formation of methyliso-
cyanate (Scheme 2). Bender and Homer [17] suggested
this mechanism for the hydrolysis of p-nitrophenyl-N-
methylcarbamate in phosphate and imidazole buffer
solutions. It involves a slow proton transfer that should
be translated by a general base catalysis. The influ-
ence of the phosphate buffer concentration at pH 11.12
and T = 21°C on the rate of BDMC hydrolysis was
carried out (Table I). According to the experimen-
tal result, we noted that the observed rate constants
of BDMC hydrolysis remain constant; so there is
no general base catalysis, and the E2 mechanism is
rejected.
Figure 4 (a) Chromatogram of the BDMC during the
hydrolysis reaction and (b) chromatogram of a 4-bromo-
3,5-dimethylphenol standard solution. [Color figure can be
viewed at wileyonlinelibrary.com]
slop value is in agreement with the limit forms obtained
for aH ꢂ Ka and aH ꢃ Ka .
k1Ka
aH
kobs
=
(3)
(4)
and
ꢂ
ꢃ
kobs = k2 OH−
Figure 5 Logarithmic variation of the observed rate constant kobs of the hydrolysis reaction of BDMC versus pH at 21°C.
[Color figure can be viewed at wileyonlinelibrary.com]
International Journal of Chemical Kinetics DOI 10.1002/kin.21113

6
ATTIG ET AL.
Scheme 1 Hydrolysis of the carbamate studied according to two possible mechanisms E1cB and BAc2.
Scheme 2 A bimolecular elimination mechanism E2 for the BDMC hydrolysis reaction.
Table I Rate Constants of BDMC Hydrolysis at
Different Phosphate Buffer Concentrations (pH 11.12) at
21°C
ing to the data available in the literature, the activation
entropy can be an argument in favor of one or the other
E1cB and BAc2 mechanisms [19]. Indeed, the positive
values of activation entropy corresponds to the mech-
2−
[HPO4
]
ࣔ
(×10−2 mol·L−1
)
1
0.75
0,5
0.35 0.25
anism E1cB (ꢀS > 0) whereas the negative values
ࣔ
present a BAc2 mechanism (ꢀS < 0) [20]. Therefore
kobs (min−1
)
0.149 0.152 0.158 0.149 0.154
ࣔ
to determine ꢀS , we measured the BDMC hydrolysis
rate constants at temperatures between 21 and 45°C
in a borax buffer solution of pH 10,33 and an ionic
strength I = 1.00 M. The value of the activation entropy
variation ꢀS= = +35.73 J mol−1 K−1 is deduced from
Effect of Temperature
that of the activation energy Ea = 93.48 KJ mol−1
,
Equations (3) and (4) are equivalent, so we cannot dif-
ferentiate between the two mechanisms [18]. Accord-
calculated from the slope of the linear of equation
International Journal of Chemical Kinetics DOI 10.1002/kin.21113

HYDROLYSIS OF 4-BROMO-3,5 DIMETHYLPHENYL N-METHYLCARBAMATE IN AQUEOUS MEDIA
7
Figure 6 Logarithmic variation of the experimental rate constant kobs versus the temperature for the BDMC hydrolysis. [Color
figure can be viewed at wileyonlinelibrary.com]
Figure 7 Bro¨nsted plot of log kOH versus pKa of the leaving group for the hydrolysis of phenyl N-phenylcarbamates (•) and
phenyl N-methylcarbamates (ꢀ). BDMC (ꢁ).
log kobs = −4.888 × 1000/T + 15.062 (R2 = 0.999)
(Fig. 6). The positive value of the activation entropy
is in agreement with the mechanism E1cB. Compara-
ble values were obtained for the hydrolysis reaction
of a series of N-methylcarbamates studied in our lab-
oratory: carbaryl [3], carbofuran [4], methiocarb [5],
bendiorab [6], zectran [7], aminocarb [8], landrin [9],
ethiofencarb [10], carzol [11], and isoprocarb [12].
The Bro¨nsted line log kOH = β pKa + cte, which
relates the logarithm of the bimolecular rate constant
to the pKa of the leaving group, can be used to eluci-
date the mechanism of the BDMC hydrolysis. Indeed
the slope β of this line is characteristic either of a mech-
anism E1cB (when β < −0.1) or of a mechanism BAc2
(β > −0.5). Williams studied the effect of substituents
on the hydrolysis rate constants of the E1cB type of a
series of phenyl N-phenylcarbamate. He pointed out a
linear relationship log kOH = −1.34 pKa + 15.2 [21].
The slope of this line is characteristic of the mechanism
E1cB.
The point corresponding to BDMC with the coor-
dinate (pKa = 9.95; log kOH = 2.89) was well intro-
duced into the graph log kOH = f (pKa) (Fig. 7). It con-
firms that the BDMC degrades according to the E1cB
mechanism. The logarithmic value of the bimolecular
hydrolysis rate constant log kOH = 2.89 relative to the
BDMC was determined from the ordinate at the origin
of the line of equation log kobs = f (pH).
Hammett Relationship
The Hammett relationship log kOH = 2.865 σ− + 2.04
established by Williams for the hydrolysis of a series
of phenyl-N-phenylcarbamates is in favor of an E1cB
International Journal of Chemical Kinetics DOI 10.1002/kin.21113

8
ATTIG ET AL.
Figure 8 Hammett plot of log kOH of hydrolysis of phenyl N-phenylcarbamates (•) and phenyl N-methylcarbamates (ꢀ) and
Hammett σ- constants. BDMC (ꢁ).
Table II Rate Constants of BDMC Hydrolysis Reaction in Surface Waters at pH 7.3 and Temperature 28°C
Samples
Oued Medjerda
0.2
STEP El Hancha (Sfax)
0.6
Barrage Aroussia
0.2
Eau Milli-Q
1a
kobs 104 (min−1
)
apH 7.6; T = 21°C.
mechanism [21]. The experimental point correspond-
ing to BDMC (σ− = −0.05; log kOH = 2.89) is po-
sitioned on the Hammett line (Fig. 8). The electronic
parameter σ− = −0.05 of the leaving group 4-bromo-
3,5-dimethylphenol was calculated from the equation
−pKa = 2.11 σ − 9.85 [22].
This study was carried out using UV spectrophotome-
try and high-performance liquid chromatography with
reverse phase polarity. The identification of 4-bromo-
3,5-dimethylphenol as a degradation product shows
the high reactivity of the carbamate function in aque-
ous medium. The hydrolysis reaction is pseudo–first
order, and the rate constant kobs calculated at pH 7.6
is equal to 0.01 × 10−2 min−1. The positive activation
ࣔ
entropy (ꢀS = +35.73 J mol−1
K
−1) and the ab-
APPLICATION
sence of general base catalysis are in favor of an E1cB
elimination. This elimination process is confirmed by
the position of the experimental points, with coordi-
nates (pKa = 9.95; log KOH = 2.89) and (σ− = –0.05;
log KOH = 2.89), respectively, on the Bro¨nsted and
Hammett plots proposed by Williams for the hydroly-
sis of phenyl N-phenylcarbamates whose degradation
proceeds according to the unimolecular process E1cB.
The potential of the method for the hydrolysis of
BDMC in surface water samples has been demon-
strated. Samples of tap and surface water from different
sampling sites (river, dam, and STEP) all over Tunisia
were collected. The values of the observed rate con-
stant of this reaction are reported in Table II. According
to the found experimental results, we noted that the rate
constant is greater in a Milli-Q water sample than in
surface waters. This could be due to the presence of
organic matter, which slows the rate of hydrolysis due
to solute–organic interactions.
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CONCLUSION
In this work, we presented the kinetic study and the
hydrolysis mechanism in aqueous media of BDMC.
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International Journal of Chemical Kinetics DOI 10.1002/kin.21113