Comparative kinetic studies on the alkaline hydrolysis of halogen substituted isocoumarins

Article abstract of DOI:10.3906/kim-0906-75

Kinetics of the hydrolysis of 3-(2'-chloro-6'-fluorobenzyl)isocoumarin (1), 3-(4'-fluorophenyl)isocoumarin (3), 3-(2'-fluorophenyl)isocoumarin (5), 3-(2'-chlorophenyl)isocoumarin (7), and 3-(4'-chlorophenyl)isocoumarin (9) were studied spectrophotometrica

Full text of DOI:10.3906/kim-0906-75

Turk J Chem
34 (2010) , 381 – 386.
¨
˙
c
ꢀ TUBITAK
doi:10.3906/kim-0906-75
Comparative kinetic studies on the alkaline hydrolysis of
halogen substituted isocoumarins
H. Badaruddin AHMAD1,∗, M. Aslam MALANA2, Muhammad YOUSAF2,
Muhammad REHAN2, Mazhar ABBAS2, ABAIDULLAH2
1Department of Chemistry B. Z. University Multan 60000, PAKISTAN
e-mail: hafizbadar@gmail.com
2Department of Chemistry GC University Faisalabad 38000, PAKISTAN
Received 25.06.2009
Kinetics of the hydrolysis of 3-(2ꢀ -chloro-6ꢀ -fluorobenzyl)isocoumarin (1), 3-(4ꢀ -fluorophenyl)isocoumarin
(3), 3-(2ꢀ -fluorophenyl)isocoumarin (5), 3-(2ꢀ -chlorophenyl)isocoumarin (7), and 3-(4ꢀ -chlorophenyl)isoco-
umarin (9) were studied spectrophotometrically in the presence of aqueous solution of potassium hydroxide.
The rates of hydrolyses for these isocoumarins were compared. The data for isocoumarin (1) were further
investigated to probe the reaction mechanism. The dependence of pseudo-first order rate constant kobs on
hydroxide ion concentration is fitted by the expression kobs = ko + k1 [OH] + k2 [OH]2 , showing the forma-
tion of monoanionic and dianionic tetrahedral intermediates during the course of reaction. The magnitude
of ko shows significant participation of solvent in the reaction mechanism.
Key Words: Hydrolysis, isocoumarin, kinetics.
Introduction
Isocoumarins are hydrolyzed to ketoacids by treating them with aqueous potassium hydroxide solution.1
The mechanism of such a reaction has not yet been studied. Various pathways have been proposed for the
hydrolysis of esters and amides.2−4 Some exceptional cases5 of such reactions involve the formation of dianionic
tetrahedral intermediates. In continuation of our previous studies,6 kinetics of hydrolysis of 3-(2ꢀ -chloro-6ꢀ -
fluorobenzyl)isocoumarin (1), 3-(4ꢀ -fluorophenyl)isocoumarin (3), 3-(2ꢀ -fluorophenyl)isocoumarin (5), 3-(2ꢀ -
chlorophenyl)isocoumarin (7), and 3-(4ꢀ -chlorophenyl)isocoumarin (9) to respective keto acids were observed
to probe the reaction mechanism and to compare the rates of reactions of isocoumarins.
∗Corresponding author
381

Comparative kinetic studies on the alkaline hydrolysis of halogen..., H. B. AHMAD, et al.,
Experimental
Kinetics of the hydrolyses of the 3-(2ꢀ -chloro-6ꢀ -fluorobenzyl)isocoumarin (1), 3-(4ꢀ -fluorophenyl)isocoumarin
(3) 3-(2ꢀ -fluorophenyl)isocoumarin (5) 3-(2ꢀ -chlorophenyl)isocoumarin (7) 3-(4ꢀ -chlorophenyl)isocoumarin (9)
were studied in the presence of various concentrations (0.2-1.0 M) of aqueous potassium hydroxide solution at
25 ◦ C. The substrates (0.1g) were dissolved in ethanol (10cm3). The reactions were initiated by injecting 0.1
cm3 of the substrate solution to 3 cm3 potassium hydroxide solution. Initial concentration of the substrate
were usually of the order 10−4 mol dm−3 and were kept at least 20-fold less than the concentration of the
most dilute potassium hydroxide solution to maintain the pseudo-first order conditions. Rate measurements
were made, by using UV-Visible Spectrophotometer. Reactions were followed at a single wavelength as a trace
of absorbance versus time (or a printout of absorbance readings against time). In some cases, the change in
absorbance with time was followed by scanning over an appropriate wavelength range at suitable time intervals.
Rate coefficients were obtained as the slope of plots of ln(A∞-At) versus time where A∞ and At are the
absorbances at the completion of reaction and that at any time (t) respectively.
Results and Discussion
The compounds, 3-(2ꢀ -chloro-6ꢀ -fluorobenzyl)isocoumarin (1), 3-(2ꢀ -fluorophenyl)isocoumarin (3), 3-(4ꢀ -fluo-
rophenyl)isocoumarin (5), 3-(4ꢀ -chlorophenyl)isocoumarin (7), and 3-(3ꢀ -chlorophenyl)isocoumarin (9) were
synthesized by a literature procedure.7 On hydrolysis of these compounds with potassium hydroxide, they afford
2-[2ꢀ -oxo-3ꢀ -(2ꢀꢀ -chloro-6ꢀꢀ -fluorophenyl)propyl]benzoic acid (2), 2-(4ꢀ -fluorobenzoyl)methylbenzoic acid (4), 2-
(2ꢀ -fluorobenzoyl)methylbenzoic acid (6), 2-(4ꢀ -chlorobenzoyl)methylbenzoic acid (8), and 2-(3ꢀ -chlorobenzoyl)
methylbenzoic acid (10). The products were confirmed by their NMR and mass spectrometric studies.
F
F
KOH
O
O
COOH
Cl
Cl
O
(1)
(2)
F
F
O
O
COOH
O
(4)
(3)
382

Comparative kinetic studies on the alkaline hydrolysis of halogen..., H. B. AHMAD, et al.,
O
O
COOH
F
F
O
(6)
(5)
Cl
Cl
O
O
COOH
(8)
O
(7)
O
O
COOH
Cl
Cl
(10)
O
(9)
Kinetic studies of these reactions were carried out spectrophotometrically. The data were obtained for
at least three half lives to calculate rate constants (kobs). Measurements were made at the wavelengths where
the changes in absorbances were maximum. The absorbances decrease with time. Plots of ln(A∞-At) versus
time, gave a straight line showing the reactions are of first order in the substrate. The rates of reactions for the
hydrolyses of compounds (1), (3), (5), (7), and (9) are compared in the Table.
Table. Comparison of rates for the hydrolysis of isocoumarins.
S No. Name of isocoumarin
2nd order rate constants
in dm3 mol−1 min−1
1
2
3
4
5
3-(2ꢀ-Chloro-6ꢀ-fluorobenzyl)isocoumarin (1)
0.0272
3-(4ꢀ-fluorophenyl)isocoumarin (3)
3-(2ꢀ-fluorophenyl)isocoumarin (5)
3-(2ꢀ-chlorophenyl)isocoumarin (7)
3-(3ꢀ-chlorophenyl)isocoumarin (9)
0.0217
0.0264
0.0252
0.0237
It is obvious from the Table that rate of reaction for compound 1 is maximum and that of compound 3
is minimum. This may be interpreted as due to the presence of anionic intermediate. In the case of compound
1, 2 halogen atoms are attached to the benzene ring. Due to their strong withdrawing inductive effect, the
anionic intermediate is stabilized, hence facilitating the reaction, and the rate of reaction is faster. Based on
comparison of the rates of reaction of compounds 5 and 7, fluorine has a stronger electron withdrawing effect
than chlorine. On comparing the rates for the hydrolyses of compounds 3 and 5 a fluorine atom is attached
at position 4 in compound 3 and on position 2 in compound 5. Hence the latter has a faster rate than the
former. The hydrolysis of 3-(2ꢀꢀ -choloro-6ꢀꢀ -fluorobenzyl)isocoumarin was further investigated to determine the
383

Comparative kinetic studies on the alkaline hydrolysis of halogen..., H. B. AHMAD, et al.,
reaction mechanism. The intercept (ko = 0.0186 per min) of the plot of pseudo-first order rate constant kobs
against hydroxide ion concentration indicates the occurrence of significant spontaneous hydrolysis. The value
of second order rate constant k (0.0272 dm3 mol−1 min−1) was calculated as a slope of this plot (Figure 1).
0.05
y = 0.0272x + 0.0186
R2 = 0.9999
0.04
0.03
0.02
0.01
0
0
0.5
1
Hydroxide Concentration
Figure 1. Plot of pseudo-first order rate constant kobs against hydroxide ion concentration.
One possible mechanism for this reaction is given in the Scheme, which is in line with previous studies.9
F
F
K1
-
+HO
O
O
Cl
Route-1
Cl
(1)
O
_
OH
-
O
OH
k1
F
-
K2
+HO
F
Route-2
k2
OH
COOH
O
Cl
F
Cl
O
_
O
_
O
COOH
Cl
(2)
Scheme
While discussing the presence of monoanionic or dianionic intermediate 2 equations are proposed:
kobs = ko + k1[OH]
(1)
(2)
kobs = ko + k1[OH] + k2[OH]2
384

Comparative kinetic studies on the alkaline hydrolysis of halogen..., H. B. AHMAD, et al.,
If the dianionic intermediate is formed then the second order equation should follow experimental data.
If it is true then Eq. (2) can be rearranged as follows:
kobs − ko/[OH] = k1 + k2[OH]
(3)
The plot of kobs – ko /[OH] for different concentrations of hydroxide ions gives a straight line. This
indicates the presence of a dianionic tetrahedral intermediate (Figure 2).
0.0218
0.0216
0.0214
0.0212
0.021
0.0208
0.0206
0.0204
0.0202
0.02
0.0198
0
0.2
0.4
0.6
0.8
1
Hydroxide Ion Concentration
Figure 2. Plot of kobs-ko/[HO− ] versus [HO− ] for the hydrolysis of 3-(2ꢀ -chloro-6ꢀ -fluorobenzyl)isocoumarin in the
presence of aqueous solution of KOH.
Taking the values of k2 and k1 as intercept and slope, respectively, kobs was calculated by using Eq. (2).
The values of kobs and kcal are in good agreement with each other for the alkaline hydrolysis of compound 1.
The overlaid data of kcal and kobs at various hydroxide ion concentrations is shown in Figure 3, where the solid
line is a plot of kcal versus hydroxide ion concentrations and the points represent the experimental values.
0.04
0.035
0.03
0.025
0.02
0.015
0.01
0.005
0
0
0.2
0.4
0.6
0.8
1
Hydroxide Ion Concentration
Figure 3. Comparison of the pseudo-first order rate constant kobs with kcal for the hydrolysis of 3-(2ꢀ -chloro-6ꢀ -
fluorobenzyl)isocoumarin in the presence of aqueous solution of KOH.
If a graph is plotted between kobs / [HO− ] and hydroxide ion concentrations, ignoring the term ko , the
plot is not linear (Figure 4). This shows the significant contribution of ko in the reaction.
385

Comparative kinetic studies on the alkaline hydrolysis of halogen..., H. B. AHMAD, et al.,
0.14
0.12
0.1
0.08
0.06
0.04
0.02
0
0
0.2
0.4
0.6
0.8
1
Hydroxide Ion Concentration
Figure 4. Plot of kobs /[HO− ] vs [HO− ] ignoring ko for the hydrolysis of 3-(2ꢀ -chloro-6ꢀ -fluorobenzyl)isocoumarin in
the presence of aqueous solution of KOH.
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386

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