Facile Hydrolysis of Esters with KOH-Methanol at Ambient Temperature

Article abstract of DOI:10.1007/s00706-003-0114-1

A simple, rapid, and efficient method is reported for the hydrolysis of a variety of mono-and diesters of aromatic, aliphatic, fatty, and heterocyclic acids with potassium hydroxide in methanol at ambient temperature (～35°C).

Full text of DOI:10.1007/s00706-003-0114-1

Monatshefte f€ur Chemie 135, 83–87 (2004)
DOI 10.1007/s00706-003-0114-1
Facile Hydrolysis of Esters
with KOH-Methanol
at Ambient Temperature
ꢀ
Jitender M. Khurana , Sushma Chauhan, and Geeti Bansal
Department of Chemistry, University of Delhi, Delhi-110007, India
Received August 4, 2003; accepted September 15, 2003
Published online November 27, 2003 # Springer-Verlag 2003
Summary. A simple, rapid, and efficient method is reported for the hydrolysis of a variety of mono-
and diesters of aromatic, aliphatic, fatty, and heterocyclic acids with potassium hydroxide in methanol
at ambient temperature (ꢁ35ꢂC).
Keywords. Esters; Hydrolysis; Potassium hydroxide; Methanol.
Introduction
Ester hydrolysis has been known for long and is usually catalyzed by acids and
bases. Both acidic and alkaline hydrolysis are equilibrium reactions [1]. However
for preparative purposes, ester hydrolysis is invariably performed in basic solution
in order to shift the equilibrium unless the compound is base sensitive. The basic
hydrolysis is carried out with aqueous hydroxides in presence of co-solvents at
high temperatures and generally requires long durations for complete ester hydro-
lysis. Micellar catalysis [2], phase transfer catalysis [3], ultrasonic irradiation [4],
and microwaves [5] have been employed to overcome the problem of heteroge-
neous systems. In view of the importance of ester hydrolysis in organic synthesis,
there is scope for facile ester hydrolysis at ambient temperature. To the best of our
knowledge, we did not find any alkaline hydrolysis method wherein water had not
been used as a co-solvent. While working on reactions of different functionalities
with Al-KOH in methanol at ambient temperature [6], we realized that esters could
be hydrolyzed rapidly at ambient temperature with potassium hydroxide and
methanol without any co-solvent. Therefore, a detailed investigation on optimizing
the reaction conditions was taken up.
ꢀ
Corresponding author. E-mail: jmkhurana@chemistry.du.ac.in

84
J. M. Khurana et al.
Results and Discussion
This paper reports a simple, rapid, and efficient procedure for the hydrolysis of a
large variety of esters at ambient temperature (ꢁ35ꢂC) using potassium hydroxide
in methanol unlike most other methods which require aqueous hydroxides with co-
solvents and refluxing of the reaction mixtures for long durations. The hydrolysis
has been carried out on different mono- and diesters of aromatic, aliphatic, fatty,
and heterocyclic acids which gave the corresponding carboxylic acids in high
yields by a simple quenching procedure (Scheme 1). All the esters underwent
complete hydrolysis in 2 to 60 min. Our results are listed in Table 1.
Scheme 1
Table 1. Hydrolysis of esters with KOH-methanola at ꢁ35ꢂC
Run no. Ester RCOOR0
Molar ratio (Ester:KOH) Time=min Method Yield=% mp (Ref. [7])=ꢂC
1
2
Methyl benzoate
1:2
1:2
1:2
1:2
1:2
1:3
1:3
1:3
1:2
1:2
1:2
1:2
1:2
1:2
10
20
60
60
60
60
60
60
5
A
A
A
A
C
C
C
C
B
B
B
A
B
A
A
B
B
A
B
A
B
A
A
Ab
A
94
96
95
92
86
87
92
95
92
89
86
84
90
83
86
80
86
96
87
93
90
87
83
70
96
122–123 (121)
123 (121)
Ethyl benzoate
3
i-Propyl benzoate
122–123 (121)
123 (121)
4
n-Butyl benzoate
5
Benzyl benzoate
121 (121)
6
Phenyl benzoate
122–123 (121)
123 (121)
7
p-Cresyl benzoate
8
o-Cresyl benzoate
122 (121)
9
Methyl p-chlorobenzoate
Ethyl p-chlorobenzoate
Methyl m-chlorobenzoate
Methyl o-chlorobenzoate
Methyl p-nitrobenzoate
Ethyl p-nitrobenzoate
242 (243)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
20
5
245 (243)
157–160 (158)
139 (141)
5
2
238 (239)
10
2
243 (239)
Methyl 3,5-dinitrobenzoate 1:2
212 (207)
Methyl m-bromobenzoate
Methyl p-bromobenzoate
Methyl cinnamate
1:2
1:2
1:2
1:3
1:2
1:3
1:2
1:2
1:3
1:2
5
153 (155)
20
25
60
60
30
20
30
60
60
250–257 (252)
131 (133)
Methyl p-anisate
183 (184)
Methyl o-anisate
97 (101)
Methyl p-toluate
182 (178)
Methyl phenylacetate
Methyl diphenylacetate
Amyl phenylacetate
Methyl phenoxyacetate
76–78 (76)
148–150 (148)
76 (76)
101 (99)
(continued)

Facile Hydrolysis of Esters
85
Table 1 (continued)
Run no. Ester RCOOR0
Molar ratio (Ester:KOH) Time=min Method Yield=% mp (Ref. [7])=ꢂC
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
Methyl p-bromophenoxyacetate 1:2
60
60
60
60
60
60
60
5
B
87
87
82
87
79
81
94
90
84
88
96
87
62
67
97
73
90
160–161 (160-1)
153 (152)
Methyl p-methylphenoxyacetate 1:2
Methyl p-chlorophenoxyacetate 1:2
B
B
158 (157)
Methyl ꢀ-naphthoate
Methyl 2-furoate
Methyl piperonoate
Methyl veratrate
Diethyl phthalate
Di n-butyl phthalate
Di n-octyl phthalate
Diethyl oxalate
1:2
1:2
1:2
1:3
1:4
1:4
1:4
1:4
1:2
1:2
1:4
1:2
1:4
1:4
B
162–163 (162)
132–134 (132)
228–230 (229)
181 (179–182)
208–209 (210)
208 (210)
A
B
A
Bc
Bc
Bc
D
D
D
D
Af
B
30
60
5
60e
60e
60
60
60
60
208 (210)
197 (198)d
Ethyl acetate
136 (136)d
Methyl chloroacetate
Dimethyl adipate
Cholesteryl acetate
Methyl stearate
156 (160)d
160 (163)d
148–149 (148.5)
65 (67-8)
Methyl aleuritate
B
97 (100)
a
b
c
Methanol used was 3 cm3=g of ester; acid obtained after washing with water; a part of the acid was obtained as its S-
benzylisothiouronium salt because of its partial solubility in water; d mp of the corresponding S-benzyl isothiouronium salt;
e
f
TLC could not be monitored and so it was worked up after 60 min; isolated yield of cholesterol
Methanol is the solvent of choice for rapid hydrolysis of esters at ambient
temperature. Methyl benzoate was also observed to undergo hydrolysis with
KOH-ethanol and KOH-n-propanol, albeit in poorer yields. This could be due to
the higher solubility of KOH in methanol compared to other protic solvents. The
reactions were carried out using 3 cm3 of methanol=g of ester. Higher dilution or
temperatures below 35ꢂC slowed the hydrolysis significantly. Hydrolysis attempted
in polar aprotic solvents like acetonitrile, dioxane, DMF, etc. under identical con-
ditions was very sluggish. Addition of water as co-solvent also affected the hydro-
lysis drastically and reactions were not complete even after 6 h at ꢁ35ꢂC.
Most esters of aromatic acids formed a solid lump within a few minutes of the
reaction suggesting the formation of insoluble sodium salt of carboxylic acid
unlike esters of aliphatic acids. The alcoholic portion of the ester was also varied
in order to study the generality of the reaction. It was observed that methyl esters
are most readily hydrolyzed and increasing bulk of the alkyl group requires longer
reaction times. Esters of aromatic acids gave clean hydrolysis products unlike
esters of aliphatic acids having ꢀ-hydrogens probably due to competing aldol type
condensations. It was also observed that aromatic esters with electron withdrawing
groups underwent hydrolysis faster than those containing electron releasing groups
in accordance with Hammett equation. Hydrolysis was very sluggish in case of
esters containing acidic protons (e.g., methyl salicylate, methyl p-hydroxybenzo-
ate, diethyl malonate, and ethyl acetoacetate) and a large amount of starting mate-
rial was recovered unchanged obviously due to the formation of stabilized anions.
This method helps to save time and energy to achieve the desired goals.

86
J. M. Khurana et al.
Experimental
Potassium hydroxide (Qualigens) and methanol (SD Fine) were used. The esters obtained from
commercial sources were distilled=recrystallized before use and others were prepared by known
procedures. The IR spectra were recorded on a Perkin Elmer FT-IR and NMR spectra were recorded
on a FT-NMR model R-600 (60 MHz) with TMS as internal standard.
General Procedure
In a typical experiment, 1 g of ester and 3 cm3 of methanol were placed in a 25 cm3 round-bottomed
flask mounted over a magnetic stirrer and maintained at ꢁ35ꢂC. KOH (see Table 1) was added and the
contents were stirred. The reactions were quenched invariably after 60min by addition of 10cm3 of
water. Unreacted ester, if any, was removed by ether extraction (2ꢃ 5 cm3) and the carboxylic acid was
recovered by one of the methods given below. The carboxylic acids were characterized by their mp,
mixed mp, and NMR spectra.
Method A: The aqueous portion was acidified to pH¼ 2 with 6 N hydrochloric acid and extracted
with ether (3ꢃ 5 cm3). The combined ether extracts were dried with Na2SO4 and concentrated on a
Buechi rotavapor. The carboxylic acid was obtained after drying under vacuum.
Method B: The aqueous portion was acidified to pH ¼ 2 with 6 N hydrochloric acid. The carboxylic
acid precipitated on standing, was filtered off, and dried under vacuum.
Method C: The aqueous portion was acidified to pH¼ 2 with 6 N hydrochloric acid and treated
with aq. sodium bicarbonate solution (ꢁ5%) with stirring till basic to litmus. The phenol was removed
by extraction with ether (2ꢃ 5 cm3). The aqueous layer was acidified with 6 N hydrochloric acid and
the acid was extracted with ether (3 ꢃ 5 cm3). The combined ether extracts were dried with Na2SO4
and concentrated on a Buechi rotavapor. The carboxylic acid was obtained after drying under vacuum.
Method D: The aqueous portion was acidified to pH¼ 2 with 6 N hydrochloric acid and treated
with aq. sodium bicarbonate solution (ꢁ5%) with stirring till basic to litmus. A saturated solution of S-
benzyl isothiouronium chloride was added and the carboxylic acid was recovered as S-benzyl iso-
thiouronium salt from the solution.
Acknowledgements
SC and GB are thankful to CSIR, New Delhi, India, for grant of Junior and Senior Research Fellowships.
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