Synthesis of salicylic acid derivatives in presence of ultrasonic irradiation using water as solvent

Article abstract of DOI:10.1081/SCC-120018940

An improved synthesis of salicylic acid using ultrasonic irradiation and water as solvent can be achieved with copper and pyridine as catalysts. A number of salicylic acids were prepared in good yield and in a short reaction time.

Full text of DOI:10.1081/SCC-120018940

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Synthesis of Salicylic Acid Derivatives in Presence of
Ultrasonic Irradiation Using Water as Solvent
Maite L. Docampo Palacios a & Rolando F. Pellón Comdom a
a Centro de Química Farmacéutica, La Habana, Cuba
Version of record first published: 17 Aug 2006.
To cite this article: Maite L. Docampo Palacios & Rolando F. Pellón Comdom (2003): Synthesis of Salicylic Acid Derivatives
in Presence of Ultrasonic Irradiation Using Water as Solvent, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 33:10, 1783-1787
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 10, pp. 1783–1787, 2003
Synthesis of Salicylic Acid Derivatives in
Presence of Ultrasonic Irradiation
Using Water as Solvent
*
Maite L. Docampo Palacios and Rolando F. Pellon Comdom
Centro de Quımica Farmaceutica, La Habana, Cuba
ABSTRACT
An improved synthesis of salicylic acid using ultrasonic irradiation
and water as solvent can be achieved with copper and pyridine as
catalysts. A number of salicylic acids were prepared in good yield
and in a short reaction time.
The development of a new synthesis of salicylic acid derivatives is
interesting, as these derivatives are widely used in organic synthesis, in
laboratory works, and as antimicrobial cleaning compositions.[1]
*Correspondence: Rolando F. Pellon Comdom, Centro de Quımica
Farmaceutica, Apartado 16042, La Habana, Cuba; Fax: (537) 336471; E-mail:
pellonrf@cqf.co.cu.
1783
DOI: 10.1081/SCC-120018940
Copyright & 2003 by Marcel Dekker, Inc.
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1784
Docampo Palacios and Pellon Comdom
Acceleration of organic reactions by the use of ultrasound irradiation
has been largely exemplified[2] and has gained popularity over usual homo-
genous and heterogeneous reactions.[3] It offers a reduction in reaction
time and a saving in energy; often these are accompanied by increased
yields and purity of products. There are few references in the literature
related to the hydrolysis of 2-halogenobenzoic acids in order to obtain
salicylic acid, the hydrolysis of 2-bromobenzoic acid is reported by Lisitsyn
and Shestakov[4] in presence of copper acetate and aqueous piperidine.
Recently, we have studied the use of copper and pyridine as catalyst
for the hydrolysis of 2-chlorobenzoic derivatives using water as solvent.[5]
In the present communication we have studied the use of ultrasound
irradiation in the synthesis of salicylic acid derivatives in order to
reduce the reaction time.
RESULTS AND DISCUSSION
The best yield obtained in our previous investigation for the hydro-
lysis of 2-chlorobenzoic acid in presence of water as solvent was reported
using 3 equivalents of potassium carbonate, 1 equivalent of pyridine, 3%
(by weight) of copper per mole of 2-chlorobenzoic acid in 2 h reaction
time. These conditions were used for the synthesis of several salicylic acid
derivatives.
First, we studied the reaction time in presence of ultrasonic irradi-
ation and we took as a model the hydrolysis of 2-chlorobenzoic acid in
the conditions previously reported. As we can see in Table 1, in only
15 min reaction time the best yield was obtained. All experiments
performed in this work were repeated five times. The yields reported
represent a media of the obtained values for each reaction.
Table 2 shows the results from several experiments for the hydrolysis
of 2-chlorobenzoic acid with different quantities of pyridine using copper
powder (3% in weight) and 3 equivalents of potassium carbonate per
mole of 2-chlorobenzoic acid, the reaction time in all cases was 15 min.
In these reaction conditions the best results were obtained using 0.5
equivalents of pyridine.

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Ultrasonic Irradiation of Salicylic Acid Derivatives
1785
Table 1. Effect of the time on the reaction yield using ultrasonic
irradiation in presence of water as solvent.
Ultrasonic irradiation
time (min)
Yield of
salicylic acid (%)
Standard deviation
(%)
30
25
20
15
10
95
96
95
94
57
2.0
1.5
1.0
2.0
2.0
Table 2. Effect of pyridine on the reaction yieid using
ultrasonic irradiation in presence of water as solvent.
Equivalents of
pyridine
% yield of
salicylic acid
Standard
deviation (S)
1.00
0.75
0.50
0.25
94
95
95
61
1.5
1.0
1.0
1.5
Once the quantity of pyridine necessary for the reaction was
established, a series of salicylic acid derivatives, employing the conditions
above studied were obtained.
Table 3 shows the results of salicylic acid derivatives synthesized
from the corresponding 2-chlorobenzoic acid derivatives, the melting
points (uncorrected), the elemental analysis, and the yields obtained were
compared with the method using reflux water during 2 h reaction time.
EXPERIMENTAL PART
General Procedure
Synthesis of Salicylic Acid Derivatives Using Water as
Solvent
A mixture of 2-chlorobenzoic acid derivative, (6.26 g; 0.04 mol), anhy-
drous potassium carbonate (8.28 g; 0.06 mol), pyridine (1.58 g; 0.02 mol),
copper powder (0.2 g) and water (25 mL) was irradiated for 15 min a sonic
horn at 20 kHz. The reaction mixture was cooled, poured into water and

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1786
Docampo Palacios and Pellon Comdom
Table 3. Salicylic acid synthesised from the corresponding 2-chlorobenzoic acid
derivatives.
Yield
using ultra-
sound (%)
Yield in
2 h at
reflux (%)
M.p.
uncorrected
(ꢀC)
M.p
Lit. (ꢀC)
No.
R1
R2
R3
1
2
3
4
5
6
7
H
H
H
H
H
95
95
96
92
97
96
92
90
88
90
84
95
93
87
159
212
158–160[6]
210–212[7]
226[8]
H
Cl
NO2
H
H
225
171
H
Cl
171–172[9]
233–235[10]
144[11]
H
H
NO2
H
234
143–144
141
NO2
H
H
H
CH3O
141[12]
Calculated and experimental microanalysis
Calculated (%)
Experimental (%)
No.
Formula
C
H
C
H
1
2
3
4
5
6
7
8
C7H6O3
60.87
48.70
45.90
48.70
45.90
45.90
57.14
48.70
4.35
2.90
2.73
2.90
2.73
2.73
4.76
2.90
61.05
48.96
46.18
48.95
45.71
45.83
56.97
48.80
4.04
2.68
2.48
2.51
2.61
2.83
4.80
2.78
C7H5ClO3
C7H5NO5
C7H5ClO3
C7H5NO5
C7H5NO5
C8H8O4
C7H5ClO3
acidified with hydrochloric acid (1:1) to pH 3. The solid was filtered and
crystallized from ethanol/water (1:2). The yield, melting point (uncor-
rected) for each salicylic acid obtained are reported in Table 3.
REFERENCES
1. Allan, A.; George, I.; Michael, R.; Rabone, K.L. Antimicrobial
cleaning compositions and their use as disinfectants (Unilever PLC;
Unilever N.V., UK). PCT Int. Appl. WO 9535364 A1 28 Dec 1995,
34 pp.

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Ultrasonic Irradiation of Salicylic Acid Derivatives
1787
2. Pestman, M.J.; Engberts, J.B.; Jong, F. Sonochemestry: Theory
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Received in the USA August 16, 2002

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