PEG-SO3H: A mild and efficient recyclable catalyst for the synthesis of coumarin derivatives

Article abstract of DOI:10.1016/j.crci.2011.10.005

A simple and efficient synthesis of coumarin derivatives through condensation reaction of substituted phenols and dicarbonyl compounds using PEG-SO₃H as a recyclable catalyst under solvent-free conditions is described.

Full text of DOI:10.1016/j.crci.2011.10.005

C. R. Chimie 15 (2012) 91–95
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Full paper/M e´ moire
PEG-SO H: A mild and efficient recyclable catalyst for the synthesis
3
of coumarin derivatives
G.M. Nazeruddin *, M.S. Pandharpatte, K.B. Mulani
Department of Chemistry (P.G. & Research Centre), Poona College of Arts, Science & Commerce, Pune, India
A R T I C L E I N F O
A B S T R A C T
Article history:
A simple and efficient synthesis of coumarin derivatives through condensation reaction of
Received 11 May 2011
substituted phenols and dicarbonyl compounds using PEG-SO
under solvent-free conditions is described.
ß 2011 Acad e´ mie des sciences. Published by Elsevier Masson SAS. All rights reserved.
3
H as a recyclable catalyst
Accepted after revision 18 October 2011
Available online 13 December 2011
Keywords:
3
PEG-SO H
Pechmann condensation
Solvent-free conditions
1
. Introduction
The synthesis of coumarin and their derivatives has
[12], periodic mesoporous silica chloride (PMSCl) [13],
benzylsulfonic acid functionalized mesoporous Zr-TMS
[14], dipyridine copper chloride[15], indium chloride [16]
have also been used. Recently, there have been also various
reports on the use of microwaves [17], However, most of
the reported methods suffer from one or more of the
disadvantages such as long reaction time, vigorous
reaction conditions, the occurrence of side reactions and
unavailability of the reagents, as well as poor yields of the
desired product. Thus, there is still a demand to develop
new and mild methods for the synthesis of coumarin
derivatives in the presence of inexpensive and bench top
reagents. Hence, it is imperative to develop a convenient,
efficient and user-friendly method for the synthesis of
coumarins.
Development of novel synthetic methodologies to
facilitate the preparation of a desired molecule is an
intense area of research. Efforts have been made
constantly to introduce new methodologies which are
efficient and more compatible with the environment. One
of the most desirable approaches to address this challenge
attracted considerable attention of organic and medicinal
chemists, because a large number of natural products
contain this heterocyclic nucleus; most of them show wide
biological activities like anthelmintic, hypnotic, insecticid-
al and anticoagulant properties [1]. They are widely used
as additives in food, cosmetics, agrochemicals, optical
brightening agents, dispersed fluorescent, tunable dye
lasers [2]. These compounds also act as intermediates for
the synthesis of fluoro coumarins, chromenes, coumar-
ones, 2-acyl resorcinols and others [3]. Many routes have
been reported for the synthesis of coumarin derivatives
including Perkin [4], Pechmann [5], Knoevenagel [6],
Reformatsky [7] and Wittig [8] reactions. The Pechmann
reaction involves the condensation of phenols with b-keto
esters in the presence of variety of acidic condensing
agents such as sulfuric acid, hydrochloric acid, trifluroa-
cetic acid, phosphoric acids, phosphorous pentoxide and
Lewis acids such as ZnCl
2 3 3
, FeCl , AlCl [9], ion exchange
resins [10], solid acid catalysts [11], cellulose sulfuric acid
constitutes
a search of surrogates for traditionally
employed organic solvents which suffer from various
health and environmental concerns [18]. For many years,
functionalized polymers have been employed as stoichio-
metric reagents and catalysts in organic synthesis.
*
Corresponding author.
E-mail address: gmnazeruddin@yahoo.co.in (G.M. Nazeruddin).
1
631-0748/$ – see front matter ß 2011 Acad e´ mie des sciences. Published by Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.crci.2011.10.005

9
2
G.M. Nazeruddin et al. / C. R. Chimie 15 (2012) 91–95
CH3
OH
O
O
PEG-SO H
3
R
0
R
+
Solvent -free ,80 C
H
3
C
OCH
3
O
O
R=CH ,OH,C H
6 5,
3
Scheme 1.
However, their development and applications in organic
synthesis are undergoing a tremendous renaissance at
present, which is undoubtedly being fueled by the special
requirements of combinatorial and green chemistry
application of solvent-free conditions [23]. A move away
from the use of solvents in organic synthesis has led in
some cases to improve the yields and more benign
synthetic procedures. Owing to the importance of PEG-
[
19,20].
From the viewpoint of green chemistry, PEG is found to
3
SO H to develop environmentally friendly reactions,
herein, we report a simple, efficient and high yielding
protocol for the synthesis of coumarin derivatives using
be an interesting solvent system. It is inexpensive,
thermally stable, non-volatile, non-toxic and easily de-
gradable, commercially available in different molecular
weights and has broad solubility profile. According to these
excellent properties, PEGs are an important group of
polymers and catalysts in several branches of chemistry,
particularly in organic synthesis [21]. Based on recent
efforts to use eco-friendly and environmentally benign
reagents in chemistry, PEGs are good candidates for these
purposes [22].
3
PEG-SO H as a catalyst for the first time under solvent-free
conditions (Scheme 1).
2. Result and discussion
The condensation of substituted phenol (1 mmol) and
dicarbonyl compounds (1.1 mmol) in the presence of PEG-
SO H (10 mol %) as a catalyst under solvent-free conditions
3
at 80 8C furnished the desired product in excellent yield.
Also the catalyst was successfully recovered and recycled
at least for three runs without significant loss in activity.
The results are shown in Table 1 and the possible
mechanism of the reaction is depicted in Scheme 2. To
In view of the emerging importance of PEGs as novel
reaction media, we wish to report a mild and highly
efficient method for the synthesis of coumarin derivatives.
The drive towards clean synthesis has encouraged the
OH
OH
OH
HO
O
O
HO
O
O
H
O
HO
OH
H
OC
2
H
5
OC H
2
5
OC
2
H
5
2
O S
H
O
n
HO
O
O
H
H
O
-C
-PEG-SO H
3
2 5
H OH
H
O
OH
O
2
S
H
O
2
S
H
O
n
O
n
HO
O
O
Scheme 2.

G.M. Nazeruddin et al. / C. R. Chimie 15 (2012) 91–95
93
Table 1
Synthesis of coumarin derivatives using PEG-SO
3
H catalyst.
Entry Phenol
b-keto ester
Product
Reaction time Yield (%) Melting
min) Point (8C)
(
3
a
10 183–184 [25]
91
O
O
O
O
HO
OH
OCH3
OCH3
HO
O
O
3
b
OH
OH
15
89
283–285 [25]
HO
OH
HO
O
O
3
3
3
c
OH
OH
20
40
20
83
78
89
250–252 [25]
131–132 [26]
244–246 [25]
O
O
O
O
O
O
OCH3
OCH3
OCH3
O
O
OH
d
OH
O
O
e
OH
OH
OH
HO
O
O
OH
OH
3
f
40
88
154–156 [26]
O
O
O
O
OCH3
O
O
3
g
OH
40
81
102–103
N
OCH3
O
O
N
3
h
OH
O
O
O
60
80
263–265
O
OEt
HO
OH
HO
OH

9
4
G.M. Nazeruddin et al. / C. R. Chimie 15 (2012) 91–95
Table 2
TLC. After completion of the reaction, the reaction mixture
was cooled to room temperature and poured into crushed
ice and stirred for 5 min. The crude product was collected
by filtration under suction, washed with ice cold water and
recrystallized from hot ethanol to afford pure coumarin
derivatives. In order to recover the catalyst totally, the
filtrate was dried under vacuum and washed with diethyl
ether and reused after drying under vacuum.
Optimum conditions for the preparation of coumarin derivatives using
different catalyst by reaction between resorcinol and methyl acetoace-
tate.
Entry
Catalyst
Reaction time
Yield (%)
1
2
3
4
5
37% BF
PEG-6000
PEG-SO
Silica sulfuric acid
SnCl
3
.SiO
2
1.5 h
8 h
65
35
3
H
10 min
5 min
2.5 h
86
80 [20]
52 [21]
2
6. Conclusion
Table 3
Optimum temperature for the preparation of coumarin derivatives using
We have developed an efficient and environmentally
PEG-SO
3
H by reaction between resorcinol and methyl acetoacetate.
benign strategy for the synthesis of coumarin derivatives
using PEG-SO H as a catalyst. This method offers several
3
Entry
Temperature in 8C
Reaction time in min
Yield (%)
advantages including high yield of products, short reaction
time, low cost, cleaner reaction profile and ease of
preparation of catalyst and ease of product isolation. Also
the catalyst was successfully recovered and recycled at
least for three runs without significant loss in activity.
1
2
3
50
60
80
45
30
10
60
78
91
compare the activity of various catalysts such as silica
sulfuric acid, SnCl , BF SiO , PEG itself with PEG-SO H,
2
3
2
3
7. The spectral data
Pechmann condensation of resorcinol and methyl acet-
oacetate in ratio (1:1.1) was carried out in the presence of
different catalyst (10 mol%) at 80 8C under solvent-free
conditions (Table 2). Excellent yield of desired product was
1
3a: H NMR (CDCl
3
+ DMSO, 200 MHz); 2.4 (s, 3H, CH3);
6.06 (s, 1H, CH); 6.80 (d, J = 8.3 Hz, Ar-2H), 7.48 (d,
J = 8.3 Hz, Ar-1H), 10.0 (s, OH); IR (KBr) 3198, 1679, 1600,
1451, 1390, 1330, 1273, 1239, 1133, 1068, 845; Anal. Calcd
3
obtained when PEG-SO H was used as a catalyst. But when
the temperature was less than 80 8C, low yield of the
product was obtained, as shown in Table 3.
for C10
H
8
O
3
: C, 68.18; H, 4.58; Found C, 68.30; H, 4.51.
3b: H NMR (CDCl , 200 MHz); 2.52 (s, 3H, CH3); 5.89 (s,
H, CH); 6.20 (d, J = 8.0 Hz, Ar-1H), 6.28 (d, J = 8.0 Hz, Ar-
1H); 10.39 (s, OH); 10.61 (s, OH); IR (KBr) 3430, 3142, 1700,
553, 1474, 1385, 1363, 1237, 1301, 1160, 1098, 1077, 930,
1
3
1
3
. Experimental
1
All reagents were purchased from Merck and Loba and
8 4
1077, 930, 832, 760; Anal. Calcd for C10H O : C, 62.50; H,
used without further purification. Melting points were
measured in open capillary and are uncorrected. The
products were characterized by IR spectra, H NMR, and
4.20; Found C, 62.67; H, 4.32.
1
3c: H NMR (DMSO, 200 MHz); 2.26 (s, 3H, CH3); 2.52
(s, 3H, CH3); 6.04 (s, 1H, CH), 6.56 (s, 1H, Ar-H), 6.61 (s, 1H,
Ar-H); 10.56 (s, OH); IR (KBr) 3392, 3052, 1656, 1613, 1512,
1404, 1380, 1339, 1251, 1150, 1098, 1074, 920, 851, 828,
1
elemental analyses. IR spectra were recorded on Perkin-
1
Elmer FT-IR-1710 instrument. H NMR was recorded on
BrukerAC-200 MHz and BrukerMSL-300 instrument using
TMS as an internal standard. Elemental analyses were
determined by an elemental analyser (CHNS-O, EA 1108-
elemental analyser, Carlo Erba instruments).
594; Anal. Calcd for C11
69.58, H, 5.43.
H
10
O
3
; C, 69.46; H, 5.30; Found C,
1
3d: H NMR (CDCl
3
, 300 MHz) 2.42 (s, 3H, CH3), 2.45
d
(s, 3H, CH3), 6.22 (s, 1H, CH), 7.09 (d, J = 6.2 Hz, Ar-1H), 7.46
d, J = 6.2 Hz, Ar-1H); IR (KBr) 2900, 2724, 2360, 1720,
1638, 1459, 1377, 1307, 1215, 1154, 1077, 964, 894, 722;
(
4
3
. Preparation of PEG-SO H catalyst
Anal. Calcd for; C11
H
10
O
2
; C, 75.84; H, 5.79; Found C, 75.98;
A catalyst was prepared according to reported proce-
dure [24] at 0 8C, chlorosulfonic acid (1.16 g, 10 mmol) was
H, 5.64.
1
3e: H NMR (DMSO,200 MHz)
d
2.38 (s.3H, CH3), 6.14 (s,
added to a solution of PEG-6000 (6.0 g, 1 mmol) in 10 mL of
1H, CH), 6.81 (d, J = 8.0 Hz, Ar-1H), 6.85 (d, 1H, 8.0 Hz, Ar-
H), 7.4 (s, OH), 7.6 (s, OH); IR (KBr) 2942, 2727, 2361, 1455,
2 2
CH Cl . Then the resulting solution was stirred at room
temperature for overnight and concentrated under vacu-
um. Followed by addition of 60 mL of ether and precipitate
obtained by filtration was washed with 30 mL of ether
8 4
1377, 1303, 1154, 1063, 964, 722; Anal. Calcd for; C10H O
C, 62.50; H, 4.20; Found C, 62.61; H, 4.29.
1
3f: H NMR (DMSO, 300 MHz)
d2.42 (s, 3H, CH3), 6.72
three times to afford the PEG-SO
3
H.
(s, 1H, CH), 7.43–8.47 (m, 6H, Ar-H); IR (KBr) 3403, 3054,
916, 1786, 1713, 1639, 1612, 1473, 1375, 1238, 1173,
1082, 943, 842, 809, 748, 890, 500; Anal. Calcd for;
; C, 79.98; H, 4.79; Found C, 79.85, H, 4.84.
2
5
. General procedure for synthesis of coumarin
derivatives
14 10 2
C H O
1
3g: H NMR (DMSO, 200 MHz)d2.38 (s, 3H, CH3), 7.30–
To a mixture of the phenolic compound (1 mmol) and
dicarbonyl compound (1.1 mmol), PEG-SO H (10 mol%)
was added and the resulting mixture was heated at 80 8C
Table 1). The progress of the reaction was monitored by
9.01 (m, 6H, Ar-H); IR (KBr) 3434, 3184, 2700, 2093, 1602,
1521, 1428, 1379, 1332, 1273, 1194, 1096, 883, 820, 773,
3
619, 559; Anal. Calcd for; C13
9 2
H NO ; C, 73.92; H, 4.29; N,
(
6.63; Found C, 74.05; H, 4.41; N, 6.71.

G.M. Nazeruddin et al. / C. R. Chimie 15 (2012) 91–95
95
1
[10] E.V.O. John, S.S. Israelstam, J. Org. Chem. 26 (1961) 240.
3
h: H NMR (DMSO, 200 MHz)
d1.65 (m, 4H, CH2), 2.35
[
[
11] T. Jin, J. Guo, Y. Yin, H. Liu, T. Li, Ind. J. Chem. 42 (2003) 2612.
12] B. Suresh Kuarm, J. Venu Madhav, S. Vijaya Laxmi, B. Rajitha, Y.
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(
1
2
m, 2H, CH2), 3.04 (m, 2H, CH2), 6.15 (s, 1H, Ar-H), 6.24 (s,
H, Ar-H), 10.13 (s, OH), 10.38 (s, OH); IR (KBr) 2924, 2727,
360, 1636, 1460, 1377, 1301, 1161, 820, 722; Anal. Calcd
40 (2010) 3358.
[
[
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7
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Acknowledgement
7
[
The authors are thankful to the University Grants
Commission, New Delhi, for financial assistance.
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[
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