KAl(SO4)2·12H2O (alum) a reusable catalyst for the synthesis of some 4-substituted coumarins via Pechmann reaction under solvent-free conditions

Article abstract of DOI:10.1007/s00706-007-0833-9

A simple, efficient, and practical procedure for the Pechmann condensation using KAl(SO₄)₂·12H₂O (alum) as a non-toxic, reusable, inexpensive, and easily available catalyst is described under solvent-free condition at 65°C. These improved reaction conditions allow the preparation of a wide variety of some new substituted coumarins in high yields (86-96%) and purity under mild reaction conditions. Compared to the classical Pechmann condensation, this new method consistently has the advantage of high yields.

Full text of DOI:10.1007/s00706-007-0833-9

Monatsh Chem 139, 805–808 (2008)
DOI 10.1007/s00706-007-0833-9
Printed in The Netherlands
à
KAl(SO4)2 12H2O (alum) a reusable catalyst for the synthesis of some
4-substituted coumarins via Pechmann reaction under solvent-free conditions
Javad Azizian1, Ali A. Mohammadi1, Ilyar Bidar2, Peiman Mirzaei1
1
Department of Chemistry, Shahid Beheshti University, Tehran, Iran
2
Department of Chemistry, Islamic Azad University-Branch Saveh, Saveh, Iran
Received 7 October 2007; Accepted 22 October 2007; Published online 9 June 2008
# Springer-Verlag 2008
Abstract A simple, efficient, and practical procedure
for the Pechmann condensation using KAl(SO4)2 ꢀ
12H2O (alum) as a non-toxic, reusable, inexpensive,
and easily available catalyst is described under sol-
vent-free condition at 65ꢁC. These improved reaction
conditions allow the preparation of a wide variety of
some new substituted coumarins in high yields (86–
96%) and purity under mild reaction conditions.
Compared to the classical Pechmann condensation,
this new method consistently has the advantage of
high yields.
in food and cosmetics [8], in preparation of insecti-
cides, optical brighteners [9], dispersed fluorescent
and laser dyes [10], and intermediates for the syn-
thesis of furocoumarins, chromenes, coumarones,
and 2-acylresorcinols [11].
Coumarins could be synthesized by various
methods, such as Pechmann [12], Perkin [13],
Knoevenagel [14], Reformatsky [15], and Witting
[16] reactions. However, the Pechmann reaction is
one of the simplest and direct methods for the syn-
thesis of coumarin since it proceeds from very sim-
ple starting materials, namely, phenols and ꢁ-keto
esters or ꢀ,ꢁ-unsaturated carboxylic acids em-
ploying various catalysts, such as sulfuric acid
[12], trifluoroacetic acid [17], phosphorus pentoxide
[18], ZrCl4 [19], TiCl4 [20], ionic liquids [21], and
Amberlyst [22]. However, these catalysts have to be
used in excess; for example, H2SO4 in 10–12 equiv.
[23], CF3CO2H in 3–4 equiv. [17], and phosphorus
pentoxide in a five-fold excess [18]. Further, such
reaction requires long duration (24h [24], 20h [25]),
or high temperature (150ꢁC) [25] and also micro-
wave irradiation [26].
Keywords Pechmann condensation; Coumarins; KAl(SO4)2 ꢀ
12H2O (alum); Phenols; Solvent-free.
Introduction
Polyheterocyclic systems with coumarin ring skele-
ton, for example calanolides [1] and hydroxylomatin
[2], have been isolated from Calophyllum genus and
roots of Angelica purpuraefolia. They are well-
known for their antitumor and anti-HIV activities
[1, 2]. In addition, coumarins show some pharmaco-
logical and biological activities including inhibition
of platelet aggregation [3], anticancer [4], inhibition
of steroid 5ꢀ-reductase [5], antibacterial [6], and
anticoagulant [7]. Also, they are used as additives
Very recently, we have reported the ability of
KAl(SO4)2 ꢀ 12H2O (alum) as an effective catalyst
in the synthesis of benzimidazole [27], cis-isoquino-
lonic acid [28], and dihydropyrimidinones [29].
Herein, we describe a high-yielding protocol for
the Pechmann condensation of phenols and ꢁ-keto
esters for the synthesis of the some new coumarins 3
Correspondence: Ali A. Mohammadi, Department of Chem-
istry, Shahid Beheshti University, P.O. Box 19839-4716,
Tehran, Iran. E-mail: a-mohammadi@cc.sbu.ac.ir

806
J. Azizian et al.
Table 1 KAl(SO4)2 ꢀ 12H2O (alum)-catalyzed condensation
of 1,3,5-trihydroxybenzene (1a) and ethyl acetoacetate (2a)
under different reaction conditionsa
Entry
Solvent
Amount of
catalyst=mol%
Yield of
3a=%b
1
2
3
4
5c
H2O
20
20
20
20
20
50
80
68
65
Scheme 1
CH3CH2OH
toluene
CH3CN
none
using KAl(SO4)2 ꢀ 12H2O (alum) under mild condi-
96, 95,
93, 90, 88
95
tions (Scheme 1).
6
7
none
none
30
10
92
Results and discussion
a
The reaction were carried out in the presence of 1,3,5-
trihydroxybenzene (1a) (1 mmol), ethyl acetoacetate (2a)
(1.2 mmol), and KAl(SO4)2 ꢀ 12H2O at 65ꢁC for 120 min
In a typical experiment, a solvent-free mixture of
phenols and ꢁ-keto esters was heated at 65ꢁC in
presence of catalytic amount of alum (20 mol%).
The reaction was monitored by TLC (ethyl ace-
tate=petroleum ether, 1=1). Then, the reaction mix-
ture was poured into ice-cold water and stirred for
5 min. The solid product was obtained by simple
filtration and recrystallization from ethanol.
We found that the Pechmann condensation is af-
fected by various solvents as is evident from Table 1.
Most excitingly, the Pechmann condensation could
also be carried out under solvent-free condition in
excellent yield. Moreover, the best results are ob-
served when the molar ratio of phenols 1 and ꢁ-keto
esters 2 was 1:1.2. In addition, the activity of the
recycled alum was also examined according to the
typical experiment conditions. We obtained the de-
b
Isolated yield
Catalyst was reused for five times
c
sired product in 96, 95, 93, 90, and 88% yields with-
in five runs (Table 1, entry 5).
In order to study the generality of this procedure, a
series of Pechmann condensation were performed
similarly. The results are summarized in Table 2.
The two-component condensation reaction pro-
ceeded smoothly at 65ꢁC and completed in 2–
3.20 h under these conditions. We carried out this
reaction with a series of substituted phenols bearing
either electron-donating or electron-withdrawing
substituents, with ꢁ-keto esters in the presence of
alum to obtain the corresponding coumarins. The
Table 2 KAl(SO4)2 ꢀ 12H2O (alum)-catalyzed synthesis of coumarinsa
Entry
Compound 1b
Compound 2
Coumarin 3
Time=min
Yieldc=%
Ref.
1d
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1b
1b
1b
1b
1b
1c
1c
ethylacetoacetate (2a)
diethyl 1,3-acetonedicarboxylate (2b)
ethyl 2-chloroacetoacetate (2c)
ethyl cyclopentanone-2-carboxylate (2d)
ethyl benzoylacetate (2e)
2a
2b
2c
2d
2e
2a
2b
3a
3b
3c
3d
3e
3f
3g
3h
3i
120
100
130
120
120
150
130
120
130
130
210
200
96
95
94
93
92
91
92
93
92
91
88
86
[20]
–
[24]
[30]
[19]
[31]
–
[24]
[32]
[19]
[25]
–
9
10
11
12
3j
3k
3l
a
Reaction conditions: phenol (1 mmol), ꢁ-keto esters (1.2 mmol), and KAl(SO4)2 ꢀ 12H2O (20 mol%), 65ꢁC
1,3,5-Trihydroxybenzene (1a), 1,3-dihydroxybenzene (1b), 1-naphthol (1c)
Isolated yield
b
c
d
The reaction was carried out in the presence of 1,3,5-Trihydroxybenzene (1a), (0.1 mol), ethyl acetoacetate (2a) (0.12 mol), and
KAl(SO4)2 ꢀ 12H2O at 65ꢁC for 260 min

Pechmann reaction under solvent-free conditions
807
(s, C¼CH), 6.20 (s, ArH), 6.21 (s, ArH),10.34 (s, OH), 10.71
(s, OH) ppm; 13C NMR (DMSO-d6): ꢃ ¼ 14.49, 41.54, 60.56,
95.05, 99.41, 102.06, 111.59, 150.64, 156.94, 157.60, 160.60,
161.68, 170.20ppm; MS: m=z (%) ¼ 264 (Mþ, 50), 219 (100),
190 (45), 162 (90), 134 (30), 69 (50), 45 (50).
experimental procedure with this catalyst is very
simple and the catalyst can be removed easily (see
Experimental). Hence there will not be any unneces-
sary acidic waste stream to create environmentally
hazardous pollution. However, substrates having
electron-donating groups in the para position to
the site of electrophilic substitution gave maximum
yields under reaction conditions in shorter times.
Interestingly, we have found that this method is use-
ful for large scale preparation (Table 2, entry 1). All
products were identified by comparison of analytical
data (IR, NMR, MS, and CHN) with those reported
for authentic samples.
In conclusion, we describe a mild, convenient
method for the preparation of some new coumarins
by the Pechmann cyclocondensation reaction of phe-
nols and ꢁ-keto esters using cheap, non-toxic, very
soluble in water, recyclable, and easily available
KAl(SO4)2 ꢀ 12H2O (alum) catalyst under solvent-
free conditions. Additionally, this new reaction
might be a useful tool for high-throughput organic
synthesis.
Ethyl 2-(7-hydroxycoumarin-4-yl)acetate (3g, C13H12O5)
White powder; mp 155–157ꢁC; IR (KBr): ꢂꢀ¼ 3225, 1713,
1680cmꢂ1
;
1H NMR (DMSO-d6): ꢃ ¼ 1.17 (t, J ¼ 7.1 Hz,
CH3), 3.92 (s, CH2), 4.10 (q, J ¼ 7.1 Hz, CH2), 6.24 (s,
C¼CH), 6.73 (d, J ¼ 2.2 Hz, ArH), 6.79 (dd, J ¼ 2.2, 8.7 Hz,
ArH), 6.82 (d, J ¼ 8.7 Hz, ArH), 7.49 (d, J ¼ 8.7 Hz, ArH),
10.61 (s, OH) ppm; 13C NMR (DMSO-d6): ꢃ ¼ 14.42, 37.35,
61.33, 102.80, 111.66, 112.57, 113.48, 127.15, 150.07,
155.50, 160.60, 161.73, 169.62 ppm; MS: m=z (%) ¼ 248
(Mþ, 75), 220 (30), 192 (25), 176 (30), 147 (100), 91(30),
65 (30), 39 (30).
Ethyl 2-(benzo[h]coumarin-4-yl)acetate (3l, C17H14O2)
White powder; mp 134–136ꢁC; IR (KBr): ꢂꢀ¼ 1718,
1
1611cmꢂ1; H NMR (CDCl3): ꢃ ¼ 1.27 (t, J ¼ 7.1 Hz, CH3),
3.87 (s, CH2), 4.21 (q, J ¼ 7.1 Hz, CH2), 6.49 (s, C¼CH), 7.56
(m, 5H, ArH), 8.57 (m, 1H, ArH) ppm; 13C NMR (CDCl3):
ꢃ ¼ 14.10, 38.66, 61.85, 114.30, 116.29, 120.09, 122.68,
123.22, 124.41, 127.31, 127.67, 128.88, 134.83, 149.05,
151.04, 160.50, 168.73ppm; MS: m=z (%) ¼ 282 (Mþ, 80),
254 (30), 208 (35), 181 (95), 152 (100), 77 (10), 63 (30), 39
(30).
Experimental
Melting points were obtained in open capillary tubes and were
measured on an electrothermal 9200 apparatus. Mass spectra
were recorded on a Shimadzu QP 1100 BX mass spectrome-
ter. IR spectra were recorded on KBr pellets on a Shimadzu
IR-470 spectrophotometer. 1H and 13C NMR spectra were
determined on a Bruker 300 DRX Avance instrument at 300
and 75 MHz.
Acknowledgement
We gratefully acknowledge financial support from the
Research Council of Shahid Beheshti University.
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