Montmorillonite Clay Catalysis. Part 7.1 An Environmentally Friendly Procedure for the Synthesis of Coumarins via Pechmann Condensation of Phenols with Ethyl Acetoacetate

Article abstract of DOI:10.1039/a703694i

Coumarins are synthesised via Pechmann condensation of phenols with ethyl acetoacetate catalysed by montmorillonite clay in satisfactory yields; the scope and limitation of the method have been investigated.

Full text of DOI:10.1039/a703694i

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38 J. CHEM. RESEARCH (S), 1998
Montmorillonite Clay Catalysis. Part 7.1 An Environmentally
Friendly Procedure for the Synthesis of Coumarins via
Pechmann Condensation of Phenols with Ethyl
Acetoacetate†
J. Chem. Research (S),
1998, 38–39†
Tong-Shuang Li,* Zhan-Hui Zhang, Feng Yang and Cheng-Guang Fu
Department of Chemistry, Hebei University, Baoding 071102, Hebei Province, P.R. China
Coumarins are synthesised via Pechmann condensation of phenols with ethyl acetoacetate catalysed by montmorillonite
clay in satisfactory yields; the scope and limitation of the method have been investigated.
K-10 or KSF
O
O
Coumarins occupy a special place in the realm of natural and
synthetic organic chemistry because many products which
contain this subunit exhibit useful and diverse biological
activity such as molluscacides,2 have anthelmintic, hypnotic
and insecticidal properties,3 or serve as anticoagulant agents4
or fluorescent brighteners.5 These compounds can also be
used for the synthesis of other products such as furocoumar-
ins, chromenes, coumarones and 2-acylresorcinols.6
O
toluene, reflux
OH
+
R
R
CO2Et
0-96 %
1
Me
2
Scheme 1
have to be used in excess, and they are subject to increasing
environmental pollution and are non-recoverable. Conse-
quently, there is a need for efficient and heterogeneous cata-
lytic methods for this reaction by using inexpensive, easily
handled and non-polluting catalysts. Cation-exchange
resins,15 Nafion-H,16 zeolite-HBEA and other solid acids17
have been employed for this purpose. More recently, micro-
wave irradiation was applied to accelerate this reaction.18
Montmorillonite clays have been used as efficient catalysts
for a variety of organic reactions.19 They are inexpensive non-
toxic powders which can be filtered easily from reaction mix-
tures and may be reused. However, syntheses of coumarins
directly catalysed by montmorillonite clays have not been
reported. In connection with our work on montmorillonite
clays catalysis,20 herein we describe an environmentally
There have been many synthetic routes to the coumarins7
including the Pechmann,8 Perkin,9 Knoevenagel,10,11 Refor-
matsky12 and Wittig5,13 reactions. However, the Pechmann
reaction has been the most widely applied method for pre-
paring coumarins since it proceeds from very simple starting
materials and gives good yields of coumarins substituted in
either the pyrone or benzene ring or in both. The course of
the reaction depends on the substituents on the phenol, on
the catalyst used and on the nature of the b-oxo ester. The
Pechmann reaction has been studied with homogeneous acid
catalysts such as sulfuric, hydrochloric, phosphoric8 and tri-
fluoroacetic acid,14 and with Lewis acids such as zinc chloride,
iron(III) chloride, tin(IV) chloride, titanium chloride and alu-
minium chloride.8 However, these conventional catalysts
Table 1 Synthesis of coumarin from phenols with ethyl acetoacetate catalysed by montmorillonite clays
Yield(%)a
Mp (T/°C)
Coumarin
substituents
Catalyst/solvent/
temp. (T/°)
Phenol
t/h
Found
Lit.
Found
Reported
18416
Resorcinol (1a)
4-Me-7-OH
K-10/none/150
K-10/toluene/reflux
KSF/none/150
4
8
96
9016
188–188.5
94
5
88
KSF/toluene/reflux
K-10/toluene/reflux
KSF/toluene/reflux
K-10/toluene/reflux
K-10/none/150
10
8
8
10
8
12
12
8
10
12
12
12
12
12
12
12
12
12
12
12
12
90
Phloroglucinol (1b)
4-Me-5,7-(OH)2
85
49.115
284–285
284.5–28515
88
Pyrogallol (1c)
m-Cresol (1d)
4-Methyl-7,8-(OH)2
4,7-Me2
66
5616
2516
234–235
131.5–132
23316
13416
69b
61b
61b
80
KSF/none/150
p-Cresol (1e)
4,6-Me2
4-Me-7,8-benzo
4-Me
K-10/none/150
014
8521
322
149–150
170.5–171
83–84
150–15124
17021
a-Naphthol (1f)
K-10/none/150
Phenol (1g)
K-10/none/150
65b
68b
83–8423
18325
2-Naphthol (1h)
4-Me-6,7-benzo
no reaction
no reaction
no reaction
no reaction
no reaction
no reaction
no reaction
no reaction
no reaction
no reaction
no reaction
K-10/none/150
2025
182–183
c
2-Nitrophenol (1i)
K-10/none-150
—
c
3-Nitrophenol (1j)
K-10/none/150
—
c
4-Nitrophenol (1k)
2-Chlorophenol (1l)
2,4-Dichlorophenol (1m)
Hydroquinone (1n)
Salicylaldehyde (1o)
4-Hydroxybenzaldehyde (1p)
2-Aminophenol (1q)
4-Aminophenol (1r)
4-(4-Nitrophenylazo)orcinol (1s)
K-10/none/150
—
c
K-10/none/150
—
c
K-10/none/150
—
c
K-10/none/150
—
c
K-10/none/150
—
c
K-10/toluene/reflux
K-10/toluene/reflux
K-10/toluene/reflux
K-10/toluene/reflux
—
c
—
c
—
c
—
aIsolated yield. bNet yield, conversion rate of 1d = 15%, conversion rate of 1e = 4%, conversion rate of 1g = 7%, conversion rate of
1h = 5%. c100% of starting materials were recovered.
friendly procedure for the synthesis of coumarins via Pech-
*To receive any correspondence (e-mail: orgsyn@hbu.edu.cn).
mann reaction catalysed by montmorillonite K-10 and KSF.
†This is a Short Paper as defined in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there-
fore no corresponding material in J. Chem. Research (M).
As shown in Table 1, in the presence of montmorillonite
clays, several phenols (1a, 1b 1f) and ethyl acetoacetate were

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J. CHEM. RESEARCH (S), 1998 39
heated in the absence of solvent or in refluxing toluene to
give the corresponding coumarins in high yields. Pyrogallol
(1c) afforded a good yield, m-cresol (1d), p-cresol (1e), phe-
nol (1g) and b-naphthol (1h) provided poor conversion rates
whereas nitrophenol (1i, 1j and 1k), 2-chlorophenol (1l),
2,4-dichlorophenol (1m), hydroquinone (1n), salicylaldehyde
(1o), p-hydroxybenzaldehyde (1p), o-aminophenol (1q),
p-aminophenol (1r) and 4-(p-nitrophenylazo)orcinol (1s) all
failed to afford the corresponding coumarins. From the
experimental results, it can be proved that phenols having
electron-donating substituents in the position meta to the
phenol hydroxy group promote the condensation. The ǹE
effects of these substituents support formation of the reactive
polarised carbonation in the ortho position. An alkyl group is
not strong enough to furnish the activation needed and thus
gives a low yield (1d). In contrast, electron-withdrawing
groups inhibit the reaction.
Generally speaking, K-10 worked better than KSF in term
of reaction time and yield. The optimum amount of the cata-
lyst used was between 25 and 30% by weight of the total
reactants. Catalysts were easily regenerated by washing with
ethanol, followed by drying at 110 °C for 12 h. The catalyst
K-10 and KSF could be reused four times in the reaction with
1a without significant loss of activity.
We are grateful to NSFC (29572039), the Science and
Technology Commission of Hebei Province and the Educa-
tion Commission of Hebei Province for financial support.
Received, 28th May 1997; Accepted, 29th September 1997
Paper E/7/03694I
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Experimental
Melting points are uncorrected. Montmorillonite K-10 and
KSF were purchased from Fluka and dried at 100 °C prior to use.
Ethyl acetoaceate and all liquid phenols were distilled before use.
The products were characterized by their melting points and/or IR
and 1H NMR spectra and by comparison with their literature
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General Procedure for the Synthesis of Coumarins.—A mixture
of the phenolic compound
1 (5 mmol), ethyl acetoaceate
(5 mmol) and montmorillonite K-10 (or KSF) (30 wt% to 1 and
ethyl acetoacetate) was refluxed in toluene (10 ml) using a Dean–
Stark apparatus to remove water (or heated at 150 °C for those
reactions in the absence of solvent) with constant stirring for
4–12 h as indicated in Table 1. The reaction was monitored by
TLC. The montmorillonite was filtered off and washed with hot
ethanol (2Å5 ml). The solvent was removed under reduced pres-
sure to afford the crude product. The crude product was purified by
column chromatography on silica gel [light peroleum (bp
60–90 °C)–ethyl acetate as eluent] to give the pure coumarin 2,
yield 0–96% (Table 1).
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