110
Chemistry Letters 2001
Solvent-Free Coumarin Synthesis
Teizo Sugino and Koichi Tanaka*
Department of Applied Chemistry, Faculty of Engineering, Ehime University, Matsuyama, Ehime 790-8577
(Received November 20, 2000; CL-001048)
The synthesis of coumarins via Pechmann and
To an equivalent mixture of resorcinol (1a, 1.1 g, 10.0
mmol) and ethyl acetoacetate (2a, 1.3 g, 10.0 mmol) was added
TsOH (0.09 g, 0.5 mmol) in a mortar and ground well with a
pestle at room temperature. The mixture was heated at 60 °C
for 10 min under atmosphere. After cooling, water was added
to the reaction mixture and the crystalline products were col-
lected by filtration to give 7-hydroxy-4-methylcoumarin (3a,
1.73 g) in 98% yield. The crude crystals thus obtained were
recrystallized from EtOH to give pure 3a as colorless prisms
(mp 185–187 °C). Similarly, solvent-free Pechmann reactions
of 1 and 2 afforded 3b, 3c, 3e, 3f, and 3g in 92, 79, 69, 81, and
66% yields, respectively (Table 1). This method is very useful
because 3b, 3d, 3e and 3f have not hitherto been obtained from
the reaction in H2SO4;5 however 3d was not formed either in
H2SO4 or in the absence of a solvent.
Knoevenagel condensation reactions under solvent-free condi-
tions is reported, in which waste minimization, simple opera-
tion and easier product work-up can be achieved.
Coumarin derivatives are important chemicals in the per-
fume, cosmetic, agricultural and pharmaceutical industries.1
However, the conventional methods for coumarin synthesis
require drastic conditions. For example, 4-methyl-7-hydroxy-
coumarin has been prepared by stirring a mixture of resorcinol
and ethyl acetoacetate in concd H2SO4 for 12–24 h.2 The
development of alternative environmentally friendly synthetic
methods of coumarins is strongly requested. Recently, synthe-
sis of 7-hydroxycoumarin derivatives via the Pechmann reac-
tion catalyzed by solid acid catalysts (e.g., zeolite H-beta) in
refluxing toluene has been reported.3 The solid base catalyzed
synthesis of coumarin-3-carboxylic acids derivatives by
Knoevenagel reaction in refluxing toluene has also been report-
ed.4 Here, we report a simple and efficient synthesis of
coumarins via the Pechmann and Knoevenagel condensation
reactions under solvent-free conditions.
Solvent-free Knoevenagel reactions of salicylaldehydes (4)
and β-keto esters (2) were also found to proceed efficiently and
under milder reaction conditions than in EtOH solution.6 For
example, a mixture of salicylaldehyde (4a, 1.22 g, 10.0 mmol),
diethyl malonate (2e, 1.60 g, 10.0 mmol) and a few drops of
piperidine was mixed and ground well for 5 min at room tem-
perature. The reaction mixture was neutralized with dil HCl
and then the crystalline product was isolated by filtration to
give 3-ethoxycarbonylcoumarin (5c, 2.07 g) in 95% yield. The
crude crystals thus obtained were recrystallized from EtOH to
give pure 5c as colorless prisms (mp 94–95 °C). Similarly, sub-
stituted coumarin derivatives were obtained in high yields
(Table 2). When 2-hydroxy-1-naphthaldehyde (6) reacted with
β-keto esters (2) under the same reaction conditions in the
absence of a solvent, benzocoumarin derivatives (7) were
obtained in high yields (Table 3). Recently, montmorillonite
KSF catalyzed Knoevenagel reaction of salicylaldehyde (4a)
and diethyl malonate (2e) in the absence of solvent at 160 °C
was found to give 5c in 44% yield.7
It has been reported that the Knoevenagel reaction of 2-
Copyright © 2001 The Chemical Society of Japan
Sugino, Teizo
