Coumarins: Fast Synthesis by Knoevenagel Condensation under Microwave Irradiation

Article abstract of DOI:10.1039/a801724g

Condensation of salicyaldehyde or its derivatives with various derivatives of ethyl acetate in the presence of piperidine leads to the synthesis of coumarins by a solvent free reaction under microwave irradiation.

Full text of DOI:10.1039/a801724g

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468 J. CHEM. RESEARCH (S), 1998
J. Chem. Research (S),
1998, 468±469$
Coumarins: Fast Synthesis by Knoevenagel
Condensation under Microwave Irradiation$
Dariusz Bogdal
/
Department of Chemistry, Politechnika Krakowska, ul. Warszawska 24, 31-155 Krakow, Poland
Condensation of salicyaldehyde or its derivatives with various derivatives of ethyl acetate in the presence of piperidine
leads to the synthesis of coumarins by a solvent free reaction under microwave irradiation.
Coumarins are nowadays an important group of organic
compounds that are used as additives to food and
cosmetics,1 optical brightening agents2 and dispersed ¯uor-
escent and laser dyes.3 The derivatives of coumarin usually
occur as secondary metabolites present in seeds, roots and
leaves of many plant species. Their function is far from
clear, though suggestions include waste products, plant
growth regulators, fungistats and bacteriostats.4 It is there-
fore of utmost importance that the synthesis of coumarin
and its derivatives should be achieved by a simple and e€ec-
tive method.
Coumarins can be synthesised by methods such as
Claisen rearrangement, Perkin reaction and Pechmann reac-
tion as well as Knoevenagel condensation.5 Some of the
industrially important coumarins contain a 4-methyl substi-
tuted group [e.g., 7-hydroxy-4-methylcoumarin (Coumarin
47 or Coumarin 460) and 7-diethylamino-4-methylcoumarin
(Umbelliferon 47)] and can be prepared by the Pechman
reaction, via readily available 1,3-disubstituted compounds
and their acetoacetic esters.2
It was recently shown that the Pechman reaction could
be quickly achieved using microwave irradiation of the
reagents in a household microwave oven.6 Since solvent
free phase-transfer catalytic reactions under microwave
irradiation is the main topic in our laboratory,7 it has
prompted us to present our results of the synthesis of
coumarins by Knoevenagel condensation under such con-
ditions. Both Knoevenagel reaction8 and synthesis of
coumarin by Knoevenagel condensation9 have been the
subject of microwave induced reactions; in the case of cou-
marins the only example that has been given is the synthesis
of 3-ethoxycarbonylcoumarin (ethyl 2-oxo-2H-1-benzopyran-
3-carboxylate).
The aim of the present paper is to show that under micro-
wave irradiation the Knoevenagel condensation can be
successfully applied to the synthesis of a number of cou-
marins, and the scope of the method is very broad. We
report a very simple, fast and general procedure where
the condensation of salicylaldehyde or its derivatives with
various derivatives of ethyl acetate (e.g., R3CH2COEt;
R3 ˆ CO2Et, COMe, CN, p-C6H4NO2) in the presence of
piperidine under solvent-free conditions leads to the syn-
thesis of coumarins (Fig. 1).
The solvent-free conditions under microwave irradiation
o€ers several advantages:10 solvents are often expensive,
toxic, dicult to remove in the case of aprotic dipolar
solvents with high boiling point, and are environmentally
polluting agents. Moreover, liquid±liquid extraction is
avoided in the isolation of reaction products, and the
absence of solvent prevents the risk of hazardous explosions
when the reaction takes place in a microwave oven. The
reactions (i.e., the synthesis of coumarins) were usually com-
plete within 1±10 min and gave improved yield over conven-
tional methods in a shorter time. Moreover, the work-up
procedure is simply reduced to the recrystallization of pro-
duct from an appropriate solvent. Experimental results are
given in Table 1.
In summary, the method leads to a notable improvement
in reaction conditions for coumarin synthesis by Knoevenagel
condensation and takes advantage of both solvent free reac-
tion conditions and microwave activation. As shown in
Table 1, the reaction time is reduced to only a few minutes
Table 1 Results of coumarin syntheses by Knoevenagel reaction under microwave irradiation
Experimental
Literature
Yield (%)
Compound
Power (%)
Time/min
Ta/C
Yield (%)
Mpb/8C
Solvent
Mp/8C
3ac
3bc
3cc
3dd
3ec
3fc
3gc
3hd
3ic
10
20
20
40
10
Ð
10
1
4
129
90
89
94
76
85
72
90
90
78
55
88
80
90
80
75
82
75
91±92
EtOH
EtOH
EtOH
MeCO2H
EtOH
butan-2-one
MeCO2H
MeCO2H
EtOH
83
Ð
93±9411
12412
120±122
182±184
274±275
89±91
167±169
224±225
294±296
80±82
152±153
225±226
265±267
117±118
186±188
296±298
297±299
201
220
131
r.t.e
r.t.e
90
220
136
165
122
170
87
65
78
62
94
35
Ð
40
74
77
87
70
79
80
76
184±18513
268±26914
88±9015
173±17415
224±22615
30016
5
10
Ð
Ð
5
6
6
10
6
5
8
10
3
Ð
10
20
20
10
10
20
10
10
20
77±7817
151±15318
22918
3jc
EtOH
3kc
3ld
MeCN
MeCN
dioxane
MeCO2H
CHCl3
26318
4ac
4bc
4cc
4dd
11819
19018
100
170
298±29919
30318
DMF
aFinal temperature reached by the reaction mixture. bMelting points, measured on a Boetius-PHMK 05 microscope plates, are
uncorrected. cHydroxyaldehyde (100 mmol), carbonyl compound (2) (110 mmol) and piperidine (2.0 mmol). dHydroxyaldehyde
(50 mmol), carbonyl compound (2) (55 mmol) and piperidine (1.0 mmol); er.t. ˆ room temperature (in this case it is not necessary to
apply microwave power).
by using microwave dielectric heating. The reactions can be
run safely in good yields, and the work-up procedure is
reduced to the recrystallization of the desired products.
$This is a Short Paper as de®ned 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).

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J. CHEM. RESEARCH (S), 1998 469
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Fig. 1 Synthesis of coumarins by Knoevenagel condensation
under microwave irradiation
Experimental
Reactions were carried out under atmospheric pressure in an
open vessel adapted to a Synthwave 402 microwave monomode
reactor (Prolabo). All the compounds were identi®ed by GC-MS,
IR and NMR and gave satisfactory results in comparison with
authentic samples. Melting points are in good agreement with
literature data (Table 1).
General Procedure.ÐA mixture of
a
hydroxyaldehyde
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(100 mmol), carbonyl compound (2) (110 mmol) and piperidine
(0.20 g, 2.4 mmol) was irradiated with microwaves for the time
indicated in Table 1. At the end of exposure to microwaves, the
reaction mixture was cooled to room temperature, and the crude
product recrystallised from an appropriate solvent (Table 1) to
obtain the coumarins 3 and 4.
Received, 2nd March 1998; Accepted, 8th May 1998
Paper E/8/01724G
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