Solvent free synthesis of coumarins

Article abstract of DOI:10.1080/10426500214560

An efficient synthesis of 3-substituted coumarins under solventless system is described.

Full text of DOI:10.1080/10426500214560

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Phosphorus, Sulfur, and Silicon and the Related
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Solvent Free Synthesis of Coumarins
a
b
a
c
Abbas Shockravi , Hashem Shargi , Hassan Valizadeh & Majid M. Heravi
a
Department of Chemistry, School of Sciences, Teacher Training University, Tehran, Iran
Department of Chemistry, School of Sciences, Shiraz University, Shiraz, Iran
Department of Chemistry, School of Sciences, Azzahra University, Vanak, Tehran, Iran
b
c
Published online: 27 Oct 2010.
To cite this article: Abbas Shockravi , Hashem Shargi , Hassan Valizadeh & Majid M. Heravi (2002) Solvent Free Synthesis of
Coumarins, Phosphorus, Sulfur, and Silicon and the Related Elements, 177:11, 2555-2559, DOI: 10.1080/10426500214560
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Phosphorus, Sulfur and Silicon, 2002, Vol. 177:2555–2559
Copyright �C 2002 Taylor & Francis
1
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DOI: 10.1080/10426500290110757
SOLVENT FREE SYNTHESIS OF COUMARINS
a
b
a
Abbas Shockravi, Hashem Shargi, Hassan Valizadeh,
and Majid M. Heravic
Department of Chemistry, School of Sciences, Teacher Training
a
University, Tehran, Iran; Department of Chemistry, School
b
of Sciences, Shiraz University, Shiraz, Iran; and Department
of Chemistry, School of Sciences, Azzahra University, Vanak,
c
Tehran, Iran
(Received January 10, 2002; accepted )
An efficient synthesis of 3-substituted coumarins under solventless sys-
tem is described.
Keywords: Coumarin; �-ketoesters; piperidine; solventless system
Coumarins are very well known natural products and many such com-
1
pounds exhibited high levels of biological activity. Coumarins are also
2
3
used as additives to food and cosmetics, optical brightening agents
4
and dispersed flurescent and laser dyes. In addition some coumarins
5
6
are of much interest as a result of their toxcicity, carcinogenity, and
7
photodynamic effects.
More than 100 years ago Knoevenagel described the solution phase
condensation of 2-hydroxybenzaldehyde and malonic acid to afford
8
3
-carboxycoumarins. Although several methods have been reported
9
for the synthesis of coumarins, the Knoevenagel reaction has kept its
importance and originality. Recently several methods based on a solid
phase synthesis utilizing the Kneovenagel condensation for the prepa-
ration of coumarins have been reported. These methods have their
own merits and disadvantages, therefore introduction of efficient and
new methods based on green methodology is still in demand.
1
0
1
1
The ability of inorganic solid supports to enhance the reaction rates is
well known for several types of organic reactions,12 and the use of them
has been the main research topics of several laboratories, including
ours.13 Resently we have reported the montmorilonite K-10 catalyzed
Address correspondence to Majid M. Heravi, Department of Chemistry, School of
Sciences, Azzahra University, Vanak, Tehran, Iran. E-mail: mmheravi@azzahra.ac.ir
2
555

2
556
A. Shockravi et al.
Knoevenagel condensation in solventless system.14 Armed with these
experiments we report herein the Knoevenagel type condensation of
salisylaldehyds 1 and 2-hydroxy-1-naphtaldehyde with a variety of
�
-ketoesters supported onto MgO in � solventless system for the rapid
one-pot synthesis of 3-substituted coumarins. It is noteworthy to men-
tion that addition of piperidine enhanced the rate of reaction drasti-
cally. Use of base as a catalyst in Kneovenagel condensation has been
1
5
previously noticed.
Thus salisylaldehyde and its derivatives 1 as well as 2-hydroxy-1-
naphtaldehyde were reacted with �-ketoesters to afford a variety of
coumarins 2, 3, 4 (Scheme 1).
SCHEME 1
In conclusion this method describes a noticeable improvement in
reaction condition for the synthesis of substituted coumarins via the
Knoevenagel condensation and takes advantages of the reaction under
solvent free condition. As shown in Table I the time of reaction is
TABLE I Physical Properties and Yields of the Prepared Compounds
Reaction
time (min)
�
Entry
Product
R
m.p. ( C) Yield (%) Cryst. solvent
1
2
3
4
5
6
7
8
9
3a
3b
3c
2a
2b
4a
4b
4c
4d
4e
CO2Et
CO2Me
CN
COMe
CO2Et
CO2Et
CO2Me
CN
6
173–5
265–7
249–51
115–8
94–7
110–2
168–70
292–5
192–5
212–5
75
78
82
85
81
86
82
88
92
90
H2O/EtOH
H2O/EtOH
H2O/EtOH
CHCl3/EtOH
CHCl3/EtOH
CHCl3/EtOH
CHCl3/EtOH
CHCl3/EtOH
CHCl3/EtOH
CHCl3/EtOH
5.5
5.5
1
1
1
0.5
0.5
0.5
0.5
COMe
COPh
1
0

Solvent Free Synthesis of Coumarins
2557
reduced to a few minutes or even a few seconds. These reaction times in
some cases are even better than those under microwave irradiation.1
The reactions can be run safely in an efficient hood and the work-up
procedure is reduced to the filteration and crystallization from suitable
solvent.
0b
EXPERIMENTAL
The reactions were carried out in an efficient hood. The melting
points (uncorrected) were measured with a Stuart Scientific apparatus.
1
H-NMR spectra were recorded on a 60 MHz Bruker spectrometer using
TMS as an internal standard. IR spectra were measured on a Perkin-
Elmer model 543.
GENERAL PROCEDURE
A mixture of the appropriate hydroxyaldehyde (2.9 mmol) and
�
-ketoester (3 mmol) were supported on MgO (1.8 g). A drop of piperi-
dine was then added and this was grinded to make an intimate mixture.
The progress of the reaction was monitored by TLC using (petroleum
ether/Ethylacetate, 70/30%) as eluent. After the completion of the re-
action, the residue was dissolved in hot EtOH and filtered off. The sol-
vent was evaporated to dryness under reduced pressure and the crude
residue was crystallized from a suitable solvent to afford the substituted
coumarins. Melting points, yields, reaction times and crystallizing sol-
vents were given in Table I.
Selected Spectroscopic Data for 3a
1H NMR � (DMSO d6): 1.52 (t, 3H, Me), 4.55 (q, 2H, OCH2), 7–7.8 (m,
3
�
H, aromatic protons), 8.68 (s, 1H, olefinic CH), OH is unobserved; IR,
(KBr disc): 1725, 1685, Up to 3000 cm (OH broad).
�
1
Selected Spectroscopic Data for 3b
1H NMR � (DMSO d6): 3.8 (s, 3H, OMe), 6.9–7.7 (m, 3H, aromatic pro-
tons), 6.69 (s, 1H, olefinic CH), OH is unobserved, IR, � (KBr disc): 1715,
�
1
1
680, Up to 3000 cm (OH, broad).
Selected Spectroscopic Data for 3c
1H NMR � (DMSO d6): 6.9–7.9 (m, 3H, aromatic protons), 8.81 (s, 1H,
olefinic CH), OH is unobserved, IR, � (KBr disc): 2230, 1685, Up to
�
1
3
000 cm (OH, broad).

2
558
A. Shockravi et al.
Selected Spectroscopic Data for 2a
1
H NMR � (CDCl3): 2.85 (s, 3H, Me), 7.3–7.85 (m, 4H, aromatic protons),
.62 (s, 1H, olefinic CH), IR, � (KBr disc): 1750, 1680 cm .
�
1
8
Selected Spectroscopic Data for 2b
1H NMR � (CDCl3): 1.52 (t, 3H, Me), 4.55 (q, 2H, OCH2), 7.4–7.9 (m,
4
1
H, aromatic protons), 8.62 (s, 1H, olefinic CH); IR, � (KBr disc): 1790,
�
1
650 cm
.
Selected Spectroscopic Data for 4a
1H NMR � (CDCl3): 1.48 (t, 3H, Me), 4.45 (q, 2H, OCH2), 7.4–8.3 (m,
6
1
H, aromatic protons); 9.32 (s, 1H, olefinic CH),); IR, � (KBr disc): 1745,
�
1
680 cm
.
Selected Spectroscopic Data for 4b
1
H NMR � (CDCl3): 4.1 (s, 3H, OMe), 7.4–8.4 (m, 6H, aromatic protons),
.4 (s, 1H, olefinic CH); IR, � (KBr disc): 1730, 1685 cm .
�
1
9
Selected Spectroscopic Data for 4c
1
H NMR � (CDCl3): 7.4–8.5 (m, 6H, aromatic protons), 9.4 (s, 1H, olefinic
�
1
CH),); IR, � (KBr disc): 2245, 1675 cm
.
Selected Spectroscopic Data for 4d
1
H NMR � (CDCl3): 2.75 (s, 3H, Me), 7.4–8.5 (m, 6H, aromatic protons),
.4 (s, 1H, olefinic CH); IR, � (KBr disc): 1735, 1675 cm .
�
1
9
Selected Spectroscopic Data for 4e
1
H NMR � (CDCl3): 7.1–8.5 (m, 6H, aromatic protons), 9.3 (s, 1H, olefinic
�
1
CH); IR, � (KBr disc): 1710, 1625 cm
.
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