One pot synthesis of barbiturates on reaction of barbituric acid with aldehydes under microwave irradiation using a variety of catalysts

Article abstract of DOI:10.1081/SCC-120022485

The condensation of barbituric acid with aldehydes under microwave irradiation in dry media has been investigated in the presence of NH ₄OAc/AcOH (4/3, w/w) (41-54%), Montmorillonite K-10 (49-60%), Silica gel (52-63%), basic Al₂O₃ (56-67%), NaCl (57-69%), Montmorillonite KSF (62-70%), and KSF + NaCl (1:1, w/w) (70-89%).

Full text of DOI:10.1081/SCC-120022485

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One Pot Synthesis of Barbiturates on Reaction of
Barbituric Acid with Aldehydes Under Microwave
Irradiation Using a Variety of Catalysts
Sharwan K. Dewan a & Ravinder Singh a
a Laboratory of Synthetic Methodologies, Department of Chemistry, M.D. University, Rohtak
(Haryana), India
Published online: 21 Aug 2006.
To cite this article: Sharwan K. Dewan & Ravinder Singh (2003): One Pot Synthesis of Barbiturates on Reaction of Barbituric
Acid with Aldehydes Under Microwave Irradiation Using a Variety of Catalysts, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 33:17, 3081-3084
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 17, pp. 3081–3084, 2003
One Pot Synthesis of Barbiturates on Reaction
of Barbituric Acid with Aldehydes Under
Microwave Irradiation Using a Variety
of Catalysts
*
Sharwan K.Dewan and Ravinder Singh
Laboratory of Synthetic Methodologies, Department of
Chemistry, M.D. University, Rohtak (Haryana), India
ABSTRACT
The condensation of barbituric acid with aldehydes under microwave
irradiation in dry media has been investigated in the presence
of NH4OAc/AcOH (4/3, w/w) (41–54%), Montmorillonite K-10
(49–60%), Silica gel (52–63%), basic Al2O3 (56–67%), NaCl
(57–69%), Montmorillonite KSF (62–70%), and KSF þ NaCl (1:1,
w/w) (70–89%).
Key Words: Barbiturates; Aldehydes; K-10; KSF; NaCl; Silica gel;
Alumina.
*Correspondence: Sharwan K. Dewan, 1167, Sector-1, Rohtak-124001, India;
E-mail: sharwandewan@rediffmail.com.
3081
DOI: 10.1081/SCC-120022485
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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3082
Dewan and Singh
Scheme 1.
The barbiturates are associated with a number of biological activities
such as antibacterial, hypotensive, and sedative.[1–3] They are synthesized
by condensing barbituric acid with aldehydes under conventional reflux-
ing conditions in aqueous medium (Sch. 1).[4] The method requires longer
reaction times and tedious work-up. Villemin recently used microwave
irradiation to prepare the barbiturates in the presence of Montmorillonite
KSF clay as a catalyst.[5] Inspired by his research work, we describe
herein our results of the synthesis of 5-arylidene barbiturates in the pre-
sence of a variety of catalysts – NH4OAc/AcOH, (4/3 : w/w) Montmor-
illonite K-10, Silica gel, basic Alumina, NaCl, Montmorillonite KSF and
KSF/NaCl (10/1:w/w) in dry media under microwave irradiation, a tech-
nique which has become very popular in organic chemistry.[6]
We started by reacting the readily available p-chloro benzaldehyde
with barbituric acid in the presence of KSF Montmorillonite clay under a
variety of irradiation levels (80 W, 160 W, 240 W, 320 W, 400W, 480 W,
560 W, 640 W, 720 W and 800 W). The bestyield of 69% was obtained at
560 W after 7 min. Hence, we carried out all the catalytic reactions
described herein at 560 W. The yields obtained in the presence of various
catalysts are depicted in Table 1.
As can be seen, the NH4OAc/AcOH, (4/3:w/w) Montmorillonite
K-10, Silica gel and Alumina proved less effective yields (41–54%,
49–60%, 52–63% and 56–67% respectively). NaCl and KSF clay proved
superior and gave almostcomparable yields (57–69% and 62–70% respec-
tively). In view of this we were interested in investigating the condensation
reaction in presence of a mixture of KSF clay and NaCl. As expected
the yields increased to 70–90%. Mechanistically, we believe that the
ClÀ ions generate the desired barbiturate anion at 5-position and the
Montmorillonite KSF clay provides the necessary Lewis and Bronsted
acidities[6,7] in these Knoevenagel type condensations.
In conclusion, the mixture of the inexpensive and convenient cata-
lysts, Montmorillonite KSF and NaCl (10/1:w/w) has proved the best
among the catalysts used in these investigations. All the products were
identified on the basis of their NMR and IR spectra and by comparison
of their m.p. and Rf values with those of authentic samples.

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Barbituric Acid with Aldehydes
3083
Table 1. Condensation of aldehydes with barbituric acid in presence of various
catalysts under microwave irradiation (560 W)a.
Yield (%) with catalyst
Melting points
Aldehydes
(entry no.)
NH4-OAc/ K-10 Silica Al2O3
AcOH
KSF KSF & Observed Lit.
(ꢀC)
clay gel basic NaCl clay NaCl
(ꢀC)
Benzaldehyde (1)
4-OH
52
41
58
50
60
52
65
57
68
61
70
62
90 256(d)
81 275(d)
256(d)[4]
275(d)[4]
benzaldehyde (2)
4-Cl
50
43
54
59
51
60
63
54
63
66
58
67
68
60
69
69
62
70
75 270(d)
70 260
271(d)[8]
260[4]
benzaldehyde (3)
2-NO2
benzaldehyde (4)
3,4-Dimethoxy
benzaldehyde (5)
Cinnamaldehyde (6)
4-OCH3
77 >290
>290[4]
46
48
54
55
55
58
60
62
63
64
65
64
86 270(d)
85 279
270(d)[4]
279[4]
benzaldehyde (7)
aThe reactions were completed in ca 7 min.
TYPICAL EXPERIMENTAL PROCEDURE
Mixed barbituric acid (0.645 g, 5 mmol), 4-chlorobenzaldehyde
(0.702 g, 5 mmol) and a catalyst NH4OAc/AcOH, (40/30 mg) Montmor-
illonite K-10 (1 g), silica gel (1 g), alumina (chromatographic) (1 g), NaCl
(100 mg), Montmorillonite KSF (1 g) and KSF/NaCl (1 g/100 mg) were
taken in an Erlenmeyer flask (100 mL). The flask was subjected to irradia-
tion at 560 W (70%) level in a Kenstar OM-9925E (800 W) unmodified
domestic microwave oven operating at 2450 MHz. The flask was allowed
to cool and DMF (50 mL) was added. The mixture was filtered and the
ꢀ
solventremoved under reduced pressure (36 C/8 mmHg) to afford the
desired barbiturate. [Orange-reddish solid; m.p. (dec) 271ꢀ lit.[8] m.p. dec
270ꢀ; H-NMR ꢀ:7.5 (d, 2H, H arom, J ¼ 8 Hz), 8.1 (d, 2H, H arom,
J ¼ 8 Hz), 8.3 (s, 1H, CH¼), 11.27 (s, 1H, NH), 11.43 (s, 1H, NH); IR
(KBr) ꢁ in cmÀ1: 3520–3480 (NH), 1750 (C¼O), 1690 (NHCONH), 1650
(C¼O), 1550, (C¼C). Rf. 0.42 (benzene:ethyl acetate, 1:1).
ACKNOWLEDGMENT
We thank Professor A. J. Bellamy for inspiration and Dr. R. Sharma
(Dayton) for gifts of Mont. K-10 and KSF clays and Mr. Yashwant for a
gift of the Microwave oven used in this investigation.

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3084
Dewan and Singh
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references therein.
8. Vvedensskii, V.M. Chem. Heterocycl. Cmpd. 1969, 5, 827.
Received in the USA December 12, 2002