One-pot synthesis of dihydropyrimidinones using polyaniline-bismoclite complex. A facile and reusable catalyst for the biginelli reaction

Article abstract of DOI:10.1055/s-2004-822925

Polyaniline-bismoclite complex was used as an efficient catalyst for the three-component condensation reaction of an aldehyde, β-ketoester, and urea in ethanol to afford the dihydropyrimidinones in excellent yields. Furthermore, after completion of reacti

Full text of DOI:10.1055/s-2004-822925

LETTER
1285
One-Pot Synthesis of Dihydropyrimidinones Using Polyaniline–Bismoclite
Complex. A Facile and Reusable Catalyst for the Biginelli Reaction
A
F
acile andReu
a
sable Catal
n
yst for the
B
d
iginelli Reac
a
tion Gangadasu,a Srinivasan Palaniappan,*b Vaidya Jayathirtha Raoa
a
Organic Chemistry Division II, Indian Institute of Chemical Technology, Hyderabad 500 007, India
b
Organic Coatings & Polymers Division, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Fax +91(40)27160757; E-mail: palani74@rediffmail.com
Received 27 February 2004
There was no appreciable reaction when p-methoxy benz-
aldehyde was allowed to react with ethyl acetoacetate and
urea in the absence of catalyst in ethanol as solvent. Also,
the use of polyaniline or bismoclite alone as the catalyst
Abstract: Polyaniline-bismoclite complex was used as an efficient
catalyst for the three-component condensation reaction of an alde-
hyde, b-ketoester, and urea in ethanol to afford the dihydropyrimi-
dinones in excellent yields. Furthermore, after completion of
reaction the catalyst could be easily recovered and reused without did not yield the desired product. However, we found that
affecting its activity.
a catalytic amount of polyaniline–bismoclite complex (5
wt% with respect to the aldehyde) leads to the correspond-
ing 3,4-dihydropyrimidinones in 2 hours (98% yield). The
mechanism of the reaction would be similar to the acid-
catalyzed reaction as proposed by Kappe.20 The complete
conversion of the reaction was monitored by TLC
(Table 1, Scheme 1).
Key words: polyaniline–bismoclite, reusable catalyst, dihydropy-
rimidinones, one-pot condensation, Biginelli reaction
Appropriately functionalized 3,4-dihydropyrimidin-
2(1H)-ones have emerged as potent calcium channel
blockers,1 antihypertensive agents,2 a-adrenergic3 and
neuropeptide Y (NPY) antagonists.4 Several marine alka-
loids possessing the dihydropyrimidinone moiety have
shown interesting biological activities,5 for instance
batzelladine alkaloid has been reported to be a potent HIV
gp–120-CD4 inhibitor.6
Likewise, several aromatic, aliphatic and heterocyclic al-
dehydes reacted under similar reaction conditions to af-
ford the products in excellent yields. Aromatic aldehydes
carrying either electron donating or withdrawing substitu-
ents afforded high product yields with high purity (entries
4a–j) with exception of the electron withdrawing nitro
group (entry 4g), which takes a slightly longer reaction
time. Acid sensitive aldehydes, such as furfural, also
worked very well using previously published methods;21
however, in this work, hexanal reacted very well with eth-
yl acetoacetate and urea in the presence of PANI–BC cat-
alyst giving the corresponding dihydropyrimidinone in
good yield (entry 4l). Thiourea was also used to prepare
dihydropyimidin-2-(1H) thiones (entries 4m and 4n),
which show biological activity.20b,22
The synthesis of dihydropyrimidinones is currently im-
portant because of their wide range of pharmaceutical and
biological properties. The most simple and straightfor-
ward procedure reported by Biginelli in 1893 involves
one-pot condensation of ethyl acetoacetate, benzaldehyde
and urea under strong acidic conditions.7 However, the
main drawback of Biginelli reaction is unsatisfactory
yields obtained in the case of substituted aromatic and al-
iphatic aldehydes.8 Until now, several improved proce-
dures have been reported using catalysts such as Lewis
acids,9–13 triflates,14–16 soluble polymer-supported liquid
phase synthesis,17 silica-sulfuric acid18 and silver salt of
heteropoly acid.19 However, in spite of their potential util-
ity, many of these methods involve expensive reagents,
strong acidic conditions, longer reaction times, and unsat-
isfactory yields. In recent years, the development of more
economical and environmentally friendly conversion pro-
cesses is gaining interest in the chemical community.
Among the various solvents such as acetonitrile, toluene,
THF, ethanol for the formation of the dihydropyrimidi-
none using PANI–BC catalyst, ethanol was found to be
the best solvent. The amount of catalyst was also varied
as 5, 10, 15 and 20 wt% of the catalyst with respect to
p-methoxy benzaldehyde and it was found that 5 wt% of
PANI–BC complex is sufficient to push the reaction for-
ward, and higher amount of the catalyst did not improve
the result.
We wish to report a facile, efficient, and practical method
for the preparation of dihydropyrimidinones in excellent
yields using a catalytic amount (5 wt%) of the polyaniline–
bismoclite (PANI–BC) complex. PANI–BC complex can
be prepared easily with useful catalytic properties such as
recovery, reusability, stability and activity.23
The feasibility of reusability of the catalyst was also ex-
amined through a series of sequential condensations of
ethyl acetoacetate and urea with p-methoxy benzaldehyde
as a model substrate. In a typical reaction, the catalyst was
simply filtered from the reaction mixture and reused for
six cycles. The reaction preceded smoothly with a yield of
97–98% and this result indicates that the catalyst does not
lose its activity and can be reused.
SYNLETT 2004, No. 7, pp 1285–1287
0
3.
0
6.
2
0
0
4
Advanced online publication: 10.05.2004
DOI: 10.1055/s-2004-822925; Art ID: G05804ST
© Georg Thieme Verlag Stuttgart · New York

1286
B. Gangadasu et al.
LETTER
Table 1 Synthesis of Substituted 3,4-Dihydropyrimidin-2-(1H)-ones Using Polyaniline–Bismoclite
Product 4a
R
X
Time (h)
Yield (%)b
Mp (°C)
Found
Reported
4a
4b
4c
4d
4e
4f
C6H5
O
O
O
O
O
O
O
O
O
O
O
O
S
2
2
5
5
4
6
6
4
5
4
4
4
5
6
94
98
88
92
96
93
93
96
88
98
85
86
85
82
200–201
199–202
209–211
228–230
169–171
257–258
209–212
192–194
247–248
229–232
203–205
161–162
153–155
193–194
201–203
199–201
210–212
227–229
172
4-(OMe)-C6H4
4-Cl-C6H4
4-OH-C6H4
4-(Me)-C6H4
4-(NMe2)-C6H4
4-(NO2)-C6H4
3-(OPh)-C6H4
1-Naphthyl
Cinnamyl
256–257
208–211
194
4g
4h
4i
246
4j
232
4k
4l
2-Furfuryl
205
Pentyl
163
4m
4n
4-(OMe)-C6H4
4-(OH)-C6H4
150–152
–
S
a All products were characterized by 1H NMR, IR as well as mass spectroscopy and compared with authentic compounds.
b Isolated and unoptimized yields as well as melting points are uncorrected.
NH
O
R
O
O
(BiOCl) 0.38
X
n
NH
X
H5C2O
H3C
+
R-CHO
+
H3C
OC2H5
H2N
NH2
N
H
Ethanol
1
2
3
∆ 2–6 hr
4
Scheme 1
In conclusion, we have demonstrated a new, efficient and
seemingly general method for the synthesis of Biginelli
dihydropyrimidinones using PANI–BC complex. In addi-
tion to its simplicity and milder reaction conditions, this
method has the ability to tolerate a wide variety of substit-
uents in the carbonyl components leading to very high
yields using only catalytic amounts of PANI–BC (5 wt%
with respect to aldehyde). The salient features of the
present one-pot protocol are simplicity, high yields, and
direct isolation of the products in pure form. Furthermore,
the catalyst can be reused without losing its activity.
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Acknowledgment
The authors are thankful to the Head of the Divisions and the Direc-
tor, IICT for their support and encouragement. BG thanks to UGC,
New Delhi for the award of fellowship.
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Synlett 2004, No. 7, 1285–1287 © Thieme Stuttgart · New York

LETTER
A Facile and Reusable Catalyst for the Biginelli Reaction
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(23) (a) Typical Procedure for the Preparation of
Polyaniline–Bismoclite Complex
(i)Preparation of polyaniline-sulfate salt: In a typical
experiment, 10 mL of aniline was added to an aqueous
solution (700 mL) containing H2SO4 (30 mL) in a 2 L-round-
bottomed flask. The solution was kept under constant
stirring at 5–10 °C. To this solution, sodium persulfate (23.8
g) in water (250 mL) was added during 15–20 min. The
reaction was allowed to continue for 4 h. The precipitated
polyaniline-sulfate salt was filtered, washed with water (5 L)
followed by acetone (500 mL). (ii) Preparation of
polyaniline base: The obtained polyaniline-sulfate salt was
dispersed in an aqueous solution of NaOH (1 L, 1 N) and
stirred for 12 h at ambient temperature. The solution was
filtered and washed several times with water to remove the
excess NaOH. The product (polyaniline base) was dried at
100 °C until a constant mass was reached. (iii) Preparation
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prepared by the above method was added to acetone (500
mL) containing 0.1 M of BiCl3. The solution was stirred for
4 h under an N2 atmosphere at ambient temperature. The
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present in polyaniline salt (51.5%); (iii) conductivity (0.004
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Synlett 2004, No. 7, 1285–1287 © Thieme Stuttgart · New York