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Krishnamurthy et al. Int. J. Res. Chem. Environ. Vol. 4 Issue 4 (115-119) October 2014
International Journal of
Research in Chemistry and Environment
Available online at: www.ijrce.org
ISSN 2248-9649
Research Paper
1- (3, 4 - Dichlorobenzenesulfonyl) -3-methyl-1H-imidazolium chloride: An
Efficient Catalyst for Bigineli Reaction
* Krishnamurthy G. and Jagannath K. V.
Department of Studies in Chemistry, Central College Campus, Bangalore University, Bangalore, INDIA
(Received 16rd July 2014, Accepted 55th August 2014)
Abstract: 1-(3, 4-Dichlorobenzenesulfonyl)-3-methyl-1H-imidazolium chloride is used as an effective catalyst for
bigineli reactions in the synthesis of octahydroquinazolinone in water. The catalyst could be easily recovered and
reused without significant decrease of the catalytic activity. All compounds have been synthesized and
characterized using melting points, IR Spectra, NMR spectra and ESI-MS.
Keywords: Biginelli reaction, ionic liquid, microwave, water
© 2014 IJRCE. All rights reserved
catalyst recycle problems[13]. Ionic liquids are of
considerable interest as they can serve as catalyst and
green media in lewis acid catalyzed bigineli reactions [14]
and also due to their unique properties such as nonvolatility, non-flammability, etc. It can be thought of
ubiquitous among ionic liquids due to their ionic
conductivity. Recently a variety of ionic liquids have
been demonstrated as practical alternative to organic
solvents
as
well
as
catalyst
in
organic
reactions/transformations [15-17]. Ionic liquids are capable
of facilitating the formation of the key catalytic
intermediate and of stabilizing them through ion-pairing
formation. The aldehyde activation is more efficient in
presence of ionic liquids [18]. In particular Sulfonyl
imidazolium salts have been demonstrated as reagents in
the synthesis of nucleoside polyphosphates [19] aryl
sulfonamides and aryl sulfonates [20].
Introduction
In recent years, Beginelli reaction is ranked as
one of the powerful route for the synthesis of
octahydroquinazolonones. These derivatives have
considerable attention since they exhibit potent
antibacterial activity against Staphylococcus aureus,
Escherichia coli, Pseudomonas aeruginosa [1] and
calcium antagonist activity [2]. Due to its biological and
pharmological importance, several methods have been
developed for the preparation of quinazolinone
derivatives. These routes usually involves the reaction of
aldehydes with SOCl2 and pyridine, then with 2aminobenzylamine in a refluxing solvent such as benzene
or xylene with azeotropic water removal [3], refluxing
ethanol/acetic acid mixture [4], and by in alkali media,
there are few reports for the synthesis of
octahydroquinazolinone derivatives using catalysts such
as TMSCl [5], Nafion-H [6], conc. H2SO4 [7], NH4VO3 [8] ,
ZrOCl2.8H2O [9], silica-sulfuric acid [10] and also in ionic
liquids [HMIM] H2SO4 in presence of TMSCl [11],
[BMIM]Br-[BMIM]BF4[12]. All the methods have their
own advantages with some disadvantages such as low
yields, requirement of organic solvents, use of expensive
catalysts, tedious workup procedure, etc.
As our keen ongoing research interest in
microwaves synthesis [21], sulfonyl imidazolium salts and
in continuation of our effort to develop the catalytic
applicability of an acidic ionic liquid 1-(3, 4-dichloro
benzene sulfonyl)-3-methyl imidazolium chloride ([3, 4dcbsmim][Cl]) [22] (Figure 1). A catalytic application was
developed
for
the
beginelli
synthesis
of
octahydroquinazolinones (OHQ) (Table 1) in the
microwave reaction of aromatic aldehydes, dimedone and
urea/thiourea using 5mol% of [3, 4-dcbsmim][Cl],
products obtained with good yields.
Due to environmental concern use of benign
solvents as alternative to volatile organic solvents is of
much interest to organic chemists. The use of water as
reaction media and catalyst as ionic liquids in
microwaves can offer a solution to solvent emission and
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Krishnamurthy et al. Int. J. Res. Chem. Environ. Vol. 4 Issue 4 (115-119) October 2014
Cl
O
N
S N+
O
Cl1-(3, 4-dichloro benzene sulfonyl)-3-methylimidazolium chloride
[3, 4-dcbsmim][Cl]
Cl
Figure 1
Material and Methods
General
procedure
for
the
synthesis
of
octahydraquinazolinone under aqueous media: A
mixture of Aldehyde (1 mmol), Dimedone(1 mmol), urea
or thiourea(1.5 mmol) and [3, 4-dcbsmim][Cl] (5 mol%)
was added with 5ml of water in a closed voil and
irradiated with Microwaves of 150W at 100oC and
pressure of 100 psi till the completion of the reaction
(Table 1). After the completion of the reaction indicated
by TLC, the reaction mixture was allowed to cool to
room temperature. The obtained precipitate was filtered
off, washed with distill water. Further the filtrate (water)
was vacuum evaporated for dryness to get a crude
catalyst and the resulting catalyst was reused directly for
the next run without purification. All the products are
known compounds and were characterized by melting
point, IR, NMR and mass spectrometry and comparison
of their physical data with literature data. The isolated
yields of the products were 88-95%
4-(4-nitroophenyl)-7,7-dimethyl-3,4,7,8tetrahydroquinazoline-2,5(1H,6H)-dione (4d)
MP = > 300 oC IR (KBr) = 3449, 2925, 2851, 1704,
1594, 1541, 1346. 1H NMR (CDCl3, 300Hz) δ=1.11 (s,
3H), 1.23 (s, 3H), 2.30 - 2.51 (m, 4H), 5.54 (s, 1H), 7.25
(m, 2H), 8.39 (b, 2H), 10.15 (s, 1H), 11.79 (s, 1H).
13
CNMR (CDCl3, 100Hz) δ = 27.5, 29.6, 31.6, 33.3,
46.5, 47.1, 115.0, 123.6, 124.4, 127.7, 130.6, 140.1,
146.2, 190.3. ESI-MS calcd for C16H17N3O4 m/z 316.15
[M+ H], found 316.2.
4-(4-methoxyphenyl)-7,7-dimethyl-3,4,7,8tetrahydroquinazoline-2,5(1H,6H)-dione (4g ).
MP = 272oC IR (KBr) = 3280, 3200, 1645, 1600 cm-1 1H
NMR (DMSO-d6, 300Hz) δ = 0.91 (s, 3H), 1.04 (s, 3H),
2.14 (m, 2H), 2.36 (s, 2H), 3.69 (s, 3H), 4.76 (s, 1H) 7.04
- 7.23 (m, 4H), 7.76 (b, 1H). 9.27 (s, 1H). 13CNMR
(DMSO-d6, 100Hz) δ= 27.3, 29.1, 31.5, 32.7, 50.6, 51.7,
55.3, 107.8, 113.4, 129.0, 135.9, 149.5, 152.5, 157.5,
196.8. ESI-MS calcd for C17H20N2O3 m/z 301.15 [M+ H],
found 301.3.
The Spectral Data of the few compounds
4-(4-chlorophenyl)-7,7-dimethyl-3,4,7,8tetrahydroquinazoline-2,5(1H,6H)-dione (4b)
MP = 291 oC IR (KBr) = 3237, 2954, 1624, 1565, 1450.
1
H NMR (CDCl3, 300Hz) δ = 0.96 (s, 3H), 1.08 (s, 3H),
2.13 (m, 2H), 2.46 (s, 2H), 4.69 (s, 1H), 7.14 - 7.23 (m,
4H), 7.26 (b,2 H) 13C NMR (CDCl3, 100Hz) δ = 27.2,
29.2, 31.4, 32.0, 40.8, 50.7, 115.0, 129.1, 129.7, 129.8,
131.9, 142.5, 162.5, 196.2. ESI-MS calcd for
C16H17ClN2O2 m/z 343.06 [M+K], found 343.2.
4-(4-methoxyphenyl)-7,7-dimethyl-2-thioxo-1,2,3,4,7,8hexahydroquinazolin-5(6H)-one (4m).
MP = 268oC IR (KBr) = 3260, 3160, 1662, 1641, 1582
cm-1.1H NMR (DMSO-d6, 300Hz) δ = 0.90 (s, 3H), 1.03
(s, 3H), 2.04 - 2.20 (m, 2H), 2.35 (m, 2H), 3.70 (s, 3H),
5.12 (s, 1H) 6.87-6.90 (m, 2H), 7.15 (s, 2H), 9.67 (s, 1H),
10.54 (s, 1H).13CNMR (DMSO-d6,100Hz) δ = 27.2, 29.3,
31.9, 39.1, 50.3, 52.6, 55.8, 105.1, 118.1, 129.7, 131.8,
148.6, 152.4, 174.8, 196.2. ESI-MS calcd for
C17H20N2O2S m/z 317.13 [M+ H], found 317.2.
R
O
O
H
NH2
+
+
O
1
H2N
[3, 4-dcbsmim] [Cl]
NH
X
Water, MW
R
2
O
3
N
H
X
4 (a-l)
R=H, 4-Cl, 4-Nitro,4-F etc
X=O or S.
Figure 2: Biginelli condensation of aldehyde, dimedone and urea/ thiourea
in aqueous medium by using the model reaction of
benzaldehyde (1 mmol), Dimedone (1 mmol) with Urea
(1.5 mmol) and 40-46 % amount of product was
Results and Discussion
First the reaction was carried out without use
of any catalyst under microwave irradiation conditions
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Krishnamurthy et al. Int. J. Res. Chem. Environ. Vol. 4 Issue 4 (115-119) October 2014
observed at different temperatures between 80-100 oC.
In presence of 10 mol% of [bmim][Cl] and 10 mol% of
[3, 4-dcbsmim][Cl] we obtained the 44% and 95% of
yield respectively under microwave irradiation at 100oC
(Table 2). However to evaluate the effect of catalyst
concentration of novel Sulfonyl salt ([3, 4dcbsmim][Cl]), we used the model reaction of
benzaldehyde (1 mmol), Dimedone (1 mmol) with Urea
(1.5 mmol) carried out at 1, 5, 10, and 20 mol% of [3,
4-dcbsmim][Cl] at 100oC in water. The products were
obtained in 80, 94, 95 and 94% yield, respectively for 6
min (Table 3). This indicates that 5 mol% of [3, 4dcbsmim][Cl] is sufficient for the best result.
Subsequently, all the reactions were carried out at 100
o
C in presence of 5 mol% of [3, 4-dcbsmim][Cl] under
aqueous
conditions
in
the
preparation
of
octahydroquinazolinone (Figure 2) and the expected
product was obtained in good yield.
Table 1
Biginelli condensation of aldehyde, ethylacetoacetate/dimedone and ureaa
Entry
R
X
Time(min)
Yieldb(%)
Mp (oC)
4a
H
O
6
94
291
4b
4-Cl
O
4
93
290
4c
4-Br
O
5
93
>300
4d
4-NO2
O
4
94
>300
4e
4-F
O
5
90
135
4f
3-OMe 4-OH
O
6
92
193
4g
4-OMe
O
5
95
272
4h
3-NO2
O
5
93
298
4i
H
S
6
89
284
4j
4-Cl
S
4
89
223
4k
4-Br
S
5
92
285
4l
4-OMe
S
6
88
268
a
Reaction condition: Dimedone (1mmol),Urea /Thio urea (1.5 mmol) [3, 4-dcbsmim][Cl] (5 mol %) in aqueous media.
b
.Isolated yield
Table 2: Screening of ionic liquid in aqueous mediuma
Entry
1
2
3
4
Catalyst
[Bmim ][Cl]
[3, 4-dcbsmim][Cl]
Solvent
Water
Water
Water
Water
Temperature
80
100
100
100
Time(min)
6
7
6
5
Yield(%)b
40
46
44
94
a
Reaction condition: Benzaldehyde (1 mmol), Dimedone (1mmol), Urea (1.5 mmol) catalyst (10 mol %) in aqueous
media
b
Isolated Yield
were vacuumed to remove solvent. The resulting catalyst
was directly used in subsequent runs without further
treatment (Table 4).
Table 4
Recycling of the catalysta
Table 3
Effect of catalyst concentration on model reactiona
Entry
Catalyst (mol %)
Yield(%)b
1
1
80
2
5
94
3
10
95
4
20
95
a
Reaction Condition: Benzaldehyde (1 mmol), Dimedone
(1mmol), Urea (1.5 mmol)
b
Isolated Yield.
Run
Time(min)
Yieldb(%)
1
6
94
2
6
90
3
7
76
a
Reaction
Condition
:
Benzaldehyde
mmol),Dimedone(1mmol),Urea (1.5 mmol) [3,
dcbsmim][Cl] (5 mol %) in aqueous media.
b
Isolated Yield.
In order to demonstrate the reusability of [3, 4dcbsmim][Cl] the experiment was performed using
benzaldehyde as a model substrate under aqueous
condition. After the reaction crude solid was recrystalized
from 95% ethanol to obtain the desired product in pure
form. The water layer consisting of [3, 4-dcbsmim][Cl]
along with some residual reactants and byproducts, which
(1
4-
A brief comparison of the present work with
those previously reported in the literature in terms of
reaction condition, reaction time, yields revels the merit
of this method for the synthesis of OHQ (Table 5).
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Krishnamurthy et al. Int. J. Res. Chem. Environ. Vol. 4 Issue 4 (115-119) October 2014
Table5
Comparison of catalyst for the synthesis of octahydroquinazolinone with different reaction conditiona
Conditions
Time
Yield(%)b
Reference
Microwave
10min
89
11
reflux
10hr
30
12
100 oC
2.5hr
92
12
60-70oC
6.5hr
94
12
Water,
6
94
Present work
Microwave
a
Reaction Condition: Benzaldehyde( 1 mmol), Dimedone(1mmol), Urea (1.5 mmol)
b
Isolated yield
5. Kantevari S., Bantu R. and Nagarapu L., TMSCl
mediated highly efficient one-pot synthesis of
Conclusion
In conclusion, we demonstrate the application of
octahydroquinazolinone
and
1,8-dioxo[3, 4-dcbsmim][Cl] is as an efficient catalyst for the
octohydroxanthane derivatives, Arkivoc., xvi, 136 (2006)
synthesis of octahydroquinazolinone derivatives in
aqueous media. The advantages offered by this method
6. Lin H., Zhao Q., Xu B. and Wang X., Nafion-H
are green reaction media, short reaction time; product
catalyzed cyclocondensation reaction for the synthesis of
isolation was easy with good yields.
octahydroquinazolinone
derivatives,
Journal
of
Molecular Catalysis A: Chemical, 268 (1-2), 221 (2007)
List of abbreviations
[bmim][Br]: 1-Butyl-3-methylimidazolium bromide
7. Hassani Z., Islami M.R. and Kalantari M., An
[bmim][Cl]: 1-Butyl-3-methylimidazolium chloride
efficient one pot synthesis of octahydroquinazolinone
[bnmim][HSO4]:
1-Benzyl-3-methyl
imidazolium
derivatives using catalytic amount of H2SO4 in water,
hydrogen sulphate
Bioorganic & Medicinal Chemistry Letteres, 16, 4479
[Hmim] [HSO4]: 1-Methylimidazolium hydrogen sulfate
(2006)
TMSCl: Chlorotrimethylsilane
[3, 4-dcbsmim][Cl]: 1-(3, 4-Dichloro benzene sulfonyl)8. Niralwad K.S., Shingate B. B. and Shingare M.S.,
3-methylimidazolium chloride
Microwave
assisted
one-pot
synthesis
of
OHQ: Octahydroquinazolinone
octahydroquinazolinone derivatives using ammonium
metavanadate under solvent free condition, Tetrahedron
Letters, 51(32), 3616 (2010)
Acknowledgement
The authors are thankful to Bangalore
University, Bangalore, for the financial support through
9. Karami S., Karami B. and Khodabakhshi S., SolventYRB-BUIRF. We also thank IPC, IISc., Bangalore for
free
Synthesis
of
Novel
and
Known
NMR Spectral analysis and Department of Organic
Octahydroquinazolinones/thione by the use of
Chemistry IISc., Bangalore for Mass Spectral analysis.
ZrOCl2.8H2O as a highly Efficient and reusable catalyst,
Journal of the Chinese chemical society, 60, 22 (2013)
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