New synthesis of 1,3-diaryl-4-nitro-1-butanones by microwave-promoted Michael addition of nitromethane to chalcones without solvent

Article abstract of DOI:10.3184/030823407X266199

The Michael addition of nitromethane to chalcones promoted by microwave irradiation without solvent afforded 1,3-diaryl-4-nitro-1-butanones in good yield. The products were characterised by IR, ¹H NMR and elemental analysis.

Full text of DOI:10.3184/030823407X266199

660 RESEARCH PAPER
NOvEMBER, 660–661
JOURNAL OF CHEMICAL RESEARCH 2007
New synthesis of 1,3-diaryl-4-nitro-1-butanones by microwave-promoted
Michael addition of nitromethane to chalcones without solvent
Shuangshuang Lia, Zengyang Xiea, Xiaoqin Biana,b and Cunde Wanga*
aCollege of Chemistry and Chemical Technology, Yangzhou University, Yangzhou 225002, P. R. China
bDepartment of Environmental and Chemical Engineering, Taizhou Polytechnic College, Taizhou 225300, P. R. China
The Michael addition of nitromethane to chalcones promoted by microwave irradiation without solvent afforded
1,3-diaryl-4-nitro-1-butanones in good yield. The products were characterised by IR, 1H NMR and elemental analysis.
Keywords: 1,3-diaryl- 4-nitro-1-butanone, Michael addition, chalcone; microwave irradiation, synthesis
1,3-Diaryl-4-nitro-1-butanones
are
versatile
synthetic
After the reaction, the 1,3-diaryl-4-nitro-1-butanones were
isolated by silica gel column chromatography, using petroleum
ether (60–90°C)-ethyl acetate as eluent.
intermediates. For example, 3-p-chlorophenyl-1-phenyl- 4-
nitro-1-butanone was used to synthesise the therapeutically
useful GABAB receptor agonist (R)-baclofen hydrochloride1
that is used to treat spasms caused by spinal cord injury or
disease. The reductive cyclisation of 4-nitro-1-butanones is a
standard method for the preparation of pyrrolidine derivatives.2
The enantioselective reduction of prochiral 1-aryl-4-nitro-1-
butanones to the corresponding nitroalcohols leads to a class
of chiral building blocks that are useful for the synthesis of a
variety of heterocyclic compounds.3
The Michael reaction of nitromethane to chalcones is the
most commonly used method for the preparation of 1,3-
diaryl-4-nitro-1-butanones. Usually, the Michael reaction
is promoted with acids, bases and metal complexes. Solid
supported reagents and micelles catalyse the process.4-7
Recently there has been a growing interest in the use of
conventional microwave heating in organic synthesis,8 and
it has been proved to be of particular benefit in promoting
reactions on solid supports with a catalyst and without a
solvent.9-11 Although recent advances have made this reaction
more attractive, some of these methods are limited by long
reaction times and expensive catalysts.12 We now report a
remarkably rapid Michael addition of chalcones nitromethane
to chalcones under microwave irradiation without solvent
leading to 1,3-diaryl- 4-nitro-1- butanones (Scheme 1).
In our search for an economical, environmentally friendly
reaction to 1,3-diaryl-4-nitro-1-butanones, we used cheap,
readily available, and nontoxic bases. In the Michael addition
of nitromethane to chalcones, it was found that the yield
depended largely on the base (Table 1). Comparing the
yields of entries 1–6, it can be seen that the reactions in the
presence of the bases K2CO3, or Na2CO3 gave better yields
than those in the presence of KF, CsF or piperidine. Amongst
these bases, KF/Al2O3 was quite effective for Michael
reactions of a,b-unsaturated compounds with nucleophiles.13
However, it readily promoted the double Michael additions
of nitromethane to chalcones, and cyclic compounds were
formed from chalcones and nitromethane under microwave
irradiation.14 Under our conditions we found that the double
addition can be avoided and chalcone was converted into
compound 3e in 70% yield using 4 times the equivalent amount
of nitromethane. A negligible amount of the cyclic compound
was formed. K2CO3/Al2O3, Na2CO3/Al2O3 are moderate basic
reagents and are widely used in organic reactions.
Table 1 The effect of base in the Michael reaction of
chalcones with nitromethane
Entry
Base
Yield of compound 3e/%
1
2
3
4
5
6
K2CO3
Na2CO3
KF
90
86
72
70
78
60
Results and discussion
The Michael reaction was carried out by simple mixing the
chalcone, nitromethane and K2CO3 adsorbed in Al2O3, and
then irradiating in an open beaker in a domestic microwave
oven for 5-8 minutes. The reaction proceeded smoothly and
yields reached 62–90%.
Et3N
piperidine
CsF
Microwave power, 200 W; reaction time, 7 min.
O2N
O
K2CO3/Al2O3
MWI, 5-8 min.
O
Ar1
Ar2
Ar1
Ar2
CH3NO2
+
62-90%
1a-j
Entry Ar1
2
3a-j
Ar2
Irrad.Time(min)
3 yield(%)
a
b
c
d
e
f
C6H5
C6H5
7
7
5
6
7
8
5
8
8
7
68
74
72
66
90
70
69
82
80
62
C6H5
C6H5
C6H5
C6H5
C6H5
p-MeOC6H4
p-MeOC6H4
p-MeOC6H4
p-MeOC6H4
p-ClC6H4
p-O2NC6H4
p-MeOC6H4
2,4-Cl2C6H3
p-HOC6H4
p-ClC6H4
p-O2NC6H4
2,4-Cl2C6H
C6H5
g
h
i
j
Scheme 1
* Correspondent. E-mail: cundeyz@hotmail.com
PAPER: 07/4918

JOURNAL OF CHEMICAL RESEARCH 2007 661
4.46–4.80 (m, 2H), 6.70–7.90 (m, 9H); Anal. Calcd. for C17H17NO4:
C, 68.23; H, 5.70; N, 4.68; Found C, 68.20; H, 5.60; N, 4.67%.
Table 2 Effect of the time of microwave irradiation on the
synthesis of 3e
1-phenyl-3-(2,4-dichloro)phenyl-4-nitro-1-butanone
(3e):
Reaction time/min
Compd 3e yield/%
4.0
62
5.0
78
6.0
86
7.0
90
8.0
83
M.p. 108–110°C (PE/EtOAc); IR: 1698, 1595, 1540, 1500, 1390 cm-1;
1H NMR: 3.42 (d, J = 17.7 Hz, 2H), 4.10–4.52 (m, 1H), 4.68–4.90
(m, 2H), 7.00–8.20 (m, 8H); Anal. Calcd. for C16H13NO3Cl2: C,
56.80; H, 3.85; N, 4.14; Found C, 56.80; H, 3.76; N, 4.00%.
Microwave power, 200 W; base: K2CO3/Al2O3.
Table 3 Effect of the power of microwave irradiation on the
synthesis of 3e
1-phenyl-3-p-hydroxyphenyl-4-nitro-1-butanone (3f): M.p. 124–
126°C (PE/EtOAc); IR: 3500–3300, 1710, 1600, 1580, 1490, 1390
1
cm-1; H NMR: 3.42 (d, J = 1.8 Hz, 2H), 4.20–4.50 (m, 1H), 4.68–
MW power/W
Compd 3e yield/%
100
42
150
75
200
90
250
82
300
53
4.86 (m, 2H), 7.00–8.02 (m, 9H), 9.80 (s, 1H); Anal. Calcd. for
C16H15NO4: C, 67.37; H, 5.26; N, 4.91; Found C, 67.56; H, 5.18; N,
4.86%.
Reaction time, 7 min; base: K2CO3/Al2O3.
1-p-methoxyphenyl-3-p-chlorophenyl-4-nitro-1-butanone
(3g):
M.p. 126–128°C (PE/EtOAc); IR: 1690, 1600, 1590, 1500, 1390 cm-1;
1H NMR: 3.41 (d, J = 18 Hz, 2H), 3.60 (s, 3H), 4.20–4.58 (m, 1H),
4.66–4.90 (m, 2H), 7.02–7.98 (m, 8H);Anal. Calcd.for C17H16NO4Cl:
C, 61.17; H, 4.80; N, 4.20; Found C, 61.10; H, 4.62; N, 4.10%.
To optimise the reaction conditions, the effect of the time
of microwave irradiation and the power of the microwave
irradiation on the synthesis of 3e were studied. As shown in
Tables 2 and 3, the reaction gave a satisfactory yield of 3e
for 6-7 min. and a longer reaction time was not necessary.
The reaction was quite microwave power dependent, and
200W is recommended. Normally, reaction occurred slowly
below 200W and the low boiling-point nitromethane quickly
evaporated when the microwave power was above 200W
(Table 3).
Under very similar conditions, the other chalcones and
nitromethane underwent the Micheal addition to yield
corresponding 1,3-diaryl- 4-nitro-1-butanones in 62–90%. As
illustrated in Scheme 1, this method is quite general and the
yields of 3a–j were not significantly affected by substituents
at aromatic ring.
In conclusion, we have developed a microwave-promoted
procedure for the Michael addition of nitromethane to
chalcones in the presence of K2CO3/Al2O3 without solvent
to prepare 1,3-diaryl-4-nitro-1-butanones (3). The yields of
the reaction are excellent and much higher than the results
obtained by using the conventional method. The structures
of compounds 3 were identified on the basis of their IR,
1H NMR data and elemental analyses.
1-p-methoxyphenyl-3-p-nitrophenyl-4-nitro-1-butanone
(3h):
M.p.162–164°C(EtOH);IR:1700,1606,1592,1500,1455,1392cm-1;
1H NMR: 3.42 (d, J = 18 Hz, 2H), 3.62 (s, 3H), 4.20–4.66 (m, 1H),
4.70–4.90 (m, 2H), 7.00–8.02 (m, 8H); Anal. Calcd. for C17H16N2O6:
C, 59.30; H, 4.65; N, 8.12; Found C, 59.20; H, 4.60; N, 8.06%.
1-p-methoxyphenyl-3-(2,4-dichloro)phenyl-4-nitro-1-butanone
(3i): M.p. 129–131°C (PE/EtOAc); IR: 1700, 1600, 1588, 1500,
1
1450, 1390 cm-1; H NMR: 3.40 (d, J = 18 Hz, 2H), 3.60 (s, 3H),
4.20–4.60 (m, 1H), 4.70–4.86 (m, 2H), 7.02–8.00 (m, 7H); Anal.
Calcd. for C17H15NO4Cl2: C, 55.43; H, 4.08; N, 3.80; Found C,
55.30; H, 4.06; N, 3.72%.
1-p-methoxyphenyl-3-phenyl-4-nitro-1-butanone (3j): M.p. 101–
103°C (PE/EtOAc); IR: 1700, 1608, 1590, 1480, 1450, 1395 cm-1;
1H NMR: 3.35 (d, J = 18 Hz, 2H), 3.60 (s, 3H), 4.10–4.60 (m, 1H),
4.70–4.86 (m, 2H), 7.00–8.02 (m, 9H); Anal. Calcd. for C17H17NO4:
C, 68.23; H, 5.69; N, 4.68; Found C, 68.17; H, 5.62; N, 4.70%.
We are grateful to the Natural Science Foundation of
Education Ministry of Jiangsu, China for financial support.
(Grant 07KJB150135)
Received 27 October 2007; accepted 23 November 2007
Paper 07/4918
doi: 10.3184/030823407X266199
Experimental
References
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Elemental analyses were obtained using a model 240 analyser,
IR spectra were measured with a model 408 infrared spectrometer,
1H NMR spectra were recorded on a JNM-90Q Spectrometer by
using TMS as an internal standard (CDCl3 as solvent).
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chalcones under microwave irradiation
A mixture of chalcones (5 mmol), nitromethane (1.22 g, 20 mmol)
and K2CO3 (0.69 g, 5 mmol) adsorbed on 5 g Al2O3 (300 mesh) was
introduced into a Galanz WP 750A domestic microwave oven in a
25 ml beaker. Microwave irradiation was performed at the microwave
power 200 W for the appropriate time. After the reaction, the mixture
was cooled to ambient temperature, the product 3 was isolated
directly by silica gel column chromatography, using petroleum ether
(60–90°C)–ethyl acetate as eluent.
1,3-diphenyl-4-nitro-1-butanone (3a): M.p. 81–83°C (PE/EtOAc);
IR: 1690, 1600, 1580, 1500, 1390 cm-1; 1H NMR: 3.38 (d, J = 18 Hz,
2H), 3.98–4.51 (m, 1H), 4.66–4.83 (m, 2H), 7.01–8.00 (m, 10H);
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3
4
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8.00 (m, 9H); Anal. Calcd. for C16H14NO3Cl: C, 63.26; H, 4.61; N,
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PAPER: 07/4918