A facile and new method for the synthesis of α-aryl-N-methylnitrones in solvent-free media using silica gel-NaOH

Article abstract of DOI:10.1080/10426500490463790

Substituted α-aryl-N-methylnitrones are prepared by the condensation reaction of N-methylhydroxylamine hydrochloride and benzaldehydes in solvent-free media using silica-gel-NaOH catalyst system. The yields are excellent regardless of the electron-donatin

Full text of DOI:10.1080/10426500490463790

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Phosphorus, Sulfur, and Silicon and the Related
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A FACILE AND NEW METHOD FOR THE SYNTHESIS OF
α-ARYL-N-METHYLNITRONES IN SOLVENT-FREE MEDIA
USING SILICA GEL-NaOH
a
b
a
M. M. Alavi Nikje , M. A. Bigdeli & H. Imanieh
a
Department of Chemistry , Qazvin, Iran
b
Faculty of Chemistry, Teacher Training University , 49 Mofateh Str., Tehran, Iran
Published online: 16 Aug 2010.
To cite this article: M. M. Alavi Nikje , M. A. Bigdeli & H. Imanieh (2004) A FACILE AND NEW METHOD FOR THE SYNTHESIS OF
α-ARYL-N-METHYLNITRONES IN SOLVENT-FREE MEDIA USING SILICA GEL-NaOH, Phosphorus, Sulfur, and Silicon and the Related
Elements, 179:8, 1465-1468, DOI: 10.1080/10426500490463790
To link to this article: http://dx.doi.org/10.1080/10426500490463790
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Phosphorus, Sulfur, and Silicon, 179:1465–1468, 2004
Copyright ꢀC Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500490463790
A FACILE AND NEW METHOD FOR THE
SYNTHESIS OF α-ARYL-N-METHYLNITRONES IN
SOLVENT-FREE MEDIA USING SILICA GEL-NaOH
a
b
a
M. M. Alavi Nikje, M. A. Bigdeli, and H. Imanieh
Department of Chemistry, Faculty of Sciences, Imam Khomeini
a
International University, Qazvin, Iran; and Faculty of
Chemistry, Teacher Training University, 49 Mofateh Str.,
Tehran, Iranb
(Received November 25, 2003)
Substituted α-aryl-N-methylnitrones are prepared by the condensation
reaction of N-methylhydroxylamine hydrochloride and benzaldehydes
in solvent-free media using silica-gel–NaOH catalyst system. The yields
are excellent regardless of the electron-donating or electron-accepting
nature of the substituents on benzaldehyde. Similar ketones are unre-
active under these conditions, rendering chemoselectivity of the method.
Keywords: α-Aryl-N-methylnitrones; chemoselectivity; silica gel-
NaOH; solvent-free media
Numerous methods of preparation of α-aryl-N-methylnitrones are
1–6
known.
Each method exhibits merits as well as shortcomings.
One of the most important methods is the condensation of N-
methylhydroxylamine hydrochloride with substituted benzaldehydes.
Decomposition of N-methylhydroxylamine hydrochloride and the need
to heat up or even to reflux the reaction mixture results in low
1
–6,10
yields.
The second factor responsible for diminished reactivity is
the formation of water in the course of the reaction which, if not re-
moved, will stop the reaction midway and hydrolyze the initially formed
nitrone. In order to find a possible way around this difficulty, and moti-
7
vated by recent interest in carrying out reactions in solvent-free media,
8
an emphasis on green chemistry, and in the continuation of our ex-
periments for the nitrone synthesis in dry media, we decided to re-
9
examine the procedure in dry media using silica-gel–NaOH catalyst
Address correspondence to Mir M. Alavi Nikje, Department of Chemistry, School of Sci-
ences, Imam Khomeini International University, Qazvin, Iran. E-mail: alavi-m@ikiu.ac.ir
1
465

1
466
M. M. Alavi Nikje et al.
TABLE I Dry Media α-aryl-N-Methylnitrones Synthesis Using
Silica-Gel–NaOH Catalyst
Nitrone
Melting point(C) Yields(%)
α-phenyl-N-methylnitrone
α-(4-methylphenyl)-N-methylnitrone
α-(2-furyl)-N-methylnitrone
α-(2-nitrophenyl)-N-methylnitrone
α-(2-hydroxyphenyl)-N-methylnitrone
α-(2,4-dimethoxyphenyl)-N-methylnitrone
α-(4-nitrophenyl)-N-methylnitrone
α-(4-chlorophenyl)-N-methylnitrone
α-(3-nitrophenyl)-N-methylnitrone
82–84
119–121
89–92
92
87
85
98
84
92
96
85
96
91–94
141–143
132–135
216–219
127–130
119–122
system which to the best of our knowledge is the first example used in
such reactions. We have found an ideal condition to carry out the reac-
tion using silica-gel–NaOH catalyst in dry media system to synthesize
α-aryl-N-methylnitrones in high yields (Table I). Benzaldehydes bear-
ing electron-accepting as well electron-donating groups react similarly
under these conditions.
We are pleased with the results not only from the point of view of
reporting an improved preparative method but also from of an environ-
mental standpoint. Our method is solvent-free, clean, and eco-friendly.
Working up procedure is simple, and the purity of the products is high
even before recrystallization.
An important piece of observation made was that the corresponding
ketones failed to react under these conditions. When one equivalent of
an aldehyde in the presence of one equivalent of a similar ketone was
treated with two equivalents of N-methylhydroxylamine hydrochloride,
only the aldehyde was selectively converted to the corresponding ni-
trone, while the ketone did not react at all (Scheme 1).
SCHEME 1 Chemoselective aldonitrones synthesis in the presence of similar
ketones.
The reaction also gave no results in dry media without the use of
silica-gel–NaOH catalyst system. Therefore, this methodology could be

Aryl-N-Methylnitrones
1467
used selectively for the preparation of α-aryl-N-methylnitrones from
compounds that contain both aldehyde- and keton-functional groups.
We believe that silica gel enhances the reaction by absorbing the water
produced during the reaction which needs to be removed in order for
the reaction to be completed. Dry media absorbs the excess water ef-
ficiently and prevents the hydrolysis of formed nitrone. In conclusion,
the reported procedure is a new, facile, and environmentally friendly
method for the preparation of α-aryl-N-methylnitrones. The reaction is
fast, the procedure is simple, and the yields are high.
EXPERIMENTAL
All benzaldehydes, sodium hydroxide flakes, silica gel 60, and N-
methylhydroxylamine hydrochloride were purchased from Merck.The
α-phenyl-N-methylnitrone is known and was characterized by compar-
ison with the melting point, IR, and NMR spectral data of an authentic
1
0
sample. For other nitrones, the IR and NMR spectra were obtained
and found to be consistent with the structures assigned.
Preparation of α-Phenyl-N-methylnitrone
General Procedure
A mixture of sodium hydroxide flakes (0.6 mmol), silica gel 60 (0.3 gr
relative to 1.2 mmol aldehyde), and N-methylhydroxylamine hydrochlo-
ride (1.2 mmol) and benzaldehyde (1.2 mmol) was grand thoroughly for
6
min. The reaction mixture was set aside for a further 4 min at am-
bient temperature. To the crude product mixture CHCl3 (2 × 10 ml)
was added and filtered. The solvent was evaporated to dryness and the
◦
residue was appropriately crystallized from petroleum ether (60–80 C)
to afford the α-phenyl-N-methylnitrone in 92% yield.
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