Solvent-free nucleophilic addition of N-alkylhydroxylamines to substituted nitroolefins: Formation of nitrones by a tandem process

Article abstract of DOI:10.1080/00397910701767031

Nucleophilic addition of 1-methyl-2-arylethylhydroxylamine to substituted β-nitrostyrene under solvent-free conditions has led to unexpected nitrones via a tandem process involving 1,4-addition and elimination. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701767031

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Solvent‐Free Nucleophilic Addition of
N‐Alkylhydroxylamines to Substituted
Nitroolefins: Formation of Nitrones by a
Tandem process
a
a
Chinnadurai Amutha & Shanmugam Muthusubramanian
a
Department of Organic Chemistry, Madurai Kamaraj University, Madurai,
India
Published online: 28 Jan 2008.
To cite this article: Chinnadurai Amutha & Shanmugam Muthusubramanian (2008) Solvent‐Free Nucleophilic
Addition of N‐Alkylhydroxylamines to Substituted Nitroolefins: Formation of Nitrones by a Tandem process,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
38:3, 328-337, DOI: 10.1080/00397910701767031
To link to this article: http://dx.doi.org/10.1080/00397910701767031
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Synthetic Communications , 38: 328–337, 2008
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701767031
Solvent-Free Nucleophilic Addition
of N-Alkylhydroxylamines to Substituted
Nitroolefins: Formation of Nitrones
by a Tandem process
Chinnadurai Amutha and Shanmugam Muthusubramanian
Department of Organic Chemistry, Madurai Kamaraj University,
Madurai, India
Abstract: Nucleophilic addition of 1-methyl-2-arylethylhydroxylamine to substituted
b-nitrostyrene under solvent-free conditions has led to unexpected nitrones via a
tandem process involving 1,4-addition and elimination.
Keywords: a-aryl-N-[1-methyl-2-arylethyl]nitrone, 1-methyl-2-arylethyl hydroxyla-
mine, nucleophilic addition, solvent-free reaction, tandem process
Nitroalkenes undergo addition reactions with oxygen and sulfur-centered
[
nucleophiles.
1,2]
[3]
Nucleophilic addition of aromatic amines and hydrazino
[
4]
bases to nitrostyrenes have also been reported. Hydroxylamines have
proved their versatility as reaction intermediates in the construction of
organic frameworks. N,O-Disubstituted hydroxylamines are important inter-
[5]
mediates in the synthesis of natural products. Diaziridines are formed when
O-substituted hydroxylamines interact with aldimines and primary aliphatic
[
amines. Hydroxylamines are also biologically important, and the mutagenic
6]
activity of several N-hydroxylamines toward strains of Escherichia coli and Sal-
Arylhydroxylamines act as
[7]
monella typhimurium has been reported.
Received in India July 13, 2007
Address correspondence to Shanmugam Muthusubramanian, Department of
Organic Chemistry, Madurai Kamaraj University, Madurai 625 021, India. E-mail:
muthumanian2001@yahoo.com
3
28

Formation of Nitrones by a Tandem Process
329
[
8]
carcinogens. In view of all this, we planned to effect nucleophilic addition of
N-alkylhydroxylamine to nitrostyrene to get N,N-diakylhydroxylamine because
the target compounds may exhibit enhanced biological activity.
We planned to investigate the nucleophilic properties of 1-methyl-2-ary-
lethylhydroxylamine 1 with different substrates under solvent-free conditions.
The hydroxylamine under discussion was prepared by the controlled careful
[
9]
[10]
reduction of b-methyl-b-nitrostyrene.
Nitroalkenes are also potential
substrates for nucleophilic attack in a 1,4-fashion addition. Thus, we
planned to effect nucleophilic addition of hydroxylamines 1 on substituted
nitrostyrenes 2 in the expectation of getting secondary hydroxylamines. The
resultant secondary hydroxylamines can be further functionalized or can be
used to generate new C-N bonds and hence can act as good precursors for
further synthetic transformations. In addition, they may be biologically
more active than the starting nitrostyrene because of the additional nitrogen.
In the present investigation, an equimolar mixture of the hydroxylamine 1
and nitrostyrene 2 was ground well and kept at room temperature (308C). The
mixture soon became a pasty mass sticking to the wall of the mortar. As the
reaction progressed, crystals came out of the mass and completely got thrown
out in 2 days. The mixture was then treated with petroleum ether (40–608C),
and the solid mass obtained was filtered. The product ultimately was found to
be a single entity, 3, with 80–85% conversion (Scheme 1). The petroleum
ether solution contained another unstable compound, 4, in a relatively poor
1
yield (less than 15%), undergoing decomposition to 3 in solution. The H
NMR spectrum of compound 3 gives a doublet around 1.5 ppm, and two
doublets of doublets around 2.8 ppm and 3.3 ppm. All the compounds
exhibited a multiplet around 4.1 ppm apart from signals due to two aromatic
1
3
C
nuclei. There was also a downfield singlet appearing around 7.1 ppm. The
NMR spectra of all the compounds showed signals around 19, 25, 30, and
3 ppm apart from the aromatic carbons. There was no nitro group in these
7
compounds as evidenced by the infrared spectra, and signals due to nitroethyl
group were absent in the NMR data. A close investigation of the structure of
these compounds based on one- and two-dimensional NMR suggests that the
compound 3 is a nitrone, a-aryl-N-[1-methyl-2-arylethyl] nitrone, which can
be easily obtained from arylaldehyde and the hydroxylamine 1.
Authentic samples of nitrones 3 were prepared from the corresponding
arylaldehydehyde and hydroxylamine 1 and were compared with the
product obtained in the previous reaction by mixed melting point and the fin-
gerprint region of their IR spectra. Thus, the compounds 3 isolated in the
present investigation are none other than the nitrones. To explore the
veracity of this nucleophilic attack, different alkyl-substituted hydroxylamines
were subjected to reaction with differently substituted b-methyl-b-nitrostyr-
enes, and in all the cases, reaction took place excellently. Incidently, all the
nitrones, except 3a, obtained by this method are hitherto unknown. The
1
13
yield, melting point, H NMR, and C NMR data of all the nitrones are
presented in Table 1.

3
30
C. Amutha and S. Muthusubramanian
Scheme 1. a) Ar ¼ phenyl, X ¼ H; b) Ar ¼ phenyl, X ¼ Cl; c) Ar ¼ phenyl,
X ¼ OH; d) Ar ¼ phenyl, X ¼ Me; e) Ar ¼ 4-chlorophenyl, X ¼ H; f) Ar ¼ 4-chlor-
ophenyl, X ¼ OMe; g) Ar ¼ 3,4-methylenedioxyphenyl X ¼ H; h) Ar ¼ 2-thienyl,
X ¼ H; i) Ar ¼ 2-thienyl, X ¼ Cl; j) Ar ¼ 3,4-dimethoxy, X ¼ H; k) Ar ¼ 2,4-
dichloro, X ¼ H; l) Ar ¼ 4-methoxyphenyl, X ¼ H; m) Ar ¼ 4-methoxyphenyl,
X ¼ Cl; n) Ar ¼ 4-methoxyphenyl, X ¼ NO ; o) Ar ¼ 4-methoxyphenyl, X ¼ Me;
2
p) Ar ¼ 4-methoxyphenyl, X ¼ OH; q) Ar ¼ 4-methoxyphenyl, X ¼ OMe; r)
Ar ¼ 4-methylphenyl, X ¼ H; s) Ar ¼ 4-nitrophenyl, X ¼ H; t) Ar ¼ 2-cholorphenyl,
X ¼ H; u) Ar ¼ phenyl, X ¼ NO .
2
The outcome is surprising, as a secondary hydroxylamine has been
expected with a possible dehydration, giving an imine 5 or 6 (Scheme 2),
which may undergo further hydrolysis. The formation of the nitrone in the
nucleophilic attack of the hydroxylamine on nitroolefin can be explained by
¯
a tandem addition–elimination sequence. The leaving ability of CH CHNO
3
2
can be understood because the nitro group is a powerful electron-withdrawing
group, thereby stabilizing the anion to a great extent. Thus nitroethane has been
eliminated from the initially formed secondary hydroxylamine by the
mechanism shown in the following scheme (Scheme 3). It should be
mentioned that such an elimination involving nitroalkane has already been
[11]
noticed in some nucleophilic attack involving amine as the nucleophile.
To prove that the reaction goes via the addition–elimination mechanism,
the reaction was deliberately stopped at an intermediate stage after 3 h, and
1
from the H NMR spectrum of the crude reaction mixture, it was found to
contain more hydroxylamine 4 and relatively poor yield of the nitrone 3.
The mass spectrum of 3a, N-(1-methyl-2-phenylethyl)-C-phenylnitrone
exhibits the molecular ion peak at 239 with relative abundance of 30%. The
base peak corresponds to m/e of 117, indicating the formation of b-methylstyrene.
This is expected as the nitrone functionality gets eliminated with the abstraction of

Table 1. Yield, melting point, and NMR spectral data of 3a–3u
Yield
(%)
1
13
Sl. no.
1
Compd.
Mp (8C)
H NMR (d scale)
C NMR (d scale)
3a
101
80
1.55, d (J ¼ 6.3 Hz), 3H; 4.09, m, 1H; 2.82, dd (J ¼ 13.5,
19.0, 39.6, 73.2, 128.4, 128.5,
128.6, 129.9, 130.2, 130.3,
132.5, 133.8, 136.1
4
.5 Hz), 1H; 3.34, dd (J ¼ 13.5, 9.3 Hz), 1 H; 7.12, s, 1H;
.80–7.30, m, 8H; 8.15, d (J ¼ 8 Hz), 2H
6
2
3
3b
3c
150
133
95
87
1.55, d (J ¼ 6.3 Hz), 3H; 4.09, m, 1H; 2.89, dd (J ¼ 13.5,
19.3, 41.0, 74.5, 127.2, 128.9,
129.0, 129.1, 129.3, 130.2,
132.9, 135.9, 138.0
5
.1 Hz), 1H; 3.33, dd (J ¼ 13.5, 8.7 Hz), 1H; 7.05, s, 1H;
.20–7.40, m, 7H; 8.1, d (J ¼ 9.3 Hz), 2H
7
1.53, d (J ¼ 6.3 Hz), 3H; 4.08, m, 1H; 2.89, dd (J ¼ 13.8,
19.0, 40.8, 73.5, 116.4, 121.1,
127.2, 128.9, 129.4, 132.3,
137.2, 137.8, 161.0
5
6
2
.4 Hz), 1H; 3.32, dd (J ¼ 13.8, 8.4 Hz), 1H; 7.01, s, 1H;
.93, d (J ¼ 8.7 Hz), 2H; 7.20, s, 5H; 8.00, d, (J ¼ 8.7 Hz),
H
4
5
3d
3e
Viscous
liquid
85
85
1.54, d (J ¼ 6.3 Hz), 3H; 4.10, m, 1H; 2.87, dd (J ¼ 13.5,
19.4, 41.0, 74.1, 22.0, 127.1,
128.1, 128.9, 129.0, 129.3,
129.5, 133.9, 138.3, 140.9
19.1, 39.7, 73.7, 128.3, 128.5,
128.5, 130.1, 130.2, 132.5,
133.4, 136.2 (one carbon
merges with another)
5.4 Hz), 1H; 3.33, dd (J ¼ 13.5, 9.0 Hz), 1H; 2.30, s, 3H;
7
.05, s, 1H; 7.17–7.25, m, 7H; 8.05, d (J ¼ 8.4 Hz), 2H
105
1.55, d (J ¼ 6.3 Hz), 3H; 4.08, m, 1H; 2.81, dd (J ¼ 13.8,
4
.8 Hz), 1H; 3.35, dd (J ¼ 13.8, 9.3 Hz), 1H; 7.08, s, 1H;
7
.12–7.37, m, 7H; 8.15, m, 2H
(
continued)

Table 1. Continued
Yield
(%)
1
13
Sl. no.
6
Compd.
Mp (8C)
H NMR (d scale)
C NMR (d scale)
3f
110
86
1.45, d (J ¼ 6.3 Hz), 3H; 3.99, m, 1H; 2.72, dd (J ¼ 13.5,
19.3, 40.1, 74.7, 55.5, 112.0,
114.2, 129.0, 129.2, 130.1,
130.3, 132.7, 135.8, 158.8
5
6
2
1
.1 Hz), 1H; 3.18, dd (J ¼ 13.5, 8.7 Hz), 1H; 6.96, s, 1H;
.60, dd (J ¼ 6.9, 1.8 Hz), 2H; 6.90, dd, (J ¼ 8.4, 1.8 Hz),
H; 7.20, dd, (J ¼ 6.90, 1.80 Hz), 2H; 8.00, dd (J ¼ 7.20,
.80 Hz), 2H; 3.64, s, 3H
7
8
9
3g
3h
3i
140
123
110
90
93
90
1.52, d (J ¼ 6.3 Hz), 3H; 4.07, m, 1H; 2.77, dd (J ¼ 13.8,
18.0, 40.2, 74.0, 100.8, 108.2,
109.2, 122.0, 128.3, 128.5,
130.1, 130.4, 131.5, 133.3,
146.2, 147.6
5
.1 Hz), 1H; 3.27, dd (J ¼ 13.8, 9.0 Hz), 1H; 7.10, s, 1H;
.05, d (J ¼ 8.4 Hz), 2H; 5.84, d (J ¼ 1.5 Hz); 5.86, d,
8
(
J ¼ 1.5 Hz); 6.60–6.70, m, 3H; 7.30–7.40, m, 3H
1.59, d (J ¼ 6.3 Hz), 3H; 4.19, m, 1H; 3.13, dd (J ¼ 15.0,
20.3, 35.9, 75.3, 125.7, 127.8,
128.4, 129.8, 130.1, 131.7,
131.8, 135.1, 140.9
4
6
2
.8 Hz), 1H; 3.61, dd (J ¼ 15.0, 9.0 Hz), 1H; 7.22, s, 1H;
.80-6.90, m, 2H; 7.41-7.46, m, 3H; 7.13, dd (J ¼ 5.1,
.4 Hz), 1H; 8.18–8.22, m, 2H
1.57, d (J ¼ 6.6 Hz), 3H; 4.10, m, 1H; 3.10, dd (J ¼ 15. 0,
18.8, 34.5, 74.0, 124.3, 126.3,
127.0, 128.7, 128.8, 129.8,
132.6, 135.6, 139.2
4
.8 Hz), 1H; 3.57, dd (J ¼ 15.0, 9.0 Hz), 1H; 7.16, s, 1H;
.35, d (J ¼ 8.7 Hz), 2H; 8.14, d (J ¼ 8.7 Hz), 2H; 7.13, dd
7
(
J ¼ 5.1, 1.2 Hz), 1H; 6.86, dd (J ¼ 3.6, 5.1 Hz), 1H; 6.82,
dd (J ¼ 3.6, 1.2 Hz), 1H
1
0
3j
140
93
1.55, d (J ¼ 6.3 Hz), 3H; 4.06, m, 1H; 2.76, dd (J ¼ 13.5,
19.0, 40.0, 74.2, 55.5, 55.7,
111.0, 111.9, 120.8, 128.3,
128.5, 130.2, 130.3, 130.4,
133.6, 147.7, 148.7
4
3
2
.2 Hz), 1H; 3.31, dd (J ¼ 13.5, 9.6 Hz), 1H; 7.05, s, 1H;
.60, s, 3H; 3.79, s, 3H; 7.34–7.37, m, 3H; 8.13–8.18, m,
H; 6.68–6.72, m, 3H

1
1
1
1
1
1
2
3
4
5
3k
3l
85
60
87
85
88
85
89
1.57, d (J ¼ 6.3 Hz), 3H; 4.26, m, 1H; 3.08, dd (J ¼ 13.5,
19.0, 37.5, 71.6, 127.2, 128.4,
128.5, 129.1, 129.7, 130.1,
130.3, 132.5, 133.4, 133.9,
134.3
4
7
7
.5 Hz), 1H; 3.36, dd (J ¼ 13.5, 9.3 Hz), 1H; 7.09, s, 1H;
.03, dd (J ¼ 8.4, 2.1 Hz), 1H; 7.18, d (J ¼ 8.4 Hz), 1H;
.38, m, 4H; 8.13, m, 2H
1.53, d (J ¼ 6.3 Hz), 3H; 4.26, m, 1H; 2.81, dd (J ¼ 13.5,
18.9, 39.7, 74.1, 55.1, 113.8,
128.3, 128.5, 129.8, 129.9,
130.0, 130.4, 133.3, 158.3
4.8 Hz), 1H; 3.29, dd (J ¼ 13.5, 9.0 Hz), 1H; 7.08, s, 1H;
6.75, d (J ¼ 8.7 Hz), 2H; 7.10, d, (J ¼ 8.7 Hz), 2H; 8.10, m,
2H; 7.36, m, 3H; 3.71, s, 3H
3m
3n
3o
110
90
1.53, d (J ¼ 6.3 Hz), 3H; 4.07, m, 1H; 2.80, dd (J ¼ 13.8,
19.3, 40.1, 74.7, 55.5, 114.2,
129.0, 129.2, 130.1, 130.3,
132.7, 135.8, 158.8 (One
carbon merges with another)
19.3, 40.3, 75.6, 55.5, 114.3,
124.0, 129.1, 129.7, 130.2,
131.9, 136.4, 147.9, 158.8
5
3
2
.1 Hz), 1H; 3.26, dd (J ¼ 13.8, 9.0 Hz), 1H; 7.04, s, 1H;
.72, s, 3H; 6.75, d (J ¼ 8.7 Hz), 2H; 7.07, d (J ¼ 8.7 Hz),
H; 7.33, d (J ¼ 8.7 Hz), 2H; 8.10, d (J ¼ 8.7 Hz), 2H
1.56, d (J ¼ 6.3 Hz), 3H; 4.18, m, 1H; 2.84, dd (J ¼ 13.8,
4
3
2
.5 Hz), 1H; 3.25, dd (J ¼ 13.8, 9.3 Hz), 1H; 7.07, s, 1H;
.70, s, 3H; 6.75, d (J ¼ 8.4 Hz), 2H; 7.07, d (J ¼ 8.4 Hz),
H; 8.20, d (J ¼ 8.7 Hz), 2H; 8.29, d (J ¼ 8.7 Hz), 2H
108
1.52, d (J ¼ 6.3 Hz), 3H; 4.05, m, 1H; 2.80, dd (J ¼ 13.5,
19.3, 40.1, 74.3, 22.0, 55.5,
114.2, 128.1, 129.0, 129.4,
130.1, 130.3, 133.8, 140.9,
158.7
5
.1 Hz), 1H; 3.29, dd (J ¼ 13.5, 8.7 Hz), 1H; 7.04, s, 1H;
.35, s, 3H; 3.72, s, 3H; 6.75, d (J ¼ 8.7 Hz), 2H; 7.09, d
2
(
(
J ¼ 8.7 Hz), 2H; 7.18, d (J ¼ 8.1 Hz), 2H; 8.06, d
J ¼ 8.1 Hz), 2H
16
3p
138
87
1.52, d (J ¼ 5.7 Hz), 3H; 4.04, m, 1H; 2.83, dd (J ¼ 13. 2,
18.9, 39.9, 73.7, 55.6, 114.3,
116.3, 121.2, 129.9, 130.4,
132.3, 137.0, 158.7, 160.9
4
3
2
.8 Hz), 1H; 3.28, dd (J ¼ 13.2, 8.7 Hz), 1H; 7.01, s, 1H;
.71, s, 3H; 6.75, d (J ¼ 7.8 Hz), 2H; 6.93, d (J ¼ 8.1 Hz),
H; 7.08, d (J ¼ 7.8 Hz), 2H; 8.06, d (J ¼ 8.1 Hz), 2H
(
continued)

Table 1. Continued
Yield
(%)
1
13
Sl. no.
Compd.
Mp (8C)
H NMR (d scale)
C NMR (d scale)
1
7
3q
92
89
1.52, d (J ¼ 6.6 Hz), 3H; 4.03, m, 1H; 2.80, dd (J ¼ 13.8,
19.3, 40.0, 74.0, 55.5, 55.7,
114.1, 114.2, 123.8, 130.3,
130.4, 130.9, 133.4, 158.7,
161.2
4
.8 Hz), 1H; 3.29, dd (J ¼ 13.8, 8.7 Hz), 1H; 7.01, s, 1H;
.72, s, 3H; 3.82, s, 3H; 6.75, d (J ¼ 8.4 Hz), 2H; 6.89, d
3
(
(
J ¼ 9.0 Hz), 2H; 7.09, d (J ¼ 8.4 Hz), 2H; 8.16, d
J ¼ 9.0 Hz), 2H
1
8
9
3r
3s
105
140
82
85
1.52, d (J ¼ 6.6 Hz), 3H; 4.03, m, 1H; 2.78, dd (J ¼ 13. 8,
18.5, 40.3, 73.8, 21.6, 127.1,
128.1, 128.9, 129.1, 129.3,
129.7, 133.9, 138.6, 140.3
18.7, 39.7, 73.6, 124.2, 128.6,
129.1, 129.4, 130.1, 130.3,
133.9, 137.2, 140.9
4
.8 Hz), 1H; 3.30, dd (J ¼ 13.8, 8.7 Hz), 1H; 7.03, s, 1H;
.30, s, 3H; 7.25, m, 7H; 8.14, d (J ¼ 9.0 Hz), 2H
2
1
1.52, d (J ¼ 6.3 Hz), 3H; 4.02, m, 1H; 2.80, dd (J ¼ 13.8,
4
8
5
.8 Hz), 1H; 3.29, dd (J ¼ 13.8, 8.7 Hz), 1H; 7.01, s, 1H;
.12, d (J ¼ 9.0 Hz), 2H; 8.00, d (J ¼ 9.3 Hz), 2H; 7.35, m,
H
2
0
1
3t
115
110
80
74
1.54, d (J ¼ 6.6 Hz), 3H; 4.02, m, 1H; 2.80, dd (J ¼ 13.8,
19.1, 39.7, 74.0, 127.2, 128.4,
128.5, 128.9, 129.1, 129.2,
130.0, 130.9, 132.5, 133.9,
4
.8 Hz), 1H; 3.32, dd (J ¼ 13.8, 8.7 Hz), 1H; 7.01, s, 1H;
.12, d, (J ¼ 9.0 Hz), 2H; 7.55, m, 7H
8
1
34.3
2
3u
1.52, d (J ¼ 6.6 Hz), 3H; 4.03, m, 1H; 2.78, dd (J ¼ 13.8,
19.3. 39.4, 74.2, 124.6, 126.1,
128.0, 128.4, 130.3, 130.3,
133.8, 133.9,140.4
4
8
5
.8 Hz), 1H; 3.30, dd (J ¼ 13.8, 8.7 Hz), 1H; 7.03, s, 1H;
.14, d (J ¼ 9.0 Hz), 2H; 8.20, d (J ¼ 9.3 Hz), 2H; 7.35, m,
H

Formation of Nitrones by a Tandem Process
335
Scheme 2.
Scheme 3.
b-hydrogen, giving the stable benzaldoxime as indicated in the fragmentation
scheme. The expected (M-16) peak, a salient feature in a,N-diaryl nitrones, is
totally absent in this system, indicating that the fragmentation dominates the
other popular fragmentations of nitrones. The benzyl radical cation also appears
dominant, with 70% relative abundance (Scheme 4). The molecular ion peak
has a poor intensity, less than 10% relative abundance, in most of the cases.
This one-pot conversion of nitrostyrene and hydroxylamine to nitrone is a
new route for the synthesis of nitrones, though the nitrone can be easily
prepared from the respective aldehydes. The same product with almost the
same yield has been obtained when the substrates were refluxed in ethanol
for 3 h. In conclusion, the nucleophilicity of the hydroxylamines has been

3
36
C. Amutha and S. Muthusubramanian
Scheme 4.
found to be very effective under solventless conditions, though the expected
hydroxylamines undergo subsequent elimination.
EXPERIMENTAL
Melting points are uncorrected. NMR spectra were recorded on a Bruker 300-
MHz/75-MHz instrument in CDCl3 using TMS as internal standard.
Chemical shifts are given in parts per million (d scale), and coupling
constants are given in hertz. Mass spectra were recorded on a Finnigan GC-
MS instrument. The substituted nitrostyrenes and other a,b-unsaturated
nitro compounds have been prepared by the condensation of the corresponding
[
10]
aldehydes with nitroethane. The partial reduction has been carried out with
utmost care to stop the reduction in the hydroxylamine stage using boron tri-
[9]
fluoride and sodium borohydride, following a known procedure.
General Procedure for the Nucelophilic Addition of 1-Methyl-2-
arylethyl Hydroxylamine to b-Nitrostyrenes
1-Methyl-2-arylethyl hydroxylamine (0.001 mol) was mixed with 0.001 mol
of substituted b-methyl-b-nitrostyrene and ground well in a mortar. The
paste obtained was left at room temperature for 2 days. The solid was
product thrown out; the nitrone (viz, C-aryl-N-1-methyl-2-arylethylamine-
N-oxide) was scratched with petroleum ether to remove the impurities. The
resulting nitrone was recrystallized from aqueous ethanol.
ACKNOWLEDGMENT
The authors thank the Department of Science and Technology, New Delhi, for
the NMR facility. One of the authors (C. A.) thanks the University Grants
Commission, New Delhi, for assistance under the Faculty Improvement
Program.

Formation of Nitrones by a Tandem Process
REFERENCES
337
1
. Ono, N.; Miyake, H.; Kamimura, A.; Hamamota, I.; Tamuri, R.; Kaji, A. Denitro-
hydrogenation of aliphatic nitro compounds a new use of aliphatic nitro
compounds as radical precursors. Tetrahedron 1985, 41, 4013.
2. (a) Kobayashi, N.; Iwai, K. Asymmetric addition of thioglycolic acid to
nitro olefins catalyzed by cinchona alkaloids. J. Org. Chem. 1981, 46, 1823;
(b) Functional polymers. 6. Unusual catalysis of polymeric cinchona alkaloids
in asymmetric reaction. Tetrahedron Lett. 1980, 21, 2167.
3
4
5
6
. Worrall, D. E. The action of ammonia and aromatic amines on 4–methylnitro-
styrene and related compounds. J. Am. Chem. Soc. 1938, 60, 2841.
. Worrall, D. E. The addition of amino and hydrazino bases to nitrostyrene. J. Am.
Chem. Soc. 1927, 49, 1598.
. Khlestkin, V. K.; Mazhukin, D. G. Recent advances in the application of N,0–dia-
lkylhydroxylamines in organic chemistry. Curr. Org. Chem. 2003, 7, 967.
. Makhova, N. N.; Petukhova, V. Y.; Khmelnitskii, L. I. Reactions of 0–substituted
hydroxylamines with aldimines and primary aliphatic amines in the synthesis of
diaziridines. Russ. Chem. Bull. 1982, 31, 2052.
7
. Pai, V.; Bloomfield, S. F.; Gorrod, J. W. Mutagenicity of N–hydroxylamines and
N–hydroxycarbamates towards strains of Escherichia coli and Salmonella
typhimurium. Fundamental and Molecular Mechanisms of Mutagenisis 1985,
151, 201.
8. Boyland, E. The mechanism of tumor induction by aromatic amines and other car-
cinogens. J. Cancer Res. Clin. Oncol. 1963, 65, 378.
9. Kabalka, G. W.; Varma, R. S. Syntheses and selected reductions of conjugated
nitroalkanes. A Review. Org. Prepn. Proced. Internatl. 1987, 19, 285.
1
1
0. Alles, G. A. dl–Beta–phenylisopropyamines. J. Am. Chem. Soc. 1932, 54, 271.
1. (a) Worrall, D. E. The addition of aromatic amines to bromonitrostyrene. J. Am.
Chem. Soc. 1921, 43, 919; (b) Worrall, D. E. Some reactions of unsaturated
nitro compounds derived from terephthalaldehyde. J. Am. Chem. Soc. 1940,
6
2, 3253.