3
348
M. A. Zolfigol et al. / Tetrahedron Letters 44 (2003) 3345–3349
Scheme 2.
ratios of 0.1–1 of NaNO (Table 1, entries 26–29). This
General procedure for N-nitrosation of secondary amines
2
means that formation of dinitrosoamines (2A and 2z )
2
2
®
began in the early stages of the reaction and their
formation is independent of the ratio of reagents. These
results are in close agreement with transnitrosation
phenomena which have been reported by Singer et
A suspension of sodium nitrite, Nafion-H (the molar
®
ratio of Nafion-H I and sodium nitrite to the substrate
1 was optimized, Table 1), amine 1 (5 mmol) and wet
SiO (2.5 g, 50% w/w) in dichloromethane (10 mL) was
2
2
4,25
al.
stirred vigorously at room temperature. The progress of
the reaction was followed by TLC. The reaction mix-
ture was filtered after completion of the reaction. The
residue was washed with CH Cl (2×5 mL). Then anhy-
In order to assess the chemoselectivity of this method a
competitive reaction was performed between diphenyl-
amine 1p and anisole. It was observed that amine
nitrosation occurred exclusively whereas anisole
remained intact in the reaction mixture after 1 h. The
nitrosation of a mixture of N-arylamine and N,N-
diarylamines shows further the chemoselectivity of the
method as the N-nitrosoarylamine was the only
product. Thus, this system behaves differently to some
2
2
drous Na SO4 (10 g) was added to the filtrate and
2
washing and separated by filtration after 20 min. The
solvent was evaporated and the N-nitroso compounds 2
was obtained. If further purification was needed, flash
chromatography on silica gel [eluent: acetone/petro-
leum ether bp 60–80°C, (10:90)] provide highly pure
28,29
2.
1
3,20
other reported methods
(
in that the nitrosonium ion
+
NO ) attacks only the nitrogen sites of the secondary
amines even where an aromatic moiety is connected
directly to the nitrogen atom (Table 1, entries 12, 13,
Acknowledgements
15–20 and 24. A typical example is shown in Scheme 2).
Furthermore, the chiral center of
hydroxy- -proline 1w and -1,2,3,4-tetrahydroiso-
L
-proline 1v, 4-
This research project has been supported by grant No.
NRCI 32-296 of National Research Projects and with
support of the National Research Council of the
Islamic Republic of Iran.
L
D
quinoline-3-carboxylic acid 1o also remained intact dur-
ing the course of the reaction (Table 1, Scheme 1,
entries 22, 23 and 15). Amino acid derivatives 2v, 2w
and 2o are precursors of mesoionic moieties in an
important class of dipolar heterocyclic compounds with
2
5
special properties.
References
Some of the N-nitrosoamines such as 2A2 and 2z2
reported in this paper are very important precursors for
the mechanistic transnitrosation studies and some could
be useful for synthesis of special NO releasing
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2
6,27
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6
, 253–259.
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wet SiO . This observation suggests that the water
1999, 189, 163–183.
2
molecule is essential for such processes. The presence of
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2
face for in situ generation of HNO . It also facilitates
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2
In conclusion, the cheapness and the availability of the
reagents, easy and clean work-up, chemoselectivity and
high yields make this method attractive for large-scale
operations. This simple procedure is highly selective
and C-nitrosation and hydroxy oxidation side-products
are avoided.
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