J . Org. Chem. 2001, 66, 3619-3620
3619
completely homogeneous reagent for the N-nitrosation
of secondary amines, and thus we have investigated a
number of different reaction conditions based upon the
in situ generation of NO+. In continuing of our studies
on the application of NOX,11 N2O4,12 metal nitrate dini-
trogen tetroxide complexes.13 and complexation of transi-
tion metals with macrocyclic ethers,14 we found that 18-
Crown-6 gives an ionic complex with N2O4 gas as
[NO+‚Crown‚H(NO3)2-] in quantitative yields. In this
communication we now report a simple and convenient
method using this new reagent for the effective N-
nitrosation of secondary amines (1) to their corresponding
N-nitroso derivatives (2) under mild conditions.
N-Nitr osa tion of Secon d a r y Am in es w ith
-
[NO+‚Cr ow n ‚H(NO3)2
]
Mohammad Ali Zolfigol,*,†
Mohammad Hassan Zebarjadian,†
Gholamabbas Chehardoli,† Hassan Keypour,†
Sadegh Salehzadeh,† and Mojtaba Shamsipur‡
Chemistry Department, College of Science, Bu-Ali Sina
University, Hamadan 65174, Iran, and Chemistry
Department, College of Science, Razi University,
Kermanshah, Iran
zolfi@basu.ac.ir.
Different types of secondary amines (1) were subjected
to the nitrosation reaction in the presence of
[NO+‚Crown‚H(NO3)2-] (I) and dry SiO2 in dichlo-
romethane. The nitrosation reactions were performed
under mild conditions at room temperature and take
place with quantitative yields (Scheme 1).
This present nitrosation reaction can be readily carried
out by placing the complex [NO+‚Crown‚H(NO3)2-] (I),
amine (1), dry SiO2 and CH2Cl2 as the solvent in a
reaction vessel and efficiently stirring the resulting
mixture at room temperature. The reactions were com-
pleted after 5 min. The reaction mixture was filtered, and
dichloromethane was also removed by water bath (40-
50 °C) and simple distillation. The highly pure ni-
trosoamines (2) were obtained by passing the residue
through a pad of silica gel.
A competitive reaction was performed between dicy-
clohexylamine (1c) and anisole. It was observed that
amine nitrosation occurred exclusively, whereas anisole
remained intact in the reaction mixture after 1 h. The
nitrosation reaction of diphenylamine shows the chemose-
lectivity of the method as the N-nitrosodiphenylamine
is the only product. This system thus behaves differently
from some reported methods2 so that the nitrosonium ion
(NO+) attacks the nitrogen sites of the secondary amines
even where an aromatic moiety is connected directly to
the nitrogen atom.
Received December 11, 2000
N-Nitrosation chemistry of amines is an important and
well-established reaction in organic synthesis.1 The most
general reagent is nitrous acid, generated from sodium
nitrite and mineral acid in water or in mixed alchohol-
water solvents.2 Other nitrosating agents, such as Fre-
my’s salt,3 bis(triphenylphosphine)nitrogen(1+) nitrite,4
N-haloamides and sodium nitrite under phase-transfer
conditions,5 oxyhyponitrite,6 dinitrogen tetroxide,7 solid
acids (i.e., oxalic acid dihydrate,8 inorganic acidic salts9
and hydrolyzable chloride salts10), and sodium nitrite
have also been used. We were interested to find a
* Fax: (+98) 811 8272404.
† Bu-Ali Sina University.
‡ Razi University.
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10.1021/jo001729t CCC: $20.00 © 2001 American Chemical Society
Published on Web 04/17/2001