1
162
ZOLFIGOL ET AL.
9
10
tetroxide, oxalic acid dihydrate, and sodium nitrite have also been used.
Very recently, we among many others have demonstrated that the hetero-
geneous reagent systems have many advantages, such as simple experi-
mental procedures, mild reaction conditions, and minimization of
1
0–13
chemical wastes, as compared to their liquid phase counterparts.
Therefore, we decided to apply a completely heterogeneous system and
we have investigated a number of different reaction conditions based upon
the in situ generation of HNO by relatively strong inorganic acidic salt, e.
2
g., potassium monopersulfate (KHSO , K ꢀ1), and sodium nitrite for the
5
p
a
nitrosation of secondary amines. We report a simple, cheap, and chemo-
selective method for the effective nitrosation of secondary amines under
mild and heterogeneous conditions.
Different types of secondary amines (1) were subjected to the nitrosa-
tion reaction in the presence of KHSO (I), NaNO (II) and wet SiO
2
5
2
(
50% w/w) in dichloromethane (Scheme). The nitrosation reactions were
performed under mild and completely heterogeneous conditions at room
temperature and took place with excellent yields (Tab.).
This present nitrosation reaction can be readily carried out by placing
KHSO (I), NaNO (II), amine (1), wet SiO (50% w/w), and CH Cl as the
5
2
2
2
2
inert solvent in a reaction vessel and efficiently stirring the resulting hetero-
geneous mixture at room temperature. The nitrosoamines (2) can be
obtained simply by filtration and evaporation of the solvent. The results
and reaction conditions are given in the Table.
To demonstrate the chemoselectivity of this method, a competitive
reaction was performed between dicyclohexylamine (1c) and anisole. It
was observed that amine nitrosation occurred exclusively, whereas anisole
remained intact in the reaction mixture after 2 h. The nitrosation reaction of
diphenylamine further shows the chemoselectivity of the method as the N-
nitrosodiphenylamine is the only product. This system thus behaves differ-
3
,4
þ
ently from some reported methods in that nitrosonium ion (NO ) attacks
the nitrogen sites of the secondary amines even where an aromatic moiety is
connected directly to the nitrogen atom.
Furthermore, the chiral center of L-proline (1e) also remained intact in
the course of the reaction so that L-nitrosoproline (2e) was obtained in
excellent yields (Table, Scheme 1, Entry 5). L-Nitrosoproline (2e) is a pre-
cursor of mesoionic moieties in an important class of dipolar heterocyclic
1
5
compounds with special properties.
Some of the amines used are very important precursors for the syn-
thesis of symmetrical and asymmetrical tripodal tetraamines (Table, Entries
1
6–18.
8
useful for synthesis of special NO-releasing complexes.
–10)
We therefore believe that their nitroso derivatives are also very