Direct formation of aromatic C-N bonds. Regioselective amination of m- dinitrobenzene via fluoride promoted nucleophilic aromatic photosubstitution for hydrogen

Article abstract of DOI:10.1016/S0040-4039(99)02035-3

Useful yields are achieved in the regioselective direct formation of anilines and aromatic amides through hydrogen nucleophilic aromatic photosubstitution of m-dinitrobenzene with primary amines and amides, promoted by fluoride anion.

Full text of DOI:10.1016/S0040-4039(99)02035-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 279–281
Direct formation of aromatic C–N bonds. Regioselective
amination of m-dinitrobenzene via fluoride promoted nucleophilic
aromatic photosubstitution for hydrogen
∗
Inma Huertas, Iluminada Gallardo and Jordi Marquet
Departament de Química, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain
Received 13 October 1999; accepted 26 October 1999
Abstract
Useful yields are achieved in the regioselective direct formation of anilines and aromatic amides through
hydrogen nucleophilic aromatic photosubstitution of m-dinitrobenzene with primary amines and amides, promoted
by fluoride anion. © 1999 Elsevier Science Ltd. All rights reserved.
Keywords: amination; arylation; photochemistry; nitro compounds.
The development of new environmentally favorable routes for the production of commercially relevant
chemical intermediates and products is an area of considerable interest. These synthetic routes will
require, in most cases, the discovery of new atomically efficient chemical reactions. In view of these
requirements, we have focused our attention on nucleophilic aromatic substitution for hydrogen reactions
1
(
NASH) as a means to generate functionalized aromatics without the need for halogenated materials or
2
intermediates. NASH reactions formally require the replacement of a hydride ion, and they happen
‘
spontaneously’ consuming part of the starting material in the oxidation of the anionic σ-complex, or
3
they are promoted by the addition of external oxidants. Low yields (with few exceptions) and lack of
generality are the main drawbacks of these synthetic procedures. In addition, some of the substances
used as oxidants, such as permanganate, are hazardous in their own right. We have recently shown that
1
2
by the use of UV irradiation (to help the redox step) and fluoride anion (to activate the nucleophile in an
4
essentially neutral medium), useful yields of C-arylated ketones, esters and nitriles could be achieved.
Several different methods for the direct amination of nitrobenzenes that do not require chlorobenzenes
have been reported. Perhaps the most synthetically useful of these is vicarious nucleophilic substitution
5
for hydrogen (VNS). In spite of the fact that this method gives rise to reasonable yields of aminated
6
7
nitrobenzenes, the requirement of an auxiliary leaving group still persists. Recently Stern et al. have
described the direct amination of nitrobenzene with aniline and amides in useful yields. However, simple
∗
Corresponding author.
0
040-4039/00/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(99)02035-3
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aliphatic amines failed. We wish to report here the photochemically induced direct coupling of amines
and amides with m-dinitrobenzene, promoted by fluoride anion.
Table 1
Photoreactions of m-DNB with amines and amides in the presence of TBAF
In Table 1 (Scheme 1), the photoreactions (UV light, pyrex filter) of m-dinitrobenzene (m-DNB) with
amines and amides, in the presence of TBAF, are described. No reaction is produced in the absence of
2
irradiation or in the absence of TBAF. At variance with what happens with carbon nucleophiles, no
precautions with the presence of oxygen are needed, and irradiation with visible light did not lead to
products. The yields when primary amines or amides are used range from fair to good considering the
starting material is also acting as an oxidant in the process, and the experimental procedure is extremely
simple. Curiously enough, secondary amines give poor yields (experiments 5, 6 and 7). Extensive
decomposition of the reaction mixture is observed in these cases. Also at variance to the reaction with
2
carbon nucleophiles, the photoreaction is totally regioselective, the product resulting from attack at the
C-4 in m-DNB being the only one that is now produced.
Scheme 1.
As far as we know, the experiments reported in Table 1 are the first examples of nucleophilic aromatic
photosubstitution of hydrogen with nitrogen nucleophiles. In addition, experiments 8 and 9 constitute a
formal ‘chlorine free’ new route to 2,4-dinitroaniline through hydrolysis of the obtained aromatic amides
(
or treatment of the amides with methanolic ammonia).7b Mechanistic studies are currently in progress
and a full account will be published in the near future.

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Acknowledgements
Financial support from DGES (MEC of Spain) through the project PB96-1145 and from Generalitat
de Catalunya through the project 1997SGR00414 are gratefully acknowledged.
References
1
. (a) Chupakhin, O. N.; Charushin, V. N.; van der Plas, H. C. Nucleophilic Aromatic Substitution of Hydrogen; Academic
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New York, 1991; Chapter 5.
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