TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 1983–1985
Direct conversion of aryl nitro compounds to formanilides under
catalytic transfer hydrogenation conditions
T. V. Pratap and S. Baskaran*
Department of Chemistry, Indian Institute of Technology Madras, Chennai 600 036, India
Received 17 November 2000; accepted 9 January 2001
Abstract—A direct and mild route to formanilides from aromatic nitro compounds bearing different functional groups under
catalytic transfer hydrogenation (CTH) conditions is described. © 2001 Elsevier Science Ltd. All rights reserved.
1
. Introduction
of aromatic nitro compounds having different sensitive
functional groups and the results are illustrated in
Table 1.
Formanilides have been widely used in the synthesis of
biologically active compounds such as N,N–diaryl
ureas, cancer chemotherapeutic agents and quinolone
antibacterials. They also constitute important precur-
sors in the synthesis of fungicides and herbicides. In
addition, N-formyl compounds are found to be the
constituents of fragrant flowers, thus finding an appli-
cation in the perfume industry. Furthermore, N-formyl
1
2
3
14
The dehalogenation of aromatic chloro compounds
4
has been reported in methanol under CTH conditions,
however the chloro functional group was found to be
inert under our reaction conditions (entry 4). The mild-
ness of the CTH reaction in acetonitrile was further
tested with oxime and keto derivatives (entries 5, 8 and
5
6
compounds are Lewis bases, which are known to cata-
9). Unlike the Pd/CꢀH system, chemoselective trans-
2
7
8
lyze allylation and hydrosilylation of carbonyl com-
pounds. Various methods have been reported for the
formation of aryl nitro compounds to the correspond-
ing N-formanilides was achieved in the presence of
9
15
selective reduction of aryl nitro compounds to anilines
ketone functionality as shown in Scheme 2. In the
as well as N-formylation of anilines with different
formylating agents. However, the direct conversion
of aryl nitro compounds to formanilides would be an
ideal choice for this class of important compounds.
case of p-nitro acetophenone (entry 9), in addition to
the N-formyl product (46%), the intermediate p-amino
acetophenone was isolated in 28% yield. The selectivity
of this methodology is further exemplified in the case of
entry 5, where the reducible oxime functional group
was found to be stable under the reaction conditions.
10
11
1
6
During the course of our study on the catalytic transfer
hydrogenation (CTH) of aryl nitro compounds with the
12
ammonium formate/PdꢀC system, we made the inter-
esting observation that ammonium formate in an
aprotic solvent like acetonitrile can function as a
2. Typical experimental procedure
1
3
formylating agent apart from being a source of hydro-
gen. Based on this observation, we have developed a
novel and highly selective procedure for the direct
conversion of aryl nitro compounds to formanilides in
acetonitrile under CTH conditions (Scheme 1).
To a stirred solution of p-nitrotoluene (100 mg, 0.73
mmol) in dry acetonitrile (3 mL) was added 10% Pd/C
(20 mg) followed by anhydrous ammonium formate
(460 mg, 7.3 mmol). The resultant heterogeneous reac-
tion mixture was allowed to reflux at 95°C (bath tem-
The selectivity and mildness of this one step reductive
N-formylation methodology was tested with a variety
NO2
NH-CHO
HCO NH , Pd - C
2
4
Keywords: reductive N-formylation; catalytic transfer hydrogenation;
formanilides; aromatic nitro and ammonium formate.
o
CH CN, 95 C (Oil bath)
X
3
X
*
Corresponding author. Fax: 0091-44-235 2545; e-mail:
Scheme 1.
0
040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00049-1
Pratap
