A convenient method for the N-formylation of secondary amines and anilines using ammonium formate

Article abstract of DOI:10.1016/S0040-4039(00)01636-1

The N-formylation of secondary amines and anilines using ammonium formate as a formylating agent is described. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01636-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 9149–9151
A convenient method for the N-formylation of secondary
amines and anilines using ammonium formate
P. Ganapati Reddy, G. D. Kishore Kumar and S. Baskaran*
Department of Chemistry, Indian Institute of Technology Madras, Chennai 600 036, India
Received 14 September 2000; accepted 20 September 2000
Abstract
The N-formylation of secondary amines and anilines using ammonium formate as a formylating agent
is described. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: ammonium formate; N-formylation; secondary amines and anilines.
Formamides are a class of important intermediates in organic synthesis. They have been
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widely used in the synthesis of pharmaceutically important compounds such as fluroquinolones,
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substituted aryl imidazoles, 1,2-dihydroquinolines, nitrogen bridged heterocycles, etc. For-
mamides are Lewis bases, which are known to catalyze reactions such as allylation and
hydrosilylation of carbonyl compounds. More recently, asymmetric allylation of aldehydes has
been achieved with chiral formamides. Furthermore, formamides are very useful reagents in
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Vilsmeier formylation reactions. In addition, they have been used in the synthesis of
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formamidines and isocyanides.
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Numerous methods are available for the N-formylation of amines,
however, many of
these methods involve reagents which are either toxic or expensive. In this communication, we
report ammonium formate as relatively less expensive and efficient N-formylating agent for
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secondary amines and anilines.
Ammonium formate mediated N-formylation of secondary amines and anilines takes place
readily in acetonitrile at reflux temperature and the yields are usually very good. However, under
*
Corresponding author. Fax: 0091-44-2350509; e-mail: bhaskars@chem.iitm.ernet.in
0
040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01636-1

9150
similar reaction conditions, primary amines give alkyl ammonium formate salts, except benzy-
lamine, which gave the desired N-formyl derivative in high yield.
The generality of this methodology has been studied with different secondary amines and
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anilines. The reaction time and yields are summarized in Table 1. The benzyl ester of
L
-proline
(
entry 3) was converted to the corresponding N-formyl compound without racemization
Table 1
N-Formylation of secondary amines and anilines with ammonium formate

9151
{
[h] =−42.9 (c 3, MeOH)}. 4-(Piperazinyl) nitrobenzene (entry 9) gave the corresponding
D
N-formyl derivative in excellent yield, which is a useful precursor in the synthesis of
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oxazolidinone antibacterial agents. It is interesting to note that an aniline with a hydroxy
group in the side chain (entry 8) undergoes chemoselective N-formylation in good yield.
Typical experimental procedure: To a solution of aniline (465 mg, 5 mmol) in dry acetonitrile
(
7.5 mL) was added anhydrous ammonium formate (473 mg, 7.5 mmol) and the resulting
mixture was heated at 95°C (bath temperature) for 11 h. Acetonitrile was removed under
reduced pressure. The residue was diluted with ethyl acetate (20 mL) and washed with water
(
2×10 mL). The organic layer was dried over anhydrous Na SO and then concentrated under
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reduced pressure to yield pure formanilide (580 mg, 96%) as a low melting solid, mp 48–50°C.
In conclusion, we have developed a convenient and mild method for N-formylation of
secondary amines and anilines in excellent yields using the less expensive ammonium formate.
We believe this novel methodology will find wide application in organic synthesis.
Acknowledgements
We thank Professor K. K. Balasubramanian for his constant encouragement and generous
support. P.G.R. (SRF) and G.D.K. (JRF) thank the CSIR, New Delhi for research fellowships.
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