A one-pot synthesis of N-alkylaminobenzenes from nitroaromatics: reduction followed by reductive amination using B10H14

Article abstract of DOI:10.1039/b005194m

N-Alkylaminobenzenes were prepared in a simple and efficient one-pot synthesis by reduction of nitrobenzenes followed by reductive amination with decaborane (B10H14) in the presence of 10% Pd/C.

Full text of DOI:10.1039/b005194m

A one-pot synthesis of N-alkylaminobenzenes from nitroaromatics: reduction
followed by reductive amination using B10H14
Jong Woo Bae, Young Jin Cho, Seung Hwan Lee, Choon-Ock Maing Yoon and Cheol Min Yoon*
Department of Life Science & Biotechnology, Graduate School of Biotechnology, Korea University, Seoul,
South Korea. E-mail: cmyoon@tiger.korea.ac.kr; Fax: +82-2-3290-3433
Received (in Corvallis, OR, USA) 27th June 2000, Accepted 27th July 2000
First published as an Advance Article on the web 14th September 2000
N-Alkylaminobenzenes were prepared in a simple and
efficient one-pot synthesis by reduction of nitrobenzenes
followed by reductive amination with decaborane (B10H14)
in the presence of 10% Pd/C.
multicomponent condensations2 and palladium-catalyzed
reactions,3 which are known to be useful owing to mild
reaction conditions and stability against other functional
groups.
Aromatic amines are important intermediates for dyes and
agricultural and pharmaceutical chemicals. One popular method
for the preparation of these amines is the reduction of
nitroaromatics using various reagents and conditions.4,5 One of
the methods for the synthesis of secondary amines is the
reductive amination of primary amines with carbonyls using a
variety of reducing reagents.6
Consecutive reactions1 have received much attention because
they give complex molecules efficiently from simple starting
materials. In the first step of these reactions, the functional
group necessary for the following transformation is formed. An
ideal place for such consecutive reactions is in one-pot
synthesis, in which all these processes occur consecutively by
successive addition of reagents, without isolation of inter-
mediates. Well known examples of one-pot processes are
In the course of our work using decaborane as a mild and
stable reducing agent,7 we found that the reduction of
Table 1 Synthesis of N-alkylaminobenzenes
DOI: 10.1039/b005194m
Chem. Commun., 2000, 1857–1858
This journal is © The Royal Society of Chemistry 2000
1857

2-one (28.9 mg, 0.401 mmol), decaborane (13.4 mg, 0.109 mmol) and 10%
Pd/C (15 mg). The resulting solution was stirred at ca. 40 °C under nitrogen
for 1.5 h. The mixture was then cooled to rt and decaborane (8.9 mg, 0.073
mmol) was added to the mixture. The resulting solution was stirred at rt
under nitrogen for 2 h. The mixture was concentrated under reduced
pressure, chromatographed on a short pad of silica gel using a solution of
ethyl acetate and n-hexane (1+8) and concentrated to give the product amine
as a pale pink syrup. Aldehyde (entry 8). To a solution of methyl
4-nitrobenzoate (50 mg, 0.276 mmol) in methanol (5 ml) was added two
drops of acetic acid, decaborane (10 mg, 0.083 mmol) and 10% Pd/C (15
mg). The resulting solution was heated to reflux under nitrogen for 0.5 h and
the mixture was cooled to rt. Propanal (17 mg, 0.303 mmol) and decaborane
(6.7 mg, 0.052 mmol) were then added to the reaction mixture. The solution
was stirred at rt under nitrogen for 2 h. The mixture was concentrated under
reduced pressure, chromatographed on a short pad of silica gel using a
solution of ethyl acetate and n-hexane (1+8), and concentrated to give the
amine as a white solid.
Scheme 1
Scheme 2
nitroaromatics using a decaborane–Pd/C system followed by
reductive amination with carbonyls using decaborane gave a
one-pot synthesis of N-alkylaminoaromatics in high isolated
yield. To the best of our knowledge, this is the first example of
1 L. F. Tietze and U. Beifuss, Angew. Chem., Int. Ed. Engl., 1993, 32, 131;
L. F. Tietze, Chem. Rev., 1996, 96, 115.
a
one-pot preparation of N-alkylaminoaromatics from
nitroaromatics.
2 Multicomponent Reactions in Organic Chemistry, I. Ugi, A. Domling
and W. Horl, Endeavour, 1994, 18, 115.
Decaborane was added in two batches in all of the examples.8
30 mol% of decaborane (B10H14) was added for the reduction of
the nitro group in the first batch, and 20 or 30 mol%9 was used
for reductive amination in the second batch. When a ketone was
used for the reductive amination (entries 1–7, Table 1), it was
added to the reaction solution at the beginning of the reaction
(Scheme 1). The reactions proceeded smoothly at 40 °C without
addition of acetic acid. However, when aldehydes were used
(entries 8 and 9, Table 1), they were added after the
completion10 of the nitro-group reduction to prevent reductive
etherification11 (Scheme 2). Under these conditions, the
reactions were complete in several hours and gave the
corresponding secondary amines chemoselectively and in high
yields. Other functional groups such as esters (entries 1, 6 and
8), amides (entry 2), nitriles (entry 4) and hydroxy groups (entry
5) were intact under the reaction conditions.†
3 S. Brase and A. de Meijere, in Metal-catalyzed Cross-coupling
Reactions, ed. F. Diederich and P. J. Stang, Wiley-VCH, Weinheim,
1998, p. 99; A. de Meijere and F. E. Meyer, Angew. Chem., Int. Ed.
Engl., 1994, 33, 2379; T. J. J. Muller, M. Ansorge and S. Aktah, Angew.
Chem., Int. Ed., 2000, 39, 1253.
4 G. Mestoni, A. Camus and G. Zassinovich, in Aspects of Homogeneous
Catalysis, ed. R. Ugo, Reidel, Dordrecht, 1981, Vol. 4, pp. 71–80.
5 G. Sauve and V. S. Rao, Comprehensive Organic Functional Group
Transformations, ed. A. R. Katritzky, O. Meth-Cohn and C. W. Rees,
Pergamon Press, Oxford, 1995, Vol. 2, pp. 737–817.
6 W. S. Emerson, Org. React., 1948, 4, 174; M. V. Klyuev and M. L.
Khidekel, Russ. Chem. Rev., 1980, 49, 14; R. Hutchins and N. R. Natale,
Org. Prep. Proced. Int., 1979, 11, 201; M. D. Bomann, I. C. Guch and
M. DiMare, J. Org. Chem., 1995, 60, 5995; N. M. Yoon, E. G. Kim,
H. S. Son and J. Choi, Synth. Commun., 1993, 23, 1595; J. Brussee,
R. A. T. M. van Benthem, C. G. Kruse and A. van der Gen, Tetrahedron:
Asymmetry, 1990, 1, 163; A. F. Abdel-Magid, K. G. Carson, B. D.
Harris, C. A. Maryanoff and R. D. Shah, J. Org. Chem., 1996, 61, 3849;
B. C. Ranu, A. Majee and A. Sakar, J. Org. Chem., 1998, 63, 370.
7 J. W. Bae, S. H. Lee, Y. J. Cho and C. M. Yoon, J. Chem. Soc., Perkin
1, 2000, 145.
In conclusion, nitroaromatics were converted into N-alkyl-
aminoaromatics in a single-pot synthesis using decaborane as a
reducing agent in the presence of Pd/C in methanol. The
reaction is efficient and chemoselective. Investigations of the
scope of this one-pot synthesis are currently underway.
The authors wish to acknowledge the financial support of the
Korea Research Foundation made in 2000.
8 The addition of 50 or 60 mol% decaborane in one batch at the beginning
of the reaction resulted in incomplete reaction.
9 In some cases (entries 1, 2 and 7), the reductive amination was slow with
20 mol% of decaborane. In these instances, 30 mol% of decaborane was
added.
10 The completion of the reduction of the nitro group was followed by TLC
using a solution of ethyl acetate and n-hexane (1+4).
11 S. H. Lee, Y. J. Park and C. M. Yoon, Tetrahedron Lett., 1999, 40,
6049.
Notes and references
† Representative experimental procedures: Ketone (entry 3). To a solution
of 4-nitrotoluene (50 mg, 0.364 mmol) in methanol (5 ml) was added butan-
1858
Chem. Commun., 2000, 1857–1858