Ultrasound-promoted highly efficient reduction of aromatic nitro compounds to the aromatic amines by samarium/ammonium chloride

Article abstract of DOI:10.1016/S0040-4039(00)00917-5

Ultrasound-promoted, highly efficient reduction of several aromatic nitro compounds to the aromatic amines was achieved by samarium/ammonium chloride mediated reaction. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00917-5

Tetrahedron Letters 41 (2000) 5603±5606
Ultrasound-promoted highly ecient reduction of aromatic
nitro compounds to the aromatic amines by
samarium/ammonium chloride
Manas K. Basu, Frederick F. Becker and Bimal K. Banik*
The University of Texas, M.D. Anderson Cancer Center, Department of Molecular Pathology, Box-89,
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515 Holcombe Blvd, Houston, TX 77030, USA
Received 5 June 2000; accepted 6 June 2000
Abstract
Ultrasound-promoted, highly ecient reduction of several aromatic nitro compounds to the aromatic
amines was achieved by samarium/ammonium chloride mediated reaction. # 2000 Elsevier Science Ltd.
All rights reserved.
The synthesis of aromatic amines by various methods has been an active area of research for
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many years. As a result, many methods are currently available in the literature. Some of these
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have signi®cant limitations based on safety and handling considerations. Further, the reaction
conditions of many of these methods can destroy many sensitive functional groups. Catalytic
hydrogenation3 and catalytic transfer hydrogenation are the most common of these methods
for the synthesis of aromatic amines by the reduction of nitro compounds. However, metals such
as palladium and Raney nickel used for this purpose, in the presence of hydrogen gas or a
hydrogen donor, are ¯ammable when exposed to air and, in many cases, the use of a vacuum
pump and high temperature are necessary.
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Recently, many novel reducing agents have been reported in the literature, such as decaborane
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in methanol, electrochemically generated Raney nickel, indium±ammonium chloride in ethanol,
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samarium iodine in methanol, N,N-dimethylhydrazine/ferric chloride, hydrazine hydrate/ferric
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oxide±magnesium oxide, diethyl chlorophosphite, and sodium borohydride±sodium methoxide
in methanol.13 In general their main drawbacks are long reaction time, non-chemoselectivity and
the requirement of re¯ux temperature.
We have been engaged in the use of polycyclic aromatic amines for the development of anti-
cancer agents and towards this goal we have already reported the biological e€ects of a large
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number of polyaromatic compounds. However, the supply of many of the parent amines from
*
Corresponding author. Fax: +1 713 792 5940; e-mail: banik@mdanderson.org
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00917-5

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604
di€erent vendors is erratic. Therefore, we began a research program aimed at developing methods
to synthesize the starting polycyclic amines rapidly and in high yield, by using ecologically
friendly reagents. In this paper, we have developed a highly e€ective reducing agent by combining
samarium metal15 with ammonium chloride under sonication (Scheme 1).16
Scheme 1.
We believe that no other methods in the literature1 can produce the aromatic amines by the
reduction of aromatic nitro compounds within this time frame and under such mild conditions.
A wide variety of aromatic nitro compounds were reacted by samarium metal and ammonium
chloride in methanol using ultrasound at room temperature (Table 1). For example, 6-nitro
chrysene (entry 2) was reduced to the 6-amino chrysene in only 10 min by this method in excellent
yield (86%). No reaction was observed in the absence of sonication.
�13
Table 1
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Ultrasound-promoted reduction of various aromatic nitro compounds by Sm/NH Cl

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605
Similarly, nitro¯uorene (entry 3) was reduced to the amino ¯uorene within 10 min. Indium/
ammonium chloride reduction of the 2-nitro ¯uorene in the presence of sonication gave no
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reduction at room temperature even after 30 min. By following one reported method we were
able to prepare 2-amino¯uorene by the reduction of 2-nitro ¯uorene at re¯ux temperature for 10 h
using methanol in the presence of indium/ammonium chloride. Iron powder in the presence of
ammonium chloride under sonication failed to produce traces of the amino compound. This
indicates that samarium/ammonium chloride has a much greater reducing ability than the indium/
ammonium chloride or iron/ammonium chloride combination, for the reduction of aromatic
nitro group. We have further veri®ed this conclusion by the facile chemoselective reduction of a
number of other aromatic nitro compounds by using samarium/ammonium chloride under
identical conditions. The reduction sensitive groups, such as bromo (entry 4), cyano (entry 5),
ester (entry 6), unsaturated bond (entry 7) and heterocyclic ring (entry 8) remained una€ected
during this transformation.
From a series of experiments, we found that 4-equiv. of samarium were required for completion
of the reaction. An increase in the amount of samarium did not reduce the time required. We
found that ammonium chloride was necessary since the reduction did not proceed in the presence
of samarium and methanol only.
The mechanism of this new reducing system is unknown to us. In an e€ort to ®nd the
mechanistic path, reduction of 6-nitro chrysene was carried out by reacting it with samarium
trichloride and samarium metal in methanol under sonication, since one can question the involve-
ment of samarium dichloride. We found that the progress of this reaction was slow in comparison
to the reaction when samarium metal and ammonium chloride were used. Therefore, we cannot
exclude the involvement of samarium dichloride as the reactive species. We observed the critical
role of methanol in this reaction as the reduction failed to produce amino compounds with any of
these substrates under identical conditions with other solvents, such as ethanol and tetrahydrofuran.
In conclusion, we have shown an expeditious method for the synthesis of aromatic amines by
the reduction of aromatic nitro compounds via samarium-induced ultrasound-promoted reaction
at room temperature within a few minutes.17
Acknowledgements
We gratefully acknowledge the funding support received for this research project from the
Hubert L. and Olive Stringer Chair and NIH Cancer Center Support Grant, 50P30-CA-16672-25,
in particular the shared resources of the Pharmacology and Analytical Center Facility.
References
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7. A representative procedure is given below: To a solution of the nitro compound (0.5 mmol) in methanol (5 mL)
(for those compounds which are not completely soluble in methanol, a few drops of dichloromethane was added
to make it soluble), solid ammonium chloride (10.0 mmol) and samarium metal (2.2 mmol, 40 mesh) were added
and the reaction mixture was sonicated18 at room temperature for 10±20 min (Table 1). The reaction started
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color of the mixtures. After the reaction was over, as indicated by TLC, water (5 mL) was added and then it was
extracted with dichloromethane, dried over sodium sulfate and concentrated. The pure product was isolated by
®
ltration through a short column over silica gel using ethyl acetate and hexanes as the solvent. The reaction can be
carried out with 1±2 g nitro compound. All products have been characterized through a comparison of mp, TLC
and NMR with authentic compounds.
8. A Bransonic Model 2210R-DTH was used for sonication.
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