September 1998
SYNLETT
1029
Indium as a Reducing Agent: Selective Reduction of the Heterocyclic Rings in Quinolines,
Isoquinolines and Quinoxalines
Christopher J. Moody and Michael R. Pitts
Department of Chemistry, University of Exeter, Stocker Road, Exeter, EX4 4QD, U.K.
Fax: + 1392 263434, E-mail: c.j.moody@exeter.ac.uk
Received 5 June 1998
Abstract: The heterocyclic ring in quinolines, isoquinolines and
quinoxalines is selectively reduced using indium metal in aqueous
ethanol.
The selective reduction of the heterocyclic ring in benzo-fused
heterocyclic compounds such as quinolines and isoquinolines is an
important transformation since the resulting tetrahydro derivatives serve
1
as useful synthetic intermediates. A number of methods have been used
for this transformation including catalytic hydrogenation or transfer
hydrogenation, lithium in liquid ammonia, diborane, sodium
borohydride in the presence of nickel(II) chloride, lithium
2
triethylborohydride, or sodium cyanoborohydride. We now report a
new method for the selective reduction of quinolines, isoquinolines and
quinoxalines using indium metal in aqueous ethanol.
Indium metal has found a few uses in organic chemistry of late, most
3,4
notably in the generation of synthetically useful allylindium species.
3
However, the first ionisation potential of indium (5.8 eV), which is
lower than zinc (9.4 eV) or tin (7.3 eV) and close to that of alkali metals
such as sodium (5.1 eV), suggests that the metal ought to participate
readily in single electron transfer processes, and therefore be a potent
reducing agent. As part of a wider study of the reducing properties of
5
indium metal, we found that it provides an extremely simple method
for the reduction of benzo-fused heterocycles such as quinolines to the
corresponding 1,2,3,4-tetrahydro derivatives.
The reduction of a series of quinolines was carried out by simply
heating the substrate with indium powder in aqueous ethanol containing
6
ammonium chloride,
and gave, after chromatography, the
corresponding 1,2,3,4-tetrahydroquinolines in modest to good yield
(Table 1). A number of functional groups are tolerated, including alkyl,
aryl, alkoxy, and amide, although the yield from 6-chloroquinoline was
poor. 2-Chloroquinoline, in which the halide is much more activated,
was completely reduced to 1,2,3,4-tetrahydroquinoline in 79% yield.
Nitro groups are also reduced; 6-nitroquinoline was cleanly reduced to
6-aminoquinoline (82%) with no further reduction of the heterocyclic
7
ring being observed.
The reduction of isoquinolines and quinoxalines was also briefly
investigated, and again the heterocyclic ring was cleanly reduced in
good yield (Table 2).
In summary, the use of indium metal provides a simple method for the
selective reduction of heterocyclic rings which proceeds readily in
aqueous solvent.
References and Notes
Acknowledgments
(1) Katritzky, A. R.; Rachwal, S.; Rachwal, B. Tetrahedron 1996, 52,
We thank the EPSRC for support of this work.
15031-15070
(2) For a compilation of references, see: reference 1, and Srikrishna,
A.: Reddy, J. R.; Viswajanani, R. Tetrahedron 1996, 52, 1631-
1636.