Tetrahedron Letters 41 (2000) 6531±6535
The reduction of aromatic nitro groups on solid supports
using sodium hydrosul®te (Na S O )
2
2 4
Randall A. Scheuerman* and David Tumelty
Aymax Research Institute, 4001 Miranda Avenue, Palo Alto, CA 94304, USA
Received 28 April 2000; revised 5 June 2000; accepted 8 June 2000
Abstract
An improved method for reducing aromatic nitro compounds on solid-phase supports using sodium
hydrosul®te is presented. Conditions have been optimized to enable the use of this reagent for reductions
on both polyethyleneglycol-polystyrene (PEG) resins and traditional polystyrene (PS) resins. # 2000
Published by Elsevier Science Ltd.
In solution-phase chemistry, the reduction of aromatic nitro groups is readily accomplished
with a wide variety of reagents. Many of these methods, however, require either heavy metal
catalysts, acidic conditions, high temperatures or pressure, which renders most of them unsuitable
for use in solid-phase organic chemistry. The most common method currently in use for reduction
1
of solid-phase bound nitro groups utilizes tin(II) chloride. This reagent works well under a
variety of conditions and generally provides reliable and clean conversion to the corresponding
aniline. Several reports have also appeared, which use other transition metal-containing
compounds, such as chromium.2
Despite the advantages of tin reduction, we have found that substantial quantities of tin
by-products remain bound within the resin matrix and are liberated upon acid cleavage of the
desired product. Several cell lines useful in biological compound screening have proven intolerant
3
to tin at these levels. Although attempts to rigorously wash away any tin species remaining
within the resin by employing a variety of methods (e.g. chelating agents, solvents, crown ethers,
mild acids and bases) were partially successful, we were prompted to investigate alternative
reducing agents. In searching for a solid-phase compatible method, which would be reliable,
inexpensive, non-toxic, non-nucleophilic, neutral, and speci®c to the reduction of nitro
compounds in the presence of other functionalities, we carried out a rigorous examination of
sodium hydrosul®te.4
*
0040-4039/00/$ - see front matter # 2000 Published by Elsevier Science Ltd.
PII: S0040-4039(00)00959-X