TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 5601–5603
Simple and chemoselective reduction of aromatic nitro
compounds to aromatic amines: reduction with hydriodic acid
revisited
J. S. Dileep Kumar, ManKit M. Ho and Tatsushi Toyokuni*
Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, UCLA School of Medicine,
700 Westwood Plaza, Los Angeles, CA 90095, USA
Received 10 May 2001; revised 15 June 2001; accepted 19 June 2001
Abstract—Reduction of aromatic nitro compounds to amines with hydriodic acid was reinvestigated. Under a milder non-reflux-
ing condition (at 90°C for 2–4 h), the reduction proceeded efficiently with excellent chemoselectivity without affecting other
functional groups including nitrile, ester, halide, carbonyl, amide, sulfonamide, imidazole and methylthio groups. © 2001 Elsevier
Science Ltd. All rights reserved.
Reduction of aromatic nitro compounds to the corre-
sponding amines is an important chemical transforma-
tion in synthetic organic chemistry. This is because the
nitro group is often used to activate the aromatic
nucleus for nucleophilic substitution reactions but the
amino group often serves as a site for further derivati-
sation towards final products. Indeed, aromatic amines
are important intermediates for a number of valuable
compounds such as pharmaceuticals, agrochemicals
and dyes. A variety of methods have so far been
reported for this transformation, many of which
employ metallic reagents.1 More chemoselective and
efficient methods are constantly being developed.2–4
solvent.4,7 Therefore, we have reinvestigated this
decades-old method under a milder non-refluxing con-
dition which might improve its chemoselectivity.
Treatment of aromatic nitro compounds with 57% HI
at 90°C for 2–4 h yielded the corresponding amines
with excellent chemoselectivity over various functional
groups that are often present in the substrate (Table 1).
Moreover, acid-labile nitrile and ester groups did not
undergo hydrolysis (entries 5 and 9, respectively). Boil-
ing HI has been used to replace the halogen atom in
pyridine5 and pyridazine8 rings with iodine. It is also
reported that such halogen exchange was possible with-
out reducing the nitro group by heating just below the
boiling point.5 Under our condition the aromatic nitro
group was reduced exclusively without any halogen
exchange reactions (entries 2, 3 and 10). It is worth
mentioning that extraction of the reaction mixture gen-
In 1947 Bruce and Perez-Medina observed that reflux-
ing hydriodic acid (HI)† efficiently reduced the nitro
group in pyridine rings to give aminopyridines.5 In 1971
Krasnec reported some chemoselectivity in the HI-
mediated reduction of aromatic nitro compounds to
aromatic amines.6 Thus, by refluxing with 57% HI the
nitro group was reduced as well as a double bond with
a high chemoselectivity over chloride and carbonyl
groups. However, acid-labile nitrile and ester groups
resulted in complete hydrolysis. Since then very little
attention has been paid to this potentially useful
method, particularly in terms of simplicity, ready
availability of the reagent and the use of water as the
1
erally yielded the product with a >95% purity (by H
NMR analysis) without purification by column chro-
matography (entries 1–5 and 11). The lower yields
(entries 6–10) were attributed to the incomplete
reactions.
A typical reaction procedure is described below. All
starting compounds are known (entries 29 and 310) or
commercially available (entries 1 and 4–11). A suspen-
sion of an aromatic nitro compound (1 mmol) in unsta-
bilized 57% HI (3 mL) was heated at 90°C for 2–4 h.
The reaction mixture became homogeneous as the reac-
tion progressed. After cooling to room temperature, the
dark purple mixture was diluted with EtOAc (50 mL)
* Corresponding author. Tel.: (310) 206-1675; fax: (310) 206-8975;
e-mail: ttoyokuni@mednet.ucla.edu
† 57% HI boils constantly at 127°C.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01083-8
Kumar, J.S.Dileep
