Hydrazinium monoformate: A new hydrogen donor. Selective reduction of nitrocompounds catalyzed by commercial zinc dust

Article abstract of DOI:10.1081/SCC-120015713

The nitro group in aliphatic and aromatic nitro compounds also containing reducible substituents such as ethene, nitrile, acid, phenol, halogen, ester, etc., are selectively and rapidly reduced at room temperature to corresponding amines in good yields by employing hydrazinium monoformate, in the presence of commercial zinc dust. It was observed that, hydrazinium monoformate is more effective than hydrazine or formic acid and reduction of nitro group occurs without hydrogenolysis in the low cost zinc dust compared to expensive metals like palladium.

Full text of DOI:10.1081/SCC-120015713

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Hydrazinium Monoformate: A New Hydrogen Donor.
Selective Reduction of Nitrocompounds Catalyzed by
Commercial Zinc Dust
a
a
a b
Shankare Gowda , B. K. Kempe Gowda & D. Channe Gowda
a
Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore,
Karnataka, India
b
Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore,
Karnataka, 570 006, India
Version of record first published: 21 Aug 2006.
To cite this article: Shankare Gowda , B. K. Kempe Gowda & D. Channe Gowda (2003): Hydrazinium Monoformate: A New
Hydrogen Donor. Selective Reduction of Nitrocompounds Catalyzed by Commercial Zinc Dust, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 33:2, 281-289
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Õ
SYNTHETIC COMMUNICATIONS
Vol. 33, No. 2, pp. 281–289, 2003
Hydrazinium Monoformate: A New Hydrogen
Donor. Selective Reduction of Nitrocompounds
Catalyzed by Commercial Zinc Dust
Shankare Gowda, B. K. Kempe Gowda, and D. Channe Gowda*
Department of Studies in Chemistry, University of Mysore,
Manasagangotri, Mysore, Karnataka, India
ABSTRACT
The nitro group in aliphatic and aromatic nitro compounds also
containing reducible substituents such as ethene, nitrile, acid,
phenol, halogen, ester, etc., are selectively and rapidly reduced at
room temperature to corresponding amines in good yields by
employing hydrazinium monoformate, in the presence of commercial
zinc dust. It was observed that, hydrazinium monoformate is more
effective than hydrazine or formic acid and reduction of nitro group
occurs without hydrogenolysis in the low cost zinc dust compared
to expensive metals like palladium.
*Correspondence: D. Channe Gowda, Department of Studies in Chemistry,
University of Mysore, Manasagangotri, Mysore, Karnataka, 570 006, India.
Fax: þ091-0821-421263/518835; E-mail: dcgowda@yahoo.com.
2
81
DOI: 10.1081/SCC-120015713
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
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Gowda, Gowda, and Gowda
Key Words: Hydrazinium monoformate; Zinc; Catalytic transfer
hydrogenation; Nitro compounds; Reduction; Amines.
Rapid and selective reduction of nitro compounds is of importance
for the preparation of amino derivatives in the organic synthesis both
practically and industrially, particularly when a molecule has other redu-
[
1–5]
cible moieties.
The synthesis and biological evaluation of aromatic
amines are also active and most important areas of research and their
[
6,7]
chemistry by derivative formation is widely studied.
reagents have been developed for the reduction of aromatic nitrocom-
pounds. Though some of these are widely used, still they have limita-
tions based on safety and handling considerations. For example, catalytic
Numerous new
[8]
[9–11]
transfer hydrogenation
of nitro or azido compounds in the presence
of metals such as palladium on carbon or platinum on carbon require
stringent precautions, because of their flammable nature in the presence
of air. In addition, some methods require compressed hydrogen gas,
which is highly diffusible and flammable, and vacuum pump to create
high pressure within reaction flask. To overcome these difficulties,
[
12,13]
several new methodologies have also been developed.
little attention has been given to the reduction of aliphatic nitro-
However,
[14–16]
compounds,
catalytic hydrogenation.
which are traditionally reduced by high-pressure
In addition to above mentioned limita-
[17–19]
tions, most of these methods are unfortunately subject to substantial
limitations as concerns the reducible functionalities and lack therefore
desired generality for the true synthetic utility. Moreover, poor selectivity
was reported in the reduction of aromatic nitro compounds, which have
halogen, nitrile, carboxyl, hydroxyl etc., as substituents. Reduction at
reflux temperature for hours together can cause rearrangements and
cyclization in poly functional nitrocompounds. Therefore, we examined
several methods to improve reduction process, and especially to obtain
selectivity over reducible or other labile substituents. In this context,
use of 5% platinumon carbon was found to be efficient but not cost
[20]
effective.
Recently, metal mediated reactions have been found to have wide
scope in organic synthesis, because of their simple work-up and
selectivity. Several methods have been developed based on the use of a
[
21]
[8,22,23]
[24]
[25]
variety of metals such as magnesium, indium,
tin, zinc. The
utility of zinc for the synthesis of b-g-unsaturated ketones by a reaction
[
26]
[27]
of an acid chloride with allyl bromide and homoallylic alcohols has
been demonstrated. Further, the zinc mediated preparation of triphenyl

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Hydrazinium Monoformate
283
Zn/H
2
2
N-NH .HCOOH
R-NO
2
R-NH
2
MeOH, r.t
R= alkyl or aryl
Scheme 1.
[
28]
[29]
phosphoniumylides,
formation
Fridel–Crafts acylation
and carbamates
[30]
has been demonstrated.
In this communication, we wish to report, a rapid and simple reduc-
tion of aliphatic and aromatic nitrocompounds to the corresponding
amino derivatives by using commercial zinc dust and hydrazinium
monoformate, at room temperature (Sch. 1). This new system reduced
with ease a wide variety of nitro compounds directly to the corresponding
amines and many functional groups are tolerated. This system is not
helpful to obtain directly an amino carbonyl compound, due to the for-
mation of hydrazone derivative with donor. However, the nitro hydra-
zones are reduced to corresponding amino hydrazones by this system.
But, the thing is, in order to get amino carbonyl derivative, hydrazone
should be subjected to hydrolysis. In both nitro aldehydes as well as nitro
ketones, the products were obtained in almost pure and comparable yields.
The reduction of nitrocompound in the presence of zinc dust and
hydrazinium monoformate was complete within one to ten min. The
course of reaction was monitored by thin layer chromatography and
IR spectra. The work-up and isolation of the products were easy.
Thus, all the compounds reduced (Table 1) by this system were obtained
in good yields (90–95%). All the products were characterized by compar-
ison of their TLC, IR spectra, and melting points with authentic samples.
A control experiment was carried out using nitro compounds with hydra-
zinium monoformate but without zinc dust, does not yield the desired
product. No other intermediates, such as nitroso or hydroxylamine
could be detected in the reaction mixture. In order to test the selectivity,
reduction was attempted with p-dichloro benzene, p-chloro-m-cresol,
b-naphthol, cinnamic acid, acetanilide, benzoic acid, anisole, benzo-
nitrile, phenyl acetate, etc., at laboratory temperature. However, the
reaction failed to give any reduced product.
Hydrazinium diformate, a white crystalline compound obtained by
the neutralization of one mole of hydrazine hydrate with two mole of
85% formic acid was found to be inactive to this system. Further, hydra-
zinium monoformate is more effective than either hydrazine or formic

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Gowda, Gowda, and Gowda

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Hydrazinium Monoformate
285

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Gowda, Gowda, and Gowda
acid with zinc dust. Most of the reactions are complete in less than one
minute as monitored by the disappearance of the starting materials and
concomitant formation of the product via TLC methods.
Thus the reduction of nitrocompounds can be accomplished with
commercial zinc dust instead of expensive platinum or palladium etc.,
with out effecting the reduction of any reducible or hydrogenolysable
substituents. The yields are virtually quantitative and analytically pure.
The obvious advantages of proposed method over previous methods are:
(
i) selective reduction of nitro compounds, in the presence of other redu-
cible or hydrogenolysable groups, (ii) easy to operate, (iii) rapid reduc-
tion, (iv) high yields of substituted amines, (v) avoidance of strong acid
media, (vi) no requirement of pressure apparatus, and (vii) less expensive.
This procedure will therefore be of general use, especially in the cases
where rapid, mild and selective reduction is required. Further investiga-
tions of other useful applications related to deblocking of protecting
groups in peptide synthesis are in progress.
Typical Procedure
The hydrazinium monoformate was prepared by neutralizing slowly,
equal moles of hydrazine hydrate and 85% formic acid in an ice water
bath, with constant stirring. Thus obtained hydrazinium monoformate
solution is used as such for reduction. A suspension of an appropriate
nitrocompound (5 mmol) and zinc dust (10 mmol) in methanol or in any
suitable solvent (3 mL) was stirred under nitrogen atmosphere with
hydrazinium monoformate (2 mL), at room temperature. The reaction
was exothermic and effervescent. After the completion of reaction (mon-
itored by TLC), the reaction mixture was filtered through celite. The
organic layer is evaporated and the residue was dissolved in chloroform
or dichloromethane or ether was washed with saturated sodium chloride
solution to remove excess of hydrazinium monoformate. The organic
layer after drying and evaporation gave the desired amino derivative.
In order to get good yield of volatile aliphatic amine, the reaction
was carried out by controlled addition of hydrazinium monoformate,
through the top of ice water circulated condenser and by immersing
the reaction flask in a cold-water bath. After filtration, whole reaction
mixture was neutralized with HCl. The solvent was evaporated under
reduced pressure. The residue was lyophilized or subjected to column
chromatography. Aliphatic amines are obtained as their hydrochloride
salts up to 80% yield.

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287
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Received in the UK November 15, 2001

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