Application of hydrazinium monoformate as new hydrogen donor

with Raney nickel: a facile reduction of nitro and nitrile moieties

Shankare Gowda and D. Channe Gowda
p
Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore, Karnataka 570 006, India
Received 26 September 2001; revised 18 December 2001; accepted 17 January 2002
AbstractThe nitro groups in aliphatic and aromatic nitrocompounds also containing reducible substituents such as ethene, acid, phenol,
halogen, ester etc., are rapidly reduced at room temperature to corresponding amines by employing hydrazinium monoformate, a new
hydrogen donor, in the presence of Raney nickel. It was observed that the nitrile function also undergoes reduction to methylamine (CH
2

NH
2
). Hydrazinium monoformate is a more effective donor than hydrazine or formic acid and reduction of nitro and nitrile groups occurs
without hydrogenolysis in the presence of low cost Raney nickel, compared to expensive metals like palladium, platinum or ruthenium. The
reduction is reasonably fast, clean and high yielding. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
Rapid and selective reduction of nitrocompounds is of
importance for the preparation of amino derivatives in
organic synthesis, both practically and industrially, particu-
larly when a molecule has other reducible moieties.
14
Numerous new reagents have been developed for the
reduction of aromatic nitrocompounds.
512
However, little
attention has been given to the reduction of aliphatic nitro-
compounds,
1315
which are traditionally reduced by high-
pressure catalytic hydrogenation.
10,16,17
Most of the
methods, viz., metal/acid reduction,
18
catalytic hydrogena-
tion,
19
electrolytic reduction,
20
homogeneous catalytic
transfer hydrogenation,
21
heterogeneous catalytic transfer
hydrogenation,
22
etc., are in practice. However, these
methods have one or more limitations: (i) metal/acid system
lacks selectivity and requires strong acid medium. (ii)
Catalytic hydrogenation employs highly diffusible, low
molecular weight, ammable hydrogen gas and requires
pressure equipment. (iii) Electrolytic reduction requires
acidic or alkaline catholite, yields are low and lack practical
utility in academic institutions. (iv) Homogeneous catalytic
transfer hydrogenation requires expensive complexes as
catalysts; work up and isolation of the products are not
easy. (v) Heterogeneous catalytic transfer hydrogenation
employs expensive bulk or supported metals like palladium,
platinum, ruthenium etc., and these supported catalysts
require stringent precautions, because of their ammable
nature in the presence of air.
Raney nickel is routinely used as a catalyst in the eld of
catalytic hydrogenation
19,23
as well as in the eld of hetero-
geneous catalytic transfer hydrogenation.
2,12,2429
It is used
for the selective reduction of nitrocompounds, dinitro
substituted diphenylsulfones, O- and N- benzyl containing
nitrocompounds, for the conversion of nitro olens into car-
bonyl derivatives,
30
and for the synthesis of halo amines
from halo nitrocompounds. In all these cases, the commonly
used hydrogen donors are hydrazine hydrate, ammonium
formate, formic acid and cyclohexene. Further, the use of
hydrazine derivatives like methyl hydrazine,
31
unsymmetri-
cal dimethyl hydrazine,
31
phenyl hydrazine,
32
and triethyl-
ammonium formate in the presence of various metals are
also in practice, but not hydrazinium monoformate.
In this communication, we wish to report a rapid and simple
reduction of aliphatic and aromatic nitrocompounds, and
nitriles to the corresponding amino derivatives by using
Raney nickel and hydrazinium monoformate, a new
hydrogen donor, at room temperature (Scheme 1). This
new system reduced with ease a wide variety of nitro and
nitrile compounds directly to the corresponding amines
and many functional groups are tolerated. Hydrazinium
monoformate is soluble in solvents like methanol, ethanol,
Tetrahedron 58 (2002) 22112213 Pergamon
TETRAHEDRON
00404020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)00093-5
Scheme 1. Ralkyl or aryl residue substituted with OH, OR, CO
2
H,
CO
2
R, CONH
2
, NHCOCH
3
, etc.
Keywords: hydrazinium monoformate; Raney nickel; catalytic transfer
hydrogenation; nitrocompounds; nitriles; reduction; new hydrogen donor.
p
Corresponding author. Tel.: 191-0821-515525, ext. 48; 191-0821-
344348; fax: 191-0821-421263; 191-0821-518835;
e-mail: dcgowda@yahoo.com
S. Gowda, D. C. Gowda / Tetrahedron 58 (2002) 22112213 2212
tetrahydrofuran, dimethylformamide and glycols. But with
solvents like dichloromethane, chloroform, benzene, etc., it
forms a biphasic system and in this system, the reactions are
rather slow. This system cannot be employed with ketonic
and nitrile solvents, as it forms hydrazones with former and
reduces the latter.
Our main intention was to reduce nitrocompounds
selectively to the corresponding amines. But surprisingly,
we observed that this system reduced nitriles to methyl-
amines, unlike the reduction of a nitrile group to methyl
group, using 10% PdC/HCOONH
4
.
33,34
In the case of
nitro nitriles, the two moieties are reduced to an amino
group and a methylamine group, respectively. This system
is not helpful to directly obtain an amino carbonyl
compound, due to the formation of a hydrazone derivative
with the donor. However, the nitro hydrazones are reduced
to the corresponding amino hydrazines by this system.
Further, hydrazinium monoformate/Raney nickel system is
more effective than either triethylammonium formate/5%
PdC
35
or cyclohexene/10% PdC
36
or hydrazine hydrate/
Fe(III)
37
and equally compatible with the systems like
HCOONH
4
/10% PdC,
1
HCOONH
4
/5% PtC
11
and
HCOONH
4
/Raney Ni.
12
Though ammonium formate is
extensively used in the eld of catalytic transfer hydrogena-
tion, it is sparingly soluble in solvents such as methanol; but
hydrazinium monoformate is freely soluble in `methanol-
like' solvents. Therefore, this system may nd its own appli-
cation in the eld of catalytic transfer hydrogenation.
The reduction of nitro aromatic compounds in the presence
of Raney nickel and hydrazinium monoformate was
complete within 210 min. The course of reaction was
monitored by thin layer chromatography (t.l.c.) 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 (9095%). All the
products were characterized by comparison of their t.l.c.,
IR spectra and melting points with authentic samples. A
control experiment was carried out using nitrocompounds
with hydrazinium monoformate but without Raney nickel,
does not yield the desired product. The t.l.c. and IR spectra
could not detect any intermediates such as nitroso or
hydroxylamine in the reaction mixture after the completion
of reaction. Since the reaction is so fast (2 min), the detec-
tion of intermediates is not possible. In order to test the
selectivity, the reduction was attempted with p-dichloro-
benzene, p-chloro-m-cresol, b-naphthol, cinnamic acid,
acetanilide, benzoic acid, anisole, phenyl acetate, etc., at
laboratory temperature. However, the reaction failed to
give any reduced product. Further, it was observed that
hydrazinium monoformate is a more effective donor than
either hydrazine or formic acid in the presence of Raney
nickel. The reduction was completed within 26 min with
the present system. The methods reported earlier for the
reduction of nitro arenes to amino arenes by using Raney
nickel and hydrazine requires longer reaction time as long as
210 h at reux temperature
24,26,28,29
and Raney nickel/
formic acid system needs 2030 min for the completion
of reduction.
12
Furthermore, both the systems are unable
to reduce nitrile function. Thus, the reduction of nitro-
compounds and nitriles can be accomplished with Raney
nickel instead of expensive platinum, palladium etc.,
without effecting the reduction of any reducible or
Table 1. Reduction of nitrocompounds and nitriles using hydrazinium monoformate/nickel
Nitro or nitrile compounds. Reaction time (in min) Product Yield
a
(%) Melting point (8C)
Found Lit.
m-Nitrophenol 2 m-Aminophenol 94 121123 123
38
o-Nitrotoluene 3 o-Toluidine
b
93 142144 144
38
p-Nitrotoluene 2 p-Toluidine 94 4445 45
38
a-Nitronaphthalene 2 a-Naphthylamine 92 5051 50
38
p-Nitroanisole 2 p-Anisidine 95 5657 57
38
m-Nitroaniline 3 m-Phenylenediamine 94 6465 64
38
m-Nitrobenzyl alcohol 3 m-Aminobenzyl alcohol 91 9698 97
38
p-Nitrobenzamide 3 p-Aminobenzamide 92 115116 114
38
p-Nitrophenyl acetate 3 p-Aminophenylacetate
c
93 148151 150
38
m-Nitrobenzoic acid 3 m-Aminobenzoic acid 94 174176 174
38
m-Nitrochloro benzene 3 m-Chloroaniline
b
92 120123 122
38
m-Nitrobromo benzene 3 m-Bromoaniline
b
94 118121 120
38
p-Nitrocinnamic acid 3 p-Aminocinnamic acid
d
90 265268 265-270
39
p-Nitroacetanilide 3 p-Aminoacetanilide 93 163165 163
38
Nitromethane 2 Methylamine
d
80 230233 232234
39
Nitroethane 2 Ethylamine
d
81 106108 107108
39
1-Nitropropane 2 1-Aminopropane
d
84 158160 160162
39
1-Nitrobutane 3 1-Aminobutane 75 7880
e
78
38
Acetonitrile 3 Ethylamine
d
75 106108 105106
39
Propiononitrile 3 n-Propylamine
d
76 158160 159160
39
Benzonitrile 5 Benzylamine
b
80 105108 105
38
Phenylacetonitrile 5 2-Phenylethylamine
b
80 115118 116
38
p-Chlorobenzonitrile 6 p-Chlorobenzylamine 70 8890 90
38
m-Methoxybenzonitrile 6 m-Methoxybenzylamine 72 110112 110
38
a
Isolated yields are based on single a experiment and the yields were not optimised.
b
Isolated as benzoyl derivative.
c
Isolated as acetyl derivative.
d
Isolated as hydrochloride salt.
e
Boiling point at 710 mm.
S. Gowda, D. C. Gowda / Tetrahedron 58 (2002) 22112213 2213
hydrogenolysable substituents except the nitrile group. The
yields are virtually quantitative and the compounds obtained
are analytically pure. The obvious advantages of the
proposed method over previous methods are: (i) selective
reduction of nitro and nitrile compounds, in the presence of
other reducible or hydrogenolysable groups, (ii) easy to
operate, (iii) rapid reduction, (iv) high yields of substituted
amines, (v) avoidance of strong acid media, (vi) no require-
ment for pressure apparatus and (vii) inexpensive. This
procedure will therefore be of general use, especially in
the cases where rapid, mild and selective reduction is
required. Further investigations of other useful applications
related to the deblocking of protecting groups in peptide
synthesis are in progress.
2. Experimental
Hydrazinium monoformate was prepared by slowly
neutralizing equal moles of hydrazine hydrate and 85%
formic acid in an ice water bath, with constant stirring.
The hydrazinium monoformate solution thus obtained was
used as such for reduction. A suspension of an appropriate
nitrocompound or nitrile (5 mmol) and Raney nickel
(100 mg) 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 (monitored by t.l.c.), the reaction mixture was
ltered through celite. The organic layer was evaporated
and the residue was dissolved in chloroform or dichloro-
methane or ether was washed with saturated sodium
chloride solution to remove excess of hydrazinium mono-
formate. The organic layer after drying and evaporation
gave the desired amino derivative.
In order to get a good yield of volatile aliphatic amines, the
reaction was carried out by controlled addition of hydra-
zinium monoformate, through the top of a condenser
circulated with ice water and by immersing the reaction
ask in a cold-water bath. After ltration, the whole reaction
mixture was neutralized with HCl. The solvent was evapo-
rated under reduced pressure. The residue was lyophilized
or subjected to column chromatography. Aliphatic amines
were obtained as their hydrochloride salts up to 80% yield.
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