Document 6432160

Tetrahedron
Letters,Vol.25,No.32,pp
Printed in Great Britain
3415-3418,1984
0040-4039/84
$3.00 + .OO
01984 Pergamon Press Ltd.
A GENERAL PROCEDURE FOR MILD AND RAPID REDUCTION OF ALIPHATIC AND AROMATIC NITRO COMPOUNDS
USING AMMONIUM FORMATE AS A CATALYTIC HYDROGEN TRANSFER AGENT
Siya Ram and Richard E. Ehrenkaufer"
Cyclotron/PET Facility, Division of Nuclear Medicine
The University of Michigan Medical School, Ann Arbor, Michigan 48109
ABSTRACT
Various aliphatic and aromatic nitro compounds were selectively and rapidly reduced to
their corresponding amino derivatives in very good yield using anhydrous ammonium formate as
a catalytic hydrogen transfer agent.
Selective and rapid reductLon of nitro compounds is still area of considerable synthetic
interestl, particularly when a molecule has several other reducible moieties. Numerous new reagents*-l4 have been developed for reduction of aromatic nitro compounds, however little attention has been paid to the reduction of aliphatic nitro compound&ry,S, which are traditionally
reduced by high pressure catalytic hydrogenation15,16* In the past 30 years catalytic transfer
hydrogenation 17-** has demonstrated great potential value in organic and biological chemistry.
Cyclohexene/Pd-Chas been most widely studied. Recently, ammonium formate has been successfully
employed as a catalytic hydrogen transfer agent in peptide chemistry for deprotection23-24instead of cyclohexene. Reduction of axides
and cyano groups26 to the corresponding amines and
methyl group has also been reported in the recent literature.
In our ongoing program, we were interested in the radioisotopicsynthesis of llC-amino acids
(llC-half life = 20.4 min) via nitro acid intermediates. We have thus examined several classes
of chemical reducing agents for e.g. FeS04/NHAOH, Cyclohexene/Pd-C, NH%-NH%/Ra-Ni, Zn/AcOH,
etc., however these systems failed to yield the amino acid. In this paper we wish to report a
mild, simple, rapid and selective reduction of aliphatic and aromatic nitro compounds to the
corresponding amino derivatives using ammonium formate (Scheme-I).
SCHEME I
HCO%NH4
R - NO2 A
R - NH%
10% Pd-C, CH30H
I
R.T.
II
R = alkyl or aryl
A typical experimental procedure for conversion of I to II is as follows.
3415
(1)
3416
TABLE
I.
Reduction
--
of alphatic
and
-No.
Nitro Compound
__-
aromatic
--__
nitro
compounds
to
corresponding
~----___-
amines.
I___-----
Reaction time
in min.
Productb
--_
Yielda
%
__II_________
1
CH3CH2CH2N02
< 30
CH3CH2CH2NH2.HC1
31=
2
CH3CH2CH2CH2N02
< 20
CH3CH2CH2CH2NH2.HCl
49c
3
(CH3)2CHCH2CH2N02
< 40
(CH3)2CHCH2CH2NH2.HCl
a2
4
C2H502CCH2N02
20
C2H502CCH2NH2.HCl
64
5
HOOC(CH2)2N02
20
-OOC(CH2)2NH3+
98
6
CB302C(CH2)3NC2
20
CH302C(CH2)3NU2
al
7
CH302CCH2CH2CH(CH3)N02
15
CH302CCH2CH2CH(CH3)NH2
75
and
5-methyl-2-pyrrolidinone
a
p-02NC6H4C02B
5-10
p-H2NC6H4C02H
52d
9
4-H3COC6H3(3-N02)C02H
5-10
4-H3COC6H3(3-NH2)C02H
75d
10
P-O~NC~H~CH~CO~H
5-10
P-H~NC~H~CH~CO~H
86
11
~-02NC6H4C02CH3
5-10
p-H2NC6H4C02CH3
a9
12
C6B5NO2
3-5
C6H5NH2
76
13
0-FC6H4N02
3-5
o-FC6H4NH2
70
14
p-H3COC6H4NO2
3-5
p-H3COC6H4NH2
93
15
4-H3CC6H3(2-N02)NH2
3-5
3,4-(NB2)2C6B4CB3
16
p-02NC6H4CH2CrN
120
p-H2NC6H4CH2CsN
a5
17
2-B,NC6H3(5-NO,)COC6H5
15
2,5-(NH2)2C6H3COC6H5
91
ia
m-O2NC6H4CH2NHC(=NH)NH2
25
wH~NC~H~CH~NHC(=NH)NH~
70
19
2-I-C6H3(4-N02)CONH2
60
p-H2NC6H4CONH2
31e
20
2-H3C-5-N02-imidazole
---
Partial
reduction,
__---__-__
(a) Isolated
yields
(b) Products
were
with rapid product
decomposition.
-_--------~--------~
are based on the single experiment
characterized
79
by
comparison
with
and yields were not optimized;
authentic
samples
(IR,
lH-NMR,
TLC
and
m-p.);
(c) The
low yields
n-butylamine
(d) These
were
of aliphatic
obtained
of p-aminobenzoic
reaction
ing product
by trituration
acid
quired for such water
(e) No
amines
are due
b.p. 78") and their volatile
with
small amount
is due to its partial
soluble
to low boiling
of water,
solubility
(n-propylamine
b-p. 48",
the low yield
in water.
Modified
in the case
workup
is re-
products;
takes place using Pd-C as the catalyst.
is the deiodinated
points
nature;
amine,
When Raney-Nickel
p-aminobenzamide.
is used the result-
3417
To a stirred suspension
in dry methanol
The resulting
temperature
reaction
layer
converted
argon,
on evaporation
into the HCl-salt
the catalyst
gave
The
residue
solvent
In
benzene
cases
of iodinated
no reaction
was
the desired
aromatic
that iodinated
compounds
m-Nitrobenzylguanidine
benzylguanidine
CH30H system
corresponding
18,
yield.
amino
derivative.
evaporation
These
however
of nitro-compounds
of other
nontoxic
the advantages
and can be used in conjunction
it may be added to the reaction
amines
speciFically
products
were
The
directly
In most cases the reaction
is
time was 120
-19 and 1-iodo-3-nitrowith 2,
p-aminobenzamide.
reduction
of
These observations
in cases where
gKOUpS
functional
of being
readily
with either Pd-C
yielding
reducing
reduced
to
5-methyl-2-pyrolidi-
inexpensive,
or Raney-Nickel
catalysts.
can be easily
be of general
rapid mild reduction
system for wide variety
for e.g. -C f N, > C = 0, etc.
available,
and products
will therefore
successfully
data.
and selective
in a single portion
procedure
7_ was
also occurred
spectroscopic
a rapid versatile
in the presence
This
yielding
or
the Pd-C catalyst.
partial cyclization
formate
mixture.
Some
as catalyst
methyl-4-nitropentanoate
Ammonium
the reaction
reduced
(10 mL - 25 mL), product
2-iodo-4-nitrobenzamide
using Raney-Nickel
by IR and IH-NMR
also has
room
through a celite
either under
cyanide 16, the reaction completion
Occurred,
Although
results demonstrate
at
of ether layer.
is shown in Table I.
may deactivate
amino acid ester,
none, which was confirmed
portion.
stirred
which was unable to be reduced to the corresponding
m-aminoof conditions 27 , was successEully reduced by 10% Pd-C/HC02NH4 -
in the variety
in 70%
with water
without
systems,
the nitro group as well as deiodination
suggest
in a single
was
by filtration
was evaporated
was triturated
procedure
observed,
(23 mmol)
effervescent)
was removed
filtrate
over within 3-40 min, however for p-nitrobenzyl
min.
and
(i.e. ether, CH2C12 OK CHC13) and dried over Na2S04.
with ethereal-HCl
The scope of this new general
(5 mmol) and 10% Pd-C (0.2 - 0.3 g)
for-mate was added
exothermic
(10 mL).
The resulting
with an organic
nitro compound
ammonium
(slightLy
with dry methanol
pressure.
was extracted
organic
mixture
for 3-40 min under
pad and washed
at normal
of an appropriate
(10 ti), anhydrous
stable
and
MOreoveK,
separated
from
use fOK the preparation
of
is required.
ACKNOWLEDGMENTS
Research
was
supported
by
NC1
Training
Graut
#5-T32-CA09015-08
and
by
NINCDS
grant
#PO1 NS15655-04.
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