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Selective Reduction of Nitro Compounds
Using Formic Acid and Raney Nickel

Synth. Commun. 30(16), 2889-2895 (2000)

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Abstract

Aliphatic and aromatic nitro compounds were selectively reduced to their corresponding amino derivatives in good yields using formic acid and Raney nickel. This system is found to be compatible with several sensitive functionalities such as halogens, -OH, -OCH3, -CHO, -COCH3, -COC6H5, -COOH, -COOEt, -CONH2, -CN, -CH=CH-COOH, -NHCOCH3. The reduction can be carried out not only with HCOOH but also with HCOONH4.

Rapid and selective reduction of nitro compounds is of importance for the preparation of amino derivatives in organic synthesis, particularly when a molecule has other reducible substituents1-5. Numerous new reagents have been developed for the reduction of aromatic nitro compounds6-8, however, little attention has been paid to the reduction of aliphatic nitro compounds9-11, which are traditionally reduced by high pressure12,13. Most of these methods are unfortunately subject to substantial limitations as concerns the presence of reducible functional groups and lack therefore the desired generality for true synthetic utility. Moreover, poor selectivity was reported in the reduction of aromatic nitro compounds which have carbonyl and halogen substituents. Therefore, we have examined several methods to improve the reduction process, and especially to obtain the selectivity over carbonyl, halogens or other labile substituents. In this context, the use of ammonium formate and 5% platinum on carbon was found to be efficient but expensive14.

Now we wish to report a selective, rapid and mild method of reduction of aliphatic and aromatic nitro compounds to the corresponding amino derivatives using Raney nickel and formic acid at room temperature. This new system reduced with ease a wide variety of nitro compounds directly to the corresponding amines and many functional groups can be tolerated. When formic acid is replaced by ammonium formate the reduction proceeds effectively and the products were obtained in almost comparable yields.

The reduction of nitro group in presence of Raney nickel and HCOOH or HCOONH4 was complete within 10-30 min. The course of the reaction was monitored by TLC and IR. The workup and isolation of the products were easy. Thus all the compounds reduced (Table 1) by this system were obtained in good yield (80-90%) . All products were characterised by comparison of their TLC, IR and melting points with authentic samples. A control experiment carried out using nitro compounds with HCOOH or HCOONH4 without nickel does not yield the desired product.

Thus the reduction of nitro compound can be accomplished with nickel instead of expensive Pt, Pd etc., without affecting the reduction of any reducible substituents including halogen and carbonyl compounds. The yields were virtually quantitative and analytically pure. Further it has been found that ammonium formate was less effective donor than formic acid with raney nickel. The obvious advantages of the proposed method over the previous methods are: (I) selective reduction of nitro compounds in the presence of other reducible groups including carbonyl and halogens, (II) ready availability and easy to operate, (III) rapid reaction, (IV) high yields of substituted anilines, (V) avoidance of strong acidic media, (VI) required no pressure apparatus and (VII) less expensive. This procedure will therefore be of general use especially in cases where rapid, mild and selective reduction is required. Further investigations of other useful applications related to deblocking of protecting groups in peptide synthesis are in progress.

Experimental

A suspension of an appropriate nitro compounds (5 mmol) and Raney nickel (0.2-0.3g) in methanol or in any suitable solvent (3 mL) was stirred with 90% HCOOH (2.5 mL) or ammonium formate (0.5 g) at room temperature. After completion of the reaction (monitored by TLC), the mixture was filtered off. The organic layer was evaporated and the residue dissolve in CHCl3 or ether was washed with saturated NaCl to remove ammonium formate. The organic layer on evaporation gave the desired amino derivatives.

Table 1:
Nickel catalyzed reduction of nitro compounds

No.Nitro Compound
Reaction Time (minutes)
Product
Yielda
HCOOH
HCOONH4
01Nitromethane
5
10
Methylamine HCl
45%b
02Nitroethane
10
15
Ethylamine HCl
50%b
031-Nitropropane
10
15
n-Propylamine HCl
55%
041-Nitrobutane
8
10
n-Butylamine HCl
60%
052-Nitroethyl ethanoate
8
10
2-Aminoethyl ethanoate
65%
061-Nitromethyl butanoate
10
10
1-Aminomethyl butanoate
80%
07Nitrobenzene
20
30
Aniline
90%
08o,m,p-Nitrophenol
10-15
15-20
o,m,p-Aminophenol
85-90%
092,4-Dinitrophenol
15
20
2,4-Diaminophenol
90%
10o,m,p-Nitrotoluene
15-20
20-25
o,m,p-Aminotoluene
89-91%
111,4-Dinitrobenzene
10
15
2,4-Diaminotoluene
90%
12o,m-Dinitrobenzene
10-15
15-20
o,m-Phenylenediamine
86-90%
131,2-Nitronaphthalene
5-10
10-15
1,2-Naphthylamine
88-90%
14o,p-Nitroanisole
8-10
5-10
o,p-Aminoanisole
89-90%
15o,m,p-Nitroaniline
5-10
5-10
o,m,p-Phenylenediamine
91-92%
16o,p-Nitrobenzaldehyde
10-15
10-20
o,p-Aminobenzaldehyde
89-90%
17o,p-Nitroacetophenone
10-15
10-20
o,p-Aminoacetophenone
90-92%
18p-Nitrobenzophenone
20
25
p-Aminobenzophenone
90%
19p-Nitrobenzamide
20
20
p-Aminobenzamide
90%
20p-Nitrophenylacetate
10
15
p-Aminophenylacetate
91%
21o,m,p-Nitrobenzoic acid
15-20
20-25
o,m,p-Aminobenzoic acid
90-92%
22o,m,p-Nitrochlorobenzene
15-20
20-25
o,m,p-Chloroaniline
90-92%
23o,m,p-Nitrobromobenzene
15-20
20-25
o,m,p-Bromoaniline
91-92%
24m-Nitroiodobenzene
10
10
m-Iodoaniline
89%
25p-Nitrocinnamic acid
10
15
p-Aminocinnamic acid
90%
26p-Nitrobenzonitrile
20
25
p-Aminobenzonitrile
92%
27p-Nitrophenylacetonitrile
20
25
p-Aminophenylacetonitrile
91%
28p-Nitrophenethylalcohol
20
25
p-Aminophenethylalcohol
90%
293,5-Dinitrosalicylic acid
15
20
3,5-Diaminosalicylic acid
89%
30p-Nitroacetanilide
10
15
p-Aminoacetanilide
90%

Notes:
a Isolated yields are based on the single experiment and yields were not optimized;
b The tow yields of aliphatic amines are due to low boiling points and their volatile nature.

References

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