Rapid and Selective Reduction of Ali- Phatic and Aromatic Nitro Compounds

Indian Journal of Chemistry Vol. 408, January 2001 , pp. 75-77

Note

l 6 Zinc-catalyzed ammonium formate reduc­ efficient but expensive . tions : Rapid and selective reduction of ali­ Recently metal mediated reactions have been found phatic and aromatic nitro compounds to have wide scope in organic synthesis because of their simple work-up and selectivity. Several methods o Channe Gowda*, B Mahesh & Shankare Gowda have been developed based on the use of a variety of . 17· d' 18· 19 d . 20 Department of studies in Chemi stry, University of Mysore. meta Is suc h as magnesium 111 lum , tll1 an Zll1C . Manasagangotri , Mysore-570006, India The utility of zinc for the synthesis of ~ , y-unsaturated Received 7 December 1999; accepted (revised) 23 ketones by a reaction of an acid chloride with ally 1 Jlllle 2000 bromide21 and homoallylic alcohols22 has been demonstrated. Further, the zinc-mediated preparation Aliphatic and aromatic nitro compounds are selectively and of triphenylphosphonium ylides23 , amide bond rapidly reduced to their corresponding amino derivatives in good formation24, Friedel-Crafts acylation,24 carbamate yields using ammonium formate and commercial zinc dust. This 24 24 system is found to be compatible with several sensitive formation and esterification of acid chlorides has , functi onalities such as halogens, -OH, -OCH3 -CHO. -COCH), - been demonstrated recently. In thi s communication we COC6Hs, -COOH. -COOC2Hs, -CONH2' -CN, -CH=CH-COOH. wish to report a selective, rapid and simple reduction of -NHCOCH, . The reduction can be carried out not only with aliphatic and aromatic nitro compounds to the HCOONH but al so with HCOOH. 4 cOiTesponding amino derivatives using commercial Rapid and selective reduction of nitro compounds is zinc dust and ammonium formate at room temperature. of importance for the preparation of amino This new system reduced with ease a wide variety of derivatives in organic synthesis, particularly when a nitro compounds directly to the cOITesponding amines l 5 and many functional groups can be tolerated. When molecule has other reducible substituents . . Numerous new reagents have been developed for the ammonium formate is replaced by formic acid the 6 8 reduction proceeds effectively and the products were reduction of aromatic nitro compounds - , however little attention has been paid to the reduction of obtained in almost comparable yields. aliphatic nitro compounds9.12, which are traditionally The reduction of nitro group in presence of reduced by high pressure catalytic hydrogenation I3.15. activated zinc (pretreated with HCI and thoroughly Most of these methods are unfortunately subject to washed with water and ether prior to use) and substantial limitations as concerns the presence of HCOONH4 or HCOOH was complete within 2 - 10 reducible functional groups and lack therefore the min. The course of the reaction was monitored by desired generality for true synthetic utility. TLC and IR . The work-up and isolation of the Moreover, poor selectivity was reported in the products were easy. Thus all the compounds reduction of aromatic nitro compounds which have reduced (Table I) by this system were obtained in carbony 1 and halogen substituents. Therefore, we good yield (90-95%). All products were have examined several methods to improve the characterized by comparison of their TLC, IR and reduction process, and especially to obtain the melting points with authentic sampl es. A control selectivity over carbony I, halogens or other labile experiment carried out using nitro compounds with substituents. In this context, the use of ammonium HCOONH4 or HCOOH without zinc dust, does not formate / 5 % platinum on carbon was found to be yield the desired product.

N~ HCOONH 1Zn. MeOH or 4 A HCOONH41Zn. MeOH or ~ HCOOHlZn. MeOH; r.t ~ and R-~ HCOOHlZn, MeOH; r.t ~ R-N~ X

x = halogen, -OH, -OCH), -CHO. -COCH,. ·COC6HS' -COOH, -COOC2Hs• -CONH2• -CN, -CH=CH-COOH, -NHCOCH;J, and R=alkyl group. 76 INDIAN J CHEM. SEC B. JANUARY 2001

Table I-Zinc catalyzed red uct ion of nitro compounds Nitro compound Reacti on time in min Product Yield"

HCOON H4 HCOOH (%) N i trometh ane 2 2 AlllinomethaneC 45 b Nitroethane 5 7 AminoethancC SOb I-Nitropropane 5 7 I-Ami nopropanec 55 I-N it robutane 2 4 I-AminobutaneC 60 I-Nitroethy lethanoate 5 5 1- Alllinoethyl ethanoate 65 4- Nitromethylbutanoatc 5 7 4-A mino Illeth ylbutanoate 80 Nitrobenzene 8 10 Anilined 90 o. IIl,p-Nitrophenol 3-5 3-5 o, lIl,p-Aminophenol , 2-93 2,4-Di nit rophenol 2 5 2,4- Di ffi lllinophenol 92 d O, IIl,p- itrotolucnc 3-5 3-5 O,IIl,p-Alllinotoluene ~ 9-9 1 2,4-Dinitrotoluene 5 5 2,4-Diaminotoluene 90 o,IIl-Dinitrobenze ne 4-6 4-6 o,lIl-Ph enylenediamin e 90-91 a /3-Nitronaphthalene 3-5 3-5 a,B-Naphthylamine 92-93 o,p-Nitroanisole 2-3 3-5 o,p-Allli noani sole 89-92 o,IIl,p-Nitroa niline 2-4 2-4 o.IIl,p-Phenylenediamine 91-95 o,p-Nitrobenza ldehyd e 8- 10 10- 15 o,p-Alll inobenzaldehyde 89-90 o.p-Nitroacetophenone 8- 10 10-15 o, p-A minoacetophenone \12-93 p-N i trobenzophenone 10 10 p -Ami nobenzophenone 92 p-Nitrobenzamide 8 10 p-Aminobenzamide 90 p-N i tropheny lacetate 5 5 p-AminophenylacetateC 9 1 o, lIl .p-N it robenzonic acid 3-5 5-6 o,IIl,p-Aminobenzoic acid 93-94 O. IIl.p-Ni troc hlorobenze nc 5-6 5-6 o,lIl,p-Chloroani line 94-95 o,IIl,p-Nitrobromobenzene 5-6 5-6 o,lIl,p-IBro moani line l) 1-92 IIl -N itroiodobenze ne 5 5 1Il-lodoaniline 89 p-Nitrocinnamic acid 5 7 p-Aminocinnamic ac id 90 p-Nitrobenzonitrile 10 IS p-Aminobenzonitrile 93 p-Nitrophenylacetonitrile 10 IS p-A mi nopheny lacetonitri Ie 93 p-Nitrophenethylalcohol IS 20 p-Aminophenethylalcohol 90 3,5-Dinitrosalicylic acid 6 6 3,5-Diaminosalicylic ac id 89 p-N itroacetanilide 5 5 p-A minoacetanilide 90 (a) Isolated yields are based on the single experiment and yields were not optimized; (b) The low yields of ali­ phatic amines are due to low boiling points and their volatile nat ure; (c) Isolated as hydrochloride salts; (d) Isolated as benzoyl deri vati ves; (e) Isolated as acetyl derivative.

Typical procedure. A suspension of an carbonyl compounds. The yields were virtually appropriate nitro compound (5 mmole) and Zn dust (6 quantitative and analytically pure. The obvious mmole) in methanol or in any suitable solvent (5 mL) advantages of the proposed method over the previous was stirred with ammonium formate (0.5 g) or 90% methods are: (i) selective reduction of nitro HCOOH (2_5 mL) at room temperature. After compounds in the presence of other reducible groups completion of the reaction (monitored by TLC), the including carbonyl and halogens, (ii) ready mixture was filtered off. The organic layer was availability and easy to operate, (iii) rapid reaction, evaporated and th e residue dissolved in CHCl) or (iv) high yields of substituted anilines, (v) avoidance ether was washed with saturated NaCI to remove of strong acidic media, (vi) no requirement of ammonium formate_ The organic layer on evaporation pressure apparatus and (vii) less expensive_ This gave the desired amino derivatives_ procedure will therefore be of general use especially Thus the reduction of nitro compounds can be in cases where rapid, mild and selective reduction is accomplished with commercial zinc dust instead of required. Further investi gations of other useful expensive Pt, Pd etc_ , without effecting the reduction applications related to deblocking of protecting of any reducible substituents including halogen and groups in peptide synthesis are in progress. NOTES 77

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