The Nitro Group in Organic Synthesis

172 CONVERSION OF NITRO COMPOUNDS INTO OTHER COMPOUNDS

compounds. Because the nitro group is a better electron acceptor than other functional groups, the reduction of nitro compounds with SmI2 proceeds selectively. Thus, p-nitrobenzonitrile is reduced to p-cyanoaniline selectively.88 Ultrasound-promoted, highly efficient reduction of aromatic nitro compounds to the aromatic amines has been achieved by samarium ammonium chloride mediated reaction.88c Intermolecular and intramolecular reductive coupling reactions between aromatic nitro compounds and nitriles are induced by SmI2 to give amidines and 2-aminoqunolines.89

6.3.2 R-NH2 From R-NO2

In general, the reduction of aliphatic nitro compounds gives amines, in which various reducing agents are as effective as they are in the reduction of aromatic nitro compounds.70 The reduction of β-nitro alcohols to the corresponding amino alcohols is the most important application of this process in organic synthesis. Hydrogenation catalyzed by Raney Ni under high pressure has been widely used for this conversion,90 and some recent examples are presented in Eq. 6.45,91 and Eq. 6.46.92 The stereochemistry of the nitro alcohol is retained by the Raney Ni-catalyzed hydrogenation.

NO2

The reduction of nitro sugars with H2 in the presence of Raney Ni is one of the standard methods for the preparation of amino sugars (Eq. 6.47).93

The hydrogenation in the presence of Pd/C is also effective for the conversion of nitro compounds to amines.94 The Michael addition of nitromethane to 2-alkenoic esters followed by catalytic hydrogenation using 10% Pd/C in acetic acid and hydrolysis is a convenient method for the preparation of 3-alkyl-4-aminobutanoic acids, which are important γ-amino acids for biological study (Eq. 6.48).94b The reduction can be carried out at room temperature and atmospheric pressure.

83%

6.3 REDUCTION OF NITRO COMPOUNDS INTO AMINES 173

Jager and co-workers have prepared various amino sugars by the reduction of the corresponding β-nitro alcohols with H2 and Pd/C, as exemplified in Eq. 6.49 (see Chapter 3).95

Hydrogen gas can be replaced by ammonium formate for the reduction of nitro compounds to amines. The ammonium formate method is efficient, and the rapid workup procedure by simple filtration makes it widely used for converting the NO2 to the NH2.96 For example, α-nitro esters are reduced to α-amino esters in excellent yields on treatment with HCO2NH4 and Pd/C in methanol.96

The reduction of γ-nitroketone acetals as in Eq. 6.50 with ammonium formate in the presence of Pd/C gives the corresponding amines in good yields. However, the reduction of γ-nitro ketones are reduced to cyclic nitrones (Eq. 6.51).97 This reduction is far superior to the classical method using Zn/NH4Cl due to improved yield and simple workup.

The reduction of β-nitro alcohols with ammonium formate in the presence of Pd/C also proceeds with retention of their configurations (Eq. 6.52).98

The reduction of β-nitro alcohols with LiAlH4 results in low yields of β-amino alcohols due to the occurrence of a retro-aldol reaction. This problem is resolved by protecting of OH of β-nitro alcohols, as shown in Eq. 6.53.99

A reagent of nickel boride/hydrazine hydrate reduces both aromatic and aliphatic nitro compounds. For example, it has been used for synthesis of 4-(benzyloxy)indole and –alkyltryp-

174 CONVERSION OF NITRO COMPOUNDS INTO OTHER COMPOUNDS

tamines, as shown in Eq. 6.54.100 This reducing agent has advantages over the method using H2 and Raney Ni because double bonds are inert to Ni2B/N2H4.

Sodium borohydride is activated in the presence of Pd/C,101 CoCl26H2O,102 Ni(OAc)2,103 CuSO4,104 and NiCl2.105 Aromatic and aliphatic nitro compounds are reduced to the corresponding amines, by these reagents as summarized in Table 6.1. The active hydrogenation catalyst is formed by the reaction of NaBH4 with metal catalysts in such reductions.106 Because reaction proceeds rapidly under mild conditions, the method using activated NaBH4 is very convenient for the reduction of a variety of nitro compounds as shown in Table 6.1.

Various other reducing methods are employed for the conversion of β-nitro alcohols to amino alcohols, namely, electrochemical reduction.107 The selective electrohydrogenation of nitroaliphatic and nitroaromatic groups in molecules containing other groups that are easy to hydrogenate (triple bond, nitrile, C-I) are carried out in methanol-water solutions at Devarda copper and Raney cobalt electrodes (Eq. 6.55).107

(6.55)

The sonochemical-promoted aluminum amalgam reduction of β-nitro alcohols provides an improved yield and accelerated conversion to the corresponding amino alcohols.108

The selective reduction of 4-nitrosteroid to the corresponding aminosteroid has been carried out by Pd/CaCO3 and quinoline (5 mol wt%) under H2 atmosphere (Eq. 6.56).109 This is the first reported catalytic reduction of an α-nitro enone to an α-amino enone. Other hydrogenation catalysts as well as the use of Na2S, Fe/AcOH, or Na2S2O4 fails to provide the aminosteroid. Reduction with SnCl2 in EtOH gives the aminosteroid in 46% yield.

A variety of Group VIII transition metal phosphine complexes are shown to be active catalysts for hydrogenation of aliphatic nitro compounds. However, chiral phosphines have been found to be noneffective to induce asymmetric induction.110

176 CONVERSION OF NITRO COMPOUNDS INTO OTHER COMPOUNDS

The conversion of nitroalkanes to ketoximes can be achieved by the reduction with Zn in acetic acid,112 or Fe in acetic acid.113 Nitroalkenes are directly reduced into saturated ketoximes by these reagents, which are precursors for ketones (see Section 6.1.4 Nef reaction). Reduction of 3-O-ace- tylated sugar 1-nitro-1-alkenes with Zn in acetic acid gives the corresponding 2,3-unsaturated sugar oximes in high yield, which is a versatile route to 2,3-unsaturated sugar derivatives (Eq. 6.58).114

As shown in Eq. 6.59, Rapoport has prepared sinefungin, nucleoside antibiotics, via nitro-aldol reaction, dehydration, and reduction with Zn in acetic acid.115a β-Nitrostyrenes are selectivity reduced to the corresponding oximes by indium metal in aqueous methanol under neutral conditions.115b