Book Review, Comprehensive Organic Functional Group Transformations

Abstract

Although a large number of methods for the reduction of aromatic nitro compounds have been developed, 1 many of these are incompatible with other functional groups in the molecule. For example, the selective reduction of nitro groups in the presence of carbonyl groups, nitriles, halides and alkenes is often difficult, and in such cases catalytic hydrogenation, which is often the method of choice for nitro reduction, is inappropriate. Thus, hydrogenation of 4-chloro-3-nitroace-tophenone over Pd/C results in hydrogenolysis of the halide, and reduction of the ketone as well as nitro groups. 2 Consequently new methods for the selective reduction of nitro groups continue to be developed. 3 We now report a mild new method for the reduction of aromatic and heteroaromatic nitro groups using tellurium metal powder (Scheme 1). Te, NH 4 Cl Ar-NO 2 (I) → Ar-NH 2 (II) aq. MeOH Scheme 1 Development of new synthetic reactions utilizing characteristics of tellurium and its compounds has recently attracted much attention. 4 As part of a wider study on the use of tellurium metal and its compounds in organic synthesis, 5 we found that the reduction of aromatic nitro compounds proceeded readily on heating the substrate with the tellurium powder in aqueous methanolic ammonium chloride. The reactions are extremely easy to carry out, are typically complete within 2-5 h, and give the corresponding aniline in good to excellent yield (Table 1). The reaction conditions are compatible with halogen substituents (Cl, Br, I; entries 1-3), carbonyl groups (acid, ester, amide; entries 4, 6, 7) and nitrile (entry 5), and the reduction is not affected by the presence of sulfur containing substituent (entry 8). In 6-nitroquinoline and 5-nitroisoquinoline, the group is reduced before the hetero-cyclic ring (entries 10, 11). In a typical procedure, to a solution of the nitro compounds (5 mmol) in methanol (50 ml) was added saturated ammonium chloride solution (5 ml, 75 mmol) tellurium powder (3.0 g, 23 mmol). The mixture was stirred under reflux. When the reaction appeared complete as monitored by TLC (typically 2-5 h), the cooled reaction mixture was diluted with water (100 ml) and filtered through Celite. The aqueous filtrate was adjusted to pH~9 with NaOH (4M) and extracted with dichloromethane/ethyl acetate (3 × 50 ml). The combined organic layers were dried (Na 2 SO 4). Removal of solvent and chromatography on silica gel gave the anticipated products. In conclusion, the use of tellurium metal powder for the selective reduction of aromatic nitro compounds is simple, occurs under mild conditions and in high yield. Therefore, this should prove a valuable addition to synthetic methodology. Treatment of a wide range of aromatic nitro compounds with tellurium powder in aqueous methanolic ammonium chloride results in selective reduction of the nitro groups; ester, nitrile, amide and halide substituents are unaffected.