Reductive monoalkylation of nitro aryls in one-pot

The scope of the serendipitous reductive monoalkylation of ethyl (4-methoxy-3-nitrophenyl) acetate taking place during reduction of the nitro functionality to the corresponding primary amine when treated with hydrogen (1 atm) over Pd/C (10%) in ethanol is investigated. Upon prolonged reaction time the reaction conducted in ethanol and methanol yields significant amount of the corresponding secondary amines, while when performed in n-butanol and i-propanol it only resulted in the formation of a small amount of the corresponding secondary amines. Further development of the reductive monoalkylation reaction provided conditions that facilitate conversion of a range of different nitro aryls in one-pot to the corresponding secondary benzyl amino aryls in mostly good to excellent yields. This is accomplished by using hydrogen (1 atm) over Pd/C (10%) as reducing agent and benzaldehyde as the benzyl source combined with a stepwise reaction sequence. This chemistry was further extended to the formation of substituted benzyl amino aryls. The yields of the latter products varied dramatically depending on the substitution patterns associated with the benzaldehyde. However, by altering the reaction conditions it was possible to improve the yields of the benzylated products.