CHLORAMPHENICOL, Ⅱ. SYNTHESIS OF α-BROMO-p-NITROACETOPHENONE

Two methods for the preparation of α-bromo-p-nitroacetophenone (Ⅵ), a useful intermediate for the synthesis of chloramphenicol, are described. Styrene bromohydrin (Ⅱ) obtained by the addition of HOBr to styrene (Ⅰ) was nitrated to α-p-nitrophenyl-β-bromoethyl nitrate (Ⅲ). The nitrate (Ⅲ) was then hydrolized directly to p-nitrostyrene bromohydrin (Ⅴ), or preferably through its acetate (Ⅳ) by alcoholysis. The bromohydrin (Ⅴ) was oxidized with chromic acid in acetic acid to give α-bromo-p-nitroacetophenone (Ⅵ) in over-all yields of 37.2% and 40.8% respectively. α-Bromo-p-nitroacetophenone (Ⅵ) can also be obtained by nitration of β-bromoethyl benzene (Ⅶ) followed by oxidation of the resulting p-nitro compound (Ⅷ) in an over-all yield of 50.8%.