APPLICATION OF ORGANOLITHIUM AND RELATED REAGENTS IN SYNTHESIS .10. METALATION-ELECTROPHILIC SUBSTITUTION SEQUENCE OF SECONDARY CHLOROBENZAMIDES

The lithiation (Bu(n)Li/THF) of 2-chloro- (1), 3-chloro- (2) and 4-chlorobenzanilides (3) and the subsequent reactions of the corresponding bis-lithiated anilides 4 - 6 with electrophiles (MeI, CH2 = CH - CH2Br, Me3SiCl, MeCHO, o-MeOC6H4CHO, p-MeOC6H4CHO, Me2NCHO and p-MeOC6H4CONMe2) towards the synthesis of the ortho substituted chlorobenzoesic acids derivatives 12 - 14 have been described. The effect of the chlorine substituent upon the generation and stability of the bis-lithiated chloro-anilides 4 - 6 has been studied. It has been found that the bis-lithiated chloro-anilide 5 derived from m-chloro-benzanilide (2) at a temperature above - 30-degrees-C converts into the corresponding benzyne 9. The anilide moiety (masking group) of the formed ortho-substituted chlorobenzanilides appeared to be effectively removable on acid-driven hydrolysis.