Friedel–Crafts cyclisations. Part III. Synthesis of derivatives of 2(1H)-quinolone (carbostyril) by aluminium chloride-catalysed cycloeliminations of cinnamanilide and related compounds

Abstract

For the conversion of cinnamanilide into 2(1H)-quinolone (carbostyril) the use of 3 mol. equiv. of the catalyst, aluminium chloride, is desirable; the low yield of 2(1 H)-quinolone obtained from 4-phenyl-3.4-dihydro-2(1H)-quinolone however, indicated that loss of the β-aryl group from cinnamanilide probably occurs virtually simultaneously with the cyclisation. Cyclisation was prevented by either a p-nitro- or a p-methoxy-group in the N-aryl nucleus, and also by an α-chloro-substituent in the cinnamoyl moiety. p-Chlorocinnamanilide was cyclised, however, to 4-phenyl-2(1H)-quinolone with loss of hydrogen chloride. The scope of the cycloelimination was indicated by the formation of 5,6,8-trichloro-2(1H)-quinolone from 2′,4′,5′-trichlorocinnamanilide. Although migration of a methyl group did not accompany the cyclisation of o′-methylcinnamanilide, cyclisation of 2′,6′-dimethylcin-namanilide was permitted by shift of an ortho-methyl group to the adjacent meta-position.