POLYMORPHISM OF BUTYROPHENONES RELATED TO HALOPERIDOL

A comparison of X-ray powder diffraction patterns, IR spectra, and crystal structures of structurally related compounds belonging to the butyrophenone family was undertaken to obtain information about the elements of chemical structure which predispose a substance to exhibit polymorphism. Five butyrophenones [haloperidol, bromperidol, 4-[4-hydroxy-4-(4-fluorophenyl)-1-piperidinyl]-1-(4-fluorophenyl)-1-butanone (I), moperone and 4-hydroxy-4-phenyl-1-piperidinyl)-1-(4-fluorophenyl)-1-butanone (II)], differing by the nature of only 1 substituent, were selected. After crystallization from 15 solvents, it appears that 2 compounds of the group exhibit more than 1 crystalline form. An explanation of the absence of polymorphism in the other compounds of the group is proposed and discussed.