IMIDAZOLE RING FORMATION AND TERTIARY AMINE CLEAVAGE UPON BASE-MEDIATED NUCLEOPHILIC SUBSTITUTION IN 1,1,3-TRICHLORO-1H-ISOINDOLE WITH α-(N-ALKYLAMINO) KETONES

Abstract

Interaction between α-(N-alkylamino) ketones and 1,1,3-trichloro-1H-isoindole in the presence of tertiary amine leads to nucleophilic substitution of three chlorine atoms and formation of 3-amino-1H-isoindol-1-ylidene-1-aminium quaternary salts possessing two amino ketone residues. Both substituents at nitrogen in aminium salts can adopt either (Z)- or (E)-configuration. Their treatment with bases in air leads via blue enolates (λ_max 595.5 nm, CHCl₃) to a relatively stable free radical, probably of a bisspiro structure. Reaction can also proceed further with isoindole ring opening and formation of (1H-imidazol-2-yl)phenyl-1,3-oxazol-3-ium derivative. Oxazolium moiety undergoes easy hydrolytic ring cleavage leading to 2-(1H-imidazol-3-ium)benzamide derivative. When N,N-dimethylbenzylamine is used as a base, the reaction proceeds via its cleavage and formation of unsymmetrical aminium salt containing both dimethylamino group along with α-(N-alkylamino) ketone residue.