Cytotoxic compounds. Part VII. α-Aryl-α-halogenoacetophenones, their enol acetates, and some related compounds

Abstract

To obtain detoxicated derivatives of α-halogenoketones, enol acetates have been prepared from ten α-aryl-α-halogenoacetophenones by reaction of the sodium enolates with acetyl chloride; the conventional method using isopropenyl acetate was completely ineffective. Simple α-halogenoacetophenones are resistant to both procedures, and the conjugative influence of an α-aryl substituent on the stability of the enolate anion is thus demonstrated. The ultraviolet and infrared absorption maxima of the enol acetates are recorded.

Evidence is presented for the structure of the α-arylphenacylpyridinium halides, and the features of their infrared and nuclear magnetic resonance spectra are discussed. The rates of reaction of several α-aryl-α-halogenoacetophenones with pyridine and with aniline have been measured, and the results are discussed from the point of view that the compounds are substituted benzyl halides. The expected reduction in reactivity brought about by conversion of an α-aryl-α-halogenoacetophenone into its enol acetate is confirmed kinetically.

Syntheses of 4-sulphamoyl-α-chloroacetophenone and of the enol phosphates of α-bromoacetophenone and of methyl bromopyruvate are described.