Synthesis and Antitumor Testing of 3-Methenylthiochroman-4-one-1,1-dioxide

Abstract

Treatment of thiochroman-4-one-1,1-dioxide (II) with paraformaldehyde and dimethylamine hydrochloride in isopropyl alcohol at reflux afforded directly in 89% yield the dimeric dihydropyran (IV), corresponding to the dimerization of the target compound 3-methenyl-thiochroman-4-one-1,1-dioxide (III). Neither the monomer III nor the expected Mannich base, 3-dimethylaminomethylthiochroman-4-one-1,1-dioxide, were isolated under conditions of the reaction. The monomer III could be prepared in 55% yield by sublimation of the dimer IV at 230-250°; however, redimerization slowly occurred at room temperature.The dimer IV was also prepared by the use of paraformaldehyde and N-methylanilinium trifluoroacetate. The monomer III was found to be marginally active at 10 mg/kg/day versus Ehrlich ascites tumor growth in mice.