Synthesis of 5,6-dihydro-2-trifluoromethyl-1,4-dioxin-3-carboxanilides through polymer-bound activated ester: Construction of dihydro-1,4-dioxin

Abstract

A new construction of dihydro-1,4-dioxin and a synthesis of 5,6-dihydro-2-trifluoromethyl-1,4-dioxin-3-carboxanilides 22 through polymer-bound activated ester are described. An intermediate beta-hydroxy ether 18 was prepared from the substitution reaction of alpha-thio-alpha-chloro compound 8 with ethylene glycol followed by treatment with Raney Ni. Replacement of hydroxy by chlorine and then dehydrochlorination afforded trifluoromethyl dihydro-1,4-dioxin ester 15. The polymer-bound trifluoromethyl dihydro-1,4-dioxin-3-carboxylic acid, 4-hydroxy-3-nitrobenzophenone ester (21) was prepared through the reaction of polystyrene-bound 4-hydroxy-3-nitrobenzophenone (19) with the trifluoromethyl dihydro-2,4-dioxin-3-carbonyl chloride (20). Refluxing of 21 with substituted aniline in acetonitrile gave the corresponding carboxanilide 22. The reaction rate depended on the nucleophilicity of nitrogen of the aniline.