Substitutive Alkylation of a-Halocarbonyl Compounds

Thiophenolates can be S-alkylated by a-halocarbonyl compounds to give (a-arylthio)carbonyl compounds 3, which in the presence of ZnCh undergo intramolecular hydroxyalkylation and subsequent H2O ehmination to afford 3-substituted benzo[b]thiophenes (4), for example ... 

Secondary aliphatic amines reacted readily with mercaptoaldimines (279), which could be prepared readily by the action of Na/NH3 on the aldehyde diacetals (278). The resulting N,N- dialkyl derivatives (280) were alkylated on sulfur by a-halocarbonyl compounds such as bromoacetic acid the resulting products (281) underwent spontaneous ring closure and aromatization via loss of the secondary amine to yield the acids (282 Scheme 97). Decarboxylation of the acids (282) furnished the substituted thieno[2,3-6 ]thiophenes (283). The use of other a-halocarbonyl compounds, such as bromoacetone or phenacyl bromide for the alkylation, led to the formation of the 2-acetyl or 2-benzoyl derivatives, (284) and (285) respectively (76AHC(19)123). 

Thiadiadiazines are prepared best by condensation of thiohydrazides with a-halocarbonyl compounds. As thiohydrazide components, most substituted thiosemicarbazides, aryl and alkyl thiocarbonylhydrazides, or 0-alkyl dithiocarbazates can be used. The cyclocondensation with thiosemicarbazides and a-halocarbonyl compounds can provide three isomeric compounds, 2-amino-l,3,4-thiadiazines A, 2-hydrazino-l,3-thiazoles or 2-hydrazono-2,3-dihy-dro-l,3-thiazoles B, and 2-alkyl(aryl)imino-3-amino-2,3-dihydro-l,3-thiazoles C (Scheme 31). The course of the cyclization of thiosemicarbazides with a-halocarbonyl compounds depends on the acidity of the reaction medium and the substituents R, R, and R. The reaction of aromatic a-halo ketones with thiosemicarbazides leads under neutral... 

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