Synthesis of 3-hydroxythiophenes and thiophen-3(2H)-ones by pyrolysis of alkylsulfanylmethylene Meldrum's acid derivatives

Abstract

3-Hydroxythiophene [thiophen-3(2H)-one]1 and a range of its 2-substituted, 2,2-disubstituted and 5-substituted derivatives have been made by flash vacuum pyrolysis (FVP) of an appropriate alkylsulfanylmethylene derivative of Meldrum's acid 3 or 4. These compounds are readily obtained, either by reaction of methoxymethylene Meldrum's acid with alkylthiols in refluxing acetonitrile, or via the bis(methylsulfanyl) compound 18 by known procedures. The pyrolysis proceeds by a hydrogen-transfer–cyclisation mechanism in which there is extensive loss of configuration of a chiral centre at the reaction site. The NMR and mass spectra of the Meldrum's acid precursors and the mass spectra of the 3-hydroxythiophenes [thiophen-3(2H)-ones] are briefly discussed.