Study On Fluorine-Containing α-Oxo Ketene Dithioacetals As Building Blocks

Synthesis and application ofα-oxo ketene dithioacetals together with application of trifluoromethyl-containing building blocks to organic synthesis was reviewed.α-oxo ketene dithioacetal is a type of multi-functional organic compounds and exhibits multiple reactivity.Tremendous development has been achieved in the synthesis and application of this type of multi-functional organic compounds,which has become one of the research hotspots in the organic synthesis.Therefore,in the dissertation we choose to introduce trifluoromethyl group intoα-oxo ketene dithioacetals to prepare fuorine-containingα-oxo ketene dithioacetals as building blocks and to study their application to synthesis of trifluoromethyl-containing heterocyclic compounds.This dissertation mainly contains the following aspects:1.Synthesis and structural characterization of fuorine-containingα-oxo ketene dithioacetals as building blocks.Ethyl trifluoroacetoacetate and trifluoroacetone were used to react with carbon disulfide and alkyl halide in one-pot reaction under a basic condition respectively to prepare fluorine-containingα-oxo ketene dithioacetals. While the reaction with ethyl trifluoroacetoacetate failed to yield the designed product, four new fluorinatedα-oxo ketene dithioacetal compounds were obtained through the one-pot reaction of trifluoroacetone with carbon disulfide and alkyl halide.The highest yield of the products reaches 66%.The structures of the new compounds were characterized with ¹H NMR,¹³C NMR,¹⁹F NMR,MS,IR and single crystal X-ray diffraction.Results of the single crystal test on compound 1,1,1-trifluoro-4-thiodibenzylacetal-3-buten-2-one showed that the molecules exist as dimers and accumulate in a lamellar structure.A possible reaction mechanism for the formation of fluorinatedα-oxo ketene dithioacetals from trifluoroacetone was proposed.2.Reactions of the prepared 1,1,1-trifluoro-4-thiopropionacetal-3-buten-2-one as a building block with phenylhydrazine under acidic,basic,or neutral conditions were studied respectively to find the optimal reaction conditions.Experimental results showed that the highest yield was obtained under acidic conditions.Then the building block was used to react with a series of hydrazine compounds under acidic condition to furnish twelve new pyrazole compounds containing a trifluoromethyl group in good yields(50%～82%).The structures of the new compounds were characterized with ¹H NMR,¹³C NMR,¹⁹F NMR,¹H-¹H COSY,MS,IR and elemental analysis.A possible mechanism for the reaction was proposed.3.1,1,1-trifluoro-4-thiopropionacetal-3-buten-2-one was used to react with o-phenyldiamine compounds in order to synthesize fluorinated benzodiazepines.One new fluorinated benzodiazepine was obtained and its structure was characterized with ¹H NMR,¹³C NMR,¹⁹F NMR,MS,IR.A possible mechanism for the reaction was proposed.4.The antibaterial activity of all the synthesized trifluoromethyl-containg heterocyclic compounds was tested in vitro with the fungus Gram-negative bacteria E. coli.The data indicated that the fluorinated heterocycles showed little effect on Gram-negative bacteria E.coli.