A route to fluorocontaining N,S-heterocycles via octafluoro-2,3-epoxybutane

The reaction of octafluoro-2,3-epoxybutane 1 with 2-aminothiophenol gave three kinds of novel fluorocontaining N,S-heterocyclic compounds depending on the solvent nature: 2,3-bis(trifluoromethyl)-3,4-dihydro-2H-1,4-benzothiazin-2-ol 2, 2-trifluoromethyl-2-[1-(2-aminophenylthio)-2,2,2-trifluoroethyl]-1,3-benzothiazolidine 6 and 5a,11a-bis(trifluoromethyl)-5a,6,11a,12-tetrahydro-5,11-dithia-6,12-diazanaphthacene 5. Use of the toluene, dioxane, tetrahydrofuran, acetonitrile and dimethoxyethane gave the unexpected dihydrobenzothiazine 2 (RS,SR > RR,SS) in good to moderate yields. In dimethylsulfoxide and N,N-dimethylacetamide, unusual cyclization occurred resulting in benzothiazolidine 6 (RS,SR/RR,SS ∼ 1:1) in moderate yields. Formation of minor 1,1,1,3,4,4,4-heptafluoro-3-(2-aminophenylthio)-2,2-dihydroxybutane 4 which was converted into bis(benzothiazine) 5 was observed in all solvents tested with the exception of toluene and dioxane. The molecular structure of the RS,SR-diastereomer of dihydrobenzothiazine 2, bis(benzothiazine) 5 and the RS,SR-diastereomer of benzothiazolidine 6 has been established by X-ray crystallography.

Graphical abstractThe reaction of octafluoro-2,3-epoxybutane with 2-aminothiophenol in dimethylsulfoxide and N,N-dimethylacetamide gave mainly 2-trifluoromethyl-2-[1-(2-aminophenylthio)-2,2,2-trifluoroethyl]-1,3-benzothiazolidine. A similar reaction in toluene, dioxane, tetrahydrofuran, dimethoxyethane and acetonitrile yielded 2,3-bis(trifluoromethyl)-3,4-dihydro-2H-1,4-benzothiazin-2-ol. Formation of minor 5a,11a-bis(trifluoromethyl)-5a,6,11a,12-tetrahydro-5,11-dithia-6,12-diazanaphthacene was observed in all solvents tested with the exception of toluene and dioxane. The molecular structure of the RS,SR-diastereomer of 2,3-bis(trifluoromethyl)-3,4-dihydro-2H-1,4-benzothiazin-2-ol, 5a,11a-bis(trifluoromethyl)-5a,6,11a,12-tetrahydro-5,11-dithia-6,12-diazanaphthacene and the RS,SR-diastereomer of 2-trifluoromethyl-2-[1-(2-aminophenylthio)-2,2,2-trifluoroethyl]-1,3-benzothiazolidine has been established by X-ray crystallography. Figure optionsDownload full-size imageDownload as PowerPoint slide