Efficient synthesis of cis-thiazolidinethiones derived from ephedrines

The reaction of chlorodeoxypseudoephedrine or chlorodeoxynorpseudoephedrine hydrochlorides with sodium dithiocarbonate in stirring ethanol at 0 °C to stereoselectively afford the corresponding cis-thiazolidinethiones in good yields (81% and 95%) is reported. The in situ formation of a cis-aziridine to explain the presence of trans-thiazolidinethione as a side product is proposed when the same reaction was carried out at room temperature. In addition, a 70:30 mixture of trans-isomers of a thiazolidinethione/isothiazolidinethione was formed when a cis-aziridine NH was reacted with carbon disulfide in refluxing ethanol. The analogous reaction with cis-aziridine N–Me stereoselectively affords the corresponding cis-thiazolidinethione. The 1H and 13C NMR data of the thiazolidinethiones were assigned. cis-3,4-Dimethyl-5-phenylthiazolidine-2-thione was crystallized from ethanol and its X-ray diffraction structure was analyzed.

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(4S,5R)-cis-4-Methyl-5-phenyl-thiazolidinethioneC10H11NS2[α]D20=-33 (c 0.2 × 10−3 g/mL, CHCl3)Source of chirality: (1R,2S)-(−)-norephedrineAbsolute configuration: (4S,5R)

(4S,5R)-cis-3,4-Dimethyl-5-phenyl-thiazolidinethioneC11H13NS2[α]D20=-18.7 (c 0.33, CHCl3)Source of chirality: (1R,2S)-(−)-ephedrineAbsolute configuration: (4S,5R)