New Optically Active Bis‐Heterocycles Derived from ( S )‐Proline

Enantiomerically pure bis‐heterocycles containing a ( S )‐proline moiety have been prepared starting from ( S )‐ N ‐benzylprolinehydrazide ( 2b ). The reactions with isothiocyanates or butyl isocyanate in refluxing MeOH led to the corresponding thiosemicarbazide 5 and semicarbazide 9 with a N ‐benzylprolinoyl residue. The structure of the tert ‐butyl derivative 5d was established by X‐ray crystallography. Base‐catalyzed cyclization of 5 and 9 led to ( S )‐3‐(pyrrolidin‐2‐yl)‐1 H ‐1,2,4‐triazole‐5(4 H )‐thiones 6 and the corresponding 5(4 H )‐one 8 , respectively, whereas, in concentrated H 2 SO 4 , compounds 5 undergo cyclization to give ( S )‐5‐amino‐2‐(pyrrolidin‐2‐yl)‐1,3,4‐thiadiazoles 7 . Furthermore, 2b reacted with hexane‐2,5‐dione in boiling i PrOH to yield the ( S )‐ N ‐(2,5‐dimethylpyrrol‐1‐yl)prolinamide 10 . In the case of the bis‐heterocycle 8 , treatment with HCOONH 4 and Pd/C in MeOH gave the debenzylated product 12 .