Synthesis of Enantiopure Bis-Heterocycles Derived from (S)-Prolinehydrazides

Abstract

A convenient synthesis of new enantiomerically pure bis-heterocycles containing a (S)-proline moiety starting from (S)-N-benzylprolinehydrazide (1) is described. The reactions of 1b with isothiocyanates in refluxing MeOH led to the thiosemicarbazide 3 with a N-benzylprolinoyl residue. Thiosemicarbazide 3 underwent cyclization reactions under basic (NaOH) and acidic (H₂SO₄) conditions to yield (S)-prolinyl-substituted 1,2,4-triazole-3-thione 4 and 1,3,4-thiadiazole-2-amine 5, respectively.

GRAPHICAL ABSTRACT

Keywords:

• Bis-heterocycles
• enantiomerically pure
• proline

Acknowledgments

The presented results summarize our recent efforts in the synthesis of enantiomerically pure bis-heterocycles containing (S)-proline moiety. Adam M. Pieczonka thanks for financial support within the project co-funded by the European Union under the European Social Fund “HUMAN – BEST INVESTMENT!.”