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


Pieczonka, Adam M; Mloston, Grzegorz; Linden, Anthony; Heimgartner, Heinz (2012). New Optically Active Bis-Heterocycles Derived from (S)-Proline. Helvetica Chimica Acta, 95(9):1521-1530.

Abstract

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)-1H-1,2,4-triazole-5(4H)-thiones 6 and the corresponding 5(4H)-one 8, respectively, whereas, in concentrated H2SO4, 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 iPrOH to yield the (S)-N-(2,5-dimethylpyrrol-1-yl) prolinamide 10. In the case of the bis-heterocycle 8, treatment with HCOONH4 and Pd/C in MeOH gave the debenzylated product 12.

Abstract

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)-1H-1,2,4-triazole-5(4H)-thiones 6 and the corresponding 5(4H)-one 8, respectively, whereas, in concentrated H2SO4, 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 iPrOH to yield the (S)-N-(2,5-dimethylpyrrol-1-yl) prolinamide 10. In the case of the bis-heterocycle 8, treatment with HCOONH4 and Pd/C in MeOH gave the debenzylated product 12.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Language:English
Date:2012
Deposited On:09 Oct 2012 13:16
Last Modified:05 Apr 2016 15:58
Publisher:Verlag Helvetica Chimica Acta
ISSN:0018-019X
Funders:European Union under the European Social Fund HUMAN – BEST INVESTMENT! .
Publisher DOI:https://doi.org/10.1002/hlca.201200400

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