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Studies on the synthesis and some reactions of (S)-proline hydrazides


Mloston, Grzegorz; Pieczonka, Adam M; Wroblewska, Aneta; Linden, Anthony; Heimgartner, Heinz (2012). Studies on the synthesis and some reactions of (S)-proline hydrazides. Tetrahedron: Asymmetry, 23:795-801.

Abstract

A convenient synthesis of (S)-proline hydrazide 2a via the reaction of ethyl (S)-N-benzylprolinate with hydrazine hydrate and subsequent deprotection of (S)-N-benzyl proline hydrazide 5 is described. The latter, in methanolic solution, reacted with aromatic aldehydes as well as with cycloaliphatic ketones at room temperature to give the corresponding hydrazones of type 7 in good yields. The structure of the product with furan-2-carbaldehyde 7b, proving the (E)-configuration of the hydrazone, was established by X-ray crystallography. In the case of the unprotected (S)-proline hydrazide 2a, the analogous reaction with aromatic aldehydes led either to the expected hydrazones 7 or the 1H-pyrrolo[1,2-c]imidazol-1-one derivatives 8, depending on the reaction conditions. The latter were formed via a secondary cyclocondensation of the initially formed 7 with a second molecule of the aldehyde. Whereas the reaction of (S)-Nbenzyl proline hydrazide 5 with butyl isocyanate and isothiocyanate gave the corresponding semicarbazide and thiosemicarbazide, respectively, of type 9, the unprotected (S)-proline hydrazide 2a yielded the 1:2 adducts 10. Thiosemicarbazide 9b underwent cyclization reactions under basic (NaOH) and acidic (H2SO4) conditions to yield (S)-prolinyl-substituted 1,2,4-triazole-3-thione 11 and 1,3,4-thiadiazole-2-amine 12, respectively.

Abstract

A convenient synthesis of (S)-proline hydrazide 2a via the reaction of ethyl (S)-N-benzylprolinate with hydrazine hydrate and subsequent deprotection of (S)-N-benzyl proline hydrazide 5 is described. The latter, in methanolic solution, reacted with aromatic aldehydes as well as with cycloaliphatic ketones at room temperature to give the corresponding hydrazones of type 7 in good yields. The structure of the product with furan-2-carbaldehyde 7b, proving the (E)-configuration of the hydrazone, was established by X-ray crystallography. In the case of the unprotected (S)-proline hydrazide 2a, the analogous reaction with aromatic aldehydes led either to the expected hydrazones 7 or the 1H-pyrrolo[1,2-c]imidazol-1-one derivatives 8, depending on the reaction conditions. The latter were formed via a secondary cyclocondensation of the initially formed 7 with a second molecule of the aldehyde. Whereas the reaction of (S)-Nbenzyl proline hydrazide 5 with butyl isocyanate and isothiocyanate gave the corresponding semicarbazide and thiosemicarbazide, respectively, of type 9, the unprotected (S)-proline hydrazide 2a yielded the 1:2 adducts 10. Thiosemicarbazide 9b underwent cyclization reactions under basic (NaOH) and acidic (H2SO4) conditions to yield (S)-prolinyl-substituted 1,2,4-triazole-3-thione 11 and 1,3,4-thiadiazole-2-amine 12, respectively.

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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:16 Jul 2012 14:47
Last Modified:04 Dec 2018 14:52
Publisher:Elsevier
ISSN:0957-4166
Funders:European Social Fund ‘HUMAN—BEST INVESTMENT!’, co-funded by the European Union.
OA Status:Green
Publisher DOI:https://doi.org/10.1016/j.tetasy.2012.05.010

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