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Accessible Unlicensed Requires Authentication Published by Oldenbourg Wissenschaftsverlag October 31, 2015

Further study of oxazolidines derived from mefloquine and arenealdehydes: diastereoisomers and polymorphs

Raoni S.B. Goncalves, Marcus V.N. de Souza, Solange M.S.V. Wardell and James L. Wardell

Abstract

The reaction between racemic erythro [(R*,S*)-2,8-bis(trifluoromethyl)quinolin-4-yl]-(2-piperidyl)methanol] and 2-formyl-5-nitrothiene in toluene generates a reaction mixture containing two diastereoisomers of 4-[3-(5-nitrothien-2-yl)-hexahydro[1,3]oxazolo[3,4-a]pyridin-1-yl]-2,8-bis(trifluoromethyl)quinoline, 6, – namely (2S*,3R*,4S*5R*)-6 (6a) and (2R*,3S*,4S*,5R*)-6 (6b) in a ratio of 5:1 as indicated by 1H NMR spectroscopy (using the 1,3-oxazolidine ring numbering scheme for the chiral centres). Isolation of each product from the mefloquine/2-formyl-5-nitrothiene reaction mixture was achieved by fractional crystallisation of an ethanol solution, but not by column chromatography on silica, which led to the destruction of the minor product, 6b. A second polymorphic form, [monoclinic, P21/c] of (2S*,3R*,4S*,5R*)-4-[3-(2-hydroxyphenyl-hexahydro[1,3]oxazolo[3,4-a]pyridin-1-yl]-2,8-bis(trifluoromethyl)quinoline (monoclinic-7) has been isolated from MeOH solution: the previously reported orthorhombic form, space group Fdd2, had been isolated from an ethanolic solution.


Corresponding author: James L. Wardell, FioCruz-Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos-Far-Manguinhos, Rua Sizenando Nabuco, 100, Manguinhos, 21041-250 Rio de Janeiro, RJ, Brazil; and Department of Chemistry, University of Aberdeen, Old Aberdeen, AB24 3UE, Scotland, UK, E-mail:

Acknowledgments

The use of the NCS crystallographic service at Southampton and the valuable assistance of the staff there are gratefully acknowledged. JLW thanks FAPERJ and CNPq, Brazil for support.

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Supplemental Material

The online version of this article (DOI: 10.1515/zkri-2015-1858) offers supplementary material, available to authorized users.

Received: 2015-5-11
Accepted: 2015-8-24
Published Online: 2015-10-31
Published in Print: 2016-1-1

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