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Tautomerism troubles: Proton transfer modifies the stereochemical assignments in diastereoisomeric structures of spirocyclic 5-methyl-2H-imidazol-4- amine dimers

Tautomerism troubles: Proton transfer modifies the stereochemical assignments in diastereoisomeric structures of spirocyclic 5-methyl-2H-imidazol-4- amine dimers
Tautomerism troubles: Proton transfer modifies the stereochemical assignments in diastereoisomeric structures of spirocyclic 5-methyl-2H-imidazol-4- amine dimers

During the racemization of a novel pharmaceutical spiro cyclic imidazole-amine compound, namely, 6′-bromo-N-(6′-bromo-4-meth oxy-4′′-methyl-3′H-di spiro[cyclo hexane-1,2′-indene-1′,2′′-imidazol]-5′′-yl)-4-meth oxy-4′′-methyl-3′H-di spiro [cyclo hexane-1,2′-indene-1′,2′′-imidazol]-5′′-imine, C36H41Br2N5O2, two impurities were isolated. These impurities were clearly dimers from mass spectroscopic analysis, however single-crystal diffraction characterization was required for the assignment of stereochemistry. The single-crystal diffraction results revealed subtly different structures to those proposed, due to an unexpected proton transfer. The dimers contain four stereocentres, but two of primary inter est, and are centrosymmetric, so after careful structure refinement and close inspection it was possible to unambiguously assign the stereochemistry of both the homochiral [(S),(S)- and (R),(R)-] and the heterochiral [(S),(R)- and (R),(S)-] compounds.

Chirality assignment, Crystal structure, Pharmaceutical
2056-9890
1311-1315
Blade, Helen
67130ef3-afa0-4b7d-ab6f-ed220586cd1d
Horton, Peter N.
154c8930-bfc3-495b-ad4a-8a278d5da3a5
Morrison, James A.
2db0e509-8286-4d4d-84e1-3f0bed861ac7
Orton, James B.
4e2a471f-9e11-4cb4-abb6-d0398047939f
Sullivan, Rachel A.
bcb33120-7ac5-491b-ba50-f30ab12e581c
Coles, Simon J.
3116f58b-c30c-48cf-bdd5-397d1c1fecf8
Blade, Helen
67130ef3-afa0-4b7d-ab6f-ed220586cd1d
Horton, Peter N.
154c8930-bfc3-495b-ad4a-8a278d5da3a5
Morrison, James A.
2db0e509-8286-4d4d-84e1-3f0bed861ac7
Orton, James B.
4e2a471f-9e11-4cb4-abb6-d0398047939f
Sullivan, Rachel A.
bcb33120-7ac5-491b-ba50-f30ab12e581c
Coles, Simon J.
3116f58b-c30c-48cf-bdd5-397d1c1fecf8

Blade, Helen, Horton, Peter N., Morrison, James A., Orton, James B., Sullivan, Rachel A. and Coles, Simon J. (2021) Tautomerism troubles: Proton transfer modifies the stereochemical assignments in diastereoisomeric structures of spirocyclic 5-methyl-2H-imidazol-4- amine dimers. Acta Crystallographica Section E: Crystallographic Communications, 77, 1311-1315. (doi:10.1107/S205698902100668X).

Record type: Article

Abstract

During the racemization of a novel pharmaceutical spiro cyclic imidazole-amine compound, namely, 6′-bromo-N-(6′-bromo-4-meth oxy-4′′-methyl-3′H-di spiro[cyclo hexane-1,2′-indene-1′,2′′-imidazol]-5′′-yl)-4-meth oxy-4′′-methyl-3′H-di spiro [cyclo hexane-1,2′-indene-1′,2′′-imidazol]-5′′-imine, C36H41Br2N5O2, two impurities were isolated. These impurities were clearly dimers from mass spectroscopic analysis, however single-crystal diffraction characterization was required for the assignment of stereochemistry. The single-crystal diffraction results revealed subtly different structures to those proposed, due to an unexpected proton transfer. The dimers contain four stereocentres, but two of primary inter est, and are centrosymmetric, so after careful structure refinement and close inspection it was possible to unambiguously assign the stereochemistry of both the homochiral [(S),(S)- and (R),(R)-] and the heterochiral [(S),(R)- and (R),(S)-] compounds.

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More information

Accepted/In Press date: 18 November 2021
Published date: 1 December 2021
Additional Information: Funding Information: We would like to thank the Engineering and Physical Sciences Research Council (UK) for funding the UK National Crystallography Service. Publisher Copyright: © 2021 International Union of Crystallography. All rights reserved. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
Keywords: Chirality assignment, Crystal structure, Pharmaceutical

Identifiers

Local EPrints ID: 454668
URI: http://eprints.soton.ac.uk/id/eprint/454668
ISSN: 2056-9890
PURE UUID: f1b56767-b96b-4cad-832b-9aefb764bf7f
ORCID for Peter N. Horton: ORCID iD orcid.org/0000-0001-8886-2016
ORCID for Simon J. Coles: ORCID iD orcid.org/0000-0001-8414-9272

Catalogue record

Date deposited: 18 Feb 2022 17:42
Last modified: 18 Mar 2024 02:51

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Contributors

Author: Helen Blade
Author: Peter N. Horton ORCID iD
Author: James A. Morrison
Author: James B. Orton
Author: Rachel A. Sullivan
Author: Simon J. Coles ORCID iD

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