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 spirocyclic imidazole–amine compound, namely, 6′-bromo-N-(6′-bromo-4-methoxy-4′′-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2′′-imidazol]-5′′-yl)-4-methoxy-4′′-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2′′-imidazol]-5′′-imine, C36H41Br2N5O2, t...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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International Union of Crystallography
2021-12-01
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| Series: | Acta Crystallographica Section E: Crystallographic Communications |
| Subjects: | |
| Online Access: | http://scripts.iucr.org/cgi-bin/paper?S205698902100668X |
| _version_ | 1798017551286927360 |
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| author | Helen Blade Peter N. Horton James A. Morrison James B. Orton Rachel A. Sullivan Simon J. Coles |
| author_facet | Helen Blade Peter N. Horton James A. Morrison James B. Orton Rachel A. Sullivan Simon J. Coles |
| author_sort | Helen Blade |
| collection | DOAJ |
| description | During the racemization of a novel pharmaceutical spirocyclic imidazole–amine compound, namely, 6′-bromo-N-(6′-bromo-4-methoxy-4′′-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2′′-imidazol]-5′′-yl)-4-methoxy-4′′-methyl-3′H-dispiro[cyclohexane-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 interest, 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. |
| first_indexed | 2024-04-11T16:09:09Z |
| format | Article |
| id | doaj.art-0229c9fcb2944f6bb65b5ba1b904f4cc |
| institution | Directory Open Access Journal |
| issn | 2056-9890 |
| language | English |
| last_indexed | 2024-04-11T16:09:09Z |
| publishDate | 2021-12-01 |
| publisher | International Union of Crystallography |
| record_format | Article |
| series | Acta Crystallographica Section E: Crystallographic Communications |
| spelling | doaj.art-0229c9fcb2944f6bb65b5ba1b904f4cc2022-12-22T04:14:44ZengInternational Union of CrystallographyActa Crystallographica Section E: Crystallographic Communications2056-98902021-12-0177121311131510.1107/S205698902100668Xdj2028Tautomerism troubles: proton transfer modifies the stereochemical assignments in diastereoisomeric structures of spirocyclic 5-methyl-2H-imidazol-4-amine dimersHelen Blade0Peter N. Horton1James A. Morrison2James B. Orton3Rachel A. Sullivan4Simon J. Coles5AstraZeneca, Oral Product Development, Pharmaceutical Technology & Development, Operations, Macclesfield, United KingdomSchool of Chemistry, Faculty of Engineering and Physical Sciences, University of Southampton, Southampton, SO17 1BJ, United KingdomAstraZeneca, Chemical Development, Pharmaceutical Technology & Development, Operations, Macclesfield, United KingdomSchool of Chemistry, Faculty of Engineering and Physical Sciences, University of Southampton, Southampton, SO17 1BJ, United KingdomAstraZeneca, Chemical Development, Pharmaceutical Technology & Development, Operations, Macclesfield, United KingdomSchool of Chemistry, Faculty of Engineering and Physical Sciences, University of Southampton, Southampton, SO17 1BJ, United KingdomDuring the racemization of a novel pharmaceutical spirocyclic imidazole–amine compound, namely, 6′-bromo-N-(6′-bromo-4-methoxy-4′′-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2′′-imidazol]-5′′-yl)-4-methoxy-4′′-methyl-3′H-dispiro[cyclohexane-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 interest, 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.http://scripts.iucr.org/cgi-bin/paper?S205698902100668Xchirality assignmentpharmaceuticalcrystal structure |
| spellingShingle | Helen Blade Peter N. Horton James A. Morrison James B. Orton Rachel A. Sullivan Simon J. Coles 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 chirality assignment pharmaceutical crystal structure |
| title | Tautomerism troubles: proton transfer modifies the stereochemical assignments in diastereoisomeric structures of spirocyclic 5-methyl-2H-imidazol-4-amine dimers |
| title_full | Tautomerism troubles: proton transfer modifies the stereochemical assignments in diastereoisomeric structures of spirocyclic 5-methyl-2H-imidazol-4-amine dimers |
| title_fullStr | Tautomerism troubles: proton transfer modifies the stereochemical assignments in diastereoisomeric structures of spirocyclic 5-methyl-2H-imidazol-4-amine dimers |
| title_full_unstemmed | Tautomerism troubles: proton transfer modifies the stereochemical assignments in diastereoisomeric structures of spirocyclic 5-methyl-2H-imidazol-4-amine dimers |
| title_short | Tautomerism troubles: proton transfer modifies the stereochemical assignments in diastereoisomeric structures of spirocyclic 5-methyl-2H-imidazol-4-amine dimers |
| title_sort | tautomerism troubles proton transfer modifies the stereochemical assignments in diastereoisomeric structures of spirocyclic 5 methyl 2h imidazol 4 amine dimers |
| topic | chirality assignment pharmaceutical crystal structure |
| url | http://scripts.iucr.org/cgi-bin/paper?S205698902100668X |
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