Determination of the tautomerism of albendazole desmotropes using solution and solid state NMR together with DFT theoretical calculations, both energies and chemical shifts

This paper reports a structural study of albendazole concerning the desmotropy of its amino and imino tautomers, ABZ-I and ABZ-II, mistakenly called polymorphs. Experimental NMR determination in solution, DMSO-d6, HMPA-d18 and CF3 CO2 H, and in the solid state, CPMAS, together with DFT calculations,...

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Detalles Bibliográficos
Autores: Claramunt, Rosa M., López García, Concepción, Sanz del Castillo, Dionisia, Elguero, José, Alkorta, Ibon
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universidad Nacional de Educación a Distancia
Repositorio:e-spacio. Repositorio Institucional de la UNED
Idioma:inglés
OAI Identifier:oai:e-spacio.uned.es:20.500.14468/23837
Acceso en línea:https://hdl.handle.net/20.500.14468/23837
Access Level:acceso abierto
Palabra clave:23 Química
Albendazole
Polymorphs
Desmotropes
NMR crystallography
DFT
GIAO
Descripción
Sumario:This paper reports a structural study of albendazole concerning the desmotropy of its amino and imino tautomers, ABZ-I and ABZ-II, mistakenly called polymorphs. Experimental NMR determination in solution, DMSO-d6, HMPA-d18 and CF3 CO2 H, and in the solid state, CPMAS, together with DFT calculations, energies and NMR chemical shifts, has allowed to understand the complex problem of prototropy combined with rotation about the benzimidazole C2-N exocyclic group that explain the disorder problem of the S-propyl group. The structure of protonated albendazole, ABZH +, has also been studied. The role of the hybrid HF/DFT B3LYP computational method at the B3LYP/6-311++G(d,p) level has been determinant to solve the problems related to the structure of albendazole in the solid state and in solution and the barrier in solution of a phenomenon resulting either from annular tautomerism or from the rotation about the exocyclic C-N bond.