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

• Published in: Journal of molecular structure 2022-08, Vol.1261, p.132883, Article 132883
• Main Authors: Claramunt, Rosa M., López, Concepción, Sanz, Dionisia, Elguero, José, Alkorta, Ibon
• Format: Article
• Language: English
• Subjects: Albendazole; Desmotropes; DFT; GIAO; NMR crystallography; Polymorphs
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2022.132883

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 CF3CO2H, 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 CN bond. •Amino-Imino tautomerism of Albendazole.•Solution and solid state NMR of Albendazole desmotropes.•Prototropy combined with rotation about the benzimidazole C2-N exocyclic group in Albendazole, DNMR studies.•Cations resulting from protonation of Albendazole.•Role of the hybrid HF/DFT B3LYP computational method at the B3LYP/6–311++G(d,p) level to solve the problems related to the structure of Albendazole. [Display omitted]