Multi-component solvent-free versus stepwise solvent mediated reactions: Regiospecific formation of 6-trifluoromethyl and 4-trifluoromethyl-1H-pyrazolo[3,4-b]pyridines

• Published in: Journal of fluorine chemistry 2012-08, Vol.140, p.31-37
• Main Authors: Aggarwal, Ranjana, Kumar, Virender, Bansal, Anshul, Sanz, Dionisia, Claramunt, Rosa M.
• Format: Article
• Language: English
• Subjects: 2-Hydrazinobenzothiazole; Pyrazolopyridines; Regiospecific reactions; Trifluoromethyl-β-diketone; α-Cyanoacetophenone
• ISSN: 0022-1139; 1873-3328
• DOI: 10.1016/j.jfluchem.2012.04.007

[Display omitted] ► Regiospecific synthesis of 6-trifluoromethyl-1H-pyrazolo[3,4-b]pyridines by MCR method under solvent-free conditions. ► Synthesis of regioisomeric, 4-trifluoromethyl-1H-pyrazolo[3,4-b]pyridines using a multistep solvent mediated process. ► MCR method was found to be more convenient than the classical stepwise solvent mediated process. ► Concluding proofs of structures were obtained by 2D NMR (1H1H) gs-COSY, (1H13C) gs-HMQC and (1H13C) gs-HMBC experiments. A simple and efficient regiospecific synthesis of 6-trifluoromethyl-1H-pyrazolo[3,4-b]pyridines has been achieved in excellent yields via a three-component reaction between 2-hydrazinobenzothiazoles, α-cyanoacetophenones and trifluoromethyl-β-diketones under solvent-free conditions. This method was found to be more convenient than the classical stepwise solvent mediated process, which furnished not only the opposite regioisomer i.e. 4-trifluoromethyl-1H-pyrazolo[3,4-b]pyridines (50–60%) but also an undesired amide, 5-acetylamino-1-(benzothiazol-2′-yl)-3-phenyl-1H-pyrazole as a side product. The structure of the two regioisomers was established with certainty on the basis of rigorous analysis of 1H, 13C, 19F-NMR spectral data and (1H13C) gs-HMQC, (1H13C) gs-HMBC experiments.