Synthesis of 1-thiazolyl-1H-indazoles from o-fluorobenzaldehyde thiazolylhydrazones

A practical and metal-free approach to 1-thiazolyl-1 H -indazoles was developed starting from readily available o -fluorobenzaldehydes. The method involves initial condensation with thiosemicarbazide and 2-bromoacetophenone to form o -fluorobenzaldehyde thiazolylhydrazones, followed by base-promoted intramolecular cyclization through nucleophilic aromatic substitution. After optimization of conditions, the reaction showed broad functional group tolerance and clear substituent effects, with halogens (Br, Cl) outperforming additional F or NO₂ due to cleaner conversions and easier isolation. The transformation proved scalable; a gram-scale experiment confirmed its practicality and enabled subsequent C Br functionalization of the indazole core, further underscoring the synthetic utility of this approach. Structural assignments were confirmed by HRMS, 1 H and 13 C NMR, and single-crystal X-ray diffraction. • Metal-free synthesis of 1-thiazolyl-1 H -indazoles developed. • Reaction proceeds via intramolecular S N Ar of o -fluorophenylhydrazones. • Broad substrate scope and tolerance to diverse substituents demonstrated. • Gram-scale synthesis confirms synthetic utility.