Synthesis and Structural Characterization of 1- and 2-Substituted Indazoles: Ester and Carboxylic Acid Derivatives

Abstract

A series of indazoles substituted at the N-1 and N-2 positions with ester-containing side chains -(CH2)nCO2R of different lengths (n = 0-6, 9, 10) are described.Nucleophilic substitution reactions on halo esters (X(CH2)nCO2R) by 1H-indazole inalkaline solution lead to mixtures of N-1 and N-2 isomers, in which the N-1 isomerpredominates. Basic hydrolysis of the ester derivatives allowed the synthesis of thecorresponding indazole carboxylic acids. All compounds were fully characterised bymultinuclear NMR and IR spectroscopies, MS spectrometry and elemental analysis; theNMR spectroscopic data were used for structural assignment of the N-1 and N-2 isomers.The molecular structure of indazol-2-yl-acetic acid (5b) was determined by X-raydiffraction, which shows a supramolecular architecture involving O2-H...N1intermolecular hydrogen bonds.

Keywords

• Indazole
• N-1 and N-2 isomers
• Spectroscopic characterization
• X-ray diffraction studies.