Synthesis and structural characterization of 1- and 2-substituted indazoles: ester and carboxylic acid derivatives

Molecules. 2006 Nov 14;11(11):867-89. doi: 10.3390/11110867.


A series of indazoles substituted at the N-1 and N-2 positions with ester-containing side chains -(CH2)(n)CO2R of different lengths (n = 0-6, 9, 10) are described. Nucleophilic substitution reactions on halo esters (X(CH2)(n)CO2R) by 1H-indazole inalkaline solution lead to mixtures of N-1 and N-2 isomers, in which the N-1 isomer predominates. Basic hydrolysis of the ester derivatives allowed the synthesis of the corresponding indazole carboxylic acids. All compounds were fully characterised by multinuclear NMR and IR spectroscopies, MS spectrometry and elemental analysis; the NMR 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-ray diffraction, which shows a supramolecular architecture involving O2-H...N1 intermolecular hydrogen bonds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetic Acid / chemistry
  • Carbon Isotopes
  • Carboxylic Acids / chemical synthesis*
  • Carboxylic Acids / chemistry*
  • Esters / chemical synthesis*
  • Esters / chemistry*
  • Hydrogen Bonding
  • Indazoles / chemical synthesis*
  • Indazoles / chemistry*
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Stereoisomerism


  • Carbon Isotopes
  • Carboxylic Acids
  • Esters
  • Indazoles
  • Acetic Acid