Approaches to the Synthesis of Dicarboxylic Derivatives of Bis(pyrazol-1-yl)alkanes

Molecules. 2021 Jan 14;26(2):413. doi: 10.3390/molecules26020413.

Abstract

Carboxylation of bis(pyrazol-1-yl)alkanes by oxalyl chloride was studied. It was found that 4,4'-dicarboxylic derivatives of substrates with electron-donating methyl groups and short linkers (from one to three methylene groups) can be prepared using this method. Longer linkers lead to significantly lower product yields, which is probably due to instability of the intermediate acid chlorides that are initially formed in the reaction with oxalyl chloride. Thus, bis(pyrazol-1-yl)methane gave only monocarboxylic derivative even with a large excess of oxalyl chloride and prolonged reaction duration. An alternative approach involves the reaction of ethyl 4-pyrazolecarboxylates with dibromoalkanes in a superbasic medium (potassium hydroxide-dimethyl sulfoxide) and is suitable for the preparation of bis(4-carboxypyrazol-1-yl)alkanes with both short and long linkers independent of substitution in positions 3 and 5 of pyrazole rings. The obtained dicarboxylic acids are interesting as potential building blocks for metal-organic frameworks.

Keywords: alkylation; bis(pyrazol-1-yl)alkanes; carboxylation; dicarboxylic acids; oxalyl chloride; pyrazole; superbasic medium.

MeSH terms

  • Alkanes / chemical synthesis*
  • Crystallography, X-Ray
  • Dicarboxylic Acids / chemistry*
  • Molecular Conformation
  • Pyrazoles / chemistry*

Substances

  • Alkanes
  • Dicarboxylic Acids
  • Pyrazoles