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

Nikita P Burlutskiy,Andrei S Potapov

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.

Highlights

Bis(pyrazol-1-yl)alkanes are bidentate ligands widely used for the synthesis of the coordination compounds [1], some of which were shown to exhibit catalytic [2,3,4,5,6], anticancer [7,8], antibacterial [9] and SOD-like activity [10,11], and electroluminescent properties [12,13]
In this contribution we report a facile synthesis of a series of 4,40 -dicarboxy-substituted bis(pyrazol-1-yl)alkanes with varied linker length and substitution in positions 3 and 5 of the pyrazole rings
Oxalyl chloride was successfully used for the carboxylation of 1-phenyl- and 1-alkylpyrazoles [28]

Summary

Introduction

Bis(pyrazol-1-yl)alkanes are bidentate ligands widely used for the synthesis of the coordination compounds [1], some of which were shown to exhibit catalytic [2,3,4,5,6], anticancer [7,8], antibacterial [9] and SOD-like activity [10,11], and electroluminescent properties [12,13]. A series of works devoted to the synthesis of metal-organic frameworks based on structurally related bis(4-carboxyphenylpyrazol-1-yl)methane was carried out by Sumby et al, the presence of the free chelating units in the structure of the framework allowed them to prepare catalysts with single metal sites [26,27]. In this contribution we report a facile synthesis of a series of 4,40 -dicarboxy-substituted bis(pyrazol-1-yl)alkanes with varied linker length and substitution in positions 3 and 5 of the pyrazole rings

Methods

Results

Conclusion