1174305-81-7 | 1-(2,2-Difluoroethyl)-1H-pyrazole-4-carboxylic acid

CAS:1174305-81-7 | 1-(2,2-Difluoroethyl)-1H-pyrazole-4-carboxylic acid,Description

“1-(difluoromethyl)-1H-pyrazole-4-carboxylic acid” is a chemical compound that is part of the pyrazole family. Pyrazoles are heterocyclic compounds that have received significant attention due to their wide range of biological activities.

Synthesis Analysis

The synthesis of pyrazole derivatives, such as “1-(difluoromethyl)-1H-pyrazole-4-carboxylic acid”, involves several steps. For instance, two pyrazol-4-carboxamides were synthesized and their structures were confirmed by the aid of 1H NMR and HRMS analyses. The synthetic route involved the reaction of ethyl-2-(ethoxymethylene)-4,4-difluoro-3-oxobutanoate and triethyl orthoformate in the presence of acetic anhydride.

Molecular Structure Analysis

The molecular structure of “1-(difluoromethyl)-1H-pyrazole-4-carboxylic acid” and related compounds has been confirmed through various methods such as 1H NMR, HRMS analyses, and X-ray diffraction.

Chemical Reactions Analysis

Difluoromethylation processes based on X–CF2H bond formation where X is C (sp), C (sp2), C (sp3), O, N or S, have been studied extensively. The last decade has witnessed an upsurge of metal-based methods that can transfer CF2H to C (sp2) sites both in stoichiometric and catalytic mode.

Scientific Research Applications

• Scientific Field: Organic Chemistry

  • Application : Difluoromethylation processes based on X–CF2H bond formation.
  • Method : This process involves the formation of X–CF2H bonds where X is C(sp), C(sp2), C(sp3), O, N, or S. The last decade has seen an increase in metal-based methods that can transfer CF2H to C(sp2) sites both in stoichiometric and catalytic mode.
  • Results : These advances have streamlined access to molecules of pharmaceutical relevance, and generated interest for process chemistry.

• Scientific Field: Green Chemistry

  • Application : Utilization of fluoroform for difluoromethylation in continuous flow.
  • Method : This process involves a continuous flow difluoromethylation protocol on sp3 carbons employing fluoroform as a reagent.
  • Results : This method enables a highly atom-efficient synthesis of the active pharmaceutical ingredient eflornithine.

• Scientific Field: Organic Chemistry

  • Application : Introduction of the difluoromethyl group at the meta- or para-position of pyridines.
  • Method : This method involves the precise site-selective installation of CF2H onto large biomolecules such as proteins. The difluoromethyl group can be introduced either at the meta-position (two atoms away from the nitrogen) or at the para-position (three atoms away from the nitrogen).
  • Results : This study solves the problem of direct difluoromethylation of the pyridine ring at the meta-position, which is particularly difficult to access in complex compounds.

• Scientific Field: Pharmaceutical Research

  • Application : Difluoromethylation of 1-(3-bromo-1H-pyrazol-1-yl)ethan-1-one.
  • Method : This process involves the replacement of a hydrogen atom in pyridines by a difluoromethyl group.
  • Results : The successful difluoromethylation of 1-(3-bromo-1H-pyrazol-1-yl)ethan-1-one is of interest considering that 3-(difluoromethyl)-1-methyl-1H-pyrazole is a motif important to the agrochemical industry.

• Scientific Field: Organic Chemistry

  • Application : Introduction of the difluoromethyl group at the meta- or para-position of pyridines.
  • Method : This method involves the precise site-selective installation of CF2H onto large biomolecules such as proteins. The difluoromethyl group can be introduced either at the meta-position (two atoms away from the nitrogen) or at the para-position (three atoms away from the nitrogen).
  • Results : This study solves the problem of direct difluoromethylation of the pyridine ring at the meta-position, which is particularly difficult to access in complex compounds.

• Scientific Field: Pharmaceutical Research

  • Application : Difluoromethylation of 1-(3-bromo-1H-pyrazol-1-yl)ethan-1-one.
  • Method : This process involves the replacement of a hydrogen atom in pyridines by a difluoromethyl group.
  • Results : The successful difluoromethylation of 1-(3-bromo-1H-pyrazol-1-yl)ethan-1-one is of interest considering that 3-(difluoromethyl)-1-methyl-1H-pyrazole is a motif important to the agrochemical industry.

Future Directions

The field of difluoromethylation has seen significant advances in recent years, streamlining access to molecules of pharmaceutical relevance and generating interest for process chemistry. Future research may focus on the development of safer and more effective formulations.

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