132794-07-1 | 4-CHLORO-2,5-DIFLUOROBENZOIC ACID

CAS:132794-07-1 | 4-CHLORO-2,5-DIFLUOROBENZOIC ACID,Description

4-Chloro-2,5-difluorobenzoic acid is a fluorinated building block. It has a linear formula of ClC6H2(F)2CO2H. It reacts with substituted 2-hydroxy acetophenones in the presence of POCl3 to afford 2-acetylphenyl-4-chloro-2,5-difluorobenzoate.

Synthesis Analysis

The synthesis of 4-Chloro-2,5-difluorobenzoic acid can be achieved from 2,5-difluoroaniline by Sandmeyer reaction, bromination, and Grignard reaction. The optimal reaction conditions of bromination were: n (2-chloro-1,4-difluorobenzene):n (Br2)=1:1.13, n (2-chloro-1,4-difluorobenzene):n (FeCl3)=1:0.03, bromination temperature=30 ℃, and bromination time=5 h.

Molecular Structure Analysis

The molecular weight of 4-Chloro-2,5-difluorobenzoic acid is 192.55 g/mol. The InChI key is PEPCYJSDHYMIFN-UHFFFAOYSA-N. The SMILES string is OC(=O)c1cc(F)c(Cl)cc1F.

Chemical Reactions Analysis

4-Chloro-2,5-difluorobenzoic acid reacts with substituted 2-hydroxy acetophenones in the presence of POCl3 to afford 2-acetylphenyl-4-chloro-2,5-difluorobenzoate.

Physical And Chemical Properties Analysis

The melting point of 4-Chloro-2,5-difluorobenzoic acid is 154-157 °C (lit.). The compound has a topological polar surface area of 37.3 Ų. It has one rotatable bond.

Scientific Research Applications

Synthesis and Chemical Properties

• Synthesis Methods : 4-Chloro-2,5-difluorobenzoic acid can be synthesized from 2,5-difluoroaniline using Sandmeyer reaction, bromination, and Grignard reaction. Optimal conditions for bromination include specific reactant ratios and temperatures, resulting in a product with 99.16% purity as confirmed by HPLC, MS, and 1H NMR (Zhao Hao-yu, 2011).
• Analytical Methods : Liquid chromatography (LC) is used to determine 2-Chloro-4,5-difluorobenzoic acid and its impurities, achieving separations with a reversed-phase isocratic system and an ion-pair reagent. The method has demonstrated precision and sensitivity for detecting impurities in commercially produced CDFBA (L. Elrod et al., 1993).

Applications in Synthesis and Drug Discovery

• Building Block for Heterocyclic Synthesis : 4-Chloro-2-fluoro-5-nitrobenzoic acid, a related compound, serves as a multireactive building block in heterocyclic oriented synthesis (HOS) for creating various condensed nitrogenous cycles, which are significant in drug discovery. This includes the preparation of benzimidazoles, benzotriazoles, and other heterocycles, highlighting its utility in synthesizing diverse libraries of potential pharmaceuticals (Soňa Křupková et al., 2013) .
• Antimicrobial Activity : Novel fluorinated chromones and pyrazoles synthesized from 4-chloro-2,5-difluorobenzoic acid have shown promising antimicrobial activity against various strains. This underscores its role in developing new antimicrobial agents (A. Gadhave et al., 2015).

Environmental and Analytical Chemistry

• Tracer Studies : In environmental studies, derivatives of 4-Chloro-2,5-difluorobenzoic acid, such as 2,5-difluorobenzoate, are used as conservative tracers for studying water movement in porous media, demonstrating similar transport properties to Bromine in certain soils (D. Jaynes, 1994).

Safety And Hazards

4-Chloro-2,5-difluorobenzoic acid is classified as Acute Tox. 4 Dermal, Acute Tox. 4 Inhalation, Acute Tox. 4 Oral, Eye Irrit. 2, Skin Irrit. 2, and STOT SE 3. It may cause respiratory irritation. Personal protective equipment such as a dust mask type N95 (US), eyeshields, and gloves are recommended.

Relevant Papers The relevant papers retrieved discuss the synthesis method of 4-Chloro-2,5-difluorobenzoic acid. The structure of the product was confirmed by MS and 1H NMR.

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