3-Chloro-2,4,5-trifluorobenzoic acid

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Cat Number

INT101513773

CAS Number

101513-77-3

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Product Detail Description Scientific Support Customer Q&A

CAS Number

101513-77-3

EINECS

630-223-4

Storage

Sealed in dry, room temperature

Molecular Formula

C7H2ClF3O2

Molecular Weight

210.54

Smiles

C1=C(C(=C(C(=C1F)F)Cl)F)C(=O)O

Melting Point

112-116℃

Boiling Point

272℃

Relative Density

1.663

pKa

2.5

General Description

3-Chloro-2,4,5-trifluorobenzoic acid is a highly functionalized aromatic carboxylic acid that serves as a fundamental building block in the pharmaceutical industry. Characterized by a benzene ring substituted with a carboxyl group, a chlorine atom, and three fluorine atoms, this compound exhibits a precise substitution pattern that is critical for the development of advanced fluoroquinolone antibiotics. Its structural rigidity and electronic properties make it a highly desirable intermediate for sophisticated medicinal chemistry applications.

Mechanism of Action

As a key synthetic precursor, 3-chloro-2,4,5-trifluorobenzoic acid provides the polyfluorinated aryl core necessary for the pharmacophore of various antimicrobial drugs. The carboxylic acid functionality allows for convenient conversion into acid chlorides or active esters, facilitating subsequent condensation with amines or other nucleophiles to form the heterocyclic quinolone backbone. The electronic influence of the chlorine and fluorine substituents on the aromatic ring is essential for tuning the biological activity of the final antibiotic, particularly in its interaction with bacterial topoisomerase enzymes and its ability to penetrate cellular membranes.

Application

3-Chloro-2,4,5-trifluorobenzoic acid is primarily utilized as a core intermediate in the production of high-potency fluoroquinolone antibiotics such as Sitafloxacin. In the pharmaceutical industry, it is employed as a raw material for synthesizing active pharmaceutical ingredients (APIs) designed to combat severe multi-drug resistant bacterial infections. It also serves as a specialized reagent in chemical research for exploring the structure-activity relationship (SAR) of halogenated benzoic acid derivatives and as a scaffold in the development of other biologically active molecules requiring specific polyfluorinated aryl motifs.

3-chloro-2,4,5-trifluorobenzoic acid was employed as a pivotal synthetic intermediate in the development of novel C-7 carbon-substituted fluoroquinolones. This intermediate was readily obtained from 3-amino-2,4,5-trifluorobenzoic acid via a Sandmeyer protocol utilizing tert-butyl nitrite and copper(I) chloride.
The synthesis of the zwitterionic derivative, which demonstrated superior activity against wild-type Gram-negative strains compared to delafloxacin, was accomplished from 3-chloro-2,4,5-trifluorobenzoic acid through conversion to the corresponding acrylate intermediate. Activation of the carboxylic acid with oxalyl chloride, followed by sequential reaction with ethyl 3-(N,N-dimethylamino)acrylate and 2,6-diamino-3,5-difluoropyridine, furnished the fluoroquinolone core. Subsequent intramolecular cyclization and functionalization at the C-7 position with an azetidine moiety afforded the final product. This synthetic route was noted to be more atom-efficient and required minimal purification compared to previously reported methods.

Fig. 1 Novel C-7 carbon substituted fourth generation fluoroquinolones. (Kirk R.; et al. 2020)

References

Kirk R, et al. Novel C-7 carbon substituted fourth generation fluoroquinolones targeting N. Gonorrhoeae infections. Bioorganic & Medicinal Chemistry Letters, 2020, 30(20): 127428.

What is the role of 3-chloro-2,4,5-trifluorobenzoic acid in antibiotic manufacturing?

It acts as the essential aromatic precursor that forms the polyfluorinated core of the quinolone antibiotic scaffold.

How should 3-chloro-2,4,5-trifluorobenzoic acid be stored?

It should be stored in a cool, dry, and well-ventilated area in a tightly sealed container to maintain its chemical integrity.

How is the quality of 3-chloro-2,4,5-trifluorobenzoic acid verified?

The identity and purity are confirmed through sophisticated analytical techniques, including High-Performance Liquid Chromatography (HPLC) and Nuclear Magnetic Resonance (NMR) spectroscopy.

Can 3-chloro-2,4,5-trifluorobenzoic acid be used as a reagent in other areas of organic chemistry?

Yes, due to its specific functionalization, it is a valuable reagent in organic synthesis for introducing polyfluorinated benzoic groups into various complex structures.