4-Chloro-2-fluoroaniline
[CAS# 57946-56-2]

Identification

• Classification: Organic raw materials >> Organic fluorine compound >> Fluoroaniline series
• Name: 4-Chloro-2-fluoroaniline
• Synonyms: 4-Chloro-2-fluorobenzenamine
• Molecular Formula: C₆H₅ClFN
• Molecular Weight: 145.56
• CAS Registry Number: 57946-56-2
• EC Number: 261-034-1
• SMILES: C1=CC(=C(C=C1Cl)F)N

Properties

• Density: 1.299
• Boiling point: 104-107 °C (28 mmHg)
• Refractive index: 1.559-1.561
• Flash point: 98 °C
• Water solubility: slightly soluble

Safety Data

• Hazard Symbols: GHS06;GHS07;GHS08 Danger
• Risk Statements: H302-H311-H312-H315-H319-H332-H335-H373
• Safety Statements: P260-P261-P262-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P316-P317-P319-P321-P330-P332+P317-P337+P317-P361+P364-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Acute toxicity	Acute Tox.	4	H312
Acute toxicity	Acute Tox.	4	H332
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335
Acute toxicity	Acute Tox.	4	H302
Acute toxicity	Acute Tox.	3	H301
Specific target organ toxicity - repeated exposure	STOT RE	2	H373
Acute toxicity	Acute Tox.	2	H330
Acute toxicity	Acute Tox.	3	H311
Eye irritation	Eye Irrit.	2A	H319

Discovery and Applications

4-Chloro-2-fluoroaniline, a fluorinated aromatic amine with the chemical formula C6H5ClF-NH2, is notable for its unique combination of functional groups, which imparts significant reactivity and application potential in various fields. The compound was first synthesized in the mid-20th century as researchers sought to explore the properties of halogenated anilines, particularly in the context of pharmaceutical and agrochemical development.

The synthesis of 4-chloro-2-fluoroaniline typically involves the substitution of chlorine and fluorine atoms on the aniline ring, allowing for the introduction of these halogens at specific positions. This substitution is achieved through various methods, including electrophilic aromatic substitution, where the appropriate halogenating agents are employed. The presence of both chloro and fluoro groups enhances the compound's electrophilic character, making it an important intermediate in organic synthesis.

One of the primary applications of 4-chloro-2-fluoroaniline is in the pharmaceutical industry, where it serves as a key building block in the synthesis of various drug molecules. The compound is utilized in the development of pharmaceutical intermediates, particularly in the synthesis of antibacterial and antiviral agents. Its unique electronic properties, derived from the presence of the halogen substituents, facilitate the design of compounds that can interact effectively with biological targets, improving their therapeutic efficacy.

In addition to its pharmaceutical applications, 4-chloro-2-fluoroaniline is also employed in the agrochemical sector. It plays a crucial role in the synthesis of herbicides and pesticides, where its halogenated structure contributes to the desired biological activity. The compound's ability to inhibit specific biochemical pathways in target organisms makes it a valuable asset in crop protection strategies, enhancing agricultural productivity.

Furthermore, 4-chloro-2-fluoroaniline is utilized in dye and pigment manufacturing. The presence of both chlorine and fluorine enhances the stability and color properties of dyes, making them suitable for a variety of applications in textiles and coatings. Its use in these industries demonstrates the compound's versatility beyond pharmaceuticals and agrochemicals.

Despite its applications, the environmental and health impacts of using halogenated anilines like 4-chloro-2-fluoroaniline are of concern. Regulatory frameworks are in place to evaluate the safety of such compounds, ensuring that their usage does not pose undue risks to human health and the environment. Ongoing research aims to optimize the synthesis and application of this compound while addressing these safety concerns.

In summary, 4-chloro-2-fluoroaniline is a significant compound in organic chemistry, with diverse applications in pharmaceuticals, agrochemicals, and dye manufacturing. Its discovery and subsequent utilization underscore the importance of halogenated compounds in developing effective chemical solutions across multiple industries.

References

2008. Ortho-Selective Cross-Coupling of Fluorobenzenes with Grignard Reagents: Acceleration by Electron-Donating Ortho-Directing Groups. Synthesis, 2008(16).
DOI: 10.1055/s-2008-1067182

2011. Understanding of the mass spectrometric fragmentation pathways of a few potentially genotoxic haloaniline isomers in their protonated form by collision-induced dissociation. Journal of Pharmaceutical and Biomedical Analysis, 56(5).
DOI: 10.1016/j.jpba.2011.07.022

2012. FT-IR, FT-Raman, NMR studies and ab initio-HF, DFT-B3LYP vibrational analysis of 4-chloro-2-fluoroaniline. Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy, 97.
DOI: 10.1016/j.saa.2012.07.040