2-Chloro-5-trifluoromethylpyridine
[CAS# 52334-81-3]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyridine compound >> Methylpyridine
• Name: 2-Chloro-5-trifluoromethylpyridine
• Synonyms: 2-Chloro-5-(trifluoromethyl)pyridine; 2,5-CTF
• Molecular Formula: C₆H₃ClF₃N
• Molecular Weight: 181.54
• CAS Registry Number: 52334-81-3
• EC Number: 257-856-5
• SMILES: C1=CC(=NC=C1C(F)(F)F)Cl

Properties

• Density: 1.417
• Melting point: 29-33 °C
• Boiling point: 152 °C
• Flash point: 65 °C

Safety Data

• Hazard Symbols: GHS07;GHS08 Danger
• Risk Statements: H302+H332-H302-H315-H319-H332-H335-H370-H372
• Safety Statements: P260-P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P308+P316-P317-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Acute toxicity	Acute Tox.	4	H332
Specific target organ toxicity - repeated exposure	STOT RE	1	H372
Specific target organ toxicity - single exposure	STOT SE	1	H370
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335
Acute toxicity	Acute Tox.	4	H312
Eye irritation	Eye Irrit.	2A	H319

Discovery and Applications

2-Chloro-5-trifluoromethylpyridine is a valuable compound with the molecular formula C6H3ClF3N. The compound is known for its unique structure, which includes a chlorine atom and a trifluoromethyl group attached to a pyridine ring. This combination gives it unique chemical properties that make it useful in a variety of industrial and pharmaceutical applications.

The discovery of 2-chloro-5-trifluoromethylpyridine can be traced back to the exploration of fluorinated organic compounds, which are known for their stability and reactivity. Fluorinated compounds have been extensively studied for their important roles in medicinal chemistry, agrochemicals, and materials science. The incorporation of a trifluoromethyl group into an aromatic ring, such as pyridine, often enhances the chemical stability, lipophilicity, and biological activity of the compound, which are desirable properties in many applications.

One of the main applications of 2-chloro-5-trifluoromethylpyridine is in the pharmaceutical industry, where it is an important intermediate in the synthesis of various active pharmaceutical ingredients (APIs). Its unique structure makes it a building block for the creation of more complex molecules, especially in the development of drugs with improved efficacy and safety. The presence of chlorine and trifluoromethyl groups can significantly affect the biological activity of the resulting compounds, making 2-chloro-5-trifluoromethylpyridine a valuable tool for drug discovery and development.

In agrochemicals, 2-chloro-5-trifluoromethylpyridine is used as an intermediate in the synthesis of herbicides, fungicides, and insecticides. The stability and reactivity of the compound make it suitable for use in the manufacture of products that protect crops from pests and diseases, thereby increasing agricultural productivity. In particular, the trifluoromethyl group can increase the metabolic stability and environmental persistence of agrochemicals, thereby improving their effectiveness and longevity.

In addition, 2-chloro-5-trifluoromethylpyridine has applications in materials science, especially in the development of advanced materials such as liquid crystals and polymers. The unique electronic properties of the compound, imparted by the trifluoromethyl and chlorine groups, can affect the thermal and mechanical properties of these materials. This makes it a useful ingredient in the manufacture of high-performance materials for electronic devices, optical applications, and specialty coatings.

The synthesis of 2-chloro-5-trifluoromethylpyridine involves several chemical processes, usually starting with the chlorination and trifluoromethylation of pyridine. These reactions require precise control of reaction conditions to achieve the desired substitution pattern on the pyridine ring. Advances in synthetic chemistry have increased the efficiency and yield of these processes, making this compound more suitable for a variety of applications.

In terms of safety and environmental impact, the handling and disposal of 2-chloro-5-trifluoromethylpyridine requires careful consideration due to its potential hazards. As with many chemical intermediates, appropriate safety measures must be taken to protect workers and the environment from exposure. Research into more environmentally friendly synthetic methods and safer handling methods remains an important aspect of the use of this compound in industry.

References

2020. Good pyridine hunting: a biomimic compound, a modifier and a unique pharmacophore in agrochemicals. Chemistry of Heterocyclic Compounds, 56(12).
DOI: 10.1007/s10593-020-02843-w

2018. Concentration and Temperature Dependences of 2-Chloro-3-(trifluoromethyl)pyridine Solubilities in (DMF + Tetrahydrofuran) and (DMF + Isopropanol) Mixtures. Russian Journal of Physical Chemistry A, 92(13).
DOI: 10.1134/s003602441813006x

2007. Position-Flexible Elaboration of Halogenated Heterocycles: Metalated Species as Key Intermediates for Synthesis. Synlett, 2007(19).
DOI: 10.1055/s-2007-992384