2-Chloro-4-(trifluoromethyl)pyridine
[CAS# 81565-18-6]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyridine compound >> Methylpyridine
• Name: 2-Chloro-4-(trifluoromethyl)pyridine
• Molecular Formula: C₆H₃ClF₃N
• Molecular Weight: 181.54
• CAS Registry Number: 81565-18-6
• EC Number: 617-242-3
• SMILES: C1=CN=C(C=C1C(F)(F)F)Cl

Properties

• Density: 1.411
• Melting point: -19 °C
• Boiling point: 146-147 °C
• Refractive index: 1.4490
• Flash point: 40 °C

Safety Data

• Hazard Symbols: GHS02;GHS07 Warning
• Risk Statements: H226-H302-H312-H315-H319-H335
• Safety Statements: P210-P233-P240-P241-P242-P243-P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P303+P361+P353-P304+P340-P305+P351+P338-P317-P319-P321-P330-P332+P317-P337+P317-P362+P364-P370+P378-P403+P233-P403+P235-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2	H319
Flammable liquids	Flam. Liq.	3	H226
Acute toxicity	Acute Tox.	4	H302
Acute toxicity	Acute Tox.	4	H312
Eye irritation	Eye Irrit.	2A	H319
Acute toxicity	Acute Tox.	3	H331
Acute toxicity	Acute Tox.	3	H301
Acute toxicity	Acute Tox.	4	H332

• Transport Information: UN 1993

Discovery and Applications

2-Chloro-4-(trifluoromethyl)pyridine is a significant chemical compound known for its versatility in various industrial and scientific applications. The discovery and subsequent utilization of this compound have made considerable impacts in the fields of pharmaceuticals, agrochemicals, and materials science.

2-Chloro-4-(trifluoromethyl)pyridine is a halogenated pyridine derivative. Its structure consists of a pyridine ring with a chlorine atom at the second position and a trifluoromethyl group at the fourth position. This particular arrangement of functional groups imparts unique chemical properties to the compound, making it highly valuable as an intermediate in organic synthesis.

The discovery of 2-Chloro-4-(trifluoromethyl)pyridine can be traced back to the mid-20th century when chemists were exploring new ways to introduce trifluoromethyl groups into aromatic compounds. The trifluoromethyl group is well-known for its ability to enhance the biological activity, stability, and lipophilicity of organic molecules. This made 2-Chloro-4-(trifluoromethyl)pyridine an attractive target for synthesis and study.

In the pharmaceutical industry, 2-Chloro-4-(trifluoromethyl)pyridine is widely used as a building block for the synthesis of various bioactive compounds. Its structure allows for the introduction of other functional groups, facilitating the creation of complex molecules with potential therapeutic effects. Researchers have utilized this compound in the development of drugs targeting a range of conditions, from infectious diseases to cancer. The presence of the trifluoromethyl group often enhances the efficacy and pharmacokinetic properties of these drugs.

In agrochemicals, 2-Chloro-4-(trifluoromethyl)pyridine plays a crucial role in the synthesis of herbicides, fungicides, and insecticides. Its ability to act as a precursor in the creation of active ingredients helps in producing compounds that are more effective and selective against pests and diseases. The compound’s chemical stability and ability to enhance the bioactivity of agrochemicals contribute to improved crop protection and yield.

Moreover, 2-Chloro-4-(trifluoromethyl)pyridine is also utilized in materials science. Its incorporation into polymers and other materials can impart desirable properties such as increased thermal stability, chemical resistance, and hydrophobicity. These characteristics are valuable in the development of advanced materials for various industrial applications, including coatings, electronics, and specialty chemicals.

The synthesis of 2-Chloro-4-(trifluoromethyl)pyridine typically involves halogenation and trifluoromethylation reactions. Advances in synthetic methodologies have improved the efficiency and yield of these processes, making the compound more accessible for research and industrial use.

References

2001. Synthesis of Novel Analogues of Marine Indole Alkaloids: Mono(indolyl)-4-trifluoromethylpyridines and Bis(indolyl)-4-trifluoromethylpyridines as Potential Anticancer Agents. Bioorganic & Medicinal Chemistry, 9(7).
DOI: 10.1016/s0968-0896(01)00070-0

2015. Decomposition of Difluorocarbene for Trifluoromethylation. Synfacts, 11(3).
DOI: 10.1055/s-0034-1380314

2013. Enantioselective Arylation. Science of Synthesis.
URL: https://science-of-synthesis.thieme.com/app/text/?id=SD-126-00055