2-Trifluoromethyl-5-bromopyridine
[CAS# 436799-32-5]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyridine compound >> Methylpyridine
• Name: 2-Trifluoromethyl-5-bromopyridine
• Synonyms: 5-Bromo-2-(trifluoromethyl)pyridine
• Molecular Formula: C₆H₃BrF₃N
• Molecular Weight: 225.99
• CAS Registry Number: 436799-32-5
• EC Number: 629-029-2
• SMILES: C1=CC(=NC=C1Br)C(F)(F)F

Properties

• Density: 1.7±0.1 g/cm³ Calc.^*
• Melting point: 40 - 43 °C (Expl.)
• Boiling point: 179.1±35.0 °C 760 mmHg (Calc.)^*, 207.7 - 210.4 °C (Expl.)
• Flash point: 62.1±25.9 °C (Calc.)^*
• Index of refraction: 1.471 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS06;GHS07 Danger
• Risk Statements: H301-H315-H319-H335
• Safety Statements: P261-P264-P264+P265-P270-P271-P280-P301+P316-P302+P352-P304+P340-P305+P351+P338-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
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.	3	H301
Skin sensitization	Skin Sens.	1B	H317
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411
Eye irritation	Eye Irrit.	2A	H319

• Transport Information: UN 2811

Discovery and Applications

2-Trifluoromethyl-5-bromopyridine is a chemical compound that belongs to the pyridine family, a class of heterocyclic compounds containing a nitrogen atom in a six-membered ring. It has gained attention due to its distinct chemical properties and potential applications in various fields, particularly in the synthesis of pharmaceuticals, agrochemicals, and materials science.

The compound is characterized by the presence of a trifluoromethyl group (-CF3) at the 2-position and a bromine atom at the 5-position on the pyridine ring. These substituents significantly influence the reactivity and properties of the molecule. The trifluoromethyl group is known for its electron-withdrawing properties, which can enhance the compound's stability and make it more reactive in certain chemical reactions. The bromine atom also plays a key role in reactivity, making the compound useful in specific synthetic transformations.

The discovery and development of 2-trifluoromethyl-5-bromopyridine are closely tied to the increasing interest in fluorinated and halogenated organic compounds, which have broad applications in medicinal chemistry and material science. The trifluoromethyl group, in particular, is widely recognized for its ability to alter the physical and chemical properties of organic molecules. Its presence can improve the pharmacological properties of drugs by enhancing their metabolic stability, bioavailability, and receptor binding affinity.

In medicinal chemistry, compounds like 2-trifluoromethyl-5-bromopyridine are used as intermediates in the synthesis of more complex molecules, including potential pharmaceuticals. The unique electronic properties imparted by the trifluoromethyl and bromine groups allow for the creation of molecules with enhanced biological activity. For example, these kinds of compounds are often involved in the development of kinase inhibitors, which are crucial for treating cancers, autoimmune diseases, and other disorders.

Beyond the pharmaceutical industry, 2-trifluoromethyl-5-bromopyridine is also of interest in the field of agrochemicals. Pyridine derivatives with halogen and trifluoromethyl substituents are often used to synthesize herbicides, insecticides, and fungicides. The trifluoromethyl group, in particular, increases the lipophilicity of the molecules, enabling better penetration through biological membranes, which can improve the efficacy of agrochemical agents.

In materials science, 2-trifluoromethyl-5-bromopyridine may be used in the preparation of specialized materials, such as polymers and liquid crystals. The incorporation of trifluoromethyl groups into these materials can modify their properties, including their thermal stability, mechanical strength, and electrical conductivity. This has applications in the development of advanced electronic devices, coatings, and other high-performance materials.

2-Trifluoromethyl-5-bromopyridine's applications extend beyond pharmaceuticals and agrochemicals. The molecule is useful in various chemical transformations, particularly in cross-coupling reactions such as Suzuki, Heck, and Sonogashira couplings. These reactions are important for the construction of complex molecular architectures, and the halogen and trifluoromethyl groups make 2-trifluoromethyl-5-bromopyridine a valuable reagent in these synthetic processes.

In summary, 2-trifluoromethyl-5-bromopyridine is a versatile compound with significant potential in multiple areas of chemical synthesis. Its unique structure, characterized by the trifluoromethyl and bromine substituents, contributes to its reactivity and utility in the development of pharmaceuticals, agrochemicals, and materials. The compound's role as an intermediate in various chemical reactions and its ability to influence the properties of the molecules it forms make it an important substance in both research and industrial applications.

References

2010. Synthesis of 3-Heteroaryloxindoles through t-BuOCl-Mediated Oxidation of 3-Heteroarylindoles. Synthesis, 2010(23).
DOI: 10.1055/s-0030-1258289

2012. Recent Developments on the Trifluoromethylation of (Hetero)Arenes. Chemistry - An Asian Journal, 7(7).
DOI: 10.1002/asia.201200211

2022. Trifluoromethylation of Prefunctionalized Arenes or Alkenes. Science of Synthesis, 1.
URL: https://science-of-synthesis.thieme.com/app/text/?id=SD-238-00138