3-Bromo-5-fluoropyridine
[CAS# 407-20-5]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyridine compound >> Fluoropyridine
• Name: 3-Bromo-5-fluoropyridine
• Molecular Formula: C₅H₃BrFN
• Molecular Weight: 175.99
• CAS Registry Number: 407-20-5
• EC Number: 627-401-9
• SMILES: C1=C(C=NC=C1Br)F

Properties

• Density: 1.7±0.1 g/cm³, Calc.^*
• Melting point: 24-28 °C (Expl.)
• Index of Refraction: 1.534, Calc.^*
• Boiling Point: 152.5±20.0 °C (760 mmHg), Calc.^*
• Flash Point: 46.0±21.8 °C, Calc.^*, 64 °C (Expl.)

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

Safety Data

• Hazard Symbols: GHS05;GHS07 Danger
• Risk Statements: H302-H315-H318-H319-H332-H335
• Safety Statements: P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P305+P354+P338-P317-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
Acute toxicity	Acute Tox.	4	H302
Specific target organ toxicity - single exposure	STOT SE	3	H335
Serious eye damage	Eye Dam.	1	H318
Eye irritation	Eye Irrit.	2	H319

Discovery and Applications

3-Bromo-5-fluoropyridine, with the molecular formula C5H3BrFN, is a halogenated pyridine derivative characterized by a bromine atom at the 3-position and a fluorine atom at the 5-position of the pyridine ring. This compound is a colorless to pale yellow liquid or solid, depending on temperature, and exhibits properties that make it valuable in the field of synthetic chemistry.

The discovery of halogenated pyridine derivatives like 3-bromo-5-fluoropyridine dates back to the development of organohalide chemistry in the early 20th century. Advances in electrophilic aromatic substitution and cross-coupling reactions enabled the selective introduction of halogen atoms into aromatic rings. Modern synthetic methods for producing 3-bromo-5-fluoropyridine typically involve direct halogenation of pyridine derivatives or multi-step synthesis using palladium-catalyzed reactions such as Suzuki or Buchwald-Hartwig coupling.

3-Bromo-5-fluoropyridine is widely used as a versatile building block in pharmaceutical and agrochemical industries. The presence of both bromine and fluorine atoms on the pyridine ring makes it an excellent precursor for further functionalization. The bromine group facilitates metal-catalyzed cross-coupling reactions, enabling the synthesis of more complex molecules. Meanwhile, the fluorine atom enhances the metabolic stability and bioactivity of the resulting compounds, which is particularly useful in drug discovery.

In pharmaceutical research, derivatives of 3-bromo-5-fluoropyridine are incorporated into molecules designed to treat a variety of conditions, including cancer, bacterial infections, and neurological disorders. The pyridine ring is a common pharmacophore that interacts with biological targets, and the addition of halogen atoms can optimize these interactions by improving binding affinity and pharmacokinetic properties. For example, fluorinated pyridines are found in kinase inhibitors and anti-inflammatory drugs, where the fluorine atom modulates molecular properties to enhance efficacy.

Agrochemical applications also benefit from 3-bromo-5-fluoropyridine as a starting material for synthesizing herbicides, fungicides, and insecticides. The halogenation pattern in this compound can contribute to the biological activity necessary to disrupt specific metabolic pathways in pests and weeds, improving crop protection.

In addition to pharmaceuticals and agrochemicals, 3-bromo-5-fluoropyridine plays a role in materials science. It is used in the synthesis of functional materials, including liquid crystals and advanced polymers, where its electronic properties and halogen substituents can influence the performance characteristics of the final material.

Recent research continues to explore new synthetic routes and applications for 3-bromo-5-fluoropyridine. Its utility in modern organic synthesis, particularly in the design of bioactive compounds and innovative materials, ensures its ongoing relevance in both industrial and academic research settings.

References

2010. Large-Scale Preparation of Aromatic Fluorides via Electrophilic Fluorination with Functionalized Aryl- or Heteroarylmagnesium Reagents. Synthesis, 2010(24).
DOI: 10.1055/s-0029-1218816