4-Bromo-2-fluorobiphenyl
[CAS# 41604-19-7]

Identification

• Classification: Organic raw materials >> Hydrocarbon compounds and their derivatives >> Hydrocarbon halide
• Name: 4-Bromo-2-fluorobiphenyl
• Synonyms: 4-Bromo-2-fluoro-1,1'-biphenyl
• Molecular Formula: C₁₂H₈BrF
• Molecular Weight: 251.10
• CAS Registry Number: 41604-19-7
• EC Number: 255-453-9
• SMILES: C1=CC=C(C=C1)C2=C(C=C(C=C2)Br)F

Properties

• Density: 1.4±0.1 g/cm³ Calc.^*, 1.4 g/mL (Expl.)
• Melting point: 39 - 41 °C (Expl.)
• Boiling point: 298.8±20.0 °C 760 mmHg (Calc.)^*, 418.3 °C (Expl.)
• Flash point: 138.3±16.6 °C (Calc.)^*, 38 °C (Expl.)
• Solubility: water:
• Index of refraction: 1.583 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07;GHS09 Warning
• Risk Statements: H302-H315-H319-H400-H410
• Safety Statements: P264-P264+P265-P270-P273-P280-P301+P317-P302+P352-P305+P351+P338-P321-P330-P332+P317-P337+P317-P362+P364-P391-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400
Skin irritation	Skin Irrit.	2	H315
Chronic hazardous to the aquatic environment	Aquatic Chronic	1	H410
Eye irritation	Eye Irrit.	2	H319

• Transport Information: UN 3152

Discovery and Applications

4-Bromo-2-fluorobiphenyl is an aromatic compound consisting of a biphenyl core substituted with a bromine atom at the 4-position and a fluorine atom at the 2-position on one of the phenyl rings. Biphenyl itself comprises two benzene rings connected by a single bond, allowing for rotational flexibility between the rings. The substitution pattern with bromine and fluorine atoms influences the electronic properties, steric effects, and reactivity of the molecule.

Synthesis of 4-bromo-2-fluorobiphenyl is typically achieved through cross-coupling reactions, such as the Suzuki–Miyaura or Ullmann coupling, using appropriately substituted halobenzenes or boronic acids as starting materials. The presence of both bromine and fluorine requires selective functionalization strategies to ensure substitution occurs at the desired positions, often involving protecting groups or stepwise reactions.

Chemically, the bromine substituent serves as a reactive site for further functionalization through palladium-catalyzed cross-coupling reactions, enabling the introduction of various aryl, vinyl, or alkyl groups. The fluorine atom, being highly electronegative, affects the electron density distribution of the aromatic system, influencing both physical properties and reactivity. Fluorine substitution can also enhance metabolic stability and lipophilicity when used in pharmaceutical design.

Applications of 4-bromo-2-fluorobiphenyl are primarily in organic synthesis as an intermediate for the construction of more complex biphenyl derivatives. Such compounds find use in materials science, agrochemicals, and pharmaceuticals. The halogen substituents provide handles for further chemical modification, allowing for the design of molecules with tailored electronic and steric characteristics.

Analytical characterization includes nuclear magnetic resonance (¹H and ¹³C NMR) spectroscopy to confirm the aromatic proton and carbon environments, mass spectrometry to verify molecular weight and fragmentation, and infrared spectroscopy to detect characteristic C–Br and C–F bond vibrations. Chromatographic methods such as gas chromatography (GC) or high-performance liquid chromatography (HPLC) may be employed to assess purity.

Physically, 4-bromo-2-fluorobiphenyl is typically a crystalline solid with moderate solubility in organic solvents such as dichloromethane, chloroform, and tetrahydrofuran. Its melting point depends on purity and crystallinity.

In summary, 4-bromo-2-fluorobiphenyl is a halogenated biphenyl derivative valued as a synthetic intermediate for further functionalization. The combination of bromine and fluorine substituents allows for diverse chemical transformations and modulation of molecular properties relevant in various chemical industries.

References

2022. Palladium-catalyzed enantioselective carbonylation reactions. Science China Chemistry, 65(1).
DOI: 10.1007/s11426-021-1165-6

2018. Synthesis and characterization of Ni(II) complex functionalized silica-based magnetic nanocatalyst and its application in C-N and C-C cross-coupling reactions. Molecular Diversity, 22(4).
DOI: 10.1007/s11030-018-9888-2

2017. Green Synthesis of Pd Nanoparticles Supported on Magnetic Graphene Oxide by Origanum vulgare Leaf Plant Extract: Catalytic Activity in the Reduction of Organic Dyes and Suzuki-Miyaura Cross-Coupling Reaction. Catalysis Letters, 147(12).
DOI: 10.1007/s10562-017-2220-4