4-Bromo-2,6-difluoroaniline
[CAS 67567-26-4]

Identification

• Classification: Organic raw materials >> Organic fluorine compound >> Fluoroaniline series
• Name: 4-Bromo-2,6-difluoroaniline
• Molecular Formula: C₆H₄BrF₂N
• Molecular Weight: 208.00
• CAS Registry Number: 67567-26-4
• EC Number: 642-485-7
• SMILES: C1=C(C=C(C(=C1F)N)F)Br

Properties

• Density: 1.8±0.1 g/cm³ Calc.^*
• Melting point: 63 - 65 °C (Expl.)
• Boiling point: 188.2±35.0 °C 760 mmHg (Calc.)^*
• Flash point: 67.6±25.9 °C (Calc.)^*
• Index of refraction: 1.57 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H312-H315-H319-H332-H335
• Safety Statements: P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P304+P340-P305+P351+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	H332
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2	H319
Acute toxicity	Acute Tox.	4	H302
Acute toxicity	Acute Tox.	4	H312
Eye irritation	Eye Irrit.	2A	H319

chemBlink Chemical Story

4-Bromo-2,6-difluoroaniline is a halogenated aromatic amine in which a benzene ring is substituted with bromine at the 4-position, fluorine atoms at the 2- and 6-positions, and an amino group at the 1-position. Compounds of this type are important intermediates in organic synthesis and medicinal chemistry due to the combination of nucleophilic, electron-withdrawing, and sterically directing substituents. The amino group allows for derivatization to form amides, sulfonamides, or azo compounds, while the halogen substituents influence electronic density and reactivity of the aromatic ring, facilitating selective transformations.

Structurally, the molecule consists of a benzene ring with two electron-withdrawing fluorine atoms at the ortho positions relative to the amino group, and a bromine atom at the para position. The amino group is nucleophilic, capable of participating in acylation, sulfonylation, or diazotization reactions, while the bromine atom provides a site for cross-coupling reactions, such as Suzuki, Heck, or Buchwald–Hartwig reactions. The fluorine substituents not only modulate electronic properties but also provide steric hindrance, which can affect reaction selectivity and stability of derivatives.

The synthesis of 4-bromo-2,6-difluoroaniline is typically carried out via selective bromination of 2,6-difluoroaniline under controlled conditions, often using molecular bromine or N-bromosuccinimide (NBS) in the presence of a solvent such as acetic acid or an inert organic medium. Reaction conditions are optimized to prevent over-bromination or electrophilic substitution at undesired positions. The resulting compound is a stable, crystalline solid suitable for further chemical transformations.

In medicinal chemistry, halogenated anilines like 4-bromo-2,6-difluoroaniline are used as building blocks for the synthesis of bioactive molecules, including enzyme inhibitors, receptor ligands, and heterocyclic derivatives. The bromine atom allows for selective introduction of additional substituents via cross-coupling, while the amino group can be modified to generate amide or sulfonamide linkages, which are common in pharmaceutical compounds. The fluorine atoms improve metabolic stability, influence lipophilicity, and can enhance binding interactions through electronic effects.

Beyond pharmaceutical applications, 4-bromo-2,6-difluoroaniline serves as a versatile intermediate in organic synthesis. The combination of reactive amino and bromine substituents allows for sequential functionalization, while the electron-withdrawing fluorines provide control over regioselectivity in further electrophilic or nucleophilic aromatic substitutions. This makes it valuable for the preparation of heterocycles, fluorinated aromatic compounds, and functionalized scaffolds in material science or chemical research.

Overall, 4-bromo-2,6-difluoroaniline is a multifunctional halogenated aromatic amine with nucleophilic, electrophilic, and electronically tunable properties. Its combination of amino, bromine, and fluorine substituents makes it a valuable intermediate for organic synthesis, medicinal chemistry, and the development of bioactive or functionalized aromatic compounds.

References

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DOI: 10.1126/science.abo7201

2022. Cyclin-Dependent Kinase 4 and 6 Inhibitors as Breast Cancer Therapy: Research Progress and Prospects. Pharmaceutical Chemistry Journal.
DOI: 10.1007/s11094-022-02599-x

2020. Synthesis of pyrazinamide analogues and their antitubercular bioactivity. Medicinal Chemistry Research.
DOI: 10.1007/s00044-020-02626-0