3,5-Difluorobenzyl bromide
[CAS# 141776-91-2]

Identification

• Classification: Organic raw materials >> Hydrocarbon compounds and their derivatives >> Hydrocarbon halide
• Name: 3,5-Difluorobenzyl bromide
• Synonyms: 1-(Bromomethyl)-3,5-difluorobenzene
• Molecular Formula: C₇H₅BrF₂
• Molecular Weight: 207.01
• CAS Registry Number: 141776-91-2
• EC Number: 627-819-1
• SMILES: C1=C(C=C(C=C1F)F)CBr

Properties

• Density: 1.6±0.1 g/cm³, Calc.^*, 1.6 g/mL (Expl.)
• Index of Refraction: 1.523, Calc.^*, 1.521 (Expl.)
• Boiling Point: 205.1±0.0 °C (760 mmHg), Calc.^*, 65 °C (4.5 mmHg) (Expl.)
• Flash Point: 81.7±0.0 °C, Calc.^*, 81 °C (Expl.)

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

Safety Data

• Hazard Symbols: GHS05 Danger
• Risk Statements: H314
• Safety Statements: P260-P264-P280-P301+P330+P331-P302+P361+P354-P304+P340-P305+P354+P338-P316-P321-P363-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin corrosion	Skin Corr.	1B	H314
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335
Serious eye damage	Eye Dam.	1	H318
Flammable liquids	Flam. Liq.	4	H227
Skin corrosion	Skin Corr.	1C	H314
Substances or mixtures corrosive to metals	Met. Corr.	1	H290

• Transport Information: UN 3265

Discovery and Applications

3,5-Difluorobenzyl bromide is an organic halogenated compound characterized by a benzene ring substituted with two fluorine atoms at the 3- and 5-positions and a bromomethyl group at the 1-position. This combination of halogen functionalities imparts unique reactivity to the molecule, making it a versatile intermediate in chemical synthesis. Its applications span pharmaceuticals, agrochemicals, and materials science.

The discovery of 3,5-difluorobenzyl bromide arose from efforts to explore the chemical potential of fluorinated benzyl halides. Fluorinated compounds are known for their enhanced stability, lipophilicity, and ability to form strong interactions with biological targets. By introducing a bromomethyl group into a fluorinated aromatic system, chemists gained access to a reactive intermediate capable of undergoing nucleophilic substitution and cross-coupling reactions. This has made 3,5-difluorobenzyl bromide a crucial building block in the preparation of more complex organic molecules.

In the pharmaceutical industry, 3,5-difluorobenzyl bromide is valued as a precursor in the synthesis of biologically active compounds. The fluorine atoms in the molecule influence metabolic stability and binding affinity to biological targets, while the bromine group facilitates its functionalization through substitution reactions. It has been employed in the development of inhibitors, receptor modulators, and drug candidates targeting cancer, inflammation, and central nervous system disorders.

In agrochemical applications, 3,5-difluorobenzyl bromide serves as a key intermediate in the synthesis of herbicides, fungicides, and insecticides. Fluorination enhances the bioactivity and environmental stability of these compounds, improving their efficacy and persistence in agricultural settings. By incorporating 3,5-difluorobenzyl bromide into active agrochemical ingredients, researchers have achieved formulations that are more selective and potent.

Materials science has also benefited from the inclusion of 3,5-difluorobenzyl bromide in polymer chemistry and the design of functional materials. Its ability to undergo polymerization or attach to larger frameworks makes it useful for producing fluorinated materials with desirable thermal and chemical properties. These materials find applications in coatings, membranes, and advanced electronics, where their robustness and performance are crucial.

Synthetic approaches to 3,5-difluorobenzyl bromide typically involve bromination of 3,5-difluorotoluene, a process optimized for yield and purity. Efforts to improve the synthesis focus on minimizing by-products and adopting greener reaction conditions. As the demand for fluorinated intermediates continues to grow, advances in sustainable and cost-effective manufacturing techniques for this compound are actively pursued.

The safety and handling of 3,5-difluorobenzyl bromide require careful attention due to its reactive nature and potential for generating toxic by-products. Research into its environmental impact, biodegradability, and safe disposal is ongoing to ensure its responsible use in industrial and research settings.

In conclusion, 3,5-difluorobenzyl bromide is a vital compound in synthetic chemistry, enabling the development of innovative pharmaceuticals, agrochemicals, and materials. Its chemical versatility and the functional properties conferred by fluorine atoms ensure its continued importance in various scientific and industrial domains.

References

2024. 1,2,4-benzothiadiazine-1,1-dioxide Analogues: Iron-Catalyzed Synthesis, Cytotoxic Evaluation and in silico Assessment. Pharmaceutical Chemistry Journal, 58(7).
DOI: 10.1007/s11094-024-03248-1

2023. Synthesis and clinical application of new drugs approved by FDA in 2022. Molecular Biomedicine, 4(1).
DOI: 10.1186/s43556-023-00138-y

2017. One-Pot Coupling-Cyclization-Alkylation Synthesis of 1,2,5-Trisubstituted 7-Azaindoles in a Consecutive Three-component Fashion. Synlett, 28(12).
DOI: 10.1055/s-0036-1590837