2-Fluoro-4-cyanobenzyl bromide
[CAS# 105942-09-4]

Identification

• Classification: Organic raw materials >> Nitrile compound
• Name: 2-Fluoro-4-cyanobenzyl bromide
• Synonyms: 4-Cyano-2-fluorobenzyl bromide; 4-(Bromomethyl)-3-fluorobenzonitrile
• Molecular Formula: C₈H₅BrFN
• Molecular Weight: 214.03
• CAS Registry Number: 105942-09-4
• EC Number: 675-411-7
• SMILES: C1=CC(=C(C=C1C#N)F)CBr

Properties

• Density: 1.6±0.1 g/cm³ Calc.^*
• Melting point: 75 - 79 ºC (Decomposes) (Expl.)
• Boiling point: 276.4±30.0 ºC 760 mmHg (Calc.)^*
• Flash point: 121.0±24.6 ºC (Calc.)^*
• Index of refraction: 1.564 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS05;GHS06;GHS07 Danger
• Hazard Statements: H301-H302-H312-H314-H315-H319-H332
• Precautionary Statements: P260-P261-P264-P264+P265-P270-P271-P280-P301+P316-P301+P317-P301+P330+P331-P302+P352-P302+P361+P354-P304+P340-P305+P351+P338-P305+P354+P338-P316-P317-P321-P330-P332+P317-P337+P317-P362+P364-P363-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin corrosion	Skin Corr.	1B	H314
Acute toxicity	Acute Tox.	3	H301
Acute toxicity	Acute Tox.	4	H332
Eye irritation	Eye Irrit.	2	H319
Acute toxicity	Acute Tox.	4	H302
Acute toxicity	Acute Tox.	4	H312
Skin irritation	Skin Irrit.	2	H315

Discovory and Applicatios

2-Fluoro-4-cyanobenzyl bromide is an aromatic halide compound that has attracted attention for its reactivity and role as an intermediate in organic synthesis. The compound features a benzene ring substituted at the 2-position with a fluorine atom, at the 4-position with a nitrile (–CN) group, and at the benzyl position with a bromomethyl (–CH₂Br) group. This particular substitution pattern imparts useful electronic and steric characteristics that influence its chemical behavior and make it valuable in multiple synthetic applications.

The discovery and availability of 2-fluoro-4-cyanobenzyl bromide stem from advancements in the selective halogenation and functionalization of fluoroaromatic compounds. The synthesis typically involves the bromination of 2-fluoro-4-cyanotoluene under controlled conditions to install the benzylic bromide functionality. This process is generally achieved using N-bromosuccinimide (NBS) in the presence of a radical initiator such as azobisisobutyronitrile (AIBN), ensuring the selective substitution of a hydrogen atom on the methyl group without affecting the aromatic ring. The presence of the electron-withdrawing nitrile and fluorine substituents further stabilizes the intermediate benzylic radical during the bromination process, leading to high reaction efficiency.

As a benzylic bromide, 2-fluoro-4-cyanobenzyl bromide is a reactive electrophile commonly used in nucleophilic substitution reactions. The bromide serves as a good leaving group, allowing for the introduction of a wide variety of nucleophiles, including amines, thiols, alcohols, and organometallic reagents. Its application is widespread in the synthesis of pharmaceutical intermediates, agrochemicals, and specialty fine chemicals. The nitrile group on the aromatic ring serves as a versatile functional handle for further transformations, such as reduction to primary amines or conversion to carboxylic acids, amides, or tetrazoles.

The compound has been used as a key intermediate in the development of central nervous system (CNS)-active agents, kinase inhibitors, and other biologically active molecules. The substitution pattern of fluorine and nitrile groups is often found in bioactive scaffolds due to their influence on metabolic stability, lipophilicity, and binding affinity to biological targets. In particular, the presence of fluorine at the ortho-position relative to the benzylic position can influence the reactivity of the compound in metal-catalyzed reactions and enhance regioselectivity.

2-Fluoro-4-cyanobenzyl bromide has also been utilized in the synthesis of labeled compounds for use in biochemical assays and diagnostic imaging. The incorporation of fluorinated aromatic groups into radiotracers and enzyme inhibitors helps in studying molecular interactions and metabolic pathways. Moreover, its bromide functionality allows for coupling reactions with organolithium or Grignard reagents, facilitating the construction of complex carbon frameworks.

In material science, derivatives of this compound have been used in the preparation of fluorinated polymers and surface-modifying agents. The ability to selectively modify the benzylic position without disturbing the aromatic substituents enables fine-tuning of polymer properties such as thermal stability and chemical resistance. The nitrile group also enables further post-polymerization modification or participation in click-type chemistry for cross-linking or surface immobilization.

Owing to its reactivity, 2-fluoro-4-cyanobenzyl bromide must be handled with care, especially under basic or moist conditions where hydrolysis or elimination reactions may occur. Proper storage under dry and inert conditions is necessary to preserve its integrity and performance in synthetic applications.

Overall, 2-fluoro-4-cyanobenzyl bromide is a well-characterized and widely employed intermediate in organic synthesis, valued for its dual functionalization and suitability in nucleophilic substitution and further derivatization.

References

2022. Osilodrostat. Pharmaceutical Substances