3-Fluorobenzyl chloride
[CAS# 456-42-8]

Identification

• Classification: Chemical reagent >> Organic reagent >> Acid halide
• Name: 3-Fluorobenzyl chloride
• Synonyms: m-Fluorobenzyl chloride; alpha-Chloro-m-fluorotoluene; 1-(Chloromethyl)-3-fluoro-benzene
• Molecular Formula: C₇H₆ClF
• Molecular Weight: 144.57
• CAS Registry Number: 456-42-8
• EC Number: 207-264-8
• SMILES: C1=CC(=CC(=C1)F)CCl

Properties

• Density: 1.194±0.1 g/cm³, Calc.^*, 1.212 g/mL (20 °C) (Expl.)
• Index of Refraction: 1.505, Calc.^*, 1.511 (Expl.)
• Boiling Point: 173.3±15.0 °C (760 mmHg), Calc.^*, 176-177 °C (Expl.)
• Flash Point: 58.9±0.0 °C, Calc.^*, 58 °C (Expl.)

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

Safety Data

• Hazard Symbols: GHS02;GHS05 Danger
• Risk Statements: H226-H314
• Safety Statements: P210-P233-P240-P241-P242-P243-P260-P264-P280-P301+P330+P331-P302+P361+P354-P303+P361+P353-P304+P340-P305+P354+P338-P316-P321-P363-P370+P378-P403+P235-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin corrosion	Skin Corr.	1B	H314
Flammable liquids	Flam. Liq.	3	H226
Specific target organ toxicity - single exposure	STOT SE	3	H335
Serious eye damage	Eye Dam.	1	H318
Acute toxicity	Acute Tox.	4	H302
Substances or mixtures corrosive to metals	Met. Corr.	1	H290
Acute toxicity	Acute Tox.	4	H312
Chronic hazardous to the aquatic environment	Aquatic Chronic	3	H412
Eye irritation	Eye Irrit.	2	H319

Discovery and Applications

3-Fluorobenzyl chloride is an organofluorine compound that has gained significance in synthetic chemistry due to its versatile reactivity. This compound consists of a benzyl chloride framework with a fluorine atom at the meta position, which influences its chemical behavior. The introduction of fluorine enhances the compound’s stability and modulates its electronic properties, making it a valuable intermediate in organic synthesis.

The discovery of 3-fluorobenzyl chloride can be traced to the broader study of benzyl halides and fluorinated aromatic compounds. Early investigations into halogenated benzyl derivatives focused on their reactivity in nucleophilic substitution and coupling reactions. The selective fluorination of benzyl chlorides was later optimized to improve their application in pharmaceutical and agrochemical research.

One of the primary applications of 3-fluorobenzyl chloride is in the synthesis of pharmaceutical compounds. The presence of fluorine can enhance metabolic stability, bioavailability, and receptor binding affinity, making fluorinated derivatives highly desirable in drug development. It serves as a key intermediate in the production of biologically active molecules, including antiviral, anti-inflammatory, and central nervous system drugs. Additionally, it is used in the synthesis of fluorinated ligands for medicinal chemistry research.

Beyond pharmaceuticals, 3-fluorobenzyl chloride finds application in agrochemicals, where it is used in the development of pesticides and herbicides. The fluorine substituent contributes to improved efficacy and environmental stability. The compound also plays a role in material science, particularly in the functionalization of polymers and surface coatings, where fluorinated groups provide enhanced resistance to degradation.

As research into fluorinated benzyl derivatives continues, 3-fluorobenzyl chloride remains a critical building block in the development of advanced materials and bioactive compounds. Ongoing studies explore its reactivity with novel catalysts and green chemistry approaches to improve its synthetic accessibility and reduce environmental impact.

References

2019. Safinamide. Pharmaceutical Substances.
URL: https://pharmaceutical-substances.thieme.com/ps/search-results?docUri=KD-19-0136

2017. Discovery of tetrahydro-ß-carboline derivatives as a new class of phosphodiesterase 4 inhibitors. Medicinal Chemistry Research, 26(10).
DOI: 10.1007/s00044-017-2011-x

2010. N-[3-Chloro-4-(3-fluorobenzyloxy)phenyl]-6-iodoquinazolin-4-amine. Acta Crystallographica Section E Structure Reports Online, 66(7).
DOI: 10.1107/s1600536810021847