3,5-Difluorobenzylamine: Properties, Handling & Lab Use Guide

3,5-Difluorobenzylamine is a fluorinated primary amine widely used as a versatile building block in pharmaceutical synthesis, medicinal chemistry research, and the preparation of agrochemical intermediates.

CAS Number

105184-38-1

Molecular Formula

C₇H₇F₂N

Molecular Weight

143.13 g/mol

Appearance

Colorless to pale yellow liquid

Functional Class

Primary benzylic amine; fluorinated aromatic building block

Aladdin SKU

D113488

Storage Condition

Store sealed under inert atmosphere, cool and dry, away from light

Chemical Identity and Physical Properties

3,5-Difluorobenzylamine (CAS 105184-38-1; Aladdin SKU D113488) is an aromatic primary amine bearing two fluorine substituents at the 3- and 5-positions of the benzyl ring. Its molecular formula is C₇H₇F₂N with a molecular weight of approximately 143.13 g/mol. The compound typically presents as a colorless to pale yellow liquid at room temperature.

The symmetrical placement of fluorine atoms at the meta positions confers distinctive electronic properties: the electron-withdrawing inductive effect of fluorine reduces the basicity of the amine nitrogen compared with unsubstituted benzylamine, while simultaneously enhancing metabolic stability of derived drug candidates by blocking oxidative aromatic hydroxylation. The C–F bonds also increase lipophilicity modestly relative to the parent benzylamine, influencing membrane permeability of derived compounds.

Key physicochemical parameters should be confirmed against the certificate of analysis (CoA) supplied with each lot, as exact values such as boiling point, density, and refractive index may vary slightly by batch.

Synthetic Applications and Research Uses

3,5-Difluorobenzylamine serves as a key building block across several areas of synthetic and medicinal chemistry:

• Amide bond formation: The primary amine reacts with activated carboxylic acids, acid chlorides, anhydrides, and NHS esters to produce amide bonds. The resulting amides are useful as pharmacophores and linkers in drug discovery programs.
• Reductive amination: The amine condenses with aldehydes or ketones in the presence of a reducing agent (e.g., sodium cyanoborohydride or sodium triacetoxyborohydride) to furnish secondary amines bearing the 3,5-difluorobenzyl motif.
• Urea and carbamate synthesis: Reaction with isocyanates or chloroformates provides urea and carbamate derivatives respectively, structural motifs common in kinase inhibitors and protease inhibitors.
• Sulfonamide formation: Treatment with sulfonyl chlorides under mild base yields sulfonamides valuable in antibacterial and antiviral research.
• Agrochemical intermediates: The fluorinated benzylamine scaffold is incorporated into herbicide and fungicide candidates requiring metabolic stability.

The 3,5-difluorobenzyl group appears in several investigational and approved drug scaffolds, making D113488 a regularly demanded reagent in pharmaceutical and biotechnology research laboratories.

Safe Handling, Storage, and Waste Disposal

Hazard overview: As a primary amine, 3,5-difluorobenzylamine is corrosive and may cause skin, eye, and respiratory tract irritation or burns. It should be treated as a potentially harmful chemical in accordance with GHS hazard guidelines. Always consult the Safety Data Sheet (SDS) before first use.

Personal protective equipment (PPE): Wear nitrile or neoprene gloves, chemical splash goggles, and a lab coat. When handling larger quantities or working in poorly ventilated areas, use a half-face respirator with organic vapour cartridges. Perform all operations in a fume hood.

Storage: Store the tightly sealed container under an inert atmosphere (nitrogen or argon) in a cool, dry, well-ventilated location away from direct light, heat sources, and incompatible materials such as strong acids, oxidisers, and acid chlorides. Recommended storage temperature is 2–8 °C for long-term preservation; short-term bench storage at room temperature is acceptable if the container is resealed promptly after use.

Waste disposal: Dispose of residues and contaminated materials as halogenated organic waste in accordance with local, national, and institutional regulations. Do not pour down the drain.

Quality, Purity, and Procurement Guidance

Purity considerations: For most synthetic applications in medicinal chemistry, a purity of ≥95% (GC) is suitable. Aladdin Scientific supplies 3,5-Difluorobenzylamine (D113488) with a certificate of analysis specifying purity, water content, and appearance for each lot. Researchers requiring higher purity for sensitive assays should request lot-specific CoA data prior to order placement.

Quantity selection: D113488 is available in multiple pack sizes to match project scale—from small quantities for exploratory chemistry to bulk quantities for process development. Contact Aladdin's technical sales team for quotations on custom quantities or bulk orders.

Verification on receipt: Upon receipt, inspect the container for damage or discolouration. Compare the lot number on the label with the CoA. If the compound has solidified due to cold shipping, warm gently to room temperature before opening. Record the date of first opening on the container.

Supplier traceability: Aladdin Scientific provides full lot traceability. Retain the CoA for regulatory, publication, and quality management records. For GLP or GMP contexts, confirm the appropriate grade with your Aladdin account manager before ordering.

Frequently asked questions

What is 3,5-Difluorobenzylamine used for in drug discovery?

3,5-Difluorobenzylamine is primarily used as a building block to introduce a metabolically stable, fluorine-substituted benzylamine motif into drug candidates. It participates in amide bond formation, reductive amination, urea synthesis, and sulfonamide coupling reactions, enabling the rapid assembly of compound libraries for medicinal chemistry SAR studies.

How should I store 3,5-Difluorobenzylamine (D113488) to maximise shelf life?

Store D113488 in a tightly sealed container under an inert atmosphere (nitrogen or argon) at 2–8 °C, away from light, moisture, strong acids, and oxidising agents. After each use, purge the headspace with inert gas before resealing. Under these conditions, the reagent is expected to remain stable for an extended period; always verify appearance and purity against the CoA before critical use.

Why do the fluorine substituents at the 3- and 5-positions matter for medicinal chemistry?

The symmetrical 3,5-difluoro substitution pattern reduces aromatic metabolic hydroxylation at those ring positions, thereby improving the metabolic stability of derived compounds. Fluorine's strong electronegativity also modulates the pKa of the amine and the overall lipophilicity (logP) of derivatives, fine-tuning pharmacokinetic parameters such as absorption and protein binding without substantially increasing molecular weight.

Is 3,5-Difluorobenzylamine compatible with reductive amination conditions?

Yes, 3,5-Difluorobenzylamine participates readily in reductive amination reactions. It condenses with aldehydes or ketones to form an imine or iminium intermediate, which is subsequently reduced by reagents such as sodium cyanoborohydride (NaBH₃CN) or sodium triacetoxyborohydride (NaBH(OAc)₃) in appropriate solvents such as methanol, dichloromethane, or 1,2-dichloroethane, typically at room temperature.

What safety precautions are essential when working with 3,5-Difluorobenzylamine?

Always work in a well-ventilated fume hood and wear nitrile gloves, chemical splash goggles, and a lab coat. 3,5-Difluorobenzylamine is corrosive and can irritate or burn skin, eyes, and the respiratory tract. In case of skin contact, wash immediately with copious water; for eye exposure, irrigate continuously and seek medical attention. Dispose of waste as halogenated organic solvent waste per institutional regulations.

References

1. Aladdin Scientific Product Page: 3,5-Difluorobenzylamine, SKU D113488. Aladdin Scientific Corp.
2. Gillis, E. P.; Eastman, K. J.; Hill, M. D.; Donnelly, D. J.; Meanwell, N. A. Applications of Fluorine in Medicinal Chemistry. J. Med. Chem. 2015, 58, 8315–8359. doi:10.1021/acs.jmedchem.5b00258
3. Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Fluorine in medicinal chemistry. Chem. Soc. Rev. 2008, 37, 320–330. doi:10.1039/b610702a
4. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford University Press: Oxford, 2012. Chapter on Amines and Reductive Amination.

Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.