3-Chloro-2,6-difluorobenzonitrile: Handling & Application Guide

3-Chloro-2,6-difluorobenzonitrile is a polyfunctional halogenated aromatic building block widely employed in pharmaceutical and agrochemical synthesis, offering orthogonal reactivity through its chloro, fluoro, and nitrile substituents.

CAS Number

To be confirmed — see SDS (review flag)

Molecular Formula

C7H2ClF2N

Molecular Weight

174.55 g/mol

SKU / Product Code

C124025

Key Functional Groups

Nitrile (–CN), two fluorines (ortho/para-activating), one chlorine

Recommended Storage

Cool, dry, well-ventilated location; away from moisture and incompatible oxidizers (verify with SDS)

Appearance

White to off-white crystalline solid (typical; verify with CoA)

Chemical Identity and Properties

3-Chloro-2,6-difluorobenzonitrile (SKU: C124025; molecular formula C₇H₂ClF₂N; MW ≈ 174.55 g/mol) is a trisubstituted aromatic compound bearing two fluorine atoms at the 2- and 6-positions, a chlorine atom at the 3-position, and a nitrile group at the 1-position. This combination of electron-withdrawing substituents renders the aromatic ring highly electron-deficient, which is the primary driver of its utility in nucleophilic aromatic substitution (S_NAr) reactions.

The strong electron-withdrawing nitrile group, combined with the flanking fluorines, makes the ring exceptionally activated toward S_NAr at the fluorine-bearing positions. The chlorine at C-3 provides an additional handle for metal-catalyzed cross-coupling chemistry (e.g., Pd-catalyzed Suzuki or Negishi coupling), giving synthetic chemists the ability to functionalize the molecule orthogonally. Always consult the current Certificate of Analysis (CoA) from Aladdin Scientific for lot-specific purity and physical data.

Safe Handling and Storage Guidelines

Personal Protective Equipment (PPE): When handling 3-Chloro-2,6-difluorobenzonitrile, wear appropriate PPE including chemical-resistant gloves (e.g., nitrile), safety goggles, and a laboratory coat. Work in a fume hood to avoid inhalation of dust or vapors. The nitrile and halogen functionality can pose irritation hazards to the skin, eyes, and respiratory tract.

Storage: Store the compound in a tightly sealed container in a cool (typically 2–8 °C or room temperature as specified on the label), dry, and well-ventilated area, away from moisture, strong oxidizers, and sources of ignition. Consult the Safety Data Sheet (SDS) for full hazard classification, GHS pictograms, first-aid measures, and disposal instructions before use.

Disposal: Dispose of waste material and containers in accordance with local, regional, and national regulations. Do not pour down drains. Consult your institution's Environmental Health and Safety (EHS) office for guidance on halogenated aromatic waste streams.

Note: All safety data provided here is general guidance. The official SDS supplied by Aladdin Scientific is the authoritative document and must be consulted prior to use.

Synthetic Applications and Reaction Protocols

Nucleophilic Aromatic Substitution (S_NAr): The electron-deficient aromatic ring of 3-Chloro-2,6-difluorobenzonitrile is highly amenable to S_NAr displacement of the fluorine atoms by O-, N-, or S-nucleophiles (e.g., amines, alcohols, thiols). Reactions are typically conducted in polar aprotic solvents such as DMF, DMSO, or NMP, in the presence of an inorganic base (e.g., K₂CO₃, Cs₂CO₃) at elevated temperatures (60–120 °C). Selectivity between the two fluorines can sometimes be achieved by tuning temperature, solvent, and nucleophile stoichiometry.

Transition-Metal-Catalyzed Cross-Coupling: The C–Cl bond at position 3 is suitable for palladium-catalyzed cross-coupling reactions, including Suzuki–Miyaura (with arylboronic acids), Negishi, and Buchwald–Hartwig amination reactions. Standard Pd(0)/Pd(II) catalyst systems (e.g., Pd(PPh₃)₄, Pd₂(dba)₃/ligand) in degassed solvents under inert atmosphere are recommended.

Nitrile Group Transformations: The nitrile can be hydrolyzed to a carboxylic acid or amide, reduced to an amine (via LiAlH₄ or catalytic hydrogenation), or converted to a tetrazole via [3+2] cycloaddition with azide sources — all of which are valuable transformations in medicinal chemistry scaffold diversification.

Pharmaceutical and Agrochemical Intermediates: Difluoro- and chloro-substituted benzonitriles are established intermediates in the preparation of active pharmaceutical ingredients (APIs) and crop-protection agents. Their fluorinated character confers metabolic stability and improved lipophilicity to drug candidates.

Quality, Purity, and Ordering Information

Specification and Purity: Aladdin Scientific's 3-Chloro-2,6-difluorobenzonitrile (SKU: C124025) is supplied with a Certificate of Analysis detailing purity (typically assessed by GC or HPLC), appearance, and identity confirmation by NMR or MS. Always verify the current lot specifications on the CoA before commencing sensitive synthetic work.

Ordering: This product can be ordered directly through the Aladdin Scientific website using SKU C124025. For bulk quantities, custom packaging, or institutional procurement, contact the Aladdin Scientific sales team. Pricing and availability are subject to change; refer to the current catalog or contact customer service for up-to-date information.

Documentation: SDS, CoA, and technical data sheets are available for download from the product page. Ensure all regulatory and import/export documentation requirements are met for your jurisdiction prior to ordering.

Frequently asked questions

What solvents and conditions are recommended for SNAr reactions with 3-Chloro-2,6-difluorobenzonitrile?

Polar aprotic solvents such as DMF, DMSO, or NMP are generally recommended, with an inorganic base (e.g., K₂CO₃ or Cs₂CO₃) and temperatures in the range of 60–120 °C. The highly electron-deficient ring facilitates fluorine displacement by N-, O-, or S-nucleophiles under these conditions. Reaction optimization (temperature, equivalents, solvent) may be required for selectivity between the two fluorines.

Can the chlorine substituent in 3-Chloro-2,6-difluorobenzonitrile be selectively functionalized via cross-coupling?

Yes. The C–Cl bond at the 3-position is amenable to palladium-catalyzed cross-coupling reactions, including Suzuki–Miyaura, Negishi, and Buchwald–Hartwig amination, under standard inert-atmosphere conditions. Care should be taken to select reaction conditions that preserve the C–F bonds when orthogonal functionalization is desired.

What are the main safety precautions when working with 3-Chloro-2,6-difluorobenzonitrile?

Always work in a chemical fume hood, wear nitrile gloves, safety goggles, and a lab coat. The compound may cause skin, eye, and respiratory irritation. Consult the Aladdin Scientific SDS for full GHS hazard classification and first-aid procedures before handling. Dispose of waste according to local regulations for halogenated aromatic compounds.

How should I confirm the identity and purity of the received 3-Chloro-2,6-difluorobenzonitrile batch?

Aladdin Scientific provides a Certificate of Analysis (CoA) with each lot, specifying purity (typically by GC or HPLC), appearance, and identity data (NMR or MS). Download the CoA for your specific lot number from the product page on our website. If additional characterization is required, ¹H NMR, ¹⁹F NMR, and GC-MS are standard techniques for verification.

References

1. Aladdin Scientific. 3-Chloro-2,6-difluorobenzonitrile (C124025) — Product Page and Certificate of Analysis. Aladdin Scientific.
2. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford University Press: Oxford, 2012. (General reference for SNAr and cross-coupling chemistry.)
3. Fluorine in Medicinal Chemistry and Chemical Biology; Ojima, I., Ed.; Wiley-Blackwell: Chichester, 2009. (Reference for fluorinated building blocks in pharmaceutical applications.)

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