2-(Difluoromethoxy)-6-fluorobenzonitrile: Properties & Uses

2-(Difluoromethoxy)-6-fluorobenzonitrile is a fluorinated aromatic building block bearing both a difluoromethoxy group and a fluorine substituent on the benzonitrile scaffold, making it a versatile intermediate for medicinal chemistry and agrochemical research.

Product Name

2-(Difluoromethoxy)-6-fluorobenzonitrile

SKU

F692746

Molecular Formula

C8H4F3NO

Functional Groups

Nitrile (–CN), difluoromethoxy (–OCHF2), aryl fluoride (Ar–F)

Molecular Weight

195.12 g/mol (calculated)

Primary Application

Pharmaceutical and agrochemical intermediate; fluorinated building block for synthesis

What Is 2-(Difluoromethoxy)-6-fluorobenzonitrile?

2-(Difluoromethoxy)-6-fluorobenzonitrile (SKU: F692746) is a polyfluorinated aromatic compound featuring a benzonitrile core substituted at the 2-position with a difluoromethoxy (–OCHF₂) group and at the 6-position with a fluorine atom. The combination of these electron-withdrawing substituents significantly modulates the electronic character of the aromatic ring, increasing the electrophilicity of the nitrile carbon and influencing the compound's lipophilicity and metabolic stability.

The difluoromethoxy motif is a bioisostere of the hydroxyl and methoxy groups and is widely employed in drug discovery to improve membrane permeability, metabolic resistance, and binding selectivity. Its presence alongside an aryl fluoride makes this compound a highly functionalized scaffold for the preparation of more complex target molecules.

Chemical Properties and Handling

As a fluorine-rich aromatic nitrile, 2-(Difluoromethoxy)-6-fluorobenzonitrile is expected to be a stable solid or low-melting solid at ambient conditions. The aryl nitrile group is susceptible to nucleophilic addition and hydrolysis under strongly basic or acidic aqueous conditions, so storage under dry, inert conditions is recommended. The difluoromethoxy group is generally robust toward mild nucleophiles but may hydrolyze under prolonged exposure to strongly acidic conditions.

Standard laboratory precautions for fluorinated organic compounds apply: use appropriate personal protective equipment (PPE) including gloves, lab coat, and eye protection. Handle in a well-ventilated fume hood. Consult the Safety Data Sheet (SDS) for detailed hazard classifications, first-aid measures, and disposal guidance before use.

Research and Synthetic Applications

This compound serves as a versatile electrophilic building block in medicinal chemistry and materials science. The nitrile group can undergo a range of transformations, including reduction to primary amines, hydrolysis to carboxylic acids or amides, cycloaddition to form tetrazoles or heterocycles, and palladium-catalyzed cross-coupling reactions. The aryl fluoride at the 6-position is activated toward nucleophilic aromatic substitution (SNAr) due to the ortho electron-withdrawing nitrile, enabling introduction of diverse nucleophiles such as amines, thiols, and alkoxides.

The difluoromethoxy group contributes to the compound's utility as a pharmacophore fragment in the synthesis of agrochemicals and active pharmaceutical ingredients (APIs), particularly in programs targeting enzyme inhibition or receptor modulation where fluorine incorporation is used to tune potency and selectivity.

Ordering, Storage, and Quality

2-(Difluoromethoxy)-6-fluorobenzonitrile is available from Aladdin Scientific under SKU F692746. For pricing, available pack sizes, and current stock status, please visit the product page on the Aladdin Scientific website or contact our customer service team. Bulk and custom quantities may be available upon request.

For optimal stability, store the compound in a tightly sealed container away from moisture, heat, and light. A dry, cool environment (typically 2–8 °C or room temperature under inert atmosphere, depending on final SDS guidance) is recommended. Each lot is subject to quality control analysis; a certificate of analysis (CoA) is available upon request to confirm identity, purity, and other specifications.

Frequently asked questions

What is the CAS number of 2-(Difluoromethoxy)-6-fluorobenzonitrile?

The CAS number for 2-(Difluoromethoxy)-6-fluorobenzonitrile is not confirmed in the current source material. Please refer to the product page for SKU F692746 on the Aladdin Scientific website or contact customer service for the verified CAS number and full spectral data.

Why is the difluoromethoxy group valuable in drug discovery?

The difluoromethoxy (–OCHF₂) group acts as a bioisostere of hydroxyl and methoxy groups, imparting improved metabolic stability, membrane permeability, and lipophilicity relative to unsubstituted analogues. The strong C–F bonds resist oxidative metabolism, which can extend the in vivo half-life of candidate drug molecules. This makes compounds bearing –OCHF₂ attractive fragments in medicinal chemistry optimization campaigns.

Can the aryl fluoride in this compound be used in nucleophilic aromatic substitution (SNAr) reactions?

Yes. The aryl fluoride at the 6-position is activated toward SNAr by the ortho-positioned electron-withdrawing nitrile group, which stabilizes the Meisenheimer complex intermediate. This allows displacement of fluoride by various nucleophiles—such as amines, alkoxides, and thiolates—under appropriate reaction conditions, making this site a useful handle for further functionalization in synthesis.

How should I store 2-(Difluoromethoxy)-6-fluorobenzonitrile to maintain its stability?

Store the compound in a tightly sealed container in a cool, dry, and well-ventilated area, protected from moisture and direct light. For specific storage temperature recommendations, please refer to the product's Safety Data Sheet (SDS) and Certificate of Analysis (CoA) available from Aladdin Scientific for SKU F692746.

What transformations can the nitrile group of this compound undergo?

The nitrile (–CN) group is highly versatile: it can be reduced to a primary amine (–CH₂NH₂) using reagents such as LiAlH₄ or catalytic hydrogenation; hydrolyzed to a carboxylic acid or amide under acidic or basic conditions; or converted to heterocycles such as tetrazoles via [3+2] cycloaddition with azides. It can also serve as a ligand in transition-metal-catalyzed coupling strategies, broadening access to diverse chemical space.

References

1. Müller K, Faeh C, Diederich F. Fluorine in pharmaceuticals: looking beyond intuition. Science. 2007;317(5846):1881-1886. doi:10.1126/science.1131943
2. Meanwell NA. Synopsis of some recent tactical application of bioisosteres in drug design. J Med Chem. 2011;54(8):2529-2591. doi:10.1021/jm1013693
3. Aladdin Scientific. Product page: 2-(Difluoromethoxy)-6-fluorobenzonitrile, SKU F692746. Aladdin Scientific website.

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