2,4-Difluoro-5-nitrophenol: Properties, Uses & FAQs

2,4-Difluoro-5-nitrophenol is a halogenated aromatic building block bearing two electron-withdrawing fluorine substituents and a nitro group, making it a versatile intermediate for pharmaceutical synthesis, agrochemical research, and materials chemistry.

Chemical Name

2,4-Difluoro-5-nitrophenol

SKU / Catalog Number

D586424

Molecular Formula

C₆H₃F₂NO₃

Molecular Weight

175.09 g/mol

Key Functional Groups

Phenol (–OH), two aryl fluorides (C–F), nitro group (–NO₂)

Typical Application

Pharmaceutical and agrochemical synthesis intermediate

What Is 2,4-Difluoro-5-nitrophenol?

2,4-Difluoro-5-nitrophenol (CAS not confirmed in source material; flagged for review) is a polyfunctional aromatic compound featuring a hydroxyl group at the 1-position, fluorine atoms at the 2- and 4-positions, and a nitro group at the 5-position of the benzene ring. The simultaneous presence of two strong electron-withdrawing fluorines and a nitro group significantly activates the ring toward nucleophilic aromatic substitution (S_NAr), particularly at the fluorine-bearing positions. The free phenolic –OH adds a site for O-alkylation, O-acylation, or further functionalization, making this compound a compact yet reactive scaffold for medicinal chemists and process chemists alike.

Key Physical and Chemical Properties

The electron-poor aromatic ring of 2,4-Difluoro-5-nitrophenol lowers the pKa of the phenolic hydroxyl relative to unsubstituted phenol (pKa ~10), because the combined inductive and resonance effects of –F and –NO₂ stabilize the phenoxide anion. Fluorine substituents also confer metabolic stability and lipophilicity modulation in drug candidates derived from this scaffold. The compound is expected to be a solid at room temperature based on its molecular weight and polarity profile; however, precise melting point, boiling point, and solubility data should be verified against the certificate of analysis (CoA) supplied with each lot.

Recommended solvents for dissolution include dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), and acetonitrile. Avoid prolonged exposure to strong bases, which may promote phenoxide-mediated side reactions.

Research and Synthetic Applications

The primary value of 2,4-Difluoro-5-nitrophenol in synthetic chemistry lies in its dual electrophilic character. Medicinal chemists routinely use fluorinated nitrophenol scaffolds as precursors to:

• Ether formation: Reaction with alcohols or phenols under basic conditions via S_NAr at the 4-fluoro position (more activated than the 2-fluoro position due to the para-nitro group).
• Amine coupling: Displacement of fluoride by primary or secondary amines to generate diaryl- or arylalkyl-amine linkages common in kinase inhibitors and other bioactive molecules.
• Nitro reduction: Catalytic hydrogenation or chemical reduction (e.g., Fe/AcOH, SnCl₂) converts the nitro group to an amine, opening access to aminofluorophenol intermediates for further elaboration.
• O-functionalization: The phenol can be protected as a methyl, benzyl, or silyl ether prior to other transformations.

These versatile transformations position 2,4-Difluoro-5-nitrophenol as a useful starting material in the synthesis of agrochemicals, fluorescent probes, and pharmaceutical APIs.

Handling, Storage, and Safety Guidance

As with all nitro-substituted aromatic compounds, appropriate laboratory safety precautions should be observed when working with 2,4-Difluoro-5-nitrophenol:

• Personal protective equipment (PPE): Wear nitrile gloves, safety goggles, and a laboratory coat. Use a fume hood for weighing and solution preparation.
• Storage: Store in a cool, dry, well-ventilated location away from strong oxidizers, reducing agents, and bases. Consult the Safety Data Sheet (SDS) for the specific storage temperature recommended for this lot.
• Disposal: Dispose of waste in accordance with local, national, and institutional regulations for halogenated organic waste.
• First aid: In case of skin or eye contact, flush with copious water and seek medical advice. Refer to the product SDS for comprehensive hazard information.

Note: Specific GHS hazard classifications, signal words, and H/P statements for this product should be confirmed in the current SDS available from Aladdin Scientific.

Ordering and Product Specifications

2,4-Difluoro-5-nitrophenol is available from Aladdin Scientific under SKU D586424. Each shipment is accompanied by a Certificate of Analysis (CoA) detailing lot-specific purity data, typically determined by HPLC or GC, as well as NMR confirmation of structure. For bulk quantities, custom pack sizes, or specific purity grades required for GMP-adjacent research, please contact Aladdin Scientific's technical sales team.

To confirm current stock, pricing, and available pack sizes, visit the product page on the Aladdin Scientific website or contact customer service directly. Expedited shipping options may be available depending on your region.

Frequently asked questions

What is the molecular formula and molecular weight of 2,4-Difluoro-5-nitrophenol?

The molecular formula of 2,4-Difluoro-5-nitrophenol is C₆H₃F₂NO₃, corresponding to a molecular weight of approximately 175.09 g/mol. Always confirm the exact value against the Certificate of Analysis provided with your specific lot.

Which fluorine position in 2,4-Difluoro-5-nitrophenol is more reactive toward nucleophilic aromatic substitution?

The 4-fluoro position is generally more reactive toward nucleophilic aromatic substitution (SₙAr) because the nitro group at the 5-position exerts a stronger activating effect in the para-relationship relative to the 2-fluoro (ortho) position. However, reaction selectivity can be influenced by solvent, temperature, and the nature of the nucleophile, so empirical optimization is recommended.

How should 2,4-Difluoro-5-nitrophenol be stored to maintain stability?

Store the compound in a tightly sealed container in a cool, dry, and well-ventilated area, away from light, moisture, strong oxidizers, and bases. Refer to the product Safety Data Sheet (SDS) for lot-specific recommended storage temperature. Standard practice for many nitrophenol derivatives is refrigerated storage (2–8 °C), but confirm with the CoA.

In what solvents is 2,4-Difluoro-5-nitrophenol soluble?

Based on its polarity and functional groups, 2,4-Difluoro-5-nitrophenol is expected to dissolve well in polar aprotic solvents such as DMSO, DMF, and acetonitrile, and to show moderate solubility in ethyl acetate or dichloromethane. Aqueous solubility is expected to be low at neutral pH but increases under alkaline conditions due to phenoxide formation. Exact solubility values should be verified experimentally.

Is 2,4-Difluoro-5-nitrophenol suitable for use as a pharmaceutical intermediate?

Yes, fluorinated nitrophenol scaffolds like 2,4-Difluoro-5-nitrophenol are widely employed in pharmaceutical synthesis as reactive building blocks for introducing fluorine atoms and amino or ether linkages into drug candidates. The product supplied by Aladdin Scientific (SKU D586424) is intended for research use; suitability for GMP or clinical-grade manufacturing must be assessed separately in consultation with Aladdin Scientific's technical team.

References

1. March, J. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure. Wiley-Interscience. General reference for nucleophilic aromatic substitution mechanisms.
2. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed. Oxford University Press, 2012. Reference for fluorine effects on aromatic reactivity and pKa modulation.
3. Aladdin Scientific product page for 2,4-Difluoro-5-nitrophenol, SKU D586424. Certificate of Analysis and Safety Data Sheet available on request.

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