This compound belongs to the class of organic compounds known as benzonitriles. These are organic compounds containing a benzene bearing a nitrile substituent.
External Descriptors
Not available
1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.
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Recensioni
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Application Protocols
Not applicable. No biological assay protocols (e.g., WB, IHC, IF, FC) are associated with this small-molecule building block. For chemical applications, refer to the Reaction & Applications and Reaction Conditions sections for general synthetic guidance.
Biological Roles
This product is a small aromatic building block intended for chemical synthesis. It does not have established endogenous biological roles.
General literature context (not specific to this item):
Aryl nitriles appear in various bioactive molecules as metabolically robust polar handles; the nitrile can modulate dipole interactions and binding without introducing basicity.
Phenolic groups engage in hydrogen bonding and can affect antioxidant capacity or binding in enzyme pockets after derivatization. However, free phenols may undergo rapid phase II metabolism (glucuronidation/sulfation) in biological systems.
No biological assays, targets, or activities are provided for this catalog item. For research use only; not for diagnostic, therapeutic, or clinical applications.
Buffer Applications
Not typically applicable. 3-Fluoro-5-hydroxybenzonitrile is a neutral organic building block rather than a buffering agent. It is not used to prepare biological or analytical buffer systems. For practical use, prepare stock solutions in suitable organic solvents (e.g., DMSO, DMF, MeOH) as needed for chemical synthesis, and avoid aqueous buffers unless the experimental design specifically calls for them.
Green Alternatives
Greener solvent and reagent choices (general guidance)
Preferred solvents for processing phenolic nitriles:
Ethyl acetate or 2-MeTHF in place of DMF/DMSO for extractions and some reactions (easier removal, better EHS profiles).
Acetone or acetonitrile as higher-volatility polar aprotics to replace NMP/DMF where feasible.
Propylene carbonate as a non-volatile polar solvent for certain base-mediated O-alkylations (tradeoff: difficult removal).
Comparison (literature-based, typical tradeoffs)
DMF vs 2-MeTHF: DMF offers superior polarity/solvation for salts; 2-MeTHF is bio-derived, lower toxicity, but less polar—may require phase-transfer catalysts or higher temperature.
DCM vs EtOAc: DCM excellent for silylations but with environmental concerns; EtOAc is greener yet may be less effective for moisture-sensitive silylations without rigorous drying.
Toluene vs cyclopentyl methyl ether (CPME): CPME has favorable safety (peroxide-resistant, higher flash point) and often similar solvency.
Reagent choices
Use catalytic hydrogenation over stoichiometric metal hydrides for nitrile reductions when compatible with –OH (protect if necessary).
Bases such as K2CO3/Cs2CO3 in greener solvents (EtOAc/alcohol mixtures under phase-transfer conditions) can sometimes replace DMF-based protocols.
Adopt solvent selection guides (e.g., GSK/ACS) to align with process safety and sustainability while validating performance experimentally.
Pharmaceutical Uses
This item is supplied for research use only. It is not an approved excipient and has no pharmacopeial monograph indicated in the product data.
General formulation context (literature-based, not item-specific):
Aryl nitrile–containing phenols can serve as intermediates in the synthesis of APIs or advanced intermediates. The –CN can be converted late-stage to primary amines or carboxylic acids, while the phenol can be diversified to ethers/esters or used as a leaving group (triflate) for cross-coupling.
As a standalone material, it is not used as a pharmaceutical excipient, preservative, or processing aid.
For any GMP or clinical manufacturing intent, obtain full quality documentation, impurity profiles, and assess suitability under relevant regulatory standards.
Physical Properties
Item-specific specifications
Appearance: Not specified for this item; refer to CoA/Spec Sheet.
Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
Literature/general properties (for reference; not item specifications)
Molecular formula: C7H4FNO
Molecular weight: ~137.11 g/mol
Physical state at ambient conditions: Typically a crystalline solid for analogous hydroxybenzonitriles.
Polarity/functional profile: Weakly polar aromatic core with one strongly polar nitrile and one hydrogen-bond-donating phenol; expected low aqueous solubility, good solubility in polar organics (e.g., DMSO, DMF, alcohols) and many moderately polar aprotics (EtOAc, acetone).
Acid-base: Phenolic OH pKa typically ~9–10 (literature, for substituted phenols); nitrile is non-basic but strongly polarizable.
Volatility: Low; aromatic nitriles generally have high boiling points and low vapor pressure.
Note: Exact MP/BP, density, refractive index, logP, UV cutoff, water content, and residual metals are not specified for this item; refer to CoA/Spec Sheet or SDS for authoritative data.
Quality and Grades
Item-specific grade/purity
Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
Guidance on grades (general information)
Research-grade aromatic building blocks are typically supplied at high assay (e.g., >95% by HPLC/GC) with residual solvent and impurity profiles appropriate for synthesis. When a specific grade is stated (e.g., 98%+, HPLC grade), it indicates verified assay methodology and impurity thresholds suited to sensitive applications.
For chromatography-intensive or medicinal chemistry workflows, tighter controls on UV cut-off, residual metals, and stabilizers may be important. Absence of a stabilizer is common for phenolic nitriles; if present, it would be stated on the CoA.
Verification: Always consult the CoA for actual assay method, impurity limits, and identity confirmation (e.g., NMR, LC-MS, IR). If heavy metal content, water content (Karl Fischer), or peroxides are critical to your process, request the current CoA/Spec Sheet.
Batch-specific documentation
CoA typically includes assay, identification (NMR/IR/MS), and chromatographic purity. Any listed residual solvents or reagents from synthesis would appear there. For regulatory or scale-up use, request extended impurity and stability data.
Reaction and Applications
Representative uses in synthesis (literature-based)
Functional handle diversification:
Nitrile transformations: Hydrolysis to amide/acid (acidic or basic conditions), reduction to primary amine (e.g., catalytic hydrogenation, BH3, or LiAlH4), or partial reduction to aldehyde (DIBAL-H at low temperature). Pinner reactions can generate imidates/esters under HCl/alcohol.
Phenolic chemistry: O-alkylation/acylation/sulfonylation to access aryl ethers/esters/sulfonates; conversion to aryl triflate enables cross-couplings (Suzuki, Buchwald–Hartwig via subsequent amination).
Directed metalation: –CN is a strong ortho-directing group; after phenol protection (e.g., O-TBDMS), lithiation at positions ortho to –CN can be achieved with s-BuLi/TMEDA, followed by electrophile quench.
Ring substitution and coupling:
The aryl fluoride is generally inert toward Pd-catalyzed cross-coupling but can engage in SNAr if sufficiently activated by additional EWGs; in this scaffold, SNAr reactivity on F is limited without further activation. Alternatively, convert –OH to halide/triflate to enter cross-coupling manifolds.
Library building: The interplay of an electron-withdrawing nitrile and a phenol enables rapid access to salicylamide/salicylic acid nitrile analogues, benzoxazoles (via amidation/cyclization), and substituted anilines (via –CN reduction) for SAR studies.
Practical tips
Protect –OH (silyl or benzyl) before strong base or hydride reductions to avoid undesired O-alkylation or over-reduction.
Maintain anhydrous conditions for reductions or organometallic steps; neutralize phenoxide before aqueous workup to minimize emulsions.
Monitor regioselectivity closely; electronic bias from –CN vs –OH can invert expected patterns under different conditions.
Reaction Conditions
General literature guidance (example conditions; verify experimentally)
Nitrile hydrolysis:
Acidic: Reflux in aqueous mineral acid (e.g., 6 M HCl) to amide/acid; extended times for full conversion. Solvent mixtures (MeOH/H2O) can improve solubility.
Basic: Aqueous NaOH/KOH (1–4 M), reflux to carboxylate; acidify to isolate acid. Phenol may ionize; control pH during workup.
Nitrile reduction:
To aldehyde: DIBAL-H (1.0–1.5 equiv) in toluene or THF at −78 to −20 °C; careful quench to avoid over-reduction.
To amine: Catalytic hydrogenation (Raney Ni, Pd/C) in alcohol or THF under H2 (1–10 bar); or LiAlH4/BH3 in THF/Et2O at 0–25 °C to reflux.
Phenol functionalization:
O-Alkylation: Alkyl halide (1.1–2.0 equiv), K2CO3/Cs2CO3 in acetone, MeCN, or DMF at 25–80 °C; phase-transfer catalysts can enable greener solvents.
Triflation: Tf2O (1.1–1.5 equiv), base (2,6-lutidine/pyridine), anhydrous DCM/MeCN at −20 to 0 °C, then warm to RT; follow with cross-coupling.
Directed ortho-metalation:
Protect –OH (e.g., TBS). Use s-BuLi (1.1–1.5 equiv) with TMEDA in hexanes/THF at −78 to −40 °C, then quench with electrophile (CO2, I2, DMF, etc.).
Typical yields are substrate- and condition-dependent; consult primary literature for optimization. Maintain anhydrous conditions for organometallic steps and hydride reductions.
Safety and Handling
Item-specific hazard information
Signal word: Not specified for this item; refer to SDS.
H-statements/GHS classification/pictograms: Not specified for this item; refer to SDS.
General safety guidance for aryl nitrile phenols (literature-based; not item-specific classification)
Likely hazards: May cause skin/eye irritation and respiratory tract irritation; phenolic compounds can be harmful if swallowed. Avoid dust generation.
Personal protective equipment (PPE): Use lab coat, safety glasses or splash goggles, and chemical-resistant gloves (e.g., nitrile). Handle in a fume hood to avoid inhalation of dust or vapors during heating.
Safe handling: Avoid contact with bases that can form phenoxide; keep away from strong oxidizers. Prevent contamination with strong acids or alkali when not intended for reaction.
First aid overview: In case of skin contact, wash with soap and water. Eye contact: rinse cautiously with water for several minutes; remove contact lenses if present. Inhalation: move to fresh air. Ingestion: rinse mouth; seek medical attention. Always follow SDS instructions.
Fire safety: Combustible organic solid. Use CO2, dry chemical, or foam to extinguish incipient fires. Thermal decomposition may produce irritating fumes.
Spill response: Avoid dust; collect mechanically or dampen and wipe while wearing appropriate PPE. Dispose of in accordance with local regulations.
Definitive hazard classifications and exposure limits must be taken from the product SDS.
Solvent Selection
General solubility and polarity (literature-based)
Expected solubility: Poor in water; good in DMSO, DMF, NMP; moderate to good in acetone, acetonitrile, ethyl acetate, and alcohols; variable in chlorinated solvents (DCM, chloroform) depending on temperature.
Polarity class: Moderately polar aromatic solid due to –CN and –OH; forms hydrogen bonds (donor) and strong dipole interactions (nitrile).
When to choose specific solvents
Spectroscopy/stock solutions: DMSO or DMF provide high solubility and stability for phenolic nitriles; methanol/ethanol acceptable at lower concentrations.
Nucleophilic chemistry on the nitrile (e.g., Pinner or partial reductions): Use dry, polar aprotics (MeCN, THF, toluene with additives) depending on reagent system.
Phenolic functionalization (O-alkylation/acylation): Employ dry acetone, MeCN, or DMF with a base (e.g., K2CO3, Cs2CO3); for silylation, use anhydrous dichloromethane, acetonitrile, or THF.
Hydrolysis/reduction of –CN: Aqueous alcoholic media for base/acid hydrolysis; strictly anhydrous ethers/aromatics (THF, toluene) for reductions with hydride reagents or DIBAL-H.
Acetonitrile/EtOAc/acetone: Easier removal, greener profiles; may require heat for complete dissolution.
Alcohols: Facilitate some acylations/transesterifications; can engage in side reactions under strong acidic/basic conditions.
Always verify actual solubility experimentally for your batch and temperature.
Storage and Reconstitution
Item-specific storage
Storage conditions: Room temperature (as provided). Ship under normal conditions.
General handling and stability (literature-based)
Keep container tightly closed in a dry, well-ventilated place. Protect from prolonged exposure to moisture and strong light to minimize potential phenolic discoloration or slow oxidative changes.
If long-term storage is anticipated, consider desiccation and inert atmosphere (e.g., nitrogen) as good practice for phenolic solids.
Reconstitution/solution preparation (for lab use)
Prepare stock solutions in dry organic solvents such as DMSO, DMF, acetonitrile, methanol, ethanol, acetone, ethyl acetate, THF, or toluene depending on downstream chemistry.
Typical stock concentrations: 10–100 mM in DMSO/DMF for screening chemistry; higher concentrations may require warming or sonication.
Filter solutions (0.2–0.45 µm PTFE) if particulate is present. For moisture-sensitive transformations, dry solvents and use anhydrous technique.
Always refer to the product CoA and SDS for batch-specific stability and handling recommendations. For research use only.
Structure and Identity
Item-specific (Product Data)
SKU: F331697
Product name: 3-Fluoro-5-hydroxybenzonitrile
CAS: 473923-95-4
PubChem CID: 21949920
InChIKey: 14796 (as provided)
Storage: Room temperature; shipped under normal conditions
Literature/computed identifiers (general reference, not item-specific specs)
Molecular formula (literature): C7H4FNO
Molecular weight (literature): ~137.11 g/mol
Canonical SMILES (literature): N#Cc1cc(F)cc(O)c1
Structural features (description)
Aromatic ring system: Monosubstituted benzonitrile core bearing two ring substituents.
Functional groups: One aryl nitrile (–C≡N), one phenolic hydroxy (–OH), and one aryl fluoride (–F).
Substitution pattern: Nitrile taken as position 1; fluorine at position 3 (meta to –CN), hydroxy at position 5 (para to –CN, meta to –F). This pattern creates distinct electronic regions on the ring.
Stereochemistry: None (achiral, planar aromatic).
Electronic character: The –CN is a strong meta-directing, electron-withdrawing group; phenolic –OH is ortho/para-directing and electron-donating; –F is weakly deactivating but ortho/para-directing by resonance. The net result is an electronically differentiated ring useful for regioselective transformations.
Synthetic Utility
Functional group leverage
–C≡N (nitrile):
Hydrolysis to amide/acid provides rapid polarity tuning and handles for further coupling.
Selective reductions yield aldehydes (DIBAL-H) or primary amines (catalytic hydrogenation, borane, LiAlH4), enabling access to anilide or benzylamine motifs after ring manipulation.
Acts as an ortho-directing group for metalation, supporting regiocontrolled electrophile installation.
–OH (phenol):
O-Alkylation or acylation enables ether/ester libraries.
Activation to triflate or nonaflate allows powerful cross-couplings (Suzuki, Negishi, Buchwald–Hartwig via subsequent amination).
Intramolecular cyclizations after amide formation can furnish benzoxazoles/benzoxazines.
–F (aryl fluoride):
Typically inert under Pd coupling; can participate in SNAr only with additional activation. Serves as a spectroscopic handle and modulator of electronics and lipophilicity.
Retrosynthetic value
The 3-F/5-OH pattern relative to –CN offers complementary reactivity: the para relationship of –OH to –CN can guide substitution and allows orthogonal protection/activation strategies.
Protecting group strategies: Silyl ethers (TBS/TBDPS) or benzyl ethers for –OH; ensure compatibility with planned nitrile transformations.
Applications
Scaffold for salicylamide/salicylate analogues bearing a nitrile.
Precursor to 3-fluoro-5-aminobenzene derivatives (via –CN reduction followed by transformations).
Intermediate toward fluorinated benzoxazole libraries (amidation of –CN, cyclodehydration).
Target Specificity
Not applicable. This product is a small-molecule building block and is not an antibody, enzyme, or biological reagent with defined target specificity. No antigen/epitope or species reactivity information is relevant.
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