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
No assay or bioanalytical protocols are provided for this small-molecule building block. Typical laboratory usage includes synthetic transformations as outlined in Reaction & Applications and Reaction Conditions. For analytical characterization, standard protocols (NMR, IR, MS, HPLC) are recommended.
Biological Roles
This is a synthetic organic building block rather than a biomolecule. No intrinsic biological role is assigned.
General notes (literature; not product-specific claims):
Aromatic nitriles and phenols can interact with proteins via π–π and H-bonding motifs and are often used as fragments or pharmacophores in medicinal chemistry.
Fluorine substitution is a common tactic to adjust metabolic stability and binding properties during structure–activity relationship (SAR) campaigns.
Research Use Note: For research use only. Not for human or veterinary use, diagnostics, or clinical applications.
Buffer Applications
Not typically applicable. 4-Fluoro-2-hydroxybenzonitrile is a neutral organic building block with low aqueous solubility and is not used as a buffering agent. For aqueous work, dissolve in a miscible co-solvent (e.g., DMSO or MeCN) before dilution if needed for assays.
Green Alternatives
Consider greener solvents and conditions without compromising reactivity.
Solvent choices (literature guidance):
Replace DMF/DMSO where possible with MeCN, acetone, 2-MeTHF, or Cyrene for SNAr or O-alkylation.
Use EtOAc or 2-MeTHF for acylations/couplings in place of DCM/THF when compatible.
Bases and reagents:
Favor inorganic carbonates (K2CO3/Cs2CO3) or organic superbases in catalytic amount over stoichiometric strong bases to minimize waste.
Employ catalytic hydrogenation (H2/Pd) for nitrile reductions when chemoselectivity permits, avoiding metal hydrides.
Workup/purification:
Aqueous workups with brine minimization and solvent recycling. Crystallization from EtOAc/hexanes preferred over extensive chromatography where feasible.
Comparison snapshot (literature, qualitative):
Conventional vs greener options:
DMF → MeCN/Cyrene: lower toxicity, easier removal; may reduce reaction rates in SNAr.
DCM → EtOAc/2-MeTHF: reduced environmental impact; may affect solubility of reagents/catalysts.
LiAlH4 → H2/Pd or BH3·THF: safer handling and fewer inorganic salts; chemoselectivity must be evaluated.
Energy and process:
Microwave or flow chemistry can reduce reaction times and solvent inventory. For SNAr, enabling bases with phase-transfer catalysts can allow lower temperatures and greener solvents.
Pharmaceutical Uses
No pharmacopeial excipient status or formulation role is specified for this item; refer to CoA/Spec Sheet if required.
General context (literature; not a therapeutic claim):
Used as a synthetic intermediate in medicinal chemistry programs to access fluorinated salicylate-derived scaffolds, benzoxazole cores, or to introduce a nitrile bioisostere.
The phenol enables prodrug strategies (e.g., carbonate/ester masks) during lead optimization; the aryl fluoride offers a diversification handle via SNAr.
Regulatory note: For research and process development use only. No claims for clinical, diagnostic, or veterinary use.
Physical Properties
Item-specific (Product Data):
Appearance: Not specified for this item; refer to CoA/Spec Sheet.
Molecular Formula: Not specified for this item; refer to CoA/Spec Sheet.
Molecular Weight: Not specified for this item; refer to CoA/Spec Sheet.
Literature/Computed (general reference values; not item specifications):
Expected physical state: crystalline solid (typical for halogenated salicylonitriles)
Approximate molecular formula and MW (by structure): C7H4FNO; ~137.11 g/mol
Acid–base: weakly acidic phenol; intramolecular H-bonding can reduce apparent basicity and affect pKa compared to phenol. Reported phenolic pKa for salicylonitriles is typically lower than phenol due to the nitrile EWG; presence of F further lowers pKa (qualitative, literature trend).
Solubility profile (qualitative, literature):
Low in water; readily soluble in polar aprotic solvents (DMSO, DMF, NMP, acetone, acetonitrile) and moderately soluble in alcohols and chlorinated solvents (DCM, CHCl3).
Volatility: negligible at ambient conditions (aromatic solid). Vapor pressure is expected to be very low (qualitative).
Spectroscopic handles: strong CN stretch in IR near ~2220–2240 cm−1 (literature); phenolic O–H stretch often broadened by intramolecular H-bonding.
Not provided for this item (consult CoA/SDS or measure as needed): melting point, boiling point, density, refractive index, logP, UV-Vis cutoff, water content, residual solvents, metal content.
Quality and Grades
Item-specific (Product Data):
Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
Guidance on grades (general information for planning):
Research/technical grade: suitable for most synthetic transformations. Verify by NMR/LC if using in SAR or quantitative work.
High-purity or HPLC grade materials (when available) feature tighter limits on residual solvents, UV-absorbing impurities, and trace metals—beneficial for photoredox, cross-coupling, or analytical development.
Stabilizers: none specified for this item. Phenolic compounds are generally stable; no peroxide formation concerns typical of ethers. If extremely low phenolic impurities are needed, consider additional purification (recrystallization or column) as appropriate.
Recommended verification for sensitive applications:
Purity: HPLC/UPLC with diode array to monitor phenolic/aryl impurities; GC may be limited due to thermal lability of phenols.
Water and inorganic content: Not specified for this item; refer to CoA/Spec Sheet if critical to your process.
Reaction and Applications
As a multifunctional aryl building block, 4-fluoro-2-hydroxybenzonitrile supports diverse transformations.
Phenolic derivatization:
O-alkylation/O-arylation: Williamson ether synthesis with alkyl halides (K2CO3/Cs2CO3, DMF/acetone). Buchwald–Hartwig or Ullmann-type arylations deliver diaryl ethers using the phenol as the nucleophile.
Acylation/carbamate formation: acid chlorides/anhydrides or CDI-based coupling to generate esters and carbonates; phenolic protection as benzyl, silyl, or carbonate groups for orthogonal strategies.
Aryl fluoride as a leaving group (literature):
SNAr with amines/thiols/alkoxides under polar aprotic conditions and heat; activation aided by the neighboring nitrile EWG. Enables late-stage installation of amines, alkoxides, or sulfur nucleophiles at the 4-position.
Nitrile transformations:
Hydrolysis to amide/acid (basic or acidic conditions; stepwise via amide often controllable under milder conditions).
Reduction: to primary amine (LiAlH4, catalytic hydrogenation) or to aldehyde (DIBAL-H at low temperature).
Cyclizations: ortho-hydroxybenzonitriles participate in heterocycle synthesis (e.g., benzoxazoles via condensation with amines or via sequential amidation–cyclodehydration; literature precedents vary by coupling partner and activating agents).
Medicinal and materials relevance (general):
Salicylonitrile scaffolds are valued in fragment and lead development; fluorine substitution modulates lipophilicity and metabolic stability. The phenol allows rapid SAR through O-functionalization while the nitrile provides a vector for polarity/lipophilicity tuning or heterocycle formation.
Reaction Conditions
General, literature-based guidance for typical transformations of 4-fluoro-2-hydroxybenzonitrile (not product specifications):
O-alkylation (Williamson ether):
Solvent: acetone, MeCN, or DMF.
Base: K2CO3 (2–3 eq) or Cs2CO3 (1.5–2 eq).
Temperature/time: reflux 2–12 h (acetone/MeCN), or 20–60 °C in DMF.
Notes: exclude water to limit competing hydrolysis of alkyl halides; monitor by TLC or LC-MS.
Base: inorganic carbonates or the nucleophile itself (for amines).
Temperature: 80–140 °C (oil bath or sealed vessel) depending on nucleophile strength.
Additives: phase-transfer catalysts or fluoride scavengers can improve rates/selectivity.
Nitrile hydrolysis:
Basic: KOH/NaOH (2–5 eq), EtOH/H2O or dioxane/H2O, 60–100 °C to amide; longer/heavier base to acid.
Acidic: H2SO4 or HCl aqueous, reflux to amide/acid; watch for phenol sensitivity.
Nitrile reduction:
To amine: LiAlH4 (THF/Et2O, 0–25 °C), or H2/Pd-C (MeOH/EtOH, 1–5 bar, 20–50 °C).
To aldehyde: DIBAL-H (−78 to −20 °C, toluene/THF), quench at low temp to avoid overreduction.
Cyclizations (heterocycles):
Amidation of the nitrile followed by cyclodehydration (POCl3, SOCl2, or PPA) to benzoxazole-like motifs; conditions vary with partner amide/amine.
Always confirm conditions with small-scale trials and literature precedents for your specific substrate set.
Safety and Handling
Item-specific (Product Data):
GHS Classification / Pictograms / Signal Word / H-statements: Not specified for this item; refer to SDS.
Storage: Room temperature, argon charged. Keep container tightly closed; protect from moisture and prolonged light exposure.
General safety considerations (literature/good practice; defer to SDS for authoritative guidance):
Likely hazards: phenolic compounds can be skin/eye irritants; aryl nitriles may cause irritation on contact or inhalation. Avoid dust formation.
PPE: lab coat, safety glasses or chemical splash goggles, and appropriate gloves (e.g., nitrile). Use in a fume hood.
Handling notes: minimize exposure to strong bases (can induce phenoxide formation and potential side reactions) and strong oxidizers. Avoid strong acids at elevated temperatures if hydrolysis of the nitrile is not desired.
Incompatibilities: strong oxidizing agents; strong bases (for storage, avoid base contamination). Metals/metal alkoxides may catalyze undesired transformations of phenols.
First aid (overview):
Inhalation: move to fresh air, seek medical attention if symptoms persist.
Skin/eye contact: rinse with water for several minutes; remove contaminated clothing; seek medical advice for persistent irritation.
Ingestion: rinse mouth; do not induce vomiting; seek medical attention.
Fire safety: use dry chemical, CO2, or foam. Decomposition may produce irritant/toxic fumes (e.g., HF traces if fluorinated aromatics burn). Have appropriate extinguishing measures available.
Waste: dispose via licensed chemical waste contractor; segregate halogenated organic waste where required.
Solvent Selection
This compound is an aromatic phenolic nitrile with low water solubility and good solubility in polar organics.
Nucleophilic substitutions (SNAr on aryl F): use polar aprotic solvents (DMSO/DMF/NMP) with inorganic bases (K2CO3, Cs2CO3) or amines; elevated temperatures often required.
O-alkylation/acylation of the phenol: acetone, acetonitrile, DMF, or MeCN with K2CO3/Na2CO3; for acid chlorides, use pyridine or triethylamine base in DCM/THF.
Nitrile transformations (hydrolysis/reduction): aqueous-organic biphasic systems or polar protic/aqueous solvents (EtOH/H2O for basic hydrolysis; MeOH/THF for catalytic hydrogenation).
Crystallization: ethyl acetate/hexanes or toluene/EtOAc mixtures frequently provide good control of precipitation for phenolic aromatics.
Quick comparison (literature, qualitative):
DMF/DMSO: maximize SNAr rates and solubility; difficult removal.
MeCN/Acetone: easier workup, lower boiling; may require higher temperatures or longer times.
DCM: ideal for acylations with acid chlorides and for rapid workups; not suitable for strong-base chemistry.
Alcohols: useful for solvolysis or base-catalyzed hydrolysis, but may compete in O-alkylation reactions.
Prepare stock solutions in dry DMSO, DMF, MeCN, or acetone. For biological assays, first dissolve in DMSO or MeCN, then dilute into aqueous media with vigorous mixing to avoid precipitation.
Typical lab concentrations: 10–100 mM in DMSO for screening libraries; filter (0.22 μm PTFE) if particulates are present.
Stability notes:
Phenolic aromatics are generally stable at ambient conditions; avoid strong bases/acids during storage.
If long-term storage is planned, consider aliquoting under argon to minimize headspace oxygen/moisture cycles.
Thaw/freeze guidance:
For solution stocks, store at −20 °C under inert gas; avoid repeated freeze–thaw by aliquoting. Solid material is robust at room temperature when kept dry and sealed.
Always refer to the current CoA/SDS for item-specific stability and handling details.
Structure and Identity
A halogenated salicylonitrile building block featuring an ortho-phenol and a para-fluoro substituent on a benzonitrile core; useful for heterocycle construction and late-stage diversification.
Storage: Room temperature, argon charged; shipped: normal
Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
Literature/Computed (general reference values; not item specifications):
Common synonyms: 4-fluoro salicylonitrile; 2-hydroxy-4-fluorobenzonitrile
Molecular formula (by structure): C7H4FNO (literature)
Molecular weight: ~137.11 g/mol (literature)
SMILES: N#Cc1cccc(F)c1O (literature)
Structural features (descriptive):
Aromatic ring bearing three key functionalities: a nitrile (–C≡N) at the benzylic ipso carbon, a phenolic hydroxyl at the ortho (2-) position, and a fluorine at the para (4-) position relative to the OH.
Functional groups: aryl fluoride, phenol, and aryl nitrile (strongly electron-withdrawing). No stereocenters.
Electronic profile: competing effects of –OH (π-donating/σ-withdrawing) and –CN/–F (σ-withdrawing). The nitrile and fluoro substituents increase ring deactivation toward electrophilic substitution but can enable nucleophilic aromatic substitution under suitably activating conditions.
Intramolecular H-bonding is possible between the phenolic OH and the nitrile nitrogen, influencing conformation and acidity (literature observation for salicylonitriles).
Synthetic Utility
Key functional elements and their strategic value:
Phenolic OH:
Protection as benzyl, silyl, or carbonate groups for orthogonal synthesis.
Diversification via O-alkylation, O-arylation (Ullmann/Buchwald), or carbonate/carbamate formation.
Aryl fluoride (para to OH):
Acts as a leaving group in SNAr with N/O/S nucleophiles under polar aprotic conditions; activation enhanced by the ring’s electron-withdrawing nitrile. Enables late-stage installation of amines, alkoxides, thiols, or heteroaryl nucleophiles.
Nitrile:
Polarity handle for tuning properties; convertible to amides/acids (hydrolysis), primary amines (reduction), or aldehydes (partial reduction, DIBAL-H).
Serves as a synthon for heterocycles: benzoxazoles or related frameworks via amidation/cyclodehydration sequences starting from the ortho-phenol.
Retrosynthetic perspective:
Positions 2 (OH) and 4 (F) allow orthogonal edits; one can first derivatize the phenol (protect or elaborate) and subsequently displace F, or vice versa, minimizing protecting-group conflicts.
The nitrile can be retained as a bioisostere of carbonyls or unveiled late as an amide/acid for convergence.
Analytical advantages:
Distinct IR CN band and 19F NMR handle aid in reaction monitoring and rapid structure confirmation.
Target Specificity
Not applicable. This product is a small-molecule building block and is not an antibody, enzyme, or biological targeting reagent. No target, epitope, clone, or isotype information applies.
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