This compound belongs to the class of organic compounds known as diarylethers. These are organic compounds containing the dialkyl ether functional group, with the formula ROR', where R and R' are aryl groups.
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.
Certificats (CoA, COO, BSE/TSE et tableau d'analyse)
C of A & Other Certificates(BSE/TSE, COO):
Analytical Chart:
Propriétés chimiques et physiques
Poids moléculaire
196.200 g/mol
XLogP3
2.400
Hydrogen Bond Donor Count
0
Hydrogen Bond Acceptor Count
3
Rotatable Bond Count
2
Exact Mass
196.064 Da
Monoisotopic Mass
196.064 Da
Topological Polar Surface Area
45.900 Ų
Heavy Atom Count
15
Formal Charge
0
Complexity
239.000
Isotope Atom Count
0
Defined Atom Stereocenter Count
0
Undefined Atom Stereocenter Count
0
Defined Bond Stereocenter Count
0
Undefined Bond Stereocenter Count
0
The total count of all stereochemical bonds
0
Covalently-Bonded Unit Count
1
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Application Protocols
No application protocols are specified for this item.
General laboratory usage examples (literature-guided, not item-specific)
Stock solution preparation: Dissolve at 10–50 mM in anhydrous DMSO; vortex and, if needed, sonicate briefly. Store aliquots to minimize freeze–thaw.
Parallel diversification via nitrile hydrolysis: Heat with 2–3 equiv KOH in 70% EtOH/H2O at reflux for 6–8 h to obtain the primary amide; purify by silica gel chromatography (hexanes/EtOAc 3:1 → 1:1).
Nitrile reduction to amine: Hydrogenate at 3 bar H2 over 10 wt% Pd/C (5–10 wt% catalyst relative to substrate) in EtOH at 25–40 °C for 6–12 h; filter through celite and concentrate.
Analytical QC: Verify identity by 1H/13C NMR (CDCl3 or DMSO-d6), LC–MS, and, if needed, IR (sharp CN stretch typically near 2220–2260 cm−1, literature). These are illustrative steps; adapt to your SOPs.
For detailed, validated procedures applicable to your lot, consult peer-reviewed literature or develop internal SOPs.
Biological Roles
Item-specific biological/biochemical roles are not specified for this research chemical.
General context (literature)
2-Phenoxynicotinonitrile is a synthetic, non-natural small molecule. It does not have an established endogenous biological role. Compounds within the nicotinonitrile family are often explored as heteroaromatic fragments or cores in medicinal chemistry due to the tunable electronics of the pyridine ring and the nitrile’s utility as a neutral H-bond acceptor and vector for late-stage diversification.
Biophysical properties: The pyridine nitrogen and nitrile provide polar functionalities capable of coordinating to metal ions weakly and engaging in dipolar interactions, which can be exploited in fragment screening or for assembling coordination complexes in chemical biology experiments.
Assay considerations: For cellular or biochemical assays, stocks are commonly prepared in DMSO and diluted to low final DMSO percentages to mitigate solvent effects. The compound’s UV absorption facilitates UV-based quantification but can interfere with absorbance assays; orthogonal detection (fluorescence, MS) is recommended when needed.
Note
For research use only. No clinical, diagnostic, or therapeutic applications are implied or recommended.
Buffer Applications
This compound is a neutral organic building block and is not used as a pH buffer or buffering agent. It lacks acid/base functionality in the physiological pH range beyond weak pyridine basicity, and is generally insoluble in water. For practical lab use with this compound, focus on organic solvent systems rather than aqueous buffers. If an aqueous-compatible formulation is required for assays, employ co-solvents (e.g., ≤1–2% DMSO) and suitable surfactants or carrier proteins as allowed by the assay design.
Green Alternatives
As a solid building block, 2-phenoxynicotinonitrile itself is not a solvent; greener choices primarily concern reaction and workup media.
Greener solvent options (literature-based)
Replace DMF/DMAc/NMP with: Cyrene (dihydrolevoglucosenone), propylene carbonate, or dimethyl sulfone in applicable transformations; or use alcohols (EtOH, i-PrOH) for hydrogenations and some condensations.
Replace chlorinated solvents with: 2-MeTHF, CPME, toluene, ethyl acetate, or methyl tert-butyl ether, balancing solubility and safety.
Ethers: 2-MeTHF and CPME are preferred over THF/diethyl ether due to lower peroxide formation rates and better process profiles.
Comparison (general guidance)
2-MeTHF vs THF: similar polarity; 2-MeTHF offers higher boiling point and improved phase-split behavior during workups; can enhance solubility of aromatic substrates.
CPME vs DCM: CPME is non-chlorinated, has wider liquid range, and reduces chlorinated waste; however, it is more hydrophobic and may require cosolvents for polar reagents.
Operational tips
For nitrile hydrolysis, aqueous ethanol or aqueous isopropanol can reduce reliance on dipolar aprotics.
For catalytic hydrogenations of the nitrile, ethanol or i-PrOH frequently serve as both solvent and hydrogen donor in transfer hydrogenation variants.
Always confirm substrate solubility/crystallization behavior when switching to greener media; conduct small-scale screens.
Pharmaceutical Uses
Item-specific pharmacopeial status or excipient roles are not specified for this item.
General context (literature/industry)
Role: 2-Phenoxynicotinonitrile is best classified as a research intermediate/building block in medicinal chemistry and process development. The nitrile group serves as a functional handle for rapid analog generation (amide, amine, tetrazole), while the 2-phenoxy substitution modulates physicochemical properties of the pyridine core.
Formulation relevance: As a non-ionizable, hydrophobic solid, it is not typically used as an excipient. However, related heteroaryl nitriles can appear as advanced intermediates in API synthesis, where crystallinity and polymorph control may become relevant in later steps.
Regulatory: No compendial monograph is known for this specific structure. If used in a regulated setting (e.g., as an intermediate), establish impurity profiles, residual solvent limits (ICH Q3C), and elemental impurity controls (ICH Q3D) as appropriate for the stage.
Note
For research use only. No therapeutic claims are made or implied.
Physical Properties
Item-specific specifications
Appearance: Not specified for this item; refer to CoA/Spec Sheet.
Molecular formula (item): Not specified for this item; refer to CoA/Spec Sheet.
Molecular weight (item): Not specified for this item; refer to CoA/Spec Sheet.
Literature/computed (non-spec) properties for 2-phenoxynicotinonitrile (reference only)
Physical state: typically a crystalline solid for closely related aryl ether nicotinonitriles (literature).
Estimated molecular weight: ~196.20 g/mol (from C12H8N2O, literature inference from name/structure).
Solubility profile: expected to be sparingly soluble in water; soluble in polar aprotic and chlorinated organic solvents (e.g., DMSO, DMF, NMP, acetonitrile, THF, dichloromethane, ethyl acetate, toluene) — literature expectation for aryl ether nitriles.
Partitioning: aromatic ether + nitrile suggest moderate lipophilicity (logP likely in the 1.5–2.5 range; computational estimates only; verify experimentally).
UV–vis: conjugated aromatic system typically shows strong UV absorption in the 200–300 nm range (literature, not item-specific). Useful for HPLC/UPLC detection.
Melting point, boiling point, density, refractive index: Not specified for this item; consult literature or measure for your application.
Practical notes
Recrystallization solvents for analogous materials include ethanol, isopropanol, ethyl acetate/hexanes, or toluene/hexanes; selection should be guided by small-scale screening.
For analytical work, DMSO-d6 or CDCl3 are typical NMR solvents; the pyridine nitrogen can shift aromatic resonances downfield relative to simple biphenyl ethers.
Quality and Grades
Item-specific quality information
Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
Guidance on interpreting grade (general)
When provided, a defined chemical grade (e.g., research grade, analytical grade, ≥98%) indicates typical assay expectations and impurity controls. For heteroaryl building blocks, common controls include HPLC purity, water content (Karl Fischer), and identity confirmation by NMR/HRMS.
UV absorbance specifications (for HPLC-grade solvents) and trace-metal specifications (for catalytic applications) are sometimes listed for reagents intended for synthesis; these are not specified here for this item.
Practical recommendations
Request the lot-specific CoA for assay, residual solvent profile, and identity data prior to critical use (e.g., SAR campaigns or scale-up).
If the target use is metal-catalyzed coupling or C–O activation chemistry, low trace-metal content in the starting material can be beneficial but is not specified for this item; verify if needed.
If chiral or polymorph considerations are relevant to your work, note that this compound is achiral and typically does not present polymorph complexity; nonetheless, verify melting behavior by DSC if solid-state properties are critical.
Reaction and Applications
Context
2-Phenoxynicotinonitrile is a heteroaryl ether bearing a conjugated nitrile on a pyridine core. It serves as a versatile building block in heterocycle synthesis and medicinal chemistry.
Representative applications (literature/general)
Nitrile-to-amide/acid: Hydrolysis under basic (e.g., NaOH, H2O/EtOH, reflux) or acidic (e.g., H2SO4 or HCl, aqueous-organic, heat) conditions affords the corresponding amide or carboxylic acid after partial/complete hydrolysis.
Nitrile reduction: Conversion to the primary amine via catalytic hydrogenation (Raney Ni, Pd/C, H2) or metal hydrides (e.g., BH3·THF, DIBAL-H → imine/amine) enables downstream urea, amide, and heterocycle formations.
Nitrile activation: Formation of amidines (e.g., with LiHMDS-activated amines), tetrazoles (azide cycloaddition under Lewis acid heat), or imidates (alcoholysis) expands structural diversity.
Directed metalation/cross-coupling: The nitrile and pyridine nitrogen influence ortho-metalation on the phenyl ring and facilitate C–H activation strategies (e.g., Pd-catalyzed annulations) in advanced synthesis.
Aryl–O cleavage/functionalization: While aryl ethers are robust, nickel- or palladium-catalyzed C–O activation can effect ether-to-C–C (Suzuki-type) or ether-to-C–N (Buchwald–Hartwig) couplings under tailored ligand sets.
N-oxide chemistry: Temporary oxidation of the pyridine to the N-oxide can direct C–H functionalization (e.g., Minisci-type or electrophilic substitution) followed by deoxygenation.
Use in discovery chemistry
The phenoxy substituent modulates electronics and lipophilicity of the nicotinonitrile core, making the scaffold useful for fragment growing or scaffold hopping while retaining a handle (nitrile) for parallel diversification.
Reaction Conditions
General literature guidance (representative, not item-specific specifications)
Nitrile hydrolysis: KOH (2–5 equiv) in H2O/EtOH (1:1 to 1:3), reflux 4–24 h to primary amide; extended time/stronger conditions (aq. HCl or H2SO4, 80–120 °C) to carboxylic acid. Workup by neutralization and extraction.
Nitrile reduction: BH3·THF (1–3 M in THF), 0 °C to reflux, 2–16 h; or H2 (1–5 bar) over Pd/C or Raney Ni in EtOH/i-PrOH at RT–60 °C for 4–24 h. Monitor by TLC/LC–MS.
Tetrazole synthesis: NaN3 (1.5–3 equiv) with ZnCl2 (cat.) in DMF or DMSO, 100–130 °C, 6–16 h; or TMSN3 with Lewis acid in toluene/MeCN, 60–110 °C.
C–O activation/amination: Ni(cod)2 (5–10 mol%), NHC or bulky phosphine ligand (10–20 mol%), base (NaOtBu), toluene/1,4-dioxane, 80–120 °C, 6–24 h. Alternatively Pd2(dba)3 (1–2 mol% Pd), BrettPhos (3–6 mol%), NaOtBu in t-BuOH/toluene.
Cross-coupling at the aryl ether carbon: more forcing than aryl chlorides; careful ligand/base choice and rigorous exclusion of moisture/air recommended.
Practical tips
Drying: If needed, dry the solid under vacuum at ambient–40 °C prior to moisture-sensitive reactions.
Degassing: For metal-catalyzed reactions, degas solvents (sparging or freeze–pump–thaw) and use inert atmosphere.
Analytical: The aromatic chromophore supports UV detection (254–300 nm). LC–MS with ESI (M+H)+ around m/z ~197 (literature estimate) is typical for tracking.
Yields
Reported yields vary widely (50–90%) depending on transformation and substitution pattern; conduct small-scale optimization.
Safety and Handling
Item-specific hazard data
Signal word: Not specified for this item; refer to SDS.
H-statements: Not specified for this item; refer to SDS.
GHS classification: Not specified for this item; refer to SDS.
Pictograms: Not specified for this item; refer to SDS.
General safety guidance for aromatic nitriles and heteroaryl ethers (literature/experience; not a substitute for the SDS)
Hazards: Aromatic nitriles may cause irritation to skin, eyes, and respiratory tract. Avoid ingestion and inhalation of dust. While aliphatic nitriles can liberate toxic metabolites, many aryl nitriles are of lower acute toxicity; nonetheless, handle conservatively.
PPE: Wear lab coat, nitrile gloves, and splash goggles. Use in a fume hood to control dust and solvent vapors during handling, weighing, and transfers.
Incompatibilities: Strong oxidizers; very strong acids/bases may lead to hydrolysis or ether cleavage under forcing conditions. Avoid sodium/alkali metals and strong reducing agents unless intended.
Thermal stability: Typical aryl ether nitriles are thermally stable under ambient conditions; avoid excessive heating and open flames.
First aid (overview): If skin contact occurs, wash with soap and water. For eye exposure, rinse cautiously with water for several minutes; remove contact lenses if present and easy to do. If inhaled, move to fresh air. If swallowed or if symptoms persist, seek medical attention. Always consult the SDS for definitive guidance.
Waste: Dispose of solid residues and contaminated materials as halogen-free organic waste unless your process introduces halogens; follow institutional and local regulations.
Solvent Selection
Compound class and polarity
2-Phenoxynicotinonitrile is a neutral, moderately polar aromatic heterocycle bearing a nitrile and an aryl–O–aryl ether. It is generally water-insoluble but dissolves in many organic solvents.
Recommended solvents (literature/practice)
High solubility: DMSO, DMF, NMP.
Good solubility: dichloromethane, chloroform, THF, acetonitrile, ethyl acetate, toluene.
Limited solubility: alcohols (MeOH, EtOH) may be moderate; hexanes/alkanes typically low.
Selection guidance by application
Reaction media: For metal-catalyzed transformations (e.g., nitrile functionalization, C–O activation), polar aprotic solvents (DMF, NMP, DMAc, DMSO) or ethers (THF, dioxane) are common. For base-sensitive sequences, toluene or CPME can be advantageous.
Purification: Normal-phase silica with gradients from hexanes to ethyl acetate/dichloromethane typically provides good separation due to the compound’s moderate polarity. Reverse-phase (C18) with acetonitrile/water + 0.1% formic acid or ammonium bicarbonate can be used for analytical HPLC/UPLC.
Analytical: Stock solutions at 10–50 mM in DMSO are convenient for bioassay screening and LC–MS; dilute into MeCN/H2O for injections.
Small comparison (literature-based)
DMSO vs DMF: DMSO offers superior solubilization and LC–MS compatibility at low %; DMF has lower viscosity and can be preferable for automated dosing. Choose based on assay or reaction constraints.
Storage and Reconstitution
Item-specific conditions
Storage conditions: Room temperature (per Product Data). Store in a tightly closed container in a cool, dry, well-ventilated place.
Shipped in: Not specified for this item; refer to CoA/Spec Sheet.
General guidance
Protect from prolonged exposure to light and moisture. For long-term storage or if using over extended campaigns, consider desiccation (e.g., in a desiccator with drying agent) to maintain low water content, especially if moisture-sensitive transformations are planned.
Reconstitution/solution preparation: Prepare concentrated stock solutions in dry DMSO, DMF, or acetonitrile. Filter (0.2 µm PTFE) if particulate is present. For assay use, dilute DMSO stocks into the desired medium ensuring final DMSO content is compatible with the system.
Freeze–thaw: If storing solutions, aliquot to minimize freeze–thaw cycles. DMSO or DMF stocks are commonly stored at −20 °C; check for precipitation/crystallization upon cooling and redissolve by gentle warming and vortexing.
Stability notes
The aryl ether and aromatic nitrile are generally robust under ambient conditions. Avoid strong acids/bases and strong oxidants during storage.
Research use notice
For research use only. Not for human or veterinary use.
Structure and Identity
Item-specific identifiers (from Product Data)
SKU: P1073646
Product name: 2-Phenoxynicotinonitrile
CAS: 14178-15-5
PubChem CID: 84242
InChIKey: 184096 (as provided)
Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
Computed/literature structural information (for reference)
Suggested molecular formula (literature inference from name): C12H8N2O
SMILES (literature/computed): N#Cc1cc(nc(c1)Oc2ccccc2) [representing a pyridine bearing a 3-cyano and 2-phenoxy substituent]
Core scaffold: substituted nicotinonitrile (i.e., 3-cyanopyridine) with a phenoxy substituent at the 2-position of the pyridine ring.
Functional groups: aromatic heterocycle (pyridine), aryl–O–aryl ether (phenoxy–pyridine C–O linkage), and a nitrile (–C≡N) conjugated to the pyridine ring.
2D structure in words: a pyridine ring with the ring nitrogen at position 1; at C2, an oxygen linker to a phenyl ring (phenoxy); at C3, a cyano group (–C≡N); remaining ring positions are unsubstituted aromatics.
Notes
Any structure descriptors not explicitly present in the Product Data are provided as literature/computational references only; verify against the CoA/Spec Sheet for the supplied lot.
Synthetic Utility
Functional group leverage
Nitrile (–C≡N): versatile handle for hydrolysis (amide/acid), reduction (primary amine), addition (e.g., organometallics → imines/amidines), and heterocycle construction (e.g., tetrazoles via [3+2] with azide).
Pyridine nitrogen: coordinates to metals, enabling directed C–H activation or acting as a ligand in catalysis; can be oxidized to N-oxide to direct electrophilic substitution and subsequently reduced.
Aryl–O–aryl ether: electronically deactivating toward classic SNAr, but accessible to nickel/palladium-catalyzed C–O activation for installing C–C, C–N, or C–S bonds under modern ligand systems.
Retrosynthetic value
Disconnection to 2-halonicotinonitrile + phenol via SNAr/Ullmann/Buchwald etherification is common; conversely, the ether linkage can be transformed, enabling two-directional diversification of the scaffold.
Reduction: BH3·THF or catalytic hydrogenation (Pd/C, H2) to primary amine.
Tetrazole formation: TMSN3 or NaN3, Lewis acid (e.g., ZnCl2), 80–120 °C.
C–O activation: Ni(cod)2 with bulky NHC/biarylphosphine ligands; Pd catalysts with BrettPhos or SPhos derived systems for amination/arylation.
Directed ortho-metalation on the phenyl ring guided by the nitrile/pyridine under strong bases (s-BuLi) followed by electrophile quench, as permitted by stability.
Utility summary
A convergence point for parallel synthesis: preserve the core, derivatize via the nitrile, and, where desired, remodel the ether via C–O activation.
Target Specificity
Not applicable. This product is a small-molecule chemical reagent, not an antibody, protein, or biological targeting agent. No antigen/epitope or species reactivity is relevant.
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