2-(4-Chlorophenoxy)nicotinonitrile - ≥98% , CAS No.82524-00-3

CAS: 82524-00-3 Cat. No.: C334843 Fórmula: C₁₂H₇ClN₂O Peso molecular: 230.65

GRADE & PURITY ≥98%

Synonyms

AKOS000172765 | MFCD09929608 | AS-8008 | 2-(4-chlorophenoxy)pyridine-3-carbonitrile | DTXSID901264931 | 2-(4-Chlorophenoxy)-3-pyridinecarbonitrile | 2-(4-Chlorophenoxy)nicotinonitrile | 2-(4-Chloro-phenoxy)-nicotinonitrile

Storage

Room temperature

Shipped In

Normal

Specifications

Sinónimos

AKOS000172765 | MFCD09929608 | AS-8008 | 2-(4-chlorophenoxy)pyridine-3-carbonitrile | DTXSID901264931 | 2-(4-Chlorophenoxy)-3-pyridinecarbonitrile | 2-(4-Chlorophenoxy)nicotinonitrile | 2-(4-Chloro-phenoxy)-nicotinonitrile

Especificações e pureza

≥98%

Condições de armazenamento de armazenamento

Room temperature

Enviado em

Normal

Pureza

≥98%

Nomes e identificadores

Pubchem Sid

488198299

Sorrisos canónicos

C1=CC(=C(N=C1)OC2=CC=C(C=C2)Cl)C#N

IUPAC Name

2-(4-chlorophenoxy)pyridine-3-carbonitrile

InChIKey

SXHKCNWJKWTOTA-UHFFFAOYSA-N

INCHI

1S/C12H7ClN2O/c13-10-3-5-11(6-4-10)16-12-9(8-14)2-1-7-15-12/h1-7H

SMILES isoméricas

C1=CC(=C(N=C1)OC2=CC=C(C=C2)Cl)C#N

Peso molecular

230.65

Reaxy-Rn

4440697

Reaxys-RN_link_address

https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=4440697&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organic oxygen compounds
    • Classe Organooxygen compounds
      • Subclass Ethers

• Kingdom: Organic compounds
• Superclass: Organic oxygen compounds
• Classe: Organooxygen compounds
• Subclass: Ethers
• Intermediate Tree Nodes: Not available
• Direct Parent: Diarylethers
• Alternative Parents: Phenoxy compounds Phenol ethers 3-pyridinecarbonitriles Chlorobenzenes Aryl chlorides Heteroaromatic compounds Nitriles Azacyclic compounds Organochlorides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Diaryl ether - Phenol ether - 3-pyridinecarbonitrile - Phenoxy compound - Chlorobenzene - Halobenzene - Aryl halide - Monocyclic benzene moiety - Pyridine - Benzenoid - Aryl chloride - Heteroaromatic compound - Nitrile - Carbonitrile - Azacycle - Organoheterocyclic compound - Organonitrogen compound - Organochloride - Organohalogen compound - Organic nitrogen compound - Hydrocarbon derivative - Cyanide - Aromatic heteromonocyclic compound
• Descrição: 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

Data sources

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.

DOI: 10.1186/s13321-016-0174-y

Propriedades químicas e físicas

• Peso molecular: 230.650 g/mol
• XLogP3: 3.100
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 2
• Exact Mass: 230.025 Da
• Monoisotopic Mass: 230.025 Da
• Topological Polar Surface Area: 45.900 Ų
• Heavy Atom Count: 16
• Formal Charge: 0
• Complexity: 267.000
• 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

Application Protocols

No application protocols (e.g., WB, IHC, IF, FC) are associated with this small-molecule building block. For synthetic use, consult the Reaction Conditions and Synthetic Utility tabs. For solution preparation in screening assays, typical practice is to prepare 10–100 mM DMSO stocks, verify solubility at working concentration after dilution into assay buffer, and include appropriate vehicle controls.

Biological Roles

• Item-specific biological data: Not specified for this item; refer to primary literature if needed.

• General information (literature/context):

  • 2-(4-Chlorophenoxy)nicotinonitrile is a synthetic, non-natural small molecule. Its heteroaromatic–nitrile framework is common in discovery chemistry, where the nitrile serves as a polar, metabolically stable functional group and weak H-bond acceptor.
  • The pyridine nitrogen can coordinate metal ions in biochemical assay buffers, potentially affecting apparent potency in metal-dependent enzymes; awareness of such interactions can help with assay design.
  • No endogenous metabolic role is known. Biotransformation, if studied, would be expected to proceed via aromatic oxidation, O-dearylation under specific enzymatic conditions, or nitrile hydrolysis pathways; these are general possibilities and not specific to this item.

Research Use Note: For research use only. Not for human or veterinary use.

Buffer Applications

This compound is a neutral, hydrophobic heteroaromatic building block and is not a buffering agent. It does not serve as a pH buffer component or electrophoresis buffer under typical laboratory conditions. For solution preparation in biological assays, prepare stocks in DMSO or DMF and then dilute into the assay buffer with attention to final cosolvent percentage (commonly ≤1–2% v/v).

Green Alternatives

• Solvent and process choices (literature/general):

  • Replace chlorinated/aromatic solvents with bio-derived ethers where feasible.

• Comparison (general guidance):

  | Use case | Conventional choice | Greener alternative | Trade-offs | |---|---|---|---| | Suzuki/Buchwald couplings | Dioxane, toluene | 2-MeTHF, CPME | Slightly lower solubility; improved EHS and easier workup | | Tetrazole formation from nitrile | DMF, NMP | Propylene carbonate, Cyrene, or aqueous ethanol | May need higher temperature/longer time; viscosity considerations | | Hydrolysis of nitrile | DMSO/DMF mixed with water | Water/EtOH or water/acetone systems | Potential phase separation; solubility management via heat | | Workup/extraction | DCM | EtOAc, MTBE | Partition coefficients and emulsions require adjustment |

• Catalysis and bases:

  • For aryl chloride couplings, use air-stable precatalysts (e.g., Pd-PEPPSI or XPhos-based) to reduce Pd loading and waste.
  • Favor inorganic bases with lower EHS impact (K3PO4, K2CO3) over strong alkoxides where compatible.

• Energy and waste minimization:

  • Consider microwave acceleration or continuous flow to reduce reaction time/energy input.
  • Crystallization-driven purifications can avoid chromatographic solvent waste when the product permits.

Pharmaceutical Uses

• Item-specific pharmacopeial/excipient status: Not specified for this item; no compendial status is claimed. Refer to your regulatory resources for any intended use beyond research.

• General context (non-clinical, non-therapeutic):

  • As a functionalized heteroaryl building block containing both an aryl chloride and a nitrile, this compound is suitable for use in medicinal chemistry and process R&D as an intermediate en route to candidate molecules.
  • Roles in formulation are not typical for this structure; it is not used as an excipient. Any presence in a drug product context would be as a synthetic intermediate or impurity standard during development.

• Analytical considerations for development:

  • Reference standards can be characterized by NMR, LC–MS, HRMS, and HPLC purity profiles. Forced degradation studies may focus on hydrolysis of the nitrile under strong acid/base and oxidative stability of the aryl ether.
  • For impurity tracking, monitor potential dechlorinated, hydrolyzed (amide/acid), and O-dearylated species by LC–MS.

Physical Properties

• Item-specific specifications:

  • Appearance: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular Formula (on label): Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular Weight (on label): Not specified for this item; refer to CoA/Spec Sheet.

• Literature/general expectations (for context; not item specifications):

  • Phase at ambient conditions: typically a crystalline solid for aromatic nitriles/aryl ethers of this size.
  • Volatility: low; negligible vapor pressure compared to common solvents.
  • Solubility profile: expected to be sparingly soluble in water; soluble in polar aprotic organic solvents (e.g., DMSO, DMF, NMP) and moderately soluble in chlorinated or aromatic solvents (e.g., dichloromethane, toluene).
  • Acid/base behavior: predominantly neutral; weakly basic pyridine nitrogen may engage in hydrogen bonding; nitrile is non-ionizable across common pH ranges.
  • Lipophilicity: moderate to high (qualitative), driven by two aryl rings and an ether; nitrile adds polarity without ionization.
  • Thermal behavior: aromatic nitriles commonly show melting points in the moderate range and high thermal stability prior to decomposition; exact MP/BP for this item are not specified.

• Refractive index, UV cutoff, residual water/metals/peroxide levels: Not specified for this item; refer to CoA/Spec Sheet.

Quality and Grades

• Item-specific quality information:

  • Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.

• Interpreting grades (general guidance):

  • Research grade materials are suitable for synthetic and analytical laboratory use. Where HPLC or LC–MS applications are intended, dedicated low-UV/low-metal grades can reduce baseline noise and ion suppression.
  • If “≥98%” or similar assay is specified on the CoA, typical analytical methods include 1H NMR, HPLC/GC, and HRMS/elemental analysis. Residual solvent and water (KF) limits are reported when relevant; for non-volatile solids, GC/HPLC area % is common.

• Stabilizers/inhibitors: None specified for this item; aryl ether nitriles generally do not require stabilizers. If any stabilizer is listed on your CoA, consider its impact on downstream reactions and purification.

• Batch-to-batch consistency: For cross-coupling building blocks (aryl chloride present), trace metals and halide content can influence catalytic performance. If catalytic coupling is intended, request metals profile on the CoA or pre-treat via silica plug or activated carbon as needed.

Always rely on the CoA/Spec Sheet packaged with the batch for definitive grade and acceptance criteria.

Reaction and Applications

• Functional group leverage (literature/general):

  • Aryl chloride handle (para to O): amenable to Pd-catalyzed cross-coupling (Suzuki–Miyaura, Buchwald–Hartwig, Sonogashira, Negishi). Modern ligand sets (e.g., XPhos, SPhos, BrettPhos) enable coupling of aryl chlorides at 60–110 °C.
  • Nitrile (on pyridine): convertible to amides/acids (hydrolysis), amidines/iminoethers (Pinner), tetrazoles (azide [3+2] cycloaddition), or reduced to amines/aldehydes (DIBAL-H, Raney Ni/H2). Retains directing capability in some metalations.
  • Pyridine nitrogen: can coordinate to metals (temporary ligand) or be quaternized for phase-tag strategies.

• Typical applications:

  • Library synthesis and SAR: diversification via cross-coupling at the aryl chloride while preserving the heteroaryl nitrile core.
  • Late-stage functionalization: selective transformations at the nitrile (e.g., tetrazole formation) to modulate polarity and H-bonding capacity without altering the biaryl ether linkage.
  • Heteroaryl ether stability: the Ar–O–Ar linkage is generally robust to many coupling and reduction conditions; cleavage typically requires strong nucleophiles or hydrogenolysis and is not commonly targeted.

• Practical tips:

  • For couplings, maintain anhydrous, oxygen-minimized conditions; employ degassed solvents and base-dried media.
  • If solubility limits rate, add a small percentage of DMF/DMSO as co-solvent.
  • Protect the nitrile from strongly basic, high-temperature conditions if hydrolysis is not desired; conversely, use controlled aqueous acid/base to effect hydrolysis when targeted.

All reactions noted are literature practices and should be optimized per substrate and scale.

Reaction Conditions

The following are literature-style general conditions for chemotypes like 2-(4-chlorophenoxy)nicotinonitrile; they are not item-specific specifications and should be optimized.

• Suzuki–Miyaura coupling (Ar–Cl → Ar–Ar):

  • Catalyst/ligand: Pd2(dba)3 (1–2 mol% Pd) with XPhos/SPhos (2–4 mol%) or Pd(dppf)Cl2 (3–5 mol%); alternative: precatalysts like XPhos Pd G3.
  • Base: K3PO4 (2–3 equiv) or Cs2CO3 (2–3 equiv).
  • Solvent: 1,4-dioxane/H2O (10:1), 2-MeTHF, or toluene with 5–10% DMF as co-solvent if needed.
  • Temperature/time: 80–110 °C, 2–16 h.

• Buchwald–Hartwig amination (Ar–Cl → Ar–NR2):

  • Catalyst/ligand: Pd(OAc)2 (1–2 mol%) + BrettPhos or RuPhos (2–4 mol%); or Pd-PEPPSI analogs.
  • Base: NaOtBu or K3PO4.
  • Solvent: toluene, 2-MeTHF, or dioxane.
  • Temperature: 80–110 °C.

• Sonogashira coupling (Ar–Cl → Ar–C≡C–R):

  • Catalyst: Pd(PPh3)2Cl2 (1–2 mol%) + CuI (5–10 mol%).
  • Base: Et3N, i-Pr2NH.
  • Solvent: THF, toluene, or 2-MeTHF.
  • Temperature: 50–80 °C; protect nitrile from strong bases at high temperature to avoid hydrolysis.

• Nitrile interconversions on the pyridine ring:

  • Hydrolysis to amide/acid: aq. H2SO4 or HCl (reflux) or aq. NaOH/KOH (reflux) in mixed solvents (EtOH/H2O); monitor to stop at amide.
  • Tetrazole formation: NaN3/NH4Cl (DMF or propylene carbonate), 100–130 °C; or TMSN3/Lewis acid (e.g., ZnBr2) under anhydrous conditions.
  • Reduction: DIBAL-H (−78 to 0 °C) to aldehyde; catalytic hydrogenation (Raney Ni or Pd/C) to primary amine.

• Notes: Degas solvents, dry glassware, and consider adding a polar co-solvent to aid dissolution. Work up with EtOAc/water; remove residual Pd by scavengers (e.g., silica–thiol, metal scavenging resins).

Safety and Handling

• GHS classification and labeling (item-specific):

  • Signal Word: Not specified for this item; refer to SDS.
  • Hazard Statements (H-Statements): Not specified for this item; refer to SDS.
  • Pictograms: Not specified for this item; refer to SDS.

• General hazards (literature/general):

  • May cause irritation to skin, eyes, and respiratory tract typical of aromatic nitriles/heteroaromatics.
  • Combustible organic solid; dust can form explosive mixtures with air if finely divided.
  • Not an ether solvent; peroxide formation is not a recognized concern for this solid aryl ether.

• Handling recommendations (general best practice; defer to SDS):

  • Use in a chemical fume hood; avoid inhalation of dust and contact with skin/eyes.
  • PPE: lab coat, safety glasses or goggles, and appropriate gloves (e.g., nitrile). For scale-up or where splashes are possible, add face shield and protective sleeves.
  • Incompatibilities: strong oxidizers; strong acids/bases may promote hydrolysis or ring activation under harsh conditions.
  • First aid (general): move to fresh air upon inhalation; rinse skin/eyes with water for at least 15 minutes; seek medical attention if irritation persists. Ingestion: rinse mouth; do not induce vomiting; seek medical attention.

• Fire safety: use CO2, dry chemical, or foam; water spray to cool containers. Thermal decomposition may release HCl/NOx; firefighters should wear SCBA.

Always consult the SDS for authoritative, item-specific safety guidance.

Solvent Selection

• Polarity/miscibility (literature/general for this chemotype):

  • Expected to be poorly soluble in water; readily soluble in polar aprotic solvents (DMSO, DMF, NMP) and miscible at useful concentrations in chlorinated (DCM, chloroform) and aromatic media (toluene, xylene). Limited solubility in lower alcohols unless heated.

• Choosing a working solvent:

  • Stock solutions for screening/biology-adjacent assays: DMSO or DMF (filter through PTFE/nylon if needed).
  • Cross-coupling and SNAr attempts: 1,4-dioxane, toluene, CPME, or 2-MeTHF with a polar co-solvent (DMF/DMSO) when required to aid dissolution; bases such as K3PO4 or Cs2CO3 are compatible with these media.
  • Hydrolysis/functional-group interconversions of the nitrile: aqueous ethanol or acetonitrile/water with mineral acid or base; for anhydrous amidoxime/imidate chemistry, use MeOH, EtOH, or i-PrOH under strictly controlled conditions.

• Comparison notes:

  • DMSO vs DMF: DMSO offers higher solvating power and is less volatile; DMF can ease workup due to lower viscosity but is more prone to decomposition at high temperature/base.
  • 2-MeTHF/CPME vs dioxane/toluene: greener profiles and easier separations, though sometimes slightly reduced solubility; consider modest heating or co-solvent addition.

Storage and Reconstitution

• Storage (item-specific from Product Data):

  • Storage Conditions: Room temperature
  • Shipped In: Normal

• General storage guidance:

  • Keep tightly closed in the original container. Store in a dry place, away from direct light and strong oxidizers. Although room temperature storage is acceptable, many users keep heteroaromatic nitriles in a desiccator to minimize moisture uptake and preserve assay reproducibility.

• Reconstitution and solution preparation (general):

  • Solvents: DMSO, DMF, or NMP for concentrated stock solutions; for synthetic operations, also soluble in chlorinated or aromatic solvents (DCM, toluene) to practical extents.
  • Typical stock concentrations: 10–100 mM in DMSO for screening; filter-sterilize through 0.22 µm PTFE if sterility is required for assays.
  • Freeze–thaw: Solid form is stable. For solutions, aliquot and store at −20 to −80 °C to avoid repeated freeze–thaw cycles; assess stability by LC–MS/HPLC prior to reuse.

• Stability notes:

  • Avoid prolonged exposure to strong acids/bases or high humidity which can promote hydrolysis or degradation. No stabilizers are indicated for this item.

Research Use Note: For research use only.

Structure and Identity

Brief description: 2-(4-Chlorophenoxy)nicotinonitrile is a bifunctional, heteroaromatic building block featuring a 3-cyanopyridine core bearing a 2-aryloxy substituent with a para-chloro substituent on the phenyl ring.

• Item-specific identifiers (from Product Data):

  • SKU: C334843
  • CAS: 82524-00-3
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet. (Provided value appears incomplete.)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/computed identifiers and features (informational, not item-specific specifications):

  • Expected molecular formula (literature inference): C12H7ClN2O
  • Approximate molecular weight (literature calculation): ~230.65 g/mol
  • Core scaffold: pyridine ring (nicotinonitrile, i.e., 3-cyanopyridine)
  • Substitution pattern: 2-(4-chlorophenoxy) on the pyridine; 3-cyano on the pyridine
  • Functional groups: aryl chloride (Ar–Cl), aryl ether (Ar–O–Ar), nitrile (–C≡N), heteroaromatic nitrogen (pyridine N)
  • 2D structural description: a 3-cyanopyridine ring where C2 is bonded to an oxygen linker that connects to a para-chloro-substituted phenyl ring; the nitrile is meta to the pyridine nitrogen.

• Stereochemistry: None (achiral, no stereocenters).

Synthetic Utility

• Strategic handles embedded in the molecule (literature/general):

  • Aryl chloride (para to oxygen): gateway to C–C (Suzuki/Negishi), C–N (Buchwald–Hartwig), C–O (Ullmann-type or Pd-catalyzed), and C–S couplings.
  • Nitrile on pyridine: convertible to carboxamide/carboxylic acid (acidic or basic hydrolysis), to tetrazole (NaN3/NH4Cl or TMSN3 with Lewis acid), to amidine/iminoether (Pinner), or to aldehyde/amine (DIBAL-H or catalytic hydrogenation respectively).
  • Pyridine nitrogen: potential for directed metalation or coordination to transiently modulate reactivity/solubility; N-oxidation can alter directing effects and reactivity in subsequent steps.

• Retrosynthetic value:

  • Enables late-stage diversification at the aryl chloride while maintaining the heteroaryl core. Such disconnection allows rapid access to analog libraries via boronic acids/esters, alkynes, amines, or thiols.
  • Orthogonality: many nitrile transformations tolerate Pd-catalyzed couplings and vice versa, enabling step economy.

• Protection/chemoselectivity notes:

  • The aryl ether is generally stable; if cleavage is undesirable, avoid strong nucleophiles at elevated temperatures.
  • Selective nitrile reduction to aldehyde (DIBAL-H, −78 to 0 °C) can precede or follow cross-couplings depending on catalyst tolerance to the aldehyde.

• Purification:

  • Products from cross-couplings often crystallize; otherwise, normal-phase silica with gradients from hexanes/EtOAc to toluene/EtOAc is typical. Monitor for strongly retained pyridine-containing species (add 0.1–1% TEA to mobile phase if tailing).

Target Specificity

Not applicable. This product is a small-molecule chemical building block, not a biological targeting reagent (e.g., antibody, enzyme inhibitor standard with defined biological target). No antigen, epitope, or species reactivity information is associated with this item.

Perguntas frequentes

What is the purity of this product?

This product is supplied at ≥98% purity (chemical assay). Lot-specific values are stated on the Certificate of Analysis.

How should this product be stored?

Store at room temperature.

How is this product shipped?

This product ships under standard ambient conditions. No temperature-controlled packaging is required.

What are the CAS number, molecular formula and molecular weight?

The CAS Number is 82524-00-3, the molecular formula is C12H7ClN2O, and the molecular weight is 230.65 g/mol. InChIKey SXHKCNWJKWTOTA-UHFFFAOYSA-N.

What documentation is provided?

Available product documentation, including Certificates of Analysis (COA), Safety Data Sheets (SDS), and specification sheets, is shown in the product document area. Document availability and access follow the current site policy.