2-(4-Chlorophenoxy)nicotinaldehyde - ≥98% , CAS No.478031-03-7

CAS: 478031-03-7 Cat. No.: C1042720 Fórmula: C₁₂H₈ClNO₂ Peso molecular: 233.65 PubChem CID: 3485254

GRADE & PURITY ≥98%

Storage

Room temperature

Specifications

Especificaciones y pureza

≥98%

Condiciones de almacenamiento de almacenamiento

Room temperature

Pureza

≥98%

Nombres e identificadores

Sonrisas canónicas

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

IUPAC Name

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

InChIKey

CQXMTALCLMFFTL-UHFFFAOYSA-N

INCHI

1S/C12H8ClNO2/c13-10-3-5-11(6-4-10)16-12-9(8-15)2-1-7-14-12/h1-8H

Isómeros SMILES

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

PubChem CID

3485254

Peso molecular

233.65

Taxonomic Classification

Taxonomy Tree

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

• Kingdom: Organic compounds
• Superclass: Organic oxygen compounds
• Clase: Organooxygen compounds
• Subclass: Ethers
• Intermediate Tree Nodes: Not available
• Direct Parent: Diarylethers
• Alternative Parents: Pyridine carboxaldehydes Phenoxy compounds Phenol ethers Chlorobenzenes Aryl-aldehydes Aryl chlorides Heteroaromatic compounds Azacyclic compounds Organonitrogen compounds Organochlorides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Diaryl ether - Phenoxy compound - Phenol ether - 3-pyridine carboxaldehyde - Chlorobenzene - Halobenzene - Aryl-aldehyde - Benzenoid - Aryl chloride - Pyridine - Monocyclic benzene moiety - Aryl halide - Heteroaromatic compound - Organoheterocyclic compound - Azacycle - Hydrocarbon derivative - Organic oxide - Organonitrogen compound - Organochloride - Organohalogen compound - Organic nitrogen compound - Aldehyde - Aromatic heteromonocyclic compound
• Descripción: 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

Propiedades químicas y físicas

• Peso molecular: 233.650 g/mol
• XLogP3: 2.800
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 3
• Exact Mass: 233.024 Da
• Monoisotopic Mass: 233.024 Da
• Topological Polar Surface Area: 39.200 Ų
• Heavy Atom Count: 16
• Formal Charge: 0
• Complexity: 229.000
• 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 antibody/assay protocols apply to this small-molecule building block. For synthetic applications, see the Reaction Conditions and Synthetic Utility sections for literature-guided procedures.

General lab usage tips:

• Prepare concentrated stock solutions in anhydrous DMSO, MeCN, or DMF if needed for high-throughput synthesis or assays; verify stability over time.
• For moisture-sensitive reactions, flame-dry glassware, use an inert atmosphere, and pre-dry solvents (molecular sieves or solvent purification systems).

Biological Roles

Item-specific biological/biochemical roles: Not specified for this item; refer to literature if investigating specific interactions.

General context:

• 2-(4-Chlorophenoxy)nicotinaldehyde is a synthetic heteroaromatic aldehyde. It is not a naturally occurring metabolite and has no established endogenous biological role.
• In chemical biology and medicinal chemistry workflows, heteroaryl aldehydes can be used as reactive handles to form reversible covalent adducts (e.g., imines/hydrazones/oximes) with biomolecule-derived nucleophiles for probe or linker construction. Such uses are strictly research-oriented and require rigorous characterization of selectivity and stability.
• The pyridine ring can participate in metal coordination; Schiff base derivatives can act as ligands in bioinorganic model studies (literature precedent).

Caveats:

• Avoid extrapolating in vitro reactivity (e.g., imine formation) to biological efficacy or safety—no clinical or therapeutic claims should be inferred.
• If using in biochemical assays, confirm DMSO stock stability and assess aldehyde reactivity with assay components to avoid artifacts.

Buffer Applications

This compound is not a buffering agent and is not typically employed to make laboratory buffers. As a hydrophobic heteroaromatic aldehyde, it lacks the acid/base conjugate pair behavior and aqueous solubility required for practical buffering.

For applications involving this compound in aqueous systems (e.g., biochemical assays), select an appropriate conventional buffer (e.g., phosphate, HEPES, MOPS) based on pH needs, and introduce the compound from a DMSO or MeCN stock solution with minimal cosolvent percentage to maintain assay integrity.

Green Alternatives

While this is a solid building block rather than a solvent, greener choices can be made around its use:

• Greener solvent selections (literature guidance):
  • Prefer EtOAc, 2-MeTHF, CPME, or MeOH/EtOH where feasible over chlorinated solvents like DCM or high-toxicity polar aprotics like DMF.
  • Use aqueous micellar catalysis (e.g., TPGS-750-M) for some condensations or cross-couplings to reduce organic solvent consumption.
• Energy efficiency:
  • Conduct condensations at ambient temperature with organocatalysts or amine catalysts when possible; use Dean–Stark only when necessary.
• Catalysis for aryl chloride activation:
  • Modern Pd–ligand systems (BrettPhos, SPhos) or Ni catalysis can enable lower temperature couplings, reducing energy input and side reactions.
• Waste minimization:
  • Telescoping imine formation/reduction (one-pot reductive amination) avoids isolation of intermediates.
  • Employ flow chemistry for hazardous reagents (e.g., organometallic additions) to improve safety and reduce solvent volumes.

Example comparison (general):

• DCM vs EtOAc for workup/extraction
  • Greenness: EtOAc preferred (biodegradable, lower toxicity)
  • Performance: DCM often dissolves more; EtOAc typically sufficient for aryl aldehydes.
• THF vs 2-MeTHF for Grignard additions
  • Greenness: 2-MeTHF from renewable sources, better safety profile
  • Performance: Comparable coordination ability; note different boiling point and water miscibility.

Pharmaceutical Uses

Item-specific pharmacopeial status or excipient role: Not specified for this item; refer to CoA/Spec Sheet.

General formulation and discovery context (non-clinical, research only):

• This compound serves as a medicinal chemistry building block. The aldehyde enables rapid derivatization (e.g., imines, secondary alcohols), and the para-chloro substituent provides a cross-coupling handle for analog expansion during SAR.
• Potential roles in discovery workflows:
  • Intermediate for synthesizing heteroaryl ethers, imines, oximes, and reduced alcohols used in screening libraries.
  • Precursor to metal-binding ligands via Schiff base condensation with diamines or amino alcohols (research tools and catalysts).
• No usage as an approved active or excipient is implied. All uses are strictly for research and process development in non-human applications unless otherwise regulated and validated.

Physical Properties

Item-specific specs (this lot): Not specified for this item; refer to CoA/Spec Sheet.

General/literature expectations for compounds of this class (heteroaromatic aldehydes with aryl chloride):

• Phase/appearance: typically low-melting solids or viscous oils depending on substitution; this substituted nicotinaldehyde is commonly isolated as a crystalline solid (literature, analogous structures).
• Solubility (qualitative, literature):
  • Poorly soluble in water.
  • Soluble in common organic solvents (e.g., dichloromethane, ethyl acetate, acetonitrile, THF, toluene); moderate solubility in alcohols (MeOH/EtOH) depending on temperature.
• UV/Vis: aromatic π→π* absorption in the 200–300 nm region; n→π* band from the aldehyde may appear at longer wavelength (literature trends for aryl/heteroaryl aldehydes).
• LogP: expected moderate hydrophobicity due to aryl chloride and aryl ether (literature expectation for analogous structures); exact value not established here.
• pKa: no acidic protons of relevance; pyridine nitrogen is basic (conjugate acid pKa typically ~5.2 for pyridines; electron-withdrawing formyl may lower basicity somewhat—literature trend).
• Density, melting point, boiling point, refractive index: Not specified for this item; refer to CoA/Spec Sheet.

Practical notes:

• The aldehyde can undergo slow oxidation to the corresponding acid and can form hemiacetals/acetals in the presence of alcohols and acid catalysts (general aldehyde behavior).
• For analytical purposes, monitor purity by HPLC/UPLC or GC (if sufficiently volatile) and verify identity by 1H/13C NMR and HRMS.

Quality and Grades

• Item-specific grade/purity: Not specified for this item; refer to CoA/Spec Sheet.

Guidance on grades and implications (general):

• Research-grade heteroaryl aldehydes are commonly supplied at high purity (typically ≥95% by HPLC/GC). Where applicable, residual solvent levels, water content, and chromatographic purity are documented on the CoA.
• Stabilizers: None are typically added to heteroaryl aldehydes; however, some suppliers package under inert gas or include molecular sieves to limit hydration/oxidation. Any stabilizer used would be disclosed on the CoA/specification—none is specified here.
• UV/HPLC suitability: For chromatographic method development, low-UV-absorbing solvents and clean baselines are important; the compound itself is UV-active and readily detected at 254–280 nm.
• What to check on receipt:
  • Appearance and physical state vs. CoA.
  • Purity by HPLC/GC and identity by NMR/HRMS as needed for critical applications.
  • Peroxide content is not applicable to this solid; if using etheric solvents in associated workups, test those solvents separately.

Note: Always defer to the product’s CoA and SDS for definitive quality metrics and any stabilizer or inhibitor information for the specific lot.

Reaction and Applications

As a 2-aryloxy-substituted nicotinaldehyde, this compound is a versatile building block combining an electrophilic aldehyde with an aryl chloride cross-coupling handle.

Key application families (literature-based):

• Carbonyl condensations:
  • Schiff base formation with primary amines to give imines; useful for ligand synthesis and as intermediates in reductive amination.
  • Knoevenagel condensations with active methylenes (e.g., malononitrile, ethyl cyanoacetate) to access push–pull olefins conjugated to the pyridine ring.
  • Wittig/Horner–Wadsworth–Emmons olefinations to introduce alkenes at the formyl position with E/Z control via reagent choice.
• Nucleophilic additions to the aldehyde:
  • Grignard/organolithium additions (under anhydrous conditions) to provide secondary alcohols; the pyridine nitrogen can coordinate, sometimes affecting reactivity—protecting as N-oxide or N-methyl may be strategic in complex settings.
• Cross-coupling at the para-chloro substituent:
  • Suzuki–Miyaura, Buchwald–Hartwig, or Stille couplings using tailored Pd catalysts/ligands (e.g., BrettPhos/SPhos for aryl chlorides) to diversify the 4-position of the phenyl ring while retaining the aldehyde.
• Further heteroarene manipulation:
  • N-oxidation of the pyridine as a directing group or for subsequent transformations.
• Applications context:
  • Common in medicinal chemistry SAR programs where the aldehyde enables rapid analog generation (Schiff bases, alcohols), and the aryl chloride allows late-stage diversification.

Practical tips:

• Protect sensitive aldehyde during strong base or cross-coupling (as acetal) when necessary.
• Employ anhydrous, oxygen-limited conditions to minimize aldehyde oxidation during prolonged reactions.

Reaction Conditions

General literature-guided conditions for common transformations of heteroaryl aldehydes and aryl chlorides. These are not item-specific specifications; optimize for your system.

• Schiff base formation:
  • Solvent: EtOH, i-PrOH, or toluene.
  • Catalyst: trace acid (AcOH) or molecular sieves; room temp to 60 °C; 1–12 h.
  • Workup: filtration or extraction; optionally reduce in situ (NaBH3CN or NaBH(OAc)3) for reductive amination.
• Knoevenagel condensation:
  • Partners: malononitrile, ethyl cyanoacetate.
  • Base: piperidine, pyridine, or ammonium acetate; EtOH or toluene; 25–110 °C; typically 70–95% yields reported for analogous nicotinaldehydes (literature).
• Wittig/HWE olefination:
  • Reagents: stabilized ylides or phosphonates; Solvent: THF/THF–toluene; 0–25 °C to reflux; 2–16 h.
• Grignard/organolithium addition:
  • Solvent: dry THF or Et2O under N2/Ar; temperature: −78 to 0 °C; quench with NH4Cl.
• Suzuki–Miyaura coupling at the para-chloro site:
  • Catalyst: Pd2(dba)3 (1–2 mol%) + BrettPhos/SPhos (2–4 mol%).
  • Base: K3PO4 or Cs2CO3; Solvent: 1,4-dioxane/H2O (3:1) or toluene/H2O; 80–110 °C; 4–16 h.
  • Note: Consider acetal protection of the aldehyde if base/catalyst conditions compromise it.
• Buchwald–Hartwig amination (aryl chloride):
  • Catalyst: Pd(OAc)2/XPhos or Pd2(dba)3/BrettPhos; Base: NaOtBu or Cs2CO3; Solvent: toluene or dioxane; 80–110 °C.

Analytics:

• Monitor by TLC (UV 254 nm), HPLC/UPLC (C18, MeCN/H2O + 0.1% formic acid), and NMR. Aldehyde proton typically ~9.8–10.2 ppm (literature for aryl/heteroaryl aldehydes).

Safety and Handling

Item-specific GHS/SDS details: Not specified for this item; refer to SDS for authoritative hazard, classification, and first-aid information.

General safety considerations for heteroaromatic aldehydes and aryl chlorides (literature-based guidance):

• Likely hazards: skin/eye/respiratory irritation; harmful if swallowed or inhaled. Aldehydes can be sensitizers in some cases. Avoid dust or aerosol generation.
• PPE: wear lab coat, chemical-resistant gloves (e.g., nitrile), splash goggles; handle in a fume hood to avoid inhalation of vapors or dust.
• Handling: minimize exposure to air and light to reduce slow oxidative degradation to the corresponding carboxylic acid. Keep containers tightly closed. Use dry, oxygen-limited conditions for moisture/air-sensitive transformations.
• Incompatibilities: strong oxidizers (risk of over-oxidation); strong bases/acids in protic media (can induce aldol-like side reactions, acetalization, or ether cleavage under harsh conditions); reactive nucleophiles (can add to the aldehyde).
• First aid (overview—consult SDS):
  • 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 if irritation continues.
  • Ingestion: rinse mouth; do not induce vomiting; get medical attention.
• Fire safety: organic combustible; use CO2, dry chemical, or foam. Combustion may release HCl and NOx due to chloro/pyridine moieties.
• Waste: collect organic waste in halogenated or non-halogenated streams as appropriate to the solvent matrix; dispose per institutional and local regulations.

Solvent Selection

This product is a heteroaromatic aldehyde building block rather than a solvent. Selection of solvents pertains to its use in reactions, purification, and analysis.

• Polarity and miscibility needs:
  • The compound is moderately nonpolar-to-polarizable due to aryl chloride/ether and polar aldehyde/pyridine. It tends to dissolve in mid-polarity organic solvents: dichloromethane (DCM), ethyl acetate (EtOAc), acetonitrile (MeCN), THF, toluene, and DMF/DMSO (literature trends).
  • Water solubility is expected to be low.
• Typical use scenarios:
  • Condensations (Schiff base/Knoevenagel): alcohols (EtOH, i-PrOH), MeCN, or toluene with azeotropic water removal (Dean–Stark) where appropriate.
  • Nucleophilic additions (Grignard/organolithium): dry THF/Et2O under inert atmosphere.
  • Cross-coupling on the aryl chloride: dioxane, THF, toluene, or MeCN, often with water cosolvent for base solubility.
• Workup and purification:
  • Partition with EtOAc/hexanes or DCM/water systems. Silica gel chromatography eluting with hexanes/EtOAc or toluene/EtOAc is commonly effective for aryl aldehydes (monitor to avoid overexposure to basic silica that can cause tailing; small triethylamine additives can sharpen bands if needed).
• Comparison notes (literature):
  • DCM vs EtOAc: DCM provides stronger elution and better dissolution; EtOAc is greener and more benign. MeCN offers good solubility and is GC-compatible.

Storage and Reconstitution

• Storage conditions (from Product Data): Room temperature.
• Shipped in: Not specified for this item; refer to CoA/Spec Sheet.
• Appearance: Not specified for this item; refer to CoA/Spec Sheet.

General handling and stability (literature-based guidance for heteroaryl aldehydes):

• Keep tightly sealed under dry air or inert gas to limit oxidation to the corresponding carboxylic acid and to prevent hydration/polymerization events.
• Protect from prolonged light exposure.
• If long-term storage is anticipated, consider storing under nitrogen with a desiccant; refrigeration (2–8 °C) can further reduce oxidative processes, though the Product Data indicates room temperature is acceptable.
• For solution stocks: prepare in dry solvents (e.g., DMSO, MeCN). Store small aliquots to minimize headspace and freeze–thaw cycles. Monitor by HPLC for degradation over time.

Reconstitution/dissolution:

• The compound typically dissolves readily in DMSO, DMF, MeCN, DCM, THF, and EtOAc (literature trend). Gentle warming and sonication can aid dissolution. Avoid aqueous media due to limited solubility.

Note: For authoritative stability limits, impurity controls, and retest dates, consult the lot-specific CoA and SDS. Research use only (per Product Data).

Structure and Identity

Brief description: 2-(4-Chlorophenoxy)nicotinaldehyde is a heteroaromatic aldehyde bearing a 3-formylpyridine (nicotinaldehyde) core substituted at the 2-position with a para-chlorophenoxy ether.

• Item-specific identifiers (from Product Data)
  • CAS: 478031-03-7
  • PubChem CID: 3485254
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• Computed/literature structural information (for reference; not item specifications)
  • Structural features:
    • Aromatic heterocycle: pyridine ring (nicotinyl) with the aldehyde (–CHO) at the 3-position (nicotinaldehyde motif)
    • 2-aryloxy substituent: –O–C6H4–Cl (para-chloro) attached at the 2-position of the pyridine
    • Functional groups: aldehyde (electrophilic carbonyl), aryl chloride (cross-coupling handle), aryl–O–aryl ether (phenoxy linkage), tertiary aromatic nitrogen (pyridine)
  • 2D description in words: a 3-formylpyridine ring where the carbon adjacent to the ring nitrogen (C-2) is bonded through an ether oxygen to a 4-chlorophenyl ring (chlorine at the para position). The aldehyde carbonyl is conjugated with the pyridine ring.
  • Empirical formula (literature/structure-based): C12H8ClNO2
  • Molecular weight (literature/structure-based): ~233.64 g/mol

Notes: The values above under “computed/literature” are provided for chemical context only and are not item specifications. Always consult the product CoA for definitive identifiers.

Synthetic Utility

Functional group leverage:

• Aldehyde (–CHO): electrophile amenable to imine formation, acyl anion equivalents (Wittig/HWE), nucleophilic additions (RMgX/RLi), and oxidations to carboxylic acids.
• Pyridine nitrogen: tunable basicity; can be N-oxidized for directing-group chemistry; coordinates to metals, impacting catalytic reactions.
• Para-chloro on phenyl: aryl chloride suitable for Pd/Ni-catalyzed cross-couplings (Suzuki, Buchwald–Hartwig, Stille, Negishi) enabling diversification.
• Aryl–O–heteroaryl ether: typically stable under neutral/basic conditions; can undergo SNAr cleavage only under forcing conditions; serves as a conformational and electronic modulator.

Retrosynthetic value:

• Enables modular construction of 2-aryloxy nicotinaldehyde scaffolds: disconnection at the aryl chloride allows late-stage coupling, while the aldehyde position provides orthogonal diversification.

Representative transformations (literature):

• Knoevenagel with malononitrile in EtOH/piperidine → E-alkenes conjugated to pyridine.
• Wittig using stabilized ylides in THF at 0–25 °C → predominantly E-olefins.
• Reductive amination (NaBH3CN or catalytic hydrogenation) after imine formation with amines in MeOH/AcOH.
• Suzuki at the 4-chloro site using Pd2(dba)3/BrettPhos, K3PO4, 1,4-dioxane/H2O, 80–100 °C.

Practical notes:

• Protect the aldehyde as an acetal (ethylene glycol, catalytic p-TsOH) if exposing to strong bases/high temperatures during cross-coupling.
• Control pyridine coordination effects by adding ligand excess or temporary N-protection where needed.

Target Specificity

Not applicable. This product is a small-molecule chemical building block, not a biological macromolecule or affinity reagent. No antigen, epitope, or species reactivity is associated with this item.