2-(4-Chlorophenoxy)-6-fluorobenzaldehyde - ≥98% , CAS No.902836-82-2

CAS: 902836-82-2 Cat. No.: C1025732 Summenformel: C₁₃H₈ClFO₂ Molekulargewicht: 250.66 EG-Nummer: 677-299-5 PubChem CID: 42553314

GRADE & PURITY ≥98%

Storage

Room temperature

Specifications

Spezifikationen & Reinheit

≥98%

Storage

Room temperature

Reinheit

≥98%

Namen und Kennungen

Kanonisches Lächeln

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

IUPAC Name

2-(4-chlorophenoxy)-6-fluorobenzaldehyde

InChIKey

JEPXYNGAXLVUMW-UHFFFAOYSA-N

INCHI

1S/C13H8ClFO2/c14-9-4-6-10(7-5-9)17-13-3-1-2-12(15)11(13)8-16/h1-8H

Isomere SMILES

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

PubChem CID

42553314

Molekulargewicht

250.66

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Klasse Benzene and substituted derivatives
      • Subclass Diphenylethers

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Klasse: Benzene and substituted derivatives
• Subclass: Diphenylethers
• Intermediate Tree Nodes: Not available
• Direct Parent: Diphenylethers
• Alternative Parents: Diarylethers Phenoxy compounds Phenol ethers Benzoyl derivatives Benzaldehydes Fluorobenzenes Chlorobenzenes Aryl fluorides Aryl chlorides Vinylogous halides Organofluorides Organochlorides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Diphenylether - Diaryl ether - Phenoxy compound - Benzaldehyde - Phenol ether - Benzoyl - Aryl-aldehyde - Chlorobenzene - Fluorobenzene - Halobenzene - Aryl chloride - Aryl fluoride - Aryl halide - Vinylogous halide - Ether - Organochloride - Organofluoride - Organooxygen compound - Aldehyde - Hydrocarbon derivative - Organic oxide - Organic oxygen compound - Organohalogen compound - Aromatic homomonocyclic compound
• Beschreibung: This compound belongs to the class of organic compounds known as diphenylethers. These are aromatic compounds containing two benzene rings linked to each other through an ether group.
• 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

Chemische und physikalische Eigenschaften

• Molekulargewicht: 250.650 g/mol
• XLogP3: 3.600
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 3
• Exact Mass: 250.02 Da
• Monoisotopic Mass: 250.02 Da
• Topological Polar Surface Area: 26.300 Ų
• Heavy Atom Count: 17
• Formal Charge: 0
• Complexity: 254.000
• 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

Not applicable. No validated bioassay protocols (e.g., WB, IHC, IF, FC) apply to this small-molecule building block.

• For chemical synthesis, follow reaction-specific procedures as outlined in the Reaction Conditions section and standard organic chemistry protocols.
• For analytical use (e.g., LC/MS reference), prepare solutions gravimetrically in suitable solvents (e.g., acetonitrile, methanol, DMSO) and filter through 0.2 µm PTFE prior to injection, as required by your method. Item-specific solution stability should be established experimentally.

Biological Roles

This product is a synthetic organic building block rather than a biomolecule.

• Not typically associated with endogenous biological roles, metabolic pathways, or signaling functions.
• Any discussion of bioactivity would pertain to downstream compounds synthesized from this aldehyde and must be evaluated independently.
• For work interfacing with biological systems (e.g., probe development), ensure removal of residual aldehyde or convert to stable derivatives (oximes, acetals) as appropriate to minimize nonspecific reactivity with biomolecules.

No medical or clinical uses are claimed or supported; for research use only.

Buffer Applications

Not typically applicable. 2-(4-Chlorophenoxy)-6-fluorobenzaldehyde is a hydrophobic aryl aldehyde and is not used as a buffering agent.

• If used in biochemical experiments, it is commonly dissolved as a stock in DMSO or DMF and then diluted into assay media; keep final cosolvent content low (e.g., ≤1–2%) to avoid perturbing biological systems.
• For pH-sensitive transformations of the aldehyde (e.g., imine formation), choose appropriate buffer systems externally (e.g., acetate for mildly acidic conditions), but the compound itself does not act as a buffer.

Green Alternatives

• Solvent choices (greener swaps)

  • Replace chlorinated solvents (e.g., DCM) with ethyl acetate or 2-MeTHF for workup and chromatography when solubility allows.
  • For polar reactions (condensations, SNAr), prefer CPME or 2-MeTHF over THF/dioxane due to better safety and sustainability; MeCN can often be replaced by propylene carbonate or EtOAc depending on reaction.

• Reagent considerations

  • For reductions of the aldehyde, catalytic hydrogenation (H2/Pd) or transfer hydrogenation (formic acid/Et3N, isopropanol/Ru) can reduce waste vs stoichiometric hydrides.
  • Oxidations to the acid: TEMPO/bleach or oxygen-mediated catalytic systems reduce chromium waste.
  • Olefinations: HWE phosphonates sometimes offer better E-selectivity with reduced byproduct handling vs classical Wittig (and facilitate aqueous workups).

• Comparative snapshot (general)

  • THF vs 2-MeTHF: similar performance; 2-MeTHF is bio-based, higher boiling (easier water removal), reduced peroxide propensity relative to THF.
  • Dioxane vs CPME: CPME less toxic, wider liquid range, forms less peroxide, and enables water separation.

• Process intensification

  • Consider solvent recycling (EtOAc, toluene) and catalytic loadings <1 mol% for Pd cross-couplings using highly active ligands to minimize precious metal use.

These recommendations are general and should be validated for your specific transformation and solubility profile.

Pharmaceutical Uses

• This product is a research-grade synthetic intermediate used to build more complex molecules. It is not an excipient or a pharmacopeial article.
• Potential roles in pharmaceutical R&D are limited to medicinal chemistry and process development as a starting material for structure–activity relationship studies or intermediate generation.
• If incorporated into GMP workflows, item-specific specifications (identity, purity, residual solvents, elemental impurities) and appropriate quality systems must be established separately. No GMP status is claimed here.

No therapeutic or clinical claims are made; for research use only.

Physical Properties

• Item-specific properties

  • Appearance: Not specified for this item; refer to CoA/Spec Sheet.
  • Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
  • Density: Not specified for this item; refer to CoA/Spec Sheet.
  • Melting point / Boiling point: Not specified for this item; refer to CoA/Spec Sheet.
  • Refractive index, UV cutoff, water/peroxide/metal limits: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/typical characteristics (qualitative; not item specifications)

  • Physical state: aromatic aldehydes of this size are often low-melting solids or high-boiling oils.
  • Polarity/solubility: expected low water solubility; freely soluble in common organic solvents (e.g., dichloromethane, THF, acetone, ethyl acetate, toluene) due to diaryl ether backbone; moderately polar functionality from –CHO.
  • Volatility: relatively low; benchtop handling is practical with minimal evaporation.
  • Acid/base behavior: neutral compound; aldehyde carbonyl can engage in H-bond acceptance; no ionizable groups in neutral aqueous media.

• Practical notes (general)

  • The aldehyde can undergo hydrate formation in strongly aqueous media and can slowly oxidize to the corresponding acid under air/light. Maintain dry conditions to preserve purity.
  • The aryl halides (Cl, F) do not materially affect basic handling but influence reactivity in cross-coupling and SNAr chemistry (see Synthetic Utility).

Quality and Grades

• Item-specific details

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

• Interpreting grades (general guidance)

  • Research/biochemical grade typically emphasizes low inorganic/organic residuals suitable for synthesis and discovery studies.
  • If offered in HPLC grade or similar, this implies stringent control of UV-absorbing impurities and particulate content for analytical applications (not specified here).
  • For building-block aldehydes, key quality attributes include: residual solvents, aldehyde content by titration or qNMR, low acid content (oxidation product), halide integrity (verified by GC/LC-MS), and water content (Karl Fischer). Refer to the CoA for item-specific acceptance criteria.

• Practical implications

  • If no stabilizer is listed, assume the neat aldehyde is provided. For long-term projects, consider aliquoting under inert gas to maintain aldehyde content.
  • For sensitive cross-couplings or stereoselective transformations, verify trace metal content and halide assay on the CoA to ensure reproducibility.

Reaction and Applications

As a halogenated diaryl ether bearing an aryl aldehyde, this molecule is a versatile intermediate for medicinal and materials chemistry.

• Transformations involving the aldehyde (general/literature)

  • Carbon–carbon bond formation: Wittig/Horner–Wadsworth–Emmons olefinations; Knoevenagel condensations with active methylenes; aldol reactions; McMurry coupling (with a second carbonyl).
  • Nucleophilic additions: Grignard/organolithium additions to give secondary alcohols; cyanohydrin formation; Strecker-type adducts after imine formation.
  • Derivatizations: Oxime/hydrazone formation, imine (Schiff base) with amines; reduction (NaBH4, catalytic hydrogenation) to benzyl alcohol; oxidation (Ag2O, TEMPO, or Jones) to the corresponding carboxylic acid.

• Leveraging the aryl halides and ether (general)

  • Aryl chloride (para on phenoxy ring): suitable for Pd-catalyzed cross-couplings (Suzuki–Miyaura, Buchwald–Hartwig, Sonogashira) with modern catalysts/ligands that activate aryl chlorides.
  • Aryl fluoride (ortho to –CHO): can participate in SNAr with strong nucleophiles due to activation by the adjacent electron-withdrawing aldehyde; also amenable to metalation under directed conditions.
  • Intramolecular strategies: the ortho-phenoxy/aldehyde motif may be leveraged for cyclizations to benzofuran frameworks after appropriate activation or two-step sequences (literature precedents).

• Application spaces

  • Scaffold elaboration for halogen scanning in SAR studies.
  • Preparation of push–pull styrenes (via HWE) and diaryl alcohols (via RMgX/RLi), preserving the ether linkage.

Practical tips: keep moisture low to avoid hemiacetal/hydrate formation during base-catalyzed steps; for couplings, pre-scrub with scavengers if trace sulfur/halide impurities are suspected.

Reaction Conditions

General literature guidance (not item specifications; optimize per substrate and scale):

• Wittig/HWE olefination

  • Solvent: THF, toluene, or DMF (2-MeTHF/CPME as greener options).
  • Base: NaH, t-BuOK, or DBU (for HWE).
  • Temp/time: 0 °C to reflux; 2–16 h.
  • Notes: Dry conditions; slow addition of ylide/phosphonate; control E/Z via reagent choice.

• Grignard addition to the aldehyde

  • Solvent: anhydrous THF or Et2O.
  • Temp: −78 to 0 °C (for reactive RMgX) or 0–25 °C for less reactive.
  • Workup: saturated NH4Cl quench; avoid over-reduction.

• Oxime/hydrazone formation

  • Solvent: EtOH, MeOH, or aqueous EtOH.
  • Catalyst: AcOH (0.1–1 equiv) to accelerate.
  • Temp: rt to 60 °C; 1–4 h.

• Suzuki–Miyaura coupling at aryl chloride (phenoxy ring)

  • Catalyst/ligand: Pd2(dba)3 (0.5–1 mol%) + bulky biaryl phosphine (e.g., XPhos/BrettPhos); or Pd-PEPPSI-type NHC.
  • Base: K3PO4, Cs2CO3, or NaOtBu.
  • Solvent: toluene/dioxane, CPME, or DMF; 60–110 °C; 4–16 h.

• SNAr at aryl fluoride (aldehyde ring)

  • Nucleophile: amines/thiolates/alkoxides (≥2–3 equiv).
  • Solvent: DMSO or DMF; Base: K2CO3–Cs2CO3 or NaH; 80–140 °C; 6–24 h.
  • Note: Electron withdrawal by the adjacent –CHO facilitates displacement; monitor for competing addition to the aldehyde.

• Oxidation to acid

  • TEMPO/NaOCl (pH ~9) or O2/catalyst; 0–25 °C; monitor to avoid over-oxidation of sensitive substituents.

Safety and Handling

• Item-specific safety (from Product Data)

  • GHS Classification: Not specified for this item; refer to SDS.
  • Signal Word: Not specified for this item; refer to SDS.
  • H-Statements: Not specified for this item; refer to SDS.
  • Pictograms: Not specified for this item; refer to SDS.
  • Research Use Note: For research use only.

• General safety guidance for aryl aldehydes (literature/typical; consult SDS for definitive measures)

  • Hazards: Many aryl aldehydes cause skin/eye irritation and may be harmful if swallowed or inhaled. Avoid breathing vapors or dust. Handle in a fume hood.
  • PPE: lab coat, nitrile gloves, splash goggles. Consider double-gloving for extended contact. Use local exhaust ventilation.
  • First aid: If on skin/eyes, rinse with water for several minutes; remove contaminated clothing. If inhaled, move to fresh air. If ingested, rinse mouth; do not induce vomiting; seek medical attention. Always follow institution protocols and SDS instructions.
  • Incompatibilities: strong oxidizers (risk of exothermic reaction/over-oxidation), strong bases (aldol/self-condensation), strong acids (acetalization; potential for corrosive conditions). Avoid amines in bulk storage (Schiff base formation).
  • Stability concerns: Aldehydes can oxidize to acids; minimize exposure to air, heat, and light. Diaryl ethers are not peroxide-forming, but general good practice is to keep containers tightly closed and dry.
  • Spill/cleanup: Absorb with inert material (vermiculite), collect for disposal. Prevent entry into drains. Dispose per regulations.

Solvent Selection

This compound is a moderately hydrophobic diaryl ether bearing an aldehyde, with very low expected aqueous solubility and good solubility in most organic media.

• Solubility/miscibility profile (general)

  • Polar aprotic: typically highly soluble in DMF, DMSO, NMP, acetone, acetonitrile, and THF.
  • Moderately polar/ether/ester: soluble in ethyl acetate, MTBE, 2-MeTHF, CPME.
  • Aromatic/aliphatic hydrocarbons: soluble in toluene, chlorobenzene, dichloromethane; limited in hexanes unless warmed.
  • Water: expected to be practically insoluble.

• Selection by operation

  • Nucleophilic additions/condensations to the aldehyde: THF, 2-MeTHF, toluene, or EtOH/i-PrOH depending on base and nucleophile; remove water for equilibrium-limited steps (Dean–Stark in toluene or azeotropes).
  • Cross-coupling at aryl chloride: toluene, dioxane, CPME, or DMF with appropriate Pd catalyst/base.
  • SNAr at aryl fluoride (if employed): DMSO/DMF with strong nucleophile/base and elevated temperature.

• Comparison notes

  • THF vs 2-MeTHF: 2-MeTHF offers similar solvation with higher hydrophobicity and greener profile; may improve phase separation workups.
  • DCM vs EtOAc: EtOAc is a greener choice for extraction/chromatography when feasible.

Always verify actual solubility with a small-scale test; consult the CoA if an analytical-grade solvent requirement is specified (not specified for this item).

Storage and Reconstitution

• Item-specific storage/shipping

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

• General storage guidance for aryl aldehydes (best practice)

  • Keep tightly closed in a dry, inert atmosphere (nitrogen/argon) to limit oxidation to the carboxylic acid.
  • Protect from prolonged light exposure and elevated heat.
  • For long-term storage, consider aliquoting to minimize headspace and repeated air exposure; include a desiccant in secondary containment.

• Reconstitution/solution preparation (general)

  • Solvents: Typically soluble in DMSO, DMF, THF, acetone, EtOAc, toluene, and dichloromethane. Verify suitability for your application.
  • Stock solutions: Prepare at known concentrations (e.g., 10–100 mM), filter if necessary (PTFE syringe filter), and store cold in amber vials. Many aldehyde solutions are stable for days to weeks at 2–8 °C; confirm by LC or NMR before use.
  • Avoid prolonged storage in alcoholic solvents unless acetal/hemiacetal formation is acceptable.

Always consult the product CoA/SDS for definitive handling and stability details.

Structure and Identity

Brief overview: 2-(4-Chlorophenoxy)-6-fluorobenzaldehyde is a dihalogenated diaryl ether bearing an ortho-fluorinated benzaldehyde core and a para-chloro phenoxy substituent. It is a versatile aryl aldehyde building block.

• Item-specific (from Product Data)

  • SKU: C1025732
  • Product Name: 2-(4-Chlorophenoxy)-6-fluorobenzaldehyde
  • CAS: 902836-82-2
  • CID: 42553314
  • InChIKey: 158391 (as provided in catalog)
  • SMILES: 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 identity (for reference; not item specifications)

  • Typical molecular formula (literature): C13H8ClFO2
  • Typical molecular weight (literature): ~250.66 g/mol
  • Core structural features: benzaldehyde (–CHO) on an anisole-like diaryl ether; F at the 6-position of the aldehyde ring; the phenoxy ring bears a para-Cl.

• 2D structure description (verbal)

  • Ring A: benzaldehyde ring with ortho (2-) phenoxy substituent and ortho (6-) fluorine relative to –CHO.
  • Ether linkage: Ring A–O–Ring B.
  • Ring B: para-chloro phenyl (4-chlorophenyl) connected via oxygen.
  • Functional groups: aryl aldehyde, aryl–O–aryl ether, aryl chloride, aryl fluoride; no stereocenters (achiral).

Synthetic Utility

Key reactive elements enable diverse elaborations:

• Aldehyde functionality

  • Electrophilic carbonyl accepts nucleophiles (RMgX/RLi, cyanide) giving secondary alcohols or cyanohydrins.
  • Carbonyl condensations (Wittig/HWE, Knoevenagel) install alkenes or conjugated systems, useful for tuning electronics in diaryl frameworks.
  • Redox versatility: selective reduction to benzyl alcohols; oxidation to benzoic acids; protection as acetals for multi-step sequences.

• Halogen handles

  • Para-chloro on the phenoxy ring: participates in Pd-catalyzed couplings with suitable ligands (e.g., BrettPhos, XPhos) enabling Suzuki–Miyaura (to aryl/alkenyl boronates), Buchwald–Hartwig (to amines), and Sonogashira (to alkynes).
  • Ortho-fluoro on the aldehyde ring: activated toward SNAr by the neighboring electron-withdrawing –CHO, allowing substitution by amines/thiols/alkoxides under strong base/heat; also serves as a handle for metal–halogen exchange under controlled conditions.

• Ether linkage

  • The aryl–O–aryl motif is robust under many coupling and condensation conditions, supporting late-stage diversification without ether cleavage.

• Strategic applications

  • Access to benzofuran or benzopyran motifs through cyclizations that exploit the ortho-phenoxy/aldehyde arrangement (after appropriate activation or two-step sequences).
  • Divergent synthesis: orthogonal use of the aldehyde (chemoselective) vs the aryl chloride/fluoride enables sequential functionalization strategies.

Target Specificity

Not applicable. This product is a small-molecule building block and does not possess biological target specificity, epitope, or clone information. No antibody or protein attributes apply.