4-Ethoxy-2,6-difluorobenzaldehyde - ≥95% , CAS No.1017779-48-4

CAS: 1017779-48-4 Cat. No.: E736190 분자식: C₉H₈F₂O₂ 분자량: 186.16 EC 번호: 816-728-4 PubChem CID: 46737615

GRADE & PURITY ≥95%

Storage

Store at 2-8°C,Argon charged

Shipped In

Wet ice

Specifications

사양 및 순도

≥95%

보관 조건

Store at 2-8°C,Argon charged

배송

Wet ice

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순수함

≥95%

이름과 식별자

• 정식 스마일: CCOC1=CC(=C(C(=C1)F)C=O)F
• IUPAC Name: 4-ethoxy-2,6-difluorobenzaldehyde
• InChIKey: SHCJRMIWXNHWJF-UHFFFAOYSA-N
• INCHI: 1S/C9H8F2O2/c1-2-13-6-3-8(10)7(5-12)9(11)4-6/h3-5H,2H2,1H3
• 이성체 SMILES: CCOC1=CC(=C(C(=C1)F)C=O)F
• PubChem CID: 46737615
• 분자량: 186.16

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • 분류 Phenol ethers

• Kingdom: Organic compounds
• Superclass: Benzenoids
• 분류: Phenol ethers
• Subclass: Not available
• Intermediate Tree Nodes: Not available
• Direct Parent: Phenol ethers
• Alternative Parents: Phenoxy compounds Benzoyl derivatives Benzaldehydes Fluorobenzenes Alkyl aryl ethers Aryl fluorides Vinylogous halides Organofluorides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Phenoxy compound - Benzaldehyde - Benzoyl - Phenol ether - Alkyl aryl ether - Fluorobenzene - Halobenzene - Aryl-aldehyde - Monocyclic benzene moiety - Aryl halide - Aryl fluoride - Vinylogous halide - Ether - Organofluoride - Organohalogen compound - Aldehyde - Organic oxide - Organic oxygen compound - Organooxygen compound - Hydrocarbon derivative - Aromatic homomonocyclic compound
• 설명: This compound belongs to the class of organic compounds known as phenol ethers. These are aromatic compounds containing an ether group substituted with a benzene ring.
• 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

화학 및 물리적 특성

• 분자량: 186.150 g/mol
• XLogP3: 1.900
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 3
• Exact Mass: 186.049 Da
• Monoisotopic Mass: 186.049 Da
• Topological Polar Surface Area: 26.300 Ų
• Heavy Atom Count: 13
• Formal Charge: 0
• Complexity: 163.000
• 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 tested bioassay protocols (e.g., WB, IHC, IF, FC) are applicable to this small-molecule building block. For synthetic usage, consult the Reaction Conditions and Synthetic Utility sections for general laboratory procedures. Always adapt to your specific substrate, scale, and safety requirements.

Biological Roles

Applicability: This product is a synthetic aromatic aldehyde used as a research chemical building block. No endogenous biological role is indicated for this specific structure.

General context (non-clinical, literature):

• Aromatic aldehydes can serve as precursors to ligands, probes, or polymers used in biochemical research, but the compound itself is not intended for biological administration.
• Fluorination (2,6-difluoro) is frequently employed in medicinal chemistry to modulate metabolic stability, binding conformation, and pKa of neighboring functionalities; incorporation at ortho positions can influence conformational bias around formyl substituents in derived scaffolds.
• The para-ethoxy substituent can be transformed to phenolic or further ether/ester motifs, enabling conjugation to tags, linkers, or polymer backbones for biochemical assay tools.

Note:

• Any biological testing should be performed under institutional approvals for research use only. No pharmacological, toxicological, or therapeutic claims are made for this product.

Buffer Applications

Not typically applicable. 4-Ethoxy-2,6-difluorobenzaldehyde is a neutral, hydrophobic aromatic building block and is not used as a buffering agent. For experimental design, focus on the Synthetic Utility, Reaction Conditions, and Solvent Selection sections for guidance on handling and reactivity in organic media.

Green Alternatives

Scope: Green considerations focus on the process using this aldehyde (solvent/base/oxidant choices), as the building block itself has no direct “green substitute” without altering the target structure.

Greener solvent choices (literature/general):

• Replace DCM/CHCl3 with toluene, ethyl acetate, MeTHF/2-MeTHF, CPME, or propylene carbonate where reaction compatibility allows.
• For olefinations and condensations, 2-MeTHF or CPME often matches THF/DCM performance with better EHS profiles and simpler aqueous workups (immiscible ethers).

Reagent and oxidation/reduction choices:

• Oxidation to the acid: use Pinnick (NaClO2 with phosphate buffer) rather than chromium(VI) reagents.
• Reductions: favor catalytic hydrogenation or transfer hydrogenation (e.g., HCO2NH4/Pd-C) over stoichiometric hydrides when feasible.
• Condensations: employ catalytic organobases (DBU, TBD) or amino acid catalysts in benign solvents (EtOH, water/EtOH cosolvent) when compatible with solubility.

Small comparison (illustrative):

• THF vs 2-MeTHF: similar polarity; 2-MeTHF derived from renewable sources, less miscible with water, often easier phase separations; THF widely available but peroxide-forming.
• DCM vs EtOAc: DCM excellent solvency but volatile chlorinated solvent; EtOAc biodegradable, low toxicity, higher bp—may require longer reaction times.

Waste minimization:

• Plan telescoped sequences (e.g., imine formation → in situ reduction) to reduce isolations and solvent usage. Employ inline scavengers to remove phosphine oxide after Wittig/HWE.

Pharmaceutical Uses

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

General, non-clinical context:

• Role in drug substance/process R&D: This aldehyde can serve as an intermediate for medicinal chemistry SAR programs, enabling introduction of difluoro-aryl motifs and aldehyde-derived linkers (e.g., via reductive amination or olefination).
• Formulation/excipient use: Not applicable—aromatic aldehydes of this type are not used as excipients.
• Manufacturability considerations: The 2,6-difluoro substitution improves stability toward oxidative metabolism in derived compounds; para-ethoxy may be deprotected to phenol to generate prodrug or conjugation handles in later-stage intermediates.

Compliance notes:

• For GMP or regulatory pathways, define impurity profiles (acid oxidation product, unreacted starting materials, residual solvents, inorganic residues) and establish suitable analytical methods (HPLC/GC, NMR, 19F NMR). This listing is for research use only.

Physical Properties

Item-specific (from Product Data):

• Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
• Appearance: Not specified for this item; refer to CoA/Spec Sheet.

Literature/general or computed values for the named structure (non-specification):

• Calculated molecular weight (for C9H8F2O2): ~186.15 g/mol (informational).
• Expected physical state: aromatic aldehydes of this size are commonly low-melting solids or mobile liquids; verify on CoA for this lot.
• Solubility (qualitative): typically soluble in common organic solvents (e.g., dichloromethane, THF, ether, toluene, acetonitrile); low water solubility expected for aryl aldehydes with ether substituents.
• Volatility: moderate; aldehydes can exhibit noticeable vapor; use in well-ventilated hoods.

Not provided for this item (treat as non-specification; consult CoA/SDS or measure as needed):

• Boiling point, melting point, density, refractive index, logP, pKa, UV-Vis cutoff/absorbance, water content, residual solvents, and metal/peroxide limits.

Practical notes (general):

• Aromatic aldehydes can slowly oxidize to the corresponding acids on air exposure; minimize headspace oxygen and light for best stability.

Quality and Grades

Item-specific:

• Grade/purity: Not specified for this item; refer to CoA/Spec Sheet for assay, impurity profile, and residual solvent data.
• Stabilizers: Not specified for this item; refer to CoA/Spec Sheet.

General guidance for interpreting grade on aromatic building blocks (informational):

• Research or reagent grade typically supports routine synthesis; higher grades may specify tight limits for GC/HPLC purity, low water content, and detailed impurity IDs.
• For aldehydes, CoA often reports: assay (% area by GC/HPLC), identity (NMR/IR/MS), acid content (oxidation product), and sometimes enolizable impurity limits. If UV applications are intended, a low-UV or HPLC grade solvent should be used for dilutions rather than implying the aldehyde itself is “HPLC grade.”

Recommendations:

• Verify lot-specific purity by NMR/GC prior to moisture/air-sensitive transformations (e.g., Wittig, organometallic additions).
• If ultra-low acid content is critical (e.g., base-sensitive steps), request or check an inhibitor/stabilizer statement and acid specification on the CoA.

Reaction and Applications

Item-specific applications (from catalog): Not specified beyond research use. The following expands on typical uses for 4-ethoxy-2,6-difluorobenzaldehyde in synthesis.

General/literature applications:

• Electrophilic aldehyde chemistry:
  • Wittig/Horner–Wadsworth–Emmons to install vinyl groups para to ethoxy; electron-withdrawing 2,6-difluoro substituents often improve E-selectivity in HWE.
  • Reductive amination with amines to give benzylic amines; electron-deficient ring may moderate imine formation rate, but improves downstream hydrogenation cleanliness.
  • Nucleophilic additions (RMgX/RLi, cyanide) to access secondary alcohols or cyanohydrins; ensure rigorous anhydrous conditions.
  • Oxidation to the acid (e.g., Pinnick oxidation) or reduction to the alcohol (NaBH4, DIBAL-H) for divergent scaffolds.
• Aromatic substitution and diversification:
  • The 2,6-difluoro pattern activates the ring toward SNAr at the 1,3,5 positions relative to strong nucleophiles; nucleophile approach ortho/para to the aldehyde is guided by both –F and –CHO.
  • The ethoxy group can be demasked to the phenol (BBr3 or HBr/AcOH) to yield 4-hydroxy-2,6-difluorobenzaldehyde as a versatile handle for ether/ester formation.
• Materials/medchem relevance:
  • Electron-poor aryl aldehydes are common in push–pull chromophores (via Knoevenagel to acceptor olefins) and as fragments in SAR studies where C–F atoms tune lipophilicity and metabolic stability.

Practical tips:

• Maintain inert atmosphere (argon as per item storage) to minimize oxidation; add antioxidants only if compatible with downstream steps.
• Monitor reactions by 19F NMR when informative; distinct ortho-F resonances aid conversion tracking.

Reaction Conditions

General literature guidance (non-specification; adjust to your system):

• Wittig/HWE olefination: 0–25 °C in THF, toluene, or DCM. For HWE, use NaH/DBU with phosphonate esters; E-selectivity often favored with stabilized ylides/acceptors. Typical times: 1–16 h. Inert atmosphere to limit aldehyde oxidation.
• Reductive amination: Condense with amine in MeOH/EtOH/MeCN (catalytic acid or molecular sieves), followed by NaBH3CN or catalytic hydrogenation (Pd/C, H2, rt–50 °C). Monitor by 19F/1H NMR or LC-MS. Times: 2–18 h.
• Nucleophilic additions: RMgX/RLi in anhydrous ether/THF at −78 to 0 °C; quench carefully to avoid over-reduction/side reactions. Employ titrated organometallics.
• Oxidation to acid (Pinnick): NaClO2, NaH2PO4 buffer, 2-methyl-2-butene (scavenger), aqueous t-BuOH/MeCN, 0–25 °C, 1–4 h.
• Demethylation analogue (for this ethoxy → phenol): BBr3 (1–3 eq) in DCM at −78 to 0 °C, then warm; for ethoxy, stronger/longer conditions than for methoxy may be required; HBr/AcOH reflux is an alternative. Protect aldehyde if necessary to avoid side reactions (e.g., as acetal).

Workup/analytics:

• Maintain argon blanket (consistent with item storage). Use antioxidants only if compatible.
• Track conversions by 19F NMR (distinct ortho-F signals), 1H NMR (aldehyde ~9.5–10 ppm), and LC-MS.

Note: The above are typical literature conditions and not specifications for this item.

Safety and Handling

Item-specific (from Product Data):

• Storage conditions: Store at 2–8 °C, argon charged.
• Shipped on: Wet ice.
• GHS/Signal word/H-statements/Pictograms: Not specified for this item; refer to SDS.

General safety (literature/experience for aromatic aldehydes; not product-specific):

• Likely hazards: Irritation to skin/eyes/respiratory tract; harmful if swallowed; may cause sensitization in susceptible individuals. Avoid inhalation of vapors.
• PPE: Laboratory coat, safety glasses or chemical splash goggles, and suitable chemical-resistant gloves (e.g., nitrile). Handle in a fume hood.
• Incompatibilities: Strong bases (can promote aldol/self-condensation), strong oxidizers (risk of rapid oxidation), strong reducing agents (reduce aldehyde). Avoid prolonged exposure to air/oxygen and light to limit oxidation to the carboxylic acid.
• Peroxide formation: Not a typical peroxide-forming class (unlike ethers as bulk solvents), but always verify stability and avoid unnecessary storage with peroxides/oxidants.
• First aid (overview; defer to SDS): Move to fresh air if inhaled; rinse skin/eyes with water for at least 15 minutes upon contact; seek medical attention for persistent irritation or ingestion. Remove contaminated clothing and wash before reuse.

Handling tips:

• Use dry, oxygen-free techniques when high purity of the aldehyde is critical (argon/nitrogen blanket as per item guidance).
• Keep containers tightly closed; wipe septa to prevent crusting from slow surface oxidation.

Solvent Selection

Applicability: This product is an aromatic aldehyde building block, not used as a bulk solvent. The following addresses solvents commonly used to dissolve or react it.

General solvent behavior (literature/general):

• Polarity: Moderately polar, aromatic; dissolves well in common organic solvents including dichloromethane (DCM), chloroform, THF, 2-MeTHF, diethyl ether, ethyl acetate, acetonitrile, and toluene. Poorly soluble in water.
• Reaction solvent choices:
  • Nucleophilic additions/umpolung: anhydrous THF, 2-MeTHF, or toluene; for organometallics, rigorously dry ethers or hydrocarbons are preferred.
  • Olefination (Wittig/HWE): THF, toluene, or DCM depending on ylide/phosphonate base.
  • Condensations (Knoevenagel/Schiff base): ethanol, toluene, MeCN, or greener options (2-MeTHF, CPME) with catalytic base/acid.
  • Reductive amination: MeOH/EtOH/i-PrOH or MeCN with hydrogenation or transfer hydrogenation catalysts.

Comparison notes:

• DCM vs toluene: DCM offers better solubility and lower reaction temps; toluene enables higher-temperature drives with easier removal and improved EHS.
• THF vs 2-MeTHF: 2-MeTHF provides greener profile and water-immiscible workups; THF often affords faster kinetics but forms peroxides on storage.

Tip: Select solvent to balance reactivity of the aldehyde (electrophilicity enhanced by 2,6-difluoro) with base/catalyst compatibility and downstream workup.

Storage and Reconstitution

Item-specific (from Product Data):

• Storage: 2–8 °C, argon charged.
• Shipping: Wet ice.

General guidance for this class of compounds:

• Keep container tightly closed under inert gas to minimize oxidation of the aldehyde to the corresponding acid. Minimize headspace and repeated warm/cold cycling.
• If transferring to septum vials, pre-flush with argon and include inert headspace. For prolonged storage, amber glass helps limit light exposure.
• Do not freeze aqueous mixtures; store neat material as supplied or as anhydrous solutions (e.g., in dry toluene or 2-MeTHF) under inert gas if frequent dispensing is expected. Clearly label concentration and solvent.
• Reconstitution: Not applicable unless supplied as a solid. If needed, dissolve in a dry, oxygen-free solvent compatible with your planned reaction (e.g., dry THF, toluene, DCM). Filter through a PTFE syringe filter if particulate is observed.

Quality checks on opening:

• Inspect for discoloration or the presence of acidic odor/solid residues, which may indicate partial oxidation. Confirm identity/purity by quick 1H/19F NMR or HPLC/GC prior to critical steps.

Research use only.

Structure and Identity

Item-specific (from Product Data):

• Product name: 4-Ethoxy-2,6-difluorobenzaldehyde (SKU E736190)
• CAS: 1017779-48-4
• CID: 46737615
• InChIKey: 335786 (as provided; truncated/unusual format in listing)
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.

Computed/structure interpretation (literature/general):

• Molecular formula (derived from the IUPAC name): C9H8F2O2
• Approx. molecular weight: ~186.15 g/mol (calculated)
• Structural features: Aromatic benzaldehyde bearing two ring fluorines at the 2- and 6-positions (ortho to the aldehyde) and an ethoxy substituent at the 4-position (para to the aldehyde). Functional groups include an aldehyde (–CHO), an aryl ether (–OCH2CH3), and two aryl C–F bonds.
• 2D structure description: A 1,3,5-trisubstituted benzene ring with –CHO at C1, –F at C2 and C6, and –OCH2CH3 at C4. Remaining ring positions (C3, C5) bear hydrogen.

Notes:

• Where an exact line notation (SMILES, InChI) is required for informatics, consult the CoA/Spec Sheet for this catalog item to avoid transcription ambiguity.

Synthetic Utility

Functional groups and handles:

• Aldehyde (–CHO): versatile electrophile for imine formation, reductive amination, Wittig/HWE olefination, cyanohydrin formation, and selective reductions/oxidations.
• Aryl ether (–OEt): can be retained for electronic/solubility tuning or deprotected (BBr3, HBr) to phenol for subsequent O-alkylation/esterification/carbamate formation.
• Two aryl C–F bonds (2,6-): increase ring electron deficiency and can direct site-selective SNAr with strong nucleophiles; can also influence conformation and reactivity in downstream transformations.

Retrosynthetic value:

• Serves as a convergent junction for aldehyde-installing disconnections (e.g., oxidation of benzylic alcohols; formylation approaches such as directed lithiation followed by DMF quench on the difluoro anisole precursor).
• The para-ethoxy substituent offers a tunable leaving group after conversion to phenol, enabling modular linker strategies.

Named/typical transformations (literature/general):

• Wittig/HWE to give difluoro-stabilized styrenes; Knoevenagel with active methylene partners for push–pull chromophores.
• Reductive amination to furnish benzylic amines bearing difluoro-aryl cores; often clean with hydrogenation catalysts.
• Selective reductions: NaBH4 (careful), DIBAL-H, or catalytic hydrogenation to benzyl alcohols; Pinnick or TEMPO/bleach to acids.

Practical points:

• Electron-poor ring attenuates electrophilic aromatic substitution; plan for SNAr or cross-couplings from prefunctionalized derivatives if further ring diversification is needed.

Target Specificity

Not applicable. This product is a small-molecule aromatic aldehyde, not a biological macromolecule or antibody. No target, epitope, clone, or isotype information applies.