Ethyl 3-fluoro-4-formylbenzoate - ≥97% , CAS No.1640117-38-9

CAS: 1640117-38-9 Cat. No.: E1018859 Formula: C₁₀H₉FO₃ Peso molecolare: 196.17 PubChem CID: 121231779

GRADE & PURITY ≥97%

Storage

Room temperature

Specifications

Specifiche e purezza

≥97%

Condizioni di conservazione di stoccaggio

Room temperature

Purezza

≥97%

Nomi e identificatori

• Sorrisi canonici: CCOC(=O)C1=CC(=C(C=C1)C=O)F
• IUPAC Name: ethyl 3-fluoro-4-formylbenzoate
• InChIKey: CAIWTFXQTNXSOY-UHFFFAOYSA-N
• INCHI: 1S/C10H9FO3/c1-2-14-10(13)7-3-4-8(6-12)9(11)5-7/h3-6H,2H2,1H3
• PubChem CID: 121231779
• Peso molecolare: 196.17

Proprietà chimiche e fisiche

• Peso molecolare: 196.170 g/mol
• XLogP3: 1.700
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 4
• Exact Mass: 196.054 Da
• Monoisotopic Mass: 196.054 Da
• Topological Polar Surface Area: 43.400 Ų
• Heavy Atom Count: 14
• Formal Charge: 0
• Complexity: 217.000
• 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 biological assay protocols (e.g., WB, IHC, IF, FC) are associated with this small-molecule building block. For synthetic procedures, see the Reaction Conditions and Synthetic Utility sections for general guidance.

Biological Roles

This is a synthetic aromatic small molecule intended as a chemical building block. No endogenous biological role is known or implied.

• Applicability

  • Not a buffer, nutrient, or biomolecule; used in chemical synthesis to prepare target compounds for research.
  • The aldehyde can form reversible adducts (imines/Schiff bases) with primary amines in biological matrices, but such reactivity is nonselective and generally undesired outside controlled synthetic contexts.

• Research-only notice

  • For research use only; not for diagnostic, therapeutic, or clinical applications.

For biological evaluations of derivatives prepared from this reagent, consult appropriate safety and regulatory guidance.

Buffer Applications

Not typically applicable. Ethyl 3-fluoro-4-formylbenzoate is a non-ionic organic building block and does not serve as a buffering agent. For practical use in aqueous systems, focus on the Synthetic Utility and Reaction Conditions sections for derivatization into more polar/ionizable species if needed.

Green Alternatives

As a multifunctional aromatic building block, the greener choices largely concern solvent/process selection rather than replacing the reagent itself.

• Greener solvent choices (literature/general)

  • Replace DCM/CHCl3 with ethyl acetate, 2-MeTHF, cyclopentyl methyl ether (CPME), or dimethyl carbonate where feasible.
  • Use 2-MeTHF instead of THF to reduce peroxide/upstream petrochemical footprint and to ease aqueous workups due to partial immiscibility.
  • Favor MeOH/EtOH or water-containing media for condensations (e.g., Knoevenagel under aqueous micellar catalysis) when compatible with chemoselectivity.

• Oxidation/reduction options

  • Oxidize the aldehyde to acid via Pinnick (NaClO2, NaH2PO4, 2-methyl-2-butene) in aqueous t-BuOH rather than chromium(VI) reagents.
  • Employ catalytic hydrogenation or transfer hydrogenation in green solvents for aldehyde reductions; avoid stoichiometric tin or borane reagents when possible.

• Workup and waste minimization

  • Choose solvent systems that enable phase cuts with minimal brine; use solvent recycling where compatible.
  • Plan sequences to avoid unnecessary protection–deprotection: leverage the innate chemoselectivity between aldehyde and ester.

• Tradeoffs

  • Greener ethers (2-MeTHF/CPME) can present higher boiling points and different solvation of bases/nucleophiles; reaction rates and selectivity may shift—small-scale scouting is recommended.

Pharmaceutical Uses

No pharmacopeial or excipient role is indicated for this item.

• Typical role (general)

  • Employed as a synthetic intermediate in medicinal chemistry and process development to access substituted benzoic acids, benzamides, cinnamate analogs, or benzyl alcohol derivatives.
  • The orthogonal reactivity of the aldehyde and ester enables convergent route design and late-stage diversification for structure–activity relationship studies.

• Compliance note

  • Not intended for human or veterinary use. For cGMP or regulatory applications, obtain a full quality package (CoA, impurity profile, residual solvent data) and qualify supplier/material per your QMS.

Physical Properties

Item-specific specifications have not been provided for this SKU. Do not treat the values below as product specifications; consult the CoA/Spec Sheet for release criteria.

• Item-specific (Product Data)

  • Appearance: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular Weight: Not specified for this item; refer to CoA/Spec Sheet. (Estimated from formula: ~196.17 g/mol; literature/derived)

• Literature/typical expectations for closely related structures (for planning only)

  • Physical state: likely low-melting solid or high-boiling liquid; aromatic ester with an aldehyde often presents as a pale solid or viscous oil depending on purity and crystal habit (literature/general)
  • Solubility: expected to be soluble in common organic solvents (DCM, THF, EtOAc, toluene, acetonitrile) and poorly soluble in water due to aromatic core and ester (literature/general)
  • Polarity: moderately polar aprotic functionality on a largely hydrophobic scaffold; suitable for normal-phase and RP-HPLC separation (literature/general)

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

  • Boiling point / melting point
  • Density / refractive index
  • pKa(s) / logP (clogP)
  • UV-Vis cutoff / extinction

Always verify exact physical constants experimentally when setting process limits.

Quality and Grades

• Item-specific (Product Data)

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

• Guidance on grades (general)

  • Research/technical grade materials are suitable for synthetic and discovery workflows where performance is defined by assay and impurity profile on the CoA.
  • If offered as “assay ≥X%,” the balance typically comprises structurally related impurities, residual solvents, and moisture—quantified on the CoA. In absence of a numeric assay, verify suitability in your method by small-scale trials.
  • For chromatography-sensitive uses, low-UV/low-peroxide specifications (HPLC grade solvents, stabilizer-free reagents) may be required; since none are specified here, confirm by CoA.

• Practical implications for this SKU

  • Aldehyde content can decline via oxidation during storage/handling. When assay is critical, verify by quick check (e.g., 1H NMR intensity of formyl singlet ~9–10 ppm or an aldehyde-specific derivatization). Re-stabilization is generally not needed; minimizing headspace oxygen and moisture is beneficial.
  • If your application is moisture-sensitive (amidation, organometallic chemistry), consider drying or passing through a short plug of basic alumina immediately prior to use.

For definitive release criteria and impurity limits, rely on the product’s CoA/Spec Sheet.

Reaction and Applications

With an aryl aldehyde, an ethyl benzoate, and an aryl fluoride on the same ring, Ethyl 3-fluoro-4-formylbenzoate is a versatile bifunctional building block for divergent synthesis.

• Aldehyde chemistry (literature/general)

  • Carbon–carbon formation: Wittig/Horner–Wadsworth–Emmons to vinyl esters; Knoevenagel condensations with active methylenes; aldol additions with enolates; imine/oxime/hydrazone formation as handles for further transformations (e.g., reductive amination after ester activation).
  • Oxidation/reduction: Pinnick oxidation to the corresponding acid (para to ester); NaBH4 or catalytic hydrogenation to benzyl alcohol with ester retention under controlled conditions.

• Ester chemistry

  • Hydrolysis to 3-fluoro-4-formylbenzoic acid (base or acid catalyzed, mindful of competing aldehyde hydration/oxidation).
  • Amidation via activation (acid chloride formation post-hydrolysis; or direct ester aminolysis under forcing conditions or with catalysts).
  • Reduction: DIBAL-H at low temperature to the aldehyde/benzyl alcohol stage with chemoselectivity planning; LiAlH4 for full reduction to diol (more forcing).

• Aryl fluoride handle

  • While C–F is robust, it can engage in SNAr if additional ring activation is present; here, conjugated carbonyls increase ring deactivation—direct SNAr may still proceed with strong nucleophiles and heat. Alternatively, metalation (e.g., ortho-lithiation directed by F) or late-stage borylation under specialized conditions can diversify the scaffold.

• Medicinal chemistry utility

  • The para-formyl/ester arrangement enables rapid library synthesis of cinnamates, benzyl alcohols, amides, and acids for SAR exploration without cross-protecting group gymnastics.

Reaction Conditions

General literature guidance for common transformations of aryl aldehyde–esters. These are not product specifications; optimize for your substrate and setup.

• Wittig/Horner–Wadsworth–Emmons on the aldehyde

  • Solvent: THF, 2-MeTHF, DCM, or toluene.
  • Base: NaHMDS or t-BuOK for stabilized ylides; DBU for HWE.
  • Temperature: −78 to 25 °C depending on reagent; 1–16 h.
  • Notes: Ester is generally compatible; minimize moisture. E/Z selectivity follows ylide type.

• Knoevenagel condensation

  • Solvent: EtOH, MeOH, toluene, or acetonitrile; catalytic piperidine or ammonium acetate.
  • Temperature: rt to reflux; 1–12 h.
  • Notes: Water removal (Dean–Stark in toluene) can drive to completion.

• Aldehyde reduction (selective)

  • NaBH4 (MeOH, EtOH, or THF/MeOH), 0–25 °C, 0.5–2 h; monitor to avoid ester transesterification.
  • Catalytic hydrogenation (Pd/C, H2 1–3 bar) in EtOAc/EtOH at rt–40 °C.

• Ester hydrolysis and amidation

  • Saponification: NaOH or K2CO3 in MeOH/H2O (1:1–9:1), 0–50 °C, 1–6 h; acidify to isolate acid.
  • Amidation: Acid chloride formed with SOCl2/oxalyl chloride (0–25 °C), then amine base (DIPEA) in DCM/THF; or EDC/HATU coupling from the acid in DMF/ACN.

• Oxidation of aldehyde to acid (Pinnick)

  • NaClO2, NaH2PO4 buffer, 2-methyl-2-butene, t-BuOH/H2O, 0–25 °C, 1–4 h.

• Global reductions (forcing)

  • LiAlH4 (THF, 0–25 °C) can reduce ester and potentially affect aldehyde—use with caution or protect the aldehyde as an acetal beforehand.

Safety and Handling

GHS details for this catalog item have not been provided. Handle based on prudent laboratory practice for aromatic aldehyde–esters and consult the SDS for authoritative information.

• Item-specific (Product Data)

  • GHS Classification, Signal Word, H-Statements, Pictograms: Not specified for this item; refer to SDS.
  • Storage: Room temperature (store tightly closed)

• General hazards for class (literature/general)

  • Aldehydes can be irritants and may form peroxides or undergo autoxidation to acids; avoid prolonged air/heat exposure.
  • Esters may cause skin/eye irritation; aromatic fluorides are generally stable but may evolve hazardous fumes on combustion.

• PPE and hygiene

  • Use lab coat, safety glasses or face shield, and appropriate chemical-resistant gloves (e.g., nitrile). Work in a fume hood to avoid inhalation of vapors/aerosols.
  • Avoid contact with oxidizers, strong bases/acids (risk of hydrolysis), and strong reducing agents (risk of uncontrolled reduction of the aldehyde/ester).

• First-aid overview (consult SDS)

  • Inhalation: move to fresh air; seek medical advice if symptoms persist.
  • Skin/eye contact: rinse with water for several minutes; remove contaminated clothing; seek medical attention for persistent irritation.
  • Ingestion: rinse mouth; do not induce vomiting; seek medical attention.

• Stability notes

  • Protect from moisture and prolonged light; aldehyde functionality is susceptible to oxidation—store under inert atmosphere for long-term stability (best practice).

Solvent Selection

This compound is a moderately lipophilic, polarizable aromatic bearing aldehyde and ester carbonyls.

• Solubility/miscibility (literature/general expectations)

  • Good: dichloromethane, chloroform, THF, 2-MeTHF, ethyl acetate, acetonitrile, toluene, DMF, DMSO.
  • Limited: alcohols (MeOH/EtOH) at room temperature may dissolve moderately; water is expected to be very poor.

• Polarity considerations

  • The carbonyls support interactions in moderately polar aprotic media, aiding rates of condensations (Wittig/Knoevenagel) and acyl substitutions (amidation after activation). Nonpolar aromatics (toluene) are suitable for high-temperature steps or where water exclusion is paramount.

• Selection tips

  • Chemoselective aldehyde reactions: choose aprotic ethereal solvents (THF, 2-MeTHF) or DCM at 0–25 °C.
  • Amidation (from the ester after activation): acetonitrile, DCM, or DMF with coupling reagents.
  • Hydrolysis or alcoholysis: alcoholic solvents with catalytic acid/base; biphasic aqueous base for saponification.
  • Oxidation of aldehyde (e.g., Pinnick): tert-butanol/water or acetonitrile/water mixtures.

• Small comparison (literature/general)

  • DCM vs EtOAc: DCM offers higher solubility and lower boiling point; EtOAc is a greener choice but may participate in transesterification under harsh basic conditions.
  • THF vs 2-MeTHF: 2-MeTHF provides comparable solvency with greener profile and better water immiscibility, often simplifying workup.

Storage and Reconstitution

• Item-specific (Product Data)

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

• Practical storage guidance (general/best practice)

  • Store in a tightly sealed amber vial at room temperature in a dry place. Minimize headspace and moisture exposure; consider storing under inert gas (N2/Ar) for extended periods to limit aldehyde oxidation.
  • Avoid prolonged exposure to light and air. Keep away from acids/bases that could promote hydrolysis or condensation.
  • If solidifies or if crystallization occurs, warm gently to ambient and homogenize before use.

• Stability/handling tips

  • Upon opening, record the date and consider retesting aldehyde content (e.g., 1H NMR) after prolonged storage.
  • If needed for moisture-sensitive reactions, dry rapidly over molecular sieves (3Å/4Å) or by brief vacuum before use.

• Reconstitution

  • Not applicable (neat reagent). If preparing stock solutions, use dry, oxygen-free solvents (e.g., anhydrous DCM, THF, or acetonitrile), store at 2–8 °C under inert gas, and use within a few days to limit oxidation/polymerization.

Always consult the product’s SDS for authoritative handling and storage recommendations.

Structure and Identity

Ethyl 3-fluoro-4-formylbenzoate is an aromatic multifunctional building block featuring an electron-withdrawing fluoro substituent and two carbonyl-derived handles (aldehyde and ethyl ester) on a benzene ring.

• Item-specific (Product Data)

  • CAS: 1640117-38-9
  • PubChem CID: 121231779
  • InChIKey: 38947 (as provided)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.
  • Storage Conditions: Room temperature
  • Research Use: For research use only

• Computed/structure description (literature/derived)

  • Molecular formula (derived from name): C10H9FO3 (aromatic ring bearing para-formyl, meta-fluoro, and benzoate ethyl ester)
  • Approximate molecular weight (from formula): ~196.17 g/mol (literature/derived)
  • Functional groups: aryl fluoride (–F), aldehyde (–CHO), ethyl ester (–CO2Et)
  • Ring system: single benzene ring; no stereocenters; planar aromatic core
  • 2D structure in words: a benzene ring bearing an ethyl benzoate moiety at C1, a formyl group para to the ester (C4), and a fluoro substituent meta to the ester (C3). The aldehyde and ester carbonyls are conjugated with the ring, imparting electron-withdrawing character and distinct chemoselectivity.

• Notes

  • Exact structural identifiers beyond those listed above should be verified against the product CoA/SDS prior to regulated use.

Synthetic Utility

Key functional handles enable diverse, chemoselective elaborations:

• Aldehyde (para to ester)

  • C–C bond formation via Wittig/HWE to vinyl aromatics; Knoevenagel with malonates/cyanoacetates; aldol additions with metal enolates; imines/oximes/hydrazones as masked aldehydes and ligation handles.
  • Redox tuning: NaBH4 or catalytic hydrogenation to benzyl alcohol; Pinnick oxidation to the carboxylic acid; selective acylation of the benzyl alcohol after reduction.

• Ethyl ester

  • Saponification to acid then amide coupling (EDC/HATU/DIC–Oxyma); direct aminolysis (catalyzed) for amide formation; alcoholysis for transesterification (ROH/H+ or base).
  • Reductions: DIBAL-H to aldehyde (chemoselectivity control vs aryl aldehyde required); LiAlH4 to primary alcohol (global reduction risk).

• Aryl fluoride

  • Generally inert toward cross-coupling but can engage in SNAr under forcing conditions or serve as a directing group for ortho-lithiation, enabling subsequent electrophile trapping (B(OR)3, Me3SiCl, DMF, etc.).

• Strategic considerations

  • Orthogonality allows stepwise modifications without protecting groups: e.g., perform Wittig on the aldehyde, then saponify the ester to acid/amidate; or reduce aldehyde selectively before ester transformations. The electron-withdrawing pattern tunes ring reactivity and can aid regioselective metalation.

Target Specificity

Not applicable. This product is a small-molecule building block and is not an antibody, enzyme, or affinity reagent. No antigen/epitope or biological target specificity is associated with this item.