Ethyl 2,3,6-trifluorobenzoate - ≥95% , CAS No.773134-90-0

CAS: 773134-90-0 Cat. No.: E1037239 Formula: C₉H₇F₃O₂ Peso molecolare: 204.15 PubChem CID: 46311437

GRADE & PURITY ≥95%

Storage

Room temperature

Specifications

Specifiche e purezza

≥95%

Condizioni di conservazione di stoccaggio

Room temperature

Purezza

≥95%

Nomi e identificatori

Sorrisi canonici

CCOC(=O)C1=C(C=CC(=C1F)F)F

IUPAC Name

ethyl 2,3,6-trifluorobenzoate

InChIKey

KTSYUGKWNTYIGK-UHFFFAOYSA-N

INCHI

1S/C9H7F3O2/c1-2-14-9(13)7-5(10)3-4-6(11)8(7)12/h3-4H,2H2,1H3

Isomeri SMILES

CCOC(=O)C1=C(C=CC(=C1F)F)F

PubChem CID

46311437

Peso molecolare

204.15

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Classe Benzene and substituted derivatives
      • Subclass Benzoic acids and derivatives

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Classe: Benzene and substituted derivatives
• Subclass: Benzoic acids and derivatives
• Intermediate Tree Nodes: Not available
• Direct Parent: Benzoic acid esters
• Alternative Parents: 3-halobenzoic acids and derivatives 2-halobenzoic acids and derivatives Benzoyl derivatives Fluorobenzenes Aryl fluorides Vinylogous halides Carboxylic acid esters Organooxygen compounds Organofluorides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Benzoate ester - 2-halobenzoic acid or derivatives - 3-halobenzoic acid or derivatives - Halobenzoic acid or derivatives - Benzoyl - Halobenzene - Fluorobenzene - Aryl halide - Aryl fluoride - Vinylogous halide - Carboxylic acid ester - Carboxylic acid derivative - Hydrocarbon derivative - Organic oxide - Organooxygen compound - Organofluoride - Organohalogen compound - Organic oxygen compound - Aromatic homomonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as benzoic acid esters. These are ester derivatives of benzoic acid.
• 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

Proprietà chimiche e fisiche

• Peso molecolare: 204.150 g/mol
• XLogP3: 2.400
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 3
• Exact Mass: 204.04 Da
• Monoisotopic Mass: 204.04 Da
• Topological Polar Surface Area: 26.300 Ų
• Heavy Atom Count: 14
• Formal Charge: 0
• Complexity: 210.000
• 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 as a validated bioassay reagent. There are no tested applications (e.g., WB, IHC, IF, FC) or recommended dilutions associated with this small-molecule building block.

For synthetic use, see Reaction Conditions and Synthetic Utility for setup guidance. Always tailor stoichiometry, solvent, temperature, and workup to your specific transformation and scale.

Biological Roles

This product is a synthetic, non-natural fluorinated aromatic ester intended for laboratory research and chemical synthesis.

• Not a known metabolite, cofactor, or biochemical building block in primary metabolism.
• Aryl fluorination is widely used in chemical biology and medicinal chemistry to modulate lipophilicity, metabolic stability, and binding interactions. In that context, Ethyl 2,3,6-trifluorobenzoate can serve as a precursor for libraries of fluorinated benzamides, anilides, and biaryl motifs.
• No endogenous biological role is attributed to this compound. Any biological testing should be performed under appropriate institutional approvals and is outside the scope of product specifications.

Research Use Only: as stated in Product Data, this material is supplied strictly for research use; no clinical or diagnostic use is intended.

Buffer Applications

Not typically applicable. Ethyl 2,3,6-trifluorobenzoate is a hydrophobic aromatic ester and is not used to make aqueous buffer systems or as a buffering agent. For laboratory work, refer instead to the Synthetic Utility, Reaction & Applications, and Solvent Selection sections.

Green Alternatives

As a building block rather than a solvent, the compound itself is not replaceable by a “green solvent.” However, greener choices can be made for media and reagents used with it.

• Greener solvent choices for common steps (general guidance)

  • SNAr: Replace DMF/NMP with MeCN, propylene carbonate, or Cyrene (where compatible with base/nucleophile). Consider DMSO with efficient workup if high polarity is essential.
  • Saponification/transesterification: Use ethanol or methanol (renewable grades) as both reagent and solvent; aqueous ethanol with catalytic base reduces solvent burden.
  • Reductions: Prefer toluene or 2-MeTHF in place of CH2Cl2/Et2O when compatible with the reductant (e.g., DIBAL-H in toluene).

• Process-intensification options

  • Microwave-assisted SNAr can shorten reaction time and reduce energy usage.
  • Solvent recycling and lower-boiling alternatives (MeCN vs DMF) facilitate solvent recovery.

• Tradeoffs

  • Very polar, high-boiling solvents (DMSO/DMF) often deliver superior rates/yields in SNAr; greener substitutes may require longer times, higher temperatures, or different bases.

• Comparative snapshot (illustrative)

  • DMF: Excellent SNAr rates; high boiling, regulatory scrutiny.
  • MeCN: Good balance of polarity/volatility; toxicity manageable with controls.
  • 2-MeTHF: Bio-based, low peroxide propensity vs ethers like THF; lower polarity may limit SNAr efficiency.

Pharmaceutical Uses

This product is not an approved excipient and has no pharmacopeial monograph listed in the Product Data. It may be used as a synthetic intermediate in discovery chemistry to access fluorinated benzamides, anilides, or biaryl motifs for SAR studies.

• No therapeutic or clinical claims are made or implied.
• For GMP or regulatory applications, obtain appropriate quality documentation and assess impurity profiles per your QMS.

Typical roles in a research setting (general)

• Intermediate en route to drug-like scaffolds via SNAr on aryl fluorides followed by amide coupling or cross-coupling after functional group interconversion.
• Fluorinated motifs can tune logP and metabolic stability; this compound enables incorporation of 2,3,6-trifluorophenyl fragments into targets during preclinical research.

Physical Properties

Item-specific physical specifications are not provided in the Product Data. Do not use the following as product specifications; consult the CoA/Spec Sheet for definitive values.

• Item-specific data

  • Appearance: 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.
  • Boiling point, melting point, density, refractive index, UV cutoff, water/peroxide/metal limits: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/general reference (for context only)

  • Estimated formula (literature): C9H7F3O2; Mr ~204.15 g/mol.
  • Volatility/phase (literature, qualitative): Aromatic ethyl benzoates are typically low-volatility liquids or low-melting solids with boiling points in the low-to-mid 200 °C range; multiple fluorines can modestly influence bp/density compared with ethyl benzoate. Specific values for this isomer are not cited here.
  • Solubility (qualitative, literature): Expected to be sparingly soluble in water and highly soluble in common organic solvents (e.g., dichloromethane, ethyl acetate, acetonitrile, toluene). Exact solubility not compiled here.

Always verify numerical properties against the CoA/SDS for your lot before process design.

Quality and Grades

• Item-specific quality information

  • 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 typical grades (general guidance)

  • When offered as “≥98%” or similar, this denotes chromatographic purity suitable for most synthetic applications; trace impurities can impact catalytic reactions or SAR workflows.
  • “Analytical” or “Reagent” grades signal suitability for routine synthesis; “HPLC” grade is typically reserved for solvents and indicates low UV-absorbing impurities, less relevant for neat reagents like this ester.

• Verification practices

  • Confirm identity by 1H/13C NMR and MS; for fluorinated arenes, 19F NMR is highly diagnostic (three ring fluorine signals with characteristic coupling patterns to 1H/13C).
  • Assess residual solvents and water (by GC and Karl Fischer, respectively) if your application is moisture-sensitive (e.g., SNAr with strong bases).
  • If metal-catalyzed transformations are planned, request a metals screen if available. Otherwise, purify (e.g., column chromatography) prior to catalysis.

• Documentation

  • For lot-specific purity, water/peroxide/metal limits, and UV characteristics: Not specified for this item; refer to CoA/Spec Sheet.

Reaction and Applications

Ethyl 2,3,6-trifluorobenzoate serves as a versatile fluorinated arene building block combining an activated aryl C–F manifold with a benzoate functional handle.

• Aryl C–F substitution (SNAr)

  • The 2,3,6-trifluoro pattern strongly activates the ring toward nucleophilic aromatic substitution. Amines, alkoxides/phenoxides, thiolates, and other hetero-nucleophiles can displace F at the most activated positions under thermal conditions.
  • Strategic introduction of anilines, phenols, or heterocycles (e.g., imidazoles) enables rapid access to densely functionalized fluorinated scaffolds relevant to agrochemical and medicinal chemistry discovery.

• Ester manifold transformations

  • Hydrolysis (saponification) to the corresponding 2,3,6-trifluorobenzoic acid for further coupling (amide formation via EDC/HATU, or acid chloride formation).
  • Transesterification to tailor protecting group or volatility (e.g., Me/Pr/tBu esters) depending on downstream steps.
  • Reduction: DIBAL-H affords the benzyl alcohol (2,3,6-trifluorobenzyl alcohol) under controlled low temperature; LiAlH4 can reduce to benzyl alcohol/benzyl derivatives.

• Cross-coupling context

  • Direct Pd-catalyzed cross-coupling of aryl fluorides is challenging; however, after SNAr installation of a better leaving group (e.g., aryl-OTf formation from a phenolic intermediate), subsequent Suzuki/Buchwald couplings become feasible.

• Orthogonal reactivity and regiocontrol

  • Fluorine substitution patterns influence regiochemistry of SNAr; 2- and 4-positions ortho/para to electron-withdrawing groups are typically most labile. Mapping 19F NMR shifts can assist in site-selective substitution strategies.

• Purification/analysis tips

  • Monitor reactions by 19F NMR (sensitive and diagnostic) alongside 1H NMR/LC–MS. Fluorinated products often show strong responses in APCI/ESI-MS.

Reaction Conditions

General literature guidance (illustrative, not product specifications). Optimize for your substrate and nucleophile; verify against primary sources.

• SNAr (displacing aryl F)

  • Nucleophiles: Primary/secondary amines, alkoxides/phenoxides, thiolates, N-heterocycles.
  • Base: Cs2CO3, K2CO3, NaH, or NaOtBu depending on nucleophile strength.
  • Solvent: DMSO, DMF, NMP, MeCN.
  • Temperature/time: 60–140 °C, 2–24 h (microwave: 120–160 °C, 10–60 min) depending on site and nucleophile.
  • Notes: More activated positions (typically ortho/para to the ester) react first; control equivalents to limit polysubstitution.

• Saponification (to 2,3,6-trifluorobenzoic acid)

  • Conditions: Aqueous NaOH or KOH (1–3 eq) in MeOH/THF/H2O, rt to reflux until complete; acidify to pH ~2 for isolation.
  • Notes: Ring fluorines are stable; avoid prolonged high-temperature aqueous acid/base if other sensitive substituents are present.

• Reduction of ester

  • DIBAL-H (1.5–2.0 eq) in toluene or CH2Cl2 at −78 to 0 °C; quench with MeOH then Rochelle’s salt; affords benzyl alcohol.
  • LiAlH4 in THF/Et2O at 0–25 °C for full reduction; exercise strict moisture control.

• Transesterification

  • Acidic: Catalytic TsOH or H2SO4 in ROH (reflux).
  • Basic: Sodium alkoxide in ROH at reflux; remove formed ethanol to drive equilibrium.

Yields and exact conditions are substrate- and nucleophile-dependent; consult primary literature for the targeted transformation.

Safety and Handling

Item-specific hazard classifications are not provided in the Product Data. The following are general, chemistry-based precautions; always consult the SDS for authoritative information.

• Item-specific GHS data

  • Signal Word / H-Statements / GHS Classification / Pictograms: Not specified for this item; refer to SDS.

• General hazards for fluorinated aromatic esters (informational)

  • May cause irritation to skin, eyes, and respiratory tract upon exposure to vapors or liquid; avoid inhalation and direct contact.
  • Combustible organic liquid/solid; keep away from ignition sources and hot surfaces.
  • Hydrolysis produces benzoic acid derivatives and ethanol; avoid strong bases/acids if not intended.

• Handling recommendations

  • Use in a fume hood with appropriate PPE: lab coat, safety glasses or goggles, and nitrile gloves; consider double-gloving for extended handling.
  • Avoid strong bases, strong acids, and strong nucleophiles unless performing a controlled reaction (SNAr, saponification, aminolysis, etc.).
  • For scale-up or heating above ~100 °C, implement engineering controls and monitor pressure buildup in closed systems.

• First-aid overview (general)

  • Skin/eye contact: Rinse with water for at least 15 minutes; remove contaminated clothing; seek medical evaluation if irritation persists.
  • Inhalation: Move to fresh air; support breathing as needed; seek medical attention if symptoms occur.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical advice.

• Spills and waste

  • Absorb small spills with inert material (vermiculite) and collect for disposal. Prevent entry to drains.
  • Dispose of waste via licensed chemical waste streams per local regulations.

Defer to the product SDS for definitive hazard classification and response measures.

Solvent Selection

This product is a synthetic building block (aromatic ester), not a solvent. Solvent selection pertains to reactions or purifications involving this compound.

• Polarity/miscibility context (general)

  • Expected to dissolve well in common organic solvents (e.g., dichloromethane, ethyl acetate, acetonitrile, THF, toluene). Water solubility expected to be low.

• Choosing solvents for typical transformations (literature guidance)

  • SNAr on aryl C–F: Polar aprotic media (DMSO, DMF, NMP, MeCN) enhance nucleophile reactivity; bases such as Cs2CO3/K2CO3/NaOtBu are commonly used.
  • Saponification/transesterification: Alcoholic solvents (MeOH, EtOH) with acid/base catalysts; for aqueous saponification, THF/H2O or dioxane/H2O mixtures improve phase homogeneity.
  • Reductions (e.g., DIBAL-H to benzyl alcohol): Non-protic solvents such as toluene or CH2Cl2 at 0 to −78 °C, quench carefully.
  • Purification: Normal-phase silica gel eluting with hexane/EtOAc or hexane/MTBE; fluorinated rings may elute slightly faster than non-fluorinated analogs.

• Comparison hints

  • DMSO/DMF maximize SNAr rates but are higher-boiling; MeCN balances polarity with easier removal; toluene/xylene allow high-temperature operations with lower polarity.

Storage and Reconstitution

• Item-specific storage

  • 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 storage guidance (for aromatic esters)

  • Store tightly closed in a dry, well-ventilated place, away from strong bases, strong acids, and strong nucleophiles.
  • Protect from prolonged light and heat. If frequent openings are expected, consider storing under inert gas to minimize moisture ingress.
  • If solidifies or becomes viscous at lower temperatures, warm gently to ambient and mix thoroughly before use.

• Reconstitution

  • Supplied as a neat compound; no reconstitution required. If preparing stock solutions, use dry, oxygen-free solvents (e.g., anhydrous MeCN, DCM, toluene) and store aliquots in sealed containers to limit evaporation and hydrolysis.

• Stability

  • Aromatic ethyl benzoates are generally stable under neutral, anhydrous conditions. Avoid prolonged exposure to strong aqueous base/acid that can cause hydrolysis.

Refer to the product CoA/SDS for any lot-specific stability notes or shipping recommendations.

Structure and Identity

Ethyl 2,3,6-trifluorobenzoate is an electron-deficient aromatic ester bearing three fluorine substituents on the benzene ring.

• Item-specific identifiers (from Product Data)

  • Product Name: Ethyl 2,3,6-trifluorobenzoate
  • CAS: 773134-90-0
  • InChIKey: 189415 (as provided in product data)
  • SKU: E1037239
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/computed identity (reference information; not item specification)

  • Typical molecular formula (literature): C9H7F3O2
  • Typical molecular weight (literature): ~204.15 g/mol
  • Representative SMILES (literature): CCOC(=O)c1c(F)c(F)cc(F)c1
  • Functional groups: Aromatic ring, ethyl ester (–CO2Et), three aryl C–F bonds at ring positions 2, 3, and 6 (relative to the ester carbonyl).
  • 2D structure (description): A benzene ring bearing an ester carbonyl substituent (benzoate) and three fluorine atoms arranged ortho, meta, and ortho (2,3,6) to the carbonyl; the ester is ethyl (–O–CH2–CH3). No stereocenters.

• Structural features and implications (general)

  • Multiple ring fluorines render the arene strongly deactivated toward electrophilic substitution but activated toward nucleophilic aromatic substitution (SNAr) at C–F sites.
  • The benzoate group serves as a versatile handle for hydrolysis, reduction, or transesterification.

Synthetic Utility

Key reactive elements and how to leverage them:

• Activated aryl C–F bonds (2,3,6-trifluoro pattern)

  • Strongly withdraw electron density, enabling SNAr with N/O/S nucleophiles. Strategic mono- or di-substitutions allow stepwise diversification of the ring.
  • Post-SNAr installation of phenols enables downstream activation (e.g., triflation) for cross-coupling.

• Benzoate ester handle

  • Hydrolysis to acid for amide coupling (EDC/HATU/T3P) or acid chloride formation (SOCl2, oxalyl chloride).
  • Reduction (DIBAL-H) to benzyl alcohol, then oxidation (e.g., Dess–Martin) to aldehyde, or conversion to benzyl halides for further substitution.
  • Transesterification to adjust protecting groups or volatility for process optimization.

• Retrosynthetic considerations

  • Enables convergent routes where aryl substitution occurs via SNAr rather than electrophilic substitution/cross-coupling, often improving regioselectivity on polyfluorinated rings.
  • Orthogonal reactivity: ester survives many SNAr conditions; sequence design can exploit stability to bases and nucleophiles at moderate temperatures.

• Analysis and control

  • 19F NMR provides clear, quantitative monitoring of substitution patterns; pair with LC–MS for rapid reaction profiling.

Overall, the compound is a versatile hub for building fluorinated aromatic frameworks with orthogonal functional-group manipulations.

Target Specificity

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