2-Ethyl-6-fluorobenzoic acid - ≥98% , CAS No.479676-22-7

CAS: 479676-22-7 Cat. No.: E1335538 Summenformel: C₉H₉FO₂ Molekulargewicht: 168.16 EG-Nummer: 994-278-9

GRADE & PURITY ≥98%

Storage

Room temperature

Shipped In

Normal

Specifications

Spezifikationen & Reinheit

≥98%

Storage

Room temperature

Verschickt in

Normal

Reinheit

≥98%

Namen und Kennungen

Kanonisches Lächeln

CCC1=C(C(=CC=C1)F)C(=O)O

IUPAC Name

2-ethyl-6-fluorobenzoic acid

InChIKey

MFXILNDORCQUKP-UHFFFAOYSA-N

INCHI

1S/C9H9FO2/c1-2-6-4-3-5-7(10)8(6)9(11)12/h3-5H,2H2,1H3,(H,11,12)

Molekulargewicht

168.16

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Klasse Benzene and substituted derivatives
      • Subclass Benzoic acids and derivatives
        • Ebene5 Halobenzoic acids and derivatives
          • Ebene6 Halobenzoic acids

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Klasse: Benzene and substituted derivatives
• Subclass: Benzoic acids and derivatives
• Intermediate Tree Nodes: Halobenzoic acids and derivatives
• Direct Parent: Halobenzoic acids
• Alternative Parents: 2-halobenzoic acids Benzoic acids Benzoyl derivatives 1-carboxy-2-haloaromatic compounds Fluorobenzenes Aryl fluorides Vinylogous halides Organooxygen compounds Organofluorides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Halobenzoic acid - 2-halobenzoic acid - 2-halobenzoic acid or derivatives - Benzoic acid - 1-carboxy-2-haloaromatic compound - Benzoyl - Fluorobenzene - Halobenzene - Aryl fluoride - Aryl halide - Vinylogous halide - Carboxylic acid derivative - Carboxylic acid - Organic oxygen compound - Organooxygen compound - Hydrocarbon derivative - Organic oxide - Organofluoride - Organohalogen compound - Aromatic homomonocyclic compound
• Beschreibung: This compound belongs to the class of organic compounds known as halobenzoic acids. These are benzoic acids carrying a halogen atom on the 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

Chemische und physikalische Eigenschaften

• Molekulargewicht: 168.160 g/mol
• XLogP3: 2.300
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 2
• Exact Mass: 168.059 Da
• Monoisotopic Mass: 168.059 Da
• Topological Polar Surface Area: 37.300 Ų
• Heavy Atom Count: 12
• Formal Charge: 0
• Complexity: 170.000
• 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 reagent. For synthetic uses, see the Reaction Conditions and Synthetic Utility sections for general laboratory guidance.

Biological Roles

• Item-specific biological information: Not specified for this item; refer to literature if required for conceptual background.

• General/literature context

  • 2-Ethyl-6-fluorobenzoic acid is a synthetic, non-natural aromatic carboxylic acid. No endogenous biological role is known.
  • Aromatic carboxylates of this class are commonly used as scaffolds in discovery chemistry to tune physicochemical properties (lipophilicity, acidity, H-bonding) of target compounds via amide/ester derivatization.
  • The ortho-ethyl and fluoro substituents increase hydrophobicity and can influence conformational preference and binding vectors when incorporated into bioactive motifs as amides, ureas, or esters.

Note: Any biological testing should be conducted under appropriate approvals. This product is supplied strictly for research use.

Buffer Applications

This compound is not typically used as a laboratory buffer.

• Rationale

  • Poor aqueous solubility in its neutral form limits utility as a buffering agent.
  • Benzoic acid analogs have pKa values around 4–4.5 (literature estimate), which lies in the acetate/citrate buffering region; however, specialized buffer systems with higher solubility and defined ionic strength are preferred.

• Practical note

  • If aqueous work is required, dissolve by forming the sodium or potassium carboxylate with stoichiometric base. This is a preparative maneuver, not a recommended buffer system.

Green Alternatives

While this product is a solid building block rather than a solvent, greener choices often relate to reagent and solvent selection in its transformations.

• Greener coupling strategies (literature)

  • Use T3P (in EtOAc/2-MeTHF) or EDCI/Oxyma instead of DCC/HOBt to reduce urea waste and mitigate explosive-sensitizer risks.
  • Employ catalytic amidation protocols (e.g., boronic acid-catalyzed amidation in toluene or solvent-free) where compatible.

• Solvent selection

  • Replace DMF/DMF-like solvents with 2-MeTHF, CPME, MeTHF/EtOAc mixtures, or propylene carbonate when solubility allows.
  • For esterification or acyl chloride generation, use toluene or 2-MeTHF with azeotropic water removal instead of chlorinated solvents when feasible.

• Decarboxylative couplings

  • Photoredox/Ni decarboxylative methods can avoid halogenated intermediates, potentially reducing waste streams compared to multistep halogenation/cross-coupling.

• Comparison (general, literature)

  • DCM vs 2-MeTHF: 2-MeTHF is bio-based, higher boiling, and less toxic; DCM offers low bp and excellent solvency but higher environmental/health impact.
  • DCC vs T3P: T3P byproducts are water-soluble, simplifying workup; DCC produces DCU solid waste requiring filtration and disposal.

Always evaluate green substitutions via small-scale trials to ensure reactivity/selectivity are maintained with this sterically encumbered acid.

Pharmaceutical Uses

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

• General context (non-clinical; literature)

  • Utilized as a synthetic intermediate in medicinal chemistry to prepare amides, esters, and isocyanates for structure–activity relationship (SAR) studies.
  • The aryl fluoride and ortho-ethyl substituent can modulate lipophilicity and metabolic stability when the acid is converted into drug-like derivatives (e.g., benzamides, ureas).

No therapeutic or clinical claims are made for this product. It is supplied for research and manufacturing development use only.

Physical Properties

• Item-specific specifications

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

• Literature/computed (general reference values; not item-specific specs)

  • Molecular weight (calculated): ~168.17 g/mol
  • Expected physical state: aromatic carboxylic acids of this size are typically low-melting solids or waxy solids (literature generalization).
  • Acid strength: pKa of benzoic acid is ~4.2; ortho-alkyl and fluoro substitution generally leads to small shifts (expected pKa in the ~4.0–4.6 range; literature estimate).
  • Solubility profile (qualitative, literature):
    • Low solubility in neutral water; readily soluble in polar aprotic organics (DMF, DMSO, NMP) and moderately soluble in chlorinated/aromatic solvents (DCM, chlorobenzene, toluene); forms water-soluble carboxylate salts in basic media.

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

  • Melting point
  • Boiling point
  • Density
  • Refractive index
  • UV/Vis characteristics
  • Residual water/peroxide/metal content

Note: Use literature values only as planning guides. For analytical or regulatory purposes, rely on the lot-specific CoA.

Quality and Grades

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

• Guidance for professional users

  • When selecting an aryl carboxylic acid building block for synthesis, key quality attributes typically include: assay (HPLC/GC), identity (1H/13C NMR, MS), residual solvents, water (KF), and trace metals (ICP) if using in metal-catalyzed couplings.
  • For chromatographic or photochemical applications, low UV-absorbing impurities and absence of fluorescent contaminants can be important.

• Stabilizers/additives

  • None indicated for this item. If present in any lot, stabilizers will be disclosed on the CoA; evaluate implications for downstream reactions (e.g., amide couplings, photoredox steps).

• Documentation

  • For specifications such as melting range, assay, and impurity profile, consult the lot-specific CoA. If regulatory documentation (REACH, RoHS) is required, request from Aladdin Scientific with the SKU E1335538.

Reaction and Applications

As a substituted benzoic acid, 2-ethyl-6-fluorobenzoic acid is a versatile aryl building block. The carboxyl group is the principal handle; the aryl fluoride and ortho-ethyl substituent define steric/electronic context.

• Representative transformations (literature)

  • Amide formation: Coupling with amines (HATU/HBTU/T3P/EDCI + base) to give 2-ethyl-6-fluorobenzamides—useful in med-chem SAR libraries.
  • Esterification: Fischer esterification or Steglich (DCC/DMAP) to install alkyl/aryl esters for protection or derivatization.
  • Acid chloride: SOCl2 or (COCl)2 (cat. DMF) to 2-ethyl-6-fluorobenzoyl chloride, enabling Friedel–Crafts acylation or amide formation.
  • Curtius rearrangement: Conversion to acyl azide (e.g., DPPA) and thermal rearrangement to the corresponding isocyanate, enabling downstream ureas/carbamates or hydrolysis to the aniline amide framework.
  • Decarboxylative cross-coupling: Formation of redox-active esters (NHPI, TCNHPI) followed by Ni/photoredox-catalyzed aryl–C, aryl–N, or aryl–B bond construction, circumventing pre-halogenation.

• Aryl fluoride considerations

  • The C–F bond is typically inert to classical SNAr without strong additional activation. It can be leveraged as a spectroscopic handle or retained for tuning lipophilicity/metabolic stability in targets.

• Practical tips

  • Ensure dryness and base selection matched to coupling reagent (e.g., DIPEA/DBU). Remove adventitious water to avoid hydrolysis/anhydride formation.
  • For sterically encumbered amides (ortho-ethyl), elevate temperature or use more reactive reagents (HATU/HBTU) and additives (Oxyma, HOAt alternatives).

Reaction Conditions

General guidance from literature for analogous substrates; adjust to your substrate/scale and consult primary references.

• Amide coupling

  • HATU (1.1–1.5 equiv), amine (1.1–1.5 equiv), DIPEA (2–3 equiv), solvent DMF or DCM, 0–25 °C to room temperature, 2–16 h. For hindered amines, warm to 40–60 °C or use T3P (50% in EtOAc) with base.

• Esterification

  • Fischer: ROH as solvent with catalytic H2SO4 or p-TsOH, reflux with Dean–Stark (for higher alcohols) or remove MeOH/EtOH under reflux; 2–24 h.
  • Steglich: DCC (1.1–1.3 equiv), catalytic DMAP (0.1 equiv), DCM, 0 °C to RT, 2–18 h; filter DCU.

• Acid chloride formation

  • SOCl2 (3–5 equiv) with a catalytic drop of DMF, DCM or toluene, reflux 1–3 h; remove volatiles under reduced pressure. Alternatively, (COCl)2 (2–3 equiv) in DCM, 0 °C to RT.

• Curtius rearrangement

  • DPPA (1.1–1.5 equiv), base (Et3N or DIPEA), toluene, 60–100 °C; trap isocyanate with alcohols/amines or hydrolyze downstream.

• Decarboxylative couplings (redox-active ester)

  • Form NHPI ester using DIC or EDCI + DMAP; then Ni/photoredox (e.g., Ir(ppy)3 or 4CzIPN, NiCl2·dme/ligand) in MeCN/DMF, blue LEDs, RT to 40 °C, 4–24 h, for C–C, C–N, or C–B formation.

• Workup tips

  • Neutral acids: wash organics with NaHCO3 to remove residual acid; for amide/ester products, acidic wash (1 M HCl) removes amines/DMAP.
  • Due to ortho sterics, allow additional time or reagent excess for complete conversion.

Safety and Handling

• GHS/SDS

  • GHS classification, pictograms, signal word, and H-statements: Not specified for this item; refer to SDS.

• General hazards (aromatic carboxylic acids; literature/good practice)

  • May cause skin/eye irritation and respiratory discomfort if dusts or aerosols are generated.
  • Combustible organic solid; fine particulates can present a dust hazard.
  • Aryl fluorides are generally stable; no specific peroxide-forming risk.

• PPE and engineering controls

  • Wear lab coat, safety glasses or face shield, and appropriate chemical-resistant gloves (e.g., nitrile). Use in a fume hood to avoid inhalation of dust or vapors during reactions (e.g., acid chloride formation).

• Incompatibilities and cautions (general)

  • Avoid strong oxidizers and strong bases unless intentionally neutralizing to the carboxylate. During chlorination (SOCl2/oxalyl chloride), HCl/SO2/CO gas evolution may occur—provide scrubbing/venting.
  • Avoid contact with reactive metals when in acidic form; carboxylic acids can promote corrosion.

• First-aid overview (general)

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

Always consult the product’s SDS for authoritative safety, toxicology, and disposal guidance.

Solvent Selection

This product is an aromatic carboxylic acid; solvent choice is primarily driven by solubility and reaction type.

• Polarity/miscibility (literature generalizations)

  • Poorly soluble in neutral water; forms soluble salts in aqueous base (NaOH, K2CO3).
  • Dissolves well in polar aprotic solvents (DMF, DMSO, DMAc, NMP). Moderate solubility in chlorinated (DCM, CHCl3) and aromatic solvents (toluene), and in alcohols upon gentle heating.

• Selection by use case

  • Amide coupling: DMF, DCM, MeCN, or EtOAc depending on reagent system (e.g., HATU/DIPEA in DMF; EDCI/HOBt in DCM or DMF).
  • Esterification (Fischer): Anhydrous ROH (MeOH, EtOH, iPrOH) with acid catalysis; remove water (Dean–Stark or molecular sieves) to drive conversion.
  • Acid chloride formation: DCM or toluene; catalytic DMF with SOCl2 or (COCl)2.
  • Curtius (to isocyanate): Anhydrous toluene or chlorobenzene for thermal rearrangement; capture with alcohols or amines.
  • Decarboxylative couplings: Polar aprotic media (MeCN, DMF) for NHPI-ester activation under photoredox/Ni catalysis.

• Quick comparison (literature)

  • DMF vs DCM: DMF maximizes solubility and base compatibility; DCM enables easy removal and low-temperature control but may limit solubility.
  • Toluene vs MeCN: Toluene suits high-temperature steps (acid chloride, Curtius); MeCN is convenient for room-temperature couplings and photochemistry.

Storage and Reconstitution

• Item-specific storage/shipping

  • Storage condition: Room temperature (per Product Data).
  • Shipped: Normal conditions.

• General handling

  • Keep container tightly closed in a cool, dry, well-ventilated place. Protect from strong acids/bases and oxidizers unless used intentionally in reaction.
  • If long-term storage is planned, consider desiccation to minimize moisture uptake and potential hydrolysis of activated derivatives.

• Reconstitution/solubilization (general guidance)

  • Dissolution solvents: DMSO, DMF, DMAc, NMP (excellent); DCM, CHCl3, EtOAc, toluene (moderate); alcohols with warming. Aqueous solubility increases on conversion to the sodium/potassium carboxylate with base.
  • For stock solutions (analytical): prepare in dry solvent at known concentration; store aliquots in amber vials if light-sensitive derivatives are formed.

• Stability notes

  • The free acid is typically stable at RT. Activated forms (acid chlorides, anhydrides, NHS/NHPI esters) should be prepared fresh and used promptly.

Always refer to the product’s CoA/SDS for definitive storage and handling instructions for your lot.

Structure and Identity

A fluorinated, ortho-ethyl–substituted benzoic acid used as an aryl carboxylic acid building block.

• Item-specific identifiers (Product Data)

  • SKU: E1335538
  • Product name: 2-Ethyl-6-fluorobenzoic acid
  • CAS: 479676-22-7
  • PubChem CID: 45480382
  • InChIKey: 218059 (as provided)
  • Storage: Room temperature; shipped under normal conditions
  • Research use: For research use only

• Computed/literature structural information (not item-specific; for reference)

  • Molecular formula (calculated): C9H9FO2
  • Molecular weight (calculated): ~168.17 g/mol
  • Functional groups: aromatic carboxylic acid (–CO2H), aryl fluoride (C–F), ortho ethyl substituent
  • One possible SMILES (literature): O=C(O)c1c(CC)ccc(F)c1
  • 2D description: A benzene ring bearing a carboxylic acid at position 1, an ethyl group at the 2-position (ortho), and a fluorine at the 6-position (the other ortho). The motif is a deactivated aryl ring due to the electron-withdrawing carboxyl and fluorine substituents.

• Notes

  • Definitive identifiers (full InChI/InChIKey, canonical SMILES) are not specified for this item; refer to the CoA/Spec Sheet for the exact registry representation used by Aladdin Scientific.

Synthetic Utility

• Functional handles

  • Carboxylic acid: amenable to activation (acid chloride, anhydride, mixed carbonate), coupling (amide/ester), rearrangement (Curtius), and decarboxylative transformations (radical cross-couplings via redox-active esters).
  • Aryl fluoride: generally retained through many steps; provides an opportunity for late-stage diversification only under specialized conditions (e.g., metal-catalyzed C–F functionalization) or for maintaining fluorine in the final product to adjust physicochemical properties.

• Retrosynthetic value (literature)

  • Serves as a convergent node for building 2-ethyl-6-fluorobenzamide/urea libraries.
  • Decarboxylative borylation/arylation can convert the acid into cross-coupling partners without prior halogenation at other ring positions.

• Named/typical reactions

  • Steglich esterification (DCC/DMAP), Fischer esterification, Schotten–Baumann amidation (via acyl chloride), Curtius rearrangement (DPPA), and modern photoredox/Ni decarboxylative couplings (NHPI esters).

• Steric/electronic notes

  • Ortho-ethyl substitution can slow couplings to hindered amines/alcohols; stronger activators (HATU/Oxyma) or modest heating are often beneficial.
  • Acidic functionality enables directed transformations (e.g., transient formation of acyl derivatives for regioselective further elaboration).

Target Specificity

Not applicable. This product is a small-molecule building block and is not an antibody, enzyme, or affinity reagent. No target, epitope, clone, isotype, or species reactivity information applies.