2,6-Difluorophenylacetic acid - 10mM in DMSO , CAS No.85068-28-6

CAS: 85068-28-6 Cat. No.: D660571 Summenformel: C₈H₆F₂O₂ Molekulargewicht: 172.13 Beilstein Registry Number: 3650109 EG-Nummer: 285-289-3

GRADE & PURITY 10mM in DMSO

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Specifications

Spezifikationen & Reinheit

10mM in DMSO

Storage

Store at -80°C

Verschickt in

Dry ice packs + Cold packs

Dieses Produkt erfordert Kühlkettenversand. Grundversand und andere Economy-Optionen sind nicht verfügbar.

Namen und Kennungen

Isomere SMILES

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

WGK Deutschland

3

Molekulargewicht

172.13

Beilstein

3650109

Reaxy-Rn

3650109

Reaxys-RN_link_address

https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=3650109&ln=

Chemische und physikalische Eigenschaften

• Schmelzpunkt (°C): 99-102°C

Application Protocols

Not applicable. No immunoassay or bioassay protocols (e.g., WB, IHC, IF, FC) are provided or typically relevant for a small-molecule building block. For synthetic applications, refer to the Reaction Conditions and Synthetic Utility sections.

Biological Roles

• Item-specific biological/biochemical role data: Not specified for this item.

General context (literature):

• Phenylacetic acid is a known simple metabolite in mammals and microbes; however, 2,6-difluorophenylacetic acid is a synthetic, fluorinated analogue with no established endogenous role.
• Fluorine substituents are frequently used in medicinal chemistry to modulate pKa, lipophilicity, metabolic stability, and binding conformations. This compound can serve as a building block to introduce an ortho-difluoro motif into drug-like scaffolds via amide/ester linkages.
• As a small organic acid, it can form salts with biogenic amines; such salts may alter physical properties (solubility/crystallinity) for research reagents.

Note: No claims are made regarding physiological activity or clinical utility. This product is intended strictly for research and laboratory use.

Buffer Applications

2,6-Difluorophenylacetic acid is not a standard biological buffer component.

• Applicability: As a weak monocarboxylic acid, it could, in principle, contribute to buffering near its pKa, but it is not commonly used for buffer preparation, cell culture, or electrophoresis systems.
• Recommendation: Use established buffer systems (e.g., acetate, phosphate, HEPES, MOPS) for pH control. Reserve this compound for synthetic and materials applications where an arylacetic acid functionality is required.

Green Alternatives

Sustainable choices often center on solvent/reagent selection rather than the substrate itself.

• Greener solvent substitutions (literature/general):

  • Replace DMF/NMP with safer polar aprotics like Cyrene, propylene carbonate, or sulfolane where compatible with coupling chemistry.
  • Use 2-MeTHF or CPME instead of dichloromethane or THF for extractions and esterifications when feasible.
  • For amide couplings, consider EtOAc or MeCN as media with water-compatible coupling systems.

• Greener coupling strategies:

  • Enabling reagents: T3P (in EtOAc), CDI (in acetonitrile or green ethers), or aqueous peptide-coupling systems can reduce hazardous by-products relative to DCC/HOBt.
  • Biocatalytic routes: Carboxylic acid reductases or acyl transferases (where applicable) can form amides/esters under mild, aqueous conditions.

• Comparison snapshot (general):

  • Traditional: DMF/DCM + DCC/HOBt → good reactivity; EHS concerns (DMF reproductive tox; HOBt explosive when dry; urea waste).
  • Alternative: 2-MeTHF/EtOAc + T3P or CDI → comparable conversions; improved safety profile; simpler workup.

Trade-offs: Some greener solvents have higher boiling points or viscosity, affecting rates and workup. Validate solubility and catalyst compatibility on small scale before substitution.

Pharmaceutical Uses

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

General context (non-clinical; research/manufacturing only):

• Building block: Frequently employed in medicinal chemistry as a precursor to amides/esters bearing an ortho-difluorophenylacyl fragment to tune potency, selectivity, and ADME properties.
• Salt screening: The free acid can participate in salt/cocrystal screening with APIs or intermediates to alter solid-state properties during process development (research only).
• Prodrug strategies: Arylacetic esters are sometimes explored as promoieties to modulate permeability or hydrolytic stability (conceptual, research stage; no therapeutic claims).

Note: No therapeutic or clinical claims are made. This compound is supplied solely for research and laboratory synthesis.

Physical Properties

• Item-specific measured properties (specs): Not specified for this item; refer to CoA/Spec Sheet.

• Literature/general properties for 2,6-difluorophenylacetic acid (for planning only; not item specifications)

  • Physical state: typically a crystalline solid (literature, appearance can vary with lot and hydration).
  • Acid character: weak carboxylic acid; expected to be deprotonated by bases ≥ pH ~7–9 (qualitative, literature behavior of arylacetic acids). Ortho fluorination generally increases acidity relative to phenylacetic acid due to inductive effects (qualitative).
  • Solubility profile (qualitative):
    • Organic: soluble in polar organics (e.g., methanol, ethanol, acetone, DMF, DMSO, acetonitrile); limited solubility in nonpolar hydrocarbons.
    • Aqueous: low solubility as the free acid at neutral pH; highly soluble as alkali metal salts at basic pH.
  • Partitioning: aromatic carboxylic acids generally exhibit moderate hydrophobicity as free acids and increased hydrophilicity upon ionization (qualitative).

Note: For exact MP/BP, density, refractive index, UV cutoff, water content, or metal limits, consult the item’s CoA/Spec Sheet.

Quality and Grades

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

Guidance on interpreting grades (general):

• Research/technical grade: Suitable for most synthetic applications where trace-level impurities are tolerable.
• Purified/≥98–99% assay (when specified): Preferred for medicinal chemistry SAR, analytical reference use, or when trace impurities affect catalytic reactions.
• HPLC grade (for solvents) or LC/MS grade (for analytes) indicate low UV background/volatile residues; not typically applicable to solid building blocks unless explicitly stated.
• Stabilizers/inhibitors: Not applicable unless noted (e.g., if supplied as acid chloride or activated ester). For this free acid, stabilizers are generally unnecessary.

Quality controls typically reviewed (general):

• Identity by 1H/13C NMR and HRMS/ESI.
• Purity by HPLC/UPLC and/or GC if volatile derivatives are used.
• Residual solvents and water by KF/GC, and melting point consistency. For exact acceptance criteria, use the product’s CoA/Spec Sheet.

Reaction and Applications

As an arylacetic acid, 2,6-difluorophenylacetic acid serves as a versatile building block in synthesis. The ortho-difluoro pattern modulates electronics and sterics, impacting reactivity and selectivity.

Representative application classes (literature/general):

• Amide/ester formation: Convert to amides via EDC·HCl/HOBt, HATU, or T3P protocols; esters via Fischer or Steglich (DCC/DMAP) methods.
• Acid activation: Transform to the acid chloride (SOCl2, oxalyl chloride) or mixed anhydrides for subsequent acylation.
• Benzylic functionalization: The α-CH2 (adjacent to carbonyl) can undergo halogenation (NBS/AIBN) or oxidation (e.g., to the corresponding keto acid after activation); difluoro ortho groups can subtly influence radical stability.
• Decarboxylative cross-couplings: Preparation of the N-hydroxyphthalimide (NHP) ester enables photoredox/Ni-catalyzed radical generation for C–C, C–N, or C–S bond formation at the benzylic position.
• Curtius/Schmidt chemistry: Conversion to acyl azide (from acid chloride + NaN3) yields isocyanate and subsequently ureas/carbamates; exercise caution with azides.
• SNAr and aryne chemistry (contextual): The 2,6-difluoro motif can participate in SNAr under strong conditions or serve as a handle in aryne-generation strategies (literature, substrate-dependent).

Practical notes:

• Ortho-F substituents withdraw electron density, increasing acidity and generally reducing electrophilic aromatic substitution reactivity.
• For peptide-like couplings, minimize racemization concerns (not applicable here) but consider benzylic acyl migration; use HOAt/DMAP judiciously.
• Maintain anhydrous conditions for acid chloride formation; quench excess thionyl chloride carefully.

Reaction Conditions

The following are literature-style general conditions for typical transformations of arylacetic acids; they are guidance, not specifications for this item.

• Amide coupling:

  • Reagents: HATU (1.1–1.5 equiv) or EDC·HCl (1.2–1.5 equiv) + HOAt/HOBt (optional) with DIPEA (2–3 equiv).
  • Solvent: DMF, NMP, or MeCN.
  • Temperature/time: 0–25°C, 1–16 h. Monitor by LC/MS or TLC.

• Steglich esterification:

  • Reagents: DCC (1.1–1.5 equiv), catalytic DMAP (5–10 mol%), ROH (2–5 equiv).
  • Solvent: DCM or 2-MeTHF.
  • Temperature/time: 0°C to rt, 2–18 h. Filter dicyclohexylurea.

• Acid chloride formation:

  • Reagents: SOCl2 (2–5 equiv), catalytic DMF.
  • Solvent: neat SOCl2 or DCM.
  • Temperature/time: reflux in SOCl2 (30–90 min). Work up under anhydrous conditions.

• NHP ester and decarboxylative coupling:

  • Step 1: Activate with N-hydroxyphthalimide + DIC (or EDC) in DCM/DMF.
  • Step 2: Photoredox (Ir(ppy)3 or Ru(bpy)3) with Ni catalyst for C–C/N/S coupling in MeCN/DMF under blue light, rt to 40°C, 2–12 h.

• Benzylic bromination (radical):

  • Reagents: NBS (1.1 equiv), AIBN (5–10 mol%).
  • Solvent: CCl4 or acetonitrile/benzene alternatives; reflux with light/heat, 1–6 h.

Expected yields for such literature procedures often range 60–90% depending on substrate and conditions; optimize for this specific compound.

Safety and Handling

• Research use: For research use only.
• GHS classification, signal word, pictograms, H-statements: Not specified for this item; refer to the product SDS for authoritative safety information.

General laboratory safety guidance for aromatic carboxylic acids (literature/typical):

• Hazards: May cause skin/eye irritation; dust may irritate respiratory tract. Avoid inhalation of particulates and contact with skin/eyes.
• PPE: Lab coat, safety glasses or goggles, and appropriate chemically resistant gloves (e.g., nitrile). Use a dust mask or work in a fume hood to avoid particulate exposure.
• Handling: Minimize dust generation. Avoid contact with strong bases and strong oxidizers. For reactions producing acid chlorides, manage HCl gas and acylating conditions in a hood.
• Incompatibilities (general): Strong oxidizing agents; strong bases may cause exothermic neutralization; convert to acid chlorides only under dry, inert conditions.
• First aid overview: In case of skin/eye contact, rinse with water for ≥15 minutes; remove contaminated clothing. If inhaled, move to fresh air. If ingested, rinse mouth; do not induce vomiting; seek medical advice. Always follow the SDS.
• Special risks: None unusual relative to other non-volatile aromatic acids; thermal decomposition can release HF only if fluorinated aryl moieties are severely degraded at high temperature—avoid overheating/combustion. Dispose of waste according to institutional and local regulations.

Solvent Selection

2,6-Difluorophenylacetic acid is a moderately lipophilic aromatic acid with improved acidity from ortho-fluorine substituents.

• Polarity/miscibility (general):

  • Readily soluble in polar aprotic solvents (DMSO, DMF, NMP, acetonitrile) and polar protic solvents (MeOH, EtOH).
  • Limited solubility in nonpolar media (hexanes, toluene) as the free acid; solubility increases upon conversion to esters or salts.
  • Aqueous solubility increases dramatically at basic pH (formation of sodium/potassium carboxylate).

• Selection by task:

  • Amide coupling: DMF, NMP, DCM, or MeCN with carbodiimide or uronium reagents; include base (DIPEA) as needed.
  • Fischer esterification: anhydrous MeOH/EtOH with catalytic acid (H2SO4, TsOH); water removal improves conversion.
  • Decarboxylative couplings (via NHP esters): MeCN/DMF mixtures under photoredox or Ni catalysis.
  • Salt formation/crystallization: water/EtOH with NaHCO3 or NaOH to form sodium salt; re-acidify to precipitate.

• Practical tips:

  • If low solubility is encountered in DCM, add DMF co-solvent (5–20%).
  • For aqueous workups, buffer to pH 2–3 to recover the free acid from its salt.
  • For chromatographic purification, start with EtOAc/hexanes or DCM/MeOH gradients; acids often tail—use 0.1–1% AcOH or formate additives if needed.

Storage and Reconstitution

• Storage (item-specific from Product Data): Store at -80°C.
• Shipping (item-specific from Product Data): Shipped on dry ice packs + cold packs.

General guidance:

• Keep container tightly closed, protected from moisture. Allow to equilibrate to room temperature in a desiccator before opening to minimize condensation.
• If long-term storage at -80°C is required, aliquot into moisture-tight vials to reduce repeated freeze–thaw and headspace humidity.

Reconstitution/stock preparation (general suggestions; not item specifications):

• Prepare concentrated stocks in dry DMSO, DMF, methanol, or ethanol (e.g., 10–100 mg/mL) depending on downstream use. Filter if particulates remain after dissolution.
• For aqueous applications, dissolve by first forming the sodium/potassium salt with stoichiometric base (e.g., 1.0 equiv NaOH), then adjust pH as needed.
• Avoid prolonged exposure of solutions to strong light/heat. Store solutions at 2–8°C for short term or at −20°C for longer term in inert headspace when feasible.

Always refer to the product’s CoA/Spec Sheet and SDS for definitive handling and stability information.

Structure and Identity

2,6-Difluorophenylacetic acid is an ortho-difluorinated phenylacetic acid derivative useful as an arylacetic acid building block.

• Item-specific identifiers (from Product Data)

  • SKU: D660571
  • Product name: 2,6-Difluorophenylacetic acid
  • CAS: 85068-28-6
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Structure description (general/literature)

  • Molecular formula (literature): C8H6F2O2
  • Molecular weight (literature): ~172.13 g/mol
  • Arene ring bearing two ortho fluorine substituents (positions 2 and 6) and a benzylic acetic acid side chain (–CH2–CO2H) para to neither F due to ortho substitution pattern.
  • Functional groups: aromatic ring, carboxylic acid, benzylic methylene, two aryl–F bonds.
  • Structural features: the two ortho fluorines increase ring deactivation and influence sterics around the benzylic side chain; the carboxylic acid provides acidity and coupling handle.

• 2D structure in words (general): a benzene ring with fluorine atoms at the two positions adjacent to the benzylic substituent; the benzylic carbon bears a methylene linking to a terminal carboxylic acid.

Synthetic Utility

Key functional elements and reactivity (literature/general):

• Carboxylic acid handle: Readily transformed into amides, esters, anhydrides, and acid chlorides. Enables conjugation to amines, alcohols, and nucleophiles.
• Benzylic methylene: Activated toward radical halogenation (NBS), oxidation (to keto derivatives after activation), and decarboxylative functionalization when converted to redox-active esters.
• Ortho-difluoro aryl ring: Strong –I effect decreases electron density and can attenuate electrophilic aromatic substitution while enabling SNAr under forcing conditions. The 2,6-difluoro motif can also influence conformational bias in adjacent linkages (e.g., amides).

Named/typical transformations:

• Steglich esterification (DCC/DMAP) to esters; HATU/EDC couplings to amides.
• Formation of acid chloride (SOCl2, catalytic DMF), followed by acylation of nucleophiles.
• Curtius rearrangement from the acyl azide to isocyanate → ureas/carbamates.
• Decarboxylative cross-couplings via NHP ester under photoredox/Ni catalysis to access substituted benzyl frameworks.

Retrosynthetic value:

• Serves as a convergent point to introduce the 2,6-difluorophenylacetyl fragment late-stage, allowing SAR exploration by varying the amine/alcohol partner while maintaining the ortho-difluoro aryl core.

Target Specificity

Not applicable. This product is a small-molecule organic acid, not an antibody, enzyme, or affinity reagent. No antigen/epitope or species reactivity information is relevant.