2,2-Difluoro-3-hydroxy-3-phenylpropanoic acid - ≥98% , CAS No.681240-18-6

CAS: 681240-18-6 Cat. No.: D929844 Summenformel: C₉H₈F₂O₃ Molekulargewicht: 202.150 EG-Nummer: 887-735-8

GRADE & PURITY ≥98%

Storage

Room temperature

Specifications

Spezifikationen & Reinheit

≥98%

Storage

Room temperature

Reinheit

≥98%

Namen und Kennungen

• Kanonisches Lächeln: C1=CC=C(C=C1)C(C(C(=O)O)(F)F)O
• IUPAC Name: 2,2-difluoro-3-hydroxy-3-phenylpropanoic acid
• InChIKey: LUTWVXSKIQMZHU-UHFFFAOYSA-N
• INCHI: 1S/C9H8F2O3/c10-9(11,8(13)14)7(12)6-4-2-1-3-5-6/h1-5,7,12H,(H,13,14)
• Molekulargewicht: 202.150

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Phenylpropanoids and polyketides
    • Klasse Phenylpropanoic acids

• Kingdom: Organic compounds
• Superclass: Phenylpropanoids and polyketides
• Klasse: Phenylpropanoic acids
• Subclass: Not available
• Intermediate Tree Nodes: Not available
• Direct Parent: Phenylpropanoic acids
• Alternative Parents: Beta hydroxy acids and derivatives Benzene and substituted derivatives Alpha-halocarboxylic acids Secondary alcohols Fluorohydrins Monocarboxylic acids and derivatives Carboxylic acids Organofluorides Organic oxides Hydrocarbon derivatives Carbonyl compounds Aromatic alcohols Alkyl fluorides
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: 3-phenylpropanoic-acid - Beta-hydroxy acid - Monocyclic benzene moiety - Hydroxy acid - Benzenoid - Alpha-halocarboxylic acid - Alpha-halocarboxylic acid or derivatives - Secondary alcohol - Fluorohydrin - Halohydrin - Carboxylic acid derivative - Carboxylic acid - Monocarboxylic acid or derivatives - Hydrocarbon derivative - Alkyl fluoride - Organohalogen compound - Organofluoride - Carbonyl group - Organic oxygen compound - Alcohol - Organooxygen compound - Organic oxide - Aromatic alcohol - Alkyl halide - Aromatic homomonocyclic compound
• Beschreibung: This compound belongs to the class of organic compounds known as phenylpropanoic acids. These are compounds with a structure containing a benzene ring conjugated to a propanoic 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

Chemische und physikalische Eigenschaften

• Molekulargewicht: 202.150 g/mol
• XLogP3: 1.300
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 3
• Exact Mass: 202.044 Da
• Monoisotopic Mass: 202.044 Da
• Topological Polar Surface Area: 57.500 Ų
• Heavy Atom Count: 14
• Formal Charge: 0
• Complexity: 212.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• Undefined Atom Stereocenter Count: 1
• 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 assay or bioanalytical application protocols are provided in the Product Data for this small molecule. Typical laboratory uses are in organic synthesis. For synthetic procedures (e.g., esterification, amide coupling, oxidations), refer to the Reaction Conditions and Synthetic Utility sections for general literature-style guidance and adjust to your system.

Biological Roles

• Product Data category places this item in “life science,” but no biological function is specified. The compound is a synthetic, fluorinated small molecule; it is not a known endogenous metabolite.
• General context (no clinical claims): Fluorinated building blocks such as 2,2-difluoro-3-hydroxy-3-phenylpropanoic acid are often used to probe structure–activity relationships because CF2 substituents can modulate lipophilicity, metabolic stability, and conformational preferences in bioactive scaffolds.
• Biochemical interactions (conceptual): The molecule presents both hydrogen-bond donor (alcohol, acid) and acceptor (carbonyls) sites, enabling engagement with protein binding pockets after derivatization. However, the free acid itself has no defined biological role provided here.
• Metabolic considerations (general): Carboxylic acids may undergo phase II conjugation (e.g., glucuronidation) in vivo; benzylic alcohols can be oxidized to ketones/acids. CF2 groups resist oxidative metabolism relative to CH2, though this is highly context dependent.

Research use limitation

• As per Product Data: For research use only. Not for human or veterinary use, diagnostic, or therapeutic applications.

Buffer Applications

This compound is not a classical buffering agent and lacks a defined, narrow pKa window suitable for routine biochemical buffering. It is generally employed as a synthetic intermediate/building block rather than as a buffer component.

• If a buffered environment is required for transformations (e.g., enzymatic resolutions of esters), choose established buffers (phosphate, acetate, Tris, HEPES) appropriate to the system.
• For aqueous workups, simple acid/base pH adjustments are used to toggle carboxylate solubility; this is not considered buffer use.

Green Alternatives

Opportunities to improve sustainability (general guidance)

• Solvent substitution
  • Replace DCM with ethyl acetate or 2-MeTHF where feasible (extractions, esterifications).
  • Favor acetonitrile or ethanol over DMF/DMSO when solubility and reactivity permit.
• Coupling chemistry
  • Consider aqueous micellar catalysis (e.g., TPGS-750-M) for amide formation using EDC·HCl to minimize organic solvent use.
  • Use propylphosphonic anhydride (T3P) in ethyl acetate as a lower-toxicity alternative to DCC/DMAP, reducing urea waste.
• Protection strategies
  • Select protecting groups removable under mild, waste-minimizing conditions (e.g., carbonate-based) to decrease harsh reagents.

Illustrative comparison (general)

• DCM vs EtOAc
  • Worker exposure and environmental impact: EtOAc preferred
  • Boiling point/workup: DCM easier to remove; EtOAc still practical
• DMF vs MeCN
  • DMF: excellent solvency; problematic EHS profile
  • MeCN: lower toxicity, readily recoverable

Process considerations

• Optimize pH-switch crystallizations to avoid chromatography.
• Employ solvent recycling and atom-economical decarboxylative couplings.

Note: The choice of “green” alternative must be balanced with required selectivity (CF2-containing substrates may be sensitive to strong bases/oxidants). Validate at small scale before implementation.

Pharmaceutical Uses

No pharmacopeial status or excipient role is specified in the Product Data. Do not construe any therapeutic claims.

General formulation/manufacturing context (research only)

• As a fluorinated carboxylic acid building block, this material can be elaborated into drug-like molecules. Common transformations include amide coupling, ester prodrugs, or conversion to bioisosteric motifs retaining the CF2 functionality.
• Salt screening: The free acid can form salts with amines to alter solubility for preformulation studies. Counterion selection (e.g., tromethamine, meglumine) is application-specific.
• Stability considerations: Protect the secondary alcohol and control moisture during acylation/coupling to reduce byproducts. The CF2 group is generally metabolically robust, an attribute often sought in medicinal chemistry leads.

Compliance note: This product is provided for research use only and is not manufactured under GMP. For any development work beyond discovery, specify purity, residual solvents, and elemental impurities via CoA and risk assessments.

Physical Properties

Item-specific specs (Product 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.

Literature/computed (general reference only; not item specifications)

• Empirical formula (literature, based on the named structure): C9H8F2O3
• Calculated formula weight: ~202.15 g/mol
• Expected physical state: low-molecular-mass aromatic carboxylic acids of this type are often crystalline solids or low-melting solids; confirm on CoA.
• Acid/base properties: contains a carboxylic acid (strongly electron-withdrawing CF2 group typically lowers pKa relative to unsubstituted 3-hydroxy-3-phenylpropanoic acid; quantitative value not provided).
• Solubility profile (qualitative, literature trends)
  • Likely soluble in polar aprotic organic solvents (acetonitrile, DMF, DMSO) and alcohols.
  • Sparingly soluble to insoluble in nonpolar alkanes; limited solubility in water expected, but deprotonated salts are water-soluble.
• Other parameters (not available): melting point, boiling point, density, refractive index, logP, UV cut-off, water/peroxide/metal content — Not specified for this item; refer to CoA/Spec Sheet.

Practical note: The gem-difluoro group increases acidity and may modestly increase volatility of derivatives, but the acid itself is typically handled as a solid. Verify exact values on the batch CoA.

Quality and Grades

• Grade/purity (Product Data): Not specified for this item; refer to CoA/Spec Sheet for assay, residual solvents, and related-substance profile.
• Impurity/stabilizer information: Not specified for this item; refer to CoA/Spec Sheet. No stabilizer is indicated in the Product Data.

How to interpret typical grades (general guidance)

• Research/technical grade: adequate for most synthetic steps; may have broader limits on related substances.
• ≥98–99% assay (if specified on CoA): suitable for structure–activity studies and building-block applications with minimal background.
• HPLC grade is a solvent designation; not applicable to this solid acid unless a “chromatography grade” is explicitly stated.

Analytical controls recommended (general)

• Identity: 1H/13C NMR (diagnostic benzylic CH–OH and CF2 coupling in 19F/1H/13C), IR (broad O–H, strong C=O ~1710–1730 cm−1), LC-MS.
• Purity: HPLC/UPLC with diode array; GC is less suitable for polar acids without derivatization.
• Residuals: Confirm water content (Karl Fischer) and residual solvents only if required; values are Not specified for this item; refer to CoA/Spec Sheet.

Procurement note: For enantioenriched needs, verify if racemate vs. single-enantiomer material is offered; stereochemistry at C3 is not specified in the Product Data.

Reaction and Applications

Representative applications for 2,2-difluoro-3-hydroxy-3-phenylpropanoic acid (general literature guidance; expand per project needs)

• Building block for gem-difluoro motifs: The –CF2– group adjacent to the carbonyl enables access to valuable fluorinated chemotypes used in agro/pharma discovery.
• Esterification and amidation: Converts to methyl/ethyl esters (Fischer or DCC/DMAP), acid chlorides (SOCl2, oxalyl chloride), and amides (EDC/HOBt, HATU). The benzylic alcohol may be protected (e.g., silyl ethers) to avoid side reactions.
• Decarboxylative transformations: Under photoredox or thermal conditions, decarboxylation can generate benzylic radicals or unveil difluorinated intermediates leading to C–C or C–X bond formation (consult literature for specific catalysts/conditions).
• Dehydration/oxidation at C3: The secondary alcohol can undergo dehydration to alkenes (acid-catalyzed) or oxidation to the corresponding ketone/acid derivatives; CF2 stabilizes adjacent cations and influences selectivity.
• Cross-coupling of derivatives: After converting the acid to redox-active esters (e.g., N-hydroxyphthalimide esters), engage in Ni/photoredox-catalyzed couplings to append diverse fragments at the benzylic position.
• Chiral chemistry: If stereochemical integrity is required at C3, use mild coupling and low-temperature protocols; racemization can occur under strong base due to benzylic/α,α-difluoro activation.

Practical tips

• Drying: Use anhydrous solvents for coupling; both –CO2H and –OH participate in H-bonding.
• Monitoring: 19F NMR provides a sensitive handle for reaction progress (CF2 typically at −115 to −130 ppm; coupling to 1H/13C observable).

Reaction Conditions

General literature guidance (illustrative; adjust to your substrate and scale)

• Acid chloride formation

  • Reagents: SOCl2 (2–3 eq) with catalytic DMF (1–2 drops/10 mmol) in DCM or toluene
  • Conditions: 0 °C to reflux, 1–3 h; exclude moisture. Quench cautiously; convert in situ to amide/ester.

• Steglich esterification

  • DCC (1.1–1.3 eq), DMAP (0.05–0.10 eq), ROH (2–5 eq), DCM/EtOAc, 0–25 °C, 2–16 h.
  • Workup: filter DCU, wash, and purify by crystallization or silica (avoid strongly basic eluents to minimize racemization at C3).

• Amide coupling (HATU/EDC/T3P)

  • Solvent: DMF or MeCN; Base: DIPEA (2.0–3.0 eq)
  • Temperature: 0–25 °C; Time: 1–6 h. Monitor by LC/MS and 19F NMR.

• Benzylic alcohol manipulations

  • Protection: TBSCl (1.2 eq), imidazole (2 eq), DMF, 0–25 °C.
  • Oxidation: DMP (1.5 eq), DCM, 0–25 °C, 0.5–2 h.
  • Dehydration: acid catalysis (TsOH, reflux in toluene or Dean–Stark) may form alkenes; confirm selectivity due to CF2 influence.

• Decarboxylative couplings (from NHPI ester)

  • Photoredox: Ir(ppy)3 (1–2 mol%), Ni catalyst (2–10 mol%), blue LEDs, MeCN/DMF, rt–40 °C, 4–16 h.

Yields are substrate- and method-dependent; consult primary literature and optimize on small scale. All conditions above are general literature-style recommendations, not product specifications.

Safety and Handling

Product Data safety fields

• Signal word: Not specified for this item; refer to SDS.
• H-statements: Not specified for this item; refer to SDS.
• GHS classification/pictograms: Not specified for this item; refer to SDS.
• Storage conditions (Product Data): Room temperature.

General laboratory safety guidance (supplemental; consult SDS for authoritative information)

• Likely hazards: Organic acids may cause skin/eye irritation and are harmful if swallowed. Fluorinated organics do not intrinsically hydrolyze to HF under ambient conditions but handle with care to avoid thermal decomposition.
• PPE: lab coat, safety glasses or face shield, and appropriate chemically resistant gloves (e.g., nitrile). Use in a fume hood to avoid inhalation of aerosols or vapors during reactions.
• Incompatibilities: Strong bases (neutralization/heat evolution), strong oxidizers, strong reducing agents. Avoid contact with reactive metals and acylation reagents unless under controlled conditions.
• First aid (overview):
  • Skin/eye contact: Rinse with copious water for at least 15 minutes; remove contaminated clothing. Seek medical attention if irritation persists.
  • Inhalation: Move to fresh air; seek medical advice if symptomatic.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
• Spills: Absorb with inert material (vermiculite, silica), collect in compatible containers for disposal per local regulations.
• Thermal/processing notes: When heating or performing dehydrations/couplings, ensure adequate ventilation and quench cautiously to control exotherms.

Always defer to the product-specific SDS for GHS, exposure limits, and emergency procedures.

Solvent Selection

Solubility and polarity considerations (general, based on functionality)

• Acidic, polar compound with hydrogen-bond donors/acceptors; best handled in polar protic or polar aprotic solvents.
• Typical good solvents: methanol, ethanol, isopropanol, acetonitrile, acetone, ethyl acetate, DMSO, DMF.
• Limited solubility expected in hexanes/heptane; toluene/MTBE provide moderate solubility for esterified derivatives.

Use-case-specific guidance

• Reaction medium for esterification/acyl chloride formation: dichloromethane (DCM), toluene, or acetonitrile with catalytic DMF; avoid water.
• Amide couplings: DMF, NMP, DCM, or MeCN with coupling reagents; include base (DIPEA) carefully to manage acid–base equilibria.
• Salt formation/crystallization: alcoholic solvents (MeOH/EtOH/iPrOH) or acetone/EtOAc with antisolvents (MTBE/hexanes) can induce crystallization of free acid or amine salts.

Small comparison (general)

• DCM vs EtOAc: DCM offers superior solubility and low boiling for workups; EtOAc is greener and often sufficient.
• DMF/DMSO vs MeCN: DMF/DMSO maximize solubility but complicate workups; MeCN balances polarity and volatility.

Tip: For aqueous workups, the carboxylate partitions to water under basic conditions and to organic under acidic conditions; leverage pH switches for efficient separations.

Storage and Reconstitution

• Storage (Product Data): Room temperature.
• Container: Store tightly capped in the original container to minimize moisture uptake and contamination; consider desiccation for long-term storage due to the presence of acidic and alcoholic functionalities.
• Atmosphere: Ambient conditions are generally acceptable; for sensitive applications, store under dry nitrogen/argon.
• Light: Protect from prolonged direct light during extended storage to minimize potential discoloration.
• Reconstitution/solution preparation: Not supplied with a reconstitution protocol. Dissolve in a suitable dry solvent (e.g., MeCN, DCM, MeOH, DMSO) immediately before use. For aqueous systems, adjust pH appropriately and consider forming a soluble salt if needed.
• Freeze–thaw: Not applicable to solids. If stock solutions are prepared, aliquot and store at appropriate temperature for the chosen solvent; avoid repeated freeze–thaw cycles.
• Stability: No item-specific stability data are provided; refer to CoA/Spec Sheet and perform a small-scale stability check under intended conditions.

Structure and Identity

Brief description: 2,2-Difluoro-3-hydroxy-3-phenylpropanoic acid is a benzylic, fluorinated α,α-difluorocarboxylic acid bearing a secondary alcohol adjacent to an aromatic ring.

• Product Data identifiers (as provided)
  • CAS: 681240-18-6
  • CID: 11637029
  • InChIKey: 209722 (as provided; atypical length—refer to CoA/SDS for confirmation)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• Literature/computed identifiers and features (for reference; not item specifications)
  • Common structural formula (literature): C9H8F2O3 (see rationale below)
  • Approx. molecular weight (calculated from literature formula): ~202.15 g/mol
  • Representative SMILES (literature): O=C(O)C(F)(F)C(O)c1ccccc1
• Structural features (general/structure description)
  • Functional groups: carboxylic acid (–CO2H), secondary alcohol (–CHOH–), geminal difluoro substituent (–CF2–), and a phenyl ring.
  • Connectivity (2D description): The three-carbon backbone has the carboxyl group at C1, a gem-difluoro-substituted methine at C2, and a benzylic secondary alcohol at C3 that is bonded to a phenyl ring. No stereocenter at C2 (CF2), while C3 is stereogenic; material may be racemic unless specified.
  • Electronic character: strong –I effect from CF2 activating the carboxyl group and acidifying the C3 alcohol environment; benzylic position enables further derivatization.

Notes: Where Product Data do not specify identifiers (SMILES/InChIKey, exact MW), consult the CoA/Spec Sheet for definitive values.

Synthetic Utility

Key reactivity handles

• Carboxylic acid: activation to acid chloride/anhydride, esterification (Fischer, Steglich), and amide coupling (EDC/HATU/T3P). Decarboxylation possible under photoredox or thermal conditions from suitable derivatives (e.g., NHPI esters).
• Secondary benzylic alcohol: protection (TBS, TBDPS), oxidation (Dess–Martin, Swern) to ketone, or conversion to leaving groups (mesylate/tosylate) for substitution/elimination.
• gem-Difluoro motif: strong –I effect tunes acidity and reactivity; facilitates formation of difluoroalkyl radicals and can stabilize adjacent cations, enabling dehydrations or rearrangements under acid.

Retrosynthetic value

• Serves as a convergent precursor to CF2-containing benzylic frameworks. From this node, divergence to amides, esters, ketones, or decarboxylated products provides rapid SAR exploration.

Select transformations (literature-style guidance)

• Steglich esterification: acid + ROH, DCC (1.1 eq), DMAP (0.1 eq), DCM/EtOAc, 0–25 °C.
• HATU amide coupling: acid (1.0 eq), amine (1.2 eq), HATU (1.1 eq), DIPEA (2.0 eq), DMF/MeCN, 0–25 °C.
• Oxidation of benzylic alcohol: DMP (1.5 eq), DCM, 0–25 °C, gives the corresponding benzoin-like ketone acid.
• Redox-active ester formation: acid + NHP, DIC/DMAP, then Ni/photoredox coupling to append aryl/alkyl groups at the benzylic position.

Target Specificity

Not applicable. This product is a small-molecule building block, not a biological macromolecule or affinity reagent. No antigen/epitope, species reactivity, clone, or isotype information applies.