Ethyl 2-(2-cyanophenyl)-2,2-difluoroacetate - ≥97% , CAS No.1335290-31-7

CAS: 1335290-31-7 Cat. No.: E1004697 Summenformel: C₁₁H₉F₂NO₂ Molekulargewicht: 225.19 EG-Nummer: 989-690-0 PubChem CID: 122129592

GRADE & PURITY ≥97%

Storage

Room temperature

Specifications

Spezifikationen & Reinheit

≥97%

Storage

Room temperature

Reinheit

≥97%

Namen und Kennungen

• Kanonisches Lächeln: CCOC(=O)C(C1=CC=CC=C1C#N)(F)F
• IUPAC Name: ethyl 2-(2-cyanophenyl)-2,2-difluoroacetate
• InChIKey: PFXQRKCMYVFNCF-UHFFFAOYSA-N
• INCHI: 1S/C11H9F2NO2/c1-2-16-10(15)11(12,13)9-6-4-3-5-8(9)7-14/h3-6H,2H2,1H3
• PubChem CID: 122129592
• Molekulargewicht: 225.19

Chemische und physikalische Eigenschaften

• Molekulargewicht: 225.190 g/mol
• XLogP3: 2.500
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 4
• Exact Mass: 225.06 Da
• Monoisotopic Mass: 225.06 Da
• Topological Polar Surface Area: 50.100 Ų
• Heavy Atom Count: 16
• Formal Charge: 0
• Complexity: 308.000
• 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 antibody/assay protocols are associated with this small-molecule reagent. For practical use, see Reaction Conditions for representative synthetic procedures and adapt to your specific substrate and scale.

Biological Roles

This material is a synthetic small-molecule building block, not a biological metabolite. No endogenous biological role is expected.

General context (literature):

• Fluorinated motifs such as –CF2– are often used in medicinal chemistry to modulate lipophilicity, metabolic stability, and conformational preferences. The ortho-cyano group provides a handle for late-stage functionalization (e.g., to amide/acid/amine), enabling SAR exploration.

Note: This information is for chemical design context only. No medical or clinical claims are made, and the product is for research use only.

Buffer Applications

Not typically applicable. This compound is a hydrophobic fluorinated aryl ester and is not used as a buffering agent. For experimental planning, focus on the Synthetic Utility, Reaction & Applications, and Reaction Conditions sections.

Green Alternatives

This product is a specialized fluorinated building block; direct “green replacement” is context-dependent. Consider the following when designing routes (literature/general guidance):

• Minimize halogenated solvent use; where possible, prefer 2-MeTHF, CPME, EtOAc, MeCN, or toluene over DCM/CHCl3.
• For difluoromethyl/difluoroalkyl installations, evaluate alternative reagents and activation modes with improved EHS profiles:

Comparison (general):

• Ethyl aryl-2,2-difluoroacetates:
  • Pros: Bench-stable ester, handles (ester, CN) for diversification; compatible with photoredox/transition-metal catalysis.
  • Cons: Fluorinated organic waste; potential persistence concerns.
• 2,2-Difluoroacetic acid or its salts:
  • Pros: Avoids ethyl alcohol emissions during hydrolysis; sometimes easier waste handling.
  • Cons: Less lipophilic; may reduce substrate solubility; can be more corrosive.
• Reagents for CF2 introduction via in situ generation (e.g., TMSCF2X surrogates, hypervalent iodine–CF2 reagents):
  • Pros: Often catalytic, milder conditions, fewer stoichiometric byproducts.
  • Cons: Specialized reagents, variable availability and cost.

Operational greening:

• Use micellar catalysis or solvent-minimized flow where viable.
• Apply photocatalysis with organic dyes instead of precious-metal catalysts when performance allows.
• Plan telescoped sequences (e.g., ester manipulation followed by cycloaddition on the nitrile) to reduce isolations.

Pharmaceutical Uses

As a research-use-only reagent, this compound is not an approved excipient and has no pharmacopeial monograph specified.

Formulation/manufacturing context (general):

• Fluorinated aryl esters can serve as intermediates en route to candidate APIs or building blocks in discovery. They are not used directly in dosage forms.
• The nitrile can be converted to amides/acids/amines that are common in drug-like scaffolds. Any downstream material intended for clinical use would require full GMP controls and specification setting independent of this catalog item.

No therapeutic or clinical claims are made for this product.

Physical Properties

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

• Literature/general expectations for this structural class (for planning only; verify experimentally):

  • Physical state/appearance (literature): Typically a colorless to pale yellow liquid or low-melting solid for closely related aryl-difluoroacetates; actual form for this item is not specified.
  • Boiling point / melting point: Not widely reported for this exact compound; consult primary literature or measure under reduced pressure as needed.
  • Density, refractive index: Not reported for this exact compound; expect values typical of aryl esters containing two fluorine atoms (density often >1.1 g/mL for liquids), but confirm experimentally.
  • Solubility (qualitative, literature): Expected to be soluble in common organic solvents (DCM, EtOAc, THF, MeCN) and sparingly soluble in water due to aromatic, ester, and CF2 content.
  • LogP (qualitative): Moderate lipophilicity anticipated for aryl ester with CF2 and cyano substituent; determine experimentally if needed for separations.

Notes: Use these literature expectations only as general guidance. For specifications required for QC, chromatography method setup, or hazard assessment, refer to the product’s CoA/SDS or determine empirically.

Quality and Grades

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

Guidance on interpreting common grades (general information):

• Research/technical grade: Suitable for synthetic transformations and screening; trace impurities may require purification for sensitive catalysis.
• Analytical reagent (AR) or ≥98%: Typically appropriate for most small-molecule syntheses; may reduce background in analytical assays.
• HPLC grade (for solvents) / Low-UV: Not applicable to this reagent class; for chromatography solvents only.

Stabilizers/inhibitors: None indicated in Product Data. If a stabilizer is present for related products (e.g., acid scavengers or antioxidants), it will be listed on the CoA and may influence reaction outcomes. When reaction sensitivity is high (e.g., low-level metal catalysis), consider an additional purification step (short-path distillation for liquids or recrystallization/flash chromatography for solids) to meet stringent specifications.

Reaction and Applications

As an aryl-difluoroacetate bearing an ortho-cyano group, this reagent serves as a versatile building block for installing CF2-containing motifs and for orthogonal diversification of the nitrile and ester handles.

Representative application families (literature/general):

• Hydrolysis/transesterification: Conversion to the corresponding acid or other esters (acidic or basic conditions) enables downstream amide coupling or decarboxylative strategies.
• Metal-mediated coupling/activation: Aryl–CF2–CO2Et scaffolds can engage in decarboxylative or alpha-activation pathways under Ni/Pd/Cu or photoredox catalysis to generate difluorinated radicals or carbanion equivalents for C–C bond formation.
• Reformatsky-type additions (difluoro variants): Difluoroacetate motifs can be transformed into nucleophilic partners under activating conditions (e.g., Zn, Mg, or SmI2) to add to carbonyl compounds, furnishing β-hydroxy esters retaining CF2 units.
• Nitrile diversification: Ortho-cyano substituent allows convergent elaborations: hydration to amide/acid, reduction to amine, or cycloadditions (e.g., [2+3] to tetrazoles via azide), enabling rapid library expansion.
• Electrophilic aromatic substitution (EAS) guidance: The ortho-cyano is strongly deactivating; further EAS on the ring is disfavored. Cross-coupling via prefunctionalized aryl derivatives is preferred for additional aryl modifications.

Practical tips:

• Maintain dry conditions for moisture-sensitive steps (metalations, coupling).
• For radical decarboxylative methods, photoredox catalysts (Ir or organic dyes) and blue light are common; oxygen exclusion improves yields.
• Monitor for ester cleavage under prolonged strong basic conditions; use buffered or non-nucleophilic bases where possible.

Reaction Conditions

The following are literature/general guidelines for transformations involving aryl-difluoroacetates and aromatic nitriles. They are not item-specific specifications.

• Ester hydrolysis to acid:

  • Basic: MeOH/H2O, NaOH or K2CO3 (1–2 equiv), 0–25 °C to reflux, 2–6 h. Acidify and extract. Avoid prolonged strong base if nitrile integrity must be maintained.
  • Acidic: AcOH/H2O or HCl(dil.) in dioxane, 50–80 °C, 2–8 h; preserves nitrile more effectively.

• Amide coupling (from acid):

  • EDCI/HOBt or HATU/DIPEA in DMF/CH2Cl2, 0–25 °C, 2–16 h; monitor for potential base-promoted side reactions.

• Transesterification:

  • ROH (5–20 equiv), catalytic acid (p-TsOH) or base (NaOEt), reflux, 2–12 h; remove ROH to drive equilibrium.

• Nitrile to amide/acid:

  • Hydration: H2SO4(aq) or Cu-catalyzed hydration in MeCN/H2O, 50–100 °C, 4–24 h.
  • Hydrolysis to acid: Aqueous mineral acid (reflux) or strong base followed by workup.

• Nitrile reduction to amine:

  • Catalytic hydrogenation (Pd/C, H2 3–5 bar) in EtOH/EtOAc, RT–50 °C, 4–16 h, or BH3·THF/LAH in THF at 0–25 °C.

• Decarboxylative difluoroalkylation (from acid or activated ester):

  • Photoredox (blue LED), Ir(ppy)3 (0.5–2 mol%), base (K2HPO4), MeCN or DMF, N2, RT, 2–12 h to forge C(sp2/sp3)–CF2 linkages.

• Reformatsky-type CF2 additions:

  • Activation with Zn or SmI2 in THF, –78 to 0 °C, then addition to aldehydes/ketones; quench with NH4Cl.

Always optimize on small scale; actual conditions depend strongly on substrates and desired chemoselectivity.

Safety and Handling

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

General safety considerations for aryl-difluoroacetates and aromatic nitriles (literature/general guidance):

• PPE: Lab coat, safety glasses, and suitable gloves (e.g., nitrile). Work in a fume hood to avoid inhalation of vapors or aerosols.
• Incompatibilities: Avoid strong bases and strong nucleophiles if ester hydrolysis is not intended. Oxidizing agents can react with organics; avoid mixing unless part of a controlled protocol.
• Thermal stability: Esters can undergo transesterification or hydrolysis under harsh conditions; CF2-containing centers are generally robust but may participate in metal-mediated transformations.
• First aid (overview): If skin contact occurs, wash with soap and water. If in eyes, rinse with water for several minutes and seek medical attention. If inhaled, move to fresh air. If ingested, rinse mouth; do not induce vomiting; seek medical attention. Always follow SDS-specific instructions.
• Environmental: Prevent release to the environment. Collect waste in halogenated-organic waste streams unless site policy dictates otherwise.
• Special risks: No particular peroxide risk (non-ether). Avoid strong base if the nitrile or ester integrity must be preserved.

Always consult the product SDS for definitive hazard classifications and response measures.

Solvent Selection

This product is a fluorinated aryl ester reagent, not a solvent. Solvent selection depends on the transformation you intend.

General guidance (literature/practice):

• Polarity needs: The compound is moderately lipophilic; it dissolves well in polar aprotic organic solvents such as DCM, THF, EtOAc, and MeCN. DMF/DMSO can be used for high-polarity conditions (e.g., nucleophilic substitutions or metalations), acknowledging more difficult workups.
• Acid/base sensitivity: Avoid strong aqueous base if ester hydrolysis is undesired. For nitrile chemistry (hydration, reduction), protic solvents or mixed aqueous-organic systems may be needed with appropriate catalysts.
• Catalysis compatibility: For Pd/Cu catalysis or radical chemistry, dry, oxygen-free solvents (THF, DMA, MeCN, toluene) are commonly used; degas as needed.

Comparison notes:

• DCM/CH2Cl2: Excellent solubility, low boiling for easy removal; consider environmental and safety aspects.
• THF/2-MeTHF: Good balance of polarity; enables organometallic steps. 2-MeTHF offers greener credentials vs THF.
• MeCN: Polar aprotic, good for photoredox or metal-catalyzed C–C activations; easy to remove.
• Toluene/EtOAc: Useful for extractions and chromatography; EtOAc can engage in transesterification under strong base at reflux—avoid in such cases.

Storage and Reconstitution

• Storage Conditions (from Product Data): Room temperature.
• Shipped In: Not specified for this item; refer to CoA/Spec Sheet.
• Reconstitution: Not applicable; provided as a neat small-molecule reagent. If solid, dissolve in a suitable dry organic solvent (e.g., DCM, THF, MeCN) immediately before use as required.

Good practices (general):

• Store tightly closed under inert atmosphere if performing moisture- or air-sensitive chemistry downstream.
• Protect from prolonged light and heat to avoid unintended degradation of ester functionality.
• If long-term storage is planned, consider amber glass and desiccation; record opening date and observe any changes in appearance before use.

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

Structure and Identity

Ethyl 2-(2-cyanophenyl)-2,2-difluoroacetate is an aryl-difluoroacetate bearing an ortho-cyano substituent on the phenyl ring. It is a fluorinated ester building block useful for synthesis and late-stage diversification.

• Item-specific identifiers (from Product Data):

  • SKU: E1004697
  • Product Name: Ethyl 2-(2-cyanophenyl)-2,2-difluoroacetate
  • CAS: 1335290-31-7
  • PubChem CID: 122129592
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Computed/structure-derived (literature/general; not item-specific specifications):

  • Molecular formula (from name): C11H9F2NO2 (computed)
  • Approx. molecular weight: ~225.19 g/mol (computed from formula)
  • Key functional groups: aromatic ring, nitrile (–C≡N), geminal difluoro (–CF2–), ethyl ester (–CO2Et)
  • 2D topology (described): An ortho-cyanophenyl ring bonded to a quaternary carbon bearing two fluorine atoms, which is alpha to an ester carbonyl connected to an ethoxy group.

• Stereochemistry: None (achiral, quaternary sp3 carbon with two identical F substituents).

Synthetic Utility

Key reactivity map:

• Ester handle (–CO2Et):
  • Hydrolysis to acid (acidic or basic), then amide coupling.
  • Transesterification to tune solubility or reactivity.
  • Decarboxylative activations under photoredox or transition-metal catalysis to access difluoroalkyl radicals.
• Gem-difluoro center (–CF2–):
  • Stabilizes adjacent carbanions/radicals; enables nucleophilic additions (e.g., Reformatsky-type variants) and radical C–C bond formations.
  • Preserves fluorine content through subsequent steps, imparting metabolic robustness.
• Ortho-cyano group:
  • Chemoselective transformations: hydration (amide/acid), reduction (primary amine), or [3+2] cycloadditions (tetrazoles) enabling heterocycle access.
  • Provides a strong –I/–M deactivating effect, steering further aromatic chemistry toward cross-coupling after prior functionalization rather than EAS.

Retrosynthetic considerations (general):

• Disconnections through the ester (back to the corresponding acid) or through radical decarboxylation (to CF2-centered fragments) enable modular route design.
• Orthogonal manipulation of nitrile vs ester maximizes diversification; sequence planning avoids base-promoted ester cleavage during nitrile transformations.

Practical notes:

• For nucleophilic additions, select non-nucleophilic bases and polar aprotic solvents; control temperature to suppress side hydrolysis.
• For photoredox decarboxylations, blue LEDs, an Ir or organic dye catalyst, and MeCN/DMF under N2 are commonly effective (literature guidance).

Target Specificity

Not applicable. This product is a small-molecule chemical reagent, not a biological targeting agent (no antigen/epitope/clone/isotype information). Refer to Synthetic Utility and Reaction & Applications for relevant use cases.