4-Ethoxy-3,5-difluorobenzamide , CAS No.1017779-23-5

CAS: 1017779-23-5 Cat. No.: E1005753 분자식: C₉H₉F₂NO₂ 분자량: 201.17 PubChem CID: 46737605

Storage

Room temperature

Specifications

보관 조건

Room temperature

이름과 식별자

• 정식 스마일: CCOC1=C(C=C(C=C1F)C(=O)N)F
• IUPAC Name: 4-ethoxy-3,5-difluorobenzamide
• InChIKey: HJUVRXABDGGYQD-UHFFFAOYSA-N
• INCHI: 1S/C9H9F2NO2/c1-2-14-8-6(10)3-5(9(12)13)4-7(8)11/h3-4H,2H2,1H3,(H2,12,13)
• 이성체 SMILES: CCOC1=C(C=C(C=C1F)C(=O)N)F
• PubChem CID: 46737605
• 분자량: 201.17

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • 분류 Benzene and substituted derivatives
      • Subclass Benzoic acids and derivatives
        • Level5 Halobenzoic acids and derivatives
          • Level6 3-halobenzoic acids and derivatives

• Kingdom: Organic compounds
• Superclass: Benzenoids
• 분류: Benzene and substituted derivatives
• Subclass: Benzoic acids and derivatives
• Intermediate Tree Nodes: Halobenzoic acids and derivatives
• Direct Parent: 3-halobenzoic acids and derivatives
• Alternative Parents: Benzamides Phenoxy compounds Phenol ethers Benzoyl derivatives Fluorobenzenes Alkyl aryl ethers Aryl fluorides Primary carboxylic acid amides Organonitrogen compounds Organofluorides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: 3-halobenzoic acid or derivatives - Benzamide - Phenoxy compound - Benzoyl - Phenol ether - Alkyl aryl ether - Fluorobenzene - Halobenzene - Aryl fluoride - Aryl halide - Primary carboxylic acid amide - Carboxamide group - Ether - Carboxylic acid derivative - Organonitrogen compound - Organooxygen compound - Organic nitrogen compound - Hydrocarbon derivative - Organic oxide - Organic oxygen compound - Organohalogen compound - Organofluoride - Aromatic homomonocyclic compound
• 설명: This compound belongs to the class of organic compounds known as 3-halobenzoic acids and derivatives. These are benzoic acids or derivatives carrying a halogen atom at the 3-position of 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

화학 및 물리적 특성

• 분자량: 201.170 g/mol
• XLogP3: 1.300
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 3
• Exact Mass: 201.06 Da
• Monoisotopic Mass: 201.06 Da
• Topological Polar Surface Area: 52.300 Ų
• Heavy Atom Count: 14
• Formal Charge: 0
• Complexity: 201.000
• 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

No vendor-validated bioassay protocols are provided for this SKU. As a small-molecule solid, typical laboratory uses include:

• Preparing analytical standards: Weigh accurately, dissolve in DMSO/MeOH to make a stock (e.g., 10–100 mM), and dilute into mobile phase for LC–MS/UPLC.
• Reaction setup: Charge under dry conditions if moisture-sensitive reagents are employed in subsequent steps (e.g., coupling reagents); monitor by LC–MS and 19F NMR.

Any detailed biological application parameters (e.g., WB/IHC/IF/FC dilutions) are not applicable to this chemical building block. Refer to your internal SOPs for method-specific preparation.

Biological Roles

Item-specific biological/biochemical roles: Not specified for this item; no biological function is provided. For research use only.

General context (literature; not product-specific):

• Aryl amides frequently serve as pharmacophore elements in discovery chemistry due to their capacity for dual hydrogen-bonding (donor NH, acceptor C=O) and their conformational preferences relative to substituted aromatics.
• Fluorination at the 3,5-positions can modulate metabolic stability and lipophilicity while subtly altering electronics of the ring without introducing heavy steric encumbrance.
• The para-ethoxy substituent provides an adjustable polarity/lipophilicity handle and may act as a metabolic soft spot (O-dealkylation) in metabolic studies of related scaffolds; such considerations are relevant to design but do not constitute a defined biological role for this specific molecule.

If biological assays are planned, determine solubility limits in assay buffers with small amounts of DMSO and confirm stability (no hydrolysis or ether cleavage) under the assay’s pH and temperature. No cell culture or organismal roles are implied for this SKU.

Buffer Applications

This compound is not a buffering reagent and does not define a conjugate acid/base pair suitable for maintaining pH. Accordingly, there are no standard buffer formulations for this item.

Practical guidance:

• For biological assays, it can be dosed into existing buffers using DMSO or ethanol cosolvent (e.g., final 0.1–1% v/v organic cosolvent), after solubility screening.
• Select buffer components (e.g., phosphate, HEPES) based on the biology being studied; this compound will not contribute to buffer capacity.

Green Alternatives

Because this item is a solid building block rather than a process solvent, “green alternatives” are best considered for the solvents and reagents used with it.

Greener solvent considerations (literature/general):

• Dissolution/stock prep: Prefer bio-based or lower-toxicity solvents when feasible (e.g., ethanol, ethyl acetate) over high-boiling dipolar aprotics, balancing solubility needs.
• Reaction media: Where DMF/DMSO/NMP would be standard, consider alternatives such as Cyrene, PC/GBL, or 2-MeTHF/EtOAc blends if the transformation tolerates them.

Comparison snapshot (general; not product-specific):

• DMF vs. Cyrene: Cyrene offers reduced reproductive toxicity concerns; viscosity and basicity differ—optimize temperature and base equivalents accordingly.
• DCM vs. EtOAc/2-MeTHF: EtOAc/2-MeTHF reduce halogenated waste; polarity differences may require catalyst/base adjustment.
• Strong dehydrating reagents (SOCl2/POCl3) vs. greener coupling: Enzyme-mediated or CDI/EDC couplings can avoid acid chloride routes for amide interconversions after hydrolysis to the acid.

Waste minimization:

• Favor catalytic over stoichiometric activations; plan telescoped sequences (e.g., hydrolysis → in situ coupling) to limit isolations and washes.

Note: Always validate greener substitutions on small scale to confirm conversion and selectivity with this substrate.

Pharmaceutical Uses

Item-specific pharmaceutical/excipient status: Not specified for this item; no pharmacopeial status is provided. For research use only.

General formulation context (not product-specific):

• As a small, non-ionic organic solid, this scaffold would typically be handled as a drug-substance candidate or intermediate in discovery chemistry rather than as an excipient.
• If used in pre-formulation studies, typical approaches include:
  • Solubility screening in biorelevant media (FaSSIF/FeSSIF), cosolvent systems, and lipid vehicles
  • Solid-state characterization (XRPD, DSC/TGA) to assess polymorphism and thermal stability
  • Compatibility studies with common excipients if progressing toward dosage-form prototyping

No therapeutic or clinical claims are made or implied for this SKU.

Physical Properties

Item-specific specifications for this SKU (BP, MP, density, water/peroxide/metal limits, UV cutoff): Not specified for this item; refer to CoA/Spec Sheet.

Literature/general expectations for this structure (for planning only; not product specifications):

• Physical state: Typically a crystalline solid for aryl benzamides with similar substitution.
• Polarity/functional groups: Polar amide (hydrogen-bond donor/acceptor) with moderately lipophilic aryl–ether and aryl–F substituents; overall moderate polarity.
• Solubility profile (qualitative, literature):
  • Good in polar aprotic solvents (DMSO, DMF, NMP, acetone, acetonitrile)
  • Moderate in alcohols (MeOH, EtOH)
  • Low in nonpolar hydrocarbons (hexanes, heptane)
  • Limited in water due to aryl content despite amide functionality
• Refractive index, pKa, logP/logD: Not specified for this item; consult literature or measure experimentally for method development.
• Thermal behavior: Aromatic amides commonly melt in the 100–200 °C range (literature trend), but an exact MP for this compound is not provided here and should be determined/verified on receipt.

Practical notes:

• For analytical method development, evaluate UV absorbance in the 200–300 nm range where aryl amides typically show strong π–π* transitions; exact λmax not specified for this item.

Quality and Grades

• Item-specific grade/purity, stabilizers, and analytical limits: Not specified for this item; refer to CoA/Spec Sheet for assay, related substances, water content, and any stabilizer information.

Guidance on typical grades for small-molecule building blocks (general):

• Research/CP grade: Suitable for most synthetic applications and SAR screening; may have broader impurity and moisture limits.

• 95–98% purity ranges (common for screening libraries): Adequate for medicinal chemistry; verify by NMR/LC if sensitive transformations are planned.

• Higher-purity grades (≥99%) are preferred for quantitative physical measurements or when trace impurities could poison catalysts.

Analytical considerations:

• For aryl amides, confirm identity/purity by a combination of 1H/13C NMR, LC–MS, and HPLC/UPLC purity. 19F NMR is particularly useful here to confirm the two fluorine environments at 3,5-positions and assess any regioisomeric impurities.
• Water, residual solvents, and inorganic residues: Not specified for this item; consult CoA for limits.

Implication for use:

• If planning water-sensitive reactions (e.g., acid chloride couplings, organometallics), pre-dry the solid under high vacuum at mild temperature and verify KF if applicable (KF limit: Not specified for this item).

Reaction and Applications

This molecule functions primarily as a substituted benzamide building block. The 3,5-difluoro substitution pattern and para-ethoxy group tune electronics and lipophilicity, useful in SAR campaigns and materials-oriented aryl amide scaffolds.

Representative application directions (literature/general; not product-specific):

• Hydrolysis to acid: Converts to 4-ethoxy-3,5-difluorobenzoic acid under aqueous base or acid (reflux), enabling re-entry into carboxylic-acid coupling manifolds.
• N-derivatization: Although a primary amide is relatively unreactive, activation (e.g., via POCl3/oxalyl chloride to a nitrile or imidoyl chloride) enables further transformations (e.g., amide to nitrile dehydration; Beckmann-like rearrangements via appropriate precursors). Caution: strong conditions required.
• Cross-coupling at aryl-F: Aryl fluorides are very poor coupling partners; classical Pd cross-couplings are generally not feasible without special activation. If cross-coupling is desired, consider starting from the corresponding aryl bromide/iodide analogs.
• SNAr on aryl-F: The 3,5-positions lack strong ortho/para electron-withdrawing activation beyond the amide at C1; therefore, SNAr displacement of F typically requires harsh conditions or is low-yielding. Evaluate only with strongly nucleophilic conditions or via Meisenheimer-favoring activation.
• Ether handle: The para-ethoxy can sometimes be demasked to phenol under forcing Lewis-acidic demethylation-type conditions (BBr3/BCl3 typically target methoxy > ethoxy; ethoxy cleavage is more challenging and may require stronger/longer conditions).

Use cases:

• Scaffold for H-bonding interactions in discovery chemistry
• Intermediate toward analogs via amide hydrolysis–re-coupling sequences
• Reference standard for analytical method development (19F NMR/LC–MS)

Reaction Conditions

General literature guidance for common transformations of this scaffold (not product-specific; optimize per lab):

• Amide hydrolysis → carboxylic acid:

  • Conditions: Aqueous NaOH or KOH (1–3 M) in EtOH/H2O or dioxane/H2O, 60–100 °C; or H2SO4/HCl aqueous reflux for acidic hydrolysis.
  • Workup: Acidify to pH ~2 to precipitate the acid; isolate by filtration/extraction.

• Acid activation → amide re-coupling (after hydrolysis):

  • Carbodiimide coupling (EDC·HCl/HOBt or Oxyma; or DIC/DMAP) in DMF/DCM/MeCN, 0–25 °C to RT; typical times 1–16 h.
  • HATU/HOAt couplings for hindered amines; base such as DIPEA or collidine.

• Dehydration of the amide → nitrile (if desired):

  • Reagents: SOCl2, POCl3, T3P or Burgess-like reagents; solvents DCM/toluene/MeCN; 0–80 °C depending on reagent.

• Ether cleavage (para-ethoxy → phenol, challenging):

  • Forcing Lewis-acidic conditions (e.g., BBr3, BCl3) at low temperature to RT; ethoxy often requires longer time/higher equivalents than methoxy and may give lower yields—run small-scale trials.

Notes:

• Cross-coupling at C–F is generally impractical under standard Pd/Ni conditions; plan alternative routes if aryl substitution is required.
• Expected yields: Highly condition-dependent; verify on small scale. No item-specific yields are provided.

Safety and Handling

Item-specific GHS data (signal word, hazard statements, pictograms, classification): Not specified for this item; refer to the SDS for authoritative safety information.

General safety considerations for aromatic benzamides (literature/good practice; not product-specific):

• Likely hazards: May cause skin/eye irritation and respiratory tract irritation if dust is generated. Avoid inhalation of dust and contact with skin/eyes.
• PPE: Use lab coat, safety glasses/goggles, and appropriate chemically resistant gloves (e.g., nitrile). Handle in a fume hood to avoid dust exposure.
• Incompatibilities: Strong oxidizers. Under strongly basic or acidic conditions, the amide may hydrolyze to the corresponding acid/amine; avoid prolonged exposure if integrity must be maintained.
• Thermal stability: Typical aromatic amides are thermally stable under normal lab conditions; avoid overheating and open flames.
• First aid (overview; consult SDS for detailed instructions):
  • Inhalation: Move to fresh air; seek medical attention if symptoms persist.
  • Skin/eye contact: Rinse thoroughly with water for several minutes; remove contaminated clothing; obtain medical advice if irritation persists.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
• Waste: Dispose of in accordance with institutional and local regulations for organic laboratory chemicals.

Always defer to the Aladdin SDS for this SKU before use.

Solvent Selection

Compound type: Aromatic benzamide with aryl ether and two aryl fluorides; moderate polarity and H-bonding capacity (amide donor/acceptor).

Practical solvent guidance (literature/general):

• Preferred solvents for dissolution and stock solutions: DMSO, DMF, NMP (excellent); MeOH/EtOH (moderate); acetone and acetonitrile (often good with warming/sonication).
• Limited solubility expected in: EtOAc (variable), toluene (low–moderate), and alkanes (poor).
• Aqueous media: Low intrinsic aqueous solubility; use cosolvent systems (DMSO or EtOH + buffer) or formulate with solubilizers if needed.

Selection by application:

• Analytical (HPLC/UPLC): Start with ACN/H2O or MeOH/H2O ± 0.1% formic acid. DMSO can be used for sample stocks; dilute ≥100× into mobile phase to avoid peak distortion.
• Synthesis: For amide hydrolysis or further derivatization, employ polar aprotic solvents (DMF, DMSO) or alcohols as needed. For coupling chemistry, dichloromethane, DMF, or MeCN are typical media depending on reagents.

Dielectric constants/logP: Not specified for this item; estimate behavior using its amide and aryl features. Always conduct a small solubility screen if solvent choice is critical.

Storage and Reconstitution

• Item-specific storage: Room temperature (per Product Data). Protect from moisture and strong light. Keep tightly closed in the original container.
• Shipping: Not specified for this item; refer to product label/CoA. In general, stable aromatic amides ship at ambient temperature.
• Stability: Aromatic amides are typically stable under ambient lab conditions. Avoid prolonged exposure to strong acids/bases if the intact amide and ether must be preserved.

Reconstitution/preparation guidance (general; not product-specific):

• Stock solutions for screening: Dissolve in DMSO or DMF (typical 10–100 mM). For aqueous use, dilute DMSO stocks into buffer (final organic 0.1–1% v/v) after confirming compatibility.
• Filtration: If particulates are present, pass the solution through a 0.2 µm PTFE filter.
• Freeze–thaw: For organic solvent stocks, aliquot to minimize freeze–thaw. DMSO stocks may be stored at −20 °C; equilibrate to RT and vortex before use.

Specifications such as water content, residual solvents, or assay are Not specified for this item; consult the CoA/Spec Sheet for definitive guidance.

Structure and Identity

Brief description: 4-Ethoxy-3,5-difluorobenzamide is an aryl amide bearing an ethoxy substituent para to the amide and two fluorine atoms at the 3- and 5-positions of the benzamide ring.

• Item-specific (from Product Data)

  • CAS: 1017779-23-5
  • CID (PubChem): 46737605
  • InChIKey: 123430 (as provided)
  • Storage conditions: Room temperature
  • Research use note: For research use only

• Literature/computed identity (informational; verify against CoA/SDS)

  • Expected molecular formula (from name analysis): C9H9F2NO2
  • Calculated molecular weight: ~201.16 g/mol (literature/computed)
  • Suggested SMILES: O=C(N)c1c(F)cc(OCC)c(F)c1 (literature)
  • Core functional groups: primary amide (–CONH2), aryl ether (–O–CH2CH3), aryl C–F bonds (meta/para arranged)

• 2D structural features (descriptive)

  • A benzamide core (benzene ring bonded to a –C(=O)NH2 at C1)
  • Fluorine atoms at the 3- and 5-positions relative to the amide carbonyl (meta to the amide; symmetrically disposed across the para axis)
  • An ethoxy (–O–CH2–CH3) substituent para to the amide (4-position), increasing lipophilicity and providing an ether handle.

Note: Exact identifiers (SMILES/InChI) should be confirmed for this SKU; defer to the CoA/Spec Sheet for final structural strings.

Synthetic Utility

Key reactivity elements:

• Primary amide: Robust under many conditions; can be hydrolyzed (acidic or basic) to the corresponding 4-ethoxy-3,5-difluorobenzoic acid for further coupling (amide/ester formation) or transformed under dehydrating conditions to the corresponding nitrile.
• Aryl ether (para-ethoxy): Electron-donating, slightly activating/ortho–para directing group; potential handle for deprotection to phenol under forcing Lewis-acidic conditions, though ethoxy cleavage is generally more challenging than methoxy.
• Aryl fluorides (3,5-): Electron-withdrawing; strongly influence electronics and ADME-relevant properties. These C–F bonds are typically inert to many cross-coupling conditions; SNAr requires enhanced activation and strong nucleophiles.

Retrosynthetic value:

• Commonly accessed from 4-ethoxy-3,5-difluorobenzoic acid (acid → amide via EDC/HATU/DCC or acid chloride).
• Alternatively, amide-first strategies from the corresponding acid derivative followed by etherification (phenol → ethyl ether) where regiocontrol is established earlier.

Analytical leverage:

• 19F NMR provides a sensitive handle to monitor conversions and detect minor regio-/chemoselective side products.

Use cases:

• SAR diversification via amide hydrolysis and re-coupling to different amines/alcohols (through the acid)
• Late-stage functionalization studies probing stability of ether and amide under oxidative or acidic conditions

Target Specificity

Not applicable. This product is a small-molecule chemical building block and is not supplied as a biological targeting reagent (e.g., antibody, ligand with defined target panel). No antigen/epitope/clone/isotype or species reactivity information applies.