3-(3,4-Difluorophenyl)propanamide - ≥95% , CAS No.1098350-17-4

CAS: 1098350-17-4 Cat. No.: D1294426 분자식: C₉H₉NOF₂ 분자량: 185.17 EC 번호: 822-501-0 PubChem CID: 43346075

GRADE & PURITY ≥95%

Storage

Room temperature

Shipped In

Normal

Specifications

사양 및 순도

≥95%

보관 조건

Room temperature

배송

Normal

순수함

≥95%

이름과 식별자

정식 스마일

C1=CC(=C(C=C1CCC(=O)N)F)F

IUPAC Name

3-(3,4-difluorophenyl)propanamide

InChIKey

XZQRRQRBAHSJDP-UHFFFAOYSA-N

INCHI

1S/C9H9F2NO/c10-7-3-1-6(5-8(7)11)2-4-9(12)13/h1,3,5H,2,4H2,(H2,12,13)

이성체 SMILES

C1=CC(=C(C=C1CCC(=O)N)F)F

PubChem CID

43346075

분자량

185.17

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • 분류 Benzene and substituted derivatives
      • Subclass Halobenzenes

• Kingdom: Organic compounds
• Superclass: Benzenoids
• 분류: Benzene and substituted derivatives
• Subclass: Halobenzenes
• Intermediate Tree Nodes: Not available
• Direct Parent: Fluorobenzenes
• Alternative Parents: Fatty amides Aryl fluorides Primary carboxylic acid amides Organonitrogen compounds Organofluorides Organic oxides Hydrocarbon derivatives Carbonyl compounds
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Fluorobenzene - Aryl fluoride - Aryl halide - Fatty amide - Fatty acyl - Carboxamide group - Primary carboxylic acid amide - Carboxylic acid derivative - Organonitrogen compound - Organofluoride - Organohalogen compound - Hydrocarbon derivative - Organic oxide - Carbonyl group - Organic oxygen compound - Organooxygen compound - Organic nitrogen compound - Aromatic homomonocyclic compound
• 설명: This compound belongs to the class of organic compounds known as fluorobenzenes. These are compounds containing one or more fluorine atoms attached to a 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: 185.170 g/mol
• XLogP3: 1.200
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 3
• Exact Mass: 185.065 Da
• Monoisotopic Mass: 185.065 Da
• Topological Polar Surface Area: 43.100 Ų
• Heavy Atom Count: 13
• Formal Charge: 0
• Complexity: 186.000
• 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 assay or immunoassay application protocols are specified for this item. As a synthetic building block, typical laboratory protocols involve:

• Preparing concentrated stock solutions in DMSO (e.g., 10–100 mM) for screening or reaction setup; dilute into reaction media or assay buffers last to avoid precipitation.
• Standard organic synthesis workups (extractions, washes, drying over MgSO4/Na2SO4) and purifications (recrystallization; flash chromatography on silica with DCM/MeOH or EtOAc/hexanes gradients).

For any specialized use, develop and validate protocols in-house, and consult the primary literature for analogous substrates.

Biological Roles

• Item-specific biological data: Not specified for this item; no biological testing data are provided.

• General context (aromatic primary amides):

  • The primary amide is a common motif in bioactive molecules due to its capacity for dual hydrogen bonding (donor and acceptor) and its conformational preferences that can mimic peptide bonds.
  • A 3,4-difluorophenyl group increases lipophilicity and can attenuate metabolic oxidation on the aryl ring; difluoro patterns influence π-stacking and dipolar interactions in protein binding sites (literature trends in medicinal chemistry).
  • As a standalone small molecule, this compound is best viewed as a synthetic intermediate or SAR probe rather than a characterized biological agent.

• Laboratory use note (Product Data): For research use only. No claims are made regarding biological activity, safety in vivo, or suitability for clinical applications.

Buffer Applications

This compound is not a buffering reagent and does not form a defined conjugate acid/base pair in the physiological pH range. It is therefore not typically used to prepare buffers or adjust pH.

• Practical note: If solutions are required for bioassays, prepare stock solutions in DMSO or DMF and dilute into pre-made biological buffers (e.g., PBS, HEPES). Monitor for precipitation upon dilution due to limited aqueous solubility.

Green Alternatives

This product is a solid building block rather than a process solvent; greenness considerations focus on transformation choices and solvent/workup selection.

• Greener solvent choices (when applicable):

  • Prefer ethanol, isopropanol, ethyl acetate, or 2-MeTHF over DMF/NMP/CH2Cl2 when solubility and reactivity allow.
  • Use water or aqueous ethanol for hydrolyses and crystallizations if the compound’s solubility permits.

• Reagent alternatives (literature comparisons):

  • Amide reduction: BH3·THF or catalytic hydrogenation (Ru/C, Raney Ni) can be considered instead of stoichiometric LiAlH4 to reduce inorganic waste, albeit with different selectivity/scope.
  • Nitrile formation: T3P (propylphosphonic anhydride) or catalytic dehydration protocols can be lower-hazard options compared with SOCl2/POCl3.
  • Couplings from the corresponding acid: employ green coupling systems (e.g., CDI, DMTMM, or EDC/HOBt-alternatives like OxymaPure) and green solvents (2-MeTHF, CPME) when feasible.

• Energy/waste considerations:

  • Favor microwave or flow conditions to reduce reaction times and energy input.
  • Design crystallization-driven purifications (antisolvent addition) to reduce chromatographic solvent use.

• Trade-offs:

  • Greener solvents may reduce solubility or reaction rates for SNAr/metalation steps; optimization may require higher temperature, longer times, or catalyst loading.
  • Hydride reductions that are greener by hazard profile may provide lower yields with sterically hindered amides; pilot on small scale first.

Pharmaceutical Uses

• Item-specific pharmacopeial/excipient status: Not specified for this item; not listed as an excipient here.

• General context:

  • 3-(3,4-Difluorophenyl)propanamide is a medicinal chemistry building block used to access related scaffolds (acids, amines, nitriles, secondary/tertiary amides). The difluorophenyl fragment is frequently explored to tune potency, permeability, and metabolic stability.
  • In formulation science, primary amides are rarely used as excipients; instead, derivatives or salts of related acids/amines are more common. Accordingly, this compound would be used upstream in drug substance synthesis rather than as a drug product component.

• Manufacturing relevance:

  • Solid-state properties (polymorphism, melting behavior) may be relevant if used as an intermediate isolated by crystallization. Such properties should be established experimentally for the intended process.
  • Residual solvent limits and impurity control strategies (ICH Q3C/Q3A) apply when integrating this intermediate into GMP routes; consult the CoA and establish specifications appropriate to the stage.

Physical Properties

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

• Literature/general expectations for this class (aromatic primary amides; C9H9F2NO):

  • Physical state: typically a crystalline solid or low-melting solid due to intermolecular H-bonding of –CONH2.
  • Polarity: moderately polar (primary amide; H-bond donor/acceptor). Expected low volatility and negligible vapor pressure at ambient conditions.
  • Solubility profile (qualitative):
    • Good solubility in polar aprotic organics (DMSO, DMF, NMP).
    • Moderate in alcohols (MeOH, EtOH) upon warming or sonication.
    • Limited in nonpolar hydrocarbons (hexanes, toluene) unless heated.
    • Water: limited to moderate (primary amides can show modest aqueous solubility; salt formation not available without derivatization).
  • pKa (amide N–H, literature): very weakly acidic (pKa typically ≳ 15–17 in DMSO; effectively non-ionizable in water under neutral conditions).
  • Partition behavior: logP expected in the low-to-moderate range for difluorophenyl amides (literature trend); increases with aryl fluorination relative to nonfluorinated analogs.

• Refractive index, density, melting/boiling point: Not specified for this item; refer to CoA/Spec Sheet. Where needed for method development, determine experimentally on the received lot or consult peer-reviewed literature for closely related analogs.

Quality and Grades

• Item-specific grade/purity: Not specified for this item; refer to CoA/Spec Sheet for assay, impurities profile, and residual solvent data.

• Interpreting common grades (general guidance):

  • Research/Chemical grade: suitable for synthetic and screening work; typical assay ≥95% unless otherwise specified by supplier.
  • High-purity/Analytical grades: tighter controls on organic/elemental impurities and residual solvents; may include NMR/LC-MS/GC documentation and tighter water limits.

• What to check on the CoA for this aromatic amide:

  • Identity confirmation: 1H/13C NMR consistent with a difluorophenyl pattern (meta-coupled aromatic signals) and propanamide methylenes; HRMS or LC-MS for [M+H]+ ≈ 186.1.
  • Purity method: HPLC/UPLC area% (report solvent system and detection λ); melting range if solid.
  • Residual solvents and water: Karl Fischer ppm and GC headspace (if provided). If not present, assess in-house if application sensitive.
  • Inorganic residues/metals: typically low for small-molecule building blocks; check only if catalysis-sensitive applications are intended.

• Stabilizers: None are typically required for primary amides; if any stabilizer is listed on the CoA, consider implications for downstream reactions and remove by recrystallization if necessary.

Reaction and Applications

As a difluorinated aromatic primary amide, this molecule is a versatile intermediate for medicinal and materials synthesis.

• Transformations of the amide moiety (literature):

  • Reduction to amine: LiAlH4 or BH3·THF converts the amide to 3-(3,4-difluorophenyl)propan-1-amine; Raney Ni/H2 at elevated T is an alternative for some systems.
  • Hydrolysis to acid: acidic (refluxing HCl) or basic (NaOH, aq/EtOH) conditions furnish 3-(3,4-difluorophenyl)propanoic acid; subsequent activation enables ester or amide coupling.
  • Dehydration to nitrile: SOCl2, POCl3, or T3P-mediated conditions yield the corresponding 3-(3,4-difluorophenyl)propanenitrile.
  • Hofmann/Curtius/Lossen rearrangements: access homologation/decarboxylative routes to arylethylamines (loss of carbonyl carbon for Hofmann).

• Aromatic fluorides reactivity:

  • SNAr potential: vicinal difluoro substitution can activate the ring toward nucleophilic aromatic substitution under strong base/high T, enabling O-, N-, or S-arylation on the aryl fluoride positions.
  • Metalation/cross-coupling (via C–F activation) is challenging; however, directed ortho metalation adjacent to F is feasible with strong bases (s-BuLi/TMEDA) for further functionalization on suitably protected derivatives.

• Application contexts:

  • Medicinal chemistry scaffold: difluorophenyl group modulates lipophilicity and metabolic stability; propanamide offers a handle for diversification to secondary/tertiary amides or conversion to alternative functional groups.
  • Materials/ligand precursors: fluorinated aryl units can enhance thermal/oxidative stability and alter electronic properties in small-molecule materials.

• Practical tips:

  • Protect the amide if harsh bases are required on the aryl ring (e.g., Boc on nitrogen or convert to imide/Weinreb amide).
  • Ensure anhydrous conditions for reductions and dehydrations; quench hydrides cautiously.

Reaction Conditions

General literature guidance for common transformations of 3-(3,4-difluorophenyl)propanamide (optimize per your substrate, scale, and equipment):

• Amide reduction → primary amine:

  • LiAlH4 (2–4 equiv) in dry THF or Et2O; 0 °C to reflux; 2–16 h. Typical isolated yields for analogous substrates: 70–95%. Careful, exothermic quench.
  • BH3·THF (3–6 equiv), 0 °C to reflux; 3–24 h. Often cleaner with less overreduction of aryl ring; quench with MeOH/H2O cautiously.

• Hydrolysis → carboxylic acid:

  • Basic: NaOH (2–5 equiv) in EtOH/H2O (1:1), reflux 4–16 h; acidify to pH ~2; extract. High conversions common.
  • Acidic: 6 M HCl, reflux 6–24 h; isolate acid by basification/extraction.

• Dehydration → nitrile:

  • SOCl2 (excess) with catalytic DMF; reflux 2–6 h; or POCl3 with base (pyridine). Workup cautiously due to acidic byproducts.
  • T3P/NEt3 in EtOAc or 2-MeTHF at 60–90 °C as a milder alternative.

• N-alkylation (to secondary/tertiary amides):

  • NaH or K2CO3 in DMF/ACN with alkyl halide; 0–80 °C; watch for O- vs N-alkylation; phase-transfer catalysts may help.

• Aromatic SNAr (on difluoro ring):

  • Nucleophile (RO−, RS−, R2NH) in DMSO/DMF; 80–140 °C; 6–24 h; cesium or potassium bases enhance rates. Product distribution depends on position/electronics; confirm by 19F NMR.

• Purification:

  • Recrystallization from EtOAc/hexanes or EtOH/H2O mixtures is often effective for amides; otherwise silica gel chromatography with DCM/MeOH (0–10% MeOH) or EtOAc/hexanes gradients.

All temperatures, times, and yields are literature-type ranges for analogous systems; validate on small scale first.

Safety and Handling

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

• General laboratory handling (aromatic primary amide; guidance only):

  • PPE: lab coat, safety glasses, and appropriate chemical-resistant gloves (e.g., nitrile). Avoid dust/aerosol generation; handle on a clean bench or in a fume hood if powdering.
  • Incompatibilities: strong oxidizing agents; aggressive dehydrating reagents (e.g., SOCl2, POCl3) will convert amides; strong bases at high temperature can induce hydrolysis; strong acids may also hydrolyze upon heating.
  • Thermal stability: primary amides are thermally stable under ambient handling; avoid excessive heat to prevent decomposition.
  • First aid (general):
    • Skin/eye contact: rinse with water for ≥15 min; remove contaminated clothing; seek medical evaluation if irritation persists.
    • Inhalation: move to fresh air; monitor for respiratory irritation.
    • Ingestion: rinse mouth; do not induce vomiting; seek medical attention.
  • Hygiene: wash hands after handling; avoid cross-contamination of weighing tools.

• Waste: collect solid/solution waste as halogenated organic waste if dissolved in halogenated solvents; otherwise, dispose per your institution’s procedures and local regulations.

Note: This compound is for research use only (Product Data). Always consult the SDS of the received lot before scale-up or new applications.

Solvent Selection

This compound is a moderately polar, hydrogen-bonding donor/acceptor (primary amide), favoring polar organic media.

• Practical solvent choices (general behavior):

  • Highly recommended: DMSO, DMF, NMP for stock solutions (screening, medicinal chemistry). These solvents maximize solubility and stability.
  • Useful: methanol, ethanol, isopropanol (warming/sonication may be needed); acetonitrile gives moderate solubility.
  • Limited: ethyl acetate, dichloromethane, toluene; often workable for chromatography but lower solubility for concentrated solutions.
  • Poor: alkanes (hexanes, heptane).

• Dielectric/polarity context (literature, typical values):

  • DMSO (ε ~47), DMF (ε ~37), MeOH (ε ~33) favor dissolution and maintain amide H-bonding equilibria; ACN (ε ~37) can be acceptable for analytics.

• When to choose what:

  • Bioassay stocks: DMSO at 10–100 mM is common; dilute into assay buffer last to avoid precipitation.
  • Synthetic operations: choose DMF/NMP for SNAr or coupling on the aryl ring; alcohols for recrystallization; EtOAc/hexanes or DCM/MeOH gradients for purification.

• Small comparison (considerations):

  • DMSO vs DMF: DMSO offers oxidative stability and lower volatility; DMF is easier to remove but can form dimethylamine under strong base/heat.
  • Alcohols: greener, but may limit concentration and can compete in H-bonding networks affecting crystallization habit.

Storage and Reconstitution

• Item-specific (Product Data):

  • Storage Conditions: Room temperature.
  • Shipped In: Normal.

• General guidance for this aromatic primary amide:

  • Store tightly capped in a dry, well-ventilated place away from strong oxidizers and moisture. While amides are not particularly hygroscopic, dryness improves weighing accuracy and stability in long-term storage.
  • Protect from prolonged light and heat. No special inert-atmosphere requirements are typical, but for long-term storage consider a desiccator.
  • If solid cakes form, gently grind in a clean, dry mortar prior to weighing.

• Reconstitution/solution preparation:

  • Prepare stock solutions in DMSO, DMF, MeOH, or EtOH. Typical screening stocks: 10–100 mM in dry DMSO. Warm gently (≤40–50 °C) and/or sonicate to aid dissolution; filter (0.2 μm PTFE) for analytical work.
  • Aqueous media: expect limited solubility; dissolve first in a miscible organic cosolvent (e.g., DMSO) before dilution into buffer. Add slowly with agitation to avoid precipitation.
  • Storage of solutions: for DMSO/DMF solutions, store aliquots at 2–8 °C or −20 °C when compatible with your application; minimize freeze–thaw cycles.

• Stability monitoring:

  • Periodically check by HPLC/LC-MS for degradation (hydrolysis or impurity growth) if stored >6–12 months or at elevated temperatures.

Research use only (as provided). Refer to the CoA/SDS for lot-specific guidance.

Structure and Identity

Aromatic amide building block featuring a 3,4-difluorophenyl group tethered via a two-carbon linker to a primary carboxamide.

• Item-specific (Product Data):
  • Product Name: 3-(3,4-Difluorophenyl)propanamide
  • SKU: D1294426
  • CAS: 1098350-17-4
  • PubChem CID: 43346075
  • InChIKey: 431546 (as provided)
  • Storage: Room temperature; Shipped: Normal
• Literature/computed (general identification; not item-specific specs):
  • Molecular formula (derived from name): C9H9F2NO
  • Molecular weight (calculated): ~185.17 g/mol
  • Representative SMILES: O=C(N)CCc1ccc(F)c(F)c1
  • Core structural features: primary carboxamide (–CONH2); 1,3-disubstituted benzene bearing vicinal fluorines at ring positions 3 and 4 (relative to the benzylic point of attachment); saturated two-carbon spacer between amide carbonyl and aryl ring (–CH2–CH2–Ar).
  • 2D description: linear propanamide chain (NH2–C(=O)–CH2–CH2–) terminating at a difluorinated phenyl ring, with F substituents ortho/para to the benzylic carbon (ring positions 3 and 4). No stereocenters; achiral.

Notes: Formal synonyms encountered in literature include 3-(3,4-difluorophenyl)propionamide and 3,4-difluoro-β-phenylpropionamide (systematic variants).

Synthetic Utility

Key functional groups and handles enable multiple divergent transformations:

• Amide handle:

  • Reduction → primary alcohol (via partial reduction, e.g., DIBAL, or more commonly to amine with LiAlH4/BH3·THF).
  • Hydrolysis → carboxylic acid; then convert to acid chloride, anhydride, or activated ester for coupling.
  • N-Functionalization → secondary/tertiary amides (alkylation or acylation) to probe SAR or modulate physicochemical properties.
  • Dehydration → nitrile; Beckmann-type pathways are not applicable directly but Curtius/Hofmann/Lossen from related derivatives enable homologation or decarbonylation strategies.

• Aryl difluoride:

  • SNAr substitutions at activated positions with hard nucleophiles (alkoxides, amines, thiolates) under elevated temperature, exploiting fluorine’s leaving ability and ortho-F activation.
  • Directed ortho metalation (DoM) adjacent to F for further elaboration (after suitable N-protection), followed by electrophile trapping (e.g., formylation, borylation after halogenation).

• Retrosynthetic value:

  • Accessible from 3,4-difluorocinnamic acid/ester hydrogenation followed by amidation, or from 3,4-difluorophenethyl derivatives via oxidation to the acid then coupling to NH3.
  • As a branch point, it can be funneled to: (a) 3,4-difluorophenethylamine (Hofmann from amide), (b) 3-(3,4-difluorophenyl)propanol/amine (reductions), or (c) aryl-heteroatom substituted analogs via SNAr on the ring.

• Practical notes:

  • For reactions sensitive to H-bond donors, N-protect (e.g., Boc, benzyl) to improve solubility/reactivity; deprotect later under mild conditions.
  • Monitor for competitive overreduction (amide → alcohol) or ring defluorination under harsh hydrogenolysis; adjust catalysts/conditions accordingly.

Target Specificity

Not applicable. This product is a small-molecule building block and is not an antibody, enzyme, or targeted biological reagent. No target/epitope or species reactivity data are provided for this item.

자주 묻는 질문

What is the purity of this product?

This product is supplied at ≥95% purity (chemical assay). Lot-specific values are stated on the Certificate of Analysis.

How should this product be stored?

Store at room temperature.

How is this product shipped?

This product ships under standard ambient conditions. No temperature-controlled packaging is required.

What are the CAS number, molecular formula and molecular weight?

The CAS Number is 1098350-17-4, the molecular formula is C9H9NOF2, and the molecular weight is 185.17 g/mol. InChIKey XZQRRQRBAHSJDP-UHFFFAOYSA-N.

What documentation is provided?

Available product documentation, including Certificates of Analysis (COA), Safety Data Sheets (SDS), and specification sheets, is shown in the product document area. Document availability and access follow the current site policy.