N-(4-Bromophenethyl)acetamide , CAS No.105871-04-3

CAS: 105871-04-3 Cat. No.: N1012786 Formula: C₁₀H₁₂BrNO Peso molecolare: 242.110

Storage

Room temperature

Specifications

Condizioni di conservazione di stoccaggio

Room temperature

Nomi e identificatori

• Sorrisi canonici: CC(=O)NCCC1=CC=C(C=C1)Br
• IUPAC Name: N-[2-(4-bromophenyl)ethyl]acetamide
• InChIKey: KPVUOSUNLUOQNR-UHFFFAOYSA-N
• INCHI: 1S/C10H12BrNO/c1-8(13)12-7-6-9-2-4-10(11)5-3-9/h2-5H,6-7H2,1H3,(H,12,13)
• Peso molecolare: 242.110

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organic acids and derivatives
    • Classe Carboxylic acids and derivatives
      • Subclass Carboxylic acid derivatives
        • Level5 Carboxylic acid amides
          • Level6 Acetamides
            • Level7 N-acetyl-2-arylethylamines

• Kingdom: Organic compounds
• Superclass: Organic acids and derivatives
• Classe: Carboxylic acids and derivatives
• Subclass: Carboxylic acid derivatives
• Intermediate Tree Nodes: Carboxylic acid amides - Acetamides
• Direct Parent: N-acetyl-2-arylethylamines
• Alternative Parents: Bromobenzenes Aryl bromides Secondary carboxylic acid amides Organonitrogen compounds Organobromides Organic oxides Hydrocarbon derivatives Carbonyl compounds
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: N-acetyl-2-arylethylamine - Bromobenzene - Halobenzene - Aryl bromide - Aryl halide - Monocyclic benzene moiety - Benzenoid - Secondary carboxylic acid amide - Organic nitrogen compound - Organonitrogen compound - Organobromide - Organohalogen compound - Organooxygen compound - Carbonyl group - Hydrocarbon derivative - Organic oxide - Organic oxygen compound - Aromatic homomonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as n-acetyl-2-arylethylamines. These are compounds containing an acetamide group that is N-linked to an arylethylamine.
• 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

Proprietà chimiche e fisiche

• Peso molecolare: 242.110 g/mol
• XLogP3: 2.200
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 1
• Rotatable Bond Count: 3
• Exact Mass: 241.01 Da
• Monoisotopic Mass: 241.01 Da
• Topological Polar Surface Area: 29.100 Ų
• Heavy Atom Count: 13
• Formal Charge: 0
• Complexity: 164.000
• 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 standardized bioassay or immunoassay protocols are specified for this item. As a small-molecule building block, typical “applications” are synthetic procedures rather than biological protocols.

General laboratory usage examples (informational):

• Stock solution preparation: Dissolve in dry DMSO or DMF to 10–100 mM, filter through 0.22 µm PTFE if particulate is observed, and aliquot.
• Cross-coupling substrate setup: Combine with boronic acid/amine/alkyne coupling partner, Pd catalyst, base, and chosen solvent under inert atmosphere; heat per Reaction Conditions guidance; monitor by TLC/HPLC.
• Deacetylation: Treat with aqueous base (e.g., KOH in EtOH/H2O) at 60–80 °C; quench, extract, and purify to obtain 4-bromophenethylamine derivatives.

For any biological testing, develop fit-for-purpose protocols and validate analytical methods (HPLC/LC–MS) to confirm concentration and integrity. Always consult the SDS before designing workflows.

Biological Roles

Item-specific biological function: Not applicable; no biological roles are provided for this research chemical.

General context (informational; not medical/clinical claims):

• Phenethylamide motifs occur in a variety of natural products and synthetic probes; the amide linkage imparts hydrogen-bonding capability and can modulate permeability and solubility relative to the parent amine.
• The para-bromophenyl group is often used as a synthetic handle rather than a bioisostere; the bromine enables late-stage diversification by cross-coupling, facilitating structure–property exploration in biochemical assays.
• As a secondary amide with an aryl bromide, this compound can serve as a precursor to diversified analogs that may be screened in enzyme or receptor-binding studies in vitro (research use only). Any observed biological activity would arise from derivatives or specific experimental context rather than from an inherent, established physiological role of the parent compound.

Caveat: No claims are made regarding efficacy, safety, or suitability for therapeutic or diagnostic applications. Use strictly for laboratory research, under appropriate approvals and controls.

Buffer Applications

This product is not a buffering agent and is not typically used to prepare biochemical buffers or pH standards.

Practical guidance:

• If dissolution in aqueous buffer is required for in vitro assays, use a cosolvent approach (e.g., prepare a concentrated DMSO stock and dilute into phosphate- or HEPES-buffered saline, maintaining final DMSO ≤1–2% v/v as assay constraints allow).
• Avoid prolonged exposure to strongly acidic or basic buffers if amide integrity must be preserved; hydrolysis rates increase with temperature and extreme pH.

For buffer recipes and pH control, refer to dedicated buffering systems (e.g., phosphate, HEPES, MOPS).

Green Alternatives

While the substance itself is a solid building block (not a solvent), greener choices relate to how you use it—particularly in cross-couplings, reductions, and workups.

• Solvent selection (greener swaps):

  • Replace DMF/DMAc with 2-MeTHF, CPME, or water/biobased surfactant systems (e.g., TPGS-750-M) for Suzuki couplings of aryl bromides.
  • Use ethanol or propylene carbonate for nucleophilic substitutions or hydrolysis steps where compatible.

• Catalyst and base economy:

  • Employ modern, highly active Pd catalysts (e.g., Pd-PEPPSI, precatalysts) at ≤0.5 mol% to reduce metal footprint; consider Ni-catalyzed couplings for aryl bromides where feasible.
  • Carbonate bases (K2CO3, Cs2CO3) in aqueous micelles can enable room-temperature couplings, lowering energy usage.

• Reduction and deprotection:

  • Favor catalytic hydrogenation (transfer hydrogenation) or safer hydride sources over stoichiometric BH3 when reducing amides, provided aryl–Br compatibility is addressed (consider protecting the halide via coupling first).

• Workup/waste minimization:

  • Opt for crystallization-driven purifications when possible to avoid extensive silica gel usage.
  • Implement solvent recovery (distillation) for higher-boiling media and use minimal DMSO/DMF volumes for stocks.

Illustrative comparison (general, not item-specific):

• Traditional: DMF + Pd(PPh3)4 (2–5 mol%) at 100–120 °C.
• Greener: water/TPGS-750-M + Pd precatalyst (0.1–0.5 mol%), 40–70 °C; or 2-MeTHF/EtOH mixtures with base, affording similar conversions with reduced EHS impact.

Pharmaceutical Uses

No pharmacopeial/excipient role is specified for this item; it is supplied for research use only.

General development context (non-clinical):

• As a bifunctional building block (aryl bromide + secondary amide), N-(4-bromophenethyl)acetamide can be used in medicinal chemistry route scouting and intermediate synthesis. Typical roles include:
  • Diversification via Pd-catalyzed cross-coupling to access analog series for in vitro ADME and SAR assessment.
  • Serving as a protected form of 4-bromophenethylamine (N-acetyl protection) that can be deacetylated downstream under controlled conditions.
• Formulation notes for in vitro tools: when used as a test article or intermediate in screening cascades, prepare DMSO or DMF stocks, filter sterilize if needed (0.22 µm PTFE), and store aliquots to minimize freeze–thaw.

Compliance reminder: Not for human or veterinary use, not for diagnostic procedures, and not formulated to any pharmacopeial monograph.

Physical Properties

Item-specific values (this SKU):

• Boiling point, melting point, density, refractive index, water/peroxide/metal limits, UV cutoff: Not specified for this item; refer to CoA/Spec Sheet.
• Appearance: Not specified for this item; refer to CoA/Spec Sheet.

General/literature-based physicochemical context (not item specifications):

• Aggregate polarity: amphiphilic aromatic amide; moderately polar due to the secondary amide, with a lipophilic aryl–bromo fragment.
• Expected solubility profile (qualitative):
  • Good solubility in polar aprotic organic solvents (DMSO, DMF, NMP, acetonitrile).
  • Soluble to moderately soluble in chlorinated and ethereal solvents (DCM, THF) depending on temperature.
  • Low aqueous solubility expected for the neutral form; higher in basic media via amide hydrogen bonding does not ionize appreciably.
• Acid–base: secondary amides are very weak bases; conjugate acid pKa typically ~–1 to 0 (literature, for secondary amides), so the compound remains largely neutral across common pH.
• Lipophilicity: aryl bromides with one amide typically show moderate logP; analogous scaffolds often fall in logP ~2–3.5 (literature trend for para-bromophenethyl amides), but actual value depends on medium and temperature.

Practical notes:

• For stock solutions, DMSO or DMF commonly enable ≥10–100 mM solutions at ambient temperature.
• Gentle warming (25–40 °C) and brief sonication can assist dissolution. Avoid prolonged heating to prevent amide hydrolysis in wet media.

Quality and Grades

Item-specific quality information:

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

How to interpret quality when provided (general guidance):

• Research grade vs. higher analytical/HPLC grades: Research-grade organics are suitable for most synthesis and screening. HPLC or LC–MS grades emphasize low UV background and low nonvolatile residue; these are relevant when the compound is used as a reference standard or for trace analytical work.
• Purity reporting: For solid building blocks, purity is typically by HPLC/GC and/or 1H NMR integration. If optical activity were relevant, [α]D would be reported; here the compound is achiral.
• Stabilizers/additives: This scaffold generally does not require stabilizers. If any stabilizer is listed in a CoA, it should be disclosed and considered in sensitive reactions (e.g., catalytic couplings).
• Trace specifications: Water, residual solvents, heavy metals, and halide content can affect palladium-catalyzed cross-couplings. If your application is coupling-intensive, request or consult the CoA for residual metal and halide analyses.

Best practices:

• Verify identity/purity by independent methods (1H/13C NMR, HRMS, HPLC) upon receipt if the material is used in SAR or route-scouting.
• For chromatography-sensitive applications, a final recrystallization or short silica plug may enhance performance; document any pre-use conditioning in your ELN.

Reaction and Applications

This scaffold offers two orthogonal handles: an aryl bromide and a secondary amide tethered via a two-carbon linker. This combination supports diverse synthetic applications in discovery and process chemistry.

• Cross-coupling at aryl–Br (literature):

  • Suzuki–Miyaura coupling to install aryl, heteroaryl, or vinyl groups, expanding SAR around the ring. Typical Pd(0/II) catalysts with bases like K2CO3 or K3PO4.
  • Buchwald–Hartwig amination to convert Ar–Br into anilines or anilides; dialkylbiaryl phosphines often excel for aryl bromides.
  • Sonogashira coupling to append alkynes; copper co-catalysis optional with modern ligands.
  • Carbonylations (Pd-catalyzed) to carboxamides/esters under CO.

• Benzylic chain/amidic chemistry:

  • N–deacetylation (hydrolysis) to 4-bromophenethylamine under acidic or basic conditions (literature), enabling further derivatization (e.g., ureas, sulfonamides). Protecting-group logic applies; control aryl–Br integrity under harsh conditions.
  • N-alkylation: deprotonation of the secondary amide (e.g., NaH in DMF) followed by alkylation to tertiary amides; consider chemoselectivity vs O-alkylation.
  • Reductive manipulations: amide reduction (e.g., BH3·THF) to the corresponding amine can deliver 4-bromophenethyl ethylamine derivatives, though conditions must be tuned to avoid aryl–Br reduction.

• Applications:

  • Building block for libraries where the aryl substituent is diversified via Pd-catalysis while retaining the polar amide handle to tune ADME-relevant properties (in vitro assays; research use only).
  • Linker chemistry: the two-carbon spacer offers conformational flexibility when anchoring to resin or attaching to tags/labels.

Practical advice: Stage couplings before amide deprotections/reductions when possible, to leverage the stability of the acetamide under Pd-catalyzed conditions.

Reaction Conditions

General literature guidance for aryl-bromide amides (not item specifications; optimize per substrate and scale):

• Suzuki–Miyaura coupling:

  • Catalyst/base: Pd(PPh3)4 (1–2 mol%) or Pd-precatalysts with SPhos/XPhos (0.5–1 mol%); K2CO3 or K3PO4 (2–3 equiv).
  • Solvent/temp: 1,4-dioxane/H2O (4:1), toluene/H2O, or CPME/H2O; 70–100 °C.
  • Time: 2–16 h. Often tolerant of secondary amides; inert atmosphere preferred.

• Buchwald–Hartwig amination (Ar–Br → aniline derivatives):

  • Catalyst/ligand: Pd2(dba)3 (1 mol% Pd) + BrettPhos or RuPhos; or Pd-PEPPSI.
  • Base/solvent: NaOtBu, K3PO4; in toluene, tBuOH, or dioxane. 60–100 °C, 4–18 h.

• Sonogashira coupling:

  • Pd(PPh3)2Cl2 (1–2 mol%) + CuI (2–5 mol%), Et3N or iPr2NH, in THF, DMAc, or EtOH; 25–60 °C.

• Carbonylation (to aryl amides/esters):

  • Pd-catalyzed under CO (1–10 bar), base (Et3N), MeOH or amines as nucleophiles; 60–90 °C.

• N-deacetylation (hydrolysis to 4-bromophenethylamine):

  • Basic: NaOH or KOH (2–5 equiv) in EtOH/H2O or THF/H2O, 50–80 °C, 2–8 h.
  • Acidic: HCl(aq), refluxing EtOH/H2O; monitor to preserve Ar–Br.

• Amide reduction (if desired):

  • BH3·THF (1–3 equiv) in THF, 0–25 °C to reflux; or catalytic hydrogenation routes with more elaborate setups. Beware of potential debromination under hydrogenation conditions.

Notes:

• Anhydrous, oxygen-free conditions improve yields in cross-couplings.
• The secondary amide can coordinate weakly; ligand choice (bulky biaryl phosphines) often mitigates deactivation.
• Always confirm compatibility of bases and temperatures with the amide to prevent undesired hydrolysis.

Safety and Handling

GHS information for this item:

• Signal Word: Not specified for this item; refer to SDS.
• Hazard Statements (H-codes): Not specified for this item; refer to SDS.
• GHS Classification and Pictograms: Not specified for this item; refer to SDS.

General safety considerations for aryl-bromide secondary amides (informational; defer to SDS for authoritative guidance):

• Expected hazards: combustible organic solid; may cause skin/eye irritation and respiratory irritation if dust is generated. Low volatility but avoid inhalation of particulates.
• Personal protective equipment: lab coat, safety glasses, and appropriate chemically resistant gloves (e.g., nitrile). Use in a fume hood to control dust and solvent vapors during processing.
• Handling: avoid moisture ingress and strong bases/acids during prolonged contact to limit hydrolysis. Prevent dust generation. Use clean, dry tools.
• Incompatibilities: strong oxidizers; strong bases or acids under heating can promote amide cleavage. For cross-coupling, bases and Pd catalysts are typical but are process reagents, not storage-compatible materials.
• First-aid overview: in case of skin/eye contact, rinse with water for at least 15 minutes; remove contaminated clothing. If inhaled, move to fresh air. If swallowed, rinse mouth with water. Seek medical attention as outlined in the SDS.
• Fire-fighting: use standard Class B extinguishing media (CO2, dry chemical, foam). Combustion may generate CO/CO2, HBr/Br-containing fumes.

Always consult the product’s SDS for definitive hazard classification, exposure controls, and disposal recommendations.

Solvent Selection

Context: N-(4-Bromophenethyl)acetamide is a moderately polar aromatic amide. Solvent choice is typically driven by the intended operation: dissolution for biological screening, preparative handling, or as a substrate in cross-coupling or substitution chemistry.

• Dissolution/stock prep:

  • Preferred: DMSO, DMF, NMP (high solubility; stable at ambient for short-term use). Acetonitrile and methanol/ethanol can work at lower concentrations.
  • Secondary options: THF, DCM, ethyl acetate; solubility may be moderate and temperature dependent.
  • Aqueous media: poor solubility in neutral water; use cosolvent strategies (DMSO 1–5% v/v) or cyclodextrins if aqueous delivery is required.

• Reaction media (general literature guidance):

  • Palladium cross-couplings of aryl bromides: 1,4-dioxane/H2O, toluene, CPME, or DMAc/DMF are commonly effective. Micellar water (e.g., TPGS-750-M) is an emerging greener alternative.
  • Base-promoted transformations/hydrolysis: alcohol/water or THF/water with NaOH or K2CO3.

• Practical tips:

  • Ensure anhydrous solvent for base- or metal-catalyzed reactions to avoid amide hydrolysis and to maximize coupling efficiency.
  • For analytical HPLC, ACN/H2O with 0.1% formic acid or MeOH/H2O gradients typically give good peak shape for amides; verify UV maxima empirically.

• Comparison (qualitative):

  • DMSO/DMF: highest solvating power, best for stock solutions; more challenging to remove.
  • EtOAc/DCM: easier removal; balance with moderate substrate solubility.
  • Alcohols: enable greener workups but can suppress some Pd-catalyzed reactions.

Storage and Reconstitution

Item-specific storage and shipping:

• Storage Conditions: Room temperature (per Product Data).
• Shipped In: Not specified for this item; refer to CoA/Spec Sheet.

General storage guidance (informational):

• Keep container tightly closed in a dry, well-ventilated place. Protect from excessive heat and direct light. Use a desiccator if ambient humidity is high. Avoid prolonged exposure to strong acids/bases.
• If long-term storage is planned, consider dividing into single-use aliquots to minimize repeated headspace and moisture exposure.

Reconstitution/preparation of solutions:

• Solvents: DMSO or DMF recommended for concentrated stocks; acetonitrile, methanol, ethanol, THF, or DCM for more dilute solutions as needed.
• Typical stock concentrations: 10–100 mM in DMSO/DMF for screening or as coupling substrate solutions; adjust to solubility and application.
• Technique: Warm gently to ambient/slightly elevated temperature (≤40 °C) and sonicate briefly if required. Filter through 0.22 µm PTFE to remove particulates when necessary.
• Stability: Solutions in hygroscopic solvents (DMSO/DMF) are best stored in sealed containers under inert gas at 2–8 °C for short term; prepare fresh as needed to avoid hydrolysis over time.

Disposal: Follow institutional and local regulations for halogenated organic waste. Consult the SDS for detailed guidance.

Structure and Identity

Brief description: N-(4-Bromophenethyl)acetamide is a para-brominated phenethylamide bearing a secondary acetamide on the ethyl chain; it combines an aryl bromide handle with an N-acylated aminoethyl linker, making it a versatile bifunctional building block.

• Item-specific identifiers (from Product Data):

  • CAS: 105871-04-3
  • SKU: N1012786
  • InChIKey: 186429 (as provided; truncated/not standard length)
  • Storage: Room temperature
  • Research Use: For research use only

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

  • Molecular Formula
  • Molecular Weight
  • SMILES

• Literature/computed identity (general reference information; not item specifications):

  • Proposed molecular formula (literature): C10H12BrNO
  • Calculated molecular weight (literature): ~242.12 g/mol
  • Representative SMILES (literature): CC(=O)NCCc1ccc(Br)cc1
  • 2D structural description: a monosubstituted benzene ring with para-bromine and a para-(CH2–CH2–NH–CO–CH3) substituent. The amide is secondary (one N–H), planar at the CONH unit; the aryl bromide is para to the side chain.
  • Functional groups/features: aryl bromide (cross-coupling handle), secondary amide (hydrogen-bond donor/acceptor), benzylic methylenes (two-carbon spacer).

Notes: Literature data are provided for context only and may differ from this specific lot; consult the CoA/SDS for definitive identifiers.

Synthetic Utility

Key functional elements and their reactivity:

• Aryl bromide (para to the side chain):
  • Highly amenable to Pd- or Ni-catalyzed cross-couplings (Suzuki, Buchwald–Hartwig, Sonogashira, Heck), enabling rapid installation of diverse aromatic, heteroaromatic, alkenyl, or alkynyl fragments.
  • Participates in metal–halogen exchange (e.g., n-BuLi at low temperature) to generate aryllithium intermediates for electrophile trapping; conditions must be tuned to avoid amide deprotonation or overreaction.
• Secondary amide (N-acetyl):
  • Robust under many coupling conditions; can be hydrolyzed (acidic or basic) to reveal the primary amine for further functionalization (sulfonylation, acylation, urea formation).
  • Deprotonation with strong base (NaH, KHMDS) allows N-alkylation/acylation to tertiary amides; monitor for O-alkylation and control with conditions/solvent selection.
• Benzylic methylenes:
  • Oxidation to amide-linked benzamide variants or selective functionalizations (e.g., halogenation) are possible; care is needed to preserve the aryl–Br.

Retrosynthetic value:

• Serves as a protected amine synthon for routes requiring orthogonal manipulation of the aryl position (via Br) prior to unveiling the amine.
• Facilitates late-stage diversification strategies: couple first at Ar–Br, then adjust the amide (deprotect, swap acyl group) to access polarity series for property tuning.

Workup/purification:

• The amide enhances polarity, aiding silica chromatography. Crystallization from EtOAc/hexanes or EtOH/water mixtures may be feasible depending on substitution installed post-coupling.

Target Specificity

Not applicable. This product is a small-molecule chemical building block and is not an antibody, enzyme, or biological probe with defined target specificity. No target, epitope, isotype, or species reactivity information is provided for this item.