2-(4-bromophenyl)-N-ethylacetamide , CAS No.223555-90-6

CAS: 223555-90-6 Cat. No.: B1055509 Formula: C₁₀H₁₂BrNO Peso molecolare: 242.110

Storage

Room temperature

Specifications

Condizioni di conservazione di stoccaggio

Room temperature

Nomi e identificatori

Sorrisi canonici

CCNC(=O)CC1=CC=C(C=C1)Br

IUPAC Name

2-(4-bromophenyl)-N-ethylacetamide

InChIKey

WYMOWHKSHZGGNX-UHFFFAOYSA-N

INCHI

1S/C10H12BrNO/c1-2-12-10(13)7-8-3-5-9(11)6-4-8/h3-6H,2,7H2,1H3,(H,12,13)

Peso molecolare

242.110

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Classe Benzene and substituted derivatives
      • Subclass Phenylacetamides

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Classe: Benzene and substituted derivatives
• Subclass: Phenylacetamides
• Intermediate Tree Nodes: Not available
• Direct Parent: Phenylacetamides
• Alternative Parents: Bromobenzenes Aryl bromides Secondary carboxylic acid amides Organopnictogen compounds Organonitrogen compounds Organobromides Organic oxides Hydrocarbon derivatives Carbonyl compounds
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Phenylacetamide - Bromobenzene - Halobenzene - Aryl bromide - Aryl halide - Carboxamide group - Secondary carboxylic acid amide - Carboxylic acid derivative - Organic nitrogen compound - Organonitrogen compound - Organobromide - Organohalogen compound - Organooxygen compound - Hydrocarbon derivative - Organic oxide - Carbonyl group - Organopnictogen compound - Organic oxygen compound - Aromatic homomonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as phenylacetamides. These are amide derivatives of phenylacetic acids.
• 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: 2.400
• 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

Not applicable. No biological assay protocols (e.g., WB, IHC, IF, FC) or kit-style procedures apply to this small-molecule building block.

General handling suggestions for research use (non-binding guidance):

• Prepare a 10–50 mM DMSO or DMF stock solution for high-throughput screening or chemistry operations; filter (0.2 µm PTFE) if necessary.
• For synthetic reactions, dry solvents and standard inert-atmosphere techniques (N2/Ar) are recommended when using moisture-sensitive catalysts/reagents.

For any application-specific protocol, follow your laboratory’s SOPs and consult peer-reviewed methods relevant to your transformation.

Biological Roles

No biological or clinical claims are made for this product. The notes below describe general biochemical relevance of structural motifs present in this molecule.

• Amide functionality (general):

  • H-bonding: Secondary amides provide a single H-bond donor (N–H) and a strong acceptor (C=O), a motif common in bioactive ligands, peptides, and enzyme substrates/inhibitors. They can improve binding orientation and specificity while often reducing basicity relative to amines.
  • Metabolic stability: Amide bonds can be hydrolyzed enzymatically (amidases/peptidases) but often confer greater stability than esters. N-alkylation (N-ethyl) can modulate clearance and permeability.

• Para-bromophenyl motif (general):

  • Recognition: Halogenated aromatics can engage in halogen bonding and hydrophobic/aromatic interactions in protein pockets; the para position often serves as a diversification point in SAR.
  • Biotransformation: Aryl bromides may undergo oxidative metabolism (e.g., aromatic hydroxylation) and dehalogenation pathways; the amide can guide metabolic soft spots away from the aryl ring.

• Fragment properties:

  • The combination of an amide and a single para-halogenated phenyl ring typically falls within fragment-like space with moderate lipophilicity, suitable for screening libraries and as a vector for rapid elaboration via cross-coupling.

These points are provided as general background for medicinal chemistry and chemical biology design. This product is supplied strictly for laboratory research use.

Buffer Applications

This compound is a neutral small-molecule arylacetamide and is not used as a buffering agent. It does not possess acid/base pairs within the physiological pH range that would make it suitable for buffer preparation.

• If dissolution into biological buffers is required for assays:
  • Prepare a concentrated DMSO stock (e.g., 10–50 mM) and dilute into buffer with vigorous mixing, keeping final DMSO content typically ≤1–2% v/v to minimize biological interference (general guidance).
  • Consider using co-solubilizers (Tween-80, cyclodextrins) if aqueous solubility is limiting.

For true buffering needs, select established buffer systems (e.g., phosphate, HEPES, Tris) appropriate to the target pH.

Green Alternatives

Greener process choices center on solvent selection, base choice, and catalyst loading for aryl bromide cross-couplings and amide manipulations.

• Solvent replacements (literature best practices):

  • Replace DMF/DMAc/NMP with 2-MeTHF, CPME, toluene, propylene carbonate, or ethyl acetate when feasible. For aqueous biphasic couplings, employ water/EtOH mixtures with micellar catalysis (e.g., TPGS-750-M).

• Bases and reagents:

  • Favor K2CO3/K3PO4 or Na2CO3 over strong alkoxides when compatible to reduce hazards. For amidations or hydrolyses, use enzymatic or solid-supported strategies where applicable.

• Catalysis efficiency:

  • Utilize high-activity Pd precatalysts (e.g., XPhos, SPhos systems) at ppm–low mol% loadings; consider Ni catalysis for certain couplings to minimize precious metal use. Recycle catalysts via immobilization or phase separation where possible.

• Energy footprint:

  • Conduct reactions at ambient temperature or under microwave with reduced times; explore flow chemistry for heat/mass efficiency.

• Workup/waste:

  • Opt for benign extracting solvents (EtOAc, iPrOAc) and minimize halogenated solvent use. Implement solvent recovery and aqueous-waste minimization strategies.

Example comparison (general):

• Conventional: Suzuki in dioxane/H2O (reflux), DMF for challenging substrates.
• Greener alternative: Suzuki in 2-MeTHF/H2O or EtOH/H2O with XPhos–Pd at 50–70 C; micellar catalysis in water with ppm Pd for many couplings.

These recommendations are general and should be validated for the specific transformation on this substrate.

Pharmaceutical Uses

No therapeutic claims are made for this product. It is supplied for research use only.

• Formulation/excipient status:

  • There is no pharmacopeial monograph known for this small-molecule building block as an excipient. It is not typically used as a pharmaceutical excipient.

• Role in pharmaceutical R&D (general):

  • Medicinal chemistry intermediate: The para-bromide enables rapid diversification via cross-coupling to explore structure–activity relationships while maintaining an amide donor/acceptor motif.
  • Prototyping: Secondary amides with N-ethyl substitution can balance permeability and solubility, offering a starting point for optimization of potency, selectivity, and ADME properties.

• Developability considerations (general):

  • Solubility: Often formulated as DMSO stocks for in vitro screening; salt formation is not applicable due to low basicity of secondary amides.
  • Stability: Amide bonds are generally robust; avoid prolonged exposure to strong acids/bases or high temperatures in aqueous media during formulation work.

For any use in regulated development, ensure independent qualification (identity, purity, residual solvents, elemental impurities) according to relevant guidelines; this catalog item is intended for non-clinical laboratory use.

Physical Properties

Item-specific physicochemical specifications (mp, bp, density, solubility, UV cutoff, water/peroxide/metals) are not provided in the Product Data.

• Item-specific values:

  • 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 properties (informational; typical of this structure, not item specifications):

  • Approximate molecular weight (computed): ~242.12 g/mol for C10H12BrNO.
  • Polarity/H-bonding: Secondary amide with one H-bond donor (N–H) and one acceptor (C=O); aromatic bromide increases lipophilicity.
  • Expected phase: Solid at ambient temperature is common for para-brominated arylacetamides; actual appearance not specified.
  • Solubility profile (qualitative, literature): Often soluble in polar aprotic organics (DMSO, DMF, NMP), moderately in ethanol/methanol and chlorinated solvents; low aqueous solubility due to aryl bromide and limited ionizable groups.
  • pKa: Amide N–H typically very weakly acidic (pKa ~15–17 in DMSO; much lower acidity in water); non-ionizable under physiological pH. Benzylic C–H not appreciably acidic.
  • LogP (qualitative): Expected moderate lipophilicity from para-bromophenyl balanced by amide polarity (fragment-likeness).

For authoritative, lot-specific values (melting point range, residual solvents, water content, elemental analysis), consult the CoA/Specification Sheet accompanying the shipment.

Quality and Grades

Grade/purity details are not supplied in the Product Data for this catalog item.

• Item-specific grade/purity:

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

• How to interpret typical grades (general guidance):

  • Research/Technical grade: Suitable for general synthesis and screening; impurity levels adequate for discovery chemistry.
  • Analytical/AR grade: Tighter controls on metal ions, loss on drying, and UV background; preferred for quantitative analytical use.
  • HPLC grade solvents (contextual): Low UV-absorbing impurities; not directly applicable to this solid, but relevant when choosing chromatography eluents.

• Purity verification recommendations (best practice):

  • Identity: 1H/13C NMR (DMSO-d6, CDCl3 as appropriate) should show characteristic secondary amide N–H (broad singlet) and benzylic CH2 adjacent to carbonyl; aromatic signals para-substituted pattern.
  • Purity: HPLC/UPLC with diode array detection; HRMS for exact mass confirmation (calc. for C10H12BrNO). Melting point can provide a quick screening metric (lot-specific).
  • Residuals/trace metals: For coupling chemistry, consider ICP-MS if metal sensitivities are critical; otherwise routine for small-molecule building blocks.

Refer to the lot-specific Certificate of Analysis for actual grade, purity percentage, and analytical results.

Reaction and Applications

The presence of a para-aryl bromide and a secondary amide makes this compound a versatile, bifunctional building block in small-molecule synthesis and SAR campaigns.

• Cross-coupling platform (literature):

  • Suzuki–Miyaura: Install diverse (hetero)aryl groups at the para position using aryl/heteroaryl boronic acids or esters. Typical Pd catalysts (Pd(PPh3)4, Pd2(dba)3/XPhos) under K2CO3/K3PO4/Na2CO3 in dioxane/H2O or toluene/H2O.
  • Buchwald–Hartwig amination: Convert the aryl bromide to anilines, morpholines, or other N-nucleophiles (Pd/XPhos, BrettPhos; NaOtBu, Cs2CO3).
  • Sonogashira/Heck: Alkynylation or vinylation at the para site to elaborate conjugation or introduce handles for click chemistry.

• Amide manifold (literature):

  • Chemoselective reductions: DIBAL or borane complexes can reduce the amide to the corresponding amine/aldehyde under controlled conditions; consider protecting strategies if N-ethyl retention or removal is important.
  • Hydrolysis: Acidic or basic hydrolysis to the corresponding 2-(4-bromophenyl)acetic acid enables divergent synthesis (esterification, amide exchange via CDI/EDC).
  • Benzylic functionalization: Alpha to carbonyl (Ar–CH2–CO–) amenable to halogenation, oxidation to ketoamide, or enolate-based alkylations (with caution due to amide acidity).

• Applications:

  • Medicinal chemistry: Para-aryl diversification with retention of an amide H-bond donor often enhances target engagement; N-ethyl modulates lipophilicity and metabolic stability.
  • Materials/ligands: The amide and aryl core can be precursors to more conjugated systems via cross-coupling.

Practical tip: Protect the amide (e.g., as N-acyl imidazole or via transient base selection) if strong bases are needed for coupling; otherwise use milder bases and modern ligands to preserve the amide integrity.

Reaction Conditions

Typical conditions below are literature guidance for aryl bromides bearing amides; verify and optimize for your specific transformation. No item-specific process conditions are provided.

• Suzuki–Miyaura coupling (para-aryl bromide):

  • Catalyst: 1–3 mol% Pd(PPh3)4 or Pd2(dba)3 (1 mol% Pd) with XPhos/SPhos (2–4 mol%).
  • Base: K3PO4 or K2CO3 (2–3 equiv).
  • Solvent: 1,4-dioxane/H2O (3:1), toluene/H2O, or 2-MeTHF/H2O.
  • Temp/Time: 60–100 C, 2–12 h. Often complete within 2–6 h for activated systems.

• Buchwald–Hartwig amination:

  • Catalyst/Ligand: Pd2(dba)3 (1 mol% Pd) + BrettPhos/XPhos (2–4 mol%) or precatalysts (e.g., XPhos-Pd G3).
  • Base: NaOtBu, Cs2CO3.
  • Solvent: Toluene, dioxane, or CPME.
  • Temp: 80–110 C; 4–16 h.

• Sonogashira:

  • Catalyst: Pd(PPh3)2Cl2 (1–2 mol%) + CuI (2–5 mol%).
  • Base: Et3N, iPr2NEt, or K2CO3.
  • Solvent: THF, toluene, or DMF.
  • Temp: rt–80 C; 2–12 h.

• Amide hydrolysis (to acid):

  • Basic: Aqueous NaOH/KOH (2–5 M), reflux (80–100 C), 2–16 h; then acidify.
  • Acidic: 6 M HCl, 80–100 C, 4–24 h.

• Amide reduction (to amine/aldehyde):

  • BH3·THF: 0 C to reflux, 2–16 h (amine).
  • DIBAL-H: −78 C to 0 C, careful quench for partial reduction (aldehyde/amine depending on conditions).

Notes: Protect the amide under strongly basic conditions; modern phosphine ligands enhance coupling efficiency at lower temperatures and catalyst loadings.

Safety and Handling

This small-molecule arylacetamide is intended for research use only. No item-specific GHS classification details are provided in the Product Data.

• Item-specific safety data:

  • 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.

• General safety guidance for aryl amides and aryl bromides (literature/best practice):

  • Hazards: May cause skin/eye irritation and respiratory irritation as a dust. Avoid inhalation and contact. Aromatic bromides are not generally volatile but handle powders to minimize dust.
  • PPE: Safety glasses, lab coat, and appropriate chemical-resistant gloves (e.g., nitrile). Use in a fume hood when weighing or dissolving, especially with volatile organic solvents.
  • Incompatibilities: Strong oxidizers (can react exothermically). Strong bases and strong acids may hydrolyze the amide at elevated temperature. Avoid sodium/potassium metals. No known tendency for peroxide formation.
  • Spill/cleanup: Collect solids by gentle sweeping with minimal dust generation; for solutions, absorb with inert material. Dispose according to institutional and local regulations.
  • First aid (overview): If on skin/eyes, rinse with water for at least 15 minutes; remove contaminated clothing. If inhaled, move to fresh air. If ingested, rinse mouth; seek medical attention in all cases. Provide SDS to medical personnel.
  • Fire safety: Use CO2, dry chemical, or foam. Combustion may produce CO/CO2/HBr; firefighters should wear SCBA.

Always consult the product SDS for authoritative hazard classification and response measures.

Solvent Selection

As a para-brominated arylacetamide with moderate polarity, this compound generally dissolves well in polar aprotic organic solvents, with limited aqueous solubility.

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

• Literature/general miscibility guidance:

  • Preferred solvents for stock solutions: DMSO, DMF, NMP (high solubility; stable toward amide functionality). For less polar media, dichloromethane, ethyl acetate, or THF can be suitable depending on concentration.
  • Alcohols: Methanol/ethanol often provide moderate solubility; isopropanol typically lower. Heating or sonication can aid dissolution.
  • Water: Low intrinsic solubility expected; co-solvent strategies (DMSO/water) or pH adjustments are generally ineffective due to the non-ionizable amide.

• Selection by application:

  • Palladium cross-couplings: Toluene, dioxane, CPME, or Me-THF mixed with aqueous carbonate or phosphate bases. For challenging couplings, DMF/DMAc/NMP offer enhanced solvation of inorganic bases and catalysts.
  • Amide stability: Avoid strongly basic alcoholic media at high temperature if preserving the amide is essential; hydrolysis can occur under harsh conditions.

• Quick comparison (general):

  • DMSO/DMF: Max solubility, but challenging removal.
  • EtOAc/MTBE: Easier workup, lower solubility.
  • Me-THF/CPME: Greener options with balanced polarity; good for scale-up.

Always verify solvent compatibility with your catalysts/reagents and run small-scale solubility tests before committing to large preparations.

Storage and Reconstitution

Item-specific storage guidance from Product Data:

• Storage conditions: Room temperature.

Additional item-specific logistics:

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

General best practices for this compound class (informational):

• Storage: Keep tightly closed in a dry, well-ventilated place. Protect from prolonged exposure to heat and direct light. Store under ambient conditions unless your process or SDS suggests otherwise.
• Moisture/air sensitivity: Secondary amides and aryl bromides are typically stable to air and ambient humidity; no special inert storage is required.
• Stability: Avoid extended contact with strong acids/bases at elevated temperature to prevent hydrolysis. For long-term archival, cool/dry storage (e.g., 2–8 C, desiccated) can further preserve quality, though not required per Product Data.

Reconstitution/dissolution (general guidance):

• Prepare concentrated stocks in DMSO, DMF, or NMP. For less polar applications, dissolve in EtOAc, DCM, Me-THF, or similar. Warm gently (≤40 C) and/or sonicate to aid dissolution.
• For biological tests, dilute DMSO stocks into buffer with vigorous mixing; keep final DMSO ≤1–2% v/v when feasible.

Always consult the item’s SDS and CoA for lot-specific handling and stability information.

Structure and Identity

A para-brominated arylacetamide featuring a secondary (N–H) amide bearing an N-ethyl substituent; the aryl group is 4-bromophenyl attached at the methylene alpha to the carbonyl.

• Item-specific identifiers (from Product Data):

  • Product Name: 2-(4-bromophenyl)-N-ethylacetamide
  • CAS: 223555-90-6
  • CID: 884783
  • InChIKey: 411367 (as provided)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/computed identifiers and features (informational, not item specifications):

  • Putative SMILES (literature/computed): CCNC(=O)CH2c1ccc(Br)cc1
  • Molecular formula (computed from name/structure): C10H12BrNO
  • Molecular weight (computed): ~242.12 g/mol
  • Functional groups: secondary amide (–CONH–), para-brominated phenyl, benzylic methylene (Ar–CH2–C(=O)–).
  • Structural description (2D): A 4-bromophenyl ring para-substituted with bromine, connected via a methylene to an acyl carbonyl (acetamide core). The amide nitrogen bears an ethyl substituent and a proton (secondary amide), enabling H-bond donation and acceptance.

• Stereochemistry: None (achiral as drawn).

• Structural implications:

  • Aryl bromide handle supports cross-coupling reactivity (Suzuki–Miyaura, Buchwald–Hartwig, Sonogashira).
  • Amide motif confers polarity, H-bonding, and resonance stabilization; benzylic position adjacent to carbonyl can engage in selective transformations (e.g., reductions, oxidations).

Synthetic Utility

This molecule serves as a bifunctional hub: an aryl bromide for cross-coupling and a secondary amide for further chemoselective manipulation.

• Aryl bromide handle (literature):

  • Suzuki–Miyaura: Introduce (hetero)aryl motifs to expand aromatic frameworks; compatible with a wide range of boron partners (RB(OH)2, Bpin).
  • Buchwald–Hartwig: Install amines (anilines, saturated N-heterocycles) to probe basicity/permeability axes.
  • Sonogashira/Heck: Append alkynes or vinyl groups to create linkers, probes, or extend conjugation.
  • Lithiation/magnesiation (with care): Directed metal–halogen exchange at low temperature to access functionalized anilides, quenching with electrophiles; amide can coordinate and influence regioselectivity.

• Amide functionality (literature):

  • Hydrolysis/transamidation: Convert to the corresponding 2-(4-bromophenyl)acetic acid or exchange the amide under activating conditions (e.g., CDI, HATU, EDCI) for library synthesis.
  • Reduction: BH3·THF, DIBAL, or catalytic hydrogenation variants to amines or aldehydes; control conditions to avoid over-reduction.
  • Alpha-functionalization: Enolate chemistry to introduce substituents at the benzylic position (e.g., halogenation, alkylation), enabling orthogonal growth vectors.

• Protecting-group strategy:

  • The N-ethyl substituent reduces amide basicity and can influence reactivity; if an N–H free amide is desired downstream, consider starting from the N–H analog or employing dealkylation strategies (often challenging) only when justified.

Overall, the scaffold is well-suited to rapid analogue generation with orthogonal diversification at the aryl para position and the benzylic/amide axis.

Target Specificity

Not applicable. This product is a small-molecule chemical building block and is not an antibody, enzyme, or biological reagent with defined target specificity.

• Item-specific bio-attributes (if any): Not specified for this item; refer to CoA/Spec Sheet.

For information on molecular targets in screening campaigns, consult your assay design and primary literature; no target-binding data are provided for this catalog item.