4'-Bromo-5'-chloro-2'-fluoroacetophenone - ≥97% , CAS No.1594605-40-9

CAS: 1594605-40-9 Cat. No.: B988751 Formula: C₈H₅BrClFO Peso molecolare: 251.48 Numero EC: 812-836-0 PubChem CID: 84804089

GRADE & PURITY ≥97%

Storage

Room temperature

Specifications

Specifiche e purezza

≥97%

Condizioni di conservazione di stoccaggio

Room temperature

Purezza

≥97%

Nomi e identificatori

Sorrisi canonici

CC(=O)C1=CC(=C(C=C1F)Br)Cl

IUPAC Name

1-(4-bromo-5-chloro-2-fluorophenyl)ethanone

InChIKey

UYZXJLRSUSUZHM-UHFFFAOYSA-N

INCHI

1S/C8H5BrClFO/c1-4(12)5-2-7(10)6(9)3-8(5)11/h2-3H,1H3

Isomeri SMILES

CC(=O)C1=CC(=C(C=C1F)Br)Cl

PubChem CID

84804089

Peso molecolare

251.48

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organic oxygen compounds
    • Classe Organooxygen compounds
      • Subclass Carbonyl compounds
        • Level5 Ketones
          • Level6 Aryl ketones
            • Level7 Phenylketones
              • Level8 Alkyl-phenylketones

• Kingdom: Organic compounds
• Superclass: Organic oxygen compounds
• Classe: Organooxygen compounds
• Subclass: Carbonyl compounds
• Intermediate Tree Nodes: Ketones - Aryl ketones - Phenylketones
• Direct Parent: Alkyl-phenylketones
• Alternative Parents: Acetophenones Benzoyl derivatives Aryl alkyl ketones Fluorobenzenes Chlorobenzenes Bromobenzenes Aryl fluorides Aryl chlorides Aryl bromides Vinylogous halides Organofluorides Organochlorides Organobromides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Alkyl-phenylketone - Acetophenone - Aryl alkyl ketone - Benzoyl - Halobenzene - Fluorobenzene - Chlorobenzene - Bromobenzene - Benzenoid - Monocyclic benzene moiety - Aryl halide - Aryl fluoride - Aryl chloride - Aryl bromide - Vinylogous halide - Organic oxide - Hydrocarbon derivative - Organofluoride - Organochloride - Organobromide - Organohalogen compound - Aromatic homomonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as alkyl-phenylketones. These are aromatic compounds containing a ketone substituted by one alkyl group, and a phenyl group.
• 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: 251.480 g/mol
• XLogP3: 3.000
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 1
• Exact Mass: 249.92 Da
• Monoisotopic Mass: 249.92 Da
• Topological Polar Surface Area: 17.100 Ų
• Heavy Atom Count: 12
• Formal Charge: 0
• Complexity: 188.000
• 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 application protocols (e.g., WB, IHC, IF, FC) apply to this small-molecule intermediate. For synthetic use, see the Reaction Conditions and Synthetic Utility sections for generalized procedures. Always validate on small scale and consult primary literature for the exact transformation of interest.

Biological Roles

This product is a small-molecule halogenated aryl ketone supplied for chemical synthesis. It is not intended for biological use in living systems.

• Item-specific biological function/role: Not applicable; none specified for this item. For research use only (per Product Data).

• General context (chemistry-driven)

  • Tri-halogenated acetophenones are commonly used as synthetic intermediates in medicinal chemistry campaigns to access diverse analogs via cross-coupling and nucleophilic substitution. Any biological activity that arises pertains to downstream, derived molecules rather than to this intermediate as supplied.

• Biochemical handling note

  • If used in chemical biology or probe synthesis workflows, ensure complete purification and characterization of final compounds before any in vitro assays. Avoid using this intermediate directly in biological buffers or cell systems.

Buffer Applications

Not typically applicable. 4'-Bromo-5'-chloro-2'-fluoroacetophenone is a hydrophobic organic building block and does not serve as a buffering agent. If incorporated into assay development, dissolve in an appropriate organic co-solvent (e.g., DMSO) before dilution into aqueous media, verifying solubility and compatibility for your system.

Green Alternatives

While the molecule itself is a halogen-rich building block (and thus not inherently “green”), greener choices can be made in solvent and catalytic systems.

• Greener process choices (literature/general)

  • Prefer 2-MeTHF or CPME over THF/toluene when feasible (renewable origin, easier separations).
  • Use aqueous-micellar catalysis (e.g., TPGS-750-M) for some Suzuki couplings at room temperature, reducing organic solvent load.
  • Explore nickel catalysis with ligand-minimized systems or Pd on reusable supports to reduce precious metal usage.
  • Replace DMF/NMP with propylene carbonate or Cyrene for SNAr when compatible with nucleophile/base.

• Compact comparison (general)

  • THF vs 2-MeTHF: similar polarity; 2-MeTHF is bio-based, higher bp, easier phase-split; may change rates/selectivity.
  • Toluene vs CPME: CPME has better safety profile (lower peroxide tendency than ethers like THF, broad immiscibility with water) and facilitates workup; toluene offers robust literature precedent.
  • DMF/NMP vs Cyrene/PC: greener carbonates/diacetal solvents avoid reproductive-toxicity concerns; check base/temperature stability.

• Waste minimization

  • Sequence-selective coupling (Br first) can reduce protecting-group steps.
  • Choose bases/additives compatible with aqueous workup to minimize halogenated solvent use.

Note: These are general sustainability suggestions; verify compatibility with your specific transformation and this substrate.

Pharmaceutical Uses

• Item-specific pharmacopeial/excipient status: Not specified for this item; no compendial status indicated. Supplied strictly for research use only.

• General context (non-clinical)

  • This scaffolding motif is frequently used in medicinal chemistry and process R&D as a versatile intermediate. Orthogonal halogens enable rapid library synthesis via cross-coupling at C–Br/C–Cl and SNAr at C–F, supporting SAR exploration.
  • In pre-formulation or screening settings, stock solutions are commonly prepared in DMSO, DMF, or EtOH due to limited aqueous solubility; filtration may be needed to ensure clarity.

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

Physical Properties

• Item-specific specifications

  • Appearance: Not specified for this item; refer to CoA/Spec Sheet.
  • Melting point (MP): Not specified for this item; refer to CoA/Spec Sheet.
  • Boiling point (BP): Not specified for this item; refer to CoA/Spec Sheet.
  • Density: Not specified for this item; refer to CoA/Spec Sheet.
  • Water content, residual metals, UV cutoff, stabilizers: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/general expectations for aryl methyl ketones bearing multiple halogens (context only)

  • Often crystalline solids or low-melting solids with moderate to low volatility due to high halogen content.
  • Solubility profile (typical): Good in chlorinated solvents (DCM, CHCl3), aromatics (toluene), ethyl acetate, THF; limited in aliphatic hydrocarbons; negligible in water.
  • LogP: Halogenated acetophenones typically show elevated lipophilicity relative to acetophenone; exact value not established here.
  • Refractive index (if liquid): Typically higher than non-halogenated analogs; item-specific value not available here.

Notes

• All numerical physical constants for this specific SKU should be taken from the Aladdin CoA/Spec Sheet for the shipped lot. Values above are general literature trends for closely related structures and are not product specifications.

Quality and Grades

• Item-specific grade/purity: Not specified for this item; refer to CoA/Spec Sheet for assay, impurity profile, and any stabilizers.

• Guidance on interpreting typical grades (general)

  • Analytical/AR grade: Tight impurity controls suitable for routine analysis and synthesis.
  • HPLC grade: Emphasis on low UV background and minimal non-volatile residues; relevant if using this compound as a reference standard or in UV-sensitive workflows.
  • Synthesis grade: Fit-for-purpose purity for discovery and route scouting; confirm residual solvent and halide content if critical to downstream steps.

• Impurity considerations for halogenated aryl ketones (general)

  • Potential impurities can include positional isomers, unhalogenated or differently halogenated analogs, residual halides, and solvents. Carbonyl-containing impurities (e.g., acetophenone) may be detectable by 1H NMR (singlet near 2.5–2.7 ppm for Ar–COCH3) and IR (C=O ~1680–1700 cm−1).
  • For cross-coupling, trace metal content and halide assay impact catalytic performance; consult CoA for metals if your process is catalyst-sensitive.

• Documentation

  • Always verify lot-specific data (assay, residual solvents, water, metals) on the Aladdin CoA/Spec Sheet prior to regulated or scale-sensitive use.

Reaction and Applications

As a tri-halogenated acetophenone, 4'-bromo-5'-chloro-2'-fluoroacetophenone offers orthogonal handles for diverse bond constructions.

• Cross-coupling electrophile (literature)

  • C–Br site: Most reactive under Pd-catalyzed Suzuki–Miyaura, Sonogashira, Negishi, and Buchwald–Hartwig conditions; enables rapid SAR diversification.
  • C–Cl site: Couplable with more active catalysts/ligands (e.g., Pd/XPhos, tBuXPhos; Ni catalysis) at higher temperatures.
  • C–F site: Typically inert to Pd-coupling but can participate in SNAr due to ortho-carbonyl activation; useful for O-, N-, or S-nucleophile substitution.

• Carbonyl/benzylic chemistry (literature)

  • Enolate generation (LDA/NaHMDS) for α-alkylation, aldol, or acylation sequences.
  • Reductions: NaBH4 or catalytic hydrogenation to the secondary benzylic alcohol; chemoselectivity vs. aryl halides is typically high.
  • Imine/oxime/hydrazone formations for downstream cyclizations (e.g., heteroaryl annulations).

• Electrophilic/nucleophilic aromatic strategies

  • The carbonyl deactivates EAS but directs meta; however, halogen handles make cross-coupling the preferred path. SNAr at C−F is favored with strong nucleophiles in polar aprotic media.

• Practical tips

  • Sequence couplings from Br → Cl → F/SNAr to exploit relative reactivity.
  • Maintain anhydrous conditions for metalations/couplings; degas solvents for Pd/Ni catalysis.
  • Monitor for halogen–metal exchange under very strong bases; control temperature to preserve halide pattern.

Use this scaffold for stepwise installation of aryl/alkenyl/alkynyl groups and for late-stage introduction of amines/alkoxides at the activated fluoro position.

Reaction Conditions

General literature guidance for transformations on tri-halogenated acetophenones similar to this substrate (adjust to your system after small-scale screening):

• Suzuki–Miyaura coupling (at Ar–Br)

  • Catalyst: Pd(PPh3)4 (1–3 mol%) or Pd2(dba)3 + XPhos/SPhos (1–2 mol% Pd)
  • Base: K2CO3, K3PO4, or Cs2CO3 (2–3 equiv)
  • Solvent: Toluene/H2O, 1,4-dioxane/H2O, or 2-MeTHF/H2O
  • Temp/Time: 70–100 °C, 2–12 h; often selective for C–Br over C–Cl

• Buchwald–Hartwig amination (Ar–Br, then Ar–Cl)

  • Catalyst/Ligand: Pd2(dba)3 (1 mol% Pd) + tBuXPhos, XPhos, or BrettPhos; or Pd-PEPPSI for robustness
  • Base: NaOtBu or Cs2CO3
  • Solvent: Toluene, dioxane, CPME
  • Temp: 80–120 °C

• Sonogashira coupling (terminal alkynes)

  • Catalyst: Pd(PPh3)2Cl2 (1–2 mol%), CuI (2–5 mol%)
  • Base: Et3N or iPr2NH
  • Solvent: THF, toluene, or DMF; 40–80 °C

• SNAr at Ar–F (activated by ortho-carbonyl)

  • Nucleophile: Primary/secondary amines, alkoxides, thiolates (2–5 equiv)
  • Solvent: DMF, DMSO, or NMP
  • Base: K2CO3, Cs2CO3, or NaH (as appropriate)
  • Temp: 60–140 °C; 2–24 h

• Enolate alkylation

  • Base: LDA or NaHMDS (1.1–1.5 equiv) in anhydrous THF/2-MeTHF
  • Temp: −78 to 0 °C; quench with electrophile (R–X, R–CHO)

• Carbonyl reduction

  • Reagent: NaBH4 (1–2 equiv) in MeOH/EtOH at 0–25 °C; 0.5–3 h

These are non-binding literature conditions; optimize catalysts, ligands, and temperatures for your specific substrate and scale.

Safety and Handling

• Item-specific hazard data

  • GHS Classification, Signal Word, H-Statements, Pictograms: Not specified for this item; refer to the product SDS.

• General safety considerations for halogenated aryl ketones (literature/good practice)

  • May cause skin/eye irritation and respiratory irritation; avoid inhalation of dust/vapors and contact with skin/eyes.
  • Use in a certified chemical fume hood. Wear appropriate PPE: lab coat, safety glasses or splash goggles, and nitrile gloves. For scale-up, consider a face shield and heavier-duty gloves.
  • Avoid strong bases and strong nucleophiles unless intended for reaction (risk of SNAr or enolate formation). Keep away from strong oxidizers and reducing agents.
  • Combustible organic; keep away from ignition sources and hot surfaces. Provide adequate grounding/bonding if transferring flammable solvents concurrently.

• First-aid overview (consult SDS for authoritative guidance)

  • Inhalation: Move to fresh air; seek medical attention if symptoms persist.
  • Skin: Wash with soap and water; remove contaminated clothing.
  • Eyes: Rinse cautiously with water for several minutes; remove contact lenses if easy; continue rinsing.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical advice.

• Spills and disposal

  • Absorb small spills with inert material (silica, vermiculite). Dispose of waste according to local regulations; halogenated organics may require specific waste segregation.

Solvent Selection

This compound is a halogenated aryl methyl ketone; solvent choice is typically dictated by the intended transformation (cross-coupling, SNAr, reductions, or enolate chemistry).

• Polarity and miscibility (general expectations)

  • Non-protic, moderately polar aromatic ketone with high halogen content.
  • Typically soluble in DCM/CHCl3, ethyl acetate, THF, DMF/DMAc, acetonitrile, and aromatics (toluene/xylene); poorly soluble in water and aliphatic hexanes.

• Selection guidance by application

  • Suzuki/Negishi/Kumada: Toluene, 1,4-dioxane, or THF with aqueous base; add IPA or water co-solvent for phase transfer as needed.
  • Buchwald–Hartwig/arylation: Toluene, dioxane, or CPME for higher-boiling operations; DMF/DMAc for polar substrates.
  • SNAr at Ar–F (activated by ortho-carbonyl): Polar aprotic solvents (DMF, DMSO, NMP) at elevated temperatures.
  • Enolate chemistry/reductions: THF, Et2O, or 2-MeTHF for LDA/NaHMDS; MeOH/EtOH or IPA for NaBH4 reductions.

• Brief comparison (general)

  • THF: excellent for enolates; peroxide formation risk in storage (solvent issue, not compound-specific).
  • Toluene/CPME: higher bp for thermal couplings; easier workup with CPME.
  • DMF/DMSO: accelerate SNAr but complicate workup; ensure thorough aqueous quench and extraction.

Always verify actual solubility of your batch at working concentration and temperature.

Storage and Reconstitution

• Item-specific storage

  • Storage Conditions: Room temperature (per Product Data). Keep container tightly closed in a dry, well-ventilated place. Minimize exposure to moisture and strong light. Store away from bases, strong nucleophiles, and oxidants.
  • Shipped In: Not specified for this item.

• Stability notes (general)

  • Aryl ketones with halogens are typically shelf-stable at ambient conditions when kept dry and sealed. Avoid prolonged exposure to high heat. If long-term storage is planned, consider storing under inert gas after opening.

• Reconstitution/solution preparation (general guidance; not item-specific specs)

  • Prepare stock solutions in dry organic solvents such as DCM, THF/2-MeTHF, ethyl acetate, toluene, DMF, or DMSO depending on intended chemistry. Filter if particulates are observed.
  • For moisture-sensitive operations (e.g., metal-catalyzed couplings, enolate chemistry), dry solvents and glassware thoroughly; degas solvents for Pd/Ni catalysis.
  • Record concentration and solvent on label; for DMSO/DMF stocks, aliquot to avoid repeated freeze–thaw.

• Research Use Note

  • For research use only. Refer to the CoA and SDS for lot-specific stability and safety information.

Structure and Identity

A halogen-rich, aryl methyl ketone building block designed for cross-coupling and orthogonal functionalization.

• Item-specific identifiers (from Product Data)

  • Product Name: 4'-Bromo-5'-chloro-2'-fluoroacetophenone
  • CAS: 1594605-40-9
  • CID (PubChem): 84804089
  • InChIKey (as provided): 372887
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/computed structural information (for context; not item-specific specs)

  • Common systematic descriptor: 1-(4-bromo-5-chloro-2-fluorophenyl)ethan-1-one (aryl methyl ketone bearing F/Cl/Br at 2/5/4 positions relative to the acyl carbonyl)
  • Representative SMILES (literature): CC(=O)c1c(F)cc(Br)c(Cl)c1
  • Molecular formula (calculated from structure): C8H5BrClFO
  • Formula weight (calculated): ~251.48 g/mol
  • Functional groups/features:
    • Aromatic ring substituted with three halogens (F, Cl, Br)
    • Conjugated aryl ketone (acetophenone motif)
    • No stereocenters (achiral)

• 2D structural description (literature)

  • A benzene ring bearing an acetyl group (–COCH3) at C1; ortho to the carbonyl (C2) is F, para (C4) is Br, and meta (C5) is Cl. The carbonyl is conjugated to the ring, enabling enolate and imine-forming chemistry at the benzylic carbon and directing effects on ring reactivity.

Synthetic Utility

Key value arises from the convergence of three aryl halides with an adjacent carbonyl, enabling orthogonal transformations and cyclizations.

• Orthogonal halide reactivity (literature)

  • Ar–Br (para): Primary site for Pd/Ni-catalyzed couplings. Rapid installation of aryl, alkenyl, alkynyl, or amine fragments.
  • Ar–Cl (meta): Addressable under more forcing coupling conditions or with tailored ligands.
  • Ar–F (ortho to carbonyl): Amenable to SNAr with amines/alkoxides/thiolates due to carbonyl activation and halogen leaving ability.

• Carbonyl manifold

  • Enolate chemistry: α-alkylation/acylation, Michael donors for cascade sequences.
  • Condensations: Oximes/hydrazones leading to heterocycles (e.g., isoxazoles via cycloaddition from oximes or N–O chemistry in multistep routes).
  • Reductive diversification: Conversion to secondary alcohols, followed by Mitsunobu or acylation for further elaboration.

• Retrosynthetic leverage

  • Serves as a branching node to install three distinct substituent classes in a controlled order, enabling route scouting toward densely substituted biaryls and anilides without protecting groups.

• Practical sequencing

  • Typical sequence: (1) Pd-catalyzed coupling at Br, (2) more forcing coupling at Cl, (3) SNAr at F with nucleophile; or interleave SNAr first if nucleophile is base-sensitive to coupling conditions.

This makes the compound a highly efficient platform for rapid analogue generation.

Target Specificity

Not applicable. This product is a small-molecule chemical intermediate and is not an antibody, enzyme, or biological reagent with defined biological targets. No antigen/epitope or species reactivity information applies.