Ethyl 6-(4-bromophenyl)-6-oxohexanoate - ≥95% , CAS No.412022-61-8

CAS: 412022-61-8 Cat. No.: E936446 Formula: C₁₄H₁₇BrO₃ Peso molecolare: 313.191 PubChem CID: 24727283

GRADE & PURITY ≥95%

Storage

Room temperature

Specifications

Specifiche e purezza

≥95%

Condizioni di conservazione di stoccaggio

Room temperature

Purezza

≥95%

Nomi e identificatori

• Sorrisi canonici: CCOC(=O)CCCCC(=O)C1=CC=C(C=C1)Br
• IUPAC Name: ethyl 6-(4-bromophenyl)-6-oxohexanoate
• InChIKey: XBAUTCKEBKXFEV-UHFFFAOYSA-N
• INCHI: 1S/C14H17BrO3/c1-2-18-14(17)6-4-3-5-13(16)11-7-9-12(15)10-8-11/h7-10H,2-6H2,1H3
• Isomeri SMILES: CCOC(=O)CCCCC(=O)C1=CC=C(C=C1)Br
• PubChem CID: 24727283
• Peso molecolare: 313.191

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: Butyrophenones Benzoyl derivatives Aryl alkyl ketones Fatty acid esters Bromobenzenes Aryl bromides Carboxylic acid esters Monocarboxylic acids and derivatives Organobromides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Alkyl-phenylketone - Butyrophenone - Benzoyl - Aryl alkyl ketone - Bromobenzene - Fatty acid ester - Halobenzene - Aryl halide - Aryl bromide - Monocyclic benzene moiety - Benzenoid - Fatty acyl - Carboxylic acid ester - Monocarboxylic acid or derivatives - Carboxylic acid derivative - Organohalogen compound - Hydrocarbon derivative - Organic oxide - Organobromide - 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: 313.190 g/mol
• XLogP3: 3.100
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 8
• Exact Mass: 312.036 Da
• Monoisotopic Mass: 312.036 Da
• Topological Polar Surface Area: 43.400 Ų
• Heavy Atom Count: 18
• Formal Charge: 0
• Complexity: 270.000
• 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 bioassay or immunoassay protocols apply to this small-molecule building block. Typical usage follows standard organic synthesis procedures.

General laboratory handling suggestions:

• For cross-couplings, prepare catalyst and base solutions under inert atmosphere; combine with the aryl bromide substrate in the selected solvent system and heat/stir as required. Monitor by TLC/LC–MS.
• For hydrolysis and amidation sequences, confirm completion by LC–MS and quench carefully to avoid overreaction or decomposition.
• Purification is commonly achieved by silica gel chromatography using EtOAc/hexanes or toluene/EtOAc gradients; crystallization may be feasible depending on the derivative.

For detailed, reaction-specific SOPs, consult standard organic synthesis references and adapt to your chosen catalyst/solvent/base.

Biological Roles

No intrinsic biological role is established for Ethyl 6-(4-bromophenyl)-6-oxohexanoate. It is a synthetic organic intermediate intended for research and chemical synthesis.

Context and usage (general, non-clinical):

• The compound’s para-bromophenyl handle and dual carbonyl functionality make it useful in medicinal chemistry campaigns as a scaffold for SAR exploration, linker design, and conjugation strategies.
• The aryl bromide enables diversification into heteroaryl motifs common in bioactive libraries via Suzuki/Buchwald–Hartwig chemistry, while the ester/ketone allow polarity and H-bonding capacity to be tuned through reduction, hydrolysis, and amide formation.
• The six-carbon spacer can be helpful when engineering bivalent ligands, affinity probes, or surface attachment chemistries where defined reach is desired.

Notes:

• Any biological testing performed with derivatives prepared from this intermediate should follow institutional biosafety policies.
• This product is supplied strictly for laboratory research; it is not a food, cosmetic, household, diagnostic, or therapeutic product.

For compound-specific bioactivity data, consult literature on your final, modified structures rather than on this intermediate.

Buffer Applications

This compound is a hydrophobic aryl ketone–ester and is not a buffering agent. It does not have a defined acid/base pair suitable for maintaining pH in aqueous systems.

• Not typically used to prepare biochemical buffers or electrophoresis running buffers.
• If aqueous handling is necessary (e.g., extractions, partitioning studies), use standard biological buffers (PBS, HEPES, MOPS) as appropriate for your assay, and dissolve this compound first in a compatible cosolvent (DMSO, DMF, or EtOH) before dilution.

For pH control and ionic strength management, select a validated buffer system appropriate to your biological assay; this product serves instead as a synthetic intermediate or small-molecule probe precursor.

Green Alternatives

While the substrate itself is a specialty building block, greener choices can be made in the processes that use it.

Greener solvent and catalyst considerations (literature/general):

• Replace high-boiling polar aprotics (DMF, NMP, DMAc) with 2-MeTHF, Me-THF/water, Cyrene, propylene carbonate, or ethanol/water mixtures where compatible.
• Prefer toluene, EtOAc, MeOH/EtOH, and water-containing biphasic systems for cross-coupling workups to reduce chlorinated waste.
• Employ aqueous Suzuki protocols with water-soluble ligands and bases (e.g., K3PO4 or Cs2CO3) to reduce organic solvent volumes.
• Consider nickel catalysis for certain couplings to minimize precious metal use, provided impurity control and selectivity meet project needs.

Tradeoffs and practical notes:

• 2-MeTHF offers improved safety and biorenewable sourcing vs THF but can alter rates/solubility; peroxide monitoring is still advised for ethers.
• Cyrene can replace DMF in some couplings but may need higher temperatures and careful base selection.
• Water-rich media often simplify workup but may increase saponification of the ethyl ester; monitor for hydrolysis.

Mini-comparison (general guidance):

• THF vs 2-MeTHF: similar solvency; 2-MeTHF is greener and less miscible with water, aiding phase separation.
• DCM vs EtOAc: EtOAc is less hazardous and biorenewable; may require adjusted chromatography.

Validate greener alternatives on small scale to confirm performance with your catalyst/base system.

Pharmaceutical Uses

No pharmacopeial monograph or excipient designation is provided for this item. It is not offered as a pharmaceutical ingredient.

Non-clinical, formulation-adjacent context (general):

• In medicinal chemistry, this type of bifunctional aryl bromide–ketone–ester is commonly used as a precursor to candidate molecules via cross-coupling and subsequent ester-to-amide transformations.
• The ester can be hydrolyzed to the acid and further converted into amides or bioisosteres (e.g., tetrazoles), enabling modulation of solubility and clearance in lead optimization.
• The para-bromophenyl ring serves as a convergent diversification node for rapid library assembly under Pd/Ni catalysis.

Regulatory and handling notes:

• Supplied strictly for research use only; not for human or veterinary use.
• Any use in drug discovery is limited to preclinical laboratory R&D. For GMP or clinical development, additional quality attributes (impurities, residual solvents, metal content, stability) and regulatory documentation would be required and are not specified for this item.

Physical Properties

Item-specific physicochemical specifications (boiling point, melting point, density, refractive index, UV cutoff, solubility limits) are Not specified for this item; refer to CoA/Spec Sheet.

General expectations based on functional groups (literature/structure-based guidance — not item specifications):

• Physical state and appearance: Aromatic ketone–ester compounds with a C6 linker often occur as low-melting solids or high-boiling oils with low volatility.
• Polarity: Moderately lipophilic due to the aryl ring and aliphatic chain; two carbonyls increase polarity relative to simple aryl bromides, improving solubility in polar aprotic solvents.
• Solubility (qualitative): Typically soluble in EtOAc, THF, DCM/CH2Cl2, chloroform, acetone, toluene, and other organic solvents; sparingly soluble in water.
• Partitioning: Expected to have a positive logP (hydrophobic) due to the aryl bromide and alkyl chain; exact value not specified for this item.
• Thermal behavior: Aryl ketone/ester motifs are generally thermally stable under ambient conditions; avoid prolonged heating with bases/acids that can induce hydrolysis or aldol-like side reactions at the ketone.

Spectroscopic notes (general):

• IR: Strong C=O stretches from the ester (~1735 cm⁻¹) and aryl ketone (~1680 cm⁻¹); aromatic C–H and C–Br features present.
• NMR: Distinct ethyl ester quartet/triplet; methylene envelope across the linker; deshielded aromatic protons (para-bromophenyl); ketone-adjacent methylenes shifted downfield.

Always verify exact values and acceptance criteria for your lot via the CoA/Spec Sheet.

Quality and Grades

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

Interpretation and guidance:

• In the absence of a declared grade (e.g., “AR,” “HPLC,” “ACS,” or “≥98%”), consult the CoA for lot-specific purity (GC/HPLC/LC–MS), residual solvents, and identity confirmation (NMR/IR/HRMS). These determine suitability for sensitive transformations (e.g., cross-couplings, medicinal chemistry intermediates).
• UV-absorbing aromatic systems can impact chromatographic baselines; if HPLC-grade solute expectations are critical for analytical uses, ensure low UV-active impurities are documented on the CoA.
• Stabilizers: None are indicated for this item. If present (e.g., acid scavengers for base-labile esters), they would be listed on the CoA. Absence of a listed stabilizer implies the neat compound is supplied without intentional additives.
• Metals background: For catalytic cross-couplings or bioactive lead synthesis, you may require low background Pd/Ni/Cu. Metal content limits are Not specified for this item; refer to CoA/Spec Sheet.
• Water/peroxide/acid value: Not specified for this item; refer to CoA/Spec Sheet.

Best practices:

• If performing moisture-sensitive couplings, consider brief vacuum drying or co-evaporation with anhydrous toluene/THF before use, consistent with your compound’s thermal stability.
• Recordkeeping: Retain CoA/SDS with your batch for regulatory and reproducibility purposes.

Reaction and Applications

Ethyl 6-(4-bromophenyl)-6-oxohexanoate is a versatile, bifunctional intermediate that combines an aryl bromide handle with ester/ketone chemistry across a six-carbon linker. This makes it valuable for constructing bifunctional spacers, PROTAC-like linkers, and medicinal chemistry analogs.

• Aryl bromide reactivity:

  • Suzuki–Miyaura coupling to install aryl, heteroaryl, or vinyl partners; broad ligand/base options (e.g., Pd(PPh3)4 or Pd-PEPPSI with K2CO3/Cs2CO3/Na2CO3; aqueous-organic media).
  • Buchwald–Hartwig amination for anilines/arylamines using Pd2(dba)3 or Pd(OAc)2 with dialkylbiaryl phosphines; bases such as NaOtBu or Cs2CO3.
  • Sonogashira coupling with terminal alkynes (Pd/Cu or Cu-free protocols), enabling alkyne-terminated linkers.
  • Negishi/Kumada for C(sp2)–C(sp3) formation with organozinc or Grignard partners under Ni/Pd catalysis.

• Carbonyl and ester transformations:

  • Saponification to the corresponding acid, then amide coupling (HATU/EDC/DIC) to introduce amine-bearing pharmacophores.
  • Reduction: Ester to alcohol (LiAlH4, DIBAL-H) or to aldehyde (DIBAL-H, low temperature); ketone to secondary alcohol (NaBH4, NaBH(OAc)3 after imine formation), enabling stereochemical diversification.
  • Oxime/hydrazone formation at the ketone; Wolff–Kishner/Borch type reductions to modulate polarity.

• Strategic use:

  • Orthogonal handles allow sequential diversification: first modify the aryl bromide (cross-coupling), then manipulate the ester/ketone for polarity and linkage tuning.
  • The six-carbon tether provides spatial separation, useful in designing bivalent ligands or surface linkers where distance matters.

All conditions above are literature-style guidance; optimize for your substrate and lab setup.

Reaction Conditions

The following are general literature-style conditions suitable for aryl bromides and for common ester/ketone manipulations. They are provided as guidance only and should be optimized for your substrate and lab environment.

• Suzuki–Miyaura coupling (Ar–Br):

  • Catalyst: 1–3 mol% Pd(PPh3)4 or Pd-precatalyst with dialkylbiaryl phosphine ligand.
  • Base: K2CO3, Cs2CO3, K3PO4 (2–3 equiv).
  • Solvent: 1,4-dioxane/H2O, toluene/H2O, or EtOH/H2O; 60–100 °C; 2–12 h.

• Buchwald–Hartwig amination:

  • Catalyst: Pd2(dba)3 or Pd(OAc)2 (1–3 mol%) + BrettPhos/XPhos ligands.
  • Base: NaOtBu, KOtBu, or Cs2CO3.
  • Solvent: Toluene, dioxane, or tBuOH; 80–110 °C.

• Sonogashira coupling:

  • Catalyst: Pd(PPh3)2Cl2 (1–2 mol%) + CuI (0.5–1 mol%) or Cu-free protocols with bulky phosphines.
  • Base: Et3N, iPr2NEt, or Cs2CO3.
  • Solvent: THF, DMF, or toluene; rt to 80 °C.

• Ester hydrolysis (to acid):

  • Basic: NaOH or KOH (1–3 equiv) in MeOH/THF/H2O, 0–25 °C; monitor by TLC/LC.
  • Acidic: HCl(aq)/dioxane or TFA in DCM (where compatible).

• Amide coupling (from acid):

  • HATU or EDCI/oxyma in DMF/DMF alternatives; DIPEA or NMM base; 0–25 °C.

• Carbonyl reductions:

  • Ketone to alcohol: NaBH4 in MeOH/EtOH or selective hydride reagents in aprotic solvents; 0–25 °C.
  • Ester to alcohol: LiAlH4 in ether solvents (−78 to 25 °C) or BH3·THF.

Notes:

• Control base strength and water content to mitigate undesired ester saponification during couplings.
• Degas solvents for Pd/Ni catalysis; rigorously exclude air/moisture as required by your catalyst system.

Safety and Handling

GHS/CLP details for this specific item (signal word, hazard statements, pictograms, classification) are Not specified for this item; refer to SDS.

General safety guidance for aryl bromide–containing ketone esters (professional good practice; not a substitute for SDS):

• Likely hazards: May cause skin/eye irritation and respiratory tract irritation if aerosolized; combustible organic liquid/solid. Avoid inhalation, ingestion, and prolonged skin contact.
• PPE: Lab coat, safety glasses or goggles, and nitrile gloves. Use in a chemical fume hood to control vapors/solvent carriers and to minimize exposure during transfers.
• Handling: Prevent contact with strong bases (risk of ester hydrolysis, enolization) and strong acids (acidic hydrolysis). For cross-couplings, control exposure to Pd/Ni catalysts and bases; quench and dispose of wastes per institutional procedures.
• Storage incompatibilities: Keep away from strong oxidizers and reducing agents. Aryl bromides are generally stable; no specific peroxide-forming risk is expected (unlike ethers), but store away from light/heat to preserve integrity.
• First aid (overview): In case of skin contact, wash with soap and water. For eye exposure, rinse with water for several minutes and seek medical attention. If inhaled, move to fresh air. If ingested, seek medical attention—do not induce vomiting unless directed.
• Spill/cleanup: Absorb small spills with inert material; collect for organic waste disposal. Ventilate area.

Authoritative information: Always consult the product SDS for definitive hazard classifications, response measures, and regulatory details. Research use only.

Solvent Selection

This compound is a moderately lipophilic aryl ketone–ethyl ester with a para-bromophenyl ring. It shows broad solubility in common organic media and minimal aqueous solubility (general expectations; verify experimentally for your lot).

• Polarity/miscibility (general):

  • Highly soluble in polar aprotic solvents: DMF, DMAc, NMP, DMSO, THF, acetone.
  • Well soluble in chlorinated and ethereal solvents: DCM/CH2Cl2, CHCl3, diethyl ether, MTBE.
  • Soluble in moderately polar hydrocarbons: ethyl acetate, toluene; variable in hexanes.
  • Negligible water solubility expected.

• Typical use scenarios:

  • Cross-coupling on the aryl bromide: DMF, toluene, dioxane, or mixtures with water/alcohols depending on base and catalyst.
  • Ester transformations (saponification, amidation): THF/MeOH/H2O blends or DMF for coupling-based amidations.
  • Ketone chemistry (oxime/hydrazone formation, reductive amination after chain modification): alcohols or aprotic solvents with acid/base catalysis as needed.

• Choosing among solvents (general comparison):

  • For fast Pd-catalyzed couplings: 1,4-dioxane/H2O or toluene often give cleaner profiles; DMF/DMAc maximize solubility at the cost of challenging removal.
  • For workup and crystallization: EtOAc/hexanes or toluene/hexanes systems frequently provide good phase behavior for aromatic ketone–esters.

Note: Optimize solvent relative to base, ligand, and nucleophile for aryl bromide chemistry. Confirm actual solubility and stability in your chosen medium on small scale.

Storage and Reconstitution

• Storage conditions (item-specific from Product Data): Room temperature.
• Shipped in: Not specified for this item; refer to CoA/Spec Sheet.

General storage guidance for aryl bromide–ketone–esters:

• Keep tightly sealed under ambient dry conditions. Store away from strong acids/bases and oxidants. Protect from prolonged light and heat to minimize degradation.
• If long-term storage is anticipated, consider an inert atmosphere (argon/nitrogen) and a desiccant in the container or cabinet.

Reconstitution and preparation for use:

• This product is supplied neat; no reconstitution is required. For solution preparation, dissolve in a suitable dry organic solvent (e.g., DCM, THF, DMF, DMSO, toluene, EtOAc) at the desired concentration. Filter if particulate matter is present.
• For moisture-sensitive transformations (e.g., cross-coupling), pre-dry the material under high vacuum at ambient temperature, avoiding excessive heat.

Freeze–thaw guidance:

• Not typically applicable to neat small molecules. If stored as a stock solution, avoid repeated freeze–thaw cycles; prepare single-use aliquots and store at controlled temperature appropriate to the solvent (e.g., −20 °C for DMSO stocks) in sealed vials.

Always consult the product’s CoA and SDS for lot-specific stability and handling instructions. Research use only.

Structure and Identity

Ethyl 6-(4-bromophenyl)-6-oxohexanoate is a bifunctional aryl–aliphatic building block featuring an ethyl ester at one terminus and an aryl ketone bearing a para-bromophenyl group at the other.

• Item-specific registry data (from Product Data):

  • CAS: 412022-61-8
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet. (Provided value appears truncated.)
  • SMILES: 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.

• Structural features (general description based on the name; literature/structure interpretation):

  • Contains an ethyl ester (–CO2Et) derived from hexanoic acid.
  • Possesses a terminal ketone at C6 (a benzoyl-type carbonyl) bonded to a para-bromophenyl ring, giving an aryl–alkyl ketone motif.
  • The aromatic ring bears a para bromine (–Br), enabling cross-coupling and other aryl halide transformations.
  • The carbon skeleton is a flexible C6 aliphatic linker connecting the ester and the aryl ketone, offering conformational reach for spacer/linker design.
  • Functional group set: aryl bromide, aryl ketone, ethyl ester (two carbonyls with distinct reactivity profiles).

• 2D structure in words (literature/interpretation):

  • Ethyl ester at one end of a hexanoyl chain; the distal (ω) carbon bears a carbonyl that is directly attached to a 4-bromophenyl ring (i.e., Ar–C(=O)–(CH2)4–C(=O)OEt, with Ar = 4-bromophenyl).

Note: For exact identifiers (SMILES/InChI) and assay-confirmed formula/MW for this specific lot, please consult the CoA/Spec Sheet.

Synthetic Utility

Key functional elements and how to exploit them:

• Aryl bromide (para-bromophenyl):

  • Gateway to diverse C–C/C–N bonds: Suzuki–Miyaura, Sonogashira, Heck, Buchwald–Hartwig, Negishi, Kumada.
  • Late-stage diversification: Install heteroarenes, vinyls, alkynes, or amines while preserving the aliphatic ketone/ester handles for orthogonal elaboration.

• Aryl ketone at C6:

  • Carbonyl derivatization: Oxime/hydrazone formation, reductions to secondary alcohols (stereochemical entry point), or Baeyer–Villiger oxidation (access to aryl esters/lactones depending on context).
  • Enolate chemistry at the methylene alpha to the ketone within the tether may allow selective functionalization, mindful of potential competition from the ester alpha position.

• Ethyl ester terminus:

  • Hydrolysis to acid; amide coupling (EDC/HOBt, HATU, DIC/oxyma) to introduce polar end groups for conjugation or PROTAC linker attachment.
  • Reduction to primary alcohol (LiAlH4, BH3·THF) enabling carbonate/ether formation or further oxidation to aldehydes/acids.

Strategic sequencing:

• Common route: First perform aryl bromide cross-coupling under Pd/Ni catalysis using bases that minimize ester saponification; then transform the ester/ketone as needed.
• Protecting-group economy: The spatial separation of the two carbonyls often allows chemoselective operations without protection; test on small scale to confirm.

Overall, the molecule serves as a convergent linker/scaffold for constructing complex, bifunctional targets.

Target Specificity

Not applicable. This product is a small-molecule chemical building block, not a biological macromolecule or affinity reagent. No antigen, epitope, species reactivity, clone, or isotype data apply.