4-Chloro-3'-methoxybenzophenone - ≥95% , CAS No.32363-45-4

CAS: 32363-45-4 Cat. No.: C1050204 Formula: C₁₄H₁₁ClO₂ Peso molecolare: 246.7 PubChem CID: 2757633

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: COC1=CC=CC(=C1)C(=O)C2=CC=C(C=C2)Cl
• IUPAC Name: (4-chlorophenyl)-(3-methoxyphenyl)methanone
• InChIKey: ITRZDZXWSBXUFZ-UHFFFAOYSA-N
• INCHI: 1S/C14H11ClO2/c1-17-13-4-2-3-11(9-13)14(16)10-5-7-12(15)8-6-10/h2-9H,1H3
• Isomeri SMILES: COC1=CC=CC(=C1)C(=O)C2=CC=C(C=C2)Cl
• PubChem CID: 2757633
• Peso molecolare: 246.7

Taxonomic Classification

Taxonomy Tree

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

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Classe: Benzene and substituted derivatives
• Subclass: Benzophenones
• Intermediate Tree Nodes: Not available
• Direct Parent: Benzophenones
• Alternative Parents: Diphenylmethanes Aryl-phenylketones Phenoxy compounds Methoxybenzenes Benzoyl derivatives Anisoles Chlorobenzenes Alkyl aryl ethers Aryl chlorides Organochlorides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Benzophenone - Diphenylmethane - Aryl-phenylketone - Anisole - Phenoxy compound - Benzoyl - Phenol ether - Aryl ketone - Methoxybenzene - Halobenzene - Chlorobenzene - Alkyl aryl ether - Aryl chloride - Aryl halide - Ketone - Ether - Organochloride - Organohalogen compound - Organic oxygen compound - Organooxygen compound - Hydrocarbon derivative - Organic oxide - Aromatic homomonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as benzophenones. These are organic compounds containing a ketone attached to two phenyl groups.
• 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: 246.690 g/mol
• XLogP3: 4.100
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 3
• Exact Mass: 246.045 Da
• Monoisotopic Mass: 246.045 Da
• Topological Polar Surface Area: 26.300 Ų
• Heavy Atom Count: 17
• Formal Charge: 0
• Complexity: 259.000
• 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 are provided for this item. For synthetic applications, consider the general procedures under “Reaction Conditions” and adapt to your substrate, scale, and equipment. For analytical characterization, standard protocols include:

• NMR: 1H/13C in CDCl3, DMSO-d6, or acetone-d6; expect signals for anisole O–CH3 (~3.7–3.9 ppm), aromatic protons (6.5–8.0 ppm), and characteristic carbonyl carbon (~195–200 ppm in 13C).
• HPLC-UV: Detection around 254–280 nm is effective for benzophenone chromophores; gradient in MeCN/H2O (0.1% formic acid) or MeOH/H2O.
• MS: ESI/APCI, monitor [M+H]+ at m/z ~247.0 (literature) alongside isotopic pattern characteristic of Cl (M+2 peak).

Biological Roles

This product is provided for research use only. It is a small-molecule aryl ketone, not a biomolecule.

• General biochemical considerations (literature; not product-specific claims)

  • Benzophenone motifs are widely used as photochemical probes because the n→π* excitation can abstract hydrogen atoms, forming radicals under UV light. Derivatives sometimes serve as photoaffinity labels after suitable functionalization; however, 4-chloro-3'-methoxybenzophenone itself is a synthetic intermediate rather than a validated biochemical probe.
  • The methoxy group increases lipophilicity and electron density on the anisole ring; the para-chloro substituent can modulate π–stacking and hydrophobic interactions in discovery chemistry contexts.

• Enzymatic/biotransformation context

  • Aryl ketones may undergo phase I reduction to benzhydrols and subsequent phase II conjugation in biological systems (literature precedence), but specific metabolic data for this exact substitution pattern are not broadly reported.

• Practical note

  • For any biological assay use, ensure appropriate solubilization in DMSO or MeCN before dilution into assay media; confirm that final cosolvent levels do not impact the system. No biological activity or target engagement is claimed or implied for this material.

Buffer Applications

Not typically applicable. 4-Chloro-3'-methoxybenzophenone is a hydrophobic organic building block and does not function as a buffer component. If dissolution in aqueous systems is needed for assays, use a water-miscible cosolvent (e.g., DMSO or MeCN) followed by dilution into the buffered medium, ensuring the final concentration remains below the compound’s aqueous solubility limit to avoid precipitation.

Green Alternatives

While the compound itself is a target building block, greener choices can be made in its synthesis, processing, and purification.

• Solvent substitutions (literature/guidelines)

  • Replace DCM/CHCl3 with EtOAc, MeTHF/2-MeTHF, CPME, or toluene when solubility/reaction kinetics permit.
  • Favor MeCN or EtOAc over THF for extractions; consider cyclopentyl methyl ether (CPME) for water-tolerant couplings.

• Cross-couplings at the aryl chloride

  • Use aqueous-micellar catalysis (TPGS-750-M, Savie) to reduce organic solvent load; enables Suzuki couplings in water-rich media.
  • Nickel catalysis may allow lower Pd usage; ligand selection (e.g., BrettPhos-type for amination) can reduce catalyst loadings.

• Oxidations and reductions

  • Choose hydrogenation (H2/Pd) or transfer hydrogenation (isopropanol/Ru or Mn catalysts) over stoichiometric hydrides when compatible.
  • For Baeyer–Villiger, employ biocatalytic Baeyer–Villiger monooxygenases (BVMOs) or H2O2 with organocatalysts rather than peracids when feasible.

• Workup and purification

  • Emphasize crystallization over chromatography to minimize solvent waste; explore antisolvent strategies (e.g., EtOAc/hexanes, toluene/EtOH).

• Trade-offs

  • Greener solvents may slow rates or alter selectivity; ensure heat/mass-transfer and mixing are optimized. Water-rich couplings may require surfactants and careful base choice to maintain activity and avoid hydrolysis of sensitive intermediates.

Pharmaceutical Uses

No pharmacopeial or excipient status is specified for this item. It is sold for research use only.

• General context (literature/industry)

  • Substituted benzophenones are common intermediates in the synthesis of drug-like scaffolds and fine chemicals. The para-chloro handle enables Pd-catalyzed diversification to access libraries of analogs; the anisole can be unmasked to phenols to tune properties such as hydrogen bonding and polarity.
  • In formulation science, benzophenone cores can act as UV absorbers; however, no claim is made for this compound as a cosmetic or pharmaceutical UV filter or excipient.

• Process development notes

  • For route scouting, this building block may serve as an advanced intermediate toward APIs or fragments. Ensure impurity profiles (especially residual palladium or halides if cross-couplings are used) meet internal specifications for research or preclinical materials. No such specifications are provided for this SKU; consult the CoA for your lot.

Physical Properties

• Item-specific (from Product Data)

  • 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 (general guidance; not item-specific specifications)

  • Molecular formula (literature): C14H11ClO2
  • Molecular weight (literature): ~246.69 g/mol
  • Physical state: typically a crystalline solid for closely related benzophenone derivatives; exact MP/appearance for this specific isomer is not widely tabulated.
  • Melting point, boiling point, density, refractive index: Not reliably reported in standard compilations for this specific substitution pattern; consult primary literature or the product CoA.
  • Solubility (qualitative, literature):
    • Water: expected very low solubility due to hydrophobic diaryl core
    • Organic solvents: good solubility in chlorinated solvents (DCM, CHCl3), aromatics (toluene), and moderately polar aprotics (THF, EtOAc, acetone, MeCN)
  • LogP (expectation, literature trend): elevated (typical of diaryl ketones with halogen and methoxy), favoring organic phases.

• Practical notes (general):

  • The conjugated aryl ketone absorbs in the near-UV; solutions can appear faintly yellow at higher concentrations.
  • The aryl chloride and methoxy substituents bias solubility toward less polar organic media; recrystallization often feasible from ethanol/toluene or hexanes/EtOAc mixtures, but optimal systems should be determined experimentally.

Quality and Grades

• Item-specific (from Product Data)

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

• General guidance on quality for aryl ketone building blocks (literature/industry practice)

  • Typical metrics reported on CoA: identity (1H NMR, 13C NMR), purity by HPLC/GC, water content (Karl Fischer), residual solvents, and occasionally metal residues (from cross-coupling synthesis). For UV-sensitive benzophenones, low-level photoproducts may be monitored by HPLC-UV.
  • Stabilizers: Not commonly required for solid benzophenones; some suppliers recommend storing under light-protected conditions to minimize photochemical byproducts. If a stabilizer is present, it will be disclosed on the CoA/specification.
  • Chromatographic suitability: For applications in photochemistry or materials research, low UV background and absence of oxidizable impurities are often desirable; HPLC-grade claims, if any, would indicate minimized UV-absorbing contaminants. None are specified for this item.
  • Batch-to-batch consistency: For multistep synthetic programs, request CoA with detailed impurity profiling to ensure reproducibility across lots.

• Documentation

  • Always consult the Certificate of Analysis and Specification Sheet for this specific SKU (C1050204) for definitive acceptance criteria, test methods, and any additional handling or storage notes.

Reaction and Applications

As a substituted benzophenone, 4-chloro-3'-methoxybenzophenone serves as a versatile intermediate in organic synthesis. Its dual functionalization (aryl chloride and aryl methoxy) and a conjugated aryl ketone enable multiple divergent transformations.

• Transformations on the aryl chloride (literature/general)

  • Cross-couplings: Suzuki–Miyaura, Buchwald–Hartwig (with appropriate ligands), Stille, Negishi to introduce aryl, vinyl, or amine substituents para to the carbonyl on one ring.
  • Metal–halogen exchange: Halogen–lithium exchange (with n-BuLi at low temperature) followed by electrophile trapping; requires careful control to avoid carbonyl addition.

• Transformations at the carbonyl

  • Reductions: NaBH4 or catalytic hydrogenation to the corresponding secondary alcohol (benzhydrol); selective over aryl chloride under mild conditions.
  • Nucleophilic additions: Grignard or organolithium reagents add to form tertiary carbinols; choice of solvent (THF/Et2O) and temperature controls selectivity.
  • Baeyer–Villiger oxidation: Converts to the corresponding aryl ester (migration aptitude can be probed by the two aryl rings’ electronics).
  • Enolate chemistry: Limited due to lack of α-hydrogens; however, directed ortho metalation (DoM) strategies on the anisole ring can be exploited.

• Aromatic substitution on the anisole ring

  • Demethylation (BBr3, AlCl3/thiols) to afford the phenolic derivative for subsequent etherification/esterification.
  • Electrophilic substitution patterns influenced by the methoxy (activating, ortho/para-directing) vs the carbonyl (deactivating, meta-directing) groups—useful for regiocontrol in further elaboration.

• Application domains (general)

  • Useful as a precursor to advanced diaryl architectures in materials, photoinitiators, agrochemical and fine-chemical discovery programs, where modular cross-coupling enables rapid diversification.

Reaction Conditions

General literature guidance for common transformations of aryl chlorides and benzophenone carbonyls (values are typical ranges; verify on small scale):

• Suzuki–Miyaura coupling at para-Cl

  • Catalyst: Pd2(dba)3 (0.5–1 mol%) with SPhos/XPhos (1–2 mol%) or Pd(PtBu3)2 (1–2 mol%)
  • Base: K3PO4, Cs2CO3, or K2CO3 (2–3 equiv)
  • Solvent: 1,4-dioxane/H2O, toluene/H2O, MeTHF/H2O
  • Temperature/time: 70–100 °C, 2–16 h
  • Notes: Add water (10–20%) to accelerate transmetalation; monitor by HPLC-UV.

• Buchwald–Hartwig amination

  • Catalyst/ligand: Pd2(dba)3 (1 mol%) with BrettPhos or RuPhos (2–3 mol%)
  • Base: NaOtBu or K3PO4
  • Solvent: toluene, dioxane, or CPME
  • Temperature: 80–110 °C

• Carbonyl reduction to benzhydrol

  • Reagent: NaBH4 (1.5–3 equiv)
  • Solvent: MeOH, EtOH, or THF/MeOH mixture
  • Temperature: 0–25 °C; 0.5–2 h
  • Alternative: H2 (1–5 bar), Pd/C (5–10 wt%), EtOH/EtOAc, 25–50 °C

• Baeyer–Villiger oxidation

  • Reagent: mCPBA (1.2–1.5 equiv)
  • Solvent: DCM or CHCl3
  • Temperature: 0–25 °C
  • Tip: Buffer with NaHCO3 to manage acid; consider H2O2 with catalyst for greener variant.

• Demethylation of anisole

  • Reagent: BBr3 (1–3 equiv) in DCM, −78 to 0 °C, then warm to RT; quench carefully to avoid overbromination.

These conditions are literature-style guidance and must be optimized for this substrate and your equipment. They are not product specifications.

Safety and Handling

• Item-specific hazard data (from Product Data)

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

• General safety considerations for substituted benzophenones (literature/analog-based; not product specifications)

  • Likely hazards: May cause skin/eye irritation and respiratory irritation if dust is generated; harmful if swallowed. Avoid inhalation of dust and contact with skin/eyes.
  • Photosensitization: Benzophenone scaffolds can act as UV photosensitizers; minimize unnecessary UV exposure to solutions and powders to avoid unintended photochemistry.
  • Environmental: Halogenated aromatics can be persistent; avoid release to the environment and manage waste according to local regulations.

• PPE and handling

  • Wear appropriate lab coat, safety glasses (ANSI Z87.1) and disposable nitrile gloves; use in a fume hood to control dust/vapors.
  • Avoid sources of ignition for hot operations; while not especially volatile, dust may form combustible mixtures in air under certain conditions.

• Storage and incompatibilities

  • Storage (per Product Data): Room temperature. Keep container tightly closed in a dry, well-ventilated place.
  • General incompatibilities: Strong oxidizers (risk of exotherm), strong reducing agents (may attack carbonyl), strong bases or Lewis acids under forcing conditions (possible demethylation or Friedel–Crafts side reactions). Protect from strong UV light to limit photoreactions.

• First aid (overview; defer to SDS)

  • Eye/skin: Rinse with water for several minutes; remove contaminated clothing; seek medical advice if irritation persists.
  • Inhalation: Move to fresh air; seek medical attention if symptoms occur.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.

Solvent Selection

This product is a solid aryl ketone building block, not a solvent. Solvent selection here refers to dissolving, processing, and reacting this compound.

• Polarity and miscibility (literature/general)

  • Polarity class: moderately polar aromatic ketone (π–π and dipolar interactions; poor hydrogen bonding as donor)
  • Expected solubility: good in DCM, chloroform, toluene, THF, acetone, ethyl acetate; limited in hexanes; very low in water and aqueous buffers.
  • Dielectric environment: carbonyl dipole favors moderately polar aprotic media for reactions and analytics (e.g., HPLC in MeCN/MeOH-water).

• Practical solvent choices by task

  • Synthesis (cross-coupling at the aryl chloride): toluene, dioxane, CPME, or DMAc/DME/THF (base-dependent); add water co-solvent for Suzuki where applicable.
  • Nucleophilic additions/reductions to the carbonyl: THF or Et2O (for organometallics); MeOH/EtOH or isopropanol (for borohydride/catalytic hydrogenation).
  • Purification: normal-phase flash (hexanes/EtOAc gradients) or recrystallization from ethanol/toluene or EtOAc/hexanes.
  • Analytics: dissolve in MeCN, MeOH, DMSO, or DCM for HPLC/GC and spectroscopic characterization.

• Comparison (general)

  • DCM vs EtOAc: DCM gives rapid dissolution and strong UV response but is less green; EtOAc is safer/greener but may require warming and larger volumes.
  • THF vs 2-MeTHF: similar solubilizing power; 2-MeTHF is often preferred for greener processing and better water partitioning.

Storage and Reconstitution

• Item-specific (from Product Data)

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

• General storage guidance for aryl ketone solids (literature/best practice)

  • Keep tightly closed in a dry container; protect from prolonged or intense light to minimize any photochemical changes typical of benzophenone scaffolds.
  • If long-term storage is planned, consider amber glass and desiccation (silica gel or molecular sieves) to control moisture, although the compound is not strongly hygroscopic.

• Reconstitution/dissolution

  • Choose a dry, compatible solvent: DCM, THF, toluene, acetone, EtOAc, MeCN, or DMSO.
  • For biological assays, prepare a concentrated stock in DMSO (e.g., 10–100 mM), filter if needed (PTFE or PVDF), and dilute into assay buffer to the desired concentration while keeping final DMSO ≤1–2% v/v as system permits.
  • Warm gently or sonicate to assist dissolution; avoid strong UV light during solution handling.

• Stability notes

  • Solutions are generally stable for hours to days under inert atmosphere and darkness; for extended storage, keep solutions at 2–8 °C in amber vials and re-check purity by HPLC before use.

Always defer to the product’s SDS and CoA for definitive handling and storage instructions for your specific lot.

Structure and Identity

Brief overview: 4-Chloro-3'-methoxybenzophenone is a substituted benzophenone featuring a para-chloro substituent on one phenyl ring and a meta-methoxy substituent on the other, with the two rings connected through a central ketone (benzophenone) carbonyl.

• Item-specific (from Product Data)

  • CAS: 32363-45-4
  • CID: 2757633
  • InChIKey: 150292 (as provided)
  • Storage Conditions: Room temperature
  • Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/computed (general identity; not item-specific specifications)

  • Synonyms: 4-Chloro-3-methoxybenzophenone; 3'-Methoxy-4-chlorobenzophenone
  • Molecular formula (literature): C14H11ClO2
  • Molecular weight (literature): ~246.69 g/mol
  • Representative SMILES (literature): Clc1ccc(cc1)C(=O)c1cccc(OC)c1
  • Structural features:
    • Core: benzophenone (diphenyl ketone) scaffold
    • Functional groups: aryl ketone (C=O), aryl chloride (para), aryl methoxy (meta on the second ring)
    • Aromaticity: two conjugated phenyl rings; carbonyl conjugated with both rings
    • Stereochemistry: achiral; planar-to-near-planar conjugated system

• 2D description in words (general): A para-chloro-substituted phenyl ring is bonded to a carbonyl carbon (benzophenone core). The carbonyl carbon is attached to a second phenyl ring bearing a meta-methoxy group (relative to the carbonyl linkage). The carbonyl lies between two π-systems, enabling conjugation across the diaryl framework.

Synthetic Utility

4-Chloro-3'-methoxybenzophenone integrates three orthogonal elements—an aryl chloride, a methoxy-substituted aryl ring, and a conjugated ketone—providing rich divergence in synthesis.

• Aryl chloride vector

  • Pd-catalyzed cross-couplings (Suzuki, Sonogashira, Buchwald–Hartwig) to append aryl, alkenyl, alkynyl, or amine substituents at the para position. Ligand tuning (e.g., XPhos, SPhos, BrettPhos) controls reactivity with (hetero)aryl boronates or amines.
  • Halogen–metal exchange (n-BuLi, t-BuLi) followed by electrophile capture, with careful protection of the carbonyl (e.g., ketalization) if needed.

• Carbonyl node

  • Reductive transformations to secondary alcohols (NaBH4, DIBAL-H, catalytic hydrogenation) or tertiary alcohols via nucleophile addition (RMgX/RLi).
  • Oxidative remodeling via Baeyer–Villiger to aryl esters; selective aryl migration can be exploited for regiocontrol.
  • Photochemistry: benzophenone triplet sensitization enables intramolecular cyclizations or intermolecular hydrogen abstraction when properly designed.

• Anisole manipulation

  • Demethylation to phenol (BBr3, AlCl3/thiol, TMSI), enabling ether/ester diversification.
  • Directed ortho metalation (DoM) adjacent to methoxy under strong base, allowing installation of electrophiles (formyl, halogen, boryl) on that ring.

• Retrosynthetic value

  • Accessible from acylation of anisole derivatives with 4-chlorobenzoyl equivalents or via benzoyl–benzene cross-coupling/benzoylation strategies, making it a convenient late-stage branching point in SAR campaigns.

Target Specificity

Not applicable. This product is a small-molecule building block, not a biological targeting reagent (e.g., antibody, enzyme, or ligand with defined biological target specificity). No target specificity data are provided for this item.