4-[(2,4-Dichlorophenyl)methoxy]-3-methoxybenzoic acid - ≥95% , CAS No.113457-31-1

CAS: 113457-31-1 Cat. No.: D989228 Formula: C₁₅H₁₂Cl₂O₄ Peso molecolare: 327.200 Numero EC: 154-870-2

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=C(C=CC(=C1)C(=O)O)OCC2=C(C=C(C=C2)Cl)Cl
• IUPAC Name: 4-[(2,4-dichlorophenyl)methoxy]-3-methoxybenzoic acid
• InChIKey: NVHDYMQROKRTPK-UHFFFAOYSA-N
• INCHI: 1S/C15H12Cl2O4/c1-20-14-6-9(15(18)19)3-5-13(14)21-8-10-2-4-11(16)7-12(10)17/h2-7H,8H2,1H3,(H,18,19)
• Peso molecolare: 327.200

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Classe Benzene and substituted derivatives
      • Subclass Benzoic acids and derivatives
        • Level5 Methoxybenzoic acids and derivatives
          • Level6 M-methoxybenzoic acids and derivatives

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Classe: Benzene and substituted derivatives
• Subclass: Benzoic acids and derivatives
• Intermediate Tree Nodes: Methoxybenzoic acids and derivatives
• Direct Parent: M-methoxybenzoic acids and derivatives
• Alternative Parents: Benzoic acids Phenoxy compounds Methoxybenzenes Dichlorobenzenes Benzoyl derivatives Anisoles Alkyl aryl ethers Aryl chlorides Monocarboxylic acids and derivatives Carboxylic acids Organochlorides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: M-methoxybenzoic acid or derivatives - Benzoic acid - Anisole - Phenoxy compound - Benzoyl - 1,3-dichlorobenzene - Phenol ether - Methoxybenzene - Halobenzene - Chlorobenzene - Alkyl aryl ether - Aryl chloride - Aryl halide - Monocarboxylic acid or derivatives - Ether - Carboxylic acid - Carboxylic acid derivative - Organohalogen compound - Organic oxygen compound - Organochloride - Organooxygen compound - Hydrocarbon derivative - Organic oxide - Aromatic homomonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as m-methoxybenzoic acids and derivatives. These are benzoic acids in which the hydrogen atom at position 3 of the benzene ring is replaced by a methoxy 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: 327.200 g/mol
• XLogP3: 4.100
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 5
• Exact Mass: 326.011 Da
• Monoisotopic Mass: 326.011 Da
• Topological Polar Surface Area: 55.800 Ų
• Heavy Atom Count: 21
• Formal Charge: 0
• Complexity: 353.000
• 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 item-specific, tested biological application protocols are provided for this small molecule. For general laboratory use:

• Stock solution prep (general): dissolve in DMSO (e.g., 10–50 mg/mL) or DMF; vortex and, if necessary, gently warm. Filter (0.22 µm PTFE) for analytical use.
• Dilution into assays: add DMSO stocks to buffers with vigorous mixing to minimize precipitation; keep final DMSO ≤1–2% v/v unless assay tolerates more.
• Synthetic handling: for coupling, dry solvents and reagents; for hydrogenolysis, degas solvents and employ appropriate hydrogenation apparatus.

For any validated, application-specific protocols, refer to the primary literature or develop method SOPs internally.

Biological Roles

• Item-specific biological roles: Not specified for this item; for research use only.

• Literature/general perspective:

  • This molecule is a small, non-natural aromatic carboxylic acid with halogenated and ether functionalities. It does not correspond to a known endogenous metabolite or cofactor.
  • Structural motifs present (aryl chlorides, benzyl ether, methoxybenzoic acid) commonly appear in medicinal chemistry scaffolds and SAR probes; the acid group enables conjugation to amines (e.g., to generate amide-linked probes), and the benzyl ether can function as a removable protecting element in bioconjugation routes.
  • The dichloroaryl unit enhances lipophilicity and aromatic stacking propensity, which can be leveraged in fragment-based design or as a hydrophobic anchor in affinity tags after derivatization.
  • In biochemical assay contexts, stock solutions are typically prepared in DMSO; care should be taken to control final DMSO content and consider potential nonspecific binding due to hydrophobicity.

No claims are made regarding bioactivity or therapeutic utility. Any use should be confined to in vitro/in vivo research as permitted by institutional guidelines.

Buffer Applications

This compound is not a conventional buffering agent. As an aromatic carboxylic acid with pKa typically in the ~4–5 range (literature for substituted benzoic acids), it can form salts but is not used to maintain precise pH in biological buffers.

• Practical note:
  • For aqueous handling, prepare DMSO stocks and dilute into pre-made buffers (PBS, HEPES, Tris) as needed; alternatively, dissolve the compound by transient basification (e.g., minimal 0.1–1 M NaOH) to form the sodium carboxylate, then adjust pH back to target after mixing.
  • If an aqueous salt form is prepared, verify pH and ionic strength impacts on your system.

Green Alternatives

While the compound itself is not a solvent, greener choices can be made for its handling and transformations.

• Greener solvent substitutions (literature guidance):

  • Replace DCM/CHCl3 with ethyl acetate, 2-MeTHF, CPME, or propylene carbonate where feasible (e.g., extractions, coupling reactions).
  • Use MeCN or EtOAc instead of DMF/NMP when coupling efficiency permits; DMF/NMP carry higher reproductive-toxicity concerns and persistence.
  • For hydrogenolysis of the benzyl ether, ethanol or 2-propanol can substitute for THF/DCM as hydrogenation media.

• Example comparison (general):

  • DCM vs 2-MeTHF: 2-MeTHF offers lower toxicity, partial renewability, and compatibility with many amide couplings; DCM offers superior silica mobility but higher EHS burden.
  • DMF vs MeCN: MeCN has lower boiling point and simpler waste profile; DMF often dissolves substrates better but is less preferred environmentally.

• Process intensification options:

  • Employ solvent recycling where possible (MeCN, EtOAc).
  • Conduct couplings at higher substrate concentration to reduce solvent volumes.
  • Use milder coupling reagents (e.g., EDCI in aqueous-organic media) to minimize hazardous byproducts.

Note: Selection must balance EHS with reaction performance; verify solubility and reactivity prior to scale-up.

Pharmaceutical Uses

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

• General formulation/manufacturing context (no therapeutic claims):

  • This structure can serve as an intermediate or reference material in process development, impurity profiling, and analytical method validation for related halogenated benzoic acid derivatives.
  • The free acid can be transformed to amide/ester derivatives used as synthetic intermediates in medicinal chemistry programs. Its dichloroaryl benzyl ether can act as a temporary protecting group, facilitating multi-step API intermediate synthesis.
  • For analytical QC, prepare reference solutions in acetonitrile or methanol at known concentrations; store refrigerated or frozen if long-term stability in solution is uncertain (consult stability studies where available).

No claims are made regarding therapeutic application, safety, or efficacy. For research use only.

Physical Properties

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

• Literature/general expectations for this structural class (for planning only):

  • Physical state: typically a crystalline solid for polyaryl carboxylic acids bearing benzylic ethers.
  • Solubility profile: sparingly soluble in water (aromatic carboxylic acid with lipophilic substituents); good solubility in polar aprotic organics (DMSO, DMF, NMP) and in chlorinated solvents; moderate in alcohols with warming or base; improved aqueous solubility upon conversion to sodium/potassium salts (base titration).
  • Acidic character: pKa for substituted benzoic acids commonly ~4.0–4.6 (literature range); electron-withdrawing dichloro substituents on the benzyl ether may slightly enhance acidity relative to unsubstituted benzoic acid.
  • Partitioning: lipophilic due to dichloroaryl and benzyl ether; expect higher logP than benzoic acid (qualitative, literature).
  • Stability: aryl chlorides are robust; benzylic aryl ethers are generally stable to neutral/weakly basic conditions but cleavable under hydrogenolysis or strong Lewis acids; methoxy aryl ethers are demethylated by BBr3/BCl3.

Note: The above are literature-based expectations for closely related structures, provided to assist method development. Consult the item’s CoA for any definitive specifications (mp, purity, water, metals, UV, etc.).

Quality and Grades

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

Guidance on grades for this compound class:

• Research/technical grade: suitable for general synthesis and screening, with routine control of organic purity by NMR/HPLC. Trace metals, water, and UV cutoff typically not constrained unless stated.
• HPLC/analytical grade (if offered): emphasizes low non-volatile residue and low UV background for chromatographic use; beneficial when compound serves as reference standard or for trace-quantitation workflows.
• Stabilizers: Not typically required for aromatic carboxylic acids/aryl benzyl ethers. If present, stabilizer identity and level would be disclosed on the CoA. Absence/presence of stabilizer is not specified for this item.

What to check on receipt (best practice):

• Verify identity by 1H/13C NMR and HRMS against the literature structure; confirm chloride count (2×) via isotopic pattern.
• Assess purity by HPLC/UPLC with diode-array detection; monitor for demethylated phenol or debenzylated phenol impurities.
• Record water content (KF) if moisture-sensitive transformations are planned; for this item, any specific water/metal limits are not specified.

Reaction and Applications

This molecule is a versatile bifunctional building block combining a carboxylic acid (for coupling) with two ether motifs and an electron-deficient dichloroaryl unit.

• Representative synthetic applications (literature/general):

  • Amide/ester coupling: convert the acid to active esters (HATU/HBTU, EDCI, DCC) to access amides (for probe/linker synthesis) or esters (prodrugs, protecting-group strategies). Mixed anhydrides or acid chlorides (SOCl2, oxalyl chloride) are also viable.
  • Protecting-group chemistry: the –O–CH2–(2,4-dichlorophenyl) is a benzyl ether; it can mask a phenol during multistep synthesis and be removed by hydrogenolysis (H2, Pd/C) or oxidative methods (DDQ), furnishing the corresponding phenol at the 4-position.
  • Aryl methyl ether manipulation: demethylation of the 3-methoxy substituent with BBr3/BCl3/AlCl3 affords the catechol-like phenol, enabling further functionalization (e.g., O-alkylation, carbonate/urethane formation).
  • Cross-coupling adjacency: though aryl chlorides reside on the benzyl partner (not directly on the coupling ring), they can participate in Pd-catalyzed cross-couplings (Suzuki, Buchwald–Hartwig) after appropriate activation if the benzyl ether is first cleaved to liberate the dichlorobenzyl fragment.
  • Late-stage diversification: carboxylate-directed ortho-functionalization on the acid-bearing ring is possible in related systems; here substitution pattern may limit positions but guides C–H activation strategies.

• Practical notes:

  • Maintain neutral-to-slightly basic conditions to minimize undesired hydrolysis; avoid strong acids during storage.
  • Monitor for debenzylation under hydrogenation conditions if aryl chlorides must be retained (optimize pressure/catalyst).

Reaction Conditions

General literature conditions for transformations of this scaffold (illustrative; optimize per lab):

• Formation of amides from the acid:
  • HATU (1.1–1.5 equiv), DIPEA (2–3 equiv), DMF or MeCN, 0–25 °C, 1–12 h; typical isolated yields 70–95% for unhindered amines.
  • EDCI (1.2–1.5 equiv), HOBt or Oxyma (1.2–1.5 equiv), DIPEA (2–3 equiv), DCM/DMF, 0–25 °C; 60–90% depending on sterics.
• Esterification:
  • Fischer: alcohol (5–10 equiv), catalytic H2SO4 or p-TsOH, Dean–Stark or evaporation of MeOH, 40–65 °C; 60–85%.
  • Via acid chloride: SOCl2 (2–4 equiv), catalytic DMF, reflux, then alcohol + base, 0–25 °C.
• Benzyl ether cleavage (to reveal phenol at 4-position):
  • Hydrogenolysis: H2 (1–4 bar), 5–10% Pd/C (5–10 wt%), MeOH/EtOH/EtOAc, 20–40 °C, 2–24 h; monitor to avoid dechlorination.
  • DDQ oxidation: DDQ (1.2–2.0 equiv), DCM or toluene/H2O, rt–50 °C, 1–6 h.
• Demethylation of aryl methyl ether:
  • BBr3 (1–3 equiv per –OMe), DCM, −78 to 0 °C, 1–4 h; quench with MeOH/H2O. BCl3 offers milder halide load.

Notes:

• Base-sensitive steps: avoid strong bases that might induce benzylic cleavage or saponification of esters.
• Workup: for acidic products, wash organic phases with NaHCO3 to remove acids; acidify aqueous phases to recover free acids.
• Always run small-scale scouts to gauge susceptibility of the dichloroaryl to hydrogenation.

Safety and Handling

• Item-specific hazard classification: Not specified for this item; refer to SDS.
• General GHS expectations for aromatic carboxylic acids/aryl chlorides (literature guidance):
  • Likely eye/skin irritant; may cause respiratory irritation if dust is generated (GHS07). Avoid inhalation and contact.
• Personal protective equipment (PPE):
  • Laboratory coat, safety glasses or goggles, and appropriate chemical-resistant gloves (e.g., nitrile). Handle powders in a fume hood to minimize dust inhalation.
• Incompatibilities and reactivity (general):
  • Strong bases form carboxylate salts; strong oxidizers may affect benzylic positions; strong Lewis acids (BBr3/BCl3) can cleave aryl methyl ethers; catalytic hydrogenation can cleave benzyl ethers. Avoid strong reducing agents in presence of aryl chlorides if preservation is needed.
• Thermal/photostability: Aromatic chlorides and benzylic ethers are typically stable under ambient light; store away from excessive heat.
• First-aid overview (consult SDS for details):
  • Inhalation: move to fresh air; seek medical advice if symptoms persist.
  • Skin/eye contact: rinse with water for several minutes; remove contaminated clothing; obtain medical attention for persistent irritation.
  • Ingestion: rinse mouth; do not induce vomiting; seek medical attention.
• Waste disposal: Treat as organic laboratory waste; dispose in accordance with institutional and local regulations.

Always consult the Aladdin SDS for authoritative hazard, first-aid, exposure limits, and firefighting measures.

Solvent Selection

• Polarity/solubility profile (literature-based expectations):
  • Poor water solubility in neutral form; soluble in polar aprotic organics (DMSO, DMF, NMP, acetone, acetonitrile) and moderately in chlorinated solvents (DCM, CHCl3). Solubility increases in alcohols upon heating. Aqueous solubility increases substantially as the carboxylate salt (e.g., Na+/K+).
• Practical choices by task:
  • Stock solutions for bioassays: DMSO (10–50 mg/mL typical) or DMF; dilute into assay buffers with attention to final DMSO ≤1–2% v/v.
  • Coupling/derivatization (amide/ester formation): DMF, DCM, THF, or MeCN with standard carbodiimide or uronium reagents; add base (DIPEA) as needed.
  • Purification: normal-phase silica with DCM/EtOAc/MeOH gradients; for strongly acidic behavior, add 0.1–1% acetic acid to suppress tailing; or use reversed-phase (MeOH/H2O or MeCN/H2O with 0.1% formic acid) for analytical work.
• Comparison to alternatives (literature):
  • For higher aqueous compatibility, pre-form the sodium salt in minimal NaHCO3 and extract if needed; reconvert to acid by acidification.
  • If UV transparency is required near 254–280 nm, prefer MeCN over DMF/DMSO for analytical detection.

Note: No item-specific solvent specifications are given; choose based on method and downstream requirements.

Storage and Reconstitution

• Storage (item-specific): Room temperature (per Product Data). Protect from excessive heat and direct sunlight. Keep tightly closed in a desiccated environment to minimize moisture uptake and hydrolysis.
• Shipped in: Not specified for this item; refer to CoA/Spec Sheet.
• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Reconstitution:
  • For analytical or bioassay stock solutions, dissolve in anhydrous DMSO or DMF to the desired concentration (e.g., 10–50 mg/mL). Gentle warming (≤40 °C) and sonication can assist dissolution.
  • For aqueous work, form the sodium salt in situ by adding minimal NaHCO3/NaOH, then dilute with buffer and adjust pH as required.
• Stability of solutions (general guidance):
  • DMSO/DMF stocks are typically stable for weeks at −20 °C in sealed, inerted vials. Minimize freeze–thaw cycles by aliquoting.
  • Avoid prolonged storage of solutions at basic pH to prevent undesired side reactions; return to neutral/acidic conditions after use.

Research Use Only. Consult the product CoA and SDS for any additional storage constraints or incompatibilities.

Structure and Identity

A dichloroaryl–benzyl ether of a methoxybenzoic acid, featuring an acid handle for derivatization and two aryl rings linked via an –O–CH2– bridge.

• Item-specific identifiers (Product Data):
  • CAS: 113457-31-1
  • CID: 2339323
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• Computed/literature identifiers and features (non-item-specific):
  • Suggested molecular formula (from structure name, literature): C15H12Cl2O4
  • Approx. molecular weight (formula-based, literature): ~327.15 g/mol
  • Structural features: benzoic acid (carboxylic acid) on ring A; 3-methoxy substituent; 4-(benzyloxy) substituent where the benzyl group bears 2,4-dichloro substitution on ring B.
  • Functional groups: carboxylic acid, aryl methyl ether (–OCH3), benzyl aryl ether (Ar–O–CH2–Ar′), aryl chlorides (2×).
  • 2D description: A substituted salicylic-acid-like ring bearing –CO2H, –OCH3 (meta to –CO2H), and –O–CH2–(2,4-dichlorophenyl) (para to –CO2H). No stereocenters present.

Synthetic Utility

• Functional group handles:

  • Carboxylic acid: readily converted to amides, esters, acid chlorides, anhydrides; participates in peptide-type couplings (EDCI/HOBt, HATU/DIPEA).
  • Benzyl aryl ether (–O–CH2–ArCl2): behaves as a benzyl protecting group for the phenolic oxygen; removable by hydrogenolysis (H2/Pd) or oxidative conditions (DDQ), enabling unveiling of a 4-phenol on the acid-bearing ring.
  • Aryl methyl ether (–OCH3): demethylation with BBr3/BCl3 affords a phenol at the 3-position, enabling selective di-phenol chemistry (e.g., carbonate/ether formation) or directing-group strategies.
  • Aryl chlorides (2,4-disubstitution on benzyl ring): opportunities for cross-coupling (Suzuki, Buchwald–Hartwig, Kumada) after appropriate activation or after liberating the chlorinated toluene/benzyl alcohol fragment from the ether.

• Retrosynthetic value:

  • Disconnection at the benzylic C–O bond suggests assembly from 3-methoxy-4-hydroxybenzoic acid (or its protected derivatives) and 2,4-dichlorobenzyl halide under Williamson ether conditions.
  • Alternative route: form the acid after etherification (hydrolysis/oxidation from corresponding methyl ester) to improve handling during O-alkylation.

• Selectivity and protection:

  • Orthogonal protection possible: benzyl ether removable under H2/Pd without affecting methyl ether; conversely, BBr3 selectively demethylates over benzyl at controlled temperatures.

Target Specificity

Not applicable. This product is a small-molecule chemical and not an antibody, enzyme, or biological ligand with defined target specificity. No antigen/epitope/isotype data apply.