4-(3,4-Dichlorophenoxymethyl)benzoic acid , CAS No.149288-42-6

CAS: 149288-42-6 Cat. No.: D942704 Summenformel: C₁₄H₁₀Cl₂O₃ Molekulargewicht: 297.100

Storage

Room temperature

Specifications

Storage

Room temperature

Namen und Kennungen

Kanonisches Lächeln

C1=CC(=CC=C1COC2=CC(=C(C=C2)Cl)Cl)C(=O)O

IUPAC Name

4-[(3,4-dichlorophenoxy)methyl]benzoic acid

InChIKey

UWBZBSMZGHDZTA-UHFFFAOYSA-N

INCHI

1S/C14H10Cl2O3/c15-12-6-5-11(7-13(12)16)19-8-9-1-3-10(4-2-9)14(17)18/h1-7H,8H2,(H,17,18)

Molekulargewicht

297.100

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Klasse Benzene and substituted derivatives
      • Subclass Benzoic acids and derivatives

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Klasse: Benzene and substituted derivatives
• Subclass: Benzoic acids and derivatives
• Intermediate Tree Nodes: Not available
• Direct Parent: Benzoic acids
• Alternative Parents: Phenoxy compounds Phenol ethers Dichlorobenzenes Benzoyl derivatives Alkyl aryl ethers Aryl chlorides Carboxylic acids Organochlorides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Benzoic acid - Phenoxy compound - Benzoyl - 1,2-dichlorobenzene - Phenol ether - Halobenzene - Chlorobenzene - Alkyl aryl ether - Aryl chloride - Aryl halide - Ether - Carboxylic acid - Carboxylic acid derivative - Organooxygen compound - Organochloride - Organohalogen compound - Hydrocarbon derivative - Organic oxide - Organic oxygen compound - Aromatic homomonocyclic compound
• Beschreibung: This compound belongs to the class of organic compounds known as benzoic acids. These are organic Compounds containing a benzene ring which bears at least one carboxyl 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

Chemische und physikalische Eigenschaften

• Molekulargewicht: 297.100 g/mol
• XLogP3: 4.900
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 4
• Exact Mass: 296.001 Da
• Monoisotopic Mass: 296.001 Da
• Topological Polar Surface Area: 46.500 Ų
• Heavy Atom Count: 19
• Formal Charge: 0
• Complexity: 303.000
• 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 as a pre-validated assay reagent. No WB/IHC/IF/FC protocols or dilutions are defined for this small-molecule building block. For synthetic applications, see the Reaction Conditions and Synthetic Utility sections for representative procedures.

Biological Roles

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

• General context (informational only; no clinical claims)

  • Aromatic carboxylic acids with halogenated phenoxy motifs are common in research chemical libraries exploring hydrophobic interactions and halogen bonding in protein pockets. The dichloro groups can modulate lipophilicity, metabolic stability (blocking sites of oxidation), and binding geometry.
  • The carboxylic acid moiety often serves as an anchoring group for conjugation to amines (forming amides) to generate tool compounds, affinity tags, or materials linkers. In ionized form, it can influence membrane permeability and target engagement profiles.
  • No endogenous biological role is expected for this synthetic small molecule; any observed bioactivity would be context- and structure-dependent within a designed series.

Buffer Applications

This compound is not used as a buffer component. As a hydrophobic aromatic carboxylic acid, it lacks a defined, narrow pKa window suitable for routine buffering and has low aqueous solubility at neutral pH. For aqueous work, prepare solutions in organic solvents (e.g., DMSO) or convert to a soluble salt for pH > 8.5. Refer instead to the Synthetic Utility and Solvent Selection sections for practical usage.

Green Alternatives

While the compound itself is a solid building block (not a solvent), its use often involves polar aprotic media and peptide-type coupling reagents. Greener choices focus on solvent and reagent selection.

• Solvent alternatives (general guidance)

  • Replace DMF/NMP with 2-MeTHF, CPME, EtOAc, or propylene carbonate when solubility and reactivity allow.
  • Use aqueous micellar media (e.g., TPGS-750-M) for some amide couplings or cross-couplings; solubilize the substrate with minimal organic co-solvent.

• Coupling reagents

  • Favor carbodiimide systems with catalytic Oxyma or green additives over benzotriazole-based reagents (avoid HOBt/HOAt where possible due to energetic hazards).
  • Enzymatic esterifications or amide formations in non-traditional media can be considered for specialized cases.

• Comparison snapshot (informational)

  | Aspect | Conventional choice | Greener alternative | Trade-offs | |---|---|---|---| | Amide coupling solvent | DMF/NMP | 2-MeTHF, EtOAc, MeCN | Solubility may limit; adjust base/reagent loadings | | Cross-coupling solvent | Dioxane, toluene | CPME, 2-MeTHF, water-miscible systems | Ligand/base re-optimization often needed | | Coupling reagent | HATU, PyBOP | EDC·HCl + Oxyma, DIC + Oxyma | May require longer times, careful control of urea byproducts |

• Waste minimization

  • Employ in situ activation and telescoped steps to reduce solvent exchanges; recover/recycle greener solvents when feasible.

Pharmaceutical Uses

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

• General formulation/manufacturing context (no therapeutic claims)

  • This scaffold serves as a research intermediate. The benzoic acid function enables conjugation to amines (e.g., to form amide-linked candidates) or temporary masking as esters for pro-lab applications. The dichlorophenoxy motif is frequently explored in medicinal and agrochemical discovery programs due to tunable physicochemical properties.
  • If used in formulation screening of research compounds, typical vehicles include DMSO stock solutions diluted into co-solvent systems or buffered aqueous media at basic pH as the sodium/potassium salt. Ensure compatibility with excipients and avoid precipitation upon dilution.
  • Any GMP, impurity profiling, or elemental analysis expectations should be defined per project; none are specified for this catalog item.

Physical Properties

• Item-specific properties (specifications)

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

• Storage and shipping

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

• Literature/typical physicochemical characteristics (for context; not product specification)

  • Physical state: expected crystalline solid (aromatic carboxylic acid with two aryl rings).
  • Acid–base: weak aromatic carboxylic acid; deprotonates in basic media to give water-soluble carboxylate salts.
  • Solubility profile: sparingly soluble in water at neutral pH; good solubility in polar aprotic solvents (DMSO, DMF, NMP). Solubility in alcohols and chlorinated solvents may require warming or base.
  • Lipophilicity: elevated due to dichloro-substituted aryl ring and benzylic ether (qualitative).
  • Boiling/melting point, density, refractive index, pKa, logP: Not specified for this item; consult literature or measure as needed for your application.

Quality and Grades

• Item-specific quality information

  • Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
  • Stabilizers/inhibitors: None indicated in Product Data; Not specified for this item.

• Guidance on interpreting grades (general)

  • Research grade: typically suitable for synthetic, screening, and general lab use. Trace impurity limits (water, metals, residual solvents) vary by supplier; confirm with the CoA for sensitive applications (e.g., catalysis, materials, analytical reference use).
  • If HPLC or LC-MS grade is required for analytical applications: look for documentation of low UV cut-off interferences and residual solvent/background ion limits. In absence of such designation, pre-purification (recrystallization or flash) and verification by NMR/LC-MS is recommended.

• Batch-specific verification

  • For coupling chemistry (amide/ester formation) and cross-coupling uses, assess: purity by 1H/13C NMR, LC purity, residual inorganic halides, and water content (Karl Fischer) as appropriate. Values are Not specified for this item; consult the CoA.
  • If metal-catalyzed reactions are planned, consider passing the reagent through a short plug or recrystallizing to minimize inhibitory impurities; verify by a small-scale test reaction.

Reaction and Applications

• Functional handles enabling diverse transformations (literature/general)

  • Carboxylic acid (para to benzylic ether): amide coupling (EDC/HOBt, HATU/HOAt, PyBOP), esterification (Fischer or Steglich), Curtius/Schmidt chemistry to access isocyanates/amines (with appropriate reagents), and decarboxylative strategies.
  • Aryl chlorides (3,4-dichloro on phenoxy ring): serve as electrophiles in Pd-catalyzed cross-couplings (Suzuki–Miyaura, Buchwald–Hartwig, Stille, Negishi) with suitable ligands optimized for aryl chlorides (e.g., XPhos, SPhos, BrettPhos).
  • Benzylic ether linkage: generally robust; can be strategically cleaved under strong acidic conditions (Lewis or Brønsted) to unmask phenol/benzyl derivatives when needed.

• Typical uses in synthesis

  • Preparation of amide-linked libraries where the dichlorophenoxy motif is retained for SAR exploration (e.g., agrochemical or probe synthesis; research use only).
  • Installation of diverse substituents on the dichloro ring via selective coupling at one or both chloro sites, allowing stepwise diversification.
  • Late-stage diversification from the acid handle to esters, amides, or activated acids (acyl chlorides, mixed anhydrides) for convergent routes.

• Practical tips

  • Dry the solid under vacuum before moisture-sensitive couplings; residual water reduces coupling efficiency.
  • For challenging aryl chloride activations, use Pd2(dba)3 or Pd(OAc)2 with bulky electron-rich ligands (Buchwald-type) and strong bases (t-BuONa, Cs2CO3) at 90–120 C.
  • Monitor for potential competitive ether cleavage under harsh acid; prefer neutral or basic conditions when possible.

Reaction Conditions

General, literature-based guidance for this scaffold (illustrative; not product specifications):

• Amide coupling (acid → amide)

  • Typical: HATU (1.1 eq), amine (1.2 eq), DIPEA (2–3 eq) in DMF or NMP, 0–25 C, 1–4 h. Alternative: EDC·HCl (1.2 eq) + Oxyma (1.2 eq) + base in DMF/MeCN/2-MeTHF, 25 C to slight warming.
  • Tips: Pre-dry starting material; avoid excess base that could promote ether cleavage under prolonged times at high temp.

• Esterification

  • Steglich: DCC (1.2 eq), catalytic DMAP in DCM, 0 C to rt, 2–16 h. Filter DCU byproduct; polish by silica.
  • Fischer: Alcohol solvent, catalytic H2SO4 or p-TsOH, reflux, Dean–Stark if water immiscible.

• Acid chloride formation

  • SOCl2 (3–5 eq) with 1–2 drops DMF, reflux 1–3 h; remove volatiles under reduced pressure; use immediately.

• Cross-coupling on aryl chlorides (phenoxy ring)

  • Suzuki–Miyaura: Pd2(dba)3 (1–2 mol%) + XPhos/SPhos (2–4 mol%), base (K3PO4 or Cs2CO3), 1,4-dioxane/H2O (or CPME/H2O), 80–110 C, 4–16 h.
  • Buchwald–Hartwig amination: Pd(OAc)2 (1–3 mol%) + BrettPhos/XPhos, NaOtBu or Cs2CO3, toluene or dioxane, 90–120 C.

• Workup/Isolation

  • Acidic washes can protonate carboxylate and aid extraction from basic media; avoid prolonged strong acid if preserving the benzylic ether is essential.

• Expected outcomes

  • Yields depend on partner reactivity and conditions; aryl chloride activation may require higher temperature and ligand optimization compared to bromides/iodides.

Safety and Handling

• GHS information (item-specific)

  • Signal word: Not specified for this item; refer to SDS.
  • Hazard statements (H-): Not specified for this item; refer to SDS.
  • GHS classification and pictograms: Not specified for this item; refer to SDS.

• General laboratory safety (applicable to aromatic carboxylic acids; informational only)

  • Likely hazards: May cause skin/eye irritation and respiratory tract irritation as a fine powder; avoid dust formation and inhalation.
  • PPE: Lab coat, safety glasses or splash goggles, and appropriate chemical-resistant gloves (e.g., nitrile). Use in a fume hood when weighing or dissolving.
  • Handling: Avoid strong bases (forms carboxylate salts, potential exotherm upon neutralization), strong oxidizers, and strong acids capable of cleaving benzylic ethers under forcing conditions.
  • First aid (summary; defer to SDS): If inhaled, move to fresh air; if on skin/eyes, rinse with water for at least 15 minutes; if ingested, rinse mouth—seek medical attention in all cases of exposure.
  • Spills: Avoid raising dust; collect with non-sparking tools into suitable container for disposal. Wash spill area with mild detergent.
  • Thermal/chemical stability: Stable under normal lab conditions; avoid prolonged heating with strong acids (possible benzylic-ether cleavage) or bases (saponification/neutralization heat).

Always consult the product-specific SDS for authoritative hazard, exposure limits, and disposal guidance.

Solvent Selection

This product is a non-volatile, hydrophobic aromatic carboxylic acid; solvent choice is driven by its ionization state and application.

• Practical solubility guidance (literature/general)

  • Polar aprotic: DMSO, DMF, NMP typically dissolve at tens of mg/mL at ambient temperature—preferred for stock solutions and coupling reactions.
  • Chlorinated/aromatic: CH2Cl2, CHCl3, toluene may require gentle heating or co-solvent with a base or tertiary amine to aid dissolution.
  • Alcohols: MeOH/EtOH can work warm; addition of a stoichiometric base (e.g., Et3N or NaOMe) improves solubility by forming the carboxylate.
  • Aqueous media: Poor solubility at neutral pH; readily soluble as carboxylate salts at pH > 8.5.

• Selection by use-case

  • Amide coupling: DMF, NMP, or DCM with base and coupling agent (e.g., HATU/DIPEA) are common.
  • Esterification: DCM or toluene for Steglich; MeOH/acid catalyst for Fischer.
  • Cross-coupling (on aryl chlorides): High-boiling polar aprotics (dioxane, toluene, CPME) often with water as co-solvent.

• Small comparison (general)

  • DMSO/DMF: Maximum solubility, but challenging workup and environmental profile.
  • 2-MeTHF/CPME: Greener alternatives with moderate solubility; good for coupling after pre-activation or as co-solvents.
  • MeCN: Cleaner workup, moderate solubility; may need base to assist dissolution.

Storage and Reconstitution

• Storage (item-specific)

  • Storage conditions: Room temperature (per Product Data). Protect from moisture; keep container tightly closed.
  • Shipped in: Not specified for this item; refer to CoA/Spec Sheet.

• Stability (general guidance)

  • Stable under ambient laboratory conditions when dry. Avoid prolonged exposure to strong acids or bases at elevated temperature that could promote benzylic ether cleavage or salt formation.

• Reconstitution and stock solutions (informational)

  • Prepare concentrated stocks in DMSO or DMF (e.g., 10–100 mM) for screening or coupling setups; filter if necessary.
  • For aqueous work, dissolve in minimal DMSO or convert to its sodium/potassium salt; adjust pH > 8.5 to maintain solubility. Add slowly to buffered media with stirring to prevent precipitation.
  • Store organic stocks at 2–8 C for medium term or at −20 C for long term, desiccated and protected from light; minimize freeze–thaw by aliquoting.

• Documentation

  • For exact storage limits, retest intervals, and any stabilizers, refer to the lot-specific CoA and SDS.

Structure and Identity

A halogenated, bifunctional aromatic building block combining a para-benzylic ether linkage with a benzoic acid handle.

• Item-specific identifiers (from Product Data)

  • SKU: D942704
  • Product name: 4-(3,4-Dichlorophenoxymethyl)benzoic acid
  • CAS: 149288-42-6
  • CID: 22682749
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/computed structural information (for general reference; not product specification)

  • Core features: two benzene rings connected by a –CH2–O– (benzylic ether) linkage; a carboxylic acid at the para position of the benzylic ring; 3,4-dichloro substitution on the phenoxy ring.
  • Functional groups: carboxylic acid (aryl–CO2H), aryl ether (Ar–O–CH2–Ar′), benzylic methylene, two aryl chlorides.
  • Molecular formula (literature): C14H10Cl2O3
  • Molecular weight (literature): ~297.14 g/mol
  • 2D description: A para-substituted benzoic acid ring bears a –CH2–O– substituent that connects to a second phenyl ring; the distal ring carries Cl at the 3- and 4-positions relative to the ether oxygen.

• Stereochemistry: None (achiral, no stereocenters).

Synthetic Utility

• Transformations from the carboxylic acid (literature/general)

  • Amide formation: HATU/EDC/DIC with bases (DIPEA, NMM) to couple to primary/secondary amines; useful for library synthesis and linker installation.
  • Ester formation: Steglich esterification (DCC/DMAP) at room temperature or Fischer esterification under acid catalysis and refluxing alcohol.
  • Acid chloride formation: SOCl2 or oxalyl chloride (DMF catalytic) to generate acyl chlorides for subsequent acylations.
  • Curtius rearrangement: via acyl azide (DPPA or imidazolyl carbamate routes) to access isocyanates/urethanes.

• Leveraging the 3,4-dichloro aryl ring

  • Cross-coupling: Suzuki with boronic acids/esters; Buchwald–Hartwig with amines; Stille/Negishi with organostannanes/zinc reagents. Use ligands optimized for aryl chlorides (e.g., XPhos, SPhos) and bases like Cs2CO3, K3PO4.
  • Selectivity: The two chloro positions can exhibit differing reactivities depending on ligand/base and electronics, enabling stepwise functionalization.

• Benzylic ether considerations

  • Generally stable under neutral/basic conditions; susceptible to Lewis/Brønsted acid-promoted cleavage at elevated temperature, offering a route to unveil phenolic or benzyl alcohol derivatives if desired.

• Strategic value

  • Orthogonal handles (CO2H and C–Cl) enable convergent, late-stage diversification, ideal for parallel synthesis and SAR campaigns.

Target Specificity

Not applicable. This product is a small-molecule building block and is not an antibody, enzyme, or affinity reagent. No target, epitope, species reactivity, clone, or isotype information is applicable.

Häufig gestellte Fragen

How should this product be stored?

Store at room temperature.

What are the CAS number, molecular formula and molecular weight?

The CAS Number is 149288-42-6, the molecular formula is C14H10Cl2O3, and the molecular weight is 297.100 g/mol. InChIKey UWBZBSMZGHDZTA-UHFFFAOYSA-N.

What documentation is provided?

Available product documentation, including Certificates of Analysis (COA), Safety Data Sheets (SDS), and specification sheets, is shown in the product document area. Document availability and access follow the current site policy.