Ethyl 2-chloro-6-methylbenzoate - ≥98% , CAS No.773139-06-3

CAS: 773139-06-3 Cat. No.: E1013568 Fórmula: C₁₀H₁₁ClO₂ Peso molecular: 198.640

GRADE & PURITY ≥98%

Storage

Room temperature

Specifications

Especificações e pureza

≥98%

Condições de armazenamento de armazenamento

Room temperature

Pureza

≥98%

Nomes e identificadores

Sorrisos canónicos

CCOC(=O)C1=C(C=CC=C1Cl)C

IUPAC Name

ethyl 2-chloro-6-methylbenzoate

InChIKey

DUKSBWBJTZVOPF-UHFFFAOYSA-N

INCHI

1S/C10H11ClO2/c1-3-13-10(12)9-7(2)5-4-6-8(9)11/h4-6H,3H2,1-2H3

Peso molecular

198.640

Taxonomic Classification

Taxonomy Tree

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

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Classe: Benzene and substituted derivatives
• Subclass: Benzoic acids and derivatives
• Intermediate Tree Nodes: Not available
• Direct Parent: Benzoic acid esters
• Alternative Parents: 2-halobenzoic acids and derivatives Benzoyl derivatives Toluenes Chlorobenzenes Aryl chlorides Vinylogous halides Carboxylic acid esters Organooxygen compounds Organochlorides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Benzoate ester - 2-halobenzoic acid or derivatives - Halobenzoic acid or derivatives - Benzoyl - Toluene - Halobenzene - Chlorobenzene - Aryl halide - Aryl chloride - Vinylogous halide - Carboxylic acid ester - Carboxylic acid derivative - Hydrocarbon derivative - Organic oxide - Organooxygen compound - Organochloride - Organohalogen compound - Organic oxygen compound - Aromatic homomonocyclic compound
• Descrição: This compound belongs to the class of organic compounds known as benzoic acid esters. These are ester derivatives of benzoic acid.
• 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

Propriedades químicas e físicas

• Peso molecular: 198.640 g/mol
• XLogP3: 3.000
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 3
• Exact Mass: 198.045 Da
• Monoisotopic Mass: 198.045 Da
• Topological Polar Surface Area: 26.300 Ų
• Heavy Atom Count: 13
• Formal Charge: 0
• Complexity: 182.000
• 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. No immunoassay or cell-based application protocols (WB, IHC, IF, FC) are associated with this small-molecule building block. Item-specific tested applications and dilutions: Not specified for this item; refer to CoA/Spec Sheet.

For synthetic use, see the Reaction Conditions and Synthetic Utility sections for general laboratory procedures.

Biological Roles

This product is an aromatic ester building block not known to have endogenous biological roles.

• General considerations (literature/general):

  • Aromatic benzoate esters are typically metabolized by esterases to the corresponding carboxylic acids and alcohols. Hydrolysis of this compound would yield 2-chloro-6-methylbenzoic acid and ethanol.
  • The aryl chloride and hydrophobic ring system suggest it would behave as a xenobiotic in biological systems, with metabolic pathways likely involving hydrolysis followed by oxidative transformations of the aromatic ring.

• Research context:

  • Any biological testing should treat this compound as a synthetic intermediate; it is not intended for use in humans or animals except for research as permitted by institutional guidelines.

• No claims of biological activity are made. For biochemical experiments requiring defined biological roles, choose validated standards or metabolites.

Buffer Applications

Not typically applicable. Ethyl 2-chloro-6-methylbenzoate is a hydrophobic organic building block and is not used as a buffering agent. If dissolution in aqueous media is required for assays, consider:

• Using co-solvents (DMSO, ethanol) at minimal percentages compatible with the system.
• Formulating with surfactants or cyclodextrins when appropriate for research assays.

For true buffer preparation, select established buffering systems (phosphate, HEPES, Tris) suited to your pH range.

Green Alternatives

While the molecule itself is fixed, greener choices can be made in solvent and catalytic system selection for its transformations.

• Greener solvent choices (literature/general):

  • Replace dioxane/DMF with 2-MeTHF, CPME, Me-THF/water, or propylene carbonate when compatible.
  • Favor toluene/EtOAc or bio-based ethyl acetate for extractions and chromatography over chlorinated solvents when resolution allows.

• Cross-coupling improvements:

  • Use ligand-enabled Pd systems effective in aqueous or semi-aqueous media (e.g., water-soluble phosphines, micellar catalysis) to reduce organic solvent usage.
  • Explore Ni-catalyzed couplings of aryl chlorides with Mn/Zn reductants under milder conditions to reduce Pd usage; consider heterogeneous catalysis when feasible.

• Energy and waste minimization:

  • Microwave or flow chemistry can shorten reaction times and reduce solvent volumes for couplings and reductions.
  • Choose bases with better EHS profiles (K3PO4, K2CO3) and avoid stoichiometric organotin reagents.

Comparison snapshot (general)

• Dioxane vs 2-MeTHF: Similar coordinating ability; 2-MeTHF is bio-derived and has better EHS profile but can absorb water—dry before moisture-sensitive steps.
• DCM vs EtOAc: DCM offers superior solvating power and easy removal but is halogenated with higher EHS concerns; EtOAc is greener and often adequate for workups/purification.

Pharmaceutical Uses

No pharmacopeial status or excipient role is provided for this item.

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

General context (for R&D only; no therapeutic claims)

• This compound can serve as a synthetic intermediate in medicinal chemistry campaigns where ortho-substituted benzoate scaffolds are explored.
• Typical roles include:
  • Aryl chloride handle for Pd-catalyzed diversification (SAR exploration).
  • Ester as a protected acid, enabling late-stage hydrolysis to the corresponding carboxylate for amide couplings.

Regulatory note

• For research use only. Not for use in diagnostic procedures or as an API/excipient without appropriate qualification and regulatory review.

Physical Properties

Item-specific specs are not provided; values below are general expectations for an aryl benzoate and should be confirmed experimentally.

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Boiling point: Not specified for this item; refer to CoA/Spec Sheet. (Aryl benzoate esters typically boil in the 200–280 °C range; literature expectation only.)
• Melting point: Not specified for this item; refer to CoA/Spec Sheet.
• Density: Not specified for this item; refer to CoA/Spec Sheet. (Aromatic esters often ~1.05–1.20 g/mL; literature expectation only.)
• Solubility (qualitative, literature/general):
  • Poorly soluble in water (aromatic ester, logP expected >2; literature/general).
  • Readily soluble in common organic solvents (e.g., DCM, EtOAc, THF, toluene, acetone; literature/general).
• Refractive index, UV cutoff, water/peroxide/metal limits: Not specified for this item; refer to CoA/Spec Sheet.
• pKa/logP: Not specified for this item; refer to CoA/Spec Sheet. (Ester is non-ionizable under neutral conditions; literature/general.)

Notes for users

• Expect a hydrophobic liquid or low-melting solid depending on purity and temperature; verify before handling.
• Verify any numeric property against the lot-specific CoA when planning distillation, formulation, or scale-up.

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.

Guidance on interpreting typical grades (general)

• Analytical/Reagent grade: Indicates low impurity levels suitable for synthesis and analytical work; may include tighter limits on acidity/alkalinity, non-volatile residue.
• Synthesis grade: Suitable for routine organic reactions; verify halide content, acidity, and residual solvents where they influence catalysis (e.g., Pd-catalyzed couplings).
• HPLC grade solvents are not applicable here; for this substrate, what matters is assay purity and residual inorganic halide or acid.

Impurities of concern (general for aryl esters)

• Hydrolysis products (2-chloro-6-methylbenzoic acid, ethanol)
• Transesterification coproducts (if processed in alcohols)
• Residual halogenated aromatics or regioisomers from synthesis

Recommendations

• Consult the lot-specific CoA for assay (%), water (Karl Fischer), and residual solvent profile, if reported.
• For cross-coupling applications, consider pre-washing with base or drying over molecular sieves to minimize adventitious acid/moisture that can inhibit catalysts.

Reaction and Applications

As a bifunctional aryl substrate, Ethyl 2-chloro-6-methylbenzoate supports diverse transformations on both the aryl chloride and the benzoate ester.

• Aryl chloride chemistry (literature/general):
  • Cross-couplings: Suzuki–Miyaura (to install aryl/alkenyl/alkyl groups), Buchwald–Hartwig amination, Negishi, Kumada, and Stille. Ortho substituents (ester/methyl) can influence oxidative addition and selectivity; bulky ligands (e.g., SPhos/XPhos/BrettPhos) often enhance reactivity of aryl chlorides.
  • Lithiation/magnesiation: Directed ortho-metalation is less relevant due to substitution pattern but lithium–halogen exchange (e.g., with iPrMgCl·LiCl or n-BuLi at low T) can generate 2-lithiated intermediates for electrophile trapping; exercise caution with ester compatibility (protect or use milder bases).
  • Nucleophilic aromatic substitution (SNAr): Generally unfavorable on simple aryl chlorides without strong ring deactivation; cross-coupling is preferred.
• Ester chemistry (literature/general):
  • Hydrolysis (acidic/basic) to 2-chloro-6-methylbenzoic acid for amide formation or further derivatization (e.g., acid chloride via SOCl2, then amidation).
  • Reductions: DIBAL-H to the aldehyde (low T, controlled equivalents) or LiAlH4/borane to benzyl alcohol derivatives.
  • Transesterification: Under acid/base catalysis to adjust protecting group or volatility.
• Applications as a building block:
  • Assembly of ortho-substituted biaryls via Suzuki couplings.
  • Introduction of anilines via Pd-catalyzed amination to access o-methyl anthranilate analogs (after modifying the ester).
  • Scaffold for agrochemical/materials intermediates where ortho substitution controls conformational bias.

Reaction Conditions

The following are literature-style, general conditions for typical transformations of aryl chlorides and benzoate esters. Optimize per substrate and scale.

• Suzuki–Miyaura coupling (aryl chloride to biaryl):
  • Catalyst: Pd(dppf)Cl2·DCM (1–3 mol%) or Pd2(dba)3 (1 mol%) with SPhos/XPhos (2–4 mol%)
  • Base: K3PO4 (2–3 equiv) or K2CO3; sometimes Cs2CO3 for challenging partners
  • Solvent: 1,4-dioxane, toluene, 2-MeTHF, or dioxane/water (10–20%)
  • Temperature/time: 80–110 °C, 2–16 h
  • Notes: Ortho substitution may necessitate higher temperature/ligand loading.
• Buchwald–Hartwig amination:
  • Catalyst/ligand: Pd2(dba)3 (1–2 mol%) with BrettPhos or RuPhos (2–4 mol%)
  • Base: NaOtBu or K3PO4
  • Solvent: Toluene, dioxane, or CPME
  • Temperature: 80–110 °C
• Ester hydrolysis to acid:
  • Basic: NaOH or KOH (1–3 equiv) in MeOH/H2O or THF/H2O, 25–65 °C, 2–12 h
  • Acidic: Aqueous HCl or H2SO4 in EtOH/H2O, reflux
  • Workup: Neutralize and isolate acid by acidification/extraction.
• Ester reduction:
  • DIBAL-H (1.1–1.5 equiv) in toluene or CH2Cl2 at −78 to −40 °C to aldehyde
  • LiAlH4 (1.5–2.0 equiv) in THF/Et2O, 0–25 °C to primary alcohol; caution with aryl chloride stability

All conditions are literature/general guidance; verify on small scale and monitor by TLC/GC/LCMS.

Safety and Handling

Authoritative safety information must be taken from the product SDS. Item-specific GHS fields are not provided in the Product Data.

• GHS classification, pictograms, signal word, H-statements: Not specified for this item; refer to SDS.
• Likely hazards (general for aromatic esters/aryl chlorides; not item-specific):
  • Combustible liquid; may cause eye/skin irritation and respiratory irritation on vapor/mist exposure.
  • Harmful if swallowed or inhaled; avoid aerosol formation.
• Incompatibilities (general):
  • Strong oxidizers (risk of exotherm/combustion)
  • Strong bases or acids (can promote hydrolysis/transesterification)
  • Powerful reducing agents (ester reduction)
• PPE (good laboratory practice):
  • Safety glasses or goggles; nitrile gloves; lab coat. Use in a fume hood to avoid inhalation of vapors.
• First-aid overview (general guidance; defer to SDS):
  • Inhalation: Move to fresh air, monitor breathing, seek medical attention if symptoms persist.
  • Skin/eye contact: Rinse with water for at least 15 minutes; remove contaminated clothing; seek medical attention as needed.
  • Ingestion: Rinse mouth; do not induce vomiting; get medical advice.
• Handling tips:
  • Avoid moisture if ester integrity is critical.
  • Keep containers tightly closed; ground/bond during transfer if large volumes are used.
• Waste: Collect organic waste according to institutional and local regulations; do not release to drains.

Solvent Selection

This compound is a hydrophobic aromatic ester/aryl chloride building block. Choose solvents to balance solubility, reaction needs, and downstream workup.

• Polarity/solubility profile (literature/general):
  • High solubility in chlorinated and aromatic solvents (DCM, chloroform, toluene, xylene)
  • Good solubility in ethers and ketones (THF, CPME, MTBE, acetone, MEK)
  • Limited solubility in alcohols; poor in water
• Typical selections by application:
  • Pd-catalyzed cross-coupling (Suzuki/Buchwald–Hartwig): Toluene, 1,4-dioxane, CPME, or 2-MeTHF; often with water/EtOH co-solvent for base dissolution.
  • Nucleophilic acyl substitution after hydrolysis (amide couplings): DMF, NMP, DCM, or EtOAc depending on coupling system.
  • Reductions of the ester (DIBAL-H/LiAlH4): Toluene/hexanes/Et2O/THF at low temperature; ensure complete dissolution for controlled addition.
• Workup/purification considerations:
  • EtOAc/hexanes systems generally provide good chromatographic resolution for benzoate esters.
  • Avoid highly protic media if hydrolysis is undesirable.
• Practical tips:
  • For poorly soluble catalytic systems, increase temperature or use polar, coordinating solvents (THF/dioxane) with modern ligands that tolerate them.
  • In aqueous biphasic couplings, add phase-transfer bases (K3PO4/K2CO3) and surfactants as appropriate.

Storage and Reconstitution

• Storage (item-specific from Product Data): Store at room temperature. Protect from moisture and strong light. Keep container tightly closed.
• Shipped in: Not specified for this item; refer to CoA/Spec Sheet.
• Reconstitution: Not typically applicable; this is a neat organic compound. If a concentrated stock solution is desired for screening:
  • Dissolve in a dry, compatible solvent (e.g., DMSO, THF, toluene, or EtOAc) under inert atmosphere if moisture-sensitive transformations are planned.
  • Filter if particulates are present; store solutions in amber vials at 2–8 °C or −20 °C depending on solvent stability.
• Stability considerations (general):
  • Esters can hydrolyze slowly in the presence of moisture, acids, or bases; minimize exposure to such conditions during storage.
  • Avoid prolonged exposure to elevated temperatures.

Always consult the lot-specific CoA/SDS for additional storage and handling details.

Structure and Identity

Brief description: Ethyl 2-chloro-6-methylbenzoate is an ortho-chloro, ortho-methyl substituted ethyl benzoate (an aromatic ester building block). The aryl chloride enables cross-coupling, while the benzoate can be transformed via hydrolysis or reduction.

• Item-specific identifiers (Product Data)
  • SKU: E1013568
  • Product Name: Ethyl 2-chloro-6-methylbenzoate
  • CAS: 773139-06-3
  • PubChem CID: 55256025
  • InChIKey: 73148 (as provided)
  • Storage: Room temperature
  • Research Use Note: For research use only
• Structure description (general/interpretive)
  • Core: Benzene ring bearing an ethyl benzoate (–CO2Et) at C1
  • Substituents: Chlorine at C2 (ortho to the ester) and methyl at C6 (the other ortho position)
  • Functional groups: Aromatic chloride (aryl–Cl), aromatic ester (benzoate, –CO2Et)
  • Stereochemistry: None (achiral)
• Computed/literature identifiers (not item-specific)
  • Molecular formula (computed from name): C10H11ClO2 (literature/computed)
  • Molecular weight (computed): ~198.65 g/mol (literature/computed)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.
  • InChI: Not specified for this item; refer to CoA/Spec Sheet.

Synthetic Utility

Functional group set: aryl chloride plus benzoate ester on an ortho-methyl substituted benzene provides orthogonal handles for selective transformations.

• Diversification at the aryl chloride (literature/general):
  • Suzuki–Miyaura: Couple with boronic acids/esters to access 2-substituted-6-methyl benzoates; ester survives typical conditions.
  • Buchwald–Hartwig amination: Install anilines with Pd/XPhos/SPhos/BrettPhos ligands; sterics from ortho substituents can aid selectivity but require robust catalysts.
  • Carbonylation chemistry: Under CO pressure with Pd to form benzoates/benzamides after hydrolysis/activation.
• Manipulation of the ester:
  • Hydrolysis to acid, then amide/acid chloride/anhydride formation as needed.
  • Alcoholysis or transesterification to tune protecting group or solubility.
  • Reductive pathways: DIBAL-H (to aldehyde) or LiAlH4/borane (to primary alcohol) with attention to possible concurrent dechlorination under harsh conditions.
• Ortho effects and reactivity:
  • The ortho methyl and ester increase steric hindrance; choose bulky/electron-rich ligands to accelerate oxidative addition to the aryl chloride.
  • Directed metalation is constrained; lithium–halogen exchange is feasible at low temperature, but the ester must be protected from strong bases or used with metal–halogen exchange agents compatible with esters (e.g., iPrMgCl·LiCl).

Synthetic planning tip: Preserve the ester during aryl chloride cross-coupling, then unmask to the acid at a late stage for convergent amide coupling.

Target Specificity

Not applicable. This product is a small-molecule building block, not a biological targeting reagent. No antigen/epitope, clone, isotype, or species reactivity applies. Item-specific targeting data: Not specified for this item; refer to CoA/Spec Sheet.