Ethyl 2-hydroxy-3-methoxybenzoate , CAS No.35030-98-9

CAS: 35030-98-9 Cat. No.: E962184 PubChem CID: 13682640

Storage

Room temperature

Specifications

Condiciones de almacenamiento de almacenamiento

Room temperature

Nombres e identificadores

• Sonrisas canónicas: CCOC(=O)C1=C(C(=CC=C1)OC)O
• IUPAC Name: ethyl 2-hydroxy-3-methoxybenzoate
• InChIKey: LTNLJNRZBZABNJ-UHFFFAOYSA-N
• INCHI: 1S/C10H12O4/c1-3-14-10(12)7-5-4-6-8(13-2)9(7)11/h4-6,11H,3H2,1-2H3
• Isómeros SMILES: CCOC(=O)C1=C(C(=CC=C1)OC)O
• PubChem CID: 13682640

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Clase 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
• Clase: 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: o-Hydroxybenzoic acid esters Salicylic acid and derivatives Methoxyphenols Phenoxy compounds Methoxybenzenes Benzoyl derivatives Anisoles Alkyl aryl ethers 1-hydroxy-4-unsubstituted benzenoids Vinylogous acids Carboxylic acid esters Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: O-hydroxybenzoic acid ester - M-methoxybenzoic acid or derivatives - Benzoate ester - Salicylic acid or derivatives - Methoxyphenol - Phenoxy compound - Anisole - Methoxybenzene - Phenol ether - Benzoyl - 1-hydroxy-4-unsubstituted benzenoid - Alkyl aryl ether - Phenol - Vinylogous acid - Carboxylic acid ester - Carboxylic acid derivative - Ether - Organooxygen compound - Hydrocarbon derivative - Organic oxygen compound - Organic oxide - Aromatic homomonocyclic compound
• Descripción: 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

Propiedades químicas y físicas

• Peso molecular: 196.200 g/mol
• XLogP3: 2.600
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 4
• Exact Mass: 196.074 Da
• Monoisotopic Mass: 196.074 Da
• Topological Polar Surface Area: 55.800 Ų
• Heavy Atom Count: 14
• Formal Charge: 0
• Complexity: 193.000
• 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 tested bioassay or analytical application protocols are provided for this catalog entry.
• General handling suggestions (non-binding)
  • Prepare concentrated stocks in dry DMSO or ethanol (e.g., 10–100 mM) for screening chemistry; filter (0.22 µm PTFE) if particulate is observed.
  • For synthetic runs, dry glassware and use anhydrous solvents to protect the ester. Validate conditions on small scale, then scale with appropriate calorimetry/controls.
• Any specific protocols, assay dilutions, or positive controls are: Not specified for this item; refer to CoA/Spec Sheet.

Biological Roles

• Item-specific (Product Data)
  • Research use: For research use only (per Product Data). Not for human or veterinary use.
• Literature/general context
  • Structural class: Salicylate-like phenolic benzoate bearing an additional methoxy substituent (anisole motif). Such scaffolds are common in plant-derived phenolics and synthetic analogs used to probe structure–activity relationships in enzyme inhibition, metal chelation, and redox behavior.
  • Phenolic functionality: Capable of hydrogen bonding and weak metal chelation (via o‑OH/carbonyl), a motif often leveraged in assays of metalloenzymes or as ligating fragments in medicinal chemistry. The methoxy group modulates lipophilicity and electron density relative to simple salicylates.
  • Metabolic considerations: In biotic systems, aryl esters can undergo hydrolysis (esterases) to yield the corresponding acid and ethanol; phenolic O‑conjugation (glucuronidation/sulfation) is a common detoxification route. These are general pathways for phenolic esters and not specific performance claims for this item.
  • Assay relevance: The balance of H‑bond donor (phenolic OH) and acceptors (carbonyl, methoxy) makes this scaffold useful in fragment-based screening or as a reference aromatic phenol in binding/partition experiments, subject to purity and solubility constraints confirmed via CoA.

Buffer Applications

• Not typically applicable. Ethyl 2‑hydroxy‑3‑methoxybenzoate is a neutral aromatic ester with a single weakly acidic phenolic OH and does not serve as a conventional buffering agent over common biochemical pH ranges.
• Practical note: If dissolved for biochemical assays, choose an appropriate co-solvent (e.g., DMSO or ethanol) and a compatible buffer system for the biological target. Avoid high pH if ester stability is required, as basic buffers promote hydrolysis.

Green Alternatives

• Context: This product is a reagent/building block rather than a process solvent. Greener practice focuses on solvent choice and transformations that minimize waste while manipulating the phenol/ester functions.
• Greener solvent choices (literature/general)
  • Prefer EtOAc, MeTHF, 2‑MeTHF, CPME, or ethanol over chlorinated solvents where feasible. Use MeCN over DMF/DMSO when solvency permits for easier workup and lower EHS footprint.
• Greener transformations
  • O‑Alkylation using green alkylating agents (e.g., dimethyl/diethyl carbonate under base catalysis) can replace alkyl halides; these routes generate benign byproducts (CO2, alcohols).
  • Enzymatic or biocatalytic transesterification (lipases) in green media (2‑MeTHF, supercritical CO2, solvent-free) for selective modification of the phenol/ester.
  • Direct amidation from the ester using catalytic systems (e.g., alkoxide catalysis or boronic catalysts) avoids separate acid activation.
• Comparison (general tradeoffs)
  • EtOAc vs DCM: EtOAc is biodegradable and less toxic but may require longer reaction times or higher temperatures for equivalent rates.
  • 2‑MeTHF/CPME vs THF: Higher hydrophobicity eases product isolation and reduces peroxide concerns (still monitor), but may impact base solubility.
  • Dimethyl carbonate vs MeI/EtBr: Far safer and greener; may need higher temperature/pressure or catalysts.
• Waste minimization
  • Use catalytic rather than stoichiometric activators (e.g., organoborates for amidation), and design telescoped sequences that avoid isolating intermediates vulnerable to hydrolysis.

Pharmaceutical Uses

• Item-specific (Product Data)
  • No pharmacopeial grade or excipient designation provided. For this catalog item: Not specified for this item; refer to CoA/Spec Sheet.
• Literature/general context (no therapeutic claims)
  • Role in development: Substituted salicylate esters like this are frequently used as intermediates or reference materials in medicinal chemistry campaigns to explore SAR around phenolic benzoates (altering lipophilicity, H‑bonding, and metabolic lability).
  • Formulation relevance: As a small aromatic ester with a phenolic OH, it can serve as a model compound for studying ester stability, esterase-mediated cleavage, and solubility enhancement strategies (salt formation requires prior derivatization, e.g., masking the phenol or converting the ester to an acid/amidic form).
  • Analytical considerations: If used in preformulation studies, confirm UV–Vis characteristics and HPLC behavior using the actual batch CoA; ensure volatile/residual solvent and non-volatile residue specifications meet internal thresholds for your analytical workflow.
  • Regulatory note: Absent compendial monographs and explicit grade claims, this material should be treated strictly as a research chemical with no implication of suitability for human or veterinary drug products.

Physical Properties

• Item-specific (Product Data)
  • Appearance: Not specified for this item; refer to CoA/Spec Sheet.
  • Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
  • Measured BP/MP, density, refractive index, UV cutoff, residuals/metals: Not specified for this item; refer to CoA/Spec Sheet.
• Literature/general (reference values; not item specifications)
  • Phase/volatility: Aromatic salicylate esters of this size (MW ~196) are typically low-volatility liquids or low-melting solids; exact MP/BP for this specific isomer should be confirmed in primary literature or CoA.
  • Solubility profile (qualitative):
    • Organic: Expected to be soluble in common organics (e.g., DMSO, DMF, acetone, EtOAc, MeOH/EtOH, CH2Cl2) due to the aromatic core and mixed polar functionality.
    • Aqueous: Phenolic/aromatic esters are generally sparingly soluble in water at neutral pH; solubility increases in basic media via phenolate formation or upon ester hydrolysis to the corresponding acid/salt.
  • Acid–base behavior: Contains one phenolic OH (weakly acidic, phenol-like). The ester is neutral; no basic centers.
  • Polarity: Moderate polarity from phenol and ester balanced by aromatic/methoxy; logP expected in the low-to-moderate range typical of substituted anisole benzoates (exact value not located).
  • Intramolecular H‑bonding between the 2‑OH and the ester carbonyl can reduce effective polarity and influence NMR/IR signatures (e.g., downfield OH, carbonyl shift).
• Practical tips
  • For weighing/dosing, warm gently if semi-solid; choose a polar aprotic (DMSO/DMF) for stock solutions, or EtOH/MeOH for bio-adjacent assays if compatible.

Quality and Grades

• Item-specific (Product Data)
  • Grade/purity and stabilizers: Not specified for this item; refer to CoA/Spec Sheet.
• General guidance on grades (context for selection)
  • Research grade: Suitable for routine synthesis and screening where trace UV-absorbers, non-volatile residues, or trace metals are not critical.
  • High-purity/analytical grades: Tighter limits on volatile/非挥发性残留、UV背景以及金属杂质，适合光谱分析或敏感催化反应。 Confirm via CoA when chromatography/photophysical studies demand low background.
  • Stabilizers/inhibitors: Not typically required for benzoate esters; if present (rare), they would be listed on the CoA. Absence/presence of stabilizer impacts downstream reactions (e.g., base-catalyzed steps). Always verify before kinetic or materials studies.
  • Batch-specific CoA: For this product, please consult the Aladdin CoA for assay, water content (Karl Fischer), residual solvents, and chromatographic purity. If you need application-specific specs (e.g., peroxides, trace metals, UV cutoff), request a targeted CoA—otherwise: Not specified for this item; refer to CoA/Spec Sheet.

Reaction and Applications

• General application profile (literature/general)
  • Versatile salicylate building block combining a chelating o‑phenol and an aryl ester. Useful in medicinal chemistry and materials discovery programs where substituted salicylates/anisoles are desired.
• Representative transformations
  • O‑Derivatization of the phenol: Alkylation (Williamson ether synthesis), acylation (to carbonate/esters), and carbamate formation. Bases: K2CO3/Cs2CO3 or NaH; solvents: DMF/MeCN/acetone; temperatures: rt–80 °C.
  • Ester chemistry: Hydrolysis (acidic or basic) to 2‑hydroxy‑3‑methoxybenzoic acid; transesterification to other alkyl esters using ROH/H+ or RO−/phase-transfer; coupling to amides via activation (e.g., DCC/DMAP, EDCI) after converting to the acid.
  • Electrophilic aromatic substitution: The phenol and methoxy activate the ring (ortho/para directors) while the ester is meta‑directing/deactivating. Strategic halogenation, nitration (mild), or Friedel–Crafts acylation can be directed to 4/6‑positions with appropriate protecting groups.
  • Metalation/chelation: The o‑OH–carbonyl motif supports intramolecular chelation, enabling directed ortho metalation or facilitating cyclizations to benzofuranone/ coumarin-like scaffolds under dehydrative conditions.
  • Cross-coupling after halogenation: Prepare aryl bromides/chlorides at desired positions, then use Suzuki/ Buchwald–Hartwig to elaborate the core while retaining or modifying the phenol (protected if necessary).
• Practical tips
  • Protect the phenol (e.g., as MOM, Bn, TBDMS) when strong bases or metal catalysts risk side reactions.
  • Anhydrous conditions minimize competing hydrolysis/transesterification of the ester during base-mediated steps.

Reaction Conditions

• General conditions (literature guidance; confirm experimentally)
  • O‑Alkylation of phenol: Base (K2CO3/Cs2CO3, 1.5–2.5 equiv) in dry DMF/MeCN/acetone, alkyl halide (1.1–1.5 equiv), 25–80 °C, 2–16 h. For hindered substrates, NaH (1.1–1.5 equiv) in THF/DMF at 0–25 °C then add electrophile.
  • O‑Acylation/carbonate: Acyl chloride or chloroformate (1.1–1.5 equiv), base (pyridine/Et3N), DCM/EtOAc, 0 °C to rt, 1–4 h; catalytic DMAP accelerates.
  • Hydrolysis of ester to acid: Aqueous NaOH or K2CO3 (1–2 M) in MeOH/H2O or THF/H2O, 25–60 °C, 1–6 h; or acid-catalyzed (HCl/MeOH reflux) as appropriate. Work up by acidification and extraction.
  • Transesterification: ROH (excess) with catalytic acid (p‑TsOH, H2SO4) under Dean–Stark or azeotropic removal of alcohol; or base-catalyzed using alkoxide in the corresponding alcohol, 25–60 °C.
  • Electrophilic aromatic substitution: For nitration/halogenation, use mild conditions (e.g., NBS/NCS in AcOH/DMF; nitration with dilute HNO3 in AcOH) due to activating methoxy/phenol; protect phenol to enhance regioselectivity.
  • Cross-coupling (after aryl halide formation): Pd catalysts (e.g., Pd(PPh3)4, Pd2(dba)3/XPhos), bases (K3PO4, Cs2CO3), solvents (toluene/DMF/dioxane), 60–110 °C, 2–18 h.
• Monitoring/analytics
  • TLC in hexanes/EtOAc or DCM/MeOH; UV 254 nm typically responsive. Intramolecular H‑bonding can shift IR ν(OH) broad and carbonyl ν(C=O) relative to non‑H‑bonded esters.
  • Quench basic reactions carefully to avoid emulsions; include brine and phase swaps as needed.

Safety and Handling

• Item-specific (Product Data)
  • GHS classification, pictograms, signal word, and H‑statements: Not specified for this item; refer to SDS.
  • Storage: Room temperature (per Product Data).
• General safety guidance (consult the SDS for authoritative instructions)
  • Likely hazards: Aromatic esters/phenols commonly cause eye/skin/respiratory irritation. Avoid inhalation of vapors/aerosols and contact with skin/eyes. Phenolic compounds can be harmful if ingested.
  • PPE: Lab coat, safety glasses, and appropriate chemically resistant gloves (e.g., nitrile). Use in a fume hood to minimize inhalation exposure.
  • Incompatibilities: Strong oxidizers (risk of exothermic reaction/oxidation), strong bases (promote transesterification or hydrolysis; phenolate formation), and strong acids (acid-catalyzed transesterification/hydrolysis). Avoid prolonged exposure to moisture if ester integrity is critical.
  • Handling: Keep container tightly closed. Minimize heat exposure if purity must be maintained. Avoid prolonged light exposure to limit potential discoloration.
  • First aid (overview):
    • Skin/eye contact: Rinse with copious water for ≥15 minutes; remove contaminated clothing; seek medical attention if irritation persists.
    • Inhalation: Move to fresh air; seek medical attention for symptoms.
    • Ingestion: Rinse mouth; do not induce vomiting; seek medical advice.
  • Spill response: Absorb with inert material (vermiculite), place in chemical waste. Prevent entry to drains. Decontaminate area with detergent/ethanol as appropriate.
  • Disposal: Treat as organic chemical waste consistent with local regulations.

Solvent Selection

• Applicability: This compound is a functionalized aromatic ester (reagent/building block), not a bulk solvent. The focus is on choosing solvents to dissolve or react it efficiently.
• Solubility/miscibility (literature/general)
  • Polar aprotics (DMSO, DMF, NMP): Excellent solvency for stock solutions and for SNAr, O‑alkylation, or metalation protocols.
  • Moderately polar organics (EtOAc, acetone, MeCN): Good for workups, extractions, and many catalytic transformations.
  • Alcohols (MeOH, EtOH, i‑PrOH): Useful for transesterification or hydrogenolysis media; phenolic H may participate in H‑bonding.
  • Nonpolar (toluene, xylene): Suitable for high‑temperature reactions, Friedel–Crafts chemistry; solubility may require heating.
  • Aqueous: Sparingly soluble at neutral pH; solubility increases in basic media (phenolate formation) but risks ester hydrolysis.
• Selection tips
  • Reaction planning: For base‑mediated O‑alkylation/acylation of the phenol, use dry polar aprotic solvents (DMF/DMSO/MeCN) with suitable bases (K2CO3, Cs2CO3, NaH) and phase-transfer catalysts if needed.
  • Avoid strong protic/basic aqueous systems when ester integrity must be preserved. Use buffered or anhydrous conditions.
  • For chromatographic purification, EtOAc/hexanes or DCM/MeOH gradients typically give clean separations of salicylate derivatives.
• Comparisons
  • MeCN vs DMF: MeCN offers easier removal and lower background; DMF gives higher solubility for salts/bases.
  • EtOAc vs DCM: EtOAc is greener and often sufficient; DCM affords higher elution strength but with higher environmental/safety burdens.

Storage and Reconstitution

• Item-specific (Product Data)
  • Storage conditions: Room temperature.
  • Shipped in: Not specified for this item; refer to CoA/Spec Sheet.
• General guidance
  • Container: Store in a tightly sealed, chemically compatible container (amber glass recommended) to limit moisture and light exposure.
  • Stability: Benzoate esters are generally stable at ambient conditions; avoid prolonged exposure to strong light, heat, or moisture to minimize hydrolysis/discoloration.
  • Reconstitution/stock solutions: Dissolve in dry DMSO, DMF, ethanol, methanol, acetone, EtOAc, or CH2Cl2 as needed. For biological assays, DMSO or ethanol stocks are typical; dilute into buffer immediately before use with vigorous mixing to avoid precipitation.
  • Freeze–thaw: If solutions must be stored, aliquot and keep at −20 to −80 °C to avoid repeated freeze–thaw. Inspect for precipitation or degradation before reuse.
  • Shelf life: For definitive retest/expiry information, refer to the Aladdin CoA/Spec Sheet for the specific lot.
  • Compatibility: Avoid strong bases/acids in storage solutions unless intentional (e.g., saponification); moisture control is recommended when ester integrity is critical.

Structure and Identity

• Item-specific (Product Data)
  • Product name: Ethyl 2-hydroxy-3-methoxybenzoate (CAS 35030-98-9)
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.
  • Storage: Room temperature (per Product Data)
• Literature/computed (for reference only; not item specifications)
  • Common description: Ethyl ester of 2-hydroxy-3-methoxybenzoic acid; a salicylate-type aromatic ester bearing both a phenolic OH (ortho to the ester) and an anisole (3‑methoxy) substituent.
  • Molecular formula (computed from name): C10H12O4
  • Molecular weight (computed): ~196.20 g/mol
  • Structural features: One benzene ring; substituents arranged as 1‑CO2Et, 2‑OH, 3‑OCH3 (relative to the carboxyl carbonyl as position 1). Functional groups include an aryl ester (benzoate), a phenolic hydroxyl capable of intramolecular H‑bonding to the carbonyl, and a methoxy ether.
  • 2D structure in words: A benzoate framework with an ethyl ester at C1. Adjacent (ortho) to the ester at C2 is a phenolic OH; at C3 (meta to carbonyl, ortho to OH) is a methoxy substituent. This o‑hydroxy/methoxy pattern creates a chelating, H‑bonded salicylate-like motif.
• General notes
  • The ortho‑OH often forms a six‑membered intramolecular H‑bond to the ester carbonyl, influencing conformation, acidity, and reactivity.

Synthetic Utility

• Functional group leverage
  • Phenolic OH (ortho to ester): Amenable to selective O‑alkylation, acylation, sulfonylation, and carbonate formation. It can be temporarily protected (MOM, Bn, TBDMS) to direct reactivity elsewhere on the ring.
  • Aryl ester: Stable to many conditions yet transformable via hydrolysis to the acid, transesterification to tune leaving group ability, or conversion to acid chlorides after hydrolysis.
  • Anisole (3‑OMe): Electron‑donating/activating; site-selectivity can be orchestrated in electrophilic aromatic substitutions with appropriate protection.
• Strategic roles in synthesis
  • Directed ortho chemistry: The o‑OH···O=C chelation motif supports directed metalation or cyclizations leading to benzofuranone/coumarin-like frameworks under dehydrative conditions (e.g., base or Lewis acid catalysis).
  • Late-stage diversification: Halogenation at positions activated by phenol/methoxy allows subsequent cross-couplings (Suzuki, Buchwald–Hartwig, Sonogashira) to access libraries of densely functionalized salicylate derivatives.
  • Linker chemistry: The ester can be a handle to introduce amide linkages (after hydrolysis/activation), enabling conjugation to amines or polymers for materials studies.
• Practical guidance
  • Control chemoselectivity by protecting the phenol when needed; otherwise, O‑alkylation may outcompete C‑arylation.
  • Maintain anhydrous conditions during base-mediated steps to prevent undesired ester cleavage; monitor by TLC/HPLC due to potential intramolecular H‑bonding affecting Rf/retention.

Target Specificity

• Not applicable. This product is a small organic reagent, not a biological targeting reagent (e.g., antibody, inhibitor with defined target annotation) in this catalog entry.
• No antigen/epitope/isotype or species reactivity information is provided in the Product Data.