3-Ethyl-4-methoxybenzoic acid - ≥98% , CAS No.22934-35-6

CAS: 22934-35-6 Cat. No.: E952920 Formula: C₁₀H₁₂O₃ Molecular Weight: 180.200

GRADE & PURITY ≥98%

Storage

Room temperature

Specifications

Specifications & Purity

≥98%

Storage

Room temperature

Purity

≥98%

Names and Identifiers

• Canonical Smiles: CCC1=C(C=CC(=C1)C(=O)O)OC
• IUPAC Name: 3-ethyl-4-methoxybenzoic acid
• InChIKey: FPHXIFFANOEDCL-UHFFFAOYSA-N
• INCHI: 1S/C10H12O3/c1-3-7-6-8(10(11)12)4-5-9(7)13-2/h4-6H,3H2,1-2H3,(H,11,12)
• Molecular Weight: 180.200

Taxonomic Classification

Taxonomy Tree

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

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Class: Benzene and substituted derivatives
• Subclass: Benzoic acids and derivatives
• Intermediate Tree Nodes: Methoxybenzoic acids and derivatives
• Direct Parent: P-methoxybenzoic acids and derivatives
• Alternative Parents: Benzoic acids Phenoxy compounds Methoxybenzenes Benzoyl derivatives Anisoles Alkyl aryl ethers Carboxylic acids Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: P-methoxybenzoic acid or derivatives - Benzoic acid - Phenoxy compound - Anisole - Methoxybenzene - Phenol ether - Benzoyl - Alkyl aryl ether - Ether - Carboxylic acid - Carboxylic acid derivative - Organic oxygen compound - Organooxygen compound - Hydrocarbon derivative - Organic oxide - Aromatic homomonocyclic compound
• Description: This compound belongs to the class of organic compounds known as p-methoxybenzoic acids and derivatives. These are benzoic acids in which the hydrogen atom at position 4 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

Chemical and Physical Properties

• Molecular Weight: 180.200 g/mol
• XLogP3: 2.300
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 3
• Exact Mass: 180.079 Da
• Monoisotopic Mass: 180.079 Da
• Topological Polar Surface Area: 46.500 Ų
• Heavy Atom Count: 13
• Formal Charge: 0
• Complexity: 179.000
• 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 tested bioassay protocols (e.g., WB, IHC, IF, FC) are associated with this small-molecule building block. For chemical synthesis use, see the Reaction & Applications and Reaction Conditions tabs for practical guidance.

Biological Roles

Applicability note

• This compound is a synthetic, substituted benzoic acid used as a chemical building block. It is not intended for biological administration. The points below provide biochemical context for benzoate derivatives only (no medical claims).

General biochemical context (literature)

• Benzoic acids and their esters are common motifs in natural products and xenobiotics. In biological systems, benzoates are typically activated (e.g., to benzoyl-CoA) prior to metabolism; aromatic ring substitutions modulate enzyme recognition and rate.
• Electron-donating methoxy groups affect aromatic hydroxylation patterns in oxidative metabolism (cytochrome P450s in mammals; dioxygenases in microbes). Alkyl substituents such as ethyl increase hydrophobicity, often reducing aqueous solubility and potentially altering partitioning into lipid phases.
• Carboxylic acids exist largely as benzoates at physiological pH, enabling active transport via organic anion transporters in some organisms; however, ring substitution can diminish transporter affinity.
• In microbial pathways, substituted benzoates may undergo ortho/para ring-cleavage after prior hydroxylation steps; bulky or electron-rich substituents can slow degradation.

Practical laboratory relevance

• When used in biochemical assays as a substrate analog or reference compound, consider pH-dependent ionization (pKa ~4.2–4.6 for para-alkoxy benzoic acids, literature) and low aqueous solubility of the neutral form. DMSO stock solutions followed by dilution into buffered media are common.

Reminder

• For research use only. Not for human or animal use.

Buffer Applications

Relevance

• 3-Ethyl-4-methoxybenzoic acid is not a standard buffering reagent. Carboxylic acids can, in principle, contribute to buffering near their pKa, but low aqueous solubility and lack of established buffer recipes limit practical use.

General guidance (literature)

• pKa expectation: Para-alkoxy benzoic acids typically exhibit pKa ~4.2–4.6. Effective buffering would occur roughly within pH 3.2–5.6. However, solubility constraints of the neutral acid reduce usable concentrations in purely aqueous media.
• Workable scenarios: As a component of mixed organic/aqueous systems (e.g., ≥10–50% MeOH, EtOH, or acetonitrile) for specialized chromatographic mobile phases, a benzoate/benzoic acid pair can impart limited buffering capacity.
• Alternative buffers: For robust aqueous buffering in this pH window, consider acetate, citrate, formate, or phthalate buffers with well-characterized recipes and regulatory acceptance.

Practical recommendation

• Use established buffers for biological/analytical work. If the compound must be present, prepare it as an analyte in a suitable buffer rather than as the buffering species. If pH-switch precipitation is desired for isolation, benzoate formation in base and re-acidification is effective for purification, but this is not a buffer application per se.

Green Alternatives

Context

• As a solid building block, the main green-chemistry levers are solvent choice, coupling reagents, and protecting-group strategy rather than substituting the molecule itself.

Greener processing options (literature/general)

• Solvents:
  • Prefer 2-MeTHF, CPME, EtOAc, ethanol, or water (where feasible) over chlorinated solvents for esterification/amide coupling and workups.
  • Use aqueous micellar catalysis (e.g., TPGS-750-M) to perform couplings or reductions in water when compatible with substrate stability.
• Coupling reagents:
  • Employ greener amide couplings (e.g., CDI, DMTMM, COMU) to reduce urea byproducts and improve atom economy; consider enzyme-catalyzed amidation/esterification in ionic liquids/green solvents if appropriate.
• Energy efficiency:
  • Microwave or flow chemistry can reduce reaction times and energy use; room-temperature couplings with organocatalysts or activating agents minimize heating.
• Workup and isolation:
  • Favor pH-switch crystallizations (benzoate formation in base, re-acidify to precipitate) to avoid extensive chromatography and reduce solvent consumption.

Illustrative comparison (general)

• Traditional: DCM + DCC/DMAP for Steglich esterification → chlorinated waste, dicyclohexylurea solid waste.
• Greener: EtOAc or 2-MeTHF + CDI (or catalytic acid in ethanol for Fischer) → easier solvent recovery, less persistent urea byproduct.

Trade-offs

• Greener solvents may alter solubility and rate; modest temperature increases or co-solvents can restore performance. Always validate with small-scale trials.

Pharmaceutical Uses

Applicability

• No pharmacopeial grade, excipient role, or formulation specifications are provided for this item. Content below reflects general, non-clinical manufacturing context.

General considerations (literature/industry practice)

• Synthetic intermediate: Substituted benzoic acids are common feedstocks for producing amides, esters, and more complex scaffolds during API route development and SAR studies.
• Salt formation/handling: The carboxylate can be converted to alkali metal salts to improve processability (solubility, crystallinity) during intermediate isolation steps.
• Analytical reference: Can serve as an internal or system suitability standard in research chromatography if purity and stability are established (assay and UV profile would need to be defined on CoA; not specified for this item).

Not typically applicable

• It is not a recognized excipient with compendial monographs (e.g., USP/NF) to the best of general knowledge; no medical or therapeutic claims are made here. Any use in pharmaceutical contexts would be as a research intermediate under GMP/QA oversight.

Documentation

• For suitability in regulated settings, request detailed CoA, impurity profile, residual solvents, and stability data specific to SKU E952920.

Physical Properties

Item-specific (from Product Data)

• Appearance: 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 product specifications)

• Phase at ambient conditions: typically a crystalline organic solid for substituted benzoic acids of this type.
• Solubility profile (qualitative):
  • Water: low solubility expected for alkyl/alkoxy-substituted benzoic acids; solubility increases in alkaline solution (formation of benzoate salt).
  • Organic solvents: good solubility expected in polar aprotics (DMF, DMSO, NMP), chlorinated solvents (DCM, CHCl3), esters (EtOAc), and alcohols upon warming; moderate in toluene/ethers.
• Acid strength: carboxylic acid pKa typically ~4.2–4.6 for para-alkoxy benzoic acids (literature). Methoxy slightly decreases acidity vs benzoic acid due to resonance donation; an additional ethyl marginally affects acidity.
• Partitioning: logP anticipated to be higher than benzoic acid due to ethyl/methoxy substituents (literature expectation: moderately lipophilic).
• Spectral features (qualitative): IR shows strong C=O stretch of aromatic acid near ~1685–1710 cm−1 (hydrogen-bonding and conjugation dependent), broad O–H 2400–3300 cm−1; 1H NMR with benzylic ethyl (triplet ~1.2–1.3 ppm, quartet ~2.6–2.8 ppm), methoxy singlet ~3.7–3.9 ppm, aromatic protons 6.7–8.1 ppm; 13C NMR: carbonyl ~165–172 ppm, methoxy ~55–57 ppm, benzylic CH2 ~28–30 ppm (literature ranges).

Notes

• Where exact numerical values (mp/bp/density/RI) are required, please refer to the CoA/Spec Sheet for this specific lot.

Quality & Grades

Item-specific (from Product Data)

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

Guidance on interpreting grades (general)

• Research/technical grade: Suitable for most synthetic and preparative work. Trace impurity limits, water content, and assay criteria vary by supplier/lot.
• Purified/assay ≥98–99%: Typical for small-molecule building blocks used in synthesis; supports reliable yields and analytical characterization.
• HPLC grade (solvents) or LC/MS grade: Not applicable to this solid; however, low-UV impurity profiles are beneficial if used as analytical standards.

Quality considerations specific to aromatic carboxylic acids

• Assay and identity: 1H/13C NMR, IR (C=O stretch), melting range, HPLC purity. Confirm substitution pattern by 2D NMR if needed.
• Residual solvents and water: Karl Fischer moisture may be reported; these can influence weight-by-weight dosing in coupling reactions. Not specified for this item; refer to CoA/Spec Sheet.
• Inorganic residues/metals: Generally low for isolated organics; ICP results may be provided for high-purity demands. Not specified for this item; refer to CoA/Spec Sheet.
• Particle size: Impacts dissolution and mixing; sieving or milling may be noted on CoA when relevant. Not specified for this item; refer to CoA/Spec Sheet.

Documentation

• For definitive specifications (assay, water, residual solvents, metals, mp), please consult the CoA/Spec Sheet for SKU E952920.

Reaction & Applications

Overview

• 3-Ethyl-4-methoxybenzoic acid is a versatile aromatic acid building block for small-molecule synthesis, materials, and probe development. The para-methoxy group activates the ring toward electrophilic aromatic substitution (EAS) at its ortho positions, while the carboxyl group can be transformed into numerous derivatives.

Representative transformations (literature/general)

• Carboxyl group chemistry:
  • Esterification: Fischer (ROH/H+, reflux), Steglich (DCC/DMAP) for mild conditions; benzyl, methyl, and tert-butyl esters commonly used as protecting/handling derivatives.
  • Amide formation: Carbodiimides (EDC/HOBt or HBTU/HATU with base), acid chloride route (SOCl2 or oxalyl chloride) followed by amination; CDI can provide clean couplings.
  • Reduction: To benzyl alcohols (BH3·THF, LiAlH4) or aldehydes (DIBAL-H at low temperature via esters/acyl chlorides).
  • Decarboxylation/functionalization: Silver-mediated or photoredox decarboxylative couplings from redox-active esters (NHP esters) to forge C–C or C–heteroatom bonds.
• Aryl ring functionalization:
  • Directed metalation possible adjacent to methoxy under strong bases (s-BuLi/TMEDA), enabling formylation or borylation after temporary protection of the acid (as ester).
  • Cross-coupling: After converting to suitable handles (e.g., aryl bromide via diazotization/Sandmeyer from pre-installed amines—requires prior functional group interconversions), methoxy directs O-demethylation/bromination sequences if desired.
• Protecting-group strategy: Convert the acid to a stable ester (e.g., tBu, Bn) prior to harsh conditions; reconvert by TFA (tBu) or hydrogenolysis (Bn).

Applications

• Intermediates for anisyl- and ethyl-substituted aryl amides/esters in materials, ligands, and fragrance analogs; SAR exploration in medicinal chemistry (as a scaffold/intermediate; no clinical claims).

Reaction Conditions

General guidance (literature; adjust to your substrate and scale)

• Esterification (Fischer): Alcohol solvent (MeOH, EtOH), catalytic H2SO4 or p-TsOH, reflux 2–16 h; remove water (Dean–Stark in toluene for higher-boiling alcohols). Typical isolated yields 70–95% depending on sterics and workup.
• Steglich esterification: DCC (1.1–1.2 eq), DMAP (0.1 eq), DCM or THF, 0 °C → rt, 4–18 h; filter DCU byproduct; 70–95% yields common.
• Amide coupling: HATU or EDC·HCl (1.0–1.2 eq), base (DIPEA 2–3 eq), DMF/DCM, 0 °C → rt, 2–12 h; typical yields 70–90% with primary amines; minimize epimerization for chiral partners by low temperature and additives (e.g., HOAt).
• Acid chloride route: SOCl2 (2–4 eq) with DMF cat., reflux 1–3 h; remove excess; quench into amine base at 0–5 °C to form amide quickly; often high yields.
• Redox-active ester formation: N-hydroxyphthalimide (1.1 eq), DIC (1.1 eq), DMAP (cat.) in DCM; then photoredox/Ni coupling in MeCN/DMF at rt with blue LEDs; 4–24 h; product distribution depends on radical partner.
• O-Demethylation (if phenol desired): BBr3 (1–3 eq) in dry DCM, −78 → 0 °C, 1–3 h; quench carefully; gives 4-hydroxy analogue.
• Benzylic oxidation of ethyl side chain: SeO2 or catalytic systems; conditions vary; monitor by LC/MS.

Solvent and atmosphere

• Use anhydrous solvents and inert atmosphere (N2/Ar) for moisture-sensitive steps (acid chloride formation, metalations). Standard glassware is sufficient; avoid prolonged base exposure to the free acid to limit salt formation.

Analytical monitoring

• HPLC/UPLC with UV at 220–275 nm typically detects anisyl benzoates strongly; TLC in EtOAc/hexanes (10–50%) is effective; visualize with UV and KMnO4.

Safety & Handling

Item-specific (from Product Data)

• GHS classification, signal word, pictograms, and H-statements: Not specified for this item; refer to SDS.
• Storage conditions: Room temperature.
• Research use: For research use only.

General safety guidance (literature/analogous compounds; defer to SDS for authoritative data)

• Likely hazards: Aromatic carboxylic acids commonly cause skin/eye irritation and may cause respiratory irritation as dusts. Treat as harmful if swallowed; avoid inhalation and contact.
• PPE: Use lab coat, safety glasses or splash goggles, and appropriate gloves (e.g., nitrile). Handle solids in a fume hood to avoid dust exposure.
• First aid overview: If inhaled—move to fresh air. Skin contact—wash with soap and water. Eye contact—rinse cautiously with water for several minutes, remove contact lenses if present and easy. Ingestion—rinse mouth; seek medical attention in all exposure scenarios. Always follow your institution’s protocols.
• Handling: Avoid generating dust; use antistatic measures when weighing dry powders. For solutions, ensure compatible containers.
• Incompatibilities (typical for carboxylic acids): Strong bases (exothermic neutralization), strong oxidizers, reactive acid chlorides/anhydrides, and reducing agents. Avoid contact with reactive metals in presence of moisture (salt formation and gas evolution possible with carbonates/bicarbonates).
• Spill/cleanup: Avoid dust; sweep up or use HEPA vacuum; dispose according to local regulations.
• Waste: Collect organic acid waste in compatible, clearly labeled containers; segregate from strong oxidizers/bases unless neutralized.

Solvent Selection

Applicability

• This product is a solid aromatic carboxylic acid (building block), not a solvent. The information below aids in selecting solvents to dissolve, process, or react it efficiently.

General solubility and polarity guidance (literature/experience)

• Expected polarity: Moderately polar (acidic functionality) with nonpolar aromatic/alkyl portions; overall amphiphilic behavior.
• Good solvents (preparative/analytical): DMSO, DMF, NMP, acetone, acetonitrile, methanol/ethanol (warm), EtOAc, CH2Cl2/CHCl3, toluene (heated). Water solubility is low at neutral pH but increases markedly in basic aqueous media (benzoate salt).
• For reactions: Choose solvent to balance reactivity and workup.
  • Amidation/esterification: dichloromethane, DMF, DCM/DMF blends, THF, or toluene depending on coupling system.
  • Metalation/cross-coupling after derivatization (e.g., conversion to acid chloride/boronate): use dry THF/2-MeTHF, toluene, dioxane, or DMAc.
  • Crystallization: EtOAc/hexanes, toluene/hexanes, or alcohol/water antisolvent systems often provide clean solids.

Small comparison (general)

• DMSO/DMF: Highest solvating power; harder to remove; excellent for NMR stock solutions.
• EtOAc/DCM: Good balance of solubility and volatility; widely used in workups and chromatography.
• Alcohols: Facilitate Fischer esterification; enhance hydrogen-bonding interactions; may need acid catalysts.
• Aqueous base: For extractions as benzoate salt; allows pH-switchable handling.

Practical tips

• Pre-warm viscous or high-melting slurries to aid dissolution; neutralize to the benzoate for aqueous operations; back-acidify to re-precipitate the product.

Storage & Reconstitution

Item-specific (from Product Data)

• Storage conditions: Room temperature.
• Shipping: Not specified for this item; refer to CoA/Spec Sheet.

General guidance for solids of this class (literature/practice)

• Container: Store in a tightly closed container under dry, ambient conditions; protect from prolonged exposure to light and moisture to avoid hydrolysis of activated derivatives (if prepared in situ). The free acid is typically robust.
• Stability: Aromatic carboxylic acids with methoxy/ethyl substituents are generally stable for years at room temperature when dry. Avoid strong bases or oxidizers in storage areas.
• Reconstitution/preparation of stock solutions:
  • Organic stock: Dissolve in dry DMSO, DMF, MeOH, EtOH, or DCM to desired concentration (e.g., 10–100 mg/mL). Warm gently and sonicate if needed.
  • Aqueous work: To achieve aqueous solubility, form the benzoate salt by adding equimolar base (e.g., NaOH) in water or buffer; adjust pH to ~7–8. Back-acidify to precipitate the free acid for isolation.
• Freeze–thaw: Not typically relevant for solids; for solution stocks, aliquot and store at low temperature (e.g., −20 °C) if using DMSO/DMF to minimize degradation. Bring to room temperature before opening to prevent moisture condensation.

Note

• For definitive shelf-life and stability-by-impurity data, consult the product’s CoA/Spec Sheet and SDS for SKU E952920.

Structure & Identity

Item-specific (from Product Data)

• SKU: E952920
• Product name: 3-Ethyl-4-methoxybenzoic acid
• CAS: 22934-35-6
• InChIKey (as provided): 88608
• SMILES: 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 identity, for reference only)

• Functional groups: aromatic ring substituted by a carboxylic acid (benzoic acid core), a para-methoxy (anisyl) group, and a meta-ethyl group (relative to –CO2H).
• Typical SMILES representations (literature example): COc1ccc(CC)c(c1)C(=O)O (one of several equivalent forms describing 3-ethyl-4-methoxybenzoic acid).
• Structural description (2D): A benzene ring bearing –CO2H at C1, –OCH3 at the para position (C4), and –CH2CH3 at the meta position (C3). The methoxy substituent is strongly electron-donating/para-directing; the carboxyl is electron-withdrawing/meta-directing; the ethyl is weakly activating.

Notes

• Stereochemistry: None (achiral, no stereocenters).
• Resonance: Carboxylate resonance typical of benzoic acids; methoxy lone-pair donation increases ring electron density, especially at positions ortho/para to OMe.
• For definitive identifiers (verified SMILES, formula, exact mass), consult the product’s CoA/Spec Sheet.

Synthetic Utility

Functional group leverage

• Carboxylic acid: Platform for amide/ester formation, acyl activation (acid chloride/anhydride), Curtius/Schmidt-type rearrangements (via acyl azide), and decarboxylative couplings after formation of redox-active esters.
• Aryl methoxy (para): Electron-donating; directs EAS ortho/para; can be transformed (e.g., O-demethylation to phenol using BBr3/AlCl3) to enable further derivatizations (etherifications, sulfonations).
• Aryl ethyl (meta): Benzylic position available for selective oxidation (to aldehyde/acid) or halogenation; side-chain functionalization expands diversity.

Retrosynthetic value

• The acid provides a convergent handle: assemble ring substitution via EAS on anisole derivatives, or introduce the ethyl side chain via Friedel–Crafts alkylation (or hydroarylation) followed by controlled oxidation to the acid. Alternatively, start from 4-methoxy-3-ethyl-toluene and oxidize the methyl to the acid (KMnO4, RuO4, or catalytic aerobic oxidation), preserving the ethyl.

Named/representative reactions (literature)

• Steglich esterification (DCC/DMAP), HATU/EDC-mediated amidation, formation of acid chlorides (SOCl2) for acylations.
• Decarboxylative cross-couplings: Photoredox/Ni dual catalysis from NHP esters to build C(sp2)–C(sp3) or C(sp2)–heteroatom bonds.
• Benzylic oxidation: SeO2 or MnO2 (allylic/benzylic), or catalytic C–H oxidation to diversify the ethyl chain.

Process tips

• Protect the acid (e.g., tBu ester) before strong base-mediated metalations; avoid conditions that induce demethylation unless desired. Control regioselectivity using directing groups and substituent effects of the para-methoxy group.

Target Specificity

Not applicable.

• This product is a small-molecule carboxylic acid building block, not a biological macromolecule or affinity reagent. No antigen/epitope, clone, isotype, or species reactivity data apply.