4-Hydroxy-3-methylphenylpropanoic acid - ≥95% , CAS No.22517-00-6

CAS: 22517-00-6 Cat. No.: H942121 分子式: C₁₀H₁₂O₃ 分子量: 180.2 PubChem CID: 15472574

GRADE & PURITY ≥95%

Storage

Room temperature

Specifications

仕様と純度

≥95%

保管条件

Room temperature

純度

≥95%

名前と識別子

• カノニカル・スマイル: CC1=C(C=CC(=C1)CCC(=O)O)O
• IUPAC Name: 3-(4-hydroxy-3-methylphenyl)propanoic acid
• InChIKey: ZPAIMGRPEHRDLH-UHFFFAOYSA-N
• INCHI: 1S/C10H12O3/c1-7-6-8(2-4-9(7)11)3-5-10(12)13/h2,4,6,11H,3,5H2,1H3,(H,12,13)
• 異性体SMILES: CC1=C(C=CC(=C1)CCC(=O)O)O
• PubChem CID: 15472574
• 分子量: 180.2

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Phenylpropanoids and polyketides
    • 分類 Phenylpropanoic acids

• Kingdom: Organic compounds
• Superclass: Phenylpropanoids and polyketides
• 分類: Phenylpropanoic acids
• Subclass: Not available
• Intermediate Tree Nodes: Not available
• Direct Parent: Phenylpropanoic acids
• Alternative Parents: Ortho cresols Toluenes 1-hydroxy-2-unsubstituted benzenoids Monocarboxylic acids and derivatives Carboxylic acids Organic oxides Hydrocarbon derivatives Carbonyl compounds
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: 3-phenylpropanoic-acid - O-cresol - 1-hydroxy-2-unsubstituted benzenoid - Phenol - Toluene - Monocyclic benzene moiety - Benzenoid - Carboxylic acid derivative - Carboxylic acid - Monocarboxylic acid or derivatives - Carbonyl group - Organic oxygen compound - Organooxygen compound - Organic oxide - Hydrocarbon derivative - Aromatic homomonocyclic compound
• 説明: This compound belongs to the class of organic compounds known as phenylpropanoic acids. These are compounds with a structure containing a benzene ring conjugated to a propanoic 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

化学的性質と物理的性質

• 分子量: 180.200 g/mol
• XLogP3: 1.700
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 3
• Exact Mass: 180.079 Da
• Monoisotopic Mass: 180.079 Da
• Topological Polar Surface Area: 57.500 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

No manufacturer-validated biological assay protocols are provided for this item. As a general chemical building block, usage protocols depend on the intended synthetic or analytical application.

Typical laboratory practices (general guidance):

• Stock solution preparation for screening: dissolve at 10–100 mM in dry DMSO, optionally filter (0.22 µm PTFE) for sterility/clarity; store aliquots at –20 °C to minimize freeze–thaw.
• Coupling reactions: see Reaction Conditions tab for general coupling setups (EDC/HATU/T3P). Run small-scale trials to optimize base, solvent, and temperature for selectivity between O- and N-acylation.
• Analytical QC: verify identity/purity by NMR, LC–MS, and HPLC. For water content-sensitive steps, determine KF before moisture-critical reactions.

For any application requiring specific conditions (e.g., enzymatic assays, materials deposition), develop and validate bespoke protocols.

Biological Roles

This section provides general biochemical context for phenylpropionic acids; it does not assign clinical or therapeutic properties to the product and is for research use only.

• Structural class: 4-hydroxy-3-methylphenylpropanoic acid is a phenylpropanoid-like aromatic hydroxy acid. Compounds in this class are related to metabolites arising from degradation or transformation of lignin-derived aromatics and dietary phenolics (literature context).
• Metabolic relevance (literature/general): microflora-mediated transformations of aromatic compounds can yield hydroxy- and methyl-substituted phenylpropionic acids. Such metabolites may be intermediates en route to ring-cleavage pathways in bacteria.
• Chemical biology utility: phenolic acids offer handles for conjugation to proteins, polymers, and surfaces via carbodiimide chemistry (amide formation) or via phenol oxidative coupling, enabling probe or material construction.
• Physicochemical behavior: the carboxylate form predominates at neutral-to-basic pH, influencing membrane permeability and transporter interactions in biological systems (general principle for aromatic acids). The phenolic OH can participate in hydrogen bonding and redox chemistry under enzyme-mimetic conditions.

Caveats:

• Specific bioactivity, targets, or pathways for this exact substitution pattern are not established here. Any biological testing should be performed under controlled research protocols.
• No medical, diagnostic, or therapeutic use is implied. Consult institutional biosafety guidelines and the SDS when handling in biological laboratories.

Buffer Applications

This compound is not a buffering agent and is not typically used to prepare defined pH buffer systems. As a weak carboxylic acid, it will form water-soluble salts above its carboxyl pKa, but dedicated buffer components (e.g., phosphate, acetate, Tris, HEPES) are preferred for controlled buffering capacity.

Practical notes (general):

• For aqueous handling, dissolve in minimal organic cosolvent (e.g., DMSO or ethanol) and dilute into buffered saline; or first neutralize with equimolar NaOH/KOH to form the carboxylate salt.
• If pH control is required, choose a standard buffer in the appropriate range and treat this compound as a solute, not the buffering component.

Green Alternatives

The compound itself is a solid building block. Greenness considerations focus on solvents, reagents, and process choices when using 4-hydroxy-3-methylphenylpropanoic acid.

Greener solvent choices (literature/practice):

• Prefer bio-based or lower-toxicity solvents when feasible:
  • 2-MeTHF or CPME instead of THF/diethyl ether (better safety, lower peroxide risk; good for extractions and some couplings).
  • Ethyl acetate and isopropanol as workup/crystallization media instead of chlorinated solvents.
  • MeCN alternatives: propylene carbonate or methanol/ethyl acetate combinations when compatible with the coupling system.

Greener coupling strategies:

• Use soluble carbodiimides (EDC) in aqueous-organic media to minimize chlorinated reagents; water-compatible buffers (pH 4.5–5.5) with NHS can afford active esters in situ.
• Enzymatic esterifications in solvent-free or ionic liquid systems (where applicable) can reduce solvent load and temperature.

Comparison snapshot (general):

• Conventional: SOCl2/oxalyl chloride (acid chloride route), DCM, DMF; efficient but corrosive/toxic reagents and high E-factors.
• Greener: EDC·HCl or CDI in EtOAc/2-MeTHF or aqueous MeOH; fewer hazardous byproducts and easier solvent recovery.

Operational tips:

• Apply solvent-recovery and azeotropic drying (e.g., EtOAc) to reduce waste.
• Consider protecting-group minimization: employ chemoselective coupling reagents to avoid separate protection of the phenol when possible.

Note: Balance greenness with performance; confirm reaction efficiency and product quality before scale-up.

Pharmaceutical Uses

No pharmacopeial/excipient listing is provided for this item. This product is supplied for research use only and is not intended for human or veterinary use.

General formulation/CMC context (literature/practice):

• As an aromatic carboxylic acid with a phenolic group, the compound can serve as a research intermediate for synthesizing esters, amides, or pro-moieties used in medicinal chemistry SAR campaigns.
• Salt formation: where appropriate, sodium/potassium salts can be generated to enhance aqueous solubility for in vitro assays. Co-solvents (DMSO, ethanol) are often used to prepare concentrated stock solutions for screening.
• Analytical characterization: typical quality packages for drug-like research intermediates include NMR (1H/13C), HRMS/LC–MS, HPLC purity, water content (KF), and residual solvents—verify via the CoA for this specific item if such data are required.

Note: No claims are made regarding compliance with USP/Ph. Eur./JP or GMP manufacturing. For any work that could progress toward regulated development, perform independent qualification of the material, including elemental impurities, residual solvents per ICH Q3C, and genotoxic impurity risk assessments.

Physical Properties

Item-specific specifications (this product):

• 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.

Literature/general values for the neutral compound (reference only; not product specifications):

• Empirical formula (literature): C10H12O3
• Molecular weight (literature): ~180.20 g/mol
• State: typically a crystalline solid (literature)
• pKa: carboxylic acid pKa typically ~4–5; phenolic OH pKa typically ~9–10 (literature ranges for related phenolic acids)
• Solubility profile (literature):
  • Water: expected low to moderate solubility at neutral pH; increased solubility as the carboxylate salt above pH > 6–7.
  • Organic solvents: soluble in polar organics such as methanol, ethanol, acetone; good solubility in DMSO and DMF; limited in nonpolar hydrocarbons.
• LogP/logD: aromatic hydroxy acids of this size commonly show logP in the ~1.5–2.5 range (literature class estimate).
• Melting point / boiling point / density / refractive index: Not specified for this item; consult literature and confirm against CoA/Spec Sheet before use in QC or method development.

Notes:

• Always verify critical physical parameters with the lot-specific CoA when these properties control fit-for-use (e.g., formulation, crystallization, chromatography).

Quality and Grades

Item-specific grade/purity details: Not specified for this item; refer to CoA/Spec Sheet for assay, impurity profile, and residual solvent limits.

Guidance on interpreting common grades (general information):

• Research grade: supports most synthetic and analytical applications; specifications typically include assay (e.g., HPLC or GC), identity (NMR/IR/MS), and basic limits for moisture and key impurities.
• High-purity/ACS/AR: tighter limits on inorganic/organic impurities suitable for analytical or sensitive synthetic work.
• LC/MS or HPLC grade (for solvents/solutes used in chromatography): emphasizes low UV background and minimal nonvolatile residue; for solutes (standards), certificates include purity by quantitative NMR or chromatographic normalization.

Stabilizers/inhibitors: None are indicated in the Product Data. If stabilization is relevant to your method (e.g., preventing oxidation or esterification), verify in the CoA whether antioxidants or residual stabilizers are present. Absence of a listed stabilizer in the Product Data should not be construed as a guarantee of “stabilizer-free” material without CoA confirmation.

Recommendations:

• For quantitative work, request or reference the lot-specific CoA with detailed analytical methods and acceptance criteria.
• If your application is moisture-sensitive (e.g., acid chloride formation in situ), consider drying the solid under vacuum at ambient temperature, then confirming Karl Fischer/water content if critical.

Reaction and Applications

Practical roles of 4-hydroxy-3-methylphenylpropanoic acid in synthesis (general/literature):

• Bifunctional handle: The molecule bears both a carboxylic acid and a phenolic OH, enabling orthogonal derivatization.

  • Carboxyl activation: conversion to acid chlorides (e.g., with oxalyl chloride or SOCl2) or mixed anhydrides; subsequent amide or ester formation. Carbodiimide couplings (EDC/HOBt, DIC/DMAP) or uronium reagents (HATU, TBTU) are commonly effective.
  • Phenol modification: O-alkylation (Williamson ether synthesis) under basic conditions (e.g., K2CO3 in acetone/DMF) to give aryl ethers; O-acylation to aryl esters; silyl (TBS/TIPS) or benzyl protection to mask the phenolic OH during carboxylate couplings.

• Aromatic chemistry: The substituted ring is moderately deactivated by the para phenol (after protection) and weakly activated in its phenolate form; electrophilic substitution is influenced by the –OH (ortho/para director) and –CH3 (ortho/para director). Nitration, sulfonylation, or halogenation can be tuned with protection strategies to control regioselectivity.

• Side-chain manipulation:

  • Decarboxylation under harsh conditions or via copper-mediated pathways to access the corresponding arylpropane derivatives (literature precedent for related acids).
  • Oxidation at benzylic positions (e.g., forming cinnamic-type systems via dehydrogenation) is achievable with selective oxidants, though conditions must be tuned to avoid phenol over-oxidation.

• Materials/ligand precursors: Ester and amide derivatives serve as monomers or crosslinkable motifs in polymer and materials chemistry; incorporation into dendrons or linkers leverages the phenolic handle.

Tips:

• Drying: oven or vacuum-dry before moisture-sensitive couplings; trace water reduces coupling efficiency.
• Base selection: mild bases (DIPEA, K2CO3) minimize phenolic side reactions; for selective O-alkylation, protect the acid or generate its ester first to avoid competing acylation.

Reaction Conditions

General literature guidance for typical transformations of phenolic aromatic carboxylic acids; adjust to your substrate and verify experimentally:

• Amide coupling (carboxyl activation):

  • Solvent: DMF, DCM, or MeCN.
  • Reagents: EDC·HCl (1.1–1.5 eq) + HOBt/HOAt or Oxyma; base DIPEA (2–3 eq). Alternatively HATU or T3P.
  • Temperature: 0–25 °C (most couplings proceed at rt); time 1–16 h.
  • Notes: If phenolic O-acylation is competitive, protect phenol or use additives (e.g., DMAP control) and amine order-of-addition to favor N-acylation.

• Esterification (Steglich):

  • Alcohol (1.5–3 eq), DCM or THF, DCC (1.2 eq), catalytic DMAP.
  • 0 °C to rt, 2–18 h; filter DCU, concentrate, purify.

• Phenol O-alkylation (Williamson):

  • Base: K2CO3 or Cs2CO3 (2–3 eq) in acetone, acetonitrile, or DMF; alkyl halide (1.2–2 eq).
  • 25–60 °C, 2–24 h.
  • For sensitive systems, NaH (1.05–1.2 eq) in THF/DMF at 0–25 °C can be used; protect the acid (as ester) to suppress carboxylate alkylation.

• Acid chloride formation:

  • SOCl2 or oxalyl chloride (2–4 eq), catalytic DMF, DCM or neat.
  • 0–40 °C, 1–3 h; remove volatiles under reduced pressure. Use immediately in coupling.

• Salt formation for aqueous applications:

  • Neutralize with NaOH or K2CO3 in aqueous ethanol/water to pH ~7.5–8.5; isolate by crystallization/lyophilization as needed.

Expected yields: dependent on substitution and protection; amide/ester couplings typically deliver good to excellent yields (literature) when moisture is controlled and stoichiometry optimized.

Safety and Handling

Item-specific hazard classification: Not specified for this item; refer to the SDS for authoritative information (GHS classification, pictograms, signal word, H/P statements).

General laboratory safety guidance for phenolic carboxylic acids (literature/practice):

• Likely hazards: may cause skin/eye irritation; dust may irritate respiratory tract. Phenolic functionality can cause defatting/irritation; carboxylic acids are weakly corrosive at high concentrations.
• Personal protective equipment (PPE): safety glasses or goggles, lab coat, appropriate chemically resistant gloves (e.g., nitrile). Use a dust mask/respirator if handling large quantities of powder that could become airborne; perform manipulations in a fume hood to minimize inhalation exposure.
• Handling: avoid dust generation; prevent contact with eyes/skin. Do not ingest or inhale. Wash thoroughly after handling.
• Storage incompatibilities: separate from strong oxidizers, strong bases (which will form salts and increase dissolution/skin penetration), and strong acids for general good practice. Avoid reactive acylation/alkylation agents near open containers.
• Fire safety: organic solids are combustible; keep away from ignition sources. If heated to decomposition, may emit irritating fumes.
• First aid (overview; defer to SDS):
  • Skin/eye contact: rinse with water for at least 15 minutes; remove contaminated clothing; seek medical attention if irritation persists.
  • Inhalation: move to fresh air; seek medical advice if symptoms occur.
  • Ingestion: rinse mouth; do not induce vomiting; seek medical attention.

Always consult the product SDS for definitive hazard and response measures prior to use.

Solvent Selection

This product is a small-molecule solid, not a solvent. Selection here refers to solvents for dissolving and processing 4-hydroxy-3-methylphenylpropanoic acid.

General solubility/miscibility guidance (literature/practice):

• Polar aprotic: DMSO and DMF typically provide excellent solubility for phenylpropionic acids and their phenolates; useful for stock solutions and coupling reactions.
• Alcohols: methanol, ethanol, isopropanol usually dissolve moderate amounts; heating and/or slight basification (e.g., triethylamine) increases solubility.
• Aqueous media: solubility is pH-dependent; deprotonation of the carboxyl group (> pH ~6–7) markedly increases solubility. Prepare sodium/potassium salts for aqueous workups or biological buffers.
• Esters/ethers: ethyl acetate and THF often dissolve these acids; THF beneficial for mixed organic–aqueous systems.

When to choose what:

• Method development or stock solutions for screening: DMSO for maximal concentration and long-term stability tests.
• Coupling chemistry (amide/ester formation): DMF, DCM, or MeCN depending on the coupling system; THF or toluene for less polar protocols after activating the acid.
• Crystallization and purification: ethyl acetate/hexanes or EtOAc/heptane systems; alcohol/water mixtures can induce crystallization of the neutral acid, while basic aqueous phases retain the carboxylate in solution.

Note: Verify exact solubility for your lot/conditions experimentally; values are system-dependent and not specified for this item.

Storage and Reconstitution

• Storage (from Product Data): Room temperature. Keep container tightly closed in a dry, well-ventilated place away from incompatible materials (e.g., strong oxidizers). Protect from excessive heat and direct sunlight.
• Shipping: Not specified for this item; refer to CoA/Spec Sheet. Given room-temperature storage, ambient shipping is typically acceptable unless otherwise stated.
• Stability: Specific shelf-life and stability data are not provided. As a general practice, limit exposure to moisture and air to prevent hydrolysis of derivatives and oxidative discoloration of phenolic materials.

Reconstitution and solution handling (general guidance):

• Solvents: DMSO, DMF, methanol, ethanol, or acetone typically dissolve phenylpropionic acids well. For aqueous systems, prepare the sodium/potassium salt by neutralization or use cosolvent strategies.
• Concentrations: prepare concentrated stocks (e.g., 10–100 mM) in dry DMSO or ethanol; store as aliquots to avoid repeated freeze–thaw.
• Filtration: use 0.22 µm PTFE or PVDF filters for organic solutions; for aqueous salt solutions, PES is acceptable.
• Stability of solutions: organic stocks are often stable for weeks at 2–8 °C and longer at –20 °C (literature/practice). Aqueous solutions of the carboxylate should be stored refrigerated and used promptly to minimize microbial growth and oxidation.

Always consult the lot-specific CoA and SDS for definitive storage and handling guidance. Research use only.

Structure and Identity

Brief overview: 4-Hydroxy-3-methylphenylpropanoic acid is a substituted phenylpropionic acid bearing a para-phenolic OH and a meta-methyl substituent relative to a benzylic propanoic acid side chain.

• Item-specific identifiers from Product Data:

  • CAS: 22517-00-6
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet. (Product Data field appears incomplete)
  • SKU: H942121
  • Category: Life Science (catalog path)

• Literature/computed identifiers (for reference only; not item specifications):

  • Synonyms: 3-methyl-4-hydroxyphenylpropionic acid; 3-methyl-4-hydroxyhydrocinnamic acid (literature)
  • Molecular formula (literature): C10H12O3
  • Molecular weight (literature): ~180.20 g/mol
  • SMILES (literature): O=C(O)CCC1=CC(C)=C(O)C=C1

• Structural features (general chemistry description):

  • Aromatic ring: a benzene ring bearing two substituents and one benzylic propanoic acid side chain (–CH2–CH2–CO2H).
  • Functional groups: a phenolic hydroxyl (para to the side chain) and a carboxylic acid at the terminus of the propyl chain; a meta methyl group on the ring.
  • Substitution pattern: relative to the benzylic carbon (position 1), the ring bears –OH at the para (4) position and –CH3 at the meta (3) position.
  • 2D description in words: a hydroxy-methyl-disubstituted phenyl nucleus connected via the benzylic carbon to a two-carbon linker terminating in a carboxylic acid; no stereocenters are present; planarity localized to the aromatic ring, with a flexible propanoic acid side chain.

Note: All literature identifiers are provided for general reference; confirm exact identity parameters for this specific item via the CoA/Spec Sheet.

Synthetic Utility

Functional group leverage:

• Carboxylic acid:
  • Amide coupling to primary/secondary amines (EDC/HOBt, HATU, T3P) for medicinal chemistry libraries.
  • Esterification (Fischer, Steglich) to introduce protecting groups or append solubilizing tails.
  • Curtius or Schmidt-type rearrangements (via acyl azide or mixed anhydrides) to access isocyanates/carbamates (literature for related acids).
• Phenolic OH:
  • O-alkylation to aryl ethers (Williamson) under K2CO3/NaH; O-acylation to aryl esters; formation of sulfonate esters (tosylates/mesylates) as leaving groups for further transformations.
  • Protection as silyl (TBS/TBDPS), benzyl, or carbonate groups to enable selective downstream chemistry on the acid.
• Aromatic ring:
  • Electrophilic substitutions guided by –OH/–CH3 directing effects; halogenation or nitration with protection to steer regioselectivity.

Retrosynthetic value:

• Serves as a convergent node between a substituted phenol fragment and a C3 carboxy side chain. Either fragment can be introduced early (via Friedel–Crafts acylation followed by reduction to propionic acid, or via Heck/hydrogenation sequences starting from a cinnamate analog), depending on route constraints.

Purification/form considerations:

• Free acid vs. ester/salt selection impacts chromatographic behavior. Temporary conversion to a methyl/benzyl ester can simplify purification and later be cleaved (saponification or hydrogenolysis).

Overall, the dual functionality and substitution pattern make this compound a versatile building block for targets requiring para-phenoxy/ether appendages and amide/ester-linked conjugates.

Target Specificity

Not applicable. This product is a small-molecule chemical, not a biological affinity reagent. No antigen/epitope/isotype or species reactivity data are associated with this item.