N-Hydroxy-4-methoxybenzamide - ≥97% , CAS No.10507-69-4

CAS: 10507-69-4 Cat. No.: N1067129 PubChem CID: 221131

GRADE & PURITY ≥97%

Storage

Room temperature

Specifications

Spécifications et pureté

≥97%

Conditions de stockage de stockage

Room temperature

Pureté

≥97%

Noms et identifiants

• Sourires canoniques: COC1=CC=C(C=C1)C(=O)NO
• IUPAC Name: N-hydroxy-4-methoxybenzamide
• InChIKey: RFCBPAJDLZMJPL-UHFFFAOYSA-N
• INCHI: 1S/C8H9NO3/c1-12-7-4-2-6(3-5-7)8(10)9-11/h2-5,11H,1H3,(H,9,10)
• Isomères SMILES: COC1=CC=C(C=C1)C(=O)NO
• CAS alternatif: 10507-69-4
• PubChem CID: 221131
• Numéro NSC: 5096

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 acids and derivatives
• Alternative Parents: Phenoxy compounds Methoxybenzenes Benzoyl derivatives Anisoles Alkyl aryl ethers Hydroxamic acids Organopnictogen compounds Organonitrogen compounds Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Benzoic acid or derivatives - Phenoxy compound - Anisole - Benzoyl - Methoxybenzene - Phenol ether - Alkyl aryl ether - Hydroxamic acid - Carboxylic acid derivative - Ether - Organic nitrogen compound - Organonitrogen compound - Organooxygen compound - Hydrocarbon derivative - Organic oxide - Organopnictogen compound - Organic oxygen compound - Aromatic homomonocyclic compound
• Description: This compound belongs to the class of organic compounds known as benzoic acids and derivatives. These are organic compounds containing a carboxylic acid substituent attached to a benzene ring.
• 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

Propriétés chimiques et physiques

• Poids moléculaire: 167.160 g/mol
• XLogP3: 0.200
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 2
• Exact Mass: 167.058 Da
• Monoisotopic Mass: 167.058 Da
• Topological Polar Surface Area: 58.600 Ų
• Heavy Atom Count: 12
• Formal Charge: 0
• Complexity: 152.000
• 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 validated bioassay or analytical protocols are provided in the Product Data for this item. Not specified for this item; refer to CoA/Spec Sheet.

General usage examples (literature-based; adapt to your system):

• Metal-binding UV–vis assay:
  • Prepare 1–2 mM ligand in MeOH/H2O (1:1), adjust pH to 8.0.
  • Titrate FeCl3 (10–100 µM) and record spectral changes to estimate binding stoichiometry and Kd.
• Preparation of O‑acyl hydroxamate:
  • Dissolve substrate in dry DCM (0.1 M), cool to 0 °C, add TEA (1.2 eq) and acyl chloride (1.1 eq), catalytic DMAP. Stir 1–2 h while warming to RT. Work up and purify by column chromatography.

These are illustrative only; develop and validate internal SOPs as required.

Biological Roles

No biological or clinical claims are made for this product. For research use only.

General biochemical context of hydroxamic acids (literature; not specific claims about this item in vivo):

• Metal chelation: Hydroxamic acids bind Fe(III) and other hard metal ions, a motif found in natural siderophores. Para‑methoxy substitution modestly tunes acidity and donor strength.
• Enzyme-binding motif: The hydroxamate functional group is a well-known zinc-binding group in histone deacetylase (HDAC) inhibitor pharmacophores and in some metalloprotease ligands. This relevance is mechanistic/biochemical, not a therapeutic claim.
• H‑bonding and acidity: The N–OH can donate/accept H‑bonds, enabling defined interactions in protein binding studies and fragment-based design.
• Spectroscopic behavior: Metal coordination often induces characteristic UV–vis shifts for hydroxamates, useful in binding assays.

If using in biochemical assays:

• Control metal ion background (use chelexed buffers) to avoid unintended complexation.
• Verify compound stability across assay pH and temperature to avoid O/N‑acyl migration or hydrolysis artifacts.

Buffer Applications

This compound is not a buffering agent and is not typically used to prepare classical pH buffers. If dissolution into aqueous media is required for assays:

• Adjust pH to mildly basic (e.g., pH 8–9) to increase solubility via partial deprotonation of the hydroxamic acid.
• Use co‑solvents (DMSO ≤1–2% v/v; ethanol) to aid dissolution before dilution into the target buffer.
• Employ metal-depleted buffers for metal-binding studies to minimize background complexation.

Green Alternatives

As a solid reagent/building block, the primary green-chemistry lever is solvent and reagent selection in transformations employing N‑hydroxy‑4‑methoxybenzamide.

Greener choices (literature/general):

• Solvents:
  • Prefer biorenewable or safer solvents where feasible: 2‑MeTHF, CPME, ethyl acetate, MeOH/EtOH, water (with pH control) instead of chlorinated solvents or DMF/DMAc.
  • For photocatalysis or coupling, acetonitrile or EtOAc may replace DMF/DMSO when solubility allows.
• Coupling and activation reagents:
  • Use carbodiimides with benign byproducts (e.g., DIC) and catalytic DMAP, or deploy green coupling systems (e.g., CDI) to avoid urea waste streams associated with EDCI/HOBt in water.
  • Enzymatic acylation (lipases) or aqueous micellar catalysis can reduce organic solvent load for O‑acyl/N‑acyl transformations.
• Energy:
  • Conduct reactions at ambient temperature when possible; use flow chemistry or microwave to shorten times and reduce solvent volumes.

Illustrative comparison (general, selection depends on solubility):

• Traditional: DMF/DCM with EDCI/HOBt for acylations; chlorinated workups.
• Greener: 2‑MeTHF or EtOAc with DIC/DMAP or CDI; aqueous micellar media (TPGS‑750‑M) for coupling; ethanol for crystallization.

Tradeoffs:

• Safer solvents may reduce solubility, requiring co‑solvents or higher temperature. Some green coupling systems have narrower substrate scopes; pilot small-scale screens to confirm feasibility.

Pharmaceutical Uses

No excipient grade or pharmacopeial designation is provided in the Product Data. Not specified for this item; refer to CoA/Spec Sheet.

General formulation/manufacturing context (literature; non-clinical, no therapeutic claims):

• Hydroxamic acid motifs are frequently explored in medicinal chemistry as metal-binding groups in enzyme inhibitor leads. N‑Hydroxy‑4‑methoxybenzamide can serve as a research intermediate or reference compound in such programs.
• As a solid research reagent, it may be formulated into screening stocks (e.g., 10–50 mM in DMSO) for biochemical or biophysical assays.
• Not typically used as a pharmaceutical excipient due to metal-chelating activity and specific reactivity of the hydroxamate functional group.

For any GMP-relevant applications, contact Aladdin for information on manufacturing controls, impurity profiles, and potential upgrade paths.

Physical Properties

Item-specific physical specifications (BP, MP, density, solubility, refractive index, pKa, logP) are not provided in the Product Data for this SKU. Not specified for this item; refer to CoA/Spec Sheet.

Literature/general information (for contextual reference; not product specifications):

• State/appearance: Typically a crystalline solid for aromatic hydroxamic acids with para‑methoxy substitution.
• Solubility profile (general):
  • Sparingly soluble to moderately soluble in water depending on pH; increased solubility under basic conditions due to deprotonation of the N–OH.
  • Readily soluble in polar organic solvents (e.g., DMSO, DMF, MeOH, EtOH) and in mixed aqueous/organic systems when basified.
• Acid–base behavior: Hydroxamic acids are weak acids (literature pKa for related benzohydroxamic acids often in the ~8.5–9.5 range); para‑methoxy substitution can slightly modulate this value.
• Hydrogen bonding: Acts as both H‑bond donor (N–OH) and acceptor (C=O, N–O), enabling strong intermolecular association that affects solubility and melting behavior.

Note: For exact numeric values applicable to this specific lot/grade (melting range, water content, residual solvents), consult the Aladdin CoA/Spec Sheet for N1067129.

Quality and Grades

• Item-specific grade/purity, stabilizers, and analytical limits (e.g., UV cutoff, metal content, water, residual solvents) are not provided in the Product Data. Not specified for this item; refer to CoA/Spec Sheet.

General guidance on quality considerations for hydroxamic acid reagents:

• Purity expectations: For synthetic and biochemical research, materials are commonly supplied at ≥95% purity. Verify by NMR, HPLC/UPLC, and HRMS as needed for your application.
• Stabilizers: Hydroxamic acids typically do not require stabilizers; however, they can undergo O‑ to N‑acyl migration or hydrolysis under harsh conditions. Minimizing moisture and extremes of pH helps maintain integrity.
• Chromatographic purity vs. functional performance: Trace metal content can impact chelation assays; if using in metal-binding studies, request metals analysis or consider pre-treating solutions with metal scavengers.
• Documentation: For method development or regulatory-supportive research, obtain and archive lot-specific CoA/SDS, including analytical methods and acceptance criteria.

Note: If a specialized grade is required (e.g., low-metal, bioassay-grade), contact Aladdin Technical Support to discuss current manufacturing controls and achievable specifications for SKU N1067129.

Reaction and Applications

N-Hydroxy-4-methoxybenzamide is a para‑anisoyl hydroxamic acid useful as a chelator, ligand fragment, and functional handle in acyl‑transfer and rearrangement chemistry.

Key application areas (literature/general):

• Metal complexation and assays:
  • Hydroxamic acids bind hard Lewis acids (e.g., Fe3+, Al3+, Zr4+) through the carbonyl and N‑oxide oxygen. The para‑methoxy group can modulate binding constant via electronic effects.
  • Employed as structural motifs to probe metal–ligand interactions or to build siderophore-mimetic ligands.
• O‑Acyl activation and rearrangements:
  • O‑acylation (e.g., with acyl chlorides or anhydrides) affords activated hydroxamates that can undergo Lossen rearrangement to isocyanates under base or Curtius-type conditions, enabling downstream urea, carbamate, and amine synthesis.
• Acyl transfer and coupling:
  • Forms amide or ester derivatives via coupling (e.g., EDCI/HOBt, DIC/DMAP) to give O‑acyl or N‑acyl products; selectivity guided by conditions and protecting groups.
• Radical or photochemical contexts:
  • Acyl oxime derivatives (from hydroxamic precursors) can serve as acyl radical precursors under photocatalysis for C–C bond formation.
• Analytical uses:
  • As a standard or competitor ligand in colorimetric/fluorimetric metal-binding assays (e.g., Fe3+ complexation), taking advantage of hydroxamate chromophore shifts upon coordination.

Practical tips:

• Control moisture and pH to prevent hydrolysis. For Lossen chemistry, pre-form O‑activated hydroxamates (e.g., p‑nitrophenyl chloroformate activation) and conduct rearrangement under anhydrous, mildly basic conditions.
• In chelation studies, maintain defined ionic strength and avoid competing ligands.

Reaction Conditions

General, literature-informed conditions for transformations involving N‑hydroxy‑4‑methoxybenzamide (guidance only; optimize for your system):

• Formation of O‑acyl hydroxamates (activation for Lossen):

  • Reagents: Acyl chloride or anhydride; base (pyridine, triethylamine); catalytic DMAP.
  • Solvent: DCM, THF, EtOAc, or 2‑MeTHF (greener choice).
  • Temperature: 0–25 °C; monitor by TLC/HPLC.
  • Notes: Maintain anhydrous conditions; control stoichiometry to favor O‑acylation over N‑acylation.

• Lossen rearrangement to isocyanate (from O‑acylated precursor):

  • Bases: Tertiary amines or DBU; sometimes thermal initiation suffices.
  • Solvents: Toluene, THF, dioxane, or MeCN.
  • Traps: Alcohols (carbamates), amines (ureas), water (amines after hydrolysis).
  • Temperature: 25–110 °C depending on substrate and base.

• Metal complexation studies:

  • Media: Aqueous buffer (pH 7–9) or MeOH/H2O; metal-free glassware.
  • Stoichiometry: Often 1:1 or 3:1 ligand:Fe(III) depending on desired complex.
  • Readouts: UV–vis shifts, ITC, or potentiometry to determine affinity.

• Stock solution preparation for assays:

  • DMSO stocks at 10–100 mM; dilute into buffer to ≤1–2% DMSO final.
  • Filtration (0.2 µm PTFE) recommended for particulate removal.

Expected outcomes and timing vary by substrate and scale; confirm via small-scale trials and analytical monitoring.

Safety and Handling

GHS classification and detailed hazard phrases are not provided in the Product Data for this item. Not specified for this item; refer to SDS.

General laboratory safety guidance for aromatic hydroxamic acids (literature-based; not a substitute for the SDS):

• Hazards: May cause irritation to skin, eyes, and respiratory tract. Hydroxamic acids can chelate metal ions; avoid contact with metal-containing biologics if chelation is undesirable.
• PPE: Wear lab coat, safety glasses, and appropriate chemical-resistant gloves (e.g., nitrile). Use in a fume hood to avoid inhalation of dusts/aerosols.
• Handling: Avoid dust generation. Keep containers tightly closed. Use clean, dry tools to prevent contamination that could catalyze decomposition.
• Incompatibilities (general): Strong oxidizers; strong bases/acids can induce hydrolysis or rearrangements. Transition metal salts may form stable complexes.
• First aid (overview; defer to SDS):
  • Skin: Wash with soap and water. Remove contaminated clothing.
  • Eyes: Rinse cautiously with water for several minutes. Remove contact lenses if present and easy to do.
  • Inhalation: Move to fresh air. Seek medical attention if symptoms persist.
  • Ingestion: Rinse mouth. Do not induce vomiting; seek medical advice.
• Fire safety: Use standard extinguishing media (CO2, dry chemical, foam). Combustion may produce CO/CO2 and nitrogen oxides; firefighters should wear self‑contained breathing apparatus.

Always consult the Aladdin SDS for N-Hydroxy-4-methoxybenzamide (SKU N1067129) for authoritative safety and regulatory information.

Solvent Selection

This product is a solid aromatic hydroxamic acid rather than a solvent. Selection focuses on dissolution for reaction or assay use.

General solvent guidance (literature-based):

• Polarity and hydrogen bonding: The hydroxamic motif benefits from polar, H‑bonding solvents.
• Effective solvents for stock solutions and reactions:
  • DMSO and DMF: Excellent solvating power; convenient for high-concentration stock solutions and coupling reactions.
  • Alcohols (MeOH, EtOH, i‑PrOH): Often dissolve adequately; useful for spectroscopic work and crystallizations.
  • Aqueous buffers: Solubility increases at basic pH (deprotonation). Avoid strong base if O‑acyl integrity is critical.
  • Less polar solvents (EtOAc, acetonitrile): Moderate utility; may require gentle warming or co‑solvent.
• Practical tips:
  • Prepare concentrated stocks in DMSO (e.g., 10–100 mM) and dilute into assay buffers, keeping final DMSO ≤1–2% v/v where relevant.
  • For metal-binding studies, use metal-free water (chelexed) and plasticware or passivate glassware to minimize adventitious metal.

Quick comparison (general):

• DMSO vs MeOH: DMSO provides higher solubility and stability across pH; MeOH is more volatile and easier to remove during workup.
• Water (pH 7) vs pH 9 buffer: Significantly higher solubility at pH 9 due to deprotonation of the hydroxamic N–OH.

Storage and Reconstitution

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

General guidance for this compound class:

• Protect from moisture and prolonged light exposure. Store in a tightly closed container under ambient, dry conditions. For long-term storage, consider desiccation.
• Reconstitution/stock solutions:
  • Prepare concentrated stocks in dry DMSO or DMF (e.g., 10–100 mM). For aqueous use, dissolve first in a miscible organic solvent, then dilute into buffer with stirring.
  • For metal-binding experiments, use metal-free solvents/buffers and dedicate plasticware/glassware to minimize contamination.
• Stability:
  • Avoid strong bases/acids and high temperatures that may promote hydrolysis or rearrangement of the hydroxamic functionality.
  • Minimize repeated freeze–thaw of solutions; aliquot stocks and store at −20 °C if solution storage is required (literature practice). Verify stability by HPLC before critical experiments.

Always consult the Aladdin CoA and SDS for SKU N1067129 for lot-specific handling and storage recommendations.

Structure and Identity

N-Hydroxy-4-methoxybenzamide is an aromatic hydroxamic acid (para-methoxy substituted). It features a benzamide core in which the amide is N‑hydroxylated, enabling bidentate metal chelation and O/N‑acyl transfer chemistry.

• Item-specific identifiers (from Product Data)

  • CAS: 10507-69-4
  • CID: 221131
  • InChIKey: 314745 (as provided)
  • SKU: N1067129

• Research use note: For research use only.

• Literature/typical identifiers and structural description (for reference; not item-specific specs)

  • Synonyms: 4-methoxybenzohydroxamic acid; p-anisoyl hydroxamic acid
  • Functional groups: aromatic ether (para‑methoxy), hydroxamic acid (–C(=O)–NHOH)
  • 2D structure (described): A para‑methoxyphenyl ring bearing a benzamide carbonyl directly attached to the ring; the amide nitrogen carries a hydroxyl substituent (N–OH). Substitution pattern is para between methoxy (–OCH3) and the amide carbonyl.
  • Approximate empirical formula (literature): C8H9NO3
  • Approximate molecular weight (literature): ~167.16 g/mol
  • Example SMILES (literature): COc1ccc(cc1)C(=O)N O (spacing added for readability; represents para‑anisoyl hydroxamic acid)

• Structural features and implications (general)

  • The hydroxamic acid moiety acts as a bidentate O,O- or N,O-chelator to hard metal ions (e.g., Fe3+).
  • The para‑methoxy substituent is electron‑donating, increasing ring electron density and modulating H‑bond acidity/basicity of the hydroxamic motif.

Synthetic Utility

Functional group leverage:

• Hydroxamic acid (–C(=O)–NHOH):
  • Bidentate chelation to hard metals (utility in coordination chemistry and as directing elements).
  • O‑acyl/N‑acyl derivatization enabling access to activated hydroxamates.
• Para‑methoxy arene:
  • Electron-donating substituent enabling electrophilic aromatic substitution (nitration, halogenation) with para/ortho control already fixed; also modulates reactivity of the acyl group.

Named/characteristic transformations (literature/general):

• Lossen rearrangement: O‑activated hydroxamates rearrange to isocyanates under base or thermal conditions; subsequent trapping affords ureas, carbamates, or amines.
• Coupling to carboxylic acids or acyl chlorides: Forms O‑acyl hydroxamates; judicious choice of base/conditions directs O‑ vs N‑acylation.
• Conversion to oxime derivatives: Through controlled transformations enabling radical precursors for acylation chemistry under photoredox.
• Complex assembly: Use as a hydroxamate ligand fragment in multidentate chelators (e.g., siderophore mimics) via attachment at the para‑methoxy position (after demethylation to phenol if needed) or via acyl side manipulations.

Practical notes:

• Protect the N–OH when incompatible with downstream steps (e.g., as O‑silyl or O‑acyl derivatives). Avoid strong base that can induce rearrangement or cleavage.
• Electron-rich anisoyl ring may facilitate selective cross-coupling after halogenation (e.g., para‑OMe directing effects), broadening diversification.

Target Specificity

Not an antibody, enzyme, or biologic. No target specificity, clone, isotype, or species reactivity is applicable to this small-molecule reagent.