4-Methoxy-3-methylbenzamide - ≥98% , CAS No.932123-52-9

CAS: 932123-52-9 Cat. No.: M979127 Formula: C₉H₁₁NO₂ Peso molecolare: 165.190

GRADE & PURITY ≥98%

Storage

Room temperature

Specifications

Specifiche e purezza

≥98%

Condizioni di conservazione di stoccaggio

Room temperature

Purezza

≥98%

Nomi e identificatori

Sorrisi canonici

CC1=C(C=CC(=C1)C(=O)N)OC

IUPAC Name

4-methoxy-3-methylbenzamide

InChIKey

KXWRQYVEKWWYHO-UHFFFAOYSA-N

INCHI

1S/C9H11NO2/c1-6-5-7(9(10)11)3-4-8(6)12-2/h3-5H,1-2H3,(H2,10,11)

Peso molecolare

165.190

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: Benzamides
• Alternative Parents: m-Toluamides Phenoxy compounds Methoxybenzenes Benzoyl derivatives Anisoles Alkyl aryl ethers Primary carboxylic acid amides Organonitrogen compounds Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Benzamide - Toluamide - M-toluamide - Anisole - Benzoyl - Phenol ether - Methoxybenzene - Phenoxy compound - Toluene - Alkyl aryl ether - Primary carboxylic acid amide - Carboxamide group - Ether - Carboxylic acid derivative - Organooxygen compound - Organonitrogen compound - Organic nitrogen compound - Hydrocarbon derivative - Organic oxygen compound - Organic oxide - Aromatic homomonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as benzamides. These are organic compounds containing a carboxamido 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

Proprietà chimiche e fisiche

• Peso molecolare: 165.190 g/mol
• XLogP3: 1.600
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 2
• Exact Mass: 165.079 Da
• Monoisotopic Mass: 165.079 Da
• Topological Polar Surface Area: 52.300 Ų
• Heavy Atom Count: 12
• Formal Charge: 0
• Complexity: 170.000
• 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 biological assay protocols (e.g., WB, IHC, IF, FC) are provided or validated for this small-molecule building block. For synthetic protocols, refer to the Reaction Conditions and Synthetic Utility sections.

Biological Roles

This compound is a small aromatic amide used primarily as a synthetic building block. No intrinsic biological role is established for 4-methoxy-3-methylbenzamide itself.

General biochemical context (literature; not product-specific):

• Aromatic amides often serve as pharmacophore fragments featuring H-bond donor/acceptor capabilities and planarity that facilitate protein pocket interactions in chemical biology probes.
• Anisamide-derived motifs (p-methoxybenzamides) have been explored as ligating handles in targeted delivery research; however, activity depends strongly on the full molecular scaffold and substituent pattern. No claims are made for this specific compound.
• Metabolic stability: Aromatic primary amides can undergo enzymatic hydrolysis to the corresponding carboxylic acids and ammonia/amine; O-demethylation of anisyl groups may occur via P450s in biological systems, but rates are highly context-dependent.

Use limitation: For research use only. Not for human or veterinary use. Any biological testing requires appropriate institutional review and safety procedures.

Buffer Applications

Not typically applicable. 4-Methoxy-3-methylbenzamide is not a buffering agent and does not form a conventional conjugate acid/base pair with a useful aqueous pKa in the physiological buffering range. For aqueous work, dissolve in suitable co-solvents (e.g., DMSO) and use established buffers (phosphate, HEPES, Tris) as needed.

Green Alternatives

While 4-methoxy-3-methylbenzamide is a substrate rather than a solvent or reagent, greener choices can be made around its use.

Greener solvent alternatives (general guidance):

• Replace DMF/DMAc with Cyrene, N-butylpyrrolidone (NBP), or propylene carbonate where feasible (e.g., amidation, N-alkylation) to reduce reproductive-tox classification risks.
• Swap chlorinated solvents (DCM/CHCl3) with 2-MeTHF, CPME, EtOAc, or toluene for extractions and crystallizations when solubility allows.
• For cross-coupling or C–H activation work, 2-MeTHF, CPME, or water/EtOH mixtures under micellar conditions can reduce environmental impact.

Reagent choices and process intensification:

• Dehydration to nitriles: Consider T3P (propylphosphonic anhydride) or cyanuric chloride as alternatives to SOCl2/POCl3 to minimize corrosive off-gassing; evaluate EHS tradeoffs.
• Base selection: Solid-supported bases or carbonate bases in greener solvents can simplify workup and reduce waste.
• Crystallization-driven purification minimizes chromatography solvent consumption; explore antisolvents like heptane or water/EtOH blends.

Comparison snapshot (illustrative):

• DMF vs 2-MeTHF: DMF offers broad solvation but is a reprotoxin; 2-MeTHF is bio-based and lower toxicity, though polarity is lower and solubility may limit.
• DCM vs EtOAc: DCM provides fast phase separations; EtOAc is biodegradable and less hazardous but has higher boiling point and can form azeotropes.

Always assess performance, safety, and regulatory context holistically before substituting.

Pharmaceutical Uses

Formulation/excipient role: None specified for this item.

General context (non-clinical; no therapeutic claims):

• As a well-defined aromatic primary amide, this compound can serve as a reference standard or synthetic intermediate during medicinal chemistry campaigns, aiding SAR exploration where the anisyl–benzamide motif is of interest.
• Solid-state properties (crystallinity, hydrogen bonding) may be leveraged in co-crystal screening or salt/co-former studies for related scaffolds. Any such applications require full characterization of purity, polymorph, and residual solvents per internal SOPs.

Regulatory status: Not specified. Not listed as a pharmacopeial excipient or API for this item. For GMP or GLP contexts, request documentation and quality suitable for your intended use.

Physical Properties

Item-specific specifications (for this SKU):

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Purity/grade: Not specified for this item; refer to CoA/Spec Sheet.
• Density, melting point, boiling point, refractive index, UV cutoff, water/peroxide/metal limits: Not specified for this item; refer to CoA/Spec Sheet.

Literature/general expectations for substituted benzamides (for planning only; not item specifications):

• Physical state: typically a crystalline solid for mono-substituted aromatic benzamides with methoxy/methyl groups.
• Solubility profile: aromatic primary amides are usually sparingly soluble in water but soluble in polar organics (DMSO, DMF, NMP) and moderately soluble in alcohols and chlorinated solvents; reduced solubility in aliphatic hydrocarbons due to polarity of the amide.
• Lipophilicity: addition of methoxy and methyl increases aromatic lipophilicity relative to benzamide; expect moderate logP (literature for analogous anisamide derivatives ~1–2.5).
• Hydrogen bonding: capable of strong intermolecular H-bonding via the amide NH/CO, often elevating melting points relative to analogous anilides.

Note: If exact values (mp, solubility in specific solvents, Karl Fischer water, etc.) are required for your method validation or processing, please consult the lot-specific CoA or request the Specification Sheet.

Quality and Grades

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

How to interpret common grades (general guidance):

• Research/Technical grade: Suitable for most synthetic and discovery workflows; impurity profiles may not be optimized for trace analyses.
• Purified/98%+ organic building block grade: Typical for heteroaromatic/aryl amides used in synthesis; adequate for coupling, metal-catalyzed transformations, and SAR programs.
• HPLC grade (for solvents) or LC/MS grade (for analytes): Not applicable here unless explicitly stated; solids rarely carry HPLC grade designations unless intended as analytical standards.

Quality considerations specific to aromatic amide building blocks:

• Residual solvents: DMF, DCM, ethyl acetate may be present in trace amounts depending on crystallization history—check CoA if relevent for regulatory filings.
• Water content: Hygroscopicity is usually low-to-moderate for aromatic amides, but they can adsorb surface moisture. Karl Fischer values, if critical, should be confirmed on the supplied lot.
• Polymorphism: Many benzamides crystallize readily; distinct forms can influence mp and filtration/drying behavior. If crystallinity is critical, request solid-state characterization.

Documentation: For this item, rely on the lot-specific Certificate of Analysis and Specification Sheet for exact assay, residual metals/solvents, and analytical methods (NMR, HPLC, GC, MS) used to release the batch.

Reaction and Applications

As a substituted benzamide, 4-methoxy-3-methylbenzamide serves as a versatile intermediate and ligand motif in synthesis and materials chemistry.

Key application families (general literature guidance):

• Dehydration to aryl nitrile: Primary amide → nitrile using SOCl2, POCl3, P2O5, or T3P; yields the corresponding 4-methoxy-3-methylbenzonitrile.
• N-Functionalization: Alkylation (NaH/alkyl halide), acylation (anhydrides/acid chlorides), or sulfonylation to access N-substituted amides for SAR libraries.
• Hydrolysis: Acidic (H2SO4, HCl, reflux) or basic (NaOH/KOH, reflux) to regenerate 4-methoxy-3-methylbenzoic acid; useful in protecting-group strategies for carboxylic acids.
• Amide as directing group: The benzamide can direct ortho-C–H activation/functionalization (e.g., Pd, Rh catalysis) at the 2- and 6-positions; subsequent DG removal or transformation expands diversity.
• Electrophilic aromatic substitution variants: The anisyl ring is activated para/ortho by –OMe and weakly by –Me; however, existing substituents impose regiocontrol; nitration, halogenation, or Friedel–Crafts acylations (on deactivated positions) may require strong conditions.
• Hydrogen-bonding motif: The –CONH– engages in supramolecular assembly and crystal engineering; useful in co-crystal screens.

Practical tips:

• Maintain dry conditions for dehydrations and N-alkylations; amide N–H acidity is modest, so strong base (NaH, t-BuOK) is typically required for clean N-alkylation.
• For metal-catalyzed C–H activation, consider installing/removing transient directing groups if sterics/electronics hinder reactivity at the desired site.
• Workups: For reactions in DMF/DMSO, aqueous quench followed by extraction with EtOAc or MTBE is effective; salt out if emulsions form.

Reaction Conditions

Typical conditions reported for analogous benzamide transformations (literature guidance; adjust to your system):

• Dehydration to nitrile:

  • Reagents: SOCl2 (3–6 equiv) with catalytic DMF; or POCl3 (3–5 equiv); or T3P (50% in EtOAc, 2–3 equiv) with base (DIPEA).
  • Solvent: Neat reagent, toluene, or CH2Cl2.
  • Temperature/time: 60–110 °C for 2–6 h (SOCl2/POCl3); 25–60 °C for 4–16 h (T3P).
  • Workup: Quench carefully into ice/water, neutralize, extract with EtOAc; silica gel purification if needed.

• Hydrolysis to acid:

  • Acidic: 6 M HCl or conc. H2SO4, reflux 4–16 h; aqueous workup yields the acid.
  • Basic: 2–4 M NaOH/KOH in EtOH/H2O, reflux 6–12 h; acidify to precipitate the acid.

• N-alkylation:

  • Base: NaH (1.2–1.5 equiv) or K2CO3 (2–3 equiv, for more reactive alkyl halides).
  • Solvent: DMF, DMSO, or MeCN.
  • Temperature/time: 0–25 °C charge, then 25–50 °C for 2–12 h.

• C–H activation (amide-directed):

  • Catalyst/base: Pd(OAc)2 (5–10 mol%), Ag2CO3/KOAc.
  • Solvent: DMSO, DMAc, or 1,4-dioxane.
  • Temperature: 80–130 °C; N2 or air as required by protocol.

Yields: Often 60–90% for dehydrations and hydrolyses; N-alkylations vary widely (40–85%) depending on electrophile. Always confirm compatibility with the anisyl OMe group and meta-methyl sterics.

Safety and Handling

Item-specific hazard information (GHS/CLP) for this SKU:

• Signal word, H-statements, pictograms, and GHS classification: Not specified for this item; refer to SDS.

General safety guidance for aromatic primary amides (informational; defer to SDS):

• Expected hazards: Typically low to moderate acute toxicity; may cause skin/eye irritation. Dusts can be nuisance particulates; avoid inhalation and contact.
• PPE: Use lab coat, safety glasses or goggles, and appropriate gloves (e.g., nitrile). Employ a fume hood to minimize dust or vapor exposure, especially during heating or when using volatile reagents.
• Handling: Avoid moisture ingress if conducting moisture-sensitive transformations (e.g., dehydrations). Prevent dust formation; handle solids gently. Wash thoroughly after handling.
• Storage incompatibilities: Keep away from strong oxidizers and strong acids/bases that can hydrolyze or degrade amides under forcing conditions. Avoid strong dehydrating agents unless intentional (e.g., SOCl2, POCl3).
• Thermal stability: Aromatic amides are generally thermally stable up to their melting/decomposition temperatures; avoid overheating to decomposition (can release irritating fumes of NOx/COx).
• First aid (overview): If on skin/eyes, rinse with water for several minutes; remove contaminated clothing. If inhaled, move to fresh air. If ingested, rinse mouth; seek medical advice. Always follow the product SDS for authoritative instructions.

Waste: Collect solid/solution waste as organic laboratory waste; do not discharge to drains. Follow institutional and local regulations.

Solvent Selection

This product is a moderately polar aromatic amide; solvent choice is typically dictated by your transformation or formulation goals.

General miscibility/solubility trends (literature; not item specifications):

• Good solvents: DMSO, DMF, NMP, DMAc; often soluble in hot ethanol/methanol and in chlorinated solvents (CH2Cl2, CHCl3).
• Moderate: Acetone, ethyl acetate, acetonitrile (solubility varies with temperature).
• Poor: Water and aliphatic hydrocarbons (hexanes, heptane) due to strong self-association via H-bonding and aromaticity.

Selection guidance by use-case:

• Reaction medium for N-alkylation/acylation: Polar aprotics (DMF/DMAc) or MeCN; ensure base compatibility and dryness.
• Dehydration to nitrile: Employ neat SOCl2 or POCl3 or use toluene/CH2Cl2 as carrier; rigorously dry conditions.
• Cross-coupling on the aryl ring (if further halogen introduced): Typical solvent sets include dioxane, toluene, CPME, MeTHF, or DMF with appropriate base.
• Purification/recrystallization: Ethanol/IPA, ethyl acetate/hexane, or toluene/EtOAc mixtures are commonly effective for benzamides; optimize empirically.

Small comparison (general):

• DMF vs DMSO: DMSO often affords higher solubility but can complicate workup; DMF easier to remove via aqueous workup then vacuum.
• EtOAc vs MeCN (crystallizations): EtOAc offers broader antisolvent pairing with hexanes; MeCN provides sharper solubility temperature dependence.

Always verify actual solubility for your batch at the intended scale and temperature.

Storage and Reconstitution

• Storage (Product Data): Room temperature.
• Shipped in: Not specified for this item; refer to CoA/Spec Sheet.
• Form: Not specified for this item; refer to CoA/Spec Sheet. Typically supplied as a solid for aromatic amides.

General guidance:

• Keep container tightly closed in a cool, dry, well-ventilated place. Protect from excessive heat and direct light.
• If long-term storage is planned, consider desiccation to minimize moisture uptake; temperature cycling should be avoided to prevent condensation inside the container.
• Reconstitution: If solution is required, dissolve in a suitable dry organic solvent (e.g., DMSO, DMF, MeOH, EtOH, or CH2Cl2) at the desired concentration. Filter if particulates remain. For biological assays, prepare concentrated DMSO stocks (e.g., 10–100 mM) and dilute into assay buffer immediately before use, ensuring final DMSO content is acceptable for the system.
• Freeze–thaw: Not applicable to solids; for prepared solutions, aliquot to avoid repeated freeze–thaw cycles.

Always consult the lot-specific CoA and SDS for definitive guidance on storage conditions and handling precautions.

Structure and Identity

Brief overview: 4-Methoxy-3-methylbenzamide is a substituted benzamide bearing a para-methoxy and meta-methyl relative to the amide on a benzene ring; it is a useful aromatic amide building block.

• Product Data (as provided for this item)

  • CAS: 932123-52-9
  • PubChem CID: 18892494
  • InChIKey: 192561 (as provided)
  • 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 identifiers and features (general reference; not item specifications)

  • Typical molecular formula (literature): C9H11NO2
  • Typical molecular weight (literature): ~165.19 g/mol
  • Representative SMILES (literature): COc1ccc(C)cc1C(=O)N
  • Structural features: one benzamide moiety (–C(=O)NH–) conjugated to an anisyl (4-methoxyphenyl) ring with a 3-methyl substituent; no stereocenters; planar aromatic core; one H-bond donor (amide NH) and two H-bond acceptors (amide C=O and methoxy O).
  • 2D description in words: A benzene ring bearing at C1 an amide carbonyl (–C(=O)NH2), at C3 a methyl (–CH3), and at C4 a methoxy (–OCH3) substituent.

Synthetic Utility

Functional group handle and transformations (general literature guidance):

• Amide handle: Enables N-alkylation, acylation, sulfonylation, and conversion to imidoyl chlorides; can be reduced (e.g., with borane) to the corresponding benzylamine derivative.
• Amide → nitrile: Dehydration with SOCl2, POCl3, P2O5, T3P affording 4-methoxy-3-methylbenzonitrile (useful cross-coupling partner after halogenation).
• Amide → acid/ester: Hydrolysis to 4-methoxy-3-methylbenzoic acid followed by Fischer or Steglich esterification.
• Directed ortho metalation/C–H activation: The –CONH– can direct ortho-functionalization to positions 2/6. Subsequent transformations allow installation of halogens, B(pin), CF3, etc.
• Protecting-group logic: The amide can mask the acid functionality during multi-step sequences and be unveiled under controlled hydrolysis.

Retrosynthetic value:

• Accessible from 4-methoxy-3-methylbenzoic acid via standard amidation protocols (acid chloride, CDI, EDC/HOBt or HATU with NH3 or ammonium salts). Alternatively, nitrile hydration (Pd/Cu catalysis or classical sulfuric acid) furnishes the amide.

Practical notes:

• For N-alkylation, pre-generate the sodium amide with NaH in dry DMF/THF at 0–25 °C before adding alkyl halide to minimize O-alkylation of the methoxy (rare but possible under harsh conditions).
• Electron-donating OMe/Me substituents increase ring activation; control electrophilic substitutions to avoid polysubstitution.

Target Specificity

Not applicable. This product is a small-molecule building block and is not an antibody, enzyme, nucleic acid, or biological probe with defined target specificity. No antigen/epitope or species reactivity data apply.