4-Methoxy-2-nitrobenzamide - ≥98% , CAS No.33844-22-3

CAS: 33844-22-3 Cat. No.: M1062369 Fórmula: C₈H₈N₂O₄ Peso molecular: 196.16 PubChem CID: 118558

GRADE & PURITY ≥98%

Storage

Room temperature

Specifications

Especificaciones y pureza

≥98%

Condiciones de almacenamiento de almacenamiento

Room temperature

Pureza

≥98%

Nombres e identificadores

• Sonrisas canónicas: COC1=CC(=C(C=C1)C(=O)N)[N+](=O)[O-]
• IUPAC Name: 4-methoxy-2-nitrobenzamide
• InChIKey: QBDIKLOJLSJNTM-UHFFFAOYSA-N
• INCHI: 1S/C8H8N2O4/c1-14-5-2-3-6(8(9)11)7(4-5)10(12)13/h2-4H,1H3,(H2,9,11)
• Isómeros SMILES: COC1=CC(=C(C=C1)C(=O)N)[N+](=O)[O-]
• PubChem CID: 118558
• Peso molecular: 196.16

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Clase Benzene and substituted derivatives
      • Subclass Nitrobenzenes

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Clase: Benzene and substituted derivatives
• Subclass: Nitrobenzenes
• Intermediate Tree Nodes: Not available
• Direct Parent: Nitrophenyl ethers
• Alternative Parents: Methoxyanilines Benzamides Phenoxy compounds Nitroaromatic compounds Methoxybenzenes Benzoyl derivatives Anisoles Alkyl aryl ethers Primary carboxylic acid amides Propargyl-type 1,3-dipolar organic compounds Organic oxoazanium compounds Organopnictogen compounds Organonitrogen compounds Organic zwitterions Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Nitrophenyl ether - Methoxyaniline - Benzoic acid or derivatives - Benzamide - Phenoxy compound - Nitroaromatic compound - Methoxybenzene - Phenol ether - Benzoyl - Anisole - Alkyl aryl ether - Organic nitro compound - Primary carboxylic acid amide - C-nitro compound - Carboxamide group - Organic 1,3-dipolar compound - Propargyl-type 1,3-dipolar organic compound - Allyl-type 1,3-dipolar organic compound - Organic oxoazanium - Ether - Carboxylic acid derivative - Organic nitrogen compound - Organic oxygen compound - Organopnictogen compound - Organic oxide - Hydrocarbon derivative - Organic zwitterion - Organooxygen compound - Organonitrogen compound - Aromatic homomonocyclic compound
• Descripción: This compound belongs to the class of organic compounds known as nitrophenyl ethers. These are aromatic compounds containing a nitrobenzene moiety that carries an ether group on the 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

Propiedades químicas y físicas

• Peso molecular: 196.160 g/mol
• XLogP3: 0.800
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 2
• Exact Mass: 196.048 Da
• Monoisotopic Mass: 196.048 Da
• Topological Polar Surface Area: 98.100 Ų
• Heavy Atom Count: 14
• Formal Charge: 0
• Complexity: 238.000
• 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 assay or bioanalytical application protocols are provided for this item.

• Item-specific tested applications, dilutions, positive controls: Not specified for this item.

• Practical lab usage (general suggestions, not product-specific):

  • For chemical synthesis, weigh under ambient conditions, dissolve in an appropriate organic solvent (e.g., DMSO, DMF, EtOH), and proceed per your synthetic protocol.
  • For in vitro exploratory studies, prepare a concentrated DMSO stock (e.g., 10–100 mM), then dilute into assay media with mixing; verify solubility and lack of precipitation. Filter sterilize only if appropriate for your assay and solvent system.

Biological Roles

This product is a small-molecule aromatic amide intended for research and synthesis. It is not a biological reagent per se, and no biological function or activity is specified for this item.

• Item-specific biological data: Not specified for this item; refer to CoA/Spec Sheet.

• General background (literature, not product-specific):

  • Benzamide motifs are common in medicinal chemistry as hydrogen-bonding pharmacophores; anisole and nitro substituents tune electronic properties. However, 4-methoxy-2-nitrobenzamide itself is best viewed as an intermediate rather than a characterized bioactive compound.
  • Nitroaromatic groups can undergo bioreduction in biological settings, but such behavior is highly context-dependent and not claimed for this material.

• Usage note:

  • For research use only. Not for drug, diagnostic, or therapeutic use. Any biological evaluations should be designed and interpreted by qualified personnel with appropriate controls and safety oversight.

Buffer Applications

This compound is not a buffering agent and is not typically used to prepare biochemical buffers.

• Item-specific buffer use: Not specified for this item.

• Practical note:

  • If preparing assay solutions, dissolve first in DMSO or DMF to make a concentrated stock, then dilute into the desired aqueous buffer with vigorous mixing to avoid precipitation. Final organic cosolvent content is commonly kept at ≤1–2% v/v in biochemical assays, but optimization is assay-specific.

Green Alternatives

While this item is a solid building block rather than a solvent or reagent prone to high EHS impact on its own, greener choices can be made in the processes where it is used.

• Solvent selection (greener options vs common choices):

  • Replace DMF/DMAc/NMP with Cyrene, GBL, propylene carbonate, or 2-MeTHF where feasible for couplings and extractions.
  • Prefer ethanol, isopropanol, or water/EtOH blends for catalytic hydrogenations instead of chlorinated solvents.

• Reduction strategies (nitro → aniline):

  • Catalytic hydrogenation (H2, Pd/C or Raney Ni) in ethanol/isopropanol is often greener and cleaner than stoichiometric tin(II) chloride or iron/acid reductions, reducing inorganic waste.

• Workup and purification:

  • Employ crystallization from green solvent pairs (EtOAc/EtOH, EtOAc/heptane) over silica-intensive chromatography when possible.

• Comparison snapshot (general):

  • DMF vs Cyrene: Cyrene offers lower toxicity and biodegradability with similar polarity; viscosity and reactivity differences require optimization.
  • THF vs 2-MeTHF: 2-MeTHF is bio-based with higher boiling point and reduced peroxide hazard relative to diethyl ether; water content management is critical.

• Energy and waste:

  • Minimize high-temperature steps that risk amide hydrolysis; leverage catalytic, room-temperature couplings (ligand-enabled) and continuous-flow hydrogenations to reduce energy and solvent footprint.

Pharmaceutical Uses

No pharmacopeial status or excipient role is provided for this item.

• Item-specific pharmaceutical/formulation information: Not specified for this item; refer to CoA/Spec Sheet.

• General context (literature, not product-specific):

  • Benzamide derivatives can appear as intermediates in API synthesis or as fragments in SAR campaigns. 4-Methoxy-2-nitrobenzamide is primarily a synthetic intermediate; any use in GMP manufacturing would require independent qualification (impurities, residual solvents, elemental impurities) per ICH Q3 guidelines.

• Formulation considerations for research only:

  • If evaluating in vitro, prepare DMSO or DMF stocks and dilute into aqueous systems while monitoring for precipitation and adsorption to plastics. Avoid clinical or diagnostic use.

Physical Properties

• Item-specific specifications: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/general reference values (for context; not product specifications):

  • Molecular formula: C8H8N2O4 (literature)
  • Molecular weight: ~196.16 g/mol (literature)
  • Physical state/appearance: Typically a crystalline solid for substituted benzamides of this type (literature/general observation).
  • Acid–base behavior: The amide is essentially nonbasic; phenyl amides have very high amide pKaH and do not protonate readily. The most acidic site is typically the amide NH (very weak acid). Exact pKa values for this specific compound are not widely tabulated (literature).
  • Solubility (general expectations): low in water; soluble to varying degrees in polar aprotic solvents (DMSO, DMF, NMP) and hot alcohols/acetone/EtOAc; sparing in nonpolar hydrocarbons (literature trends for aromatic amides).
  • LogP/logS: Not broadly reported for this exact structure; expect moderate polarity due to amide and nitro groups (literature inference).

• Practical handling notes (general):

  • For solution preparation, DMSO or DMF typically provide the highest solubility; warm ethanol/2-propanol or EtOAc can assist for preparative work. Filter hot if necessary, then cool to crystallize.

Quality and Grades

• Item-specific grade/purity: Not specified for this item; refer to CoA/Spec Sheet.

• How to interpret grades (general guidance):

  • Research grade: suitable for most synthetic and analytical uses in R&D; impurity profiles can vary by lot. For chromatography or trace analysis, HPLC/GC grades emphasize low UV absorbance and minimal volatile/nonvolatile residues.
  • If a stabilizer is present, it will be declared on the CoA/Spec Sheet; stabilizers can influence downstream reactions (e.g., base-sensitive steps). None is indicated in the provided Product Data.

• Practical quality considerations for 4-methoxy-2-nitrobenzamide (general):

  • Typical organic impurities include regioisomers from nitration/methoxylation steps, residual nitration byproducts, and acylation reagents or solvents (e.g., DMF, acetic acid). Inorganics may include trace acids or metal residues from hydrogenation catalysts used upstream.
  • For sensitive applications, review the CoA for water content, residual solvents, and chromatographic purity. If UV transparency is needed (e.g., photophysics), verify UV–Vis background in your solvent of choice.

• Verification steps (recommendations):

  • Confirm identity by 1H/13C NMR and HRMS; confirm purity by HPLC/UPLC. Melting point determination can assist batch-to-batch comparison if reported on the CoA.

Reaction and Applications

As a functionalized benzamide bearing both a nitro and methoxy substituent, 4-methoxy-2-nitrobenzamide is a versatile intermediate for heterocycle construction and for divergent aryl functionalization.

• Representative transformations (literature/general):

  • Nitro reduction to 2-amino-4-methoxybenzamide using catalytic hydrogenation (H2/Pd-C, H2/Raney Ni) or transfer hydrogenation; chemoselectivity is typically high, delivering the aniline for subsequent coupling or cyclization.
  • Directed cyclizations: The o-amino amide (post-reduction) can condense to benzoxazoles/benzimidazoles under dehydrating conditions (e.g., POCl3, PPA), enabling rapid entry to bioinspired heterocycles.
  • Cross-coupling after aniline formation: Convert the aniline to diazonium salts for Sandmeyer-type substitutions or to (trifluoro)acetamide-protected derivatives amenable to C–N coupling (Buchwald–Hartwig) at the aryl C–X site introduced subsequently.
  • Electrophilic aromatic substitution patterns are tunable: the strong para-directing methoxy and deactivating nitro/meta-directing group create distinct reactivity windows for nitrations, sulfonylations, or halogenations.

• Synthetic roles:

  • Building block for anisamide-derived scaffolds, enabling libraries of substituted benzamides and benzoxazole/benzimidazole frameworks.
  • Precursor to ligands or fragments where the amide serves as a H-bonding element; the methoxy modulates electronics and lipophilicity.

• Practical tips:

  • For selective nitro reduction in presence of amide, mild catalytic hydrogenation in alcohols or AcOH/EtOH mixtures often suffices. Monitor for O-demethylation under harsh conditions.
  • Maintain anhydrous conditions for moisture-sensitive coupling reagents (e.g., when activating the amide for further elaboration). Degas solvents for metal-catalyzed steps to improve reproducibility.

Reaction Conditions

General literature guidance for representative transformations of 4-methoxy-2-nitrobenzamide (not product specifications):

• Nitro group reduction → aniline:

  • Catalytic hydrogenation: H2 (1–5 bar) with 5–10 wt% Pd/C in EtOH, i-PrOH, or EtOAc at 20–50°C, 1–6 h; monitor by TLC/HPLC. Isolated yields commonly high (70–95%) for similar substrates.
  • Transfer hydrogenation: NH4HCO2 or cyclohexene as H-donor with Pd/C in alcohols at 40–80°C.
  • Metal/acid: Fe (3–5 equiv) in AcOH/H2O or SnCl2·2H2O (2–3 equiv) in EtOH/HCl, 50–80°C; convenient but generates inorganic waste.

• O-Demethylation (anisole → phenol):

  • BBr3 (1–3 equiv) in CH2Cl2, −78°C to rt, 2–16 h; workup with MeOH/H2O to quench boron complexes.
  • Alternative: AlCl3 with thiols or HBr under reflux (substrate dependent). Monitor for amide stability.

• Cyclodehydration to benzoxazoles (from o-anilide):

  • After nitro reduction, treat the o-aminobenzamide with POCl3 (3–5 equiv) in toluene or neat at 80–110°C, 2–6 h; or with polyphosphoric acid (PPA) at 120–150°C. Typical yields vary (50–85%) depending on substitution.

• Workup and purification tips:

  • Charcoal polish hydrogenation mixtures to remove Pd/C fines; filter through Celite. Recrystallize products from EtOAc/hexanes or EtOH/water. Maintain oxygen exclusion for air-sensitive steps (e.g., metal-mediated reductions). Always confirm compatibility of the nitro group before applying strong bases or nucleophiles.

Safety and Handling

• Item-specific hazard data from Product Data/SDS: Not specified for this item; refer to SDS for authoritative classification, pictograms, and H-statements.

• General hazards of nitrobenzamide derivatives (literature, not product-specific):

  • May cause skin/eye irritation; harmful if swallowed or inhaled. Dust may irritate the respiratory tract. Thermal decomposition can release nitrogen oxides (NOx).

• Recommended PPE and controls (good laboratory practice):

  • Wear lab coat, safety glasses/goggles, and appropriate chemical-resistant gloves (e.g., nitrile). Handle powders in a fume hood to minimize dust exposure. Avoid inhalation and contact with skin and eyes.
  • Ensure adequate ventilation; avoid generation of dust and aerosols.

• Incompatibilities and reactivity (general):

  • Strong oxidizers and strong reducing agents may pose hazards. Avoid strong bases or acids if not required by protocol; hydrolysis of amide possible under forcing conditions. Combustion/overheating may produce COx and NOx.

• First-aid overview (consult SDS for details):

  • Inhalation: Move to fresh air; seek medical attention if symptoms persist.
  • 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; continue rinsing.
  • Ingestion: Rinse mouth; seek medical advice. Do not induce vomiting unless directed by medical personnel.

• Fire-fighting (general):

  • Use water fog, CO2, dry chemical, or foam. Avoid high-pressure water streams that may spread solid. Fire may produce hazardous NOx; firefighters should wear self-contained breathing apparatus.

Solvent Selection

This product is a solid aromatic amide; solvent choice is driven by intended use (reaction medium vs. sample preparation) and required concentration.

• Solubility/miscibility profile (general trends):

  • Highest solubility: DMSO, DMF, NMP (polar aprotic). Often soluble at 10–100 mg/mL at room temperature; heat if necessary.
  • Moderate solubility: hot EtOH, MeOH, 2-propanol, acetone, acetonitrile, and ethyl acetate.
  • Low solubility: water, toluene, hexanes, MTBE.

• Choosing a solvent by application:

  • Reaction medium for reductions (e.g., nitro-to-aniline): ethanol, methanol, isopropanol, acetic acid, or THF with hydrogenation catalysts; for metal-mediated reductions (Fe/AcOH), use acetic acid/ethanol mixtures.
  • Cyclizations/amide manipulations: polar aprotic solvents (DMF, DMAc) facilitate intramolecular condensations or coupling steps.
  • Analytical stocks: prepare concentrated DMSO or DMF stocks, then dilute into assay buffers/organic blends while avoiding precipitation.

• Practical tips:

  • Warm and sonicate to aid dissolution; filter hot solutions for recrystallization from EtOAc/hexanes or alcohol/water mixtures.
  • Avoid highly basic aqueous media if hydrolysis is a concern; the amide is relatively stable but can slowly hydrolyze under strong base/acid at elevated temperature.

• Quick comparison (general):

  • DMSO vs DMF: DMSO offers higher solvating power and lower volatility; DMF simplifies removal under vacuum. Alcohols enable catalytic hydrogenations and are greener than chlorinated alternatives.

Storage and Reconstitution

• Item-specific storage and shipping:

  • Storage conditions: Room temperature (as provided in Product Data). Protect from moisture and strong light sources to preserve material quality.
  • Shipped in: Not specified for this item; refer to CoA/Spec Sheet.

• Stability considerations (general):

  • Aromatic amides and nitroaromatics are typically stable solids at ambient conditions. Avoid prolonged exposure to strong acids/bases or elevated humidity which may promote hydrolysis or degradation.

• Reconstitution/preparation (general guidance for lab use; not product specification):

  • For stock solutions, dissolve in dry DMSO or DMF to the desired concentration (e.g., 10–100 mg/mL or 10–100 mM, solubility permitting). Gentle warming (30–40°C) and sonication can aid dissolution.
  • For aqueous assay use, dilute the organic stock into buffer with vigorous mixing to avoid precipitation; maintain final DMSO ≤1–2% v/v when compatible with the assay.
  • Store aliquoted solutions at 2–8°C or −20°C, protected from light and moisture. Avoid repeated freeze–thaw cycles; prepare single-use aliquots.

• Expiry and verification:

  • If long-term storage is anticipated, periodically verify identity/purity by HPLC and NMR. Observe for changes in appearance or solubility that might indicate degradation.

• Note: For definitive stability, reconstitution conditions, and shelf life, consult the lot-specific CoA/SDS.

Structure and Identity

A substituted benzamide featuring an ortho-nitro and para-methoxy substitution pattern on the benzamide ring.

• Item-specific (from Product Data):

  • SKU: M1062369
  • Product name: 4-Methoxy-2-nitrobenzamide
  • CAS: 33844-22-3
  • InChIKey: 292338 (as provided)
  • Storage conditions: Room temperature
  • Research use note: For research use only
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/computed identity details (general reference information, not item-specific specifications):

  • Preferred IUPAC name (literature): 4-methoxy-2-nitrobenzamide
  • Molecular formula (literature): C8H8N2O4
  • Molecular weight (literature): ~196.16 g/mol
  • Key functional groups: aromatic amide (–CONH2), nitro (–NO2), anisole-type methoxy (–OCH3)
  • 2D structural description: A benzene ring bearing an amide carbonyl (benzamide) at C1, a nitro substituent at the ortho (C2) position, and a methoxy substituent at the para (C4) position relative to the amide. The ring thus has three remaining ring hydrogens (C3, C5, C6). No stereogenic centers.

• Structural features relevant to reactivity (general):

  • The amide is moderately deactivating/meta-directing for further EAS; the methoxy is strongly activating/ortho-para-directing; the nitro is strongly deactivating/meta-directing. The combined pattern creates a differentiated arene for regioselective transformations.
  • The amide can serve as a hydrogen-bond donor/acceptor; the nitro and methoxy tune electronics for downstream reductions, cyclizations, or cross-couplings after appropriate derivatization.

Synthetic Utility

• Functional group handles and reactivity (general):

  • Nitro group: convertible to an aniline (reduction), a versatile synthon for subsequent diazotization, Sandmeyer reactions, and construction of heterocycles.
  • Methoxy group: modulates ring activation; can be demethylated (e.g., BBr3, AlCl3/thiols) to the phenol for further derivatization (etherification, esterification, SNAr enabling).
  • Amide: robust directing group; can participate in intramolecular cyclizations or be activated (e.g., to acid chlorides via hydrolysis to the acid or to imidazolides) for coupling.

• Retrosynthetic value:

  • Serves as a branch point to 2-amino-4-methoxybenzamide and 4-hydroxy-2-nitrobenzamide, each enabling distinct downstream libraries (benzoxazoles, benzimidazoles, salicylamide analogs).

• Named/representative transformations:

  • Nitro reduction (H2/Pd-C; Fe/AcOH; SnCl2/HCl), followed by cyclodehydration to benzoxazoles (e.g., with POCl3 or PPA).
  • Electrophilic halogenation on the anisamide ring guided by substituent electronics; subsequent cross-couplings (Suzuki–Miyaura, Buchwald–Hartwig) after appropriate handle installation.
  • Directed ortho metalation (DoM) can be explored on suitably protected derivatives; care needed due to nitro sensitivity.

• Practical considerations:

  • Protect the aniline (after reduction) as acyl/ sulfonyl carbamate for cross-coupling robustness. Avoid harsh bases in presence of nitro or amide unless temperature is controlled.

Target Specificity

Not applicable. This product is a small-molecule chemical and not a biological targeting reagent (e.g., antibody, enzyme, or ligand with defined target binding provided).

• Item-specific targeting data: Not specified for this item.