5-Methoxy-2-methyl-1-oxo-1lambda~5~-pyridine - ≥95% , CAS No.35392-66-6

CAS: 35392-66-6 Cat. No.: M1024138 Formula: C₇H₉NO₂ Molecular Weight: 139.150 EC Number: 102-447-8

GRADE & PURITY ≥95%

Storage

Room temperature

Specifications

Specifications & Purity

≥95%

Storage

Room temperature

Purity

≥95%

Names and Identifiers

Canonical Smiles

CC1=[N+](C=C(C=C1)OC)[O-]

IUPAC Name

5-methoxy-2-methyl-1-oxidopyridin-1-ium

InChIKey

HAMUUCVAFXJSLN-UHFFFAOYSA-N

INCHI

1S/C7H9NO2/c1-6-3-4-7(10-2)5-8(6)9/h3-5H,1-2H3

Molecular Weight

139.150

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organic oxygen compounds
    • Class Organooxygen compounds
      • Subclass Ethers

• Kingdom: Organic compounds
• Superclass: Organic oxygen compounds
• Class: Organooxygen compounds
• Subclass: Ethers
• Intermediate Tree Nodes: Not available
• Direct Parent: Alkyl aryl ethers
• Alternative Parents: Methylpyridines Pyridinium derivatives Heteroaromatic compounds Azacyclic compounds Organonitrogen compounds Organic salts Organic oxides Hydrocarbon derivatives Organic cations
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Methylpyridine - Alkyl aryl ether - Pyridinium - Pyridine - Heteroaromatic compound - Azacycle - Organoheterocyclic compound - Organic nitrogen compound - Organic oxide - Hydrocarbon derivative - Organic salt - Organonitrogen compound - Organic cation - Aromatic heteromonocyclic compound
• Description: This compound belongs to the class of organic compounds known as alkyl aryl ethers. These are organic compounds containing the alkyl aryl ether functional group with the generic formula R-O-R' , where R is an alkyl group and R' is an aryl 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: 139.150 g/mol
• XLogP3: 0.200
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 1
• Exact Mass: 139.063 Da
• Monoisotopic Mass: 139.063 Da
• Topological Polar Surface Area: 34.700 Ų
• Heavy Atom Count: 10
• Formal Charge: 0
• Complexity: 108.000
• 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 validated bioassay or immunoassay protocols are provided for this small-molecule reagent. If using in screening assays, standard compound handling applies: prepare concentrated stocks in DMSO (e.g., 10–100 mM), filter if necessary, and dilute into assay buffer while respecting final DMSO limits. Verify solubility and stability under your specific assay conditions.

Biological Roles

Applicability

• This product is intended for research use only. No medical or clinical claims are made.

General background (literature; not item-specific claims)

• Pyridine N-oxides occur as Phase I/II metabolites of pyridine-containing xenobiotics and natural products. Flavin monooxygenases (FMO) and cytochrome P450s can generate N-oxides from tertiary nitrogen heterocycles.
• N-oxides often increase polarity and can affect transporter recognition and distribution in biological systems. They can serve as pro-forms that are reduced back to the parent amine/aza-arene in vivo in some organisms.
• Methoxy and methyl substitution on a pyridine N-oxide modulate lipophilicity and electron density, impacting binding and reactivity in biochemical assays, though specific targets for 5-methoxy-2-methylpyridine N-oxide are not established here.

Practical implication for lab biology workflows

• Increased polarity may improve aqueous compatibility in certain assay buffers compared with the corresponding pyridine, but solubility remains highly context dependent. Co-solvents (DMSO) are frequently employed for stock solutions.
• When screening in enzyme or receptor assays, be aware that N-oxides can undergo bioreduction under cellular or microsomal conditions, potentially complicating SAR interpretation. Include stability controls (chemical and metabolic) where relevant.

Buffer Applications

Not typically applicable.

• This compound is a heteroaromatic building block, not a buffering agent. It lacks a defined conjugate acid/base pair with a pKa profile typically exploited for buffering at physiological ionic strengths.
• For experimental use in biochemical assays, prepare stocks in DMSO or a miscible polar solvent, then dilute into your chosen buffer (e.g., phosphate, HEPES) while keeping final co-solvent below assay tolerance. Determine apparent pKa values empirically if ionization behavior is relevant to your study (literature pKa data for substituted pyridine N-oxides vary with substitution and are not specified for this item).

Green Alternatives

Context

• This is a heteroaromatic building block, not a volatile solvent. Green considerations therefore focus on reaction media and reagents used with it.

Greener solvent choices (literature/general)

• Replace chlorinated solvents (CH2Cl2, DCE) with:
  • 2-Methyltetrahydrofuran (2-MeTHF): Bio-based, reusable; good for extractions and many metal-catalyzed reactions.
  • Ethyl acetate (EtOAc): Low toxicity, readily biodegradable; suitable for workups and some reactions.
  • Dimethyl carbonate (DMC) or propylene carbonate: Low toxicity polar aprotics; consider for acylations or SN reactions where applicable.
  • Cyrene (dihydrolevoglucosenone) and PolarClean: Emerging dipolar aprotics replacing DMF/NMP in certain transformations.

Reagent alternatives and process tweaks

• N-oxide reductions: Prefer Zn/AcOH or catalytic hydrogenation over phosphorus chlorides to minimize halogenated phosphorus waste, where compatible with sensitive groups.
• Electrophilic halogenations: Use N-halosuccinimides (NXS) under catalytic conditions rather than molecular halogens to reduce hazard and waste.
• Energy efficiency: Many N-oxide rearrangements proceed under mild heating; adopt microwave or flow where appropriate to shorten cycle times and reduce solvent volumes.

Trade-offs

• Greener solvents may alter regioselectivity or rates in N-oxide–directed chemistry; small-scale scouting is advised. Some bio-based solvents hold more water, requiring drying to maintain outcomes.

Waste considerations

• N-oxide chemistry can produce acidic byproducts (e.g., carboxylates from anhydrides); neutralize and segregate aqueous/organic streams per local regulations.

Pharmaceutical Uses

Scope of use

• For research use only. No therapeutic or clinical use is implied.

Formulation/excipient role

• Not used as a common excipient. Its primary value in the pharmaceutical space is as a synthetic intermediate or directing-group-bearing scaffold to access substituted pyridines and related motifs during API discovery and route scouting.

Process chemistry relevance (general)

• Temporary activation: The N-oxide can be introduced and later removed (reduced) to manage regioselectivity in pyridine functionalization en route to API targets.
• Handle generation: Directed halogenation or acyloxymethylation from the 2-methyl N-oxide provides potent convergence points for cross-couplings or nucleophilic substitutions in late-stage diversification.

Regulatory considerations

• No pharmacopeial monograph is indicated for this specific substituted N-oxide. For cGMP campaigns, request extended impurity profiling, residual solvent data, and nitration/halogenation impurity controls if those steps are part of your route.

Stability/compatibility (general)

• Typically stable at ambient storage when dry and protected from strong light/heat. Avoid strong reducing conditions during storage/handling if the N-oxide functionality must be retained.

Physical Properties

Item-specific (from Product Data)

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

Literature/computed (non-spec; for context only)

• Expected physical state: Low-molecular-weight heteroaromatic N-oxides are typically crystalline solids or viscous oils at ambient temperature (literature, general trend).
• Polarity/partitioning: N-oxides display elevated polarity versus the parent pyridine; logP values are typically lower than corresponding pyridines due to the N→O polarity (literature, general trend).
• Solubility profile: Commonly soluble in polar organic solvents (MeOH, EtOH, MeCN, acetone, DMSO) and variably soluble in moderately polar aprotic solvents (EtOAc, CH2Cl2). Water solubility is modest to moderate depending on substitution (literature, general trend).
• Spectroscopic identifiers: N-oxides show characteristic strong IR bands for N→O stretch around 1250–1350 cm−1 and downfield 15N/13C perturbations; 1H NMR typically shows deshielding of ring protons adjacent to the N-oxide and anisole-like methoxy singlet near δ 3.7–3.9 ppm (literature, general ranges).

Not provided/Do not infer as item specs

• Melting point, boiling point, density, refractive index, UV cutoff, water/peroxide/metal content: Not specified for this item; refer to CoA/Spec Sheet.

Quality & Grades

Item-specific (from Product Data)

• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
• Research use note: For research use only.

Guidance on quality considerations (general)

• Research grade: Suitable for synthetic, analytical, and method-development work in R&D settings. If HPLC/LCMS suitability is critical (e.g., analytical reference), request chromatographic purity profile, residual solvents, and residual inorganic content.
• N-oxide integrity: The N-oxide functionality can be reduced inadvertently under certain workup/storage conditions. High-quality material should show a clean N→O IR band (ca. 1250–1350 cm−1), a single set of aromatic resonances in 1H/13C NMR without signals for the corresponding pyridine, and correct elemental analysis/high-resolution MS.
• Stabilizers: None specified for this item. If stabilizers or inhibitors are critical for your application (e.g., to prevent reduction), consult the Spec Sheet.
• Documentation: For regulated workflows, request CoA lots with assay (area%), chromatographic method, and impurity profile. If chiral or polymorphic issues existed (not anticipated here), they would be disclosed—none are specified for this item.

Reaction & Applications

Compound type and reactivity (general for pyridine N-oxides; tailored to 2-methyl-5-methoxy substitution)

• Directing group power: The N-oxide redirects ring electron density, facilitating regioselective electrophilic substitutions (e.g., halogenation, nitration) often at C-4 or C-3 depending on substitution. The 5-methoxy substituent further activates the ring and modulates selectivity.
• Boekelheide rearrangement: 2-Methyl pyridine N-oxides are classic substrates. Acylation at the N-oxide followed by [1,2]-rearrangement furnishes 2-(acyloxy)methyl derivatives; hydrolysis then gives 2-hydroxymethyl products. The preinstalled 5-methoxy group can steer additional functionalization downstream.
• Polonovski/related processes: Activation of the N-oxide with acylating agents can generate cationic intermediates enabling C–C or C–O bond formation under mild conditions.
• Cross-coupling handles: After selective halogenation directed by the N-oxide, standard Pd-catalyzed couplings (Suzuki–Miyaura, Buchwald–Hartwig amination on activated positions) provide rapid library expansion.
• Reductive unmasking: Reduction of the N-oxide (e.g., with PCl3, P(OEt)3, Zn/AcOH) regenerates the corresponding 5-methoxy-2-methylpyridine, enabling “temporary activation” strategies.
• Oxidation at benzylic site: The 2-methyl substituent adjacent to the ring nitrogen is uniquely predisposed to oxidation/rearrangement pathways via the N-oxide (e.g., to hydroxymethyl or acyloxymethyl), offering access to alcohols, aldehydes, and further derivatives.

Use contexts

• Heteroarene diversification programs, medicinal chemistry SAR, and synthesis of pyridine-containing ligands or intermediates where N-oxide serves as both a protecting and directing group.

Reaction Conditions

General literature guidance (non-spec; optimize per substrate)

• Boekelheide rearrangement

  • Conditions: Ac2O or (CF3CO)2O (3–10 equiv), 0–25 °C to form N-acyl intermediate, then heat to 60–120 °C (neat or in MeCN/CH2Cl2) for 1–6 h.
  • Workup: Quench with water/MeOH, neutralize, then hydrolyze acyloxymethyl to hydroxymethyl with aqueous base or acid as needed.
  • Notes: The 2-methyl group is essential; 5-methoxy substitution typically tolerated and may accelerate.

• Directed halogenation (example)

  • NBS (1.05–1.5 equiv) in MeCN or AcOH, 0–25 °C to rt, 0.5–4 h; catalytic acids or light can promote. Monitor by TLC/LCMS.
  • Follow with cross-coupling: Pd(PPh3)4 (1–3 mol%), base (K2CO3/Cs2CO3), solvent (dioxane/MeCN/2-MeTHF), 60–100 °C, 2–12 h.

• Reduction of N-oxide

  • P(OEt)3 (1.5–3 equiv) in toluene or THF, reflux 1–3 h; or Zn/AcOH (3–5 equiv Zn) at rt–50 °C, 1–4 h.
  • Caution: Control exotherm and phosphorus-containing waste; ensure complete consumption to avoid mixtures.

• C–H functionalization (illustrative)

  • Pd- or Rh-catalyzed arylation with aryl halides/boron reagents in DMAc/DMSO/MeCN, base (KOAc/K2CO3), 80–130 °C, 6–24 h, under inert atmosphere.

Yields

• Highly substrate- and substitution-dependent; for 2-methyl pyridine N-oxides, Boekelheide often affords 60–85% to acyloxymethyl intermediates (literature range). Always conduct small-scale scouting.

Safety & Handling

Item-specific (from Product Data)

• Storage conditions: Room temperature.
• GHS signal word/H-statements/classification/pictograms: Not specified for this item; refer to SDS.

General safety guidance for pyridine N-oxides (literature/practice; defer to SDS)

• Hazard overview: Aromatic N-oxides are typically of low to moderate acute toxicity but can be irritants. Avoid inhalation of dust/vapors and skin/eye contact. Always consult the product-specific SDS for authoritative hazard classifications and exposure limits.
• PPE: Use lab coat, nitrile gloves, and safety goggles as a minimum. Handle in a fume hood to avoid inhalation of vapors or dust. Wash thoroughly after handling.
• Incompatibilities: Avoid strong reducing agents (e.g., POCl3/PCl3, TiCl3, metal hydrides) that can reduce the N-oxide to the corresponding pyridine; avoid strong acids/bases that may lead to decomposition or demethylation of the methoxy group under forcing conditions. Separate from powerful oxidizers only to prevent exothermic redox scenarios.
• Reactivity notes: The N-oxide is a mild internal oxidant and potent directing group; it can undergo rearrangements (e.g., Boekelheide) in the presence of acylating agents and bases.
• First aid (overview): Eye/skin exposure—rinse with plenty of water for at least 15 minutes; remove contaminated clothing. Inhalation—move to fresh air; seek medical attention if symptoms persist. Ingestion—not a normal route; seek medical advice. Provide SDS to responders.
• Fire: Use CO2, dry chemical, or foam. Combustion may produce NOx/CO/CO2; wear SCBA.

Always defer to the item-specific SDS for definitive handling and emergency measures.

Solvent Selection

Applicability

• This product is a heteroaromatic N-oxide building block rather than a process solvent. Solvent selection pertains to dissolving and reacting it efficiently.

General solubility/polarity guidance (literature/general)

• Polarity class: Moderately polar, hydrogen-bond acceptor rich (N→O and methoxy oxygen). Limited hydrogen-bond donation capacity.
• Likely good solvents: DMSO, DMF, MeCN, acetone, methanol, ethanol. Often soluble in EtOAc and CH2Cl2; solubility in ethers (THF, MTBE) may be moderate; limited in hexanes.
• Water: N-oxides can show modest water solubility; substitution (methyl, methoxy) typically reduces it. Co-solvents may be required for aqueous-phase chemistry.

When to choose which solvent (use-case oriented)

• Electrophilic substitution/halogenation on N-oxides: Acetic acid, HFIP, or MeCN commonly employed; N-oxide directs regioselectivity.
• Boekelheide rearrangement: Acylation in acetic anhydride or trifluoroacetic anhydride; base-assisted rearrangement often run neat or in chlorinated/aprotic solvents.
• Metalation/C–H activation: Polar aprotics (DCE, MeCN, DMAc) often used with Pd/Rh catalysts; avoid protic solvents if base-sensitive steps are involved.
• Reductive transformations (N-oxide → pyridine): Use of PCl3, Zn/AcOH, or P(OEt)3 typically in toluene, THF, or MeCN; ensure appropriate quench protocols.

Practical tips

• Pre-dry polar aprotic solvents (DMF/DMSO/MeCN) if strong bases or water-sensitive reagents are used.
• For workup, partitioning between water and EtOAc/MTBE is generally effective; monitor pH to avoid demethylation of the methoxy group.

Storage & Reconstitution

Item-specific (from Product Data)

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

General handling guidance (literature/practice)

• As supplied: Keep container tightly closed in a dry, well-ventilated place. Protect from excessive heat and direct light. If hygroscopicity is observed, store under inert gas or with desiccant.
• Solution preparation: For stock solutions, dissolve in dry polar organics (DMSO, MeCN, MeOH, acetone). Filter through 0.2 μm PTFE if particulate is present. Record concentration by weight or quantitative NMR if required.
• Stability of solutions: N-oxides are generally stable in aprotic solvents for weeks at 2–8 °C; avoid prolonged storage in the presence of strong acids/bases or reducing agents. For long-term solution storage, aliquot and keep at −20 °C to minimize freeze–thaw and adventitious reduction.
• Reconstitution: Not applicable if supplied neat. If provided as a solid, warm gently to room temperature before opening to avoid moisture condensation. If an oil, use positive-displacement pipettes for accurate dosing.

Specifications not provided

• Appearance, concentration limits, stabilizers, and shelf life: Not specified for this item; refer to CoA/Spec Sheet.

Structure & Identity

Item-specific (from Product Data)

• SKU: M1024138
• Product name: 5-Methoxy-2-methyl-1-oxo-1lambda~5~-pyridine (i.e., 5-methoxy-2-methylpyridine N-oxide)
• CAS: 35392-66-6
• InChIKey: 116441 (as provided; format appears atypical)
• 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.

Structural description (general/literature)

• Core scaffold: Aromatic six-membered pyridine ring bearing an N→O (pyridine N-oxide) functionality. The N-oxide is best depicted as an N+–O− zwitterion.
• Substitution pattern: A methyl group at the 2-position (α to the ring nitrogen) and a methoxy group at the 5-position (para to the 2-position in usual pyridine numbering), giving an electron-rich ring with a strongly directing N-oxide.
• Functional groups: Aromatic heterocycle (pyridine), N-oxide (N+–O−), anisole-type methoxy ether, benzylic-type methyl at C2.
• Stereochemistry: None (achiral, planar aromatic system).
• 2D depiction in words: The ring nitrogen (position 1) bears an exocyclic oxygen (N-oxide). Moving clockwise, position 2 carries a methyl substituent; positions 3 and 4 are unsubstituted ring carbons; position 5 carries a methoxy (–OCH3); position 6 is unsubstituted.

Notes

• The N-oxide significantly changes electron distribution versus pyridine, enhancing electrophilic substitution at defined positions and enabling characteristic rearrangements (e.g., Boekelheide).

Synthetic Utility

Key functional elements

• N→O functionality: Serves as a powerful directing group for electrophilic substitution and as a temporary protecting/activating group for pyridines.
• 2-Methyl substituent: Benzylic C–H adjacent to the ring nitrogen is predisposed to oxidation/rearrangement pathways (Boekelheide) to install a hydroxymethyl/acyloxymethyl at C2.
• 5-Methoxy substituent: Electron-donating, modulates ring reactivity and can be revealed (e.g., demethylated) to phenolic analogs on other heteroarenes; on pyridines, it primarily tunes electronics and can serve as a leaving group after activation (e.g., under SNAr on suitably activated systems).

Representative transformations (literature)

• Boekelheide rearrangement: RCO2-activation of the N-oxide followed by rearrangement/hydrolysis → 2-(hydroxy)methyl derivatives; oxidation → aldehydes/acids.
• Directed halogenation: NBS/NCS-mediated C–H halogenation at positions activated by N-oxide; subsequent Suzuki/Buchwald–Hartwig couplings.
• Reduction: P(OEt)3 or PCl3 to revert to 5-methoxy-2-methylpyridine, enabling “on/off” control of pyridine basicity and directing effects.
• C–H activation: Rh/Pd-catalyzed arylations/alkenylations leveraging the N-oxide as a directing group at C-2/C-4 positions (substitution pattern-dependent).

Retrosynthetic value

• Provides a masked handle for benzylic oxidation at C2 and a platform for regioselective diversification before final deoxygenation to the corresponding pyridine.

Target Specificity

Not applicable.

• This product is a small-molecule heteroaromatic building block and is not an antibody, enzyme, or affinity reagent. No target/cellular specificity, clone information, or species reactivity applies.