2-Ethyl-6-methoxypyridine - ≥95% , CAS No.199273-56-8

CAS: 199273-56-8 Cat. No.: E1041540 Formula: C₈H₁₁NO Molecular Weight: 137.18 PubChem CID: 5324777

GRADE & PURITY ≥95%

Storage

Room temperature

Specifications

Specifications & Purity

≥95%

Storage

Room temperature

Purity

≥95%

Names and Identifiers

• Canonical Smiles: CCC1=NC(=CC=C1)OC
• IUPAC Name: 2-ethyl-6-methoxypyridine
• InChIKey: QORIWACGFMMFAH-UHFFFAOYSA-N
• INCHI: 1S/C8H11NO/c1-3-7-5-4-6-8(9-7)10-2/h4-6H,3H2,1-2H3
• Isomeric SMILES: CCC1=NC(=CC=C1)OC
• PubChem CID: 5324777
• Molecular Weight: 137.18

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: Pyridines and derivatives Heteroaromatic compounds Azacyclic compounds Organonitrogen compounds Hydrocarbon derivatives
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Alkyl aryl ether - Pyridine - Heteroaromatic compound - Azacycle - Organoheterocyclic compound - Organic nitrogen compound - Hydrocarbon derivative - Organonitrogen compound - 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: 137.180 g/mol
• XLogP3: 2.000
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 2
• Exact Mass: 137.084 Da
• Monoisotopic Mass: 137.084 Da
• Topological Polar Surface Area: 22.100 Ų
• Heavy Atom Count: 10
• Formal Charge: 0
• Complexity: 95.300
• 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 antibody- or kit-style validated applications (e.g., WB, IHC, IF, FC) are associated with this small-molecule product in the provided data. For synthetic use, follow reaction-specific protocols under “Reaction Conditions” and standard organic synthesis practices.

Biological Roles

Applicability

• This is a synthetic small molecule intended for research use. No biological activity or clinical use is claimed for this catalog item.

General context for substituted pyridines (literature)

• Pyridine rings are prevalent bioisosteres of phenyl groups, enhancing polarity and introducing a basic H-bond acceptor site at nitrogen.
• Electron-donating methoxy at C6 and an alkyl group at C2 modulate pKaH and lipophilicity, affecting permeability, solubility, and metabolic stability trends observed in discovery chemistry.
• Typical biotransformations for related motifs include N-oxidation (via CYP450 or FMOs), O-dealkylation (O-demethylation), and side-chain oxidation at benzylic-like positions.

Use in research settings

• As a scaffold or intermediate for synthesizing libraries that probe structure–property relationships (H-bonding, pKa tuning, vector geometry at C2/C6 of pyridines).

Reminder

• For research use only (per Product Data). Not for human or animal therapeutic or diagnostic use.

Buffer Applications

Not typically used as a buffer.

Context (general)

• While pyridines are weak bases, substituted pyridines such as 2-ethyl-6-methoxypyridine are not employed as classical buffering agents. The conjugate acid pKa for 6-alkoxypyridines typically lies near the lower physiological range (literature ca. 5–6), giving narrow buffering capacity under acidic conditions only.

Practical note

• If a buffer near pH ~5–6 is required, standard systems such as acetate, MES, or citrate are preferred due to defined composition, low UV absorbance, and biocompatibility.

Recommendation

• Use this compound as a synthetic intermediate rather than a buffering component. For pH control, select validated Good’s buffers or pharmacopeial buffers appropriate to the application.

Green Alternatives

Scope

• This product is a specialty building block, not a bulk process solvent. Green-chemistry considerations mainly concern solvent choice and transformation strategy rather than replacing the molecule itself.

Greener choices for common operations (general guidance)

• N-alkylation/quaternization: Prefer MeCN, acetone, or 2-MeTHF over DMF/DMSO when feasible. Employ solid-supported bases to simplify workup.
• N-oxidation: Use aqueous H2O2 in alcohols or AcOH rather than peracids where selectivity allows; minimize chlorinated solvents.
• O-demethylation: Consider catalytic transfer demethylation methodologies or iodide-mediated protocols that avoid large excesses of BBr3; evaluate solvent swaps to EtOAc or 2-MeTHF where compatible.
• Cross-coupling: Utilize aqueous micellar catalysis (TPGS-750-M, Savie) or ethanol/water systems with low-Pd loadings; consider Ni catalysis for arylations.

Comparison snapshot (process-level tradeoffs)

• Traditional: DCM, dioxane, DMF; strong Lewis acids (BBr3), peracids (mCPBA).
• Greener alternative: 2-MeTHF, CPME, EtOAc, aqueous ethanol; H2O2, catalytic demethylation; micellar media.

Waste and energy

• Favor telescoped sequences (e.g., N-oxide formation and functionalization without isolation). Use continuous-flow for exothermic halogenation or demethylation to improve safety and reduce solvent inventory.

Note: Selection depends on target transformation and tolerance to water/oxygen; always validate at lab scale.

Pharmaceutical Uses

Role

• This product is offered for research use only. It is not an excipient or approved pharmaceutical ingredient.

General context (discovery/manufacturing research)

• Substituted pyridines are common fragments in medicinal chemistry campaigns for tuning basicity, solubility, and target-binding vectors. 2-Ethyl-6-methoxypyridine can serve as a synthetic intermediate toward candidate molecules, salts, or prodrugs during early-stage research.

Formulation relevance

• As a neat base or freebase intermediate, it could be converted to a pyridinium salt to adjust crystallinity or handling in process research. However, no pharmacopeial status or monograph applies to this specific compound (not specified for this item).

Compliance note

• No therapeutic claims are made. Any use in drug manufacturing would require independent qualification, impurity profiling, and regulatory assessment specific to the intended application.

Physical Properties

Item-specific specs

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

Storage and shipping

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

Literature/computed (general guidance; not item specifications)

• Phase at ambient conditions: Typically a colorless to pale liquid for closely related 2-alkyl/6-alkoxypyridines.
• Typical boiling range (literature for analogous 2-ethyl/6-alkoxy pyridines): mid-to-high 100s °C under ambient pressure; vacuum distillation commonly used to purify such compounds.
• Density/refractive index: Often comparable to other alkoxy-substituted pyridines (density ~1.0–1.1 g/mL; nD in the 1.49–1.53 range), but exact values should be confirmed experimentally.
• Solubility profile (general): Good solubility in common organic solvents (EtOAc, toluene, DCM, THF, MeCN, alcohols). Aryl–O–Me plus ring N impart moderate polarity; water solubility is expected to be limited-to-moderate relative to pyridine itself.
• Acid–base: The ring nitrogen is basic (conjugate acid pKa for 6-alkoxypyridines commonly ~5–6 in water, literature). Substituents at C2 and C6 can reduce basicity vs pyridine due to inductive/anisotropy effects.
• Partitioning: LogP expected to be higher than pyridine due to ethyl and methoxy groups (qualitative).

Note: For authoritative numerical specifications (bp, mp, density, RI, assay), consult the CoA/Spec Sheet for this specific lot.

Quality & Grades

Item-specific quality

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

Interpreting common grades (general guidance)

• Research grade: Suitable for most synthetic and analytical R&D. CoA typically includes identity (NMR/GC–MS/LC–MS), assay, and limited impurity profile.
• High-purity/anhydrous grades (when applicable): Lower water and UV-absorbing impurities; important for moisture-sensitive reactions (e.g., strong bases, organometallics) or trace analysis.

Stabilizers/inhibitors

• Not indicated for this item. If present (e.g., acid scavengers for basic heterocycles), they should be disclosed on the CoA and may affect certain reactions (e.g., quaternization or metal-catalyzed couplings). Always review the CoA.

What to check on receipt (practical checklist)

• Identity: Compare NMR (1H, 13C) with literature for 2-ethyl-6-methoxypyridine; look for characteristic OCH3 singlet and ethyl triplet/quartet pattern; confirm aromatic pattern consistent with 2,6-disubstitution.
• Purity: GC or HPLC area %; verify absence of pyridinium salts or demethylated phenolic impurity.
• Water: If Karl Fischer is relevant to your process, verify as needed (not specified for this item).
• Color: Many pyridines slowly darken upon air/light exposure; slight yellowing can correlate with trace oxidation—repurify if critical.

Reaction & Applications

Role in synthesis (general)

• Heteroaromatic building block featuring (i) a nucleophilic/basic ring nitrogen, (ii) an anisole-like methoxy at C6, and (iii) a benzylic-like 2-ethyl side chain. This substitution pattern enables diverse downstream derivatizations and SAR expansion in discovery chemistry.

Representative transformations (literature examples)

• N-alkylation/quaternization: Alkyl halides or dialkyl sulfates produce pyridinium salts (phase-transfer agents, ionic tags) under mild conditions.
• N-oxidation: mCPBA or H2O2 affords the N-oxide, enabling directed C–H functionalization (e.g., Minisci-type or electrophilic substitution proximal to N).
• O-demethylation: BBr3, BCl3, or strong Lewis acids convert the 6-methoxy to 6-hydroxy; alternative routes include NaSEt/thiolate or TMSI.
• Side-chain oxidation at C2-ethyl: SeO2 (allylic/benzylic oxidation conditions) or metal-catalyzed aerobic methods can access the corresponding acetyl or aldehydic derivatives.
• Cross-coupling (after pre-functionalization): Bromination/chlorination at suitable ring positions, then Suzuki–Miyaura, Buchwald–Hartwig, or Negishi couplings broaden substitution.
• Lithiation/metalation: Directed ortho metalation is generally disfavored adjacent to pyridine N without strong directing groups; N-oxide or transient protection strategies can assist.

Use contexts

• Common in medicinal and agrochemical discovery as a benzene bioisostere offering H-bond acceptance and modulated electronics.
• Ligand/base component: The pyridine nitrogen can coordinate to metals (e.g., transient ligation in catalysis) or form transient salts to modulate reactivity.

Practical tips

• Basic impurities and water can impact quaternization and Lewis-acid steps—dry solvents and glassware are beneficial.
• Protect methoxy if demethylation is not desired under strong Lewis-acidic conditions.

Reaction Conditions

General literature conditions for typical transformations (guidance only; optimize per substrate)

• N-alkylation/quaternization

  • Reagents: Alkyl halides or dialkyl sulfates (1.1–2.0 equiv)
  • Base/solvent: K2CO3 in MeCN or acetone; or neat with excess alkylating agent
  • Temperature/time: RT to 60 °C, 2–16 h
  • Notes: Monitor by LC–MS; quench with base; isolate pyridinium salt by precipitation.

• N-oxidation to pyridine N-oxide

  • Reagents: mCPBA (1.1–1.5 equiv) in DCM, or H2O2 (30%) in MeOH/AcOH
  • Temperature: 0 °C to RT
  • Notes: Control exotherm; remove acid by wash; N-oxide enables directed functionalization.

• O-demethylation (6-methoxy → 6-hydroxy)

  • Reagents: BBr3 (1–3 equiv) in dry DCM
  • Temperature: −78 to 0 °C addition, then 0–25 °C, 1–4 h
  • Workup: Quench into MeOH/water carefully; neutralize; extract.

• Benzylic (2-ethyl) functionalization

  • Radical bromination: NBS (1.1–1.5 equiv), AIBN, CCl4 or refluxing C6H6/PhMe; or photochemical alternatives in greener solvents.
  • Oxidation: SeO2 (cat./stoich.) in toluene or dioxane, 80–110 °C; or MnO2 for benzylic alcohol oxidation (after initial hydroxylation).

• Cross-coupling (on halo-derivatives of this scaffold)

  • Suzuki: Pd(PPh3)4 (1–2 mol%), K2CO3, dioxane/H2O (80–100 °C)
  • Buchwald–Hartwig: Pd2(dba)3 + dialkylbiaryl phosphine, NaOtBu, toluene (90–110 °C)

Notes

• Dry, oxygen-free conditions improve outcomes for Lewis-acid steps and metal catalysis. Adjust equivalents and temperatures to minimize overreaction at the benzylic position.

Safety & Handling

GHS/SDS

• Signal word, hazard statements, GHS classification, and pictograms: Not specified for this item; refer to the SDS for authoritative information.

General hazards for substituted pyridines (literature/experience-based)

• May cause skin, eye, and respiratory irritation; harmful if swallowed or inhaled. Many pyridine derivatives are combustible liquids.
• Aminobase behavior: forms salts with strong acids; avoid contact with oxidizers and strong electrophiles.

Handling guidance (professional lab practice)

• PPE: Wear lab coat, safety glasses, and appropriate chemical-resistant gloves (e.g., nitrile). Use in a fume hood to avoid inhalation of vapors.
• Incompatibilities: Strong oxidizers, strong acids/bases (exotherm and salt formation), acid chlorides/anhydrides (acylation at N), and alkylating agents (quaternization). Avoid peroxides only if solvent carriers are etheric; this compound itself is not an ether solvent.
• Spill/cleanup: Absorb liquid spills with inert material; ventilate area; dispose of waste in accordance with institutional and local regulations.
• First aid (overview; defer to SDS): Eye/skin contact—rinse with water for at least 15 min and remove contaminated clothing. Inhalation—move to fresh air. Ingestion—rinse mouth; seek medical attention in all cases of exposure.

Fire safety

• Extinguishing media: Dry chemical, CO2, or foam. Cool containers with water spray.

Waste

• Collect as halogen-free organic waste unless contaminated; follow institutional waste segregation policies.

Solvent Selection

Applicability

• 2-Ethyl-6-methoxypyridine is a heteroaromatic building block, not typically used as a bulk solvent. This section focuses on selecting solvents for its handling, purification, and reactions where it is a substrate.

Polarity and miscibility (general guidance)

• Polarity class: Moderately polar, basic heteroarene; dissolves well in polar aprotic solvents (MeCN, DMF, DMSO), ethers (THF, MTBE), chlorinated solvents (DCM, CHCl3), and many hydrocarbons (toluene, xylenes). Water miscibility is limited-to-moderate.

Practical choices by use-case

• N-alkylation/quaternization: Polar aprotics (MeCN, DMF, acetone) with soluble bases. For greener choices, consider MeCN or 2-MeTHF vs DMF.
• Electrophilic functionalization via N-oxide: Perform N-oxidation in AcOH/Ac2O or H2O2/MeOH; subsequent reactions often in DCM, DCE, or AcOH.
• Demethylation (to phenolic 6-hydroxypyridine): Conduct with BBr3 in DCM or CH2Cl2/hexanes at low temperature; quench into MeOH or aqueous buffer.
• Metal-catalyzed cross-coupling on pre-halogenated analogs: Toluene/EtOH/H2O or dioxane/H2O for Suzuki; DMF/MeCN for Buchwald–Hartwig N-arylation (if using this as a ligand/base component).

Purification

• Column chromatography on silica with EtOAc/hexanes or DCM/MeOH gradients. Basic additives (0.1–1% Et3N) help mitigate tailing due to the pyridine nitrogen.

Storage & Reconstitution

Item-specific storage

• Storage Conditions: Room temperature (per Product Data).
• Shipped In: Not specified for this item; refer to CoA/Spec Sheet.

General handling

• Keep container tightly closed in a dry, well-ventilated area. Minimize exposure to air and light to limit gradual discoloration sometimes seen with pyridines.
• If long-term storage is anticipated, consider storing under inert gas after opening.

Stability

• Substituted pyridines are typically stable at ambient conditions. Avoid strong oxidants and strong acids/bases that could lead to salt formation or degradation.

Reconstitution

• Not applicable; supplied as a neat compound. If solidification occurs at low temperatures, gently warm to ambient and mix thoroughly before use.

Documentation

• For definitive shelf-life, impurity limits, and any stabilizer information, consult the product’s CoA/Spec Sheet and SDS.

Structure & Identity

Overview: 2-Ethyl-6-methoxypyridine is a substituted pyridine bearing an ethyl group at C2 and a methoxy group at C6. The ring nitrogen (sp2) is a strong hydrogen-bond acceptor and a basic site for salt formation.

Item-specific identifiers (from Product Data)

• SKU: E1041540
• Product Name: 2-Ethyl-6-methoxypyridine
• CAS: 199273-56-8
• PubChem CID: 5324777
• InChIKey: 302484 (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/structure description (general)

• Core scaffold: six-membered aromatic pyridine ring (one ring nitrogen, no stereocenters).
• Substituents: ethyl at the 2-position (α to N), methoxy at the 6-position (ortho to N across the ring). The 2/6 pattern creates peri-like proximity to N, influencing basicity and steric environment.
• Functional groups: aromatic heterocycle (pyridine), anisole-like aryl methyl ether (–OCH3), alkyl side chain (–CH2–CH3).
• 2D description in words: A planar pyridine ring with nitrogen at the top; moving clockwise, C2 bears –CH2CH3, C3–C5 are ring CH units, and C6 bears –OCH3. The methoxy oxygen is bound to C6 and carries a terminal methyl group.

Synthetic Utility

Functional handles and reactivity (general)

• Ring nitrogen (Lewis basic site): amenable to salt formation, quaternization, and transient coordination to metals.
• Aryl methyl ether at C6: convertible to phenol (BBr3/TMSI) for further diversification (etherification, carbamate/urea formation).
• 2-Ethyl side chain: benzylic-like reactivity enables oxidation to acyl derivatives, halogenation, or radical functionalization.

Strategic value

• Vector geometry: 2,6-disubstitution places two substituent vectors flanking the ring nitrogen—useful in designing bidentate ligands or intramolecular H-bond motifs after O-demethylation.
• N-oxide approach: Temporarily increasing ring activation/directing power to access otherwise challenging C–H functionalizations, then reducing back to the pyridine.
• Downstream cross-coupling: After pre-halogenation, deploy Suzuki, Negishi, or Kumada couplings to elaborate the scaffold.

Representative transformations

• Quaternization → pyridinium salts (handles for SNAr/Umpolung or as phase-transfer catalysts).
• O-demethylation → phenol → Mitsunobu etherification or Chan–Lam O-arylation.
• Side-chain chemistry → oxidation (SeO2, MnO2), radical bromination (NBS/AIBN) followed by substitution.

Analytical cues

• 1H NMR: O–CH3 singlet (~3.7–4.1 ppm), ethyl triplet (~1.1–1.3 ppm) and quartet (~2.5–3.0 ppm), three aromatic protons split by 2,6 pattern; 13C NMR shows anisole-like C–O signal (~155–165 ppm, literature ranges).

Target Specificity

Not applicable.

• This product is a small-molecule heteroaromatic and does not possess target specificity data (e.g., antigen, epitope, clone, isotype). No biological binding specificity is provided in the Product Data.