3-Ethoxyisonicotinonitrile - ≥97% , CAS No.78790-86-0

CAS: 78790-86-0 Cat. No.: E992048 分子式: C₈H₈N₂O 分子量: 148.160

GRADE & PURITY ≥97%

Storage

Room temperature

Specifications

仕様と純度

≥97%

保管条件

Room temperature

純度

≥97%

名前と識別子

• カノニカル・スマイル: CCOC1=C(C=CN=C1)C#N
• IUPAC Name: 3-ethoxypyridine-4-carbonitrile
• InChIKey: RCGBFDXSJLKYNK-UHFFFAOYSA-N
• INCHI: 1S/C8H8N2O/c1-2-11-8-6-10-4-3-7(8)5-9/h3-4,6H,2H2,1H3
• 分子量: 148.160

Taxonomic Classification

Taxonomy Tree

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

• Kingdom: Organic compounds
• Superclass: Organic oxygen compounds
• 分類: Organooxygen compounds
• Subclass: Ethers
• Intermediate Tree Nodes: Not available
• Direct Parent: Alkyl aryl ethers
• Alternative Parents: Pyridines and derivatives Heteroaromatic compounds Nitriles Azacyclic compounds Hydrocarbon derivatives
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Alkyl aryl ether - Pyridine - Heteroaromatic compound - Azacycle - Organoheterocyclic compound - Nitrile - Carbonitrile - Organic nitrogen compound - Cyanide - Hydrocarbon derivative - Organonitrogen compound - Aromatic heteromonocyclic compound
• 説明: 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

化学的性質と物理的性質

• 分子量: 148.160 g/mol
• XLogP3: 0.900
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 2
• Exact Mass: 148.064 Da
• Monoisotopic Mass: 148.064 Da
• Topological Polar Surface Area: 45.900 Ų
• Heavy Atom Count: 11
• Formal Charge: 0
• Complexity: 161.000
• 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 tested bioassay or immunoassay application protocols (e.g., WB, IHC, IF, FC) are relevant to this small-molecule building block. For synthetic applications, refer to the Reaction & Applications and Reaction Conditions sections for general procedural guidance and adjust to your laboratory’s standards.

Biological Roles

No intrinsic biological role is assigned to 3-ethoxyisonicotinonitrile; it is supplied strictly for research and chemical synthesis. The following are general, non-clinical considerations for heteroaromatic nitriles:

• As a fragment or scaffold: substituted pyridines bearing nitriles are frequently used as fragments or core motifs in medicinal chemistry SAR due to their capacity for hydrogen-bond acceptance (ring N, nitrile N) and for tuning electronics and lipophilicity (ether substituent). These features affect permeability and metabolic stability in structure–property studies (general medicinal chemistry knowledge).
• Metabolic liabilities (conceptual): aryl nitriles are often metabolically stable, while the pyridine nitrogen can undergo N-oxidation; ether side chains may be susceptible to oxidative O-dealkylation by P450s (literature trends). These are design considerations rather than product claims.
• Bioconjugation relevance: the nitrile can serve as a latent handle for transformation to amides/acids/amines that enable conjugation to linkers, resins, or reporter tags.

Important: Aladdin Scientific supplies this product for research use only. No statements herein imply suitability for therapeutic, diagnostic, or in vivo use.

Buffer Applications

This compound is not a buffering agent and is not typically used to prepare biochemical buffers. As a neutral heteroaromatic building block, it lacks the conjugate acid/base pairs and high aqueous solubility characteristic of buffer systems.

• If aqueous manipulation is needed (e.g., workups or salt formation), conventional laboratory buffers (phosphate, citrate, acetate) may be used around the target pH, but these are unrelated to the function of this compound itself.
• For enhanced aqueous handling, transient protonation to the corresponding pyridinium salt with mineral acid can increase water solubility; neutralize after processing.

Green Alternatives

This product is a specialty building block, not a commodity solvent or reagent, so “green alternatives” typically concern the choice of reaction media and reagents used with it rather than substituting the molecule itself.

Greener choices during common transformations (general literature guidance):

• Nitrile hydrolysis:
  • Prefer aqueous alcohols (EtOH/H2O) and catalytic mineral acids over strong sulfuric media where feasible; employ microwave or flow conditions to reduce time/energy.
  • Base-catalyzed hydrolysis can be conducted in water-rich mixtures, minimizing dipolar aprotics.
• Reductions:
  • Consider catalytic hydrogenation (H2, Pd/C) in ethanol or 2-MeTHF as an alternative to stoichiometric metal hydrides (LiAlH4) in ether solvents when chemoselectivity allows.
  • For nitrile-to-aldehyde reductions, evaluate safer hydride sources (e.g., diisobutylaluminum hydride handling in continuous flow, or catalytic transfer hydrogenation strategies) to limit pyrophoric reagents.
• Solvent selection hierarchy:
  • Favor EtOAc, MeTHF, CPME, or alcohols over chlorinated solvents where compatible with reactivity.
  • Use MeCN, DMF, and DMSO judiciously; capture and dispose via solvent recovery programs.

Compact comparison (illustrative):

• Traditional: LiAlH4 in THF/Et2O (high hazard, pyrophoric) vs Greener: H2/Pd in EtOH (lower EHS footprint, but potential over-reduction).
• Traditional: conc. H2SO4 hydrolysis vs Greener: aqueous HCl or solid acid catalysis in water/EtOH under microwave.

Trade-offs: Greener conditions may alter chemoselectivity (e.g., ether stability, partial reductions); validate on small scale with in-process analytics.

Pharmaceutical Uses

No pharmacopeial monograph or excipient status is indicated for this item, and it is sold strictly for research use only.

In a research/manufacturing context (general, non-clinical):

• Role: heteroaromatic intermediate for the synthesis of candidate APIs or advanced intermediates. The nitrile provides a convergent handle for late-stage diversification to amides, acids, tetrazoles, or amines; the pyridine ring offers a privileged scaffold common in discovery programs.
• Process chemistry considerations:
  • Robustness: aryl nitriles often withstand many cross-coupling and protection/deprotection conditions.
  • Salt forms: transient formation of pyridinium salts may assist in purification or crystallization screening.
  • Impurity control: track potential hydrolysis products (amide/acid), ether cleavage products (phenolic analog), and N-oxide in oxidative steps.

Regulatory note: Not intended for use as an active ingredient, excipient, or in any clinical application. Verify residual solvents, elemental impurities (ICH Q3D), and related substances profiles per internal R&D quality standards if used in preclinical route scouting.

Physical Properties

Item-specific specifications are not provided in the Product Data.

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

Literature/general expectations for the 3-ethoxy-4-cyanopyridine scaffold (for context only; not product specifications):

• Physical state: small heteroaromatic nitriles of similar size are often low-melting solids or high-boiling liquids; exact phase depends on crystal packing and is compound-specific.
• Polarity/solubility: polar, aprotic heteroaromatic; typically soluble in common organic solvents (e.g., DCM, EtOAc, MeCN, THF, toluene) and variably soluble in alcohols; limited miscibility in water is common for aryl nitriles. Actual solubility must be determined empirically.
• Acidity/basicity: pyridine nitrogen is weakly basic (pKaH for unsubstituted pyridine ~5.2, literature); ring deactivation by a para nitrile generally lowers basicity further (context).

Important: For experimental design, confirm concrete physical constants and analytical release specs directly from the supplied CoA/Spec Sheet for SKU E992048.

Quality and Grades

• Grade/purity: Not specified for this item; refer to CoA/Spec Sheet. Any stated assay, residual solvent profile, or chromatographic purity limits should be taken from the current batch CoA.
• Stabilizers/inhibitors: Not specified for this item; refer to CoA/Spec Sheet. This scaffold typically does not require an added stabilizer; if any is used it will be declared on the CoA.
• What the grade implies (general guidance): • Research-grade heteroaromatic building blocks are typically qualified by HPLC/GC purity, identity by NMR/HRMS, and residual solvent/water content (Karl Fischer) where applicable.
  • If “97%+” or “98%+” assay is indicated on the CoA, that generally supports use in discovery-scale synthesis without further purification; sensitive transformations may still benefit from a quick column or recrystallization.
• Lot-to-lot consistency: Expect identity and purity confirmation per Aladdin Scientific QA practices. For chromatography-critical work (e.g., medicinal chemistry SAR), verify UV profile and impurity pattern from the batch CoA prior to scale-up.
• Regulatory note: For research use only; not intended for food, drug, household, or diagnostic applications.

Reaction and Applications

3-Ethoxyisonicotinonitrile is a versatile heteroaromatic nitrile building block suited to diverse transformations in heterocycle, agrochemical, and medicinal chemistry.

Representative application families (literature/general guidance):

• Nitrile functional group interconversions:
  • Hydrolysis to primary amide (controlled) or carboxylic acid (complete) under acidic (mineral acid, heat) or basic (alkoxide/NaOH, reflux) conditions.
  • Pinner reaction to imidate esters (RO–C(=NH)–OR′) followed by conversion to amidines or amides.
  • Reduction to the corresponding 4-aminomethyl (via BH3·THF or LiAlH4) or to the aldehyde (DIBAL-H, low temperature).
  • [3+2] cycloaddition with azide (Lewis/Bronsted acid activation) to give tetrazoles.
• Ring manipulations and derivatizations:
  • N-oxidation to the pyridine N-oxide (mCPBA), enabling further regioselective substitutions (e.g., the Boekelheide rearrangement).
  • Quaternization at the ring nitrogen (alkyl/benzyl halides) forming pyridinium salts for phase-transfer or further transformations.
  • Directed lithiation or metalation at positions activated by the nitrile/N-oxide (with appropriate protecting strategies), enabling C–C or C–X bond formation after electrophile quench.
• Cross-coupling context: while this scaffold lacks a halogen, prefunctionalization (e.g., via selective C–H activation or introduction of a halide) allows Suzuki/Negishi/Sonogashira couplings to elaborate the ring.

Practical notes:

• The para nitrile strongly deactivates the ring toward electrophilic substitution; plan for nucleophilic pathways or transition-metal methods.
• Maintain anhydrous conditions when targeting partial nitrile reductions; water promotes over-reduction or hydrolysis.
• The 3-ethoxy substituent is generally stable; harsh nucleophiles/bases at high temperature can effect ether cleavage—monitor by LC/MS.

Reaction Conditions

General literature guidance for typical transformations of a 3-ethoxy-4-cyanopyridine scaffold (not item-specific specifications):

• Hydrolysis of nitrile: • Acidic: reflux in 6 M HCl or H2SO4/MeOH–H2O to amide (shorter) or acid (longer), 70–110 °C; monitor by LC.
  • Basic: NaOH or KOH in EtOH/H2O (1:1 to 3:1), reflux 4–24 h; work up by acidification to precipitate the acid.
  • Catalysis/microwave: aqueous mineral acid or base under microwave 120–160 °C can reduce times to 10–60 min.
• Reduction of nitrile: • To aldehyde: DIBAL-H (1.2–1.5 equiv) in toluene or THF, −78 to −20 °C, then quench at low temperature; avoid over-reduction.
  • To amine: BH3·THF (3–6 equiv), reflux 4–16 h; or H2 (20–50 bar) with Raney Ni/Pd/C in EtOH/MeOH at 25–60 °C until uptake ceases.
• Tetrazole formation: • [3+2] cycloaddition with NaN3 (1.2–2.0 equiv) in DMF or DMSO, with ZnCl2 or AlCl3 as Lewis acid promoter, 80–120 °C, 6–24 h (caution with azides; follow strict safety protocols).
• N-oxidation of pyridine: • mCPBA (1.1–1.5 equiv) in DCM at 0–25 °C, 1–4 h; subsequent rearrangements or substitutions as desired.

Practical controls:

• Dry, oxygen-controlled conditions improve yields for hydride reductions and metal-catalyzed steps.
• The substrate can coordinate catalysts via the ring N; adjust ligand sets or add acid/base to moderate binding when needed.
• Always confirm compatibility of the ethoxy ether with chosen conditions (e.g., avoid extended strong base at reflux if ether retention is required).

Safety and Handling

Always consult the SDS for SKU E992048 before use. Item-specific GHS details are not provided in the Product Data.

• GHS information: Signal word, hazard statements, pictograms, and classification: Not specified for this item; refer to SDS.
• Likely hazards (general for substituted pyridines/nitriles; not product-specific): may cause skin/eye irritation and respiratory tract irritation; harmful if swallowed. Nitrile functionality in organic molecules is not equivalent to cyanide salts but may hydrolyze under harsh conditions; handle to minimize exposure.
• Personal protective equipment (PPE): lab coat, safety glasses or splash goggles, and appropriate chemically resistant gloves (e.g., nitrile). Work in a certified chemical fume hood to control vapors and dust/aerosols.
• Handling practices: • Avoid inhalation of vapors or mists; avoid skin contact.
  • Use clean, dry tools; prevent contamination with strong acids/bases that could promote hydrolysis.
  • Keep away from ignition sources; although not a designated solvent, treat organic liquids/low-melting solids as combustible.
• Incompatibilities (general): strong oxidizers; strong acids/bases for extended periods (risk of hydrolysis/ether cleavage); powerful nucleophiles under forcing conditions.
• First aid (general): • Skin: wash with soap and water; remove contaminated clothing.
  • Eyes: rinse cautiously with water for several minutes; seek medical attention if irritation persists.
  • Inhalation: move to fresh air; seek medical advice if symptoms occur.
  • Ingestion: rinse mouth; do not induce vomiting; seek medical attention.
• Spill/leak: absorb with inert material; place in chemical waste. Prevent release to the environment; follow institutional protocols.

Solvent Selection

As a polar, aprotic heteroaromatic nitrile/ether, 3-ethoxyisonicotinonitrile shows broad solubility in common organic media. Item-specific solubility values are not provided; select solvents empirically with these guidelines:

• Polarity/miscibility (general expectations): • Good: DCM, chloroform, THF, EtOAc, acetone, acetonitrile, toluene, DMF, DMSO.
  • Variable: lower alcohols (MeOH, EtOH) depending on temperature and concentration.
  • Poor: water (typical of aryl nitriles), though modest aqueous solubility can occur with cosolvents or upon protonation of the ring nitrogen.
• Selection by use-case: • Reaction medium for nitrile transformations (hydrolysis, reductions): mixed solvents such as THF/H2O (base hydrolysis), dioxane/HCl(aq) (acid hydrolysis), or ethereal solvents for hydride reductions (LiAlH4 in THF/Et2O).
  • Metal-catalyzed hydrogenations: alcohols, esters, or THF under H2 with Raney Ni/Pd catalysts.
  • SNAr or ring functionalization on pyridines: polar aprotic solvents (DMF, DMSO, NMP) often improve rates.
• Practical tips: • Begin with DCM or EtOAc for workup/extraction; switch to MeOH/MeCN for LC analysis.
  • For aqueous handling, protonate with HCl to form a pyridinium salt and enhance water solubility; neutralize during workup.
• Comparison note: Relative to more lipophilic aryl nitriles, the ring nitrogen in this scaffold modestly increases polarity, improving solubility in mid-polar solvents like EtOAc/MeCN (general/literature insight).

Storage and Reconstitution

• Storage conditions: Room temperature (provided). Keep container tightly closed in a cool, dry, well-ventilated place. Protect from moisture and prolonged exposure to light or heat.
• Shipped in: Not specified for this item; refer to CoA/Spec Sheet.
• Reconstitution: Not applicable; supplied as a neat chemical. If a stock solution is desired for automated dosing, prepare in a compatible dry solvent (e.g., DMSO, MeCN, or DCM) at a convenient concentration, filter if needed (PTFE, 0.2–0.45 µm), and store aliquots to minimize headspace and moisture uptake.
• Stability considerations (general): • Nitrile group is typically robust; avoid extended exposure to strong acids/bases if hydrolysis is not intended.
  • The pyridine ring may undergo slow oxidation to N-oxide under harsh oxidizing environments; store away from oxidizers.
  • The aryl ether is stable under neutral conditions; prevent prolonged heating with strong nucleophiles/bases if ether integrity is required.
• Shelf life: Use the batch CoA for best-by dating and any retest intervals.
• Research use note: For research use only.

Structure and Identity

Research-use chemical building block: a substituted pyridine bearing a nitrile and an ethoxy ether substituent.

• Product name: 3-Ethoxyisonicotinonitrile (systematic description: 3-ethoxy-4-cyanopyridine)
• CAS: 78790-86-0 (literature identifier)
• CID (PubChem): 12866695 (provided)
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
  • Note: A 3-ethoxy-4-cyanopyridine scaffold would be expected to contain one ring nitrogen (pyridine), one nitrile nitrogen, and one ether oxygen (literature/general knowledge).
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.

Structural features (general description):

• Heteroaromatic core: a six-membered pyridine ring (sp2 carbons with one ring nitrogen).
• Functional groups: an aryl nitrile (–C≡N) at the 4-position (isonicotinonitrile motif) and an aryl ethoxy ether (–O–CH2–CH3) at the 3-position.
• Electronic character: the ring nitrogen is electron-withdrawing; the para nitrile further deactivates the ring toward electrophilic substitution while enabling certain nucleophilic aromatic substitutions under appropriate activation. The ether substituent is weakly electron donating by resonance/inductive balance but on a pyridine the net effect is modest.
• 2D depiction in words: a pyridine ring with the ring nitrogen at position 1, a nitrile substituent para to it (position 4), and an ethoxy substituent at the adjacent meta position (position 3). No stereocenters; fully planar conjugated core.

Synthetic Utility

Key reactivity elements of 3-ethoxyisonicotinonitrile enabling diverse transformations (literature/general knowledge):

• Nitrile (para to ring N): • Hydrolysis sequence: –C≡N → amide → acid; enables installation of carboxyl-derived functions (esters, amides, acids, tetrazoles via [3+2] with azide).
  • Reductive chemistries: partial to aldehyde (DIBAL-H, −78 to 0 °C), full to primary amine (BH3·THF, LiAlH4, or catalytic hydrogenation).
  • Nucleophilic additions: organometallic additions (RMgX/RLi) to give imines/enamines after workup (with caution due to pyridine basicity/coordination).
• Pyridine nitrogen: • Quaternization to pyridinium salts (alkyl halides, MeOTf), enabling SN2-type functionalization and altering solubility/crystallinity.
  • N-oxidation (mCPBA) to direct regioselective substitutions (e.g., amination, hydroxylation) and facilitate rearrangements (Boekelheide).
  • Coordination chemistry: serves as a ligand or directing group in C–H activation (e.g., Pd, Ru catalysis) to install new C–C/C–N bonds ortho/remote to N under appropriate catalyst/auxiliary design.
• 3-Ethoxy substituent: • Acts as a weakly donating substituent modulating electronics; generally stable under many conditions.
  • Under strongly nucleophilic/basic conditions and heat, aryl ether cleavage to the corresponding phenolic pyridine derivative can occur; this can be leveraged to access 3-hydroxyl analogs.

Retrosynthetic value: The scaffold can bridge nitrile-bearing and ether-bearing pyridine series, enabling parallel synthesis libraries via orthogonal transformation of either handle.

Target Specificity

Not applicable. This product is a small-molecule chemical building block and is not an antibody, probe, enzyme, or biological macromolecule with defined target specificity. No antigen, epitope, clone, or isotype information applies.