5-Ethyl-2-methylisonicotinonitrile , CAS No.98952-72-8

CAS: 98952-72-8 Cat. No.: E972750 Formule: C₉H₁₀N₂ Poids moléculaire: 146.190

Storage

Room temperature

Specifications

Conditions de stockage de stockage

Room temperature

Noms et identifiants

• Sourires canoniques: CCC1=C(C=C(N=C1)C)C#N
• IUPAC Name: 5-ethyl-2-methylpyridine-4-carbonitrile
• InChIKey: LLQJPGWFCMFCFT-UHFFFAOYSA-N
• INCHI: 1S/C9H10N2/c1-3-8-6-11-7(2)4-9(8)5-10/h4,6H,3H2,1-2H3
• Poids moléculaire: 146.190

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Classe Pyridines and derivatives
      • Subclass Methylpyridines

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Classe: Pyridines and derivatives
• Subclass: Methylpyridines
• Intermediate Tree Nodes: Not available
• Direct Parent: Methylpyridines
• Alternative Parents: Heteroaromatic compounds Nitriles Azacyclic compounds Hydrocarbon derivatives
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Methylpyridine - Heteroaromatic compound - Azacycle - Nitrile - Carbonitrile - Organic nitrogen compound - Cyanide - Hydrocarbon derivative - Organonitrogen compound - Aromatic heteromonocyclic compound
• Description: This compound belongs to the class of organic compounds known as methylpyridines. These are organic compounds containing a pyridine ring substituted at one or more positions by a methyl 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

Propriétés chimiques et physiques

• Poids moléculaire: 146.190 g/mol
• XLogP3: 1.800
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 1
• Exact Mass: 146.084 Da
• Monoisotopic Mass: 146.084 Da
• Topological Polar Surface Area: 36.700 Ų
• Heavy Atom Count: 11
• Formal Charge: 0
• Complexity: 168.000
• 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 manufacturer-validated biological or analytical application protocols are provided for this item.

• General usage suggestions (chemical synthesis)

  • For nitrile reductions/hydrolyses, see Reaction Conditions for representative setups. Always perform small-scale trials to establish selectivity and stability on this substituted pyridine scaffold.
  • For handling during chromatography, consider adding 0.1–1% Et3N to suppress adsorption/tailing on silica.
  • For moisture- or air-sensitive steps (e.g., organolithium at benzylic positions), employ oven-dried glassware, inert atmosphere, and anhydrous solvents.

• Research Use Note

  • For research use only. Not for human or animal therapeutic or diagnostic use.

Biological Roles

• Item-specific biological data: Not specified for this item; refer to primary literature if needed.

• General context (literature; no clinical claims)

  • 5-Ethyl-2-methylisonicotinonitrile is a synthetic, non-natural small molecule. The isonicotinonitrile scaffold is a common heteroaromatic motif in medicinal chemistry because it presents an electron-deficient pyridine that can engage as a hydrogen-bond acceptor and π-stacking partner in protein binding sites.
  • The nitrile group is a polar, weakly Lewis-basic functionality that can serve as a metabolic stability handle or a bioisostere for carbonyl groups. It can also act as a synthetic linchpin to access amides, acids, tetrazoles, and amines, enabling rapid exploration of structure–property relationships.
  • Alkyl substitution (methyl, ethyl) tunes basicity and lipophilicity of the pyridine, potentially influencing passive permeability and solubility in lead-optimization programs. However, specific ADME or biological target data for this exact compound are not provided here and should not be inferred.

• Use note

  • For research use only. If used in biochemical assays or as a fragment, characterize purity and residual metals/solvents per internal QC standards and ensure proper negative/positive controls.

Buffer Applications

This compound is not a buffering agent and is not typically used to prepare pH buffer systems.

• Guidance
  • If aqueous work is required (e.g., hydrolysis studies), select an appropriate external buffer system (e.g., acetate pH 4–5.5, phosphate pH 6–8, carbonate pH 9–10) compatible with the planned transformation. Avoid conditions that would undesirably hydrolyze or protonate the pyridine unless intended.
  • No item-specific buffer recipes or application data are available for this product.

Green Alternatives

Because this is a synthetic intermediate rather than a solvent or auxiliary, green considerations focus on reaction media and reagent choices used with it.

• Preferable solvents (literature guidance)

  • Replace chlorinated solvents (e.g., DCM) with ethyl acetate or 2-MeTHF where feasible (e.g., for extractions and many reductions).
  • Use 2-MeTHF or CPME instead of THF for organometallic steps; benefits include higher boiling point, improved safety, and partial biorenewability (2-MeTHF).
  • For hydrolysis or catalytic hydrogenation, aqueous ethanol or isopropanol can replace more hazardous media.

• Reagents and catalysts

  • Hydrogenation: favor H2 with recyclable Pd/C or Raney Ni under mild pressures over stoichiometric metal hydrides when selectivity permits.
  • Nitrile-to-amide: employ catalytic hydration systems (e.g., Ru, Ni, or MOF catalysts) in water/green cosolvents rather than concentrated mineral acids, where compatible.
  • Tetrazole formation: explore solvent-free or water-enabled protocols with catalytic Zn(II) or Cu(II) salts to minimize polar aprotic dipolar solvents.

• Comparison snapshot (general)

  • Conventional: THF, DMF, DCM; stoichiometric LiAlH4, POCl3, or oxalyl chloride.
  • Greener alternative: 2-MeTHF/CPME, EtOAc, aqueous alcohols; catalytic hydrogenation, catalytic dehydrations, or flow chemistry with reduced solvent volumes.

• Waste and workup

  • Implement aqueous-organic biphasic systems for easy phase separations; use brine minimization and solvent recovery. Consider crystallization-driven purifications to avoid silica waste.

Pharmaceutical Uses

• Item-specific pharmacopeial status: Not specified for this item; not listed as an excipient.

• General formulation/manufacturing context (no therapeutic claims)

  • Heteroaromatic nitrile building blocks such as isonicotinonitriles are commonly employed in medicinal chemistry campaigns as intermediates for SAR exploration. They are typically used to access libraries of amides, tetrazoles, and amines via diversification of the nitrile.
  • In process development, the nitrile can be a protecting/activating group en route to amide/acid functions. The pyridine nitrogen may be temporarily quaternized to improve crystallinity or isolation of salts in API intermediate stages.
  • When incorporated into an API candidate, residual levels, polymorphism, and impurity profiles would be tightly controlled per ICH guidelines. For this catalog item, no pharmacopoeial monograph or excipient application is specified.

• Practical notes

  • For route scouting, this building block can shorten sequences by convergently installing the 4-cyano-2-methyl-5-ethylpyridine motif, avoiding late-stage cyanation on sensitive scaffolds.
  • Ensure any downstream salt formation, crystallization solvent selection, and purge of potential genotoxic impurities (e.g., residual cyanation reagents in other routes) are addressed in development contexts.

Physical Properties

• Item-specific specifications

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

• Literature/computed values (for general reference; not item specifications)

  • Empirical formula: C9H10N2 (derived from the substitution pattern on pyridine-4-carbonitrile).
  • Formula weight: ~146.19 g/mol (calculated from atomic weights).
  • Physical state: likely an organic solid or low-melting solid/liquid depending on crystal packing; specific MP/BP not located in standard references for this substitution pattern.
  • Solubility: expected to be soluble in common organic solvents (e.g., dichloromethane, ethyl acetate, acetone, acetonitrile, THF) and sparingly soluble in water due to the hydrophobic alkyl groups and only moderate basicity of the ring nitrogen.
  • Acid/base properties: weakly basic aromatic nitrogen (pyridine-type). The para nitrile withdraws electron density, reducing basicity relative to unsubstituted pyridine (qualitative).
  • Polarity: polar aprotic heteroaromatic with one H-bond acceptor on the ring N and one on the nitrile N; no H-bond donors.

• Data not located in literature for this exact isomer (use CoA/SDS for specifics)

  • Melting point, boiling point, density, refractive index, logP/cLogP, and pKa: Not specified for this item; refer to CoA/Spec Sheet.

• Practical note

  • The combination of a polar nitrile and a basic ring N typically affords good chromatographic behavior on silica; elution strength increases with small amounts of amine modifiers if tailing is observed.

Quality and Grades

• Item-specific grade/purity

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

• How to interpret typical grades (general guidance)

  • Research or synthetic grade: Suitable for most synthetic applications; trace impurity levels (e.g., water, residual solvents, inorganic ash) are not tightly controlled unless stated.
  • High-purity or 95–98% stated assay: Useful for SAR/medchem and for reactions sensitive to electrophile/nucleophile impurities. Confirm by NMR/LC as needed.
  • HPLC grade (solvents) or LC/MS grade (solutes): Emphasizes low UV background/volatile impurities; not applicable unless specified for this item.

• Stabilizers and additives

  • None listed for this item. If stabilizers were present, they would be declared on CoA. Absence of stabilizers is generally preferred for building blocks used in catalysis.

• Verification best practices

  • For heteroaromatics, confirm identity by 1H/13C NMR, HRMS, and, if needed, elemental analysis. The nitrile carbon typically appears near 115–120 ppm (13C) and is diagnostic.
  • Water/volatiles: If reaction is moisture-sensitive (e.g., organolithium at benzylic positions), consider brief high-vacuum drying or azeotropic removal. Specific water content for this item is Not specified; refer to CoA/Spec Sheet.

Reaction and Applications

As a 4-cyanopyridine bearing benzylic 2-methyl and 5-ethyl substituents, this building block is versatile for heteroarene functionalization and nitrile transformations.

• Nitrile group interconversions (literature)

  • Reduction to primary amine: catalytic hydrogenation (Raney Ni, Pd/C) or hydride routes (BH3·THF, Ni2B/NaBH4). DIBAL-H at low temperature can afford the aldehyde; over-reduction gives alcohol/amine depending on conditions.
  • Hydrolysis to amide/acid: acid- or base-catalyzed; often conducted in aqueous alcohols, dioxane/H2O, or neat mineral acid. Nitrile→amide via partial hydrolysis is feasible under controlled conditions.
  • Imidate/amidine formation: Pinner reaction in dry alcohol/HCl, or metalated amidines from aminolysis under dehydrating conditions.
  • Cycloaddition: [3+2] click to tetrazoles with azide under Lewis acid or transition-metal catalysis; tetrazoles are bioisosteres of carboxylic acids.

• Heteroaromatic (pyridine) chemistry (literature)

  • N-oxidation: mCPBA or H2O2/acetic acid to access N-oxides for further rearrangements (e.g., Boekelheide) enabling hydroxymethylation at benzylic positions.
  • Directed lithiation/metalation: Electron-withdrawing para nitrile plus ring N can influence regiochemistry; however, the presence of 2-methyl/5-ethyl provides benzylic C–H sites amenable to deprotonation (e.g., LDA, s-BuLi/TMEDA) and subsequent electrophile trapping.
  • Cross-coupling on pre-functionalized derivatives: Bromination/chlorination at benzylic carbons (NBS/NCS) followed by Suzuki/Negishi at sp3 centers, or oxidation to aldehydes/acids for further elaboration.

• Medchem and materials context (non-clinical)

  • The isonicotinonitrile motif is a privileged, electron-poor heteroarene; the nitrile adds polarity and a vector for diversification, while alkyl groups tune lipophilicity. Useful for fragment growth and as a precursor to pyridylamines, amides, acids, and tetrazoles.

Reaction Conditions

Representative literature-style conditions for common transformations of pyridyl nitriles and benzylic heteroarenes (general guidance; optimize for your system):

• Nitrile reduction to primary amine

  • Catalytic hydrogenation: 10% Pd/C (5–10 wt%), H2 3–5 bar, MeOH or EtOH, 20–40 °C, 4–16 h; workup by filtration and acid/base extraction. Alternative: Raney Ni under similar conditions.
  • Borane reduction: BH3·THF (2–4 equiv) in THF or 2-MeTHF, 0 °C to reflux, 2–6 h; quench cautiously with MeOH then aqueous base.

• Partial reduction to aldehyde

  • DIBAL-H (1.2–1.5 equiv) in toluene or 2-MeTHF, −78 to −40 °C, 1–2 h; quench with MeOH at low temperature then Rochelle’s salt. Avoid over-reduction by temperature control.

• Hydrolysis to amide/acid

  • Amide: aq. H2SO4 (3–6 M) in dioxane/H2O, 60–90 °C, 6–24 h. Acid: stronger acid or extended time; or NaOH (2–5 M) reflux in EtOH/H2O followed by acidification.

• Tetrazole formation

  • TMSN3 (1.5–2.0 equiv) with ZnBr2 (10–20 mol%) in MeCN, 60–80 °C, 6–16 h; or NaN3 with catalytic Cu(II)/Zn(II) in DMF or solvent-free protocols.

• Benzylic functionalization

  • Radical bromination: NBS (1.1–1.5 equiv), AIBN (10 mol%), CCl4 or greener: PhCF3/MeCN, reflux or hv, 1–6 h; follow with nucleophilic substitution or cross-coupling.
  • Deprotonation/alkylation: LDA (1.1–1.5 equiv) in THF, −78 to 0 °C, then alkyl/ carbonyl electrophile; TMEDA may improve lithiation adjacent to pyridine N.

• Analytics and workup

  • Monitor by TLC/LC–MS; quench reactive hydrides at low temperature; include amine modifiers in chromatography to suppress pyridinium interactions.

Safety and Handling

• Regulatory/GHS (item-specific)

  • Signal word: Not specified for this item; refer to SDS.
  • GHS hazard statements/classification/pictograms: Not specified for this item; refer to SDS.

• General safety guidance for heteroaromatic nitriles (literature; consult SDS for authoritative instructions)

  • Hazards: Aromatic nitriles can cause irritation to skin, eyes, and respiratory tract. Some nitriles may liberate toxic gases on thermal decomposition. Avoid ingestion, inhalation of dust/vapors, and skin contact.
  • PPE: Use appropriate lab coat, nitrile gloves, and splash goggles. Handle in a fume hood.
  • First aid (overview): Inhalation—move to fresh air; seek medical advice 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. Ingestion—rinse mouth; do not induce vomiting; seek medical attention.
  • Incompatibilities: Strong oxidizers; strong acids or bases may promote decomposition or N-oxidation/side reactions. Avoid strong reducing agents at elevated temperatures unless intended (e.g., for nitrile reductions).
  • Fire safety: Likely combustible organic. Use CO2, dry chemical, or foam. Combustion can produce NOx, CO, and HCN; firefighters should wear SCBA.
  • Environmental: Prevent release to the environment. Collect spillage with inert absorbent and dispose according to local regulations.

• Handling tips

  • Minimize exposure to moisture and acid gases that can form pyridinium salts. For weigh-outs, close bottles promptly to limit odor and humidity uptake.

Solvent Selection

This product is a solid/liquid organic building block, not a solvent. Solvent choice therefore pertains to its use in synthesis, purification, and analysis.

• Polarity and miscibility (general expectations)

  • Polar aprotic heteroaromatic; readily soluble in many organic solvents (DCM, EtOAc, acetone, MeCN, THF). Limited water solubility expected.
  • For chromatography, mixtures of hexanes/EtOAc or DCM/MeOH (with 0.1–1% Et3N to suppress tailing) are common.

• Typical solvent choices by transformation

  • Nitrile reductions (to amines/amidines): alcohols (MeOH, EtOH, iPrOH) or ethereal solvents (THF, 2-MeTHF) under catalytic hydrogenation or hydride conditions.
  • Nitrile hydrolysis: aqueous alcoholic solvents or dioxane/water with acid/base catalysts.
  • Benzylic functionalization at the 2-methyl/5-ethyl positions: polar ethereal solvents (THF, CPME) for deprotonation with strong bases; DMSO/DMF for radical or SN2-based benzylic chemistry.
  • N-oxide formation: CH2Cl2 or AcOH/Ac2O systems, depending on the oxidant.

• Analytical solvents

  • LC: acetonitrile/water or methanol/water with 0.1% formic acid or ammonium formate for MS-compatibility.
  • NMR: CDCl3 or DMSO-d6; trace base may sharpen signals by reducing protonation of the ring N.

• When to choose alternatives

  • If enhanced water solubility is required, transform the ring nitrogen to a pyridinium salt in situ or use co-solvents (MeCN, DMSO). For greener solvent choices, see Green Alternatives.

Storage and Reconstitution

• Item-specific storage and shipping

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

• General storage guidance for heteroaromatic nitriles

  • Keep tightly closed in the original container, protected from excessive heat and direct sunlight.
  • Store under dry conditions; include a desiccant if long-term storage is anticipated to minimize moisture uptake or formation of pyridinium salts under acidic atmospheres.
  • Avoid storing near strong oxidizers or acids/bases.

• Stability

  • Nitriles and pyridines are typically shelf-stable at ambient conditions when protected from moisture and light. No stabilizer is indicated for this item.

• Reconstitution/Preparation for use

  • If solid: dissolve in a suitable organic solvent (e.g., DCM, EtOAc, MeCN, THF) to prepare stock solutions. If any insolubles are observed, gentle warming or sonication can assist dissolution.
  • If LC/MS quantitation is required, prepare gravimetric stock in MeCN or MeOH and store aliquots at 2–8 °C or −20 °C; allow to equilibrate to room temperature before opening to avoid condensation.

• Shelf-life

  • No item-specific expiry provided. For best results, retest identity/purity (e.g., NMR/LC) if stored >12 months or after multiple open/close cycles.

Structure and Identity

Research-use heteroaromatic nitrile building block featuring a substituted isonicotinonitrile (pyridine-4-carbonitrile) core.

• Item-specific (from Product Data)

  • Product name: 5-Ethyl-2-methylisonicotinonitrile (SKU E972750)
  • CAS: 98952-72-8
  • InChIKey: 202867 (as provided)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/computed identifiers and features (for reference; not item specifications)

  • Core scaffold: pyridine ring bearing a nitrile at the 4-position (isonicotinonitrile), with additional alkyl substituents: methyl at C2 and ethyl at C5.
  • Functional groups: aromatic heterocycle (pyridine), nitrile (–C≡N), benzylic positions at the 2-methyl and 5-ethyl substituents.
  • Stereochemistry: none (achiral).
  • 2D structural description: a six-membered aromatic ring containing one ring nitrogen. Para to the ring nitrogen (position 4) is a –C≡N substituent. Adjacent to the ring nitrogen (position 2) is a methyl group, and at position 5 is an ethyl group.
  • Empirical formula (derived from name; literature): C9H10N2.
  • Formula weight (calculated): ~146.19 g/mol.

• Notes

  • The isonicotinonitrile motif is an electron-deficient pyridine due to the para nitrile; 2-methyl and 5-ethyl groups add lipophilicity and provide benzylic C–H sites amenable to functionalization.

Synthetic Utility

• Functional handles inherent to the molecule

  • Nitrile (para to ring N): platform for reduction (amine), partial reduction (aldehyde), hydrolysis (amide/acid), Pinner chemistry (imidates/amidines), and [3+2] cycloaddition to tetrazoles.
  • Benzylic positions (2-methyl, 5-ethyl): amenable to hydrogen abstraction, radical bromination (NBS/AIBN), oxidation (to benzyl alcohol/aldehyde/acid analogs), and deprotonation (picolyl-type anions) for C–C bond formation.
  • Ring nitrogen: N-oxidation, quaternization (pyridinium salts) to tune reactivity/solubility, and coordination to metals (ligand behavior).

• Retrosynthetic value

  • Serves as a convergent synthon for electron-poor 4-cyanopyridine frameworks with preinstalled lipophilicity at C2 and C5. Avoids regioselectivity issues inherent to pyridine functionalization.

• Downstream elaborations (literature)

  • Reductive amination of the DIBAL-derived aldehyde to elaborate side chains.
  • Tetrazole formation as a carboxylate bioisostere for binding and pKa modulation.
  • Benzylic cross-coupling at sp3 centers after halogenation (e.g., Suzuki with alkylboranes, Negishi/Kumada with organozincs/magnesium reagents).
  • Directed C–H activation on suitably modified analogs (e.g., via pyridine N-oxide or transient directing groups) to access further substitution patterns.

• Purification/analytics

  • Normal-phase silica TLC/HPLC with amine modifier if tailing occurs. 1H NMR: diagnostic downfield pyridine protons; 13C NMR: nitrile carbon typically ~115–120 ppm (literature). HRMS provides clear [M+H]+ at m/z ~147.1.

Target Specificity

This product is a small-molecule chemical building block and is not an antibody, enzyme, or biological reagent with defined target specificity.

• Item-specific biological target, epitope, species reactivity, clone/isotype: Not applicable for this item.

• Guidance

  • If used as a ligand precursor or fragment in biochemical assays, any target interactions are project-specific and must be determined empirically.