2-Ethynyl-6-methylpyrazine , CAS No.1374115-58-8

CAS: 1374115-58-8 Cat. No.: E963704 Formula: C₇H₆N₂ Molecular Weight: 118.14 PubChem CID: 57303259

Storage

Room temperature

Specifications

Storage

Room temperature

Names and Identifiers

• Canonical Smiles: CC1=CN=CC(=N1)C#C
• IUPAC Name: 2-ethynyl-6-methylpyrazine
• InChIKey: LCZBGXQGBAPDLK-UHFFFAOYSA-N
• INCHI: 1S/C7H6N2/c1-3-7-5-8-4-6(2)9-7/h1,4-5H,2H3
• Isomeric SMILES: CC1=CN=CC(=N1)C#C
• PubChem CID: 57303259
• Molecular Weight: 118.14

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Class Diazines
      • Subclass Pyrazines

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Class: Diazines
• Subclass: Pyrazines
• Intermediate Tree Nodes: Not available
• Direct Parent: Pyrazines
• Alternative Parents: Heteroaromatic compounds Azacyclic compounds Acetylides Organonitrogen compounds Hydrocarbon derivatives
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Pyrazine - Heteroaromatic compound - Acetylide - Azacycle - Organic nitrogen compound - Hydrocarbon derivative - Organonitrogen compound - Aromatic heteromonocyclic compound
• Description: This compound belongs to the class of organic compounds known as pyrazines. These are compounds containing a pyrazine ring, which is a six-member aromatic heterocycle, that consists of two nitrogen atoms (at positions 1 and 4) and four carbon atoms.
• 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: 118.140 g/mol
• XLogP3: 0.500
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 1
• Exact Mass: 118.053 Da
• Monoisotopic Mass: 118.053 Da
• Topological Polar Surface Area: 25.800 Ų
• Heavy Atom Count: 9
• Formal Charge: 0
• Complexity: 133.000
• 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 tested biological assay protocols (e.g., WB, IHC, IF, FC) or application dilutions are provided for this product. As a synthetic intermediate, practical protocols correspond to organic synthesis operations such as CuAAC, Sonogashira, and Glaser couplings. See the “Reaction Conditions” section for representative procedures and adjust to your substrates and scale. For any analytical use (GC/LC/NMR), prepare solutions at appropriate concentrations using dry, compatible solvents and standard sample preparation practices.

Biological Roles

This product is intended as a synthetic building block for research and laboratory use; no biological role is assigned for the isolated compound in this catalog context. Any discussion below is general information about the pyrazine motif and terminal alkyne functionality and is not product-specific nor a claim of biological activity.

• Pyrazine ring systems occur in natural products and flavor chemistry, and the diazine scaffold can modulate physicochemical properties (basicity, H-bonding) of small molecules used in chemical biology experiments.
• The terminal alkyne is a key bioorthogonal handle for CuAAC “click” ligations to azide-bearing biomolecules, surfaces, and polymers (research applications only). This chemistry enables site-directed conjugation in proteomics and materials science workflows.

No pharmacology, toxicity thresholds, ADME, or in vivo roles are provided or implied for this SKU. For any biological testing, ensure appropriate institutional approvals and consult the SDS for hazard guidance.

Buffer Applications

Not typically applicable. 2-Ethynyl-6-methylpyrazine is a small organic building block rather than a buffering agent. It does not form a defined conjugate-acid/base pair in the physiological pH range suitable for buffering applications. For practical use, focus on the “Reaction & Applications,” “Synthetic Utility,” and “Reaction Conditions” sections for guidance on synthetic transformations.

Green Alternatives

Greenness considerations relate mainly to solvent/catalyst choice rather than the substrate itself.

• Greener solvent swaps (general guidance):
  • Replace DCM with EtOAc or 2-MeTHF for extractions and chromatography when feasible.
  • Use 2-MeTHF or CPME instead of THF/diethyl ether for couplings (higher bp, lower peroxide tendency, biorenewable sources for 2-MeTHF).
  • Favor aqueous t-BuOH/H2O or EtOH/H2O for CuAAC when solubility permits.
• Catalyst and base choices:
  • Sonogashira without copper (Pd-only) reduces copper waste and risk of Glaser byproducts.
  • Employ supported Pd catalysts (e.g., Pd/C, Pd-EnCat) for easier recovery and lower metal ppm in product.
  • For CuAAC, use low copper loadings with stabilizing ligands (TBTA, BTTAA) to minimize copper leaching; consider polymer-supported Cu catalysts.
• Energy and safety:
  • Microwave or flow-assisted couplings can cut reaction time/energy vs prolonged reflux.
  • Avoid excess amine bases; consider inorganic bases (K2CO3, Cs2CO3) in polar aprotics when compatible.

Concise comparison (general):

• THF vs 2-MeTHF: Similar solvency; 2-MeTHF is biorenewable, higher bp, easier phase separations.
• DCM vs EtOAc: EtOAc is less toxic/ozone-impacting, biodegradable; DCM offers stronger solvency but with higher environmental and safety burdens.

Pharmaceutical Uses

No pharmacopeial status, excipient role, or formulation specifications are provided for this item. Not specified for this item; refer to CoA/Spec Sheet.

General, non-clinical context:

• In medicinal chemistry research, heteroaromatic alkynes are commonly used as intermediates to access libraries of analogs (e.g., via CuAAC to triazoles, or Sonogashira to aryl-alkynes). Any such use of this SKU is strictly for research and development in the lab.
• If materials made from this building block are intended for further development, control of residual metals (Pd, Cu) and process impurities should be established; none are specified for this item and should be determined in-house.

No therapeutic or clinical claims are made or implied.

Physical Properties

Item-specific numerical specifications (bp, mp, density, refractive index, UV cutoff, water/peroxide/metal content) are not provided in the Product Data for this SKU. Not specified for this item; refer to CoA/Spec Sheet.

Literature/computed descriptors for the scaffold (informational, not product specifications):

• Approximate formula: C7H6N2 (computed from name)
• Approximate molecular weight: 118.14 g/mol (computed)
• Volatility/phase: Low-mass heteroaromatic with a terminal alkyne; commonly encountered as a liquid or low-melting solid in analogous systems. Exact mp/bp for this exact substitution pattern are not widely reported; check CoA.
• Solubility (general expectations for alkynyl pyrazines):
  • Good solubility in common organic solvents (e.g., dichloromethane, ethyl acetate, THF, acetonitrile, toluene). Limited water solubility due to aromatic core and low polarity.
• Polarity/logP (qualitative): Moderately nonpolar with basic ring nitrogens; expected to show modest polarity vs. hydrocarbon alkynes, aiding solubility in polar aprotic solvents.
• Acid/base behavior: Terminal alkyne C–H (pKa ~25, literature for phenylacetylenes/heteroaryl acetylenes), enabling deprotonation with strong bases; ring nitrogens are weak bases (pyrazine pKaH ~0.6–1, literature), typically unprotonated in neutral organic media.

Note: Use the SDS/CoA for definitive physical constants and handling parameters.

Quality & Grades

• Item-specific grade/purity, stabilizers, and absorbance/metal limits: Not specified for this item; refer to CoA/Spec Sheet.

Guidance on typical grades for small-molecule building blocks (general information):

• Research/technical grade: Suitable for most synthetic applications. Trace impurities may include residual solvents or close structural isomers; verify suitability for sensitive catalysis.
• Purification notes: Alkynes can oligomerize or oxidize under harsh conditions; if ultra-high purity is needed (e.g., for photophysics or materials), consider brief column chromatography or bulb-to-bulb distillation under inert gas.
• Water/peroxide/metal content: Not specified for this item; consult CoA. If using in Pd/Cu catalysis, trace sulfur or amines in impurities can poison catalysts; a pre-run or ligand/base choice can mitigate.
• Stabilization: This class typically does not require inhibitors; store under inert gas if long-term storage is planned to minimize oxidative changes.
• Verification: Confirm identity by 1H/13C NMR (alkynyl proton ~δ 3–4 ppm, sp carbons ~70–90 ppm), HRMS (M+H+ expected at m/z ~119.1), and GC/LC purity as appropriate.

Reaction & Applications

2-Ethynyl-6-methylpyrazine is a versatile building block combining an electron-deficient pyrazine ring with a terminal alkyne. This enables rich coupling and cycloaddition chemistry.

• Copper-catalyzed azide–alkyne cycloaddition (CuAAC, “click”): Forms 1,4-disubstituted triazoles tethered to a pyrazinyl group. Mild, aqueous-compatible conditions; ideal for conjugation to azides on polymers, surfaces, or biomolecules (research use only).
• Sonogashira cross-coupling: Couples the terminal alkyne to aryl/vinyl halides or triflates to generate diynes or aryl-alkynes appended to the pyrazine. Use Pd(0/II) with CuI co-catalyst and an amine base.
• Glaser–Hay oxidative homocoupling: Dimerizes terminal alkynes to diynes under Cu/O2, furnishing symmetric pyrazinyl diynes.
• Hydrofunctionalization of the alkyne: Hydroboration (e.g., catecholborane, 9-BBN) gives vinyl boronates; hydrosilylation affords vinyl silanes; hydrohalogenation/hydration under appropriate catalytic systems yields halo- or carbonyl-containing derivatives.
• N-oxide/annulation chemistry on the ring: Pyrazine can be N-oxidized (e.g., mCPBA) to modulate electronics, enabling further nucleophilic aromatic substitution or annulations.
• Deprotonation/alkynyl anion chemistry: Strong bases (n-BuLi, LDA, NaHMDS) generate the acetylide for addition to electrophiles (e.g., carbonyls) or transmetalation (Cu, Zn) in cross-couplings.

Practical tips:

• Exclude oxygen/moisture for metal-catalyzed couplings.
• For CuAAC, include a reducing agent (sodium ascorbate) to generate Cu(I) in situ; add TBTA or similar ligands to enhance selectivity.
• Protect the alkyne as TMS-alkyne if incompatibilities with reaction conditions are anticipated; deprotect with K2CO3/MeOH.

Reaction Conditions

Representative conditions from literature for terminal alkynes and pyrazine derivatives (general guidance; not product-specific):

• CuAAC click to azides:
  • Catalyst: CuSO4·5H2O (1–5 mol%) + sodium ascorbate (5–20 mol%) to generate Cu(I) in situ; optional ligand (TBTA/BTTAA, 1–5 mol%).
  • Solvent: t-BuOH/H2O (1:1) or EtOH/H2O; for poorly soluble partners use DMF/H2O.
  • Temp/time: rt to 50 °C, 1–16 h. Typical isolated yields: 70–95% (literature, substrate-dependent).
• Sonogashira coupling (to aryl/vinyl iodides/bromides):
  • Catalyst: Pd(PPh3)2Cl2 (1–3 mol%) or Pd2(dba)3/PPh3 with CuI (2–5 mol%).
  • Base: Et3N, i-Pr2NH, or K2CO3 (if using polar aprotics like DMF/DMA/MeCN).
  • Solvent: THF, toluene, dioxane, DMA.
  • Temp/time: 40–90 °C, 2–18 h. Typical yields: 60–90% (literature).
• Glaser–Hay homocoupling:
  • Catalyst: CuCl or CuI (5–10 mol%) with TMEDA under O2/air.
  • Solvent: Pyridine, DMF, or toluene. Temp: rt–60 °C; time: 2–12 h.
• Hydroboration of the alkyne:
  • Reagents: Catecholborane or 9-BBN (1.1–1.5 equiv) with Pd or Rh catalysts, or base-promoted systems.
  • Workup: Oxidation (H2O2/NaOH) to give enols/ketones or cross-couple via formed vinyl boronates.

Always run small-scale trials to optimize conditions for this specific substrate and verify with analytical monitoring (TLC/GC/LC–MS).

Safety & Handling

Product-specific GHS classification, signal word, pictograms, and H-statements are not provided in the Product Data. Not specified for this item; refer to SDS for authoritative safety information.

General safety guidance for small alkynyl heteroaromatics (literature-based; not product-specific):

• Hazards: Many low-MW heteroaromatics are flammable liquids/solids and can be irritants. Terminal alkynes may form copper acetylides; avoid contact with copper salts unless intended and controlled. Prevent aerosol formation and ignition sources.
• Incompatibilities: Strong oxidizers. For terminal alkynes, avoid uncontrolled contact with strong bases in the presence of protic solvents that could lead to exotherms. Copper/Ag salts can precipitate sensitive metal acetylides; handle with care.
• PPE: Lab coat, nitrile gloves, splash goggles. Work in a fume hood to control vapors and ensure good ventilation.
• Handling: Keep away from heat/sparks/open flames. Ground/bond containers when transferring flammable liquids. Use dry glassware if moisture-sensitive transformations are planned.
• First aid (overview; defer to SDS):
  • Inhalation: Move to fresh air; seek medical attention if symptoms persist.
  • Skin/eye: Rinse with water for 15 minutes; remove contaminated clothing.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
• Waste: Collect organic waste in appropriate halogenated/non-halogenated containers per your institution’s policy; terminal alkynes used in Cu-catalysis may contain copper residues—segregate as required.

Solvent Selection

This compound is a heteroaromatic terminal alkyne. While item-specific solubility data are not provided, analogous alkynyl pyrazines exhibit good solubility in many organic solvents.

• Polarity/miscibility (general expectations):
  • Polar aprotic: Acetonitrile, DMF, DMSO, THF—typically excellent solvents for coupling chemistry and analytics.
  • Moderately polar aprotic: Ethyl acetate, MTBE, CPME—useful for workups and chromatography.
  • Nonpolar aromatics: Toluene—beneficial for high-temperature couplings.
  • Alcohols: MeOH/EtOH may be suitable, but terminal alkynes can undergo side reactions in strongly basic alcoholic media.
• Selection by application:
  • CuAAC click reactions: t-BuOH/H2O or EtOH/H2O mixtures are common; DMF/H2O for poorly soluble azides.
  • Sonogashira couplings: THF, dioxane, toluene, or DMA with amine bases (Et3N, i-Pr2NH).
  • Glaser homocoupling: Pyridine, DMF, or Et3N under O2.
• Comparison notes:
  • THF vs 2-MeTHF: 2-MeTHF offers greener profile and higher boiling point; solubility typically comparable.
  • DCM vs EtOAc: EtOAc is greener and often sufficient for extraction/chromatography; DCM can maximize solubility but with higher environmental cost.

Always confirm solubility/compatibility on small scale before committing to process-scale operations.

Storage & Reconstitution

• Storage conditions (from Product Data): Room temperature.
• Container: Store in a tightly closed container. For long-term storage, consider an inert atmosphere (argon/nitrogen) and protection from light to minimize oxidative changes typical of terminal alkynes.
• Stability: Item-specific stability/shelf-life is not provided. Not specified for this item; refer to CoA/Spec Sheet. In general, terminal alkynes are reasonably stable when dry and protected from strong bases/oxidants.
• Handling before use:
  • If moisture sensitive chemistry is planned, dry the material under vacuum or over molecular sieves and handle under inert gas.
  • Inspect by NMR/GC for any signs of diyne formation or oxidation if the material has been stored for extended periods.
• Reconstitution: If received as a solid or viscous oil, dissolve in a compatible dry solvent (e.g., THF, MeCN, DCM, toluene) to prepare stock solutions at convenient molarity (e.g., 0.1–1.0 M) for coupling chemistry.
• Shipping: Not specified in Product Data. For most small heteroaromatics, ambient shipment is typical unless otherwise noted.

Structure & Identity

Brief description: 2-Ethynyl-6-methylpyrazine is a substituted pyrazine bearing a terminal alkyne at C2 and a methyl group at C6 of the diazine ring, making it a compact N,N-diazine building block with a reactive terminal C≡C–H.

• Product identifiers (from Product Data)
  • CAS: 1374115-58-8
  • CID: 57303259
  • InChIKey: 196384 (as provided)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• Structure description (from chemical name; general structural knowledge)
  • Core: Pyrazine (1,4-diazine) aromatic ring containing two ring nitrogens para to each other.
  • Substitution pattern: Position 2 = ethynyl (–C≡CH, terminal alkyne); Position 6 = methyl (–CH3). The 2D structure shows a six-membered aromatic diazine with N atoms at positions 1 and 4; an sp-hybridized C≡C–H at C2; and an sp3 methyl at C6.
• Molecular formula and mass (computed from name; literature/computed, not item-specific specs)
  • Molecular formula: C7H6N2 (computed)
  • Molecular weight: 118.14 g/mol (computed)
• Functional groups and features (general)
  • Aromatic diazine ring (electron-poor heteroaromatic)
  • Terminal alkyne (acidic C–H, capable of CuAAC, Sonogashira, Glaser couplings)
  • Small hydrophobic methyl substituent influencing ring electronics and regioselectivity.

Synthetic Utility

Key functional elements enabling diverse transformations:

• Terminal alkyne (–C≡CH):
  • Powerful handle for conjugation (CuAAC) to azides forming 1,4-triazoles.
  • Readily engaged in Sonogashira couplings with aryl/vinyl halides to extend conjugation or install linkers.
  • Forms acetylide anions with strong bases; suitable for nucleophilic additions to carbonyls or transmetalation (Cu/Zn) steps.
  • Susceptible to oxidative dimerization (Glaser–Hay) to give DIYNEs; can be leveraged synthetically.
• Pyrazine ring:
  • Electron-deficient; enables nucleophilic aromatic substitution at activated positions (after N-oxidation or with good leaving groups installed).
  • Coordinates to metals; can influence catalytic outcomes in some cross-couplings.
  • Regioselective further functionalization possible via directed lithiation or Minisci-type reactions under appropriate conditions.
• Methyl at C6:
  • Modulates electronics and sterics, potentially improving selectivity in metal-catalyzed steps.
  • Can be oxidized (e.g., benzylic oxidation) to the corresponding aldehyde/acid, opening routes to diversified derivatives.

Strategic value in retrosynthesis:

• Serves as a convergence point for late-stage installation of linkers, fluorophores, affinity tags, or cross-coupling partners while retaining the heteroaromatic core.

Target Specificity

Not applicable. This SKU is a small-molecule building block, not a biological macromolecule, antibody, or inhibitor with defined target specificity. No target, epitope, clone, or species reactivity is provided in the Product Data.