Methyl 3-(3-Pyridyl)propiolate - ≥97% , CAS No.78584-30-2

CAS: 78584-30-2 Cat. No.: M691663 Formule: C₉H₇NO₂ Poids moléculaire: 161.16 PubChem CID: 12716670

GRADE & PURITY ≥97%

Storage

Room temperature

Specifications

Spécifications et pureté

≥97%

Conditions de stockage de stockage

Room temperature

Pureté

≥97%

Propriétés du produit

• ALogP: 1.3

Noms et identifiants

• Sourires canoniques: COC(=O)C#CC1=CN=CC=C1
• IUPAC Name: methyl 3-pyridin-3-ylprop-2-ynoate
• InChIKey: JSDWMTRFFZEDCX-UHFFFAOYSA-N
• INCHI: 1S/C9H7NO2/c1-12-9(11)5-4-8-3-2-6-10-7-8/h2-3,6-7H,1H3
• Isomères SMILES: COC(=O)C#CC1=CN=CC=C1
• PubChem CID: 12716670
• Poids moléculaire: 161.16

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Lipids and lipid-like molecules
    • Classe Fatty Acyls
      • Subclass Fatty acid esters

• Kingdom: Organic compounds
• Superclass: Lipids and lipid-like molecules
• Classe: Fatty Acyls
• Subclass: Fatty acid esters
• Intermediate Tree Nodes: Not available
• Direct Parent: Fatty acid esters
• Alternative Parents: Pyridines and derivatives Ynoate esters Methyl esters Heteroaromatic compounds Monocarboxylic acids and derivatives Azacyclic compounds Organonitrogen compounds Organic oxides Hydrocarbon derivatives Carbonyl compounds
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Fatty acid ester - Pyridine - Methyl ester - Ynoate ester - Alpha,beta-unsaturated carboxylic ester - Heteroaromatic compound - Carboxylic acid ester - Organoheterocyclic compound - Carboxylic acid derivative - Monocarboxylic acid or derivatives - Azacycle - Carbonyl group - Organic oxygen compound - Organooxygen compound - Organonitrogen compound - Organic nitrogen compound - Hydrocarbon derivative - Organic oxide - Aromatic heteromonocyclic compound
• Description: This compound belongs to the class of organic compounds known as fatty acid esters. These are carboxylic ester derivatives of a fatty acid.
• 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: 161.160 g/mol
• XLogP3: 1.300
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 2
• Exact Mass: 161.048 Da
• Monoisotopic Mass: 161.048 Da
• Topological Polar Surface Area: 39.200 Ų
• Heavy Atom Count: 12
• Formal Charge: 0
• Complexity: 223.000
• 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 immunoassay or bioassay protocols (WB, IHC, IF, FC) are associated with this small-molecule reagent. For synthetic procedures involving this compound, see Reaction Conditions and Synthetic Utility sections.

Biological Roles

This is a synthetic heteroaromatic building block rather than a native metabolite or biopolymer component.

• Biological function: None known as an endogenous metabolite. The pyridine ring is a privileged motif in medicinal chemistry, but methyl 3-(3-pyridyl)propiolate itself is a research intermediate.
• Reactivity toward biomolecules (literature): Activated alkynes (propiolates) can react with nucleophilic residues (e.g., cysteine, lysine) under suitable conditions, which underlies their use as electrophilic probes in chemical biology. Such uses must be designed and controlled; this product is provided strictly for research use.
• Permeability/ionization: The basic pyridine (pKaH ~5 for 3-substituted pyridines, literature) is predominantly unprotonated at physiological pH, conferring moderate lipophilicity; however, no ADME properties are defined for this item.

Research Use Note: For research use only. Not for human or veterinary use, diagnostics, or clinical applications.

Buffer Applications

Not typically applicable. Methyl 3-(3-pyridyl)propiolate is a reactive organic building block, not a buffering agent. It does not form defined buffer systems in aqueous media. For aqueous work, see Solvent Selection and Safety & Handling regarding hydrolysis and compatibility.

Green Alternatives

For this building block, “greener” considerations primarily concern solvent choice and process conditions rather than replacing the reagent itself.

• Preferred greener solvents for common operations (literature guidance):
  • Replace DCM/chloroform with EtOAc, 2-MeTHF, CPME, or toluene when reaction compatibility allows.
  • For polar catalysis, MeCN can be replaced by propylene carbonate or EtOAc in some cases; 2-MeTHF often balances polarity and sustainability.
  • For extractions, use EtOAc or MTBE rather than chlorinated solvents.

Comparison (general; pros/cons):

• EtOAc vs DCM
  • Pros: lower toxicity, biodegradable, higher flash point.
  • Cons: higher boiling point, may slow chromatography.
• 2-MeTHF vs THF
  • Pros: bio-based, less peroxide-prone, better phase separation in workups.
  • Cons: slightly different polarity; may impact catalyst solubility.
• CPME vs toluene
  • Pros: broad liquid range, hydrophobic, low peroxide tendency.
  • Cons: Odor and cost considerations.

Process-intensity reductions:

• Employ flow photochemistry for thiol–yne additions to reduce initiator load.
• Favor catalytic over stoichiometric metal reagents (e.g., Au or Ag ppm-level loadings for hydration using ligand-accelerated systems).

Note: No greener “substitute reagent” is generally applicable because the unique reactivity of the activated alkyne (propiolate) is often required.

Pharmaceutical Uses

• Role: This material is a synthetic intermediate for research and process development. It is not an approved active ingredient or excipient.
• Potential formulation relevance (general/literature): Propiolate-containing fragments are occasionally employed in covalent-ligand discovery or prodrug synthesis as electrophilic handles; in such contexts, this reagent would be used upstream in API intermediate synthesis, not in final formulations.
• Pharmacopeial status: Not listed; no monograph known. Any use in GMP settings would require independent specification development, impurity profiling, and validation.
• Processing cautions: Control residual reagent carryover and hydrolysis products (acid, alcohols) in downstream steps; include appropriate impurity standards and orthogonal analytics (HPLC/GC/MS) when used in medicinal chemistry or process-route scouting.

Physical Properties

Item-specific physical constants are not provided in the Product Data. Where useful, literature/computed expectations are summarized for planning purposes.

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Boiling point: Not specified for this item; literature for analogous aryl-propiolate methyl esters suggests thermal stability up to >200 °C under reduced pressure (literature, general guidance only).
• Melting point: Not specified for this item; refer to CoA/Spec Sheet.
• Density (20–25 °C): Not specified for this item; refer to CoA/Spec Sheet.
• Refractive index: Not specified for this item; refer to CoA/Spec Sheet.
• Solubility (literature expectations):
  • Organic: expected to be soluble in common aprotic organics (DCM, EtOAc, THF, MeCN, toluene) and alcohols; sparingly soluble in alkanes.
  • Aqueous: expected to be very low due to hydrophobic/aromatic core; ester hydrolysis may occur under basic/acidic aqueous conditions.
• LogP: Internal aryl–alkynyl methyl esters of this size often show moderate lipophilicity (cLogP ~1–2; literature/computed range), but item-specific value is not established.
• pKa: Aromatic pyridine N (conjugate acid pKaH typically ~5.2 for 3-substituted pyridines; literature). The ester does not ionize in the neutral range.

Note: All non-specified parameters above are planning-level literature expectations only and are not product specifications.

Quality and Grades

• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
• What grade means (general guidance):
  • For synthetic building blocks like methyl aryl-propiolates, commonly offered grades include “98%” or higher assay for research use. Higher grades may control aldehydes, acids (hydrolysis products), and residual solvents.
  • HPLC or GC area % is typically used for purity determination; additional controls can include water content (KF), residual acid content, and stabilizers (if any). None are specified here.
• Stabilizers: Not specified for this item; refer to CoA/Spec Sheet. Many propiolates are supplied neat without stabilizers; if stabilizers are present, they can influence radical additions or polymerization kinetics.
• Documentation: For project-critical work (e.g., medicinal chemistry SAR or materials synthesis), request the current CoA to verify purity method, chromatographic profile, and assay basis.
• Batch-to-batch considerations (general): Monitor for hydrolysis to the corresponding acid and for transesterification products if stored with alcohols; low-level peroxide formation is not typically an issue for esters but confirm by CoA if relevant to your application.

Reaction and Applications

The methyl 3-(3-pyridyl)propiolate motif combines an electron-deficient internal alkyne with a Lewis-basic pyridine, enabling diverse transformations.

Representative application families (literature):

• Conjugate additions (thiol-yne/aminolysis): Propiolate esters are potent Michael acceptors. Thiols or amines add across the C≡C to give vinyl sulfides/amides or β-amino acrylates under base, radical, or photochemical initiation. The pyridine can coordinate catalysts and sometimes modulate regioselectivity.
• Cycloadditions:
  • Nitrile oxide 1,3-dipolar cycloaddition to form isoxazoles (often Cu-catalyzed), giving heteroaromatic isoxazoles fused to the pyridyl-alkenyl ester framework.
  • Diels–Alder with electron-rich dienes (aza-Diels–Alder variants) onto activated alkynes at elevated temperatures.
• Metal-catalyzed hydration/oxyfunctionalization: Au(III), Pt(II), or Hg(II) catalyze Markovnikov hydration of internal propiolates to α,β-unsaturated carbonyls or β-keto esters; nucleophiles (ROH, H2O) trap intermediates.
• Radical additions and photochemistry: Photoinitiated thiol–yne and seleno–yne couplings; visible-light photocatalysis permits hydrofunctionalizations using Eosin Y or Ir/Ru complexes.
• Ester derivatization: Hydrolysis to the acid, conversion to amides via standard coupling (EDC/HATU), or transesterification to other alkyl esters.
• Heteroaryl elaboration: The pyridine nitrogen can undergo N-oxidation or quaternization for further diversification; ring halogenation/nitration strategies enable subsequent cross-coupling (after introducing a handle).

Use cases in medicinal and materials chemistry (literature): alkynyl–pyridyl esters serve as electrophilic warheads in covalent-fragment screening, as linkers in conjugated materials, and as precursors to heterocycles via cycloaddition.

Note: Manufacturer Applications field is blank for this item; the above reflects general literature uses for aryl-propiolate esters.

Reaction Conditions

General literature conditions for transformations of aryl–propiolate methyl esters (guidance only; optimize for your substrate set):

• Thiol–yne additions (to give vinyl sulfides):
  • Radical: AIBN (5–10 mol%) or photoinitiator (blue LED), solvent: toluene, MeCN, or 2-MeTHF; 0.1–0.5 M; rt–80 °C; 1–6 h; often Z/E mixtures controllable by conditions.
  • Base-catalyzed: DBU/Et3N (5–20 mol%), solvent: MeCN or THF; 0–25 °C; minutes to hours.
• Aminolysis/Michael addition (β-amino acrylates):
  • Amine (1.0–1.5 equiv), catalyst: Et3N or no catalyst; solvent: THF/MeCN; 0–25 °C; 0.5–4 h; typical isolated yields 60–90% (literature ranges).
• Nitrile oxide cycloaddition (isoxazoles):
  • In situ generation from oximes (e.g., chlorination, then base); Cu(I) salts may accelerate; solvent: toluene or MeCN; 25–110 °C; 2–16 h.
• Au-catalyzed hydration:
  • Catalyst: AuCl3 (1–5 mol%) or Ph3PAuNTf2 (1–2 mol%) with additive acid (e.g., HBF4·Et2O, 1–10 mol%); solvent: MeOH/H2O, MeCN/H2O, or toluene with added nucleophile; 25–60 °C; 1–8 h; affords β-keto esters/enol esters.
• Ester transformations:
  • Saponification: K2CO3/MeOH–H2O (0–25 °C), or NaOH/THF–H2O; 0.5–2 h, then acidic workup.
  • Amide coupling: HATU or EDCI (1.1–1.5 equiv) with amine and base (DIPEA) in DMF/MeCN; 0–25 °C; 1–12 h.

Notes:

• Exclude moisture/strong base if preserving the alkyne/ester is essential.
• The pyridine nitrogen can coordinate metals; if catalyst inhibition occurs, consider N-oxide formation as a temporary modulator or add competing ligands.
• Monitor by TLC (UV-active, 254 nm) and LC–MS; the alkyne typically shows characteristic IR band near ~2200–2260 cm−1 (literature).

Safety and Handling

• GHS classification: Not specified for this item; refer to SDS.
• Signal word / H-statements / pictograms: Not specified for this item; refer to SDS.
• General hazards (class-based): Aromatic alkynyl esters may cause skin/eye irritation and respiratory irritation upon vapor/aerosol exposure (literature). Avoid inhalation and contact.
• PPE: Use lab coat, safety glasses or splash goggles, and appropriate chemically resistant gloves (e.g., nitrile). Handle in a fume hood.
• Incompatibilities: Strong bases or acids (ester hydrolysis/transesterification), strong nucleophiles (conjugate addition to activated alkyne), and strong oxidizers. Avoid prolonged moisture exposure.
• Special risks for alkynes/esters:
  • Propiolate esters are potent Michael acceptors; unintended reaction with thiols/amines is possible—avoid contact with free thiol-containing reagents unless intended.
  • Aromatic organic liquids/solids can be combustible—keep away from ignition sources and hot surfaces.
• First aid (overview; defer to SDS):
  • Skin/eye contact: Rinse with water for ≥15 minutes; remove contaminated clothing; seek medical evaluation if irritation persists.
  • Inhalation: Move to fresh air; obtain medical attention if symptoms occur.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical advice.
• Spill/cleanup: Absorb with inert material (vermiculite, sand), place in chemical waste; ventilate area.
• Waste: Dispose according to local regulations; segregate halogen-free organic waste as required.

Always consult the SDS for authoritative hazard classification and response measures.

Solvent Selection

This compound is a moderately lipophilic, polar-aprotic aryl–alkynyl methyl ester with a basic pyridine nitrogen.

• Polarity/miscibility (literature expectations):
  • Good solubility in DCM, chloroform, THF, EtOAc, MeCN, acetone, toluene; limited in hexanes/heptane; poor in water.
  • Protonation of the pyridine in strong acids increases aqueous affinity but risks ester hydrolysis.
• Choosing a solvent (guidance):
  • Synthesis and reactions: Use dry, oxygen-free aprotic solvents (DCM, THF, MeCN, toluene) for nucleophilic additions, cycloadditions, and metal catalysis. MeOH/EtOH can participate in transesterification or Michael additions under basic conditions.
  • Purification: Normal-phase silica with hexanes/EtOAc or DCM/MeOH gradients often works; add 0.1–1% triethylamine if strong tailing from pyridine occurs. Reverse-phase (C18) is viable when needed.
  • NMR: CDCl3 or DMSO-d6 give clean spectra; CD3CN for coordination chemistry studies; avoid strongly acidic deuterated media to prevent decomposition.
• Comparison (general):
  • DCM vs EtOAc: DCM offers faster chromatography and high solubility; EtOAc is a greener alternative with higher polarity and safer profile.
  • THF vs MeCN: THF better for radical additions; MeCN often preferred for transition-metal catalysis and polar mechanisms.
  • Toluene: Suited to high-temperature cycloadditions and Au-catalyzed hydrations due to thermal stability.

Storage and Reconstitution

• Storage conditions (from Product Data): Room temperature.
• Container: Store tightly closed in an inert, compatible container (amber glass recommended) to minimize light exposure and adventitious moisture uptake.
• Atmosphere: For long-term storage, consider an inert headspace (N2/Ar) to minimize oxidative side reactions; while propiolate esters are generally stable, they are electrophilic and can slowly react with nucleophiles.
• Moisture considerations: Avoid humid environments; ester hydrolysis and Michael additions from adventitious nucleophiles are possible over time.
• Shipping: Not specified for this item; refer to CoA/Spec Sheet.
• Reconstitution: Not applicable; supplied neat unless otherwise stated. If solidified upon cold storage, gently warm to ambient and ensure homogeneity before use.
• Stability: No item-specific shelf-life provided. As a best practice, confirm purity by NMR/GC/HPLC prior to critical experiments, especially after extended storage.

Always consult the product CoA and SDS for definitive guidance on handling and storage.

Structure and Identity

Methyl 3-(3-pyridyl)propiolate is an electron-deficient internal alkyne bearing a methyl ester conjugated to a 3-substituted pyridine ring.

• SKU: M691663
• Product name: Methyl 3-(3-Pyridyl)propiolate
• CAS: 78584-30-2
• CID: 12716670
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
• SMILES: Typical representation (literature): COC(=O)C#Cc1cccnc1
• Molecular formula: Typical for this structure (literature/computed): C9H7NO2
• Molecular weight: Typical for this structure (literature/computed): ~161.16 g/mol

Structural features (general description):

• Core scaffold: a methyl propiolate fragment (–CO2Me conjugated to –C≡C–) directly attached to the 3-position of a pyridine ring.
• Functional groups: an internal alkyne (activated by the ester), a methyl ester (–CO2Me), and a heteroaromatic pyridine nitrogen (basic site).
• Substitution pattern: 3-pyridyl–C≡C–CO2Me (no stereocenters; linear alkyne geometry).
• 2D description: a six-membered aromatic ring with one ring nitrogen (pyridine) bearing at the meta position a linear –C≡C–CO2Me substituent; the ester methyl projects away from the alkyne terminus.

Synthetic Utility

Key functional elements and their synthetic value:

• Activated internal alkyne (–C≡C–CO2Me):
  • Powerful Michael acceptor enabling nucleophile additions (S-, N-, O-additions) to give stereodefined alkenes.
  • Entry to heterocycles via 1,3-dipolar cycloadditions (nitrile oxides → isoxazoles; azomethine ylides → pyrrolidines, conditions permitting).
  • Platform for Au/Pt-catalyzed hydration to β-keto esters or enol esters; halofunctionalization (e.g., I2, NBS) across the alkyne.
• Methyl ester:
  • Converts to the acid (saponolysis) and onward to amides/anhydrides using standard coupling reagents (EDC/HATU/DCC) or acid chlorides (SOCl2, oxalyl chloride).
  • Transesterification to tune sterics/electronics (e.g., tert-butyl, benzyl esters) for protecting-group strategies.
• Pyridine nitrogen:
  • Modulates coordination in catalysis (binding to Au, Cu, Pd), potentially influencing regioselectivity and rate.
  • Amenable to N-oxidation and N-alkylation for subsequent transformations; ring-functionalization (e.g., electrophilic halogenation after protection/activation) can introduce cross-coupling handles.

Retrosynthetic perspective (literature): Typically accessible via Sonogashira-type coupling of methyl propiolate with 3-halopyridines (to give the internal alkyne) or via esterification of 3-(3-pyridyl)propiolic acid. The reagent thus sits at a convergence point for late-stage diversification of the pyridyl ring and downstream heterocycle formation.

Target Specificity

Not applicable. This product is a small-molecule reagent/building block and does not have biological target specificity (no antigen/epitope/clone/isotype information).