3-Ethynyl-1-methylpiperidine - ≥95% , CAS No.91324-40-2

CAS: 91324-40-2 Cat. No.: E941892 Fórmula: C₈H₁₃N Peso molecular: 123.200

GRADE & PURITY ≥95%

Storage

Room temperature

Specifications

Especificações e pureza

≥95%

Condições de armazenamento de armazenamento

Room temperature

Pureza

≥95%

Nomes e identificadores

• Sorrisos canónicos: CN1CCCC(C1)C#C
• IUPAC Name: 3-ethynyl-1-methylpiperidine
• InChIKey: DKTJIPHWHWSTIG-UHFFFAOYSA-N
• INCHI: 1S/C8H13N/c1-3-8-5-4-6-9(2)7-8/h1,8H,4-7H2,2H3
• Peso molecular: 123.200

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Classe Piperidines

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Classe: Piperidines
• Subclass: Not available
• Intermediate Tree Nodes: Not available
• Direct Parent: Piperidines
• Alternative Parents: Trialkylamines Azacyclic compounds Acetylides Organopnictogen compounds Hydrocarbon derivatives
• Molecular Framework: Aliphatic heteromonocyclic compounds
• Substituents: Piperidine - Tertiary aliphatic amine - Tertiary amine - Acetylide - Azacycle - Organic nitrogen compound - Organopnictogen compound - Hydrocarbon derivative - Organonitrogen compound - Amine - Aliphatic heteromonocyclic compound
• Descrição: This compound belongs to the class of organic compounds known as piperidines. These are compounds containing a piperidine ring, which is a saturated aliphatic six-member ring with one nitrogen atom and five 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

Propriedades químicas e físicas

• Peso molecular: 123.200 g/mol
• XLogP3: 1.100
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 1
• Rotatable Bond Count: 0
• Exact Mass: 123.105 Da
• Monoisotopic Mass: 123.105 Da
• Topological Polar Surface Area: 3.200 Ų
• Heavy Atom Count: 9
• Formal Charge: 0
• Complexity: 131.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• Undefined Atom Stereocenter Count: 1
• 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. There are no immunoassay or bioassay protocols (WB, IHC, IF, FC) associated with this small-molecule building block. For synthetic use, refer to the Reaction Conditions section for general literature procedures.

Biological Roles

This product is a synthetic organic building block and is not intended for biological use as a metabolite or biochemical reagent.

• General context (literature; not specific to this item)
  • The N‑methylpiperidine motif appears in numerous bioactive small molecules due to its basicity and solubilizing properties.
  • Terminal alkynes are commonly used as chemical biology handles for bioorthogonal ligation (e.g., CuAAC) after installing the alkyne into a biomolecule; in such applications, the alkyne-bearing fragment is typically part of a larger conjugate rather than used neat.

No inherent biological role or pathway participation is assigned to 3‑ethynyl‑1‑methylpiperidine itself. Use is restricted to research and laboratory synthesis per the Research Use Note.

Buffer Applications

Not typically applicable. 3‑Ethynyl‑1‑methylpiperidine is a small organic base used as a synthetic building block, not a buffering agent. While tertiary amines can accept protons, this compound is not used to formulate defined buffer systems. For aqueous handling, convert to an ammonium salt if increased water solubility is desired.

Green Alternatives

As a building block, substitution is generally structure-driven; however, greener choices can be made in solvents, reagents, and process design when using 3‑ethynyl‑1‑methylpiperidine.

• Greener process choices (literature guidance)
  • Solvents: favor 2‑MeTHF, CPME, EtOAc, or toluene over DMF/DMAc/NMP where feasible (lower toxicity/reprotox concerns).
  • Bases: use inorganic bases (K2CO3, K3PO4) or less-volatile amines (iPr2NH) in place of Et3N; consider aqueous micellar media for couplings.
  • Catalysts: employ ligand‑enabled Pd at ppm levels or Cu‑free Sonogashira variants; explore photoredox/Ni dual catalysis to reduce precious metal use.
  • Workup: design salt‑switch crystallizations or biphasic extractions to minimize chlorinated solvents.

Comparison snapshot (general)

• Conventional: Sonogashira in DMF/iPr2NH with Pd/Cu → high efficiency, DMF waste, copper removal required.
• Greener: Sonogashira in 2‑MeTHF or EtOAc with K2CO3 and Pd–NHC at low loading, or micellar water with surfactant → reduced solvent impact, simpler metal removal.

Trade-offs

• Greener solvents may alter solubility and rate; catalyst/ligand tuning is often needed.
• Micellar systems can be sensitive to substrate basicity; tertiary amine may disrupt micelle structure—screen conditions.

Pharmaceutical Uses

This product is provided for research use only and is not an excipient or finished drug substance.

• General notes (literature context)

  • N‑methylpiperidine fragments are common in medicinal chemistry as basic solubilizing groups. 3‑Ethynyl substitution provides a vector for late‑stage diversification (e.g., click chemistry) during lead optimization.
  • In process development, amine building blocks like this may serve as intermediates en route to APIs. Any GMP or pharmacopeial suitability would require dedicated qualification—not specified for this item.

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

• Regulatory use: Not for human or veterinary use. For research and laboratory synthesis only.

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.
• Density, refractive index, water/peroxide/metal content, UV cutoff: Not specified for this item; refer to CoA/Spec Sheet.

Literature/general reference values (for context only; not item specifications)

• Physical state: low‑molecular-weight tertiary amines are typically colorless liquids with amine odor.
• Boiling point: tertiary piperidines in this mass range often boil in the 150–200 °C range (literature context for analogous structures; check CoA for this item).
• Basicity: pKaH of N‑methylpiperidine is ~10.1–11 (aqueous, literature); 3‑ethynyl substitution is not expected to drastically change basicity trend.
• Alkyne acidity: terminal alkyne pKa typically ~25 (DMSO, literature).
• Solubility: tertiary amines usually mix well with most organic solvents and show appreciable water solubility when protonated; free base solubility in water is moderate to low (literature generalization).
• LogP: small tertiary amines with one ring and one methyl often have cLogP ~1–2 (literature estimation for fragments of similar size).

Notes

• Use the item’s CoA/SDS for authoritative property values. Do not treat the above literature notes as product specifications.

Quality and Grades

• Item-specific grade/purity: Not specified for this item; refer to CoA/Spec Sheet.
• What grade means in practice (general guidance)
  • Research grade: suitable for synthetic and discovery workflows; impurity thresholds are fit for purpose but may not meet pharmacopeial monographs.
  • High-purity/GC or HPLC grade (if offered): emphasizes low volatile/nonvolatile impurities and low UV background—useful when the amine is employed as an internal standard, derivatization substrate, or in photometric detection workflows.
  • Stabilizers: Not specified for this item; refer to CoA/Spec Sheet. Tertiary amine/alkyne mixtures typically do not require stabilizers, but trace antioxidant or acid scavengers are sometimes used in related materials; verify on the CoA.
• Quality control pointers (general)
  • Identity: 1H/13C NMR should show characteristic terminal alkyne proton (~1.8–2.5 ppm, literature) and N‑methyl singlet; IR with strong C≡C–H stretch near ~3300 cm⁻¹ and C≡C stretch ~2100–2200 cm⁻¹.
  • Purity: GC or GC–MS suitable for low‑boiling amines; amine derivatization can improve chromatographic performance if needed.
  • Residual metals/halides: If used in cross-coupling, monitor Pd/Cu by ICP-OES in the final product when relevant.

Reaction and Applications

This molecule combines a basic tertiary amine with a terminal alkyne, enabling diverse synthetic transformations. The tertiary amine can modulate catalysis (ligating/base behavior) while the terminal alkyne serves as a versatile coupling handle.

• Representative transformations (literature; not item-specific)
  • Sonogashira coupling: aryl/ vinyl halides or triflates to install aryl/vinyl fragments at the terminal alkyne (Pd(0)/CuI, amine base), followed by optional hydrogenation or cyclization.
  • Glaser–Hay oxidative coupling: dimerization to 1,3‑diynes (Cu, O2), mindful of tertiary amine–Cu interactions.
  • CuAAC (“click chemistry”): azide–alkyne cycloaddition to 1,4‑disubstituted 1,2,3‑triazoles using Cu(I) catalysts; the tertiary amine can help solubilize Cu(I) but may necessitate ligand control.
  • Hydrofunctionalization: hydroamination or hydrosilylation across the C≡C bond with appropriate catalysts; intramolecular variants can build N‑heterocycles.
  • Metal–acetylide formation: strong bases (e.g., n‑BuLi, NaNH2) generate acetylides for nucleophilic additions to carbonyls or for further cross‑couplings.
• Use in discovery chemistry
  • As a fragment for SAR: the N‑methylpiperidine scaffold is a common basic pharmacophore; the terminal alkyne enables late-stage diversification (click, coupling) without disturbing the amine center.
  • Handles for conjugation: preparation of triazole-linked libraries, polymer attachments, or surface modification via alkyne-azide chemistry.
• Practical considerations
  • Protecting/protonation strategies: convert to the ammonium salt to increase crystallinity/handling; deprotect with base before alkyne chemistry.
  • Competitive basicity: substrate can sequester catalysts (Pd/Cu); adjusting catalyst/ligand loading or temporary protonation can mitigate.

Reaction Conditions

General literature conditions for common transformations of terminal alkynes bearing tertiary amines (guidance only; optimize per substrate and scale):

• Sonogashira coupling

  • Typical: Aryl bromide/iodide (1.0 eq), alkyne (1.2 eq), Pd(PPh3)2Cl2 (1–3 mol%), CuI (2–5 mol%), iPr2NH or Et3N, 50–80 °C, 2–12 h, inert atmosphere. Alternatives: Pd–NHC at 0.1–0.5 mol% in 2‑MeTHF with K2CO3.
  • Notes: The tertiary amine can coordinate Pd/Cu; increase ligand/Pd ratio or use copper‑free protocols to reduce Glaser byproducts.

• CuAAC (azide–alkyne “click”)

  • Typical: Organic azide (1.0 eq), alkyne (1.0–1.5 eq), CuSO4·5H2O (1–5 mol%), sodium ascorbate (5–10 mol%), t‑BuOH/H2O (1:1), rt–50 °C, 1–8 h.
  • Notes: Add TBTA or related ligands if the tertiary amine perturbs Cu(I) speciation.

• Glaser–Hay oxidative dimerization

  • Typical: CuI (5–10 mol%), TMEDA (10–20 mol%), O2 or air, toluene or THF, rt–50 °C.
  • Notes: Competes with Sonogashira; exclude O2 when not desired.

• Acetylide formation/addition

  • Typical: n‑BuLi (1.1 eq) or NaNH2 (1.5 eq) in THF/Et2O at −78 to 0 °C to form the lithium/sodium acetylide; then add electrophile (e.g., carbonyl). Quench at low temperature.
  • Notes: Strong bases may also deprotonate the ammonium form; ensure free base and rigorously anhydrous conditions.

• Hydrogenation/hydrofunctionalization

  • Lindlar (semi-hydrogenation) or Pd/C (full reduction) to alkene/alkane; catalytic hydroboration followed by oxidation for aldehyde/ketone synthesis from alkynes.

Yields/timeframes vary with substrate and conditions; consult primary literature and run small-scale screens.

Safety and Handling

Item-specific hazard information

• Signal Word: Not specified for this item; refer to SDS.
• H-Statements: Not specified for this item; refer to SDS.
• GHS Classification and Pictograms: Not specified for this item; refer to SDS.

General safety profile for tertiary amines and terminal alkynes (literature/good practice; defer to SDS)

• Likely hazards: skin/eye irritation, respiratory irritation, harmful if swallowed; many low‑MW amines are corrosive at high concentrations and flammable as liquids/vapors. Terminal alkynes are flammable and can form metal acetylides with strong bases or copper/silver surfaces.
• PPE: lab coat, safety goggles/face shield, nitrile gloves; use in a fume hood to control vapors and odors.
• Handling: avoid contact with acids/oxidizers; tertiary amines can react exothermically with strong acids and may form salts. Avoid contact with copper/silver surfaces if deprotonated alkyne formation is a concern.
• Incompatibilities: strong oxidizers; strong acids (salt formation); CO2/moisture can be absorbed by amine bases; avoid prolonged exposure to air if purity is critical.
• First aid (overview): rinse skin/eyes with water for ≥15 min if exposed; move to fresh air if inhaled; do not induce vomiting if ingested—seek medical attention. Always follow the SDS.
• Fire safety: use CO2, dry chemical, or alcohol-resistant foam. Vapors may form explosive mixtures with air at elevated temperature—ground/bond containers.

Always consult the product SDS for definitive hazard classifications and response measures.

Solvent Selection

Applicability: This product is a small, basic, nonpolar-to-moderately polar liquid (tertiary amine with a terminal alkyne). It is primarily a building block, not a solvent; however, understanding solvent compatibility is important for its use in synthesis.

• Polarity/miscibility (literature expectations)
  • Miscible with common organic solvents (Et2O, THF, DCM, MeCN, toluene).
  • Moderate water solubility as free base; high water solubility as the protonated ammonium salt in acidic media.
  • Can act as a weak ligand/base in coordinating solvents.
• Solvent choice by transformation
  • Sonogashira couplings: DMF, DMAc, NMP, dioxane, THF, or toluene; amine bases (iPr2NH, Et3N) frequently used—be mindful of competitive coordination from the substrate’s tertiary amine.
  • CuAAC (“click”): t‑BuOH/H2O or DMSO/H2O mixtures; chelation by the tertiary amine may affect copper speciation—buffer with excess ligand or choose water/tert‑BuOH for robustness.
  • Deprotonation to acetylide: anhydrous ethereal solvents (THF, Et2O) or hydrocarbons (toluene, hexanes) at low temperature.
• Practical tips
  • Dry, oxygen-free conditions improve outcomes in metal-catalyzed alkyne chemistry.
  • If a protic acid is present, the compound will form an ammonium salt and shift into the aqueous phase; adjust pH for extractions.
  • Avoid strongly acidic chlorinated solvents in the presence of strong bases to prevent amine quaternization/side reactions.

Storage and 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 guidance for tertiary amine/alkyne liquids

• Store tightly closed under inert gas if long-term storage is planned to minimize uptake of CO2/moisture and prevent oxidative discoloration.
• Keep away from strong oxidizers and acids. Use amber glass if extended light exposure is expected, although terminal alkynes are typically not light‑sensitive.
• If an ammonium salt form is prepared for handling/crystallinity, store the salt dry and protect from humidity; regenerate the free base with aqueous base before use.
• Bring to room temperature before opening to reduce condensation. For air- and moisture‑sensitive transformations, pre-dry over molecular sieves or distill under reduced pressure if appropriate (follow SDS and CoA for any distillation guidance).

Reconstitution

• Not applicable; supplied as a neat liquid (typical for compounds of this class). If solidified at low temperature, gently warm to ambient and mix thoroughly before aliquoting.

Always consult the product’s CoA and SDS for definitive storage and handling instructions.

Structure and Identity

Brief description: 3-Ethynyl-1-methylpiperidine is a tertiary amine (N-methylpiperidine) bearing a terminal alkyne at the 3-position of the saturated six‑membered ring. It combines a basic cyclic amine with a nucleophilic/acidic terminal C≡C–H handle.

• Item-specific identifiers (from Product Data)

  • SKU: E941892
  • Product Name: 3-Ethynyl-1-methylpiperidine
  • CAS: 91324-40-2
  • InChIKey: 66041 (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/computed structural information (for context; not item-specific specifications)

  • Functional groups: tertiary amine (N-methyl), terminal alkyne (ethynyl, HC≡C–)
  • Representative 2D description: saturated piperidine ring (chair conformation) with an N‑methyl substituent; at the carbon 3 position, a –C≡CH substituent projects equatorially/axially depending on conformation; no stereocenters.
  • Typical molecular formula (literature): C8H14N
  • Typical molecular weight (literature): ~124.21 g/mol
  • Representative SMILES (literature example): CN1CCC(C#C)C1

• Structural features of interest

  • The tertiary amine is strongly basic and nucleophilic; it can coordinate metals and is readily protonated to a water‑soluble ammonium salt.
  • The terminal alkyne proton is acidic (pKa ~25, literature) enabling formation of metal acetylides and participation in Sonogashira/Glaser/CuAAC-type chemistries (subject to compatibility with the tertiary amine).

Synthetic Utility

Key functional elements

• Tertiary amine (N‑methylpiperidine): strong base/nucleophile; forms stable ammonium salts; coordinates to transition metals and can influence catalytic cycles.
• Terminal alkyne: versatile C(sp)–H handle enabling coupling, cycloaddition, and nucleophilic chemistry.

Retrosynthetic value (literature)

• Divergent elaboration via the alkyne:
  • Cross-coupling (Sonogashira) to aryl/vinyl acetylenes; further hydrogenation → saturated side chains; hydroboration/oxidation → carbonyls; carbo-/hydrofunctionalizations → diverse motifs.
  • CuAAC to 1,2,3‑triazoles for library generation and conjugation.
• Amine-centered manipulations:
  • Quaternization to ammonium salts for phase-transfer roles or separations;
  • N‑oxide formation followed by Polonovski-type chemistry (where applicable) to adjust electronics;
  • Temporary protonation to direct regio-/stereoselectivity or to attenuate metal coordination during catalysis.

Orthogonality

• The alkyne and tertiary amine are largely orthogonal: the alkyne tolerates many bases/nucleophiles; the tertiary amine tolerates many redox conditions but can poison certain catalysts—ligand/catalyst selection mitigates this.

Analytical handles

• IR: ≈3300 cm⁻¹ (≡C–H), 2100–2200 cm⁻¹ (C≡C);
• NMR: terminal alkyne proton ~1.8–2.5 ppm; N‑Me singlet; ring methylenes 1–3 ppm;
• MS: base peak often at M+ or fragments from α‑cleavage next to nitrogen (literature).

Target Specificity

Not applicable. This product is a small-molecule building block, not a biological targeting reagent (e.g., antibody, ligand with defined biomolecular target). No antigen/epitope or species reactivity information applies.