1-(Prop-2-yn-1-yl)piperidine
[CAS# 5799-75-7]

Identification

• Classification: Organic raw materials >> Heterocyclic compound >> Piperidines
• Name: 1-(Prop-2-yn-1-yl)piperidine
• Molecular Formula: C₈H₁₃N
• Molecular Weight: 123.20
• CAS Registry Number: 5799-75-7
• EC Number: 837-125-2
• SMILES: C#CCN1CCCCC1

Properties

• Density: 0.9±0.1 g/cm³ Calc.^*
• Boiling point: 157.6±23.0 °C 760 mmHg (Calc.)^*
• Flash point: 41.5±19.5 °C (Calc.)^*
• Index of refraction: 1.479 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS02;GHS05;GHS07 Danger
• Risk Statements: H226-H314-H335
• Safety Statements: P210-P233-P240-P241-P242-P243-P260-P261-P264-P271-P280-P301+P330+P331-P302+P361+P354-P303+P361+P353-P304+P340-P305+P354+P338-P316-P319-P321-P363-P370+P378-P403+P233-P403+P235-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Flammable liquids	Flam. Liq.	3	H226
Skin corrosion	Skin Corr.	1B	H314
Specific target organ toxicity - single exposure	STOT SE	3	H335

Discovery and Applications

1-(Prop-2-yn-1-yl)piperidine is a secondary amine in which a piperidine ring is N-substituted with a propargyl group (–CH₂C≡CH). This structural motif combines the chemical reactivity of a tertiary alkyne with the basicity and nucleophilicity of a cyclic secondary amine, making it a versatile intermediate in organic synthesis.

The compound can be prepared via N-alkylation of piperidine with propargyl halides under controlled conditions. Careful selection of solvent, base, and temperature allows selective formation of the N-propargyl derivative while minimizing side reactions such as multiple alkylation or polymerization of the alkyne. The product is typically isolated as a colorless liquid with a characteristic amine odor and moderate solubility in common organic solvents.

1-(Prop-2-yn-1-yl)piperidine has been employed as a building block in medicinal chemistry for the synthesis of pharmacologically active molecules. The propargyl group is particularly useful in introducing alkynyl moieties into heterocycles or for subsequent transformations via click chemistry, Sonogashira coupling, or oxidation reactions. The piperidine ring contributes to conformational rigidity and basicity, often affecting the pharmacokinetics and receptor-binding properties of the resulting compounds.

Beyond pharmaceutical applications, the compound is also used in the synthesis of functionalized ligands for catalysis. The combination of nitrogen lone pairs and a terminal alkyne enables coordination to transition metals, facilitating the design of metal complexes with tailored electronic and steric properties. Such complexes are employed in asymmetric catalysis, cycloaddition reactions, and polymerization processes.

Physically, 1-(Prop-2-yn-1-yl)piperidine is generally handled under standard laboratory conditions. It is moderately volatile and hygroscopic, requiring storage under inert atmosphere to prevent oxidation or reaction with moisture. Its basicity and nucleophilicity necessitate careful handling, especially in large-scale reactions, to avoid side reactions or exothermic events.

Overall, 1-(Prop-2-yn-1-yl)piperidine serves as a versatile intermediate for both medicinal and synthetic chemistry. Its unique combination of a nucleophilic amine and a reactive alkyne allows diverse chemical transformations, making it an important building block in research and industrial applications.

References

2024. Rational design, synthesis, biological evaluation, and molecular modeling of novel naphthamide derivatives possessing potent, reversible, and competitive inhibitory mode of action over human monoamine oxidase. Molecular Diversity.
DOI: 10.1007/s11030-024-10841-9

2023. Mass Spectra of New Heterocycles: XXVI. Electron Impact Ionization Study of N-(5-Aminothiophen-2-yl)- and N-[2-(Methylsulfanyl)-1,3-thiazol-5-yl]isothioureas. Russian Journal of Organic Chemistry, 59(7).
DOI: 10.1134/s1070428023070035