1-Cbz-4-methylenepiperidine
[CAS# 138163-12-9]

Identification

• Classification: Organic raw materials >> Heterocyclic compound >> Piperidines
• Name: 1-Cbz-4-methylenepiperidine
• Synonyms: Benzyl 4-methylidenepiperidine-1-carboxylate
• Molecular Formula: C₁₄H₁₇NO₂
• Molecular Weight: 231.29
• CAS Registry Number: 138163-12-9
• EC Number: 974-654-9
• SMILES: C=C1CCN(CC1)C(=O)OCC2=CC=CC=C2

Properties

• Density: 1.1±0.1 g/cm³ Calc.^*
• Boiling point: 346.1±41.0 °C 760 mmHg (Calc.)^*
• Flash point: 163.1±27.6 °C (Calc.)^*
• Index of refraction: 1.559 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335
• Safety Statements: P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Discovery and Applications

1-C bz-4-methylenepiperidine is a carbobenzyloxy (Cbz) protected piperidine derivative where the nitrogen atom bears a benzyl carbamate and a methylene (═CH₂) substituent is positioned at the 4-carbon of the piperidine ring. Its molecular formula is C₁₄H₁₇NO₂, and it exhibits a molecular weight of approximately 231.29 g/mol. The compound commonly appears as a white crystalline solid with good solubility in organic solvents such as dichloromethane, ethyl acetate, and methanol.

This compound is primarily used as an intermediate in organic synthesis, particularly in pharmaceutical and peptide chemistry. The Cbz protecting group serves to mask the basic secondary amine functionality during multi-step syntheses, preserving it for later deprotection under mild acidic or hydrogenolytic conditions. The presence of the methylene group at the 4-position introduces a reactive handle, enabling further elaboration via olefin chemistry such as Michael additions, epoxidations, or cross-coupling reactions. This dual functionality—protection of the amine and availability of a reactive alkene—makes 1-C bz-4-methylenepiperidine a valuable building block in the synthesis of complex nitrogen-containing molecules.

Synthetic access to this compound typically begins with 1-Cbz-4-piperidone. Through Wittig or Tebbe olefination techniques, the ketone is converted to the methylene derivative. The reaction proceeds under mild conditions using phosphonium ylides or metal-mediated methylenation reagents, preserving the integrity of the Cbz-protected nitrogen. The resulting product is purified by standard chromatographic or crystallization methods, yielding a solid product suitable for downstream synthetic pathways.

Commercial availability of 1-C bz-4-methylenepiperidine is common through fine chemical suppliers, typically offered at purities ≥ 95%. It is stored under ambient or refrigerated conditions to maintain stability. Handling should include standard precautions for protected amine compounds, including use of gloves and eye protection and storage in a well-ventilated lab area.

From a practical standpoint, the compound enables the synthesis of novel piperidine scaffolds by harnessing the methylene group to install additional functional groups or ring systems. Applications extend to medicinal chemistry projects targeting central nervous system receptors, enzyme inhibitors, and other bioactive small molecules. The protected amine allows for regioselective functionalization, while maintaining the option to unmask the nitrogen at a strategic point in synthesis.

In summary, 1-C bz-4-methylenepiperidine is a versatile synthetic intermediate defined by its protecting group and reactive methylene substituent. It finds utility in complex amine syntheses, providing synthetic chemists with a protected scaffold capable of diverse derivatization.

References

2019. Vicinal Fluoro(trifluoromethyl)alkanes from Alkenes. Science of Synthesis.
URL: https://science-of-synthesis.thieme.com/app/text/?id=SD-134-00332

2018. Tris(acetylacetonato) Iron(III): Recent Developments and Synthetic Applications. Synthesis, 51(06).
DOI: 10.1055/s-0037-1610393