Piperidines belong to a valuable category of heterocyclic compounds, which consist of a six membered nitrogen-containing ring and one secondary amine group. Piperidine derivatives are widely abundant in nature, numerous biologically active compounds contain the piperidines moiety as structural framework. Most piperidine analogs are obtained by complete hydrogenation reaction from the corelative pyridine. It is noteworthy that piperidine is flammable and highly stimulated, more importantly, piperidine is 1st catalogue precursor chemical and controlled drug, which is not allowed to be purchased without permission. Every care should be taken during its use and storage.
Fig.1. Piperidine compounds
Unmodified piperidines are totally water-soluble, because the existence of unconjugated six-member rings and the nitrogen atom can form hydrogen bond with water molecule which coordinatively promote its solubility. Piperidine is a strong organic base with strong reducibility, all the piperidines possess secondary amine group as a major reaction site (red region in Fig 1). Their chemical properties are similar to that of aliphatic secondary amines, which can react with inorganic acids to produce corelative salts or participate in N-methylation to produce tertiary amines. Most piperidines are prepared by the hydrogenation of pyridine and piperidine compounds are the key active constituent parts of natural products, advancing the fabrication of various modern medicine and bioactive molecules.
Due to the presence of the polar secondary amine group, piperidine can be compatible with many polar substances. Besides, colorless piperidine contributes to the observation of reaction phenomena. Therefore, piperidines have been widely used in related fields, they are generally utilized as solvent for rubber, paints, varnishes, and as condensation agent to react with other electrophilic reagents.
Piperidine compounds are widespread in biological products and psychogenic medicines. Their derivatives are usually used to fabricate potential medicine candidates, which possess remarkable pharmacological and physiological activities, such as antibacterial, anticonvulsant, anti-tumor and anti-inflammatory behavior, etc. The bioactivity and solubility of the piperidine derivatives can be adjusted by modifying different functional groups to achieve optimal effect (Fig 2).
Fig.2. Representative psychiatric drugs with the piperidine framework
(Bioorganic & Medicinal Chemistry 2008, 16(2): 601-635.)
Inspired by the antibacterial activity in medicinal precursors, piperidine derivatives can be applied as fungicides, insecticide, herbicide and so on. a variety of piperidine compounds are designed as intermediate for plant growth regulators for further commercial manufacture (Fig 3).
Fig.3. Representative antibacterial chemicals with piperidine framework
(Helv. Chim. Acta 2012, 95, 1181-1197.)