The piperidine is an organic compound which is condensed formula (CH 2) 5 NH. It consists of a cyclic secondary amine, where the amino group, NH, is part of a hexagonal ring, which is heterocyclic, due to the presence of the nitrogen atom.
Piperidine is the nitrogenous version of cyclohexane. For example, note in the image below the structural formula of piperidine: it is very similar to that of cyclohexane, with the only difference that one of the methylene groups, CH 2, has been replaced by an NH.
Structural formula of piperidine. Source: NEUROtiker / Public domain
The curious name of this amine comes from the Latin word 'piper', which means pepper, as it was in black pepper that it was first found and synthesized. In fact, the aroma of piperidine is mistaken for that of a mixture of pepper and fish.
Its hexagonal and heterocyclic ring is also present in many alkaloids and drugs, so piperidine is used for the organic synthesis of such products; such as morphine, minoxidil, and resperidone.
Structure
Molecular structure of piperidine. Source: Benjah-bmm27 / Public domain
In the upper image we have the molecular structure of piperidine, represented by a model of spheres and bars. The black spheres, corresponding to the carbon atoms, make up the skeleton that would be the same as cyclohexane if it were not for the nitrogen atom, that of the bluish sphere.
Here you can see the five methylene units, CH 2, and the way their hydrogen atoms are arranged. Likewise, the secondary amino group, NH, is clearly observed, whose electronegative nitrogen provides polarity to the molecule.
Therefore, piperidine has a permanent dipole moment, in which the negative charge density is concentrated around NH.
As piperidine has a dipole moment, its intermolecular forces or interactions are predominantly of the dipole-dipole type.
Among the dipole-dipole interactions, the hydrogen bonds established by the NH-NH groups of neighboring piperidine molecules are present. As a result, the piperidine molecules coalesce in a liquid that boils at a temperature of 106ºC.
Conformations
The hexagonal ring of piperidine, like that of cyclohexane, is not flat: its hydrogen atoms alternate in axial (above or below) and equatorial (directed sideways) positions. Thus, piperidine adopts various spatial conformations, the chair being the most important and stable.
The previous image shows one of the four possible confomers in which the hydrogen atom of the NH group is located in the equatorial position; whereas the pair of electrons not shared of the nitrogen, they are located in axial position (upwards, in this case).
Axial conformation of piperidine. The hydrogen atom in the axial position increases the steric tension on the ring by being too close to the other axial and adjacent hydrogens. Source: Benjah-bmm27 / Public domain
Now another conformer is shown (upper image), in which this time the hydrogen atom of the NH group is in an axial position (upwards); and the pair of non-shared electrons of nitrogen, in the equatorial position (to the left).
So in total there are four conformers: two with the hydrogen of NH in axial and equatorial positions, and another two in which the relative positions of the pair of electrons of nitrogen with respect to the chair are varied.
The conformers in which the hydrogen of NH is in the equatorial position are the most stable, due to the fact that they suffer from lower steric tensions.
Synthesis
The first syntheses of piperidine proceeded from piperine, one of its natural derivatives that is part of black pepper and is responsible for several of the organoleptic properties of this seasoning. Piperine reacts with nitric acid, releasing the heterocyclic unit whose structure has already been revised.
However, on industrial scales, the synthesis of piperidine by catalytic hydrogenation of pyridine is preferred:
Hydrogenation of pyridine to obtain piperidine. Source: Steffen 962 via Wikipedia.
The hydrogens, H 2, bind to the pyridine ring, breaking its aromatic system, for which the help of metallic catalysts is needed.
Derivatives
Piperine
Much more important than piperidine itself is its structural unit, recognizable in countless alkaloids and substances of plant origin. For example, below is the molecular structure of piperine:
Structural formula of piperine. Source: Neurotiker via Wikipedia.
Piperine has a highly conjugated structure; that is, it has several coordinated double bonds that absorb electromagnetic radiation, and that in one way or another, make it a non-toxic compound for human consumption. If not, black pepper would be poisonous.
Coniína
The heterocyclic and hexagonal ring of piperidine is also found in conin, a neurotoxin extracted from hemlock, responsible for its unpleasant odor, and which was also used to poison Socrates. Its structure is:
Structural formula of coniin. Source: NEUROtiker / Public domain
Note that coniin is hardly different from piperidine by the presence of a propyl substituent on the carbon adjacent to the NH group.
Thus, derivatives of piperidine are obtained by substituting the hydrogens of the ring, or the hydrogen of the NH group itself, by other groups or molecular fragments.
Morphine
Structural formula of morphine. Source: NEUROtiker / Public domain
Morphine is another of the natural derivatives of piperidine. This time the piperidine ring is fused with other rings, and points out of the plane, in the direction of the observer. It is identified because it forms a bond with the CH 3 group.
Drugs
Piperidine and its derivatives are used for the design and synthesis of different types of drugs. Therefore, they are synthetic derivatives of piperidine. Three of them are listed below along with their respective structural formulas:
Risperidone, an atypical antipsychotic prescribed for the treatment of multiple mental disorders. Source: Fvasconcellos (talk • contribs) / Public domain
Minoxidil, a vasodilator generally used to deal with alopecia. Source: Vaccinationist / Public domain
Icaridin or picaridin, an insect repellent that makes up the formulation of OFF repellants. Source: Arrowsmaster / CC BY-SA (https://creativecommons.org/licenses/by-sa/4.0)
References
- Graham Solomons TW, Craig B. Fryhle. (2011). Organic Chemistry. (10 th edition.). Wiley Plus.
- Carey F. (2008). Organic Chemistry. (Sixth edition). Mc Graw Hill.
- Morrison and Boyd. (1987). Organic chemistry. (Fifth edition). Addison-Wesley Iberoamericana.
- Wikipedia. (2020). Piperidine. Recovered from: en.wikipedia.org
- National Center for Biotechnology Information. (2020). Piperidine. PubChem Database., CID = 8082. Recovered from: pubchem.ncbi.nlm.nih.gov
- Elsevier BV (2020). Piperidine. ScienceDirect. Recovered from: sciencedirect.com
- Harold D. Banks. (1992). Piperidine Synthesis.. Recovered from: apps.dtic.mil