Piperidine

Key takeaways

Piperidine belongs to chemistry; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Piperidine to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Piperidine from memory before moving on to harder problems.

Reference excerpt

Piperidine is an organic compound with the molecular formula (CH2)5NH. This heterocyclic amine consists of a six-membered ring containing five methylene bridges (–CH2–) and one amine bridge (–NH–). It is a colorless liquid with an odor described as objectionable, human sperm-like, typical of amines. The name comes from the genus name Piper, which is the Latin word for pepper. Although piperidine is a common organic compound, it is best known as a representative structure element within many pharmaceuticals and alkaloids, such as naturally-occurring solenopsins.

Production Piperidine was first reported in 1850 by the Scottish chemist Thomas Anderson and again, independently, in 1852 by the French chemist Auguste Cahours, who named it. Both of them obtained piperidine by reacting piperine with nitric acid. Industrially, piperidine is produced by the hydrogenation of pyridine, usually over a molybdenum disulfide catalyst:

C5H5N + 3 H2 → C5H10NH Pyridine can also be reduced to piperidine via a modified Birch reduction using sodium in ethanol.

Natural occurrence of piperidine and derivatives Piperidine itself has been obtained from black pepper, from Psilocaulon absimile (Aizoaceae), and in Petrosimonia monandra. The piperidine structural motif is present in numerous natural alkaloids. These include piperine, which gives black pepper its spicy taste. This gave the compound its name. Other examples are the fire ant toxin solenopsin, the nicotine analog anabasine of tree tobacco (Nicotiana glauca), lobeline of Indian tobacco, and the toxic alkaloid coniine from poison hemlock, which was used to put Socrates to death.

Conformation Piperidine prefers a chair conformation, similar to cyclohexane. Unlike cyclohexane, piperidine has two distinguishable chair conformations: one with the N–H bond in an axial position, and the other in an equatorial position. After much controversy during the 1950s–1970s, the equatorial conformation was found to be more stable by 0.72 kcal/mol in the gas phase. In nonpolar solvents, a range between 0.2 and 0.6 kcal/mol has been estimated, but in polar solvents the axial conformer may be more stable. The two conformers interconvert rapidly through nitrogen inversion; the free energy activation barrier for this process, estimated at 6.1 kcal/mol, is substantially lower than the 10.4 kcal/mol for ring inversion. In the case of N-methylpiperidine, the equatorial conformation is preferred by 3.16 kcal/mol, which is much larger than the preference in methylcyclohexane, 1.74 kcal/mol.

Reactions Piperidine is widely used to convert ketones to enamines. Enamines derived from piperidine are substrates in the Stork enamine alkylation reaction. Upon treatment with calcium hypochlorite, piperidine converts to N-chloropiperidine, a chloramine with the formula C5H10NCl. The resulting chloramine undergoes dehydrohalogenation to afford the cyclic imine.

NMR chemical control 13C NMR: (CDCl3, ppm) 47, 27.2, 25.2 1H NMR: (CDCl3, ppm) 2.79, 2.19, 1.51

Uses Piperidine is used as a solvent and as a base. The same is true for certain derivatives: N-formylpiperidine is a polar aprotic solvent with better hydrocarbon solubility than other amide solvents, and 2,2,6,6-tetramethylpiperidine is a highly sterically hindered base, useful because of its low nucleophilicity and high solubility in organic solvents. A significant industrial application of piperidine is for the production of dipiperidinyl dithiuram tetrasulfide, which is used as an accelerator of the sulfur vulcanization of rubber.

List of piperidine medications

Piperidine and its derivatives are ubiquitous building blocks in pharmaceuticals and fine chemicals. The piperidine structure is found in, for example:

Icaridin (Insect repellent) SSRIs (selective serotonin reuptake inhibitors) Paroxetine Stimulants and nootropics: Methylphenidate Ethylphenidate Pipradrol Desoxypipradrol Histamine 1 (H1) receptor antagonists/inverse agonists: Loratadine Histamine 3 (H3) receptor antagonists/inverse agonists: Pitolisant SERM (selective estrogen receptor modulators) Raloxifene Vasodilators Minoxidil Antipsychotic medications: Droperidol Haloperidol Melperone Mesoridazine Risperidone Thioridazine Opioids: Dipipanone Fentanyl and analogs Loperamide Pethidine (meperidine) Prodine Arylcyclohexylamines: PCP and analogs anticholinergic chemical weapons Ditran N-Methyl-3-piperidyl benzilate (JB-336, BZ) Piperidine is also commonly used in chemical degradation reactions, such as the sequencing of DNA in the cleavage of particular modified nucleotides. Piperidine is also commonly used as a base for the deprotection of Fmoc-amino acids used in solid-phase peptide synthesis. Piperidine is listed as a Table II precursor under the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances due to its use (peaking in the 1970s) in the clandestine manufacture of phencyclidine.

References

External links Media related to Piperidine at Wikimedia Commons

Illustrations

Worked examples

Example 1 — a first encounter with Piperidine

Start with the simplest possible case. Write down what Piperidine claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In chemistry, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Piperidine before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Piperidine ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Piperidine

In research: Piperidine appears in chemistry research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Piperidine in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Piperidine is common in secondary-school and first-year university syllabi. It links to neighbouring topics Amine solvents, Foul-smelling chemicals, Piperidines, so understanding it makes those chapters shorter.
In everyday life: Look for Piperidine outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

How to study Piperidine in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Piperidine means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Piperidine out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Piperidine in simple terms?

Piperidine is an organic compound with the molecular formula (CH2)5NH. This heterocyclic amine consists of a six-membered ring containing five methylene bridges (–CH2–) and one amine bridge (–NH–).

Why does Piperidine matter?

Because it connects several chemistry ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Piperidine?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Piperidine.