Piperidine
Piperidine.gif

Piperidine occurs naturally in black pepper. It has a burning peppery taste.[9]

It occurs naturally in humans as a product of L-lysine metabolism.

Piperidine is a colorless, water-soluble liquid that can be obtained from the alkaloid piperine or from pyridine. It's used chiefly as a solvent.


Natural Sources

Plant part Percent
Black Pepper peppercorns 0.5-5% [3]
Black Pepper peppercorns 0.56% [2]
Black Pepper peppercorns < 0.0703% [6]
White Pepper peppercorns 0.1322% [6]
White Pepper peppercorns 0.32% [2]

20 grams of black pepper contains approximately 0.1-1 gram of piperidine.


Black Pepper Tea

To brew a piperidine rich drink from black pepper without extracting most of the piperine, mix course ground black pepper in cold water. Let it steep overnight in the refrigerator. Filter out the solids and discard them. The piperine in the black pepper is very poorly soluble in cold water and most remains in the black pepper grounds.

One 8 ounce cup of tea prepared in this way from 8 grams of black pepper will contain up to 400 mg of piperidine, and up to only 9.4 mg of piperine.


Separating Piperidine from Piperine in Black Pepper

Black pepper contains substantial amounts of piperine and lesser amounts of piperidine.

Piperine is a very weak base and practically insoluble in water (40 mg/L @ 18 C), and less so in cold water. It does not form salts with weak acids. Piperine hydrochloride is not stable and is practically insoluble in water because it decomposes into hydrochloric acid and piperine on contact with water. Most piperidine salts are very stable, and extremely soluble in water. Piperidine freebase is also highly water soluble.

The boiling point of freebase piperidine (106.3 C) is close to that of water (100 C). In freebase form it distills along with water. It's salt forms boil at much higher temperatures and cannot be distilled along with water. Piperine melts at 130 C and decomposes at higher temperatures. No form of piperine will distill with water.

These highly different characteristics allow these two amines to be easily separated from each other after extraction from black pepper. Piperidine can be easily separated from piperine by freebasing a black pepper water extract and then distilling the water. The piperidine will collect in the distillate along with the water, and the piperine will not.


Dosage

Up to 2 grams for adults as pure piperidine are reported in literature.


Pharmacology

Piperidine is absorbed through the GI tract, through the skin and by inhalation.

Piperidine is found naturally in the brain and other tissues of vertebrates and invertebrates; it is a biogenic amine and acts as a neuromodulator (Giacobini, 1976).[4]

Piperidine stimulates and blocks actions on ganglia, chemoreceptors, and neuromuscular junctions. It acts on chemoreceptors, which stimulates respiration; acts on sympathetic ganglia releasing catecholamines, which raises blood pressure; acts on parasympathetic ganglia, which stimulates contraction of smooth muscle; and acts on end plates, which stimulates contraction of skeletal muscle (Kase and Miyata, 1976).[4]

Piperidine interacts with cholinergic receptor sites of muscle end plates and with nicotinic receptors on sympathetic and parasympathetic ganglia to cause effects mimicking those of acetylcholine (Giacobini, 1976).[4]

Piperidine also acts on the central nervous system (CNS) where it also mimics the nicotinic effects of acetylcholine on synaptic sites in the brain (Kase and Miyata, 1976).[4]

Piperidine affects CNS responses related to emotional behavior, physiological processes of sleep, and extrapyramidal motor function (ataxia, head turning, and nystagmus) (Giacobini, 1976; Kase and Miyata, 1976).[4]

In a study using volunteers that received iv infusions of 100 mg piperidine for 30 minutes starting at sleep onset, sleep-related secretion of growth hormone was enhanced.[7]

Piperidine has a pronounced emetic effect in humans. When administered to schizophrenic patients at doses of 1 to 6 g/day, it was shown to cause nausea and a subjective sense of well being.[8]


Metabolism

In rats most of an ip dose of piperidine was excreted unchanged. Two major metabolites were identified as 3-hydroxypiperidine and 4-hydroxypiperidine (Okano et al., 1978).[4]


Half-Life

When injected iv into rats, piperidine disappeared exponentially with a half-life of 20 min.[5]


Toxicity

Smyth et al. (1962) reported an oral LD50 for piperidine of 520 mg/kg for the rat; values reported by Trochimowicz et al. (1994) ranged from 133 to 337 mg/kg. Oral administration of piperidine causes weakness, respiratory distress, and convulsions. Van den Heuvel et al. (1990) reported LD50 values of 445 27 mg/kg for male and female rats combined; clinical signs associated with dosing included ptosis, respiratory effects, lethargy, ataxia, tremors, salivation, and lacrimation.[4]


Chemical Properties

Freebase Piperidine

PubChem CID: 8082
Molecular Weight: 85.14754 [g/mol]
Molecular Formula: C5H11N
XLogP3: 0.8
IUPAC Name: piperidine
InChI: InChI=1S/C5H11N/c1-2-4-6-5-3-1/h6H,1-5H2
InChIKey: NQRYJNQNLNOLGT-UHFFFAOYSA-N
Canonical SMILES: C1CCNCC1
CAS No.: 110-89-4 [4]
Physical State: colorless liquid [4]
Taste: burning peppery taste [9]
Freezing point: -13 to -7 C [4]
Boiling point: 106.3 C [4]
Solubility: 1600g/L of water @ 20 C [4]; miscible in ethanol; soluble in ethyl ether, acetone, benzene, chloroform [10]
pH: 12.6 @ 100g/L, 20 C [4]
pKb: 2.88 [4]

Piperidine HCl

PubChem Compound ID: 2723721
Molecular Weight: 121.60848 [g/mol]
Molecular Formula: C5H12ClN
IUPAC Name: piperidine;hydrochloride
InChI: InChI=1S/C5H11N.ClH/c1-2-4-6-5-3-1;/h6H,1-5H2;1H
InChIKey: VEIWYFRREFUNRC-UHFFFAOYSA-N
Canonical SMILES: C1CCNCC1.Cl
Physical State: White crystalline powder.
Boiling point: 247 C; 241 - 244 C (note: quite a few sources state the melting point is 245-249 C at 760 mmHg with a lower boiling point of 106.4 C at 760 mmHg. This cannot be correct. These errors have unfortunately been replicated in several sources making it very difficult to determine the true melting point of this compound. An example of this error is found here: http://www.lookchem.com/cas-609/6091-44-7.html)
Solubility: soluble in water and alcohol

Piperidine Phosphate

Boiling point: 204-206 C

Piperidine bitartrate

Physical State: colourless crystals [1]
Solubility: soluble in water [1]
Dosage: 10 to 15 grains [1]

Bibliography
1.
http://chestofbooks.com
2. Chemist & Druggist, Volume 34
Benn Brothers, 1889; the University of Michigan
3. L. D. Kapoor;
Handbook of Ayurvedic Medicinal Plants, Volume 2 of Herbal Reference Library; CRC Press, 2001; ISBN 0849329299, 9780849329296
4. ACUTE EXPOSURE GUIDELINE LEVELS (AEGLs) FOR PIPERIDINE
NAC/AEGL FACA Committee; INTERIM 1: 09/2007; (Download Attached PDF Document)
5. Snyder, R. (ed.).
Ethyl Browning's Toxicity and Metabolism of Industrial Solvents. 2nd ed. Volume II: Nitrogen and Phosphorus Solvents; Amsterdam-New York-Oxford: Elsevier, 1990., p. 253
6. Chemical toxicants in Chinese foods: 4. Contents and Biological Significance of Piperidine in Black Pepper, White Pepper, Red Pepper and Other Species.
Lin, J.K.; Hwa, J.J.; Lee, Y.J. 1981. Kexue Fazhan Yuekan, 9, 557-566 (1981).
7. Toxikologische Bewertung Nr. 72. Piperidin
BG Chemie; CAS-Nr. 110-89-4; ISSN 0937-4248; November 2000
8. Ethel Browning's Toxicity and Metabolism of Industrial Solvents. 2nd ed. Volume II: Nitrogen and Phosphorus Solvents.
Robert Snyder; Elsevier, 1990, p. 255; ISBN 0444813160, 9780444813169
9. Fenaroli's Handbook of Flavor Ingredients. Second Edition. Volume 2.
Giovanni Fenaroli, NicoloĢ Bellanca, George A Burdock, Thomas E Furia; Boca Raton, Fla. [u.a.] CRC Press 1975; ISBN: 0878195327 9780878195329
10. CRC Handbook of Chemistry and Physics 86TH Edition
David R. Lide; CRC Press; 86 edition (23 Jun. 2005); ISBN-10: 0849304865; ISBN-13: 978-0849304866
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