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Pempidine

Identifiers
IUPAC name 1,2,2,6,6-Pentamethylpiperidine
CAS Number	79-55-0
PubChem CID	6603
ChemSpider	6353
UNII	N5I18JI9D6
ChEMBL	ChEMBL1617409
CompTox Dashboard (EPA)	DTXSID7046962
ECHA InfoCard	100.001.102
Chemical and physical data
Formula	C10H21N
Molar mass	155.285 g·mol
3D model (JSmol)	Interactive image
SMILES CC1(CCCC(N1C)(C)C)C

Pempidine is a ganglion-blocking drug, first reported in 1958 by two research groups working independently, and introduced as an oral treatment for hypertension.

Pharmacology

Reports on the "classical" pharmacology of pempidine have been published. The Spinks group, at ICI, compared pempidine, its N-ethyl analogue, and mecamylamine in considerable detail, with additional data related to several structurally simpler compounds.

Toxicology

LD₅₀ for the HCl salt of pempidine in mice: 74 mg/kg (intravenous); 125 mg/kg (intraperitoneal); 413 mg/kg (oral).

Chemistry

Pempidine is an aliphatic, sterically hindered, cyclic, tertiary amine, which is a weak base: in its protonated form it has a pK_a of 11.25.

Pempidine is a liquid with a boiling point of 187–188 °C and a density of 0.858 g/cm.

Two early syntheses of this compound are those of Leonard and Hauck, and Hall. These are very similar in principle: Leonard and Hauck reacted phorone with ammonia, to produce 2,2,6,6-tetramethyl-4-piperidone, which was then reduced by means of the Wolff–Kishner reduction to 2,2,6,6-tetramethylpiperidine. This secondary amine was then N-methylated using methyl iodide and potassium carbonate.

Hall's method involved reacting acetone with ammonia in the presence of calcium chloride to give 2,2,6,6-tetramethyl-4-piperidone, which was then reduced under Wolff–Kishner conditions, followed by N-methylation of the resulting 2,2,6,6-tetramethylpiperidine with methyl p-toluenesulfonate.

References

1. Spinks A, Young EH (May 1958). "Polyalkylpiperidines: a new series of ganglion-blocking agents". Nature. 181 (4620): 1397–1398. Bibcode:1958Natur.181.1397S. doi:10.1038/1811397a0. S2CID 4196802.
2. ^ Spinks A, Young EH, Farrington JA, Dunlop D (December 1958). "The pharmacological actions of pempidine and its ethyl homologue". British Journal of Pharmacology and Chemotherapy. 13 (4): 501–20. doi:10.1111/j.1476-5381.1958.tb00246.x. PMC 1481871. PMID 13618559.
3. Muggleton DF, Reading HW (June 1959). "Absorption, metabolism and elimination of pempidine in the rat". British Journal of Pharmacology and Chemotherapy. 14 (2): 202–208. doi:10.1111/j.1476-5381.1959.tb01384.x. PMC 1481796. PMID 13662574.
4. ^ Hall HK (1957). "Steric Effects on the Base Strengths of Cyclic Amines". Journal of the American Chemical Society. 79 (20): 5444–5447. doi:10.1021/ja01577a031.
5. Leonard NJ, Hauck Jr FP (October 1957). "Unsaturated amines. X. The mercuric acetate route to substituted piperidines, Δ-tetrahydropyridines and Δ-tetrahydroanabasines". Journal of the American Chemical Society. 79 (19): 5279–5292. doi:10.1021/ja01576a056.
6. The boiling point of 147 °C given by these authors for their 1,2,2,6,6-pentamethylpiperidine is significantly below the range of approximately 182–188 °C reported by other chemists.

External links

• Pempidine at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

• Nicotinic antagonists
• Piperidines
• Reagents for organic chemistry