Pempidine

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Pempidine is a nicotinic antagonist drug, first reported in 1958 by two research groups working independently, and introduced as an oral treatment for hypertension.[1]

Pharmacology

Reports on the "classical" pharmacology of pempidine have been published.[2][3] 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.[2]

Toxicology

LD50 for the HCl salt of pempidine in mice: 74 mg/kg (intravenous); 125 mg/kg (intraperitoneal); 413 mg/kg (oral).[2]

Chemistry

Pempidine is an aliphatic, sterically hindered, cyclic, tertiary amine, which is a weak base: in its protonated form it has a pKa of 11.25.[4]

Pempidine is a liquid with a boiling point of 187–188 °C and a density of 0.858 g/cm3.[2]

Two early syntheses of this compound are those of Leonard and Hauck,[5] and Hall.[4] 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.[6]

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

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  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.

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External links

Template:Antihypertensives Template:Nicotinic acetylcholine receptor modulators