title: Pempidine
text: # Pempidine
  
  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
  
  $LD_{50}$ for the HCl salt of pempidine in mice: 74 mg/kg (i.v.); 125 mg/kg (i.p.); 413 mg/kg (p.o.).
  
  ## 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 $g/cm^3.$
  
  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.
  
  