Coniine and the Hemlock Alkaloids

 

 

 

Synthesis

 

The first synthesis of coniine was carried out by Ladenburg in 1886.  He heated methylpyridinium iodide at 300oC to obtain 2-methyl pyridine.  On treatment with acetaldehyde with a Lewis base 2-propenylpyridine was obtained and this was reduced to ()-coniine by reduction with sodium in alcohol.  Enantiomeric separation was achieved by fractional crystallisation of the diastereoisomers of the salt obtained with (+)-tartaric acid

A further synthesis of coniine was carried out in 1932 by Bergmann, et al.  The starting material for this synthesis was 2-methylpyridine and this was converted to the corresponding alkyl lithium compound using phenyl lithium.  Nucleophilic substitution using bromo ethane was then followed by reduction using sodium in ethanol as in the Ladenburg synthesis

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