Chichibabin Tschitschibabin pyridine synthesis

First described in 1905, the Chichibabin reaction was carried out by passing vapors of aliphatic aldehyde 31 and ammonia over alumina at 300-400°C to produce the corresponding pyridine derivative 32. As a consequence, this method generates 2,3,5-trisubstiluted pyridines. 

From a mechanistic standpoint, ammonia serves two functions 1) it behaves as a base to catalyze an aldol reaction between 2 equivalents of 31 to generate the corresponding enal 33, and 2) it is the source of nitrogen for the resultant pyridyl ring. This occurs through formation of enamine 34 with a third equivalent of 31. The Michael addition of 34 to 33 followed by cyclization gives rise to 32. 

The close relationship of this reaction scheme with that for the Hantzsch protocol becomes obvious upon careful examination. The use of AcOH/NRtOAc as the solvent/nitrogen source has dramatically improved on the experimental ease and yield of this reaction.  

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Galatasis, P. Chichibabin (Tschitschibabin) Pyridine Synthesis In Name Reactions in Heterocyclic Chemistry, Li, J. J. Corey, E. J., Eds. Wiley Sons Hoboken, NJ, 2005, 308-309. (Review). 

Guareschi-Thorpe pyridine synthesis Chichibabin (Tschitschibabin) pyridine synthesis Bohlmann-Rahtz pyridine synthesis Krohnke pyridine synthesis... 

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