Petrenko-Kritschenko piperidone synthesis

While mechanistically this reaction is related to the Robinson-Schopf reaction for the generation of the tropinone skeleton, it also has similarities to the Hantzsch reaction. Here the heterocyclic ring 75 is assembled by the condensation of an equivalent of acetonedicarboxylic ester 72 with 2 equivalents of aldehyde 73 in the presence of ammonia or primary amine 74. 

In an approach to opioid receptor ligands,diazabicyclononanones were prepared in a double Petrenko-Kritschenko reaction. Diester 76, in the presence of methylamine and aryl aldehydes, was converted to piperidone 77. This was immediately resubmitted to the reaction conditions however, in this iteration formaldehyde replaced the aryl aldehyde component. The outcome of this reaction produced 78 which was further investigated for its use in rheumatoid arthritis. 

Stevens reported an interesting variation in which the amine and the aldehydes were linked by a tether. Combining bisacetalamine 79 with 76 under acidic conditions generated the single diastereomer 80. This tricyclic species was then converted into the ladybug defense alkaloid precoccinelline 81. 

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This reaction is related to the Guareschi-Thorpe Pyridine Synthesis, Chichibabin Pyridine Synthesis, KrOhnke Pyridine Synthesis, and Petrenko-Kritschenko Piperidone Synthesis. 

This reaction was first reported by Petrenko-Kritschenko in 1906. It is the preparation of piperidone via a double Mannich Reaction from acetonedicarboxylic ester, two equivalents of aldehyde, and ammonia (or a primary amine), and is known as the Petrenko-Kritschenko piperidone synthesis. In this reaction, the mixture of reaction components is usually refluxed in an aqueous or alcoholic solution, and the resulting product is difficult to purify. It has been found that the addition of acid to the reaction medium is useful for this reaction.2... 

Other references related to the Petrenko-Kritschenko piperidone synthesis are cited in the literature. ... 

This reaction is related to the Petrenko-Kritschenko Piperidone Synthesis. 

Petrenko-Kritschenko Piperidone Synthesis Pfau-Plattner Azulene Synthesis Pfitzinger Reaction PFitzner-Moffatt Oxidation... 

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