| Petrenko-Kritschenko piperidone synthesis | |||||||||||||||
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| Named after | Paul Petrenko-Kritschenko | ||||||||||||||
| Reaction type | multicomponent ring-condensation | ||||||||||||||
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| Typical solvents | typically water or alcohols at room temperature | ||||||||||||||
The Petrenko-Kritschenko reaction is a classic multicomponent name reaction[1] that is closely related to the Robinson-Schöpf tropinone synthesis, but was published 12 years earlier.
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In the original publication[2] diethyl-α-ketoglurate, a derivative of acetonedicarboxylic acid, is used in combination with ammonia and benzaldehyde. The relative stereochemistry was not elucidated in the original publication, structural analysis using x-rays or NMR was not available in these days. In the absence of ammonia or ammonium salts a 4-oxotetrahydropyran is formed[3].
In contrast to the Robinson synthesis, it does not employ dialdehydes like succinaldehyde or glutaraldehyde but simpler aldehydes like benzaldehyde. Therefore the product of the reaction is not a bicyclic structure (see tropinone and pseudopelletierine) but a 4-piperidone. The synthesis of tropinone can be seen as a variation of the Petrenko-Kritschenko reaction in which the two aldehyde functions are covalently linked in a single molecule. Apart from the Hantzsch synthesis the Petrenko-Kritschenko reaction is one of the few examples in which a symmetric pyridine precursor can be obtained in a multicomponent ring-condensation reaction followed by an oxidation. The oxidation by chromium trioxide in acetic acid leads to a symmetrically substituted 4-pyridone, decarboxylation yields the 3,5-unsubstituted derivative[2].
Acetoacetate can be used instead of diethyl-α-ketoglurate in the presence of indiumsalts [4]. The use of anilin has also been reported in the original Publication[2]. The product of this reaction shows transoid configuration of the phenyl groups at C-2 and C-6.
The reaction has been used to prepare precoccinellin, an alkaloid found in certain ladybugs[1].
When benzaldehyde is substituted with 2-pyridinecarboxaldehyde the reaction can be used to prepare precursors for bispidone-ligands[5]. Essentially this method is based on two subsequent Petrenko-Kritschenko reactions. These ligands can be used to prepare compounds containing high-valent iron, that are able to oxidize cyclohexane in the presence of hydrogen peroxide.
