The Petrenko-Kritschenko reaction is a classic multicomponent-

name reaction A name reaction is a chemical reaction named after its discoverers or developers. Among the tens of thousands of organic reactions that are known, hundreds of such reactions are well-known enough to be named after people. Well-known examples include ...

Jie-Jack Li; "Name reactions in heterocyclic chemistry"; 2005 John Wiley & Sons; ; pp313 that is closely related to the Robinson–Schöpf

tropinone Tropinone is an alkaloid, famously synthesised in 1917 by Robert Robinson as a synthetic precursor to atropine, a scarce commodity during World War I. Tropinone and the alkaloids cocaine and atropine all share the same tropane core structure. It ...

synthesis, but was published 12 years earlier.

Classic reaction

In the original publicationP. Petrenko-Kritschenko "Über die Kondensation des Acetondicarbonsäureesters mit Aldehyden, Ammoniak und Aminen" Journal für Praktische Chemie Volume 85, Issue 1, pages 1–37, 20 May 1912; diethyl-α-ketoglurate, a derivative of

acetonedicarboxylic acid Acetonedicarboxylic acid, 3-oxoglutaric acid or β-ketoglutaric acid is a simple dicarboxylic acid. Preparation Acetonedicarboxylic acid can also be prepared by decarboxylation of citric acid in fuming sulfuric acid: : Applications Acetonedicar ...

, 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.P. Petrenko-Kritschenko "Über Tetrahydropyronverbindungen" Journal für Praktische Chemie; Volume 60, Issue 1, pages 140–158, 27 December 1899; PKreaction1

In contrast to the Robinson synthesis, it does not employ dialdehydes like

succinaldehyde Succinaldehyde or succindialdehyde is an organic compound with the formula (CH2CHO)2. Typical of other dialdehydes, succinaldehyde is highly reactive and is rarely observed as the dialdehyde. Usually, it is handled as the hydrates or methanol-de ...

glutaraldehyde Glutaraldehyde is an organic compound with the formula . The molecule consists of a five carbon chain doubly terminated with formyl (CHO) groups. It is usually used as a solution in water, and such solutions exists as a collection of hydrates, c ...

but simpler aldehydes like benzaldehyde. Therefore, the product of the reaction is not a bicyclic structure (see

and

pseudopelletierine Pseudopelletierine is the main alkaloid derived from the root-bark of the pomegranate tree (''Punica granatum''), along with at least three other alkaloids: pelletierine, isopelletierine, and methylpelletierine (C9H17ON), which yield 1.8, 0.52, 0 ...

) 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 Chromium trioxide (also known as chromium(VI) oxide or chromic anhydride) is an inorganic compound with the formula CrO3. It is the acidic anhydride of chromic acid, and is sometimes marketed under the same name. This compound is a dark-purple s ...

in acetic acid leads to a symmetrically substituted 4-pyridone, decarboxylation yields the 3,5-unsubstituted derivative.

Modern variants

Acetoacetate can be used instead of diethyl-α-ketoglurate in the presence of

indium Indium is a chemical element with the symbol In and atomic number 49. Indium is the softest metal that is not an alkali metal. It is a silvery-white metal that resembles tin in appearance. It is a post-transition metal that makes up 0.21 parts ...

salts.Clarke, Paul A.; Zaytzev, Andrey V.; Whitwood, Adrian C. "Pot, atom and step economic (PASE) synthesis of highly functionalized piperidines: a five-component condensation" Tetrahedron Letters Volume 48, Issue 30, 23 July 2007, Pages 5209–5212; The use of aniline has also been reported in the original Publication. The product of this reaction shows transoid configuration of the phenyl groups at C-2 and C-6. PKreaction3

Natural product synthesis

The reaction has been used to prepare precoccinellin, an alkaloid found in certain

ladybugs Coccinellidae () is a widespread family of small beetles ranging in size from . They are commonly known as ladybugs in North America and ladybirds in Great Britain. Some entomologists prefer the names ladybird beetles or lady beetles as they ...

Applications to coordination chemistry

When benzaldehyde is substituted with 2-pyridinecarboxaldehyde the reaction can be used to prepare precursors for bispidone-ligands.Comba, Peter; Kerscher, Marion; Merz, Michael; Müller, Vera; Pritzkow, Hans; Remenyi, Rainer; Schiek, Wolfgang; Xiong, Yun "Structural Variation in Transition-Metal Bispidine Compounds" Chemistry – A European Journal Volume 8, Issue 24, pages 5750–5760, 16 December 2002; {{doi, 10.1002/1521-3765(20021216)8:24<5750::AID-CHEM5750>3.0.CO;2-P Essentially this method is based on two subsequent Petrenko-Kritschenko reactions. These ligands can be used to prepare compounds containing

high-valent iron High-valent iron commonly denotes compounds and intermediates in which iron is found in a formal oxidation state > 3 that show a number of bonds > 6 with a coordination number ≤ 6. The term is rather uncommon for hepta-coordinate compounds of ir ...

, that are able to oxidize cyclohexane in the presence of

hydrogen peroxide Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscous than water. It is used as an oxidizer, bleaching agent, and antiseptic, usually as a dilute solution (3%� ...

References

External links

* A picture of Paul Petrenko-Kritschenko taken at the Kazan School of Chemistry in 1928 (1st row, first on the left): http://www.ksu.ru/chmku/images/30b.jpg Name reactions Ring forming reactions