Pyrylium cation and pyrones

The pyrylium cation is isoelectronic with pyridine it has the same number of electrons and, therefore, we also have aromaticity. Oxygen is normally divalent and carries two lone pairs. If we insert oxygen into the benzene ring structure, then it follows that, by having one electron in a p orbital contributing to the aromatic sextet, there is a lone pair in an sp orbital, 

Flavonoids are natural phenolic systems containing pyrylium and pyrone rings, and provide the most prominent examples. We have met some of these systems under antioxidants (see Box 9.2). Coumarins contain a 2-pyrone system. Note that all of these compounds are fused to a benzene ring and are strictly benzopyran or benzopyrylium systems. 

Warfarin provides us with a slightly incongruous state of affairs it is used as a drug and also as a rat poison. It was developed from a natural product, dicoumarol, and provides us with a nice example of how pyrone chemistry resembles that of conjugated lactones rather than aromatic systems. 

Many plants produce coumarins coumarin itself is found in sweet clover and contributes to the smell of new-mown hay. However, if sweet clover is allowed to ferment, oxidative processes initiated by the microorganisms lead to the formation of 4-hydroxycoumarin rather than coumarin. 4-Hydroxycoumarin then reacts with formaldehyde, also produced via the microbial degradative reactions, and provides dicoumarol. 

4-Hydroxycoumarin can be considered as an enol tautomer of a 1,3-dicarbonyl compound conjugation with the aromatic ring favours the enol tautomer. This now exposes its potential as a nucleophile. Whilst we may begin to consider enolate anion chemistry, no strong base is required and we may formulate a mechanism in which the enol acts as the nucleophile, in a simple aldol reaction with formaldehyde. Dehydration follows and produces an unsaturated ketone, which then becomes the electrophile in a Michael reaction (see Section 10.10). The nucleophile is a second molecule of 4-hydroxycoumarin. 

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