We started this chapter by looking at a molecule that contained about 33% enol in solution— dimedone (shown on the right). In fact, this is just one example of the class of 1,3-dicarbonyl compounds (also called β-dicarbonyl), many of which contain substantial amounts of enol and may even be completely enolized in polar solvents. We need now to examine why these enols are so stable. The main reason is that this unique (1,3) arrangement of the two carbonyl groups leads to enols that are conjugated—rather like a carboxylic acid.

Look back at the NMR spectrum of dimedone (p. 450) and you’ll see that the two CH2 groups within the ring seem to be the same, although they are different (a and b)—even the delocalization we have just proposed does not make them equivalent. This must mean that the enol is in rapid equilibrium with another identical enol. This is not delocalization—a proton is moving—so it is tautomerism.

Once again, this is very like the situation in a carboxylic acid. The two enols equilibrate (tautomerize) so fast in CDCl₃ solution that the NMR spectrometer records an ‘averaged’ spec trum. By contrast, equilibration between the enol and keto forms is sufficiently slow that the NMR spectrometer records separate signals for the keto and enol forms. Other 1,3-dicarbonyl compounds also exist largely in the enol form. In some examples there is an additional stabilizing factor, intramolecular hydrogen bonding. Acetylacetone (propane-2,4-dione) has a symmetrical enol stabilized by conjugation. The enol form is also stabilized by a very favourable intramolecular hydrogen bond in a six-membered ring.

The hydrogen-bonded enol structure looks unsymmetrical, but in fact, as with dimedone, the two identical enol structures interconvert rapidly by proton transfer, that is, by tautomerism. The 1,3-dicarbonyl compound need not be symmetrical, and if it is not then two different enol forms will interconvert by proton transfer. Below is a cyclic keto-aldehyde that exists entirely as a pair of rapidly equilibrating enols. The proportions of the three species can be measured by NMR: there is <1 % keto-aldehyde, 76% of the fi rst enol, and 24% of the second.

More examples of stable enols

Pfizer’s anti-inflammatory drug ‘Feldene’ (used to treat arthritis) is a stable enol based on a 1,3-dicarbonyl compound. It also contains amide and sulfonamide groups but you should be able to pick out the enol part.

Stable enols occur in nature too. Leptospermone is a herbicide produced by Callistemon citrinus, the bottle-brush plant, to keep down competitors, and it has been used commercially as ‘Callisto’ to protect maize. It is a tetraketone, but exists entirely as a mixture of tautomeric enols. Note that the carbonyl group in orange is unable to form an enol: it has no α hydrogens. Vitamin C has a five-membered ring containing two carbonyl groups but normally exists as a very conjugated ene-diol.

We can show the delocalization and explain why vitamin C is called ascorbic acid at the same time. The green enol proton is acidic because the anion is delocalized over the 1,3-dicarbonyl system.

The ultimate in stable enols has to be the Ph-enol. Aromatic alcohols, or phenols, which prefer the substantial advantage of aromaticity to the slight advantage of a C=O over a C=C double bond. They exist entirely in the phenol form. Like ascorbic acid, phenol is also quite acidic (pKa 10)—it used to be called carbolic acid.

مواضيع ذات صلة

The Robinson annelation

Intramolecular aldol reactions

How to control aldol reactions of aldehydes

How to control aldol reactions of esters

Specifi c enol equivalents from 1,3-dicarbonyl compounds

Conjugated Wittig reagents as specific enol equivalents

Silyl enol ethers in aldol reactions

Lithium enolates in aldol reactions

The Mannich reaction

Base-promoted halogenation

Halogenation

Racemization