Tautomerism formation of enols by proton transfer

An enol is exactly what the name implies an ene-ol. It has a C=C double bond and an OH group joined directly to it. Simple carbonyl compounds have enols too—in the margin is the enol of cyclohexanone (just dimedone without the extras). 

In the case of dimedone, the enol must be formed by a transfer of a proton from the central CH2 group of the keto form to one of the OH groups. 

Notice that there is no change in pH—a proton is lost from carbon and gained on oxygen. The reaction is known as enolization as it is the conversion of a carbonyl compound into its enol. It is a strange reaction in which little happens. The product is almost the same as the starting 

This is because the combination of a C=C double bond and an 0-H single bond is (slightly) less stable than the combination of a C 0 double bond and a C-H single bond. The balance between the bond energies is quite fine. On the one hand, the O-H bond in the enol is a stronger bond than the C-H bond in the ketone but, on the other hand, the C=0 bond of the ketone is much more stable than the C=C bond of the enol. Here are some average values for these bonds.  

Typical amounts of enols in solution are about one part in 10 for normal ketones. So why do we think they are important Because enolization is just a proton transfer, it is occurring all the time even though we cannot detect the minute proportion of the enol Let us look at the evidence for this statement. 

Any reaction that simply involves the intramolecular transfer of a proton, and nothing else, is called a tautomerism. Here are two other examples. 

This sort of chemistry was discussed in Chapter 8, where the acidity and basicity of atoms were the prime considerations. In the first case the two tautomers are the same and so the equilibrium constant must be exactly 1 (the mixture must be exactly 50 50). In the second case (imidazole-containing compounds appear on p. 178) the equilibrium will lie on one side or the other depending on the nature of R. 

When we were looking at the spectra of carhonyf compounds in Chapters 13 and 18 we saw no signs of enols in IR or NMR spectra. Dimedone is exceptional (we wiU discuss why later) and while any carbonyl compound with protons adjacent to the carhonyl group can enolize, simpler carbonyl compounds like cyclohexanone or acetone have only a trace of enol present under ordinary conditions. The equUihrium Ues well over towards the keto form (the equilibrium constant K for acetone enolization is about 10 ). 

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A mechanism for the piperazine-catalyzed formation of 4//-chromenes is complex cascade of reactions, starting with piperazine acting as a base which activates malononitrile, promoting Knoevenagel condensation, and also formation of an enamine, followed by Michael condensation, proton transfer, intermolecular cycliza-tion via a nucleophilic addition of the enolate oxygen to the nitrile group (hetero-Thorpe-Ziegler), and finally hydrolysis and tautomerization. 

It is well established that the reaction of carbenoids with At-alkylindoles delivers zwitterionic intermediates. The reason why this scenario is favored can be ascribed to the fact that the positive charge of the intermediate is stabilized by the electron-rich indole while the negative charge is stabilized by the carbenoid component. In other words, the site of C3 is highly reactive in metal carbenoid insertion reactions. In 2010, Lian and Davies described such a process in their seminal work on Rh-catalyzed [3 + 2] annulation of indoles. In the presence of 1,2-dimethylindole 53, Rh2(S-DOSP)4 induced the decomposition of methyl a-phenyl-a-diazoacetate la and C—H bond insertion of indole, providing the C3 functionalization product 54 in 95% yield but negligible asymmetric induction (<5% ee). It is proposed that the poor chiral induction in the formation of C—H bond insertion product 54 can be attributed to the rapid proton transfer from the zwitterionic intermediate A to the achiral enol B, which can further tautomerize into the observed C—H bond insertion product 54 (Scheme 1.18). 

When 1-hexyne is treated with a catalytic amount of sulfuric acid in an aqueous solvent, initial reaction with the acid gives the expected secondary vinyl carbocation 103, and the most readily available nucleophile in this reaction is water (from the aqueous solvent). Nucleophilic addition of water to 103 leads to the vinyl oxonium ion 104. Loss of a proton in an acid-base reaction (the water solvent is the base) generates a product (105) where the OH unit is attached to the C=C unit, an enol. Enols are unstable and an internal proton transfer converts enols to a carbonyl derivative, an aldehyde, or a ketone. This process is called keto-enol tautomerization and, in this case, the keto form of 105 is the ketone 2-hexanone (106). (Enols are discussed in more detail in Chapter 18, Section 18.5.) Note that the oxygen of the OH resides on the secondary carbon due to preferential formation of the more stable secondary carbocation followed by reaction with water, and tautomerization places the carbonyl oxygen on that same carbon, so the product is a ketone. When a disubstituted alkyne reacts with water and an acid catalyst, the intermediate secondary vinyl cations are of equal stability and a mixture of isomeric enols is expected each will tautomerize, so a mixture of isomeric ketones will form. 

Hydrolysis of a cyano group in aqueous base involves initial formation of the anion of an imidic acid, which, after proton transfer from water, undergoes keto-enol tautomerism to give an amide. The amide is then hydrolyzed by aqueous base, as we saw earlier, to the carboxylate anion and ammonia. 

The solid-state proton transfer and keto - enol tautomeric transformations were accomplished by heating or by mechanochemical treatment (Scheme 13.10). The thermal transition was monitored by in situ time-resolved PXRD and IR methods. The in situ monitoring revealed that the keto-enol transition proceeded through the formation of metastable enol polymorph, which finally converted to the thermodynamically stable form of enol polymorph. 

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