Tautomerization in acid

The initial product has a hydroxy group attached to a carbon-carbon double bond. Compounds such as this are called enols (ene + ol) and are very labile—they cannot usually be isolated. Enols such as this spontaneously rearrange to the more stable ketone isomer. The ketone and the enol are termed tautomers. This reaction, which simply involves the movement of a proton and a double bond, is called a keto—enol tautomerization and is usually very fast. In most cases the ketone is much more stable, and the amount of enol present at equilibrium is not detectable by most methods. The mechanism for this tautomerization in acid is shown in Figure 11.6. The mercury-catalyzed hydration of alkynes is a good method for the preparation of ketones, as shown in the following example ... 

Obviously optically active furanones are equilibrated by keto-enol tautomerism in acidic media. Thus, enantioselective analysis cannot be applied to assign the origin of chiral 3 [2H]-furanones [62]. This can only be expected by stable isotope measurements [104, 105]. 

Mechanism 11.3 Tautomerization in Acid Step [1] Protonation of the enol double bond... 

Tautomerization in Acid 883 Tautomerization in Base 884 Acid-Catalyzed Halogenation at the a Carbon 893 Halogenation at the a Carbon in Base 894 The Haloform Reaction 895... 

Clearly, in the case of (66) two amide tautomers (72) and (73) are possible, but if both hydroxyl protons tautomerize to the nitrogen atoms one amide bond then becomes formally cross-conjugated and its normal resonance stabilization is not developed (c/. 74). Indeed, part of the driving force for the reactions may come from this feature, since once the cycloaddition (of 72 or 73) has occurred the double bond shift results in an intermediate imidic acid which should rapidly tautomerize. In addition, literature precedent suggests that betaines such as (74) may also be present and clearly this opens avenues for alternative mechanistic pathways. 

In this initial section the reactivities of the major types of azole aromatic rings are briefly considered in comparison with those which would be expected on the basis of electronic theory, and the reactions of these heteroaromatic systems are compared among themselves and with similar reactions of aliphatic and benzenoid compounds. Later in this chapter all the reactions are reconsidered in more detail. It is postulated that the reactions of azoles can only be rationalized and understood with reference to the complex tautomeric and acid-base equilibria shown by these systems. Tautomeric equilibria are discussed in Chapter 4.01. Acid-base equilibria are considered in Section 4.02.1.3 of the present chapter. 

There is very little published information on the UV spectra of 1,2-benzisothiazoles, though more data are available on the 2,1-isomers. The spectra are complex with as many as six maxima above 200 nm. Representative wavelengths of maxima are collected in Table 12. In all cases the most intense bands (e > 15 000) are those at short wavelengths, but all the bands indicated in the table have molar absorptivities greater than 4000, except those of 3-amino-2,l-benzisothiazole. Saccharin absorbs weakly at 350 nm and 277 nm, with intense bands below 230 nm (ethanol solvent) (82UP41700>. It exists as the anion except in acid solutions. The UV spectra of cations formed from 3-amino-2,l-benzisothiazole are discussed in (69CB1961>. Further applications of UV spectroscopy in studying tautomeric... 

Many of the cyclic and chain dichloro derivatives (NPCl2)n can be hydrolysed to n-basic acids and the lower members form well-defined salts frequently in the tautomeric metaphosphimic-acid form, e.g. ... 

The hydrochloride of (3) holds water rather tenaciously, and the infrared spectrum indicates that the water is covalently bound. Mild oxidation of the cation (3) gives 4-hydroxyquinazoline in high yield and ring-chain tautomerism is excluded on the grounds that quinazo-line does not give a positive aldehyde test in acid solution, 2-Methyl-quinazoline also has an anomalous cationic spectrum and a high basic strength (see Table I), but 2,4-dimethylquinazoline is normal in both these respects, which supports the view that abnormal cation formation entails attack on an unsubstituted 4-position. ... 

The tautomeric equilibrium 151 152 has been discussed by Cromwell and David.Ultraviolet spectral data indicate that 151 predominates in neutral aqueous solution, and infrared data are in essential agreement. It was further concluded that in acid solution the equilibrium favors 152, but no ionization constants were reported,... 

Similar considerations apply to nitrogen-containing heterocycles carrying acidic groups, for example 2-hydroxypteridine, but the situation is further complicated by lactam-lactim tautomerism in the neutral species. Thus, hydroxypteridines exist predominantly as lactams, such as 6, in dynamic equilibrium with small amounts of lactims, such as 7. There is, in consequence, a decrease in the aromatic... 

A possible side reaction in A-acyliminium chemistry is caused by deprotonation, giving rise to the formation of an enamide. Though this tautomerization is in principle reversible in acid media, this is not always the case. The enamide may react as a nucleophile with the /V-acyliminium ion still present, to produce dimers14. 

Scheme 17. Importance of Tautomerism in Mispairing of Nucleic Acid Bases...

Nor can there be any question of real tautomerism in the case of phenol. In its chemical properties phenol resembles the aliphatic enols in all respects. We need only recall the agreement in the acid character, the production of colour with ferric chloride, and the reactions with halogens, nitrous acid, and aromatic diazo-compounds (coupling), caused by the activity of the double bond and proceeding in the same way in phenols and aliphatic enols. The enol nature of phenol provides valuable support for the conception of the constitution of benzene as expressed in the Kekule-Thiele formula, since it is an expression of the tendency of the ring to maintain the aromatic state of lowest energy. In this connexion the hypothetical keto-form of phenol (A)—not yet obtained—would be of interest in comparison with... 

The reaction of metal ion M"+ with the keto, enol tautomeric mixture of acetylacetone (acacH) in acidic aqueous solution has been treated by a similar approach to that outlined above (see Prob. 16). 

The tautomeric nitronic acids of secondary nitroalkanes or their nitronate salts react with nitrous acid or alkali metal nitrites to yield pseudonitroles.These pseudonitroles are often isolated as their colourless dimers (78b) but are deep blue in monomeric form (78a). Primary nitroalkanes also form pseudonitroles (80b) but these rapidly isomerise to the nitrolic acid (80a).Reactions are commonly conducted by slowly acidifying a mixture containing the nitronate salt and the metal nitrite, during which, the nitronic acid reacts with the nitrite anion. These reactions, first discovered by Meyer, have been used to prepare 2-nitroso-2-nitropropane (78a) and acetonitrolic acid (80a) from 2-nitropropane (76) and nitroethane (22) respectively. ... 

In acid solution the half-wave potentials for these processes are pH dependent. The overall reaction involves two electrons and is irreversible. Bond cleavage is believed to lead to the enol as shown in Scheme 5.4. Where, as with acetophenone, the ketone product is electroactive at more negative potentials, the wave height for ketone reduction is less than expected and is limited by the rate of enol to ketone tautomerism. This is because the enol is not electroactive. 

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