Keto—enol tautomerism mechanism

The aldehyde or ketone is called the keto form and the keto enol equilibration referred to as keto-enol isomerism or keto-enol tautomerism Tautomers are constitu tional isomers that equilibrate by migration of an atom or group and their equilibration IS called tautomerism The mechanism of keto-enol isomerism involves the sequence of proton transfers shown m Figure 9 6... 

The mixture of quinone methides initially formed by combination of the coniferyl radicals in their various mcsomeric forms, i.e. (I), (III), (V), (IX) and others, can be detected by means of their characteristic spectrum with a maximum at about 312 mp (52) the haU-hfe of the mixture in 70 % aqueous dioxan is 1 hour. Those quinone methides that can rearomatize by keto-enol tautomerism, e.g. (IX), or intramolecular additions, e.g. (I) or (III) may become stabilized faster than those of type (V) which rely on addition of a foreign molecule. The quinone methides that rearomatize intramolecularly appear to react exclusively in this way, probably by a concerted mechanism that represents collapse of the activated transition state. 

The more complex structures are inappropriate for consideration here, but the two compounds orsellinic acid and phloracetophenone exemplify nicely the enolate anion mechanisms we have been considering, as well as the concept of keto-enol tautomerism. 

Problem 17.3 Compare the mechanisms for (a) base-catalyzed and (b) acid-catalyzed keto-enol tautomerism. 

Pron et al.569) looked at polyacetylene treated from the gas phase with H2S04 which leads to HS04 counter-ions. They found that the conductivity drops in air with the appearance of C=O bands in the ir, although the rate of decay is much lower than would be expected for undoped samples. The polymer was more rapidly degraded by exposure to water but could be redoped with further acid treatment. Pron et al.570) have also reported hydrolytic instability in polyacetylene with A1C14 as the counterion. In both cases the proposed mechanism involves addition of OH" to the chain and keto-enol tautomerism to form carbonyl groups. 

Fig. Acid-catalysed mechanism for keto-enol tautomerism.

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 ... 

Under basic conditions, the keto-enol tautomerism operates by a different mechanism than it does in acid. In base, the proton is first removed from its old position in the OH group, and then replaced on carbon. In acid, the proton was first added on carbon, and then removed from the hydroxyl group. 

Compare the base-catalyzed and acid-catalyzed mechanisms shown for keto-enol tautomerism. In base, the proton is removed from the a carbon, then replaced on oxygen. In acid, oxygen is protonated first, then the a carbon is deprotonated. Most proton-transfer mechanisms work this way. In base, the proton is removed from the old location, then replaced at the new location. In acid, protonation occurs at the new location, followed by deprotonation at the old location. 

In the proteins and nucleic acids the configurational mechanism has to be invoked to explain any hydrogen-bond disorder involving )N-H or NH groups where there is no orientational flexibility. This is shown in the two examples, below (the second describing amino/imino and keto/enol tautomeric states) ... 

Figure 12.1 Reaction mechanism of the 5-monosubstituted hydantoins keto-enol tautomerism under alkaline conditions.

We shall take up first the behavior of ketones toward the halogens, and see evidence that carbanions do indeed exist at the same time, we shall see an elegant example of the application of kinetics, stereochemistry, and isotopic tracers to the understanding of reaction mechanisms. And while we are at it, we shall see something of the role that keto-enol tautomerism plays in the chemistry of carbonyl compounds. 

Butlerov found out that in alkaline medium (calcium hydroxide), formaldehyde HCHO polymerizes to form about 20 different sugars as racemic mixtures, Butlerov 1861. The reaction requires a divalent metal ion. Breslow found a detailed mechanism of reaction that explains the reaction products, (Breslow 1959). He found that glycol-aldehyde is the first product that is subsequently converted into glyceral-dehyde (a triose), di-hydroxy-acetone, and then into various other sugars, tetrose, pentose, and hexose. The formose reaction advances in an autocatalytic way in which the reaction product is itself the catalyst for that reaction with a long induction period. The intermediary steps proceed via aldol and retro-aldol condensations and, in addition, keto-enol tautomerizations. It remains unexplained how the phosphorylation of 3-glyceraldehyde leads to glycral-3-phosphate (Fig. 3.6). Future work should study whether or not ribozymes exist that can carry out this reaction in a stereo-specific way. 

Crabtree and Kemp proposed a keto-enol tautomerism as an extension of the mechanism involving vibration at a hydrogen bond [5]. Heat is released in the reverse step in Figure 4.4. This mechanism may supplement the primary mechanism for energy dissipation in UV absorbers. 

DHFR catalyzes the reduction of 7,8-dihydrofolate (H2F) to 5,6,7,8-tetrahydrofolate (H4F) using nicotinamide adenine dinucleotide phosphate (NADPH) as a cofactor (Fig. 17.1). Specifically, the pro-R hydride of NADPH is transferred stereospecifi-cally to the C6 of the pterin nucleus with concurrent protonation at the N5 position [1]. Structural studies of DHFR bound with substrates or substrate analogs have revealed the location and orientation of H2F, NADPH and the mechanistically important side chains [2]. Proper alignment of H2F and NADPH is crucial in enhancing the rate of the chemical step (hydride transfer). Ab initio, mixed quantum mechanical/molecular mechanical (QM/MM), and molecular dynamics computational studies have modeled the hydride transfer process and have deduced optimal geometries for the reaction [3-6]. The optimal C-C distance between the C4 of NADPH and C6 of H2F was calculated to be 2.7A [5, 6], which is significantly smaller than the initial distance of 3.34 A inferred from X-ray crystallography [2]. One proposed chemical mechanism involves a keto-enol tautomerization (Fig. 

Figure 17.2. The keto/enol tautomerization that plays a role in one of the proposed chemical mechanisms for hydride transfer.

Several mechanisms have been proposed to explain the variations of the bioluminescence color for native and mutant luciferases. According to White at al1 changes in bioluminescence spectra are the result of keto-enol tautomerization of oxyluciferin (LO). The efficiency of this process depends on a correct location of the B, and B2 bases in proximity of the thiazole ring for effective transformation of the ketone form of LO (L0=0) to the enol (LO-OH) which can interact with the B3 base to form enolate-ion (LO-O ). When the Bi base is absent or protonated (e g. at pH < 6.0) bioluminescence of the L0=0 will be observed with Xmax in the red region of the spectrum. At intermediate pH all forms L0=0, LO-OH and (LO-O ) - will be observed in the bioluminescence spectra.2... 

Keto-enol tautomerism also plays a part in the mechanism of catalytic hydrogenation of a, 3-unsaturated carbonyls leading to the two monomeric products (see Scheme 1). ... 

How would you prepare the soluble Phenytoin Sodium from Phenytoin Explain the mechanism of reaction involving keto-enol tautomerism. 

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