Acidic conditions keto-enol tautomerism

Aldol condensations also take place under acidic conditions. The enol serves as a weak nucleophile to attack an activated (protonated) carbonyl group. As an example, consider the acid-catalyzed aldol condensation of acetaldehyde. The first step is formation of the enol by the acid-catalyzed keto-enol tautomerism, as discussed earlier. The enol attacks the protonated carbonyl of another acetaldehyde molecule. Loss of the enol proton gives the aldol product. 

The colour of curcumin varies with the pH of the medium. Under acid conditions a bright yellow is obtained but under alkaline conditions a reddish brown hue is obtained. This colour shift occurs because curcumin undergoes keto-enol tautomerism. 

A mechanistic study of acetophenone keto-enol tautomerism has been reported, and intramolecular and external factors determining the enol-enol equilibria in the cw-enol forms of 1,3-dicarbonyl compounds have been analysed. The effects of substituents, solvents, concentration, and temperature on the tautomerization of ethyl 3-oxobutyrate and its 2-alkyl derivatives have been studied, and the keto-enol tautomerism of mono-substituted phenylpyruvic acids has been investigated. Equilibrium constants have been measured for the keto-enol tautomers of 2-, 3- and 4-phenylacetylpyridines in aqueous solution. A procedure has been developed for the acylation of phosphoryl- and thiophosphoryl-acetonitriles under phase-transfer catalysis conditions, and the keto-enol tautomerism of the resulting phosphoryl(thiophosphoryl)-substituted acylacetonitriles has been studied. The equilibrium (388) (389) has been catalysed by acid, base and by iron(III). Whereas... 

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. 

Equilibrium favors the keto form largely because a C=0 is much stronger than a C=C. Tautomerization, the process of converting one tautomer into another, is catalyzed by both acid and base. Under the strongly acidic conditions of hydration, tautomerization of the enol to the keto form occurs rapidly by a two-step process protonation, followed by deprotonation as shown in Mechanism 11.3. 

Carbonyl (or keto) compounds are interconvertible with their corresponding enols. This rapid interconversion of structural isomers under ordinary conditions is known as tautomerism. Keto-enol tautomerism is catalysed by acids or bases. 

It is also possible to induce aldol condensation reactions under acidic conditions. When 137 was treated with tosic acid in hot benzene (40-50°C), the normal keto-enol tautomerism equilibrium was shifted to favor enol 138. The enol attacked the carbonyl on the pyridone in an intramolecular aldol cyclization, producing aldol 139. Elimination of water under the reaction conditions gave an 84% yield of 140 in Comins synthesis... 

STEP 1 Keto-enol tautomerism (Section 12.8A). A small amount of enol is formed under acid-catalyzed conditions ... 

It also has become clear that the protons of the amino and imino groups of the base derivatives can exchange directly in non-aqueous atomosphere, if appropriate conditions are satisfied. Although the experiment were carried out on the monomer systems, there is no reason to deny the proton exchange in interior of nucleic acids. The exchange is possibly due to the presence of the keto-enol tautomerism, and we may estimate the frequency of tautomerism from the present date. 

The mechanism of a keto-enol tautomerization has two steps (1) protonate and then (2) deprotonate. To draw this mechanism, it is essential to remember where to protonate in the first step. There are two places where protonation could possibly occur the OH group or the double bond. In fact, under these conditions, both sites are reversibly protonated (in acidic conditions, protons are transferred back and forth, wherever possible). In order to choose where to protonate, let s carefully consider the positions of the protons involved in this transformation ... 

We will now explore a mechanism for keto-enol tautomerism. We said that compounds will tau-tomerize in the presence of either add or base, so we will need to explore two mechanisms one under acidic conditions, and one under basic conditions. 

Know how to recognize or draw the keto and enol forms of a molecule, and know the mechanism of a keto-enol tautomerization under acid- and base-catalyzed conditions. 

Hydantoinase process, outlined in Fig. 1, includes two hydrolases—hydantoin-hydrolyzing enzyme (hydantoinase) and AT-carbamoyl amino acid-hydrolyzing enzyme (carbamoylase)—and is one of the most efficient and versatile methods for the production of optically active a-amino acids. DL-5-Monosubstituted hydantoins, which are used as common precursors for the chemical synthesis of DL-a-amino acids [1], are the starting material of this enzymatic process. Keto-enol tautomerism is a typical feature of the hydantoin structure. Under neutral conditions, the keto form is dominant in alkaline solution, enolization between the 4 and 5 positions can occur, as has been concluded from the fact that optically pure hydantoins readily racemize. This feature is of practical relevance for the complete conversion of racemic hydantoin derivatives to optically pure L- or D-a-amino acids without any chemical racemization step. A variety of hydantoinase and carbamoylase with different stereospecificity were found. They are D-specific hydantoinase (D-hydantoinase), L-specific hydantoinase (L-hydantoinase), none-specific hydantoinase (DL-hydantoinase), D-specific carbamoylase (D-carbamoylase), and L-specific carbamoylase (L-carbamoylase). With the combination of these enzymes, optically pure amino acids are obtained from DL-5-monosubstituted hydantoins (Fig. 2). The wide substrate range of hydantoinases and carbamoylases also gives generality to the hydantoinase process. 

Step 2 Formation of the cis-fused 5,6 ring is thermodynamically preferred. The acidic conditions lead to the equilibration (epimerization) of one of the bridgehead positions via enol-keto tautomerization due to the acidity of the y-hydrogen, activated by the enone and ester groups. 

Also termed ethyl acetoacetate, or CH3COCH2COOC2-H5. As an ester, it can be hydrolyzed under certain conditions to acetoacetic acid (CH3COCH2COOH) as a ketone, it reacts with reagents for the carbonyl (C = O) group. Peculiarly, it also behaves like a hydroxyl (OH-) compound. It is the prototype of the phenomenon of tautomerism, and its isomeric forms are termed the keto and the enol forms. 

The tautomerism is acid/base catalyzed and its rate controls the height of the more negative wave. The second reduction in the case R = phenyl can be identified with acetophenone but at a concentration determined by the rate of enolization to produce the keto form which is electroactive in the protonated condition. 

Decarboxylation, or loss of CO2, is not a typical reaction of carboxylic acids under ordinary conditions. However, j8-ketoacids are unusually prone to decarboxylation for two reasons. First, the Lewis basic oxygen of the 3-keto function is ideally positioned to bond with the carboxy hydrogen by means of a cyclic six-atom transition state. Second, this transition state has aromatic character (Section 15-3), because three electron pairs shift around the cyclic six-atom array. The species formed in decarboxylation are CO2 and an enol, which tautomerizes rapidly to the final ketone product. 

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