Keto-enol tautomerism synthesis

Keto-enol tautomerism, 264, 842-844 Kiliani, Heinrich, 994 Kiliani-Fischer synthesis, 994-995 Kimbail, George, 216 Kinetic control, 491 Kinetics, 362... 

Another approach for the synthesis of enantiopure amino acids or amino alcohols is the enantioselective enzyme-catalyzed hydrolysis of hydantoins. As discussed above, hydantoins are very easily racemized in weak alkaline solutions via keto enol tautomerism. Sugai et al. have reported the DKR of the hydantoin prepared from DL-phenylalanine. DKR took place smoothly by the use of D-hydantoinase at a pH of 9 employing a borate buffer (Figure 4.17) [42]. 

From a synthetic point of view, the CHT-NCD equilibrium has been exploited in a total synthesis of colchicine and, more recently, in syntheses of tropones (115) and tropolones (119) from 7-halobicy-clo[4,1.0]heptenones (112) or 7-halobicyclo[4.1.0]heptane-3,4 diones (116), respectively. Keto-enol tautomerism of (112) to (113) followed by ring opening to the cycloheptatrienols (114) and loss of HX would explain the formation of the tropone (115). The tropolone (119) probably results from a similar sequence. These examples represent one of few cases that exemplify 6e retro electrocyclizations presented dius far in this review. Additional examples will be presented later in Section 6.2.4.1. 

Problem 27.5 Acrolein, CH2 CHCHO, is prepared by heating glycerol with sodium hydrogen sulfate, NaHS04. (a) Outline the likely steps in this synthesis, which involves acid-catalyzed dehydration and keto-enol tautomerization. (Hinf Which OH is easier to eliminate, a primary or a secondary ) (b) How could acrolein be converted into acrylic acid ... 

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... 

Dihydroxyimidazoles are involved in keto-enol tautomerism, and the diketo structure, which is known as hydantoin (9.42), is favored. This is the framework for many valuable compounds with anticonvulsant activity. These are nonh5 notic and are used in the treatment of epilepsy. Dilantin (9.55) is the best known of these. Its synthesis is shown in Scheme 9.29. The Strecker reaction of benzophenone with HCN gives an alpha-aminonitrile, which adds ammonia to form compound 9.54 (an amidine). The ring is then closed with phosgene or diethyl carbonate. Hydrolysis gives phenytoin (dilantin, Pfizer, Inc.). 

For example, n-p-hydroxyphenylglydne, a key intermediate in the synthesis of semisynthetic cephalosporins and penicillins, is currently manufactured on a multi-thousand ton scale. The hydantoinase-catalysed reaction is also suitable for the production of unnatural D-amino acids, although the in situ racemization of the remaining substrate via keto-enol tautomerization is generally slow. To facilitate the stereoinversion, base or hydantoin racemase of Pseudomonas and Arthrobacter strains is often used. 

Even more complicated processes occur in the case of ligands that isomerize during the formation and polymerization of MCMs. For example, methacryloylace-tone (5-methylhex-5-ene-2,4-dione), which is the initial monomer for the synthesis of dicarbonyl type chelates, is susceptible to keto-enol tautomerism (scheme 24). ... 

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. 

This is another exampie of substrate-level phosphorylation, but differs from the earlier example that involved hydrolysis of a mixed anhydride. Here, we have merely the hydrolysis of an ester, and thus a much lower release of energy. In fact, with 1,3-diphosphoglycerate, we specifically noted the difference in reactivity between the anhydride and ester groups. So how can this reaction lead to ATP synthesis The answer lies in the stability of the hydrolysis product, enolpyruvic acid. Once formed, this enol is rapidly isomerized to its keto tautomer, pyruvic acid, with the equilibrium heavily favouring the keto tautomer (see Section 10.1). The driving force for the substrate-level phosphorylation reaction is actually the position of equilibrium in the subsequent tautomerization. 

AGE2731). (Product 146 during its synthesis, unlike analog 95a, does not suffer acid hydrolysis of the N-methylanilino group after the aza-Diels-Alder reaction.) Ethynyl enol 147 is isolated in a very small 5deld the corresponding (2S)-ferf-butyldimethylsilyloxymethyl compound exists in its tautomeric 1-keto form. 

Thus, it was shown that the tautomerization may be of importance in the thermal dehalogenation of chloroaromatics14. The formation of diarylamines in this reaction can be also explained by the presence of aniline tautomers in the reaction mixtures14. One of the well-known types of aniline tautomerism is the enol-imine-keto-amine equilibrium. In effect, it is a reversible conversion of Schiff bases into enamines that is frequently employed for the synthesis of photochromic compounds, as well as of mesomorphic... 

On the basis of Betti s initial work, the Betti reaction has been extended to both primary amines and secondary amines. The resulting Betti amines have been applied as ligands or chiral auxiliaries in asymmetric synthesis. In addition, the Betti reaction has also been extended to the reaction among aldehydes, secondary amines, and compounds of active methylene moiety, such as dibenzyl ketones which can tautomerize to enols and mimic naphthol. Moreover, the reaction of aromatic aldoximes and 0-keto esters to afford isoxazolones should also be considered as an extension of the Betti reaction. 

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