Tautomerization acid-catalyzed

Repeating this process several times replaces all hydrogen atoms with deuterium atoms. The first line represents the mechanism for acid-catalyzed tautomerization of a ketone. 

Intermediate 4-66 undergoes acid-catalyzed tautomerization to give the product. 

In the process shown in Eq. (11), N-unsubstituted a-amino esters are employed instead of N-substituted derivatives. The reaction of methyl gly-cinate with carbonyl compounds produces iminium hydroxide intermediates, which are then dehydrated generating N-unsubstituted azomethine ylides 85 (86CL1271 87BCJ4067). Therefore, this method is closely related to the tautomerization route, especially to the acid-catalyzed tautomerization (Section II,C). Benzaldehyde, phenylglyoxal, 2-methylpropanal, and cyclohexanone can be used as carbonyl compounds the corresponding azomethine ylides are trapped with N-methylmaleimide in excellent yields. 

After the first /1-hydride elimination, it is reasonable simply to allow the enol to dissociate from Pd and then undergo acid-catalyzed tautomerization. 

Polyethers consisting of alkoxypyrimidine units undergo an acid-catalyzed tautomeric change from the alkoxypyrimidine to pyrimidone, releasing dienes (Fig. 112) [345]. 

This reaction was first reported by Fischer and Jourdan in 1883. It is a synthesis of indole derivatives by the treatment of aryl hydrazones coupled from aromatic hydrazines and ketones or aldehydes with either a mineral or Lewis acid. Therefore, it is generally known as the Fischer indole synthesis. In addition, it is also referred to as Fischer cyclization, Fischer indole cyclization, Fischer indole reaction, Fischer indolization, Fischer reaction, and Fischer indole annulation. Although the mechanism has been extensively studied, the one formulated by Robinson and Robinson is now generally accepted. It involves the following steps (a) initial acid-catalyzed tautomerization of an aromatic hydrazone to an ene-hydrazine, b) a [3,3]-sigmatropic rearrangement of ene-hydrazine to a M-imine intermediate, (c) re-aromatization to aniline, d) intramolecular nucleophilic attack to form aminal, and (e) extrusion of an ammonia to afford the indole. 

A plausible overall mechanism for the reactions leading to 29 is shown in Scheme 18.5. 2-Methylpropanal (26) first undergoes acid-catalyzed tautomerization to its enol form 30, in which the adelocalized cation 31, which is more electrophilic than the unprotonated form. Because 30 is a weak nucleophile relative to an enolate ion, the formation of 31 facilitates the next stage of the reaction, which results in a new carbon-carbon bond between 26 and 27 to give the enol 32. The boldfaced atoms in structure 32 show that the a-C-H bond of 26 has added in a conjugate-, or 1,4-, manner to 27. Acid-catalyzed tautomerization of 32 leads to the thermodynamically more stable keto form 28. 

Acid-catalyzed tautomerization of an aldehyde (see Chapter 11) gives an enol as the starting point. Protonation of the alcohol attached to the (i-carbon makes it a good leaving group. In the second step, a lone pair on the enol OH is used as an electron source to expel the water. Deprotonation of the carbonyl yields the final product in a last step. 

Let s examine the electron pushing for an acid-catalyzed tautomerization (Scheme 11.1). Protonation of the carbonyl oxygen of a ketone or aldehyde renders the a-hydrogens even more acidic than normal. This leads to facile deprotonation and the formation of an enol. 

In the first step of acid-catalyzed tautomerization of the keto form, hydronium ion proton-ates the carbonyl oxygen atom. Then, water removes the a-hydrogen atom to give the enol. Each of the reactions is reversible, so the acid-catalyzed conversion of the enol into the keto form occurs by the reverse of each step of the mechanism. 

Use curved arrows to show the mechanism of an acid-catalyzed tautomerization. 

Figure 12.18 Sketch of possible mechanism for the acid-catalyzed tautomerization in E/Z switching process of 1,2,3-tricarbonyl-2-arylhydrazones (R R ).

When drawing a mechanism for the acid-catalyzed tautomerization of an enol, the first step is protonation. Students sometimes get confused about where to place the proton during this first step. Indeed, there are two possible locations where protonation could occur (a lone pair or the n bond) ... 

Whenever possible, avoid the formation of high-energy intermediates that are unlikely to form. This is a general mle that should be followed whenever you are drawing a mechanism (exceptions are rare). The correct first step for acid-catalyzed tautomerization of an enol is protonation of the 71 bond to generate a resonance-stabilized cation ... 

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