Mechanism acid-catalyzed enol formation

Figure 22.1 MECHANISM Mechanism of acid-catalyzed enol formation. The protonated intermediate can lose H+, either from the oxygen atom to regenerate the kelo tautomer or from the a carbon atom to yield an enol.

Q Acid-catalyzed enol formation occurs by the usual mechanism. 

In the presence of an electrophile, tautomerization of a substrate with a C=0 double bond to its enol only takes place when catalyzed by either a Bronsted- or a Lewis acid. The proton-catalyzed mechanism is shown for the ketone — enol conversion B — iso-B (Figure 12.4), the carboxylic acid —> enol conversion A — E (Figure 12.6), the carboxylic acid bromide — enol conversion E —> G (Figure 12.7) and the carboxylic acid ester — enol conversion diethyl-malonate —> E (Figure 12.9). Each of these enol formations is a two-step process consisting of the protonation to a carboxonium ion and the latter s deprotonation. The mechanism of a Lewis acid-catalyzed enolization is illustrated in Figure 12.5, exemplified by the ketone —> enol conversion A —> iso-A. Again, a protonation to a carboxonium ion and the latter s deprotonation are involved the Lewis acid-complexed ketone acts as a proton source (see below). 

The first two steps of the Lapworth mechanism are the same as the general mechanism of acid-catalyzed enolization (Mechanism 20.5, p. 899). Formation of the enol is rate-determining. Once formed, the enol reacts rapidly with bromine in step 3 to give, after transferring a proton to water in step 4, the a-bromo ketone. 

The mechanism for formation of the cycloheptenone is exactly the same as discussed in the book. After a Diels-Alder reaction, the enol ether is hydrolyzed to the ketone by an acid-catalyzed mechanism. 

Section 17-1 we can be sure that this is related to enolization. Formation of either the enol or the enolate anion will destroy the asymmetry of the a carbon so that, even if only trace amounts of enol are present at any given time, eventually all of the compound will be racemized. However, the mechanism requires both that there be an a hydrogen and that the center of symmetry be located at this a carbon. Otherwise, acids and bases are ineffective in catalyzing racemization. 

Mechanism 22-4 Base-Catalyzed Keto-EnolTautomerism 1047 Mechanism 22-5 Acid-Catalyzed Keto-EnolTautomerism 1047 22-3 Alkylation of Enolate Ions 1050 22-4 Formation and Alkylation of Enamines 1051 22-5 Alpha Halogenation of Ketones 1054... 

The mechanism is similar to other acid-catalyzed a halogenations the enol form of the acyl bromide serves as a nucleophilic intermediate. The first step is formation of acyl bromide, which enolizes more readily than does the acid. 

Mechanism The reaction is believed to involve the formation of the intermediate methylene-ammonium salt 3.32, which condenses either with enol form of the ketone (acid catalyzes the conversion of keto form into enol form) or with the carbanion derived from the ketone (small amount of amine acting as a base and abstracts the a-hydrogen) to give the corresponding Mannich base (Scheme 3.15). 

The above mechanism for the acid-catalyzed formation of the enol accords with Lapworth s interpretation of the halogenation, but for basic catalysis some modification is necessary. The proposed mechanism involves the anion (II) as an intermediate in the formation of the enol,... 

We have seen numerous examples of acid-catalyzed dehydration of alcohols. Thus, it may seem strange that aldols can undergo dehydration in basic solution. This is another example of how the acidity of a hydrogens affects the reactivity of carbonyl compounds. As shown in Mechanism 20.2, elimination can occur by initial formation of an enolate, which then loses hydroxide to form the a,p-unsaturated aldehyde. In general, the alkenes formed by the dehydration of aldols are primarily the E stereoisomers. 

The mechanism begins with the acid-catalyzed formation of the enol. 

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. 

The mechanism of an acid-catalyzed aldol reaction involves three steps, the first two of which are preparation of the aldehyde or ketone for formation of the new carbon-carbon bond. The key step is attack of the enol of one molecule on the protonated carbonyl group of a second molecule. 

Although outside the scope of this section, the concurrent development of the Pd-catalyzed allylation of /3-ketocarboxylic acids via the formation and decomposition of allyl /3-ketocarboxylates is noteworthy (Sects. V.2.1.1 and V.2.1.2). The mechanism shown in Scheme 4, which involves (i) oxidative addition of allyl /3-ketocarboxylates, (ii) decarboxylation, and (iii) intermolecular enolate allylation was proposed and experimentally supportedUnfortunately, a-allylation with y-disubstituted allyl derivatives, such as geranyl carboxylates, proceeds in low yields, and there are some indications that the reaction may lack some specificity features, for example, stereospecificity of the allylic moiety. 

The by-product of a bromination is HBr, which is an acid and is capable of catalyzing the first part of the mechanism (enol formation). As a result, the reaction is said to be autocatalytic, that is, the reagent necessary to catalyze the reaction is produced by the reaction itself. 

The acid-catalyzed step imposes the formation of iminium salt with a strongly electrophilic C-atom of the C=N group. It reacts with propiophenone enolized under acidic conditions. This mechanism reveals the double role of acid, usually protic acid, but Lewis acids can also be used. 

In the mechanism of the Biginelli synthesis [265], the rate-determining step is the acid-catalyzed formation of an acylimine 35 from aldehyde and urea. By N-protonation (or metal-N-coordination), the imine 35 is activated (as an iminium ion) and intercepted by the P-ketoester (as enol or metal enolate) to give rise to an open-chain ureide 36, which subsequently cyclizes (via the cyclic ureide 37 and its dehydration) to afford the dihydropyrimidinone 33. Biginelli compounds of type 33 have been synthesized independently in multistep sequences [266]. 

Mechanism of enol formation under both acid-catalyzed and base-catalyzed conditions, (a) Acid catalysis involves (D) initial protonation of the carbonyl oxygen followed by ( ) removal of H from the a position, (b) Base catalysis involves (Q) initial deprotonation of the a position to give an enolate ion, followed by (0) reprotonation on oxygen. 

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