Mechanism base-catalyzed enol formation

Mechanism of base-catalyzed enol formation. The intermediate enolate ion, a resonance hybrid of two forms, can be protonated either on carbon to regenerate the starting keto tautomer or on oxygen to give an enol. 

The mechanism is presumed to involve a pathway related to those proposed for other base-catalyzed reactions of isocyanoacetates with Michael acceptors. Thus base-induced formation of enolate 9 is followed by Michael addition to the nitroalkene and cyclization of nitronate 10 to furnish 11 after protonation. Loss of nitrous acid and aromatization affords pyrrole ester 12. 

The mechanism of the Fiesselmann reaction between methylthioglycolate and a,P-acetylenic esters proceeds via consecutive base-catalyzed 1,4-conjugate addition reactions to form thioacetal Enolate formation, as a result of treatment with a stronger base, causes a Dieckmann condensation to occur providing ketone 8. Elimination of methylthioglycolate and tautomerization driven by aromaticity provides the 3-hydroxy thiophene dicarboxylate 9. 

The mechanism of the base-catalyzed reaction involves equilibrium formation of the enolate ion, followed by addition of the enolate to a carbonyl group of the aldehyde or ketone. 

From the base-catalyzed degradation of D-fructose (pH 8.0), Shaw and coworkers147 identified 18 compounds, none of which was (a) isomeric with the starting material, or (b) a simple dehydration product. Among the products, the hydroxy-2-butanones and 1-hydroxy-2-propanone (acetol) were shown to participate in forming the carbo-cyclic products identified, but the mechanism of their formation was not elucidated. Several furan derivatives were isolated, but no lactic acid was isolated. In a similar study but with weak acid,41 most of the products were formed by a combination of enolization and dehydration steps, with little fragmentation. 

The mechanism of base-catalyzed dehydration of aldols involves formation of an enolate anion by removal of a proton from the C2 or alpha carbon and subsequent elimination of the hydroxyl group as hydroxide ion ... 

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. 

The supposed mechanism for Al(salen)Cl/amine catalyzed 1,4-addition involves a crucial stereo controlled formation of an intermediate octahedral Schiff base-aluminum enolate 132 as depicted in Fig. 2. 

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 Knoevenagel condensation is a base-catalyzed aldol-type reaction, and the exact mechanism depends on the substrates and the type of catalyst used. The first proposal for the mechanism was set forth by A.C.O. Hann and A. Lapworth Hann-Lapworth mechanism) In 1904." When tertiary amines are used as catalysts, the formation of a p-hydroxydlcarbonyl Intermediate is expected, which undergoes dehydration to afford the product. On the other hand, when secondary or primary amines are used as catalyst, the aldehyde and the amine condense to form an Imlnlum salt that then reacts with the enolate. Finally, a 1,2-ellmlnatlon gives rise to the desired a,p-unsaturated dicarbonyl or related compounds. The final product may undergo a Michael addition with the excess enolate to give a bis adduct. 

The mechanism of the base-catalyzed reaction involves equilibrium formation of the enolate ion, followed by addition of the enolate to the carbonyl group of the aldehyde or ketone. These reactions of aldehydes occur in dilute basic solution at or below room temperature. Under somewhat more vigorous conditions, such as higher temperature or increased base concentration, the elimination step occurs. 

FIGURE 5.2 Mechanisms for base-catalyzed and uncatalyzed enolization of monocarbonyl and dicarbonyl compounds. Enolate formation from monocarbonyl compounds was modeled using two reaction dimensions C-O proton transfer and geometry change. Dicarbonyl compounds required an additional dimension proton transfer. Based on structures in Ref. [47]. 

As described in A Word About... Water Treatment and the Chemistry of Enols/Enolates, carbonyl compounds can become halogenated by treatment with a base and a halogen source, such as Clj. As shown on page 279, base-catalyzed chlorination of acetone leads to 1,1,1-trichloroacetone. For acetone, provide a mechanism that rationalizes the formation of 1,1,1-trichloroacetone vs. chlorination on both sides of the carbonyl group. 

Draw the two possible enols that can be formed from 3-methyl-2-butanone, and show a mechanism of formation of each under base-catalyzed conditions. 

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. 

Acyclic a,a-disubstituted tin enolates 6 inevitably form as cis/trans-mixtures. Nevertheless, application of the chromium alkylation protocol with the modified salen complex 7 provides fair enantioselectivity with various alkylating agents R CH2X hke allyl bromide, benzyl bromide, allyl iodide, and ethyl iodoacetate, as outlined in Scheme 5.5. A plausible explanation is based on the assumption of a rapid cis/trans-isomerization of the tin enolates 6 through the C-bound tautomer and the postulate that one of the enolate diastereomers reacts distinctly faster than the other. The role of the additive BugSnOMe, which has a beneficial effect on the enantioselectivity, might be to catalyze the cis/trans-isomerization of the enolate. Several models have been proposed for the mechanisms of the enantioselective enolate alkylation like transmetallation of tin into a chromium enolate, formation of a stannate by iodine transfer from chromium to tin, as well as activation of the alkyl halide by chromium [5]. 

Both nucleophilic and Brpnsted acid/base catalyzed pathways previously discussed were suggested as possible relevant mechanisms for the formation of enol esters 51. From a stereochemical point of view, the two mechanisms differ mainly in that the nucleophilic pathway would involve a diastereoseleclive protonation of the chiral zwitterionic enolate 47 (Scheme 3.22), while in the Brpnsted add/base mechanism, the catalyst may be considered as a chiral proton shuttle taking part in both deprotonation of diphenylacetaldehyde and enantioselective protonation of the prochiral enolate 52 (Scheme 3.23). Although a number of experiences have been conducted to gain insights into the mechanism, no clear-cut evidence was obtained to decide between these two relevant mechanisms. 

It is not the aldehyde or ketone itself that is halogenated, but the corresponding enol or enolate ion. The purpose of the catalyst is to provide a small amount of enol or enolate. The reaction is often done without addition of acid or base, but traces of acid or base are always present, and these are enough to catalyze formation of the enol or enolate. With acid catalysis the mechanism is... 

The first step, as we have already seen (12-3), actually consists of two steps. The second step is very similar to the first step in electrophilic addition to double bonds (p. 970). There is a great deal of evidence for this mechanism (1) the rate is first order in substrate (2) bromine does not appear in the rate expression at all, ° a fact consistent with a rate-determining first step (3) the reaction rate is the same for bromination, chlorination, and iodination under the same conditions (4) the reaction shows an isotope effect and (5) the rate of the step 2-step 3 sequence has been independently measured (by starting with the enol) and found to be very fast. With basic catalysts the mechanism may be the same as that given above (since bases also catalyze formation of the enol), or the reaction may go directly through the enolate ion without formation of the enol ... 

With basic catalysts the mechanism may be the same as that given above (since bases also catalyze formation of the enol), or the reaction may go directly through the enolate ion without formation of the enol ... 

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