Enolate ions formation

Enolate ion formation (Section 18.6) An a hydrogen of an aldehyde or a ketone is more acidic than most other protons bound to carbon. Aldehydes and ketones are weak acids, with pK s in the 16 to 20 range. Their enhanced acidity is due to the electron-withdrawing effect of the carbonyl group and the resonance stabilization of the enolate anion. 

Acidity of Alpha Hydrogen Atoms Enolate Ion Formation... 

Figure 22.5 Mechanism of enolate ion formation by abstraction of an a proton from a carbonyl compound. The enolate ion is stabilized by resonance, and the negative charge (red) is shared by the oxygen and the a carbon atom, as indicated by the electrostatic potential map.

Because carbonyl compounds are only weakly acidic, a strong base is needed for enolate ion formation. If an alkoxide such as sodium ethoxide is used as base, deprotonation takes place only to the extent of about 0. l% because acetone is a weaker acid than ethanol (pKa - 16). If, however, a more powerful base such as sodium hydride (NaH) or lithium diisopropylamide ILiNO -CjHy ] is used, a carbonyl compound can be completely converted into its enolate ion. Lithium diisopropylamide (LDA), which is easily prepared by reaction of the strong base butyllithium with diisopropylamine, is widely used in the laboratory as a base for preparing enolate ions from carbonyl compounds. 

As an example of enolate-ion reactivity, aldehydes and ketones undergo base-promoted o halogenation. Even relatively weak bases such as hydroxide ion are effective for halogenation because it s not necessary to convert the ketone completely into its enolate ion. As soon as a small amount of enolate is generated, it reacts immediately with the halogen, removing it from the reaction and driving the equilibrium for further enolate ion formation. 

The three-step sequence of 0) enolate ion formation, (2) alkylation, and (3) hydrolvsis/decarboxylation is applicable to all /Tketo esters with acidic a hydrogens, not just to acetoacetic ester itself. For example, cyclic /3-keto esters such as ethyl 2-oxocycIohexanecarboxylate can be alkylated and decarboxy-lated to give 2-substituted cyclohexanones. 

G If one of the carbonyl partners is much more acidic than the other and so is transformed into its enolate ion in preference to the other, then a mixed aldol reaction is likely to be successful. Ethyl acetoacetate, for instance, is completely converted into its enolate ion in preference to enolate ion formation from monocarbonyl partners. Thus, aldol condensations of monoketones with ethyl acetoacetate occur preferentially to give the mixed product. 

Amides also have rather acidic protons, though not, of course, as acidic as those of carboxylic acids. Attempted enolate ion formation in base removes an N-H proton rather than a OH proton. Amides are also the least reactive and the least enolizable of all acid derivatives, and their enols and enolates are rarely used in reactions. 

The most reliable method for making the enone is to alkylate the Mannich base with Mel and then treat the ammonium salt with base. Enolate ion formation leads to an ElcB reaction rather like the dehydration of aldols, but with a better leaving group. 

Acidity of Alpha hydrogen Atoms Enolate Ion Formation 851... 

Enolate Ion Formation This mechanism suggests that the reaction begins when the sodium methoxide (catalyst) attacks the acidic hydrogen from the carbon a to the carbonyl carbon to produce an enolate structure (Figure 4). This reaction produces a carbanion, which is a strong nucleophile. The enolate anion then reacts... 

Mechanism of enolate ion formation by abstraction of an a proton from a carbonyl... 

The Hell-Volhard-Zelinskii Reaction 909 Acidity of Alpha Hydrogen Atoms Enolate Ion Formation Reactivity of Enolate Ions 915... 

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