Reactivity of Enolate Ions

Enolate ions are more useful than enols for two reasons. First, pure enols can t normally be isolated. They are usually generated only as short-lived intermediates in low concentration. By contrast, stable solutions of pure enolate ions are easily prepared from most carbonyl compounds by reaction with a strong base. Second and more important, enolate ions are much more reactive than enols and undergo many reactions that enols don t. Whereas enols are neutral, enolate ions are negatively charged, making them much better nucleophiles. Thus, the a carbon atom of an enolate ion is highly reactive toward electrophiles. An electrostatic potential map of acetone enolate ion, for instance, shows the electron-rich character (red) of the a carbon. 

Two modes of reaction of an enolate ion with an electrophile, E Reaction on carbon to yield an a-substltuted carbonyl product Is the more common path. 

Halogenation of aldehydes and ketones occurs under both basic and adib conditions. As you might expect, the base-promoted reaction occurs throa f an enolate ion intermediate. Even relatively weak bases such as hydradjM ion are effective for halogenation because it s not necessary to convert. ttP ketone completely into its enolate ion. As soon as a small amount of enolate is generated, it reacts immediately with the halogen. 

Base-promoted halogenation of aldehydes and ketones is little used in practice because it s difficult to stop the reaction at the monosubstituted product. An a-halogenated ketone is generally more acidic than the star ing, unsubstituted ketone because of the electron-withdrawing inductiv effect of the halogen atom. Thus, monohalogenated products are themselvi rapidly turned into enolate ions and further halogenated. 

If excess base and halogen are used, a methyl ketone is triply hal genated and then cleaved by base in the haloform reaction. The produc are a carboxylic acid plus a so-called haloform. (chloroform, CHCU bromo-form, CHBr3 or iodoform, CHL). Note that the second step of the reaction is a nucleophilic acyl substitution of CXg by OH. That is, a carbanion act as a leaving group. 

Why do you suppose ketone halogenations in acidic media are referred to as being acid-catalyzed, whereas halogenations in basic media are base-promoted In other words, why is a full equivalent of base required for halogenation  

Identify the most acidic hydrogens in each of the following compounds, and rank the compounds in order of increasing acidity  

Strategy Hydrogens on carbon next to a carbonyl group are acidic. In general, a j8-dicarbonyl compound is most acidic, a ketone or aldehyde is next most acidic, and a carboxylic acid derivative is least acidic. Remember that alcohols, phenols, and carboxylic acids are also acidic because of their -OH hydrogens. 

Solution The acidity order is (a) (c) (b). Acidic hydrogens are shown in red. 

Problem 22.8. Draw a resonance structure of the acetonitrile anion, CH2C K, and account for 1 the acidity of nitriles. 

Identify the most acidic hydrogens in each of the following molecules 

---

The rate of alkylation of enolate ions is strongly dependent on the solvent in which the reaction is carried out.41 The relative rates of reaction of the sodium enolate of diethyl n-butylmalonate with n-butyl bromide are shown in Table 1.3. Dimethyl sulfoxide (DMSO) and iV,Ai-dimethylformamide (DMF) are particularly effective in enhancing the reactivity of enolate ions. Both of these are polar aprotic solvents. Other... 

DMSO and /V, A- dime th y I fo nn a in i d c (DMF) are particularly effective in enhancing the reactivity of enolate ions, as Table 1.2 shows. Both of these compounds belong to the polar aprotic class of solvents. Other members of this class that are used as solvents in reactions between carbanions and alkyl halides include N-mcthyI pyrro I i donc (NMP) and hexamethylphosphoric triamide (HMPA). Polar aprotic solvents, as their name implies, are materials which have high dielectric constants but which lack hydroxyl groups or other... 

Mendez F, Gazquez JL. Chemical reactivity of enolate ions the local hard and soft acids and bases principle viewpoint. J Am Chem Soc 1994 116 9298-9301. 

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

Scamehorn, R. G., Hardacre, J. M., Lukanich, J. M., and Sharpe, L. R., Thermally initiated Sr I reactions of ketone enolates with iodobenzene in dimethyl sulfoxide relative reactivities of enolate ions with phenyl radical, /. Org. Chem., 49, 4881,1984. 

---