Acidity of Alpha Hydrogen Atoms Enolate Ion Formation

Alpha Bromination of Carboxylic Acids The Hell-Volhard-Zelinskii Reaction 

Interactive to use a web-based palette to predict products from a variety of halogenation reactions of carbonyls and carboxylic acids. 

The a bromination of carbonyl compounds by in acetic acid is limited tc aldehydes and ketones because acids, esters, and amides don t enolize to a suffi cient extent. Carboxylic acids, however, can be a brominated bv a mixture of Br and PH13 in the Hell-Volharcl-Zelinskii (UVZ) reaction. 

Ihe Hell-Volhard-Zelinskii reaction is a bit more complex than it looks and actually involves substitution of an acid bromide enol rather than a carboxylic acid enok The process begins with reaction of the carboxylic acio with to form an acid bromide plus MBr (Section 21.4). The HBr then catalyzes enolization of the acid bromide, and the resultant enol reacts with Br2 in an a-substitution reaction to give an a-bromo acid bromide. Addition of water hydrolyzes the acid bromide in a nucleophilic acyl substitution reacliou and yields the a-bromo carboxylic acid product. 

If metlianol rather than water is added at the end of a Heil-Volhard-Zelinskii reac tion, an ester rather than an acid is jnoduced. Show how you could carr out the following transformation, and propose a mechanism for the ester-forming step. 

If methanol rather than water Is added at the end of a Hell-Volhard-Zelinskii reaction, an 

5 Acidity of Alpha Hydrogen Atoms Enolate Ion Formation 

As noted in Section 22.1, a hydrogen on the a position of a carbonyl compound is weakly acidic and can be removed by a strong base to yield an enolate ion. In comparing acetone (pKa = 19.3) with ethane (piCg 60), for instance, the presence of a neighboring carbonyl group increases the acidity of the ketone over the alkane by a factor of 10 °. 

Because carbonyl compounds are only weakly acidic, a strong base is needed for enolate ion formation. If an alkoxide ion, such as sodium ethoxide, is used as base, deprotonation takes place only to the extent of about 0.1% because acetone is a weaker acid than ethanol (pKa = 16). If, however, a more powerful base is used, then a carbonyl compound is completely converted into its enolate ion. 

During the discussion of base-catalyzed enol formation in Section 22.1, we said that carbonyl compounds can act as weak protic acids. That is, a strong base can abstract an acidic a hydrogen atom from a carbonyl compound to yield an enolate ion. 

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 

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

Lithium diisopropylamide (LDA) is easily prepared by reaction betweea butyliithium (BuLi) and diisopropyiamine and is widely used as a base fin preparing enolate ions from carbonyl compounds. LDA has nearly ideal properties  

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

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

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