Carbonyl α-substitution reaction

Remarkably, ketone halogenation also occurs in biological systems, particularly in marine algae, where dibromoacetaldehyde, bromoacetone, 1, l,l -tribromoacetone, and other related compounds have been found.

[1]: 846 A hydrogen on the α 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 (pKa= 60), for instance, the presence of a neighboring carbonyl group increases the acidity of the ketone over the alkane by a factor of 1040.

If an alkoxide 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 such as sodium hydride (NaH) or lithium diisopropylamide (LDA) is used, a carbonyl compound can be completely converted into its enolate ion.

Many types of carbonyl compounds, including aldehydes, ketones, esters, thioesters, carboxylic acids, and amides, can be converted into enolate ions by reaction with LDA.

This enhanced acidity of β-dicarbonyl compounds is due to the stabilization of the resultant enolate ions by delocalization of the negative charge over both carbonyl groups.

First, pure enols can't normally be isolated but are instead 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.