Clarke Earley, Ph.D.
Department of Chemistry
Kent State University Stark Campus
North Canton, OH 44720
Alkyl hydrogen atoms bonded to a carbon atom in a a (alpha) position relative to a carbonyl group display unusually high acidity. While the pKa values for alkyl C-H bonds is typically on the order of 40-50, pKa values for these alpha hydrogens is usually within the range of 19-20. This can most easily be explained by resonance stabilization of the carbanion product, as illustrated in the diagram below (where :B- represents a base).
In the presence of a proton source, the product can either revert back into the starting ketone or aldehyde or can form a new product, the enol. The keto form (which may be either a ketone or an aldehyde) is generally strongly favored in this reaction. The equilibrium reaction between the ketone or aldehyde and the enol form is commonly referred to as keto-enol tautomerism. Tautomers are isomers that differ from each other only by: (1) position of a single H atom, and (2) movement of electron pairs.
The acidity of a-hydrogens is a crucial component of the formation of aldols. The general mechanism for aldol condensation is shown below. In the first step of this reaction, the acidic proton of an aldehyde is abstracted by a base. The resonance-stabilized carbanion then attacks a second aldehyde molecule at the carbonyl carbon (which bears a partial positive charge due to the electronegativity of the oxygen atom). This reaction results in formation of a new carbon-carbon bond (shown in red). The negative charge initially located on the a-carbon atom moves to an oxygen atom. This oxygen anion can then abstract a proton to form the aldol (aldehyde-alcohol) product.
While this reaction can also be performed with ketones, the equilibrium usually strongly favors starting material.
While in principle it should be possible to obtain aldol (or enal) products by simply mixing two different aldehydes in the presence of base, this typically leads to a complicated mixture of products. However, this reaction can be practical if one of the aldehydes doesn't contain any a-hydrogens. Consider the following reaction:
The benzaldehyde molecule doesn't contain any acidic hydrogen atoms. In the first step of this reaction, the base will abstract an alpha-hydrogen from 3-pentanone. The resulting nucleophile could attack either a second molecule of 3-pentanone or the benzaldehyde. Since aldehydes are typically more reactive than ketones, nucleophilic addition to the carbonyl carbon on the benzaldehyde is preferred.