Alkylation of Enolate Ions

Alkylation of Enolate Ions The malonic ester synthesis The acetoacetic ester synthesis Direct alkylation of ketones, esters and nitriles

Relative acidity of selected organics StructurepKa 5 9 11 13 These compounds are MORE ACIDIC than CH3CH2OH (pKa = 16); NaOCH2CH3 can deprotonate them.

Relative acidity of selected organics StructurepKa 16 17 19 These compounds are SLIGHTLY LESS ACIDIC than CH3CH2OH; NaOCH2CH3 would result in only a small amount of deprotonation.

Relative acidity of selected organics StructurepKa 25 25 35 40 These compounds are MUCH LESS ACIDIC than CH3CH2OH; to deprotonate the top two, a base such as the R2N anion must be used.

Acidity of b-dicarbonyl compounds A base removes a proton a to both carbonyl groups: Resonance stabilizes the resulting anion:

General mechanism for alkylation The anion attacks the carbon bearing a leaving group: A second equivalent of base can remove the second proton :

Introduction of a second alkyl group: This anion can be alkylated by a second alkyl halide

Hydrolysis and Decarboxylation a substituted malonic ester a substituted acetic acid

Hydrolysis and Decarboxylation a substituted acetoacetic ester a substituted acetone

Overall Process, single substitution, using abbreviations

Overall Process, double substitution, using abbreviations

Forming a ring that includes the a-carbon Substituted acetic acids having a ring that includes the a-carbon can be synthesized similarly using diethyl malonate: 5- or 6-membered rings can be made using a 4- or 5-carbon alkyl dihalide

Direct alkylation of ketones, esters, and nitriles (but NOT aldehydes)

Alkylation of Enolate Ions