Aldol Condensation of Aldehydes with Ketones Promoted by the Copper(II) Ion. Orientation to the Chemical Model for Metalloaldolases

Abstract

The aldol condensation reactions of aromatic aldehydes such as 1 through 4 and 7 through 13, and aliphatic aldehydes such as 5 and 6, with a number of ketones promoted by the copper(II) ion were examined. The reactions were specifically promoted by the copper(II) ion, while such metal ions as zinc, cobalt(II), manganese(II), and magnesium were quite inactive as catalysts. All the aldehydes but 7 and 8 reacted with all the aliphatic ketones except ethyl acetoacetate, acetonitrile, and nitromethane to varying degrees in the Claisen-Schmidt type of reaction. Acetylacetone gave a condensation product of the Knoevenagel type. In the reaction of aldehydes with 2-butanone, aldehydes regiospecifically attacked the methylene group at C3 of 2-butanone. Amines inhibited the reaction, while the coexistence effect of zinc or cobalt(II) was observed. It was shown that there existed a substrate selectivity depending greatly on the kinds of ketones in the reaction promoted by the copper(II) ion. As a consequence, possible intermediates in the reaction were proposed and the relationship of the aldol condensation reaction promoted by the copper(II) ion with the metalloaldolases was discussed, particularly in the light of the role of the metal ions in both catalytic mechanisms.