Kinetic Study of the Acetate-catalyzed Aldol Reaction Between Chloral and Alkyl Methyl Ketones

Abstract

A kinetic study of the acetate-catalyzed crossed aldol reaction of chloral with butanone, 2-heptanone, and 4-methyl-2-pentanone, respectively, in glacial acetic acid at 60" has been carried out. A comparison of the condensation rates with those for the acetate-catalyzed deuterium exchange of the ketones in glacial acetic acid at 60' indicates that the carbon--carbon bond formation in the aldol reaction is the rate-determining step. The relative rate constants for the crossed aldol reaction and the deuterium exchange of the corresponding ketones are best interpreted in terms of steric rather than polar effects.On a entrepris une etude cinetique de la reaction aldolique catalysee par acetate, du chloral avec la butanone, I'heptanone-2, et la methyl-4 pentanone-2, respectivement dans I'acide acktique glacial a 60".Une comparaison des vitesses de condensation avec celles obtenues pour 1'6change de deutbium catalyse par adtate des cetones dans I'acide acetique glacial a 60" indique que la formation du lien carbonecarbone dans la reaction aldolique est 1'6tape dkterminante. Les constantes de vitesse relative pour la reaction aldolique et l'tchange de deuterium des cetones correspondantes sont mieux interpretees en termes d'effets steriques que polaires. Canadian Journal of Chemistry, 49, 3648 (1971)The mechanistic aspects of aldol reactions have been the subject of intensive studies by various investigators. The fundamental studies by Bonhoeffer and Walters (1) and Bell and Smith (2, 3) firmly established the two-step enolization-addition mechanism through kinetic and deuterium exchange experiments with acetaldehyde.Although the aldol reaction is catalyzed by acids and bases, the latter are more frequently employed. The base-catalyzed mechanism (4-6) may be described by eqs. 1 to 5. For the formation of aldols in concentrated solutions of acetaldehyde (7), propanal (8), and butanal (91, the proton abstraction step 1 is rate-limiting (k, < k,). On the other hand, the formation of the new carbon--carbon bond [2] is the ratelimiting step (k, > k,) in many aldol reactions involving ketones, for example the ethoxidecatalyzed condensation of aromatic aldehydes with acetophenones (lo), the formation of diacetone alcohol from acetone (3), the condensation of benzaldehyde and acetone (ll), and the condensation of formaldehyde with acetone (12).As a continuation of our interest in the crossed aldol reaction between chloral and alkyl methyl ketones in glacial acetic acid -acetate medium (13), we have now carried out a kinetic study of the aldol reaction of chloral with butanone, 2-heptanone, and 4-methyl-2-pentanone, respectively, in glacial acetic acid -acetate medium, as well as the deuteration of these ketones under conditions similar to the aldol reaction. A com~arison of these two sets of rate constants shouli settle, among other things, the question of the rate-limiting step in the crossed aldol reaction. Experimental ReagentsThe commercially available ketones were purified by fractional distillation. Pure anhydrous chlora...