The Effect of Changes in Structure of the Reactants on the Rate of Enamine Formation
Creators: name: Marchese, James Salvatore
Publisher: name: Digital Repository at the University of Maryland
Year: 1964

description: It has been found that the rate of formation of a wide variety of enamines can be accurately determined by observing the rate at which the by-product water collects in a Dean-Stark trap. On the basis of the results observed upon varing the reactant ratio, the catalyst concentration and the temperature, 0.125 mole of carbonyl compound, 0.375 mole of amine and .001 mole of p-toluenesulfonic acid dissolved in sufficient benzene to give a total volume of 500 ml. were employed in the standard procedure. The solution of reactants was heated under reflux in an apparatus fitted with a water trap and frequent readings of time and water volume were taken until the reaction was complete. Nearly quantitative (98 to 100%) yields of water were ordinarily obtained and 85 to 100% yields of enamine were usually isolated. As the structure of the carbonyl component was varied an extremely wide range of reaction rates was encountered. The relative reactivity of many of these compounds had not been determined preciously. It was found that the rate decreased markedly among cyclic ketones as the ring was expanded from five to six to seven members and also when the methyl group of methylcylohexanones were shifted from the four to the three to the two position, Steric effects appear to be responsible for these rate differences. Somewhat unexpectedly ∝-tetralone did not react while β-tetralone reacted smoothly. Although the literature contains very little information on the formation of enamines of diketones a number of these were converted to the mono-enamines very smoothly. The rate decreased in the sequence, 1, 3-cyclohexanedione, dimedone, acetylacetone, benzoylacetone and 2-acetylcyclopentanone. Some evidence that ketones having planar structures reacted faster than those with non-planar structures was found, but no obvious correlation between degree of enolization and rate of reaction was observed. The reaction of acetophenones was much improved when the reaction temperature was changed from 82° to 112° by using toluene as a solvent. As the electron attracting ability of the para substitute was inreased in the order, CH3, H, Cl and N02 the rate consistently increased. Phenylacetone reacted smoothly under the standard conditions, but heptanone-2 gave only a 27% yield of water in five days . The importance of steric factors is emphasized by the fact that cyclohexanone gave a 98% yield of water in two hours. Typical aliphatic aldehydes reacted so rapidly that in order to increase the accuracy of t;he rate measurements 0.000125 mole of catalyst was used in place of the standard 0.001 mole. The order of decreasing rate was phenylacetaldehyde, It is apparent that the rate decreasing effect of chain branching at the alpha position diminishes when the branches are joined into a ring. The results for phenylacetaldehyde and phenylacetone indicated that aldehydes react over one thousand times as fast as ketones. The rate of formation of enamines from cyclohexanone and a variety of amines was also determined under the standard conditions. Shifting a methyl group on the piperidine ring from the four to the three to the two position greatly decreased the rate and pyrrolidine reacted faster than both piperidine the and hexamethylene imine. Morpholine and especially N methylpiperazine reacted much faster than piperidine while n-butylmethylamine reacted most slowly of all the amines mentioned. In only a few special cases was integral order kinetics obtained. The results can, however, be quite well correlated with a straightforward mechanism if it is assumed that both the step in which the amine adds to the carbonyl group and the step in which this addition product is dehydrated ordinarily affect the overall rate.