The Effect of Changes in Structure of the Reactants on the Rate of Enamine Formation
The Effect of Changes in Structure of the Reactants on the Rate of Enamine Formation
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Date
1964
Authors
Marchese, James Salvatore
Advisor
Pratt, Ernest F.
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Abstract
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.