Enamine Reduction, 22 Factorial Design

Enamines can be reduced to the corresponding saturated amines by treatment with formic acid. A very simple experimental procedure can be used in which formic acid is added to the neat enamine at such a rate that foaming due to evolution of carbon dioxide can be kept under control. The reduction of the morpholine enamine from camphor was studied in a two-level factorial design in order to determine whether or not an excess of formic acid should be used and at which temperature the reaction should be run. 

The experimental design and yields of bomylamine obtained are shown in Table 1. The scaling of the variables x1 the amount of formic acid, and x2, the reaction temperature, are given in a note to Table 1. 

The second-order interaction model obtained from the experiments was 

From the model it is seen that the best yield if found when xt is at its low level (—1) which corresponds to a stoichiometric amount of formic acid and that an excess is detrimental to the yield (the coefficient is negative). The temperature x2 is the most important factor and should be at its upper level. The experimental conditions established for this very simple procedure could be applied as a method for the reduction of a number of enamines [17]. 

A plot showing the shape of the fitted response surface model is shown in Fig. 3. Three-dimensional projections of response surface models make it easy to see how 

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