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There are only a limited number of experiments that a student can do each semester in an undergraduate organic chemistry course. Therefore, it is important for each experiment to illustrate as many different techniques and principles as possible. The experiment discussed in this article demonstrates the following principles and techniques: (i) kinetic versus thermodynamic control of a reaction, (ii) methods to be used and pitfalls to be avoided in identification of reaction products, (iii) use of molecular modeling for identification of the thermodynamically controlled reaction product.
The reaction of morpholine with t-butyl acetoacetate in a one-to-one molar ratio results in one of two products, enamine ester 1 or ketoamide 2 (eq 1). The reaction of a secondary amine with an acetoacetic ester to form an enaminoester is well known (1-3). The t-butyl ester was used in our experiment instead of the more common ethyl ester because t-butyl morpholine enamine 1 (4) is a solid that melts well above room temperature. The corresponding ethyl enaminoester possesses a melting point very near to room temperature (5) and is therefore difficult to crystallize. The reaction of a secondary amine with an acetoacetic ester to form a ketoamide has been reported (5, 6). It has been demonstrated that the enaminoester is the kinetically controlled product and the ketoester is the thermodynamically controlled product (7).
These reactions provide the basis for an experiment in which the competition between thermodynamic control and kinetic control takes place between two functional groups on a single molecule competing for a single reagent. This is in contrast to a traditional experiment used to demonstrate this principle, which is found in many organic laboratory manuals (8). In that experiment two different molecules (cyclohexanone and 2-furaldehyde) compete for a single reagent (semicarbazide).
During a discussion of the reaction, the students are informed of the identities of the two possible products. Conditions under which one might expect kinetic control of a reaction product as contrasted with conditions for thermodynamic control are discussed.
Experimental Procedure
Students place a mixture consisting of a 1: 1 molar ratio of morpholine and t-butyl acetoacetate into a beaker cooled with ice water. A very few molecular sieve pellets OA, 4-8 mesh) are put into the beaker (two pellets for 0.05 mol works well)....