Piperazine → N-1,4-Benzodioxane-2-carbonyl piperazine

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Reaction Steps

As an illustration of the improved synthesis, 1,4-benzodioxan-2-ethylcarboxylate and piperazine were reacted to form N-(1,4-benzodioxan-2-ylcarbonyl)piperazine. Since piperazine includes secondary amines, it is known that the amidization reaction can proceed only in the presence of a solvent and catalyst, e.g., a Lewis acid, strong base, or enzyme. Therefore, the solvent, e.g, THF, acetonitrile, benzene, toluene, or chlorine-containing solvent, was used to dissolve 1,4-benzodioxan-2-ethylcarboxylate and piperazine. The reactants were dissolved in anhydrous THF and potassium carbonate was added to catalyze the reaction. The mixture was stirred under nitrogen and heated to 110° C. After extraction and purification, it was found that the yield of 1-(1,4-benzodioxan-2-yl-carbonyl)piperazine (compound 1) was very low. The yield was less than 5%. Most of the product was 1,4-benzodioxan-2-carboxylic acid, which was obtained from hydrolysis of the reactant 1,4-benzodioxan-2-ethyl carboxylate.

Provenance & Evidence