The paper presents the results of the study of phase equilibrium in the system containing acetone, isopropanol, water, methyl isobutyl ketone, methyl isobutyl carbinol, and diisobutyl ketone. Mathematical modeling in AspenPlus V.10.0 was chosen as a method of studying. Thermodymanic-topological analysis was used to analyze the structure of the VLE diagram. The technique of studying the full composition diagram based only on a two-dimensional scan (determining the presence of a three-dimensional separatric manifold and distillation regions) was presented and demonstrated on the example of five components constituent of the mixture. It is shown that, in some cases, it is sufficient to study the two-dimensional scan of the phase diagram to predict its internal structure. Two separation flowsheets based on the use of direct and sharp distillation were considered, and the operating column parameters corresponding to minimum energy consumption were determined. The sharp distillation was proved to be less energy-intensive.