The sequential design method is presented as a complementary tool of the systematical synthesis procedure that allows to define a clear connection among the different types of distillation column sequences. In particular, the connection with the simple column subspace is considered, since this subspace represents the comparison reference for all the alternatives considered. The sequential design procedure, based on the sents the correspondence between the functionality of the column's section among the simple columns and the derived sequences, is compared with a mathematical based optimization algorithm. The separations of a four-component near ideal mixture and the azeotropic ethanol-water mixture are considered as case studies and the designs obtained applying both methods have been compared. The results confirmed that the sequential design method is a fast and reliable tool in the optimal design of the column sequence. (C) 2013 Elsevier Ltd. All rights reserved.