The thermally coupled distillation flowsheets for separation of five-component mixtures are studied based on the total annual costs. Fourteen simple column sequences and some feasible thermally coupled configurations with side strippers and/or side rectifiers are considered. The costs of the flowsheets are calculated and compared for several real five-component mixtures with various relative volatility distributions and a wide range of feed compositions. Several heuristics are proposed for the synthesis of multicomponent thermally coupled distillation flowsheets.