Although reactive distillation columns represent a promising technology for process intensification between reaction operation and separation operation, it is difficult to use for the separation of reacting mixtures with the most and the least volatile reactants (i.e., the most unfavorable ranking of relative volatilities). To overcome the difficulty, we propose two novel configurations featured a top bottom external recycle for the separation of exothermic and endothermic reactions, respectively. While the external recycle should be directed from the top to the bottom for the exothermic reactions, it should be from the bottom to the top for the endothermic reactions. With the arrangement of a reactive section at the bottom for the exothermic reactions and at the top for the endothermic reactions, the two process configurations proposed favor considerably internal mass integration and internal energy integration between the reaction operation and the separation operation involved and help, consequently, to enhance the thermodynamic efficiencies of the reactive distillation columns. A simple and effective procedure for process synthesis and design is devised, and four examples, including an ideal quaternary exothermic reaction, an ideal quaternary endothermic one, the esterification of latic acid with methanol, and the esterification of palmitic acid with isopropanol, are chosen to evaluate the two configurations proposed. The obtained results show that they are definitely superior to those with two or one reactive sections at both or either ends in the aspect of capital investment and operating cost They are also demonstrated to be highly competitive alternatives to the conventional reactor/separator/recycle systems.