For the separations of ternary/quaternary reacting mixtures with the most unfavorable relative volatilities (i.e., the reactants are the lightest and the heaviest components with the product/products as the intermediate one/ones), the reactive distillation column with a top-bottom external recycle (RDC-TBER) was already demonstrated to be considerably advantageous over the currently available process schemes [Chen, H.; Huang, K.; Liu, W.; Zhang, L.; Wang, S.; Wang, S.J. Enhancing Mass and Energy Integration by External Recycle in Reactive Distillation Columns. AIChE J. 2013, 59 (6), 2015]. In the present study, the RDC-TBER is further evaluated in terms of the separations of two more complicated reacting systems: the adipic acid and glutaric acid esterifications, which feature a two-stage cascade reaction kinetics besides the most unfavorable ranking of relative volatilities (i.e., the relative volatilities of the intermediate and final products are within those of the lightest and heaviest reactants). In comparison with the flowsheet by conventional reactive distillation column, the flowsheet by the RDC-TBER leads to sharply reduced capital investment, operating cost, and total annual cost (TAC). Moreover, the reduction of the TAC tends to increase in case the two-stage cascade reaction involved becomes difficult to proceed. These outcomes indicate that the arrangement of a top-bottom external recycle helps to enhance internal mass integration and/or internal energy integration between the reaction operation and the separation operation involved and facilitates the RDC-TBER to be a favorable option for the separations of adipic acid and glutaric acid esterifications.