The synthesis and design of reactive distillation columns with two reactive sections (RDC-TRS) are attempted for the separations of reacting mixtures with somewhat unfavorable ranking of relative volatilities (RM-SURRV, i.e., two reactants are the light and heaviest components and two products the lightest and heavy ones). With the deliberate arrangement of the two reactive sections, the disadvantages by the unfavorable relative volatility can be substantially alleviated, facilitating consequently the reaction operation and separation operation involved. The separations of a hypothetical quaternary reaction, the esterification of acetic acid with methanol, and the transesterification of butyl acetate with ethanol are employed to evaluate the RDC-TRS. The process is found considerably superior to the reactive distillation column with a single reactive section and this demonstrates its feasibility and effectiveness in the separations of RM-SURRV. The RDC-TRS is found to present comparable or even improved performance in comparison with the reactive distillation column with an external recycle from bottom to reactive section and this corroborates it a potentially competitive alternative for the separations of the RM-SURRV. The RDC-TRS is also highlighted for the other kind of RM-SURRV (i.e., two reactants are the lightest and heavy components and two products the light and heaviest ones). (C) 2015 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.