In many cases, the volatilities of the reactants and products are unfavorable for separation and purification; therefore, special designs for reactive distillation (RD) are required. In this study, RD configurations with total reflux and total boil-up designs are analyzed and evaluated under such scenarios to determine their applicability and disadvantages. Subsequently, simple and economical solutions were proposed to improve the performance of the existing RD using special designs for such cases, such as removing the product in the side stream: this enables more flexibility in design and allows more chances for improving reaction and separation efficiency. Response surface methodology handling both structural and operating variables simultaneously was used for optimizing the proposed configuration. An industrial case was simulated to demonstrate the proposed configuration. Furthermore, a novel dual-effect side stream RD was proposed to improve energy performance. As a result, the proposed retrofitted sequence could enhance energy efficiency up to 54% and reduce CO2 emissions of up to 52% compared to that for the existing sequence. This work also showed that this solution can bring an increase in capacity up to 15% with a small investment and short payback period. (C) 2019 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.