Reactive distillation (RD) in the face of azeotrope(s) in the separation of a Mixture from an RD column might. need debottlenecking design and more columns to obtain high-purity products. Under such circumstances, the integration of heat with the process becomes an effective consideration for reducing costs. In this study, all RD process to produce ethyl acetate and n-butanol from ethanol and n-butyl acetate by conducting a transesterification reaction is presented. The products from the RD column include n-butanol and an ethanol/ethyl acetate Mixture. Designs with alternative configurations are used to illustrate plantwide designs of the process with heat integration/coupling. Among these alternatives are two with three Columns and one with two columns. In the three-column configurations, separation of ethanol/ethyl-acetate mixtures from the top product of the RD Column is conducted by extractive distillation or pressure-swing distillation. The other configuration consists of all RD column followed by a conventional distillation Column operated at high pressure. Systematic design procedures are used to optimize the flowsheets of different configurations by minimizing the total annual cost. Heat integration and thermal Coupling technologies are used in these three configurations to attempt to provide more economical designs. The results show that the selection of separation system depends oil whether heat integration/coupling is considered, In this case, the two-column reactive distillation process with heat integration yields high-purity products and the lowest total annual cost.