An important class of reaction systems which can be efficiently performed by catalytic distillation comprises two reactants (A, B) and two products (C, D). Often, one product is the high-boiling species and is obtained as bottom stream, while the other is involved in a low-boiling heterogeneous azeotrope and is obtained as distillate. The heterogeneity of the azeotrope makes possible a liquid–liquid split, where the product-rich phase is on the side of the distillation boundary which allows obtaining the top-product with a relatively high-purity. Integration of reaction and separation in a single unit reduces the investment and operating costs. However, the controllability of the process is as important as the economics. In this contribution, a novel class of control structures with one-point temperature control is presented. The flow rate of one fresh reactant sets the production rate. The product purity is achieved by temperature control manipulating the reboiler duty, while monitoring the phase ratio organic/aqueous and adjusting the second reactant feed ensures the correct stoichiometric ratio. This control philosophy can be implemented in different ways. Moreover, design modifications with the purpose of increasing the control flexibility are suggested. Overall, given the range of disturbances applied to the esterification system studied in this work, the performance of the new one-point temperature control structures is comparable with that of the different schemes present in the literature.