The reactor network synthesis problem involves determining the type, size, and interconnections of the reactor units, optimal concentration and temperature profiles, and the heat load requirements of the process. A general framework is presented for the synthesis of optimal chemical reactor networks via an optimization approach. The possible design alternatives are represented via a process superstructure which includes continuous stirred-tank reactors and cross-flow reactors along with mixers and splitters that connect the units. The superstructure is mathematically modeled using differential and algebraic constraints, and the resulting problem is formulated as an optimal control problem. The solution methodology for addressing the optimal control formulation involves the application of a control parametrization approach where the selected control variables are discretized in terms of time-invariant parameters. The dynamic system is decoupled from the optimization and solved as a function of the time-invariant parameters. The algorithmic framework is implemented in the optimization package MINOPT, which is used as a tool for solving the reactor network synthesis problem. The proposed approach is applicable to general problem formulations, and its utility is illustrated through the application to numerous examples including both constant and variable density problems, isothermal and nonisothermal operation, and complex reaction mechanisms with the kinetic and thermodynamic data provided by Chemkin.