The chemical reactivity of molecules can be significantly enhanced when they are trapped in a confined space. Although such a confinement effect can be found in many self-assembled nanostructures, dissipation after completing the reaction to release the product remains elusive. Here we report substrate-directed transient self-assembly for accelerating a chemical reaction and spontaneous disassembly with releasing the products. The hydrophobic substrates mediate self-assembly of a dissolved pyridine-based amphiphile to provide a confined space to promote an aromatic nucleophilic substitution (SNAr) reaction in water. The chemical reaction triggers disassembly of the aggregates with simultaneous release of the product that can be spontaneously separated out of the solution by precipitation. Neutralization of the amphiphilic molecule leads to a new cycle of self-assembly entrapping substrates and disassembly with releasing the product.