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Mesoporous silica SBA-15 is shown to be a very efficient alternative to phase transfer catalyst salts for two-phase nucleophilic substitutions. The two-phase reaction can efficiently take place in the absence of PTCs. The high catalytic activity and reaction rates can be attributed to the amphiphilic and negatively charged surface of SBA-15 as well as the rapid ingress of the reactants and egress of the products.