Catalysis in aromatic nucleophilic substitution. Part 6. Reactions of 2-methoxy-3-nitrothiophen with cyclic secondary amines in methanol and benzene

Abstract

The kinetics of the reactions of 2-methoxy-3-nitrothiophen (I) with pyrrolidine in methanol and benzene and with perhydroazepine in benzene have been studied as a function of amine concentration. The pyrrolidino-substitution of (I) in methanol is second-order overall whereas the corresponding piperidino-substitution is base-catalysed. The reactions of (I) with pyrrolidine, piperidine, and perhydroazepine in benzene are all catalysed by the nucleophile and by diazabicyclo[2.2.2]octane but the pattern of catalysis depends on the ring size of the cyclic amine. The data are most consistent with the specific base–general acid mechanism for base catalysis. The remarkable difference in behaviour between pyrrolidine and piperidine is suggested to stem from conformational effects concerning the amino-moieties in the transition state for the general acid-catalysed departure of methoxy-group.