Reactivity of 2‐fluoro‐5‐nitrothiophene towards sodium thiophenoxide and piperidine. Comparison with other 2‐halogeno‐5‐nitrothiophenes

Abstract

Abstract2‐Fluoro‐5‐nitrothiophene reacts with sodium thiophenoxide and piperidine much faster than other 2‐halogeno‐5‐nitrothiophenes. In methanol the reactions with both nucleophiles follow overall second order kinetics, while in benzene the observed second order rate constants of the reaction with piperidine show a linear dependence by the piperidine concentration. Such a dependence, which is mild for the chloro, bromo and iodo derivative, becomes strong for the fluoro compound. Moreover, the reaction of 2‐fluoro‐5‐nitrothiophene with [1‐2H]piperidine shows the absence of a primary isotope effect. The results are interpreted within the framework of the two‐stage, intermediate‐complex mechanism, the first stage (attack of the nucleophile on the substrate) being rate determing for the reactions of 2‐fluoro‐, ‐chloro‐, ‐bromo‐ and ‐iodo‐5‐nitrothiophene with thiophenoxide in methanol and of 2‐chloro‐, ‐bromo‐ and ‐iodo‐5‐nitrothiophene with piperidine in benzene. In the case of the reaction of 2‐fluoro‐5‐nitrothiophene with piperidine in benzene the data are in agreement with a mechanism in which the rate determining step is the decomposition of the tetrahedral intermediate into products. The intervention of a second amine molecule in the transition state of the rate determining step can be rationalized in terms of bifunctional catalysis. A comparison of reactivity of thiophenoxide and piperidine towards 2‐halogeno‐5‐nitrothiophenes (Hal = F, Cl, Br, I) indicates a greater sensitivity of the reaction with piperidine than that with thiophenoxide to the change of the leaving group.