The reactivity of pseudoaromatic compounds. Part IV. Normal substitutions of 2-substituted tropones by secondary or tertiary amines; abnormal behaviour of 2-fluorotropone

Abstract

2-Fluorotropone reacts with piperidine in benzene to give 2-piperidinotropone quantitatively. Experiments with 2-fluoro[3,5,7-²H₃]tropone show normal substitution of fluorine by the nitrogen atom of piperidine. A kinetic investigation shows (i) that this reaction is of overall second-order (first-order with respect to both reagents) and (ii) that the free energy of activation is 4–5 kcal mol^–1 lower than the corresponding values found for 2-chloro-, 2-bromo-, 2-iodo-, and 2-methoxy-tropone. Clearly, the reaction does not follow the isokinetic relationship observed for the other tropones. The behaviour of 2-fluorotropone towards quinuclidine depends on the solvent; in dimethyl sulphoxide, substitution of fluorine by quinuclidine gives 1-{2-[N-oxocyclohepta-1,3,5-trien-1-yl)-piperidin-4-yl]ethyl}-1-azoniabicyclo[2,2,2]octane fluoride at a rate comparable to that for similar reaction of 2-iodo- or 2-chloro-tropone, but in benzene at room temperature 2-fluorotropone does not react with quinuclidine unlike the chloro- or iodo-compound. Under reflux, only intractable tars are obtained.

1-Halogeno-2,4-dinitrobenzenes behave similarly; they undergo clean substitution of the halogen atom by protic amines in both dimethyl sulphoxide and benzene. However, the fluoro-compound is unreactive towards quinuclidine whereas under similar conditions the chloro-compound gives 1-{2-[N-(2,4-dinitrophenyl)piperidin-4-yl]ethyl}-1-azoniabicyclo[2,2,2]octane chloride. Under forcing conditions piperidinium 2,4-dinitrophenolate is formed by hydrolysis (due to moisture) of 1-fluoro-2,4-dinitrobenzene. Intramolecular base catalysis by the ‘carbonyl’ oxygen atom is suggested as the basis of the isokinetic relationship in the reactions of the troponoid system with protic amines, and the observed data are consistent with this hypothesis.