MECHANISMS AND STEREOCHEMISTRY OF AMINE SUBSTITUTION-REACTIONS AT THE CARBON NITROGEN DOUBLE-BOND

The reaction of (Z)-O-methyl-p-nitrobenzohydroximoyl chloride [4-NO2C6H4C(Cl)=NOCH3] with morpholine, piperidine, pyrrolidine, and azetidine gives the corresponding (Z)-amidoximes [4-NO2C6H4C(NR1R2)=NOCH3]. The rate equations for these reactions in benzene solution contain both first-order and second-order terms in amine. The rates of these reactions increase with increasing basicity [k(pyrrolidine > k(morpholine)] and d size of the amine [k(azetidine) > k(pyrrolidine) > k(piperidine)]. The approximate Hammett rho-values for the reaction of (Z)-hydroximoyl chlorides with azetidine are +1.0 for the amine-catalyzed process and 0 for the uncatalyzed pathway. The element effect, k(p-nitrobenzohydroximoyl bromide)/k(p-nitrobenzohydroximoyl chloride), is 11.9 for the amine-catalyzed reaction and 8.16 for the uncatalyzed reaction. These results suggest that the reactions proceed by an addition-elimination mechanism (A(N) + D(N)) in which the amine is deprotonating the zwitterionic tetrahedral intermediate in the amine-catalyzed process. The slow reaction of azetidine in benzene solution with (E)-O-methyl-p-nitrobenzohydroximoyl chloride gives a mixture of the (Z)- and (E)-amidoxime with the E isomer predominating (E/Z is-approximately-equal-to 98:2). The rate equation for this reaction contains first-order and third-order terms in azetidine. It is suggested that the amine-catalyzed route involves nucleophilic attack by an amine monomer to form a tetrahedral intermediate which breaks down with the assistance of an amine dimer (or the homoconjugate acid of the amine). The difference in the observed rate equations for (Z)- and (E)-hydroximoyl chlorides with azetidine is attributed to stereoelectronic effects.