Mechanisms and Stereochemistry of Amine Substitution Reactions at the Carbon-Nitrogen Double Bond

Article abstract of DOI:10.1021/jo00043a022

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(morpholine)> and decreasing size of amine k(pyrrolidine) > k(piperidine)>.The approximate Hammett ρ-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 ca. 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.