The ANRORC mechanism, that is, nucleophilic addition (addition of the nucleophile) + ring-opening (ring-opening) + ring-closing (ring-closing) mechanism, is a substitution reaction mechanism.

Commonly seen in nucleophilic substitution reactions of heterocyclic compounds.

The ANRORC reaction using metal amino salts (such as sodium amide) as nucleophiles and substituted pyrimidines (4-phenyl-6-bromopyrimidine, 1 in the figure below) in liquid ammonia at low temperatures has been studied in depth.

The specific reaction mechanism is shown in Figure 3.

The mechanism is mainly known through the following methods: 1) The main product of the reaction is 4-phenyl-6-aminopyrimidine (2) produced by replacing bromine with amino.

The reaction does not produce 5-substituted isomers, indicating that the reaction does not pass through benzyne intermediates.

2) When lithium piperidine is used as the base, a ring-opened nitrile intermediate (generated after elimination of hydrogen bromide) can also be isolated during the reaction, which also denies the existence of Meisenheimer intermediates.

3) The C5 of the substrate is labeled with deuterium, but no deuterium atoms are found in the reaction product.

This phenomenon can be explained by the rapid H-D exchange caused by tautomerism between 4a and 4b in the figure below.

4) Each of the two nitrogen atoms of pyrimidine was labeled with 3% N, and it was found that the isotope content in the final product 4 was approximately reduced by half, indicating that one ring nitrogen atom has been replaced by a nitrogen atom in the reagent used.