Figure 7. Geometries of the stationary points in the intramolecular reaction of intermediate med1 to form 3a .
For path 1, we assumed that the H+ in solution is not involved in the cyclization process. Although various configurations were tested, the transition state of this process was not found using either the ts, qst2, or qst3 method. The C(8)–O(14) bond length was scanned flexibly. The structural changes and energy curve during the scan are shown in Figures 8 and 9, respectively. The scan shows that as C(8) and O(14) become far away from each other, the energy of the system continuously increases without reaching the highest point in energy. When C(8) and O(14) are not bonded, the C(8)–N(7) bond is broken and a very unstable 8-membered ring system is formed. At the same time, after the structure of intermediate med1-1 is optimized, the C(8)–O(14) bond breaks and cannot form a stable five-membered ring, which proves that med1-1 is unstable under these conditions. Therefore, path 1 cannot occur, and it was hypothesized that H+ participates in the formation of the five-membered ring.