A DFT study on the reaction pathway involved in the metal-ion-templated synthesis of benzo-21-crown-7(B21C7) from catechol and hexaethylene glycol ditosylate in the presence of base

This present work explores the mechanism of the alkali metal-ion (Na+ and K+) aided benzo-21-crown-7(f) formation from catechol and hexaethylene glycol di-p-toluenesulfonate in the presence of base. The density functional theory (DFT)-based studies (in gas-phase and in acetonitrile) have identified two S(N)2 steps along the reaction path, where each step is characterized by an energy barrier due to the presence of a transition state (TS). The metal-ion template effect eases the binding between the catechol oxygen and the carbon atom holding the tosyl leaving group. This metal-ion framework facilitates the cyclization process, which is responsible for the better yield of the crown ether. In case of K+-coordinated system in solution, the TS dipole moment value for this step is 10 Debye higher than the corresponding reactant, whereas for Na+-coordinated system, this difference is much smaller (similar to 7.5 Debye). A comparison of the barrier heights of this intramolecular S(N)2 step in acetonitrile shows a higher value for Na+ ion system (30 kcal/mol) than that of K+-coordinated system (22 kcal/mol). Expectedly, a higher rate constant for the cyclization has been found from the kinetics study of the latter, which is in-line with the reported experimental results. Additionally, we have also explored the consequences of the involvement of a second metal ion in the process, a possibility, which was predicted earlier for large ring-sized crown ethers.