Title : Mechanism of spiro-heterocycle formation: Density functional theory approach
Literature is hugely deficient in theoretical kinetic and thermodynamic data on formation mechanisms of some bioactive spiro-heterocycles. Formation of 1’-((((aminoxy)carbonyl)amino)methyl)-2’-(1-hydroxynaphthalen-2-yl)-2’-methyl-1’,2’,5’,6’,7’-7a’-hexahydrospiro[indoline-3,3’pyrrolo[1,2-a]imidazol]-2-one was theoretically investigated using ab initio method. For more accurate result, density functional theory at B3LYP with 6-311+G** basis set was employed. There were bond length alterations (C9–N10, C9–C12, C13–N10 and C8–N10) as the interaction between the reacting species progressed through the stationary points to the product. The HOMO–LUMO energy gap suggested that pyrrolidine-2-carboxylic acid (?E = –6.27 eV) acted as Lewis acid while indolin-2,3-dione (?E = –3.90 eV) acted as a Lewis base for the intermediate formation step. The formation of Van der Waals Complex 1 (VWC 1) step was computed to be exothermic (-72.95 kJmol-1) and slightly endergonic (+1.78 kJmol-1), while the transition step leading to the formation of transition state 1 has the rate constant, k, value of 1.87× ?10?^(-1) dm3mol-1s-1. From the mechanism of the reaction, the rate of formation of the product was found to be dependent on the isatin, [A] and pyrrolidine-2-carboxylic acid, [B] concentration by the expression (d[P])/dt= (?k_2^2 k?_2^' k_1^')/(k_(2^' ) k_1 ?(k?_(-2)^'+ k_2)) [A][B].