Mechanistic Study of 1,4-Benzodiazepine-2,5-diones from Diphenylamine and Diethyl 2-Phenylmalonate by Density Functional Theory.

The mechanisms for the reaction between diphenylamine and diethyl 2-phenylmalonate were investigated using M06-2X-D3/6-31+G(d,p) method and level, and the SMD model was applied to simulate the solvent effect. The computational results suggested that diphenylamine and diethyl 2-phenylmalonate can convert into 4-hydroxy-1,3-diphenylquinolin-2(1)-one via a series of reactions (addition reaction, dealcoholization reaction, enolization reaction, dealcoholization reaction, ring-closure reaction, and H-shift reaction). And HO, as the catalyst, can play an important role to promote these reactions. In the following reaction, there are two paths to yield the second product 3-chloro-1,3-diphenylquinoline-2,4(1,3)-dione and the computational results indicated that the first path (blue line) with the rate-determining step of 24.9 kcal/mol is favorable. With the participation of methanamine, a SN2 reaction happened and the third product 3-(methylamino)-1,3-diphenylquinoline-2,4(1,3)-dione had been yielded in the effect of methanamine or Cl anion. The analysis of Gibbs free energy surfaces shows that methanamine is better than Cl anion to extract the proton via an exothermic reaction. Finally, the third product 3-(methylamino)-1,3-diphenylquinoline-2,4(1,3)-dione would go through a ring-enlargement reaction, promoted by base (TMG or Triton B), to yield the final product. The computational results demonstrated that this reaction can release much energy with Triton B than that with TMG. And the energy of the highest point is 10.1 kcal/mol (16.8 kcal/mol), which can readily occur at the room temperature. The results could provide valuable insights into these types of interactions and related ones.