Dual Pathways, One Framework: Theoretical Insights into the Benzimidazole × Benzodiazepine Crossroads from <i>o</i> -Phenylenediamine and 2-Cyanoacrylate Derivatives

Ketene dithioacetals represent a significant class of molecules with a pivotal role in organic synthesis, particularly as versatile building blocks for the development of novel pharmaceutical compounds. We employed density functional theory (DFT) calculations in both ethanol and the gas phase to elucidate the specific mechanism of the reaction between methyl 2-cyano-3,3-bis-(methylthio)-acrylate and <i>o</i>-phenylenediamine. This approach provides a theoretical basis for understanding the system's behavior and reactivity at the molecular scale. Our study evaluates the competition between two reported products: 4-methylsulfanyl-2-oxo-2,5-dihydro-1<i>H</i>-benzo-[<i>b</i>]-[1,4]-diazepine-3-carbonitrile and methyl 2-cyano-2-(1,3-dihydro-2<i>H</i>-benzo-[<i>d</i>]-imidazole-2-ylidene)-acetate. The present findings reveal that both reactions are exothermic, with the formation of methyl 2-cyano-2-(1,3-dihydro-2<i>H</i>-benzo-[<i>d</i>]-imidazole-2-ylidene)-acetate being more thermodynamically favorable. This combination of experimental evidence and computational analysis bridges the gap between synthetic applications and mechanistic understanding, enhancing the design and optimization of organic reactions.