Theoretical Study on the Synthesis Efficiency and Yield of Imidazole Derivatives Based on the Glyoxal and Diamine

ABSTRACT Imidazole structures are significant molecular frameworks in pharmaceutical and energetic material research. The synthesis efficiency and yield of their derivatives often vary greatly, making it challenging to establish reaction regularity. In this study, we investigated two types of imidazole derivatives with notably different synthesis efficiencies and yields. Our findings reveal that the catalysis of H 2 O molecules is crucial for ensuring synthesis efficiency, while side reactions are influenced by the acidity of the solution during the process, thereby affecting the synthesis yield. We observed that the energy barrier for the H 2 O‐catalyzed ipsilateral H transfer process was reduced to 12.0 from 40.1 kcal/mol, significantly enhancing the reaction efficiency. The synthesis of 34‐dihydroxyimidazolidine‐2‐ketone was found to have a low yield of 19.2% due to competitive side reactions in the reaction system, which have higher energy barriers compared to the desired synthesis pathway. These findings provide a theoretical foundation for future research to optimize the synthesis of imidazole derivatives. Enhancing synthesis conditions could significantly benefit pharmaceutical applications and the development of advanced energetic materials.