A chemical synthesis method that involved aldol condensation and betenediol epoxidation was designed with the aid of Gaussian 09 and Materials Studio 6.0 software to accomplish simulation of the corresponding preparation processes of (R)‐1,2,4‐butanetriol trinitrate (BTTN) and its crucial (R)‐1,2,4‐butanetriol (BT) precursor. The aim of this work was to construct a comparative model that closely approached the real reaction environment. By regulation of the reaction temperature and reagent concentration, and employing detailed kinetics analysis and thermodynamic equilibrium computation, we aimed to explore potential reaction routes and enhance the production yield. The simulation reaction used ethanal and glyoxal as starting materials to obtain (R)‐BTTN, and the computational results revealed that with an increase in reaction temperature, a regular trend of a decrease in the overall energy barrier was observed. For the reaction process of BT preparation via 3‐butene‐1,2‐diol epoxidation, including all exothermic elementary reaction steps, the activation energy of each stage decreased in a stepwise manner, with a simultaneous lowering of the temperature. In summary, controlling the reagent at a concentration of 0.25 M and the reaction temperature at 283 K promoted rapid reaction and a high product yield. The results of this study could be used as a reference when performing laboratory experiments.

In respective water or ethanol polarizable continuum cavity environments, simultaneous aldol condensation was performed using density functional theory (DFT) computational method to model the synthesis of optically active (RS)-1,2,4-butanetriol trinitrate (BTTN). The results of reaction energy barrier analysis suggested feasible routes with lower activation energies to obtain either the (R)- or (S)-configuration product in ethanolic solution. In addition, local analysis of average inter-particulate distances of reaction species revealed that a stronger inter-particulate interaction accompanied a shorter average distance in the ethanol system. The stabilization effect also indicated that related syntheses would be able to proceed in ethanol. Furthermore, relative to the production of (R)-BTTN, a lower overall energy of 425.3 kJ/mol was required for the synthesis of (S)-BTTN. Through analysis of the effects of temperature on the reaction rates of individual parallel stages of (R)- and (S)-species synthesis, it was simple to adjust the reaction temperature accordingly to differentiate between relative rates in order to obtain a product of a specific configuration. Graphical abstract ᅟ.