Real-time process analysis and optimization of nitroguanidine synthesis in microflow using inline Raman spectroscopy

Non-contact inline Raman spectroscopy is used as a fast, flexible, and safe method for monitoring and optimizing continuous-flow processes involving highly hazardous and corrosive materials. The synthesis of nitroguanidine (NQ), an energetic material, was characterized and optimized as a model for hazardous reactions. The contactless, flexible, and real-time analysis in this environment was implemented using a clip-on adapter for a Raman probe downstream of the microflow reactor. Initial experiments focus on characterizing the in situ formation of the nitration agent, the nitronium ion (NO₂⁺), and identifying an optimal nitric acid volume fraction between 10 and 20% v/v for maximum NO₂⁺ yield. The PAT setup was then used to rapidly optimize reaction parameters (residence time, reactor temperature, and stoichiometry) to enhance reactor output while maintaining high yield. Increasing the reaction temperature to 70 °C effectively reduces system pressure due to the lower viscosity of the reaction stream, while simultaneously increasing yield. Reduced residence times enable higher output with only minimal yield loss (6.3 min, 97%). The analysis of the molar ratio of the reagents further revealed that using a slight excess of nitric acid maintains the yield while avoiding product losses due to back reaction during subsequent processing. To verify the long-term repeatability of the reactor for synthesis, the reaction was performed several times under optimized conditions.