Synthesis of amines: From a microwave batch reactor to a continuous milliflow reactor with heterogeneous feed and product

Abstract

The aminolysis reaction is used to prepare amines or amides and is mainly performed in a batch reactor. Increased safety, product yield and quality are important drivers to convert batch to flow processes. However, handling of suspensions in flow reactors remains challenging due to sedimentation and clogging. This research investigates an aminolysis reaction with heterogeneous feed and product. Solvent screening is performed in a batch reactor to select the optimal non-hazardous solvent. Next, the influence of the reaction parameters are researched with 3-6 equivalents of aqueous ammonia, temperature of 180-240 degrees C and residence time (RT) of 5-15 min. Results show that polar aprotic solvents are most suitable and the highest obtained yield was 86.4%. Although, lowering of the RT to 5 min, lowers the amount of side product. Finally, the optimal reaction conditions are successfully applied in a pulsatile flow reactor. With 0.85 M starting material (solid content 22m%), feed and product are both heterogeneous, the reactor works without clogging. The obtained product yield is 97% at 210 degrees C and 5 min of RT, corresponding to a production of 6 g/min. In conclusion, by focusing on solid transport during reactor design, the aminolysis reaction is an excellent candidate for continuous synthesis.