Study On The Acid Catalyzed Synthesis Of Triazoles Under Continuous-flow Conditions

Because 1,2,3-triazoles derivatives have unique chemical properties and pharmacological activity,it is widely used in pharmaceutical chemistry,material chemistry,organometallic chemistry and so on.However,the synthesis method of these heterocyclic compounds is still limited,which makes the catalytic synthesis of 1,2,3-triazole compounds become a hotspot in recent years.In this thesis,we first investigate the synthesis of nitroalkene compounds and sodium azide in the presence of acid.We found that When 2.5 equivalents of acetic acid were added,93%yield of triazoles were obtained at 60? for 1h.For this kind of reaction,we designed and built a complete set of continuous-flow microreactor to replace the traditional reaction device to explore the relevant experiments.Continuous-flow microreactor has very good heat and mass transfer performance,not only shorten the reaction time,reduce the risk index from the reaction process,but also avoided the amplification effect in the scale-up experiments which existed in batch reactions.We also used nitrostyrene and sodium azide as the substrate to explore the reaction time,reaction temperature,reaction pressure and other conditions.It was found that 93%yield of triazoles was obtained in continuous-flow reaction device can at 200? for 3.3 minutes.This kind of device can greatly improve the efficiency and safety of the reaction.Through the development of the substrate,it was found that the impurity derivatives existing in the tube sealing reaction can be decomposed under the high temperature condition of the continuous-flow,and more pure products can be obtained.In the second part,the synthesis of triazoles from non-nitrostyrenes has been investigated.To our Surprise,when the benzaldehyde,sodium azide and nitromethane in accordance with a certain percentage were put into a sealed tube with quantify acetic acid and ammonium acetate as additives,97%yield was obtained at 140? for 80 minutes.This breakthrough has succeeded in avoiding the separation and purification of nitrostyrene,making the preparation process of triazole more convenient and efficient.At the same time,we studied the synthesis of benzyl azide and methyl 2,3-dibromopropionate in the presence of bismuth trichloride and heating at 80? for 12 hours.A very good yield was also obtained.