Study On Synthesis Of6-chloroimidazo [1,2-b] Pyridazine

6-chloroimidazo [1,2-b] pyridazine is a major intermediate on the synthesis ofCefozopran. This thesis mainly synthetizes6-chloroimidazo [1,2-b] pyridazine withmaleic anhydride as starting material undergoing condensation, chlorination, amination,cyclization. Melting points analysis and nuclear magnetic resonance spectrumrepresentation of the products match the theory fundamentally, Suitable reactionconditions of each step are studied.The suitable condition of synthetizing maleic hydrazide is as follows: Sulfuricacid acts as reaction media, the mole ratio of maleic anhydride and hydrazine hydrateis1:1.1, the reaction temperature is105℃, the reaction time is13.5h, water is theelution solvent, dry products under50℃, color of the product is pure white, themelting point of maleic hydrazide is298-300℃when measured, the yield is91%.The suitable condition of synthetizing3,6-dichloropyridazine is as follows: Theamount of substance of Maleic hydrazide and PCl3O is1:18, the reaction temperatureis125℃, the reaction time is4h, test the reaction end point with methylene chlorideand methanol as developing solvent whose volume ratio is10:1, pour the reactionsolution into ice water to quench the reaction, add25%-28%of the ammonia solutionand regulate the PH to8or so, extract the solution with methylene chloride orchloroform, n-hexane acts as recrystallization solvent, the product presents whiteneedle pinnate, the melting point of the product is67-70℃, the yield is82%. The suitable condition of synthetizing3-amino-6-chloropyridazine is as follows:The mole ratio of the raw materials including3,6-dichloropyridazine, ammoniumchloride and ammonia water is1:1:3, the reaction temperature is105℃,the reactiontime is17h, the mass fraction of the ammonia water is15%, anaerobic environment,the pressure is0.45MPa, cool the solution to room temperature of about25℃, theelution solvent is water, the product presents as yellowish-white needle crystal, themelting point of the product is210-213℃, the yield is88%.The suitable condition of synthetizing6-chloroimidazo [1,2-b] pyridazine is asfollows: The mole ratio of the raw materials including3-amino-6-chloropyridazine andchloroacetaldehyde is1:2.5, the ethanol acts as reaction solvent, the reactiontemperature is80℃, the reaction time is3.5h, the volume ratio of methanol andmethylene chloride is1:10which act as the TLC developing agent to test the reactionending point. Add sodium bicarbonate solid to regulate the solution alkalescent withthe PH close to7-7.5, extract the solution with ethyl acetate, the product presents aslight yellow solid, the melting point of the product is107-109℃, the yield is91.5%.In addition,6-chloroimidazo [1,2-b] pyridazine can go through hydrogenation toproduce imidazo [1,2-b] pyridazine with Pd/C catalyst, which is preliminary research.