Research On Microwave-assisted Synthesis Of Balsalazide Disodium

Ulcerative colitis is a chronic inflammatory disease, confined to mucosa and submucosa of the inflammatory process. The disease still can not cure, and is in higher incidence in the world. Ulcerative colitis was considered as one of disease which was difficult to cure. In recent years, the incidence of ulcerative colitis in China was upward, and the number of patients compared with 50 years the previous century increased 10 times.Balsalazide disodium is a new type of "non-specific" salicylic acid anti-inflammatory drugs, which can be used to treat ulcerative colitis. It has advantages of rapid onset, better efficacy, side effects compared with other similar drugs. At present, there are some reports about synthesis of balsalazide disodium, but their technology wasn't very good.The purpose of this paper is on synthesis of balsalazide disodium and improve previous synthesis method, optimize reaction conditions to improve the yield of balsalazide disodium.The optimum synthesis conditions of balsalazide disodium were got:The optimal reaction conditions of synthesis of N-p-nitorbenzoyl-β-alnaine were:solvent volume H2O 50 mL, reaction time 10 s, temperature 52℃, molar ratio (nitrobenzoyl chloride:β-alanine) of 1:3.5, microwave power 420 W. The yield of N-p-nitorbenzoyl-p-alnaine was 96.8%..The optimal reaction conditions of synthesis of N-p-aminobenzoyl-β-alnaine were: reaction solvent ethyl acetate,5% Pd/Ccatalyst, reaction time 3.8 h, temperature 39℃.The yield of N-p-aminobenzoyl-β-alnaine was 94.2%.The optimal reaction conditions of synthesis of balsalazide acid were:molar ratio(HCl: amino-benzoyl-β-alanine) 1.46:1,molar ratio(p-aminobenzoyl-β-alanine:SA)0.952:1, crystalli-zation solvent 70% acetic acid. The yield of balsalazide acid was 78.2%.At last, balsalazide disodium was synthesized by balsalazide acid salt formation, and the yield of it was 96.5%.Balsalazide disodium was synthesiezd fom 4-nitrobenzyl chloride andβ-alnaine via acylation, reduction, diazotization, coupling and salt formation, and the structure was confirmed by NMR and IR. The total yield of the target compound was 68.8%, and it was higher than the yield which was reported in other literature.The reaction route is unique in that microwave-assisted synthesize sodium balsalazide disodium, and two hours were shorten in the whole reaction time, save production costs by response surface methodology and use green solvents to reduce environmental pollution in the all reaction process. Overall, this process route is reasonable and reliable, and suitable for industrial production.