Gliclazide The Synthesis

Gliclazide is a second-generation oral sulphonylurea drug. It is used for diabetes mellitus. Its functions have both reducing the amount of blood sugar and improving the power of cruor. It not only can improve the metabolism of the diabetes mellitus patients and also can improve or suspend the occurrence of blood vessel complication. On the basis of combining the relevant references, the paper is seeking for a synthetic route suitable for the large-scale industrial manufacturing.The paper investigates the synthetic route of preparing Gliclazide, which is synthesized from O-pentadicarboximide by deoxidation, nitrosation, deoxidation and conden sation with p-Tolylsulphonure in this synthetic route. It focuses on the effect of the yield caused by each factor during each manufacturing step.In the reduction reaction of imide, LiAlH₄ and AlCl₃ are replaced with KBH4 and ZnCl₂ respectively. In this reaction, tetrahydrofuran (THF) is also replaced with toluene and tetrahydrofuran. Through these improvements, both cost and environmental pollution can be decreased. The emphasis was placed on investigating the influences of toluene-THF ratio, KBH₄ -ZnCl₂ ratio, reaction time, reaction temperature and purification. Based on this investigation, the reaction conditions can be optimized and the yield can be 85%.In the nitrosation reaction, the emphasis was placed on investigating the influences of temperature, pH and concentration. The reaction was preceded almost at equivalent amount and the yield can be as high as 99.5%.In the reduction reaction of nitroso-compound, LiAlH₄ is replaced with Zn and HCl. In this reaction, ZnCl₂ is deposited with NaOH. In such way, the cost can be decreased and the waste can also be easily treated. The emphasis was placed on the selection of reductant and acid. Make the best selection to let it be suitable for the industrial production. The yield can be 93.1%.In the synthesis reaction of gliclazide, the emphasis was placed on investigating the influences of reaction time, temperature, side chain, material input amount and water addition amount.The whole synthetic route has a total yield of 69%, calculated based on O-pentadicarboximide.The synthetic route applied enjoys such advantages: simplicity, material-easy-obtaining, high-yield, low-expenditure. And this synthetic route is suitable for the large-scale industrial manufacturing.