Sulfasalazine synthesis process

Abstract

The present invention relates to the technical field of sulfasalazine, specifically to a sulfasalazine synthesis process. The used technical scheme comprises that a compound represented by a formula I or a salt thereof and a compound represented by a formula II or a salt thereof are subjected to a reaction to prepare a compound represented by a formula III (the formulas I, II and III are defined in the specification), wherein R is hydrogen atom, alkyl, cycloalkyl, phenyl, and aralkyl, R2 is hydrogen and COR3, and R3 is alkyl, aryl, and aralkyl. With the technical scheme of the invention, the strict control of the reaction temperature is not required, and the production of the unstable diazonium salt can be avoided so as to avoid the production of the byproduct; and the product sulfasalazine can be directly precipitated through the simple treatment, the yield of the reaction is high, and the yield can achieve more than 90%.

Description

technical field [0001] The invention relates to the field of sulfasalazine, in particular to the field of synthesis technology of sulfasalazine. Background technique [0002] Sulfasalazine is also known as 5-[p-(2-pyridinesulfamoyl)benzene]azosalicylic acid, which has the following structure: [0003] [0004] It is a sulfonamide antimicrobial used in the treatment of inflammatory bowel disease. After oral administration, it is broken down by intestinal bacteria into 5-aminosalicylic acid and sulfapyridine. After 5-aminosalicylic acid complexes with the connective tissue of the intestinal wall, it stays in the intestinal wall tissue for a long time to play an antibacterial, anti-inflammatory and immunosuppressive role. [0005] The synthesis of sulfasalazine mainly takes sulfapyridine (I) as raw material at present, [0006] [0007] Sodium nitrite is a diazotization reagent, which is obtained by coupling with salicylic acid after diazotization in the water phase, f...

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Problems solved by technology

[0007] Sodium nitrite is a diazotization reagent, which is obtained by coupling with salicylic acid after diazotization in the water phase, for example, refer to the preparation method provided in WO2002018330; there is also isoamyl nitrite as a diazotization reagent , the reaction is carried out in an organic solvent, for example, can refer to the method provided in Apoptosis 2005,10(3), 481-491, but the current synthetic methods all have a long reaction time, partial reaction overheating, strict control of the reaction temperature, diazo Salt is prone to hydrolysis and other problems, resulting in by-products, resulting in low yield of sulfasalazine

[0008] Synthetic Chemistry 20 (4), 524-526, 2012 has improved on the basis of these documents, so that the reaction yield has been improved, but the method it provides needs to be carried out in a tubular reactor, which is difficult for large-scale industrial production There are many limitations, and it can be seen from the published comparative experiments that the temperature will have an impact on the reaction yield. It is also mentioned that the temperature is high, and the diazonium salt is prone to hydrolysis, and the reaction with sodium nitrite is Exothermic, so it is necessary to strictly control the temperature of the reaction solution during the reaction to ensure that the temperature is not too high, so the temperature requirements are higher

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