Preparation method of sulfasalazine

Abstract

The invention relates to the technical field of sulfasal, in particular to a synthesis technology of environment-friendly sulfasalazine. A nitroso compound is condensed with ammonia to obtain the sulfasalazine. After adoption of the technical scheme, raw materials are cheap, easy to obtain and stable, and production of unstable diazonium salt is avoided, so that production of a byproduct is avoided; after adoption of the technical scheme, the product sulfasalazine can be directly separated out through simple treatment, so that the reaction yield is high.

Description

technical field [0001] The invention relates to the technical field of sulfasalazine, in particular to a synthesis method of sulfasalazine. Background technique [0002] Sulfasalazine (SASP), also known as 5-[p-(2-pyridinesulfamoyl)benzene]azosalicylic acid. Molecular formula is C18H14N4O5S, molecular weight: 398.39. Its molecular structural formula is as follows: [0003] [0004] SASP is mainly used for the treatment of non-specific ulcerative colitis. This product has a special affinity for connective tissue and plays a therapeutic role by releasing sulfapyridine and 5-aminosalicylic acid in the intestinal wall. It is also used clinically for the treatment of rheumatic joints inflammation. Although this product is an old product, the market demand is still very large, especially its quality requirements are getting higher and higher. [0005] In the prior art, there are few disclosures on its preparation method. British Patent GB 11296655 discloses a synthetic met...

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Problems solved by technology

[0006] The starting material 4-(4-acetoxy group-3-carbonylmethoxyphenyl azo)-benzenesulfonyl chloride of this method is not commercially available at present and the comparatively difficult method of synthesis, and source is less; In addition, this method is owing to existence Hydrolysis reaction, its yield and product purity are not ideal

[0007] At present, the synthesis of sulfasalazine mainly uses sulfapyridine as a raw material, sodium nitrite as a diazotization reagent, and is obtained by coupling with salicylic acid after a diazotization reaction in an aqueous phase. For example, refer to the preparation provided in WO2002018330 Method; also have isoamyl nitrite as diazotization reagent, and reaction is carried out in organic solvent, for example can refer to the method that provides in Apoptosis2005,10 (3), 481-491, but present synthetic method all exists reaction time long , the local reaction is overheated, the reaction temperature needs to be strictly controlled, the diazonium salt is prone to hydrolysis and other problems, and by-products are produced, resulting in a 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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