Preparation method of sulfadoxine

Abstract

A preparation method of sulfadoxine belongs to the field of sulfanilamide antimicrobial drug preparation. Cyclization reaction comprises the following steps of: firstly pouring a sodium methoxide solution into a reactive pan, then successively adding methanamide and methyl ethyl methoxymalonate, keeping warm, recovering methanol, cooling for crystallization, drying by centrifugation, discharging,and drying to obtain 5-methoxy-4,6-disodium dihydroxypyrimidine; Chlorination reaction comprises the following steps of: firstly putting phosphorus oxychloride into a reaction vessel for heating, adding 5-methoxy-4,6-disodium dihydroxypyrimidine into the reaction vessel to react, decompressing and recovering phosphorus oxychloride until the material is dry, cooling, adding trichloro ethylene withuniformly stirring, putting into a hydrolysis pan for hydrolyzation, collecting a trichloro ethylene layer after standing and delaminating, followed by a neutralization reaction, controlling pH value, washing, removing a water layer, recovering trichloro ethylene, and releasing crystals to obtain 5-methoxy-4,6-dichloropyrimidine. The preparation method provided by the invention can be used to guarantee the product purity, prolong the service life of equipment, avoid the damage to the environment and human body, reduce emission, and save energy, and accords with foreign pharmacopoeia standard requirements.

Description

technical field [0001] The invention belongs to the technical field of preparation of sulfonamide antibacterial drugs, and in particular relates to a preparation method of sulfadoxine. Background technique [0002] The chemical name of sulfadoxine (SDM) is: 4-(p-aminosulfonamide) 5,6-dimethoxypyrimidine; the English name is: Sulfadoxine; the Latin name is: Sulphamethoxinum or Sulfadimoxine; the molecular formula is C 12 h 14 o 4 N 4 S; molecular weight 310.33. [0003] Sulfadoxine, also known as Zhouxiao sulfonamide, sulfa-o-dimethoxine or 4-sulfa-5,6-dimethoxypyrimidine, is a white or off-white crystalline powder with a slightly bitter taste, odorless, and gradually changes color when exposed to light. Slightly soluble in water, methanol and ethanol, insoluble in ether, soluble in sodium hydroxide and dilute inorganic acids, belonging to sulfonamide antibacterial drugs. Sulfadoxine has the characteristics of long curative effect and low toxicity. It can tre...

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Problems solved by technology

[0008] According to the analysis of the applicant for many years, one of the reasons for the above-mentioned problem (the related substances are high impurities) is that the product is highly viscous due to the application of the cyclization reaction mother liquor, which makes the impurities wrapped and difficult to separate, and difficult to crystallize and dehydrate. Dry, it is easy to bring impurities into the finished product, and it must be precipitated under acidic conditions, and the acidic environment will cause corrosion to equipment such as pipelines, centrifuges and drying rooms; , N-xylidine", which not only pollutes the environment, but also is highly toxic and harmful to the human body, and the catalyst N, N-xylidine used must be recycled and applied mechanically, resulting in a dark red appearance of the product quality, which is not It is beneficial to the next reaction and seriously affects the quality of the final product