Preparation method of sulfadoxine

Abstract

The invention relates to a preparation method of sulfadoxine, which comprises the following steps: (1) reacting methyl methoxyacetate and excessive diethyl oxalate to generate 3-methoxy-2-oxo-methylethyl succinate, and decarbonylating to obtain 2-methoxy-methylethyl malonate; (2) reacting the 2-methoxy-methylethyl malonate and formamide to generate a cyclocompound; (3) carrying out chlorination reaction; (4) carrying out condensation reaction; and (5) carrying out methoxylation reaction. The purity of the 2-methoxy-methylethyl malonate obtained in the step (1) is strictly controlled, and the cyclocompound in the step (2) is controlled to exist in the form of anhydrous hydroxy sodium salt; in the step (3), no catalyst, including N,N-dimethylaniline, is used; and in the step (5), solid sodium hydroxide is substituted for sodium methoxide solution. The invention is easy to operate, has the advantage of high product quality, greatly lowers the production cost, and has obvious economic benefit and environmental benefit.

Description

technical field [0001] The invention belongs to the technical field of preparation of sulfonamides, in particular to a method for preparing sulfonamides. Background technique [0002] Sulfonamide, the chemical name is 4-(p-aminobenzenesulfonyl)-5,6-dimethoxypyrimidine, and its structural formula is as follows: [0003] [0004] Sulfonamide can be used clinically to treat general inflammation, such as upper respiratory tract infection tonsillitis, bacillary dysentery enteritis, skin infection, etc. It can also be used in combination with other medicines to treat pulmonary tuberculosis and lymphatic tuberculosis; it also has a certain effect on leprosy (madness). It can also treat malaria. In addition, sulfonamide can also be used as a preventive drug for rheumatic venereal diseases. When used for the above purposes, sulfonamide has the characteristics of long curative effect and low toxicity. [0005] Sulfonamide has gone through several generations of research and devel...

AI Technical Summary

Problems solved by technology

[0017] 1, step (1) Kjeldahl reaction makes raw material carry out in sodium ethylate / ethanol solution, and after decarbonylation, removes low boiler (comprising unreacted raw material, intermediate A3 etc.) by first fractional distillation, then fractional distillation obtains intermediate 2-methoxy-methyl ethyl malonate, the purity of the method's gained 2-methoxy-methyl ethyl malonate is lower (generally lower than 92%), which is unfavorable for subsequent reactions, especially in large During the trial production, the quality and yield of Zhouxiao Sulfa products were affected

[0018] 2, step (2) ring closure reaction gained ring compound quality is poor: traditional method makes ring compound separate out under acidic condition, gained ring compound (A5 ) can exist in two forms of hydroxy substance and hydroxy sodium salt. Because the hydroxy substance has a certain solubility in water, the mother liquor of the cyclization reaction must be applied mechanically repeatedly in the traditional process, and the salt concentration in the mother liquor is equivalent due to the application of the mother liquor. large, resulting in poor quality of cyclic compounds (nearly 40% of which are salt), sticky materials, difficult to dry and other shortcomings; and the acidic environment has corrosion effects on equipment pipes, centrifuges, and drying rooms, and the production site is not easy clean

[0019] 3, the preparation of step (3) chloride (A6) must adopt N,N-dimethylaniline as catalyst, so that the recovery and mechanical application of the catalyst produce a large In addition, the quality of the chloride is dark red, which is obviously unfavorable to the next condensation reaction. The reddish color of the condensation reaction will directly affect the yellowish color of the finished product (quality)

[0020] 4, step (5) methoxide reaction adopts sodium methylate / methanol solution, in post-treatment stage, recovery methanol is not easy, and the longer heating time of recovery stage may As a result, the material at the bottom of the (product) reactor is heated unevenly, causing local overheating, resulting in decomposition, and the color of the crude product is not ideal

[0021] In summary, the total yield of the traditional method is only about 65%, the production cost is relatively high, and the quality of the product needs to be further improved

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