A method for preparing tiamectin

Abstract

The invention discloses a method for preparing tiamectin. The method comprises the following steps in turn: using tiamectin thiocyanate as a raw material, reacting with N,N-diethylethylamine-2-halide under the condition of sodium sulfide to obtain the tiamectin crude product, Then obtain tiamectin fine product by recrystallization. The invention proposes a set of brand-new reaction conditions, the raw materials used have mature technology, sufficient market supply and wide sources, mild reaction conditions, simple process and reduced production cost.

Description

technical field [0001] The invention relates to a preparation method of veterinary antibiotics, in particular to a method for preparing tiamectin. Background technique [0002] Tiamulin is a diterpene antibiotic for livestock and poultry. It was first proposed by Kavangh in Australia in 1951 and extensively studied in the 1960s. It is one of the top ten veterinary antibiotics in the world. As a bacteriostatic antibiotic, tiamectin has an antibacterial mechanism that binds to the 50s subunit of bacterial ribosomes to inhibit bacterial protein synthesis. It also has a bactericidal effect on sensitive bacteria at very high concentrations. [0003] At present, the final synthesis step of tiamulin generally uses 2-diethylaminoethanethiol and protected pleuromutilin as main raw materials, but the compound itself of 2-diethylaminoethanethiol has relatively high toxicity. At the same time, it is also the main raw material for the synthesis of nitrogen mustard, a chemical weapon. ...

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Problems solved by technology

[0003] At present, the final synthesis step of tiamulin generally uses 2-diethylaminoethanethiol and protected pleuromutilin as main raw materials, but the compound itself of 2-diethylaminoethanethiol has relatively high toxicity. At the same time, it is also the main raw material for the synthesis of chemical weapon nitrogen mustard. While the country strictly controls it, it has a greater impact on the safety of production, which restricts the market size and cost control of this product.

[0004] Although the method disclosed in CN104892476A avoids the use of diethylaminoethanethiol, the reaction raw material compound D it uses is a mercapto derivative, which not only has an unpleasant smell, but also causes a bad working environment for workers, and the mercapto compound The stability is poor, and persulfur compounds (R-S-S-R) are produced during storage, which are difficult to refine and remove in the subsequent product preparation process and pollute the finished product

In addition, in the process of preparing product A by heating compound D under the condition of strong alkali sodium hydroxide, due to the use of strong alkali, intermediate D is more likely to form persulfur compound (R-S-S-R) under alkaline and heating conditions, which seriously affects the yield of product A. efficiency and quality, in addition, under strong alkali heating conditions, there are ester groups in both intermediate D and product A molecules, and partial ester hydrolysis will occur under these reaction conditions, thereby seriously affecting the yield and quality of the prepared product A

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