A kind of preparation method of pharmaceutical grade dibenzothiazole disulfide

Abstract

The invention discloses a preparation method of pharmaceutical grade dibenzothiazole disulfide, comprising the following steps: step 1, adding crude product 2-mercaptobenzothiazole into a reactor, and using a mixed solvent composed of alcohol solvent and water to dissolve Step 2, adding reducing agent in the reactor to react colored substances; Step 3, adding adsorbent in the reactor to filter out insoluble matter; Step 4, adding dispersant ethanolamine in the reactor, adding hydrogen peroxide dropwise, and 2- Mercaptobenzothiazole is oxidized to dibenzothiazole disulfide, cooled to grow crystals, filtered, and dried to obtain the product; step 5, take half of the mother liquor produced and use it in the next batch, and add solvent according to the component water and the amount of water. The present invention realizes the "one-pot method" to prepare fine-quality DM available for pharmaceutical grades with crude M. The method of the present invention is low in cost, and high-purity fine-quality DM suitable for medical use can be obtained, and it is also environmentally friendly; the present invention is suitable for preparing pharmaceutical-grade High-purity boutique DM used.

Description

technical field [0001] The invention belongs to the field of synthesis of pharmaceutical intermediates, and in particular relates to a preparation method of high-purity fine dibenzothiazole disulfide (DM). Background technique [0002] DM, the chemical name is: dibenzothiazole disulfide, the chemical structure is as follows: [0003] [0004] Product performance and use [0005] Vulcanization accelerator DM is light yellow crystal, slightly toxic, odorless and slightly bitter. It is a widely used general-purpose thiazole accelerator and a very important intermediate in drug synthesis. As a general-purpose vulcanization accelerator for natural rubber, synthetic rubber and reclaimed rubber, it can quickly vulcanize rubber under normal temperature, and the vulcanization curve is relatively flat. DM itself is easy to disperse in the rubber compound and does not pollute. ), when the temperature is higher than 140 °C, the activity is enhanced, there is a significant after-eff...

AI Technical Summary

Problems solved by technology

[0008] Path 1 produces a large amount of waste salt, and the cost of solid-liquid treatment is high. Path 2 has problems such as toxic solvents used, difficult to recycle, and high energy consumption for the reaction; such as:

[0009] 1) CN1876698A, a kind of production method of rubber vulcanization accelerator is provided, and this method is that thick M is dissolved into M-Na salt with alkaline sodium solution, and the mixed solution of hydrogen peroxide and sulfuric acid is added dropwise that M is oxidized into DM. The initial melting point of the prepared DM is only 173°C, and at the same time, a large amount of sodium sulfate waste salt is produced, and the solid waste treatment is complicated

[0010] 2) CN101899019A, provides a preparation method of DM as a medical raw material, the method is to dissolve crude M with alkaline sodium solution, add isopropanol solvent, drop the mixture of hydrogen peroxide and sulfuric acid to oxidize M into DM, the method The initial melting point of the prepared DM can reach 178°C, but this process also has the problem of producing a large amount of waste solids and difficult recycling

The feature of this method is to use a catalyst that improves oxidation, but this process needs to use high-quality M, otherwise the product color and even content cannot be guaranteed

[0013] 5) CN107365281A, provides a kind of preparation method of medical raw material DM, this method is to dissolve M in ammonia water, add urotropine and 1-amino-2 nafine-4-sulfonic acid as catalyst, drop hydrogen peroxide to oxidize M The crude DM is made, and the crude DM is refined into medical DM by heating up the crude DM with acetone or toluene and then cooling down to crystallize. The melting point of the product prepared by this method is only 173°C-176°C, which is low in melting point. Low, while using the more dangerous solvents of acetone and toluene

2. Dissolve the crude M with acetone, add water to precipitate after decolorization, this can not remove the colored groups in the crude M, and the prepared refined M is still yellow instead of white (the acid-base method is white), and dissolve the crude M M needs at least 5 times the amount of solvent, and add water to reverse the precipitation of refined M, the amount of water added is at least 10 times that of M, the amount of waste water is huge, difficult to handle, and acetone is easy to poison, and the price is relatively high

[0015] To prepare DM from refined M, generally use iron sulfate, copper sulfate, cobalt sulfate, etc. It is difficult to deal with ionic wastewater; it is also reported that triethylbenzyl ammonium chloride is used as a catalyst, but its price is relatively expensive

[0016] Generally speaking, none of the existing processes can prepare high-quality DM in one pot, and the product obtained by preparing refined M by acid-base method is better, but M cannot be further oxidized to DM in the aqueous phase; the method of refining M with a solvent cannot be removed Colored group, poor decolorization effect, the prepared DM is light yellow, which affects the color of the downstream preparation of AE active ester

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