Method for refining pharmaceutical dibenzothiazyl disulfide

Abstract

The invention provides a method for refining pharmaceutical dibenzothiazyl disulfide (DM). In the method, a crude product DM, an ethyl acetate solvent and an ethanol solvent are used as the raw materials. The method comprises the following steps of: mixing ethyl acetate and ethanol according to the volume ratio of 1: (4 to 8); adding the crude product DM into the mixture with stirring, wherein the mass ratio of the crude product DM to ethyl acetate is 1.00: (0.35 to 0.55); controlling a temperature in the range of 65 to 75 DEG C so that the crude product DM is totally dissolved, then adding 0.1 to 5 percent of activated carbon into solution, stirring the solution for 1 to 2 hours, carrying out extraction filtration to separate out the activated carbon, cooling mother liquor to the temperature of 0 to 30 DEG C and separating out DM crystals; and stopping stirring, carrying out vacuum extraction filtration, washing by mixed solution with the volume ratio of ethyl acetate to ethanol of 1: (4 to 8) to obtain wet refined DM, drying the wet refined DM to obtain white acicular crystals, i.e. the pharmaceutical DM. The crude product DM has the initial melting point of lower than or equal to 176 DEG C and purity of lower than or equal to 98 percent and contains impurities of resin, M (2-mercaptobenzothiazole) and the like. Due to the adoption of the method, the pharmaceutical DM can be produced greenly, efficiently and safely. The obtained pharmaceutical DM product has high quality and low integrated cost, is obviously superior to the product obtained by the existing refining process and can meet the requirement of the international high-end market.

Description

1. Technical field [0001] The invention belongs to a method for refining a pharmaceutical intermediate, in particular to a method for refining a pharmaceutical intermediate dibenzothiazole disulfide. 2. Background technology [0002] Dibenzothiazole disulfide (also known as DM) is a good medium-speed vulcanization accelerator, which is widely used in the rubber industry because of its vulcanization critical temperature and higher operating safety than M (2-mercaptobenzothiazole) Among them, at present, some well-known rubber processing enterprises at home and abroad have a growing demand for high-quality DM. In the field of modern pharmaceutical synthesis, DM, as a new type of pharmaceutical intermediate, replaces PyS (2-thiol pyrimidine) in the synthesis of β-lactam, thus successfully synthesizing the target product β-lactam. β-lactam antibiotics have the advantages of high efficiency, low toxicity, and broad spectrum, and are the mainstream varieties of antibiotics at hom...

AI Technical Summary

Problems solved by technology

However, the biggest problem of this method is that the solubility of toluene to DM is small, so that the batch output is low, and the consumption of toluene is high. The production of 1 ton of refined DM consumes about 700 kg of toluene, up to 1 ton. Therefore, the toluene method The cost of refining pharmaceutical grade DM is high, but the quality is often not ideal

In order to make up for the shortcomings of the toluene method, some domestic DM manufacturers have proposed to use tetrachlorethylene instead of toluene as a solvent to refine pharmaceutical grade DM, and the product quality and batch yield have been improved. ℃, so the energy consumption is large, and the solvent itself has a relatively high boiling point (b.p.=121.2 ℃), which makes the recovery cost of the solvent relatively high. Operators bring potential hazards. Using tetrachlorethylene as a solvent will carry chloride ions in the purified pharmaceutical grade DM, which will increase the allergy of the final drug

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