阅读说明：本技术 医药级二硫化四乙基秋兰姆的环保安全高效制备工艺 (The efficient preparation process of the Environmental Safety of pharmaceutical grade tetraethylthiuram disulfide ) 是由 李志安 于 2018-05-25 设计创作，主要内容包括：本发明公开了一种医药级二硫化四乙基秋兰姆的环保安全高效制备工艺,采用叔丁醇构建反应体系,以二乙胺和二硫化碳为反应原料通过缩合氧化反应制备医药级目标产品,反应母液和/或产品洗滤液通过盐析操作回收叔丁醇循环使用,实现医药级二硫化四乙基秋兰姆的环保安全高效制备。本发明的制备工艺能够满足医药级别的安全性要求,同时具有环保、低成本、高效率的特点。(The invention discloses a kind of efficient preparation processes of Environmental Safety of pharmaceutical grade tetraethylthiuram disulfide, reaction system is constructed using the tert-butyl alcohol, pharmaceutical grade target product is prepared by condensation oxidation reaction using diethylamine and carbon disulfide as reaction raw materials, reaction mother liquor and/or product washing filtrate are recycled by the operation recycling tert-butyl alcohol of saltouing, and realize that the Environmental Safety of pharmaceutical grade tetraethylthiuram disulfide is efficiently prepared.Preparation process of the invention can satisfy the other security requirement of pharmaceutical grade, while have the characteristics that environmentally friendly, inexpensive, efficient.)

1. the efficient preparation process of the Environmental Safety of pharmaceutical grade tetraethylthiuram disulfide, it is characterised in that: use tert-butyl alcohol structure Reaction system is built, pharmaceutical grade target product is prepared by condensation oxidation reaction using diethylamine and carbon disulfide as reaction raw materials, instead It answers mother liquor and/or product washing filtrate to be recycled by the operation recycling tert-butyl alcohol of saltouing, realizes the pharmaceutical grade tetraethyl base autumn The Environmental Safety of blue nurse is efficiently prepared.

2. the efficient process of preparing of Environmental Safety of pharmaceutical grade tetraethylthiuram disulfide according to claim 1, It is characterized by: the operation of saltouing is using potassium carbonate and/or potassium fluoride.

3. the efficient process of preparing of Environmental Safety of pharmaceutical grade tetraethylthiuram disulfide according to claim 2, It is characterized by: the operation of saltouing is using potassium carbonate.

4. the efficient process of preparing of Environmental Safety of pharmaceutical grade tetraethylthiuram disulfide according to claim 3, It is characterized by: brine strength is not less than 57% w/v when being saltoutd using potassium carbonate.

5. the efficient process of preparing of Environmental Safety of pharmaceutical grade tetraethylthiuram disulfide according to claim 1, It is characterized by: the weight fraction ratio of the tert-butyl alcohol and the diethylamine is (1000-1800): (380-480).

6. the efficient process of preparing of Environmental Safety of pharmaceutical grade tetraethylthiuram disulfide according to claim 5, It is characterized by: the weight fraction ratio of the tert-butyl alcohol and the diethylamine is (1200-1600): (400-450).

7. the efficient process of preparing of Environmental Safety of pharmaceutical grade tetraethylthiuram disulfide according to claim 1, It is characterized by: being put in proportion into the tert-butyl alcohol and diethylamine into reaction vessel first, carbon disulfide is then added while stirring； When adding carbon disulfide to reaction system, pass through control adding speed and control cooling water amount, it is ensured that the temperature of reaction system Degree is between 30-40 DEG C.

8. the efficient process of preparing of Environmental Safety of pharmaceutical grade tetraethylthiuram disulfide according to claim 1, It is characterized by: described carry out step condensation oxidation instead to diethylamine and carbon disulfide by adding hydrogen peroxide in the reaction system It answers；When adding hydrogen peroxide in the reaction system, pass through control adding speed and control cooling water amount, it is ensured that reaction system Temperature is not higher than 40 DEG C.

9. the efficient process of preparing of Environmental Safety of pharmaceutical grade tetraethylthiuram disulfide according to claim 1, It is characterized by: reaction terminates to obtain reaction mother liquor after filtration is handled, the faint yellow granular solids product of filtering gained is rushed with water It washes to obtain washing filtrate, reaction mother liquor and washing filtrate is merged into addition solid carbonic acid potassium and carry out operation of saltouing, tertiary fourth after static liquid separation Alcohol organic layer is recycled, and water layer recycles potassium carbonate through processing.

10. the efficient process of preparing of Environmental Safety of pharmaceutical grade tetraethylthiuram disulfide according to claim 9, It is characterized by: the gained tert-butyl alcohol is recycled after supplementing tret after saltouing.

Technical field

The present invention relates to technical field of chemical synthesis, especially a kind of environmental protection of tetraethylthiuram disulfide, safety, height Effect and inexpensive preparation process.

Background technique

Tetraethylthiuram disulfide belongs to thiurams rubber accelerator, and abridge TETD, structural formula are as follows:, molecular formula: C10H20N2S4, molecular weight: 296.55, fusing point: 69-71 DEG C.Such promotor incipient scorch Fastly, curingprocess rate is also fast, belongs to ultra-rapid vulcanization promotor；Though vulcanizing flat small, tensile strength can be obtained, stretching strength is high Vulcanized rubber.Therefore it can be used as helping vulcanization accelerator or without sulfur vulcanizing agent, also can be used as low unsaturated rubber for polydiene The vulcanization accelerator of glue.

On the other hand, tetraethylthiuram disulfide is taken in already to states' pharmacopeia such as the U.S., Britain and Japan, takes this medicine Period, once drink i.e. there is characteristic abstinence from alcohol to the disulfiram (being commercially referred to as " disulfiram ") for treating alcohol dependence Reaction of Salmon-Saxl, it is expected to establish the conditioning to wine and detest reflection, disulfiram is still the ancillary drug for treating mental disorder so far. On December 7th, 2017, International Academic periodical " nature " (Nature) have delivered the cancer in cancer association, Denmark research center online The newest fruits of biologist Jiri Bartek et al., this from Denmark, Czech and the U.S., which cooperates team for the first time, confirmed The antitumaous effect of disulfiram.

Working system generally uses chlorine method or sodium nitrite method both at home and abroad at present, and technics comparing is mature but there are serious peaces Full environmental issue.In addition there are also electrolysis method and oxygen methods, and electrolysis method complex process, energy consumption are higher, oxygen method risk is too big. Peroxide passivation is first condensed under the conditions of sodium hydroxide with diethylamine and carbon disulfide, generates diethyl-dithio amidocarbonic acid sodium, Sulfuric acid is added dropwise afterwards to be aoxidized with hydrogen peroxide etc. simultaneously, through cooling, filtering be dry, pulverize.Peroxide passivation is compared with above method It is the developing direction for synthesizing tetraethylthiuram disulfide from now on stronger advantage.This production technology comparative maturity, but disappear A large amount of sodium hydroxides and sulfuric acid are consumed, process is generated with a large amount of high-salt wastewaters, and the product norm quota of consumption is higher, and it is tight that there is the three wastes Weight, exerts heavy pressures on to environmental protection.Improved method is to replace water using organic solvents such as Yi Chun ﹑ isopropanols, does not use hydrogen-oxygen Change sodium and sulfuric acid, no brine waste generates, therefore only simple washing can obtain high-grade TETD product, product ash content Few, appearance uniform, quality is stablized.But in order to reduce the method that cost uses recycling design isopropanol, due to recycling organic solvent Mass energy is consumed, while tetraethylthiuram disulfide has certain solubility in isopropanol, causes many solid wastes raw At keeping cost still higher.Lian Qianrong (Chinese patent CN1316422) makees solvent with isopropanol, has synthesized tetraethyl base Thiuram has synthesized in order to reduce cost and need to be recovered by distillation isopropanol, herein due to using isopropanol organic solvent In the process, since product section is dissolved in isopropanol, to make to be distilled to recover viscous containing a large amount of black in the mother liquor of isopropanol Thick liquid, chromatography show the mixtures of impurities generated including tetraethylthiuram disulfide and reaction, and kettle is residual after distillation In a large amount of solid wastes generate, processing solid waste increases the cost of production product, while recycling isopropanol and consuming superheated steam, and increasing Product cost is added, distillation organic solvent also has security risk, and the usual solvents rate of recovery is below 90%.But it is directed to For the preparation of pharma grade product, using strong acid production isopropanol in a kind of carcinogenic substance inventory, isopropanol it is clear in 3 class carcinogenic substances Dan Zhong inevitably also limits isopropanol and does solvent production pharmaceutical grade curing four in finished product with the presence of isopropanol solvent Ethyl thiuram technique.

Summary of the invention

The technical problem to be solved by the present invention is to overcome various deficiencies of the prior art, provide a kind of pharmaceutical grade curing four The efficient preparation process of the Environmental Safety of ethyl thiuram has the characteristics that safe and environment-friendly, inexpensive, efficient.

In order to solve the above technical problems, the technical solution used in the present invention is as follows.

The efficient preparation process of the Environmental Safety of pharmaceutical grade tetraethylthiuram disulfide constructs reactant using the tert-butyl alcohol System, which is reaction raw materials using diethylamine and carbon disulfide, prepares pharmaceutical grade target product by condensation oxidation reaction, reaction mother liquor with/ Or product washing filtrate is recycled by the operation recycling tert-butyl alcohol of saltouing, and realizes the environmental protection of pharmaceutical grade tetraethylthiuram disulfide Safe and efficient preparation.

As a preferred technical solution of the present invention, the operation of saltouing is using potassium carbonate and/or potassium fluoride.

As a preferred technical solution of the present invention, the operation of saltouing is using potassium carbonate.

As a preferred technical solution of the present invention, when being saltoutd using potassium carbonate, brine strength is not less than 57% w/v。

As a preferred technical solution of the present invention, the weight fraction ratio of the tert-butyl alcohol and the diethylamine is (1000-1800): (380-480).

As a preferred technical solution of the present invention, the weight fraction ratio of the tert-butyl alcohol and the diethylamine is (1200-1600): (400-450).

As a preferred technical solution of the present invention, the tert-butyl alcohol and diethyl are put in proportion into reaction vessel first Then amine adds carbon disulfide while stirring；When adding carbon disulfide to reaction system, pass through control adding speed and control Cooling water amount, it is ensured that the temperature of reaction system is between 30-40 DEG C.

As a preferred technical solution of the present invention, it is described by add in the reaction system hydrogen peroxide to diethylamine and Carbon disulfide carries out a step and is condensed oxidation reaction；When adding hydrogen peroxide in the reaction system, pass through control adding speed and control Cooling water amount processed, it is ensured that the temperature of reaction system is not higher than 40 DEG C.

As a preferred technical solution of the present invention, reaction terminates to obtain reaction mother liquor after filtration is handled, and filters institute Faint yellow granular solids product is rinsed with water to obtain washing filtrate, reaction mother liquor and washing filtrate are merged be added solid carbonic acid potassium into Capable operation of saltouing, tert-butyl alcohol organic layer is recycled after static liquid separation, and water layer recycles potassium carbonate through processing.

As a preferred technical solution of the present invention, the gained tert-butyl alcohol recycles after supplementing tret and makes after saltouing With.

The beneficial effects of adopting the technical scheme are that

The tetraethylthiuram disulfide product prepared using method of the invention, can reach U.S.'s medicine by simply recrystallizing Allusion quotation USP40-NF35 version index (69-72 DEG C of fusing point, content 98-102%).

Reparation technology non-environmental-pollution of the invention and good product quality, make solvent using the tert-butyl alcohol and not only meet medicine The security requirement of product, and in preparation process, it can be recycled after simple liquid separation can only being needed without distillation, There is no the generation of the solid waste of high disposal cost, potassium carbonate can be reused by centralized recovery, achieve the purpose that energy-saving and emission-reduction, Greatly reduce the production cost of tetraethylthiuram disulfide.

The present invention also has a large amount of water can be in dropwise addition process due to there is water generation in the synthesis process, and in hydrogen peroxide In enter in reaction solution, after reaction, filtered mother liquor contains the tert-butyl alcohol and water, we are by being added the salts such as potassium carbonate Substance achievees the purpose that make water to separate, and the organic layer after liquid separation directly carries out next secondary response, by being repeated 10 times above point From with reuse organic solvent, no matter product Nei Zhi Liang ﹑ appearance and yield have repeatability.

Specific embodiment

The present invention is described in detail in following embodiment.Various raw materials used in the present invention and items of equipment are conventional city Product is sold, can be bought and be directly obtained by market.