Applications of dimethyl sulfoxide_industrial additives

Application background and overview of dimethyl sulfoxide

Dimethylsulfoxide (DMSO) is a transparent liquid containing sulfur compounds. It is widely used in medicine, petroleum, chemical industry, metallurgy, and electronics. , coatings and polymer materials and other fields. In recent years, its applications in the electronic industry and carbon fiber fields have increased, so the prospects for application and development are very broad. Because it has a special solvent effect for chemical reactions and can dissolve many substances, it has always been called a “universal solvent”. It can absorb more than 70% of its own weight of moisture when the relative humidity is 65% at 20°C, and its chemical properties are stable below 140°C.

Dimethyl sulfoxide can penetrate dissolved drugs into the body through skin application, and is harmless to the body. It can replace oral administration or injection, so it is also called “universal” medicine”. Since dimethyl sulfoxide has no mutagenicity found in experiments such as the Ames method, it is widely used as a non-genotoxic organic solvent. However, studies in recent years have shown that dimethyl sulfoxide has serious toxic effects and interacts with protein hydrophobic groups, leading to protein denaturation, vascular toxicity, liver and kidney toxicity, etc.

Application physical and chemical properties and structure of dimethyl sulfoxide

Dimethyl sulfoxide is colorless and odorless at room temperature, has a high boiling point, is highly hygroscopic, has a slightly bitter taste, and can dissolve various polar organic gases other than alkanes. , liquid or polymer, which is an aprotic polar solvent. Dimethyl sulfoxide is an extremely important aprotic polar solvent that is soluble in both water and organic solvents. It is a good penetration enhancer in cell biology research. It has also been reported that dimethyl sulfoxide can cause an increase in extracellular sodium, potassium and calcium concentrations, and that dimethyl sulfoxide has many functions in aspects such as ion transporters and ion pumps.

2 Biotransformation of dimethyl sulfoxide The metabolites of dimethyl sulfoxide are dimethyl sulfone (Dimethylsulfone, dimethyl sulfoxide 2) and dimethyl sulfoxide Dimethylsulfide (DMS) is present in urine and feces. DMS has a garlic or oyster smell and is mainly excreted through the kidneys and excreted in the urine without renal accumulation. Dimethyl sulfoxide, a metabolite of dimethyl sulfoxide, is present in small amounts in human urine; DMS is also found naturally in plants, atmosphere, lakes and oceans. Both metabolites (dimethyl sulfoxide, DMS) are easily excreted from the human body.

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Applications of dimethyl sulfoxide

1. Synthesis of methyl mercaptan and dimethyl sulfoxide to produce dimethyl disulfide

Methyl mercaptan reacts with dimethyl sulfoxide and catalyst under corresponding temperature and pressure conditions to generate dimethyl disulfide. The chemical reaction mechanism is as follows: 2CH3SH+(CH3)2SO=(CH3)2S+(CH3)2S2+H2O. Pass methyl mercaptan and dimethyl sulfoxide into the reactor at a molar ratio of 2:0.95. In the presence of alumina catalyst The synthesis reaction is carried out at a reaction temperature of 250°C and a reaction pressure of 0.3MPa. The reaction products are dimethyl disulfide, dimethyl sulfide and water. After condensation and cooling, the reaction products are left to stand and separated to obtain crude dimethyl disulfide. Sulfur is then distilled to obtain qualified dimethyl disulfide finished product.

2. Preparation of dimethyl sulfone from dimethyl sulfoxide

At a temperature of 60°C and a pressure of 0.5MPa, use ozone (15% volume ratio, the rest is oxygen) as the oxidant, and combine dimethyl sulfoxide, Ozone and solvent acetone react at a molar ratio of 1:1:1. The results of the reaction for 2 hours are as follows: dimethyl sulfoxide conversion rate is 74%; ozone effective utilization rate is 76%; dimethyl sulfone selectivity is 99%.

Dimethyl sulfoxide, as an excellent solvent, is widely used in petroleum, chemical, pharmaceutical, electronics, synthetic fibers, plastics, printing and dyeing and other industries, especially in the following industries: With the development of the production of new quinolone antibiotics such as norfloxacin and flufenac and intermediates such as fluorochloroaniline in the pharmaceutical industry, the demand for DM-SO is increasing year by year.

(1) Pharmaceutical industry

Dimethyl sulfoxide is widely used as a reaction solvent in the synthesis of medicines and pharmaceutical intermediates. For example, 3,4-dichloronitrobenzene and potassium fluoride are reacted in dimethyl sulfoxide to prepare fluorochloroaniline. The methylpyridine intermediate is used to synthesize the third-generation quinolone antibacterial drug-norfloxacin ( An important raw material of norfloxacin) and ciprofloxacin. Dimethyl sulfoxide is also used in the synthesis of 2,3,4,-trifluoronitrobenzene. This intermediate can be used to synthesize the third-generation quinolone antibacterial drugs–ofloxacin (flurazinic acid), fluorine Synthesis of loxacin (doflufloxacin), lomefloxacin hydrochloride, and rulfloxacin hydrochloride.

In addition, dimethyl sulfoxide has been used in the synthesis of levamisole inositol hydroxylate, levamisole phosphate, berberine, sucrose fatty acid polyesters and the extraction of traditional Chinese medicine. get applied. Dimethyl sulfoxide itself has anti-inflammatory and analgesic effects, promotes blood circulation and wound healing, has diuretic and sedative effects, and can increase drug absorption and improve efficacy. At present, external medicines such as Guyouling, athlete’s foot medicine, and hydrosone ointment produced in my country and external preparations in major hospitals have been widely used.

At present, dimethyl sulfoxide is mainly used in the pharmaceutical industry in my country for the synthesis of pharmaceutical intermediates fluorochloroaniline and 2,3,4,-trifluoronitrobenzene. , In addition, drug synthesis, traditional Chinese medicine extraction, and external medicines and ointments also consume a certain amount of dimethyl sulfoxide. Norfloxacin, ciprofloxacin and flufenac are the new generation of fluoroquinolone synthetic antibacterial drugs. They have the characteristics of broad spectrum, high efficiency, low side effects and low price. In recent years, domestic production has developed very rapidly. , so the demand for the solvent dimethyl sulfoxide is also growing.

Dimethylsulfonate is also consumed in the synthesis of fluoxinic acid, polyfluoropenic acid and the intermediate-2,3,4,-trifluoronitrobenzene. Sulfone solvent; the synthesis of berberine, levamisole, mebendazole and other drugs requires about the consumption of dimethyl sulfoxide. At present, the total demand for dimethyl sulfoxide in the pharmaceutical industry is about 3,500 tons. It is expected that the demand for dimethyl sulfoxide in the pharmaceutical industry will grow steadily in the future, and the demand will reach about 4,500 tons in 2005.

Preparation for application of dimethyl sulfoxide

Add a certain amount of dimethyl sulfide and acetone into a 1000mL four-neck flask, install a thermometer and a stirrer, and use a constant pressure dropping funnel to Drop in hydrogen peroxide at a high speed, and control a certain reaction temperature and time to carry out the reaction while stirring and cooling the four-necked flask with water in the kettle jacket. When the dropwise addition of hydrogen peroxide is completed, continue stirring until the reaction temperature drops below 10°C. Stop stirring.

Move the obtained reaction solution into a 1000mL single-neck flask for simple distillation (use a capillary tube instead of zeolite to prevent bumping), condense and reflux with frozen brine, and 35 The ~40°C fraction (for dimethyl sulfide) is collected and returned to the original reaction vessel for oxidation, the 55-60°C fraction (for acetone recovery) is collected for recycling, and the 98-102°C water fraction is distilled Out, a viscous oily transparent liquid is obtained. After cooling the liquid, perform vacuum distillation under vacuum, collect the 100-105°C/0.084MPa fraction to obtain crude dimethyl sulfoxide, and finally add a certain amount of calcium oxide for vacuum filtration to obtain Dimethyl sulfoxide.

The purification method of high-purity chromatographic grade dimethyl sulfoxide, the steps are as follows:

(1) Pour the raw material dimethyl sulfoxide (approximately 99.5% content) into a mixing tank and add approximately 10% of the weight of activated alumina adsorbent. Stir with an electric stirrer for about 2 hours. The dimethyl sulfoxide and the activated alumina adsorbent in the tank are fully contacted so that the organic impurities are adsorbed. After the quality of the adsorbed effluent is tested to be close to qualified, all indicators of the effluent are close to the chromatographic grade. The technical index requirements, the specific technical index requirements are shown in Table 1, let it stand and proceed to the next step;

(2) Pour the above-mentioned static dimethyl sulfoxide into the distillation clodroxypyridine kettle, add about 2% calcium hydride into the kettle, and distill under reduced pressure , distillation pressure 12mmHg column, distillation temperature about 76°C (distillation temperature not higher than 90°C), discard the first fraction;

(3) After passing the inspection, collect the finished product into a storage tank filled with nitrogen and equipped with 4A molecular sieve.