SMM7 March 24: today, at the "2020 small Metal Industry Summit" hosted by SMM, Wu Manshe, chief engineer of Xingping Yuehua Electronic Materials Co., Ltd., brought a speech on the theme of "present situation and development prospect of organic bismuth compounds", mainly from the development history, present situation and development prospect of organic bismuth compounds. He said that at present, countries around the world pay more and more attention to environmental protection, and organic bismuth compounds have green and safe properties such as low cost, easy to treat, low toxicity and low radioactivity, and have been used in medicine, polyurethane, waterborne coatings, lubricants and other fields. The scientific research and application of organic bismuth compounds are deepening day by day, and the types and usage of organic bismuth compounds are also increasing.

Development and present situation of Organic Bismuth compounds

In 1850, the first triethyl bismuthane capable of spontaneous combustion in air was synthesized by Schweitzer (Schweizer) et al., which was the beginning of organic bismuth chemistry. In 1887, Michaelis (Michaelis) and Boris (Polis) synthesized stable triphenylbismuth compounds in the air, and organic bismuth chemistry really began to develop. In 1952, Wittig (Wittig) and Klaus (Clauss) synthesized tetraaryl and pentaaryl bismuth compounds for the first time, and then a large number of Bi "and Bi … Organic compounds have developed many new applications. Professor (Suzuki) Suzuki, a Japanese scholar, published < Organobismuth Chemistry > in 2002, which systematically collected the research achievements of bismuth chemistry for many years. It is also the only English monograph that introduces the research results of organic bismuth chemistry in detail so far. In recent years, both the synthesis of new organic bismuth compounds and the application of organic bismuth compounds in organic synthesis, catalysis and biomedicine are in the stage of rapid development. Professor Zhong Guoqing, a domestic scholar, published a review on Bi (Ⅲ) complexes in Chemical Progress in 2006, which mainly summarized the synthesis and structure of trivalent bismuth ion complexes. So far, there is no review on the application of organic bismuth compounds in detail in the past 10 years. From the perspective of the depth and breadth of the study, Japanese scholars are in the forefront of the international research work on organic bismuth chemistry, which has replaced the previous leading position of European countries, and only a small number of domestic scholars are engaged in the research of organic bismuth chemistry. The organic bismuth products produced by advanced foreign countries have a history of more than 30 years and have been supplied to European and American markets for many years. China started relatively late. Before 2000, there were no manufacturers producing organic bismuth products, and organic bismuth manufacturers have grown rapidly in recent years. According to incomplete statistics, there are about 25 domestic organic bismuth manufacturers, among which, Xingping Yuehua Electronic Materials Co., Ltd. is a manufacturer specializing in organic bismuth products, with an annual production scale of 3000 tons of organic bismuth products, commonly used products include bismuth isooctanoate and bismuth naphthenate. The pharmaceutical intermediates of bismuth lactate, new bismuth sunate, bismuth acetate, bismuth citrate, bismuth salicylate and bismuth are mainly used in medicine, lubricating oil, polyurethane, coating and so on. The development and application of organic bismuth compounds in China is still in the initial stage of development.

Development Prospect of Organic Bismuth compounds

Application of organic bismuth compounds in biomedicine

Many organic bismuth compounds can treat gastric ulcer, duodenal ulcer, gastritis, indigestion, colon and peptic ulcer, toxic diarrhea, dermatitis, hemorrhoids, syphilis and other diseases. At present, the widely used bismuth agents are colloidal bismuth subcitrate, basic salicylate bismuth salt (PeptoBismol@), ranitidine bismuth citrate, bismuth pectin and so on, which have the functions of anti-secretion, cytoprotection and anti-Helicobacter pylori. Although organic bismuth drugs used as gastrointestinal anti-ulcer drugs have made landmark achievements in the past few decades, there are still a large number of scholars to design and develop new high-efficiency, low-toxic or non-toxic organic bismuth agents and explore their molecular mechanism of anti-sterilization.

Another major research focus of the application of organic bismuth compounds in the field of medicine is to explore their anticancer and antineoplastic activities. Because many organic bismuth and organic germanium compounds have antibacterial / sterilizing activities, Professor Li Jinshan of Nankai University synthesized 15 kinds of triphenylgermanyl propanoic acid alkyl bismuth salts by making comprehensive use of the advantages of these two compounds. and try to reveal the effect of bismuth-linked organic ligands on their antitumor activity. The results of anti-tumor and activity experiments showed that they all had anti-tumor activity and were higher than triphenylmethylgermanyl propionate without bismuth, among them, one had the highest efficiency of inhibiting the proliferation of HCT-8, the other had the highest anti-tumor activity against KB cells, and its IC50 (IC50) was much higher than that of cisplatin (cisplatin), (0.005ug/ml). Bi (V) oxophenone complex and aminophenylthiourea complex also had a good effect on the removal of Helicobacter pylori. Because Helicobacter pylori is also associated with gastric lymphoma, eradication of this organism can make the disease decline or cure, so they have anti-tumor effect. Organic bismuth mercaptan MeBi (SMe) 2 and MeBi (SR) 2 have antitumor activity against mice inoculated with Ehrlich ascites cancer cells. Within the range of 2Mel 160 mg/kg dose, the 100% cure dose was 15 Mel 20 mg/kg. Follow-up studies reported a series of data on cytotoxicity and antitumor activity of bismuth compounds including organic bismuth compounds. When bismuth compounds are attached to monoclonal antibodies, they are very effective cytotoxins for tumors such as leukemia and lymphoma. In addition, the a particles emitted by bismuth compounds have the potential to be used as radiotherapy agents, and bismuth nuclei have more advantages than other radiopharmaceuticals. Although great achievements have been made in the application of organic bismuth compounds in biomedicine, they are still faced with great challenges. for example: how to combine the design and synthesis of new organic bismuth compounds with the development of new drugs for the treatment of malignant tumors, cardiovascular and cerebrovascular diseases, AIDS and other major diseases to obtain effective bismuth agents for the treatment of these diseases; The biological coordination of bismuth (111) with proteins, enzymes and cell membranes was studied by simulating the biological related environment, and the thermodynamics and kinetics of chemical and biological reactions of bismuth under these conditions were revealed. the qualitative and quantitative relationship between the structure of bismuth compounds and their efficacy was revealed, and the toxic and side effects of low content bismuth compounds were studied. The detailed distribution and residue of Bi in human body. It is expected that organic bismuth can play an active role in the treatment of cancer, malignant tumor, cardio-cerebrovascular disease and AIDS in the future.

China is not only a big country of medicine, but also a big country of drug use. The total production of APIs is second only to the United States and is one of the major exporters of chemical APIs in the world. However, there is a large gap between China and foreign countries in terms of preparation products and dosage forms, and there is also a large gap between the internal quality of preparation products and similar foreign products. A good preparation or compound preparation can give full play to the therapeutic effect of the drug or reduce its toxic and side effects to the lowest level, which is as important as the development of a new type of chemical. For example, the commonly used stomach medicine Lede stomach tablets (imported from the Netherlands), China has also produced more than a dozen similar products, and the internal formula is the same, with sub-Bismuth nitrate as the main raw material (Dutch products are mostly imported from China for secondary Bismuth nitrate processing), but the efficacy of domestic products is far less than that of Dutch imports, so they have to spend a lot of foreign exchange on imports, which shows that there is still a big gap in the production of bismuth preparations in China. The price ratio of pharmaceutical products in developed countries is generally 1 / 10, while in our country it is generally 1 / 3. How to improve the research, development, design and production technology of bismuth medicine by making use of the superior resources of bismuth in China will be a great challenge for the bismuth pharmaceutical industry in China. The export market and domestic market of bismuth preparation products have a bright future. According to the statistics and forecast of foreign pharmaceutical market, the sales of digestive tract drugs reached more than 30 billion US dollars.

Application of organic bismuth compounds in polyurethane

Organic bismuth compounds have better hydrolytic stability than tin compounds, can promote NCO+OH reaction, avoid side reactions of NCO groups, and reduce the selectivity of reaction with water. In waterborne PU systems, organic bismuth compounds can reduce the side reactions between water and NCO groups. In one-component systems, they often release water-shielded amines instead of promoting the reaction of NCO with water.

Organic bismuth compounds have strong gel catalysis, which shows the viscosity of the delayed system when the intermolecular reaction level is low at the initial stage of the reaction. Promote the completion of the reaction in the later stage. In polyurethane reaction system, microcellular elastomer system, high-density semi-hard foam system, enhance the stability of the reaction, low freezing point, easy to operate, low volatility, low odor or odorless. It can improve the stability of the system combined with organotin catalyst in the atmospheric environment in the normal humidity range, and has a strong gel catalytic effect on polyurethane reaction system, elastomer polyether system and resin prepolymer system. With the enhancement of people's awareness of environmental protection and the country's strict requirements for environmental protection, it is an inevitable trend for environment-friendly organic bismuth to replace toxic lead-mercury catalysts.

According to the data collected by the prospective Industrial Research Institute, the consumption of polyurethane in China reached 13 million tons in 2018, and increased year by year. Therefore, organic bismuth has a broad application prospect in polyurethane catalysis.

Application of organic bismuth in coatings

At the end of December 2016, the State Council issued a comprehensive work plan for energy conservation and emission reduction in the 13th five-year Plan, proposing to promote green life and choose low-volatile water-based coatings and environmentally friendly materials as far as possible. In recent years, the national requirements for VOCs emissions are very strict, and various places have issued explicit requirements to control the total amount of VOCs emissions, and from January 1, 2018, benzene, toluene and other VOCs environmental taxes are levied, so the external cost of continuing to use solvent-based coatings will be greatly increased, and the economy of waterborne coatings will begin to highlight.

Organic bismuth can be easily used in waterborne coatings with good stability and catalytic effect in cathodic electrophoretic coatings. it can shorten grinding time, ensure smaller fineness of coatings, and lower curing temperature than lead and tin catalysts. environmental protection, energy saving and can improve product quality.

According to the "Analysis report on Market demand and Investment Planning of China's Waterborne Coatings Industry from 2018 to 2023" released by the prospective Industrial Research Institute, the national paint production increased year by year from 2012 to 2016. By the end of 2016, the output was 18.9978 million tons, an increase of 10.61 percent over the same period last year. It is estimated that the output of paint reached 20.33 million tons in 2017.

Since the 1990s, in order to meet the environmental standards, European and American automobile factories began to use environment-friendly automotive coatings to replace the traditional organic solvent-based automotive coatings.

At present, cathodic electrophoretic primers are used in almost all passenger cars in China, and traditional alkyd, phenolic or epoxy primers are used only on some passenger cars and trucks. According to estimates, the market demand for automotive primer (electrophoretic paint) in China is about 150000 tons in 2016 and is expected to reach 180000 tons in 2018.

Application of organic bismuth in lubricating oil

With the development of modern science and technology, the performance requirements of oil products are getting higher and higher. for modern oil products, in addition to excellent extreme pressure anti-wear performance and anti-oxidation stability, it is also required to have good environmental adaptability and green environmental protection performance. For many years, sulfur and phosphorus additives have played a leading role in extreme pressure antiwear agents of lubricating grease because of their excellent lubrication properties. However, with the improvement of people's environmental awareness and increasingly stringent environmental laws and regulations, the use of sulfur and phosphorus additives has been more and more strictly restricted because of the greater problem of environmental pollution. In order to reduce the corrosion caused by sulfur, the emission of acidic components and the influence of phosphorus on the exhaust purification unit, it has become a hot topic to find new additives that can replace or reduce the content of sulfur and phosphorus. Bismuth is a non-toxic heavy metal, and its use can greatly reduce the content of sulfur in the additive. The combination of organic bismuth compounds and organic sulfur can obtain high extreme pressure bearing properties at low sulfur content. In addition, organic bismuth compounds can also be used in some high extreme pressure situations. Sulfur-bismuth compound instead of sulfur-lead compound can reduce the harm of lead to human body and has better properties than sulfur-lead additive. Bismuth sulfur additive has been developed rapidly in the world in recent years because of its excellent extreme pressure lubrication performance.

According to imedia data, in 2019, the output of lubricating oil in China is about 6.3 million tons, which is relatively stable and shows an upward trend as a whole.

5 Summary

To sum up, with the enhancement of people's environmental awareness and the increasingly stringent requirements for environmental protection at home and abroad, using non-toxic or low-toxic substances to replace toxic lead and mercury substances in industrial production and application, green development will be the long-term development direction. Organic bismuth compound has the characteristics of relatively low price, environmental protection and safety, so it is an ideal choice to replace lead and mercury, so it has a broad application prospect in medicine, polyurethane, waterborne coatings and lubricating oil antiwear agents.

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