Fluorine chemistry： there is a big world in small elements

　　Author: Hu Jinbo (Dean of Shanghai Branch of Chinese Academy of Sciences, researcher of Shanghai Institute of Organic Chemistry)

　　The matter in the universe is composed of various chemical elements, among which there is a unique and magical element, that is, fluorine. The new fluorine-containing materials can make the Water Cube of Beijing Olympic Games and the China Pavilion of Shanghai World Expo shine brilliantly. Many new drugs contain fluorine atoms, and the display screens of mobile phones and computers also use liquid crystal materials containing fluorine … … Although fluorine chemistry has a history of more than 200 years, this "ancient" discipline is still full of vitality, and more new structures, reactions and functions are still being discovered, thus affecting and changing the world.

　　　Strange and important fluorine element

　　Fluorine is not uncommon in life. The main swimming pool of the 2008 Beijing Olympic Games — — Water Cube, whose membrane structure is made of fluorine-containing materials — — Tetrafluoroethylene. This material has good corrosion resistance, heat preservation and strong self-cleaning ability, and is a new environmental protection material. Fluorocarbon coatings have also shined brilliantly in the Shanghai World Expo. The magnificent China Pavilion was sprayed with polyvinylidene fluoride fluorocarbon coatings, forming a gorgeous "China Red".

　　In the international scientific field of fluorine chemistry, there are two words to summarize the importance of fluorine. The first one is unique. It is the most subversive element. Why can we use "most" to describe a chemical element? This is because fluorine is electronegative and its chemical properties are extremely extreme. This makes many fluorine-containing raw materials very active, but the fluorine-containing products are very stable — — When active fluorine-containing raw materials react chemically, they will release a lot of energy, but the fluorine-containing products obtained after energy release are particularly stable. This process is a bit like popcorn, which has experienced "explosion" and then settled down. Fluorine can also form the strongest chemical bond with carbon atoms, which makes fluorine-containing materials very stable. For example, Teflon, a plastic mesh, is one of the most stable materials.

　　The atomic radius of fluorine is very small, which is also a major feature of fluorine. Using these three properties, many very unique and important fluorine-containing materials can be manufactured.

　　The second word to describe fluorine is useful. 20% of the newly registered drugs in the world & mdash; 25% contains fluorine atoms. Some patients do PET— 18F— should also be used in CT examination; FDG, or fluorodeoxyglucose. Fluorine-containing liquid crystal materials will be used in the display screens of electronic devices such as mobile phones and computers.

　　Fluorine-containing materials are also widely used in the field of national defense. In the aerospace field, gyro oil, high and low temperature lubricating oil and so on are all fluorine-containing materials. Fluorine-containing materials also occupy an important place in the advanced defense materials needed for atomic bombs.

　　Fluorine-containing materials are so important, but it is strange that all the fluorine-containing materials that are useful to human beings at present are made by human beings relying on their own wisdom. Although there are many inorganic fluorides in nature, such as calcium fluoride, those that are useful to human society contain carbon — Fluorine (C— F) bond organic fluoride is very rare.

　　　A brand-new scientific viewpoint "negative fluorine effect"

　　It is precisely because fluorine is so magical and has made such a great contribution to human society that understanding and mastering the scientific reaction law of fluorine chemistry and realizing the efficient synthesis of fluorine-containing organic molecules are of course the frontier fields of current chemical research.

　　In this regard, China has made great progress. After more than 10 years of in-depth research and thinking, after further studying the fluoroalkylation reaction of alkylene oxide, the research team in China put forward a brand-new scientific viewpoint for the first time in the world — — "Negative fluorine effect", that is, the more fluorine atoms replace the center of carbanion, the nucleophilic reactivity of carbanion to many electrophilic substrates will often decrease. This view has been recognized by peers at home and abroad, and has been written into the textbook of Intermediate Organic Chemistry.

　　Based on the new theory, our researchers have developed three types of more than 10 new fluorine chemical synthesis reagents, including sulfone reagent series, sulfoxide imine reagent series, difluorocarbon reagent and so on. These reagents based on "negative fluorine effect" have solved the problems of monofluoromethylation and difluoromethylation, difluoroenylation and difluorocarbon chemistry. These reagents have been used by more than 250 companies or research institutions for more than 528 times. American scientists have used these reagents many times when studying fluorine-containing biochemical active substances, and Japanese scientists have also used sulfoximine reagents among them. They all call these reagents "Hu reagents" in published papers.

　　In the science of fluorine chemistry, there is still a big problem that is difficult to solve for a long time — — Fluorocarbon chain extension is easy to explode. In 2017, our research team made a breakthrough in this respect, and realized the reaction that one carbon in trifluoromethyl trimethylsilane catalyzed by sodium iodide changed into two carbons to form tetrafluoroethylene. The reaction was evaluated as "a breakthrough method for preparing tetrafluoroethylene" by the American Chemical and Engineering News.

　　Subsequently, our research team also realized the extension of fluorocarbon chain from one carbon to two carbons and from one carbon to three carbons promoted by copper. This method of extending fluorocarbon chain can sweep away the original explosion hidden danger and can be extended controllably according to the wishes of researchers. In 2020, an Italian chemist wrote that it was a pioneer in this research direction.

　　On the basis of these research results, the transformation of fluorine chemistry has also achieved remarkable results. Cooperate with related enterprises, China’s original fluorine chemical reagent — — Sulfoxfluor has realized the commercial production and sales in batches. Recently, a tonnage production process of fluorine reagent has also been successfully implemented. Prior to this, this reagent was sold by American companies around the world.

　　These scientific research achievements of fluorine chemistry in China have achieved good response in the world. Pfizer, an internationally renowned pharmaceutical company, also took the initiative to invite our scientific research team to help solve the latest problem of drug production for cancer treatment. After half a year’s efforts, the two sides cooperated to solve the problem of efficiently introducing difluoromethyl into drugs.

　　The future of fluorine chemistry science can be expected

　　Based on the breakthrough scientific theory, coupled with the new reagents and reaction systems constructed from it, the current fluorine chemistry can develop more new fluorine-containing functional molecules for the country’s major needs and economic and social development.

　　Take the purification of lithium as an example, the natural lithium resource — — The price of a ton of lithium carbonate is about 180,000 RMB at present, but after purification, the price of 99.9% lithium 7 in the international market is about 100 million RMB at present. If the purity is higher, what is the price of 99.99% lithium 7 in the international market? 230 million yuan/ton.

　　It can be seen from the huge price difference that the difficulty of lithium purification lies. At present, the method of purifying lithium in the world is still the lithium 7 amalgam exchange method by American scientists in 1936. It takes 1000 tons of mercury to separate 1 ton of lithium isotope, and mercury is a toxic metal. Using mercury in such a large amount is not only costly, but also very harmful to the environment.

　　As early as 1967, Chinese scientists put forward the idea of using organic methods to realize lithium isotope separation. After two generations of innovation, our younger generation of scientists stood on the shoulders of the older generation of scientists and followed this idea to invent a new fluorine-containing extractant, which greatly improved the stability and economy of chemical processes. At present, in the engineering development stage, with this new fluorine-containing extractant, we can purify the natural 92.5% lithium 7 isotope to more than 99%, which is the first time in the world to purify lithium by organic extraction. In the laboratory, 99.9% lithium 7 can be enriched to more than 99.99%, which is the first time in the world to be achieved by organic extraction, which has never been reported internationally before.

　　This achievement is not only praised by scientists in China, but also considered as a very new green advanced technology after communicating with their American counterparts.

　　After years of continuous innovation, China’s fluorine chemistry research has also won praise from international counterparts. In 2022, the American Chemical Society’s Chemical Creative Work Award was awarded to China’s team. Previously, our team had also won the fluorine chemistry award in royal society of chemistry. In the field of fluorine chemistry science, there have been three Nobel Prizes. Although this subject has developed for more than 200 years, it still has new vitality. This is because chemical science mainly lies in discovering new structures, new reactions and new functions, and a new generation of scientists can still create substances with unique structures and functions on the basis of predecessors, serving the society and benefiting the people. In the future, we will continue to work hard to make molecules create value, influence and change the world.

　　(Guangming Daily reporter Zhan Yuan finishing)

　　Guangming Daily (16th edition, November 23rd, 2023)