The occurrence of chemical reactions depends on the generation of free radical intermediates. Free radical intermediates are atoms or groups with unpaired electrons formed by the homogenization of covalent bonds. The breaking of covalent bonds in traditional chemical reactions often requires extreme conditions such as high temperature and pressure, or substances with harmful radioactivity to provide chemical bonds for breaking. The energy starts the reaction. For the later production and synthesis of a large number of APIs, these methods are undoubtedly an infinite amplification of pollution, hazards, and expenditures, which are contrary to the purpose of sustainable development and green chemistry.
More than ten years ago, when scientists applied photo-redox catalysts to chemical synthesis for the first time, a major step towards green chemistry technology was taken. Medicilon has been vigorously developing new technologies over the years, integrating emerging methods of green chemistry into its services to customers, using currently popular green enzyme chemistry, photo-redox catalysts, continuous reactions, etc., to provide the company with high-quality economic solutions Program.
On an ordinary day in 2008, Professor David MacMillan of the Department of Chemistry at Princeton University and his postdoctoral student Dave Nicewicz were discussing how to add an asymmetric carbon-carbon bond to acetaldehyde. This is a problem that has been discussed for a long time in the industry. If a solution to it is found, it will have an immeasurable significance for the synthesis of complex organic molecules in the pharmaceutical and chemical fields. In previous experiments, they tried to successfully induce synthesis with ultraviolet light. However, the ultraviolet light source is expensive and complicated to operate, which is not suitable for widespread use.
Under their mutual inspiration, MacMillan got inspiration from the widely reported solar energy conversion research and used a household fluorescent light bulb to make the reaction smoothly. The specific operation is that he used a catalyst, ruthenium bipyridine, which can absorb the energy in visible light to achieve a catalytic function. This innovative application has opened a new chapter in chemical synthesis, turning the extreme environment used in traditional reactions into controllable and mild.
Common photo-redox catalysts mainly include metal catalysts of ruthenium and iridium, and some organic dyes. Under the excitation of visible light, the electrons of the metal ions in the metal catalyst are transferred to the ligands in the catalyst, forming a triplet excited state with a relatively long survival time. The catalyst in this excited state participates in the transfer of single electrons with organic molecules, and induces the formation of new covalent bonds in organic reactions. It is worth mentioning that this excited molecule can be used as a strong oxidant or as a strong reducing agent to participate in the reaction, expanding the types of reactions that this kind of catalyst can act. At the same time, this combination of metal ions and ligand molecules also gives chemists a lot of room for modification and optimization, allowing chemists to predictably modify catalyst molecules for individual reactions. MacMillan said: “The photoredox reaction not only makes the synthesis faster, but also makes possible molecular synthesis reactions that were previously unthinkable, and you only need one step!”
However, despite the huge potential of photo-redox catalysts, there are still some difficulties if they are to be practiced in large quantities in industrial production.
- Insufficient visible light intensity. The flux of photons in visible light will decrease significantly with the extension of the propagation path and the increase of the medium concentration. Therefore, in a large reactor, the excited photoredox catalyst only exists on the surface of the reaction solution with strong light intensity, and the relatively large volume of the reaction solution in the reactor does not start to react due to insufficient light intensity. This phenomenon leads to too long reaction time and low efficiency in large-scale reactions;
- The synthesis of metal catalysts is difficult, and the cost of the metal elements in it is very high. It is also expensive to use in the catalysis of large-scale reactions.
In order to improve the efficiency of the photo-redox reaction in industrial production and shorten the reaction time, in view of the above two stumbling blocks, both the scientific and industrial circles are interested in optimizing and innovative methods and equipment.
The problem of visible light intensity has been basically solved in recent years. The latest technology adopted by the current technology first uses LED to cancel the traditional household visible light source, and the overall light intensity has been improved. In addition, the integration of light sources with different frequencies and different intensities can provide each photo-redox catalyst with light of a specific wavelength and intensity it needs. The small-scale integrated light source reactor designed by MacMillan and his colleagues is optimized based on the above two points. The instrument can emit the maximum energy LED beam at a specific wavelength. The reaction kettle can effectively shorten the reaction time, and the wavelength change of the light source can cover the optimal light wavelength of 8 common photo-redox catalysts.
Due to the high cost of rare metals among the metal catalysts, organic photo-redox catalysts have also appeared in recent years to replace the first discovered metal catalysts. Emerging organic catalysts can achieve cheap and efficient catalytic redox reactions after modification and design.
Green chemistry is increasingly being applied to the production process. Because of its mild reaction conditions and simultaneous redox dual identity, photooxidoreductase has spawned many emerging reactions to synthesize important compound intermediates in the field of medicine. The more companies and research institutes use it.