Phosgene (COCl2) is used as a precursor and pharmaceutical intermediate for polymers. The global phosgene market continues to grow at a rate of several percentage points per year, with an annual production of approximately 8 to 9 million tons. However, phosgene is highly toxic. For safety reasons, research and development are underway to find alternatives. In a world first discovery, Associate Professor Tsuda's research team irradiated chloroform with ultraviolet light to react with oxygen and produce high yields of phosgene (patent number: no. 5). 5900920). In order to achieve this in a safer and easier way, the research team has discovered a method that can immediately produce a reaction of phosgene. They first dissolve the reactants and catalysts in chloroform, and then irradiate the solution with light to produce phosgene (patent number 6057449). In this way, organic synthesis based on phosgene can be carried out like without using phosgene.
The research team named their discovery "On Demand Organic Synthesis Method" and successfully synthesized many useful organic chemicals and polymers using it. For example, they successfully synthesized large amounts of chloroform esters and carbonates in a safe, inexpensive, and simple manner by simply irradiating a mixture of chloroform and alcohol with light (adding alkali as needed).
The highly original reactions developed by Kobe University have been improved through collaboration with domestic chemical companies, and the ultimate goal of this research is practical implementation. With funding from JST A-STEP, further application research is being conducted and functional polyurethane is being developed using this synthesis method.
The on-demand organic synthesis method has high safety and economy, and has little impact on the environment. Therefore, as a sustainable chemical synthesis method, it has received attention from both industry and academia (Tsuda Laboratory Highlights in Japanese).
This study used chloroform and α- Amino acids were used as raw materials and prepared using the on-demand method α- Amino acid n-carboxylic acid hydrides (NCAs). NCA is a peptide precursor. α- Amino acids are easily soluble in water, but they are not easily soluble in chloroform. This means that the research team is unable to synthesize NCA using the previous on-demand photography method. However, they found that by adding acetonitrile (CH3CN), it can be mixed with water and chloroform as solvents to produce high yield (approximately 91%) NCA. Due to the absorption of light by acetonitrile, which hinders the photooxidation of chloroform, it is expected that the reaction will not proceed normally.
Surprisingly, researchers found that despite this obstacle, reactions still occurred, which led to the successful results of this study. In addition to the raw material (amino acid) that is photodegradation, the photo reaction can also be used to produce NCAs that are usually synthesized by phosgene method. So far, the research team has successfully synthesized 11 types of NCA using this photoreaction.
The detailed breakdown of the synthesis method is as follows. first, α- Amino acids are suspended in a mixed solution of chloroform and acetonitrile. Then irradiate with light for two to three hours at 70 ° C. After the light is turned off, NCA is generated by heating and stirring the solution for approximately one hour. This product can be extracted and refined to obtain high-purity NCA. The photooxidation of chloroform is promoted by the free radical chain reaction initiated by photocleavage of C-Cl bonds. Therefore, as long as the size of the reaction vessel is increased and the light source remains unchanged, synthesis can be achieved on a scale of up to 10 grams. I hope that by further expanding the scale of this method, it can be applied in a wide range of fields from academia to the chemical industry.
