“Revolutionary Chemical Synthesis System Developed Using Chloroform as Precursor, Replacing Toxic Phosgene”

In a groundbreaking development, researchers from Kobe University Graduate School of Science have successfully developed a new flow photo-on-demand synthesis system that uses chloroform as a precursor, replacing the highly toxic phosgene. The system, developed in collaboration with industry, has been hailed as a safer, more efficient, and environmentally friendly alternative to the traditional method of synthesizing various chemical products such as polymers and pharmaceutical intermediates.

The research group, led by Associate Professor TSUDA Akihiko, achieved a high conversion rate of over 96% in synthesizing these useful compounds in a short period of time (a minute or less of light exposure). The system is safe, inexpensive, simple, and has a low environmental impact. It can continuously produce large quantities of various chemical products, making it a promising model for industrial production in the near future.

Patents for this innovative system were filed in Japan in February 2021 and internationally in January 2022. Following the patent announcement in August 2022, the related academic paper was published online in Organic Process Research & Development (OPR&D) on November 11, 2022.

The research team successfully synthesized pharmaceutical intermediates and polymers from chloroform and commercially available alcohol at a highly efficient rate and in a short amount of time. The new method improves safety compared to the standard method of producing phosgene, which involves a strong exothermic reaction of carbon monoxide and chlorine gas using a carbon catalyst. The chloroform used as a precursor in the new method is easy to store safely, and the chemical reaction can be controlled by exposure to light.

The byproduct of this new method is mostly hydrogen chloride, which is neutralized by alkali. This means that dirt does not build up inside the system apparatus, reducing the need for cleaning and thus lessening the environmental impact and lowering costs. The system achieves continuous production without the additional use of organic solvents.

Phosgene (COCl2) is used as a precursor for polymers and as a pharmaceutical intermediate. The global phosgene market continues to grow by several percent each year, with around 8 to 9 million tonnes produced annually. However, phosgene is extremely toxic, and for safety reasons, research and development are being conducted to find alternatives.

The research group has named their discovery ‘photo on demand organic synthesis method’ and have successfully used it to synthesize numerous useful organic chemicals and polymers. These highly original reactions developed at Kobe University have been improved through cooperation with domestic chemical companies, and the eventual aim of this research is practical implementation.

The photo-on-demand organic synthesis method is highly safe and economical, in addition to having a low impact on the environment. Consequently, it has garnered attention from both industry and academia as a sustainable chemical synthesis method.

In this research, a flow photo-on-demand system was redesigned for the photo-oxidation reaction of chloroform. By irradiating this gaseous mixture of vaporized chloroform and oxygen under ultraviolet light, the majority (over 96%) was converted into phosgene. Furthermore, the phosgene continuously reacted with the alcohol inside the system, which meant that the system could be used to continuously synthesize high yields of chloroformate, carbonates, and polycarbonates on a gram scale.

The photo-on-demand synthesis method is expected to spark new innovation in how various chemical products are synthesized with phosgene as a precursor. With this new flow photo-on-demand system, it is possible to avoid the dangers of directly using phosgene produced from carbon monoxide and chlorine because the phosgene reaction occurs within the closed environment inside the system. This safe and simple versatile system can be used for the small to large-scale synthesis of various chemical products and the apparatus of this basic model can be customized to suit specific chemical reactions. It is hoped that this system can be used for industrial production by refining the process according to the scale of production. However, this system is not only for large scale chemical production; it will also be of great benefit to chemical manufacturers who need to produce various products on a small to medium scale. It is hoped that it can be used in new ventures, as well as to replace existing set-ups that are wearing out.

This research was supported by the Adaptable and Seamless Technology Transfer Program through Target-driven R&D (A-STEP) from the Japan Science and Technology Agency (JST).