Illuminating Synthesis: Photo-on-Demand Phosgenation for Safe and Versatile Organic Compound Production

Significance 

Phosgene, a highly toxic and reactive C1 building block, is integral in the production of a large number of organic chemicals and polymers, including chloroformates, carbonate esters, N-substituted ureas, isocyanates, and polycarbonates. Despite its wide industrial use, the inherent risks associated with phosgene handling necessate the development of safer, phosgene-free synthetic routes. Some of the traditional methods of phosgene production involve the reaction of carbon monoxide and chlorine gas over a carbon catalyst or the decomposition of triphosgene or diphosgene in the presence of an organic base, each has their own advantages but also significant limitations in terms of scale, safety, and environmental impact.

To address this, a new study published in ACS Omega led by Associate Professor Akihiko Tsuda, Naoko Ozawa, Ryo Muranaka, Tomoya Kuwahara, Ayako Matsune, and Fengying Liang from Kobe University, the authors developed a novel method for synthesizing organic compounds through a photo-on-demand in situ phosgenation process. This innovative approach involves a heterogeneous solution of chloroform (CHCl3) and aqueous sodium hydroxide (NaOH) containing either an aryl alcohol or an amine. The method leverages the photochemical oxidation of chloroform to phosgene (COCl2) under ultraviolet (UV) light irradiation, which then reacts with the substrates to produce valuable organic compounds such as carbonate esters, polycarbonates, and N-substituted ureas.

In their experimental setup, the researchers used a low-pressure mercury lamp to generate UV-C light, which induces the photochemical oxidation of chloroform in the presence of oxygen, leading to the formation of phosgene. The reaction setup included a quartz glass jacket for the lamp, a cooling condenser, and a vigorous stirring mechanism to ensure effective mixing and control over the reaction environment. Oxygen was bubbled through the reaction mixture to facilitate the photo-oxidation of chloroform.

The generated phosgene reacts in situ with aryl alcohols or amines at the interfaces between the organic and aqueous phases, as well as between the aqueous and gas phases. For aryl alcohols, the presence of NaOH enhances nucleophilicity and hydrophilicity by forming aryl alkoxide ions, facilitating the reaction with COCl2. For amines, the reaction mechanism involves the neutralization of the HCl generated during the process by the aqueous NaOH, leading to the formation of N-substituted ureas.

The research team conducted optimization studies to understand the effects of various reaction parameters on the yield and efficiency of the desired products. Factors such as the choice of base, substrate concentration, reaction temperature, and time were systematically varied to maximize product yields. The authors’ new method showed good yields for the synthesis of carbonate esters from aryl alcohols, with specific conditions leading to optimal product formation. They also showed their developed phosgenation reaction is versatile because they applied it to synthesize a range of compounds. Moreover, the researchers successfully synthesized carbonate esters, polycarbonates, and N-substituted ureas, showcasing the method’s broad applicability to different types of organic compounds. The process was also shown to be scalable, indicating its potential for larger-scale synthesis in industrial settings.

According to the authors, the reported photo-on-demand approach allows for the generation of phosgene in situ, minimizing the risks associated with handling this highly toxic compound. The method offers a safer alternative to traditional phosgenation reactions, with the potential for lower environmental impact due to reduced hazardous byproducts and waste. The photo-on-demand in situ phosgenation process leverages the power of light to initiate chemical reactions, opening new avenues for the synthesis of complex molecules with broad applications in materials science, pharmaceuticals, and polymer industries.

Illuminating Synthesis: Photo-on-Demand Phosgenation for Safe and Versatile Organic Compound Production - Advances in Engineering

About the author

Prof. Dr. Akihiko Tsuda

Akihiko Tsuda is an associate professor in Graduate School of Science at Kobe University. He received B.E. degree from Shinshu University in 1997, and then received M.E. degree from Osaka University in 1999. He obtained his Ph.D from Kyoto University in 2002. He then started an academic career as an assistant professor at the University of Tokyo. He has been an associate professor at Kobe University since 2008. He has also served as a visiting associate professor at Shiga University of Medical Science since 2017 and as a visiting professor at Inner Mongolia Medical University from 2018–2023. Tsuda’s research program focuses on the photo-on-demand in situ phosgenation reactions, developing safe, inexpensive, and simple reaction systems capable of using for a wide variety of organic syntheses. Tsuda will also serve as CEO of Photo-on-Demand Chemical Co., Ltd., a startup company that will begin in April 2024 to produce bio-based chemicals through the photo-on-demand phosgenation reactions.

Reference

Tsuda A, Ozawa N, Muranaka R, Kuwahara T, Matsune A, Liang F. Photo-on-Demand In Situ Phosgenation Reactions That Cross Three Phases of a Heterogeneous Solution of Chloroform and Aqueous NaOH. ACS Omega. 2023;8(30):27802-27810. doi: 10.1021/acsomega.3c04290.

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