クロロホルムを用いるクロロギ酸エステルとビルスマイヤー試薬の光オン・デマンド合成：有機化学薬品のワンポット合成への利用

概要

Phosgene (COCl2) is an extremely important C1 building block in organic synthesis. Beside its significant importance in a wide range of organic syntheses, it is well known that it has high toxicity owing to its high reactivity.

There are mainly two preparation methods of phosgene. As a general method, it is synthesized with carbon monoxide (CO) and chlorine (Cl2) with activated carbon as a catalyst. This method has been used mainly in industry for a century. However, not only the produced COCl2, both the reactants CO and Cl2 also has high toxicity. With this reason, there is a potential risk of their leakage in the production processes. As an alternative safe method, COCl2 can be produced from base-catalyzed decomposition of phosgene oligomers such as triphosgene (BTC) and diphosgene (TCF), which can be used as solid and liquid at room temperature, respectively. But recently, some research groups have reported that both BTC and TCF also need highly strict operations because they also have high toxicity.

Despite the high toxicity of COCl2, it attracts organic chemists because of its many practical advantages in organic synthesis. It allows high yield syntheses without notable side products through the simple efficient organic reactions. Consequently, in situ production and consumption of COCl2, which allows presence of a few amounts of COCl2 formed temporally in the reaction system, are very important for the safety use of COCl2. In this background, our research group recently developed a photo-on-demand synthesis of COCl2 from CHCl3, which is available in situ for a variety of organic syntheses.

In the present study, the above photochemical reaction has applied successfully to novel in situ UV photo-on-demand syntheses of chloroformates and Vilsmeier reagent with a chloroform (CHCl3) solution. When a CHCl3 solution containing an alcohol was exposed to UV light with a low-pressure mercury lamp under O2 bubbling, the corresponding chloroformate was obtained in practical high yield. Then, it further allowed one-pot conversion to carbonate and carbamate upon addition of an alcohol or amine, respectively, with or without an organic base to the sample solution. With similar procedures, Vilsmeier reagent, a general formylation reagent, was also obtained from a chloroform solution containing N,N-dimethylformamide (DMF) or N,N-dimethylacetamide(DMA). Their direct applications to the next reactions allowed one-pot synthesis of a lot of useful chemicals, such as aldehydes, acid chlorides, formates, ketones, and esters. In these novel in situ photo-on-demand syntheses, CHCl3 plays dual roles of solvent and reactant. COCl2 generated upon UV-irradiation in the CHCl3 solution may consumed immediately in situ via the reaction with substrates dissolved in the CHCl3.

The study was further extended to use visible light. In comparison with the reactions using the higher energy UV light, it has an advantage to decrease photochemical decompositions of the reaction substrates and/or products. The in situ photo-on-demand synthesis of Vilsmeier reagent with the visible light has been achieved upon addition of catalytic amounts of Cl2 to the system. Under exposure to the visible light (LED lamp), Cl2 causes a homolytic cleavage to give Cl•, which may extract H• from CHCl3 to accelerate radical chain reactions with O2 to give COCl2. The produced COCl2 reacts immediately with DMF to give Vilsmeier reagent.

It is known that CHCl3 undergoes oxidative photo-decomposition to give phosgene in analytical scale. However, this phenomenon has never been utilized in practical organic synthesis. The present study makes innovation, and provides many benefits to the chemical syntheses that use phosgene in both laboratory and industry.

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