Organolithium reagents are among the most commonly used reagents in organic synthesis. However, metallic lithium is a limited resource, prompting the search for alternatives. Sodium, which belongs to the same group of elements as lithium and is far more abundant, is a promising candidate. However, the synthesis of organosodium reagents has faced challenges: it requires pre-activated, expensive sodium sources, large amounts of organic solvents, and complex procedures.
A research group led by Professor Hajime Ito and Associate Professor Koji Kubota from the Institute for Chemical Reaction Design and Discovery (WPI-ICReDD) at Hokkaido University, together with a collaborative group including Lecturer Roly J. Armstrong from Newcastle University, UK, and Associate Professor Erli Lu from the University of Birmingham, UK, has successfully synthesized organosodium reagents using a mechanochemical method. This approach directly mixes organic halides with sodium metal in a ball mill (a type of grinder). By simply placing the necessary materials in the ball mill under room temperature air and running it for just five minutes, the reagents can be easily synthesized with a yield of 99% without the use of organic solvents. The group also successfully synthesized various compounds by adding electrophiles to the organosodium reagents they had prepared and processing them in the ball mill. Their findings were published online in Nature Synthesis.
Provided by Hokkaido University
Organic synthetic chemistry has a history of more than 120 years, during which the use of petroleum-derived organic solvents to synthesize various useful molecules has been the norm. Organic synthesis reactions require molecules to come into extremely close contact with one another. In a solvent where molecules are suspended at high concentrations, they come into proximity more frequently from a statistical standpoint, which is favorable for organic synthesis.
However, the amount of organic solvent needed to synthesize a desired compound is typically 10 to 100 times the amount of the compound itself. Since most of the widely used organic solvents are disposed of by incineration, they are a source of carbon dioxide emissions.
This ball mill-based organic synthesis uses no organic solvents, making it environmentally friendly. To synthesize sodium reagents, sodium metal cut with scissors into roughly 5 mm pieces is placed into the ball mill and grinded with halide, yielding sodium reagents with over 99% yield. It is thought that as ordinary metallic sodium is covered with an oxide layer on its surface, the metal balls striking this surface physically break through the oxide layer, resulting in high reactivity.
Kubota commented: "To link sustainable synthesis without organic solvents to the production of pharmaceuticals, organic electronic materials, and plastics, we founded the startup company Mechanocross. Currently, we have contracts with 23 companies, including major pharmaceutical and chemical manufacturers, cover 29 research themes, and aim to accelerate the implementation of this technology in society."
Journal Information
Publication: Nature Synthesis
Title: Mechanochemical synthesis of organosodium compounds through direct sodiation of organic halides
DOI: 10.1038/s44160-025-00949-7
This article has been translated by JST with permission from The Science News Ltd. (https://sci-news.co.jp/). Unauthorized reproduction of the article and photographs is prohibited.