Natural acids as catalysts for the continuous flow production of the green solvent 2,2,5,5-tetramethyltetrahydrofuran

As the demand for chemists to adhere to green chemistry principles increases, so does the demand for green solvents. Unfortunately, many green solvents, such as 2,2,5,5-tetramethyltetrahydrofuran (TMTHF), are costly and difficult to source. Traditional synthesis of TMTHF from 2,5-dimethyl-2,5-hexanediol has been reported to be catalysed by acids such as phosphoric and sulfuric acid, or, more recently, by H-beta zeolite. Although H-beta zeolite catalysts are high-yielding and selective, the energy required for their regeneration is high, and their production has questionable environmental impacts. A new approach was developed using flow technologies and naturally occurring acids as catalysts for TMTHF synthesis. Flow technologies are scalable, safe, efficient, and reproducible for daily chemical reactions, aligning with principles of green chemistry. This study observed several key improvements, including i) the use of a natural acid as a catalyst, ii) the use of water as a solvent, and iii) a continuous process for multigram-scale synthesis of TMTHF using citric acid monohydrate, with a yield of 72 %, resulting in a throughput of 8.24 g h −1 (9.43 kg L −1 h −1 space-time yield).