2,2,5,5-Tetramethyloxolane as a Nonperoxide-Forming Alternative Solvent for Microwave-Assisted Glucose Conversion to 5-Hydroxymethylfurfural in a Biphasic System

2,2,5,5-Tetramethyloxolane (TMO) has been utilized as a highly efficient, safer, and sustainable alternative solvent for the biphasic microwave-assisted conversion of glucose to 5-hydroxymethylfurfural (5-HMF). Excellent partitioning of 5-HMF into the organic phase (5-HMForg/5-HMFaq) was observed, which is an important role for extraction of 5-HMF, leading to a maximum yield of 48% in TMO. 5-HMF yield in TMO was significantly higher than that obtained in traditionally problematic solvents, including tetrahydrofuran, 1,4-dioxane, 2-methyltetrahydrofuran, and toluene. The high hydrogen-bond-accepting ability of TMO strongly stabilized 5-HMF and prevented rehydration, reducing side reactions to unwanted byproducts. The effects of catalysts, temperature, time, and catalyst loading have been elucidated to obtain optimized conditions. Sodium chloride improved the partitioning of 5-HMF into the organic phase, promoting dehydration of fructose to 5-hydroxymethylfufural without the addition of Brønsted acids. TMO as a solvent provided a robust and efficient new production route to 5-HMF.