2,2,6,6-Tetramethyloxane as an Alternative Hindered Ether Solvent for Organic Synthesis

A new hindered ether solvent, namely, 2,2,6,6-tetramethyloxane, has been successfully synthesized in excellent yields (90% from 2,6-dimethyl-2,6-heptanediol and 80% from 2,6-dimethyl-5-hepten-2-ol). The physical and solvation properties of 2,2,6,6-tetramethyloxane were evaluated, which indicated its potential to replace hydrocarbon solvents and also that it imparts strong hydrogen-bond-accepting ability. VEGA models (SARpy, KNN, ISS, and CAESAR), the lazy structure-activity relationship model (Salmonella typhimurium), and the Toxicity Estimation Software Tool indicated this solvent to be nonmutagenic. The application of 2,2,6,6-tetramethyloxane in model organic reactions including the Biginelli reaction, glucose conversion to 5-hydroxymethylfurfural, and the Sonogashira reaction, importantly, validates the nonpolar nature of this solvent and exhibits its potential as an alternative solvent to hazardous hydrocarbon solvents (including toluene).