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

TY - JOUR

T1 - 2,2,6,6-Tetramethyloxane as an Alternative Hindered Ether Solvent for Organic Synthesis

AU - Sangon, Suwiwat

AU - Supanchaiyamat, Nontipa

AU - Sherwood, James

AU - Macquarrie, Duncan J.

AU - Hunt, Andrew J.

N1 - Publisher Copyright: © 2025 The Authors. Published by American Chemical Society.

PY - 2025/3/27

Y1 - 2025/3/27

N2 - 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).

AB - 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).

KW - Biginelli reaction

KW - ether

KW - glucose conversion

KW - HMF

KW - Sonogashira reaction

KW - sustainable solvent

UR - http://www.scopus.com/inward/record.url?scp=105001108715&partnerID=8YFLogxK

U2 - 10.1021/acssuschemeng.4c09195

DO - 10.1021/acssuschemeng.4c09195

M3 - Article

AN - SCOPUS:105001108715

SN - 2168-0485

JO - ACS Sustainable Chemistry and Engineering

JF - ACS Sustainable Chemistry and Engineering

ER -