2,5-Diethyl-2,5-Dimethyloxolane (DEDMO) as a Nonpolar, Nonperoxide-Forming Ether Solvent for Organic Synthesis

Abstract

The development of safer and more sustainable solvents is an important discipline in the context of stricter regulations and environmental protection. This work demonstrates the sustainable synthesis of a potentially bio-based, inherently nonperoxide-forming ether solvent, namely, 2,5-diethyl-2,5-dimethyloxolane (DEDMO), in quantitative yields with high atom economy (97%) and reaction mass efficiency (94%) from renewable sources. Quantum mechanical calculations of theoretical NMR chemical shifts and DP4+ probability modeling indicated that the cis isomer of DEDMO was most plausible (with a probability value of 99.98%); however, the actual NMR data suggested a 1:1 mixture of cis and trans isomers for DEDMO. The solvation properties of DEDMO have also been evaluated using Kamlet–Abboud–Taft (KAT) parameters, Hansen solubility parameters (HSPs), and in silico modeling COSMO-RS. The KAT parameter relating to a combined effect of solvent polarity and polarizability (π*) was 0.32 for DEDMO, which was lower than other quaternary ethers such as 2,2,5,5-tetramethyloxolane (TMO) (0.35) and cineole (0.41). In silico COSMO-RS modeling suggested that DEDMO has similar characteristics to hydrocarbon solvents such as n-hexane or toluene. The substitution of all hydrogen atoms at the α-position to the ethereal oxygen with an alkyl group, such as the methyl and ethyl groups of DEDMO, inhibits its ability to form explosive peroxides. Moreover, the steric concealment of the ethereal oxygen of DEDMO leads to similar properties to hydrocarbon solvents rather than traditional ether solvents. The performance of DEDMO as a solvent is demonstrated in an enzymatic esterification, as well as heterocyclic synthesis by means of a Biginelli reaction, and annulation reactions. Application testing of DEDMO revealed that its behavior was similar in solvent properties to hydrocarbon solvents; in fact, results were typically between those of toluene and n-hexane. The presence of ethyl groups enhances its nonpolar character, and as such, DEDMO was demonstrated to perform better than the green quaternary ethers TMO in some reactions. Preliminary in silico toxicity predictions indicate that DEDMO is nonmutagenic, and thus DEDMO is a potentially green hindered ether solvent for the substitution of conventional nonpolar solvents.

Sustainable solvents for β-diketone extraction from wheat straw wax and their molecular self-assembly into nano-structured tubules for hydrophobic coatings

“…TMO shared similar properties with toluene, however, it provided greater tubule formation than toluene according to its lower π* of 0.35 (Table S2†). 50,51 DEDMO revealed a lower π* value (0.31, Table S2†) 51 than TMO leading to providing better molecular self-assembly of nano-structured tubules. Although petroleum ether contains a mixture of aliphatic hydrocarbons, which showed a significant low π* (−0.16, Table S2†) and provided tubule structure for β-diketone, it cannot provide tubule structure for unrefined wheat straw wax.…”

“…29 A newly developed sustainable and potentially bio-based solvent, namely DEDMO, is a promising alternative to traditional toxic nonpolar solvents such as toluene and hexane. 51 DEDMO contains two ethyl groups in the structure that promoted the nonpolar character compared to TMO and provided better extraction performance for lipophilic compounds similar to non-polar petroleum ether. When using DEDMO, hentriacontane-14,16-dione was extracted at an amount of 23.7% (68.8% yield), which was comparable to that of petroleum ether.…”

“…H-beta zeolite (25 : 1) was supplied by Alfa Aesar. TMO and DEDMO were synthesized following literature procedures, 50,51 by the ring closure dehydration of 2,5-dimethyl-2,5-hexanediol (purchased from Sigma-Aldrich) for TMO and 3,6-dimethyl-3,6-octanediol for DEDMO in the presence of H-beta zeolite (25 : 1). Infrared (IR) spectrum was measured on a Bruker tensor 27 Fouriertransform infrared (FT-IR) spectrophotometer.…”

“…Likewise, in this work, the tubule formation of b-diketone could be impacted by the solvent's ability to promote the tautomerisation equilibrium of b-diketone which showed the relationship with the Kamlet-Ta parameter of a combined measure of dipolarity and polarizability (p*) as low p* can encourage the enol form of b-diketone. 58 Toluene showed a low performance to promote enol form due to its moderate p* of 0.51 (Table S2 †), 50,51 resulting in no tubule structure formed. TMO shared similar properties with toluene, however, it provided greater tubule formation than toluene according to its lower p* of 0.35 (Table S2 †).…”

1,3-Dioxolane compounds (DOXs) as biobased reaction media

“…More recently, other valuable green alternative solvents have been proposed in the literature, such as 2,2,5,5-tetramethyltetrahydrofuran (TMTHF) and 2,5-diethyl-2,5-dimethyloxolane (DEDMO) as non-polar and non-peroxide forming ether solvents. 11,12 3-Methoxybutan-2-one (MO) has been used instead of chlorinated solvents. 13 γ-Valerolactone (GVL) is a polar aprotic solvent effective in supporting cross-coupling reactions [14][15][16][17][18][19][20] and is (amongst) the best established bio-based alternatives to conventional dipolar aprotic solvents (e.g., DMF, NMP and DMSO).…”