A Speculation concerning How to more easily Work-Up Reactions with High Boiling Glymes as Solvent

THIS IS A SPECULATION that is why it can be a subject for undergraduate or graduate study.

The glymes are methyl ethers of polyethylene oxide. They aren’t particularly popular solvents for organic synthesis because they are high boiling and therefore difficult to remove from reaction products. Also because they are quite soluble both in organic solvents and water they cannot so easily be removed by liquid-liquid partitioning. The speculation is whether it might be removable by solid-liquid partitioning!  

Urea is a solid below its melting point of 153℃. But urea will dissolve in hot methanol and glyme molecules of greater length than 8 atoms crystallize as inclusion complexes with urea from methanol. So adding a hot solution or slurry of urea in methanol into a reaction mixture in which a glyme had been the solvent might be expected to crystallize out the glyme-urea inclusion complex leaving the rest of the reaction mixture dissolved in methanol containing some residual urea.

For most organic chemical reactions a homogeneous liquid medium ( a solvent) is used to efficiently bring reaction partners into contact under conditions compatible with their reaction together. Generally, reaction occurs more smoothly and completely if all reactants, reagents, and processing chemicals dissolve in the liquid medium. Since a medium’s physical properties determine what it can dissolve perhaps a mixture of materials might be able to dissolve a wider range of substances. The downside is using a complex solvent system.

Suppose the solvent mixture separated itself? Urea dissolves in methanol. Tetraglyme, which is a liquid linear polyether, forms complexes with urea. In excess methanol, it can perhaps be expected that the straight-chain tetraglyme might fill the channels within the crystalline urea so that it crystallizes as the bulk methanol cooled. Filtering might leave in the filtrate only some residual urea and a methanol solution of whatever remains from the reaction mixture that is soluble in methanol alone. What is unknown is  (i) how complete is the precipitation of tetraglyme with crystallizing urea in methanol (ii) is the volume of urea-methanol needed to crystallize tetraglyme practical (iii) whether the components that it is hoped will involve themselves in reacting together interfere with the inclusion complex formation and (iv) whether they might interfere in the complete crystallization of the urea inclusion complex.

Certainly, when hot, methanol, urea, and tetraglyme together should be a good environment for dissolving a wide range of different reagents and substrates. Methanol would provide hard acid protons and hard base oxygen, urea would provide soft base electron pairs from nitrogen and oxygen and tetraglyme could present a multidentate ligand to wrap around any metal ions.

The methodology could also be used to work-up reactions done in tetraglyme alone. Certainly, there are many reaction types that could benefit from tetraglyme as solvent. The urea and methanol could in these cases be added to free the reaction mixture of tetraglyme. Finally, after removing insoluble urea-tetraglyme inclusion complex the residual liquid medium could be diluted with water and extracted with a cheap immiscible organic solvent to extract away key reaction products.