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. 

Separating Sulphur-containing from Sulphur-free Compounds both in the Lab and At Scale

Long ago, In 1964, G.M.Badger, N. Kowanko and W.H. F. Sasse submitted a short communication  to J. Chromatog. 13, (1964) 234 titled, Chromatography on a column of Raney cobalt.The small experimental read as follows:

“The freshly prepared Raney cobalt (ca 7.5 g) was mixed with clean sand and packed into a chromatographic column (1.2 cm X 10 cm.). A mixture of isoeugenol (0.5 g) and 2,5-dimethylthiophene (0.5 g) was applied to the column and eluted with methanol ( a 3-ft head of liquid was required). Evaporation of the first fraction 930 ml) gave sulfur-free isoeugenol (0.477 g). Subsequent fractions contained only trace amounts of isoeugenol and were also sulfur-free. The dimethylthiophene was subsequently recovered by Soxhlet extraction of the cobalt-containing solid with methanol.” (my italics).

The discussion pointed out that active cobalt metal binds sulfur containing compounds by chemisorption; however, unlike Raney nickel, Raney cobalt has a much reduced tendency to desulfurize. Nevertheless, this binding is powerful, much stronger than simple adsorption, as the rigorous conditions described for removing the dimethylthiophene from the solid phase attested.

What this suggested to me was that the method would not need to be conducted as a column chromatography. It would probably work simply by stirring the solid with a solution containing the sulfurous material, passing through filter aid, and washing. Thus, the method could separate sulfur- containing from sulfur-free materials by filtration as easily as an insoluble polymer is separated from a solution.

That  desulfurization under the conditions of a separation is unlikely is further suggested by another paper [1960] by the same authors which contains the sentence “Desulphurisation with Raney cobalt was similar to that with W7-J Raney nickel in that, although little reaction occurred in boiling methanol, it was complete in diethyl phthalate at 220.”

It would seem that, besides obviously being able to separate the sulfur containing from sulfur free compounds, the technology should be adaptable to separate compounds that have been derivatized with a sulfur a containing reagent from compounds without such an appendage.

It might be that the method of recovery of the chemisorbed compound could be improved. Eluting with a solvent containing carbon disulfide or COS might speed the recovery without ireversibly contaminating the eluting solvent.

Also, a chemisorbant simpler to prepare than Raney cobalt might be available by reducing a cobalt salt with sodium borohydride to give a Cobalt boride analogous to the Nickel boride catalysts called P-1 and P-2 developed by H. C.Brown et al.