Uncommon Solvent Immiscibilities

 KiloMentor is always on the lookout for methods to separate components of a mixture by partitioning between immiscible liquids. Better known ones are methanol or acetonitrile with hydrocarbons. Many different solvent pairs may show immiscibility between ambient temperature and -20 C and this temperature range is easily accessible inside a jacketed reactor where liquid-liquid partitioning is done at scale. It is in the laboratory that this temperature range is inconvenient to achieve.

Below are listed some less-common immiscible pairs that may prove useful.

Dimethylsulfoxide - Xylene

Dimethylsulfoxide - Diethyl Ether

Dimethylformamide - Xylene

Dimethylformamide -Diisopropylether

Trichloroethylene - Xylene

Acetic acid - Hexane

Methyl t-Butyl Ether (TBME) -Sulfolane

The DMF /Diisopropyl ether immiscibility suggests that one look for an Upper Critical SolutionTemperature (UCST) between DMF and TBME at below room temperature. A small amount of water could be added to the DMF to raise the UCST.

Since DMSO and diethyl ether have immiscibility it suggests that one explore for a UCST between DMSO and TBME below ambient temperature.

What would the miscibility be between a mixture of xylene and diethyl ether with DMSO? Both xylene and diethyl ether are separately immiscible with DMSO.

To get rid of the diethyl ether suppose we try a mixture of xylene and TBME with DMSO?

How about a mixture of DMSO and trichloroethylene with xylene? Both DMSO and trichloroethylene are separately immiscible with xylene.

Dimethylsulfoxide or DMF reactions could be worked up by extraction into m-Xylene followed by azeotropically removing the xylene as an azeotrope with water after cold extracting the xylene to remove residual dipolar aprotic solvent.

Both m-xylene and isopropylbenzene form azeotropes with water that can be used to quickly remove the organic as a clean phase. Can either of these be useful for isolating organics formed in the solvents DMF or DMSO? You tell me- I’m retired; you have a lab.

Diphenylphosphine Oxide Containing Compounds: Intermediates almost guaranteed to be Crystalline

 

 Stuart Warren, in an article in Accounts of Chemical Research 11 (11) 401 (1978), wrote that almost all diphenylphosphine oxide-containing compounds are highly crystalline white solids. KiloMentor is, therefore, proposing the use of compounds containing the diphenylphosphine oxide substructure as one of the preferred intermediate types in ‘paper’ syntheses.

It is well known that the reaction of a primary alkyl halide with triphenylphosphine produces a quaternary phosphonium salt that is both an ionic salt and crystalline. Hydrolysis of such a compound in aqueous base liberates benzene and provides the phosphine oxides. These compounds in turn can be alkylated with other alkyl halides using butyllithium and TMEDA as co-solvent. [J. Chem. Soc. Perkin Trans. I, 550 (1977)] Warren predicts that these also will be highly crystalline solids.

The KiloMentor strategy for paper synthesis route design emphasizes the advantages of selecting a route that can easily be scaled up. To be preferred, intermediates need to have an increased likelihood of being easily separated and purified, preferably by acid-base extraction. This is proposed to be an overarching advantage over competing routes, whose intermediates almost always have to be purified by crystallization. The problem with these competing routes is that the crystallizability of an intermediate from a paper synthesis cannot be dependably predicted.  

Besides those intermediates, purifiable by extraction, other intermediates would also be preferred if, even when still unknown and existing only ‘on paper’, they contained a functional group that could pretty well guarantee they would be found to be crystalline. There are not many of these and they are not celebrated for this property. Usually, the ease of crystallization for a compound depends upon the entire molecular structure and cannot be predicted, but diphenylphosphine oxide appears to be one that should come with a guarantee.