PEG 400 (Polyethylene Glycol liquid) as a Useful Organic Reaction Solvent

Distillation at-scale often uses a chaser because, otherwise, a volume equal to the minimum stirrable volume must be left in the still pot and this can often seriously reduces the product’s recovery yield http://www.kilomentor.com/2007/01/chemical-definitions-used-in-kilomentor-process-development .
If you are contemplating distilling a product out of a chemical process step’s reaction mixture, you ought to consider using PEG 400 as the solvent or co-solvent. Being a polymer it has a very high boiling point and will not co-distil in your product fraction but will act as a nonvolatile chaser. It should be used in at least the amount needed to fill up the minimal stirrable volume.

The use of PEG 400 as a reaction solvent is not new. {Enzo Santaniello, Ada Manzocchiand Piero Sozzani, Polyethylene glycols as Host Solvents: Application to Organic Synthesis, Tet. Let. 47 4581-4582 (1979)}. These authors identified the advantages of low cost, ready availability, low vapor pressure, and the good solubility of a wide range of inorganic salts when as a reaction solvent. They also noted PEG 400s miscibility with water and immiscibility with pentane as tools that could be used during isolations. They further noted and demonstrated that some products could be distilled directly from the reaction mixtures. All that I wish to add is the special recovery yield benefit achievable using the PEG as a distillation chaser at scale.

Sozzani et al. contemplated using PEG 400 as solvent for displacement reactions with inorganic anions in the same way that DMSO is used to activate the same class of reactions. Oxidations and reductions were also demonstrated. Because of its special utility for enhancing distillation recoveries, however, it should be considered for many other applications. Because PEG 400 always has some residual water, polyethylenglycol should be considered for hydrolysis of tertiary amides as contemplated by Gassman et al. { JACS 98, 1275-1276, 91976}. This method would hydrolyze a t-amide in the presence of primary and secondary amides! Elimination reactions would also be preferred applications.

PEG has one apparent disadvantage. Recycling this material would require the removal of inorganic salts. Separations of inorganic salts from polyethylene glycol polymers has been described in a paper published online at http://www.ffc-asso.fr/opcd_2/diapos/Polyethylene_glycol_and_solutions_of_PEG_as_green_reaction_media.pdf
The method is called aqueous biphasic separations (ABS). This paper also contains many examples of different reactions that can be run in neat PEG and mixtures of PEG and water and reviews the use of PEG as an inexpensive phase transfer catalysis.
Recovery may not be of concern. Many batch processes do not recycle solvents, but rather send them away for destruction or to be recovered at specialty companies. Recover and reuse, despite the raves of green chemists, has its own problem getting consistent COAs for the solvents when they are returned from the recovery.

P>S> PEG should be considered as an improvement on using ethanol as solvent.