A Chromatography-free Method for the Isolation of Products from Mechanochemical Reactions - Ball Milling Towards Green Synthesis: Applications, Projects, Challenges - page 197

Figure 8.2 Pre-milled polymer resin (A); resin after 15 min of milling (B). 34
take merely one solvent to swell the bead, but rather a combination of polar
and non-polar solvents. A biphasic method using water/THF and phase
transfer catalyst has been shown to be effective. 30-33
In lieu of using a solution to conduct the polymer supported Wittig
reaction, the use of polymer supported reagents under mechanochemical
conditions was shown to be very effective. 34 Through mechanical grinding,
the functional sites on the polymer bead could be accessed through in-
creasing the surface area of the resin; more specifically, pulverizing the
resin into smaller particle sizes (Figure 8.2). Before being ball milled, the
functional resin particle size consistently measured between 75 and
125 mm.
Following ball milling, the resin measured approximately 1-5 mm. Tra-
ditionally, non-polar, organic solvents such as benzene or dichloro-
methane are needed to swell functional resins, allowing reagents to
diffuse through the crosslinked pores of the resin. Although these solvents
are a good choice for swelling the resin, they are not environmentally
desirable. Polar solvents, such as ethyl acetate and ethanol, are much
more desirable from an environmental perspective, but these solvents do
not swell the functional resin. When comparing the Wittig reaction using
solid support in an ethanol environment only 13% of the product stilbene
was isolated over a two-day period. However, where pre-milled resin
particles were used in the reaction 56% of the product stilbene was
isolated in a two-hour period. When triphenylphosphine-functionalized
polystyrene was used in the Wittig reaction under solvent-free mechano-
chemical conditions, the product stilbene was only recovered in 17% yield
after 16 h of milling. This demonstrated, under mechanochemical con-
ditions, that the unpredictable method of swelling is an unnecessary
component of the reaction. However, for the polymer supported
Wittig reaction, even through the use of mechanical activation, a polar
environment is still necessary.
Liquid assisted grinding is a method whereby a small amount of liquid is
used to aid in the grinding process. It was shown that by adding a small