A Chromatography-free Method for the Isolation of Products from Mechanochemical Reactions - Ball Milling Towards Green Synthesis: Applications, Projects, Challenges - page 193

Cl Cl

Cl

Polymerization

+

Cl

Cl Cl Cl

n

Scheme 8.1 Synthesis of polystyrene polymer resin cross-linked with 1,4-divinyl

benzene.

to the polymer support will remain. Therefore, instead of conducting chro-
matography to isolate the peptide, you can simply wash away all of the un-
desired by-products, leaving behind the desired peptide attached to the
polymer support. Subsequently, the desired peptide can be isolated by
cleaving it from the polymer support (Scheme 8.2).
Use of this model of synthesis has been expanded to solid phase organic
synthesis (SPOS), allowing for a wide variety of synthetic methods. 20-22 In
principle this is a very clean and simple method for the isolation of com-
pounds. Unfortunately, to use polymer supported resins, the resin needs to
be activated in a solvent that allows the polymer to swell. Similar to the
problems with column chromatography, the solvent choice to swell the
polymer resin cannot be easily replaced by greener alternatives.
One of the major drawbacks of polymer supported resins is that only
roughly 1% of the functionality resides on the outside of the polymer sur-
face. 23 For the rest of the polymer supported reagents to be accessible to the
reaction they must be placed in an organic solvent and swollen. The action
of swelling allows the substrates to fit through the pores of the crosslinked
polymer and interact with the internal reagents. Unfortunately, the act of
swelling polymer supported reagents requires hazardous organic solvents
such as benzene, toluene, or dichloromethane to name a few. Further, de-
pending on the nature of the polymer resin, as well as the polarity of the
reagents, the ability to swell the polymer can be unpredictable. As an ex-
ample Hoff and co-workers used an analogue of the Corey-Bakshi-Shibata
reagent attached to a poly-methacrylate polymer bead. 24 They discovered
that THF and dichloromethane were suitable solvents to swell the polymer
bead in order to conduct the reaction. However, similar ethereal solvents