Phenylboronic Acid: A Functional Tag to Enable Simple Removal of Excess Reagent or Coproduct using Chromotropic Acid

Chromotropic Acid for Extracting Boronates

The KiloMentor Blog articles emphasize ways to make the workup, separation, and purification of the product from organic reactions more cost-effective. Often this is enabled by phase switching methods that quickly take the desired material into one bulk phase and byproducts, coproduces, and the processing chemicals into another.

One way to dot this is to use a reagent or coreactant that has built into its structure some functionality that allows it to be subsequently extracted into an aqueous phase. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride is an example of such a reagent. The pendant dimethylamino functional group makes an excess reagent or coproduce or byproduct basic and so soluble in aqueous acid.

A functional fragment that can be used in this way but has rarely been adopted is the p-dihydroxy-boryl benzyl function.  This substructure appears in the Dobz protecting group for peptide synthesis [D.S. Kemp and David C. Roberts, Tet. Lett. 52, 4629-4632, 1975]. The dihydroxyboryl group forms a strong covalent linkage with the sodium salt of chromotropic acid [1,8-dihydroxynaphthalene-3,6-disulfonic acid] which is very soluble in water.

In the absence of complexing species, boronic acids are in reversible equilibrium with their cyclic trimers and water. Other species containing the group may be partially converted to Boronic anhydrides.

Although many reactions can be conducted in the presence of the free Boronic acid function  as a second option the Boronic acid can itself be protected as the N-methyldiethanolamine complex. N-methylethanolamine is of course itself readily taken into water in a workup.