A Novel Purification Method in Organic Synthesis Using Hydrogen Bonding

Abstract

A new workup and purification method based on quadruple hydrogen‐bonding interactions is reported. Substrates containing a hydrogen‐bonding affinity tag – either directly connected or through a cleavable linker – were conveniently separated from a reaction mixture and purified using a resin containing self‐complementary affinity tags. Several Ugi products and nucleophilic aromatic substitution products were successfully purified by this hydrogen‐bonding‐based affinity‐separation protocol.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Lesser-Known Enabling Technologies for Organic Synthesis

“…In a recent example, two self-complementary hydrogen-bonding ureidopyrimidinone units were used, one present as a tag on the molecule to be phase-switched, 125, and one present on the solid support, 126 (Scheme 23). 63 The dimerisation constants of 6 × 10 7 M -1 in chloroform and 6 × 10 8 M -1 in toluene allow complete sequestration of the tagged species in these non-protic solvents. A series of nucleophilic aromatic substitutions were carried out using the affinity tag as a means to effect 'catch and release' pu-rification of the tagged products and as a means to separate the tag after subsequent cleavage.…”

Experimental and computational thermochemistry: how strong is the intramolecular hydrogen bond in alkyl 2-hydroxybenzoates (salicylates)

“…3 An important structural feature of alkyl salicylates is the presence of a hydroxyl group, which is able to form intraand inter-molecular hydrogen bonds. Hydrogen bonds, in turn, are important for various physical-chemical processes: molecular recognition, 4,5 as a purification method in organic synthesis, 6 self-assembly of nanoparticles, 7 formation of protein clusters, 8 etc. It should be noted that intra-molecular hydrogen bonding (intra-HB) has been studied to a much lesser extent in contrast to inter-molecular hydrogen bonding (inter-HB).…”

Supramolecular Substitution Reactions between Hydrazide-Based Molecular Duplex Strands: Complexation Induced Nonsymmetry and Dynamic Behavior

“…Heterocycle-based building blocks (usually urea derivatives) – and linear materials composed of arrays of hydrogen-bonding sites – have gained great success. In particular, Meijer’s ureidopyrimidone (UPy) building block, , with its characteristic simplicity in synthesis and exceedingly high dimerization constant ( K dim ∼ 10 7 M −1 in CDCl 3 ), has found widespread applications in the construction of various nanostructures, material science, separation, catalysis, etc. Gong’s oligoamide system and Zimmerman’s ureidonaphthyridine system are successful examples of other building blocks.…”