Modulating Supramolecular Reactivity Using Covalent “Switches” on a Pyrazole Platform

Abstract

Systematic co-crystallizations of halogen- methyl- and nitro-substituted pyrazoles with a library of 20 aromatic carboxylic acids have been carried out using melt and solution-based experiments. The solids resulting from all reactions were screened using infrared spectroscopy in order to determine if a reaction (co-crystal or salt) had taken place. The halogenated pyrazoles, including their dimethyl analogues, gave a supramolecular yield of 55–70%. Replacing a halogen atom (R-X, X = Cl, Br, I) with a nitro (R-NO2) group drops the success rate significantly to 10% due to the reduced charge on the basic nitrogen atom of the pyrazole. Eleven crystal structures were obtained: six were co-crystals and five were salts (including one hydrate). In all six co-crystals, dimeric pyrazole···acid assemblies were constructed via a combination of O–H---N(pyz) and N–H---O hydrogen bonds corresponding to a 100% supramolecular yield. A variety of weaker halogen-bonds CN---I, I---I and X---O– connect dimers into infinite on...