Controlling the Interface between Salts, Solvates, Co-crystals, and Ionic Liquids with Non-stoichiometric Protic Azolium Azolates

Abstract

A non-stoichiometric approach to control the solid-state behavior of protic ionic liquids (PILs) was demonstrated by direct mixing of 4,5-dicyanoimidazole (HDCNim) with either 1-ethylimidazole (C2im) or 1-butylimidazole (C4im) in different mole fractions. Isolation and characterization of three crystalline materials (all having melting points < 100 °C, thus fitting the PIL definition) revealed three different but closely related systems. The structure of [HC2im]­[DCNim] consists of a confused proton system, which is so named for the fast proton exchange between basic and acidic fragments and the formation of hydrogen-bonded anionic oligomers. The compound [HC2im]­[DCNim]·HDCNim consists of an oligomeric delocalized anion (a confused proton located between two azole fragments, in which one acts as a neutral moiety while the other as an ionic fragment, DCNim-H-DCNim) and [HC4im][DCNim]·HDCNim can be classified as a salt co-crystal. We believe that these observations will allow a deeper understanding of the behavior of “confused protons” and provide additional strategies for controlling the properties of important classes of materials such as active pharmaceutical ingredients.

Introductory Chapter: Azoles, Their Importance, and Applications

“…The review explored the 122 known so far azolate-containing ionic liquids which were prepared from only 39 disparate azolate anions, with a goal to highlight not only their well pronounced utility as IL components, but also the ways in which their advantageous properties may be used by the broader scientific community for design of new tailored materials. In this context, it is also worthwhile to mention another work by Easton et al [35] where a non-stoichiometric approach to control the solid-state behavior of protic ionic liquids (PILs) was demonstrated by direct mixing of 4,5-dicyanoimidazole (HDCNim) with either 1-ethylimidazole (C2im) or 1-butylimidazole (C4im) in different mole fractions.…”

Bioinspired Ion Pairs Transforming Papaverine into a Protic Ionic Liquid and Salts

“… 14 − 16 PILs are prepared in a simple neutralization reaction of certain Brønsted acids and Brønsted bases in an equimolar ratio. 17 , 18 A subset of PILs is the protic oligomeric ILs (OILs), which are the result of a reaction of several equivalents of a Brønsted acid with one equivalent of a Brønsted base to form H-bonded acid oligomer-based ILs. 19 , 20 …”

“…14−16 PILs are prepared in a simple neutralization reaction of certain Brønsted acids and Brønsted bases in an equimolar ratio. 17,18 A subset of PILs is the protic oligomeric ILs (OILs), which are the result of a reaction of several equivalents of a Brønsted acid with one equivalent of a Brønsted base to form H-bonded acid oligomer-based ILs. 19,20 The effect of organic acids or other dispersants with low molecular weight is mainly based on the charging of the surface of the powder particles, thereby increasing the repulsive double-layer forces.…”

“…An alternative approach to overcome these drawbacks is the development of bioinspired ILs, which are solely composed of naturally occurring moleculescomponents having well characterized biodegradable and toxicological properties . Larger counterions reduce lattice forces within crystals, which is why bulky natural carboxylic acids might be particularly valuable for PIL formation of basic, poorly water-soluble APIs with the ultimate goal of improved apparent solubility and/or dissolution rates. − PILs are prepared in a simple neutralization reaction of certain Brønsted acids and Brønsted bases in an equimolar ratio. , A subset of PILs is the protic oligomeric ILs (OILs), which are the result of a reaction of several equivalents of a Brønsted acid with one equivalent of a Brønsted base to form H-bonded acid oligomer-based ILs. , …”