Quaternary and quinary molecular solids based on structural inequivalence and combinatorial approaches: 2-nitroresorcinol and 4,6-dichlororesorcinol

Abstract

A synthetic strategy for the formation of stoichiometric quaternary and nonstoichiometric quinary solids is outlined. A series of 2-nitroresorcinol-based quaternary cocrystals were developed from binary precursors in two conceptual stages. In the first stage, ternary solids are synthesized based on the structural inequivalence at two recognition sites in the binary. In the second stage, the ternary is homologated into a stoichiometric quaternary based on the same concept. Any cocrystal without an inequivalence becomes a synthetic dead end. The combinatorial approach involves lower cocrystal systems with different structural environments and preferred synthon selection from a synthon library in solution. Such are the stepping stones for the isolation of higher cocrystals. In addition, a quaternary cocrystal of 4,6-dichlororesorcinol is described wherein an unusual synthon is observed with two resorcinol molecules in a closed loop with two different ditopic bases. The concept of the virtual synthon in binaries with respect to isolated ternaries is validated for the 4,6-dichlororesorcinol system. It is possible that only some binary systems are amenable to homologation into higher cocrystals. The reasons for this could have to do with the existence of preferred synthon modules, in other words, the critical components of the putative higher assembly that cannot be altered. Addition of the third and fourth component might be more flexible, and the choices of these components, possible from a larger pool of chemically related molecules.

Quaternary Cocrystals of 3,5-Dihydroxybenzoic Acid

“…From the above observation, it seems clear that DHB:PHE:PYR gets converted into 2:1:2:1 DHB:TMP:PHE:PYR, whereas DHB:TMP:PYR leads to formation of 2:2:1:2 DHB:TMP:PHE:PYR during the crystallization. Interestingly, DHB:TMP:PHE:PYR (2:1:2:1) forms a symmetrical synthon D (two connecting bases are identical, i.e., PHE), whereas an unsymmetrical synthon E (two bases are different, i.e., TMP and PHE) is found in DHB:TMP:PHE:PYR (2:2:1:2), which is rare and only recently observed. , The appearance of two variant crystal structures in this system highlights the existence of competitive and kinetically favored synthons in the supersaturated solution prior to crystallization . The solvent of crystallization for both pseudopolymorphs is different, and hence, the anomalous synthon D is considered as a virtual synthon with respect to synthon E, and vice versa.…”

“…2), which is rare and only recently observed. 13,42 The appearance of two variant crystal structures in this system highlights the existence of competitive and kinetically favored synthons in the supersaturated solution prior to crystallization. 43 The solvent of crystallization for both pseudopolymorphs is different, and hence, the anomalous synthon D is considered as a virtual synthon with respect to synthon E, and vice versa.…”

“…Crystal engineering , for synthesis of multicomponent cocrystals − empowers supramolecular chemists to proceed in the direction of one-pot synthesis of ternary, − quaternary, , and higher cocrystals , with flexibility of addition and/or enhancement of desirable physicochemical properties of crystalline products. − Bringing three or four different components within the same crystal lattice is a complicated and daunting task that is accompanied by simultaneous optimization of intermolecular interactions ,− (hydrogen and halogen bonding interaction) and geometrical recognition based on structural inequivalence , and long-range synthon Aufbau modules (LSAM) strategies. However, a vast number of higher (three or four components) cocrystals remain undiscovered.…”

“…However, a vast number of higher (three or four components) cocrystals remain undiscovered. Despite the fact that five component solid solutions ,,, are reported, achieving a stoichiometric quinary cocrystal is a far-fetched dream. On the other hand, pseudopolymorphism, a kind of supramolecular isomerism, is the phenomenon wherein a compound is obtained in variant crystalline forms that differ in the nature or stoichiometry of the solvent molecules included .…”

Polymorphism and photoluminescence seen in (2-amino-5-chloropyridine)·(9-anthracenecarboxylic acid)·(trinitrobenzene): a further example of the salt-cocrystal continuum observed by virtue of isolating multiple crystal forms

“…Designing and isolating multi-component adducts is a delicate process since crystallisation is essentially a purification technique, which will often preferentially result in the formation of crystals of the individual starting materials. 1 Desiraju and co-workers 2 have been at the forefront of developing design strategies for the synthesis of higher order cocrystals, including ternary (three-component) cocrystals, 1,3,4 quaternary (four-component) cocrystals, [5][6][7] and more recently quinary/quintinary (five-component) 6,7 and senary (sixcomponent) 8 solid-solution cocrystals. In the past few years, many other research groups have also synthesized and studied ternary and quaternary cocrystals.…”