Separation and In Situ Cocrystallization of C-Ethylresorcin[6]arenes with 1-(2-Pyridylazo)-2-naphthol

Abstract

Macrocyclic compounds are useful in a variety of application such as gas sorption/separation as a result of their unique molecular shape and ease of synthesis. In particular, one pot synthesis of conventional resorcin­[n]­arenes (n = 4) made resorcin[4]­arenes popular for the development of novel framework materials. However, synthesis of higher resorcin­[n]­arenes (n = 5, 6) possesses difficulty in separation of a particular form from mixture of isomers and/or oligomers. This difficulty in the synthesis limits the use of higher resorcin­[n]­arene for post synthetic applications. Here, we report separation and in situ construction of novel cocrystals of C-ethylresorcin­[6]­arene separated from its tetrameric counterpart, C-ethylresorcin­[4]­arene. Structural features of three novel cocrystals of C-ethylresorcin­[6]­arene with 1-(2-pyridylazo)-2-naphthol in methanol, ethanol, and acetonitrile are discussed herein as well.

Molecular Recognition with Resorcin[4]arene Cavitands: Switching, Halogen-Bonded Capsules, and Enantioselective Complexation

“…For example, we had achieved large enhancement in biological affinity by properly establishing halogen-bonding interactions between proteins and designed ligands. ,, The intrinsic strength of individual halogen bonds was subsequently established by study of model systems in solution. , Resorcin[4]­arene cavitands have played an enduring role in this development, with continuing studies on their synthesis and properties enabling them to become an even more powerful tool for the future construction of supramolecular receptors and in-depth molecular recognition studies. Routes to efficiently access and selectively functionalize higher resorcin­[ n ]­arenes ( n > 4) would represent a considerable advance, allowing to study of cavitands with larger internal cavities, further broadening the scope of their applications.…”

“…The majority of research is centered around resorcin[4]­arene derivatives, , as the higher homologues are more challenging to access and purify, with efforts ongoing to generate improved methods for their preparation and isolation While the Brønsted-acid-catalyzed condensation of resorcinol and an aldehyde remains the most common method for the preparation of octols (Figure ), modular post-functionalization methods as well as alternative synthetic strategies , provide access to a diversity of resorcin[4]­arene cavitands for widespread applications in host–guest chemistry. ,, These synthetic protocols have been extensively reviewed elsewhere and only a few key structural aspects specifically relevant to the construction of resorcin[4]­arene-based receptors are presented here.…”

Application of Cocrystallization for the Separation of C-Ethylresorcin[6]arene from C-Ethylresoricn[4]arene

“…38,39 In our recent article, we applied the cocrystallization technique for separation of hexameric C-ethylresorcin [6]arenes (4-RsC2) from Cethylresorcin [4]arenes (6-RsC2) using 1-(2-pyridylazo)-2 naphthol. 11 Thus, to extend this class of cocrystals based on RsCn, we separated tetrameric 4-RsC2 from hexameric 6-RsC2 and in situ synthesized two novel cocrystals of each macrocycle with bpy. The effects of solvent and stoichiometric ratio of components on the structural arrangements of the cocrystals are also investigated here.…”

“…These structural features of 4-RsCn and 4-PgCn offer a variety of intermolecular interactions such as hydrogen bonds through the hydroxyl groups, π–π interactions through the aromatic resorcinol or pyrogallol, H−π interactions through π-electron cloud of the 4-RsCn/4-PgCn bowl, and van der Waals forces through the C -alkyl chains. − Usually, crystallization of 4-RsCn or 4-PgCn entities yields bilayer, hexameric, or tubular arrangements of these macrocycles in the crystalline solid state. , However, cocrystallization of 4-RsCn and 4-PgCn with organic molecules such as 4,4′-bipyridine (bpy) results in a variety of framework architectures ranging from extended bilayers, wave-like arrangements, skewed bricks, extended capsules, and extended 1D to 2D frameworks. ,− Cocrystallization of 4-RsCn/4-PgCn with various small molecules is also employed to investigate host–guest interactions, and gas sorption ability of framework materials. ,− However, higher homologues of 4-RsCn/4-PgCn such as C -alkylresorcin­[5]­arenes and C -alkyresorcin­[6]­arenes (Scheme ) have not been explored much for construction of supramolecular frameworks since the synthesis and separation of these higher homologues are difficult . A typical acid-catalyzed condensation reaction for synthesis of resorcinarenes produces thermodynamically stable 4-RsCn; however, other oligomers and stereoisomers are also formed in minor concentrations. , Previous studies have explained that it is easier to functionalize and purify a reaction mixture than isolation of each oligomer from the mixture. , In our recent article, we applied the cocrystallization technique for separation of hexameric C -ethylresorcin­[6]­arenes (4-RsC2) from C -ethylresorcin­[4]­arenes (6-RsC2) using 1-(2-pyridylazo)-2 naphthol . Thus, to extend this class of cocrystals based on RsCn, we separated tetrameric 4-RsC2 from hexameric 6-RsC2 and in situ synthesized two novel cocrystals of each macrocycle with bpy.…”

“…Recently, cocrystallization is emerging as an alternative approach to improve the physical or chemical properties of crystalline materials. Particularly for pharmaceutical solids, cocrystallization may improve solubility, stability, dissolution rate, and dielectric properties of active pharmaceutical ingredients (APIs). − Apart from pharmaceuticals, cocrystals also have potential applications in scientific fields such as green chemistry, , electronics, , energy storage, , organic synthesis/separation, , and luminescent materials. , Formation of cocrystals results from noncovalent intermolecular interactions such as hydrogen bonds, halogen bonds, cation−π interactions, π–π interactions, and van der Waals forces between two or more different molecules in a given medium . Thus, these noncovalent interactions are influenced by molecular shape and functional groups on the molecules involved in the cocrystallization …”