Salt or Cocrystal? Using XRPD to Infer Proton Transfer in Three Adducts of Iodoxybenzoic Acid by Analyzing Iodine–Oxygen Bond Lengths

Abstract

2-Iodoxybenzoic acid (IBX) is a versatile oxidant, which has been used for a plethora of reactions through the years. Its explosive properties and low solubility, the major limitations to a more widespread use of this reactant, have led to the search for derivatives, adducts, or mixtures with comparable oxidative properties but better characteristics. In this paper, different adducts of IBX, in particular with pyridine (PIBX), quinoline (QUIBX), and nicotinamide (B3-IBX), have been structurally characterized using state-of-the-art X-ray powder diffraction (XRPD) methods. Their oxidative properties have been tested and compared to those of pristine IBX. While generally structure determination from XRPD does not allow us to investigate the proton position, a strategy was devised based on the investigation of iodine–oxygen exocyclic bond lengths to discriminate between single and double iodine–oxygen bonds. The final aim was to attempt to use XRPD to answer an elusive question: salt or cocrystal?

Crystal structure of the 1:1 co-crystal 4-(dimethylamino)pyridin-1-ium 8-hydroxyquinoline-5-sulfonate–N,N-dimethylpyridin-4-amine

“…Ionic co-crystals have much attention in pharmaceuticals for the development of improved drugs based on crystal engineering (Bolla et al, 2022) and in organic functional materials for achieving rare and multifunctional properties through tunable structures, morphologies, and sizes in co-crystal assemblies (Sun et al, 2019). In structural chemistry, ionic cocrystals containing pyridine-pyridinium derivatives bridged by an N-H� � �N hydrogen bond have already been proposed (Doring & Jones, 2016;Fabry et al, 2017;Zhang et al, 2018;Vladiskovic et al, 2023). In addition, the supramolecular synthon preference of pyridinium salts to 8-hydroxyquinoline-5-sulfonate (HqSA À ) and various sulfonates has been investigated (Ganie et al, 2021).…”

“…A search for compounds containing a pyridine-protonated pyridine skeleton gave 15 hits. In these compounds, the dihedral angles between two pyridine rings are close to 0 � in seven structures, which are essentially coplanar due to unique hydrogen-bonding networks stemming from the substituents on the pyridine rings (BAYBIN; Kobayashi et al, 2003;BECHOG;Glidewell et al, 1982;KIFBIO;Vladiskovic et al, 2023;WAZNET;Lackova et al, 2014;WEVHOX;Zhang et al, 2018;XACFOW;Mautner & Goher, 1998;XOHWAT;Santra et al, 2008). In single crystals of salts of the mellitate anion, which is obtained by deprotonation of mellitic acid (benzene hexacarboxylic acid), with substituted pyridinium derivatives, the triangular hydrogen-…”

Chiral resolution methods for racemic pharmaceuticals based on cocrystal formation

“…The components of cocrystals were connected by non-covalent interactions, especially hydrogen bonding. [33][34][35] There is no arbitrary borderline between salts and cocrystals. Both of them must be stoichiometric, and salts must have anionic and cationic components, as illustrated in Fig.…”

Deciphering the degree of proton-transfer in pyrido-cyclophanes by chiroptical outcomes in non-aqueous solvents

“…in the final species of each titration. Different techniques have been used for this purpose, including NMR, 36 IR, 18,37 XRPD 7,38 and polarography, 39 although mainly in carboxylic acids. Here we apply a simple and intuitive Brønsted correlation, plotting the log K 2 obtained from the mathematical fits (Table S3 †) against the pK a of the tested oxoacids.…”