Pyridine-4-thiol as halogen-bond (HaB) acceptor: influence of the noncovalent interaction in its reactivity

Abstract

The study of pyridine-4-thiol as a halogen-bond (HaB) acceptor has allowed the isolation of its cocrystal with the HaB donor IC6F4I, namely, 1,2,4,5-tetrafluoro-3,6-diiodobenzene bis(pyridin-1-ium-4-ylsulfanide), C6F4I2·2C5H5NS (1), where the S atom is the HaB acceptor, while the pyridine position is blocked by the proton. Furthermore, the S atom acts a dual acceptor and also establishes an interaction with the pyridinium proton from an adjacent molecule. The presence of these interactions in 1 contributes to the stabilization of the zwitterionic form. This pre-organization seems to have an influence on the reactivity of the compound since when left in dichloromethane solution, an unusual activation of the C—Cl bond is observed that leads to the formation of the bis[(pyridin-1-ium-4-yl)sulfanyl]methane dication, while the Cl atoms are still present as chloride counter-ions, i.e. 4,4′-[methanediyldi(sulfanediyl)]dipyridinium dichloride, C11H12N2S2 2+·2Cl− (2). In the crystal structure of 2 it is observed that the S atom is now acting as the donor part of a chalcogenide bond with the chloride anions.

Halogen bonds, chalcogen bonds, pnictogen bonds, tetrel bonds and other σ-hole interactions: a snapshot of current progress

“…The study is supported by density functional theory (DFT) calculations and a statistical analysis of C-X� � �N C halogen-bond geometries using the CSD. Finally, Mosquera et al (2023) link halogen bonding and reactivity in their study of pyridine-4-thiol (4-mercaptopyridine). Cocrystallization with the ditopic halogen-bond donor 1,4-diiodotetrafluorobenzene leads to tautomerization of the thiol to give the zwitterionic analogue with thiolate and pyridinium groups.…”

“…(d) Bending crystals of 4-halobenzonitrile containing C-X� � �N C halogen bonds(Veluthaparambath et al, 2022). (e) C-I� � �S halogen-bonded cocrystals -links to the nucleophilic substitution reaction(Mosquera et al, 2023). All figures are reproduced from the cited references with permission.…”

Definition of the Halogen Bond (IUPAC Recommendations 2013): A Revisit

“…Halogen bonds were often abbreviated as XBs, ,,,− although recently the abbreviation HaB has come into use. − Formal definitions became desirable with the increasing appreciation of the significance of noncovalent interactions in areas as diverse as crystal engineering, chemistry; physics; molecular biology; crystallography; and polymer, supramolecular, medicinal, and materials sciences, among others.…”