Crystal Engineering with Iodoethynylnitrobenzenes: A Group of Highly Effective Halogen-Bond Donors

Abstract

The benefits of employing a 'double activation' strategy for promoting effective practical cocrystal synthesis through halogen bonding was explored in a systematic supramolecular synthetic study of iodoethynylnitrobenzenes, where the positive electrostatic potential on the iodine atom was enhanced through a combination of an sp-hybridized carbon atom and one or more electronwithdrawing nitro groups. Three model compounds, 1-(iodoethynyl)-4-nitrobenzene (4N-I), 1-(iodoethynyl)-3-nitrobenzene (3N-I) and 1-(iodoethynyl)-3,5-dinitrobenzene (3,5DN-I) were synthesized and characterized, and calculated molecular electrostatic surface potential values on the halogen-bond donor site were about 20-40 kJ/mol higher than those observed for previously well-established halogen-bond donors. The ability of these molecules to drive co-crystal formation was evaluated through a total of 45 co-crystallization experiments with 15 different acceptor molecules. IR spectroscopic data for the resulting products showed that each reaction in the formation of a co-crystal driven by either C-I···N or C-I···O halogen bonds. The analogues bromo-compounds displayed a 60% success rate whereas the chloro-analogues did not yield any co-crystals, emphasizing the importance of the magnitude of the electrostatic aspects of halogen bonding for practical supramolecular synthesis. Ten new crystal structures are presented and the outcome (in terms of stoichiometry and connectivity) is largely predictable. A comparison of I···acceptor distances found in these structures with relevant data from the CSD shows that iodoethynylnitrobenzenes consistently give rise to a larger reduction of combined van der Waals radii (for C-X···acceptor) than do other well-known halogen bond donor moieties.

Pillars of assembled pyridyl bis-urea macrocycles: a robust synthon to organize diiodotetrafluorobenzenes

“…2b illustrates the pillars of 1, which are held together through two different hydrogen bond acceptors: the urea oxygen (NIJH)⋯O, 2.904(2) Å) and the pyridyl nitrogen (NIJH)⋯N, 3.082(2) Å). 10 Along a single pillar, the oxygen atoms on the macrocyclic assembly of 1 are oriented on opposite sides, one pointing up and the other pointing down. This arrangement results in the available oxygen lone pairs being approximately linear to each other (Fig.…”

“…In each co-crystal, CO⋯I interactions ranging from 2.760(4) to 2.853(4) Å were observed that were significantly shorter than the sum van der Waals radii of the atoms involved and are among the shortest reported for neutral organic molecules. 10 To further estimate the strength of the O⋯I interaction, their interaction energies in the co-crystals were calculated by Q-Chem quantum chemistry package in the electronic ground-state using dispersion corrected density function theory (DFT-D). Taking the basis set super position error (BSSE) into account reduces the uncorrected values by 2-3 kJ mol −1 where ΔE represent the uncorrected halogen bond interaction Table 2).…”

Exploring the (Very Flat) Potential Energy Landscape of R−Br⋅⋅⋅π Interactions with Accurate CCSD(T) and SAPT Techniques

“…13–15 A halogen bond is a short-range RX…YZ interaction, where X is a halogen (typically chlorine, bromine, or iodine) that is part of the molecule RX and YZ is a Lewis base; Y is often an atom, such as oxygen, nitrogen, or sulfur, that has a lone pair. Halogen bonds can be said to be analogous in many ways to hydrogen bonds (of the form RH…YZ).…”

Strength, character, and directionality of halogen bonds involving cationic halogen bond donors

“…1–9 These noncovalent interactions have been observed in protein-ligand complexes, 9–13 crystal structures of neutral molecules, 14–16 and crystals composed of molecular ions. 17, 18 A halogen bond is an interaction of the type RX…YZ, where X is a halogen (chlorine, bromine, or iodine) that is part of the molecule, or molecular ion, RX, and YZ is a Lewis base.…”