Establishing Halogen‐Bond Preferences in Molecules with Multiple Acceptor Sites

Abstract

The interplay between hydrogen bonds (HBs) and halogen bonds (XBs), has been addressed by co‐crystallizing two halogen bond donors, 1,4‐diiodotetrafluorbenzene(DITFB) and 1,3,5‐trifluoro‐2,4,6‐triiodobenzene(TITFB) with four series of targets; N‐(pyridin‐2‐yl)benzamide (Bz‐X), N‐(pyridin‐2‐yl)picolinamides (2Pyr‐X), N‐(pyridin‐2‐yl)nicotinamides (3Pyr‐X), N‐(pyridin‐2‐yl)isonicotinamides (4Pyr‐X); X=H/Cl/Br/I. The structural outcomes were compared with interactions in the targets themselves. 13 co‐crystals were analysed by single‐crystal X‐ray diffraction (SCXRD). In all three co‐crystals from the 2Pyr series, the intramolecular HB remained intact while the XB donors engaged with the N(pyr) or O=C sites. In the ten co‐crystals from the other three series, the intermolecular HBs present in the individual targets were disrupted in 9/10 cases. Overall, the acceptor sites selected by the halogen‐bond donors in these targets were distributed as follows; N(pyr)=81 %, O=C (15 %) or π (4 %).

The amphoteric role of nitrogen in the NX2 unit within crystals

“…Overall, our results demonstrate the presence of NX 2 (X = Cl, Br, I) units, equivalent to the X 3 synthon reported for halogen (X) bonding. 61 (ii) GAKGAB, 62 (iii) HEZGAW, 63 (iv) OJIHIA, 64 (v) PESZOE, 65 (vi) TUNXIM, 66 (vii) UXARIX, 67 (viii) VIXXAE 68 and (ix) YANPIP. 69 Table 3 Interaction energies of the NI 2 unit in each centroid structure and its classification.…”

“…Fig.9Molecular graphs of the centroid structures with the NI 2 unit. The CSD codes are: (i) BUNGEY,61 (ii) GAKGAB,62 (iii) HEZGAW,63 (iv) OJIHIA,64 (v) PESZOE,65 (vi) TUNXIM,66 (vii) UXARIX,67 (viii) VIXXAE 68 and (ix) YANPIP 69. …”

Variable Cl···O Halogen Bonding Modes in Dimorphs of a Room Temperature Liquid Ethyl Chloroformate Revealed by In Situ Cryo-Crystallography

“…In addition to the theoretical studies, a number of experimental X-ray charge density studies on halogen bonding, − chalcogen bonding, ,− carbon bonding, and pnicogen bonding , have by now established their n → σ* nature and that they are predominantly of electrostatic originas direct interaction of a charge-depleted region on the bond donor atom and charge concentrated region on the acceptor atom. Halogen bond (XB), where one of the bonding partners is halogen atom or ion [as a charge depletion site, i.e., δ+ or Lewis acid center], has now attained the status of “structure directing noncovalent interaction”, not only in the solid state but also in the solution and gaseous states. , Ever increasing reports on the role halogen bonds in crystal engineering, supramolecular assemblies, and biological systems indicate its capability as a structure driving force with interaction energies comparable to that of hydrogen bonds. − In complex molecules with multifunctional groups, the halogen mediated interactions are often looked at as “surrogates” with intermolecular packing mainly guided by established noncovalent bonding such as strong hydrogen bonds . Hence, molecular systems without any strong hydrogen bond donor–acceptor pairs are considered to be the most suitable substrates to study the real effect of halogen bonding interactions .…”

Halogen-Bonded Cocrystals of 1,3,5-Triiodo-2,4,6-trifluorobenzene and Structural Isomers of Benzoylpyridine

“…Generally, it has been shown that molecules comprising both N and O potential acceptor sites exhibit a definite preference for the formation of I···N halogen bonds in crystal structures. − As a result, the instances when I···O and I···N halogen bonds coexist in a given crystal structure are relatively rare. It has been well documented that in hydrogen-bonded structures, the introduction of polytopic hydrogen-bond donors increases the probability of weaker acceptors being involved in hydrogen bonds (and vice versa ). − Extending this approach to halogen-bonded materials, a halogen-bond donor molecule that comprises multiple donor sites (a di- or tritopic donor) is more likely to form both I···N and I···O halogen bonds with ambidentate acceptors.…”