Organic Chlorine as a Hydrogen‐Bridge Acceptor: Evidence for the Existence of Intramolecular OH⋅⋅⋅ClC Interactions in Somegem‐Alkynols

Abstract

The acceptor capabilities of "organic" halogen, CX (X=F, Cl, Br, I), with respect to hydrogen bonding are controversial, and unactivated organic chlorine is generally deemed to be a poor acceptor. Hydrogen bridges of the type O--H...Cl--C are uncommon and occur mainly in an intramolecular situation when the donor group is sterically hindered, so that the formation of intermolecular interactions is difficult. In this paper, intramolecular O--H...Cl--C interactions in a series of chloro-substituted gem-alkynols are studied. We describe various features of this interaction using crystallographic, spectroscopic and computational methods. The O--H...Cl--C interaction occurs in five of the six compounds under consideration here (CDDA, 14DDDA, 15DDDA, 18DDDA, 15MKA). Solution (1)H NMR spectroscopy shows that the interaction is intramolecular and that it is a true hydrogen bond. DFT calculations give a stabilisation energy around 4.0 kcal mol(-1). In the crystal structures of the compounds studied, the intramolecular O--H...Cl--C interactions fit into the overall scheme of cooperative interactions. These structures may be derived from that of the unsubstituted compound DDA by means of synthon exchange and the O--H...Cl--C interaction fares surprisingly well in the presence of competing stronger acceptors. The crystal structures show an unusual degree of modularity for compounds that generally form interactions that are weak and variable. It is noteworthy that the so-called "weak" acceptor, organic chlorine, is able to sustain a good intramolecular hydrogen bridge that is of an attractive and stabilizing nature and which is of potential importance in crystal engineering and supramolecular chemistry.

Supramolecular chemistry and crystal engineering

“…Intramolecular O-H⋅⋅⋅Cl hydrogen bond in 1-chloro derivatives of trans-9,10-diethynyl-9,10-dihydroanthracene-9,10-diols (DDA, figure 2) was confirmed by NMR spectroscopy and X-ray diffrac-tion. 8 The intramolecular O-H⋅⋅⋅Cl hydrogen bond (d = 2⋅25-2⋅40 Å) persisted in five out of six structures with varying number of Cl groups on the aromatic core. Of the two OH groups, the free OH resonates at δ 2⋅8 ppm in the NMR spectrum whereas the hydrogen bonded OH is significantly downfield at 4⋅4-4⋅6 ppm.…”

Organic fluorine involved intramolecular hydrogen bonds in the derivatives of imides: NMR evidence corroborated by DFT based theoretical calculations

“…The nuclear magnetic resonance (NMR) and X-ray crystallographic studies have been reported on the N-H … F-C HB in foldamers and benzanilides 37,38 . It is also well known that organic fluorine generally does not get involved in the intramolecular HB [39][40][41][42][43][44][45] . The report by Dunitz and co-workers concluded that ''organic fluorine hardly ever accepts hydrogen bonds'' [46][47][48][49] .…”

Ab initio calculations on halogen‐bonded complexes and comparison with density functional methods

“…That is to say, halogen atoms can form both a halogen bond with nucleophiles (electronegative atoms/groups) displaying roughly linear arrangement and a hydrogen bond with electrophiles (hydrogen bond donors) occurring in the side‐on fashion. The type of the interaction via side‐on mode is often referred to as hydrogen bonding or dipole interaction,43, 44 and the benchmark tests on some representative systems can be found in the literatures 45…”