The Role of Halogen Bonding in Crystal Structures of 3-Halogeno Cytisine Derivatives

Abstract

The crystal structures of three 3-halogeno derivatives of 13N-substituted cytisine have been determined by X-ray diffraction. The two 13-acetyl substituted compounds, 3-bromo (1) and 3-iodo (2) are isostructural, with the isostructurality index as high as 99%. They both crystallize in monoclinic P2 1 space group, with unit cell parameters of a = 8.4709(10) Å , b = 9.2266(12) Å , c = 8.6051(10) Å , b = 98.528 (11)8 (1) and a = 8.2322(6) Å , b = 9.1724(7) Å , c = 8.5494(6) Å , b = 98.181 (7)8 (2). In turn, 3-bromo-13-t-butyl-carbonate derivative (3) crystallizes in orthorhombic P2 1 2 1 2 1 space group with a = 6.8171(3) Å , b = 7.8994(4) Å , c = 31.4657(15) Å . Conformation of the cytisine skeleton is similar in all three molecules, with almost planar A ring, sofa conformation of B-ring and C ring being an almost ideal chair. However, the orientations of the double C=O bonds in 13N-substituents are completely different: in 1 and 2 it is cis with respect to C12 (C12-N13-C14-O15 torsion angle is 3.3(4)8 in 1 and 1.3(6)8 in 2) while in 3 it is trans (-175.4(3)8). In the structures of 1 and 2 the driving force of the crystal architecture are quite strong C-HÁÁÁX halogen bonds with CÁÁÁX distances far shorter than the sums of van der Waals radii (CÁÁÁBr in 1 is 2.9430(19) Å and CÁÁÁI in 2 2.974(3)). In contrast in 3-partially as the consequence of different orientation of the substituent-there are no halogen bondings but instead some weak C-HÁÁÁO contacts organize the molecules into two-dimensional patterns.

Halogen Bonding in Supramolecular Chemistry

“…While examples of chloride, bromide, and iodide as XB acceptors are known, 148,207 only one report of fluoride exists. 208 Farnham, Dixon, and Calabrese's study on fluoride showed that discrete ion pairs were formed when pentafluorophenyl iodide was used as the XB donor. However, a polymeric chain could be formed when ditopic diiodooctafluorobutane was used as the XB donor with fluoride bridges.…”

“…A number of groups have prepared remarkable solid-state architectures with XB as the predominant intermolecular interaction responsible for the stability of these structures. In addition to the above examples, chains are formed with bis­( N -heterocycle)­diacetylenes with ditopic iodo donors and with bifunctional molecules (containing both XB donor and acceptor moieties) that displayed remarkable synthon robustness in the presence of typically structure-destabilizing and bulky substituents. The formation of chainlike structures is useful in the preparation of materials with conducting and magnetic properties as well as noncentrosymmetric crystals capable of second harmonic generation in optical devices.…”

(−)-Cytisine and Derivatives: Synthesis, Reactivity, and Applications

“…Despite these conditions, large amounts of unreacted protected cytisine were Recently, the crystal structures of N-acetyl-9-bromocytisine 110a, N-acetyl-9-iodo cytisine 119a, and N-Boc 9-bromocytisine 107a have been determined by X-ray diffraction. 132 In the N-acetyl derivatives, the molecules are connected by relatively strong interactions C−X•••O. These interactions are weak in the N-Boc bromo derivative 107a but contribute nevertheless to organize the two-dimensional structure.…”

“…Recently, the crystal structures of N -acetyl-9-bromocytisine 110a , N -acetyl-9-iodo cytisine 119a , and N -Boc 9-bromocytisine 107a have been determined by X-ray diffraction . In the N -acetyl derivatives, the molecules are connected by relatively strong interactions C–X···O.…”