Utilizing Sulfoxide···Iodine Halogen Bonding for Cocrystallization

Abstract

The propensity of a range of different sulfoxides and sulfones to cocrystallize with either 1,2- or 1,4-diiodotetrafluorobenzene, via I···O=S halogen bonding, was investigated. Cocrystallization occurred exclusively with 1,4-diiodotetrafluorobenzene in either a 1:1 or 1:2 stoichiometry of the organohalide and the sulfoxide, respectively, depending on the sulfoxide used. It was found that the stoichiometry observed was not necessarily related to whether the oxygen acts as a single halogen bond acceptor or if it is bifurcated; with I···π interactions observed in two of the cocrystals synthesized. Only those cocrystals with a 1:2 stoichiometry exhibit C–H···O hydrogen bonding in addition to I···O=S halogen bonding. Examination of the Cambridge Structural Database shows that (i) the I···O=S interaction is similar to other I···O interactions, and (ii) the I···π interaction is significant, with the distances in the two cocrystals among the shortest known.

Role of halogen-involved intermolecular interactions and existence of isostructurality in the crystal packing of —CF3 and halogen (Cl or Br or I) substituted benzamides

“…The importance of interactions involving halogens in the absence of strong hydrogen bonds has been well established in the crystal engineering community (O'Hagan, 2008;Mondal et al, 2018). The evaluation of weak interactions involving halogens in the presence of strong hydrogen bonds has generated extensive interest in recent literature, particularly in the areas of isostructurality (Dey & Chopra, 2017), polymorphism (Prohens et al, 2012;Cruz Cabeza & Bernstein, 2014), cocrystals (Chattoraj et al, 2014;Mondal, Rao et al, 2017;Eccles et al, 2012), crystal structure prediction (Hulme et al, 2005), host-guest chemistry (Noa et al, 2016), nanoindentation (Mondal, Kiran et al, 2017;Rupasinghe et al, 2015) and supramolecular chemistry (Mondal, Yadav et al, 2017;Nagarajan et al, 2014).…”

Impurity Exclusion and Retention during Crystallisation and Recrystallisation — The Phenacetin by Ethylation of Paracetamol Process

“…This is likely to be a consequence of iodide induced cleavage of the benzylic C-O bond. A further O-ethylation step gave the diethylated derivative (30). In both derivatives, ethylation at the amide group was found to occur on nitrogen rather than oxygen, i.e.…”

“…The intensity of the impurity peak suggested its presence in approximately 1% quantity, assuming a structural similarity to phenacetin. Likely candidates for this impurity were compounds (28) or (29) in Figure 15, arising from competing Nor O-ethylation at the amide groups, or di-ethylated analogues (30) or (31). To confirm or reject these compounds as the unknown impurity, it was necessary to independently synthesise both the amide-ethylated (28 or 29) and di-ethylated (30 or 31) derivatives.…”

“…Co-crystallisation was attempted using physical mixtures of phenacetin and paracetamol in 1:1 and 1:2 ratios. Mixtures recrystallised from ethanol or were ground in a Retsch MM400 ball mill [30].…”

“…Calibration curves for phenacetin and paracetamol had R 2 values of 0.9993 and 0.9985 respectively. (28) and (30) Paracetamol 27…”