High Proportion of Chiral Crystallization of Achiral Indolyl Sulfonamides: Effect of Intermolecular Interactions

We investigated the effect of indole moieties on chiral crystallization. In this regard, we assessed the influence of intermolecular interactions and contacts on the assembly of these molecules. A systematic analysis of 62 crystal structures of secondary aromatic sulfonamides bearing 4-, 5-, 6-, and 7-aminoindolyl groups revealed that the proportion of indolyl compounds showing chiral crystallization was apparently higher (21%, except for kryptoracemate) than that of nonindolyl sulfonamides (11%). Moreover, 33% (5 out of 15 crystals) and 44% (7 out of 16 crystals) of 4- and 7-indolyl sulfonamide derivatives preferred chiral crystallization, respectively. This suggested a correlation between the type of contact and the chirality of the assembly of adjacent molecules. Specifically, the proportion of achiral indolyl sulfonamides undergoing chiral crystallization was drastically increased by N(indole)H···O interactions, slightly increased by C(sp2)H···π interactions, and decreased owing to π···π interactions. These tendencies were also true for sulfonamides with different substituents, which suggested that the T-shape contact would be more favorable than π···π interactions for chiral crystallization.