Stereoselective Synthesis of New 4-Aryl-5-indolyl-1,2,4-triazole S- and N-β-Galactosides : Characterizations, X-ray Crystal Structure and Hirshfeld Surface Analysis

Abstract

5-(1H-Indol-2-yl)-4-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-thione 1a and 4-(4-chlorophenyl)-5-(1H-indol-2-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione 1b were galactosylated in the presence of NaHCO3 in ethanol to produce S-galactosides 3,4, whereas, in the presence of K2CO3 in acetone they produced a mixture of S- and N-galactosides 3-6 with a higher yield of S-galactosides over the respective N-galactosides. Improvement in the yields of N-galactosides was produced by thermal migration of the galactosyl moiety from sulfur to nitrogen using fusion. β-Stereoselectivity of galactosylation was determined using the coupling constant value 3J1,2, which exceeded 9.0 Hz in all prepared galactosides. The precursors 1a and 1b alkylated with 3-bromopropan-1-ol 7 in K2CO3 and acetone produced the S-alkylated products 8 and 9, respectively. Structural determinations of new compounds 5 and 9 are presented. The phenyl and indole moieties were found to be twisted from the triazole ring mean in both compounds. For compound 5, the twist angles were 66.24° and 18.86°, respectively, while the corresponding values for 9 were in the ranges of 73.15–77.29° and 13.96–20.70°, respectively. Hence, the crystal system of 9 is triclinic while the space group is P-1. Detailed analysis of the intermolecular interactions in the crystal structure of 5 is presented using Hirshfeld calculations. The O…H, N…H, C…H, and S…H contacts appeared as red spots in the dnorm Hirshfeld surface indicating short distance intermolecular interactions. Their percentages were estimated based on the decomposition of the fingerprint plot to be 25.6, 2.4, 14.0, and 6.3%, respectively.