Unexpected formation of 1-[4-chloromethylphenyl]-5-[4-(methylsulfonyl)benzyl]-1H-tetrazole and 1-[4-chloromethylphenyl]-5[4-(aminosulfonyl)phenyl]-1H-tetrazole: Crystal structure, bioassay screening and molecular docking studies

During the cyclization reaction of benzyl alcohol containing amides, using NaN3 and SiCl4, additional unique chlorination development was observed to yield the novel azoles 1-14-chloromethylphenyl]-5-14(methylsulfonyl)benzyl]-1H-tetrazole (3a) and 1-[4-chloromethylpheny1]-5-[4-(aminosulfonyl)phenyl]1H-tetrazole (3b). Control experiments showed that the SiCl4 or SiCl3N3 has the major role for such functional group transformation in such a clean reaction and quantitative yield. Their molecular structures have been ascertained using the X-ray crystallography technique in addition to the spectroscopic analyses. Both compounds 3a and 3b crystallize in the monoclinic space group P2(1/c). The cell parameters of azole 3a are a = 22.3827 (8), angstrom, b = 5.1602 (2) angstrom, c = 13.4994 (5) angstrom(3), beta = 95.2352 (14)degrees, V= 1552.67 (10) angstrom(3), and Z= 4. While the cell parameters of azole 3b are a =20.582 (2), angstrom, b = 5.8947 (7) angstrom, c = 13.0796 (16) angstrom(3), beta = 104.376 (4)degrees, V = 1537.2 (3) angstrom(3), and Z= 4. The central tetrazole ring of both compounds is planar and bears (4-chloromethylphenyl) at position one (N-1) of the central moiety, However, the substituents 4-(methylsulfonyl)phenyl and 4-(aminosulfonyl)phenyl of azoles 3a and 3b, respectively, are attached to the C-5 of the same central unit. The phenyl rings at N-1, (C2-C7) and C9-C14 in (3a); (C2-C7) and (C8-C14) in (3b) are inclined compared to the tetrazole ring with dihedral angles of 21.74 and 83.94 degrees in 3a and 25.85 degrees and 65.13 degrees in 3b. The two phenyl rings, at N-1 and C-5, are rotated against each other by 87.73 degrees (in 3a) and 72.21 degrees (in 3b). In the crystal, intermolecular interactions between molecules of 3a,b are dominated by C-H center dot center dot center dot O and C-H center dot center dot center dot N hydrogen bonds. Additional CI center dot center dot center dot pi interactions add extra supramolecularity. All intermolecular interaction motifs consolidate a three dimensional network lattice. The molecular docking studies were carried out to understand the interaction of compounds 3a and 3b within the active site of the cyclooxygenase-2 enzyme, followed by a comparison study with the celecoxib drug as a reference compound. The in vitro bioassay screenings of azoles 3a and 3b showed that both compounds have poor selectivity and weak inhibition potency toward cyclooxygenase-2 enzyme. (C) 2018 Elsevier B.V. All rights reserved.