Synthesis and anti-leukemia activity mensuration of 1-phenethyl-4-hydroxy-4-substituted piperidinium hydrochlorides: Structure of bis[1-phenethyl-4-hydroxy-4-(3-fluorophenyl) piperidinium hydrochloride] studied by X-ray and DFT methods

Four unknown compounds have been synthesized based on the molecular motif of 1-phenethyl-4-hydroxy piperidinium hydrochloride with a variety of the substituted groups R on the same carbon atom bearing the hydroxy group, such as 3-fluorophenyl (3a), 4-methoxyphenyl (3b), 4-methylphenyl (3c) and cyclohexanyl (3d), and their molecular structures were characterized by 1H NMR, MS and IR. To account for the stereo structure and provide more information on the effect of counter ions, hydrogen bonds on molecular conformation, the structure of [1-phenethyl-4-hydroxy-4-(3-fluorophenyl) piperidinium hydrochloride] [PHFPH.Cl] 3a was determined by the single-crystal X-ray analysis and optimized by the B3LYP/6-31G (d, p) calculations. Two chloride anions, two PHFPH cations and a dichloromethane molecule formed a five-membered structure ([(PHFPH)2Cl2]·CH2Cl2) via the intermolecular hydrogen bonds. The core of the five-membered structure ([(PHFPH)2Cl2]·CH2Cl2) is formed by two PHFPH cations linked by N(1B)–H(2)⋯Cl(2) hydrogen bonds of lengths 3.033(4), which is engaged in two hydrogen bonds: N(1A)–H(1)⋯Cl(1) of 3.110(4) Å and O(1B)–H(2B)⋯Cl(1) of 3.099(4) Å. The anti-tumor activity tests indicated that these compounds could inhibit the growth of the K562 cells to some extent and have the potential bioactivity of anti-leukemia.