Synthesis and X-ray crystallographic analysis of free base and hexafluorophosphate salts of 3,4-dihydroisoquinolines from the Bischler–Napieralski reaction

Abstract

The Bischler–Napieralski reaction of N-phenylethyl cinnamamides was investigated in acetonitrile and 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim]PF₆). Strong effects on the nature of the isolated products were observed depending on the structure of the starting materials and the solvent used. The corresponding 3,4-dihydroisoquinoline as a free base was isolated when acetonitrile was employed, but the respective 3,4-dihydroisoquinolines, as hexafluorophosphate salts, were obtained when [bmim]PF₆ was used as a reaction medium due to an anion metathesis between the reaction intermediates and the solvent. A full X-ray crystallographic analysis of a 1-phenethyl-3,4-dihydroisoquinoline derivative is reported for the first time and reveals that, in this core, as a free base, the C10–N1–C9–C8 torsion angle allows the existence of two conformers, crystallizing in a centrosymmetric P2₁/n space group. However, only one conformer crystallized in the hexafluorophosphate salt, therefore describing an enantiomorphic P6₁ space group. The absence of type II symmetry operations allowed the formation of 1D-channels that contain the PF₆⁻ anions and cross the entire structure along the [001] direction giving interesting potential uses as an ionic conductor. Additionally, CE-B3LYP model energies showed that, in both crystal structures, dispersion forces have an important role in the supramolecular architecture. Nevertheless, in the hexafluorophosphate salt electrostatic forces increase the structural stability to a total packing energy of −173.6 kJ mol⁻¹, compared with the free base with a value of −135.0 kJ mol⁻¹.