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

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 P2(1)/n space group. However, only one conformer crystallized in the hexafluorophosphate salt, therefore describing an enantiomorphic P6(1) 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).

Automated summary

The Bischler-Napieralski reaction of N-phenylethyl cinnamamides was studied in acetonitrile and [bmim]PF6, showing significant effects on the isolated products depending on the starting materials and solvent. The use of [bmim]PF6 as a reaction medium led to the formation of hexafluorophosphate salts, while acetonitrile resulted in the isolation of free base products. X-ray crystallographic analysis revealed different conformers and structural stabilities in the two crystal structures.