Crystal structure, Hirshfeld surface analysis, and molecular dynamics simulations of two isostructural N-propargyl-4-(2-oxopyrrolidin-1-yl)-1,2,3,4-tetrahydroquinolines

Two new N-propargyl-4-(2-oxopyrrolidin-1-yl)-1,2,3,4-tetrahydroquinoline derivatives (4a and 4b), have been efficiently prepared through a one-pot InCl3-catalyzed cationic Povarov reaction between N-propargylanilines (1a and 1b), formaldehyde (2) and N-vinyl-pyrrolidin-2-one (3). These compounds were characterized by ATR-FTIR spectroscopy, H-1/C-13 NMR spectroscopy, ESI-IT mass spectrometry, and by single-crystal X-ray diffraction. N-propargyl-6-methyl-4-(2'-oxopyrrolidin-1'-yl)-1,2,3,4-tetrahydroquinoline (4a) and N-propargyl-6-chloro-4-(2'-oxopyrrolidin-1'-yl)-1,2,3,4-tetrahydroquinoline (4b) are isostructural and crystallize in space group P2(1)/c. The crystal structures are characterized by inversion-related interpenetrated helices along the b-axis that form columns along the c-axis. C-H center dot center dot center dot O, C-H center dot center dot center dot C, and C-H center dot center dot center dot pi(aryl) for 4a and C-H center dot center dot center dot O, C-H center dot center dot center dot Cl, and C-H center dot center dot center dot pi(aryl) for 4b interactions occur within the columns which are connected by C-H center dot center dot center dot pi(propargyl) interactions. These features were further visualized by Hirshfeld surface analysis and energy frameworks calculations and evaluated by the E-XY enrichment ratio. Molecular dynamics simulations show that these compounds are promising monoamine oxidase B (MAO-B) inhibitors, since they interact with MAO-B in a similar manner as rasagiline, a drug commonly used in the treatment of Parkinson's and Alzheimer's diseases. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

In this study, two new tetrahydroquinoline derivatives were synthesized through a one-pot reaction and characterized by various techniques. The crystal structures and intermolecular interactions were analyzed, and the compounds showed potential as monoamine oxidase B (MAO-B) inhibitors, similar to the drug rasagiline commonly used in Parkinson's and Alzheimer's diseases.