Synthesis and Structural Evaluation of 5-Methyl-6-acetyl Substituted Indole and Gramine

• Main Authors: Lovel Kukuljan, Krištof Kranjc, Franc Perdih
• Format: Article
• Language: English
• Published: Slovenian Chemical Society 2016-11-01
• Series: Acta Chimica Slovenica
• Subjects: Indoles; Gramines; Crystal structure; Hydrogen bonds; C–H•••π interaction; π•••π interaction
• Online Access: https://journals.matheo.si/index.php/ACSi/article/view/2911

The synthesis and crystal structures of 1-(5-methyl-1H-indol-6-yl)ethan-1-one (7), C11H11NO, and 1-{3-[(dimethylamino)methyl]-5-methyl-1H-indol-6-yl}ethan-1-one (8), C14H18N2O, are reported. The synthesis is based on the Diels–Alder cycloaddition of a substituted 2H-pyran-2-one derivative, followed by an acid-catalyzed cyclization and concomitant deprotection (the last two steps were carried out as a one-pot domino process) yielding substituted indole 7, which was further derivatized via Mannich reaction to the gramine derivative 8. Both structures 7 and 8 were determined on the basis of IR, 1H NMR and mass spectroscopy, as well as by the elemental analysis and melting point determination. According to the single-crystal X-Ray diffraction analysis, the structure 7 has a single unique molecule in the asymmetric unit whereas the structure 8 contains four unique molecules in the asymmetric unit. Molecules 7 are linked via N­–H···O hydrogen bonds between the secondary amine group and carbonyl moiety of the acetyl group of adjacent molecules, whereas molecules 8 are linked via N–H···N hydrogen bonds between the secondary and tertiary amine groups of adjacent molecules. Both structures are further stabilized by weak C–H···O, C–H···π and π···π interactions.