A New, Simple, One-Pot Route for the Synthesis of Triazepin-8-one Derivatives

Abstract

Table of Contents Materials and Methods S2 General Procedure for the Synthesis of Dihydropyrrolo[1,2-a]imidazol-one 1 S2 Characterization data of Dihydropyrrolo[1,2-a]imidazol-one 1 S2 General Procedure for the Synthesis of N-Substituted imidazol-6-ones 1b-1p S3 Characterization data of imidazol-6-ones 1b-1p S3-S6 General Procedure for the Synthesis of N-phenyl imidazol-6-one 1r S7 Characterization data of N-phenyl imidazol-6-one 1r S7 General Procedure for the Preparation of Tetrahydropyrrolotriazepin-8-ones 5a-5q S7 Characterization data of Tetrahydropyrrolotriazepin-8-ones 5a-5q S8-S13 S2 Materials and Methods: Melting points (mp) were recorded on a Büchi B540 apparatus (Büchi Labortechnik AG, Flawil, Switzerland) and are uncorrected. Nuclear Magnetic Resonance (NMR) spectra were recorded on a Bruker AM-400 ( 1 H at 400MHz, 19 F at 376 MHz and 13 C at 100MHz) spectrometer with DMSO-d 6 as the solvent and TMS as the internal standard. Chemical shifts are reported in δ (parts per million) values. Coupling constants n J were reported in Hz. High-resolution mass spectra were recorded under electron impact (70 eV) condition using a MicroMass GCT CA 055 instrument. Analytical thin-layer chromatography (TLC) was carried out on precoated plates (silica gel 60 F 254 ), and spots were visualized with ultraviolet (UV) light. X-ray diffraction was performed with a Bruker Smart 1000 instrument. The following abbreviations were used to explain the multiplicities: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet. Unless otherwise indicated, all common reagents and solvents were used as obtained from commercial suppliers without further purification.General Procedure for the Synthesis of Dihydropyrrolo[1,2-a]imidazol-one 1 2-(nitromethylene)imidazolidine (12.9 g, 100 mmol), prepared using the previously reported method, was dissolved in dichloromethane (150 ml), and then methylglyoxal (120 mmol) was added. The mixture was stirred at room temperature for 1 h. The precipitate formed was filtered and washed with acetone to provide tetrahydro-1H-pyrrolo[1,2-a]imidazole-5,6-diol as a white solid (15.0 g, 75%). Then AlCl 3 (7.5 mmol) was added to a solution of tetrahydro-1H-pyrrolo[1,2-a]imidazole-5,6-diol (75 mmol) in acetone (150 ml) and the progress of the reaction was monitored by TLC. After completion, the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (DCM :MeOH = 15:1) to give the pure product 1. Characterization data of Dihydropyrrolo[1,2-a]imidazol-one 15-Methyl-7-nitro-2,3-dihydro-1H-pyrrolo[1,2-a]imidazol-6(5H)-one (1).