A Green One-Pot Synthesis of vic-Amidino (Hetero)aromatic Acids from 1,2-Dinitriles

Abstract

H and 13 C NMR spectra copies of synthesized compounds X-ray diffraction data for compounds 5e, 5c, 17, 20, 21a, 4 Experimental Section Materials and Instrumentation General: Melting points were determined on a Boetius microscope hot plate apparatus. Elemental analyses (C, H, N) were conducted using the Vario Micro Cube. Mass spectra were recorded on an Agilent 1100 LCMSD SL instrument by chemical ionization (CI). 1 H and 13 C NMR spectra (in D 2 O or DMSO-d 6 , 25 °C) were measured on a Mercury Varian-400 (400 MHz for 1 H, 100 MHz for 13 C) and a Bruker Avance 400 (400 MHz 1 H, 100 MHz for 13 C) instruments with tetramethylsilane as an internal reference. A drop of conc. HCl was added to D 2 O solutions of compounds 5d and 5e for a better solubility. IR spectra were recorded with a Perkin-Elmer Spectrum BX FTIR Spectrometer as KBr disk. TLC analyses were carried out on silica gel coated aluminium plates (Merck) in CHCl 3 /MeOH, 9:1 and spots were visualized with UV light. Starting dinitriles were synthesized by known methods: pyridine-2,3-dicarbonitrile 10 1 , pyrazine-2,3-dicarbonitrile 12 2 , quinoxaline-2,3-dicarbonitrile 15 3 , 1H-imidazole-4,5-dicarbonitrile 18. 2 3-methoxybenzene-1,2-dicarbonitrile (7) was prepared according to the procedure for the synthesis of 4-methoxybenzene-1,2-dicarbonitrile. 5 To the solution of 3-nitrophthalonitrile 6 (3.46 g, 20 mmol) in DMF (25 mL) K 2 CO 3 (5.52 g, 40 mmol) and MeOH (5 mL) were added. After stirring the suspension for 30 h at ambient temperature, 500 mL of distilled water were added with continued stirring. The precipitate was collected by filtration, washed with distilled water, dried and crystallized from MeOH (20 mL). Off-white needle-shaped crystals; yield: 2.72 g (86%), mp 175-176 ºC (Lit. 178-179 ºC 6).