Uses
Imidazole rings are found in numberous natural compounds such as enzymes, nucleic acid, and alkaloids that play a role in biological processes.
Synthesis
General procedure for the synthesis of 3-(1H-imidazol-4-yl)pyridine from the compound (CAS:93103-29-8): 3-(1H-imidazol-4-yl)-4-(pyridin-3-yl)-1H-imidazole-2(3H)-thione (1.0 wt. portion; 1.00 equiv.), which had been prepared in step 3.1, was added to a reactor, followed by the addition of deionized water (8 vols. ). Sodium nitrite (0.58 wt. portions; 1.5 eq.) was added to the reactor, the reaction mixture was cooled to 5 °C and 65% nitric acid (1.97 vol. portions; 5 eq.) was added slowly. The inner wall of the reactor was rinsed with deionized water (2 vol. parts). The reaction mixture is heated to 35°C within 1 hour and stirred at that temperature for not less than 6 hours. In some embodiments, the reaction mixture may be heated to 85°C (e.g., for 3 hours, followed by stirring for an additional 2 hours). The mixture is cooled to 15°C and sodium carbonate (2.0 wt.) (or other base, such as sodium hydroxide) is slowly added. The solution was then heated to 30°C and saturated with sodium chloride. To the aqueous layer is added isopropanol (4 v/v) and stirred for no less than 30 minutes (the temperature may be increased in some embodiments during this process, e.g. to 55/60°C). The phases are separated, sodium chloride (2 wt. portions) is added to the aqueous layer, and the extraction of the aqueous layer is repeated once with isopropanol (4 vol. portions), and once more with isopropanol (2 vol. portions) (other solvents are optional, e.g., 2-methyltetrahydrofuran). The mixture was concentrated under vacuum to 2 vol%. The purity of the product was determined by HPLC and the structure was confirmed by NMR (see Figures 9 and 10). The yield was stable between 84-92% in multiple production runs.
