78430-91-8

288-32-4

1592-20-7

78430-91-8

Sodium bicarbonate (NaHCO3, 5.25 g, 62.40 mmol, 1.25 eq.) was added to a solvent mixture of acetone and water (1:1 v:v, 160 mL) and stirred for 1 hour. Imidazole (13.61 g, 199.00 mmol, 4 eq.) was added to the mixture and stirred until completely dissolved, then 4-chloromethylstyrene (7.1 mL, 49.80 mmol, 1 eq.) was added slowly and dropwise at room temperature. After the dropwise addition, the reaction mixture was heated to 50 °C with continuous stirring for 20 h (the reaction progress was monitored by thin layer chromatography TLC). Upon completion of the reaction, the acetone was removed by distillation under reduced pressure and the remaining aqueous phase was extracted with ether. 2M hydrochloric acid (HCl) was added dropwise to the combined organic phases until the pH reached 4-5, followed by washing with 2M HCl (aqueous phase was retained). The pH was adjusted to 7-8 by adding 4M sodium hydroxide (NaOH) solution to the retained aqueous phase (the solution became turbid) and extracted again with ether. The final organic phases were combined, dried with anhydrous sodium sulfate (Na2SO4), and the ether was removed by distillation under reduced pressure to afford the target product 1-(4-vinylbenzyl)-1H-imidazole (S5, 6.55 g, 71% yield).