Regioselective formation of imidazol-2-yllithium, imidazol-4-yllithium, and imidazol-5-yllithium species

Assembly of the Bis(imidazolyl)propene Core of Nagelamides C and S by Double Grignard Reaction

“…[12] Magnesation with EtMgBr was preferred over lithiation, because the latter may generate 2-lithioimidazoles in competition. [13] Breslow et al, [14] Katritzky et al, [15] Imanishi et al [16] and Nicholas et al [17] reacted 5-lithiated imidazoles with aldehydes, esters, and alkyl carbonates obtaining hydroxy-alkylated imidazoles, bis(imidazolyl) carbinols, and tris(imidazolyl) carbinols. 4-Iodo-1-tritylimidazole has also been treated with EtMgBr and the resulting Grignard nucleophiles were treated with DMF, N-formylpiperidine, [18] substituted benzaldehydes, [19] thiophenecarbaldehydes, esters, [20] and Weinreb amides.…”

Properties of haloimidazoles (review)

“…Thus, from 4(5)-bromo(iodo)imidazole (11) the imidazole (9) was obtained with a 98% yield, and during decomposition of the intermediate 4-lithioimidazole with deuteromethanol the 4(5)-deuteroimidazole (D-9) was obtained [19]. The imidazole 13 was obtained similarly with a 70% yield by the deiodination of 4-iodoimidazole 12 [20]. When treated with sodium in ethanol the 5-chloroimidazoles 5 are reduced to the imidazoles 14 [21,22].…”

“…The latter are also obtained with high yields (72-99%) by hydrogenation of the chlorides 5 in the presence of Raney nickel [23][24][25] The hydrogenation of 1-benzyl-5-chloro-2-phenylimidazole (15) in the presence of Raney nickel (H 2 pressure 100 atm) leads to various compounds depending on the temperature: 1-benzyl-2-phenylimidazole (16) is obtained at 20°C (yield 94%), and 2-cyclohexylimidazole (17) is obtained at 100°C (yield 13%) [24,25]. Selective hydrogenation in the presence of Raney nickel and reduction with Na 2 SO 3 were studied for 1-methyl-substituted 4,5-diodo-and 2,4,5-triiodoimidazoles 18 and 19 and led to the 4-iodo-1-methylimidazole (20) with yields of 56-63% [26]. Under analogous conditions 5-chloro-4-iodo-1-methylimidazole 22 was obtained with a yield of 69% by the hydrogenation of 5-chloro-2,4-diiodo-1-methylimidazole 21.…”

“…PhSNa i-PrOH 1-Alkyl(aralkyl)-2,4,5-tribromo(triiodo)imidazoles 29 are reduced by the action of butyllithium [20,29] and ethylmagnesium bromide [29,31,32] to the 4,5-dibromo(diiodo)imidazoles 30 (yields 40-99%). If the amount of butyllithium is doubled, the reaction goes further with the formation of 4-bromo(iodo)imidazoles 31 (yields 71-85%) [20,28,32].…”

“…If the amount of butyllithium is doubled, the reaction goes further with the formation of 4-bromo(iodo)imidazoles 31 (yields 71-85%) [20,28,32]. From the presented data, it follows that the reduction and catalytic hydrogenation of 2,4,5-tribromo-(triiodo)imidazoles and their N-alkyl(aralkyl)-substituted derivatives take place in the opposite order to the bromination and iodination of imidazoles: the halogen atom at position 2 is affected first, and then those at positions 5 and 4 of the imidazole ring are affected.…”