Reactions
2-Iodopyridine and 3-alkoxy-2-iodopyridines are oxidized by DMDO to give PyIO2 , which serve as oxidants for alcohols and sulfides.
In palladium-catalyzed aminocarbonylation of 2-iodopyridine, 3-iodopyridine and iodopyrazine were coupled with CO and various primary and secondary amines. The biologically relevant N-substituted nicotinamides and 3-pyridyl-glyoxylamides were obtained from 3-iodopyridine as a result of simple and double carbon monoxide insertions, respectively. The chemoselectivity towards the ketoamide can be increased by the elevation of CO pressure. On the other hand, N-alkyl and N-aryl-carboxamides were obtained exclusively from CO pressure of 1 to 90 bar by using 2-iodopyridine and iodopyrazine.
Pd-catalyzed aminocarbonylation of 2-iodopyridine and 3-iodopyridine with primary and secondary amines.
Synthesis
General procedure for the synthesis of 2-iodopyridine from 2-bromopyridine: the aromatic Finkelstein reaction is used. Since copper(I) iodide is sensitive to moisture and oxygen, the reaction needs to be carried out under argon protection using the standard Schlenk technique. In a two-necked pear-shaped flask equipped with a reflux condenser, (het) aryl bromine feedstock, NaI (using 2 equivalents per bromine exchange) and CuI (using 5 mol% per bromine exchange) were added. N,N'-dimethylethylenediamine (L1) or N,N'-dimethyl-1,2-cyclohexanediamine (L2) (10 mol% per bromine exchange used) and anhydrous 1,4-dioxane (0.5 mL per 1 mmol of NaI used) were subsequently added. The resulting suspension was heated to 110 °C and maintained for 18 hours. After completion of the reaction, it was cooled to room temperature and the mixture was poured into a 25% aqueous NH3 solution. The blue solution was diluted to twice the original volume with H2O and extracted three times with CH2Cl2. For the case of 2,2'-bipyridine, the combined organic phases were additionally washed with aqueous EDTA; otherwise, the combined organic phases were simply washed with brine and dried with MgSO4. The solvent is removed by distillation under reduced pressure to give pure 2-iodopyridine. If necessary, the crude product can be further purified by column chromatography or recrystallization.
References
[1] Tetrahedron Letters, 1999, vol. 40, # 23, p. 4339 - 4342
[2] Tetrahedron, 2000, vol. 56, # 10, p. 1349 - 1360
[3] Synthesis (Germany), 2014, vol. 46, # 8, p. 1085 - 1090
[4] Phosphorus and Sulfur and the Related Elements, 1984, vol. 21, p. 197 - 204
[5] Chemistry - A European Journal, 2010, vol. 16, # 41, p. 12425 - 12433
