Heterocyclic chemistry

Imidazole: Synthesis, Functionalization and Physicochemical Properties of a Privileged Structure in Medicinal Chemistry

“…Imidazole 1 has a pKaH of 7.1 ( Figure 4 ), acting as a strong base [ 8 ]. The basicity of imidazole is above that of pyridine 4 (pKaH of 5.2) due to the amidine-like 5 resonance, which allows both nitrogens to participate equally in charge accommodation [ 7 , 8 , 9 ]. Comparatively, the basicity of imidazole 1 contrasts with the basicity of pyrrole 6 (pKaH of 0.4), which is an extremely weak base, because when pyrrole 6 is protonated, there is a loss of aromaticity which is built with the participation of the nonbonding electron pair of N -1 nitrogen [ 7 ].…”

“…The presence of the N -1 nitrogen in the imidazole 1 structure makes it tautomer, which becomes evident in non-symmetrically substituted compounds, such as methyl imidazole 9 ( Figure 6 ) [ 9 ]. This curious feature of imidazole chemistry means that simply writing “4-methylimidazole” would be incorrect, considering the rapid tautomeric equilibrium with the 5-methylimidazole structure [ 9 , 17 ].…”

“…Despite the existence of the tautomeric effect in imidazole 1 , the ratio in terms of proportion of these tautomers varies according to the substituent added to the ring. The tautomer ratio observed in the 4(5)-nitroimidazole 10 derivative is approximately 400:1 for 4-nitroimidazole [ 9 ]. Reports in the literature suggest a relationship between tautomers 1.4 and 1.5 in the following proportion: log ([1.4]/[1.5]) = 4 × σ m [ 17 , 18 ].…”

Transition Metal‐Catalyzed Synthesis of Monocyclic Five‐Membered Aromatic Heterocycles

“…The successful application of furans and pyrroles in these and many other ways and their significance in applied and fundamental areas have placed them at the forefront of contemporary organic chemistry. A variety of methodologies and different protocols for their synthesis have been reported [1][2][3][10][11][12][13][14][15][16][17][18][19][20][21][22][23] and become well established throughout decades. Among the variety of novel approaches for the synthesis of furans and pyrroles, transition metal-catalyzed transformations are arguably the most attractive methodologies .…”