Metal-free synthesis of imidazoles and 2-aminoimidazoles

Progress on the Synthesis and Applications of Aminals: Scaffolds for Molecular Diversity

“…The latter can go through an intramolecular cyclization to give imidazoline derivatives (6a and 6b). Alternatively, 11 can dissociate into the α-lactam (13), that can tautomerize to the 1,3-dipole (12), and the pyrroline (15). The pyrroline (15) can tautomerize to the exocyclic imine (14) to react via a 1,3-dipole addition with 12 (R 1 = Me) to forge the spiro aminal (7).…”

“…Moreover, metal-free methodologies often employ milder reaction conditions, and demonstrate greater functional group tolerance and increased atom economy, further underscoring their advantages in facilitating the synthesis of aminals with improved efficiency and selectivity. 13,14 Tsuge and co-workers, 15 in 1979, reported their serendipitous discovery on the reaction of ketenimines and cyclic nitrones to prepare imidazolidinone and diazaspiro- [4.4]nonanone derivatives (Scheme 2a). When trying to prepare the indolone derivative 3, the authors found that by replacing benzylideneaniline N-oxides 2 with cyclic nitrones, such as 5,5-dimethyl-1-pyrroline 1-oxide (4a), nucleophilic attack as in the case of 3 did not happen.…”

“…Scheme 13 Tsujihara's diastereoselective direct amidation/aza-Michael cascade reaction to synthesize cis-1,3-disubstituted isoindolines Finally, distinguished by its innovative use of practical and direct C(sp 3 )-H functionalization for the swift preparation of unsubstituted aminals, Wang et al 35…”

“…Moreover, metal-free methodologies often employ milder reaction conditions, and demonstrate greater functional group tolerance and increased atom economy, further underscoring their advantages in facilitating the synthesis of aminals with improved efficiency and selectivity. 13 14…”

5-(4-Chlorophenyl)-N,1-di-o-tolyl-1H-imidazole-2-amine

“…Indeed, in heterocycle synthesis, the use of deep eutectic solvents (DESs) as a green and sustainable alternative to toxic and hazardous VOCs is recently gaining great interest [14]. The classic synthetic methods for 2-aminoimidazoles include several categories of chemical transformations, such as condensation reactions, nucleophilic substitutions, coupling reactions, ring transformations [10,11], and metal-mediated cyclization reactions [12,13]. Despite the great variety of strategies present in the literature, the preparation of 2-aminoimidazoles is often performed in volatile organic solvents (VOCs) as reaction media (e.g., dioxane, DMF, DMSO, toluene), and generally requires an inert atmosphere with strict exclusion of humidity [10,11].…”