Groebke‐Blackburn‐Bienaymé Multicomponent Reaction Catalysed by Reusable Brønsted‐Acidic Ionic Liquids

Abstract

In the present work, the use of Brønsted acidic ionic liquids (BAIL) as catalysts for Groebke‐Blackburn‐Bienaymé (GBB) multicomponent reactions was systematically investigated. A series of four 1‐(butyl‐4‐sulfonic)‐3‐methylimidazolium salts bearing different anions was easily prepared and screened as acidic catalysts for this transformation. The best reaction conditions were stablished as 20 mol % of catalyst [(SO3H)4C4C1Im][OTf] in refluxing EtOH or MeOH under conventional heating and in sealed tube at 150 °C for 1–4 hours under microwave heating, affording a series of imidazo‐fused heterocycles in moderate to excellent yields (42–93 %). The homogeneous BAIL catalyst could be recycled and reused in four consecutive reaction cycles, despite of a laborious recovery procedure employed. This approach represents the first example of a task‐specific reusable homogeneous Brønsted acidic catalyst in GBB reactions and opens new opportunities for the exploration of acidic ionic liquid phases as catalysts for this fascinating multicomponent reaction.

Synthesis of Fused Imidazoles and Pyrimidinones from 2‐Aminoazines

“…Biocatalysts, such as lipase enzymes, have also been used in the GBB reaction. [27] In addition to standard heating (compound 15), [28] advanced techniques that include MW irradiation (compounds 14, 17 and 22), [20,23,24] solid phase synthesis [22] and Brønsted acidic ionic liquids [29] have also been applied.…”

“…The recent examples of fused imidazoles synthesized from α-halocarbonyl compounds are presented in Figure 4. [36,37] imidazo[1,2a]pyrazines 42, [38,29] imidazo[1,2-a]pyrimidines 43 a-43 b, [40,41] and imidazo[1,2-a][1,3,5]triazine 43 c. [42] Variations of the halide compounds have also been investigated. Peese et al [43] developed a protocol for the synthesis of electron-deficient imidazopyridine 45 by heating 2aminopyridine (1 g, 1.0 equiv.)…”

The Synthesis of Nitrogen- and Oxygen-Containing Heterocyclic Scaffolds Assisted by Ionic Liquids: A 2022 Literature Survey

“…Scheme 39 Catalytic transformation of glucose (66) into 121 using Brønsted-Lewis acidic tetraimidazolyl ILs Longo and co-workers have reported 1-(butyl-4-sulfonic)-3-methylimidazolium [(SO 3 H) 4 C 4 C 1 Im][OTf] ILs for the catalysis of Groebke-Blackburn-Bienayme reactions during the synthesis of imidazo[1,2-a]pyridines 125 using substituted aminopyridines 122, tert-butyl isocyanide (123) and substituted aldehydes 124 (Scheme 40). 101 The reaction in a sealed tube in ethanol/methanol under microwave irradiation was performed for 1-4 hours at 150 °C. The key ILs were prepared using 1-methylimidazole and 1,4-butane sultone to yield zwitterions, which were further reacted with different acids.…”

“…ILs for the catalysis of Groebke-Blackburn-Bienayme reaction in synthesis of imidazo[1,2-a]pyridines (125) using substituted aminopyridine (122), tert-butyl isocyanide (123) and substituted aldehydes (124, Scheme 40). 100 The reaction in a sealed tube in ethanol/methanol under microwave irradiation was performed for 1-4 h at 150 o C. The key ILs were prepared using 1-methylimidazole and 1,4-butanesultone yielding zwitterions, which was further reacted with different acids.…”

Efficient One‐Pot Synthesis of 2‐Amino‐4H pyran‐3‐carbonitriles Using Ionic Liquid: Reactions, Quantum‐Chemical Calculations, and Antiproliferative Activity

“…[27] Incorporating the synergistic effects of ultrasound-assisted multicomponent reactions (MCRs) and the utilization of ILs offers a promising approach for the rapid synthesis of polyfunctional heterocycles with diverse applications in therapeutic technology. [27,28] Therefore, in this study, we aim to develop a sustainable and efficient protocol for the synthesis of 2-amino-4-aryl-tetrahydro-4H-chromene-3-carbonitriles. This approach relies on the benefits of ultrasonic irradiation, enabling improved reaction profiles, and atom-economic conditions.…”