Imidazo[1,2-a]pyridine A3-Coupling Catalyzed by a Cu/SiO2 Material

Abstract

In this work, we report the preparation of a copper-silica material (Cu/SiO 2) by a sol-gel methodology and its characterization concerning composition and textural properties. The Cu/SiO 2 material was successfully applied as a Lewis acid heterogeneous catalyst for the A 3-coupling from 2-aminopyridine, aldehydes and alkynes to imidazo[1,2-a]pyridines (45-82%), which are relevant pharmacological scaffolds. The synthesis shows a number of advantages, such as easy separation from the reaction media and the minimal formation of metal aqueous wastes. Investigation of the mechanism supports the involvement of the formation of reaction intermediates inside the pores of the mesoporous material prior to 5-exo-dig cyclization.

SBA-15 obtained from rice husk ashes wet-impregnated with metals (Al, Co, Ni) as efficient catalysts for 1,4-dihydropyridine three-component reaction

“…From the results presented in Table 4, all materials featured a similar pore size of around 4 nm (mesopores), which is consistent with the accommodation and approximation of a carbonyl reagent and intermediate molecules coordinated to the metals, increasing its reactivity towards the nucleophilic addition inside the pores of the SBA-15 framework. 50,63,94 Although Al-SBA-15 showed an intermediate surface area compared to the other materials, the structure of the active metal oxide site is much more well defined, as evidenced by XRD playing an important role as a catalyst for the 1,4-DHP synthesis. The slightly higher surface area and quantity of catalytic sites may also increase its availability on the surface and inside the SBA-15 pores with less particle aggregation.…”

Synthesis of Catalyst Using Bio‐benign Precursors and Its Application in One‐Pot Catalytic Synthesis of Imidazo[1,2‐a]pyridines

“…After finalizing the reaction media, reactions were repeated with 3.0, 2.0, 1.0, and 0.5 mol% catalyst loading at 80 °C (Table 1, entry 4-7), and optimum yield was considered with 2.0 mol% catalyst because the efficiency is almost as good as that of 3 mol%. Three reports are available with comparable catalyst loading, but reactions require hazardous solvents, [16,19,35] higher temperature [16,19,[34][35] and longer reaction time, [16,19,34] while the present method provides maximum yield in 6 hours (Table 1, entry 5, 8-13). It is also noteworthy to mention that with the decrease in temperature longer time is required for the completion of the reaction (Table 1, entry [15][16][17][18][19][20].…”

“…Three reports are available with comparable catalyst loading, but reactions require hazardous solvents, [16,19,35] higher temperature [16,19,[34][35] and longer reaction time, [16,19,34] while the present method provides maximum yield in 6 hours (Table 1, entry 5, 8-13). It is also noteworthy to mention that with the decrease in temperature longer time is required for the completion of the reaction (Table 1, entry [15][16][17][18][19][20]. Replacement of the catalytic system with 5 mol% of cupric acetate only resulted in 10.7 and 17.9 % yield after 24 and 48 hours, respectively (Table 1, entry [22][23].…”

Recent Advances in the Synthesis of Imidazo[1,2‐a]pyridines: A Brief Review

“…The use of metal/silica materials as catalysts in the synthesis of other types of heterocycles in multi‐component reactions showed promising advantages [52] . Copper‐catalyzed synthesis of imidazo[1,2‐ a ]pyridines 48 by coupling from 2‐aminopyridine 12 , benzaldehyde 46 and phenylacetylene 47 in good to excellent yields was reported by de Salles et al [53] . in 2019.…”