Iodine-catalyzed three component reaction: a novel synthesis of 2-aryl-imidazo[1,2-a]pyridine scaffolds

Abstract

A facile and efficient protocol for the synthesis of novel imidazo[1,2-a]pyridines has been developed by one-pot reaction of aromatic aldehydes with 2-amino-5-chloropyridine and tertbutylisocyanide in the presence of I 2 in toluene at 70 °C . The present approach offers the advantages of simple methodology, clean, high atom-economy, mild condition, short reaction time, wide substrate scope, low environmental impact and high yield. Key WordsIodine, Imidazopyridines, Imidazo[1,2-a]pyridine, 2-aminopyridine, tert-butylisocyanide. IntroductionMulti-component synthesis have received considerable attention of organic chemists and emerged as a powerful tool for the construction of novel and complex molecular structures due to their advantages over conventional multistep synthesis. The major advantages of MCR's include low cost, shorter reaction times, high atom economy, energy saving and avoidance of time consuming and expensive protection, deprotection, isolation and purification process Result and discussionFirst the optimization of the reaction was studied for which the reaction of 2-chloropyridine-3-carbaldehyde, 5-chloro-pyridin-2-ylamine and tert-butylisocyanide was selected as a The role of solvents on the synthesis of imidazo[1,2-a]pyridine was then studied and the results are depicted (Table 2). Replacing the ethanol by chloroform produced the model in an A probable mechanistic pathway for the formation of imidazo[1,2-a]pyridine is outlined, ConclusionIn conclusion, a straightforward and efficient protocol for the one pot synthesis of Exprimental General informationThe melting points were determined by open capillary method using electric melting point apparatus and are uncorrected. The IR spectra (KBr disc) were recorded on a Shimadzu-8400SFT-IR Spectrophotometer.1 H NMR spectra were recorded on Bruker 300 MHz spectrometer and solution. The organic layer was separated and aqueous layer was extracted with ethyl acetate (15 ml X 3). The combined organic phase were washed with water, dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford a crude product which was purified on silica gel using hexane and ethyl acetate (7:3). 56.9, 104.5, 110.8, 117.3, 120.7, 121.3, 121.8, 123.2, 124.5, 126.0, 127.0, 128.6, 154.5 55.9, 117.8, 120.5, 121.7, 122.7, 125.7, 126.4, 131.1, 136.6, 140.7, 148.8, 149 3, 30.5, 56.8, 117.3, 119.9, 121.4, 122.8, 125.3, 125.6, 126.5, 132.3, 140.0, 140 C, 60.08: H, 5.67: N, 13.14: S, 10.02. Found: C, 59.91: H, 5.54: N, 13.01: S, 9.97. 0, 56.7, 109.8, 113.3, 117.5, 120.0, 120.7, 121.6, 124.7, 126.0, 130.8, 140.6, 151.8 56.7, 109.8, 113.3, 117.5, 120.0, 120.7, 121.6, 124.7, 126.0, 130.8, 140.6, 151.8 55, 57.31, 105.08, 114.07, 114.11, 117.26, 117.92, 121.14, 131.17, 140.89, 140.93, 145.86, 149.71, 150.56, 152.50 N-tert-butyl-6-chloro-2-(1H-imidazol-4-yl)H-imidazo[1,2-a]pyridin-3-amine (2g)

Synthesis of α-amino amidines through molecular iodine-catalyzed three-component coupling of isocyanides, aldehydes and amines

“…3 which is analogous to the established mechanism reported in the literature [28–29]. Iodine can serve as a catalyst for the activation of imine.…”

The Groebke‐Blackburn‐Bienaymé Reaction

“…Overview of GBB catalysts that performed best in reported catalyst screenings (single hits were omitted for clarification). TiO 2 NPs (nanopowders) [170] TMSCl 7 [37,38,53,152,155,169,176] ZnO NPs [116] Montmorillonite K-10 clay 6 [19,64,65,70,121,192] Methanesulfonic acid [52] Magnesium chloride (MgCl 2 ) 5 [134,136,193,194] Zeolite HY [195] Ytterbium triflate (Yb(OTf) 3 ) 4 HCl dioxane 4 [72,73,84,117] Bromodimethylsulfonium bromide (BDMS) [69] Indium triflate (In(OTf) 3 ) 3 [108,109,122] γ-Fe 2 O 3 @SiO 2 -OSO 3 H [71] Trifluoroacetic acid (TFA) 2 [82,165] Cationic polyurethane dispersions (CPUDs) [76] Bismuth chloride (BiCl 3 ) 2 [81,91] pTsCl [77] Silica sulfuric acid 2 [126,148] Iodine [135] Lanthanum chloride (LaCl 3 •7H 2 O) 2 [92,104] (TBBDA) [83] Piperidine 2 [162,163] (PBBS)…”

Efficient one-pot synthesis of functionalised imidazo[1,2-a]pyridines and unexpected synthesis of novel tetracyclic derivatives by nucleophilic aromatic substitution

“…1), to mention just a few. Other reports indicate activity as gastric proton pump inhibitors 4 and as antifungal, 5 antibacterial 6 and anxiolytic 7 agents.…”