An Efficient Synthesis of Tri- and Tetrasubstituted Imidazoles from Benzils Using Functionalized Chitosan as Biodegradable Solid Acid Catalyst

Abstract

An environmentally benign, highly efficient one pot four component synthesis of highly functionalised imidazole derivatives using different aldehydes, substituted amines, benzil and ammonium acetate in the presence of biodegradable and highly efficient catalyst chitosan-SO 3 H were described. Chitosan-SO 3 H was found to be heterogeneous acidic catalyst which allowed easy recovery of the catalyst. Use of microwave irradiation along with chitosan-SO 3 H for the synthesis of imidazole derivatives make this protocol green. Moreover, excellent yields, shorter reaction time, chromatography-free purification, and elimination of environmentally hazardous solvents are other advantages of this protocol which leads to sustainability.

An Efficient One‐Pot Synthesis of 7,7‐Dimethyl‐2‐(2‐oxo‐2H‐chromen‐3‐yl)‐4‐aryl‐7,8‐dihydroquinolin‐5(6H)‐one Derivatives Using Chitosan–SO3H as Biodegradable Organocatalyst

“…Chitosan sulfonic acid as a stable reagent is easily prepared as reported previously by the reaction of CS with chlorosulfonic acid (Scheme ).…”

“…Chitosan is a biopolymer that can be used as green catalyst in many organic transformations such as Michael additions , synthesis of pyridazines , synthesis of α‐amino nitriles , synthesis of 2,4,5‐trisubstituted imidazoles , transamidation of carboxamides with amine , synthesis of 2 H ‐indazolo[2,1‐ b ]phthalazine‐triones , synthesis of trisubstituted and tetrasubstituted imidazoles , synthesis of 1,4‐dihydropyridines , synthesis of 5‐substituted hydantoins , and synthesis of 2,4‐diamino‐5 H ‐[1]benzopyrano[2,3‐ b ]pyridine‐3‐carbonitriles 5‐(arylthio) or 5‐[(arylmethyl)thio] substituted . Meanwhile, the sulfonic acid groups were introduced onto CS, and the catalytic activity increased as the amount of sulfonic acid groups present in CS increased .…”

Benefits and applications of microwave-assisted synthesis of nitrogen containing heterocycles in medicinal chemistry

“…al. 64 utilized a multicomponent condensation of polycyclic heterocycles jointly with green chemistry to develop a powerful pathway to synthesize tri-and tetra-substituted imidazoles. Benzyl 77 was reacted with various aromatic aldehydes 78 with ammonium acetate or substituted aniline 79 under MW heating, using functionalized chitosan as a biodegradable solid acid catalyst to yield imidazoles 80 and 81, respectively (Scheme 5).…”

Catalytic Synthesis of 1,2,4,5‐Tetrasubstituted 1H‐Imidazole Derivatives: State of the Art

“…[84] Scheme 21. b-CD-PSA-catalyzed synthesis of tetrasubstituted-1H-imidazoles 15 Notably, compound 15z (Figure 4), which was synthesized in 73% yield according to this protocol, proved to exhibit local anesthetic activity higher than that of lidocaine (Figure 4), which was used as standard agent for comparison. [84] O Ph Still in 2015, chitosan-supported sulphuric acid (CTSA) (Figure 5) was identified as an effective biodegradable solid acid catalyst for the one-pot four-component synthesis of tetrasubstituted-1Himidazoles 38a-h. [85] Figure 5. Chemical structure of chitosan-supported sulphuric acid (CTSA) Compounds 38 were obtained in high yields by reaction of a-diketones 10 (1 mmol), primary amines 8 (1 mmol), 5-chloro-4-formyl-3-methyl-1phenylpyrazole (37) (1 mmol), AcONH4 (3 mmol) and CTSA (100 mg) in EtOH under reflux or in a microwave reactor cavity at 5-10 Watt for 12 h (Scheme 22).…”