Synthesis of benzo[4,5]imidazo[1,2-a]pyrimidines and 2,3-dihydroquinazolin-4(1H)-ones under metal-free and solvent-free conditions for minimizing waste generation

Abstract

Brønsted acidic ionic liquid was found to be an efficient and recyclable catalyst for the synthesis of benzo [4,5]imidazo[1,2-a]pyrimidines and 2,3-dihydroquinazolin-4(1H)-ones. The reactions proceeded smoothly with a broad scope of substrates providing the expected products in good to excellent yields under an atom-economical pathway. The low-cost recyclable catalyst, metal-and solvent-free conditions, and the ease of product isolation are the highlighted advantages in solving the issue of trace metal contamination in synthesized pharmaceuticals. Results and discussion Synthesis of benzo[4,5]imidazo[1,2-a]pyrimidinesPyrimidine derivatives are backbones of various pharmaceutical drugs with various applications including anticancer, 25-29 anti-inammatory, 30-32 antibacterial, 31,33-35 and antifungal activities. [35][36][37] Over the past decade, many approaches have been achieved for the preparation of pyrimidine derivatives. [38][39][40][41][42]

Pyrimido[1,2-a]benzimidazoles: synthesis and perspective of their pharmacological use

“…Thus, the synthesis of 1,4-dihydropyrimido[1,2- a ]benzimidazole-3-carboxylates 169a – y using ionic liquids 167 , 168 as catalysts and in the absence of solvents (Scheme 43 ) was presented. 111 , 112 It was noted that when using these catalysts condensation proceeded smoothly with a wide range of substrates 165 , 166 , and the products were obtained in good or excellent yields (Table 4 ). In addition, the low cost of catalysts and the possibility of their reuse, as well as the ease of product isolation, are the main advantages of the developed methods.…”

“…A large number of studies [103][104][105][106][107][108][109][110][111][112][113][114][115][116][117][118][119][120] devoted to the synthesis of pyrimidobenzimidazoles 157 using MCR of keto esters and their various derivatives 155 as well as malononitrile (156) are presented in general in Scheme 40.…”

“…Keto esters and diketones are important substrates for the construction of the pyrimidobenzimidazole scaffold. [111][112][113][114][115][116][117][118][119][120] In these studies, the present synthetic strategy for the preparation of pyrimidobenzimidazoles corresponds to the approach shown in Scheme 36. The relevance of the research lies in demonstrating the broad capabilities of various catalysts and their systems in MCRs.…”

One‐Pot Synthesis of Benzo[4,5]imidazo[1,2‐a]pyrimidin‐2‐ones Using a Hybrid Catalyst Supported on Magnetic Nanoparticles in Green Solvents

“…This approach has been developed by other groups using various catalysts and conditions. [ 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 ] In the rest of these works, we report a new consecutive four‐component reaction for the synthesis of 3,4‐dihydrobenzo[4,5]imidazo[1,2‐ a ]pyrimidin‐2(1 H )‐ones by successive addition of aniline, DMAD, benzaldehyde derivatives and 2‐aminobenzimidazole in the presence of new organic‐inorganic hybrid nanomagnetic catalyst in water/EtOH as a green solvent.…”

“…In this reaction, 4 H ‐pyrimido[2,1‐ b ]benzazoles are synthesized using 2‐aminobenzimidazole, an aldehyde, and a β ‐ketoester in the presence of 1,1,3,3‐ N , N , N’ , N ’‐tetramethylguanidinium trifluoroacetate as an ionic liquid (Scheme 1). This approach has been developed by other groups using various catalysts and conditions [43–50] . In the rest of these works, we report a new consecutive four‐component reaction for the synthesis of 3,4‐dihydrobenzo[4,5]imidazo[1,2‐ a ]pyrimidin‐2(1 H )‐ones by successive addition of aniline, DMAD, benzaldehyde derivatives and 2‐aminobenzimidazole in the presence of new organic‐inorganic hybrid nanomagnetic catalyst in water/EtOH as a green solvent.…”