Metal‐Free, Photoredox‐Catalyzed Synthesis of Quinazolin‐4(3H)‐ones and Benzo[4,5]imidazo[1,2‐c]quinazolines Using Trialkylamines as Alkyl Synthon

Abstract

Highly functionalized quinazolin‐4(3H)‐ones were synthesized from reactions of N‐aryl‐2‐aminobenzamides with trialkylamines under photocatalytic conditions by using eosin Y (EY) as a catalyst. The reaction proceeds under mild conditions in aqueous acetonitrile and has a broad substrate scope. Mechanistic studies disclosed the electron‐donor nature of the intermediate 2,3‐dihydroquinazolin‐4(1H)‐one (3’) in the photocatalytic cycle to afford the 2,3‐disubstituted‐quinazolin‐4(3H)‐ones (3). This methodology has been extended to synthesize benzo [4,5] imidazole[1,2‐c] quinazolines and 3 aa on a large scale. Furthermore, the synthesis of potent central nervous system depressant (CNS) drug molecules such as methaqualone (3 la) and mecloqualone (3 pa) was also achieved successfully.

An Extensive Analysis of Current Synthetic Methodologies and Applications of Imidazo/Benzimidazo[1,2‐c]Quinazolines

“…Eosin Y (EY) as a photocatalyst (Scheme 38). [57] This process operated effectively with different trialkylamines in order to produce the required compounds in yields ranging from 61 % to 91 %. Unfortunately, it did not work in substrates like benzene-1,2-diamine, The reduced EY (E 1/2 (EY/EY *À ) = À 1.08 V vs. SCE in acetonitrile) was then brought back to its ground state through an aerobic oxidation process (E 1/2 (O 2 *À /O 2 ) = À 0.57 V vs. SCE in acetonitrile) through a single electron transfer (SET) process.…”

“…The most important acyl intermediate C was formed by the hydrolysis of B, and dialkylamine was released in the process (Scheme 39). [57] In order to produce 5,6-dihydro-benzo [4,5]…”

“…reported (2023) the photocatalytic synthesis of biologically relevant benzo[4,5]imidazo[1,2‐ c ]quinazolines from 2‐(2‐aminophenyl)‐1 H‐ benzimidazole utilising trialkylamines as alkyl synthon and Eosin Y (EY) as a photocatalyst (Scheme 38). [57] This process operated effectively with different trialkylamines in order to produce the required compounds in yields ranging from 61 % to 91 %. Unfortunately, it did not work in substrates like benzene‐1,2‐diamine, 2‐(1 H ‐pyrrol‐1‐yl)aniline and 2‐(phenylethynyl)aniline.…”

“…The most important acyl intermediate C was formed by the hydrolysis of B , and dialkylamine was released in the process (Scheme 39). [57] In order to produce 5,6‐dihydro‐benzo[4,5]imidazo[1,2‐ c ]quinazoline ( E ), 2‐(2‐aminophenyl)‐1 H benzimidazole must undergo condensation with aldehyde intermediate C , followed by 6‐endo‐tricyclization via the formation of Schiff base intermediate D . A repeated reductive quenching cycle of EY employing E as an electron donor will produce the required benzo[4,5]imidazo[1,2‐ c ]quinazolines with the aid of the intermediates F and G .…”

Recent Approaches for the Synthesis of Imidazoquinazolines and Benzimidazoquinazolines

“…A domino synthetic approach for benz [4,5]imidazo[1,2-c]quinazoline formation was the reaction of benzimidazolyl anilines (39a-d) with ethynyl benzene (40) using I 2 and CuI as catalysts in DMSO at 120°C to afford the desired products (41a-d) in moderate to good yields [64]. Highly functionalized benz [4,5]imidazo[1,2-c] quinazolines (43a-d) were synthesized under metal-free, photocatalytic conditions by reacting benzimidazolyl (39a-d) with trialky amine (42a-d) using eosin Y (EY) as a catalyst in aqueous acetonitrile in the presence of blue LED at room temperature for 27-50 h to obtain the desired products [65].…”