Green Catalyst‐ and Additive‐Free Three‐Component Deamination Cyclization Synthesis of 3‐Substituted‐4‐ oxo‐2‐quinazolinonyl Sulfides

Abstract

An efficient three‐component deamination annulation of 2‐aminobenzamides, isothiocyanates and alkyl bromides for the synthesis of valuable 3‐substituted‐4‐oxo‐2‐quinazolinonyl sulfides is reported. The reaction proceeds in the absence of any external catalysts and additives. The facile process has the advantages of broad substrate scopes, mild reaction conditions and environmental friendliness, which might provide the synthetic applications for 3‐substituted‐4‐oxo‐2‐quinazolinonyl sulfides as potential anti‐cancer agents in medicinal chemistry.

Green synthesis of 2‐thioxo‐4‐quinazolinones from 2‐aminobenzamide and isothiocyanates

“…27 Due to their importance, many other synthetic routes have been explored for the synthesis of these 2-thioxo-4quinazolinone compounds, 28 of which the most common methods are through condensation of anthranilic acid, the ester of anthranilic acid, and 2-nitrobenzamides with isothiocyanates. 27,[29][30][31] The reaction of isatoic © 2024 Vietnam Academy of Science and Technology and Wiley-VCH GmbH.…”

“…Due to their importance, many other synthetic routes have been explored for the synthesis of these 2‐thioxo‐4‐quinazolinone compounds, 28 of which the most common methods are through condensation of anthranilic acid, the ester of anthranilic acid, and 2‐nitrobenzamides with isothiocyanates 27,29–31 . The reaction of isatoic anhydride with amines and subsequent addition of carbon disulfide, 9,32 one‐pot multicomponent synthesis of methyl 2‐bromobenzoate, phenylisothiocyanate catalyzed by CuBr, 33 some special catalysts such as NiFe 2 O 4 @SiO 2 –PPA, 34 H 3 [PW 12 O 40 ], 35 magnetic Fe 3 O 4 nanoparticles 36 have also been developed for the synthesis of 2‐thioxo‐4‐quinazolinones (See Scheme 1).…”

Green Synthesis of 2‐Thioxo‐4‐quinazolinone Derivatives in Water

“…2-Thixo-4-quinazolinones display a wide range of biological interests such as potential anti-melanogenesis agents with a tyrosinase inhibitory activity, [1] EGFR inhibitors, [2] anti-HIV, [3] antitubercular and antibacterial activities, [4] VEGFR-2 inhibitors with potential activity against the hepatocellular carcinoma, [5] anti-cancer, [6] HSP90 Inhibitors towards breast cancer targeting, [7] and dual and selective inhibitors of dynaminrelated protein 1 (Drp1) and puromycin-sensitive aminopeptidase (PSA) (Figure 1). [9] Therefore, several synthetic methods for 2-thixo-4-quinazolinones have been developed to date (Scheme 1), which include the reaction of an isatoic anhydride and amine followed by treating with carbon disulfide (Scheme 1, eq.…”

“…1), [1] condensation of anthranilic acid, anthranilic acid ester, and/or 2-aminobenzamide with isothiocyanate (Scheme 1, eq. 2), [2][3][4] Cu-catalyzed one-pot synthesis (Scheme 1, eq. 3), [8] and condensation of methyl 2-isothiocyanatobenzoate and aniline (Scheme 1, eq.…”