Biginelli Synthesis of Regioisomeric 5,6-Dihydro-4 H -benzo[4,5]imidazo[1,2- a ]pyranopyrimidin-4-ones
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nelli Synthesis of Regioisomeric 5,6-Dihydro-4H-benzo[4,5]imidazo[1,2-a]pyranopyrimidin-4-ones I. V. Kanevskayaa,*, A. S. Bondartsovaa, and O. V. Fedotovaa a
Institute of Chemistry, Chernyshevsky Saratov National Research State University, Saratov, 410012 Russia *e-mail: [email protected] Received July 4, 2020; revised July 16, 2020; accepted July 20, 2020
Abstract—A modified version of the three-component Biginelli reaction of 4-hydroxy-6-methyl-2H-pyran-2one with aromatic aldehydes and 1H-benzimidazol-2-amine has been studied under thermal and microwave activation. Depending on the substituent in the initial aldehyde, angularly fused 5,6-dihydro-4H-benzo[4,5]imidazo[1,2-a]pyranopyrimidin-4-ones or 2-amino-1H-benzimidazol-3-ium arylbis(4-hydroxy-6-methyl-2-oxo2H-pyran-3-yl)methanides have been obtained. A plausible mechanism of their formation has been proposed. Keywords: 2H-pyran-2-one, 2-aminobenzimidazole, one-pot synthesis, Biginelli reaction, benzimidazopyranopyrimidinones
DOI: 10.1134/S1070428020100139 2H-Pyran-2-one derivatives exhibit a broad spectrum of biological activity and are used in medicine and agriculture. They show antifungal [1], antitumor [2], antimicrobial [3], cyto-, phyto-, and neurotoxic [4], and plant growth regulating activities [5]. 3-Substituted 4-hydroxy-2H-pyran-2-ones are promising scaffolds for the synthesis of various heterocyclic and hybrid structures. 4-Hydroxy-2H-pyran-2-ones and their benzo analogs were previously used to obtain hybrid compounds via one-pot multicomponent Biginelli and Hantzsch reactions [6–8]. Herein we report a modified version of the threecomponent Biginelli reaction of a cyclic keto ester, 4-hydroxy-6-methyl-2H-pyran-2-one (1), with aromatic aldehydes 2a–2d and a heterocyclic nitrogen polynucleophile, 1H-benzimidazol-2-amine (3). As shown previously [6, 9], a benzo analog of 1, 4-hydroxy-2H-chromen-2-one (4) reacted with aromatic aldehydes 2a and 2c and 1H-benzimidazol-2-amine to give mixtures of regioisomeric chromenopyrimidobenzimidazolones, angularly fused 7-(R-phenyl)-7,8-dihydro-6H-chromeno[3′,4′:5,6]pyrimido[1,2-a]benzimidazol-6-ones 6a and 6b and linearly fused 7-(R-phenyl)7,14-dihydro-6H-chromeno[4′,3′:4,5]pyrimido[1,2-a]benzimidazol-6-ones 7a and 7b (Scheme 1). Conditions for the selective formation of the linearly fused isomers (compounds 7a and 7b) were also found [9]. We have found that, unlike benzo-fused analog 4, the reaction of 1 with aromatic aldehydes 2 and hetero-
cyclic amine 3 could give rise to both classical Biginelli condensation products, substituted benzimidazopyranopyrimidinones, and other systems. For instance, one-pot reaction of 1, 2a, and 3 under both thermal and microwave activation conditions afforded only angularly fused 2-methyl-5-phenyl-5,6-dihydro4H-benzo[4,5]imidazo[1,2-a]pyranopyrimidin-4-one (8) in 58 and 83% yield, respectively, whereas no linearly fused isomer 10 was formed (Scheme 2). Compound 8 was isolated as hydrochloride, which may be due to high basicity of the imidazopyrimidine fragment and the use o
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