Cycloaddition of 2-acylmethyl-1H-benzimidazoles to 4-arylidene-1,3-oxazol-5-ones

Abstract

Pyrido[1,2-a]benzimidazoles possess a broad spectrum of biological activity [1][2][3][4][5][6], have fluorescence properties [7], and are a component of light sensitive materials [8,9]. We hoped to prepare previously unavailable derivatives on the basis of the reaction of 2-acylmethyl-1H-benzimidazoles of type 1 with 4-arylidene-1,3-oxazol-5-ones (azlactones) of type 2 and 3 for the following reasons. 2-Aminobenzimidazole reacts regioselectively with azlactones to give pyrimido[1,2-a]benzimidazoles, in such a way that the exocyclic amino group is acylated as a result of opening of the oxazole ring and the endocyclic by addition to the arylidene fragment [10]. It is advisable to use compounds of type 1 as the 1,3-dinucleophile component. In the first place 2-phenacyl-1H-bezimidazole 1a is acylated by carboxylic acid anhydrides at the active methylene group [11]. In the second, azlactones are analogs of cyclic anhydrides which react with active methylene compounds to form C-acylation products [12].We have found that the reaction of compound 1 with azlactones 2a-f, 3a-c indeed occurs efficiently via the cycloaddition of a 1,3-dinucleophile to a 1,3-dielectrophile. However, the products of the expected structure 4 or any kind of prototropic isomers were not formed. A contrary scheme of regioselective construction or the ring is achieved via acylation at a benzimidazole nitrogen atom (possible by the intermediate formation of compound 5) and Michael addition of the methylene group to the arylidene fragment to give the previously unknown N-(3-aryl-4-benzoyl-1-oxo-1,2,3,4-tetrahydropyridino[1,2-a]benzimidazol-2-yl)benz-and -acetamides 6a-f, 7a-c.The reaction was carried out by refluxing in pyridine and is complete after 1 h. The product yields were 70-95%.

Synthesis of heterocyclic scaffolds through 6-aminouracil-involved multicomponent reactions

“…72 Dzvinchuk and Lozinskii investigated the reaction between p-(dimethylamino)benzaldehyde 7, 2-acylmethyl-1H-benzimidazoles 69, and 6-amino-1,3-dimethyluracil 1 in boiling acetic acid for the synthesis of 6-(1H-benzimidazol-2-yl)pyrido [2,3-d] pyrimidino-2,4(1H,3H)-diones 70 (Scheme 26). 73 The reaction proceeds in accordance with the Hantzsch reaction to form 1,4dihydropyridine-bearing compounds A followed by aromatization as a result of cleavage of N,N-dimethylaniline.…”