Heterocycles of biological importance: Part 6. The formation of novel biologically active pyrimido[1,2-a]benzimidazoles from electron deficient alkynes and 2-aminobenzimidazoles

Abstract

2-Aminobenzimidazole (1a) and its 5,6-dimethyl derivative 1b react with phenylpropynenitrile (2) to give 2-amino-4-phenylpyrimido[1,2-a]benzimidazoles 8a,b in excellent yields. Of these compounds, 2-amino-7,8-dimethyl-4-phenylpyrimido[1,2-a]benzimidazole (8b) has been shown to possess diuretic properties. Acetylenic aldehydes 9a,b also react with 1a,b to give pyrimido[1,2-a]benzimidazoles 13a-13d in good yield.

Regioselective Synthesis of 4′-amino-1′H-spiro[cyclohexane-1,2′-(pyrimido [1,2-a]benzimidazole)]-3′-carbonitrile in Aqueous Medium

“…The multi-component condensation reaction of 1, 2a and 3 gives a product of molecular formula C 16 H 17 N 5 . Based on literature survey, two possible isomeric structures 4 and 5 may be proposed, as both the amino function and ring nitrogen in 2-aminobenzimidazole are active sites for nucleophilic attack on αβ-unsaturated nitriles [15][16][17][18]21 (Scheme 3).…”

“…[2][3][4][5][6][7][8][9] These biological activities have prompted the development of new general procedures for the synthesis of pyrimido[1,2-a] benzimidazoles. Conventionally, these compounds have been synthesised by reaction of 2-aminobenzimidazole with substituted cinnamic acids, 10 with sulfones in acetonitrile, 11 with suitable halogeno-β-diketones, 12 with αβ-unsaturated ketones and hydrochlorides of Mannich base, 13 with ethyl α-arylazo-β-oxobutyrates, 14 with allenic nitriles, 15 with 3-phenylpropyne nitriles, 16 with hydroxyacetylenic nitriles, 17 and with enaminonitriles. 18 Pyrimido[1,2-a]benzimidazoles are also synthesised by reaction of 1-ethyl-2-amino-benzimidazoles with 1-bromo-3-chloropropane in toluene, 19 and by the reaction of 1,2-diaminobenzimidazoles with β-dielectrophiles.…”

“…Consequently there is need for milder conditions, increased variety of the substituents in the component, and improvement in yields. There is also controversy regarding the structure of the products obtained by the reaction of 2-aminobenzimidazole, including those with allyl, 15 alkyne 16,17 or enaminonitriles. 18,21 An extensive literature survey of reactions of 2-aminobenzimidazole leading to the formation of pyrimido[1,2-a]benzimidazoles indicated that there is a definite need to study the detailed mechanistic pathway and regiochemistry of the * Correspondent.…”

Microwave-Assisted Synthesis of Benzo[4,5]imidazo[1,2-a]pyrimidines from β-Bromo-α,β-unsaturated Aldehydes and 2-Aminobenzimidazoles

“…

β-Bromo-α,β-unsaturated aldehydes react with 2-aminobenzimidazoles by microwave irradiation in the presence of a base and magnesium sulfate to give the corresponding benzo [4,5]imidazo [1,2a]pyrimidines in moderate to good yields.

…”

“…It is known that benzimidazole-fused pyrimidines, benzo [4,5]imidazo [1,2-a]pyrimidines, exhibit a wide spectrum of biological activities, such as anti-inflammatory, 1 cytotoxic, 2 antimicrobial, 3 antimalarial, 4 diuretic, 5 antiparasitic, 6 antibacterial, 7 antiarrhythmic, 8 herbicidal 9 as well as fluorescence properties (Scheme 1). 10,11 Thus, many benzo [4,5]imidazo [1,2-a]pyrimidine-containing compounds have been synthesized and tested for such activities and properties.…”