Abstract

Background: The synthesis of octahydroquinazolin-2,5-dione derivatives via multi-component condensation reaction of aromatic aldehydes, dimedone and urea in the presence of catalytic amounts of acidic ionic liquids such as 2-pyrrolidonium hydrogensulfate, N-methyl-2-pyrrolidonium hydrogensulfate, N-methyl-2 pyrrolidonium dihydrogenphosphate and 1,3-disulfonic acid imidazolonium chloride is described. This protocol includes some advantages, such as reusability of ionic liquids with high activity, excellent yields of product, short reaction times (11-23 min). In addition to these, reactions were performed at room temperature.

Method: The mixture of the aldehyde (1 mmol), dimedone (0.14g, 1 mmol), urea (0.1g, 1.5 mmol) and ILs containing [H-NMP][HSO4] (0.03gr, 15 mol%), [H-NMP][H2PO4] (0.03 gr, 15 mol%), [H-NHP] [HSO4] (0.027gr, 15 mol%), and [Dsim]Cl (0.04gr, 15 mol%) as catalyst was stirred at 25oC under solvent- free conditions for the specific time. After completion of the reaction (11-23 min), 5 mL of water were added to the mixture. The IL was dissolved in water, and the solution was filtered for separation of the crude product. The separated product was washed twice with water (2×5 mL). The solid product was purified by recrystallization in ethanol (96 %). All the desired products were characterized by comparison of their physical data with those of known compounds.

Results: We studied the effect of catalyst loading and temperature in the three-component condensation reaction for the synthesis of 4-Phenyl-7,7-dimethyl-1,2,3,4,5,6,7,8-octahydro-quinazoline-2,5-dione in the presence of the IL, N-methyl-2-pyrrolidonum hydrosulfate ([H-NMP]HSO4 was selected as a model (Table 1). The generality of the reaction was investigated by using diverse aryl aldehydes under optimized conditions (Table 2). The wide ranges of substituted and structurally diverse aryl aldehydes synthesize the corresponding products in high to excellent yields using the four Brønsted acidic ILs as catalysts.

Conclusion: In this research, four acidic ILs [H-NMP][HSO4], [H-NMP][H2PO4], [H-NHP][HSO4] and [Dsim]Cl were used for the preparation of octahydroquinazolin-2,5-diones under solvent-free conditions for the first time. The attractive features of this protocol are simple procedure, cleaner reaction and use of inexpensive and reusable ILs as catalysts. Satisfactory yields of products, as well as a simple experimental, isolation and purification of the products make it a useful protocol for the green synthesis of these compounds.

Keywords: Ambient conditions, green catalyst, ionic liquid, multi-component reaction, recrystallization, tetrahydroquinazoline- 2, 5(1H, 6H)-dione.

Graphical Abstract