Tandem Aldol-Michael reactions in aqueous diethylamine medium: a greener and efficient approach to dimedone-barbituric acid derivatives

Abstract

BackgroundGreen chemistry is a rapidly developing new field that provides us with a proactive avenue for the sustainable development of future science and technologies. Green chemistry uses highly efficient and environmentally benign synthetic protocols to deliver lifesaving medicines, accelerating lead optimization processes in drug discovery, with reduced unnecessary environmental impact. From this view point, it is desirable to use water instead of organic solvents as a reaction medium, since water is safe, abundant and an environmentally benign solvent.ResultsA convenient one-pot method for the efficient synthesis of the novel Zwitterion derivatives 4a-pvia a three-component condensation reaction of barbituric acid derivatives 1a,b, dimedone 2, and various aldehydes 3 in the presence of aqueous diethylamine media is described. This new approach is environmentally benign, with clean synthetic procedure, short reaction times and easy work-up procedure which proceeded smoothly to provide excellent yield (88-98%). The synthesized products were characterized by elemental analysis, IR, MS, NMR and CHN analysis. The structure of 4a was further confirmed by single crystal X-ray diffraction. The compound crystallizes in the orthorhombic space group Pbca with α = 14.6669 (5) Å, b = 18.3084 (6) Å, c = 19.0294 (6) Å, α = 90°, β = 90°, = 90°, V = 5109.9 (3) Å3, and Z = 8. The molecules are packed in crystal structure by weak intermolecular C–H⋅ ⋅ ⋅O hydrogen bonding interactions.ConclusionsAn environmentally benign Aldol-Michael protocol for the synthesis of dimedone-barbituric derivatives using aqueous diethylamine medium is achieved.

Crystal structure of diethylammonium 1,3-dimethyl-2,4,6-trioxohexahydropyrimidin-5-ide, C10H19N3O3

“…In the meanwhile, barbituric acid has been found to be associated with important biological activities including anti-hypertensive, anti-in ammatory, antitumor, anticonvulsant and hypnotic drugs [1][2][3][4][5][6][7][8][9][10][11][12]. We have succeeded to separate the active species which can act as nucleophile generated by aqueous diethylamine medium.…”

Crystal structure of diethylammonium 5-((4-fluorophenyl)(6-hydroxy-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)methyl)-1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-olate, C23H30FN5O6

“…Thus, several substituted 1,3-dimethylbarbituric acid were reported to exhibit marked chemotherapeutic activities such as antioxidant, anti-in ammatory, HIV-1 and HIV-2 protease inhibitors, anticancer, anticonvulsant and sedative-hypnotic [2][3][4][5]. In continues of our research program we report the crystal structure of a target molecule in this class of compounds.…”

Crystal structure of 5,5′-((4-(trifluoromethyl)phenyl)methylene)bis(1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione) – diethylamine – dichloromethane (1/1/1) C25H32Cl2F3N5O6

“…Thus, several substituted pyrimidine-triones were reported to exhibit marked biological activities such as HIV-1 and HIV-2 protease inhibitors, anticonvulsant sedative-hypnotic, antioxidant, anti-in ammatory, and anticancer agents [2][3][4][5][6][7][8][9][10][11].…”