الفهرس | Only 14 pages are availabe for public view |
Abstract Among the most important quinazoline families, quinazoline-2,4(1H,3H)-dione de- rivatives are considered one of the most notable pharmacophores in drug discovery due to its broad spectrum of biological activities. It is a core scaffold for the struc- ture of more than 200 naturally occurring alkaloids isolated from different plant families and various microorganisms. Quinazolinedione is widely used as a func- tional material for synthetic chemistry and drug molecules.Quinazoline- 2,4(1H,3H)-dione (1) synthesized from anthranilic acid, followed by N-alkylation with ethyl chloroacetate in stirring dimethyl formamide in the presence of potassi- um carbonate at room temperature. The key intermediate 2,2’-(2,4- dioxoquinazoline-1,3(2H,4H)-diyl)di(acetohydrazide) (3) was afforded via the hy- drazinolysis reaction of diethyl 2,2’-(2,4-dioxoquinazoline-1,3(2H,4H)- diyl)diacetate (2) at the reflux condition. Alternatively, synthesized from 2,2’-(2,4- dioxoquinazoline-1,3(2H,4H)- diyl)diacetonitrile (4), the hydrolysis of the respec- tive nitrile groups to afford the acid derivative 5, was followed by esterification in the presence of sulfuric acid and methanol. The resulting dimethyl 2,2’-(2,4- dioxoquinazoline-1,3(2H,4H)-diyl)diacetate (6) underwent the hydrazinolysis re- action to afford the key intermediate 3 in a good yield of 72%. The crucial deriva- tive 7 was prepared from cyclization of dihydrazide 3 by treatment with carbon di- sulfide in the presence of potassium hydroxide. |