Benzoic Acid → HCID 70020865, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-methyl-3-nitroaniline (54.8 g, 0.36 mol) and ethyl chloroformate (100 ml, 1 mol) in 1,4-dioxane (500 ml) was heated at 65° C. for 24 hours. The clear solution was evaporated to dryness to give white crystals in quantitative yield. The crystals were dissolved in pyridine (250 ml) and water (250 ml) and warmed to 80° C. Potassium permanganate (142 g, 0.9 mol) was added portionwise during 4 hours, maintaining the temperature at 80-95° C. After another 1 hour, the black mixture was filtered through celite and the manganese dioxide cake was carefully washed with hot water (800 ml). The collected yellowish mother-liquor was treated with conc. hydrochloric acid to adjust the pH to 3-4 and then extracted with dichloromethane. The organic solvent was removed and the residue was worked up with aq. sodium bicarbonate (100 ml), unsolved material was filtered off, and the solution was acidified to give pure orange colored crystals. This benzoic acid (10 g, 0.04 mol) was dissolved in 1,4-dioxane (40 ml) and thionyl chloride (7.2 g. 0.06 mol) was added. The mixture was warmed at 50° C. during night, cooled, and the formed 5-nitro-isatoic anhydride was collected by filtration and dried. The anhydride (6.4 g, 0.031 mol) was dissolved in N,N-dimethylacetanide (30 ml) and sodium hydride (75%) (2.6 g, 0.08 mol) was added portionwise. Then, methyl iodide (5.3 g, 0.037 mol) was added and the mixture stirred for 30 minutes. Diethyl malonate (8.9 g, 0.056 mol) was added and the mixture warmed to 100° C. and stirred at this temperature for 6 hours. After cooling, water (120 ml) was added and the pH adjusted to 3-4. On standing a crystalline precipitate was formed which was filtered off, washed with water, and dried to give the title compound as beige crystals (7.1 g).

Provenance & Evidence