Benzoic Acid → HCID 70020865, compound

HRID 395291Notes

Reaction equation

HRID 395291 reaction equation
C[C:2]1[C:8]([N+:9]([O-:11])=[O:10])=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].Cl[C:13]([O:15][CH2:16][CH3:17])=[O:14].[Mn]([O-])(=O)(=O)=O.[K+].[C:24](O)(=O)C1C=CC=CC=1.S(Cl)(Cl)=O.[H-].[Na+].CI.[C:41]([O:49]CC)(=O)[CH2:42][C:43]([O:45]CC)=O>O1CCOCC1.N1C=CC=CC=1.O>[CH2:16]([O:15][C:13]([C:42]1[C:41](=[O:49])[N:4]([CH3:24])[C:3]2[C:2]([C:43]=1[OH:45])=[C:8]([N+:9]([O-:11])=[O:10])[CH:7]=[CH:6][CH:5]=2)=[O:14])[CH3:17]

Participants

12

Reactant 8

HCID 243Benzoic AcidHCID 6328Methyl iodideHCID 7761Diethyl MalonateHCID 10928Ethyl chloroformateHCID 117832-Methyl-3-nitroanilineHCID 24386Thionyl ChlorideHCID 24758Sodium hydrideHCID 516875Potassium Permanganate

Product 1

HCID 70020865HCID 70020865, compoundYield 60.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 1049PyridineSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
65 °C

Procedure

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).

Workup

  1. customThe clear solution was evaporated to dryness
  2. customto give white crystals in quantitative yield
  3. temperaturemaintaining the temperature at 80-95° C
  4. filtrationthe black mixture was filtered through celite
  5. washthe manganese dioxide cake was carefully washed with hot water (800 ml)
  6. additionThe collected yellowish mother-liquor was treated with conc. hydrochloric acid
  7. extractionextracted with dichloromethane
  8. customThe organic solvent was removed
  9. filtrationwas filtered off
  10. customto give pure orange colored crystals
  11. temperatureThe mixture was warmed at 50° C. during night
  12. temperaturecooled
  13. filtrationthe formed 5-nitro-isatoic anhydride was collected by filtration
  14. customdried
  15. additionwas added portionwise
  16. temperaturethe mixture warmed to 100° C.
  17. stirringstirred at this temperature for 6 hours
  18. temperatureAfter cooling
  19. customwas formed which
  20. filtrationwas filtered off
  21. washwashed with water
  22. customdried

Sources & evidence

ORD record
ord-04add9f7993b409980279b2713af4c3e
Source dataset
uspto-grants-2003_08
Patent number
US06605616B1

Reaction notes

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