Phthalic Anhydride → HCID 76684066, compound

HRID 918901Notes

Reaction equation

HRID 918901 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[C:4]=1[O:11][CH3:12].[Cl-].[Al+3].[Cl-].[Cl-].[C:17]1(=O)[O:22][C:20](=O)[C:19]2=[CH:23][CH:24]=[CH:25][CH:26]=[C:18]12.Cl.[CH2:29]([NH:36][NH2:37])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C([O-])(=O)C.[K+]>ClCCl.C(O)C>[CH2:29]([N:36]1[N:37]=[C:17]([C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[C:4]([O:11][CH3:12])[C:5]=2[O:9][CH3:10])[C:18]2[C:19](=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:20]1=[O:22])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

8

Reactant 5

HCID 6811Phthalic AnhydrideHCID 124621,2,3-TrimethoxybenzeneHCID 14084Hydrazine, (phenylmethyl)-, hydrochloride (1:1)HCID 517044Potassium AcetateHCID 6451240Aluminum(III) Chloride

Product 1

HCID 76684066HCID 76684066, compoundYield 28%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

1,2,3-trimethoxybenzene (2.0 g, 11.9 mmol) was slowly added to a suspension of aluminum chloride (1.6 g, 11.9 mmol) in dichloromethane (50 mL) at 0° C. After the addition was complete phthalic anhydride (1.76 g, 11.9 mmol) was added. The resulting solution heated to reflux and stirred overnight. After that time, the reaction was cooled to rt, concentrated under reduced pressure and cautiously quenched with ice-water. The resulting mixture was extracted with dichloromethane (3×100 mL). The organic phase was dried and concentrated under reduced pressure. The resulting material was combined with N-benzylhydrazine hydrochloride (0.68 g, 3.5 mmol) and potassium acetate (1.62 g, 16.5 mmol) in ethanol (100 mL). The mixture was heated to reflux for 18 h. After that time, the reaction was cooled to rt, concentrated under reduced pressure and diluted with dichloromethane (200 mL). The organic phase was washed with saturated NaHCO3, then water, dried over Na2SO4 and concentrated under reduced pressure. The product was purified by flash column chromatography (silica gel, hexanes/ethyl acetate) to give 2-benzyl-4-(2,3,4-trimethoxyphenyl)phthalazin-1(2H)-one (0.37 g, 28%) as a colorless solid: mp 144-145° C.; 1H NMR (400 M Hz, CDCl3) δ 8.49 (d, J=7.4 Hz, 1H), 7.76-7.66 (m, 2H), 7.49 (d, J=7.4 Hz, 2H), 7.41 (d, J=7.8 Hz, 1H), 7.34-7.28 (m, 2H), 7.27-7.22 (m, 1H), 7.04 (d, J=8.6 Hz, 1H), 6.80 (d, J=8.6 Hz, 1H), 5.47 (s, 2H), 3.94 (s, 6H), 3.64 (s, 3H); ESI MS m/z 389.1 [M+H]+.

Workup

  1. additionAfter the addition
  2. additionwas added
  3. temperatureThe resulting solution heated
  4. temperatureto reflux
  5. concentrationconcentrated under reduced pressure
  6. customcautiously quenched with ice-water
  7. extractionThe resulting mixture was extracted with dichloromethane (3×100 mL)
  8. customThe organic phase was dried
  9. concentrationconcentrated under reduced pressure
  10. temperatureThe mixture was heated
  11. temperatureto reflux for 18 h
  12. temperatureAfter that time, the reaction was cooled to rt
  13. concentrationconcentrated under reduced pressure
  14. additiondiluted with dichloromethane (200 mL)
  15. washThe organic phase was washed with saturated NaHCO3
  16. dry with materialwater, dried over Na2SO4
  17. concentrationconcentrated under reduced pressure
  18. customThe product was purified by flash column chromatography (silica gel, hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-688989d50680450caaf0888259d93edf
Source dataset
uspto-grants-2016_03
Patent number
US09271978B2

Reaction notes

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