Nitric Acid → 2-Nitro-8,9-dihydro-5H-benzo[7]annulen-7(6H)-one

HRID 1919462Notes

Reaction equation

HRID 1919462 reaction equation
S(=O)(=O)(O)O.[N+:6]([O-:9])(O)=[O:7].[CH:10]1[C:15]2[CH2:16][CH2:17][C:18](=[O:21])[CH2:19][CH2:20][C:14]=2[CH:13]=[CH:12][CH:11]=1>[N+](C)([O-])=O>[N+:6]([C:12]1[CH:11]=[CH:10][C:15]2[CH2:16][CH2:17][C:18](=[O:21])[CH2:19][CH2:20][C:14]=2[CH:13]=1)([O-:9])=[O:7]

Participants

5

Reactant 3

HCID 944Nitric AcidHCID 1118Sulfuric AcidHCID 122344855,6,8,9-Tetrahydro-7H-benzo[7]annulen-7-one

Product 1

HCID 457903192-Nitro-8,9-dihydro-5H-benzo[7]annulen-7(6H)-oneYield 40%

Reagents, catalysts & solvents 1

HCID 6375NitromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of cold (0° C.) concentrated sulfuric acid (15 mL) was added 70% nitric acid (15 mL) dropwise over 30 min. The addition was controlled to maintain the internal reaction temperature below 5° C. After the addition, the resulting solution was transferred into an addition funnel and was added dropwise to a solution of 8,9-dihydro-5H-benzo[7]annulen-7(6H)-one (14 g, 87.5 mmol) in nitromethane (80 mL) at 0° C. over a period of 40 min. After the addition, the reaction mixture was stirred at 0° C. for 2 h. Then ice water (˜80 mL) was added to the reaction mixture, and the mixture was stirred for additional 30 min. Then the mixture was transferred to a separatory funnel where the layers were separated. The aqueous layer was extracted with ethyl acetate (3×80 mL). The combined layers were washed with cold water, sat. NaHCO3 solution and brine. After being dried (MgSO4), filtered, and concentrated, the residue was purified by flash column chromatography on silica gel (hexanes/EtOAc=3:1 to 2:1) to afford the mixture of nitro regioisomers (˜15 g), which was then purified by recrystallization from MTBE (tert-butyl methyl ether, 180 mL) to yield 7.3 g of 2-nitro-8,9-dihydro-5H-benzo[7]annulen-7(6H)-one (40% yield) as a yellow solid: 1H NMR (300 MHz, CDCl3) δ: 8.10-8.06 (m, 2H), 7.40-7.37 (m, 1H), 3.04-3.00 (m, 4H), 2.67-2.65 (m, 4H); LC-MS: 206 (M+H)+.

Workup

  1. additionThe addition
  2. temperatureto maintain the internal reaction temperature below 5° C
  3. additionAfter the addition
  4. customthe resulting solution was transferred into an addition funnel
  5. additionAfter the addition
  6. stirringthe mixture was stirred for additional 30 min
  7. customThen the mixture was transferred to a separatory funnel
  8. customwhere the layers were separated
  9. extractionThe aqueous layer was extracted with ethyl acetate (3×80 mL)
  10. washThe combined layers were washed with cold water, sat. NaHCO3 solution and brine
  11. dry with materialAfter being dried (MgSO4)
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customthe residue was purified by flash column chromatography on silica gel (hexanes/EtOAc=3:1 to 2:1)
  15. customto afford
  16. customwas then purified by recrystallization from MTBE (tert-butyl methyl ether, 180 mL)

Sources & evidence

ORD record
ord-1e703759794142d692b1fc5190328188
Source dataset
uspto-grants-2012_05
Patent number
US08168636B2

Reaction notes

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