Reaction #487584

Reaction equation

8,9-dihydro-5H-benzo[7]annulen-7(6H)-one

sulfuric acid

nitric acid

→

2-nitro-8,9-dihydro-5H-benzo[7]annulen-7(6H)-one

Yield 40.0%

Solvents

nitromethane

Conditions

Workup

1. 1
   workup.ADDITIONThe addition
2. 2
   Temperatureto maintain the internal reaction temperature below 5° C
3. 3
   workup.ADDITIONAfter the addition
4. 4
   Otherthe resulting solution was transferred into an addition funnel
5. 5
   workup.ADDITIONAfter the addition
6. 6
   workup.STIRRINGthe mixture was stirred for additional 30 min
7. 7
   OtherThen the mixture was transferred to a separatory funnel
8. 8
   Otherwhere the layers were separated
9. 9
   ExtractionThe aqueous layer was extracted with ethyl acetate (3×80 mL)
10. 10
    WashThe combined layers were washed with cold water, sat. NaHCO3 solution and brine
11. 11
    DryingAfter being dried (MgSO4)
12. 12
    Filtrationfiltered
13. 13
    Concentrationconcentrated
14. 14
    Otherthe residue was purified by flash column chromatography on silica gel (hexanes/EtOAc=3:1 to 2:1)
15. 15
    Otherto afford
16. 16
    Otherwas then purified by recrystallization from MTBE (tert-butyl methyl ether, 180 mL)

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)+.

Source