Acetic Acid → 2-(Bromomethyl)-4-chloro-1-nitrobenzene
Reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([Cl:10])=[CH:6][C:5]=1[CH3:11])([O-:3])=[O:2].[Br:12]N1C(C)(C)C(=O)N(Br)C1=O.N(C1(C#N)CCCCC1)=NC1(C#N)CCCCC1.C(O)(=O)C>C1(Cl)C=CC=CC=1>[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([Cl:10])=[CH:6][C:5]=1[CH2:11][Br:12])([O-:3])=[O:2]Participants
Conditions
- Temperature
- 40 °C
Procedure
2-Nitro-5-chlorotoluene (6.0 g, 35.0 mmol), 1,3-dibromo-5,5-dimethyl hydantoin (10.6 g, 37.1 mmol), and 1,1-azobis-(cyclohexanecarbonitrile) (VAZO 88, 400 mg, 16 μmol) were combined in 275 mL of C6H5Cl and stirred. Glacial acetic acid (200 μL) was added and the reaction was heated to 40° C. for 120 h. The reaction was washed with 150 mL of warm saturated bicarbonate, extracted with warm bicarbonate (4×150 mL) and washed with water (150 mL). The organic layer was dried over MgSO4 and the solvent was removed to yield a pink-red oily solid that consists of 2-nitro-5-chlorotoluene (˜40%) and the desired product (˜60%) and can be carried on to the next reaction without further purification. Flash chromatography on silica gel (25:1 hexanes:EtOAc) yields the pure brominated product as a brown solid (38%). 1H NMR (CDCl3, 300 MHz) δ 8.0 (1H, dd), 7.56 (1H, d), 7.45 (1H, dd), 4.79 (2H, s). 13C NMR (CDCl3, 300 MHz) δ 28.43, 127.02, 129.61, 132.37, 134.64, 139.91, 145.96. FTIR (KBr, cm−1) 1604, 1569, 1522, 1474, 1443, 1338, 1306, 1227, 1202, 1109, 1064, 908, 827, 757, 706.93, 827, 757, 707, 685, 524. HRMS (EI) calcd M+, 248.9187; found, 248.9186.
Workup
- washThe reaction was washed with 150 mL of warm saturated bicarbonate
- extractionextracted with warm bicarbonate (4×150 mL)
- washwashed with water (150 mL)
- dry with materialThe organic layer was dried over MgSO4
- customthe solvent was removed
- customto yield a pink-red oily solid
Sources & evidence
- ORD record
- ord-f0188a83ebb644f5ae051474fde83024
- Source dataset
- uspto-grants-2008_07
- Patent number
- US07399639B2
Reaction notes
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