Benzoyl Peroxide → 2-Benzyl-5-nitroisoindoline

HRID 890534Notes

Reaction equation

HRID 890534 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]([CH3:11])[C:7]([CH3:10])=[CH:8][CH:9]=1)([O-:3])=[O:2].C1C(=O)N(Br)C(=O)C1.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+].[CH2:44]([NH2:51])[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1>CC(C)=O.O.C(Cl)(Cl)(Cl)Cl>[CH2:44]([N:51]1[CH2:11][C:6]2[C:7](=[CH:8][CH:9]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)[CH2:10]1)[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1

Participants

9

Reactant 5

HCID 7187Benzoyl PeroxideHCID 74404-Nitro-o-xyleneHCID 7504BenzylamineHCID 10340Sodium CarbonateHCID 67184N-bromobutanimide

Product 1

HCID 120659772-Benzyl-5-nitroisoindolineYield 33%

Reagents, catalysts & solvents 3

HCID 180AcetoneSolvent2×HCID 962WaterSolventHCID 5943Carbon TetrachlorideSolvent

Procedure

Part A. A solution of 4-nitro-o-xylene (38.64 g, 255.9 mmol), NBS (91.1 g, 511.8 mmol), benzoyl peroxide (1.239 g, 5.118 mmol), and CCl4 (400 mL) was heated at reflux for 1 day, then at rt for 2 days. The solid was filtered off and washed with CCl4. The filtrate was evaporated to give the crude dibromo product (80 g). A portion of which (20 g) was dissolved in acetone (170 mL) and water (45 mL), then Na2CO3 (43.1 g, 407 mmol) was slowly added, followed by BnNH2 (7.05 mL, 64.6 mmol) in acetone (22 mL). After 10 h, the solution was concentrated to one-fourth its volume, the salt solid was filtered off, and the filtrate was evaporated. The residue was dissolved in EtOAc, washed with water and brine, dried over sodium sulfate, filtered, and evaporated. The residue was purified by column chromatography to provide the corresponding 2-benzyl-5-nitro-2,3-dihydro-1H-isoindole (5.41 g, 33% yield, over 2 steps): 1H NMR (300 MHz, CDCl3) δ 8.11 (d, 1H), 8.04 (s, 1H), 7.48–7.20 (m, 6H), 4.02 (s, 4H), 3.92 (s, 2H).

Workup

  1. temperatureat reflux for 1 day
  2. filtrationThe solid was filtered off
  3. washwashed with CCl4
  4. customThe filtrate was evaporated
  5. customto give the crude dibromo product (80 g)
  6. waitAfter 10 h
  7. concentrationthe solution was concentrated to one-fourth its volume
  8. filtrationthe salt solid was filtered off
  9. customthe filtrate was evaporated
  10. dissolutionThe residue was dissolved in EtOAc
  11. washwashed with water and brine
  12. dry with materialdried over sodium sulfate
  13. filtrationfiltered
  14. customevaporated
  15. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-fea30af5b6a3492a94044e42366e2466
Source dataset
uspto-grants-2006_02
Patent number
US06995172B2

Reaction notes

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