Hydrogen Bromide → 4-Bromo-7-bromomethyl-benzo[1,2,5]thiadiazole

HRID 1505240Notes

Reaction equation

HRID 1505240 reaction equation
BrBr.[CH3:3][C:4]1[C:12]2[C:8](=[N:9][S:10][N:11]=2)[CH:7]=[CH:6][CH:5]=1.[Br:13]N1C(=O)CCC1=O.N(C(C)(C)C#N)=NC(C)(C)C#N.[BrH:33]>S(S([O-])=O)([O-])(=O)=O.[Na+].[Na+].FC(F)(F)C1C=CC=CC=1.ClCCl.Cl>[Br:33][C:7]1[C:8]2=[N:9][S:10][N:11]=[C:12]2[C:4]([CH2:3][Br:13])=[CH:5][CH:6]=1

Participants

10

Reactant 5

HCID 260Hydrogen BromideHCID 6547AzobisisobutyronitrileHCID 24408BromineHCID 67184N-bromobutanimideHCID 27812624-Methyl-2,1,3-benzothiadiazole

Product 1

HCID 114155784-Bromo-7-bromomethyl-benzo[1,2,5]thiadiazole

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolventHCID 7368(Trifluoromethyl)benzeneSolventHCID 656671Sodium PyrosulfiteSolvent

Procedure

Bromine (9.78 ml) was added to a solution of 4-methylbenzo[c][1,2,5]thiadiazole (commercially available) (15 g) in aqueous hydrobromic acid (48% w/v) (100 ml). The reaction mixture was heated at reflux temperature for 2 hours. The reaction mixture was allowed to cool to ambient temperature and diluted with aqueous sodium metabisulfite (20 g in 250 ml water). The mixture was extracted twice with dichloromethane. The combined organic phases were washed with water and brine, dried over sodium sulfate, and concentrated to give a mixture of brominated products. This mixture was suspended in α,α,α-trifluorotoluene (250 ml) and N-bromosuccinimide (“NBS”) (13.88 g) and 2,2′-azobis(2-methylpropionitrile) (“AIBN”) (0.640 g) were added. The reaction mixture was heated at 90° C. for 3 hours. The reaction mixture was allowed to cool to ambient temperature and was diluted with dichloromethane (600 ml) and aqueous hydrochloric acid (1M) (300 ml). The phases were separated and the organic layer was washed successively with aqueous hydrochloric acid (1M) (2×250 ml), water (200 ml) and brine (200 ml), dried over sodium sulfate and concentrated to give 4-bromo-7-bromomethyl-benzo[1,2,5]thiadiazole (29.05 g) as a yellow solid. 1H-NMR (400 MHz, CDCl3): 7.82 (d, 1H), 7.54 (d, 1H), 4.94 (s, 2H) ppm.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux temperature for 2 hours
  3. extractionThe mixture was extracted twice with dichloromethane
  4. washThe combined organic phases were washed with water and brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customto give
  8. additiona mixture of brominated products
  9. temperatureThe reaction mixture was heated at 90° C. for 3 hours
  10. temperatureto cool to ambient temperature
  11. customThe phases were separated
  12. washthe organic layer was washed successively with aqueous hydrochloric acid (1M) (2×250 ml), water (200 ml) and brine (200 ml)
  13. dry with materialdried over sodium sulfate
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-476899f0f7e84885a9d0841292394b7e
Source dataset
uspto-grants-2015_12
Patent number
US09216973B2

Reaction notes

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