Sulfuric Acid → 4-bromo-5-methoxyisatin

HRID 1418982Notes

Reaction equation

HRID 1418982 reaction equation
[CH:1]1[CH:6]=[CH:5][C:4]([NH:7][C:8](/[CH:10]=N\O)=[O:9])=[CH:3][CH:2]=1.[OH:13]S(O)(=O)=O.[K+].[Br-:19].C[CH2:21][O:22]C(C)=O.CCCCCC>>[Br:19][C:6]1[C:1]([O:22][CH3:21])=[CH:2][CH:3]=[C:4]2[C:5]=1[C:10](=[O:13])[C:8](=[O:9])[NH:7]2

Participants

5

Reactant 4

HCID 1118Sulfuric AcidHCID 253877Potassium BromideHCID 6398991HCID 6398991, compoundHCID 21226206Ethyl acetate hexane

Product 1

HCID 99925494-bromo-5-methoxyisatinYield 25%

Conditions

Temperature
65 °C

Procedure

Vacuum dried α-Isonitrosoacetanilide (12) (3.0 g; 11 mmol) was slowly added to 8 ml conc. H2SO4 at 50° C. while being stirred. The reaction mixture first became yellow, and then turned dark. The temperature was raised to 65° C. for 10 minutes, and the reaction was followed by TLC (EtOAc/hexane; 40:60). Heating at 65°-70° C. was resumed until all the starting material was consumed as judged by TLC. Upon completion, the reaction mixture was cooled and added to 80 g of crushed ice with stirring. A dark red a solid formed and was filtered off, washed free of acid by water and dried under vacuum. The resulting substance was purified by chromatography on a flash silica column using a gradient system of EtOAc/hexane; 40:60; 50:50; 60:40; 70:30; 80:20. The undesired isomer, 6-Bromo-5-methoxyisatin eluted first, followed by the desired isomer (13), which was isolated as a red solid (0.71 g; 25% yield). M.P. 250°-251° C. IR (KBr) 2064, 1758, 1750, 1634, 1278 cm-1 ; 1H NMR (CDCl3, one drop DMSO-d6) δ 3.91 (s, 3H), 6.84 (d, 1H, J=8.8 Hz), 7.09 (d, 1H, J=8.8 Hz), 10.88 (s, 1H). Anal. Calcd. for C9H6BrNO3 : C, 42.19; H, 2.34; Br, 31.25; N, 5.47. Found: C, 42.27; H, 2.37; Br, 31.30; N, 5.42.

Workup

  1. temperatureHeating at 65°-70° C.
  2. customwas consumed
  3. temperatureUpon completion, the reaction mixture was cooled
  4. additionadded to 80 g of crushed ice
  5. stirringwith stirring
  6. customA dark red a solid formed
  7. filtrationwas filtered off
  8. washwashed free of acid by water
  9. customdried under vacuum
  10. customThe resulting substance was purified by chromatography on a flash silica column
  11. customwhich was isolated as a red solid (0.71 g; 25% yield)

Sources & evidence

ORD record
ord-7a0b7a957c7b49e99c7360f92aafd6b2
Source dataset
uspto-grants-1999_03
Patent number
US05885996

Reaction notes

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