Sulfuric Acid → 4-bromo-5-methoxyisatin

HRID 725810Notes

Reaction equation

HRID 725810 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 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 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-2f01515dda3a412a96d4e0cdf8678535
Source dataset
uspto-grants-1998_01
Patent number
US05707992

Reaction notes

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