Hydrochloric Acid → 3,8-Dichloroisoquinoline

HRID 40663Notes

Reaction equation

HRID 40663 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[CH:10]=[N:9][C:8](N)=[CH:7]2.N([O-])=O.[Na+].C(=O)(O)[O-].[Na+].[ClH:22]>>[Cl:22][C:8]1[N:9]=[CH:10][C:11]2[C:6]([CH:7]=1)=[CH:5][CH:4]=[CH:3][C:2]=2[Cl:1]

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 23668193Sodium NitriteHCID 534190528-Chloroisoquinolin-3-amine

Product 1

HCID 596364133,8-DichloroisoquinolineYield 45%

Conditions

Temperature
0 °C

Procedure

8-Chloroisoquinolin-3-amine (724 mg, 4.05 mmol) was suspended in 10 M HCl and cooled to 0° C. Sodium nitrite (336 mg, 4.86 mmol) was added in portions over 10 minutes. The reaction mixture was stirred for 2 hours, slowly warming to room temperature over an additional 1 hour. After 3 hours, the mixture was poured cautiously into saturated sodium bicarbonate solution, and extracted into ethyl acetate. The organic extract was washed with brine, dried (Na2SO4) and concentrated. Flash chromatography on silica, eluting with dichloromethane, gave the title compound as a white solid (362 mg, 1.83 mmol, 45%). 1H NMR (d6-DMSO, 400 MHz) δ 9.40 (br t, 1H, J=0.8 Hz), 8.20 (br s, 1H), 8.00-7.98 (m, 1H), 7.88-7.81 (m, 2H). LCMS (3) Rt=2.49 min; m/z (ESI+) 198 (MH+).

Workup

  1. temperatureslowly warming to room temperature over an additional 1 hour
  2. waitAfter 3 hours
  3. extractionextracted into ethyl acetate
  4. extractionThe organic extract
  5. washwas washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. washFlash chromatography on silica, eluting with dichloromethane

Sources & evidence

ORD record
ord-05326b20bf374a4eb0e25f658dab1423
Source dataset
uspto-grants-2013_09
Patent number
US08530468B2

Reaction notes

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