Sulfuric Acid → 5-Bromoisoquinoline

HRID 887178Notes

Reaction equation

HRID 887178 reaction equation
OS(O)(=O)=O.[CH:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]=[CH:8][N:7]=1.[Br:16]N1C(=O)CCC1=O.[NH4+].[OH-]>CCCCCCC>[Br:16][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]2[C:10]=1[CH:9]=[CH:8][N:7]=[CH:6]2

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 8405IsoquinolineHCID 14923Ammonium HydroxideHCID 67184N-bromobutanimide

Product 1

HCID 7364875-Bromoisoquinoline

Reagents, catalysts & solvents 1

HCID 8900HeptaneSolvent

Conditions

Temperature
-10 °C

Procedure

Concentrated H2SO4 (260 mL) was cooled to −25° C. while stirring with a mechanical stirrer. Isoquinoline (30 mL, 0.25 mol) was added slowly so the temperature did not exceed 0° C. After the addition was complete, the red solution was recooled to −25° C. and treated with N-bromosuccinimide (55.49 g, 0.31 mol) in small portions so that the temperature did not exceed −20° C. The reaction mixture was stirred for 5 hours keeping the temperature between −30° C. and −18° C. The reaction mixture was then allowed to warm to −10° C. and was poured carefully over 600 g of ice. The resulting slurry was adjusted to pH 10 using 25% NH4OH. The mixture was then extracted with diethyl ether (3×600 mL). The ether fractions were combined, filtered through a celite plug and the filtrate concentrated under reduced pressure. The residue was suspended in hot heptane (600 mL). The heptane was decanted. This procedure was repeated with hexane (2×200 mL). The combined heptane and hexane fractions were concentrated under reduced pressure to give a mustard yellow solid. The title compound was obtained by recrystallization from heptane (26.37 g, 50%). mp 78°-80° C.; MS (ESI+) m/z 209 (M+H)+; 1H NMR (DMSO, 300 MHz) δ 7.65 (t, J 7.9, 1H), 7.94 (d, J 8.1, 1H), 8.17 (dd, J 1.0, 7.4, 1H), 8.22 (d, J 8.1, 1H), 8.68 (d, J 6.1, 1H), 9.37 (s, 1H); Anal. Calcd for C9H6BrN: C, 51.96; H, 2.91; N, 6.73; Br, 38.41. Found: C, 51.24; H, 2.79; N, 6.52; Br, 38.81.

Workup

  1. customdid not exceed 0° C
  2. additionAfter the addition
  3. customwas recooled to −25° C.
  4. customdid not exceed −20° C
  5. stirringThe reaction mixture was stirred for 5 hours
  6. customthe temperature between −30° C. and −18° C
  7. extractionThe mixture was then extracted with diethyl ether (3×600 mL)
  8. filtrationfiltered through a celite plug
  9. concentrationthe filtrate concentrated under reduced pressure
  10. customThe heptane was decanted
  11. concentrationThe combined heptane and hexane fractions were concentrated under reduced pressure
  12. customto give a mustard yellow solid

Sources & evidence

ORD record
ord-6073bc39fa1541e49f9215be7728b54d
Source dataset
uspto-grants-2012_08
Patent number
US08247413B2

Reaction notes

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