Formaldehyde → 5,6,7,8-Tetrahydroisoquinoline 2-oxide

HRID 1637760Notes

Reaction equation

HRID 1637760 reaction equation
[CH:1]1[C:10]2[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=2[CH:4]=[CH:3][N:2]=1.[OH:11]O.C=O>C(O)(=O)C>[CH:1]1[C:10]2[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=2[CH:4]=[CH:3][N+:2]=1[O-:11]

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 784Hydrogen PeroxideHCID 1190105,6,7,8-Tetrahydroisoquinoline

Product 1

HCID 140842165,6,7,8-Tetrahydroisoquinoline 2-oxideYield 86%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
97.5 °C

Procedure

5,6,7,8-Tetrahydroisoquinoline (13.3 g, 100 mmole) is dissolved in 35 ml glacial acetic acid in a 200 ml one neck round bottom flask. The solution is warmed to 95-100° C. and is treated dropwise with 30% hydrogen peroxide (28 ml). The reaction is stirred at 95-100° C. for 6h, is treated portionwise with paraformaldehyde until negative to starch iodide paper, and the volatiles are removed in vacuo. The residue is azeotroped with 2×100 ml toluene and the crude material is chromatographed over 500 g silica gel (230-400 mesh), eluting with 4 l 6% methanol/dichloromethane followed by 1 l 10% methanol/dichloromethane while collecting 50 ml fractions. Fractions 39-82 are combined and concentrated to afford 12.8 g (86%) of 5,6,7,8-tetrahydroisoquinoline-N-oxide.

Workup

  1. customthe volatiles are removed in vacuo
  2. customThe residue is azeotroped with 2×100 ml toluene
  3. customthe crude material is chromatographed over 500 g silica gel (230-400 mesh)
  4. washeluting with 4 l 6% methanol/dichloromethane
  5. customwhile collecting 50 ml fractions
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-ebbf10941f134be087421f659df97cdb
Source dataset
uspto-grants-2000_03
Patent number
US06043248

Reaction notes

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