Hydroxylamine → 2-Chloro-9-formyl-9,10-dihydro-9,10-methanoanthracene

HRID 862720Notes

Reaction equation

HRID 862720 reaction equation
N[C:2]12[CH:18]([OH:19])[CH2:17][CH:9]([C:10]3[CH:11]=[CH:12][C:13]([Cl:16])=[CH:14][C:15]=31)[C:8]1[C:3]2=[CH:4][CH:5]=[CH:6][CH:7]=1.N([O-])=O.[Na+].N([O-])=O.NO>C(O)(=O)C.O.C(OCC)(=O)C>[Cl:16][C:13]1[CH:12]=[CH:11][C:10]2[CH:9]3[CH2:17][C:2]([CH:18]=[O:19])([C:3]4[C:8]3=[CH:7][CH:6]=[CH:5][CH:4]=4)[C:15]=2[CH:14]=1

Participants

8

Reactant 4

HCID 787HydroxylamineHCID 946NitriteHCID 19698696(9RS,10RS,12RS)-9-Amino-2-chloro-12-hydroxy-9,10-dihydro-9,10-ethanoanthraceneHCID 23668193Sodium Nitrite

Product 1

HCID 196986392-Chloro-9-formyl-9,10-dihydro-9,10-methanoanthraceneYield 53.6%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
10 °C

Procedure

(9RS,10RS,12RS)-9-Amino-2-chloro-12-hydroxy-9,10-dihydro-9,10-ethanoanthracene prepared as in Example 1i (445.5 g, 1.64 moles) was dissolved in glacial acetic acid (4.0 L), and the resulting solution cooled to 10° C. A solution of sodium nitrite (340.0 g, 4.93 moles) in water (1.4 L) was added to the reaction mixture over a period of 1.75 h. The temperature of the mixture was maintained at 10° C. during the addition of the nitrite, and for 4 h thereafter. The mixture was then stirred overnight and allowed to warm to room temperature. TLC analysis [silica gel/toluene:ethyl acetate (4:1)] showed complete conversion of the amino alcohol (Rf =0.12) to the desired aldehyde (Rf =0.80). The reaction mixture was diluted with water (4 L) which caused precipitation of a reddish-brown tar. The aqueous supernatant was decanted away from the tar, diluted with an equal volume of crushed ice, then adjusted to pH=5-6 with solid sodium hydroxide. The resulting aqueous mixture was extracted with ethyl acetate (3×1.5 L). The combined ethyl acetate extracts were used to redissolve the tar, and the resulting solution washed with brine (2×1 L) then dried over magnesium sulfate. Filtration, followed by removal of the solvent in vacuo, gave the crude product as a thick brown oil. Purification of this material by column chromatography over silica gel, eluting with a solvent mixture of methylene chloride:hexane (1:1), afforded a thick yellow oil which crystallized on standing (311.7 g, 74.6%). Trituration with diethyl ether:hexane (1:6-700 ml) gave a first crop of pure title compound as an off-white crystalline solid (224.1 g, 53.6%), mp 91°-92° C.

Workup

  1. temperatureto warm to room temperature
  2. customprecipitation of a reddish-brown tar
  3. customThe aqueous supernatant was decanted away from the tar
  4. additiondiluted with an equal volume of crushed ice
  5. extractionThe resulting aqueous mixture was extracted with ethyl acetate (3×1.5 L)
  6. dissolutionto redissolve the tar
  7. washthe resulting solution washed with brine (2×1 L)
  8. dry with materialthen dried over magnesium sulfate
  9. filtrationFiltration
  10. customfollowed by removal of the solvent in vacuo
  11. customgave the crude product as a thick brown oil
  12. customPurification of this material by column chromatography over silica gel
  13. washeluting with a solvent mixture of methylene chloride:hexane (1:1)
  14. customafforded a thick yellow oil which
  15. customcrystallized

Sources & evidence

ORD record
ord-1ff9b537ce934a81be05042f4b559864
Source dataset
uspto-grants-1998_02
Patent number
US05719166

Reaction notes

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