Hexamethylenetetramine → Benzo[b]thiophene-5-carboxaldehyde, 6-fluoro-

HRID 1739713Notes

Reaction equation

HRID 1739713 reaction equation
[F:1][C:2]1[C:10]2[CH:9]=[CH:8][S:7][C:6]=2[CH:5]=[CH:4][C:3]=1[CH3:11].[F:12][C:13]1[C:14]([CH3:22])=[CH:15][C:16]2[CH:20]=[CH:19][S:18][C:17]=2[CH:21]=1.BrN1C(=[O:29])CCC1=O.C1N2CN3CN(C2)CN1C3>C(Cl)(Cl)(Cl)Cl.C(O)(=O)C.O.C(OCC)(=O)C>[F:1][C:2]1[C:10]2[CH:9]=[CH:8][S:7][C:6]=2[CH:5]=[CH:4][C:3]=1[CH:11]=[O:29].[F:12][C:13]1[C:14]([CH:22]=[O:29])=[CH:15][C:16]2[CH:20]=[CH:19][S:18][C:17]=2[CH:21]=1

Participants

10

Reactant 4

HCID 4101HexamethylenetetramineHCID 67184N-bromobutanimideHCID 186915724-Fluoro-5-methyl-benzo[b]thiopheneHCID 186915786-Fluoro-5-methyl-benzo[b]thiophene

Product 2

HCID 15408579Benzo[b]thiophene-5-carboxaldehyde, 6-fluoro-HCID 154085854-Fluorobenzo[b]thiophene-5-carbaldehyde

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 962WaterSolvent2×HCID 5943Carbon TetrachlorideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 15.9 g of a mixture of 4-fluoro-5-methyl-benzo[b]thiophene and 6-fluoro-5-methyl-benzo[b]thiophene in 160 ml of carbon tetrachloride are added 17 g of N-bromosuccinimide and 0.31 g of 2,2'-azobisisobutylonitrile. The resulting mixture is refluxed for two hours. After cooling, insolubles are removed from the thus cooled mixture by filtration, and the filtrate obtained is concentrated under reduced pressure. The residue obtained is suspended in 75 ml of acetic acid and 75 ml of water, and 26.8 g of hexamethylenetetramine is added thereto, after which the resulting mixture is refluxed for two hours. After cooling, 150 ml of water and 200 ml of ethyl acetate are added to the thus cooled mixture, and the resulting organic layer is separated, washed successively with water, an aqueous saturated sodium carbonate solution and a saturated saline solution and then dried over anhydrous magnesium sulfate. Thereafter, the solvent is removed from the thus dried layer by distillation under reduced pressure. The residue thus obtained is purified by a moderate pressure column chromatography [eluent:hexane:ethyl acetate=15:1], to obtain 1.71 g of 4-fluorobenzo[b]thiophene-5-carbaldehyde and 5.82 g of 6-fluorobenzo[b]thiophene-5-carbaldehyde.

Workup

  1. temperatureThe resulting mixture is refluxed for two hours
  2. temperatureAfter cooling
  3. custominsolubles are removed from the thus cooled mixture by filtration
  4. customthe filtrate obtained
  5. concentrationis concentrated under reduced pressure
  6. customThe residue obtained
  7. temperatureafter which the resulting mixture is refluxed for two hours
  8. temperatureAfter cooling
  9. customthe resulting organic layer is separated
  10. washwashed successively with water
  11. dry with materialan aqueous saturated sodium carbonate solution and a saturated saline solution and then dried over anhydrous magnesium sulfate
  12. customThereafter, the solvent is removed from the thus dried layer by distillation under reduced pressure
  13. customThe residue thus obtained
  14. customis purified by a moderate pressure column chromatography [eluent:hexane:ethyl acetate=15:1]

Sources & evidence

ORD record
ord-8acdcfa69c0b4aca999e412df868f505
Source dataset
uspto-grants-1999_10
Patent number
US05968935

Reaction notes

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