Hydrochloric Acid → 2-[(4-Fluorophenyl)methyl]thiophene

HRID 233127Notes

Reaction equation

HRID 233127 reaction equation
[Cl-].[Cl-].[Cl-].[Al+3].[F:5][C:6]1[CH:14]=[CH:13][C:9]([C:10](Cl)=O)=[CH:8][CH:7]=1.[S:15]1[CH:19]=[CH:18][CH:17]=[CH:16]1.Cl>ClC1C=CC=CC=1>[F:5][C:6]1[CH:14]=[CH:13][C:9]([CH2:10][C:16]2[S:15][CH:19]=[CH:18][CH:17]=2)=[CH:8][CH:7]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8030ThiopheneHCID 678794-Fluorobenzoyl chlorideHCID 6451240Aluminum(III) Chloride

Product 1

HCID 105839052-[(4-Fluorophenyl)methyl]thiopheneYield 71.6%

Reagents, catalysts & solvents 1

HCID 7964ChlorobenzeneSolvent2×

Conditions

Temperature
80 °C

Procedure

33.8 g of aluminium trichloride were suspended in 217 g of chlorobenzene, and a solution of 40.3 g of 4-fluorobenzoyl chloride in 37.4 g of chlorobenzene was added dropwise to this at 0° C. over the course of 15 minutes. The mixture was then stirred for 1 hour and then, at 0° C., 21.8 g of thiophene were added dropwise over the course of 20 minutes. The resulting hydrogen chloride was drawn off and absorbed in sodium hydroxide solution. The mixture was subsequently heated to 80° C. and the remaining hydrogen chloride was removed. The resulting solution was added dropwise to a suspension of 7.2 g of sodium borohydride in 47.2 g of digylme while stirring at 70° C. over the course of 45 minutes. The reaction mixture was then stirred for 90 minutes and then cooled to room temperature and discharged into a mixture of 250 g of ice, 44.6 g of concentrated aqueous hydrochloric acid and 500 g of water. The organic phase which formed thereby was separated off, the aqueous phase was extracted by shaking with chlorobenzene, and the combined organic phases were distilled. 35.0 g of product with a boiling point of 83° C./1.0 mbar and a purity of 99.7% (GC) were obtained. This corresponds to 73.9% of theory. The product contained less than 0.1% by weight of defluorinated compounds (GC).

Workup

  1. customabsorbed in sodium hydroxide solution
  2. customthe remaining hydrogen chloride was removed
  3. additionThe resulting solution was added dropwise to a suspension of 7.2 g of sodium borohydride in 47.2 g of digylme
  4. stirringwhile stirring at 70° C. over the course of 45 minutes
  5. stirringThe reaction mixture was then stirred for 90 minutes
  6. temperaturecooled to room temperature
  7. additiondischarged into a mixture of 250 g of ice, 44.6 g of concentrated aqueous hydrochloric acid and 500 g of water
  8. customThe organic phase which formed
  9. customthereby was separated off
  10. extractionthe aqueous phase was extracted
  11. stirringby shaking with chlorobenzene
  12. distillationthe combined organic phases were distilled

Sources & evidence

ORD record
ord-703d8cd7e84345249f8b55cc33300f3f
Source dataset
uspto-grants-1997_01
Patent number
US05591869

Reaction notes

Loading…