Hydrochloric Acid → 2-(2,4-Dichloro-5-fluorobenzyl)thiophene

HRID 233130

Reaction equation

HRID 233130 reaction equation
[Cl-].[Al+3].[Cl-].[Cl-].[Cl:5][C:6]1[CH:14]=[C:13]([Cl:15])[C:12]([F:16])=[CH:11][C:7]=1[C:8](Cl)=O.[S:17]1[CH:21]=[CH:20][CH:19]=[CH:18]1.Cl.[BH4-].[Na+]>ClC1C=CC=CC=1.COCCOCCOC.O>[Cl:5][C:6]1[CH:14]=[C:13]([Cl:15])[C:12]([F:16])=[CH:11][C:7]=1[CH2:8][C:18]1[S:17][CH:21]=[CH:20][CH:19]=1

Participants

9

Reactant 5

HCID 313Hydrochloric Acid2×HCID 8030ThiopheneHCID 27368212,4-Dichloro-5-fluorobenzoyl chlorideHCID 4311764Sodium borohydrideHCID 6451240Aluminum(III) Chloride

Product 1

HCID 98166672-(2,4-Dichloro-5-fluorobenzyl)thiophene

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 7964ChlorobenzeneSolvent4×HCID 8150DiglymeSolvent

Conditions

Temperature
0 °C

Procedure

3.8 g of aluminium chloride were suspended in 162.5 ml of chlorobenzene, and a solution of 58.9 g of 2,4-dichloro-5-fluorobenzoyl chloride in 33.8 ml of chlorobenzene was added dropwise to this at 0° C. over the course of 30 minutes. The mixture was stirred at 0° C. for 90 minutes and then, at 0° C., a solution of 21.8 g of thiophene in 33.8 ml of chlorobenzene was added dropwise over the course of 30 minutes. The mixture was stirred at 0° C. for a further 2 hours and finally heated to reflux for 15 minutes until evolution of hydrogen chloride ceased. The resulting solution was added dropwise to a suspension of 7.2 g of sodium borohydride in 50 ml of diglyme at 70° C. over the course of 30 minutes, and the reaction mixture was subsequently stirred at 70° C. for 90 minutes and then discharged into a mixture of 250 g of ice, 200 ml of water and 62.5 g of concentrated aqueous hydrochloric acid. After addition of 100 ml of chlorobenzene and stirring, the phases were separated. The organic phase was extracted by shaking with 100 ml of water and was subsequently concentrated. Yield: 78.5 g of crude substance with a content of 76.7% by weight (GC) of 2-(2,4-dichloro-5-fluorobenzyl)thiophene, corresponding to 92.3% of theory. Distillation resulted in a 97.2% pure (GC) product, boiling point 140° to 145° C./8 mbar, melting point 60° to 61° C.

Workup

  1. stirringThe mixture was stirred at 0° C. for a further 2 hours
  2. temperaturefinally heated
  3. stirringthe reaction mixture was subsequently stirred at 70° C. for 90 minutes
  4. stirringstirring
  5. customthe phases were separated
  6. extractionThe organic phase was extracted
  7. stirringby shaking with 100 ml of water
  8. concentrationwas subsequently concentrated
  9. distillationDistillation
  10. customresulted in a 97.2% pure (GC) product, boiling point 140° to 145° C./8 mbar, melting point 60° to 61° C.

Sources & evidence

ORD record
ord-a2cc0fbc6090417ab8bf5a1e29fabca2
Source dataset
uspto-grants-1997_01
Patent number
US05591869

Linked notes

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