3-Chloro-2-methylaniline → 2-(3-Chloro-2-methylphenyl)thiophene

HRID 905330Notes

Reaction equation

HRID 905330 reaction equation
[Cl:1][C:2]1[C:3]([CH3:9])=[C:4]([CH:6]=[CH:7][CH:8]=1)N.N(OC(C)(C)C)=O.[S:17]1[CH:21]=[CH:20][CH:19]=[CH:18]1>[Cu]>[Cl:1][C:2]1[C:3]([CH3:9])=[C:4]([C:18]2[S:17][CH:21]=[CH:20][CH:19]=2)[CH:6]=[CH:7][CH:8]=1

Participants

5

Reactant 3

HCID 68943-Chloro-2-methylanilineHCID 8030Thiophene2×HCID 10906Tert-Butyl nitrite

Product 1

HCID 132434162-(3-Chloro-2-methylphenyl)thiopheneYield 62.2%

Reagents, catalysts & solvents 1

HCID 23978CopperCatalyst

Procedure

During a 30 minute period a solution of 3-chloro-2-methylaniline (8.3 g, 0.2 mole) in thiophene (100 ml) was added dropwise to a stirred mixture of t-butyl nitrite (30.9 g, 0.3 mole) and copper powder (10.0 g, 0.16 mole) in thiophene (1.9 l). After complete addition, the mixture was heated at 60° for two hours, then at reflux for approximately 18 hours. The reaction mixture was cooled, filtered, and the filtrate evaporated under reduced pressure to leave a residue. The residue was subjected to column chromatography on silica gel, elution with toluene. The toluene was evaporated under reduced pressure to leave a residue which was rechromatographed on silica gel, elution with n-heptane. The fractions which contained the desired product was combined and evaporated under reduced pressure to leave an oil. The oil was purified by distillation under reduced pressure to yield 2-(3-chloro-2-methylphenyl)thiophene (25.9 g, 62.2% yield, bp 93°/0.1 mm). This experiment is designated Run 5/1 in the following tabulation of several experiments conducted with and without copper, but under otherwise similar conditions.

Workup

  1. additionAfter complete addition
  2. temperaturethe mixture was heated at 60° for two hours
  3. temperatureat reflux for approximately 18 hours
  4. temperatureThe reaction mixture was cooled
  5. filtrationfiltered
  6. customthe filtrate evaporated under reduced pressure
  7. customto leave a residue
  8. washThe residue was subjected to column chromatography on silica gel, elution with toluene
  9. customThe toluene was evaporated under reduced pressure
  10. customto leave a residue which
  11. customwas rechromatographed on silica gel, elution with n-heptane
  12. customevaporated under reduced pressure
  13. customto leave an oil
  14. distillationThe oil was purified by distillation under reduced pressure

Sources & evidence

ORD record
ord-a8e2f85a5b634bd8929419ef4e629915
Source dataset
uspto-grants-1983_12
Patent number
US04423234

Reaction notes

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