Ethanethiol → 4-Chloro-2-ethylsulfanyl-6-methyl-benzonitrile

HRID 515140Notes

Reaction equation

HRID 515140 reaction equation
Cl[C:2]1[CH:9]=[C:8]([Cl:10])[CH:7]=[C:6]([CH3:11])[C:3]=1[C:4]#[N:5].P([O-])([O-])([O-])=O.[K+].[K+].[K+].N1CCC[C@H]1C(O)=O.[CH2:28]([SH:30])[CH3:29]>CN(C=O)C.O.[Cu]I>[Cl:10][C:8]1[CH:7]=[C:6]([CH3:11])[C:3]([C:4]#[N:5])=[C:2]([S:30][CH2:28][CH3:29])[CH:9]=1

Participants

8

Reactant 4

HCID 6343EthanethiolHCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 28009652,4-Dichloro-6-methylbenzonitrile

Product 1

HCID 866997224-Chloro-2-ethylsulfanyl-6-methyl-benzonitrileYield 23%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 2,4-dichloro-6-methyl-benzonitrile (5.0 g, 26.9 mmol) in DMF (50 ml) in a sealed tube are added tripotassium phosphate (5.7 g, 26.9 mmol) and L-proline (0.62 g, 5.37 mmol) at RT. The reaction mixture is degassed and flushed with argon for 30 min and then are added CuI (0.51 g, 2.68 mmol) and ethanethiol (6.0 ml, 80.6 mmol) at RT. The reaction mixture is stirred at 80° C. for 16 h. After completion of the reaction (monitored by TLC), the reaction mixture is diluted with water (50 ml) and extracted with ethyl acetate (50×3 ml). The organic layer is washed with water (50 ml), brine (15 ml) dried over anhydrous sodium sulfate and evaporated to get the crude which is purified by column chromatography (silica gel, 5% acetone/hexane) to yield 4-chloro-2-ethylsulfanyl-6-methyl-benzonitrile (1.3 g, 6.14 mmol, 23%).

Workup

  1. customThe reaction mixture is degassed
  2. customflushed with argon for 30 min
  3. customAfter completion of the reaction (monitored by TLC)
  4. extractionextracted with ethyl acetate (50×3 ml)
  5. washThe organic layer is washed with water (50 ml), brine (15 ml)
  6. dry with materialdried over anhydrous sodium sulfate
  7. customevaporated
  8. customto get the crude which
  9. customis purified by column chromatography (silica gel, 5% acetone/hexane)

Sources & evidence

ORD record
ord-ac63fb02ed4d42fd88eca5aea4327670
Source dataset
uspto-grants-2015_08
Patent number
US09108936B2

Reaction notes

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