2,4-Difluorobenzonitrile → 4-Fluoro-2-(methylsulfanyl)benzonitrile
Reaction equation
F[C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[CH3:11][S-:12]>C(Cl)Cl>[F:10][C:8]1[CH:7]=[CH:6][C:3]([C:4]#[N:5])=[C:2]([S:12][CH3:11])[CH:9]=1Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 90 °C
Procedure
2,4-difluorobenzonitrile (2.0 g, 14.38 mmol) and thiomethoxide (1.02 g, 14.38 mmol) were placed in an oven dried 100 mL round bottom flask fitted with a reflux condenser. Toluene (40 mL) was added and the reaction solution was put under an atmosphere of Argon. The reaction was heated to 90° C. over 48 hours. The crude reaction was cooled and concentrated in vacuo. The residue was taken up in methylene chloride and extracted with water. The organic phase was dried (MgSO4), filtered and concentrated to afford a white solid. The solid was dissolved in a minimal amount of methylene chloride and purified on an ISCO column (110 g silica) with a gradient of 100% to 80% hexanes/20% ethylacetate over 15 min at 45 ml/min, then 20% EtOAc/80% Hexanes for 5 min. The collected fractions were evaporated in vacuo to afford the desired material in a 7.5:1 ratio 4-fluoro-2-(methylthio)benzonitrile:2-fluoro-4-(methylthio)benzonitrile. The white solid was carried on to the next step without further purification.