Reaction #2487436

Reaction equation

4-(bromomethyl)-3-fluorobenzonitrile

thiourea

→

3-Fluoro-4-(mercaptomethyl)benzonitrile

Solvents

ethyl alcohol

Conditions

Workup

1. 1
   Temperaturewas heated
2. 2
   Temperatureto reflux for 1 h
3. 3
   Concentrationconcentrated under reduced pressure
4. 4
   WashThe residue was washed with EtOAc (50 mL)
5. 5
   workup.ADDITIONtreated with 1.6 N NaOH
6. 6
   workup.ADDITIONdiluted with Et2O (50 mL)
7. 7
   WashThe organic layer was washed with H2O (25 mL) and brine (25 mL)
8. 8
   Dryingdried over anhydrous Na2SO4
9. 9
   Concentrationconcentrated under reduced pressure
10. 10
    Otherto afford the crude I-2 (300 mg)
11. 11
    OtherThe crude material was used without further purification

Procedure

A mixture of 4-(bromomethyl)-3-fluorobenzonitrile (0.8 g, 3.7 mmol) and thiourea (0.57 g, 7.4 mmol) in ethyl alcohol (EtOH; 20 mL) was heated to reflux for 1 h. The progress of the reaction was monitored by TLC; the reaction mixture was cooled to RT and concentrated under reduced pressure. The residue was washed with EtOAc (50 mL), treated with 1.6 N NaOH and stirred for 20 h at RT. The reaction mixture was adjusted to pH˜4 with concentrated HCl and diluted with Et2O (50 mL). The organic layer was washed with H2O (25 mL) and brine (25 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford the crude I-2 (300 mg). The crude material was used without further purification. 1H NMR (500 MHz, CDCl3): δ 7.45 (dd, J=9.5 Hz, 1.5 Hz, 1H), 7.40-7.37 (m, 2H), 3.76 (s, 2H).

Source