反应 #941

反应方程式

2,6-difluorobenzonitrile

DMSO

3-bromo-5-methoxytoluene

sec-BuLi

sulfur

→

2-Fluoro-6-[(3 -methyl-5-methoxyphenyl)thio]benzonitrile

溶剂

—

ice water

dry ice acetone

THF

water

反应条件

后处理

1. 1
   workup.ADDITIONwas added in one portion
2. 2
   其他was brought to room temperature
3. 3
   workup.WAITleft
4. 4
   workup.STIRRINGstirring for 12 h
5. 5
   萃取extracted with 3×50 mL of EtOAc
6. 6
   洗涤The EtOAc solution was washed with 1N NaOH, water
7. 7
   干燥dried over MgSO4Removal of EtOAc under vacuo
8. 8
   其他resulted in a crude product which
9. 9
   其他was chromatographed on silica gel (flash; EtOAc/Hexane 1:9)
10. 10
    其他This resulted in 0.63 g (46%) of 2-fluoro-6-[(3-methyl-5-methoxyphenyl)thio]benzonitrile

实验过程

A solution of 1 g (0.005 mol) of 3-bromo-5-methoxytoluene in 10 mL of freshly distilled THF was cooled in dry ice/acetone and stirred under a N2 atmosphere. To this was added dropwise via a syringe 8.46 mL (0.011 mol) of sec-BuLi (1.3M in cyclohexane). The resultant mixture was stirred for 10 min after which 0.19 g of elemental sulfur was added in one portion. The reaction mixture was brought to room temperature and left stirring for 12 h. The mixture was cooled in ice/water bath. 0.69 g (0.005 mol) of 2,6-difluorobenzonitrile in 5 mL of dry DMSO was added. After sitting for 20 min, the mixture was poured into water (100 mL) and extracted with 3×50 mL of EtOAc. The EtOAc solution was washed with 1N NaOH, water, and dried over MgSO4Removal of EtOAc under vacuo resulted in a crude product which was chromatographed on silica gel (flash; EtOAc/Hexane 1:9). This resulted in 0.63 g (46%) of 2-fluoro-6-[(3-methyl-5-methoxyphenyl)thio]benzonitrile: mp 94°-95° C.; NMR (Me2SO-d6, 200 MHz) δ 2.28 (s, 3H), 3.7 (s, 3H), 6.8-7 (m, 4H), 7.34 (apparent d, 1H), 7.62 (dd, 1H). Anal. Calc. for C15H12NOSF: C, 65.92; H, 4.43; N, 5.12; S, 11.73. Found: C, 66.03; H, 4.49; N, 5.09; S, 11.8.

来源