反応 #1691

反応方程式

dimethylformamide

n-butyllithium

citric acid

2-thiophenecarbonitrile

dry ice acetone

diisopropylamine

→

2-cyano-5-formyl-thiophene

収率 84.0%

溶媒

THF

water

THF

反応条件

後処理

1. 1
   その他To a flame-dried 3 neck 1 L round bottom flask
2. 2
   workup.ADDITIONwas added via syringe
3. 3
   workup.STIRRINGto stir for 2 h at -78° C.
4. 4
   その他Volatile solvents were removed in vacuo
5. 5
   その他the residue was partitioned between diethyl ether and brine (200 mL each)
6. 6
   その他Layers were separated
7. 7
   洗浄the aqueous phase was washed once with diethyl ether
8. 8
   洗浄The combined organic phase was washed once with brine
9. 9
   乾燥dried (MgSO4)
10. 10
    ろ過filtered
11. 11
    濃縮concentrated in vacuo
12. 12
    その他to give a yellow solid which
13. 13
    その他was purified by silica gel chromatography
14. 14
    workup.ADDITIONFractions containing pure product
15. 15
    濃縮concentrated in vacuo

実験手順

To a flame-dried 3 neck 1 L round bottom flask was added diisopropylamine (9 mL, 66 mmol) and THF (150 mL) under a nitrogen atmosphere. The flask was cooled to an internal temperature of -78° C. (dry ice/acetone). To this stirring solution was added n-butyllithium (1.6M in hexanes, 41.3 mL, 66.1 mmol) via syringe and the mixture was allowed to stir for 5 min. To this solution was added a solution of 2-thiophenecarbonitrile (6.55 g, 60 mmol) in THF (30 mL) over 10 min. The resulting bright red solution was allowed to stir at -78° C. for 45 min, at which time dimethylformamide (23.3 mL, 300 mmol) was added via syringe. This mixture was allowed to stir for 2 h at -78° C. and then solid citric acid (about 10 g) was added followed by water (60 mL). Volatile solvents were removed in vacuo and the residue was partitioned between diethyl ether and brine (200 mL each). Layers were separated and the aqueous phase was washed once with diethyl ether. The combined organic phase was washed once with brine, dried (MgSO4), filtered and concentrated in vacuo to give a yellow solid which was purified by silica gel chromatography using an ethyl acetate/hexanes gradient (hexanes to 50% ethyl acetate/hexanes). Fractions containing pure product were pooled and concentrated in vacuo to give 6.9 g (84%) of 2-cyano-5-formyl-thiophene.

出典