Réaction #1691

Équation de réaction

dimethylformamide

n-butyllithium

citric acid

2-thiophenecarbonitrile

dry ice acetone

diisopropylamine

→

2-cyano-5-formyl-thiophene

Rendement 84.0%

Solvants

THF

water

THF

Conditions de réaction

Traitement

1. 1
   AutreTo 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
   AutreVolatile solvents were removed in vacuo
5. 5
   Autrethe residue was partitioned between diethyl ether and brine (200 mL each)
6. 6
   AutreLayers were separated
7. 7
   Lavagethe aqueous phase was washed once with diethyl ether
8. 8
   LavageThe combined organic phase was washed once with brine
9. 9
   Séchagedried (MgSO4)
10. 10
    Filtrationfiltered
11. 11
    Concentrationconcentrated in vacuo
12. 12
    Autreto give a yellow solid which
13. 13
    Autrewas purified by silica gel chromatography
14. 14
    workup.ADDITIONFractions containing pure product
15. 15
    Concentrationconcentrated in vacuo

Mode opératoire

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.

Source