Reacción #46223

Ecuación de reacción

(4-hydroxyphenyl)acetonitrile

paraformaldehyde

toluene-4-sulfonic acid monohydrate

→

2-(4H-benzo[d][1,3]dioxin-6-yl)acetonitrile

Disolventes

toluene

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaThe reaction mixture was heated
2. 2
   Temperaturaat reflux for 1 hour
3. 3
   OtroToluene was removed by evaporation
4. 4
   workup.ADDITIONWater (150 mL) and ethyl acetate (150 mL) were added
5. 5
   OtroThe organic layer was separated
6. 6
   Extracciónthe aqueous layer was extracted with ethyl acetate
7. 7
   LavadoThe combined organics were washed with brine
8. 8
   Secadodried over Na2SO4
9. 9
   Otroevaporated under vacuum
10. 10
    OtroThe residue was separated by preparative HPLC

Procedimiento

To a solution of (4-hydroxyphenyl)acetonitrile (17.3 g, 0.13 mol) in toluene (350 mL) were added paraformaldehyde (39.0 g, 0.43 mmol) and toluene-4-sulfonic acid monohydrate (2.5 g, 13 mmol) at room temperature. The reaction mixture was heated at reflux for 1 hour. Toluene was removed by evaporation. Water (150 mL) and ethyl acetate (150 mL) were added. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organics were washed with brine, dried over Na2SO4 and evaporated under vacuum. The residue was separated by preparative HPLC to give 2-(4H-benzo[d][1,3]dioxin-6-yl)acetonitrile (7.35 g, 32%). 1H NMR (400 MHz, CDCl3) δ 7.07-7.11 (m, 1H), 6.95-6.95 (m, 1H), 6.88 (d, J=11.6 Hz, 1H), 5.24 (s, 2H), 4.89 (s, 2H), 3.67 (s, 2H).

Fuente