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

HRID 1879893

Reaction equation

HRID 1879893 reaction equation
OC1C=CC([CH2:8][C:9]#[N:10])=CC=1.[CH2:11]=[O:12].[OH2:13].[C:14]1([CH3:24])[CH:19]=[CH:18][C:17](S(O)(=O)=O)=[CH:16][CH:15]=1>C1(C)C=CC=CC=1>[O:12]1[C:15]2[CH:16]=[CH:17][C:18]([CH2:8][C:9]#[N:10])=[CH:19][C:14]=2[CH2:24][O:13][CH2:11]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 265484-Hydroxybenzyl cyanideHCID 521998p-Toluenesulfonic acid monohydrate

Product 1

HCID 591662212-(4H-benzo[d][1,3]dioxin-6-yl)acetonitrileYield 9,757.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

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).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 1 hour
  3. customToluene was removed by evaporation
  4. additionWater (150 mL) and ethyl acetate (150 mL) were added
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted with ethyl acetate
  7. washThe combined organics were washed with brine
  8. dry with materialdried over Na2SO4
  9. customevaporated under vacuum
  10. customThe residue was separated by preparative HPLC

Sources & evidence

ORD record
ord-5f66244673db4ae092be02795af0f0df
Source dataset
uspto-grants-2012_11
Patent number
US08318733B2

Linked notes

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