Epichlorohydrin → 2-Hydroxymethyl-1,4-benzodioxan-6-carbaldehyde

HRID 1466202Notes

Reaction equation

HRID 1466202 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[OH:10])[CH:5]=[O:6].[H-].[Na+].Cl[CH2:14][CH:15]1[CH2:17][O:16]1>CN(C=O)C.[OH-].[Na+]>[OH:16][CH2:17][CH:15]1[O:10][C:9]2[CH:8]=[CH:7][C:4]([CH:5]=[O:6])=[CH:3][C:2]=2[O:1][CH2:14]1

Participants

6

Reactant 3

HCID 7835EpichlorohydrinHCID 87683,4-DihydroxybenzaldehydeHCID 24758Sodium hydride

Product 1

HCID 156593722-Hydroxymethyl-1,4-benzodioxan-6-carbaldehydeYield 11.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 14798Sodium HydroxideSolvent

Procedure

To a cold (5° C.) solution of 3,4-dihydroxybenzaldehyde (3.20 g, 23.2 mmol) in DMF (70 mL) is carefully added NaH (1.96 g 55% in mineral oil, 48.5 mmol) in portions. The temperature rises to 12° C. Upon completion of the addition, the cooling is removed and a solution of 2-chloromethyl-oxirane (2.57 g, 27.7 mmol) in DMF (3 mL) is added. The reaction mixture is stirred at rt overnight. The mixture is diluted with 1N aq. NaOH (150 mL) and extracted with EA (2×200 mL). The organic extracts are washed with 1 M aq. NaOH (2×200 mL) and water (200 mL), combined, dried over MgSO4, filtered and concentrated. The remaining residue is purified by column chromatography on silica gel eluting with heptene/EA 5:1 to 1:1 to afford the title aldehyde (0.53 g) as a solid. LC: tR=0.69 min. 1H NMR (D6-DMSO): δ 9.77 (s, 1H), 7.41 (dd, J=2.3, 8.2 Hz, 1H), 7.36 (d, J=2.3 Hz, 1H), 7.04 (d, J=8.2 Hz, 1H), 5.10 (t, J=5.9 Hz, 1H, D2O exchangeable), 4.37 (dd, J=2.3, 11.1 Hz, 1H), 4.30-4.23 (m, 1H), 4.05 (dd, J=7.6, 11.1 Hz, 1H), 3.67-3.60 (m, 2H).

Workup

  1. customrises to 12° C
  2. additionUpon completion of the addition
  3. customthe cooling is removed
  4. extractionextracted with EA (2×200 mL)
  5. washThe organic extracts are washed with 1 M aq. NaOH (2×200 mL) and water (200 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe remaining residue is purified by column chromatography on silica gel eluting with heptene/EA 5:1 to 1:1

Sources & evidence

ORD record
ord-1e50f0ea60e7428489329d5448b9eee8
Source dataset
uspto-grants-2015_04
Patent number
US09000018B2

Reaction notes

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