2,4-Dihydroxybenzaldehyde → HCID 10537643, compound

HRID 322958Notes

Reaction equation

HRID 322958 reaction equation
[OH:1][C:2]1[CH:9]=[C:8]([OH:10])[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].[H-].[Na+].Cl[CH2:14][C:15]1[CH:19]=[CH:18][S:17][CH:16]=1>CN(C)C=O>[OH:1][C:2]1[CH:9]=[C:8]([O:10][CH2:14][C:15]2[CH:19]=[CH:18][S:17][CH:16]=2)[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5]

Participants

5

Reactant 3

HCID 72132,4-DihydroxybenzaldehydeHCID 24758Sodium hydrideHCID 124874623-(Chloromethyl)thiophene

Product 1

HCID 10537643HCID 10537643, compoundYield 14.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
70 °C

Procedure

A stirred solution of 2,4-dihydroxybenzaldehyde (31.8 g) in dry dimethylformamide (150 mL) at ambient temperature is treated with sodium hydride (11.96 g; 60% w/v dispersion in mineral oil; 300 mmol), portionwise, during 30 minutes. After a further period of 15 minutes, the mixture is treated, dropwise, with a solution of 3-chloromethylthiophene (35 g) in dimethylformamide (50 mL). The mixture is stirred at 70° C. for 2 hours, then it is cooled and the solvent is evaporated. The residue is partitioned between ethyl acetate (200 mL) and hydrochloric acid (200 mL; 0.5 M), and the aqueous layer is extracted further with ethyl acetate (2×100 mL). The combined organic extracts are washed with brine (100 mL), dried over magnesium sulphate, and concentrated in vacuo. The residue is subjected to flash chromatography on silica gel, eluting with a mixture of ethyl acetate and pentane (1:4 v/v), to give a colourless oil, which crystallises on standing. This solid is recrystallised from diisopropyl ether, to give 2-hydroxy-4-(3-thienylmethoxy)benzaldehyde (8 g), in the form of a white solid.

Workup

  1. waitAfter a further period of 15 minutes
  2. additionthe mixture is treated
  3. temperatureit is cooled
  4. customthe solvent is evaporated
  5. customThe residue is partitioned between ethyl acetate (200 mL) and hydrochloric acid (200 mL; 0.5 M)
  6. extractionthe aqueous layer is extracted further with ethyl acetate (2×100 mL)
  7. washThe combined organic extracts are washed with brine (100 mL)
  8. dry with materialdried over magnesium sulphate
  9. concentrationconcentrated in vacuo
  10. washeluting with a mixture of ethyl acetate and pentane (1:4 v/v)
  11. customto give a colourless oil, which
  12. customcrystallises
  13. customThis solid is recrystallised from diisopropyl ether

Sources & evidence

ORD record
ord-4fde780db6764cfc904598c5bacb3b91
Source dataset
uspto-grants-2001_04
Patent number
US06211234B1

Reaction notes

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