Hydrochloric Acid → 4-Hydroxy-3-(2-propyn-1-yloxy)benzaldehyde

HRID 1260135Notes

Reaction equation

HRID 1260135 reaction equation
[H-].[Na+].[OH:3][C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][C:11]=1[OH:12])[CH:7]=[O:8].[CH2:13](Br)[C:14]#[CH:15].Cl>CS(C)=O>[CH2:15]([O:3][C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][C:11]=1[OH:12])[CH:7]=[O:8])[C:14]#[CH:13]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 7842Propargyl bromideHCID 87683,4-DihydroxybenzaldehydeHCID 24758Sodium hydride

Product 1

HCID 529215204-Hydroxy-3-(2-propyn-1-yloxy)benzaldehydeYield 69.3%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Conditions

Temperature
0 °C

Procedure

In a dry two-neck flask with a nitrogen inlet, NaH (4.8 g, 200 mmol, 2 equiv) was added into anhydrous DMSO (50 mL) in small portions. While stirring and cooling this solution to 0° C., anhydrous DMSO (60 mL) containing 3,4-dihydroxybenzaldehyde (13.8 g, 100 mmol, 1 equiv) was added dropwise into the flask. This reaction mixture was stirred at rt for 30 min. Propargyl bromide (11.1 mL 100 mmol, 1 equiv) was then added dropwise via syringe and the mixture was stirred at rt overnight. The mixture was poured onto ice, neutralized by a 1 M HCl solution and the product was extracted with ethyl acetate (3×250 mL). The combined organic extracts were concentrated to about 250 mL, washed with brine (5×250 mL) and dried over MgSO4. After filtration the solvent was removed under vacuum to afford crude product as a brownish powder. This was chromatographed on a silica gel column with an eluent of ethyl acetate/hexane/acetic acid (20/80/1) to give 8 as a white powder (12.2 g, yield: 69%). 1H NMR δ=9.84 (s, 1H, —CHO), 7.53 (d, J=1.7, 1H), 7.49 (dd, J1=1.7, J2=8, 1H), 7.09 (d, J=8, 1H), 6.22 (s, 1H, —OH), 4.84 (d, J=2.5, 2H, —OCH2), 2.60 (t, J=2.5, 1H, —C≡CH). 13C NMR δ=190.92 (—CHO), 152.20, 145.37, 129.96, 128.14, 115.35, 111.36, 77.41 (—C≡CH), 77.10 (—C≡CH), 57.23 (—OCH2). HRMS calculated for C10H8O3 (M+), 176.0473; found, 176.0465.

Workup

  1. additionwas added dropwise into the flask
  2. stirringThis reaction mixture was stirred at rt for 30 min
  3. stirringthe mixture was stirred at rt overnight
  4. additionThe mixture was poured onto ice
  5. extractionthe product was extracted with ethyl acetate (3×250 mL)
  6. concentrationThe combined organic extracts were concentrated to about 250 mL
  7. washwashed with brine (5×250 mL)
  8. dry with materialdried over MgSO4
  9. filtrationAfter filtration the solvent
  10. customwas removed under vacuum
  11. customto afford crude product as a brownish powder
  12. customThis was chromatographed on a silica gel column with an eluent of ethyl acetate/hexane/acetic acid (20/80/1)

Sources & evidence

ORD record
ord-2f98dd43f6874d41a38d6278c27d8584
Source dataset
uspto-grants-2013_06
Patent number
US08470587B2

Reaction notes

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