4-Hydroxybenzaldehyde → (2-Quinolinyl)-methoxyl-benzaldehyde

HRID 37697Notes

Reaction equation

HRID 37697 reaction equation
[Na].O[C:3]1[CH:10]=[CH:9][C:6]([CH:7]=[O:8])=[CH:5][CH:4]=1.ClC[C:13]1[CH:22]=[CH:21][C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[N:14]=1.Cl.[CH2:24]([OH:26])C>>[N:14]1[C:15]2[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:21]=[CH:22][C:13]=1[C:4]1[C:5]([O:26][CH3:24])=[C:6]([CH:9]=[CH:10][CH:3]=1)[CH:7]=[O:8]

Participants

6

Reactant 5

HCID 1264-HydroxybenzaldehydeHCID 313Hydrochloric AcidHCID 702Ethanol3×HCID 203942-(Chloromethyl)quinolineHCID 5360545Sodium

Product 1

HCID 86748706(2-Quinolinyl)-methoxyl-benzaldehyde

Procedure

To a solution of sodium metal (0.9 g, 39.13 g.a.) in absolute ethanol (50 mL) is added dropwise under nitrogen a solution of 4-hydroxybenzaldehyde (5 g, 40.94 mmole) in absolute ethanol (50 mL). The mixture is gently refluxed for 1 hour and then treated dropwise with a solution of 2-chloromethylquinoline (free base, 7.24 g, 40.76 mmole), freshly prepared from the HCl salt) in ethanol (50 mL). The mixture is refluxed for 24 hours, the solvent is evaporated and the residue is partitioned between water and ethyl acetate. The organic layer is washed with 5% NaOH (pH 8), water, brine to neutral and dried (MgSO4). Removal of the solvent yields the title compound as a yellow solid (9.81 g). The crude material is further purified by flash chromatography (on silica Merck-60, hexane-ethyl acetate 9:1 to remove less polar impurities and 8:2 to elute the product). Yield: 7.37 g (71.5%), m.p. 82°-83° C.

Workup

  1. temperatureThe mixture is gently refluxed for 1 hour
  2. temperatureThe mixture is refluxed for 24 hours
  3. customthe solvent is evaporated
  4. customthe residue is partitioned between water and ethyl acetate
  5. washThe organic layer is washed with 5% NaOH (pH 8), water, brine to neutral and
  6. dry with materialdried (MgSO4)
  7. customRemoval of the solvent

Sources & evidence

ORD record
ord-bd82b15bb44b4042a08c15a5a826b8bc
Source dataset
uspto-grants-1995_05
Patent number
US05420289

Reaction notes

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