3-Hydroxybenzaldehyde → HCID 14349171, compound

HRID 414854Notes

Reaction equation

HRID 414854 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH:5]=[O:6].[H-].[Na+].C([C:14]1[CH:15]=[C:16]([CH:18]=[CH:19][CH:20]=1)[O-:17])=O.[Na+].[Na].[Cl-].[NH4+]>C1COCC1.CO>[O:17]([CH2:8][CH2:9][CH2:2][CH2:3][CH2:4][CH:5]([C:4]1[CH:3]=[C:2]([OH:1])[CH:9]=[CH:8][CH:7]=1)[OH:6])[C:16]1[CH:15]=[CH:14][CH:20]=[CH:19][CH:18]=1

Participants

8

Reactant 5

HCID 1013-Hydroxybenzaldehyde2×HCID 24758Sodium hydride2×HCID 25517Ammonium ChlorideHCID 5360545SodiumHCID 23692255HCID 23692255, compound

Product 1

HCID 14349171HCID 14349171, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 3-hydroxybenzaldehyde (5.0 g, 41 mmole) in dry THF (50 ml) was added dropwise to a well-stirred suspension of sodium hydride (2.5 g, 52 mmol; 50% oil dispersion) in dry THF (50 ml) at room temperature. The temperature was not allowed to go above ca. 40° C. After the addition of 3-hydroxybenzaldehyde was complete (ca. 30 min.) the slightly cloudy solution was warmed to 45°-50° C. and stirred for 1 hour at this temperature. The resulting clear solution of sodium 3-formyl phenoxide was cooled to room temperature and added dropwise using a cannula, to the well-stirred solution of the Grignard reagent (whose preparation was described above). A thick precipitate immediately formed. This mixture was maintained at 40°-45° C. during the addition of the sodium salt. After the addition was complete (ca. 2 hours), the reaction mixture was stirred at this temperature for another hour, and then cooled in an ice bath. The excess reactive materials (sodium hydride, Grignard reagent, etc.) were dsstroyed slowly by carefully adding methanol (30 ml), and then a saturated ammonium chloride solution (350 ml) was added to dissolve all solids. The organic layer was separated, and the aqueous layer was extracted with ether (2×75 ml). The combined organics were washed with water, brine, and then dried over anhydrous magnesium sulfate. After drying the extract, all volatiles were removed to obtain a dark liquid. This oil was triturated with a 1:1 mixture of ether and petroleum ether (35°-55° C.) when an off-white solid was obtained (12 g). This can be crystallized from methanol-ethyl acetate to give a white solid, mp 148°-9° C.

Workup

  1. customto go above ca. 40° C
  2. custom(ca. 30 min.)
  3. temperaturewas warmed to 45°-50° C.
  4. additionadded dropwise
  5. customA thick precipitate immediately formed
  6. additionAfter the addition
  7. custom(ca. 2 hours)
  8. stirringthe reaction mixture was stirred at this temperature for another hour
  9. temperaturecooled in an ice bath
  10. dissolutionto dissolve all solids
  11. customThe organic layer was separated
  12. extractionthe aqueous layer was extracted with ether (2×75 ml)
  13. washThe combined organics were washed with water, brine
  14. dry with materialdried over anhydrous magnesium sulfate
  15. customAfter drying the extract
  16. customall volatiles were removed
  17. customto obtain a dark liquid
  18. customThis oil was triturated with a 1:1 mixture of ether and petroleum ether (35°-55° C.) when an off-white solid
  19. customwas obtained (12 g)
  20. customThis can be crystallized from methanol-ethyl acetate
  21. customto give a white solid, mp 148°-9° C.

Sources & evidence

ORD record
ord-69e5e8e495d540b7a30da2b7e5ac0f8e
Source dataset
uspto-grants-1988_12
Patent number
US04794188

Reaction notes

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