3-Hydroxybenzaldehyde → HCID 14349165, compound

HRID 414846Notes

Reaction equation

HRID 414846 reaction equation
[Mg].II.[Cl:4][C:5]1[CH:6]=[C:7]([CH:15]=[CH:16][CH:17]=1)[O:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]Br.[OH:18][C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=1)[CH:22]=[O:23].[H-].[Na+].C(C1C=C(C=CC=1)[O-])=O.[Na+].[Na]>C1COCC1>[Cl:4][C:5]1[CH:6]=[C:7]([CH:15]=[CH:16][CH:17]=1)[O:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH:22]([C:21]1[CH:20]=[C:19]([OH:18])[CH:26]=[CH:25][CH:24]=1)[OH:23]

Participants

9

Reactant 7

HCID 1013-Hydroxybenzaldehyde2×HCID 807Iodine2×HCID 24758Sodium hydrideHCID 5360545SodiumHCID 5462224MagnesiumHCID 14575312HCID 14575312, compoundHCID 23692255HCID 23692255, compound

Product 1

HCID 14349165HCID 14349165, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Procedure

To a gently refluxing dry tetrahydrofuran (75 ml) containing magnesium turnings (1.3 g; 53 mmol) and a small crystal of iodine, was added dropwise from a dropping funnel a solution of 5-(3-chlorophenoxy)pentyl bromide (13.87 g, 50 mmol) in dry THF (55 ml). After about 5-7 minutes, the Grignard reaction started as indicated by the disappearance of the brown iodine color. The heating was adjusted so that the solution refluxed gently. After the addition of the halide was complete (ca. 30 min.), the clear solution was refluxed for about 1 hour. This solution of the Grignard reagent was cooled to room temperature. A solution of 3-hydroxybenzaldehyde (5.5 g, 45 mmol) in dry THF (50 ml) was added dropwise to a well-stirred suspension of sodium hydride (2.8 g, 58 mmol) (50% oil dispersion) in dry THF (75 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 the 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, and the solution was difficult to stir. This reaction mixture was maintained 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 destroyed 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.) until an off-white solid was obtained (11.1 g; 78% yield). This can be crystallized from methanolethyl acetate to give a white solid, m.p. 125°-127° C.; mass spectrum: m/e (intensity observed at 320 (86.9%) and 322 (29.5%) which correspond to the molecular ion. The crude material was, however, pure enough to be used for the next reaction.

Workup

  1. customthe Grignard reaction
  2. temperaturerefluxed gently
  3. custom(ca. 30 min.)
  4. temperaturethe clear solution was refluxed for about 1 hour
  5. customto go above ca. 40° C
  6. custom(ca. 30 min.)
  7. temperaturewas warmed to 45°-50° C.
  8. additionadded dropwise
  9. customA thick precipitate immediately formed
  10. stirringto stir
  11. additionAfter the addition
  12. custom(ca. 2 hours)
  13. stirringthe reaction mixture was stirred at this temperature for another hour
  14. temperaturecooled in an ice bath
  15. customThe excess reactive materials (sodium hydride, Grignard reagent, etc.) were destroyed slowly by carefully adding methanol (30 ml)
  16. additiona saturated ammonium chloride solution (350 ml) was added
  17. dissolutionto dissolve all solids
  18. customThe organic layer was separated
  19. extractionthe aqueous layer was extracted with ether (2×75 ml)
  20. washThe combined organics were washed with water, brine
  21. dry with materialdried over anhydrous magnesium sulfate
  22. customAfter drying the extract
  23. customall volatiles were removed
  24. customto obtain a dark liquid
  25. customThis oil was triturated with a 1:1 mixture of ether and petroleum ether (35°-55° C.) until an off-white solid
  26. customwas obtained (11.1 g; 78% yield)
  27. customThis can be crystallized from methanolethyl acetate
  28. customto give a white solid, m.p. 125°-127° C.
  29. customhowever, pure enough to be used for the next reaction

Sources & evidence

ORD record
ord-40058e34563f42fb93d17105f40f7b3e
Source dataset
uspto-grants-1988_12
Patent number
US04794188

Reaction notes

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