Formaldehyde → 9-hydroxymethyl-9-fluorene carboxylic acid

HRID 1768160Notes

Reaction equation

HRID 1768160 reaction equation
[CH:1]1[C:13]2[CH:12]([C:14]([OH:16])=[O:15])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.C([Li])CCC.[CH2:22]=[O:23].O>C1COCC1>[OH:23][CH2:22][C:12]1([C:14]([OH:16])=[O:15])[C:13]2[CH:1]=[CH:2][CH:3]=[CH:4][C:5]=2[C:6]2[C:11]1=[CH:10][CH:9]=[CH:8][CH:7]=2

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 962WaterHCID 748099-CarboxyfluoreneHCID 178418339Butyllithium

Product 1

HCID 3450269-hydroxymethyl-9-fluorene carboxylic acidYield 81.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

9-fluorene carboxylic acid (4.98 g, 23.7 mmol) and anhydrous THF (300 ml) were introduced into a flame-dried reaction vessel in which the atmosphere had been replaced by nitrogen, the reaction solution was cooled to −78° C., and n-butyl lithium (41.0 ml of 1.6M hexane solution, 71.0 mmol) was added. After stirring the reaction solution at −78° C. for 30 minutes, paraformaldehyde (2.30 g, 75.0 mmol) dissolved in anhydrous THF (100 ml) was added at −78° C., and stirred at room temperature for 13 hours. Distilled water was added, the solution was extracted with ether, and the pH of the aqueous layer was adjusted to 2 using 1N hydrochloric acid. It was then extracted again with chloroform, and the organic layer was dried by anhydrous magnesium sulfate. The low-boiling fraction was distilled under reduced pressure with the rotary evaporator, and 4.21 g of crude product was thus obtained. The methylene chloride-insoluble fraction of this crude product was collected, and the target compound (4.60 g, 19.3 mmol, 80.5%) was thus obtained. 1H-NMR (500 MHz, CDCl3) d: 7.78 (d, J=7.5, 2H), 7.67 (d, J=7.5, 2H), 7.46 (dd, J=7.0, 2H), 7.54 (dd, J=8.0, 2H), 4.02(s, 4H).

Workup

  1. additionwas added at −78° C.
  2. stirringstirred at room temperature for 13 hours
  3. extractionthe solution was extracted with ether
  4. extractionIt was then extracted again with chloroform
  5. dry with materialthe organic layer was dried by anhydrous magnesium sulfate
  6. distillationThe low-boiling fraction was distilled under reduced pressure with the rotary evaporator, and 4.21 g of crude product
  7. customwas thus obtained
  8. customThe methylene chloride-insoluble fraction of this crude product was collected

Sources & evidence

ORD record
ord-98d1e735b8ee45a59585865579519e3a
Source dataset
uspto-grants-2007_06
Patent number
US07235620B2

Reaction notes

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