phenol + formaldehyde -> 2,4,6-Tris-hydroxymethyl-phenolIn reply to
Post 240358
(Antoncho: "OTC 3,4,5-TMBA from _phenol_ in 3 steps!", Novel Discourse)...planning Dakin reaction (H2O2/NaOH)
__> 3,4,5-trihydroxy-benzaldehyde
...then methylation
__> 3,4,5-trimethoxy-benzaldehyde
Martin.
J.Amer.Chem.Soc. (1952) 74:3024.
282g of phenol was dissolved in a solution containing 198g of 83% KOH and 100ml H2O. The phenate solution was cooled to 40°C and 500g of 36.3% formalin, cooled to 17°C, was added. The reaction mixture was kept at 25-35°C for 48h. Approximately 300ml H2O was distilled at a pressure of 15-20mmHg. The pot temperature was not allowed to exceed 50°C and for the most part was kept well below this temperature. [The reaction products were separated by fraction distillation of their trimethylsilyl derivatives.]
Martin.
J.Amer.Chem.Soc. (1951) 74:3952-3954.
One mole of phenol was dissolved in 1.1 moles of 50% NaOH. The solution was cooled to 25-30°C, at which temperature it solidified. Formalin (270ml of 40% by volume) was added to the sodium phenate and the solution was stirred to dissolve the sodium phenate. External cooling was employed during the first 1-2 hours of reaction so that the temperature never exceeded 40°C. The reaction mixture was allowed to stand several days at room temperature or maintained at 40°C for 24 hours. The reaction mixture was then poured into three liters of ethanol, giving a white granular precipitate. After standing for 2 hours, the precipitate of sodium tris-( hydroxymethy1)-phenate was filtered, rinsed with acetone and ether and then dried in a vacuum desiccator; yield 165 g.; theory. 206 g.
Freeman.
J.Amer.Chem.Soc. (1952) 74:6257-6258.
Preparation of Sodium 2,4,6-Trimethylolphenate. 4.0g NaOH (0.1 mole) was dissolved in 10ml of water and added to 9.4g (0.1 mole) of phenol. After cooling to room temperature, 24.4g (0.3 mole) of formalin (37%) was added to the solution of sodium phenate. No further cooling was necessary except for larger batches. (Martin employed more concentrated alkali with the result that sodium phenate crystallized out of solution. He also used a 20% excess of formaldehyde and 10% excess sodium hydroxide.) The solution gradually turned yellow and was allowed to stand for 6-7 days, then poured into 300ml of isopropyl alcohol. An immediate thick white precipitate formed and was removed by filtration after 10-15 minutes, washed with isopropyl alcohol, and dried in a vacuum desiccator several days; yield 90-99%. Chromatograms run on the mother liquor and on the product (sodium salt) showed only the trimethylolphenol as the product, no by-products or intermediates by this method. Repeat experiments using double and treble the amounts indicated were equally successful. The sodium salt deteriorates on standing. After several months the white solid had become reddish-brown and the odor of formaldehyde WaS noticeable on opening the container. Attempts to neutralize the salt at this stage gave only resinous products.
Neutralization of Sodium 2,4,6-Trimethylolphenate. Preparation of 2,4,6-Trimethylolphenol. The sodium salt of 2,4,6-Trimethylolphenol (20.6g, 0.1 mole) was suspended in 500ml of C.P. acetone and 150ml of acetone containing 6.0g (0.1 mole) of glacial acetic acid was added slowly with stirring. The salt dissolved and sodium acetate precipitated. After 10 min the faintly acidic solution was filtered. The filtrate was concentrated to 90-100ml by warming at 50°C, cooled, and 50-60ml of ether added in portions. On standing in a desiccator a yellow oil precipitated. On three occasions this oil gradually crystallized forming white waxy crystals. The residual solvent was decanted and the product dried in vacuum; yield 71%, m.p. 74-75°C. Attempted further purification by recrystallization was not satisfactory due to considerable resinification. Addition of a few drops of 10% NaOH to a sample of trimethylolphenol in isopropyl alcohol reverses the reaction as evidenced by an immediate white precipitate.
From Beilstein:
Reagent LiOH:
Seto, Horiuchi.
Kogyo Kagaku Zasshi (1953) 56:419;
Chem.Abstr. (1955) 6872.
Reagent NaOH:
Davis et al.
J.Appl.Chem. (1957; 7:521-525.
Reese.
Angew.Chem. (1952) 64:399.
Lamartine, Perrin, Vicens, Gamet, Perrin, et al.
Mol.Cryst.Liq.Cryst. (1986) 134:219-236.
Reagent CaO, H2O:
Patent US2889373
