J. Chem. Soc. Perk. Trans. I 1823 (1994) R. Aldred et al.: Magnesium-mediated ortho-specific formylation and formaldoximation of phenols.2-OH-5-MeO-benzaldehyde from 4-MeO-phenol, Mg(OMe)2, and paraformaldehyde in methanol / toluene. Yield: 97%
Phenol (37.6 g, 0.4 mol) was added to magnesium methoxide (259 g of 8% wt.% solution in methanol; 20.7 g, 0.24 mol) and the mixture was heated to reflux. Approximately half of the methanol was distilled off and toluene (300 g) was added to the residue. The azeotropic mixture of toluene and and methanol was removed by fractional distillation, until the temperature of the reaction rose to 95°C. A slurry of paraformaldehyde powder (43.2 g, 1.44 mol) in toluene (75 g) was added in small portions over 1 h to the reaction mixture at 95°C with concurrent removal of the volatile materials by didtillation. Stirring was continued at 95°C for 1 h, after which the mixture was cooled to 25°C and added slowly to 10% sulfuric acid (450 g), The resulting mixture was stirred at 30-40°C, after which the aqueous layer was separated and extracted with toluene (2 x 100 g). The combined organic layers and extracts were washed with 10% sulfuric acid (50 g) and water (50 g) and evaporated under reduced pressure to give the aldehyde as a pale yellow oil (48.35 g, 84% w/w by GC and 1H-NMR comparisn against a reference standard and against a commercial sample of known purity; 83% yield).
In similar reactions they used the following conditions:
Magnesium raspings (7.3 g, 0.3 mol), methanol (112 g), toluene (48.5 g) and magnesium methoxide (1.6 g of 8% w/w solution in methanol; 1.5 mmol) were heated under reflux for 2 h untile the magnesium had dissolved and hydrogen evolution had ceased. 4-Nonylphenol (112 g, 0.5 mol) was added to the mixture ...
Acta Chemica Scandinavica 53, 258 (1999) N. U. Hofsløkken, L. Skattebøl: Convenient method for the ortho-formylation of phenols.2-OH-5-MeO-benzaldehyde (5-MeO-salicylaldehyde) from 4-MeO-phenol, MgCl2, NEt3, and paraformaldehyde in MeCN. Yield: 97%, reaction time: 2 h
General procedure:
Dry (P2O5) paraformaldehyde (135 mmol) was added to a mixture of the phenolic derivative (20 mmol), commercially available anhydrous magnesium dichloride (30 mmol) and dry (Na) triethylamine (75 mmol) in acetonitrile (100 ml; distilled over CaH2), and the mixture was heated under reflux for the reaction time recorded. The mixture was cooled to room temperature after which 5% aq. HCl was added and the product extracted with ether. The dried (MgSO4) extract was evaporated and the residue purified by flash chromatography on silica gel.
