Preparation of Methoxyphenols by Baeyer-Villiger Oxidation of Methoxybenzaldehydes
By Ian M. Godfrey and Melvyn V. Sargent, John A. Elix
J. Chem. Soc. Perkin. Trans. 1, 1353-1554 (1974)
Abstract:
Baeyer-Villiger Oxidation of methoxybenzaldehydes with m-chlorobenzoic acid in boiling DCM followed by hydrolysis of the resultant formates, is shown to be a convenient method for the preparation of methoxyphenols.
In connection with our work on depsidones we required a convenient route to some dimethoxymethylphenols. The Baeyer-Villiger oxidation of the corresponding benzaldehydes appeared to be an attractive method since the aldehydes are easily available. This type of oxidation had previously been carried out by using peracetic acid under a variety of conditions.1-6 The reported yields were often low3-4 (see however ref. 7), or the use of anhydrous peracetic acid was required.5-6
We now report that such oxidations can conveniently be carried out by using the commercially available m-chlorobenzoic acid in boiling DCM. Under these conditions the formates were usually produced in almost quantitative yields and they were hydrolyzed to the phenol under mild conditions. The overall yield for the more complex compounds (see Table) were generally high.
The required benzaldehydes were easily prepared by the Vilsmeier-Haack method. The usual literature procedure 8 often gave rise to a violently exothermic reaction. The modification described (see Experimental) was found to be preferable.
Experimental:
MP’s were determined on a Kofler hot-stage apparatus. Light petroleum refers to the fraction at BP: 58-65*C. NMR spectra were determined for solutions in deuteriochloroform with a Varian A-60A spectrometer.
Vilsmeier-Haack Reactions
The Vilsmeier complex was prepared by the dropwise addition of freshly distilled phosphoryl chloride (55ml) to dry N,N-dimethylformamide (100ml) during 15 minutes with stirring and cooling in ice. The complex was allowed to warm to RT and was then added during 1-1.5hours to a stirred solution of the substrate (0.5mol) in dry DMF (100ml) at 100-110*C (bath). Heating and stirring were then continued until TLC indicated that substrate had been consumed (usually 1-2hours). The mix was poured onto ice-water, made just basic by the addition of sodium carbonate aqueous solution and then exhaustively extracted with ethyl acetate. The combined extracts were washed successively with dilute HCl, water, and sat. NaCl, then dried over Na2SO4. The crude product was then purified by distillation under reduced pressure or by crystallization. The following substituted benzaldehydes were obtained:
4-MeO-2,5-dimethyl (76%) as an oil that had; BP: 85-86*C/0.4mmHg (lit. 9 147-149*C at 12mmHg) which crystallized on cooling
2,4-dimethoxy (99%) as pale yellow needles that had; MP: 68-69*C (from ethanol) (lit10 71-72*C)
2,4-dimethoxy-5-methyl (84%) as needles that had MP: 65-66*C (From DCM/light petroleum) (lit11 64-66*C)
2,4-dimethoxy-3-methyl (83%) glistening needles that had; MP: 52-53*C (from light petroleum) (lit10 54-55*C)
2,4-dimethoxy-5-methyl (87%) from the toluene12 as needles that had; MP: 118-119*C (lit13 117-118*C) (from methanol)
2,4-dimethoxy-3,6-dimethyl-(93%) from beta-orcinol di-O-methylether14 as needles that had; MP: 49-50.5*C (from light pet.) (lit 15 47-48*C)
2,4,5-trimethoxy (88%) from 1,2,4-trimethoxybenzene16 as needles (from water) that had; MP: 112-112.5*C (lit17 114*C)
2,3,4,6-tetramethoxy (86%) from 1,2,3,5-tetramethoxybenzene18 as needles (from light pet.) that had; MP: 87-88*C (lit 1988-89.5*C)
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