This variation on an old theme uses much less pyridine than earlier methods, and may also give higher yields.
Synthetic Communications Volume 32, Issue 4, Pages 641-649 (2002)
A simple, economical, selective and high-yielding procedure for the rapid demethylation of nitro-catechol methyl ethers has been developed using reagents and solvents suitable for production of medicinal products. This procedure is superior to other demethylation methodologies especially for larger-scale operations. The method should prove generally useful for the rapid demethylation of ortho-hydroxy arylmethyl ethers.
1-(3,4-Dihydroxy-5-nitrophenyl)-2-phenyl-ethanone (1)
To a stirred yellow suspension of 1-(4-hydroxy-3-methoxy-5-nitrophenyl)-2-phenyl-ethanone ((6), 50.0 g, 174 mmol) in ethyl acetate (500 ml) at room temperature was added aluminium chloride (27.84 g, 209 mmol) in one portion. To the resulting orange/red suspension was added dropwise pyridine (55.1 g, 56.2 ml, 696 mmol) causing the internal temperature to rise to 45°C. The orange solution was then heated at reflux (77°C) for 2 h and then allowed to cool to 60°C whereupon the reaction mixture was carefully added to a mixture of ice/concentrated hydrochloric acid (200 ml). After stirring at 50°C for 1 h, the mixture was cooled in an ice/water bath for 1 h and then filtered. The filter cake was washed by water and the product then dried (70°C, 0.02 mmHg, 5 h) to afford the title product as a yellow solid, 47.21 g, (99.4%) of m.p. 177.6–178.8°C.
3,4-Dihydroxy-5-nitrobenzaldehyde (Entry 5)
Yellow-orange crystals, m.p. 142–143°C (lit12 m.p. 145–146°C).
