2-(2,3,5-Trimethoxy-4-methylbenzoyl)benzoic acid page 442

H₂SO₄

(MeO)₂SO₂

K₂CO₃

A mixture of 2-(2,3,5-trimethoxy-4-methyl-benzoyl)-benzoic acid (15 g, 45.5 mmol) and concentrated sulfuric acid (100 cm³) was magnetically stirred on an oil bath at 50-52 ºC for 6 h. After standing overnight the dark red solution was poured on to ice and the deep orange-brown precipitate filtered and washed with water. After drying 11 g (83%) of partially demethylated product was obtained. The partially demethylated product (3.5 g) was heated with magnetic stirring under reflux with dimethyl sulfate (9 cm³), K₂CO₃ (12 g) and 2-butanone (50 cm³) for 6 h. The suspension was filtered and the residue washed with 2-butanone (2 x 20 cm³). Evaporation of the filtrate gave 1,2,4-trimethoxy-3-methyl-anthraquinone as yellow brown needles (3.5 g), mp. 122.2 ºC.

H₂SO₄ cyclisation of the methoxyl-substituted benzoyl benzoic acid gave a mixture of partially demethylated anthraquinones. Remethylation with (MeO)₂SO₂ and K₂CO₃ in 2-butanone gave yellow 1,2,4-trimethoxy-3-methyl-anthraquinone as the only product.

Reaction conditions of 150-160 ºC, 30 m reportedly lead to complete demethylation and a 5% yield of the trihydroxymethyl-anthraquinone (Raistrick H, Robinson R, Todd AR, J Chem Soc 1937, 80-88, doi: 10.1039/JR9370000080). Recommended conditions for similar reactions (Smith CW, Ambler SJ, Steggles DJ, Tet Lett 1993, 34(46), 7447-7450, doi:10.1016/S0040-4039(00)60149-1), 1 h ambient temperature, gave only recovered starting materials. Reaction conditions of 50-52 ºC for 6 h gave a 1:1 mixture of one red 3-methyl-2-methoxy-1,4-dihydroxy- and two yellow isomers 3-methyl-2,4-dimethoxy-1-hydroxy-  and 3-methyl-1,2-dimethoxy-4-hydroxy- anthraquinones. 1,2,4-Trimethoxy-3-methyl-anthraquinone (2 g) was crystallised from hexane (60 cm³) to give yellow needles (1.48 g). [Hirose Y, Chem Pharm Bull, 1960, 8(5), 417-426, yellow needles, mp. 126-127 ºC (MeOH)].

δ_H (CDCl₃) 8.19m (2H), 7.73m (2H), 3.99s (3H), 3.97s (3H), 3.92s (3H), 2.33s (3H)

Raistrick H, Robinson R, Todd AR, J Chem Soc 1937, 80-88, doi: 10.1039/JR9370000080

Smith CW, Ambler SJ, Steggles DJ, Tet Lett 1993, 34(46), 7447-7450, doi:10.1016/S0040-4039(00)60149-1