phthalic acid monomethyl ester page 428

2,3,6-trimethoxyltoluene page 426

trifluoroacetic anhydride (Aldrich)

Trifluoroacetic anhydride (6 cm³, 43 mmol) was added to phthalic acid monomethyl ester (1.8 g, 10 mmol) which dissolved in 1 m. After 5 m a solution of 2,3,6-trimethoxyltoluene (1.8 g, 10 mmol) in CH₂Cl₂ (6 cm³) was added dropwise over 5 m at 25 ºC. After 6 h the solvents were evaporated to give a dark green oil. Recrystallisation from cyclohexane (70 cm³) gave white crystals (1.97 g) and a further amount (0.28 g, a total yield of 81%) after reducing the volume to 25 cm³.

Trifluoroacetic anhydride mediated coupling of methyl 3-methoxyphthalate with 2,6-dimethoxytoluene reportedly gives 84% yield of the substituted benzoyl benzoate (R D Gleim, S Trenbeath, F Suzuki and C J Sih, Chem Comm 1978, 242b-244, doi: 10.1039/C3978000242b). On a larger scale using 7.09 g of trimethoxytoluene a yield of 75% was obtained. A similar reaction of 1,2,4-trimethoxybenzene with methyl phthalate at 25 – 30 ºC for 45 m gave mainly the required product with 20% of the corresponding phthalide (G Bargellini, Gazz. Chim. Ital. 1914, 44, 193-200).

The product had a m.p. 117.8 ºC

δ_H (CDCl₃) 7.90dd (1.8, 7.4), 7.54td, 7.49td, 7.40dd (1.8, 7.0), 7.22s, 3.85s, 3.84s, 3.70s, 3.27s, 2.14s

δ_C (CDCl₃) 195.16, 167.31, 153.52, 152.30, 148.99, 143.51, 131.41, 129.65, 129.41, 129.41, 127.72, 126.27, 126.12, 111.07, 61.31, 60.26, 55.88, 52.22, 9.56.

R D Gleim, S Trenbeath, F Suzuki and C J Sih, Chem Comm 1978, 242b-244, doi: 10.1039/C3978000242b.