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Trifluoroacetic anhydride mediated benzoylation; Methyl 2-(2,3,5-Trimethoxy-4-methylbenzoyl)benzoate

SyntheticPage 441
DOI: 10.1039/SP441
Submitted Jul 20, 2010, published Jul 21, 2010
Christopher Cooksey (rsc@chriscooksey.demon.co.uk)
A contribution from R J H Clark Group, UCL


			Reaction Scheme: <SPAN class="csm-chemical-name csm-not-validated" id=csm1283071665425 title="Trifluoroacetic anhydride">Trifluoroacetic anhydride</SPAN> mediated benzoylation

Chemicals Used

phthalic acid monomethyl ester page 428

2,3,6-trimethoxyltoluene page 426

trifluoroacetic anhydride (Aldrich)

Procedure

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.

Author's Comments

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).

Data

The product had a m.p. 117.8 ºC

δH (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

δC (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.

Lead Reference

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

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Keywords: benzoylation, esters, ketones

Post new comment
  • Guest Vedran HasimbegovicApr 17 2011 6:52AMRegiochemistry

    Hi, Are you sure you've got that regioisomer? To my mind the electrophile should go para to the methoxy group.

    • Registered user Christopher CookseyApr 19 2011 8:43AMRegiochemistry

      No. It seems to be a single isomer (NMR). My notes say "could be resolved by a long range INEPT experiment irradiating the aromatic proton singlet." But it never happened. Either isomer would give the required product (page 443).

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