2,4,6-Trimethylbenzoic Acid

[480-63-7]  · C10H12O2  · 2,4,6-Trimethylbenzoic Acid  · (MW 164.22)

(mild, hindered Brønsted acid; protecting group for carbohydrates)

Alternate Names: mesitoic acid; mesitylenecarboxylic acid.

Physical Data: needles (prisms from pet ether); mp 154-155 °C; pKa 4.43 (25 °C); pKa1 3.45 (25 °C).1

Solubility: sol alcohol, ether, acetone, CHCl3; slightly sol H2O.

Form Supplied in: crystalline solid.

Preparative Method: many are described, including the addition of CO2 to the Grignard reagent derived from bromomesitylene.10

Purification: crystallized from H2O, pet ether, or CCl4.11

Handling, Storage, and Precautions: gloves should be worn while handling; may cause irritation.

Catalysis of Sigmatropic Rearrangements.

Mesitoic acid has been used on numerous occasions for orthoester Claisen rearrangements and related processes, where its character as a mild, not readily esterified, Brønsted acid is of virtue. The examples cited (eqs 1-3)2-4 are typical; see also Trudell and Cook.5

Reductive Carbonylation.

In the presence of mesitoic acid and 1,10-phenanthroline, palladium metal on alumina support is an effective catalyst for the reductive carbonylation of nitrobenzenes to generate isocyanates, ArNCO;6 the additional presence of alcohols results in the formation of urethanes.7

Synthesis of Sugar Derivatives.

In a recent synthesis of 6-deoxy-6-fluorolactosides, the mesitoyl moiety was utilized as a protecting group (eq 4). Esterification of the free hydroxy groups of disaccharide (1) was accomplished using the mixed anhydride of mesitoic acid and Trifluoroacetic Acid. Use of mesitoyl groups in (2) allowed for the selective hydrolysis of the butyrate ester. Following incorporation of a fluorine into the molecule, the mesitoyl groups were removed reductively with AlH3 without affecting the C-F bond.8

Mesitoyl groups have also been used for the selective protection of 1,4:3,6-dianhydro-D-glucitol.9

Related Reagents.

Acetic Acid; Hydrochloric Acid; Methanesulfonic Acid; Oxalic Acid; p-Toluenesulfonic Acid.

1. Dictionary of Organic Compounds, 5th ed.; Chapman and Hall: New York, 1982; Vol. 5, p 5546.
2. Posner, G. H.; Crouch, R. D.; Kinter, C. M.; Carry, J.-C. JOC 1991, 56, 6981.
3. Raucher, S.; Chi, K.-W.; Jones, D. S. TL 1985, 26, 6261.
4. Raucher, S.; MacDonald, J. E.; Lawrence, R. F. TL 1980, 21, 4335.
5. Trudell, M. L.; Cook, J. M. JACS 1989, 111, 7504.
6. Alessio, E.; Mestroni, G. JOM 1985, 291, 117.
7. Cenini, S.; Ragaini, F.; Pizzotti, M.; Porta, F.; Mestroni, G.; Alessio, E. J. Mol. Catal. 1991, 64, 179.
8. Cai, S.; Hakomori, S.; Toyokuni, T. JOC 1992, 57, 3431.
9. &CCbreve;eković, Z.; Tokić, Z. S 1989, 610.
10. Bowen, D. M. OSC 1955, 3, 553, 555.
11. Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory Chemicals, 3rd ed.; Pergamon: New York, 1988; p 299.

Gregory S. Hamilton

Scios Nova, Baltimore, MD, USA

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