An Improved Synthesis of Hydroxy Aryl Ketones by Fries Rearrangement with Methanesulfonic Acid/Methanesulfonic Anhydride

Abstract

Methanesulfonic acid treated with methanesulfonic anhydride effectively mediates the Fries rearrangement of aryl esters to give hydroxy aryl ketones with high yields.

Key words

rearrangement - ketones - esters - methanesulfonic acid - methanesulfonic anhydride

• References and Notes

• 1 Martin R. Org. Prep. Proced. Int. 1992; 24: 369
• 2 Gerecs A. The Fries Reaction in Friedel–Crafts and Related Reactions . Olah GA. Interscience; New York: 1964. Part 1, Vol. 3

For HF-mediated reactions, see:
• 3a Davenport KG. EP 251552, 1988
• 3b Yanagawa T. JP 63132 855, 1988
• 3c Patton JR. EP 228172, 1987
• 3d Fukuoka S. JP 62114927, 1987
• 4 For HF-, AlCl₃-, and BF₃-mediated reactions, see: Hocking MB. J. Chem. Technol. Biotechnol. 1980; 30: 626
• 5 For TiCl₄- and SnCl₄-mediated reactions, see: Ramesh BB. IN 171970, 1993
• 6 For BF₃-mediated reaction, see: Boyer JL. J. Org. Chem. 2000; 65: 4712
• 7 Mouhtady O, Iloughmane HG, Roques N, Roux CL. Tetrahedron Lett. 2003; 44: 6379
• 8 Commarieu A, Hoelderich W, Laffitte JA, Dupont MP. J. Mol. Catal. A.: Chem. 2002; 182: 137
• 9a Staniland PA. EP 57503, 1982
• 9b Kusuda M. JP 62234041, 1987
• 9c Behr A. DE 19736905, 1998
• 10 Sharghi H. J. Chem. Res., Synop. 1998; 10: 628
• 11 Kaboudin B. Tetrahedron 1999; 55: 12865
• 12 Springbor Laboratories, Inc., An acute oral toxicity study in rats with methanesulfonic acid, SLI Study No. 3255.11, November 7, 1997.
• 13 Typical Procedure for the Fries Rearrangement with MSA/Methanesulfonic Anhydride The methanesulfonic anhydride (59.1 mmol) was added to a MSA (384 mL) at 90 °C. The reaction mixture was stirred for 1 h, at this time KF (%) was measured. To MSA/methane-sulfonic anhydride solution, 139.43 g of 3-bromophenyl 2-(2,5-dibromophenyl)acetate (295 mmol, Table 3, entry 9) was added under nitrogen atmosphere at 65 °C. The resulting solution was stirred for 22–24 h, at this time TLC indicated completion. After reaction was completed, batch was cooled to r.t. followed by addition of 2-PrOH–H₂O (3:1, 1115 mL) while maintaining batch temperature at below 65 °C. Batch was then stirred for 20 min, filtered, and dried to afford 108 g (81% yield) of the desired product as a crystalline solid (Table 3, entry 9). ¹H NMR (500 MHz, DMSO-d ₆): δ = 11.60 (s, 1 H), 7.87 (d, J = 8.5 Hz, 1 H), 7.67 (d, J = 2.4 Hz, 1 H), 7.59 (d, J = 8.7 Hz, 1 H), 7.45 (dd, J = 8.7, 2.4 Hz, 1 H), 7.26 (d, J = 1.9 Hz, 1 H), 7.20 (dd, J = 8.4, 1.8 Hz, 1 H), 4.59 (s, 2 H). ¹³C NMR (125 MHz, DMSO-d ₆): δ = 199.5, 160.7, 138.4, 135.5, 134.5, 132.6, 132.1, 129.2, 124.5, 123.0, 121.5, 120.9, 120.8, 47.9.