Hammet Constants Effects in Microwave Cascade Etherification-Cyclization-Krapcho Reaction to Access [2,3]-Dihydrobenzofuran-3-ones from Salicylic Derivatives

Abstract

Two methods were evaluated for the synthesis of substituted [2,3]-dihydro-2-methyl-benzofuran-3-ones from corresponding salicylate esters under microwave irradiation. A two-step sequence via ether intermediates was convenient for various substituted salicylate derivatives, while the second strategy involving a one-pot procedure was efficient for electron-donating substituted salicylates. Results allowed correlation of the Hammett constants effects in the intramolecular cyclization of O-ethoxycarbonyl ether of salicylic esters.

GRAPHICAL ABSTRACT

Keywords:

• Benzofuranone
• Hammet constants
• Krapcho reaction
• microwave
• salicylate

ACKNOWLEDGMENT

The authors thank La Ligue Contre le Cancer and Cancéropôle Grand Ouest for funding this research.

Notes

^a Reagents and conditions (see sequence in Scheme 1): (ii) K₂CO₃ (1 equiv.), 9 (1 equiv.), DMF, rt, overnight; (iii) DMF, reflux, 4 h; (iv) HCl 6 N.

^b See reference 5 for more details.

^c Yield of isolated product after flash chromatography.

^d Yield after acidic hydrolysis.

^a Experiment performed at 140 °C.

^b Experiment performed at 70 °C (higher temperature was not accessible with our apparatus because of high-pressure limitation).

^c Ratio evaluated on ¹H NMR spectrum of the crude material.

^d Decomposition was observed.

^a Yield of isolated product after flash chromatography.

^a Reagents: DMF (1 mL), K₂CO₃ (1.5 equiv.).

^b Ratio evaluated on ¹H NMR spectrum of the crude material.

^a Reagents and conditions: 8a (2 mmol), methyl 2-bromopropionate 9 (2.5 mmol), carbonate salt (3 mmol), solvent (1 mL), 170 °C, 300 W, 90 min.

^b Ratio evaluated on ¹H NMR spectrum of the crude material.

^a Yield of isolated product after flash chromatography.

^a Reagents: K₂CO₃ (1.5 equiv.), 9 (1.25 equiv.).

^b 5 min at 60 °C followed by 30 min at 155 °C.

^c Yield of isolated product after flash chromatography.

^d We were not able to analyze this complex mixture.