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Iodine-Mediated Domino Protocol for the Synthesis of Benzamides from Ethylarenes via sp3 C-H Functionalization

Kamlesh S. Vadagaonkar, Hanuman P. Kalmode, Sattey Prakash, Atul C. Chaskar*

*Department of Dyestuff Technology, Institute of Chemical Technology, Mumbai 400019, India, Email:

K. S. Vadagaonkar, H. P. Kalmode, S. Prakash, A. C. Chaskar, Synlett, 2015, 26, 1677-1682.

DOI: 10.1055/s-0034-1380210

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An efficient, metal-free domino protocol for the synthesis of benzamides from ethylarenes proceeds through the formation of triiodomethyl ketone intermediate in the presence of iodine as the promoter and TBHP as an oxidant followed by nucleophilic substitution with aqueous ammonia. This operationally simple, functional-group-tolerant tandem approach provides an easy access to the broad range of biologically important benzamides.

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The following procedure offers a better yield:

A sealed tube equipped with magnetic stirring bar was charged with ethylarene 1 (1.0 mmol), tert-butyl hydroperoxide (TBHP, 2.0 mmol, 70% aq. solution) and water (3.0 mL). To this reaction mixture was added I2 (0.2 mmol) at room temperature. The resulting mixture was heated to 100C for 1.0 h. The reaction mixture was cooled to room temperature, monitored by TLC which showed formation of acetophenone. Then to this reaction mixture was added I2 (3.0 mmol) and aqueous ammonia (25% aq. solution, 10.0 mmol) at room temperature. The reaction mixture was again heated to 100C; for 2.0 h. After completion of the reaction (monitored by TLC), 5 mL of saturated Na2S2O3 solution was added to the reaction mixture and it was extracted with ethyl acetate (2 * 10 mL). The organic layer was washed with brine solution (10 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography on 100:200 mesh silica gel using ethyl acetate: n-hexane (1:2) as the eluent to obtain the corresponding benzamide 3.

Atul C. Chaskar, August 19, 2016

Key Words

ethylarenes, sp3 C-H functionalization, haloform reaction, amides (oxidation, substitution), iodine, tert-butyl hydroperoxide (TBHP)

ID: J60-Y2015