Iodine as an Efficient Catalyst for One-Pot Multicomponent Synthesis of β-Acetamido Ketones [1]

Abstract

Iodine efficiently catalyzes the three-component coupling of aromatic aldehydes, enolizable ketones or keto esters, and acetonitrile in the presence of acetyl chloride to afford β-acetamido ketones in good yields at room temperature.

Key words

β-acetamido ketone - iodine - multicomponent reaction

1

Part 85 in the series,‘Studies on Novel Synthetic Methodologies’. IICT Communication No. 03336.

References and Notes

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1

Part 85 in the series,‘Studies on Novel Synthetic Methodologies’. IICT Communication No. 03336.

7

General Procedure: To a mixture of an aldehyde (1 mmol), enolizable ketone (1 mmol), and AcCl (1 mmol) in MeCN (or PhCN) (5 mL) molecular iodine (10 mol%) was added. The mixture was stirred at r.t. and the reaction was monitored by TLC. When the reaction was complete the mixture was treated with a solution of aq Na₂S₂O₃ and extracted with EtOAc (3 × 10 mL). The extract was concentrated and the residue was purified over silica gel to obtain β-acetamido ketones.
When the reaction was carried out with ketoesters (instead of ketones) a nitrogen atmosphere was required.
Compound 3d: ¹H NMR (CDCl₃, 200 MHz): δ = 8.21 (d, 2 H, J = 8.9 Hz), 7.88 (d, 2 H, J = 8.9 Hz), 7.63-7.42 (m, 5 H), 7.02 (d, 1 H, J = 8.1 Hz), 5.62 (m, 1 H), 3.82 (dd, 1 H, J = 17.0, 4.4 Hz), 3.46 (dd, 1 H, J = 17.0, 5.2 Hz), 2.06 (s, 3 H). FABMS: m/z = 313 [M + H]⁺.
Compound 3l: ¹H NMR (CDCl₃, 200 MHz): δ = 7.82, (d, 3 H, J = 8.0 Hz), 7.45 (m, 1 H), 7.40-7.31 (m, 2 H), 7.22 (d, 2 H, J = 8.0 Hz), 6.93 (d, 2 H, J = 8.0 Hz), 5.48 (t, 1 H, J = 9.0 Hz), 4.09 (m, 1 H), 2.19 (s, 3 H), 1.92 (s, 3 H), 1.27 (d, 3 H, J = 7.0 Hz). FABMS: m/z = 296 [M + H]⁺.
Compound 3t: ¹H NMR (CDCl₃, 200 MHz): δ = 7.3-7.22, (m, 4 H), 6.98 (d, 1 H, J = 8.9 Hz), 5.69 (dd, 1 H, J = 8.9, 5.9 Hz), 4.21 (q, 2 H, J = 7.0 Hz), 4.01 (d, 1 H, J = 5.9 Hz), 2.19 (s, 3 H), 2.04 (s, 3 H), 1.28 (t, 3 H, J = 7.0 Hz). FABMS: m/z = 314, 312 [M + H]⁺.
Compound 3w: ¹H NMR (CDCl₃, 200 MHz): δ = 8.16 (d, 2 H, J = 8.0 Hz), 7.94 (d, 2 H, J = 8.0 Hz), 7.64-7.20 (m, 5 H), 7.36 (d, 1 H, J = 9.0 Hz), 5.80 (dd, 1 H, J = 9.0, 5.2 Hz), 4.92 (d, 1 H, J = 5.2 Hz), 4.18 (q, 2 H, J = 7.0 Hz), 2.00 (s, 3 H), 1.19 (t, 3 H, J = 7.0 Hz). FABMS: m/z = 376, 374 [M + H]⁺.
Compound 3x: ¹H NMR (CDCl₃, 200 MHz): δ = 8.18 (d, 2 H, J = 8.3 Hz), 7.96-7.84 (m, 5 H), 7.63-7.44 (m, 8 H), 5.82 (m, 1 H), 3.92 (dd, 1 H, J = 17.3, 4.5 Hz), 3.56 (dd, 1 H, J = 17.3, 5.3 Hz). FABMS: m/z = 375 [M + H]⁺.