One-Pot Synthesis of Dihydropyrimidinones Using Iodotrimethylsilane. Facile and New Improved Protocol for the Biginelli Reaction at Room Temperature [1]

Abstract

A novel one pot condensation of an aldehyde, β-ketoester and urea has been performed using TMSI in acetonitrile for the first time at room temperature affording dihydropyrimidinones in excellent yields.

Biginelli reaction - dihydropyrimidinones - iodotrimethyl silane - one-pot condensation - room temperature

References

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15

One-Pot Synthesis of Dihydropyrimidinone. Typical Procedure: TMSCl (8 mmol) was added to a stirred mixture of benzaldehyde (10 mmol), β-ketoester (10 mmol), urea (12 mmol), and NaI (8 mmol) in MeCN at r.t. Immediately the solid product precipitated out and the reaction was complete in 30 min as monitored by TLC. The precipitate was filtered and the product was washed with 20% EtOAc in hexane to give pure dihydropyrimidinone 4a in 98% yield. Spectral data for selected compounds. 4b: Mp 205-206 °C. ¹H NMR (200 MHz, DMSO-d ₆): δ = 1.00 (t, 3 H, J = 8.0 Hz), 2.40 (s, 3 H), 3.90 (q, 2 H, J = 8.0 Hz), 5.80 (sd, 1 H, J = 3.0 Hz), 6.42 (br s, NH), 7.38-7.68 (m, 3 H, ArH), 7.82 (d, 1 H, J = 8.5 Hz, ArH), 9.20 (br s, NH). IR (KBr): 1592, 1652, 1705, 1720, 2983, 3238 cm^-1. 4h: Mp 207-208 °C. ¹H NMR (200 MHz, CDCl₃): δ = 1.20 (t, 3 H, J = 8.5 Hz), 2.25 (s, 3 H), 4.10 (q, 2 H, J = 8.5 Hz), 5.55 (sd, 1 H, J = 3.5 Hz), 6.80-7.00 (m, 2 H, ArH), 7.10 (m, 1 H), 7.40 (br s, NH), 9.00 (br s, NH). IR (KBr): 1695, 1715, 3240 cm^-1. 4i: Mp 195-196 °C. ¹H NMR (300 MHz, DMSO-d ₆): δ = 0.75 (d, 3 H, J = 6.2 Hz), 0.90 (d, 3 H, J = 6.2 Hz), 1.25 (t, 3 H, J = 7.0 Hz), 1.75 (m, 1 H), 2.25 (s, 3 H), 4.0 (t, 1 H, J = 3.5 Hz), 4.05 (q, 2 H, J = 8.5 Hz), 7.0 (br s, NH), 8.80 (br s, NH).
IR (KBr): 1650, 1700, 3109, 3245 cm^-1. 4k: Mp 206-207 °C. ¹H NMR (200 MHz, DMSO-d ₆): δ = 1.15 (t, 3 H, J = 7.0 Hz), 2.30 (s, 3 H), 4.05 (q, 2 H, J = 7.0 Hz), 5.22 (sd, 1 H, J = 3.5 Hz), 7.25 (m, 4 H, ArH), 7.70 (s, 1 H), 9.30 (br s, NH), 9.95 (br s, NH). IR (KBr): 1585, 1672, 3100, 3185, 3338 cm^-1. 6a: Mp 161-163 °C. ¹H NMR (200 MHz, DMSO-d ₆): δ = 0.90 (t, J = 7.1 Hz, 3 H), 2.99 (d, J = 10.7 Hz, 1 H), 3.85 (q, J = 7.1 Hz, 1 H), 4.85 (d, J = 10.7 Hz, 1 H), 6.95 (br s, NH), 7.15 (br s, NH). IR (KBr): 1685, 1710, 3200, 3450 cm^-1.

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