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DOI: 10.1055/s-2003-38734
One-Pot Synthesis of Dihydropyrimidinones Using Iodotrimethylsilane. Facile and New Improved Protocol for the Biginelli Reaction at Room Temperature [1]
Publikationsverlauf
Publikationsdatum:
17. April 2003 (online)
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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.
Key words
Biginelli reaction - dihydropyrimidinones - iodotrimethyl silane - one-pot condensation - room temperature
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References
IICT Communication No. 01/10/03.
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.