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DOI: 10.1055/s-2003-36216
Bismuth Triflate Catalyzed One-Pot Synthesis of 3,4-Dihydropyrimidin-2 (1H)-ones: An Improved Protocol for the Biginelli Reaction
Publication History
Publication Date:
18 December 2002 (online)
Abstract
An efficient synthesis of 3,4-dihydropyrimidinones (DHPMs) using bismuth triflate as the catalyst for the first time from an aldehyde, β-keto ester and urea in acetonitrile is described. Compared to the classical Biginelli reaction conditions, this new method consistently has the advantage of excellent yields (58-95%) and short reaction time (1-4 h) at room temperature.
Key words
Biginelli reaction - dihydropyrimidinones - bismuth triflate - one-pot condensation
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References
Typical Experimental
Procedure: A solution of an appropriate β-keto ester
(2.5 mmol), corresponding aldehyde (2.5 mmol), urea or thiourea
(3.7 mmol), and Bi(OTf)3 (2 mol%) in anhyd CH3CN
(10 mL) was stirred at r.t. for a certain period of time as required
to complete the reaction (TLC). The solvent was removed under reduced pressure
to yield a solid, which was washed thoroughly with water, filtered
and recrystallized from ethanol to afford pure product.
Spectroscopic
data for compound 4a: 1H
NMR (DMSO-d
6): δ = 9.17
(s, 1 H), 7.72 (s, 1 H), 7.21-7.32 (m, 5 H), 5.14 (s, 1
H), 3.98 (q, J = 7.2
Hz, 2 H), 2.24 (s, 3 H), 1.08 (t, J = 7.2 Hz,
3 Hz). Compound 4d: 1H
NMR (DMSO-d
6): δ = 9.07
(s, 1 H),7.57 (s, 1 H), 7.02 (d, J = 8.4
Hz, 2 H), 6.64 (d, J = 8.4 Hz,
2 H), 5.02 (s, J = 3.2
Hz, 1 H), 3.96 (q, J = 7.2
Hz, 2 H), 2.22 (s, 3 H), 1.10 (t, J = 7.2
Hz,3 H). Compound 4q: 1H NMR
(DMSO-d
6): δ = 9.79
(s, 1 H), 8.03 (d, J = 5.0
Hz, 1 H), 7.90 (s, 1 H), 7.78 (d, 1 H), 7.52 (d, J = 3.8
Hz, 1 H), 7.34-7.11 (m, 5 H), 5.25 (s, 1 H). Compound 4s: 1H NMR (DMSO-d6): δ = 9.13
(s, 1 H), 8.47 (m, 1 H), 7.71 (m, 2 H), 7.51(d, 1 H), 7.23 (m, 1
H), 5.31 (d, J = 3.3
Hz, 1 H), 2.21 (s, 3 H), 2.17 (s, 3 H). Compound 4t:
1H NMR (DMSO-d
6): δ = 9.33
(s, 1 H), 7.86 (d, J = 2.9
Hz, 1 H), 7.72 (d, J = 8.2 Hz,
2 H), 7.47 (d, J = 8.2
Hz, 2 H), 5.25 (d, J = 2.8
Hz, 1 H), 4.00 (q, J = 7.1
Hz, 2 H), 2.27 (s, 3 H), 1.12 (t, J = 7.1
Hz, 3 H).