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DOI: 10.1055/s-2004-815419
A New Biginelli Reaction Procedure Using Potassium Hydrogen Sulfate as the Promoter for an Efficient Synthesis of 3,4-Dihydropyrimidin-2(1H)-one
Publication History
Publication Date:
12 January 2004 (online)
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Abstract
Simple and improved conditions have been found to carry out the Biginelli reaction for the synthesis of 3,4-dihydropyrimidin-2(1H)-one derivatives. This synthesis was performed using potassium hydrogen sulfate as the promoter in glycol solution. Compared with the classical Biginelli reaction conditions, this new method has the advantage of excellent yields (85-99%) and short reaction time (0.5-2 h).
Key words
dihydropyrimidin-2(1H)-one - Biginelli reaction - potassium hydrogen sulfate - cyclic 1,3-dicarbonyl compounds
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References
The general procedure is as follows: A solution of the appropriate aldehyde (3 mmol) or dialdehyde (1.5 mmol), 1,3-dicarbonyl compound (3 mmol), urea (3.6 mmol), and KHSO4 (0.75 mmol) in glycol (10 mL) was heated at 100 °C with stirring for 0.5-2 h before cooled down to r.t. The mixture was then poured into 50 mL of ice-water. The solid product was filtered, washed with ice-water and EtOH (95%), and subsequently dried and recrystallized from EtOH to give pure product. All products (except 8a,b, 6a-e, 9a,b) are known compounds, which were characterized by mp, IR and 1H NMR spectral data. Compound 4p: mp 280-282 °C. IR (KBr): 3539, 3232, 3108, 2954, 1702, 1644, 1530 cm-1. 1H NMR (DMSO-d
6): δ = 9.38 (s, 1 H, NH), 8.13-8.11 (m, 2 H, Ar-H), 7.91 (s, 1 H, NH), 7.66-7.61 (m, 2 H, Ar-H), 5.29 (d, J = 3.1 Hz, 1 H, CH), 3.53 (s, 3 H, OCH3), 2.26 (s, 3 H, CH3). Compound 4t: mp 205 °C. IR (KBr): 3413, 3239, 3119, 2984, 1702, 1644, 1457 cm-1. 1H NMR (DMSO-d
6
):
δ = 9.22 (s, 1 H, NH), 7.74 (s, 1 H, NH), 7.53 (s, 1 H, furanH), 6.33 (d, J = 2.8 Hz, 1 H, furanH), 6.07 (d, J = 2.8 Hz, 1 H, furanH), 5.20 (s, 1 H, CH), 3.98 (q, J = 7.2 Hz, 2 H, CH2), 2.22 (s, 3 H, CH3), 1.09 (t, J = 7.2 Hz, 3 H, CH3). Compound 6d: mp >300 °C. IR (KBr): 3283, 3258, 3065, 2962, 1706, 1676, 1617, 1442, 1371, 1243, 1189, 1132, 1021, 946, 758 cm-1. 1H NMR (DMSO-d
6
): δ = 9.59 (s, 1 H, NH), 7.83 (s, 1 H, NH), 7.59 (d, J = 8.4 Hz, 1 H, Ar-H), 7.43 (s, 1 H, Ar-H), 7.21 (d, J = 8.4 Hz, 1 H, Ar-H), 5.19 (s, 1 H, CH), 1.82-2.45 (m, 6 H, CH2). Compound 8b: mp >300 °C. IR (KBr): 3231, 3112, 2973, 1700, 1458, 1374, 1321, 1227, 1171, 1094, 808, 663 cm-1. 1H NMR (DMSO-d
6
): δ = 9.18 (s, 2 H, NH), 7.69 (s, 2 H, NH), 7.17 (s, 4 H, Ar-H), 5.09 (s, 2 H, CH), 3.97 (q, J = 7.2 Hz, 4 H, OCH2), 2.22 (s, 6 H, CH3), 1.09 (t, J = 7.2 Hz, 6 H, CH3). Compound 9b: mp >300 °C. IR (KBr): 3241, 2948, 1699, 1672, 1613, 1369, 1240, 1181, 806, 764 cm-1. 1H NMR (DMSO-d
6): δ = 9.45 (s, 2 H, NH), 7.69 (s, 2 H, NH), 7.01-7.19 (m, 4 H, Ar-H), 5.05-5.11 (m, 2 H, CH), 1.93-2.49 (m, 12 H, CH2).