Heteropolyacid-Catalyzed One-Pot Synthesis of 2-Pyridone Derivatives

Abstract

An efficient Keggin-type heteropolyacid-catalyzed reaction for the synthesis of 2-pyridone derivatives using amines, acetylenic esters, and malonic esters or acid is reported. Optimum conditions were developed in i-PrOH at 60–100 °C. The activity of immobilized H₃PW₁₂O₄₀ on the traditional amorphous silica was also examined.

Key words

2-pyridone - heteropolyacid - acetylenic ester - heterogeneous catalyst - multicomponent reaction

• References and Notes

• 1 Timofeeva MN. Appl. Catal., A. 2003; 19
• 2 Romanelli G, Bennardi D, Palermo V, Vázquez P, Tundo P. Lett. Org. Chem. 2007; 4: 544
• 3 Okuhara T. Appl. Catal., A. 2001; 63
• 4 Dolbecq A, Dumas E, Mayer CR, Mialane P. Chem. Rev. 2010; 110: 6009
• 5 Izumi Y, Hasebe R, Urabe K. J. Catal. 1983; 84: 402
• 6 Rocchiccioli-Deltcheff C, Amirouche M, Herve G, Fournier M, Che M, Tatibouet JM. J. Catal. 1990; 126: 591
• 7 Edwards JC, Thiel CY, Benac B, Knifton JF. Catal. Lett. 1998; 51: 77
• 8 Lopez-Salinas E, Hernandez-Cortez JG, Schifter L, Torres-Garcia E, Navarrete J, Gutierrez-Carrillo A, Lopez T, Lottici PP, Bersani D. Appl. Catal. A. 2000; 193: 215
• 9 Rafiee E, Shahbazi F. J. Mol. Catal. A. Chem. 2006; 250: 57
• 10 Heravi MM, Sadjadi S. J. Iran. Chem. Soc. 2009; 6: 1
• 11 Clatworthy AE, Pierson E, Hung DT. Nat. Chem. Biol. 2007; 3: 541
• 12 Lee YM, Almqvist F, Hultgren SJ. Curr. Opin. Pharmacol. 2003; 3: 513
• 13 Aberg V, Almqvist F. Org. Biomol. Chem. 2007; 5: 1827
• 14 Pinkner JS, Remaut H, Buelens F, Miller E, Aberg V, Pemberton N, Hedenström M, Larsson A, Seed P, Waksman G, Hultgren SJ, Almqvist F. Proc. Natl. Acad. Sci. U.S.A. 2006; 103: 17897
• 15 Rawson JM, Winpenny RE. P. Coord. Chem. Rev. 1995; 139: 313
• 16 Yavari I, Souri S. Synlett 2007; 2969
• 17 Pathak S, Kundu A, Pramanik A. Tetrahedron Lett. 2012; 53: 3030
• 18 Ghosez L, Jnoff E, Bayard P, Sainte F, Beaudegnies R. Tetrahedron 1999; 55: 3387
• 19 Gibson KR, Hitzel L, Mortishire-Smith RJ, Gerhard U, Jelley RA, Reeve AJ, Rowley M, Nadin A, Owens AP. J. Org. Chem. 2002; 67: 9354
• 20a Samzadeh-Kermani A. Monatsh. Chem. 2014; 145: 611
• 20b Samzadeh-Kermani A. Synlett 2014; 25: 1839
• 20c Samzadeh-Kermani A. Synlett 2015; 26: 643
• 21 Catalyst Preparation The heteropolyacids were prepared by a hydrothermal synthesis method.²² As an example H₄PMo₁₂O₄₀ was prepared according to the following procedure: A mixture of of phosphoric acid (0.98 g) and of molydenum trioxide (14.4 g) was suspended in distilled H₂O (150 mL) and the mixture stirred for 6 h at 80 °C. After cooling to 20 °C and removal of insoluble molybdates, the heteropolyacid solution was evaporated and dried at 85 °C for 24 h to give orange crystals. Silica-supported HPA was prepared by the standard literature procedure.²³ A mixture of silica (Davisil^TM, 200–425 mesh, 150 Å) and HPA in H₂O–i-PrOH or MeCN was stirred at 25 °C for 24 h. The catalyst was washed with deionized H₂O and dried at 110 °C for 12 h. The supported catalyst was then calcinated at 200 °C for 3 h.
• 22 Tsigdinos GA, Hallada C. J. Inorg. Chem. 1968; 7: 437
• 23 Izumi Y, Hasebe R, Urabe K. J. Catal. 1983; 84: 402
• 24 Bardin BB, Bordawekar SV, Neurock M, Davis RJ. J. Phys. Chem. B. 1998; 102: 10819
• 25 Typical Procedure for the Preparation of 4 A mixture of acetylenic ester (1.0 mmol) and amine (1.0 mmol) was stirred at 0 °C for 20 min. A solution of malonate ester or malonic acid (3.0 mmol) in i-PrOH (3 mL) and HPA (0.1 mmol) were added in one portion. The resulting mixture was heated to the appropriate temperature for 7–12 h. After completion of reaction, the mixture was diluted with EtOAc (5 mL), and a sat. NH₄Cl solution (5 mL) was added. The mixture was stirred for additional 30 min, and two layers were separated. The aqueous layer was extracted with EtOAc (3 × 7 mL). The combined organic layers were dried over MgSO₄, filtered, and concentrated in vacuum. The residue was purified by chromatography (silica gel; hexane–EtOAc, 3:1) to give the pure product. Representative Analytical Data Dimethyl 1-tert-Butyl-1,6-dihydro-4-hydroxy-6-oxopyridine-2,3-dicarboxylate (4b) Colorless solid, mp 79–81.5 °C. Yield 0.25 g (87%). IR (KBr): ν_max = 3185, 1739, 1681, 1653, 1521, 1213 cm^–1. ¹H NMR (500.1 MHz, CDCl₃): δ = 1.52 (9 H, s, 3 CH₃), 3.61 (3 H, s, OCH₃), 3.82 (3 H, s, OCH₃), 6.06 (H, s, CH), 10.91 (H, s, OH). ¹³C NMR (125.7 MHz, CDCl₃): δ = 27.7 (3 CH₃), 53.0 (OCH₃), 53.2 (OCH₃), 59.3 (C), 99.2 (CH), 102.5 (C), 146.2 (C), 161.9 (C), 162.3 (C), 162.8 (C), 166.5 (C). MS: m/z (%) = 283 (2) [M⁺], 226 (13), 168 (67), 94 (21), 57 (100). Anal. Calcd for C₁₃H₁₇NO₆ (283.28): C, 55.12; H, 6.05; N, 4.94. Found: C, 55.23; H, 6.12; N, 4.92. Dimethyl 1,6-Dihydro-4-hydroxy-6-oxo-1-phenylpyridine-2,3-dicarboxylate (4c) Colorless solid, mp 128–130 °C. Yield 0.25 g (81%). IR (KBr): ν_max = 3180, 1734, 1684, 1662, 1544, 1236 cm^–1. ¹H NMR (500.1 MHz, CDCl₃): δ = 3.62 (3 H, s, OCH₃), 3.80 (3 H, s, OCH₃), 6.13 (H, s, CH), 7.03 (2 H, d, ³ J = 6.7 Hz), 7.13-7.28 (3 H, m), 10.65 (H, s, OH). ¹³C NMR (125.7 MHz, CDCl₃): δ = 53.1 (OCH₃), 53.2 (OCH₃), 97.3 (CH), 101.3 (C), 121.0 (2 CH), 123.8 (CH), 128.5 (2 CH), 135.4 (C), 146.1 (C), 162.1 (C), 162.4 (C), 164.8 (C), 166.9 (C). MS: m/z (%) = 303 (7) [M⁺], 226 (47), 168 (61), 110 (28), 94 (21), 77 (100). Anal. Calcd for C₁₅H₁₃NO₆ (303.27): C, 59.41; H, 4.32, N, 4.62. Found: C, 59.54; H, 4.45, N, 4.69.