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Synlett 2008(15): 2348-2354  
DOI: 10.1055/s-2008-1078272
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

An Efficient Protocol for Multicomponent Stereoselective Synthesis of 3-Amino-2(1H)-pyridinones Using CeCl3˙7H2O/NaI as a Reaction Promoter

Lal Dhar S. Yadav*, Ritu Kapoor
Green Synthesis Lab, Department of Chemistry, University of Allahabad, Allahbad 211 002, India
Fax: +91(532)2460533; e-Mail: ldsyadav@hotmail.com;
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Publication History

Received 20 May 2008
Publication Date:
21 August 2008 (online)

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Abstract

An efficient and convenient diastereoselective synthesis of 3-amino-2(1H)-pyridinones by CeCl3˙7H2O/NaI-promoted [3+2+1] three-component coupling reactions of chalcones, 2-phen­yl-1,3-oxazolon-5-one, and amines is reported. The protocol involves sequential Michael addition, condensation, ring transformation, and acid hydrolysis. Operational simplicity, ambient temperature, high yields, and diastereoselectivity are the key features of the present synthetic protocol. The reaction is an excellent illustration of Ce(III)-catalyzed C-C and C-N bond formations in a one-pot procedure

Key words:

multicomponent reaction - Lewis acid - chalcones - heterocycles - stereoselective synthesis

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General Procedure for the Synthesis of 3-Benzamido-2 (1 H )-pyridinones 5 A mixture of 1,3-oxazolon-5-one 1 (5 mmol), chalcone 2 (5 mmol), amine 3 (5 mmol), CeCl3˙7H2O (1 mmol), and NaI (1 mmol) in EtOH (25 mL) was stirred at r.t. for 3-5 h. After completion of the reaction, as indicated by TLC (hexane-EtOAc, 8:2, v/v), the solvent was evaporated under reduced pressure, the residue thus obtained extracted with Et2O (3 × 15 mL). The extract was evaporated to leave the crude product which was recrystallized from EtOH to afford a distereomeric mixture (>96:<4; in the crude products the ratio was >94:6 as indicated by ¹H NMR spectroscopy). The product on second recrystallization from EtOH furnished analytically pure pale yellow crystal of a single diastereomer 4, which was assigned the trans stereochemistry on the basis of ¹H NMR spectra. Characterization Data for Representative Compounds Compound 7 (Ar¹ = Ar² = R = Ph): pale yellow crystals; yield 82%; mp 124-125 ˚C. IR (KBr): νmax = 3340, 3023, 1745, 1642, 1605, 1585, 1455, 755, 712 cm.-¹. ¹H NMR (400 MHz, DMSO-d 6 and D2O-TMS): δ = 3.99 (d, 1 H, J = 10.0 Hz, 3-H), 4.19 (dd, 1 H, J = 10.0, 5.9 Hz, 4-H), 5.93 (d, 1 H, J = 5.9 Hz, 5-H), 7.10-7.70 (m, 20 Harom). ¹³C NMR(100 MHz, DMSO-d 6): δ = 39.9, 59.0, 114.2, 117.6, 119.0, 120.1, 121.3, 124.0, 125.2, 126.4, 127.5, 128.5, 129.6, 130.8, 132.0, 133.1, 134.2, 135.5, 137.4, 143.4, 172.6, 174.2. MS (EI): m/z = 444 [M+]. Anal. Calcd for C30H24N2O2: C, 81.06; H, 5.44; N, 6.30. Found: C, 80.70; H, 5.74; N, 6.10.
Compound 7 (Ar¹ = 4-MeOC6H4; Ar² = R = Ph): pale yellow crystals; yield 80%; mp 133-134 ˚C. IR (KBr): 3340, 3021, 1742, 1640, 1600, 1582, 1400, 752, 710 cm.-¹. ¹H NMR (400 MHz, DMSO-d 6 and D2O-TMS): δ = 3.79 (s, 3 H, OMe), 4.01 (d, 1 H, J = 10.0 Hz, 3-H), 4.18 (dd, 1 H, J = 10.0, 5.9 Hz, 4-H), 5.99 (d, 1 H, J = 5.9 Hz, 5-H), 7.18-7.99 (m, 19 Harom). ¹³C NMR (100 MHz, DMSO-d 6): δ = 39.2, 56.0, 59.2, 114.0, 117.5, 119.2, 120.3, 122.4, 124.0, 125.1, 126.2, 127.3, 128.3, 129.4, 130.5, 131.6, 132.9, 134.0, 135.2, 137.5, 143.9, 172.9, 174.8. MS (EI):
m/z = 474 [M+]. Anal. Calcd for C31H26N2O3: C, 78.46; H, 5.52; N, 5.90. Found: C, 78.81; H, 5.30; N, 5.56.

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General Procedure for the Synthesis of 3-Amino-2 (1 H )-Pyridinone 4
Compound 5 (2.0 mmol) was refluxed in H2SO4-H2O (15 mL, 4:3, v/v) for 30 min in an oil bath. The reaction mixture was cooled, filtered, and the desired product 4 was precipitated by adding concentrated NH4OH (d = 0.88) under ice cooling and recrystallized from EtOH to afford an analytically pure sample of 4 (Table  [¹] ).
Characterization Data for Representative Compounds Compound 4 (Table  [²] , entry 1): pale yellow crystals; yield 90%; mp 135-134 ˚C. IR (KBr): 3342, 3011, 1699, 1608, 1540, 1430, 749, 703 cm-¹. ¹H NMR (400 MHz, DMSO-d 6 and D2O-TMS): δ = 3.96 (d, 1 H, J = 9.9 Hz, 3-H), 4.15 (dd, 1 H, J = 9.9, 5.9 Hz, 4-H), 5.90 (d, 1 H, J = 5.9 Hz, 5-H), 7.19-7.90 (m, 15 Harom). ¹³C NMR(100 MHz, DMSO-d 6 ): δ = 39.7, 58.5, 114.0, 120.0, 122.1, 125.0, 126.2, 127.4, 128.7, 129.8, 130.8, 131.9, 133.0, 134.7, 141.0, 143.0, 172.6. MS (EI): m/z = 340 [M+]. Anal. Calcd for C23H20N2O: C, 81.15; H, 5.92; N, 8.23. Found: C, 80.83; H, 5.62; N, 8.43.
Compound 4 (Table  [²] , entry 7): pale yellow crystals; yield 87%; mp 140-141 ˚C. IR (KBr): νmax = 3340, 3021, 1742, 1640, 1600, 1582, 1400, 752, 710 cm-¹. ¹H NMR (400 MHz, DMSO-d 6 and D2O-TMS): δ = 3.78 (s, 3 H, OMe), 3.98 (d, 1 H, J = 9.9 Hz, 3-H), 4.13 (dd, 1 H, J = 9.9, 5.9 Hz, 4-H), 5.92 (d, 1 H, J = 5.9 Hz, 5-H), 7.19-7.86 (m, 14 Harom). ¹³C NMR (100 MHz, DMSO-d 6 ): δ = 39.2, 55.6, 58.3, 114.1, 120.2, 122.0, 125.1, 126.3, 127.5, 128.5, 129.8, 130.9, 132.0, 133.6, 134.8, 141.2, 144.0, 172.4. MS (EI): m/z = 370 [M+]. Anal. Calcd for C24H22N2O2: C, 77.81; H, 5.99; N, 7.56. Found: C, 78.12; H, 6.29; N, 7.26.