Synlett 2003(10): 1443-1446
DOI: 10.1055/s-2003-40827
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

One-Pot Synthesis of Pyridines or Pyrimidines by Tandem Oxidation-Heteroannulation of Propargylic Alcohols

Mark C. Bagley*, David D. Hughes, Halima M. Sabo, Paul H. Taylor, Xin Xiong
Department of Chemistry, Cardiff University, PO Box 912, Cardiff, CF10 3TB, UK
Fax: +44(29)20874030; e-Mail: Bagleymc@cf.ac.uk;
Further Information

Publication History

Received 5 June 2003
Publication Date:
24 July 2003 (online)

Abstract

Pyridines and pyrimidines are prepared in a single step from propargylic alcohols by in situ oxidation with o-iodoxybenzoic acid or manganese dioxide and reaction with enamines or amidines, respectively, under either thermal or microwave-assisted conditions in a new one-pot tandem oxidation-heteroannulation procedure. The reaction of α β-ketoester, propargylic alcohol and ammonium acetate, with in situ oxidation, constitutes a highly facile three-component reaction for the synthesis of pyridines that accomplishes four distinct synthetic operations in one-pot, good yield and with total regiocontrol.

    References

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9

Typical Procedure for the One-Pot Synthesis of Pyrimidines 4. A mixture of 1-phenyl-2-propyn-1-ol (1a) (0.13 g, 1.0 mmol), benzamidine hydrochloride salt (2a˙HCl) (0.19 g, 1.2 mmol), Na2CO3 (0.25 g, 2.4 mmol) and activated MnO2 (0.87 g, 10 mmol) in acetonitrile (5 mL) was irradiated for 40 min in a self-tunable CEM microwave synthesizer at 120 °C (initial power 90 W) and then allowed to cool. The solution was filtered through Celite® and evaporated in vacuo. Purification by flash chromatography on silica gave pure 2,4-diphenylpyrimidine (3a) [8] as a pale yellow solid (0.19 g, 84%).

12

Typical Procedure for the One-Pot Synthesis of Pyridines 6 from Enamines 5. A solution of IBX (0.56 g, 2.0 mmol) in DMSO-HOAc (5:1) (18 mL) was stirred at 65 °C until homogeneous. A solution of 1-phenyl-2-propyn-1-ol (1a) (0.26 g, 2.0 mmol) and ethyl β-aminocrotonate (5a) (0.13 g, 1.0 mmol) in DMSO (1 mL) was added and the resulting solution was stirred at 65 °C overnight. Water (10 mL) was added and the mixture was stirred for 10 min, allowed to cool, diluted with water (40 mL) and extracted with EtOAc (2 × 30 mL). The organic extracts were combined, washed sequentially with sat. aq NaHCO3 solution (20 mL) and brine (20 mL), dried (Na2SO4) and evaporated in vacuo. Purification by flash chromatography on silica gave pure ethyl 2-methyl-6-phenylpyridine-3-carboxylate (6a) [5a] as a pale yellow solid (169 mg, 70%).

13

Typical Procedure for the One-Pot Synthesis of Pyridines 6 from β-Ketoesters 7. A solution of ethyl acetoacetate (7a) (39 mg, 0.3 mmol), 1-(4-chloro-phenyl)prop-2-yn-1-ol (1d) [5a] (100 mg, 0.6 mmol), ammonium acetate (0.46 g, 6.0 mmol)) and activated MnO2 (0.52 g, 6.0 mmol) in toluene-glacial acetic acid (5:1)
(5 mL) was heated at reflux overnight. The mixture was allowed to cool, filtered through Celite®, partitioned between sat. aq NaHCO3 solution (30 mL) and EtOAc
(30 mL) and the aqueous layer was further extracted with EtOAc (20 mL). The combined organic layers were washed sequentially with sat. aq NaHCO3 solution (20 mL) and brine (20 mL), dried (Na2SO4) and evaporated in vacuo. Purification by flash chromatography on silica gave pure pyridine 6d [5a] as a pale yellow solid (80 mg, 96%).