Acetylenic Ester Promoted Tandem Ring Opening of Dienyl Thiazolidin-4-ones and Cyclizations: A Facile and Chemoselective Synthesis of Functionalized Pyridine-2-carboxylates

Abstract

Acetylenic ester promoted ring opening of dienyl-thiazolidin-4-ones and subsequent electrocyclization affords 5-phenyl-6-aryl pyridine-2-carboxylates in good to excellent yields.

Key words

pyridine-2-carboxylate - dienyl-thiazolidin-4-one - acetylenic ester - cyclization - 5,6-diarylpyridine

• References and Notes

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• 24 General procedure for the preparation of alkyl 6-(aryl)-5-phenylpyridine-2-carboxylate (3a–h): To a solution of compound 1 (0.1 g, 0.2544 mmol, 1 equiv) in xylene (10 mL), DMAD (3 equiv) was added and the reaction mixture was heated to 170 °C for 16 h. Progress of the reaction was monitored by TLC taking 1 as the limiting reactant. After completion of reaction, the solvent was removed under reduced pressure. The crude product was purified by column chromatography, using a 20–25% mixture of ethyl acetate in hexane as eluent to obtain 3 as the pure product.
• 25 Methyl 6-(2,5-dimethylphenyl)-5-phenylpyridine-2-carboxylate (3a): White solid; ¹H NMR (300 MHz, CDCl₃): δ = 1.83 (s, 3 H), 2.25 (s, 3 H), 4.00 (s, 3 H), 6.91 (d, J = 7.8 Hz, 1 H), 6.98 (dd, J = 7.8, 1.2 Hz, 1 H), 7.04 (s, 1 H), 7.10–7.15 (m, 2 H), 7.20–7.23 (m, 3 H), 7.88 (d, J = 7.8 Hz, 1 H), 8.19 (d, J = 7.8 Hz, 1 H); ¹³C NMR (CDCl₃): δ = 19.1, 20.8, 52.9, 123.7, 127.7, 128.1, 128.9, 129.1, 129.9, 130.9, 132.6, 134.9, 138.4, 139.0, 140.1, 146.2, 158.6, 166.0; LRMS: m/z = 318.2 [M+1]; HRMS: m/z calcd for C₂₁H₂₀NO₂ [MH⁺]: 318.1494; found: 318.1490.
• 26 Ethyl 6-(2,5-dimethylphenyl)-5-phenylpyridine-2-carboxylate (3e): Yellow solid; ¹H NMR (300 MHz, CDCl₃): δ = 1.25 (t, J = 7.8 Hz, 3 H), 1.85 (s, 3 H), 2.22 (s, 3 H), 4.23 (q, J = 7.8 Hz, 2 H), 6.94–7.05 (m, 3 H), 7.13–7.25 (m, 5 H), 7.89 (d, J = 7.5 Hz, 1 H), 8.16 (d, J = 7.5 Hz, 1 H); ¹³C NMR (CDCl₃): δ = 15.5, 18.9, 20.8, 60.5, 123.7, 127.8, 128.3, 128.7, 129.9, 130.4, 131.0, 132.6, 135.2, 138.4, 139.1, 139.9, 146.2, 158.4, 165.7; LRMS: m/z = 332 [M+1]; HRMS: m/z calcd for C₂₂H₂₂NO₂ [MH⁺]: 332.1651; found: 332.1655.