Formamidine-Induced Translocative Rearrangement of 2-Pyrones to 2-Pyridone Analogues with a 1,5-Diketo Motif

Abstract

A new formamidine-induced translocative rearrangement of 2-pyrone analogues into 2-pyridone derivatives with a 1,5-diketo motif was identified. All the products were characterized by spectroscopic analysis. In addition, single-crystal X-ray structural studies of two molecules were performed.

Key words

ring transformation - rearrangement - pyrones - pyridones - diketones - medicinal chemistry

Publication History

Received: 26 November 2022

Accepted after revision: 21 January 2023

Accepted Manuscript online:
21 January 2023

Article published online:
14 March 2023

• References and Notes

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• 16 Compounds 2a–g; General Procedure Formamidine acetate (0.45 g, 4.35 mmol) and KOH (0.83 g, 14.5 mmol) were dissolved in anhyd DMF, and the resulting mixture was stirred for 10–15 min under N₂. The appropriate pyrancarboxamide 1a–g (1 g, 2.9 mmol) was added and the resulting mixture was stirred at rt for 6–8 h. When the reaction was complete [TLC; R_f = 0.5 (30% EtOAc–hexane)], the mixture was poured into ice-cooled water and the precipitate was collected by filtration. The filtrate, which contained some product, was extracted with EtOAc (3 × 20 mL), and the organic layer was dried (Na₂SO₄) and concentrated under reduced pressure. The precipitate and the extracted crude from the organic layer were combined and then purified by column chromatography (silica gel, EtOAc–hexane). 5-Benzoyl-4-(methylsulfanyl)-2-oxo-N-phenyl-1,2-dihydropyridine-3-carboxamide (2a) White powder; yield: 70%; mp 235–238 ℃; IR (KBr): 1658 (C=O), 3089 (NH) cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 2.19 (s, 3 H, SMe), 7.02–7.06 (m, 1 H, ArH), 7.28–7.32 (m, 2 H, ArH), 7.51–7.56 (m, 3 H, ArH), 7.62–7.67 (m, 3 H, ArH), 7.76–7.78 (m, 2 H, ArH), 10.42 (s, 1 H, NH), 12.32 (s, 1 H, NH). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 18.0, 119.5, 120.1, 124.9, 129.4, 129.5, 129.9, 130.2, 134.5, 137.0, 138.5, 139.2, 150.2, 159.6, 163.9, 193.5. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₀H₁₇N₂O₃S: 365.0954; found: 365.0933. 5-Benzoyl-N-(3-methylphenyl)-4-(methylsulfanyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (2b) Yellow powder; yield: 75%; mp 165–167 ℃. IR (KBr): 1666 (C=O), 3332 (NH) cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 2.19 (s, 3 H, SMe); 2.25 (s, 3 H, Me); 6.85–6.87, (m, 1 H, ArH); 7.15–7.19 (m, 1 H, ArH); 7.39–7.41 (m, 1 H, ArH); 7.49–7.56 (m, 4 H, ArH); 7.63–7.67 (m, 1 H, ArH); 7.76–7.78 (m, 2 H, ArH), 10.36 (s, 1 H, NH); 12.32 (s, 1 H, NH). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 18.2, 21.7, 116.8, 120.1, 124.7, 129.3, 129.9, 130.1, 133.9, 137.7, 138.5, 139.0, 139.5, 148.8, 159.4, 163.4, 192.6. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₁H₁₉N₂O₃S: 379.1111; found: 379.1085.