In-Water Synthesis of Quinazolinones from 1,1-Dichloro-2-nitroethene and Anthranilamides

Abstract

An efficient synthetic methodology was developed for direct formation of quinazolinones with 2-nitromethyl substituent via 1,1-dichloro-2-nitroethene and anthranilamides. This strategy provides an alternative for quinazolinones construction with merits of proceeding in water, easy purification, and no addition of catalysts.

Key words

synthetic methodology - quinazolinones - 2-nitromethyl - 1,1-dichloro-2-nitroethene - anthranilamides

• References and Notes

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• 28 Procedure for the Preparation of 2-(Nitromethyl)quinazolin-4(3H)-one (3a) 2-Aminobenzamide (136.1 mg, 1 mmol) and 1,1-dichloro-2-nitroethene (169.1 mg, 1.2 mmol) were added to 5 mL of water in a 25 mL round-bottom flask. Then stirred at 70 °C for 2.5 h, after completion, the product precipitated from the reaction mixture and can be easily separated by filtration to give the pure products; yellowish powder; yield 181 mg (88%); mp 165.9–166.4 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 10.82 (s, 1 H), 7.87 (d, J = 8.0 Hz, 1 H), 7.80–7.64 (m, 2 H), 7.43 (t, J = 7.2 Hz, 1 H), 5.67 (s, 2 H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 160.90, 138.73, 134.06, 133.53, 126.50 , 125.28, 116.35, 106.86, 78.68. ESI-HRMS: m/z calcd for C₉H₆N₃O₃ [M – H]^–: 204.0409; found: 204.0406.
• 29 Procedure for the Preparation of 2-(Nitromethyl)benzofuro[3,2-d]pyrimidin-4(3H)-one (3m) 3-Aminobenzofuran-2-carboxamide (176.1 mg, 1 mmol) and 1,1-dichloro-2-nitrothene (169.1 mg, 1.2 mmol) were added to 5 mL of water in a 25 mL round-bottom flask. Then stirred for 8 h at 10–15 °C, after completion, the mixture was purified by silica gel column chromatography (PE–EtOAc, 3:2) to give the pure product; yellowish powder; yield 98 mg (40%); mp 183.0–183.5 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 11.49 (s, 1 H), 7.95 (d, J = 7.6 Hz, 1 H), 7.71 (d, J = 7.6 Hz, 1 H), 7.663–7.626 (m, 1 H), 7.497–7.462 (m, 1 H), 5.78 (s, 1 H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 160.62, 153.48, 129.57, 127.44, 124.30, 121.41, 120.57, 117.49, 112.15, 111.81, 78.32. HRMS (EI): m/z calcd for C₁₁H₇N₃O₄ ⁺: 245.0437; found: 245.0438.
• 30 Procedure for the Preparation of N-[2-(3-Methyl-4-oxo-3,4-dihydroquinazolin-2-yl)phenyl]-2-nitroacetamide (3o) 2-Amino-N-methylbenzamide (150.1 mg, 1 mmol) and 1,1-dichloro-2-nitroethene (169.1 mg, 1.2 mmol) were added to 2 mL of water in a 10 mL round-bottom flask. Then stirred for 4 h at 10 °C, after completion, the mixture was purified by silica gel column chromatography (CH₂Cl₂–EtOAc, 9:2) to give the pure product; yellowish powder; yield 42 mg (25%); mp 180.5–181.2 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 10.19 (s, 1 H), 8.20 (d, J = 6.8 Hz, 1 H), 7.88–7.79 (m, 2 H), 7.67 (d, J = 8.0 Hz, 1 H), 7.56–7.60 (m, 3 H), 7.39 (t, J = 7.6 Hz, 1 H), 5.42 (s, 2 H), 3.27 (s, 3 H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 161.70, 160.67, 153.62, 147.19, 134.12, 134.06, 130.29, 129.62, 128.48, 127.19, 126.90, 126.01, 125.61, 124.13, 120.62, 78.71, 32.74. HRMS (EI): m/z calcd for C₁₇H₁₄N₄O₄ ⁺: 338.1015; found: 338.1014.
• 31 CCDC 1455026 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.