Facile Route for Novel Quinazolinone-Fused Azauracils through Cyclodesulfurization of Thioquinazolinones

Abstract

An efficient, novel, short, and high-yielding one-pot protocol for the synthesis of diverse quinazolinone-fused azauracil heterocycles through cyclodesulfurization and intramolecular cyclization of thioquinazolinone using silver cyanate is described.

Key words

thioquinazolinone - cyclodesulfurization - benzotriazole - cyclization - fused heterocycles

References and Notes

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10

Typical Experimental Procedure for the Synthesis of Quinazolinone-Fused Azauracil Compounds 3a-h
Diverse 2-thioxo-2,3-dihydroquinazolin-4 (1H)-ones 2a-h were obtained in good yield by the one-pot reaction of anthranilic acid/esters, primary amines, and bis(benzo-triazol-1-yl)methanethione in presence of the amidine base as per ref. 7. Thioquinazolinone (2a, 0.5 g 1.96 mmol) was added in anhyd MeCN (8 mL) and stirred for 10 min then AgCNO (0.59 g, 3.93 mmol) was added in above solution. Solid precipitated out within 5 min and reaction mixture was further stirred for 30 min, where reaction mass turns into greenish color. Progress of reaction was monitored by TLC (25% EtOAc in n-hexane). After completion of reaction, product was filtered, dried, and subjected to column chromatography (25% EtOAc in n-hexane) to obtain pure white solid (90-95% yield).
Compound 3a: yield 91%; mp 160-162 ˚C. IR (KBr): ν_max = 3429 (NH), 1676, 1591, 1568, 1508 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 8.04 (d, J = 7.5 Hz, 1 H), 7.83 (t, J = 7.2 Hz, 1 H), 7.71 (d, J = 8.4 Hz, 1 H), 7.43 (m, 4 H), 6.77 (m, 2 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 166.10, 161.03, 145.95, 139.88, 134.52, 129.39, 129.16, 128.14, 128.04, 126.49, 124.01, 119.64 ppm. Anal. Calcd for C₁₆H₁₀N₄O₃: C, 62.74; H, 3.29; N, 18.29. Found: C, 62.51; H, 3.75; N, 18.88.
Compound 3b: yield 91%; mp 178-180 ˚C. IR (KBr): ν_max = 3431 (NH), 1669, 1596, 1569, 1511 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 11.02 (br s, 1 H, NH), 7.96 (d, J = 7.8 Hz, 2 H), 7.67 (t, J = 8.4 Hz, 2 H), 7.48 (d, J = 8.4 Hz, 1 H), 7.34 (t, J = 8.4 Hz, 1 H), 7.04 (t, J = 8.7 Hz, 2 H), 6.69 (s, 1 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 167.84, 162.0, 140.91, 134.79, 134.79, 133.17, 133.06, 130.66, 129.96, 126.84, 123.90, 123.41, 118.27 ppm. Anal. Calcd for C₁₉H₁₁N₅O₃S: C, 58.61; H, 2.85; N, 17.99. Found: C, 58.22; H, 3.01; N, 18.45.
Compound 3c: yield 91%; mp 187-188 ˚C. IR (KBr): ν_max = 3430, 1677, 1593, 1577, 1507 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 9.82 (br s, NH, 1 H), 8.42 (d, J = 9.0 Hz, 2 H), 8.23 (m, 2 H), 7.77 (t, J = 7.8 Hz, 1 H), 7.48 (d, J = 8.7 Hz, 1 H), 7.38 (m, 1 H), 7.15 (d, J = 8.7 Hz, 1 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 165.5, 159.90, 145.33, 143.27, 137.98, 133.80, 129.00, 125.60, 124.35, 122.55, 122.42, 114.37, 114.17, 110.53 ppm.
Compound 3d: yield 91%; mp 171-173 ˚C. IR (KBr): ν_max = 3433 (NH), 1677 (O=CN), 1622, 1529 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 8.35 (d, J = 8.7 Hz, 2 H), 7.99-7.89 (m, merged with J = 7.2 Hz, 2 H), 7.75 (d, J = 8.4 Hz, 1 H), 7.49 (d, J = 8.1 Hz, 2 H), 7.33 (t, J = 7.5 Hz, 1 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 165.10, 159.07, 145.90, 139.54, 135.41, 130.72, 130.27, 130.17, 127.27, 126.27, 126.10, 124.39, 124.34 ppm. Anal. Calcd for C₁₆H₉FN₄O₃: C, 59.26; H, 2.80; N, 17.28. Found: C, 59.93; H, 2.74; N, 17.97.