A Novel One-Pot Rearrangement Reaction of 2,3-Epoxydiaryl Ketones: Synthesis of (±)-5,5-Disubstituted Imidazolones and 5,5-Disubstituted Hydantoins

Abstract

A novel one-pot rearrangement reaction, involving ­sequential epoxide rearrangement, condensation, cyclization and phenyl migration took place when 2,3-epoxydiphenyl ketones were treated with guanidine hydrochloride or urea in the presence of a base like sodium hydride and new type of imidazolone derivatives were obtained in good to excellent yields.

one-pot - epoxydiphenyl ketones - rearrangement - guanidine - imidazolone

References and Notes

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11

General Procedure for Preparation for 3,5-Disubstituted Imidazolones: Typical experimental procedure for synthesis of 3,5-disubstituted imidazolones as exemplified for 2a. Guanidine hydrochloride (95.5 mg, 1 mmol) was added to a solution of 2,3-epoxydiphenyl ketone (334 mg, 1 mmol) in anhyd THF (10 mL). To this was added NaH (48 mg, 2 mmol) at r.t. After 30 min, the reaction mixture was stirred at reflux temperature for 5 h; TLC analysis indicated that the reaction was complete. The reaction mixture was filtered, solvent was removed by rotatory evaporator and the residue passed through a silica gel column (CHCl₃-MeOH) afforded 2a (315 mg, 72%) as a white solid; mp 281-284 °C. ¹H NMR (600 MHz, DMSO-d ₆): δ = 2.97 (d, J = 13.2 Hz, 1 H), 3.11 (d, J = 13.2 Hz, 1 H), 3.57 (s, 3 H, OCH₃), 3.65 (s, 6 H, 2 × OCH₃), 3.72 (s, 3 H, OCH₃), 6.41 (s, 2 H), 6.89 (d, J = 9.0 Hz, 2 H), 7.42 (d, J = 9.0 Hz, 2 H), 8.34 (s, 1 H). ¹³C NMR (125 MHz, DMSO-d ₆): δ = 44.8, 55.8 56.3, 60.6, 70.6 108.2, 114.0, 127.4, 132.4, 33.8, 136.7, 152.6, 158.9, 171.2, 189.0. IR (KBr): 3346.2, 32.2, 1698.2, 1645.4, 1593.4, 1299.3, 1127.9, 828.4 cm^-1. MS (ESI): m/z = 386.2 [M + H], 408.0 [M + Na]. Anal. Calcd for C₂₀H₂₃N₃O₅: C, 62.32; H, 6.01; N, 10.90. Found: C, 62.13; H, 6.15; N, 11.20.
2b: White solid; mp 298-302 °C. ¹H NMR (200 MHz, DMSO-d ₆): δ = 2.99 (d, J = 13.4 Hz, 1 H), 3.21 (d, J = 13.4 Hz, 1 H), 3.67 (s, 3 H, OCH₃), 3.72 (s, 3 H, OCH₃), 6.73 (d, J = 8.9 Hz, 2 H), 6.9 (d, J = 8.8 Hz, 2 H), 7.03 (d, J = 9.1 Hz, 2 H), 7.41 (d, J = 8.8 Hz, 2 H), 8.20 (s, 1 H). ¹³C NMR (125 MHz, DMSO-d ₆): δ = 42.6, 54.8, 70.5, 113.1, 125.5, 127.0, 127.9, 128.0, 131.2, 141.0, 157.9, 170.2, 187.9. IR (KBr): 3347.6, 1698.3, 1652.2, 1613.4, 1513.4, 1257.6, 1033.7, 837.6 cm^-1. MS (ESI): m/z = 325.2 [M + H]. Anal. Calcd for C₁₈H₁₉N₃O₃: C, 66.45; H, 5.89; N, 12.91. Found: C, 66.71; H, 6.05; N, 12.73.
3a: White solid; mp 238-241 °C. ¹H NMR (600 MHz, DMSO-d ₆): δ = 2.88 (d, J = 13.5 Hz, 1 H), 3.35 (d, J = 13.5 Hz, 1 H), 3.59 (s, 3 H, OCH₃), 3.69 (s, 6 H, 2 × OCH₃), 3.73 (s, 3 H, OCH₃), 6.48 (s, 2 H), 6.95 (d, J = 8.9 Hz, 2 H), 7.51 (d, J = 8.9 Hz, 2 H), 8.51 (s, 1 H), 10.46 (s, 1 H). ¹³C NMR (125 MHz, DMSO-d ₆): δ = 44.9, 55.8, 56.4, 60.5, 68.6, 108.4, 114.4, 127.5, 131.1, 132.0, 137.2, 152.9, 156.8, 159.6, 176.6. IR (KBr): 3444.1, 3342.0, 1766.7, 1709.4, 1586.6, 1241.9, 1129.9, 839.2 cm^-1. MS (ESI): m/z = 385 [M - H], 409.2 [M + Na]. Anal. Calcd for C₂₀H₂₂N₂O₆: C, 62.16; H, 5.73; N, 7.25. Found: C, 62.13; H, 6.14; N, 7.36.
3b: White solid; mp 204-207 °C. ¹H NMR (200 MHz, DMSO-d ₆): δ = 2.96 (d, J = 13.5 Hz, 1 H), 3.34 (d, J = 13.5 Hz, 1 H), 3.74 (s, 3 H, OCH₃), 6.96 (d, J = 8.8 Hz, 2 H), 7.16 (m, 4 H), 7.51 (d, J = 8.8 Hz, 2 H), 8.59 (s, 1 H). ¹³C NMR (125 MHz, DMSO-d ₆): δ = 43.0, 55.6, 70.5, 113.9, 114.6, 114.8, 127.1, 132.4, 132.5, 133.5, 158.6, 160.5, 160.6, 162.6, 170.9, 188.6. IR (KBr): 3373.9, 1757.5, 1713.4, 1608.3, 1511.7, 1403.6, 1257.7, 1225.7, 845.8 cm^-1. MS (ESI): m/z = 315 [M + H]. Anal. Calcd for C₁₇H₁₅FN₂O₃: C, 64.96; H, 4.81; N, 8.91. Found: C, 65.08; H, 5.09; N, 8.97.

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