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.

Key words

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

References and Notes

• 1a Trost BM. Science  1991,  254:  1471 
• 1b Trost BM. Angew. Chem., Int. Ed. Engl.  1995,  34:  259 
• 1c Trost BM. Transition Metals for Organic Synthesis   Beller M. Bolm C. Wiley-VCH; Weinheim: 1998.  p.1 
• 2a Weber L. Curr. Med. Chem.  2002,  9:  1241 
• 2b Bienayme H. Hulme C. Oddon G. Schmidt P. Chem. Eur. J.  2000,  6:  3321 
• 2c Zhu J. Eur. J. Org. Chem.  2003,  1133 
• 2d Orru RVA. de Greef M. Synthesis  2003,  1471 
• 2e Domling A. Ugi I. Angew. Chem. Int. Ed.  2000,  39:  3168 
• 2f Lee D. Sello JK. Schreiber SL. Org. Lett.  2000,  2:  709 
• 3a Greenlee WJ. Siegl PKS. Ann. Rep. Med. Chem.  1992,  27:  59 
• 3b Shilcrat SC. Mokhallalati MK. Fortunak JMD. Pridgen LN. J. Org. Chem.  1997,  62:  8449 
• 3c Rizzi JP. Nagel AA. Rosen T. McLean S. Seeger T. J. Med. Chem.  1990,  33:  2721 
• 3d Shapiro G. Gomez-Lor B. J. Org. Chem.  1994,  59:  5524 
• 3e Adams JL. Boehm JC. Kassis S. Gorycki PD. Webb EF. Hall R. Sorenson M. Lee JC. Ayrton A. Griswold DE. Gallagher TF. Bioorg. Med. Chem. Lett.  1998,  8:  3111 
• 4a Laufer S. Wagner G. Kotschenreuther D. Angew. Chem. Int. Ed.  2002,  41:  2290 
• 4b Sarshar S. Zhang C. Moran EJ. Krane S. Rodarte JC. Benbatoul KD. Dixon R. Mjalli AMM. Bioorg. Med. Chem.  2000,  10:  2599 
• 4c Zhang C. Sarshar S. Moran EJ. Krane S. Rodarte JC. Benbatoul KD. Dixon R. Mjalli AMM. Bioorg. Med. Chem.  2000,  10:  2603 
• 4d Bilodeau MT. Cunningham AM. J. Org. Chem.  1998,  63:  2800 
• 5 Lamothe M. Lannuzel M. Perez M. J. Comb. Chem.  2002,  4:  73 
• 6 Kirk-Othmer Encyclopedia of Chemical Technology   3rd ed., Vol. 12:  John Wiley and Sons; New York: 1983.  p.692-700  
• 7a Faghihi K. Mirsamie A. Sangi R. Eur. Polym. J.  2002,  39:  247 
• 7b Faghihi K. Zamani K. Mallakpour S. Iranian Polym. J.  2002,  11:  339 
• 8a For an overview on the synthesis of imidazoles, see: Ebel K. In Houben-Weyl: Methoden der Organischen Chemie, Hetarene III, 1H-Imidazole   Schaumann E. Georg Thieme Verlag; Stuttgart, New York: 1994.  p.1-215  
• For recent imidazole syntheses, see:
• 8b Henkel B. Tetrahedron Lett.  2004,  45:  2219 
• 8c Sezen B. Sames D. J. Am. Chem. Soc.  2003,  125:  5274 
• 8d Tan KL. Bergman RG. Ellmann JA. J. Am. Chem. Soc.  2002,  124:  13964 
• 8e Faghihi K. Zamani K. Mobinikhaledi A. Turk. J. Chem.  2004,  28:  345 
• 8f Mahmoodi NO. Khodace Z. Mendeleev Commun.  2004,  304 
• 9a Payne GB. J. Am. Chem. Soc.  1959,  81:  4901 
• 9b Payne GB. J. Org. Chem.  1959,  24:  2048 
• 9c Adams R. Johnson JR. Wilcox CF. Laboratory Experiments in Organic Chemistry   5th ed.:  The Macmillan Company; New York: 1963.  p.381 
• 10 Bhat BA. Dhar KL. Puri SC. Saxena AK. Shanmugavel M. Qazi GN. Bioorg. Med. Chem. Lett.  2005,  15:  3177 
• 12a Cleeland R, Grunberg E, Leimgruber W, and Weigele M. inventors; US Patent,  4045487.  ; Chem. Abstr. 1977, 87, 167872
• 12b Baranes RP. Chigbo FE. J. Org. Chem.  1963,  28:  1644 

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.