Synthesis of Symmetrically and Unsymmetrically Substituted N,N′-Diaryl­imidazolin-2-ones by Copper-Catalyzed Arylamidation under Microwave-Assisted­ and Conventional Conditions

Abstract

A convenient synthesis of unsymmetrically substituted N,N′-diarylimidazolin-2-ones is reported. Starting from 2,2-dimethoxyethylamine, the first aryl group was introduced by reaction with arylisocyanate and subsequent cyclization to afford N-arylimidazolin-2-ones. The second arylation step was then accomplished by microwave-assisted copper-catalyzed arylamidation of the N-arylimidazolin-2-ones with a variety of aryliodides and arylbromides to give unsymmetrically substituted N,N′-diarylimidazolin-2-ones. Symmetrically substituted N,N′-diarylimidazolin-2-ones could also be prepared from imidazolin-2-one in a two-fold copper-catalyzed arylamidation, however, the nature of the substrate limits the use of this reaction.

Key words

amination - arylation - copper - homogeneous catalysis - heterocycles

References

• 1a Muchmore SW. Souers AJ. Akritopoulou-Zanze I. Chem. Biol. Drug Design.  2006,  67:  174 
• 1b Schwink L, Stengelin S, Gossel M, Boehme T, Hessler G, Rosse G, and Walser A. inventors; PCT Int. Appl. WO  2004011438.  ; Chem. Abstr. 2004, 140, 163866
• 1c Wilde RG, Takasugi JJ, Hwang S, Welch EM, and Chen G. inventors; PCT Int. Appl. WO  2004009558.  ; Chem. Abstr. 2004, 140, 146137
• 1d Himmelsbach F, Pieper H, Austel V, Linz G, Weisenberger J, Eisert W, and Mueller T. inventors; U.S. Patent US  5852192.  ; Chem. Abstr. 1999, 130, 665504
• 1e Felix RA. inventors; U.S. Patent US  4724261.  ; Chem. Abstr. 1988, 108, 167475
• 2a Tanaka K, and Doi M. inventors; Japan Patent JP  4343365.  ; Chem. Abstr. 1993, 118, 263846
• 2b Klüpfel KW, Stumpf HR, Behmenburg H, Neugebauer W, Süs O, and Tomanek M. inventors; German Patent Appl. DE  1060713.  ; Chem. Abstr. 1961, 55, 110603
• 3a Brazier SA. McCombie H. J. Chem. Soc.  1912,  101:  2352 
• 3b Schönherr HJ. Wanzlick HW. Chem. Ber.  1970,  103:  1037 
• 4 Watabe Y, Kondo T, and Watabe Y. inventors; Japan Patent JP  5004970.  ; Chem. Abstr. 1993, 118, 254934
• 5 Lozanova K. Kalcheva V. Simov D. Chem. Heterocycl. Compd. (Engl. Transl.)  1988,  24:  1129 
• 6 Wendeborn S. Winkler T. Foisy I. Tetrahedron Lett.  2000,  41:  6387 
• 7a Mann G. Hartwig JF. Driver MS. Fernández-Rivas C. J. Am. Chem. Soc.  1998,  120:  827 
• 7b Yang BH. Buchwald SL. J. Organomet. Chem.  1999,  576:  125 
• 7c Shekhar S. Ryberg P. Hartwig JF. Mathew JS. Blackmond DG. Strieter ER. Buchwald SL. J. Am. Chem. Soc.  2006,  128:  3584 
• 8a Ullmann F. Ber. Dtsch. Chem. Ges.  1903,  36:  2382 
• 8b Goldberg I. Ber. Dtsch. Chem. Ges.  1906,  39:  1691 
• 8c Sugahara M. Ukita T. Chem. Pharm. Bull.  1997,  45:  719 
• 8d Strieter ER. Blackmond DG. Buchwald SL. J. Am. Chem. Soc.  2005,  127:  4120 
• 8e Haider J. Kunz K. Scholz U. Adv. Synth. Catal.  2004,  346:  717 
• 8f Beletskaya IP. Cheprakov AV. Coord. Chem. Rev.  2004,  248:  2337 
• For examples of palladium-catalyzed reactions with urea, see:
• 9a Artamkina GA. Sergeev AG. Beletskaya IP. Tetrahedron Lett.  2001,  42:  4381 
• 9b Sergeev AG. Artamkina GA. Beletskaya IP. Tetrahedron Lett.  2003,  44:  4719 
• For examples of copper-catalyzed reactions with urea, see:
• 9c Buchwald SL, Klapars A, Antilla JC, Job GE, Wolter M, Kwong FY, Nordmann G, and Hennessy EJ. inventors; PCT Int. Appl. WO  02085838.  ; Chem. Abstr. 2002, 137, 352492
• 9d Nandakumar MV. Tetrahedron Lett.  2004,  45:  1989 
• 9e Trost BM. Styles DT. Org. Lett.  2005,  7:  2117 
• For examples with benzimidazolinones, see:
• 9f Ward RE. Meyer TY. Macromolecules  2003,  36:  4368 
• 10 Yang GX. Chang LL. Truong Q. Doherty GA. Magriotis PA. de Laszlo SE. Li B. MacCoss M. Kidambi U. Egger LA. McCauley E. Van Riper G. Mumford RA. Schmidt JA. Hagmann WK. Bioorg. Med. Chem. Lett.  2002,  12:  1497 
• 11a Mann G. Hartwig JF. Driver MS. Fernández-Rivas C. J. Am. Chem. Soc.  1998,  120:  827 
• 11b Grasa GA. Viciu MS. Huang J. Nolan SP. J. Org. Chem.  2001,  66:  7729 
• 11c Vargas VC. Rubio RJ. Hollis TK. Salcido ME. Org. Lett.  2003,  5:  4847 
• 11d Klapars A. Antilla JC. Huang X. Buchwald SL. J. Am. Chem. Soc.  2001,  123:  7727 
• 11e Antilla JC. Baskin JM. Barder TE. Buchwald SL. J. Org. Chem.  2004,  69:  5578 
• 12 Kiyomori A. Marcoux J.-F. Buchwald SL. Tetrahedron Lett.  1999,  40:  2657 
• For reviews, see:
• 13a Nilsson P. Olofsson K. Larhed M. Top. Curr. Chem.  2006,  266:  103 
• 13b Wan Y. Alterman M. Hallberg A. Synthesis  2002,  1597 
• 13c Yadav LDS. Yadav BS. Rai VK. Synthesis  2006,  1868 
• 13d Lange JHM. Hofmeyer LJF. Hout FAS. Osnabrug SJM. Verveer PC. Kruse CG. Feenstra RW. Tetrahedron Lett.  2002,  43:  1101 
• 13e For a review involving urea, see: Wannberg J. Dallinger D. Kappe CO. Larhed M. J. Comb. Chem.  2005,  7:  574 
• 14 Forrest TP. Dauphinee GA. Chen FMF. Can. J. Chem.  1974,  52:  2725 
• 16 Marckwald W. Ber. Dtsch. Chem. Ges.  1892,  25:  2354 
• 17 Duchinsky R. Dolan LA. J. Am. Chem. Soc.  1946,  68:  2351 
• 18 Golovko VV. Statsenskaya AI. Baskakov YA. Putsykin YG. Chem. Heterocycl. Compd.  1986,  22:  1084 
• 19 Cortes S. Liao Z.-K. Watson D. Kohn H. J. Med. Chem.  1985,  28:  601 

15

Leadbeater has shown that when the Powermax cooling function is used, the standard IR sensor does not give accurate temperature measurements. In DMSO at a nominal temperature of 100 °C, the actual temperature was 20 °C higher, whereas in hexane, the actual temperature was 20 °C lower. We have used dioxane so the respective effects could level out, however the real temperature could vary by about ±20 °C from the given value in the case of the experiments reported in Table [3] .