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.

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 

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] .

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