Download PDF
Synlett 2011(5): 619-622  
DOI: 10.1055/s-0030-1259696
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Reaction between N-Isocyaniminotriphenylphosphorane, Aldimines, Meldrum’s Acid and Water: Diastereoselective Synthesis of 3,4-Disubstituted N-Aminopyrrolidine-2,5-diones

Mehdi Adib*a, Samira Ansaria, Hamid Reza Bijanzadehb
a School of Chemistry, University College of Science, University of Tehran, PO Box 14155-6455, Tehran, Iran
Fax: +98(21)66495291; e-Mail: madib@khayam.ut.ac.ir;
b Department of Chemistry, Tarbiat Modarres University, PO Box 14115-175, Tehran, Iran
Further Information

Publication History

Received 23 September 2010
Publication Date:
25 February 2011 (online)

    Permissions and Reprints All articles of this category

Abstract

A multicomponent synthesis of 3,4-disubstituted N-aminopyrrolidine-2,5-diones is described. A mixture of N-isocyan­iminotriphenylphosphorane, an aldimine and Meldrum’s acid undergoes an addition reaction under mild conditions in aqueous THF to produce 1-amino-4-aryl-2,5-dioxo-N ³-aryl-3-pyrrolidinecarboxamides diastereoselectively in good to excellent yields. ¹H NMR analysis showed that the two substituents on C-3 and C-4 ­positions of the obtained pyrrolidine-2,5-diones are trans.

Key words

N-isocyaniminotriphenylphosphorane - aldimines - Meldrum’s acid - 3,4-disubstituted N-aminopyrrolidine-2,5-diones - diastereoselective synthesis - multicomponent reactions

    References and Notes

  • 1 Hargreaves MK. Pritchard JG. Dave HR. Chem. Rev.  1970,  70:  439 
    CrossrefGoogle Scholar
  • 2 Galatina AI. Derkach LG. Kilimenchuk HD. Kondratyeva RV. Novikova NS. Jarovoy JK. Liq. Cryst.  2000,  27:  1229 
    CrossrefGoogle Scholar
  • 3a Malawska B. Curr. Top. Med. Chem.  2005,  5:  69 
    Google Scholar
  • 3b Kornet MJ. J. Pharm. Sci.  1983,  73:  405 
    Google Scholar
  • 3c Kaminski K. Obniska J. Acta Pol. Pharm. Drug Res.  2008,  65:  457 
    Google Scholar
  • 4a Brière JF. Charpentier P. Dupas G. Quèguiner G. Bourguignon J. Tetrahedron  1997,  53:  2075 
    Google Scholar
  • 4b Reddy PY. Kondo S. Toru T. Ueno Y. J. Org. Chem.  1997,  62:  2652 
    Google Scholar
  • 4c King RW. Tetrahedron Lett.  1981,  22:  2837 
    Google Scholar
  • 4d Reuschling D. Mitzlaff M. Kühlein K. Tetrahedron Lett.  1976,  4467 
    Google Scholar
  • 5 Obrecht D. Abrecht C. Altorfer M. Bohdal U. Grieder A. Kleber M. Pfyffer P. Müller K. Helv. Chim. Acta  1996,  79:  1315 
    CrossrefGoogle Scholar
  • 6 Abell AD. Oldham MD. J. Org. Chem.  1997,  62:  1509 
    CrossrefGoogle Scholar
  • 7 Whomsley R. Smith HJ. Nicholls PJ. Nazareth W. Ahmadi M. J. Enzyme Inhib. Med. Chem.  1993,  6:  317 
    CrossrefGoogle Scholar
  • 8 Fredenhagen A. Tamura SY. Kenny PTM. Komura H. Naya Y. Nakanishi K. Nishiyama K. Sugiura M. Kita H. J. Am. Chem. Soc.  1987,  109:  4409 
    CrossrefGoogle Scholar
  • 9a Needham J. Kelly MT. Ishige M. Andersen RJ.
    J. Org. Chem.  1994,  59:  2058 
    Google Scholar
  • 9b Oclarit JM. Okada H. Ohta S. Kaminura K. Yamaoka Y. Iizuka T. Miyashiro S. Ikegami S. Microbios.  1994,  78:  7 
    Google Scholar
  • 10 Liu X. Fortin PD. Walsh CT. Proc. Natl. Acad. Sci. U.S.A.  2008,  105:  13321 
    CrossrefGoogle Scholar
  • 11 Robert F. Gao HQ. Donia M. Merrick WC. Hamann MT. Pettetier J. RNA  2006,  12:  717 
    CrossrefPubMedGoogle Scholar
  • 12 Malochet-Grivois C. Roussakis C. Robillard N. Biard JF. Riou D. Debitus C. Verbist JF. Anticancer Drug Des.  1992,  7:  493 
    Google Scholar
  • 13 Sandler SR. Karo W. In Organic Functional Group Preparations   Vol. 3, 3rd ed.:  Blomquist AT. Wasserman H. Academic Press; New York: 1972.  p.241 
    Google Scholar
  • 14 Reddy PY. Kondo S. Toru T. Ueno Y. J. Org. Chem.  1997,  62:  2652 ; and references cited therein
    CrossrefPubMedGoogle Scholar
  • 15a Zerrer R. Simchen G. Synthesis  1992,  922 
    Google Scholar
  • 15b Darcy PJ. Heller HG. Patharakorn S. Piggott RD. Whittall J. J. Chem. Soc., Perkin Trans. 1  1986,  315 ; and references cited therein
    Google Scholar
  • 16 Hatakeyama S. Sugawara K. Takano S. J. Chem. Soc., Chem. Commun.  1992,  953 
    Google Scholar
  • 17 Leigh WJ. Mitchell DS. J. Am. Chem. Soc.  1992,  114:  5005 
    CrossrefGoogle Scholar
  • 18 Furukawa I. Abe T. Fujisawa H. Ohta T. Tetrahedron  1997,  53:  17643 
    CrossrefGoogle Scholar
  • 19a Souldozi A. Ramazani A. Bouslimani N. Welter R. Tetrahedron Lett.  2007,  48:  2617 
    Google Scholar
  • 19b Souldozi A. Ramazani A. Tetrahedron Lett.  2007,  48:  1549 
    Google Scholar
  • 20a Adib M. Riazati Kesheh M. Ansari S. Bijanzadeh HR. Synlett  2009,  1575 
    Google Scholar
  • 20b Adib M. Ansari S. Feizi S. Bijanzadeh HR. Synlett  2010,  921 
    Google Scholar
  • 20c Adib M. Ansari S. Fatemi S. Bijanzadeh HR. Zhu LG. Tetrahedron  2010,  66:  2723 
    Google Scholar
  • 21a Adib M. Mohamadi A. Sheikhi E. Ansari S. Bijanzadeh HR. Synlett  2010,  1606 
    Google Scholar
  • 21b Adib M. Ansari S. Mohamadi A. Bijanzadeh HR. Tetrahedron Lett.  2010,  51:  30 
    Google Scholar
  • 21c Adib M. Ansari S. Feizi S. Asgarian Damavandi J. Mirzaei P. Synlett  2009,  3263 
    Google Scholar
  • 21d Adib M. Sheibani E. Bijanzadeh HR. Zhu LG. Tetrahedron  2008,  64:  10681 
    Google Scholar
  • 21e Adib M. Mohammadi B. Bijanzadeh HR. Synlett  2008,  3180 
    Google Scholar
  • 21f Adib M. Mohammadi B. Bijanzadeh HR. Synlett  2008,  177 
    Google Scholar
  • 21g Adib M. Sayahi MH. Ziyadi H. Bijanzadeh HR. Zhu LG. Tetrahedron  2007,  63:  11135 
    Google Scholar
  • 23a Matsuo T. Bull. Chem. Soc. Jpn.  1964,  37:  1844 
    Google Scholar
  • 23b Stamboliyska BA. Binev YI. Radomirska VB. Tsenov JA. Juchnovski IN. J. Mol. Struct.  2000,  516:  237 
    Google Scholar
  • 24a Ugi I. Isonitrile Chemistry   Academic Press; London: 1971. 
    Google Scholar
  • 24b Ugi I. Angew. Chem., Int. Ed. Engl.  1982,  21:  810 
    Google Scholar
  • 24c Walborsky HM. Periasamy MP. In The Chemistry of Functional Groups, Supplement C   Patai S. Rappaport Z. Wiley; New York: 1983.  Chap. 20. p.835-837 
    Google Scholar
  • 24d Dömling A. Chem. Rev.  2006,  106:  17 
    Google Scholar
  • 24e Dömling A. Ugi I. Angew. Chem. Int. Ed.  2000,  39:  3169 
    Google Scholar
22

General Procedure for the Preparation of Compounds 4a-i: A mixture of N-isocyaniminotriphenylphosphorane (1 mmol), the appropriate imine (1 mmol) and Meldrum’s acid (1 mmol) in THF (5 mL) was stirred at ambient temperature for 48 h. The progress of the reaction was monitored by TLC. Then, the solvent was removed under the reduced pressure and the residue was purified by column chromatography using n-hexane-EtOAc (3:1) as eluent. The solvent was removed and the product was recrystallized from n-hexane-EtOAc (1:1).
1-Amino-4-(4-methylphenyl)-2,5-dioxo- N ³ -phenyl-3-pyrrolidinecarboxamide (4c):
yield: 0.28 g (86%); colorless crystal; mp 152-154 ˚C. IR (KBr): 3340, 3275, 3192 (NH), 1772, 1693 (C=O), 1600, 1534, 1438, 1312, 1191, 1106, 903, 815, 748, 691 cm-¹. ¹H NMR (500.1 MHz, DMSO-d 6): δ = 2.28 (s, 3 H, Me), 4.01 (d, J = 5.0 Hz, 1 H, CH), 4.34 (d, J = 5.0 Hz, 1 H, CH), 5.16 (br s, 2 H, NH2), 7.09 (t, J = 7.4 Hz, 1 H, CH), 7.17-7.21 (m, 4 H, 4 × CH), 7.33 (dd, J = 8.1, 7.7 Hz, 2 H, 2 × CH), 7.59 (d, J = 7.7 Hz, 2 H, 2 × CH), 10.49 (s, 1 H, NHCO). ¹³C NMR (125.8 MHz, DMSO-d 6): δ = 20.53 (Me), 47.26, 54.72 (2 × CH), 119.19, 123.97, 127.95, 128.79, 129.30 (5 × CH), 133.41, 137.02, 138.21 (3 × C), 164.82, 171.06, 174.59 (3 × C=O). EI-MS: m/z (%) = 323 (10) [M+], 279 (13), 236 (9), 203 (21), 167 (31), 149 (86), 115 (17), 97 (23), 83 (37), 71 (42), 69 (78), 57 (89), 55 (65), 43 (100), 41 (72). Anal. Calcd for C18H17N3O3 (323.35): C, 66.86; H, 5.30; N, 13.00. Found: C, 67.0; H, 5.4; N, 12.8.
1-Amino-4-(4-chlorophenyl)-2,5-dioxo- N ³ -phenyl-3-pyrrolidinecarboxamide (4e): yield: 0.33 g (96%); colorless crystal; mp 172-174 ˚C. IR (KBr): 3321, 3234, 3172 (NH), 1787, 1704, 1667 (C=O), 1603, 1537, 1493, 1440, 1414, 1321, 1257, 1215, 1094, 1051, 1007, 965, 830, 790, 743, 693, 658 cm-¹. ¹H NMR (500.1 MHz, DMSO-d 6): δ = 4.04 (d, J = 5.3 Hz, 1 H, CH), 4.45 (d, J = 5.3 Hz, 1 H, CH), 5.15 (s, 2 H, NH2), 7.09 (t, J = 7.4 Hz, 1 H, CH), 7.33 (dd, J = 8.1, 7.7 Hz, 2 H, 2 × CH), 7.38 (d, J = 8.5 Hz, 2 H, 2 × CH), 7.45 (d, J = 8.5 Hz, 2 H, 2 × CH), 7.59 (d, J = 7.7 Hz, 2 H, 2 × CH), 10.50 (s, 1 H, NHCO). ¹³C NMR (125.8 MHz, DMSO-d 6): δ = 46.93, 54.39 (2 × CH), 119.30, 124.09, 128.76, 128.89, 130.25 (5 × CH), 132.56, 135.34, 138.27 (3 × C), 164.75, 171.00, 174.27 (3 × C=O). EI-MS: m/z (%) = 345 (13) [M+ + ³7Cl], 343 (35) [M+ + ³5Cl], 315 (31), 295 (11), 284 (7), 273 (17), 236 (15), 223 (53), 207 (32), 196 (29), 179 (24), 165 (48), 152 (17), 137 (33), 111 (22), 102 (33), 93 (47), 83 (43), 77 (45), 69 (80), 57 (100), 43 (98), 41 (84). Anal. Calcd for C17H14ClN3O3 (343.77): C, 59.40; H, 4.10; N, 12.22. Found: C, 59.4; H, 4.0; N, 12.1.