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Synlett 2009(20): 3263-3266  
DOI: 10.1055/s-0029-1218381
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A One-Pot, Four-Component Synthesis of N-Substituted 2,4-Diarylimidazoles

Mehdi Adib*a, Samira Ansaria, Shahzad Feizia, Jafar Asgarian Damavandib, Peiman Mirzaeic
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 Faculty of Chemistry, Teacher Training University, Tehran 15614, Iran
c Department of Chemistry, Shahid Beheshti University, Tehran, Iran
Further Information

Publication History

Received 26 June 2009
Publication Date:
18 November 2009 (online)

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Abstract

A one-pot, four-component synthesis of 1,2,4-trisubstituted 1H-imidazoles is described. Heating a mixture of a 2-bromoacetophenone, an aldehyde, a primary amine, and ammonium acetate under solvent-free conditions affords functionalized imidazoles in good to excellent yields.

Key words

1,2,4-trisubstituted 1H-imidazoles - aldehydes - primary amines - four-component reactions - cyclizations - heterocycles

    References and Notes

  • 1a Multicomponent Reactions   Zhu J. Bienaymé H. Wiley; Weinheim: 2005. 
    Google Scholar
  • 1b Basso A. Banfi L. Riva R. Guanti G. J. Org. Chem.  2005,  70:  575 
    Google Scholar
  • 1c Ramón DJ. Yus M. Angew. Chem. Int. Ed.  2005,  44:  1602 
    Google Scholar
  • 2 Grimmett MR. In Comprehensive Heterocyclic Chemistry I   Vol. 5:  Katritzky AR. Rees CW. Potts KT. Pergamon Press; New York: 1984.  p.457-497  
    Google Scholar
  • 3 Grimmett MR. In Comprehensive Heterocyclic Chemistry II   Vol. 3:  Katritzky AR. Rees CW. Scriven EFV. Pergamon Press; New York: 1996.  p.77-220  
    Google Scholar
  • 4 Xi N. Huang Q. Liu L. In Comprehensive Heterocyclic Chemistry III   Vol 4:  Katritzky AR. Ramsden CA. Scriven EFV. Taylor RJK. Elsevier Science; Oxford: 2008.  p.143-348  ; and references therein
    Google Scholar
  • 5 De Luca L. Curr. Med. Chem.  2006,  13:  1 
    CrossrefGoogle Scholar
  • 6 Rotstein DM. Kertesz DJ. Walker KAM. Swinney DC. J. Med. Chem.  1992,  35:  2818 
    CrossrefGoogle Scholar
  • 7a Lee JC. Laydon JT. McDonnell PC. Gallagher TF. Kumar S. Green D. McNulty D. Blumenthal MJ. Keys JR. Vatter SWL. Strickler JE. McLaughlin MM. Siemens IR. Fisher SM. Livi GP. White JR. Adams JL. Young PR. Nature (London)  1994,  372:  739 
    Google Scholar
  • 7b Takle AK. Brown MJB. Davies S. Dean DK. Francis G. Gaiba A. Hird AW. King FD. Lovell PJ. Naylor A. Reith AD. Steadman JG. Wilson DM. Bioorg. Med. Chem. Lett.  2006,  16:  378 
    Google Scholar
  • 7c Khanna IK. Weier RM. Yu Y. Xu XD. Koszyk FJ. Collins PW. Koboldt CM. Veenhuizen AW. Perkins WE. Casler JJ. Masferrer JL. Zhang YY. Gregory SA. Seibert K. Isakson PC. J. Med. Chem.  1997,  40:  1634 
    Google Scholar
  • 7d Lange JHM. Van Stuivenberg HH. Coolen HKAC. Adolfs TJP. McCreary AC. Keizer HG. Wals HC. Veerman W. Borst AJM. de Loof W. Verveer PC. Kruse CG. J. Med. Chem.  2005,  48:  1823 
    Google Scholar
  • 8a de Laszlo SE. Hacker C. Li B. Kim D. MacCoss M. Mantlo N. Pivnichny JV. Colwell L. Koch GE. Cascieri MA. Hagmann WK. Bioorg. Med. Chem. Lett.  1999,  9:  641 
    Google Scholar
  • 8b Eyers PA. Craxton M. Morrice N. Cohen P. Goedert M. Chem. Biol.  1998,  5:  321 
    Google Scholar
  • 8c Newman MJ. Rodarte JC. Benbatoul KD. Romano SJ. Zhang C. Krane S. Moran EJ. Uyeda RT. Dixon R. Guns ES. Mayer LD. Cancer Res.  2000,  60:  2964 
    Google Scholar
  • 8d Antolini M. Bozzoli A. Ghiron C. Kennedy G. Rossi T. Ursini A. Bioorg. Med. Chem. Lett.  1999,  9:  1023 
    Google Scholar
  • 8e Wang L. Woods KW. Li Q. Barr KJ. McCroskey RW. Hannick SM. Gherke L. Credo RB. Hui Y.-H. Marsh K. Warner R. Lee JY. Zielinsky-Mozng N. Frost D. Rosenberg SH. Sham HL. J. Med. Chem.  2002,  45:  1697 
    Google Scholar
  • 8f Maier T, Schmierer R, Bauer K, Bieringer H, Buerstell H, and Sachse B. inventors; US Patent;  4820335.  ; Chem. Abstr. 1989, 111, 19494w
  • 9a Dupont J. de Souza RF. Suarez PAZ. Chem. Rev.  2002,  102:  3667 
    Google Scholar
  • 9b Chowdhury S. Mohan RS. Scott JL. Tetrahedron  2007,  63:  2363 
    Google Scholar
  • 10a Bourissou D. Guerret O. Gabbai FP. Bertrand G. Chem. Rev.  2000,  100:  39 
    Google Scholar
  • 10b Arnold PL. Liddle ST. Chem. Commun.  2006,  3959 
    Google Scholar
  • 10c Kühl O. Chem. Soc. Rev.  2007,  36:  592 
    Google Scholar
  • 11 Lantos I. Zhang WY. Shui X. Eggleston DS. J. Org. Chem.  1993,  58:  7092 
    CrossrefGoogle Scholar
  • 12a Zhang C. Moran EJ. Woiwode TF. Short KM. Mjalli AMM. Tetrahedron Lett.  1996,  37:  751 
    Google Scholar
  • 12b Sarshar S. Siev D. Mjalli AMM. Tetrahedron Lett.  1996,  37:  835 
    Google Scholar
  • 13 Claiborne CF. Liverton NJ. Nguyen KT. Tetrahedron Lett.  1998,  39:  8939 
    CrossrefGoogle Scholar
  • 14 Lee HB. Balasubramanian S. Org. Lett.  2000,  2:  323 
    CrossrefGoogle Scholar
  • 15 Das Sharma S. Hazarika P. Konwar D. Tetrahedron Lett.  2008,  49:  2216 ; and references cited therein
    CrossrefGoogle Scholar
  • 16a Adib M. Mohammadi B. Bijanzadeh HR. Synlett  2008,  3180 
    Google Scholar
  • 16b Adib M. Sheibani E. Bijanzadeh HR. Zhu LG. Tetrahedron  2008,  64:  10681 
    Google Scholar
  • 16c Adib M. Sayahi MH. Ziyadi H. Zhu LG. Bijanzadeh HR. Synthesis  2008,  3289 
    Google Scholar
  • 16d Adib M. Mohammadi B. Bijanzadeh HR. Synlett  2008,  177 
    Google Scholar
  • 16e Adib M. Sayahi MH. Ziyadi H. Bijanzadeh HR. Zhu LG. Tetrahedron  2007,  63:  11135 
    Google Scholar
  • 16f Adib M. Aali Koloogani S. Abbasi A. Bijanzadeh HR. Synthesis  2007,  3056 
    Google Scholar
  • 16g Adib M. Sheibani E. Abbasi A. Bijanzadeh HR. Tetrahedron Lett.  2007,  48:  1179 
    Google Scholar
  • 16h Adib M. Sheibani E. Mostofi M. Ghanbary K. Bijanzadeh HR. Tetrahedron  2006,  62:  3435 
    Google Scholar
  • 18 Sharma AK. Mazumdar SN. Mahajan MP. J. Chem. Soc., Perkin Trans. 1  1997,  3065 
    CrossrefGoogle Scholar
17

1-Benzyl-2-(4-nitrophenyl)-4-phenyl-1 H -imidazole (4b); Typical Procedure
A mixture of 4-nitrobenzaldehyde (0.302 g, 2 mmol), benzylamine (0.214 g, 2 mmol), 2-bromo-1-phenylethanone (0.398 g, 2 mmol), and ammonium acetate (0.231 g, 3 mmol) was stirred at 130 ˚C for 2 h, then the reaction mixture was cooled to r.t. and the product precipitated from a 1:1 mixture of acetone-H2O and then recrystallized from n-hexane-EtOAc (1:1) as colorless crystals. Yield: 0.67 g (95%); mp 178 ˚C. IR (KBr): 1594, 1513, 1502, 1489, 1477, 1446, 1414, 1357, 1330, 1289, 1200, 1176, 1103, 1026, 940, 854, 761, 731, 710 cm-¹. ¹H NMR (500.1 MHz, DMSO-d 6): δ = 5.48 (s, 2 H, CH2), 7.10 (d, J = 7.3 Hz, 2 H, 2 × CH), 7.24 (t, J = 7.6 Hz, 1 H, CH), 7.26 (t, J = 7.5 Hz, 1 H, CH), 7.32 (dd, J = 7.2, 7.7 Hz, 1 H, CH), 7.38 (dd, J = 7.6, 7.8 Hz, 1 H, CH), 7.84 (d, J = 7.3 Hz, 2 H, 2 × CH), 7.95 (d, J = 8.8 Hz, 2 H, 2 × CH), 7.97 (s, CH, 1 H, CH), 8.28 (d, J = 8.8 Hz, 2 H, 2 × CH). ¹³C NMR (75.5 MHz, DMSO-d 6): δ = 50.83 (CH2), 121.23, 124.29, 124.90, 127.05, 127.29, 128.21, 129.08, 129.33 and 129.53 (9 × CH), 134.18, 136.89, 137.40, 141.23, 145.30 and 147.41 (6 × C). MS: m/z (%) = 355 (87) [M+], 116 (12), 92 (80), 90 (20), 89 (60), 77 (20), 65 (100). Anal. Calcd for C22H17N3O2 (355.40): C, 74.35; H, 4.82; N, 11.82. Found: C, 74.3; H, 4.8; N, 11.7.
1,2,4-Triphenyl-1 H -imidazole (4a)
Colorless crystals; mp 88-89 ˚C (lit.¹8 92-94 ˚C). IR (KBr): 1598, 1496, 1361, 1333, 1205, 1101, 1048, 784, 693 cm-¹. ¹H NMR (300.1 MHz, CDCl3): δ = 7.26-7.33 (m, 6 H, 6 × CH), 7.39-7.52 (m, 8 H, 8 × CH), 7.93 (d, J = 7.8 Hz, 2 H, 2 × CH). ¹³C NMR (75.5 MHz, CDCl3): δ = 118.56, 125.06, 125.86, 127.03, 128.21, 128.24, 128.47, 128.64, 128.84 and 129.51 (10 × CH), 130.32, 133.87, 138.49, 141.71 and 147.0 (5 × C). Anal. Calcd for C21H16N2 (296.37): C, 85.11; H, 5.44; N, 9.45. Found: C, 85.0; H, 5.5; N, 9.4. MS: m/z (%) = 296 (7) [M+], 279 (6), 225 (8), 197 (20), 180 (6), 167 (11), 149 (28), 105 (100), 77 (52), 51 (12).
1-Benzyl-2-(3-nitrophenyl)-4-phenyl-1 H -imidazole (4c)
Colorless crystals; mp 183-185 ˚C. IR (KBr): 1605, 1549, 1488, 1463, 1434, 1374, 1345, 1304, 1240, 1207, 1152, 1099, 939, 855, 818, 766, 667 cm-¹. ¹H NMR (300.1 MHz, DMSO-d 6): δ = 5.44 (s, 2 H, CH2), 7.12 (d, J = 7.3 Hz, 2 H, 2 × CH), 7.21-7.43 (m, 6 H, 6 × CH), 7.73 (dt, J = 1.4, 8.0 Hz, 1 H, CH), 7.84 (d, J = 7.7 Hz, 2 H, 2 × CH), 7.95 (s, 1 H, CH), 8.09 (d, J = 7.6 Hz, 1 H, CH), 8.24 (d, J = 8.2 Hz, 1 H, CH), 8.38 (d, J = 1.4 Hz, 1 H, CH). ¹³C NMR (75.5 MHz, DMSO-d 6): δ = 50.92 (CH2), 120.27, 123.17, 123.49, 125.06, 127.11, 127.18, 128.18, 128.92, 129.23 and 130.58 (10 × CH), 132.57 and 134.49 (2 × C), 134.71 (CH), 137.33, 141.15, 145.39 and 148.62 (4 × C). MS: m/z (%) = 355 (5) [M+], 155 (3), 111 (12), 91 (100), 80 (38), 71 (59), 57 (82). Anal. Calcd for C22H17N3O2 (355.40): C, 74.35; H, 4.82; N, 11.82. Found: C, 74.2; H, 4.9; N, 11.6.
2-(4-Nitrophenyl)-4-phenyl-1-propyl-1 H -imidazole (4e)
Colorless crystals; mp 104 ˚C. IR (KBr): 1595, 1510, 1475, 1384, 1329, 1203, 1100, 1017, 946, 913, 847, 804, 759, 691 cm-¹. ¹H NMR (300.1 MHz, CDCl3): δ = 0.95 (t, J = 7.4 Hz, 3 H, CH3), 1.85 (sext, J = 7.3 Hz, 2 H, CH 2CH3), 4.06 (t, J = 7.2 Hz, 2 H, NCH2), 7.29 (t, J = 7.0 Hz, 1 H, CH), 7.40 (s, 1 H, CH), 7.41 (dd, J = 7.0, 7.5 Hz, 2 H, 2 × CH), 7.84 (d, J = 7.5 Hz, 2 H, 2 × CH), 7.88 (d, J = 8.6 Hz, 2 H, 2 × CH), 8.35 (d, J = 8.6 Hz, 2 H, 2 × CH). ¹³C NMR (75.5 MHz, CDCl3): δ = 11.12 (CH3), 24.47 and 49.04 (2 × CH2), 117.72, 123.93, 124.92, 127.16, 128.67 and 129.50 (6 × CH(, 133.64, 137.08, 142.18, 145.49 and 147.60 (5 × C). MS: m/z (%) = 307 (24) [M+], 279 (20), 167 (42), 151 (13), 149 (100), 113 (10), 105 (12), 83 (10), 77 (9), 71 (18), 57 (31), 55 (17), 43 (26). Anal. Calcd for C18H17N3O2 (307.35): C, 70.34; H, 5.58; N, 13.67. Found: C, 70.3; H, 5.6; N, 13.6.
2-(4-Nitrophenyl)-1,4-diphenyl-1 H -imidazole (4h)
Colorless crystals; mp 154 ˚C. IR (KBr): 1593, 1506, 1418, 1387, 1331, 1200, 1166, 1102, 1073, 974, 913, 849, 745, 692 cm-¹. ¹H NMR (300.1 MHz, CDCl3): δ = 7.28-7.35 (m, 3 H, 3 × CH), 7.45 (dd, J = 7.4, 8.0 Hz, 2 H, 2 × CH), 7.50 (s, 1 H, CH), 7.51-7.53 (m, 3 H, 3 × CH), 7.66 (d, J = 8.6 Hz, 2 H, 2 × CH), 7.91 (d, J = 7.8 Hz, 2 H, 2 × CH), 8.13 (d, J = 8.5 Hz, 2 H, 2 × CH). ¹³C NMR (75.5 MHz, CDCl3): δ = 120.13, 123.54, 125.10, 125.94, 127.50, 128.77, 129.04, 129.08 and 129.98 (9 × CH), 133.27, 136.26, 137.95, 142.70, 144.37 and 147.22 (6 × C). MS: m/z (%) = 341 (6) [M+], 279 (20), 167 (43), 149 (100), 113 (10), 105 (9), 83 (10), 71 (19), 57 (31). Anal. Calcd for C21H15N3O2 (341.37): C, 73.89; H, 4.43; N, 12.31. Found: C, 73.8; H, 4.5; N, 12.2.
2-(4-Chlorophenyl)-1,4-diphenyl-1 H -imidazole (4i)
Colorless crystals; mp 146-148 ˚C. IR (KBr): 1596, 1489, 1447, 1413, 1240, 1206, 1170, 1087, 1013, 975, 912, 830, 751, 691 cm-¹. ¹H NMR (300.1 MHz, CDCl3): δ = 7.24-7.35 (m, 5 H, 5 × CH), 7.41-7.47 (m, 8 H, 8 × CH), 7.92 (d, J = 8.0 Hz, 2 H, 2 × CH). ¹³C NMR (75.5 MHz, CDCl3): δ = 118.85, 125.06, 125.87, 127.17, 128.51, 128.52 and 128.69 (7 × CH), 128.79 (C), 129.69 and 130.01 (2 × CH), 133.69, 134.52, 138.25, 141.89 and 145.84 (5 × C). MS: m/z (%) = 332 (45) [M+, ³7Cl], 330 (100) [M+, ³5Cl], 329 (21), 227 (65), 192 (26), 165 (39), 139 (30), 105 (75), 89 (27), 77 (72), 51 (32). Anal. Calcd for C21H15ClN2 (330.82): C, 76.25; H, 4.57; N, 8.47. Found: C, 76.1; H, 4.7; N, 8.3.