Molecular Diversity

, Volume 19, Issue 3, pp 577–623 | Cite as

Current advances in the synthesis and biological potencies of tri- and tetra-substituted 1H-imidazoles

  • Majid M. Heravi
  • Mansoureh Daraie
  • Vahideh Zadsirjan
Comprehensive review


In this report, we review the current chemistry progress and in particular the synthesis approaches of tri- and tetra-substituted imidazoles.


Tri-aryl-1\(H\)-imidazoles Tetra-aryl-1\(H\)-imidazoles Biological activity 



The authors are thankful to the Department of Chemistry for the honors and moral support, and the Alzahra University Research Council for financial supports.


  1. 1.
    Coura JR, de Castro SL (2002) Critical review on Chagas disease chemotherapy. Mem Inst Oswaldo Cruz 97:3–24. doi: 10.1590/S0074-02762002000100001 Google Scholar
  2. 2.
    Debus H (1858) Ueber die Einwirkung des Ammoniaks auf Glyoxal. Justus Liebigs Ann Chem 107:199–208. doi: 10.1002/jlac.18581070209 Google Scholar
  3. 3.
    Wasserscheid P, Keim W (2000) Ionic liquids-new “solutions” for transition metal catalysis. Angew Chem Int Ed 39:3772–3789. doi: 10.1002/1521-3773(20001103)39:21 Google Scholar
  4. 4.
    Welton T (1999) Room-temperature ionic liquids. Solvents for synthesis and catalysis. Chem Rev 99:2071–2083. doi: 10.1021/cr980032t PubMedGoogle Scholar
  5. 5.
    Bourissou D, Guerret O, Gabbaï FP, Bertrand G (2000) Stable carbenes. Chem Rev 100:39–92. doi: 10.1021/cr940472u PubMedGoogle Scholar
  6. 6.
    Zhang Ch, Huang J, Trudell ML, Nolan SP (1999) Palladium-imidazol-2-ylidene complexes as catalysts for facile and efficient Suzuki cross-coupling reactions of aryl chlorides with arylboronic acids. J Org Chem 64:3804–3805. doi: 10.1021/jo990554o Google Scholar
  7. 7.
    Herrmann WA (2002) \(N\)-Heterocyclic carbenes: a new concept in organometallic catalysis. Angew Chem Int Ed 41:1290–1309. doi: 10.1002/1521-3773(20020415)41:8 Google Scholar
  8. 8.
    De-Luca L (2006) Naturally occurring and synthetic imidazoles: their chemistry and their biological activities. Curr Med Chem 13:1–23. doi: 10.2174/0929867310607010001 PubMedGoogle Scholar
  9. 9.
    Grimmett MR (1970) Advances in imidazole chemistry. Adv Heterocycl Chem 12:103–183. doi: 10.1016/S0065-2725(08)60973-3 Google Scholar
  10. 10.
    Grimmett MR (1997) Imidazole and benzimidazole synthesis. Academic, San DiegoGoogle Scholar
  11. 11.
    Grimmett MR (2002) Product class 3: imidazoles. Sci Synth 12:325–528. doi: 10.1002/chin.200346256 Google Scholar
  12. 12.
    Grimmett MR (1996) Comprehensive heterocyclic chemistry. In: Katritsky AR, Rees CW, Scriven EFV (eds) Heterocyclic chemistry II. Elsevier Science, Oxford, pp 77–220Google Scholar
  13. 13.
    Harju K, Kauhaluoma Y (2004) Progress in the synthesis of five-membered nitrogen-containing heterocycles via 1,3-dipolar cycloaddition. J Recent Res Dev Org Chem 8:111–157. doi: 10.1002/chin.200517272 Google Scholar
  14. 14.
    Murry JA (2003) Synthetic methodology utilized to prepare substituted imidazole p38 MAP kinase inhibitors. Curr Opin Drug Discov Dev 6:945–965. doi: 10.1002/chin.200425277 Google Scholar
  15. 15.
    Sisko J, Mellinger M (2002) Development of a general process for the synthesis of highly substituted imidazoles. Pure Appl Chem 74:1349–1357. doi: 10.1351/pac200274081349 Google Scholar
  16. 16.
    Hoffmann H, Lindel T (2003) Synthesis of the pyrrole-imidazole alkaloids. Synthesis: 1753–1783. doi: 10.1055/s-2003-41005
  17. 17.
    Dolensky B, Nam G, Deng W-P, Narayanan J, Fan J, Kirk KL (2004) Synthesis of side-chain fluorinated biologically important imidazoles and indoles. J Fluorine Chem 125:501–508. doi: 10.1016/j.jfluchem.2003.12.013 Google Scholar
  18. 18.
    Jin Z (2005) Muscarine imidazole, oxazole and thiazole alkaloids. Nat Prod Rep 22:196–229. doi: 10.1039/C0NP00074D PubMedGoogle Scholar
  19. 19.
    Zificsak CA, Hlasta DJ (2004) Current methods for the synthesis of 2-substituted azoles. Tetrahedron 60:8991–9016. doi: 10.1016/j.tet.2004.07.016 Google Scholar
  20. 20.
    Du H-W, He Y, Sivappa R, Lovely CJ (2006) New methods of imidazole functionalization from imidazole to marine alkaloids. Synlett: 965–992 doi: 10.1055/s-2006-939720
  21. 21.
    Van Leusen D, Van Leusen AM (2001) Synthetic uses of tosylmethyl isocyanide (TosMIC). Org React 57:417–666. doi: 10.1002/0471264180.or057.03 Google Scholar
  22. 22.
    Bellina F, Cauteruccio S, Rossi R (2007) Synthesis and biological activity of vicinal diaryl-substituted 1\(H\)-imidazoles. Tetrahedron 63:4571–4624. doi: 10.1016/j.tet.2007.02.075 Google Scholar
  23. 23.
    Shalini K, Sharma PK, Kumar N (2010) Imidazole and its biological activities: a review. Der Chemica Sinica 1:36–47Google Scholar
  24. 24.
    Kumar JR (2010) Review of imidazole heterocyclic ring containing compounds with their biological activity. Pharmacophore 1:167–177Google Scholar
  25. 25.
    Chawla A, Sharma A, Sharma AK (2012) Review: A convenient approach for the synthesis of imidazole derivatives using microwaves. Der Pharma Chemica 4:116–140Google Scholar
  26. 26.
    Bhatnagar A, Sharma PK, Kumar N (2011) Review on “Imidazoles”: their chemistry and pharmacological potentials. Int J PharmTech Res 3:268–282Google Scholar
  27. 27.
    Khaghaninejad S, Heravi MM (2014) Chapter Three—Paal–Knorr reaction in the synthesis of heterocyclic compounds. Adv Heterocycl Chem 111:95–146. doi: 10.1016/B978-0-12-420160-6.00003-3 Google Scholar
  28. 28.
    Sadjadi S, Heravi MM (2011) Recent application of isocyanides in synthesis of heterocycles. Tetrahedron 67:2707–2752. doi: 10.1016/j.tet.2011.01.086 Google Scholar
  29. 29.
    Heravi MM, Khaghaninejad S, Nazari N (2014) Chapter Five—Bischler–Napieralski reaction in the synthesis of isoquinolines. Adv Heterocycl Chem 112:183–234. doi: 10.1016/B978-0-12-800171-4.00005-6 Google Scholar
  30. 30.
    Heravi MM, Talaei B (2014) Ketenes as privileged synthons in the synthesis of heterocyclic compounds, part 1: three- and four-membered heterocycles. Adv Heterocycl Chem 113:143–244. doi: 10.1016/B978-0-12-800170-7.00004-3 Google Scholar
  31. 31.
    Heravi MM, Alishiri T (2014) DMAD as a privileged scaffold in heterocyclization. Adv Heterocycl Chem 113:1–66. doi: 10.1016/B978-0-12-800170-7.00001-8 Google Scholar
  32. 32.
    Heravi MM, Asadi Sh, Lashkariani BM (2013) Recent progress in asymmetric Biginelli reaction. Mol Divers 17:389–407. doi: 10.1007/s11030-013-9439-9 PubMedGoogle Scholar
  33. 33.
    Heravi MM, Hamidi H (2013) Recent advances in synthesis of 2-pyridones: a key heterocycle is revisited. J Iran Chem Soc 10:265–273. doi: 10.1007/s13738-012-0155-7 Google Scholar
  34. 34.
    Heravi MM, Alishiri T (2012) Application of nanomaterials in heterocyclic chemistry. Heterocycles 85:545–586. doi: 10.3987/REV-11-725 Google Scholar
  35. 35.
    Heravi MM, Hashemi E, Azimian F (2014) Recent developments of the Stille reaction as a revolutionized method in total synthesis. Tetrahedron 70:7–21. doi: 10.1016/j.tet.2013.07.108 Google Scholar
  36. 36.
    Heravi MM, Hajiabbasi P (2012) Recent advances in Kumada–Tamao–Corriu cross-coupling reaction catalyzed by different ligands. Monatsh Chem 143:1575–1592. doi: 10.1007/s00706-012-0838-x Google Scholar
  37. 37.
    Heravi MM, Asadi Sh (2012) Recent applications of organocatalysts in asymmetric aldol reactions. Tetrahedron Asymmetry 23:1431–1465. doi: 10.1016/j.tetasy.2012.10.002 Google Scholar
  38. 38.
    Heravi MM, Hashemi E (2012) Recent applications of the Suzuki reaction in total synthesis. Tetrahedron 68:9145–9178. doi: 10.1016/j.tet.2012.08.058 Google Scholar
  39. 39.
    Zh Li X, Wang L, Long L, Xiao J, Hu Y, Li S (2009) Synthesis and biological evaluation of 1,2,4-trisubstituted imidazoles and 1,3,5-trisubstituted pyrazoles as inhibitors of transforming growth factor \(\upbeta \) type 1 receptor (ALK5). Bioorg Med Chem Lett 19:4868–4872. doi: 10.1016/j.bmcl.2009.04.066 Google Scholar
  40. 40.
    Talley JJ, Brown DL, Carter JS, Graneto MJ, Koboldt CM, Masferrer JL, Perkins WE (2000) 4-[5-Methyl-3-phenylisoxazol-4-yl]- benzenesulfonamide, valdecoxib: a potent and selective inhibitor of COX-2. J Med Chem 43:775–777. doi: 10.1021/jm990577v PubMedGoogle Scholar
  41. 41.
    Kanyiva KS, Löbermann F, Nakao Y, Hiyama T (2009) Regioselective alkenylation of imidazoles by nickel/Lewis acid catalysis. Tetrahedron Lett 50:3463–3466. doi: 10.1016/j.tetlet.2009.02.195 Google Scholar
  42. 42.
    Husain A, Drabu S, Kumar N (2009) Synthesis and biological screening of di- and trisubstituted imidazoles. Acta Pol Pharm 66:243–248PubMedGoogle Scholar
  43. 43.
    Husain A, Siddigui N, Sarafroz MD, Khatoon Y, Rasid M, Ahmad N (2011) Synthesis, anticonvulsant and neurotoxicity screening of some novel 1,2,4-trisubstituted-1\(H\)-imidazole derivatives. Acta Pol Pharm 68:657–663PubMedGoogle Scholar
  44. 44.
    Hempel AA, Camerman N, Camerman A, Mastropaolo D (2005) Nafimidone monohydrate: an imidazole anticonvulsant. Acta Crystallogr 61E:1387–1389. doi: 10.1107/S1600536805011487 Google Scholar
  45. 45.
    Thenmozhiyal JC, Peter TSW, Wai-Keung C (2004) Anticonvulsant activity of phenylmethylenehydantoins: a structure–activity relationship study. J Med Chem 47:1527–1535. doi: 10.1021/jm030450c PubMedGoogle Scholar
  46. 46.
    Rostom SAF, Ashour HMA, El-Razik HAA, El-Fattah AEFHA, El-Din NN (2009) Azole antimicrobial pharmacophore-based tetrazoles: synthesis and biological evaluation as potential antimicrobial and anticonvulsant agents. Bioorg Med Chem 17:2410–2422. doi: 10.1016/j.bmc.2009.02.004 PubMedGoogle Scholar
  47. 47.
    Cai Z-J, Wang ShY, Ji S-J (2012) CuI/BF\(_{3}\,\cdot \,\)Et\(_{2}\)O cocatalyzed aerobic dehydrogenative reactions of ketones with benzylamines: facile synthesis of substituted imidazoles. Org Lett 14:6068–6071. doi: 10.1021/ol302955u PubMedGoogle Scholar
  48. 48.
    Zhang GW, Miao JM, Zhao Y, Ge HB (2012) Copper-catalyzed aerobic dehydrogenative cyclization of \(N\)-Methyl-\(N\)-phenylhydrazones: synthesis of cinnolines. Angew Chem Int Ed 51:8318–8321. doi: 10.1002/anie.201204339 Google Scholar
  49. 49.
    Frank PV, Poojary MM, Damodara N, Chikkanna Ch (2013) Synthesis and potential antimicrobial studies on some Mannich bases carrying imidazole moiety. Acta Pharm 63:231–239. doi: 10.2478/acph-2013-0016 PubMedGoogle Scholar
  50. 50.
    Tang D, Wu P, Liu X, Chen YX, Guo SB, Chen WL, Li JG, Chen B (2013) Synthesis of multisubstituted imidazoles via copper-catalyzed [3 + 2] cycloadditions. J Org Chem 78:2746–2750. doi: 10.1021/jo302555z PubMedGoogle Scholar
  51. 51.
    Liu X, Wang D, Chen B (2013) Iron(III)-catalyzed synthesis of multi-substituted imidazoles via [3+2] cycloaddition reaction of nitroolefins and N-aryl benzamidines. Tetrahedron 69:9417–9421. doi: 10.1016/j.tet.2013.08.077 Google Scholar
  52. 52.
    Yeagley AA, Su Zh, Mc-Cullough KD, Worthington RJ, Melander C (2013) \(N\)-Substituted 2-aminoimidazole inhibitors of MRSA biofilm formation accessed through direct 1,3-bis(tert-butoxycarbonyl)guanidine cyclization. Org Biomol Chem 11:130–137. doi: 10.1039/C2OB26469B PubMedGoogle Scholar
  53. 53.
    Brown CA, Yamashita A (1975) Saline hydrides and superbases in organic reactions. IX Acetylene zipper exceptionally facile contrathermodynamic multipositional isomeriazation of alkynes with potassium 3-aminopropylamide. J Am Chem Soc 97:891–892. doi: 10.1021/ja00837a034 Google Scholar
  54. 54.
    Rogers SA, Bero JD, Melander C (2010) Chemical synthesis and biological screening of 2-aminoimidazole-based bacterial and fungal antibiofilm agents. ChemBioChem 11:396–410. doi: 10.1002/cbic.200900617 PubMedGoogle Scholar
  55. 55.
    Su Z, Yeagley AA, Su R, Peng L, Melander C (2012) Structural studies on 4,5-disubstituted 2-aminoimidazole-based biofilm modulators that suppress bacterial resistance to \(\upbeta \)-lactams. Chem Med Chem 7:2030–2039. doi: 10.1002/cmdc.201200350 PubMedGoogle Scholar
  56. 56.
    Hamada T, Ye X, Stahl SS (2008) Copper-catalyzed aerobic oxidative amidation of terminal alkynes: efficient synthesis of ynamides. J Am Chem Soc 130:833–835. doi: 10.1021/ja077406x PubMedGoogle Scholar
  57. 57.
    Li J, Neuville L (2013) Copper-catalyzed oxidative diamination of terminal alkynes by amidines: synthesis of 1,2,4-trisubstituted imidazoles. Org Lett 15:1752–1755. doi: 10.1021/ol400560m PubMedGoogle Scholar
  58. 58.
    Guo Ch, Zhang Ch, Li X, Li W, Xu Zh, Bao L, Ding Y, Wang L, Li S (2013) Synthesis and biological evaluation of 1,2,4-trisubstituted imidazoles as inhibitors of transforming growth factor-\(\upbeta \) type I receptor (ALK5). Bioorg Med Chem Lett 23:5850–5854. doi: 10.1016/j.bmcl.2009.04.066 PubMedGoogle Scholar
  59. 59.
    Lange JHM, van Stuivenberg HH, Coolen HKAC (2005) Bioisosteric replacements of the Pyrazole Moiety of Rimonabant: synthesis, biological properties, and molecular modeling investigations of thiazoles, triazoles, and imidazoles as potent and selective CB\(_{1}\) cannabinoid receptor antagonists. J Med Chem 48:1823–1838. doi: 10.1021/jm040843r PubMedGoogle Scholar
  60. 60.
    Venkatesan AM, Gu YS, Santos OD (2004) Structure–activity relationship of 6-methylidene penems bearing tricyclic heterocycles as broad-spectrum \(\upbeta \)-lactamase inhibitors: crystallographic structures show unexpected binding of 1,4-thiazepine intermediates. J Med Chem 47:6556–6568. doi: 10.1021/jm049680x PubMedGoogle Scholar
  61. 61.
    Madsen C, Jensen AA, Liljefors T (2007) 5-substituted imidazole-4-acetic acid analogues: synthesis, modeling, and pharmacological characterization of a series of novel \(\upgamma \)-aminobutyric acid\(_{{\rm C}}\) Receptor agonists. J Med Chem 50:4147–4161. doi: 10.1021/jm070447j PubMedGoogle Scholar
  62. 62.
    Rohmer T, Lang C, Bongards C (2010) Phytochrome as molecular machine: revealing chromophore action during the Pfr \(\rightarrow \) Pr photoconversion by magic-angle spinning NMR spectroscopy. J Am Chem Soc 132:4431–4437. doi: 10.1021/ja9108616 PubMedGoogle Scholar
  63. 63.
    Li XZ, Zhou XM, Zheng ZB (2009) Short synthesis of 1-(3-tert-Butyl-1-phenyl-1\(H\)-pyrazol-5-yl)-3-(5-(2-morpholinoethoxy)-2\(H\)-chromen-8-yl) Urea derivatives. Synth Commun 39:3999–4009. doi: 10.1080/00397910902883603 Google Scholar
  64. 64.
    Romera JL, Cid JM, Trabanco A (2004) A potassium iodide catalysed monoalkylation of anilines under microwave irradiation. Tetrahedron Lett 45:8797–8800. doi: 10.1016/j.tetlet.2004.10.002 Google Scholar
  65. 65.
    Schmidt MU, Hofmann DWM, Buchsbaum C (2006) Crystal structures of pigment red 170 and derivatives, as determined by X-ray powder diffraction. Angew Chem Int Ed 45:1313–1317. doi: 10.1002/anie.200502468 Google Scholar
  66. 66.
    Paone DV, Shaw AW (2008) Synthesis of tri- and tetra-substituted imidazoles. Tetrahedron Lett 49:6155–6159. doi: 10.1016/j.tetlet.2008.08.036 Google Scholar
  67. 67.
    Scheibye S, Pederson BS, Lawesson SO (1978) Studies on organophosphorus compounds XXI. The dimer of \(p\)-methoxyphenylthionophosphine sulfide as thiation reagent. a new route to thiocarboxamides. Bull Soc Chim Belg 87:229–232. doi: 10.1002/bscb.19780870311 Google Scholar
  68. 68.
    Hadizadeh F, Hosseinzadeh H, Motamed-Shariaty VS (2008) Synthesis and antidepressant activity of \(N\)-substituted imidazole-5-carboxamides in forced swimming test model. Iran J Pharm Res 7:29–33Google Scholar
  69. 69.
    Hadizadeh F, Ghodsi R (2005) Synthesis of novel \(N\)-substituted imidazolecarboxylic acid hydrazides as monoamine oxidase inhibitors. Farmaco 60:237–240. doi: 10.1016/j.farmac.2004.12.007 PubMedGoogle Scholar
  70. 70.
    Maddani MR, Prabhu KR (2010) A concise synthesis of substituted thiourea derivatives in aqueous medium. J Org Chem 75:2327–2332. doi: 10.1021/jo1001593 PubMedGoogle Scholar
  71. 71.
    Tripathy H, Krishnanand ST, Adhikary L, Chandrashekar J (2010) Microwave assisted parallel synthesis of 1,4,5-tri substituted imidazoles and their pharmacological evaluation. Res J Pharm Biol Chem Sci 1:23–30Google Scholar
  72. 72.
    Umarani N, Ilango K, Garg G, Srinivas BK, Hemalatha V (2011) Exploring the effects of newer three component aminobenzylated reactions of triphenyl imidazole motif as potent antimicrobial and anti-inflammatory agents. Int J Pharm Pharm Sci 3:62–65Google Scholar
  73. 73.
    Radziszewski B (1882) Ueber die Constitution des Lophins und verwandter Verbindungen. Chem Ber 15:1493–1496. doi: 10.1002/cber.18820150207 Google Scholar
  74. 74.
    Japp FR, Robinson HH (1882) Constitution des Lophins und des Amarins. Chem Ber 15:1268–1270. doi: 10.1002/cber.188201501272 Google Scholar
  75. 75.
    Li B, Chiu CKF, Hank RF, Murry J, Roth J, Tobiassen H (2002) An optimized process for formation of 2,4-disubstituted imidazoles from condensation of amidines and \(\upalpha \)-haloketones. Org Proc Res Dev 6:682–683. doi: 10.1021/op025552b Google Scholar
  76. 76.
    Zhang PF, Chen ZC (2001) Hypervalent iodine in synthesis 81: a one-pot procedure for the synthesis of 1\(H\)-imidazole derivatives by cyclocondensation of ketones with [hydroxy(tosyloxy)iodo]benzene and amidines. Synthesis 14:2075–2077. doi: 10.1055/s-2001-18059 Google Scholar
  77. 77.
    Gallagher TF, Fier-Thompson SM, Garigipati RS, Sorenson ME, Smietana JM, Lee D, Bender PE, Lee JC, Laydon JT, Griswold DE, Chabot-Fletcher MC, Breton JJ, Adams JL (1995) 2,4,5- triarylimidazole inhibitors of IL-1 biosynthesis. Bioorg Med Chem Lett 5:1171–1176. doi: 10.1016/0960-894X(95)00189-Z Google Scholar
  78. 78.
    Gallagher TF, Seibel GL, Kassis S, Laydon JT, Blumenthal MJ, Lee JC, Lee D, Boehm JC, Fier-Thompson SM, Abt AW, Sorenson ME, Smietana RF, Hall RS, Garigipati PE, Bender KF, Erhard AJ, Krog GA, Hofmann JM, Sheldrake PL, McDonnell PC, Kumar S, Young PR, Adams JL (1997) Regulation of stress-induced cytokine production by pyridinylimidazoles; inhibition of CSBP kinase. Bioorg Med Chem 5:49–64. doi: 10.1016/S0968-0896(96)00212-X PubMedGoogle Scholar
  79. 79.
    Antolini M, Bozzoli A, Ghiron C, Kennedy G, Rossi T, Ursini A (1999) Analogues of 4,5-bis(3,5-dichlorophenyl)-2-trifluoromethyl-1\(H\)-imidazole as potential antibacterial agents. Bioorg Med Chem Lett 9:1023–1028. doi: 10.1016/S0960-894X(99)00112-2 PubMedGoogle Scholar
  80. 80.
    de Laszlo SE, Hacker C, Li B, Kim D, MacCoss M, Mantlo N, Pivnichny JV, Colwell L, Koch GE, Cascieri MA, Hagmann WK (1999) Potent, orally absorbed glucagon receptor antagonists. Bioorg Med Chem Lett 9:641–646. doi: 10.1016/S0960-894X(99)00081-5 PubMedGoogle Scholar
  81. 81.
    Revesz L, Blum E, Padova FED, Buhl T, Feifel R, Gram H, Hiestand P, Manning U, Rucklin G (2004) Novel p38 inhibitors with potent oral efficacy in several models of rheumatoid arthritis. Bioorg Med Chem Lett 14:3595–3599. doi: 10.1016/j.bmcl.2004.03.106 PubMedGoogle Scholar
  82. 82.
    Zhang C, Sarshar S, Moran EJ, Krane S, Rodarte JC, Benbatoul KD, Dixon R, Mjalli AMM (2000) 2,4,5-Trisubstituted imidazoles: novel nontoxic modulators of P-glycoprotein mediated multidrug resistance, part 2. Bioorg Med Chem Lett 10:2603–2605. doi: 10.1016/S0960-894X(00)00521-7 PubMedGoogle Scholar
  83. 83.
    Deprez P, Mandine E, Vermond A, Lesuisse D (2002) Imidazole-based ligands of the Src SH\(_{2}\) protein. Bioorg Med Chem Lett 12:1287–1289. doi: 10.1016/S0960-894X(02)00138-5 PubMedGoogle Scholar
  84. 84.
    Wang L, Woods KW, Li Q, Barr KJ, McCroskey RW, Hannick SM, Gherke L, Credo RB, Hui YH, Marsh K, Warner R, Lee JY, Zielinsky-Mozng N, Frost D, Rosenberg SH, Sham HL (2002) Potent orally active heterocycle-based combretastatin A-4 analogues: synthesis, structure–activity relationship, pharmacokinetics, and in vivo antitumor activity evaluation. J Med Chem 45:1697–1711. doi: 10.1021/jm010523x PubMedGoogle Scholar
  85. 85.
    Weinstein DS, Liu W, Ngu K, Langevine C, Combs DW, Zhuang S, Chen C, Madsen CS, Harper TW, Robl JA (2007) Discovery of selective imidazole-based inhibitors of mammalian 15-lipoxygenase: highly potent against human enzyme within a cellular environment. Bioorg Med Chem Lett 17:5115–5117. doi: 10.1016/j.bmcl.2007.07.011 PubMedGoogle Scholar
  86. 86.
    Lange JHM, Van Stuivenberg HH, Coolen HKAC, Adolfs TJP, McCreary AC, Keizer HG, Wals HC, Veerman W, Borst AJM, de Looff W, Verveer PC, Kruse CG (2005) Bioisosteric replacements of the pyrazole moiety of rimonabant: synthesis, biological properties, and molecular modeling investigations of thiazoles, triazoles, and imidazoles as potent and selective \(\rm CB_{1}\) cannabinoid receptor antagonists. J Med Chem 48:1823–1838. doi: 10.1021/jm040843r
  87. 87.
    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 (2006) The identification of potent and selective imidazole-based inhibitors of B-Raf kinase. Bioorg Med Chem Lett 16:378–381. doi: 10.1016/j.bmcl.2005.09.072 PubMedGoogle Scholar
  88. 88.
    Dabiri M, Movahed SK, MaGee DI (2013) One-pot synthesis of 2,4,5-triaryl-1\(H\)-imidazoles linked 1,4-disubstituted 1,2,3-triazoles based on a merging multicomponent condensation with Huisgen 1,3-dipolar cycloaddition in ionic liquid. Res Chem Intermed. doi: 10.1007/s11164-013-1436-1
  89. 89.
    Deng X, Zhou Z, Zhang A, Xie G (2013) Brønsted acid ionic liquid [Et\(_{3}\)NH][HSO\(_{4}\)] as an efficient and reusable catalyst for the synthesis of 2,4,5-triaryl-1\(H\)-imidazoles. Res Chem Intermed 39:1101–1108. doi: 10.1007/s11164-012-0669-8 Google Scholar
  90. 90.
    Pandey J, Tiwari VK, Verma SS, Chaturvedi V, Bhatnagar S, Sinha S, Gaikwad AN, Tripathi RP (2009) Synthesis and antitubercular screening of imidazole derivatives. Eur J Med Chem 44:3350–3355. doi: 10.1016/j.ejmech.2009.02.013 PubMedGoogle Scholar
  91. 91.
    Zang H, Su Q, Mo Y, Cheng BW, Jun S (2010) Ionic liquid [EMIM]OAc under ultrasonic irradiation towards the first synthesis of trisubstituted imidazoles. Ultrason Sonochem 17:749–751. doi: 10.1016/j.ultsonch.2010.01.015 PubMedGoogle Scholar
  92. 92.
    Khosropour AR (2008) Synthesis of 2,4,5-trisubstituted imidazoles catalyzed by [Hmim]HSO\(_{4}\) as a powerful Brönsted acidic ionic liquid. Can J Chem 86:264–269. doi: 10.1139/v08-009 Google Scholar
  93. 93.
    Qasim SS, Ali SS (2011) Microwave assisted a novel synthesis for new substituted imidazoles. Der Pharma Chemica 3:518–522. doi: 10.1248/cpb.58.375 Google Scholar
  94. 94.
    Tuan TA (2010) Ytterbium trifluoromethansulfonate. Synlett 12:1880–1881. doi: 10.1055/s-0030-1258101 Google Scholar
  95. 95.
    Karami B, Dehghani FM, Eskandari Kh (2012) Facile and rapid synthesis of polysubstituted imidazoles by employing Y(NO\(_{3}\))\(_{3}\times 6\)H\(_{2}\)O as catalyst. Croat Chem Acta 85:147–153. doi: 10.5562/cca1979 Google Scholar
  96. 96.
    Yu C, Lie M, Su W, Xie Y (2007) Europium triflate-catalyzed pne-pot synthesis of 2,4,5-trisubstituted-1\(H\)-imidazoles via a three-component condensation. Synth Commun 37:3301–3309. doi: 10.1080/00397910701483589 Google Scholar
  97. 97.
    Sharma SD, Hazarika P, Konwar D (2008) An efficient and one-pot synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles catalyzed by InCl\(_{3}\cdot 3\)H\(_{2}\)O. Tetrahedron Lett 49:2216–2220. doi: 10.1016/j.tetlet.2008.02.053 Google Scholar
  98. 98.
    Sharma GVM, Jyothi Y, Lakshmi PS (2006) Efficient room-temperature synthesis of tri- and tetrasubstituted imidazoles catalyzed by \(\rm ZrCl_{4}\). Synth Commun 36:2991–3000. doi: 10.1080/00397910600773825
  99. 99.
    Sangshetti JN, Kokare ND, Kotharkar SA, Shinde DB (2008) \(\rm ZrOCl_{2}\cdot 8\rm H\rm _{2}\)O catalyzed one-pot synthesis of 2,4,5-triaryl-1\(H\)-imidazoles and substituted 1,4-di(4,5-diphenylimidazol-yl)benzene. Chin Chem Lett 19:762–766. doi: 10.1016/j.cclet.2008.05.007
  100. 100.
    Sharma RK, Sharma Ch (2012) An efficient and one pot synthesis of polysubstituted imidazoles catalyzed by \(\rm BiCl_{3}\). Indian J Chem 51B:1489–1493Google Scholar
  101. 101.
    Jourshari S, Mamaghani M, Shirini F, Tabatabaeian Kh, Rassa M, Langar H (2013) An expedient one-pot synthesis of highly substituted imidazoles using supported ionic liquid-like phase (SILLP) as a green and efficient catalyst and evaluation of their anti-microbial activity. Chin Chem Lett 24:993–996. doi: 10.1016/j.cclet.2013.06.005 Google Scholar
  102. 102.
    Ramesh K, Murthy SN, Karnakar K, Nageswar YVD, Vijayalakhshmi K, LA Devi BP, Prasad RBN (2012) A novel bioglycerol-based recyclable carbon catalyst for an efficient one-pot synthesis of highly substituted imidazoles. Tetrahedron Lett 53:1126–1129. doi: 10.1016/j.tetlet.2011.12.092 Google Scholar
  103. 103.
    Mirjalili BF, Bamoniri A, Mirhoseini MA (2013) Nano- SnCl\(_{4}\,\cdot \) SiO\(_{2}\): an efficient catalyst for one-pot synthesis of 2,4,5-tri substituted imidazoles under solvent-free conditions. Scientia Iranica C 20:587–591. doi: 10.1016/j.scient.2013.02.008 Google Scholar
  104. 104.
    Sadeghi B, Mirjalili BF, Hashemi MM (2008) BF\(_{3}\,\cdot \,\)SiO\(_{2}\): an efficient reagent system for the one-pot synthesis of 1,2,4,5-tetrasubstituted imidazoles. Tetrahedron Lett 49:2575–2577. doi: 10.1016/j.tetlet.2008.02.100 Google Scholar
  105. 105.
    Kantevari S, Vuppalapati SVN, Biradar DO, Nagarapu L (2007) Highly efficient, one-pot, solvent-free synthesis of tetrasubstituted imidazoles using HClO\(_{4}\)-SiO\(_{2}\) as novel heterogeneous catalyst. J Mol Catal A 266:109–113. doi: 10.1016/j.molcata.2006.10.048 Google Scholar
  106. 106.
    Karimi AR, Alimohammadi Z, Azizian J, Mohammadi AA, Mohmmadizadeh MR (2006) Solvent-free synthesis of tetrasubstituted imidazoles on silica gel/NaHSO\(_{4}\) support. Catal Commun 7:728–732. doi: 10.1016/j.catcom.2006.04.004 Google Scholar
  107. 107.
    Shaabani A, Rahmati A, Farhangi E, Badri Z (2008) Silica sulfuric acid promoted the one-pot synthesis of trisubstituted imidazoles under conventional heating conditions or using microwave irradiation. Catal Commun 8:1149–1152. doi: 10.1016/j.catcom.2006.10.035 Google Scholar
  108. 108.
    Heravi MM, Bakhtiari K, Oskooie HA, Taheri S (2007) Synthesis of 2,4,5-triaryl-imidazoles catalyzed by NiCl\(_{2}\cdot 6\)H\(_{2}\)O under heterogeneous system. J Mol Catal A 263:279–281. doi: 10.1016/j.molcata.2006.08.070 Google Scholar
  109. 109.
    Kumar D, Kommi DN, Bollineni N, Patel AR, Chakraborti AK (2012) Catalytic procedures for multicomponent synthesis of imidazoles: selectivity control during the competitive formation of tri- and tetrasubstituted imidazoles. Green Chem 14:2038–2049. doi: 10.1039/C2GC35277J Google Scholar
  110. 110.
    Pandit ShS, Bhalerao SK, Aher US, Adhav GL, Pandit VU (2011) Amberlyst A-15: reusable catalyst for the synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted-1\(H\)-imidazoles under MW irradiation. J Chem Sci 123:421–426. doi: 10.1007/s12039-011-0097-0 Google Scholar
  111. 111.
    Wang L, Cai C (2009) Polymer-supported zinc chloride: a highly active and reusable heterogeneous catalyst for one-pot synthesis of 2,4,5-trisubstituted imidazoles. Monatsh Chem 140:541–546. doi: 10.1007/s00706-008-0086-2 Google Scholar
  112. 112.
    Rostamnia S, Zabardasti A (2012) SBA-15/TFE (SBA-15/2,2,2-trifluoroethanol) as a suitable and effective metal-free catalyst for the preparation of the tri- and tetra-substituted imidazoles via one-pot multicomponent method. J Fluorine Chem 144:69–72. doi: 10.1016/j.jfluchem.2012.07.006 Google Scholar
  113. 113.
    Ziarani GM, Badiei A, Lashgari N, Farahani Z (2013) Efficient one-pot synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles using SBA-Pr-SO\(_{3}\)H as a green nano catalyst. J Saudi Chem Soc. doi: 10.1016/j.jscs.2013.01.005
  114. 114.
    Borhade AV, Tope DR, Gite SG (2012) Synthesis, characterization and catalytic application of silica supported tin oxide nanoparticles for synthesis of 2,4,5-tri and 1,2,4,5-tetrasubstituted imidazoles under solvent-free conditions. Arabian J Chem. doi: 10.1016/j.arabjc.2012.11.001
  115. 115.
    Xu X, Li Y (2013) Ferric(III) nitrate supported on kieselguhr: a reusable and inexpensive catalyst for one-pot three-component synthesis of 2,4,5-trisubstituted imidazole derivatives under solvent-free conditions. Res Chem Intermed. doi: 10.1007/s11164-013-1520-6
  116. 116.
    Sivakumar K, Kathirvel A, Lalitha (2010) A simple and efficient method for the synthesis of highly substituted imidazoles using zeolite-supported reagents. Tetrahedron Lett 51:3018–3021. doi: 10.1016/j.tetlet.2010.04.013 Google Scholar
  117. 117.
    Safari J, Khalili SD, Rezaei M, Banitaba SH, Meshkani F (2010) Nanocrystalline magnesium oxide: a novel and efficient catalyst for facile synthesis of 2,4,5-trisubstituted imidazole derivatives. Monatsh Chem 141:1339–1345. doi: 10.1007/s00706-010-0397-y Google Scholar
  118. 118.
    Teimouria A, Najafi ChA (2011) An efficient and one-pot synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles catalyzed via solid acid nano-catalyst. J Mol Catal A 346:39–45. doi: 10.1016/j.molcata.2011.06.007 Google Scholar
  119. 119.
    Karami B, Eskandari Kh, Ghasemi A (2012) Facile and rapid synthesis of some novel polysubstituted imidazoles by employing magnetic Fe\(_{3}\)O\(_{4}\) nanoparticles as a high efficient catalyst. Turk J Chem 36:601–614. doi: 10.3906/kim-1112-49 Google Scholar
  120. 120.
    Heravi MM, Sadjadi S, Oskooie HA, Hekmatshoara R, Bamoharramb FF (2008) The one-pot synthesis of 2,4,5-triaryl-imidazoles using heteropolyacids as heterogeneous and recyclable catalysts. J Chin Chem Soc 55:1199–1203. doi: 10.1002/jccs.200800178 Google Scholar
  121. 121.
    Samai S, Nandi GCh, Singh P, Singh MS (2009) L-Proline: an efficient catalyst for the one-pot synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles. Tetrahedron 65:10155–10161. doi: 10.1016/j.tet.2009.10.019 Google Scholar
  122. 122.
    Murthy SN, Madhav B, Nageswar YVD (2010) DABCO as a mild and efficient catalytic system for the synthesis of highly substituted imidazoles via multi-component condensation strategy. Tetrahedron Lett 51:5252–5257. doi: 10.1016/j.tetlet.2010.07.128 Google Scholar
  123. 123.
    Zheng H, Shi Q-Y, Du K, Mei Y-J, Zhang P-F (2013) One-pot synthesis of 2,4,5-trisubstituted imidazoles catalyzed by lipase. Catal Lett 143:118–121. doi: 10.1007/s10562-012-0920-3 Google Scholar
  124. 124.
    Maske PV, Makhija SJ (2013) Papain catalyzed: multicomponent synthesis of trisubstituted imidazoles. Asian J Biomed Pharm Sci 3:63–65. doi: 10.15272/ajbps.v3i20.295 Google Scholar
  125. 125.
    Mirjalili BF, Bamonirib A, Mohaghegha N (2013) One-pot synthesis of 2,4,5-tri-substituted-1\(H\)-imidazoles promoted by trichloromelamine. Curr Chem Lett 2:35–42. doi: 10.5267/j.ccl.2012.12.001 Google Scholar
  126. 126.
    Vikrant K, Ritu M, Neha S (2012) Synthesis of substituted imidazoles via a multi-component condensat-ion catalyzed by \(p\)-toluene sulfonic acid, PTSA. Res J Chem Sci 2:18–23Google Scholar
  127. 127.
    Maleki B, Keshvari H, Mohammadi A (2012) Ammonium chloride: an effective catalyst for the one-pot synthesis of 2,4,5-trisubstituted imidazoles. Orient J Chem 28:1207–1212. doi: 10.13005/ojc/280316 Google Scholar
  128. 128.
    Jaberi ZK, Barekat M (2010) One-pot synthesis of tri- and tetra-substituted imidazoles using sodium dihydrogen phosphate under solvent-free conditions. Chin Chem Lett 21:1183–1186. doi: 10.1016/j.cclet.2010.06.012 Google Scholar
  129. 129.
    Mukhopadhyay Ch, Tapaswi PK, Drew MGB (2010) Room temperature synthesis of tri-, tetrasubstituted imidazoles and bis-analogues by mercaptopropylsilica (MPS) in aqueous methanol: application to the synthesis of the drug trifenagrel. Tetrahedron Lett 51:3944–3950. doi: 10.1016/j.tetlet.2010.05.102 Google Scholar
  130. 130.
    Sangshetti JN, Kokare ND, Kotharkar SA, Shinde DB (2008) Sodium bisulfite as an efficient and inexpensive catalyst for the one-pot synthesis of 2,4,5-triaryl-1\(H\)-imidazoles from benzil or benzoin and aromatic aldehydes. Monatsh Chem 139:125–127Google Scholar
  131. 131.
    Shaabani A, Maleki A, Behnam M (2009) Tandem oxidation process using ceric ammonium nitrate: three-component synthesis of trisubstituted imidazoles under aerobic oxidation conditions. Synth Commun 39:102–110. doi: 10.1080/00397910802369661 Google Scholar
  132. 132.
    Marzouk AA, Abbasov VM, Talybov AH (2012) Short time one-spot synthesis of 2,4,5-trisubstituted-imidazoles using morpholinium hydrogen sulphate as green and reusable catalysts. Chem J 2:179–184Google Scholar
  133. 133.
    Marzouk AA, Abbasov VM, Talybov AH, Mohamed SK (2013) Synthesis of 2,4,5-triphenyl imidazole derivatives using diethyl ammonium hydrogen phosphate as green, fast and reusable catalyst. World J Org Chem 1:6–10. doi: 10.12691/wjoc-1-1-2 Google Scholar
  134. 134.
    Dake SA, Khedkar MB, Irmale GhS, Ukalgaonkar SJ, Thorat VV, Shintre SA, Pawar RP (2012) Sulfated tin oxide: a reusable and highly efficient heterogeneous catalyst for the synthesis of 2,4,5-triaryl-1\(H\)-imidazole derivatives. Synth Commun 42:1509–1520. doi: 10.1080/00397911.2010.541744 Google Scholar
  135. 135.
    Maleki A, Alirezvani Z, Ghamari N (2013) UHP as a mild and efficient catalyst for the synthesis of substituted imidazoles via multicomponent condensation strategy. In: The 17th international electronic conference on synthetic organic chemistry. doi: 10.3390/ecsoc-17-a031
  136. 136.
    Niknam K, Deris A, Naeimi F, Majleci F (2011) Synthesis of 1,2,4,5-tetrasubstituted imidazoles using silica-bonded propylpiperazine \(N\)-sulfamic acid as a recyclable solid acid catalyst. Tetrahedron Lett 52:4642–4645. doi: 10.1016/j.tetlet.2011.06.105 Google Scholar
  137. 137.
    Kurumurthy C, Kumar GS, Reddy GM, Nagender P, Rao PSh, Narsaiah B (2012) A facile strategy for the synthesis of highly substituted imidazole using tetrabutyl ammoniumbromide as catalyst. Res Chem Intermed 38:359–365. doi: 10.1007/s11164-011-0352-5 Google Scholar
  138. 138.
    Mohammadi AA, Mivechi M, Kefayati H (2008) Potassium aluminum sulfate (alum): an efficient catalyst for the one-pot synthesis of trisubstituted imidazoles. Monatsh Chem 139:935–937. doi: 10.1007/s00706-008-0875-7 Google Scholar
  139. 139.
    Roy HN, Rahman MM, Pramanick PK (2013) Rapid access of some trisubstituted imidazoles from benzil condensed with aldehydes and ammonium acetate catalyzed by l-cystein. Indian J Chem 52B:153–159Google Scholar
  140. 140.
    Teimouri A, Chermahini AN (2011) An efficient and one-pot synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles catalyzed via solid acid nano-catalyst. J Mol Catal A 346:39–45. doi: 10.1016/j.molcata.2011.06.007 Google Scholar
  141. 141.
    Bogevig A, Kumaragurubaran N, Juhl K, Zhuang W, Jorgensen KA (2002) Direct organo-catalytic asymmetric \(\upalpha \)-amination of aldehydes—a simple approach to optically active \(\upalpha \)-amino aldehydes, \(\upalpha \)-amino alcohols, and \(\upalpha \)-amino acids. Angew Chem Int Ed 41:1790–1793. doi: 10.1002/1521-3773(20020517)41:10 Google Scholar
  142. 142.
    Wolkenberg SE, Wisnoski DD, Leister WH, Wang Y, Zhao Z, Lindsley CW (2004) Efficient synthesis of imidazoles from aldehydes and 1,2-diketones using microwave irradiation. Org Lett 6:1453–1456. doi: 10.1021/ol049682b PubMedGoogle Scholar
  143. 143.
    Usyatinsky AY, Khmelnitsky YL (2000) Microwave-assisted synthesis of substituted imidazoles on a solid support under solvent-free conditions. Tetrahedron Lett 41:5031–5035. doi: 10.1016/S0040-4039(00)00771-1 Google Scholar
  144. 144.
    Khaksar S, Alipour M (2013) Lewis acid catalyst free synthesis of substituted imidazoles in 2,2,2-trifluoroethanol. Monatsh Chem 144:395–398. doi: 10.1007/s00706-012-0834-1 Google Scholar
  145. 145.
    Koch P, uerlein ChBa, Jank H, Laufer S (2008) Targeting the ribose and phosphate binding site of p38 Mitogen-Activated Protein (MAP) kinase: synthesis and biological testing of 2-alkylsulf-anyl-, 4(5)-aryl-5(4)-heteroaryl-substituted imidazoles. J Med Chem 51:5630–5640. doi: 10.1021/jm800373t Google Scholar
  146. 146.
    Lantos I, Gombatz K, McGuire M, Pridgen L, Remich J, Shilcrat S (1988) Synthetic and mechanistic studies on the preparation of pyridyl-substituted imidazothiazoles. J Org Chem 53:4223–4227. doi: 10.1021/jo00253a012 Google Scholar
  147. 147.
    Neber PW, Burgard A (1932) Über den Reaktionsverlauf einer neuen Art von Umlagerung bei Ketoximen. III. Justus Liebigs Ann. Chem. 493:281–294. doi: 10.1002/jlac.19324930119 Google Scholar
  148. 148.
    Laufer S, Wagner G, Kotschenreuther D (2002) Ones thiones, and \(N\)-Oxides: an exercise in imidazole chemistry. Angew Chem Int Ed 41:2290–2293. doi: 10.1002/1521-3773(20020703)41:13<2290:AID-ANIE2290>3.0.CO;2-R
  149. 149.
    Laufer S, Koch P (2008) Towards the improvement of the synthesis of novel 4(5)-aryl-5(4)-heteroaryl-2-thio-substituted imidazoles and their p38 MAP kinase inhibitory activity. Org Biomol Chem 6:437–439. doi: 10.1039/B717605H PubMedGoogle Scholar
  150. 150.
    Kim DK, Jung SH, Lee HS, Dewang PM (2009) Synthesis and biological evaluation of benzenesulfonamide-substituted 4-(6-alkylpyridin-2-yl)-5-(quinoxalin-6-yl)imidazoles as transforming growth factor-\(\upbeta \) type 1 receptor kinase inhibitors. Eur J Med Chem 44:568–576. doi: 10.1016/j.ejmech.2008.03.024 PubMedGoogle Scholar
  151. 151.
    Jiang B, Wang X, Shi F, Tu SJ, Ai T, Ballew A, Li G (2009) Microwave enabled umpulong mechanism based rapid and efficient four- and six-component domino formations of 2-(2\(^\prime \)-azaaryl)imidazoles and anti-1,2-Diarylethylbenzamides. J Org Chem 24:9486–9489. doi: 10.1021/jo902204s Google Scholar
  152. 152.
    Wu XJ, Jiang R, Xu XP, Su XM, Lu WH, Ji ShJ (2010) Practical multi-component synthesis of di- or tri-aryl (heteraryl) substituted 2-(pyridin-2-yl)imidazoles from simple building blocks. J Comb Chem 12:829–835. doi: 10.1021/cc100079b PubMedGoogle Scholar
  153. 153.
    Mamedov VA, Zhukova NA, Beschastnova TN, Gubaidullin AT, Rakov DV, Rizvanov IKh (2011) A simple and efficient method for the synthesis of highly substituted imidazoles using 3-aroylquinoxalin-2(1\(H\))-ones. Tetrahedron Lett 52:4280–4284. doi: 10.1016/j.tetlet.2011.06.014 Google Scholar
  154. 154.
    Morisue M, Ogawa K, Kamada K, Ohtab K, Kobuke Y (2010) Strong two-photon and three-photon absorptions in the antiparallel dimer of a porphyrin-phthalocyanine tandem. Chem Commun 46:2121–2123. doi: 10.1039/b921278g Google Scholar
  155. 155.
    Kameyama K, Satake A, Kobuke Y (2004) Light-harvesting composites of directly connected porphyrin–phthalocyanine dyads and their coordination dimers. Tetrahedron Lett 45:7617–7620. doi: 10.1016/j.tetlet.2004.08.101 Google Scholar
  156. 156.
    Mroz P, Bhaumik J, Dogutan DK, Aly Z, Kamal Z, Khalid L, Kee HL, Bocian DF, Holten D, Lindsey JS, Hamblin MR (2009) Imidazole metalloporphyrins as photosensitizers for photodynamic therapy: role of molecular charge, central metal and hydroxyl radical production. Cancer Lett 282:63–76. doi: 10.1016/j.canlet.2009.02.054 PubMedCentralPubMedGoogle Scholar
  157. 157.
    El-Khouly ME, Rogers LM, Zandler ME, Suresh G, Fujitsuka M, Ito O, Souza FD (2003) Studies on intra-supramolecular and intermolecular electron-transfer processes between zinc naphthalocyanine and imidazole-appended fullerene. Chem Phys Chem 4:474–481. doi: 10.1002/cphc.200200540 PubMedGoogle Scholar
  158. 158.
    Youngblood YW (2006) Synthesis of a new trans-A\(_{2}\)B\(_{2}\) phthalocyanine motif as a building block for rodlike phthalocyanine polymers. J Org Chem 71:3345–3356. doi: 10.1021/jo052122l PubMedGoogle Scholar
  159. 159.
    Akçay HT, Bayrak R, Karslioğlu S, Ahin ES (2012) Synthesis characterization and spectroscopic studies of novel peripherally tetra-imidazole substituted phthalocyanine and its metal complexes, the computational and experimental studies of the novel phthalonitrile derivative. J Organomet Chem 713:1–10. doi: 10.1016/j.jorganchem.2012.03.016 Google Scholar
  160. 160.
    Li B, Gu Q, He Y, Zhao T, Wang Sh, Kang J, Zhang Y (2012) Facile synthesis of trisubstituted imidazoles from 1,2-di(furan-2-yl)-2-oxoethyl carboxylates and their chemiluminescence. C R Chimie 15:784–792. doi: 10.1016/j.crci.2012.06.005 Google Scholar
  161. 161.
    Joshi AA, Viswanathan CC (2006) Docking studies and development of novel 5-heteroarylamino-2,4-diamino-8-chloropyrimido-[4,5-b]quinolines as potential antimalarials. Bioorg Med Chem Lett 16:2613–2617. doi: 10.1016/j.bmcl.2006.02.038 PubMedGoogle Scholar
  162. 162.
    Li YZ, Zhang F, Jia XF, Gao DW, Sun JK, Zhang YM, Zhao TQ, Chen XD (2006) Synthesis of 2,3-di(furan-2-yl)-5,6-dihydro-1,4-dioxane. Heterocycl Commun 12:361–364. doi: 10.1515/HC.2006.12.5.361 Google Scholar
  163. 163.
    Assadieskandar A, Amini M, Ostad SN, Riazi GhH, Cheraghi-Shavi T, Shafiei B, Shafiee A (2013) Design, synthesis, cytotoxic evaluation and tubulin inhibitory activity of 4-aryl-5-(3,4,5-trimethoxyphenyl)-2-alkylthio-1\(H\)-imidazole derivatives. Bioorg Med Chem 21:2703–2709. doi: 10.1016/j.bmc.2013.03.011 PubMedGoogle Scholar
  164. 164.
    Salimi M, Amini M, Shafiee A (2005) Synthesis of 2-alkylthio-(4,5-diaryl)imidazoles. Phosphorus Sulfur Silicon Relat Elem 180:1587–1592. doi: 10.1080/104265090884265 Google Scholar
  165. 165.
    Rozwadowska MD (1985) Cyanohydrins as substrates in benzoin condensation: regiocontrolled mixed benzoin condensation. Tetrahedron 41:3135–3140. doi: 10.1016/S0040-4020(01)96667-0 Google Scholar
  166. 166.
    Tomi IHR, Al-Daraji AHR, Abdula AM, Al-Marjani MF (2013) Synthesis, antimicrobial and docking study of three novel 2,4,5-triarylimidazole derivatives. J Saudi Chem Soc. doi: 10.1016/j.jscs.2013.03.004
  167. 167.
    Puterova’ Z, Sterk H, Krutosıkova’ A (2004) Reaction of substituted furan-2-carboxaldehydes and furo[\(b\)]pyrrole type aldehydes with hippuric acid. Molecules 9:11–21. doi: 10.3390/90400241 Google Scholar
  168. 168.
    Chen ChY, Hu WP, Yan PCh, Senadi GCh, Wang JJ (2013) Metal-free acid-promoted synthesis of imidazole derivatives via a multicomponent reaction. Org Lett 15:6116–6119. doi: 10.1021/ol402892z PubMedGoogle Scholar
  169. 169.
    Beale TM, Myers RM, Shearman JW, Charnock-Jones DS, Brenton JD, Gergely FV, Ley SV (2010) Antivascular and anticancer activity of dihalogenated A-ring analogues of combretastatin A-4. Med Chem Commun 1:202–208. doi: 10.1039/C0MD00095G Google Scholar
  170. 170.
    Islam A, Tsou CC, Hsu HJ, Shih WL, Liu CH, ChengC H (2002) Design and synthesis of imidazole derivatives with iodine as catalyst via multi-component reaction. Tamkang J Sci Eng 5:69–80Google Scholar
  171. 171.
    Bahrami K, Khodaei M, Nejati A (2011) One-pot synthesis of 1,2,4,5-tetrasubstituted and 2,4,5-trisubstituted imidazoles by zinc oxide as efficient and reusable catalyst. Monatsh Chem 142:159–162. doi: 10.1007/s00706-010-0428-8 Google Scholar
  172. 172.
    Dobler MR (2003) Design and novel synthesis of aryl-heteroaryl-imidazole MAP kinase inhibitors. Tetrahedron Lett 44:7115–7117. doi: 10.1016/S0040-4039(03)01834-3 Google Scholar
  173. 173.
    Seko N, Yoshino K, Yokota K, Tsukamoto G (1991) Synthesis and platelet aggregation inhibitory activity of diphenylazole derivatives. Part 1. Thiazole and imidazole derivatives. Chem Pharm Bull 39:651–657. doi: 10.1002/chin.199134166 PubMedGoogle Scholar
  174. 174.
    Yamada Sh, Kuramoto M, Kikugawa Y (1969) The reaction of cyanopyridines with sodium borohydride in aprotic solvents. Tetrahedron Lett 10:3101–3104. doi: 10.1016/S0040-4039(01)88359-3 Google Scholar
  175. 175.
    Zhang XJ, Fan W, Fu LP, Jiang B, Tu ShJ (2015) Domino [3+1+1] heterocyclization providing an efficient umpolung strategy for synthesis of 2-(2\(^\prime \)-azaaryl)imidazoles. Res Chem Intermed. 41:773–783. doi: 10.1007/s11164-013-1227-8 Google Scholar
  176. 176.
    Christmann M (2005) New developments in the asymmetric Stetter reaction. Angew Chem Int Ed 44:2632–2634. doi: 10.1002/anie.200500761 Google Scholar
  177. 177.
    Zeitler K (2005) Extending mechanistic routes in heterazolium catalysis—promising concepts for versatile synthetic methods. Angew Chem Int Ed 44:7506–7510. doi: 10.1002/anie.200502617 Google Scholar
  178. 178.
    Heravi MM, Derikvand F, Haghighi M (2008) Highly efficient, four component, one-pot synthesis of tetrasubstituted imidazoles using a catalytic amount of FeCl\(_{3}\cdot 6\)H\(_{2}\)O. Monatsh Chem 139:31–33. doi: 10.1007/s00706-007-0736-9 Google Scholar
  179. 179.
    BandgarB P, Patil AV, Kamble VT (2007) Fluoroboric acid adsorbed on silica gel catalyzed synthesis of bisindolyl alkanes under mild and solvent-free conditions. Arkivoc xvi:252–259. doi: 10.3998/ark.5550190.0008.g25
  180. 180.
    Wu L, Jing X, Zhu H, Liu Y, Yan C (2012) One-pot synthesis of polysubstituted imidazoles from arylaldehydes in water catalyzed by NHC using microwave irradiation. J Chil Chem Soc 57:1204–1207. doi: 10.4067/S0717-97072012000300002 Google Scholar
  181. 181.
    Mohammadizadeh MR, Hasaninejad A, Bahramzadeh M (2009) Trifluoroacetic acid as an efficient catalyst for one-pot, four-component synthesis of 1,2,4,5-tetrasubstituted imidazoles under microwave-assisted, solvent-free conditions. Synth Commun 39:3232–3242. doi: 10.1080/00397910902737122 Google Scholar
  182. 182.
    Raya S, Dasa P, Bhaumikb A, Duttab A, Mukhopadhyaya Ch (2013) Covalently anchored organic carboxylic acid on porous silica nano particle: a novel organometallic catalyst (PSNP-CA) for the chromatography-free highly product selective synthesis of tetrasubstituted imidazoles. Appl Catal A 458:183–195. doi: 10.1016/j.apcata.2013.03.024 Google Scholar
  183. 183.
    HekmatShoar R, Rahimzadeh G, Derikvand F, Farzaneh M (2010) Four-component, one-pot synthesis of tetra-substituted imidazoles using a catalytic amount of MCM-41 or p-TsOH. Synth Commun 40:1270–1275. doi: 10.1080/00397910903068204 Google Scholar
  184. 184.
    Zamani L, Mirjalili BF, Namazian M (2013) One-pot synthesis of 2,4,5-trisubstituted-1\(H\)-imidazoles promoted by nano-TiCl\(_{4}\,\)SiO\(_{2}\): An experimental and theoretical study. Chemija 24:312–319Google Scholar
  185. 185.
    Kannan V, Sreekumar K (2013) Clay supported titanium catalyst for the solvent free synthesis of tetrasubstituted imidazoles and benzimidazoles. J Mol Catal A 376:34–39. doi: 10.1016/j.molcata.2013.04.004 Google Scholar
  186. 186.
    Gwiazda M, Reissig HU (2008) Highly substituted imidazole derivatives from a new four-component synthesis employing methoxyallene. Synthesis: 990–994 doi: 10.1055/s-2007-990933
  187. 187.
    Recent ZhuJ (2003) Developments in the isonitrile-based multicomponent synthesis of heterocycles. Eur J Org Chem 2003:1133–1144. doi: 10.1002/ejoc.200390167 Google Scholar
  188. 188.
    Krimen LI, Cota DJ (1969) The Ritter reaction. Org React 17:213–325. doi: 10.1002/0471264180.or017.03 Google Scholar
  189. 189.
    Sharma GVM, Jyothi Y, Sree Lakshmi P (2006) Efficient room-temperature synthesis of tri- and tetrasubstituted imidazoles catalyzed by \(\text{ ZrCl }_{4}\). Synth Commun 36:2991–3000. doi: 10.1080/00397910600773825 Google Scholar
  190. 190.
    Nagarapu L, Satyender A, Srinivas K (2006) Potassium dodecatugstocobaltate trihydrate (K\(_{5}CoW_{12}O_{40}\cdot 3\)H\(_{2}\)O): a mild and efficient reusable catalyst for the one-pot synthesis of 1,2,4,5-tetrasubstituted imidazoles under conventional heating and microwave irradiation. J Mol Catal A 266:104–108. doi: 10.1016/j.molcata.2006.10.056 Google Scholar
  191. 191.
    Nagarapu L, Satyender A, Rajashaker B, Srinivas K, Ruparani P, Radhika K, Subhashini G (2008) Synthesis and antimicrobial activity of novel C-linked imidazole glycoconjugates. Bioorg Med Chem Lett 18:1167–1171. doi: 10.1016/j.bmcl.2007.11.118 PubMedGoogle Scholar
  192. 192.
    Gleave RJ, Walter DS, Beswick PJ, Fonfria E, Michel AD, Roman ShA, Tang SPh (2010) Synthesis and biological activity of a series of tetrasubstituted-imidazoles as P2X\(_{7}\) antagonists. Bioorg Med Chem Lett 20:4951–4954. doi: 10.1016/j.bmcl.2010.05.018 PubMedGoogle Scholar
  193. 193.
    Kantevari S, Addla D, Bagul PK, Sridhar B, Banerjee SK (2011) Synthesis and evaluation of novel 2-butyl-4-chloro-1-methylimidazole embedded chalcones and pyrazoles as angiotensin converting enzyme (ACE) inhibitors. Bioorg Med Chem 19:4772–4781. doi: 10.1016/j.bmc.2011.06.085 PubMedGoogle Scholar
  194. 194.
    Srinivas K, Nair CKS, Parthasaradhi M (2004) A rapid and efficient synthesis of 2-butyl-5-chloro-3\(H\)-imidazole-4-carboxaldehyde. Synthesis: 506–517. doi: 10.1055/s-2004-815961
  195. 195.
    Chien TCh, Saluya SS, Drach DC, Towsend LB (2004) Synthesis and antiviral evaluation of polyhalogenated imidazole nucleosides: dimensional analogs of 2,5,6-trichloro-1-(beta-D-ribofuranosyl)benzimidazole. J Med Chem 47:5743–5752. doi: 10.1021/jm040016q PubMedGoogle Scholar
  196. 196.
    Tomioka H, Yano T, Takada X, Takeda H, Hirata N (1991) Insecticidal activity of novel trihaloimidazole derivatives against a wild colony of German cockroaches (Blattella germanica). Agric Biol Chem 55:1601–1606. doi: 10.1271/bbb1961.55.1601 Google Scholar
  197. 197.
    Almansa C, Alfon J, de Arrida AF, Cavalcanti FL, Escamilla J, Gomes LA, Miralles A, Soliva R, Bartroli J, Carseller E, Merlos M, Garcia-Bofanell J (2003) Synthesis and structure–activity relationship of a new series of COX-2 selective inhibitors: 1,5-diarylimidazoles. J Med Chem 46:3463–3475. doi: 10.1021/jm030765s PubMedGoogle Scholar
  198. 198.
    Albuquerque JFC, Rolea-Filho JA, Brandao SST, Lima MCA, Ximenes EA, Galdino SL, Pitta IR, Chantegrel J, Perrisin M, Luu-Duc C (1999) Synthesis and antimicrobial activity of substituted imidazolidinediones and thioxoimidazolidinones. Farmaco 54:77–82. doi: 10.1016/s0014-827x(98)00105-0 PubMedGoogle Scholar
  199. 199.
    Beckurts Y, Frerich G, Beckurts H (1899) Beiträge zur Kenntnis der Ureïde und der acidylierten Carbaminsäureester. Ueber die Einwirkung von aromatischen aminen auf chloracetylurethane und chloracetylharnstoffe. Arch Pharm 237:331–346. doi: 10.1002/ardp.18992370503 Google Scholar
  200. 200.
    Chornous VA, Grozav AM, Rusanov EB, Nesterenko AM, Vovk MV (2011) Polyfunctional imidazoles: II. Synthesis and reactions with nucleophilic reagents of 1-substituted 2,4-dichloro-1\(H\)-imidazole-5-carbaldehydes. Russ J Org Chem 47:702–709. doi: 10.1134/S1070428011050083 Google Scholar
  201. 201.
    Mekheimer RA, Hameed AMA, Mansour SAA, Sadek KU (2009) Solar thermochemical reactions III: a convenient one-pot synthesis of 1,2,4,5-tetrasubstituted imidazoles catalyzed by high surface area SiO\(_{2}\) and induced by solar thermal energy. Chin Chem Lett 20:812–814. doi: 10.1016/j.cclet.2009.02.017 Google Scholar
  202. 202.
    Balalaie S, Hashemi MM, Akhbari M (2003) A novel one-pot synthesis of tetrasubstituted imidazoles under solvent-free conditions and microwave irradiation. Tetrahedron Lett 44:1709–1711. doi: 10.1016/S0040-4039(03)00018-2 Google Scholar
  203. 203.
    Uçucu Ü, Gündoğdu N, Işikadağ I (2001) Synthesis and analgesic activity of some 1-benzyl-2-substituted-4,5-diphenyl-1\(H\)-imidazole derivatives. Farmaco 56:285–290. doi: 10.1016/S0014-827X(01)01076-X PubMedGoogle Scholar
  204. 204.
    Jayabharathi J, Thanikachalam V, Srinivasan N, Perumal MV (2012) Fluorescence spectral studies of some imidazole derivatives. Spectrochim Acta A Mol Biomol Spectrosc 90:125–130. doi: 10.1016/j.saa.2012.01.030 PubMedGoogle Scholar
  205. 205.
    Chen Y, Gu Q, Li B, Chen Q, Chen X, Zhang Y, Liu J (2013) Efficient synthesis of 1–R1-2-R-4,5-di(furan-2-yl)-1\(H\)-imidazoles and their luminescence properties. C R Chimie 16:1103–1110. doi: 10.1016/j.crci.2013.05.014 Google Scholar
  206. 206.
    Zhao B, Zhou YC, Fan MJ, Li ZhY, Wang LY, Deng QG (2013) Synthesis, fluorescence properties and selective Cr(III) recognition of tetraaryl imidazole derivatives bearing thiazole group. Chin Chem Lett 24:257–259. doi: 10.1016/j.cclet.2013.01.031 Google Scholar
  207. 207.
    Kamaraj K, Kim E, Galliker B, Zakharov LN, Rheingold AL, Zuberbühler AD, Karlin KD (2003) Copper(I) and Copper(II) complexes possessing cross-linked imidazole-phenol ligands: structures and dioxygen reactivity. J Am Chem Soc 125:6028–6029. doi: 10.1021/ja034263f PubMedGoogle Scholar
  208. 208.
    Fridman N, Kaftory M, Eichen Y, Speiser S (2007) Spectroscopy, photophysical and photochemical properties of bisimidazole derivatives. J Photochem Photobiol A 188:25–33. doi: 10.1016/j.jphotochem.2006.11.014 Google Scholar
  209. 209.
    Suzuke Y, Bakar A, Tanoi T, Nomura N, Sato M (2011) Synthesis of unsymmetrical benzils using N-heterocyclic carbene catalysis. Tetrahedron 67:4710–4715. doi: 10.1016/j.tet.2011.04.020 Google Scholar
  210. 210.
    Yang X, Zheng S, Bottger R, Chae HS, Tanaka T, Li S, Mochizuki A, Jabbour GE (2011) Efficient fluorescent deep-blue and hybrid white emitting devices based on carbazole/benzimidazole compound. J Phys Chem C 115:14347–14352. doi: 10.1021/jp203115c Google Scholar
  211. 211.
    Park S, Kwon JE, Kim SH, Seo J, Chung K, Park SY, Jang DJ, Medina BM, Gierschner J, Park SY (2009) A White-light-emitting molecule: frustrated energy transfer between constituent emitting centers. J Am Chem Soc 131:14043–14049. doi: 10.1021/ja902533f PubMedGoogle Scholar
  212. 212.
    Luo W, Li YP, He Y, Huang SL, Tan JH, Ou TM, Li D, Gu LQ, Huang ZS (2011) Design, synthesis and evaluation of novel tacrine-multialkoxybenzene hybrids as dual inhibitors for cholinesterases and amyloid beta aggregation. Bioorg Med Chem 19:763–770. doi: 10.1016/j.bmc.2010.12.022 PubMedGoogle Scholar
  213. 213.
    Costa JS, Lopes JPB, Russowsky D, Petzhold CL, Borges ACA, Ceschi MA, Konrath E, Batassini C, Lunardi PS, Gonçalves CAS (2013) Synthesis of tacrine-lophine hybrids via one-pot four component reaction and biological evaluation as acetyl- and butyrylcholinesterase inhibitors. Eur J Med Chem 62:556–563. doi: 10.1016/j.ejmech.2013.01.029 PubMedGoogle Scholar
  214. 214.
    Zhang Y, Lai SL, Tong QX, Lo MF, Ng TW, Chan MY, Wen ZC, He J, Jeff KS, Tang XL, Liu WM, Ko CC, Wang PF, Lee CS (2012) High efficiency nondoped deep-blue organic light emitting devices based on imidazole-\(\uppi \)-triphenylamine derivatives. Chem Mater 24:61–70. doi: 10.1021/cm201789u
  215. 215.
    Huang H, Yang X, Pan B, Wang L, Chen J, Ma D, Yang C (2012) Benzimidazole-carbazole-based bipolar hosts for high efficiency blue and white electrophosphorescence applications. J Mater Chem 22:13223–13230. doi: 10.1039/C2JM31765F Google Scholar
  216. 216.
    Hu MK, Lu CF (2000) A facile synthesis of bis-tacrine isosteres. Tetrahedron Lett 41:1815–1818. doi: 10.1016/S0040-4039(00)00036-8 Google Scholar
  217. 217.
    Hu MK (2001) Synthesis and in-vitro anticancer evaluation of bis-tacrine congeners. J Pharm Pharmacol 53:83–88. doi: 10.1211/0022357011775046 PubMedGoogle Scholar
  218. 218.
    Nagarajan N, Prakash A, Velmurugan G, Shakti N, Katiyar M, Venuvanalingam P, Renganathan R (2014) Synthesis, characterisation and electroluminescence behaviour of \(\uppi \)-conjugated imidazole-isoquinoline derivatives. Dyes Pigments 102:180–188. doi: 10.1016/j.dyepig.2013.11.002 Google Scholar
  219. 219.
    Zampieri D, Mamolo MG, Vio L, Banfi E, Scialino G, Fermeglia M, Ferrone M, Pricl S (2007) Synthesis, antifungal and antimycobacterial activities of new bis-imidazole derivatives, and prediction of their binding to P450\(_{14{\rm DM}}\) by molecular docking and MM/PBSA method. Bioorg Med Chem 15:7444–7458. doi: 10.1016/j.bmc.2007.07.023 PubMedGoogle Scholar
  220. 220.
    Hubele A, Riebli P (1993) Arylphenyl ether derivatives, compositions containing these compounds and use thereof. US Patent 5266585Google Scholar
  221. 221.
    Singh J, Verma PK, Tiwari K, Singh ShB (2011) Synthesis of novel pyrazole derivative containing aryl phenyl ether as potential antifungal agent. J Korean Chem Soc 55:153–156. doi: 10.5012/jkcs.2011.55.2.153 Google Scholar
  222. 222.
    Satapathy R, Wu YH, Lin HC (2012) Novel thieno-imidazole based probe for colorimetric detection of Hg\(^{2+}\) and fluorescence turn-on response of Zn\(^{2+}\). Org Lett 14:2564–2567. doi: 10.1021/ol300867e PubMedGoogle Scholar
  223. 223.
    Hu WP, Chen YK, Liao CC, Yu HS, Tsai YM, Huang SM, Tsai FY, Shen HC, Chang LS, Wang JJ (2010) Synthesis, and biological evaluation of 2-(4-aminophenyl)benzothiazole derivatives as photosensitizing agents. Bioorg Med Chem 18:6197–6207. doi: 10.1016/j.bmc.2010.04.082 PubMedGoogle Scholar
  224. 224.
    Wang Z, Lu P, Chen S, Gao Z, Shen F, Zhang W, Xu Y, Kwok HS, Ma Y (2011) Phenanthro[9,10-d]imidazole as a new building block for blue light emitting materials. J Mater Chem 21:5451–5456. doi: 10.1039/C1JM10321K Google Scholar
  225. 225.
    Sarshar S, Siev D, Mjalli AMM (1996) Imidazole libraries on solid support. Tetrahedron Lett 37:835–838. doi: 10.1016/0040-4039(95)02334-8 Google Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Majid M. Heravi
    • 1
  • Mansoureh Daraie
    • 1
  • Vahideh Zadsirjan
    • 1
  1. 1.Department of Chemistry, School of ScienceAlzahra UniversityTehranIran

Personalised recommendations