Download PDF
Synthesis 2011(24): 4068-4076  
DOI: 10.1055/s-0031-1289599
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Three-Component Synthesis of Some Novel N-Heterocycle Methyl-O-oxime Ethers

Mohammad Navid Soltani Rad*a, Somayeh Behrouz*a, Abdo Reza Nekoeia, Zeinab Faghihb, Ali Khalafi-Nezhadb
a Department of Chemistry, Shiraz University of Technology, Shiraz 71555-313, Iran
Fax: +98(711)7354520; e-Mail: soltani@sutech.ac.ir; e-Mail: behrouz@sutech.ac.ir;
b Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran
Further Information

Publication History

Received 12 August 2011
Publication Date:
09 November 2011 (online)

    Permissions and Reprints All articles of this category

Abstract

A convenient and highly efficient protocol for one-pot synthesis of some novel N-heterocycle methyl-O-oxime ethers is described. In this method, three-component coupling of different types of ketoximes, with methylene iodide and nitrogen heterocycles, including imidazoles, benzimidazole, benzotriazole, and theophylline in the presence of an equimolar mixture of K2CO3/Et3N in refluxing MeCN furnished the corresponding N-heterocycle methyl-O-oxime ethers in good yields. This methodology is highly efficient for the synthesis of various structurally diverse N-heterocycle methyl-O-oxime ethers. The results of quantum mechanical studies on reaction intermediates are discussed.

Key words

three-component reaction (3CR) - oxime - O-oxime ether - methylene iodide - N-heterocycle

    References

  • 1a March J. Advanced Organic Chemistry   Wiley; Singapore: 2005. 
  • 1b Kleeman A. Engel J. Kutscher B. Reichert D. Pharmaceutical Substances   3rd ed.:  Thieme; Stuttgart: 1999. 
    Search in Google Scholar
  • 1c Freeman JP. Chem. Rev.  1973,  73:  283 
    Search in Google Scholar
  • 1d Gowenlock BG. Richter-Addo GB. Chem. Rev.  2004,  104:  3315 
    Search in Google Scholar
  • 2a Phillpotts RJ. Delong DC. Wallace J. Jones RW. Reed SE. Tyrrell DAJ. Lancet  1981,  1:  1342 
    Search in Google Scholar
  • 2b Hayden FG. Gawaltney JM. Antimicrob. Agents Chemother.  1982,  21:  892 
    Search in Google Scholar
  • 2c Dewolfe Miller F. Monto AS. Delong DC. Exelby A. Bryan ER. Srivastava S. Antimicrob. Agents Chemother.  1985,  27:  102 
    Search in Google Scholar
  • 3 Sakene K. Kawabata K. Inamoto Y. Yamanaka H. Takaya T. Yakugaku Zasshi  1993,  113:  605 ; Chem. Abstr. 1994, 120, 94531v
    Search in Google Scholar
  • 4a Mixich G. Thiele K. Arzneim.-Forsch.  1979,  29:  1510 
    Search in Google Scholar
  • 4b Wihbi Y. Caujolle R. Tournaire C. Payard M. Linas MD. Seguela JP. Eur. J. Med. Chem.  1995,  30:  955 
    Search in Google Scholar
  • 5a Mordi MN. Pelta MD. Boote V. Morris GA. Barber J. J. Med. Chem.  2000,  43:  467 
    Search in Google Scholar
  • 5b Gharbi-Benarous J. Delaforge M. Jankowski CK. Girault JP. J. Med. Chem.  1991,  34:  1117 
    Search in Google Scholar
  • 6a De Clerk F. Beetens J. Van de Water A. Vercammen E. Janssen PAJ. Thromb. Haemostasis  1989,  61:  43 
    Search in Google Scholar
  • 6b Bossche HV. Willemsens G. Bellens D. Janssen PAJ. Biochem. Pharmacol.  1992,  43:  739 
    Search in Google Scholar
  • 7 Zhu J. Bienaymé H. Multicomponent Reactions   Wiley-VCH; Weinheim: 2005. 
  • 8 Strecker D. Ann. Chem. Pharm.  1850,  75:  27 
    Search in Google Scholar
  • 9a Hantzsch A. Liebigs Ann. Chem.  1882,  215:  1 
    Search in Google Scholar
  • 9b Hantzsch A. Ber. Dtsch. Chem. Ges.  1890,  23:  1474 
    Search in Google Scholar
  • 10a Biginelli P. Ber. Dtsch. Chem. Ges.  1891,  24:  1317 
    Search in Google Scholar
  • 10b Biginelli P. Ber. Dtsch. Chem. Ges.  1893,  26:  447 
    Search in Google Scholar
  • 11 Mannich C. Krösche W. Arch. Pharm. Ber. Dtsch. Pharmaz. Ges.  1912,  250:  647 
    Search in Google Scholar
  • 12a Passerini M. Gazz. Chim. Ital.  1921,  51:  126 
    Search in Google Scholar
  • 12b Passerini M. Gazz. Chim. Ital.  1921,  51:  181 
    Search in Google Scholar
  • 13 Ugi I. Angew. Chem., Int. Ed. Engl.  1962,  1:  8 
    Search in Google Scholar
  • 14a Gewald K. Chem. Ber.  1965,  98:  3571 
    Search in Google Scholar
  • 14b Gewald K. Schinke E. Böttcher H. Chem. Ber.  1966,  99:  94 
    Search in Google Scholar
  • 15a Khalafi-Nezhad A. Soltani Rad MN. Hakimelahi GH. Mokhtari B. Tetrahedron  2002,  58:  10341 
    Search in Google Scholar
  • 15b Soltani Rad MN. Khalafi-Nezhad A. Babamohammadi S. Behrouz S. Helv. Chim. Acta  2010,  93:  2454 
    Search in Google Scholar
  • 16a

    Khalafi-Nezhad A., Salehi M. H., Soltani Rad M. N.; Abstracts from First Iranian Congress on Biochemistry and Biophysics; Tehran, Iran, 16 January, 2001;

  • 16b Abstract: Khalafi-Nezhad A. Salehi MH. Soltani Rad MN. Iranian Biomed. J.  2000,  4:  147 
    Search in Google Scholar
  • 17 Amirghofran Z. Khalafi-Nezhad A. Tasdighi F. Iranian J. Med. Sci.  2001,  26:  16 
    Search in Google Scholar
  • 18a Soltani Rad MN. Behrouz S. Dianat M. Synthesis  2008,  2055 
  • 18b Soltani Rad MN. Khalafi-Nezhad A. Behrouz S. Helv. Chim. Acta  2009,  92:  1760 
    Search in Google Scholar
  • 18c Soltani Rad MN. Khalafi-Nezhad A. Karimitabar F. Behrouz S. Synthesis  2010,  1724 
  • 19 Buck JS. Ide WS. Org. Synth. Coll. Vol. 2   Wiley; New York: 1943.  p.622 
  • 20 Wasilke J.-C. Chem. Rev.  2005,  105:  1001 
    Search in Google Scholar
  • 21 Smith PAS. Robertson JE. J. Am. Chem. Soc.  1962,  84:  1197 
    Search in Google Scholar
  • 22 Buehler E. J. Org. Chem.  1967,  32:  261 
    Search in Google Scholar
  • 23 Smith SG. Milligan DV. J. Am. Chem. Soc.  1968,  90:  2393 ; and references cited therein
    Search in Google Scholar
  • 24a Deorge RF. Wilson and Grisvold’s Textbook of Organic Medicinal and Pharmaceutical Chemistry   8th ed.:  J. B. Lippincott Company; Philadelphia: 1982. 
    Search in Google Scholar
  • 24b Thomas G. Medicinal Chemistry   Wiley; New York: 2000. 
  • 25 Liu Z.-Z. Chen H.-C. Cao S.-L. Li R.-T. Synth. Commun.  1993,  23:  2611 
    Search in Google Scholar
  • 26a Khalafi-Nezhad A. Soltani Rad MN. Mohabatkar H. Asrari Z. Hemmateenejad B. Bioorg. Med. Chem.  2005,  13:  1931 
    Search in Google Scholar
  • 26b Butler K. Howes HL. Lynch JE. Pirie DK. J. Med. Chem.  1967,  10:  891 
    Search in Google Scholar
  • 27 Frisch MJ. Trucks GW. Schlegel HB. Scuseria GE. Robb MA. Cheeseman JR. Montgomery JA. Vreven T. Kudin KN. Burant JC. Millam JM. Iyengar SS. Tomasi J. Barone V. Mennucci B. Cossi M. Scalmani G. Rega N. Petersson GA. Nakatsuji H. Hada M. Ehara M. Toyota K. Fukuda R. Hasegawa J. Ishida M. Nakajima T. Honda Y. Kitao O. Nakai H. Klene M. Li X. Knox JE. Hratchian HP. Cross JB. Adamo C. Jaramillo J. Gomperts R. Stratmann RE. Yazyev O. Austin AJ. Cammi R. Pomelli C. Ochterski JW. Ayala PY. Morokuma K. Voth GA. Salvador P. Dannenberg JJ. Zakrzewski VG. Dapprich S. Daniels AD. Strain MC. Farkas O. Malick DK. Rabuck AD. Raghavachari K. Foresman JB. Ortiz JV. Cui Q. Baboul AG. Clifford S. Cioslowski J. Stefanov BB. Liu G. Liashenko A. Piskorz P. Komaromi I. Martin RL. Fox DJ. Keith T. Al-Laham MA. Peng CY. Nanayakkara A. Challacombe M. Gill PMW. Johnson B. Chen W. Wong MW. Gonzalez C. Pople JA. Gaussian 03, Revision B. 05   Gaussian, Inc.; Pittsburgh PA (USA): 2003. 
  • 28 Glendening ED. Badenhoop JK. Reed AE. Carpenter JE. Bohmann JA. Morales CM. Weinhold F. NBO 5.0   Theoretical Chemistry Institute, University of Wisconsin; Madison WI (USA): 2001.