Download PDF
Synlett 2012; 23(8): 1191-1198
DOI: 10.1055/s-0031-129036
letter
© Georg Thieme Verlag Stuttgart · New York

8-Bromocaffeine (8-BC): A New Versatile Reagent for Conversion of ­Aldoximes into Nitriles

Mohammad Navid Soltani Rad*
Department of Chemistry, Shiraz University of Technology, Shiraz 71555-313, Iran, Fax: +98(711)7354520   Email: soltani@sutech.ac.ir   Email: behrouz@sutech.ac.ir
,
Somayeh Behrouz*
Department of Chemistry, Shiraz University of Technology, Shiraz 71555-313, Iran, Fax: +98(711)7354520   Email: soltani@sutech.ac.ir   Email: behrouz@sutech.ac.ir
,
Abdo-Reza Nekoei
Department of Chemistry, Shiraz University of Technology, Shiraz 71555-313, Iran, Fax: +98(711)7354520   Email: soltani@sutech.ac.ir   Email: behrouz@sutech.ac.ir
› Author Affiliations
Further Information

Publication History

Received: 09 February 2012

Accepted after revision: 12 March 2012

Publication Date:
26 April 2012 (online)

    Permissions and Reprints All articles of this category


Abstract

A rapid and highly convenient synthesis of nitriles from the corresponding aldoximes using 8-bromocaffeine (8-BC) is described. In this protocol, aldoximes react with 8-BC in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and N,N-dimethylformamide (DMF) to furnish the corresponding nitriles under both microwave-assisted and/or conventional heating (reflux) conditions in short times and in good to excellent yields. This methodology is highly efficient for structurally diverse aldoximes including aliphatic, aromatic, and heteroaromatic oximes.

Key words

nitriles - oximes - synthetic methods - dehydration
 

  • References and Notes

  • 1 Friedrich K, Wallenfels K In The Chemistry of the Cyano Group . Rappaport Z. Wiley; New York: 1970
    Google Scholar
  • 2 Fatiadi AJ In Preparation and Synthetic Applications of Cyano Compounds . Patai S, Rappaport Z. Wiley; New York: 1983
    Google Scholar
  • 3 March J. Advanced Organic Chemistry . 4th ed. John Wiley & Sons (Asia) Ltd; Singapore: 2005
    Google Scholar
  • 4 Larock RC. Comprehensive Organic Transformations . 2nd ed. Wiley; New York: 1999
    Google Scholar
  • 5 Anand N, Owston NA, Parker AJ, Slatford PA, Williams JM. J. Tetrahedron Lett. 2007; 48: 7761
    Crossref
  • 6 Hegarty AF, Tuohey PJ. J. Chem. Soc., Perkin Trans. 2 1980; 1313
  • 7 Kim HS, Kim SH, Kim JN. Tetrahedron Lett. 2009; 50: 1717
    Crossref
  • 8 Soltani Rad MN, Khalafi-Nezhad A, Behrouz S, Amini Z, Behrouz M. Synth. Commun. 2010; 40: 2429
    Crossref
  • 9 Yang SH, Chang S. Org. Lett. 2001; 3: 4209
    CrossrefPubMed
  • 10 Lee K, Han SB, Yoo EM, Chung SR, Oh H, Hong S. Synth. Commun. 2004; 34: 1775
    Crossref
  • 11 Olah GA, Vankar YD. Synthesis 1978; 702
    Article in Thieme Connect
  • 12 Kim JN, Chung KH, Ryu EK. Synth. Commun. 1990; 20: 2785
    Crossref
  • 13 Gabriel S, Meyer R. Ber. Dtsch. Chem. Ges. 1881; 14: 2332
    Crossref
  • 14 Dulcere J.-P. Tetrahedron Lett. 1981; 22: 1599
    Crossref
  • 15 Miller CP, Kaufman DH. Synlett 2000; 1169
    Article in Thieme Connect
  • 16 Chakrabarti JK, Hotten TM. J. Chem. Soc., Chem. Commun. 1972; 1226
  • 17 Kim S, Yi KY. Tetrahedron Lett. 1986; 27: 1925
    Crossref
  • 18 Konwar D, Boruah RC, Sandhu JS. Tetrahedron Lett. 1990; 31: 1063
    Crossref
  • 19 Iranpoor N, Zeynizadeh B. Synth. Commun. 1999; 29: 2747
    Crossref
  • 20 Boruah M, Konwar D. J. Org. Chem. 2002; 67: 7138
    CrossrefPubMed
  • 21 Li D, Shi F, Guo S, Deng Y. Tetrahedron Lett. 2005; 46: 671
    Crossref
  • 22 Khan TA, Peruncheralathan S, Ila H, junjappa H. Synlett 2004; 2019
    Article in Thieme Connect
  • 23 Bentley TJ, McGhié JF, Barton DH. R. Tetrahedron Lett. 1965; 2497
    • 24a Block J, Beal JM. Wilson & Gisvold’s Textbook of Organic Medicinal and Pharmaceutical Chemistry. 11th ed. Lippincott, Williams & Wilkins; Baltimore: 2003
      Google Scholar
    • 24b Kleeman A, Engel J, Kutscher B, Reichert D. Pharmaceutical Substances . 3rd ed. Thieme; Stuttgart: 1999
      Google Scholar
  • 25 Soltani Rad MN, Khalafi-Nezhad A, Behrouz S, Faghihi MA. Tetrahedron Lett. 2007; 48: 6779
    Crossref
    • 26a Zhu J, Bienaymé H. Multicomponent Reactions . Wiley-VCH; Weinheim: 2005
      CrossrefGoogle Scholar
    • 26b Khalafi-Nezhad A, Soltani Rad MN, Hakimelahi GH, Mokhtari B. Tetrahedron 2002; 58: 10341
      Crossref
    • 26c Soltani Rad MN, Khalafi-Nezhad A, Babamohammadi S, Behrouz S. Helv. Chim. Acta 2010; 93: 2454
      Crossref
    • 26d Soltani Rad MN, Behrouz S, Nekoei AR, Faghih Z, Khalafi-Nezhad A. Synthesis 2011; 4068
      Article in Thieme Connect
  • 27 Wang E.-C, Lin G.-J. Tetrahedron Lett. 1998; 39: 4047
    Crossref
  • 28 Kokel B, Menichi G, Hubert-Habart M. Synthesis 1985; 201
    Article in Thieme Connect
  • 29 Lai G, Bhamare NK, Anderson WK. Synlett 2001; 230
  • 30 Meshram HM. Synthesis 1992; 943
    Article in Thieme Connect
  • 31 Mizuno A, Hamada Y, Shioiri T. Synthesis 1980; 1007
    Article in Thieme Connect
  • 32 Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Montgomery JA. Jr, 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 PM. W, Johnson B, Chen W, Wong MW, Gonzalez C, Pople JA. Gaussian 03, Revision B.05. Gaussian Inc; Pittsburgh: 2003
    Google Scholar
  • 33 Glendening ED, Badenhoop JK, Reed AE, Carpenter JE, Bohmann JA, Morales CM, Weinhold F. NBO 5.0. Theoretical Chemistry Institute (University of Wisconsin–Madison); Madison: 2001
    Google Scholar
  • 34 Yu CL, Kale Y, Gopishetty S, Louie TM, Subramanian M. J. Bacteriol. 2008; 190: 772
    Crossref
  • 35 Ghiaci M, Nasr Esfahani R, Aghaei H. Catal. Commun. 2009; 10: 777
    Crossref
  • 36 8-BC [CAS Number: 10381-82-5] is commercially available; however, using freshly prepared 8-BC affords more favorable results. Fresh 8-BC can be easily prepared by using the following procedure: To a round-bottom flask (500 mL) containing freshly distilled CH2Cl2 (300 mL) was added caffeine (19.4 g, 0.1 mol) and NBS (35.2 g, 0.2 mol). When the solids had dissolved in solvent, water (100 mL) was added and the container was closed and stirred for 5 d. The solution was transferred into a separator funnel and solution of cold NaOH (100 mL, 2 M) was added the mixture was shaken to decolorize the mixture. The organic layer was separated, washed with water (2 × 200 mL), dried over Na2SO4 (30 g), filtered, and evaporated to provide pure 8-BC (26 g, ca. 100%)
  • 37 General procedure for microwave-assisted conversion of aldoximes into nitriles by using 8-BC: Into a laboratory microwave oven equipped with a condenser, was inserted a round-bottom flask (50 mL) containing a solution of aldoxime (5 mmol), DBU (5 mmol), and 8-BC (6 mmol) in DMF (6 mL). The mixture was then irradiated at 300 W for the indicated time (Table 5). When TLC monitoring indicated no further improvement in the reaction, the crude products were suspended in CH2Cl2 (30 mL) and washed with H2O (2 × 100 mL). The organic layer was dried over Na2SO4 (10 g) and concentrated to afford the crude product, which was purified by column chromatography on silica gel (n-hexane–EtOAc). All products were characterized by 1H NMR, 13C NMR, IR, CHN and MS analysis
  • 38 Selected spectral data: 4-(Allyloxy)-3-methoxy benzonitrile (Table 5, Entry 8): White solid; Rf = 0.47 (EtOAc–n-hexane, 1:5); mp 59–60 °C; 1H NMR (250 MHz, CDCl3): δ = 3.93 (s, 3 H, CH3), 4.60 (dd, J = 1.3, 5.1 Hz, 2 H, OCH2), 5.48 (dd, J = 1.5, 11.2 Hz, 2 H, =CH2), 6.11–6.14 (m, 1 H, =CH), 7.01 (d, J = 8.1 Hz, 1 H, ArH), 7.13 (s, 1 H, ArH), 7.25 (d, J = 8.1 Hz, 1 H, ArH); 13C NMR (250 MHz, CDCl3): δ = 54.17, 68.43, 104.51, 114.03, 115.94, 119.70, 119.93, 128.21, 134.58, 157.04, 161.37; MS: m/z (%) = 189.08 (30); Anal. Calcd for C11H11NO2: C, 69.83; H, 5.86; N, 7.40. Found: C, 69.74; H, 5.94; N, 7.52. 3-(4-Methoxybenzyloxy) benzonitrile (Table 5, Entry 10): White solid; Rf = 0.31 (EtOAc–n-hexane, 1:9); mp 94–95 °C; 1H NMR (250 MHz, CDCl3): δ = 3.86 (s, 3 H, OCH3), 5.30 (s, 2 H, OCH2), 7.11 (d, J = 8.2 Hz, 2 H, ArH), 7.25–7.30 (m, 3 H, ArH), 7.39–7.46 (m, 3 H, ArH); 13C NMR (250 MHz, CDCl3): δ = 51.16, 69.45, 112.86, 115.37, 118.70, 121.57, 123.97, 127.05, 128.14, 130.91, 132.28, 158.76, 162.29; MS: m/z (%) = 239.09 (36); Anal. Calcd for C15H13NO2: C, 75.30; H, 5.48; N, 5.85. Found: C, 75.42; H, 5.60; N, 5.80. 2-[2-(1,3-Dioxoisoindolin-2-yl)ethoxy]benzonitrile (Table 5, Entry 15): White solid; Rf = 0.48 (EtOAc–n-hexane, 1:1); mp 148–149 °C; 1H NMR (250 MHz, CDCl3): δ = 4.03 (t, J = 5.9 Hz, 2 H, NCH2), 4.22 (t, J = 5.9 Hz, 2 H, OCH2), 6.88–6.91 (m, 2 H, aryl), 7.36–7.42 (m, 2 H, aryl), 7.58–7.63 (m, 2 H, aryl), 7.68–7.73 (m, 2 H, aryl); 13C NMR (250 MHz, CDCl3): δ = 36.52, 65.19, 102.29, 112.29, 115.88, 121.31, 123.34, 131.86, 133.59, 133.76, 134.11, 159.66, 167.89; MS: m/z (%) = 292.08 (52); Anal. Calcd for C17H12N2O3: C, 69.86; H, 4.14; N, 9.58. Found: C, 69.82; H, 4.17; N, 9.63. 2-[5-(2-Methyl-4-nitro-1H-imidazol-1-yl)pentyloxy]-benzonitrile (Table 5, Entry 16): Bright yellow oil; Rf = 0.45 (EtOAc); 1H NMR (250 MHz, CDCl3): δ = 0.73–0.75 (m, 2 H, CH2), 1.05 (m, 4 H, 2 × CH2), 1.59 (s, 3 H, CH3), 3.20 (m, 4 H, NCH2, OCH2), 6.16–6.19 (m, 2 H, ArH), 6.67–6.68 (m, 2 H, ArH), 7.13 (s, 1 H, C(5)-H, imidazole); 13C NMR (250 MHz, CDCl3): δ = 12.42, 22.37, 27.68, 29.28, 46.51, 68.12, 100.81, 111.99, 116.02, 120.23, 132.97, 134.15, 144.42, 145.57, 159.94, 161.84; MS: m/z (%) = 314.10 (48); Anal. Calcd for C16H18N4O3: C, 61.13; H, 5.77; N, 17.82. Found: C, 61.15; H, 5.81; N, 17.79