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 (eFirst)

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.

 
  • References and Notes

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  • 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