Supporting Information
An Efficient and Mild Strecker-Type Reaction of Nitrones Catalyzed by MgI2 Etherate
Zhili Chen, Xinyu Zhou, Xiaoqiang Xie, Xingxian Zhang*
College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, Zhejiang 310032, P. R. China.
E-mail address:
Contents:
I. General Information...... S1
II. General procedure for the synthesis of α-cyanohydroxylamines...... S2
III.Spectral charaterization of all the compounds...... S2-S5
IV. References...... S5
V. 1H, 13C NMR,HMRS spectra of compounds2a-2r...... S6-S19
VI.1H, 13C NMR,HMRS spectra of compounds3a-3e...... S19-S22
General information:All reagents were commercially available and directly used without further treatment. Melting points were performed on X-4B microscopic melting point meter.1H NMR spectra were recorded at 500 MHz in CDCl3 using TMS as internal standard. 13C NMR spectral measurements were performed at 125 MHz using TMS as an internal standard. EI-MS were determined on a PerkinElmer spectrometer. HRMS(ESI) were determined on a Therm LCQ TM Deca XP plus spectrometer. HRMS (TOF-EI) were determined on GCT premier spectrometer. IR spectroscopy was performed on a Nicolet 6700 infrared spectrometer.For product purification by flash column chromatography, silica gel (200~300 mesh) and light petroleum ether (PE, b.p. 60~90 oC) were used.
General procedure for the synthesis of α-cyanohydroxylamines (2a-2r):To a solution of the corresponding nitrones 1 (1.0 mmol) in CH2Cl2 (5 mL) was added trimethylsilyl cyanide (1.5 mmol) and a freshly prepared MgI2 etherate (0.05 mmol, 1.0 mol/L inEt2O/toluene 1:1, 5.0 mol %). The reaction mixture was stirred at room temperature for 10 to 15 minutes. The solvent was evaporated after completion of reaction, and the resulting mixture was treated with 2.0 mol/L HCl/MeOH (2 mL). Saturated NaHCO3 aqueous was added and the resulting mixture was extracted with dichloromethane (320 mL). The combined organic phase was washed with brine and concentrated. The residue was purified by flash column chromatography on a silica gel to give the cyanated product 2a-2r.
Spectral charaterization of all the compounds:
Spectral data of α-cyanohydroxylamines (2a-2r)
2-(hydroxy(phenyl)amino)-2-phenylacetonitrile (2a)[1]. Yellow solid; Rf 0.40 (PE:EA=5:1); mp 125.9-126.4 C (lit. 127.5-128.5 C);H (CDCl3) 5.41 (s, 1H), 5.59 (s, 1H), 7.18 (t, J = 7.5 Hz, 1H), 7.29 (d, J = 7.5 Hz, 2H), 7.38 (t, J = 8.5 Hz, 2H), 7.43-7.45 (m, 3H), 7.56-7.59 (m, 2H) ppm.
2-(hydroxy(phenyl)amino)-2-(p-tolyl)acetonitrile (2b)[2]. Yellow solid; Rf 0.38 (PE:EA=3:1); mp 132.9-134.7 C;H (CDCl3) 2.40 (s, 3H), 5.39 (s, 1H), 5.52 (s, 1H), 7.17 (t, J = 7.5 Hz, 1H), 7.24 (d, J = 8.0 Hz, 2H), 7.28 (dd, J = 2.0, 9.5 Hz, 2H), 7.34-7.39 (m, 2H), 7.46 (d, J = 8.0 Hz, 2H) ppm.
2-(hydroxy(phenyl)amino)-2-(4-methoxyphenyl)acetonitrile (2c)[3]. Yellow solid; Rf 0.35 (PE:EA=3:1); mp 127.9-129.0C;H (CDCl3) 3.85 (s, 3H), 5.37 (s, 1H), 5.51 (s, 1H), 6.94 (d, J = 9.0 Hz, 2H), 7.17 (t, J = 7.0 Hz, 1H), 7.26-7.28 (m, 2H), 7.37 (t, J = 7.6 Hz, 2H), 7.48 (d, J = 8.5 Hz, 2H) ppm.
2-(2-chlorophenyl)-2-(hydroxy(phenyl)amino)acetonitrile (2d). Yellow solid; Rf 0.38 (PE:EA=3:1); mp 114.5-115.9 C;H (CDCl3) 5.72 (s, 1H), 6.00 (s, 1H), 7.18 (t, J = 7.0 Hz, 1H), 7.27 (td, J = 1.5, 7.5 Hz, 1H), 7.30-7.42 (m, 6H), 7.73 (dd, J = 1.5, 7.5 Hz, 1H) ppm;C (CDCl3) 62.8, 114.8, 118.6, 125.2, 127.0, 129.0, 129.7, 129.8, 131.0, 131.6, 133.8, 149.4 ppm; IR (KBr):3270(-OH), 3066, 2856, 2247(-CN), 1593, 1486, 1444, 1283, 1193, 962, 833, 752, 696 cm-1. HRMS (ESI): calcd. for C14H12N2OCl [M+H]+ 259.0633; found 259.0641.
2-(2-fluorophenyl)-2-(hydroxy(phenyl)amino)acetonitrile (2e). Yellow solid; Rf 0.38 (PE:EA=3:1); mp 116.5-117.6 C;H (CDCl3) 5.66 (s, 1H), 5.71 (s, 1H), 7.13 (t, J = 8.5 Hz, 1H), 7.17-7.23 (m, 2H), 7.31 (dd, J = 1.5, 8.5 Hz, 2H), 7.36-7.45 (m, 3H), 7.71 (td, J = 1.0, 7.5 Hz, 1H) ppm;C (CDCl3) 59.3(d, J = 2.4 Hz, 1C), 114.8, 115.6 (d, J = 20.9 Hz, 1C), 118.9, 120.0 (d, J = 12.7 Hz, 1C), 124.3 (d, J = 3.5 Hz, 1C), 125.3, 129.1, 131.1 (d, J = 2.0 Hz, 1C), 131.6 (d, J = 8.3 Hz, 1C), 149.4, 160.0 (d, J = 249.1 Hz, 1C) ppm;IR (KBr): 3280(-OH), 3073, 2854, 2247(-CN), 1594, 1494, 1460, 1238, 1195, 1016, 955, 755, 700 cm-1. HRMS (ESI): calcd. for C14H12FN2O [M+H]+ 243.0934; found 243.0944.
2-(thiophen-2-yl)-2-(hydroxy(phenyl)amino)acetonitrile (2f). Yellow solid; Rf 0.51 (PE:EA=3:1); mp 89.4-91.5C;H (CDCl3) 5.58 (s, 1H), 5.78 (s, 1H), 7.03 (dd, J = 3.5, 5.0 Hz, 1H), 7.18 (t, J = 7.3 Hz, 1H), 7.28-7.31 (m, 3H), 7.37-7.40 (m, 3H);C (CDCl3) 60.9, 115.1, 118.9, 125.3, 126.9, 127.6, 128.8, 129.1, 134.6, 148.8 ppm;IR (KBr): 3277(-OH), 3051, 2949, 2243(-CN), 1594, 1487, 1428, 1193, 1024, 935, 794, 695 cm-1. HRMS (ESI): calcd. for C12H11N2OS [M+H]+ 231.0592; found 231.0598.
2-(3-methylthiophen-2-yl)-2-(phenyl((trimethylsilyl)oxy)amino)acetonitrile (2g). Yellow solid; Rf 0.71 (PE:EA=3:1); mp 92.5-92.9C;H (CDCl3) 0.03 (s, 9H), 2.24(s, 3H), 5.40 (s, 1H), 6.84 (d, J = 5.0 Hz, 1H), 7.17-7.20 (m, 1H), 7.26 (d, J = 5.0 Hz, 1H), 7.30-7.35 (m, 4H);C (CDCl3) -1.14, 13.8, 60.5, 115.8, 120.9, 125.8, 125.9, 127.2, 128.7, 129.9, 138.0, 150.1 ppm;IR (KBr): 3272(-OH), 2968, 2858, 2244(-CN), 1603, 1483, 1444, 1283, 1293, 965, 833, 753, 693 cm-1. HRMS (ESI): calcd. for C13H13N2OS [M+H]+ 245.0749; found 245.0755.
(E)-4-phenyl-2-(phenyl((trimethylsilyl)oxy)amino)but-3-enenitrile (2h)[4]. Brownness liquid; Rf 0.66 (PE:EA=3:1);H (CDCl3) 0.11 (s, 9H), 4.87 (dd, J = 1.5, 6.5 Hz, 1H), 6.26 (dd, J = 6.0, 16.0 Hz, 1H), 6.86 (d, J = 16.0 Hz, 1H), 7.31-7.33 (m, 6H), 7.39-7.42 (m, 4H) ppm.
2-phenyl-2-(benzyl(hydroxy)amino)acetonitrile (2i)[1]. White solid; Rf 0.61 (PE:EA=3:1); mp 103.5-104.1 C;H (CDCl3) 3.78 (d, J =12.5 Hz, 1H), 3.86 (d, J =12.5 Hz, 1H), 4.64 (s, 1H), 6.50 (br, s, 1H), 7.31-7.41 (m, 5H), 7.42-7.48 (m, 5H) ppm.
2-(4-methoxyphenyl)-2-(benzyl(hydroxy)amino)acetonitrile (2j)[5]. Pale yellow solid; Rf 0.47 (PE:EA=3:1); mp 102.5-103.1 C;H (CDCl3) 3.79 (s, 3H), 3.82 (s, 2H), 4.61 (s, 1H), 6.49 (br, s,1H), 6.91 (d, J = 8.5 Hz, 2H), 7.32 (t, J = 7.5Hz, 3H), 7.35-7.37 (m, 4H) ppm.
2-(2-methoxyphenyl)-2-(benzyl(hydroxy)amino)acetonitrile (2k). White solid; Rf 0.46 (PE:EA=3:1); mp 145.2-147.9 C;H (CDCl3) 3.34 (d, J = 12.0 Hz, 1H), 3.69 (s, 3H), 3.70 (d, J = 13.0 Hz, 1H), 4.95 (s, 1H), 6.89 (d, J = 8.0 Hz, 1H), 6.98 (t, J = 7.5 Hz, 1H), 7.23 (dd, J = 6.5, 8.0 Hz, 3H), 7.31-7.38 (m, 4H), 7.70 (dd, J = 1.5, 8.0 Hz, 1H) ppm;C (CDCl3) 55.1, 55.4, 61.8, 110.7, 115.8, 120.3, 120.6, 128.1, 128.4, 129.7, 130.7, 130.9, 134.9, 156.6 ppm;IR (KBr): 3235(-OH), 2855, 2234(-CN), 1792, 1604, 1493, 1464, 1437, 1253, 1113, 1030, 762, 690 cm-1. HRMS(ESI): calcd. for C13H13N2OS [M+H]+ 245.0749; found 245.0755.
2-(2,6-dimethylphenyl)-2-(benzyl(hydroxy)amino)acetonitrile (2l).Pale yellow solid; Rf 0.66 (PE:EA=3:1); mp 118.5-119.4 C;H (CDCl3) 2.58 (s, 6H), 3.82 (t, J = 13.0 Hz, 2H), 5.16 (s, 1H), 5.82 (br, s, 1H), 7.11 (d, J = 7.5 Hz , 2H), 7.22 (t, J = 7.5 Hz, 1H), 7.31-7.38 (m, 5H) ppm;C (CDCl3) 20.7, 58.1, 60.7, 117.1, 127.6, 128.3, 128.7, 129.2, 129.3, 129.5, 136.2, 138.1 ppm; IR (KBr): 3274(-OH), 2947, 2243(-CN), 1590, 1487, 1283, 1095, 1024, 935, 784, 695 cm-1.HRMS (ESI): calcd. for C17H18N2NaO [M+Na]+ 289.1311; found 289.1320.
2-(4-chlorophenyl)-2-(benzyl(hydroxy)amino)acetonitrile (2m)[5]. White solid; Rf 0.37 (PE:EA=3:1); mp 114.8-115.1 C;H (CDCl3) 3.91 (d, J = 12.5 Hz, 1H), 3.98 (d, J = 12.5 Hz, 1H), 4.77 (s, 1H), 5.78 (br, s, 1H), 7.32-7.38 (m, 5H), 7.41 (dd, J = 8.5, 17.0 Hz, 4H) ppm.
2-(2-chlorophenyl)-2-(benzyl(hydroxy)amino)acetonitrile (2n). White solid; Rf 0.50 (PE:EA=3:1); mp 125.5-128.4 C;H (CDCl3) 3.83 (d, J = 12.6 Hz, 1H), 3.92 (d, J = 12.6 Hz, 1H), 5.23 (s, 1H), 5.86 (s, 1H), 7.32-7.38 (m, 7H), 7.44 (dd, J = 3.5, 5.5 Hz, 1H), 7.83 (dd, J = 3.5, 5.5 Hz, 1H) ppm;C (CDCl3) 59.1, 62.4, 115.1, 127.1, 128.3, 128.6, 129.7, 130.0, 130.4, 130.9, 131.6, 134.2, 134.8 ppm;IR (KBr): 3270(-OH), 2967, 2244(-CN), 1684, 1587, 1428, 1293, 1174, 1024, 935, 797, 696 cm-1. HRMS(ESI):calcd. for C15H14ClN2O [M+H]+ 273.0795; found 273.0802.
2-(thiophen-2-yl)-2-(benzyl(hydroxy)amino)acetonitrile (2o). Pale yellow solid; Rf 0.59 (PE:EA=3:1); mp 108.2-109.0 C;H (CDCl3) 3.87 (d, J = 12.5 Hz, 1H), 3.93 (d, J = 12.5 Hz, 1H). 4.92 (s, 1H), 6.32 (br, s, 1H), 7.04 (dd, J = 3.5, 5.0 Hz, 1H). 7.26-7.28 (m, 1H), 7.32-7.39 (m, 5H), 7.41 (dd, J = 1.0, 5.5 Hz, 1H) ppm;C (CDCl3) 58.4, 60.3, 114.9, 126.9, 127.7, 128.0, 128.2, 128.6, 129.6, 134.4, 135.35 ppm; IR (KBr): 3228(-OH), 2863, 2234(-CN), 1942, 1574, 1474, 1439, 1347, 1078, 1035, 763, 690 cm-1. HRMS (ESI): calcd. for C13H12N2NaOS [M+Na]+ 267.0563; found 267.0564.
2-phenyl-2-(tert-butyl(hydroxy)amino)acetonitrile (2p)[6]. Yellow liquid; Rf 0.41 (PE:EA=3:1);H (CDCl3) 1.32 (s, 9H), 4.94 (s, 1H), 5.00 (s, 1H), 7.37-7.41 (m, 3H), 7.51 (d, J =7.0 Hz, 2H) ppm.
2-(butyl(hydroxy)amino)pentanenitrile (2q)[7]. Yellow liquid; Rf 0.45 (PE:EA=3:1); H (CDCl3) 0.86 (dt, J = 7.5, 20.0 Hz, 6H), 1.25-1.32 (m, 2H), 1.38-1.51 (m, 4H), 1.69-1.79 (m, 2H), 2.59 (dt, J = 7.5, 12.0 Hz, 1H), 2.82 (dt, J = 7.0, 12.5 Hz, 1H), 3.57 (t, J = 8.0 Hz, 1H), 5.68 (s, 1H) ppm.
2-phenyl-2-(hydroxy((S)-1-phenylethyl)amino)acetonitrile (2r). White solid; Rf 0.54 (PE:EA=3:1); mp 132.9-134.5 C;H (CDCl3) 1.51 (d, J = 7.0 Hz, 1.13H), 1.59 (d, J = 6.5 Hz, 1.87H), 4.08 (dd, J = 6.6, 13.0 Hz, 0.37H), 4.17 (dd, J = 6.0, 12.5 Hz, 0.63H), 4.67 (s, 0.63H), 4.87 (s, 0.37H), 5.01 (s, 0.63H), 5.09 (s, 0.37H), 7.35-7.55(m, 10H) ppm; IR (KBr): 3240(-OH), 2836, 2242(-CN), 1674, 1474, 1439, 1347, 1078, 977, 763 cm-1.HRMS (ESI):calcd. for C16H16N2NaO [M+Na]+ 275.1160; found 275.1165.
Spectral data of cyanoimines (3a-3e):
(Z)-4-bromo-N-phenylbenzimidoyl cyanide (3a)[8]. Yellow solid; Rf 0.76 (PE:EA=3:1); mp 103.8-104.7C; H (CDCl3) 7.22 (d, J = 7.5 Hz, 2H), 7.36 (t, J = 7.5 Hz, 1H), 7.50 (t, J = 8.0 Hz, 2H), 7.69 (dt, J = 9.0, 2.0 Hz, 2H), 8.03 (dt, J = 8.5, 2.5 Hz, 2H) ppm.
(Z)-4-chloro-N-phenylbenzimidoyl cyanide (3b)[9]. Yellow needle crystal; Rf 0.70 (PE:EA=3:1); mp 107.5-108.4C (lit. 108 C);H (CDCl3) 7.22 (d, J = 7.5 Hz, 2H), 7.35 (t, J=7.5 Hz, 1H), 7.51 (m, 4H), 8.11(m, 2H) ppm.
(Z)-N-phenyl-4-(trifluoromethyl)benzimidoyl cyanide (3c). Light yellow solid; Rf 0.74 (PE:EA=3:1); mp 79.7-82.4C;H (CDCl3) 7.29 (d, J = 7.5 Hz, 2H), 7.40 (t, J = 7.5 Hz, 1H), 7.53 (t, J = 8.0 Hz, 2H), 7.82 (d, J = 8.5 Hz, 2H), 8.30 (d, J = 8.0 Hz, 2H) ppm;C (CDCl3) 110.6, 120.6, 122.5, 124.6, 126.0 (q,J = 3.7 Hz, 1C), 128.1, 128.5, 129.4, 136.6, 138.1, 148.1 ppm; IR (KBr): 2863, 2234(-CN), 1942, 1674, 1568, 1439, 1347, 1078, 1035, 763, 696 cm-1.HRMS (TOF-EI): calcd. for C15H9N2F3 [M]+ 274.0718; found 274.0720.
(E)-N-phenylfuran-2-carbimidoyl cyanide (3d). Yellow solid; Rf 0.46 (PE:EA=3:1); mp 97.5-99.9C;H (CDCl3) 6.65 (q, J = 2.0 Hz, 1H), 7.25-7.29 (m, 3H), 7.33(t, J = 7.5 Hz, 1H), 7.47 (t, J = 8.0 Hz, 2H), 7.70 (d, J = 1.2 Hz, 1H) ppm;C (CDCl3) 110.3, 112.9, 118.4, 120.9, 127.7, 128.4, 129.3, 147.4, 148.3, 149.7 ppm; IR (KBr): 2883, 2243(-CN), 1874, 1670, 1628, 1274, 1087, 935, 773, 700 cm-1. HRMS (TOF-EI): calcd. for C12H8N2O [M]+196.0637; found 196.0643.
3,4-dihydroisoquinoline-1-carbonitrile (3e)[5]. Pale yellow liquid; Rf 0.39 (PE:EA=3:1);H (CDCl3) 2.82 (t, J = 7.5 Hz, 2H), 3.97 (t, J = 8.0 Hz, 2H), 7.22 (d, J = 7.5 Hz, 1H), 7.39 (t, J = 7.5 Hz, 1H), 7.48 (t, J = 1.0, 7.5 Hz, 1H), 7.64 (d, J = 7.5 Hz, 1H) ppm.
Reference：
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2a1H NMR
2b1H NMR
2c1H NMR
2d 1H NMR
2d13C NMR
2e1H NMR
2e13C NMR
2f1H NMR
2f13C NMR
2g1H NMR
2g13C NMR
2h1H NMR
2i1H NMR
2j1H NMR
2k1H NMR
2k13C NMR
2l1H NMR
2l13C NMR
2m1H NMR
2n1H NMR
2n13C NMR
2o1H NMR
2o13C NMR
2p1H NMR
2q1H NMR
2r1H NMR
3a1H NMR
3b1H NMR
3c1H NMR
3c13C NMR
3d1H NMR
3d13C NMR
3e1H NMR
S1