Supporting Information for Organoselenium-Catalyzed Mild Dehydration of Aldoximes: An Unexpected Practical Method for Organonitrile Synthesis Lei Yu,*,,, Hongyan Li, Xu Zhang,, Jianqing Ye, Jianping Liu, Qing Xu,*,, and Mark Lautens Zhejiang Key Laboratory of Carbon Materials, College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou, Zhejiang 325035, China School of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, Jiangsu 225002, China Davenport Chemistry Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, ON, M5S 3H6, Canada E-mail: qing-xu@wzu.edu.cn; yulei@yzu.edu.cn CONTENTS Detailed Condition and Catalyst Screening Table S2 Experimental and Detailed Synthetic Procedures....S3 Characterization of the Products... S5 References....S9 Copies of 1 H and 13 C NMR Spectra of the Products.......S10 S 1.
Table S1. Catalyst Screening and Condition Optimization of the Organoselenium-Catalyzed Aldoxime Dehydration Reaction. a Ph NOH H 1a cat. (RSe) 2 /H 2 O 2 under air, Me 65 o C, 24 h Ph O H 3a + Ph 4a entry (PhSe) 2 (mol %) H 2 O 2 (mol %) 3a% b 4a% b 1 (PhSe) 2 (1) 10 16 25 2 (PhSe) 2 (1) 4 7 48 3 (PhSe) 2 (1) 2 6 37 4 (PhSe) 2 (4) 4 7 85 (74) 5 (PhSe) 2 (4) 0 0 0 6 (PhSe) 2 (0) 4 0 0 7 (PhSe) 2 (1) 4 7 48 8 (PhSe) 2 (2) 4 7 78 9 (PhSe) 2 (10) 4 8 71 10 (PhSe) 2 (4) 5 7 72 11 (PhSe) 2 (4) 8 7 64 12 (PhSe) 2 (4) 12 11 31 13 (C 6 H 5 CH 2 Se) 2 (4) 4 9 50 14 (c-c 6 H 11 Se) 2 (4) 4 7 82 15 (1-C 10 H 7 Se) 2 (4) 4 8 34 16 (4-MeOC 6 H 4 Se) 2 (4) 4 7 65 17 (4-Me 2 NC 6 H 4 Se) 2 (4) 4 7 23 18 (3,5-(CF 3 ) 2 C 6 H 3 Se) 2 (4) 4 6 29 19 (2-FC 6 H 4 Se) 2 (4) 4 7 58 20 (4-FC 6 H 4 Se) 2 (4) 4 9 73 21 (3-FC 6 H 4 Se) 2 (4) 4 8 91 (81) 22 (3-ClC 6 H 4 Se) 2 (4) 4 8 72 23 c (3-FC 6 H 4 Se) 2 (4) 4 - (83) a The mixture of 1a (5 mmol), a diselenide, and H 2 O 2 (30% w/w aqueous solution) was stirred in commercial Me (5 ml). b GC yields based on 1a with diphenyl used as the internal standard. Isolated yields were shown in parenthesis. c Reaction carried out under N 2. S 2.
Experimental General. Aldoximes were prepared from aldehydes and H 2 NOH HCl according to the literature method (Org. Synth. 1943, Coll. Vol. 2, 622). Diorganyl diselnides were commercially purchased or prepared according to the literature method (Sharpless, K. B.; Young, M. W. J. Org. Chem. 1975, 40, 947). Other precatalysts and solvents were purchased and used as received. Unless otherwise noted, all reactions were carried out under air in round-bottomed flask equipped with a condenser and then monitored by GC-MS and/or TLC by using biphenyl as the internal standard. Products of small scale reactions were all purified by column chromatography on silica gel using petroleum ether and ethyl acetate as the eluent. Products of large scale reactions were obtained by vacuum distillation of the reaction mixtures. 1 H and 13 C NMR spectra were recorded on a Bruker Avance 600 instrument (600 MHz for 1 H and 150 MHz for 13 C NMR spectroscopy) by using CDCl 3 as the solvent and Me 4 Si as the internal standard. Chemical shifts for 1 H and 13 C NMR were referred to internal Me 4 Si (0 ppm) and J-values were shown in Hz. Mass spectra were measured on a Shimadzu GCMS-QP2010 Ultra spectrometer (EI). Melting points were measured by a WRS-2A digital melting pointing instrument. General Procedure for Organoselenium-Catalyzed Dehydration of Aldoximes to Organonitriles (small scale reactions). To a 10 ml round-bottomed flask equipped with a condenser containing aldoxime 1 (5 mmol) and (3-FC 6 H 4 Se) 2 (70 mg, 0.2 mmol, 4 mol%) was added a solution of H 2 O 2 (30% w/w, 23 mg, 0.2 mmol, 4 mol%) in Me (5 ml) via a syringe under air. The mixture was then stirred at 65 o C under air for 24 h and monitored by GC-MS and/or TLC. After completion of the reaction, the solvent was evaporated under reduced pressure. The residue was then separated by column chromatography on silica gel using petroleum ether and ethyl acetate (12/1) as the eluent, giving the corresponding organonitriles. General Procedure for Organoselenium-Catalyzed Dehydration of Aldoximes to Organonitriles (large scale reactions in Table 2 of the Text). To a 250 ml round-bottomed flask equipped with a condenser were added aldoxime 1l or 1m (155 mmol) and (3-FC 6 H 4 Se) 2 (2.17 g, 6.2 mmol, 4 mol %) under air. Then, a solution of H 2 O 2 (30% w/w, 0.71g, 6.2 mmol, 4 S 3.
mol%) in Me (155 ml) was added to the flask and the reaction mixture stirred at 65 o C under air for 24 h. Solvent Me was then distilled off at the ambient pressure (80-84 o C). The product nitriles were then obtained pure by vacuum distillation of the oil residue at reduced pressure (4l: b.p. 73-77 o C/15 mmhg; 4m: b.p. 91-93 o C/15mmHg). Detailed Typical Procedure for the Investigation on Organoselenium Catalyst Recycling and Reuse (Figure 1 in the Text). To a 50 ml round-bottomed flask equipped with a condenser were added aldoxime 1a (3.0 g, 25 mmol) and (3-FC 6 H 4 Se) 2 (0.35 g, 1 mmol, 4 mol %) under air. Then, a solution of H 2 O 2 (30w/w%, 114 mg, 1 mmol, 4 mol %) in Me (25 ml) was added to the flask and the reaction mixture stirred at 65 o C under air for 24 h. Solvent Me was then distilled off at the ambient pressure (80-84 o C). The oil residue was transferred to a 5 ml round-bottomed flask and equipped with a vacuum distillation apparatus. Benzonitrile 4a was then obtained pure by vacuum distillation of the residue at reduced pressure (b.p. 75-81 o C/15mmHg). After the vacuum distillation, the deep yellow and sticky oily residue containing the non-volatile organoselenium catalyst was collected and transferred to a 50 ml round-bottomed flask equipped with a condenser, recharged with aldoxime 1a (3.0 g, 25 mmol), and a solution of H 2 O 2 (30w/w%, 114 mg, 1 mmol, 4 mol % ) in Me (25 ml). Repeating the procedures as described above gave moderate to good yields of 4a by vacuum distillation. Organoselenium catalyst recycling and reuse reactions for conversion of aldoximes 1b, 1d or 1o to nitriles 4b, 4d or 4o were all operated in a similar way. Note: In catalyst recycling and reuse, H 2 O 2 (4 mol %) had to be added again to reactivate the organoselenium catalyst, for we found that only low yields of the nitrile may be obtained if H 2 O 2 was not added. This is most possibly because the active organoselenium catalysts can be reduced easily to give diselenides in the reaction media. See our previous finding for reference (ref. 13b): Yu, L.; Wang, J.; Chen, T.; Ding, K.-H.; Pan, Y. Chin. J. Org. Chem. 2013, 13, 1096. S 4.
Table S2. Detailed Results of Reactions for Organoselenium Catalyst Recycling and Reuse. a R 4a NOH 1 H (3-FC 6 H 4 Se) 2 /H 2 O 2 (4/4 mol %) F under air, Me, 65 o C, 24 h 25 mmol scales 4b Cl 4d R 4 n-c 6 H 13 - entry cycle no. 4a% b 4b% b 4d% b 4o% b 1 1 84 85 77 77 2 2 82 87 76 74 3 3 77 86 75 76 4 4 74 84 70 76 5 5 67 84 69 75 6 6 58 83 67 73 a See the above procedure for detailed reaction conditions and operations. b Isolated yields obtained by vacuum distillation based on 1. 4o Characterization of the Products Benzonitrile 4a. Oil. IR (film): 3067, 2229, 1489, 1447, 758, 687, 547 cm -1 ; 1 H NMR (600 MHz, CDCl 3, TMS, ppm): δ 7.66 (d, J = 7.8 Hz, 2H), 7.61 (t, J = 7.8 Hz, 1H), 7.48 (t, J = 7.5 Hz, 2H); 13 C NMR (150 MHz, CDCl 3, ppm): δ 112.4, 118.9, 129.2, 132.1, 132.8; MS (EI, 70 ev): m/z (%):103 [M + ] (100), 76 (19); Known compound. 1 F 4-Fluorobenzonitrile 4b. Oil. IR (film): 3111, 3077, 2232, 1602, 1505, 1410, 1239, 1160, 1099, 842, 753, 684, 545 cm -1 ; 1 H NMR (600 MHz, CDCl 3, TMS, ppm): δ 7.68-7.70 (m, 2H), 7.19 (t, J = 8.4 Hz, 2H); 13 C NMR (150 MHz, CDCl 3, ppm): δ 108.6 (d, J C-F = 3.45 Hz), 116.9 (d, J C-F = 22.65 Hz), 118.1, 134.7 (d, J C-F = 9.3 Hz), 165.1 (d, J C-F = 255 Hz); MS (EI, 70 ev): m/z (%):121 [M + ] (100), 94 (64); Known compound. 1 Cl 2-Chlorobenzonitrile 4c. Solid, m.p. 43.8-44.5 o C (lit. 45 o C). 2 IR (KBr): 2228, 1586, 1470, S 5.
1437, 1265, 1202, 1133, 1056, 758, 675, 557, 502, 458 cm -1 ; 1 H NMR (600 MHz, CDCl 3, TMS, ppm): δ 7.61 (d, J = 7.8 Hz, 1H), 7.44-7.49 (m, 2H), 7.31 (t, J = 7.2 Hz, 1H); 13 C NMR (150 MHz, CDCl 3, ppm): δ 112.5, 114.9, 126.1, 129.1, 132.8, 133.0, 135.9; MS (EI, 70 ev): m/z (%):137 [M + ] (100), 102 (42); Known compound. 1,2 Cl 3-Chlorobenzonitrile 4d. Oil. IR (film): 3075, 2231, 1639, 1565, 1468, 1415, 1269, 1193, 1165, 1088, 880, 842, 794, 674, 579, 449 cm -1 ; 1 H NMR (600 MHz, CDCl 3, TMS, ppm): δ 7.55 (s, 1H), 7.47-7.52 (m, 2H), 7.36 (t, J = 7.8 Hz, 1H); 13 C NMR (150 MHz, CDCl 3, ppm): δ 114.0, 117.5, 130.3, 130.5, 132.0, 133.3, 135.3; MS (EI, 70 ev): m/z (%):137 [M + ] (100), 102 (45); Known compound. 1 Cl 4-Chlorobenzonitrile 4e. Solid, m.p. 92.8-94.3 o C (lit. 93-94 o C). 3 Oil. IR (KBr): 3092, 2220, 1587, 1478, 1396, 1085, 1011, 829, 583, 542 cm -1 ; 1 H NMR (600 MHz, CDCl 3, TMS, ppm): δ 7.61 (d, J = 8.4 Hz, 2H), 7.46 (d, J = 8.4 Hz, 2H); 13 C NMR (150 MHz, CDCl 3, ppm): δ 110.8, 118.0, 129.7, 133.4, 139.6; MS (EI, 70 ev): m/z (%):137 [M + ] (100), 102 (40); Known compound. 1,3 Br 4-Bromobenzonitrile 4f. Solid, m.p. 112.6-113.7 o C (lit. 113-114 o C). 4 IR (KBr): 2223, 1582, 1477, 1399, 1066, 1012, 824, 541 cm -1 ; 1 H NMR (600 MHz, CDCl 3, TMS, ppm): δ 7.639 (d, J = 7.8 Hz, 2H), 7.528 (d, J = 7.8 Hz, 2H); 13 C NMR (150 MHz, CDCl 3, ppm): δ 111.3, 118.1, 128.0, 132.7, 133.4; MS (EI, 70 ev): m/z (%)183 (48), 181 [M + ] (54), 102 (100); Known compound. 1,4 F 3 C 4-(Trifluoromethyl)benzonitrile 4g. Oil. IR (film): 1410, 1326, 1170, 1067, 1019, 846, 753, 599, 542 cm -1 ; 1 H NMR (600 MHz, CDCl 3, TMS, ppm): δ 7.74 (d, J = 8.4 Hz, 2H), 7.68 (d, J = 7.8 Hz, 2H); 13 C NMR (150 MHz, CDCl 3, ppm): δ 115.1, 116.5, 122.1 (d, J C-F = 271.2 Hz), 125.2 (d, J C-F = 3.6 Hz), 131.7, 133.5 (d, J C-F = 33.2 Hz); MS (EI, 70 ev): m/z (%) 171 [M + ] (100), 152 (53), 121 (68); Known compound. 1, 5 S 6.
Me 4-Methylbenzonitrile 4h. Oil. IR (film): 2228, 1699, 1608, 1508, 1449, 1176, 1117, 1037, 817, 755, 705, 546 cm -1 ; 1 H NMR (600 MHz, CDCl 3, TMS, ppm): δ 7.47 (d, J = 7.8 Hz, 2H), 7.20 (d, J = 7.8 Hz, 2H), 2.35 (s, 3H); 13 C NMR (150 MHz, CDCl 3, ppm): δ 21.8, 109.3, 119.2, 129.9, 132.1, 143.7; MS (EI, 70 ev): m/z (%) 118 (7), 117 [M] (100), 116 (63); Known compound. 1 Me 3-Methylbenzonitrile 4i. Oil. IR (film): 2925, 2863, 2731, 2229, 1703, 1585, 1485, 1457, 1382, 1286, 1248, 1215, 1143, 1097, 1044, 920, 883, 788, 686 cm -1 ; 1 H NMR (600 MHz, CDCl 3, TMS, ppm): δ 7.46-7.45 (m, 2H), 7.40 (d, J = 7.8 Hz, 1H), 7.35 (t, J = 7.8 Hz, 1H), 2.39 (s, 3H); 13C NMR (150 MHz, CDCl3, ppm): δ 21.2, 112.3, 119.0, 129.0, 129.3, 132.5, 133.6, 139.2; MS (EI, 70 ev): m/z (%) 117 (100) [M + ], 105 (9), 90 (48); Known compound. 1 MeO 4-Methoxylbenzonitrile 4j. Solid, m.p. 60.1-61.7 o C (lit. 61-62 o C). 6 IR (KBr): 2218, 1638, 1606, 1572, 1511, 1418, 1305, 1261, 1176, 1023, 830, 682, 547 cm -1 ; 1 H NMR (600 MHz, CDCl 3, TMS, ppm): δ 7.51 (d, J = 9.0 Hz, 2H), 6.88 (d, J = 9.0 Hz, 2H), 3.79 (s, 3H); 13 C NMR (150 MHz, CDCl 3, ppm): δ 55.6, 104.0, 114.8, 119.2, 134.0, 162.9; MS (EI, 70 ev): m/z (%)134 (9), 133 [M] (100), 103 (44); Known compound. 1,6 Bu t 4-tert-Butylbenzonitrile 4k. Oil. IR (film): 2965, 2874, 2228, 1607, 1504, 1469, 1402, 1366, 1270, 1207, 1110, 1020, 839, 588 cm -1 ; 1 H NMR (600 MHz, CDCl 3, TMS, ppm): δ 7.59 (d, J = 8.4 Hz, 2H), 7.49 (d, J = 8.4 Hz, 2H), 1.23 (s, 9H); 13 C NMR (150 MHz, CDCl 3, ppm): δ 31.0, 35.3, 109.3, 119.1, 126.2, 132.0, 156.7; MS (EI, 70 ev): m/z (%)160 (2), 159 [M + ] (24), 144 (100), 116 (60); Known compound. 1 1-Naphthonitrile 4l. Solid, m.p. 37.4-38.6 o C (lit. 37-38 o C). 7 IR (KBr): 3059, 2222, 1691, 1585, 1507, 1378, 1339, 1268, 1218, 1158, 802, 770, 450 cm -1 ; 1 H NMR (600 MHz, CDCl 3, TMS, S 7.
ppm): δ 8.20 (d, J = 8.4 Hz, 1H), 8.04 (d, J = 7.8 Hz, 1H), 7.87-7.90 (m, 2H), 7.66 (t, J = 7.5 Hz, 1H), 7.59 (t, J = 7.5 Hz, 1H), 7.49 (t, J = 7.8 Hz, 1H); 13 C NMR (150 MHz, CDCl 3, ppm): δ 110.1, 117.9, 125.0, 125.1, 127.6, 128.6, 128.7, 132.3, 132.7, 132.9, 133.3; MS (EI, 70 ev): m/z (%) 153 [M + ] (100), 126 (44). Known compound. 1,7 O 4-(Allyloxy)benzonitrile 4m (Containing 19% of 3m unable to be separated. The yield has been corrected according to the ration of 4m and 3m in 1 H NMR spectra). Oil. IR (film): 2224, 1692, 1603, 1507, 1459, 1423, 1365, 1306, 1259, 1165, 1112, 1000, 933, 835 cm -1 ; 1 H NMR (600 MHz, CDCl 3, TMS, ppm): δ 7.50 (d, J = 8.4 Hz, 2H), 6.89 (d, J = 8.4 Hz, 2H), 5.93-5.99 (m, 1H), 5.35 (d, J = 17.4 Hz, 1H), 5.26 (d, J = 10.8 Hz, 1H), 4.51 (d, J = 5.4 Hz, 2H); 13 C NMR (150 MHz, CDCl 3, ppm): δ 69.0, 115.0, 115.5, 131.9, 132.1, 133.9, 161.8, 163.6; MS (EI, 70 ev): m/z (%) 159 [M + ] (88), 144 (18), 119 (27), 41 (100); Known compound. 8 n-heptanenitrile 4o. Oil. IR (film): 2958, 2933, 2862, 2247, 1642, 1566, 1464, 1427, 1380, 1274, 747 cm -1 ; 1 H NMR (600 MHz, CDCl 3, TMS, ppm): δ 2.34 (t, J = 7.2 Hz, 2H), 1.64-1.67 (m, 2H), 1.44-1.46 (m, 2H), 1.30-1.34 (m, 4H), 0.90 (t, J = 6.6 Hz, 3H); 13 C NMR (150 MHz, CDCl 3, ppm): δ 13.9, 17.1, 22.3, 25.3, 28.3, 30.9, 119.8; MS (EI, 70 ev): m/z (%) 112[M + +1] (14), 96 (20), 82 (100); Known compound. 1 n-nonanenitrile 4p. Oil. IR (film): 2958, 2933, 2862, 2247, 1642, 1566, 1464, 1427, 1380, 1274, 747 cm -1 ; 1 H NMR (600 MHz, CDCl 3, TMS, ppm): δ 2.33 (t, J = 6.9 Hz, 2H), 1.63-1.67 (m, 2H), 1.43-1.46 (m, 2H), 1.28-1.31 (m, 8H), 0.89 (t, J = 6.3 Hz, 3H); 13 C NMR (150 MHz, CDCl 3, ppm): δ 14.0, 17.0, 22.5, 25.4, 28.6, 28.7, 28.9, 31.7, 119.7; MS (EI, 70 ev): m/z (%) 140[M + +1] (100), 126 (35), 111 (54); Known compound. 1 Cinnamonitrile 4q. Oil. IR (film): 2217, 1619, 1575, 1494, 1448, 1416, 967, 913, 747 cm -1 ; 1 H NMR (600 MHz, CDCl 3, TMS, ppm): δ 7.37-7.44 (m, 6H), 5.87 (d, J = 16.2 Hz, 1H); 13 C NMR S 8.
(150 MHz, CDCl 3, ppm): δ 96.4, 118.2, 127.4, 129.1, 131.2, 133.6, 150.6; MS (EI, 70 ev): m/z (%) 130 (10), 129 [M + ] (100), 128 (26); Known compound. 1 References 1. AIST: Integrated Spectral Database System of Organic Compounds. (Data were obtained from the National Institute of Advanced Industrial Science and Technology (Japan)) http://sdbs.riodb.aist.go.jp/sdbs/cgi-bin/cre_index.cgi 2. Brady, O. L.; Jarrett, S. G. J. Chem. Soc. 1950, 1227-1232. 3. Hauser, C. R.; Hoffenberg, D. S. J. Org. Chem. 1955, 20, 1491-1495. 4. Mai, K.; Patil, G. Tetrahedron Lett. 1986, 27, 2203-2206. 5. Knauber, T.; Arikan, F.; Röschenthaler, G.-V.; Gooβen, L, J. Chem. Eur. J. 2011, 17, 2689-2697. 6. Gucma, M.; Golebiewski, W. M. Synthesis 2008, 1997-1999. 7. West, B. L. J. Am. Chem. Soc. 1920, 42, 1656-1669. 8. Murakami, H.; Minami, T.; Ozawa, F. J. Org. Chem. 2004, 69, 4482-4486. S 9.
1 H and 13 C NMR Spectra of the Products S 10.
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