P. Vitale et al. / Tetrahedron 67 (2011) 6944e6952
6951
13.85%]; nmax (neat) 2923, 2851, 2230, 1736, 1593, 1464, 1380, 1360,
1262, 1101, 800, 703 cmꢁ1
dH (400 MHz, CDCl3) 7.44e7.33 (4H, m,
214 (6, Mþ), 200 (15), 199 (100), 145 (11), 144 (5), 143 (9), 129 (14),
102 (20), 90 (1), 77 (2) 75 (43), 55 (6) 41 (4).
;
ArH), 3.11 (2H, q, J 7.0 Hz), 1.10 (9H, s), 0.82 (3H, t, J 7.0 Hz); dC
(125 MHz, CDCl3) 149.7, 134.7, 133.1, 128.1, 119.1, 112.1, 55.6, 41.6, 28.1,
15.1; m/z (70 eV, rel Int.) 202 (Mþ, 6),188 (13),187 (100),159 (14),143
(8), 131 (38), 102 (11), 57 (10), 41 (6).
4.2.29. 4-[(2R,6S)-2,6-Dimethylpiperidin-1-yl]benzonitrile
(3o). Yield 57% (89 mg). Yellow oil. Rf (1% EtOAc/petroleum ether,
alumina) 0.71; [Found: C, 78.51; H, 8.33; N, 13.01. C14H18N2 re-
quires C, C, 78.46; H, 8.47; N, 13.07%]; nmax (neat): 2949, 2925,
2858, 2211, 1604, 1513, 1458, 1365, 1316, 1234, 1160, 1123, 1090,
4.2.24. 4-(tert-Butyl(ethyl)amino)benzonitrile (3l). Yield 46% (68 mg).
Yellow oil. Rf (1% EtOAc/petroleum ether, alumina) 0.38; [Found: C,
77.22; H, 8.51; N, 13.73. C13H18N2 requires C, 77.18; H, 8.97; N,
13.85%]; nmax (neat) 2967, 2927, 2854, 2225, 1734, 1602, 1501, 1466,
982, 909, 817, 734 cmꢁ1
; dH (400 MHz, CDCl3) 7.46 (2H, d, J 9.0 Hz,
ArH), 6.80 (2H, d, J 9.0 Hz, ArH), 4.10e3.97 (2H, m, 2CH(CH3)),
1.92e1.64 (4H, m), 1.60e1.44 (2H, m), 1.14 (6H, d, J 7.0 Hz,
2CH(CH3)); dC (100 MHz, CDCl3) 151.2, 133.5, 129.7, 125.0, 120.5,
113.4, 47.5, 33.4, 31.0, 20.3, 18.5, 14.7; m/z (70 eV, rel Int.) 214 (10,
Mþ), 200 (15), 199 (100), 157 (6), 145 (11), 144 (6), 143 (8), 129 (17),
102 (20), 81 (1), 75 (3), 55 (6).
1452, 1363, 1264, 1200, 1177, 1096, 1022, 846, 800, 739 cmꢁ1
; dH
(400 MHz, CDCl3) 7.51 (2H, d, J 8.4 Hz, ArH), 7.13 (d, 2H, J 8.4 Hz,
ArH), 3.25 (2H, q, J 7.0 Hz), 1.22 (9H, s), 0.85 (3H, t, J 7.0 Hz); dC
(100 MHz, CDCl3) 153.2, 132.1, 126.4, 119.7, 104.7, 56.0, 41.7, 28.6,
15.4; m/z (70 eV, rel Int.) 202 (Mþ, 8), 188 (14), 187 (100), 159 (16),
143 (10), 131 (46), 102 (14), 57 (12), 41 (6).
4.2.30. (4-Chlorophenyl)[(2R,6S)-2,6-dimethylpiperidin-1-yl]meth-
animine (5o). Yield 95% (173 mg). Yellow semi-solid. [Found: C,
67.36; H, 7.77; N, 11.19. C14H19ClN2 requires C, 67.05; H, 7.64; N,
11.17%]; nmax (neat) 3313, 2966, 2934, 2869, 2854, 1574, 1558, 1425,
4.2.25. N-tert-Butyl-N-ethyl-4-chlorobenzamidine (5l). Yield 20%
(20 mg). Yellow oil; [Found: C, 65.21; H, 7.77; N, 11.51. C13H19ClN
requires C, 65.40; H, 8.02; N, 11.73%]; nmax (neat) 3303, 2964, 2926,
2872, 2855, 1584, 1407, 1360, 1209, 1186, 1089, 1042, 1014, 837, 796,
1248, 1184, 1117, 1090, 1052, 1015, 902, 836, 790, 734, 683cmꢁ1
; dH
(400 MHz, CDCl3) 7.32 (d, 2H, J 7.7 Hz, ArH), 7.21 (d, 2H, J 7.7 Hz,
ArH), 5.60e5.30 (1H, br s, NH, exchanges with D2O), 4.23e4.07 (2H,
m, 2CH(CH3)), 1.90e1.75 (1H, m), 1.73e1.58 (2H, m), 1.58e1.45 (3H,
m),1.20 (6H, d, J 7.0 Hz, 2CH(CH3)); dC (100 MHz, CDCl3) 168.0,137.9,
134.3, 128.7, 127.7, 47.4, 30.3, 20.3, 14.0; m/z (70 eV, rel Int.) 252 (12,
Mþþ2), 251 (29), 250 (37, Mþ), 249 (71), 237 (2), 235 (6), 223 (6),
221 (16), 210 (9), 209 (37), 208 (28), 207 (100), 196 (5), 195 (19), 194
(14), 193 (40), 181 (10), 168 (9), 167 (5), 166 (28), 141 (11), 140 (30),
139 (51), 138 (82), 137 (49), 132 (8), 113 (11), 112 (14), 111 (26), 103
(6), 102 (29), 98 (52), 76 (10), 75 (25), 70 (28), 56 (12), 55(13), 50
(11), 44 (12), 42 (21), 41 (17).
687 cmꢁ1
; dH (400 MHz, CDCl3) 7.34e7.26 (4H, m, ArH), 4.60e3.90
(1H, br s, NH, exchanges with D2O), 3.17 (2H, q, J 7.1 Hz), 1.5 (9H, s),
0.98 (3H, t, J 7.1 Hz); dC (100 MHz, CDCl3) 168.8, 139.8, 134.6, 128.5,
128.0, 56.7, 42.0, 29.0, 16.5; m/z (70 eV, rel Int.) 240 (1, Mþþ2), 239
(2), 238 (2, Mþ), 237 (6), 223 (1), 195 (2), 184 (4), 183 (20), 182 (24),
181 (48), 169 (32), 168 (11), 167 (89), 140 (22), 139 (37), 138 (68), 137
(96), 111 (18), 102 (30), 86 (100), 75 (22), 58 (31), 57 (13), 50 (14), 44
(12), 41 (18).
4.2.26. 4-Chloro-N,N-dipropylbenzamidine (5m). Yield 80e94%
(139 mg). Yellow oil. [Found: C, 65.28; H, 7.68; N, 11.52. C13H19ClN
requires C, 65.40; H, 8.02; N, 11.73%]; nmax (neat) 3318, 3045, 2964,
2932, 2873, 1679, 1582, 1459, 1425, 1380, 1211, 1173, 1090, 1015, 928,
4.2.31. (S)-N-Benzyl-4-chloro-N0-methyl-N-(1-phenylethyl)benzimi-
damide (9). Yield 90% (237 mg). Yellow oil. [Found: C, 76.20; H,
893, 836, 785, 743, 682 cmꢁ1
.
dH (400 MHz, CDCl3) 7.35e7.32 (2H,
6.29; N, 7.66. C23H23ClN2 requires C, 76.12; H, 6.39; N, 7.72%]; ½a D20
ꢃ
m, ArH), 7.24e7.22 (2H, m, ArH), 4.8 (s,1H), 3.20 (2H, t, J 7.5 Hz),1.58
(s, 2H, J 7.5 Hz), 0.84 (3H, t, J 7.5 Hz); dC (100 MHz, CDCl3) 168.0,
137.8, 134.4, 128.6, 128.0, 49.6, 21.0, 11.2; m/z (70 eV, rel Int.) 240
(10, Mþþ2), 239 (32), 238 (28, Mþ), 237 (83), 223 (2), 211 (4), 209
(13), 197 (8), 195 (25), 181 (3), 169 (34), 168 (21), 167 (100), 153 (4),
140 (26), 139 (12), 138 (79), 137 (14), 125 (4), 113 (7), 111 (19), 102
(14), 86 (3), 75 (10), 72 (18), 58 (13), 41 (9).
ꢁ87.8 (c 0.5, CHCl3); nmax 3087, 3060, 3028, 2972, 2928, 2863, 1617,
1609, 1490, 1449, 1394, 1307, 1089, 831, 727, 697 cmꢁ1
; dH
(400 MHz, CDCl3) 7.40e7.20 (9H, m, ArH), 7.19e7.10 (4H, m, ArH),
5.16e4.95 (1H, br q, CHMe), 4.62 (br d, 1H, J 16.0 Hz, PhCHaN), 4.02
(d, 1H, J 16.0 Hz, PhCHaN), 2.77 (s, 3H), 1.43 (d, 3H, J 6.9 Hz); dC
(100 MHz, CDCl3) 161.7, 142.3, 140.7, 134.3, 133.0, 129.0, 128.9, 128.4,
127.9, 127.1, 127.0, 126.8, 126.1, 55.3, 46.3, 38.1, 18.1; m/z (70 eV, rel
Int.) 364 (0.4, Mþþ2), 362 (2, Mþ), 273 (16), 271 (43), 259 (13), 257
(41), 214 (3), 166 (2), 154 (33), 152 (100), 138 (7), 113 (3), 111 (10),
105 (13), 91 (22), 77 (10), 65 (5), 51 (2).
4.2.27. (4-Chlorophenyl)-1-morpholinomethanimine
(5n). Yield
87e95% (142 mg). Yellow oil. [Found: C, 58.56; H, 5.40; N, 12.11.
C11H13ClN2O requires C, 58.80; H, 5.83; N, 12.4%]; nmax (neat) 3305,
2963, 2917, 2896, 2852,1590,1563,1455,1428,1367,1176,1142,1115,
4.2.32. 2-(Diisopropylamino)benzonitrile(11). Yield 13e16% (19 mg).
Yellow semi-solid. [Found: C, 77.41; H, 9.22; N, 13.74. C13H18N2 re-
quires C, 77.18; H, 8.97; N, 13.98%]; Rf (5% EtOAc/petroleum ether)
0.78; nmax (neat): 2963, 2920, 2850, 2228, 1592, 1486, 1463, 1382,
1089, 1008, 877, 831, 747 cmꢁ1
; dH (400 MHz, CDCl3) 7.27 (2H, d, J
8.4 Hz, ArH), 7.19 (2H, d, J 8.4 Hz, ArH), 6.12e5.64 (1H, br s, NH, ex-
changes with D2O), 3.62e3.58 (4H, m, 2CH2O), 3.24e3.21 (4H, m,
2CH2N); dC (100 MHz, CDCl3) 168.6, 135.8, 135.3, 128.9, 128.3, 66.5,
46.5; m/z (70 eV, rel Int.) 226 (7, Mþþ2), 225 (34), 224 (17, Mþ) (17),
223 (100),195 (17),193 (44),181 (4),179 (4),169 (3),168 (3),167 (10),
166 (6),140 (21),139 (19),138 (63),137 (24),113 (7),111 (21),102 (17),
86 (11), 76 (10), 75 (20), 57 (21), 56 (13), 51 (5), 50 (8), 42 (5).
1261, 1097, 1018, 799 cmꢁ1
; dH (400 MHz, CDCl3) 7.61 (1H, dd, J 7.7,
1.8 Hz, ArH), 7.51e7.46 (1H, m, ArH), 7.32 (1H, dd, J 8.8, 0.7 Hz, ArH),
3.60 (2H, heptet, J 6.2 Hz, CH(CH3)2), 1.05 (d, 6H, J 6.2 Hz, CH(CH3)2);
dC (100 MHz, CDCl3) 151.8, 133.2, 132.2, 129.5, 125.0, 118.9, 116.5,
50.0, 21.3; m/z (70 eV, rel Int.) 202 (6, Mþ), 188 (5), 187 (36), 159 (3),
146 (11), 145 (100), 129 (6), 118 (4), 117 (3), 102 (8), 91 (2), 77 (4), 75
(2), 43 (3).
4.2.28. 3-[(2R,6S)-2,6-Dimethylpiperidin-1-yl]benzonitrile(2o). Yield
24% (37 mg). Purified just in little amount from 4-[(2R,6S)-2,6-
dimethylpiperidin-1-yl]benzonitrile (3o) as a yellow oil; Rf (1% EtOAc/
petroleum ether) 0.72; diagnostic analytical data for meta isomer:
nmax (neat) 2927, 2857, 2229,1602,1591,1512,1494,1454,1363,1314,
4.2.33. 2-Chloro-N,N-diisopropylbenzimidamide (12a). Yield 35%.
Pale yellow powder. Mp 81e83 ꢀC. [Found: C, 65.79; H, 8.19; N,
11.94. C13H19ClN2 requires C, 65.40; H, 8.02; N, 11.73%]; nmax (KBr)
3304, 3056, 2972, 2930, 1578, 1445, 1367, 1221, 1090, 1025, 870, 831,
1065, 1005, 699 cmꢁ1
; dH (400 MHz, CDCl3) 7.36e7.32 (1H, m, ArH),
7.28e7.22 (3H, m, ArH), 3.35e3.25 (2H, m, 2CH(CH3)),1.92e1.44 (6H,
m), 0.88 (6H, d, J 6.6 Hz, 2CH(CH3)); dC (100 MHz, CDCl3) 150.7,126.4,
119.3, 112.8, 97.9, 53.4, 31.9, 29.3, 22.6, 20.2, 14.1; m/z (70 eV, rel Int.)
777, 751, 741 cmꢁ1 dH (60 ꢀC, 400 MHz, CD3OD) 7.49e7.29 (4H, m,
;
ArH), 3.90e3.40 (2H, br m, 2CHMe2), 1.43e1.23 (12H, br m,
2CHMe2); dC (25 ꢀC,100 MHz, CDCl3) 163.4,138.7,130.5,129.7,129.3,