2610
D. Urankar et al. / Tetrahedron 66 (2010) 2602–2613
0.12 mmol, 2.5 mol % relative to 1), and granular copper (0.58 g,
9.1 mmol, 1.8 equiv relative to 1) in wet MeOH (80%, 20 mL) was
stirred at room temperature for 2 h. The reaction mixture was di-
luted with saturated aq NH4Cl (50 mL), filtered, and extracted with
CH2Cl2 (4ꢂ20 mL). The combined organic layers were washed with
saturated aq NH4Cl (2ꢂ50 mL) and brine (10 mL). Each time the
product was back-extracted from the water layers with few milli-
liters of CH2Cl2. The combined organic layers were dried over
Na2SO4, filtered, and the solvent of the filtrate was removed in
vacuo to give triazole 6, >95% pure as determined by 1H NMR.
When necessary, the crude product was for analysis re-crystallized
from an appropriate solvent, as indicated below.
Found: C, 58.00; H, 4.88; N, 28.12. C17H17N7O2 requires C, 58.11; H,
4.88; N, 27.90%; nmax (KBr) 3220, 1705, 1503, 1260, 1143 cmꢁ1
dH
;
(300 MHz, DMSO-d6) 3.88 (3H, s), 4.53 (2H, d, J 5.9 Hz), 5.72 (2H, s),
7.15 (2H, d, J 9.0 Hz), 7.28 (1H, d, J 7.8 Hz), 7.32 (1H, dd, J 7.3, 5.1 Hz),
7.78–7.90 (3H, m), 8.12 (1H, s), 8.55 (1H, d, J 4.5 Hz), 9.01 (1H, br t, J
5.8 Hz); dC (75 MHz, DMSO-d6) 35.4, 54.3, 55.8, 114.7, 122.2, 123.2,
123.8, 125.2, 137.3, 144.2, 145.2, 149.4, 155.0, 162.8, 163.4; m/z (ESIþ)
374.1 (100, MNaþ), 352.2 (20, MHþ), 216.1 (35%).
4.10.6. 2-(4-Fluorophenyl)-N-((1-(pyridin-2-ylmethyl)-1H-1,2,3-tri-
azol-4-yl)methyl)diazenecarboxamide (6g). Orange needles, mp
116–117 ꢀC (ethyl acetate/light petroleum), yield: 1.7 g (4.9 mmol),
98% (relative to 1g). Found: C, 56.50; H, 4.12; N, 28.91. C16H14FN7O
requires C, 56.63; H, 4.16; N, 28.89%; nmax (KBr) 3261, 1721, 1503,
4.10.1. 2-Phenyl-N-((1-(pyridin-2-ylmethyl)-1H-1,2,3-triazol-4-yl)-
methyl)diazenecarboxamide (6a). Orange needles, mp 129–131 ꢀC
(ethyl acetate), yield: 1.59 g (4.95 mmol), 99% (relative to 1a).
Found: C, 59.66; H, 4.65; N, 30.54. C16H15N7O requires C, 59.80; H,
4.71; N, 30.51%. nmax (KBr) 3185, 3130, 2977, 1719, 1510, 1254, 1148,
1223, 1136, 852, 762 cmꢁ1
; dH (300 MHz, DMSO-d6) 4.54 (2H, d, J
5.8 Hz), 5.72 (2H, s), 7.30 (1H, d, J 7.8 Hz), 7.32 (1H, dd, J 7.2, 5.3 Hz),
7.42–7.51 (2H, m), 7.82 (1H, ddd, J 7.7, 7.7, 1.7 Hz) 7.88–7.98 (2H, m),
8.14 (1H, s), 8.55 (1H, d, J 4.4 Hz), 9.05 (1H, br t, J 5.7 Hz); dC (75 MHz,
DMSO-d6) 35.4, 54.3, 116.5, 116.8, 122.2, 123.2, 123.9, 125.4, 125.5,
137.3, 144.0, 147.8, 149.4, 155.0, 162.6, 163.1, 166.5; m/z (ESIþ) 362.1
(100, MNaþ), 340.1 (20, MHþ), 216.1 (30), 188.1 (24), 145.1 (29%).
766 cmꢁ1
; dH (300 MHz, DMSO-d6) 4.53 (2H, d, J 5.8 Hz), 5.71 (2H,
s), 7.30 (1H, d, J 7.8 Hz), 7.35 (1H, dd, J 7.1, 5.3 Hz), 7.55–7.70 (3H, m),
7.76–7.88 (3H, m), 8.13 (1H, s), 8.55 (1H, d, J 4.2 Hz), 9.10 (1H, br t, J
5.6 Hz); dC (75 MHz, DMSO-d6) 35.4, 54.3, 122.2, 122.8, 123.2, 123.9,
129.6, 133.2, 137.3, 144.0, 149.4, 151.1, 155.0, 162.8; m/z (ESIþ) 344.1
(55, MNaþ), 322.1 (27, MHþ), 214.1 (88), 158.0 (100), 141.0 (89%).
4.10.7. 2-(4-Nitrophenyl)-N-((1-(pyridin-2-ylmethyl)-1H-1,2,3-tri-
azol-4-yl)methyl)diazenecarboxamide (6h). Brick-red needles, mp
166–168 ꢀC (CH2Cl2/ethyl acetate), yield: 1.70 g (4.65 mmol), 93%
(relative to 1h). Found:C, 52.22; H, 3.78; N, 30.44. C16H14N8O3 requires
4.10.2. N-((1-(Pyridin-2-ylmethyl)-1H-1,2,3-triazol-4-yl)methyl)-2-
p-tolyldiazenecarboxamide (6b). Orange solid, mp 90–91 ꢀC (ethyl
acetate), yield: 1.6 g (4.9 mmol), 98% (relative to 1b). Found: C,
60.62; H, 4.98; N, 29.32. C17H17N7O requires C, 60.88; H, 5.11; N,
C, 52.46; H, 3.85; N, 30.59%; nmax (KBr) 3205,1728,1521,1347 cmꢁ1
; dH
(300 MHz, DMSO-d6) 4.56 (2H, d, J 5.7 Hz), 5.72 (2H, s), 7.31 (1H, d, J
7.8 Hz), 7.33 (1H, dd, J 7.3, 5.4 Hz), 7.83 (1H, ddd, J 7.7, 7.7, 1.5 Hz), 8.03
(2H, d, J 8.9 Hz), 8.16 (1H, s), 8.45 (2H, d, J 8.9 Hz), 8.55 (1H, d, J 3.9 Hz),
9.27 (1H, br t, J 5.5 Hz); dC (75 MHz, DMSO-d6) 35.4, 54.3, 122.2, 123.2,
123.7, 124.0, 125.1, 137.3, 143.7, 149.4, 149.5, 154.2, 155.0, 162.3; m/z
(ESIþ) 389.1 (100, MNaþ), 367.1 (39, MHþ), 188.1 (29%).
29.24%. nmax (KBr) 3213, 1720, 1476, 1148, 765 cmꢁ1
; dH (300 MHz,
DMSO-d6) 2.41 (3H, s), 4.51 (2H, d, J 6.0 Hz), 5.71 (2H, s), 7.29 (1H, d,
J 7.8 Hz), 7.35 (1H, dd, J 7.3, 5.0 Hz), 7.44 (2H, d, J 8.1 Hz), 7.75 (2H, d,
J 8.1 Hz), 7.82 (1H, dd, J 7.7, 7.7 Hz), 8.11 (1H, s), 8.55 (1H, br d, J
4.5 Hz), 9.05 (1H, br t, J 5.6 Hz); dC (75 MHz, DMSO-d6) 21.1, 35.4,
54.3, 122.2, 122.9, 123.2, 123.9, 130.1, 137.3, 143.8, 144.1, 149.2, 149.4,
155.0, 162.9; m/z (ESIþ) 358.1 (100, MNaþ), 336.2 (8, MHþ), 216.1
(33), 145.1 (39%).
4.11. General procedure for the synthesis of triazoles 7a–d,f,h
(Scheme 4, Table 4)
An appropriate alkyne 1 (5.00 mmol), 1-azido-2-aminoethane
5b (452 mg, 5.25 mmol), and CuSO4$5H2O (31 mg, 0.12 mmol,
2.5 mol % relative to 1) were dissolved in wet MeOH (80%, 20 mL)
(Table 4, entries 2, 4, and 6–9). Granular copper (0.58 g, 9.1 mmol,
1.8 equiv relative to 1) was added when appropriate (Table 4, en-
tries 1, 3, and 5). The reaction mixture was stirred at room tem-
perature for 5 min, and when appropriate filtered to remove
granular copper. Water (50 mL) and NH4OH (25%, 1 mL) were
added, and the product was extracted with CH2Cl2 (8ꢂ20 mL). The
combined organic layers were washed with brine (5 mL), dried over
Na2SO4, filtered, and evaporated to dryness to give triazole 7. When
necessary, the crude product was for analysis re-crystallized from
an appropriate solvent, as indicated below.
4.10.3. 2-(4-Chlorophenyl)-N-((1-(pyridin-2-ylmethyl)-1H-1,2,3-tri-
azol-4-yl)methyl)diazenecarboxamide (6c). Orange solid, mp 114 ꢀC
(ethyl acetate), yield: 1.7 g (4.9 mmol), 98% (relative to 1c). Found:
C, 53.86; H, 3.85; N, 27.50. C16H14ClN7O requires C, 54.01; H, 3.97; N,
27.56%. nmax (KBr) 3216, 1705, 1505, 1260, 1143 cmꢁ1
; dH (300 MHz,
DMSO-d6) 4.53 (2H, d, J 5.8 Hz), 5.71 (2H, s), 7.30 (1H, d, J 7.8 Hz),
7.35 (1H, dd, J 7.1, 5.2 Hz), 7.70 (2H, d, J 8.7 Hz), 7.78–7.89 (3H, m),
8.13 (1H, s), 8.55 (1H, d, J 4.4 Hz), 9.13 (1H, br t, J 5.6 Hz); dC
(75 MHz, DMSO-d6) 35.4, 54.3, 122.2, 123.2, 123.9, 124.5, 129.8,
137.3, 137.8, 143.9, 149.4, 149.6, 155.0, 162.6; m/z (ESIþ) 378.1 (100,
MNaþ), 356.1 (50, MHþ), 129.1 (57%).
4.10.4. N-((1-(Pyridin-2-ylmethyl)-1H-1,2,3-triazol-4-yl)methyl)-2-
(4-(trifluoromethyl)phenyl)diazenecarboxamide (6d). Yellow solid,
mp 140–144 ꢀC, yield: 1.93 g (4.95 mmol), 99% (relative to 1d).
Found: C, 52.12; H, 3.48; N, 25.02. C17H14F3N7O requires C, 52.44; H,
3.62; N, 25.18%; nmax (KBr) 3198, 3015, 1724, 1628, 1112, 1065, 858,
4.11.1. N-((1-(2-Aminoethyl)-1H-1,2,3-triazol-4-yl)methyl)-2-phe-
nyldiazenecarboxamide (7a). Red solid, mp 114 ꢀC, yield (with
copper additive, entry 1): 1.09 g (3.99 mmol), 80% (relative to 1a),
yield (without additive, entry 2): 1.33 g (4.87 mmol), 97% (relative
to 1a). Found: C, 52.29; H, 5.70; N, 35.58. C12H15N7O requires C,
52.74; H, 5.53; N, 35.88%; nmax (KBr) 3351, 3294, 3141, 2931, 1712,
756 cmꢁ1
; dH (300 MHz, DMSO-d6) 4.58 (2H, d, J 5.8 Hz), 5.73 (2H,
s), 7.32 (1H, d, J 8.1 Hz), 7.35 (1H, dd, J 7.2, 5.0 Hz), 7.83 (1H, ddd, J
7.7, 7.7, 1.6 Hz), 7.96–8.06 (4H, m), 8.17 (1H, s), 8.56 (1H, d, J 4.2 Hz),
9.16 (1H, br t, J 5.6 Hz); dC (75 MHz, DMSO-d6) 35.4, 54.4, 122.2,
123.2, 123.4, 123.7 (q, J 272.7 Hz), 124.0, 126.8 (q, J 3.8 Hz), 132.2 (q, J
32.1 Hz), 137.3, 143.8, 149.4, 153.2 (q, J 1.2 Hz), 155.0, 162.4; m/z
(ESIþ) 214.1 (100, MNaþ), 390.1 (9, MHþ), 188.1 (23%).
1553, 1501, 1276, 1147, 1021, 939, 782, 682 cmꢁ1
; dH (300 MHz,
CDCl3) 1.52 (4H, br s), 4.32 (2H, br s), 4.77 (2H, d, J 6.0 Hz), 7.07 (1H,
br s), 7.55 (3H, m), 7.76 (1H, s), 7.94 (2H, m); dC (75 MHz, DMSO-d6)
35.4, 41.8, 52.6, 122.8, 123.4, 129.6, 133.2, 143.6, 151.1, 162.8; m/z (EI)
274 (6, MHþ), 210 (4), 168 (100), 77 (85), 68 (60%); m/z (FAB) 274
(100, MHþ), 168 (74), 91 (43), 71 (61), 55 (75%).
4.10.5. 2-(4-Methoxyphenyl)-N-((1-(pyridin-2-ylmethyl)-1H-1,2,3-
triazol-4-yl)methyl)diazenecarboxamide (6f). Orange solid, mp 117–
118 ꢀC (ethyl acetate), yield: 1.74 g (4.95 mmol), 99% (relative to 1f).
4.11.2. N-((1-(2-Aminoethyl)-1H-1,2,3-triazol-4-yl)methyl)-2-p-tol-
yldiazenecarboxamide (7b). Orange plates, mp 138–140 ꢀC (light