The Journal of Organic Chemistry
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125.6, 121.7, 121.5, 109.1, 53.4; HRMS (CI-TOF) m/z calcd. for
C14H12N2 [M]+ 208.1000, found 208.0999.
NMR (125.8 MHz, CDCl3) δ 140.3, 139.6, 133.9, 129.1, 128.8, 120.,
+
119.1, 110.5, 106.0, 55.2; HRMS (ESI-TOF) m/z calcd. for C14H14N3
1-(4-(Methoxy)benzyl)-1H-pyrazole (3a). Pale yellow oil (52 mg,
56%): IR (neat) 1612, 1514, 1395, 1248, 1176, 1088, 1033, 822, 668
cm−1; 1H NMR (500 MHz, CDCl3) δ 7.53 (s, 1H), 7.34 (s, 1H), 7.18 (d,
J = 8.5 Hz, 2H), 6.78 (d, J = 8.5 Hz, 2H), 6.25 (s, 1H), 5.23 (s, 2H), 3.76
(s, 3H); 13C NMR (125.8 MHz, CDCl3) δ 159.3, 139.3, 129.1, 128.8,
128.4, 114.0, 105.7, 55.3; HRMS (ESI-TOF) m/z calcd. for
C11H13N2O+ [M + H]+ 189.1028, found 189.1022.
1-(4-Cyanobenzyl)-1H-pyrazole (3b). Pale yellow powder (74 mg,
81%): mp 73−75 °C; IR (neat) 2961, 2921, 2852, 2229, 1511, 1392,
1275, 1086, 1044, 966, 860, 828, 762, 746, 688, 616 cm−1; 1H NMR (500
MHz, CDCl3) δ 7.60 (d, J = 8.0 Hz, 2H), 7.56 (s, 1H), 7.44 (s, 1H), 7.22
(d, J = 8.0 Hz, 2H), 6.31 (t, J = 4 Hz, 1H), 5.37 (s, 2H); 13C NMR (125.8
MHz, CDCl3) δ 142.0, 140.1, 132.4, 129.6, 127.7, 118.3, 111.7, 106.4,
55.0; HRMS (ESI-TOF) m/z calcd. for C11H10N3+ [M + H]+ 184.0875,
found 184.0871.
1-(4-Nitrobenzyl)-1H-pyrazole (3c). Pale yellow powder (77 mg,
76%): mp 77−80 °C; IR (neat) 1607, 1517, 1396, 1340, 1312, 1275,
1088, 1108, 1047, 968, 918, 874, 860, 804, 753, 719, 641 cm−1; 1H NMR
(500 MHz, CDCl3) δ 8.19 (d, J = 8.5 Hz, 2H), 7.59 (s, 1H), 7.46 (s, 1H),
7.30 (d, J = 8.5 Hz, 2H), 6.34 (t, J = 4 Hz, 1H), 5.43 (s, 2H); 13C NMR
(125.8 MHz, CDCl3) δ 147.5, 144.0, 140.35, 136.4, 129.7, 127.9, 124.0,
106.6, 54.9; HRMS (ESI-TOF) m/z calcd. for C10H10N3O2+ [M + H]+
204.0773, found 204.0781.
[M + H]+ 224.1188, found 224.1186.
5-((1H-Pyrazol-1-yl)methyl)-2-methoxypyridine (3j). Colorless oil
(77 mg, 82%): IR (neat) 1611, 1571, 1492, 1395, 1290, 1221, 1088,
1025, 833, 753, 618 cm−1; 1H NMR (360 MHz, CDCl3) δ 8.09 (s, 1H),
7.53 (s, 1H), 7.47 (d, J = 6.1 Hz, 1H), 7.36 (s, 1H), 6.71 (d, J = 8.6 Hz,
1H), 6.27 (s, 1H), 5.24 (s, 2H), 3.92 (s, 3H); 13C NMR (90.5 MHz,
CDCl3) δ 164.1, 146.1, 139.7, 138.4, 128.8, 124.9, 111.2, 106.1, 111.2,
106.1, 53.5, 52.9; HRMS (ESI-TOF) m/z calcd. for C10H12N3O+ [M +
H]+ 190.0980, found 190.0976.
2-((1H-Pyrazol-1-yl)methyl)pyrazine (3k). Pale yellow oil (48 mg,
60%): IR (neat) 1514, 1405, 1281, 1088, 1053, 1019, 967, 835, 757, 643
cm−1; 1H NMR (360 MHz, CDCl3) δ 8.49−8.51 (m, 2H), 8.34 (s, 1H),
7.54−7.57 (m, 2H), 6.32 (s, 1H), 5.47 (s, 2H); 13C NMR (90.5 MHz,
CDCl3) δ 151.9, 143.9, 143.6, 140.3, 129.9, 106.4, 55.1; HRMS (ESI-
TOF) m/z calcd. for C8H9N4+ [M + H]+ 161.0827, found 161.0827.
1-(4-(Methoxy)benzyl)-1H-indole (4a). Pale yellow oil (86 mg,
73%): IR (neat) 1612, 1512, 1462, 1304, 1246, 1175, 1032, 821, 739
cm−1; 1H NMR (300 MHz, CDCl3) δ 7.62 (d, J = 7.8 Hz, 1H), 7.27 (d, J
= 8.2 Hz, 1H), 7.05−7.18 (m, 5H), 6.80 (d, J = 8.7 Hz, 2H), 6.50 (d, J =
3.8 Hz, 1H), 5.20 (s, 2H), 3.72 (s, 3H); 13C NMR (75.4 MHz, CDCl3) δ
159.0, 136.2, 129.4, 128.7, 128.1, 128.0, 121.5, 120.9, 119.4, 114.0, 109.6,
101.4, 55.2, 49.5; HRMS (ESI-TOF) m/z calcd. For C16H16NO+ [M +
H]+ 238.1232, found 238.1237.
1-(4-Fluorobenzyl)-1H-pyrazole (3d). Pale yellow oil (53 mg, 60%):
IR (neat) 1607, 1510, 1395, 1223, 1158, 1088, 1048, 925, 824, 741, 616
cm−1; 1H NMR (500 MHz, CDCl3) δ 7.56 (s, 1H), 7.38 (s, 1H), 7.18−
7.21 (m, 2H), 7.01−7.04 (m, 2H), 6.29 (t, J = 4 Hz, 1H), 5.29 (s, 2H);
13C NMR (125.8 MHz, CDCl3) δ 163.3, 161.4 (d, J = 246 Hz), 139.6,
132.4, 129.3, 129.0, 115.7, 105.9, 55.0; 19F NMR (470.8 MHz, CDCl3) δ
−114.2; HRMS (CI-TOF) m/z calcd. for C10H9N2F [M]+ 176.0750,
found 176.0751.
1-(2-Methoxybenzyl)-1H-indole (4b). Yellow powder (92 mg, 78%):
mp 75−77 °C; IR (neat) 1599, 1492, 1460, 1437, 1360, 1302, 1248,
1115, 743 cm−1; 1H NMR (300 MHz, CDCl3) δ 7.68 (d, J = 7.6 Hz, 1H),
7.38 (d, J = 7.9 Hz, 1H), 7.12−7.30 (m, 4H), 6.74−6.95 (m, 3H), 6.57
(d, J = 2.9 Hz, 1H), 5.37 (s, 2H), 3.92 (s, 3H); 13C NMR (75.4 MHz,
CDCl3) δ 156.6, 136.3, 128.6, 128.5, 127.9, 125.8, 121.4, 120.7, 120.5,
119.2, 110.0, 109.7, 101.2, 55.2, 45.0; HRMS (ESI-TOF) m/z calcd. for
C16H16NO+ [M + H]+ 238.1232, found 238.1232.
1-(3-Methoxybenzyl)-1H-indole (4c). Pale yellow oil (95 mg, 80%):
IR (neat) 1600, 1587, 1510, 1489, 1462, 1335, 1262, 1147, 1049, 739
cm−1; 1H NMR (360 MHz, CDCl3) δ 7.63 (d, J = 8.2 Hz, 1H), 7.24 (d, J
= 8.3 Hz, 1H), 7.06−7.18 (m, 4H), 6.75 (d, J = 8.1 Hz, 1H), 6.62 (m,
2H), 6.52 (d, J = 3.8 Hz, 1H), 5.22 (s, 2H), 3.67 (s, 3H); 13C NMR (75.4
MHz, CDCl3) δ 159.9, 139.2, 136.3, 129.7, 128.7, 128.2, 121.6, 120.9,
119.5, 119.0, 112.7, 112.6, 109.6, 101.7, 55.1, 49.9; HRMS (ESI-TOF)
m/z calcd. for C16H16NO+ [M + H]+ 238.1232, found 238.1235.
1-(4-Cyanobenzyl)-1H-indole (4d). Pale yellow oil (70 mg, 94%): IR
1-(Naphthalene-2-ylmethyl)-1H-pyrazole (3e). Pale yellow powder
(75 mg, 72%): mp 86−88 °C; IR (neat) 1510, 1445, 1396, 1283, 1087,
1
1051, 894, 824, 774, 762, 623 cm−1; H NMR (300 MHz, CDCl3) δ
7.81−7.85 (m, 3H), 7.69 (s, 1H), 7.62 (s, 1H), 7.48−7.52 (m, 2H),
7.33−7.43 (m, 2H), 6.33 (m, 1H), 5.50 (s, 2H); 13C NMR (75.4 MHz,
CDCl3) δ 139.5, 133.9, 133.2, 132.9, 129.1, 128.6, 127.8, 127.6, 126.6,
126.3, 126.1, 125.3, 105.9, 56.0; HRMS (ESI-TOF) m/z calcd. for
C14H13N2+ [M + H]+ 209.1079, found 209.1080.
1-(3,5-Dimethoxybenzyl)-1H-pyrazole (3f). Pale yellow powder (68
g, 63%): mp 29−31 °C; IR (neat) 1611, 1594, 1477, 1429, 1397, 1360,
1314, 1203, 1167, 1087, 1062, 1046, 934, 821, 755, 642 cm−1; 1H NMR
(300 MHz, CDCl3) δ 7.62 (s, 1H), 7.49 (s, 1H), 6.39 (t, J = 2.4 Hz, 1H),
6.35 (s, 2H), 6.29 (s, 1H), 5.26 (s, 2H), 3.75 (s, 6H); 13C NMR (75.4
MHz, CDCl3) δ 161.0, 139.4, 138.9, 129.2, 105.9, 105.5, 99.7, 55.8;
1
(neat) 2227, 1728, 1609, 1462, 1317, 1245, 1180, 818, 741 cm−1; H
NMR (300 MHz, CDCl3) δ 7.64 (d, J = 7.2 Hz, 1H), 7.47 (d, J = 8.1 Hz,
2H), 7.06−7.13 (m, 6H), 6.56 (d, J = 3.3 Hz, 1H), 5.30 (s, 2H); 13C
NMR (75.4 MHz, CDCl3) δ 143.0, 136.0, 132.5, 128.7, 128.1, 127.1,
122.0, 121.1, 119.9, 118.5, 111.3, 109.3, 102.4, 49.5; HRMS (ESI-TOF)
m/z calcd. for C16H13N2+ [M + H]+ 233.1079, found 233.1082.
1-(2-Cyanobenzyl)-1H-indole (4e). Pale yellow oil (101 mg, 87%):
IR (neat) 2223, 1514, 1482, 1462, 1435, 1356, 1312, 1244, 1190, 740
cm−1; 1H NMR (300 MHz, CDCl3) δ 7.69−7.74 (m, 2H), 7.35−7.46
(m, 2H), 7.15−7.29 (m, 4H), 6.83 (d, J = 7.8 Hz, 1H), 6.65 (d, J = 3.0
Hz, 1H), 5.58 (s, 2H); 13C NMR (90.5 MHz, CDCl3) δ 141.3, 136.1,
133.4, 132.9, 128.8, 128.3, 128.1, 127.4, 122.1, 121.2, 120.0, 117.2, 110.7,
109.4, 102.6, 48.1; HRMS (ESI-TOF) m/z calcd. for C16H13N2+ [M +
H]+ 233.1079, found 233.1080.
+
HRMS (ESI-TOF) m/z calcd. for C12H15N2O2 [M + H]+ 219.1134,
found 219.1132.
Methyl 3-((1H-Pyrazol-1-yl)methyl)benzoate (3g). Pale yellow oil
(85 mg, 61%): IR (neat) 1720, 1433, 1395, 1286, 1200, 1107, 1084,
1048, 730, 623 cm−1; 1H NMR (300 MHz, CDCl3) δ 7.96 (d, J = 6.9 Hz,
1H), 7.90 (s, 1H), 7.54 (s, 1H), 7.37−7.40 (m, 3H), 6.28 (t, J = 2.1 Hz,
1H), 5.34 (s, 2H), 3.88 (s, 3H); 13C NMR (75.4 MHz, CDCl3) δ 166.5,
139.7, 137.0, 131.9, 130.6, 129.2, 129.1, 128.8, 128.6, 106.1, 55.3, 52.0;
+
HRMS (ESI-TOF) m/z calcd. for C12H13N2O2 [M + H]+ 217.0977,
1-(3-Cyanobenzyl)-1H-indole (4f). Pale yellow oil (105 mg, 90%):
IR (neat) 2231, 1512, 1482, 1462, 1435, 1313, 1253, 1186, 741 cm−1; 1H
NMR (300 MHz, CDCl3) δ 7.74 (d, J = 7.5 Hz, 1H), 7.55 (d, J = 7.8 Hz,
1H), 7.15−7.42 (m, 7H), 6.65 (d, J = 3.0 Hz, 1H), 5.35 (s, 2H); 13C
NMR (75.4 MHz, CDCl3) δ 139.2, 135.9, 131.2, 130.9, 129.9, 129.5,
128.8, 127.9, 122.0, 121.2, 119.9, 118.4, 112.8, 109.3, 102.4, 49.1; HRMS
found 217.0976.
1-(4-((1H-Pyrazol-1-yl)methyl)phenyl)ethan-1-one (3h). Pale yel-
low powder (77 mg, 73%): mp 79−81 °C; IR (neat) 1673, 1607, 1396,
1357, 1266, 1086, 1048, 964, 862, 755, 704 cm−1; 1H NMR (300 MHz,
CDCl3) δ 7.93 (d, J = 8.1 Hz, 2H), 7.57 (s, 1H), 7.43 (s, 1H), 7.26 (d, J =
8.4 Hz, 2H), 6.32 (s, 1H), 5.38 (s, 2H), 2.57 (s, 3H); 13C NMR (75.4
MHz, CDCl3) δ 197.3, 141.9, 139.8, 136.6, 129.4, 128.7, 127.4, 106.1,
55.2, 26.5; HRMS (ESI-TOF) m/z calcd. for C12H13N2O+ [M + H]+
201.1028, found 201.1031.
1-(4-(1H-Pyrrol-1-yl)benzyl)-1H-pyrazole (3i). Pale yellow powder
(88 mg, 58%): mp 75−77 °C; IR (neat) 1613, 1524, 1396, 1327, 1277,
1125, 1069, 1016, 920, 809, 757, 727, 643 cm−1; 1H NMR (500 MHz,
CDCl3) δ 7.59 (s, 1H), 7.43 (s, 1H), 7.38 (d, J = 8.5 Hz, 2H), 7.28 (d, J =
8.5 Hz, 2H), 7.08 (s, 2H), 6.36 (s, 2H), 6.32 (s, 1H), 5.35 (s, 2H); 13C
+
(ESI-TOF) m/z calcd. for C16H13N2 [M + H]+ 233.1079, found
233.1077.
4-((1H-Indol-1-yl)methyl)benzaldehyde (4g). Pale yellow oil (95
mg, 81%): IR (neat) 1692, 1606, 1462, 1316, 1210, 1168, 1013, 848,
808, 741 cm−1; 1H NMR (300 MHz, CDCl3) δ 9.98 (s, 1H), 7.83 (d, J =
8.1 Hz, 2H), 7.69−7.72 (m, 1H), 7.16−7.27 (m, 6H), 6.64 (d, J = 3.9 Hz,
1H), 5.42 (s, 2H); 13C NMR (90.5 MHz, CDCl3) δ 191.6, 144.5, 136.2,
135.8, 130.2, 128.8, 128.2, 127.1, 126.8, 122.0, 121.2, 119.8, 109.5, 102.3,
G
dx.doi.org/10.1021/jo4009589 | J. Org. Chem. XXXX, XXX, XXX−XXX