The Journal of Organic Chemistry
Note
6-Bromo-3,8-dimethylimidazo[1,2-a]pyridine (2j):
2H), 6.66 (d, J = 7.0 Hz, 1H), 7.13−7.22 (m, 7H), 7.86 (d, J = 7.0 Hz,
1H); 13C NMR (50 MHz, CDCl3) (ppm) 21.1, 30.2, 114.5, 116.1,
121.8, 122.4, 126.8, 128.2, 128.7, 131.9, 134.5, 136.7, 146.1; IR (KBr)
3053, 3025, 2919, 2854, 1643, 1495, 1437, 1311, 1119, 1030, 866, 770,
705; HRMS calcd for C15H15N2 223.1236, found 223.1230; MS m/z
147 [M + H]+, 209, 147, 139, 109, 91, 73, 55.
(eluent, 1:1 EtOAc/hexane); white solid; 75% yield (75 mg); mp 67.4
°C; 1H NMR (500 MHz, CD3OD) (ppm) 2.32 (s, 3H), 2.36 (s, 3H),
6.98 (s, 1H), 7.18 (s, 1H), 8.06 (s, 1H); 13C NMR (125 MHz,
CD3OD) (ppm) 8.9, 16.8, 108.1, 123.0, 127.4, 128.8, 131.2, 144.8; IR
(KBr) 3069, 2954, 2921, 1547, 1491, 1355, 1306, 1145, 1036, 842,
776, 746; HRMS calcd for C9H10BrN2 225.0028, found 225.0022; MS
m/z 225 [M + H]+, 147, 133, 109, 91,73, 55.
General Procedure for Synthesis of Imidazo[1,2-a]pyridine-
3-carbaldehyde 3a:12
3-Methyl-6-phenylimidazo[1,2-a]pyridine (2k):31
100 mg (0.757 mmol) of 1a, AgNO3 (2.5 mg, 0.015 mmol), TMEDA
(8.7 mg, 0.075 mmol), and CH3CN (2 mL) was placed in a 50 mL
round bottomed flask. The mixture was heated in an oil bath at 60 °C
for 4 h under oxygen atmosphere (balloon). After completion of the
reaction, the flask was allowed to attain room temperature; the mixture
was poured into 20 mL of saturated NaCl solution, and the product
was extracted with DCM (20 mL × 3). After removal of the solvent
under reduced pressure, the residue left out was subjected to column
chromatography on silica gel (1:1 EtOAc/hexane). The product 3a
was obtained in 85% yield (94 mg, 0.643 mmol).1H NMR (500 MHz,
CDCl3) (ppm) 7.15 (t, J = 7.0 Hz, 1H), 7.57 (t, J = 7.0 Hz, 1H), 7.82
(d, J = 8.0 Hz, 1H), 8.33 (s, 1H), 9.51 (d, J = 7.0 Hz, 1H), 9.95 (s,
1H); 13C NMR (125 MHz, CDCl3) (ppm) 115.4, 117.7, 128.6, 130.1,
146.7, 149.2, 177.8; IR (KBr) 2926, 2856, 1658, 1522, 1490, 1439,
1389, 1314, 1255, 1173, 1089, 1024, 803, 768; MS m/z 147 [M + H]+,
117, 93, 78, 63, 51, 39.
(eluent, 1:1 EtOAc/hexane); white solid; 92% yield (92 mg); 1H
NMR (200 MHz, CD3OD) (ppm) 2.46 (s, 3H), 7.29−7.50 (m, 4H),
7.51 (s, 2H), 7.62 (d, J = 7.2 Hz, 2H), 8.25 (s, 1H); 13C NMR (50
MHz, CD3OD) (ppm) 8.8, 117.1, 121.9, 122.6, 126.0, 127.9, 128.1,
128.9, 130.1, 131.2, 138.4, 145.3; IR(KBr) 3055, 2925, 2855, 1484,
1454, 1430, 1379, 1313, 1131, 835, 763, 698; MS m/z 209 [M + H] +,
172, 152, 102, 73, 55.
3-Methylimidazo[1,2-a]pyrazine (2l):
(eluent, 10% CH3OH in EtOAc); brown solid; 76% yield (76 mg); mp
175−180 °C; 1H NMR (500 MHz, CD3OD) (ppm) 2.42 (s, 3H), 7.47
(s, 1H), 7.75 (d, J = 4.5 Hz, 1H), 8.13 (d, J = 3.5 Hz, 1H), 8.77 (s,
1H); 13C NMR (125 MHz, CD3OD) (ppm) 8.4, 118.8, 124.6, 129.7,
134.4, 141.5, 143.2; IR (KBr) 3051, 3028, 2966, 1528, 1493, 1438,
1345, 1300, 1146, 1025, 891, 805, 703, 640; HRMS calcd for C7H8N3
7-Methylimidazo[1,2-a]pyridine-3-carbaldehyde (3b):
+
1
134.0719, found 134.0713; MS m/z 134 [M + H] , 112, 91, 73, 55.
white solid; 80% yield (88 mg); mp 63.5 °C; H NMR (500 MHz,
Methylimidazo[2,1-a]isoquinoline (2m):
CDCl3) (ppm) 2.50 (s, 3H), 6.97 (d, J = 6.5 Hz, 1H), 7.56 (s, 1H),
8.26 (s, 1H), 9.34 (d, J = 7.0 Hz, 1H), 9.88 (s, 1H); 13C NMR (125
MHz, CDCl3) (ppm) 21.6, 116.4, 117.8, 124.7, 127.7, 141.9, 147.0,
149.7, 177.4; IR (KBr) 3099, 2967, 2924, 2828, 1656, 1525, 1485,
1463, 1316, 1256, 1193,1166, 1033, 854, 795, 728, 628; HRMS calcd
for C9H9N2O 161.0716, found 161.0708; MS m/z 161 [M + H]+, 142,
133, 129, 109, 102, 92, 73, 59, 55.
(eluent, 1:1 EtOAc/hexane); white solid; 95% yield (95 mg); mp 48
1
°C; H NMR (500 MHz, CD3OD) (ppm) 2.17 (s, 3H), 6.77 (d, J =
8-Methylimidazo[1,2-a]pyridine-3-carbaldehyde (3c):12
7.2 Hz, 1H), 6.97 (s, 1H), 7.29−7.50 (m, 4H), 8.19 (d, J = 7.6 Hz,
1H); 13C NMR (125 MHz, CD3OD) (ppm) 8.7, 113.9, 121.8, 123.3,
123.7, 124.1, 128.1, 128.6, 129.0, 129.1, 130.4, 143.3; IR (KBr) 3182,
2923, 2857, 1512, 1443, 1371, 1332, 1248, 844, 790, 743, 695; HRMS
calcd for C12H11N2 183.0923, found 183.1020; MS m/z 183 [M + H]+,
1175, 161, 147, 102, 91, 68. Anal. Calcd for C12H10N2: C, 79.09; N,
15.37; H, 5.53. Found: C, 78.82; N, 15.31; H, 5.55.
1
67% yield (73.5 mg); H NMR (200 MHz, CDCl3) (ppm) 2.67 (s,
3-Benzylimidazo[1,2-a]pyridine (2n):15
3H), 7.03 (t, J = 7.6 Hz, 1H), 7.37 (d, J = 8.0 Hz, 1H), 8.29 (s, 1H),
9.36 (d, J = 6.8 Hz, 1H), 9.93 (s, 1H); 13C NMR (125 MHz, CDCl3)
(ppm) 16.8, 115.4, 125.3, 126.3, 127.7, 129.1, 146.1, 149.4, 177.8; IR
(KBr) 3105, 3029, 2962, 2837, 1653, 1516, 1486, 1430, 1314, 1252,
1159, 1081, 880, 785, 763, 638, 603; MS m/z 161 [M + H]+, 142, 133,
118, 109, 100,92, 79, 65.
(eluent, 1:1 EtOAc/hexane); 92% yield (92 mg); 1H NMR (500 MHz,
CD3OD) (ppm) 4.22 (s, 2H), 6.78 (s, 1H), 7.18−7.50 (m, 6H), 7.31
(s, 1H), 7.48 (d, J = 9.5 Hz, 1H), 7.97 (d, J = 6.5 Hz, 1H); 13C NMR
(125 MHz, CD3OD) (ppm) 30.6, 113.6, 117.6, 125.2, 126.0, 127.9,
129.5, 129.8, 132.0, 138.2, 146.7; IR (KBr) 3104, 3073, 3023, 2917,
2857, 1784, 1726, 1631, 1517, 1496, 1352, 1450, 1306, 1249, 1131,
1069, 1028, 865, 721, 604; MS m/z 209 [M + H]+, 194,152, 128, 111,
91, 73, 55.
5-Methylimidazo[1,2-a]pyridine-3-carbaldehyde (3d):12
1
55% yield (60 mg); H NMR (500 MHz, CDCl3) (ppm) 2.92 (s, 3
H), 6.86 (d, J = 7.0 Hz, 1H), 7.42 (t, J = 8.0 Hz, 1H), 7.61 (d, J = 8.0
Hz, 1H), 8.35 (s, 1H), 9.85 (s, 1H); 13C NMR (125 MHz, CDCl3)
(ppm) 23.0, 115.7, 116.2, 128.1, 130.0, 140.0, 149.6, 151.9, 175.9; IR
(KBr) 3925, 2925, 2885, 1631, 1542, 1490, 1423, 1378, 1304, 1279,
1159, 1083, 1031, 892, 854, 784, 633; MS m/z 161 [M + H]+, 143,
133, 109, 92, 74, 55.
3-Benzyl-7-methylimidazo[1,2-a]pyridine (2o):
(eluent, 1:1 EtOAc/hexane); white solid; 95% yield (95 mg); mp
119.2 °C; 1H NMR (200 MHz, CD3OD) (ppm) 2.31 (s, 3H), 4.20 (s,
E
dx.doi.org/10.1021/jo3025303 | J. Org. Chem. XXXX, XXX, XXX−XXX