Synthesis of Multi-Substituted 2-Iminopyridine
21.3, 21.1 ppm. HRMS (EI): calcd. for C24H25NO 343.1936 [M]+; methane/methanol, 20:1) to give 2-iminopyridine (3d) as a light
found 343.1931.
brown solid (44.4 mg, 51%).
3d: M.p. 142–143 °C. IR (KBr): ν = 3316, 2947, 2832, 1718, 1624,
˜
Synthesis of 2-Iminopyridines 3a–c (Conditions A): A solution of
ethyl 2-cyanopropanoate (1a) (131 mg, 1.0 mmol) in diethylene
glycol dimethyl ether (2.0 mL) was added to KHMDS (1.3 mL,
0.62 in toluene, 0.80 mmol) at room temperature. The reaction
mixture was stirred at room temperature for 10 min and then to it
was added a solution of alkynyl imine 2a (49.9 mg, 0.20 mmol) in
diethylene glycol dimethyl ether (2.0 mL). The resulting reaction
mixture was stirred at 160 °C for 3.0 h and then cooled to room
temperature. Saturated aqueous NaHCO3 (10 mL) was added to
quench the reaction. The mixture was extracted with dichlorometh-
ane (3ϫ15 mL). The combined organic layers were dried with so-
dium sulfate. The solvents were evaporated in vacuo and then the
residue was purified by preparative TLC on silica gel (ammonia
solution in dichloromethane/methanol, 20:1) to give 2-iminopyr-
idine 3a as a brown oil (50.8 mg, 70%).
1553, 1511, 1438, 1388, 1360, 1302, 1244, 1208, 1173, 1120, 1077,
1
1031, 961, 874, 799, 762, 701 cm–1. H NMR (500 MHz, CDCl3):
δ = 8.01 (s, 1 H), 7.38–7.42 (m, 2 H), 6.89–7.20 (m, 12 H), 5.19 (s,
2 H), 3.89 (q, J = 7.0 Hz, 2 H), 3.82 (s, 3 H), 0.85 (t, J = 7.0 Hz,
3 H) ppm. 13C NMR (67.8 MHz, CDCl3): δ = 165.3, 159.7, 159.4,
143.4, 142.9, 138.6, 135.4, 130.5, 130.2, 129.8, 128.4, 128.4, 127.7,
127.4, 127.0, 126.5, 114.3 107.7, 60.1, 55.2, 53.8, 13.6 ppm. HRMS
(EI): calcd. for C28H26N2O3 438.1943 [M]+; found 438.1997.
3h: White solid; m.p. 118–119 °C. IR (CHCl ): ν = 3444, 3061,
˜
3
2970, 2842, 1694, 1619, 1562, 1510, 1447, 1372, 1303, 1229, 1143,
1081, 1021, 923, 836, 797, 702 cm–1. 1H NMR (500 MHz, CDCl3):
δ = 8.02 (s, 1 H), 7.39–7.42 (m, 2 H), 7.17–7.20 (m, 2 H), 7.08–7.14
(m, 4 H), 7.00–7.05 (m, 4 H), 6.95–6.98 (m, 2 H), 3.94 (q, J =
7.2 Hz, 2 H), 3.85 (s, 3 H), 0.92 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR
(126 MHz, CDCl3): δ = 165.2, 159.5, 143.7, 138.5, 130.5, 128.4,
128.1, 127.4, 127.1, 126.6, 114.9, 108.0, 60.2, 55.5, 13.7 ppm.
HRMS (EI): calcd. for C27H24N2O3 424.1787 [M]+; found
424.1797.
3a: IR (neat): ν = 3348, 3058, 2983, 2837, 1695, 1624, 1566, 1513,
˜
1445, 1369, 1294, 1250, 1177, 1109, 1032, 958, 916, 845, 772,
704 cm–1. 1H NMR (270 MHz, CDCl3): δ = 7.97 (s, 1 H), 7.29–
7.39 (m, 5 H), 7.05–7.07 (m, 2 H), 6.89–6.92 (m, 2 H), 5.19 (s, 2
H), 3.88 (q, J = 7.0 Hz, 2 H), 3.79 (s, 3 H), 1.74 (s, 3 H), 0.87 (t,
J = 7.0 Hz, 3 H) ppm. 13C NMR (67.8 MHz, CDCl3): δ = 165.3,
159.7, 159.3, 142.9, 141.4, 139.7, 129.5, 127.9, 127.8, 127.8, 127.0,
123.6, 114.2, 107.5, 60.0, 55.2, 53.8, 15.3, 13.6 ppm. HRMS (EI):
calcd. for C23H24N2O3 376.1787 [M]+; found 376.1786.
3i: Brown solid; m.p. 110–111 °C. IR (CHCl ): ν = 3431, 2930,
˜
3
2838, 1719, 1622, 1559, 1511, 1442, 1368, 1308, 1256, 1201, 1080,
1128, 1074, 1024, 900, 837, 799, 766, 737, 704, 603 cm–1. 1H NMR
(500 MHz, CDCl3): δ = 7.88 (s, 1 H), 7.20–7.30 (m, 5 H), 7.06–
7.10 (m, 2 H), 6.90–6.95 (m, 2 H), 5.18–5.22 (m, 1 H), 4.14 (q, J
= 7.2 Hz, 2 H), 3.76 (s, 3 H), 1.05–2.15 [m, 11 H, including a triplet
at δ = 1.20 (J = 7.2 Hz, 3 H)] ppm. 13C NMR (126 MHz, CDCl3):
δ = 164.8, 160.6, 159.4, 146.5, 143.7, 135.7, 135.5, 134.8, 129.5,
128.3, 128.0, 127.5, 126.0, 114.8, 107.8, 60.3, 55.5, 29.3, 24.8, 22.3,
21.5, 14.3 ppm. HRMS (EI): calcd. for C27H28N2O3 428.2100
[M]+; found 428.2127.
3b: Yellow oil. IR (neat): ν = 3352, 3020, 2936, 2858, 2838, 1710,
˜
1626, 1560, 1513, 1442, 1371, 1293, 1249, 1218, 1181, 1107, 1034,
979, 919, 780, 765, 748, 735, 669 cm–1. 1H NMR (500 MHz,
CDCl3): δ = 7.90 (s, 1 H), 7.26–7.28 (m, 2 H), 6.88–7.05 (m, 2 H),
5.32–5.37 (m, 1 H), 5.16 (d, J = 14.5 Hz, 1 H), 5.11 (d, J = 14.5 Hz,
1 H), 4.14–4.21 (m, 2 H), 3.78 (s, 3 H), 2.19–2.26 (m, 1 H), 2.11–
2.16 (m, 2 H), 1.97 (s, 3 H), 1.86–1.93 (m, 1 H), 1.72–1.78 (m, 3
H), 1.58–1.67 (m, 1 H), 1.26 (t, J = 7.3 Hz, 3 H) ppm. 13C NMR
(67.8 MHz, CDCl3): δ = 165.0, 159.9, 159.2, 145.2, 141.6, 136.7,
129.4, 127.9, 123.7, 122.1, 114.2, 107.1, 60.1, 55.2, 53.7, 29.1, 25.0,
22.7, 21.9, 14.6, 14.4 ppm. HRMS (EI): calcd. for C23H28N2O3
380.2100 [M]+; found 380.2101.
3j: Brown oil. IR (neat): ν = 3314, 2928, 1710, 1619, 1559, 1507,
˜
1459, 1416, 1367, 1296, 1223, 1173, 1071, 1035, 833, 797, 736,
710 cm–1. 1H NMR (500 MHz, CDCl3): δ = 8.00 (s, 1 H), 7.44–
7.47 (m, 2 H), 7.31–7.39 (m, 3 H), 7.18–7.22 (m, 2 H), 6.99–7.02
(m, 2 H), 4.25 (q, J = 7.2 Hz, 2 H), 3.83 (s, 3 H), 2.50–2.57 (m, 2
H), 1.33–1.40 (m, 2 H), 1.31 (t, J = 7.2 Hz, 3 H), 1.14–1.21 (m, 2
H), 0.73 (t, J = 7.3 Hz, 3 H) ppm. 13C NMR (126 MHz, CDCl3):
δ = 165.2, 160.5, 159.4, 145.5, 144.3, 135.9, 134.8, 130.1, 129.9,
129.1, 128.1, 128.0, 114.8, 107.0, 60.3, 55.5, 32.4 30.9, 22.8, 14.3,
13.6 ppm. HRMS (EI): calcd. for C25H28N2O3 404.2100 [M]+;
found 404.2104.
3c: Brown oil. IR (neat): ν = 3352, 2956, 1705, 1627, 1560, 1512,
˜
1444, 1378, 1287, 1251, 1211, 1165, 1076, 1031, 959, 918, 815,
773 cm–1. 1H NMR (500 MHz, CDCl3): δ = 7.92 (s, 1 H), 7.23–
7.26 (m, 2 H), 6.87–6.90 (m, 2 H), 5.13 (s, 2 H), 4.21 (q, J = 7.0 Hz,
2 H), 3.79 (s, 3 H), 2.83 (t, J = 7.6 Hz, 2 H), 2.01 (s, 3 H), 1.39–
1.46 (m 4 H), 1.29 (t, J = 7.0 Hz, 3 H), 0.94 (t, J = 6.9 Hz, 3
H) ppm. 13CNMR (126 MHz, CDCl3): δ = 165.3, 159.4, 159.1,
143.6, 141.8, 129.1, 127.9, 122.3, 114.0, 106.7, 60.0, 55.1, 53.6, 31.7,
29.8, 22.9, 14.1, 13.8, 13.4 ppm. HRMS (EI): calcd. for
C21H28N2O3 356.2100 [M]+; found 356.2063.
3k: Brown solid; m.p. 113–114 °C. IR (KBr): ν = 3433, 3058, 2959,
˜
1705, 1633, 1562, 1505, 1414, 1365, 1312, 1284, 1248, 1218, 1175,
1132, 1029, 903, 852, 767, 701 cm–1. 1H NMR (500 MHz, CDCl3):
δ = 7.92 (s, 1 H), 7.32–7.40 (m, 5 H), 7.15–7.20 (m, 2 H), 7.03–7.08
(m, 2 H), 5.74–5.88 (m, 1 H), 4.92–5.06 (m, 2 H), 3.91 (q, J =
7.0 Hz, 2 H), 3.86 (s, 3 H), 3.03 (d, J = 4.9 Hz, 2 H), 0.91 (t, J =
7.0 Hz, 3 H) ppm. 13C NMR (126 MHz, CDCl3): δ = 165.1, 159.7,
144.2, 142.3, 139.0, 134.7, 128.3, 127.7, 127.6, 127.1, 116.0, 115.1,
107.8, 60.1, 55.5, 33.5, 13.7 ppm. HRMS (EI): calcd. for
C24H24N2O3 388.1787 [M]+; found 388.1789.
Synthesis of 2-Iminopyridines 3d, 3h–l, 9 and 11 (Conditions B): A
solution of ethyl 2-cyano-2-phenylacetate (1b) (189 mg, 1.0 mmol)
in 1,4-dioxane (2.0 mL) was added to solid 95% KHMDS (168 mg,
0.80 mmol) at room temperature. The reaction mixture was stirred
at room temperature for 10 min and then a solution of the alkynyl
imine 2a (49.9 mg, 0.20 mmol) in 1,4-dioxane (2.0 mL) was added.
The resulting reaction mixture was stirred under reflux for 45.0 h
and then cooled to room temperature. A saturated aqueous
NaHCO3 solution (10 mL) was added to quench the reaction. The
mixture was extracted with dichloromethane (3ϫ15 mL). The
combined organic layers were dried with sodium sulfate. The sol-
vents were evaporated in vacuo and then the residue was purified
by preparative TLC on silica gel (ammonia solution in dichloro-
3l: Brown solid; m.p. 109–111 °C. IR (KBr): ν = 3304, 3074, 2930,
˜
2837, 1715, 1629, 1564, 1510, 1414, 1366, 1286, 1247, 1170, 1122,
1030, 913, 838, 783, 734 cm–1. 1H NMR (500 MHz, CDCl3): δ =
7.86 (s, 1 H), 7.26–7.29 (m, 2 H), 7.00–7.03 (m, 2 H), 5.83–5.93 (m,
1 H), 5.43–5.47 (m, 1 H), 5.10 (d, J = 17.1 Hz, 1 H), 5.05 (d, J =
10.1 Hz, 1 H), 4.15–4.24 (m, 2 H), 3.85 (s, 3 H), 3.34 (dd, J = 15.0,
5.6 Hz, 1 H), 3.24 (dd, J = 15.0, 5.8 Hz, 1 H), 2.25–2.32 (m, 1 H),
2.13–2.18 (m, 2 H), 1.94–2.01 (m, 1 H), 1.73–1.81 (m, 3 H), 1.60–
Eur. J. Org. Chem. 2008, 1411–1417
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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