PAPER
Regioselective Preparation of Pyridin-2-yl Ureas from 2-Chloropyridines
921
13C NMR (75 MHz, DMSO-d6): d = 154.7 (C), 154.3 (C), 146.9
(CH), 136.4 (CH) 118.6 (CH), 118.2 (CH), 44.3 (CH2), 39.7 (CH2),
21.9 (CH2).
1H NMR (300 MHz, DMSO-d6): d = 10.99 (1 H, NH), 8.62 (1 H,
N¢H), 8.32 [dd, J = 4.9, 1.7 Hz, 1 H, H-6 (Py)], 7.95 [dd, J = 7.9, 1.7
Hz, 1 H, H-4 (Py)], 7.53 [dd, J = 8.5, 1 Hz, 2 H, H-2 (Ph), H-6 (Ph)],
7.29 [m, 2 H, H-3 (Ph), H-5 (Ph)], 7.11 [dd, J = 7.9, 4.9 Hz, 1 H, H-
5 (Py)], 7.01 [tt, J = 7.5, 1 Hz, 1 H, H-4 (Ph)].
MS (EI): m/z (%) = 177 (100) [M+], 133 (10), 119 (57), 78 (34).
HRMS (EI): m/z [M] calcd for C9H11N3O: 177.0902; found:
177.0899.
13C NMR (75 MHz, DMSO-d6): d = 151.3 (C), 148.6 (C), 145.2
(CH), 139.0 (CH), 138.6 (C), 128.9 (2 × CH), 122.9 (CH), 119.3
(2 × CH), 119.2 (CH), 118.5 (C).
MS (EI): m/z (%) = 249 (9.5) [M+ + 2], 247 (30) [M+], 130 (30), 128
(100), 93 (26), 73 (99).
1-(Pyridin-2-yl)imidazolidin-2-one (9c)
Mp 159–162 °C (DMSO–H2O) (Lit.37 165–167 °C, EtOH); Rf 0.15
(CHCl3–EtOAc, 6:4).
IR (KBr): 3233, 3106, 1706, 1589, 1472, 1402, 1272, 777 cm–1.
HRMS (EI): m/z [M] calcd for C12H1035ClN3O: 247.0512; found:
247.0503.
1H NMR (300 MHz, DMSO-d6): d = 8.23 (ddd, J = 5.1, 2, 0.9 Hz, 1
H, H-6), 8.12 (ddd, J = 8.5, 0.9, 0.9 Hz, 1 H, H-3), 7.64 (ddd, J =
8.5, 7.2, 2 Hz, 1 H, H-4), 7.12 (br s, 1 H, NH), 6.02 (ddd, J = 7.2,
5.1, 0.9 Hz, 2 H, H-5), 3.94 (br t, J = 8 Hz, 2 H, NCH2CH2NH), 3.35
(br t, J = 8 Hz, 2 H, NCH2CH2NH).
Anal. Calcd for C12H10ClN3O: C, 58.19; H, 4.07; N, 16.97. Found:
C, 57.83; H, 4.05; N, 16.97.
N-(4-Chloropyridin-2-yl)-N¢-phenylurea (12b)
Mp 198–202 °C (CHCl3–hexane); Rf 0.57 (CHCl3–EtOAc, 6:4).
IR (KBr): 3041, 2998, 1695, 1595, 1566, 1449, 1378, 753 cm–1.
1H NMR (300 MHz, DMSO-d6): d = 9.89 (1 H, NH), 9.49 (1 H,
N¢H), 8.22 [d, J = 5.5 Hz, 1 H, H-6 (Py)], 7.70 [d, J = 1.7 Hz, 1 H,
H-3 (Py)], 7.46 [dd, J = 8.3, 1.1 Hz, 2 H, H-2 (Ph), H-6 (Ph)], 7.28
[m, 2 H, H-3 (Ph), H-5 (Ph)], 7.10 [dd, J = 5.5, 1.7 Hz, 1 H, H-5
(Py)], 6.99 [tt, J = 7.4, 1.1 Hz, 1 H, H-4 (Ph)].
MS (EI): m/z (%) 163 (100) [M+], 162 (60), 119 (97), 78 (50).
HRMS (EI): m/z [M] calcd for C8H9N3O: 168.0746; found:
163.0715.
1,3-Di-(pyridin-2-yl)-tetrahydro-pyrimidin-2(1H)-one (10b)
Mp 79–83 °C (CHCl3); Rf 0.27 (CHCl3–EtOAc, 6:4); eluted in col-
umn chromatography with CHCl3–EtOAc (8:2).
IR (KBr): 1666, 1586, 1460, 1402, 1285, 1192, 786, 739 cm–1.
13C NMR (75 MHz, DMSO-d6): d = 153.9 (C), 151.8 (C), 148.9
(CH), 144.1 (C), 138.7 (C), 128.9 (2 × CH), 122.7 (CH), 118.7 (2 ×
CH), 117.7 (CH), 111.1 (CH).
MS (EI): m/z (%) = 249 (0.17) [M+ + 2], 247 (5) [M+], 128 (49), 93
(47), 73 (100).
1H NMR (300 MHz, DMSO-d6): d = 8.36 (ddd, J = 4.9, 1.7, 1.0 Hz,
2 H, H-6), 7.69 (m, 4 H, H-3, H-4), 7.10 (ddd, J = 7.2, 4.9, 0.9 Hz,
2 H, H-5), 3.94 [t, J = 5.9 Hz, 4 H, H-4, H-6 (pyrimidine)], 2.11
[quint, J = 5.9 Hz, 2 H, H-5 (pyrimidine)].
13C NMR (75 MHz, DMSO-d6): d = 154.7 (C), 153.7 (2 × C), 147.3
(2 × CH), 136.7 (2 × CH), 119.9 (2 × CH), 119.6 (2 × CH), 45.3
(2 × CH2), 22.2 (CH2).
MS (EI): m/z (%) = 254 (100) [M+], 160 (29), 133 (44), 119 (48), 78
(35).
HRMS (EI): m/z [M] calcd for C12H1035ClN3O: 247.0512; found:
247.0516.
N-(5-Chloropyridin-2-yl)-N¢-phenylurea (12c)
Mp 203–204 °C (dioxane–hexane) (Lit.5a 200–203 °C); Rf 0.5
(CHCl3–EtOAc, 6:4).
HRMS (EI): m/z [M] calcd for C14H14N4O: 254.1168; found:
254.1154.
IR (KBr): 3046, 2985, 1693, 1596, 1562, 1479, 1369, 1315, 1225,
833, 757 cm–1.
Anal. Calcd for C14H14N4O: C, 66.13; H, 5.55; N, 22.03. Found: C,
65.72; H, 5.49; N, 22.20.
1H NMR (300 MHz, DMSO-d6): d = 9.75 (1 H, NH), 9.42 (1 H,
N¢H), 8.28 [dd, J = 2.5, 0.4 Hz, 1 H, H-6 (Py)], 7.82 [dd, J = 8.9, 2.5
Hz, 1 H, H-4 (Py)], 7.67 [dd, J = 8.9, 0.4 Hz, 1 H, H-3 (Py)], 7.45
[dd, J = 8.5, 1.1 Hz, 2 H, H-2 (Ph), H-6 (Ph)], 7.27 [m, 2 H, H-3
(Ph), H-5 (Ph)], 6.98 [tt, J = 7.5, 1.1 Hz, 1 H, H-4 (Ph)].
13C NMR (75 MHz, DMSO-d6): d = 151.8 (C), 151.5 (C), 145.6
(CH), 138.9 (C), 138.1 (CH), 128.9 (2 × CH), 123.4 (C), 122.6
(CH), 118.7 (2 × CH), 113.0 (CH).
MS (EI): m/z (%) = 249 (11) [M+ + 2], 247 (35) [M+], 130 (30), 128
(100), 93 (43).
HRMS (EI): m/z [M] calcd for C12H1035ClN3O: 247.0512; found:
247.0500.
1,3-Di-(pyridin-2-yl)imidazolidin-2-one (10c)
Mp 182–184 °C (DMSO–H2O); Rf 0.37 (CHCl3–EtOAc, 6:4).
IR (KBr): 1711, 1588, 1465, 1433, 1389, 1298, 1238, 1141, 773,
739 cm–1.
1H NMR (300 MHz, DMSO-d6): d = 8.33 (ddd, J = 4.9, 1.9, 0.9 Hz,
2 H, H-6), 8.20 (ddd, J = 8.6, 1.0, 0.9 Hz, 2 H, H-3), 7.76 (ddd, J =
8.6, 7.2, 1.9 Hz, 2 H, H-4), 7.05 (ddd, J = 7.2, 4.9, 0.9 Hz, 2 H, H-
5), 4.05 (s, 4 H, NCH2CH2N).
13C NMR (75 MHz, DMSO-d6): d = 153.7 (C), 151.7 (2 × C), 147.6
(2 × CH), 137.5 (2 × CH), 118.3 (2 × CH), 112.5 (2 × CH), 40.4
(2 × CH2).
N-(6-Chloropyridin-2-yl)-N¢-phenylurea (12d)
Mp 197.7–198.0 °C (dioxane-hexane); Rf 0.48 (CHCl3–EtOAc,
6:4).
MS (EI): m/z (%) = 240 (68) [M+], 162 (6), 119 (100), 78 (30).
HRMS (EI): m/z [M] calcd for C13H12N4O: 240.1011; found:
240.0998.
IR (KBr): 3201, 3092, 3040, 2979, 1696, 1596, 1568, 1457, 1396,
1258, 1164, 785, 755 cm–1.
1H NMR (300 MHz, DMSO-d6): d = 9.50 (1 H, NH), 9.29 (1 H,
N¢H), 7.76, 7.71 [m, AB portion of the ABX system, JAB = 8.29 Hz,
JAX = 7.68 Hz, JBX = 0.6 Hz, 2 H, H-3 (Py), H-4 (Py)],38 7.42 [dd,
J = 8.5, 1.9 Hz, 2 H, H-2 (Ph), H-6 (Ph)], 7.28 [m, 2 H, H-3 (Ph), H-
Anal. Calcd for C13H12N4O: C, 64.99; H, 5.03; N, 23.32. Found: C,
64.64; H, 4.98; N, 23.13.
N-(3-Chloropyridin-2-yl)-N¢-phenylurea (12a)
Mp 135–137 °C (CHCl3–hexane); Rf 0.70 (CHCl3–EtOAc, 6:4);
eluted in column chromatography with CHCl3.
5 (Ph)], 7.06 [m, X part of the ABX system, JAX = 7.68 Hz, JBX
0.6 Hz, 1 H, H-5 (Py)], 6.99 [tt, J = 7.5, 1.1 Hz, 1 H, H-4 (Ph)].
=
IR (KBr): 3241, 3025, 1686, 1594, 1561, 1486, 1446, 1280, 750
cm–1.
Synthesis 2005, No. 6, 915–924 © Thieme Stuttgart · New York