Molecules 2012, 17
4539
2,4-Dichloro-5-methylpyrimidine (2b). Obtained from 2,4-dihydroxy-5-methylpyrimidine (37.8 g),
POCl3 (54 mL), and pyridine (24.3 mL) after distillation (114–116 °C/1 mm Hg). Yield: 43.0 g, 88%;
1
13
Purity: 98%; H-NMR (CDCl3, δ, ppm):8.36 (s, 1H), 2.30(d, J = 0.4 Hz, 3H); C-NMR (CDCl3, δ,
ppm):162.3, 160.0, 157.9, 129.0, 15.7; MS (ESI, m/z): 163.1.
2,4,5-Trichloropyrimidine (3b). Obtained from 2,4-dihydroxy-5-chloropyrimidine (44.1 g), POCl3 (54 mL)
and pyridine (24.3 mL) after distillation (94–96 °C/12 mm Hg). Yield: 48.9 g, 89%; Purity: 96%;
13
1H-NMR (CDCl3, δ, ppm):8.59 (s, 1H); C-NMR (CDCl3, δ, ppm): 159.9, 158.7, 157.9, 129.2; MS
(ESI, m/z): 183.0.
2,4-Dichloro-6-aminopyrimidine (4b). Obtained from 6-amino-2,4-dihydroxypyrimidine (38 g), POCl3
(54 mL) and pyridine (24.3 mL) after filtration. Yield: 41.8 g, 85%; Purity: 97%; m.p.: 253–254 °C;
1H-NMR (DMSO, δ, ppm): 7.75 (d, br, J = 32 Hz, 2H), 6.45(s, 1H); 13C-NMR (DMSO, δ, ppm):
166.4, 159.4, 158.4, 102.2; MS (ESI, m/z): 164.1.
2,4-Dichloro-6-methylpyrimidine (5b). Obtained from 2,4-dihydroxy-6-methylpyrimidine (37.8 g),
POCl3 (54 mL) and pyridine (24.3 mL) after distillation (98–100 °C/1 mm Hg). Yield: 41.8 g, 85%;
Purity: 98%; m.p.: 46–47 °C; 1H-NMR (CDCl3, δ, ppm): 7.19 (d, J = 2.8 Hz, 1H), 2.54(d, J = 4.4 Hz,
3H); 13C-NMR (CDCl3, δ, ppm): 171.8, 162.3, 160.4, 119.4, 23.8; MS (ESI, m/z): 163.1.
2-Chloro-6-aminopyrimidine (6b). Obtained from 6-amino-2-hydroxypyrimidine (33 g), POCl3 (27 mL)
and pyridine (24.3 mL) after filtration. Yield: 31.0 g, 83%; Purity: 97%; m.p.: 205–207 °C;
1H-NMR (CDCl3, δ, ppm): 7.94 (d, J = 6 Hz, 1H), 7.39 (s, br, 2H), 6.39 (d, J = 5.6 Hz, 1H); 13C-NMR
(CDCl3, δ, ppm): 165.7, 160.3, 157.2, 104.5; MS (ESI, m/z): 130.1.
3.4. Quinoxaline and Pyridopyrazine Products
2-Chloroquinoxaline (15b). Obtained from 2-hydroxyquinoxaline (43.8 g), POCl3 (27 mL) and
pyridine (24.3 mL) after filtration. Yield: 48.5 g, 94%; Purity: 98%; m.p.: 48–50 °C; 1H-NMR (CDCl3,
13
δ, ppm): 8.78 (s, 1H), 8.07 (m, 1H), 7.97 (m, 1H), 7.75 (m, 2H); C-NMR (CDCl3, δ, ppm): 147.3,
144.9, 141.9, 140.9, 131.1, 130.1, 129.3, 128.5; MS (ESI, m/z): 165.1.
2,3-Chloroquinoxaline (16b). Obtained from 2,3-dihydroxyquinoxaline (48.6 g), POCl3 (54 mL) and
1
pyridine (24.3 mL) after filtration. Yield: 57.3 g, 96%; Purity: 97%; m.p.: 148–150 °C; H-NMR
(CDCl3, δ, ppm): 8.04 (m, 2H), 7.82 (m, 2H); 13C-NMR (CDCl3, δ, ppm): 145.4, 140.6, 131.2, 128.2;
MS (ESI, m/z): 200.1.
2,6-Chloroquinoxaline (17b). Obtained from 2-hydroxy-6-chloroquinoxaline (54.2 g), POCl3 (27 mL)
1
and pyridine (24.3 mL) after filtration. Yield: 51.4 g, 86%; Purity: 98%; m.p.: 156–158 °C; H-NMR
(CDCl3, δ, ppm): 8.04 (m, 2H), 7.82 (m, 2H); 13C-NMR (CDCl3, δ, ppm): 145.4, 140.6, 131.2, 128.2;
MS (ESI, m/z): 199.0.
7-Bromo-2,3-dichloropyrido[2,3-b]pyrazine (18b). Obtained from 2,3-dihydroxy-7-bromo pyrido[2,3-
b]pyrazine (73.0 g), POCl3 (54 mL) and pyridine (24.3 mL) after filtration. Yield: 79.0 g, 94%; Purity: