B. Han et al. / Tetrahedron 67 (2011) 5615e5620
5619
NH); 13C NMR (100.6 MHz, CDCl3):
d
13.6, 18.6, 56.2, 60.9, 61.7, 105.4,
d
1.13 (t, 3H, J¼7.2 Hz), 2.53 (s, 3H), 2.60 (s, 3H), 3.85 (s, 3H), 4.21 (q,
111.6, 113.7, 140.4, 153.1, 158.3, 166.4; EI-MS m/z (relative intensity,
%): 348 (3.8), 290 (28.6), 197 (58.2), 169 (57.4), 84 (100), 43 (67.9);
ESI-HRMS: m/z calcd for C17H20N2O6þHþ: 349.1394, found 349.1388.
2H, J¼7.2 Hz), 6.93e6.96 (m, 2H), 7.63e7.66 (m, 2H); 13C NMR
(100.6 MHz, CDCl3): d 13.7, 14.1, 29.6, 55.3, 61.6, 113.9, 120.4, 129.96,
130.02,161.4,162.6,165.1,168.5,172.2; EI-MS m/z (relative intensity,
%): 318 (100), 289 (22.0), 243 (11.0),199 (17.0),159 (20.0),103 (18.0),
67 (37.0), 45 (50.0); ESI-HRMS: m/z calcd for C16H18N2O3SþHþ:
319.1111, found 319.1118.
4.4.9. Ethyl 4-(4-chlorophenyl)-1,2-dihydro-6-methyl-2-oxo-pyrimi-
dine-5-carboxylate (2i)8c. Pale yellow solid; mp 172e174 ꢀC. 1H
NMR (400 MHz, CDCl3):
2H, J¼7.2 Hz), 7.42 (d, 2H, J¼8.4 Hz), 7.56 (d, 2H, J¼8.4 Hz), 13.70 (br
s, 1H, NH); 13C NMR (100.6 MHz, CDCl3):
13.5, 18.9, 61.7, 111.3,
d
1.02 (t, 3H, J¼7.2 Hz), 2.63 (s, 3H), 4.10 (q,
4.5.3. Ethyl 4-(4-chlorophenyl)-6-methyl-2-(methylthio)-pyrimidine-
d
5-carboxylate (4c). Pale yellow solid; mp 60e61 ꢀC. 1H NMR
128.7, 129.4, 137.2, 158.2, 165.8; EI-MS m/z (relative intensity, %):
294 (14.0), 292 (41.6), 263 (100), 247 (62.1), 219 (25.9), 138 (36.9),
110 (23.6), 75 (26.0), 42 (78.5); ESI-HRMS: m/z calcd for
C14H13ClN2O3þHþ: 293.0687, found 293.0692.
(400 MHz, CDCl3):
4.19 (q, 2H, J¼7.2 Hz), 7.42 (d, 2H, J¼8.4 Hz), 7.59 (d, 2H, J¼8.4 Hz);
13C NMR (100.6 MHz, CDCl3):
13.7, 14.1, 22.6, 61.8, 120.7, 128.7,
129.7, 136.1, 136.4, 162.2, 165.6, 167.9, 172.6; EI-MS m/z (relative
intensity, %): 322 (100), 294 (29.8), 277 (15.8), 248 (15.5), 195 (14.8),
163 (10.1), 67 (10.4); ESI-HRMS: m/z calcd for C15H15ClN2O2SþHþ:
323.0616, found 323.0611.
d
1.11 (t, 3H, J¼7.2 Hz), 2.56 (s, 3H), 2.61 (s, 3H),
d
4.4.10. Ethyl 4-(4-fluorophenyl)-1,2-dihydro-6-methyl-2-
oxopyrimidine-5-carboxylate (2j). Pale yellow solid; mp 170e171 ꢀC.
1H NMR (400 MHz, CDCl3):
d
1.02 (t, 3H, J¼6.8 Hz), 2.62 (s, 3H), 4.10
(q, 2H, J¼6.8 Hz), 7.13 (dd, 2H, J¼8.8 Hz, J¼8.4 Hz,), 7.63 (dd, 2H,
4.5.4. Ethyl 4-isopropyl-6-methyl-2-(methylthio)pyrimidine-5-
J¼5.2 Hz, J¼8.8 Hz), 13.66 (br s, 1H, NH); 13C NMR (100.6 MHz,
carboxylate (4d). White oil. 1H NMR (400 MHz, CDCl3):
d 1.26 (d,
CDCl3):
d
13.6, 19.0, 61.7, 111.3, 115.4, 115.5 (J¼22 Hz), 130.3 (J¼8 Hz),
6H, J¼6.8 Hz), 1.39 (t, 3H, J¼7.2 Hz), 2.45 (s, 3H), 2.57 (s, 3H), 3.06
158.2, 163.1, 164.4 (J¼250 Hz), 165.9; EI-MS m/z (relative intensity,
%): 276 (40.9), 247 (100), 203 (28.5), 190 (25.8), 122 (25.1), 42
(14.5); ESI-HRMS: m/z calcd for C14H13FN2O3þHþ: 277.0983, found
277.0985.
(m, 1H), 4.40 (q, 2H, J¼7.2 Hz); 13C NMR (100.6 MHz, CDCl3):
d 14.0,
14.1, 21.6, 22.6, 33.4, 61.6, 121.1, 164.2, 167.9, 171.9, 172.2; EI-MS m/z
(relative intensity, %): 254 (96.1), 225 (69.8), 211 (37.5), 154 (42.2),
67 (100), 39 (75.4); ESI-HRMS: m/z calcd for C12H18N2O2SþHþ:
255.1162, found 255.1167.
4.4.11. Ethyl 1,2-dihydro-4-isopropyl-6-methyl-2-oxopyrimidine-5-
carboxylate (2k). Pale yellow solid; mp 164e166 ꢀC. 1H NMR
4.5.5. Ethyl 4-methyl-2-(methylthio)pyrimidine-5-carboxylate
(400 MHz, CDCl3):
d
1.31 (d, 6H, J¼6.4 Hz),1.39 (t, 3H, J¼7.2 Hz), 2.52
(5d). White solid; mp 59e60 ꢀC. 1H NMR (400 MHz, CDCl3):
(s, 3H), 3.20 (m, 1H), 4.37 (q, 2H, J¼7.2 Hz), 13.62 (br s, 1H, NH); 13C
d
1.40 (t, 3H, J¼7.2 Hz), 2.60 (s, 3H), 2.77 (s, 3H), 4.38 (q, 2H,
NMR (100.6 MHz, CDCl3):
d
14.0, 21.0, 33.4, 61.7, 111.6, 158.8, 165.9;
J¼7.2 Hz), 8.94 (s, 1H); 13C NMR (100.6 MHz, CDCl3):
d 14.2, 24.4,
EI-MS m/z (relative intensity, %): 224 (20.9), 209 (46.5), 195 (62.6),
179 (35.3), 124 (39.5), 110 (32.0), 67 (35.2), 42 (100); ESI-HRMS: m/z
calcd for C11H16N2O3þNaþ: 247.1053, found 247.1056.
61.2, 118.4, 158.7, 164.9, 168.7, 175.3; EI-MS m/z (relative intensity,
%): 212 (100), 184 (60.6), 167 (22.5), 138 (41.5), 53 (11.6); ESI-HRMS:
m/z calcd for C9H12N2O2SþHþ: 213.0692, found 213.0696.
4.4.12. Ethyl 4-hexyl-1,2-dihydro-6-methyl-2-oxopyrimidine-5-
4.5.6. Ethyl 4-hexyl-6-methyl-2-(methylthio)pyrimidine-5-
carboxylate (2l). Pale yellow solid; mp 75e77 ꢀC. 1H NMR
carboxylate (4f). Pale yellow oil. 1H NMR (400 MHz, CDCl3):
(400 MHz, CDCl3):
d
0.89 (t, 3H, J¼6.4 Hz),1.28e1.40 (m, 6H),1.39 (t,
d
0.88 (t, 3H, J¼6.8 Hz), 1.25e1.37 (m, 6H), 1.39(t, 3H, J¼7.2 Hz), 1.70
3H, J¼7.2 Hz),1.70 (m, 2H), 2.54 (s, 3H), 2.81(t, 2H, J¼8.0 Hz), 4.37 (q,
(m, 2H), 2.47 (s, 3H), 2.56 (s, 3H), 2.72 (t, 2H, J¼7.6 Hz), 4.40 (q, 2H,
2H, J¼7.2 Hz), 13.59 (br s, 1H, NH); 13C NMR (100.6 MHz, CDCl3):
J¼7.2 Hz); 13C NMR (100.6 MHz, CDCl3):
d 13.88, 13.94, 22.4, 22.8,
d
13.9,14.1, 22.4, 28.8, 29.1, 31.4, 61.6,111.4,158.3,165.5; ESI-MS: m/z
28.6, 29.00, 29.05, 31.5, 35.8, 61.5, 121.5, 164.5, 167.6, 168.0, 172.0;
ESI-MS m/z requires 298, found ([MþHþ], 299); ESI-HRMS: m/z
calcd for C15H24N2O2SþHþ: 297.1631, found 297.1638.
266 ([MþHþ], 267); ESI-HRMS: m/z calcd for C14H22N2O3þHþ:
267.1703, found 267.1708.
4.5. A typical procedure for the NHPI/CoII system catalyzed
aerobic oxidation of dihydropyrimidines 3
4.5.7. Ethyl 4-(4-fluorophenyl)-2-(methylthio)-6-phenylpyrimidine-
5-carboxylate (4g). White solid; 76e78 ꢀC. 1H NMR (400 MHz,
CDCl3):
7.12e7.17 (m, 2H), 7.43e7.49 (m, 3H), 7.66e7.72 (m, 4H); 13C NMR
(100.6 MHz, CDCl3):
128.3, 128.4, 130.1, 130.5 (d, J¼8.0 Hz), 133.4 (d, J¼3.0 Hz), 137.3,
163.0, 163.9 (d, J¼250.5 Hz), 164.4, 168.0, 172.7; EI-MS m/z (relative
intensity, %): 368 (100), 339 (35.5), 273 (36.0), 216 (43.1), 149 (73.8),
95 (58.3), 43 (63.1); ESI-HRMS: m/z calcd for C20H17FN2O2SþHþ:
369.1068, found 369.1063.
d
0.96 (t, 3H, J¼7.2 Hz), 2.65 (s, 3H), 4.04 (q, 2H, J¼7.2 Hz),
A mixture of dihydropyrimidine 3a (290 mg, 1 mmol), NHPI
(16 mg, 10 mol %), and Co(OAc)2$4H2O (1 mg, 0.5 mol %) was placed
in a 25 mL three-necked flask in (CH2Cl)2 (4 mL) and stirred at 80 ꢀC
under oxygen atmosphere for 1 h. When the starting materials were
consumed completely monitored by TLC, the reaction mixture was
concentrated by vacuum and then the product was isolated by silica
gel column chromatography to give white oil 4a 278 mg (yield: 97%).
d
13.4, 14.2, 61.8, 115.5 (d, J¼21.1 Hz), 120.6,
4.5.1. Ethyl 4-methyl-2-(methylthio)-6-phenylpyrimidine-5-
4.5.8. Ethyl 4-isopropyl-2-(methylthio)-6-phenylpyrimidine-5-
carboxylate (4a). White oil. 1H NMR (400 MHz, CDCl3):
d
1.04 (t,
carboxylate (4h)8a. Pale yellow oil. 1H NMR (400 MHz, CDCl3):
3H, J¼7.2 Hz), 2.57 (s, 3H), 2.61 (s, 3H), 4.15 (q, 2H, J¼7.2 Hz),
d
1.03 (t, 3H, J¼7.2 Hz),1.32 (d, 6H, J¼6.8 Hz), 2.62 (s, 3H), 3.20 (m,1H),
7.43e7.46 (m, 3H), 7.63e7.65 (m, 2H); 13C NMR (100.6 MHz, CDCl3):
4.14 (q, 2H, J¼7.2 Hz), 7.41e7.45 (m, 3H), 7.62e7.65 (m, 2H); 13C NMR
d
13.6, 14.1, 22.5, 61.6, 120.9, 128.3, 128.4, 130.0, 137.8, 163.6, 165.4,
(100.6 MHz, CDCl3): d 13.6, 14.2, 21.6, 33.1, 61.6, 120.4, 128.2, 128.4,
168.1, 172.5; EI-MS m/z (relative intensity, %): 288 (100), 259 (62.0),
243 (31.0), 159 (37.0), 115 (46.0), 77 (72.0), 67 (91.2), 45 (88.0); ESI-
HRMS: m/z calcd for C15H16N2O2SþHþ: 289.1005, found 289.1006.
129.9, 137.9, 163.6, 168.2, 172.5, 172.9; EI-MS m/z (relative intensity,
%): 316 (100), 287 (42.7), 216 (17.4), 129 (12.4), 77 (5.4), 41 (3.2).
4.5.9. Ethyl 2-(methylthio)-6-phenylpyrimidine-5-carboxylate
4.5.2. Ethyl 4-(4-methoxyphenyl)-6-methyl-2-(methylthio)-pyrimi-
(5h)8a. White solid; mp 57e58 ꢀC. 1H NMR (400 MHz, CDCl3):
dine-5-carboxylate (4b). White oil. 1H NMR (400 MHz, CDCl3):
d
1.12 (t, 3H, J¼7.2 Hz), 2.63 (s, 3H), 4.20 (q, 2H, J¼7.2 Hz), 7.44e7.49