HETEROCYCLES, Vol. 83, No. 1, 2011
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8.27 (s, 1H, 3-NH), 9.79 (s, 1H, 1-NH); 13C NMR (150 MHz, DMSO-d6): δ 18.1, 54.0, 92.8, 121.3, 122.7,
126.4, 126.9, 129.1, 130.4, 131.3, 133.1, 145.9, 147.7, 147.8, 151.4, 166.9, 174.5; MS (EI, 70 eV): m/z (%)
= 377 (M+, 21), 319 (67), 255 (100), 219 (49); Anal. Calcd for C19H15N5O4 (%): C, 60.47; H, 4.01; N, 18.56.
Found: C, 60.19; H, 4.06; N, 18.30.
5-(4-(4-Methoxyphenyl)-6-methyl-3,4-dihydro-2(1H)-pyrimidinon-5-yl)-3-phenyl-1,2,4-oxadiazole
(4g). White solid; yield: 95%; mp 235–237 C; IR (KBr) ν: 3321, 1695, 1658, 1251 cm-1; 1H NMR (600
MHz, DMSO-d6): δ 2.47 (s, 3H, 6-CH3), 3.70 (s, 3H, OCH3), 5.40 (d, J = 2.4 Hz, 1H, 4-CH), 6.89 (d, J = 7.8
Hz, 2H, m-H {R2}), 7.27 (d, J = 7.8 Hz, 2H, o-H {R2}), 7.55–7.54 (m, 3H, m-H + p-H {R1}), 7.93 (s, 1H,
3-NH), 7.96 (d, J = 6.6 Hz, 2H, o-H {R1}), 9.59 (s, 1H, 1-NH); 13C NMR (150 MHz, DMSO-d6): δ 18.0,
53.8, 55.6, 94.0, 113.9, 126.5, 126.9, 127.6, 129.1, 131.3, 136.0, 146.6, 151.6, 158.7, 166.9, 174.8; MS (EI,
70 eV): m/z (%) = 362 (M+, 42), 285 (100),255 (73); Anal. Calcd for C20H18N4O3 (%): C, 66.29; H, 5.01; N,
15.46. Found: C, 66.12; H, 5.17; N, 15.38.
General procedure for the preparation of 5-(2-pyrimidinol-5-yl)-1,2,4-oxadiazoles (5a–k).
5-(3,4-Dihydro-2(1H)-pyrimidinon-5-yl)-1,2,4-oxadiazoles 4 (5 mmol, 1 equiv), CuCl2 (0.03 g, 0.25 mmol,
5 mol%), Cs2CO3 (0.8 g, 2.5 mmol, 0.5 equiv), tetrabutylammonium bromide (0.16 g, 0.5 mmol, 10 mol%)
and 1,2-dichloropropane (50 mL) were mixed in a 100-mL flask. The suspension was heated to 90 C and
treated with tert-butylhydroperoxide (65% in water) (3.5 g, 25mmol, 5.0 equiv) over 60 min with vigorous
agitation. After 4–6 h, TLC indicated the consumption of the starting material. The solution was cooled to
room temperature and washed with water. The two phases were separated and the organic phase was
concentrated to the minimum agitation volume via reduced pressure distillation. The residue was purified
by flash column chromatography (eluent: petroleum ether/EtOAc, 1:2) to afford the product 5 as a white or
slight yellow powder. Yields, melting points and spectroscopic data for selected
5-(2-pyrimidinol-5-yl)-1,2,4-oxadiazoles are listed as follows.
5-(4-Methyl-6-propyl-2-pyrimidinol-5-yl)-3-phenyl-1,2,4-oxadiazole (5a). White solid; yield: 91%; mp
198–199 C; IR (KBr) ν: 3433, 2959, 1660, 1608, 702 cm-1; 1H NMR (600 MHz, DMSO-d6): δ 0.97 (t, J =
7.2 Hz , 3H, Pr-CH3), 1.71–1.69 (m, 2H, CH2), 2.46 (s, 3H, 6-CH3), 2.72 (t, J = 7.2 Hz , 2H, CH2),
7.58–7.61 (m, 3H, m-H + p-H), 8.08 (d, J = 6.6 Hz, 2H, o-H), 12.55 (s, 1H, 2-OH); 13C NMR (150 MHz,
DMSO-d6): δ 13.7, 16.9, 17.9, 50.56, 126.0, 126.9, 129.0, 131.6, 146.7, 152.4, 167.0, 167.6, 173.1, 174.9;
MS (EI, 70 eV): m/z (%) = 297 (M+ + 1, 23), 267 (81), 236 (42), 219 (100), 159 (45); Anal. Calcd for
C16H16N4O2 (%): C, 64.85; H, 5.44; N, 18.91. Found: C, 64.39; H, 5.21; N, 19.02.
5-(4-Methyl-6-phenyl-2-pyrimidinol-5-yl)-3-phenyl-1,2,4-oxadiazole (5b). Slight yellow solid; yield:
90%; mp 251–253 C. IR (KBr) ν: 3432, 2910, 1649, 1606, 707 cm-1. 1H NMR (600 MHz, DMSO-d6): δ =
2.50 (s, 3 H, 6-CH3), 7.55–7.26 (m, 8 H, Ar-H {R2} + m-H + p-H {R1}), 7.97 (d, J = 7.6 Hz, 2 H, o-H {R1}),