316 JOURNAL OF CHEMICAL RESEARCH 2016
1479, 1415, 1340, 1253, 1200, 1113, 1066 (C–O), 985, 916, 889, 867,
825, 706, 669; 1H NMR (400.1 MHz, CDCl3): δ 2.44 (s, 3H, CH3), 3.55
(s, 6H, 2 × OCH3), 5.73 (s, 1H, CH), 7.31 (d, J = 8.4 Hz, 2H, 2 × CH),
8.03 (d, J = 8.4 Hz, 2H, 2 × CH); 13C NMR (100.6 MHz, CDCl3): δ
21.6, 53.9, 96.1, 123.4, 127.6, 129.6, 141.8, 168.4, 174.2; EI-MS: m/z (%)
= 234 ([M]+, 36), 203 (22), 175 (19), 132 (28), 116 (9), 91 (17), 75 (100),
51 (5); Anal. calcd for C12H14N2O3 (234.25): C, 61.53; H, 6.02; N, 11.96;
found: C, 61.57; H, 6.09; N, 11.86%.
8.08 (ddd, J = 8.0, 1.6, 1.2 Hz, 1H, CH), 8.32 (t, J = 1.6 Hz, 1H, CH);
13C NMR (100.6 MHz, CDCl3): δ 53.9, 96.0, 123.0, 126.1, 128.2, 130.4,
130.6, 134.4, 167.3, 174.7; EI-MS: m/z (%) = 300 ([M]+ 81Br, 20), 298
([M]+ 79Br, 20), 269 (28), 241 (7), 239 (8), 198 (5), 196 (5), 157 (5), 155
(5) 102 (9), 75 (100), 50 (7); Anal. calcd for C11H11BrN2O3 (299.12): C,
44.17; H, 3.71; N, 9.37; found: C, 44.05; H, 3.63; N, 9.25%.
3-(3-Bromophenyl)-5-(diethoxymethyl)-1,2,4-oxadiazole (7j): Pale
yellow oil; yield: 0.589 g (90%); IR (KBr) (νmax/cm–1): 1561, 1466,
1408, 1309, 1268, 1188, 1075, 997, 893, 812, 784, 673; 1H NMR (400.1
MHz, CDCl3): δ 1.32 (t, J = 7.2 Hz, 6H, 2 × CH2CH3), 3.78 and 3.82
5-(Diethoxymethyl)-3-(4-methylphenyl)-1,2,4-oxadiazole
(7d):
Colourless oil; yield: 0.503 g (96%); IR (KBr) (νmax/cm–1): 1595, 1479,
1334, 1283, 1117, 1062, 910, 821, 748; 1H NMR (400.1 MHz, CDCl3): δ
1.32 (t, J = 7.2 Hz, 6H, 2 × CH2CH3), 2.42 (s, 3H, CH3), 3.78 and 3.82
(2 × dq, 2J = 9.6, 3J = 7.2 Hz, 4H, 2 × OCH2CH3), 5.80 (s, 1H, CH), 7.29
(d, J = 8.4 Hz, 2H, 2 × CH), 8.02 (d, J = 8.4 Hz, 2H, 2 × CH); 13C NMR
(100.6 MHz, CDCl3): δ 15.0, 21.6, 62.6, 94.5, 123.5, 127.5, 129.5, 141.7,
168.3, 174.8; EI-MS: m/z (%) = 263 ([M + H]+, 60), 218 (43), 189 (18),
161 (13), 133 (43), 118 (13), 103 (100), 91 (16), 75 (34), 65 (7); Anal.
calcd for C14H18N2O3 (262.31): C, 64.11; H, 6.92; N, 10.68; found: C,
64.30; H, 7.07; N, 10.49%.
2
3
(2 × dq, J = 9.6, J = 7.2 Hz, 4H, 2 × OCH2CH3), 5.83 (s, 1H, CH),
7.36 (t, J = 8.0 Hz, 1H, CH), 7.64 (ddd, J = 8.0, 1.6, 1.2 Hz, 1H, CH),
8.06 (ddd, J = 8.0, 1.6, 1.2 Hz, 1H, CH), 8.29 (t, J = 1.6 Hz, 1H, CH);
13C NMR (100.6 MHz, CDCl3): δ 15.0, 62.7, 94.4, 122.9, 126.1, 128.3,
130.4, 130.6, 134.3, 167.2, 175.4; EI-MS: m/z (%) = 328 ([M]+ 81Br, 13),
326 ([M]+ 79Br, 13), 284 (82), 255 (49), 253 (46), 225 (16), 199 (93), 184
(31), 183 (82), 182 (31), 159 (17), 157 (17), 118 (23), 102 (100), 75 (84),
50 (27); Anal. calcd for C13H15BrN2O3 (327.18): C, 47.72; H, 4.62; N,
8.56; found: C, 47.58; H, 4.43; N, 8.40%.
5-(Dimethoxymethyl)3-(4-fluorophenyl)-1,2,4-oxadiazole (7e): Pale
yellow oil; yield: 0.433 g (91%); IR (KBr) (νmax/cm–1): 1605, 1507, 1479,
1417, 1336, 1286, 1232, 1196, 1158, 1119, 1069 (C–O), 985, 906, 844,
755, 685; 1H NMR (400.1 MHz, CDCl3): δ 3.51 (s, 6H, 2 × OCH3), 5.70
(s, 1H, CH), 7.15 (dd, 3JFH = 8.8, 3JHH = 8.8 Hz, 2H, 2 × CH), 8.10 (dd,
3JHH = 8.8, 4JFH = 5.6 Hz, 2H, 2 × CH); 13C NMR (100.6 MHz, CDCl3): δ
53.8, 96.0, 116.1 (d, 2JFC = 22.0 Hz), 122.5 (d, 4JFC = 3.3 Hz), 129.8 (d, 3JFC
= 8.8 Hz), 164.7 (d, 1JFC = 250.3 Hz), 167.5, 174.5; EI-MS: m/z (%) = 238
([M]+, 27), 207 (36), 179 (23), 151 (10), 136 (25), 121 (13), 109 (10), 95
(13), 75 (100), 57 (9); Anal. calcd for C11H11FN2O3 (238.22): C, 55.46; H,
4.65; N, 11.76; found: C, 55.38; H, 4.72; N, 11.64%.
5-(Dimethoxymethyl)-3-(3-methylphenyl)-1,2,4-oxadiazole (7k):
Colourless oil; yield: 0.435 g (93%); IR (KBr) (νmax/cm–1): 1580,
1520, 1460, 1335, 1284, 1197, 1118, 1070 (C–O), 984, 907, 848, 799,
742, 688; 1H NMR (400.1 MHz, CDCl3): δ 2.43 (s, 3H, CH3), 3.54 (s,
6H, 2 × OCH3), 5.73 (s, 1H, CH), 7.33 (d, J = 7.6 Hz, 1H, CH), 7.38 (t,
J = 7.6 Hz, 1H, CH), 7.94 (d, J = 7.6 Hz, 1H, CH), 7.97 (s, 1H, CH);
13C NMR (100.6 MHz, CDCl3): δ 21.3, 53.9, 96.0, 124.7, 126.1, 128.2,
128.8, 132.2, 138.7, 168.4, 174.3; EI-MS: m/z (%) = 234 ([M]+, 45),
203 (36), 175 (27), 147 (9), 132 (27), 116 (10), 91 (24), 75 (100), 51 (6);
Anal. calcd for C12H14N2O3 (234.25): C, 61.53; H, 6.02; N, 11.96; found:
C, 61.37; H, 5.95; N, 11.88%.
5-(Diethoxymethyl)-3-(4-fluorophenyl)-1,2,4-oxadiazole
(7f):
5-(Diethoxymethyl)-3-(3-methylphenyl)-1,2,4-oxadiazole
(7l):
Colourless oil; yield: 0.490 g (92%); IR (KBr) (νmax/cm–1): 1606, 1480,
Colourless oil; yield: 0.493 g (94%); IR (KBr) (νmax/cm–1): 1581, 1457,
1
1
1416, 1333, 1284, 1229, 1118, 1062, 913, 847, 755; H NMR (400.1
1333, 1285, 1210, 1118, 1064, 914, 790, 686; H NMR (400.1 MHz,
MHz, CDCl3): δ 1.31 (t, J = 7.2 Hz, 6H, 2 × CH2CH3), 3.78 and 3.81
CDCl3): δ 1.31 (t, J = 7.2 Hz, 6H, 2 × CH2CH3), 2.42 (s, 3H, CH3), 3.78
and 3.81 (2 × dq, 2J = 9.6, 3J = 7.2 Hz, 4H, 2 × OCH2CH3), 5.82 (s, 1H,
CH), 7.32 (d, J = 7.6 Hz, 1H, CH), 7.37 (t, J = 7.6 Hz, 1H, CH), 7.92 (d,
J = 7.6 Hz, 1H, CH), 7.95 (s, 1H, CH); 13C NMR (100.6 MHz, CDCl3):
δ 15.0, 21.3, 62.6, 94.5, 124.7, 126.2, 128.2, 128.7, 132.1, 138.6, 168.4,
174.9; EI-MS: m/z (%) = 262 ([M]+, 35), 218 (74), 189 (55), 161 (28),
133 (100), 118 (54), 103 (88), 91 (68), 86 (20), 75 (80), 65 (29); Anal.
calcd for C14H18N2O3 (262.31): C, 64.11; H, 6.92; N, 10.68; found: C,
64.15; H, 7.04; N, 10.49%.
(2 × dq, 2J = 9.6, 3J = 7.2 Hz, 4H, 2 × OCH2CH3), 5.81 (s, 1H, CH), 7.17
3
3
3
4
(dd, JFH = 8.8, JHH = 8.8 Hz, 2H, 2 × CH), 8.13 (dd, JHH = 8.8, JFH
= 5.6 Hz, 2H, 2 × CH). 13C NMR (100.6 MHz, CDCl3): δ 15.0, 62.6,
2
4
3
94.4, 116.0 (d, JFC = 21.9 Hz), 122.6 (d, JFC = 3.3 Hz), 129.8 (d, JFC
1
= 8.8 Hz), 164.7 (d, JFC = 250.3 Hz), 167.7, 175.1; EI-MS: m/z (%) =
266 ([M]+, 14), 222 (59), 199 (19), 193 (33), 137 (100), 122 (32), 103
(91), 95 (25), 86 (20), 75 (73); Anal. calcd for C13H15FN2O3 (266.27): C,
58.64; H, 5.68; N, 10.52; found: C, 58.62; H, 5.76; N, 10.44%.
3-(4-Chlorophenyl)-5-(dimethoxymethyl)-1,2,4-oxadiazole
(7g):
White solid; yield: 0.483 g (95%); m.p. 78–79 °C; IR (KBr) (νmax/cm–1):
1591, 1565, 1466, 1408, 1337, 1199, 1112, 1069 (C–O), 1010, 986, 899,
867, 834, 744, 701, 663; 1H NMR (400.1 MHz, CDCl3): δ 3.52 (s, 6H,
2 × OCH3), 5.71 (s, 1H, CH), 7.45 (d, J = 8.8 Hz, 2H, 2 × CH), 8.05 (d,
J = 8.8 Hz, 2H, 2 × CH); 13C NMR (100.6 MHz, CDCl3): δ 53.9, 96.0,
124.7, 128.9, 129.2, 137.6, 167.5, 174.6; EI-MS: m/z (%) = 256 ([M]+
37Cl, 7), 254 ([M]+ 35Cl, 20), 223 (24), 195 (11), 152 (16), 137 (9), 102
(9), 75 (100), 50 (5); Anal. calcd for C11H11ClN2O3 (254.67): C, 51.88;
H, 4.35; N, 11.00; found: C, 51.87; H, 4.36; N, 10.98%.
This research was supported by the Research Council of
University of Tehran.
Received 22 January 2016; accepted 11 March 2016
Published online: 27 April 2016
References
1
P.G. Sammes, Comprehensive medicinal chemistry, eds. C. Hansch, P.G.
Sammes and J.B. Taylor, Pergamon, Oxford, 1990, Vol. 2, Chap. 7.1, pp.
255–270.
3-(4-Chlorophenyl)-5-(diethoxymethyl)-1,2,4-oxadiazole
(7h):
Colourless oil; yield: 0.542 g (96%); IR (KBr) (νmax/cm–1): 1596, 1472,
1407, 1331, 1117, 1062 (C–O), 1015, 911, 837, 741, 700; 1H NMR (400.1
MHz, CDCl3): δ 1.31 (t, J = 7.2 Hz, 6H, 2 × CH2CH3), 3.77 and 3.81
2
3
D.A. Erlanson, R.S. McDowell and T. O’Brien, J. Med. Chem., 2004, 47,
3463.
2
3
C.B. Vu, E.G. Corpuz, T.J. Merry, S.G. Pradeepan, C. Bartlett, R.S.
Bohacek, M.C. Botfield, B.A. Lynch, I.A. MacNeil, M.K. Ram, M.R. van
Schravendijk, S. Violette and T.K. Sawyer, J. Med. Chem., 1999, 42, 4088.
J.W. Clithirow, P. Beswick, W.J. Irving, D.I.C. Scopes, J.C. Barnes, J.
Clapham, J.D. Brown, D.J. Evans and A.G. Hayes, Bioorg. Med. Chem.
Lett., 1996, 6, 833.
K. Hemming, Comprehensive heterocyclic chemistry III, eds. A.R.
Katritzky, C.A. Ramsden, E.F.V. Scriven and R.J.K. Taylor, Elsevier
Science, Oxford, 2008, Vol. 5, Chap. 4, pp. 243–309; and references therein.
J.C. Jochims, Comprehensive heterocyclic chemistry II, eds. A.R.
Katritzky, C.W. Rees and E.V.F. Scriven, Pergamon Press, London, 1996,
Vol. 4, Chap. 4, pp. 179–228; and references cited therein.
N.P. Rai, V.K. Narayanaswamy, T. Govender, B.K. Manuprasad, S.
Shashikanth and P.N. Arunachalam, Eur. J. Med. Chem., 2010, 45, 2677.
(2 × dq, J = 10.4, J = 7.2 Hz, 4H, 2 × OCH2CH3), 5.82 (s, 1H, CH),
7.46 (d, J = 8.4 Hz, 2H, 2 × CH), 8.06 (d, J = 8.4 Hz, 2H, 2 × CH);
13C NMR (100.6 MHz, CDCl3): δ 15.0, 62.7, 94.4, 124.9, 128.9, 129.2,
137.5, 167.5, 175.2; EI-MS: m/z (%) = 284 ([M]+ 37Cl, 10), 282 ([M]+
35Cl, 29), 238 (67), 209 (65), 181 (22), 153 (100), 138 (40), 111 (29), 103
(51), 75 (57); Anal. calcd for C13H15ClN2O3 (282.73): C, 55.23; H, 5.35;
N, 9.91; found: C, 55.41; H, 5.39; N, 9.79%.
4
5
6
7
3-(3-Bromophenyl)-5-(dimethoxymethyl)-1,2,4-oxadiazole
(7i):
Pale yellow oil; yield: 0.544 g (91%); IR (KBr) (νmax/cm–1): 1564, 1518,
1452, 1402, 1332, 1195, 1114, 1067, 985, 905, 797, 740, 681; 1H NMR
(400.1 MHz, CDCl3): δ 3.55 (s, 6H, 2 × OCH3), 5.73 (s, 1H, CH),
7.38 (t, J = 8.0 Hz, 1H, CH), 7.66 (ddd, J = 8.0, 1.6, 1.2 Hz, 1H, CH),