2.4. Synthesis of (E)-3-phenyl-5-(2-aryl-vinyl)-1,2,4-oxadiazoles (9–25)

The suitable benzamidoxime (27a–b) (1.14 mmol) and 350 mg (2.53 mmol) of dry potassium carbonate were added to a sealed vessel containing 3.0 mL of anhydrous dichloromethane under a dry N2 atmosphere. Then, the suitable 3-aryl-acryloyl chlorides (29a–l) were diluted in 3.0 mL anhydrous dichloromethane and added dropwise under stirring at room temperature. After complete consumption of the reagents, 1 g silica gel (60–120 mesh) was added, and the solvent was removed under low pressure. The solid-supported reaction was then conducted under microwave irradiation (75 W, 100–105 °C) over 5–45 min (monitored by TLC). The pure products were obtained after column chromatography in silica gel (60–120 mesh) eluted with hexanes/ethyl acetate (9:1).

2.4.1. (E)-3-phenyl-5-[2-phenylvinyl]-1,2,4-oxadiazole 9White solid, weight = 192.5 mg (0.78 mmol, yield 68%); m.p. 85–87 °C; 1H NMR (500 MHz, CDCl3) δ ppm: 7.11 (d, J 16 Hz, 1H), 7.46–7.48 (m, 3H), 7.53–7.56 (m, 3H), 7.64–7.66 (m, 3H), 7.92 (d, J 16 Hz, 1H), 8.15–8.17 (m, 2H); 13C NMR: (125 MHz, CDCl3) δ ppm: 110.25, 126.95, 127.47, 127.96, 128.88, 129.10, 130.56, 131.19, 134.43, 142.74, 168.74, 175.26; IR (cm−1): 960.52, 1359.77, 1440.78, 1539.15, 1577.72, 1641.37, 3028.15, 3062.86; HRMS (ESI+) for C16H13N2O+ [M+H]+, calcd. 249.1022 found 249.1028. Product characterization was consistent with the available data [34]. 2.4.2. (E)-3-phenyl-5-[2-(3-methoxyphenyl)vinyl]-1,2,4-oxadiazole 10

White solid, weight = 237.9 mg (0.86 mmol, yield 75%); m.p. 88–90 °C; 1H NMR (500 MHz, CDCl3) δ ppm: 3.89 (s, 3H), 7.00 (dd, J1 8 Hz, J2 2 Hz, 1H), 7.09 (d, J 15 Hz, 1H), 7.15 (t, J 2 Hz, 1H), 7.24 (dd, J1 8 Hz, J2 2 Hz), 7.38 (t, J 8 Hz, 1H), 7.51–7.55 (m, 3H), 7.89 (d, J 15 Hz, 1H), 8.15 (dd, J1 8 Hz, J2 2 Hz, 2H); 13C NMR: (125 MHz, CDCl3) δ ppm: 55.37, 110.53, 112.83, 116.41, 120.63, 126.92, 127.46, 128.88, 130.10, 131.19, 135.77, 142.65, 160.03, 168.74, 175.19; IR (cm−1): 966.3, 1049.24, 1265.26, 1363.63, 1442.71, 1556.51, 1606.65, 1637.51, 2835.27, 2956.78, 3010.79, 3084.08; HRMS (ESI+) for C17H15N2O2+ [M+H]+, calcd. 279.1128 found 279.1133.

2.4.3. (E)-3-phenyl-5-[2-(4-methoxyphenyl)vinyl]-1,2,4-oxadiazole 11

White solid, weight = 190.4 mg (0.68, yield: 65%); m.p. 132–135 °C; 1H NMR (500 MHz, CDCl3) δ ppm: 3.89 (s, 3H), 6.96 (d, J 15 Hz, 1H), 6.98 (d, J 8 Hz), 7.50–7.53 (m, 3H), 7.59 (d, J 8 Hz, 2H), 7.87 (d, J 15 Hz, 1H), 8.15 (dd, J1 8 Hz, J2 2 Hz, 2H); 13C NMR: (125 MHz, CDCl3) δ ppm: 55.45, 107.76, 114.54, 127.07, 127.20, 127.44, 128.85, 129.64, 131.10, 142.37, 161.60, 168.63, 175.63; IR (cm−1): 966.22, 1026.01, 1245.87, 1361.59, 1441.62, 1537.09, 1599.77, 1639.30, 2840.82, 2972.92, 3005.71, 3069.35; HRMS (ESI+) for C17H15N2O2+ [M+H]+, calcd. 279.1128 found 279.1133.

2.4.4. (E)-3-phenyl-5-[2-(3,4,5-trimethoxyphenyl)vinyl]-1,2,4-oxadiazole 12

Pale brown solid, weight = 270 mg (0.80 mmol, yield 70%); m.p. 132–135 °C; 1H NMR (500 MHz, CDCl3) δ ppm: 3.93 (s, 3H), 3.95 (s, 6H), 6.87 (s, 1H), 7.01 (d, J 16 Hz, 1H), 7.51–7.55 (m, 3H), 7.83 (d, J 16 Hz, 1H), 8.15 (dd, J1 8 Hz, J2 2 Hz, 2H); 13C NMR: (125 MHz, CDCl3) δ ppm: 56.21, 61.06, 105.04, 109.49, 126.93, 127.43, 128.90, 129.93, 131.21, 140.30, 142,64, 153.58, 168.70, 175.22; IR (cm−1): 995.15, 1128.23, 1240.08, 1336.51, 1415.51, 1548.66, 1581.44, 1625.80, 2833.10, 2991.25, 3066.46; ESI-HRMS (m/z): HRMS (ESI+) for C19H19N2O4+ [M+H]+, calcd. 339.1339 found 339.1358.

2.4.5. (E)-3-phenyl-5-[2-(3,4-methylenedioxy-phenyl)vinyl]-1,2,4-oxadiazole 13

White solid, weight = 213.3 mg (0.73 mmol, yield 64%); m.p. 157–159 °C; 1H NMR (500 MHz, CDCl3) δ ppm: 6.06 (s, 2H), 6.89 (d, J 8 Hz, 1H), 6.91 (d, J 15 Hz, 1H), 7.12 (dd, J1 8 Hz, J2 2 Hz, 1H), 7.15 (d, J 2 Hz, 1H), 7.51–7.54 (m, 3H), 7.82 (d, J 15 Hz, 1H), 8.13–8.15 (m, 2H); 13C NMR: (125 MHz, CDCl3) δ ppm: 101.70, 106.22, 108.20, 108.74, 124.53, 127.01, 127.44, 128.85, 128.90, 131.13, 142.37, 148.56, 149.88, 168.66, 175.44; IR (cm−1): 967.19, 1032.76, 1245.87, 1349.05, 1441.62, 1553.48, 1596.87, 1635.45, 2850.46, 2950.74, 3021.14, 3066.46; HRMS (ESI+) for C17H13N2O3+ [M+H]+, calcd. 293.0921 found 293.0926.

2.4.6. (E)-3-phenyl-5-[2-(3,4-ethylenedioxy-phenyl)vinyl]-1,2,4-oxadiazole 14

White solid, weight = 244.4 mg (0.80 mmol, yield): 70%; m.p. 143–145 °C; 1H NMR (500 MHz, CDCl3) δ ppm: 4.32 (m, 4H), 6.92 (d, J 8 Hz, 1H), 6.93 (d, J 15 Hz, 1H), 7.15 (dd, J1 8 Hz, J2 2 Hz, 1H), 7.17 (d, J 2 Hz, 1H), 7.51–7.54 (m, 3H), 7.78 (d, J 15 Hz, 1H), 8.13–8.15 (m, 2H); 13C NMR: (125 MHz, CDCl3) δ ppm: 64.24, 64.60, 108.36, 116.55, 117.90, 121.98, 127.03, 127.44, 128.13, 128.85, 131.11, 142.29, 143.86, 145.92, 168.64, 175.50; IR (cm−1): 980.69, 1057.83, 1244.91, 1284.44, 1360.62, 1443.55, 1538.05, 1604.59, 1644.12, 2876.49, 2978.71, 3040.52, 3058.75; HRMS (ESI+) for C18H15N2O3+ [M+H]+, calcd. 307.1077 found 307.1083.

2.4.7. (E)-3-phenyl-5-[2-pyridyn-3-yl-vinyl]-1,2,4-oxadiazole 15

Pale brown solid, weight = 193.2 (0.78 mmol, yield 68%); m.p. 107–110 °C; 1H NMR (500 MHz, CDCl3) δ ppm: 7.17 (d, J 16 Hz, 1H), 7.42 (dd, J1 8 Hz, J2 4 Hz, 1H), 7.51–7.57 (m, 3H), 7.91 (d, J 16 Hz, 1H), 7.96 (dt, J1 8 Hz, J2 2 Hz, 1H), 8.15 (dd, J1 8 Hz, J2 4 Hz, 2H), 8.67 (dd, J1 8 Hz, J2 2 Hz, 1H), 8.87 (d, J 2 Hz, 1H); 13C NMR: (125 MHz, CDCl3) δ ppm: 112.34, 123.92, 126.73, 127.47, 128.93, 130.24, 131.32, 133.95, 138.95, 149.69, 151.23, 168.86, 174.56; IR (cm−1): 972.01, 1024.08, 1116.65, 1292.16, 1355.80, 1417.51, 1444.52, 1542.87, 1643.16, 3033.67, 3056.82; HRMS (ESI+) for C15H12N3O+ [M+H]+, calcd. 250.0975 found 250.0964.

2.4.8. (E)-3-phenyl-5-[2-fur-2-yl-vinyl]-1,2,4-oxadiazole 16

Pale brown solid, weight = 165.7 (0.70 mmol, yield 61%); m.p. 83–85 °C; 1H NMR (500 MHz, CDCl3) δ ppm: 6.55 (m, 1H), 6.72 (d, J 5 Hz, 1H), 6.97 (d, J 15 Hz, 1H), 7.50–7.57 (m, 4H), 7.78 (d, J 15 Hz, 1H), 8.13–8.15 (dd, J1 8 Hz, J2 2 Hz, 2H); 13C NMR: (125 MHz, CDCl3) δ ppm: 107.85, 112.59, 115.22, 126.98, 127.44, 128.80, 128.85, 131.14, 145.12, 150.81, 168.73, 175.28; IR (cm−1): 958.59, 1261.41, 1290.34, 1359.77, 1442.71, 1527.58, 1583.51, 1641.37, 3066.72, 3124.59; HRMS (ESI+) for C14H11N2O2+ [M+H]+, calcd. 239.0815 found 239.0820.

2.4.9. (E)-3-phenyl-5-[2-thiophen-2-yl-vinyl]-1,2,4-oxadiazole 17

Pale yellow solid, weight = 165.3 mg (0.65 mmol, yield 57%); m.p. 93–95 °C; 1H NMR (500 MHz, CDCl3) δ ppm: 6.89 (d, J 16 Hz, 1H), 7.13 (t, J 5 Hz, 1H), 7.37 (d, J 5 Hz, 1H), 7.47 (d, J 5 Hz, 1H), 7.51–7.56 (m, 3H), 8.01 (d, J 16 Hz, 1H), 8.13–8.15 (m, 2H); 13C NMR: (125 MHz, CDCl3) δ ppm: 108.98, 126.94, 127.44, 128.35, 128.87, 131.08, 131.17, 135.15, 139.72, 168.70, 175.03; IR (cm−1): 956.66, 1359.77, 1444.64, 1502.50, 1552.65, 1635.59, 3059.01, 3097.58; HRMS (ESI+) for C14H11N2OS+ [M+H]+, calcd. 255.0587 found 255.0592.

2.4.10. (E)-3-phenyl-5-[2-(4-fluorophenyl)vinyl]-1,2,4-oxadiazole 18

White solid, weight = 167.0 mg (0.63 mmol, yield 55%); m.p. 105–107 °C; 1H NMR (500 MHz, CDCl3) δ ppm: 7.02 (d, J 16 Hz, 1H), 7.16 (dd, J1 5 Hz, J2 5 Hz, 2H); 7.47–7.57 (m, 3H), 7.63 (dd, J1 8 Hz, J2 5 Hz, 2H); 7.88 (d, J 16 Hz, 1H), 8.15 (dd, J1 8 Hz, J2 2 Hz, 2H); 13C NMR: (125 MHz, CDCl3) δ ppm: 107.75, 116.29 (d, 2JC–F 22 Hz), 126.87, 127.45, 128.89, 129.85 (d, 3JC–F 9 Hz), 130.69 (d, 4JC–F 3 Hz), 131.22, 141.39, 164.03 (d, 1JC–F 250 Hz), 168.72, 175.10; IR (cm−1): 974.02, 1224.76, 1359.77, 1442.71, 1544.93, 1595.08, 1643.30, 3049.36; HRMS (ESI+) for C16H12FN2O+ [M+H]+, calcd. 267.0928 found 267.0934.

2.4.11. (E)-3-phenyl-5-[2-(4-chlorophenyl)vinyl]-1,2,4-oxadiazole 19White solid, weight = 161.2 mg (0.63 mmol, yield 50%); m.p. 151–153 °C; 1H NMR (500 MHz, CDCl3) δ ppm: 7.07 (d, J 16 Hz, 1H), 7.44 (d, J 8 Hz, 2H); 7.52–7.58 (m, 5H), 7.87 (d, J 16 Hz, 1H), 8.14–8.15 (m, 2H); 13C NMR: (125 MHz, CDCl3) δ ppm: 110.78, 126.85, 127.45, 128.90, 129.08, 129.40, 131.24, 132.90, 136.50, 141.25, 168.79, 174.97; IR (cm−1): 815.86, 975.95, 1361.70, 1444.64, 1543.01, 1571.94, 1645.23, 3037.79, 3060.94; HRMS (ESI+) for C16H12ClN2O+ [M+H]+, calcd. 283.0633 found 283.0638. Product characterization was consistent with the available data [34]. 2.4.12. (E)-3-phenyl-5-[2-(4-nitrophenyl)vinyl]-1,2,4-oxadiazole 20

Pale yellow solid, weight = 264.1 mg (0.9 mmol, yield 79%); m.p. 205–208 °C; 1H NMR (500 MHz, CDCl3) δ ppm: 7.24 (d, J 16 Hz, 1H), 7.52–7.58 (m, 3H), 7.80 (d, J 8 Hz, 2H), 7.95 (d, J 16 Hz, 1H), 8.14–8.15 (m, 2H), 8.33 (d, J 8 Hz, 2H); 13C NMR: (125 MHz, CDCl3) δ ppm: 114.34, 124.39, 126.59, 127.47, 128.52, 128.96, 131.42, 139.69, 140.41, 148.59, 168.99, 174.25; IR (cm−1): 975.87, 1361.70, 1512.98, 1445.48, 1548.66, 1595.91, 1645.09, 3034.64, 3108.89; HRMS (ESI+) for C16H12N3O3+ [M+H]+, calcd. 294.0873 found 294.0879.

2.4.13. (E)-3-(3,4,5-trimethoxyphenyl)-5-[2-phenylvinyl]-1,2,4-oxadiazole 21

White solid, weight = 281.3 (0.86 mmol, yield 73%); m.p. 138–140 °C; 1H NMR (400 MHz, CDCl3) δ ppm: 3.95 (s, 3H), 3.99 (s, 6H, 7.10 (d, J 16 Hz, 1H), 7.52–7.58 (m, 3H), 7.80 (d, J 8 Hz, 2H), 7.40 (s, 2H), 7.46–7.48 (m, 3H), 7.63–7.66 (m, 2H), 7.92 (d, J 16 Hz, 1H); 13C NMR: (500 MHz, CDCl3) δ ppm: 56.31, 61.00, 104.52, 110.15, 122.14, 127.95, 129.12, 130.62, 134.39, 140.50, 142.87, 153.57, 168.57, 175.21; IR (cm−1): 995.15, 1129.19, 1229.48, 1363.51, 1413.66, 1557.34, 1595.95, 1636.41, 2832.14, 2962.32, 3037.79, 3060.94; HRMS (ESI+) for C19H19N2O4+ [M+H]+, calcd. 339.1339 found 339.1345.

2.4.14. (E)-3-(3,4,5-trimethoxyphenyl)-5-[2-(3-methoxyphenyl)-vinyl]-1,2,4-oxadiazole 22

White solid, weight = 252.0 mg (0.68 mmol, yield 60%); m.p. 117–119 °C; 1H NMR (500 MHz, CDCl3) δ ppm: 3.88 (s, 3H), 3.94 (s, 3H), 3.99 (s, 6H), 7.00 (dd, J1 5 Hz, J2 2 Hz, 1H), 7.08 (d, J 16 Hz, 1H), 7.15 (sl, 1H), 7.22 (dl, J 5 Hz, 1H), 7.37 (d, J 5 Hz, 1H), 7.40 (s, 2H), 7.88 (d, J 16 Hz, 1H); 13C NMR: (125 MHz, CDCl3) δ ppm: 55.35, 56.30, 60.98, 104.51, 110.42, 112.85, 116.41, 120.62, 122.12, 130.11, 135.72, 140.49, 142.76, 153.56, 160.03, 168.55, 175.12; IR (cm−1): 974.02, 1128.32, 1230.55, 1361.70, 1417.64, 1554.58, 1602.80, 1641.37, 2831.41, 3033.93, 3062.86; HRMS (ESI+) for C20H21N2O5+ [M+H]+, calcd. 369.1445 found 369.1451.

2.4.15. (E)-3-(3,4,5-trimethoxyphenyl)-5-[2-(3,4,5-trimethoxyphenyl)-vinyl]-1,2,4-oxadiazole 23

Off-white solid, weight = 371.2 mg (0.86 mmol, yield 76%); m.p. 118–120 °C; 1H NMR (500 MHz, CDCl3) δ ppm: 3.93–3.94 (m, 12H), 3.98 (s, 6H), 6.86 (s, 2 Hz, 1H), 7.00 (d, J 16 Hz, 1H), 7.39 (s, 2H), 7.83 (d, J 16 Hz, 1H); 13C NMR: (125 MHz, CDCl3) δ ppm: 56.21, 56.30, 61.00, 61.06, 104.50, 105.08, 109.41, 122.12, 129.89, 140.40, 140.51, 142.76, 153.57, 160.03, 168.54, 175.16; IR (cm−1): 962.37, 995.15, 1120.51, 1230.44, 1336.51, 1415.59, 1485.02, 1583.37, 1647.02, 2835.03, 2937.24, 3000.89; HRMS (ESI+) for C22H25N2O7+ [M+H]+, calcd. 429.1656 found 429.1608.

2.4.16. (E)-3-(3,4,5-trimethoxyphenyl)-5-[2-(3,4-methylenedioxy-phenyl)vinyl]-1,2,4-oxadiazole 24

White solid, weight = 261.5 mg (0.68 mmol, yield 60%); m.p. 177–180 °C; 1H NMR (500 MHz, CDCl3) δ ppm: 3.93 (s, 3H), 3.95 (s, 6H), 6.86 (s, 2H), 7.01 (d, J 15 Hz, 1H), 7.51–7.55 (m, 3H), 7.83 (d, J 15 Hz, 1H), 8.14–8.16 (m, 2H); 13C NMR: (125 MHz, CDCl3) δ ppm: 59.30, 60.99, 101.73, 104.50, 106.20, 108.10, 108.75, 122.22, 124.56, 128.87, 142,51, 148.58, 149.52, 153.55, 168.49, 175.40; IR (cm−1): 996.12, 1032.76, 1130.15, 1245.87, 1230.44, 1354.84, 1414.62, 1539.98, 1597.84, 1647.02, 2836.96, 2983.53, 3009.57, 3103.10; HRMS (ESI+) for C20H19N2O6+ [M+H]+, calcd. 383.1238 found 383.1243.

2.4.17. (E)-3-(3,4,5-trimethoxyphenyl)-5-[2-(fur-2-yl)vinyl]-1,2,4-oxadiazole 25

Pale brown solid, weight = 228.3 (0.70 mmol, yield 62%); m.p. 144–146 °C; 1H NMR (500 MHz, CDCl3) δ ppm: 3.93 (s, 3H), 3.97 (s, 6H), 6.53–6.54 (m, 1H), 6.72 (d, J 5 Hz, 1H), 6.95 (d, J 16 Hz, 1H), 7.15 (s, 1H), 7.38 (s, 2H), 7.56 (s, 1H), 7.64 (d, J 16 Hz, 1H, =C–H); 13C NMR: (125 MHz, CDCl3) δ ppm: 56.04, 60.73, 104.25, 107.51, 112.35, 115.02, 121.94, 128.64, 140.20, 144.93, 150.53, 153.29, 168.30, 174.97; IR (cm−1): 972.01, 999.01, 1126.30, 1178.37, 1228.51, 1359.66, 1413.66, 1456.09, 1486.94, 1544.80, 1567.94, 1594.95, 1637.37, 2835.03, 2937.24; 2966.27, 3008.60, 3072.25, 3159.03; HRMS (ESI+) for C17H17N2O5+ [M+H]+, calcd. 329.1132 found 329.1107.