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X.-M. Zhang et al. / Bioorg. Med. Chem. 19 (2011) 6518–6524
372.06 (C17H14N3O5S, [M+H]+). Anal. Calcd for C17H13N3O5S: C,
54.98; H, 3.53; N, 11.31. Found: C, 54.67; H, 3.32; N, 11.54.
4.2.11. 2-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-5-(2-
methylbenzylthio)-1,3,4-oxadiazole (6k)
White powder, yield: 60.36%, mp: 117–118 °C. 1H NMR
(500 MHz, CDCl3) d: 2.60 (s, 3H), 4.29–4.32 (m, 4H), 4.47 (s, 2H),
6.94 (d, J = 8.3 Hz, 1H), 7.12 (t, J = 8.6 Hz, 2H), 7.33–7.35 (m, 1H),
7.48 (d, J = 8.2 Hz, 2H), 7.70–7.73 (d, J = 3.7 Hz, 1H). MS (ESI):
341.09 (C18H17N2O3S, [M+H]+). Anal. Calcd for C18H16N2O3S: C,
63.51; H, 4.74; N, 8.23. Found: C, 63.40; H, 4.55; N, 8.35.
4.2.4. 2-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-5-(2-
fluorobenzylthio)-1,3,4-oxadiazole (6d)
Light yellow crystal, Yield: 79.5%. mp: 108 °C. 1H NMR
(500 MHz,CDCl3) d: 4.28–4.31 (m, 4H), 4.52 (s, 2H), 6.94 (d,
J = 8.2 Hz, 1H), 7.04–7.11 (m, 2H), 7.28 (d, J = 7.8 Hz, 1H), 7.46–
7.49 (m, 2H), 7.52 (q, J = 6.3 Hz, 1H). MS (ESI): 345.06
(C17H14FN2O3S, [M+H]+). Anal. Calcd for C17H13FN2O3S: C, 59.38;
H, 3.83; N, 8.21. Found: C, 59.20; H, 3.62; N, 8.38.
4.2.12. 2-(2-Bromobenzylthio)-5-(2,3-
dihydrobenzo[b][1,4]dioxin-6-yl)-1,3,4-oxadiazole (6l)
White powder, yield: 63.4%, mp: 128–129 °C. 1H NMR
(500 MHz, CDCl3) d: 4.28–4.31 (m, 4H), 4.52 (s, 2H), 6.94 (d,
J = 8.2 Hz, 1H), 7.08–7.12 (m, 1H), 7.24 (d, J = 7.8 Hz, 1H), 7.46–
7.49 (m, 2H), 7.52–7.56 (m, 2H). MS (ESI): 404.98 (C17H14BrN2O3S,
[M+H]+). Anal. Calcd for C17H13BrN2O3S: C, 50.38; H, 3.23; N, 6.91.
Found: C, 50.20; H, 3.41; N, 6.68.
4.2.5. 2-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-5-(2-
nitrobenzylthio)-1,3,4-oxadiazole (6e)
White solid, yield: 70.2%, mp: 109 °C. 1H NMR (500 MHz, CDCl3)
d: 4.28–4.31 (m, 4H), 4.83 (s, 2H), 6.93 (d, J = 8.4 Hz, 1H), 7.44–7.49
(m, 3H), 7.58–7.60 (m, 1H), 7.85 (d, J = 10.2 Hz, 1H), 8.13 (d,
J = 8.3 Hz, 1H). MS (ESI): 372.06 (C17H14N3O5S, [M+H]+). Anal. Calcd
for C17H13N3O5S: C, 54.98; H, 3.53; N, 11.31. Found: C, 54.66; H,
3.52; N, 11.49.
4.2.13. 2-(3-Bromobenzylthio)-5-(2,3-
dihydrobenzo[b][1,4]dioxin-6-yl)-1,3,4-oxadiazole (6m)
White powder, yield: 62.1%, mp: 112–113 °C. 1H NMR
(500 MHz, CDCl3) d: 4.28–4.31 (m, 4H), 4.52 (s, 2H), 6.94 (d,
J = 8.2 Hz, 1H), 7.40–7.47 (m, 1H), 7.51–7.53 (m, 3H), 7.54–7.57
(m, 2H). MS (ESI): 404.98 (C17H14BrN2O3S, [M+H]+). Anal. Calcd
for C17H13BrN2O3S: C, 50.38; H, 3.23; N, 6.91. Found: C, 50.24; H,
3.57; N, 6.72.
4.2.6. 2-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-5-(4-
methylbenzylthio)-1,3,4-oxadiazole (6f)
White crystal, yield: 76%, mp: 133–135 °C. 1H NMR(500 MHz,
CDCl3) d: 3.4 (m, 3H), 4.29–4.32 (m, 4H), 4.47 (s, 2H), 6.94 (d,
J = 8.3 Hz, 1H), 7.02 (t, J = 8.6 Hz, 2H), 7.33 (d, J = 7.9 Hz, 2H), 7.48
(d, J = 9.2 Hz, 2H). MS (ESI): 341.09 (C18H17N2O3S, [M+H]+). Anal.
Calcd for C18H16N2O3S: C, 63.51; H, 4.74; N, 8.23. Found: C,
63.30; H, 4.52; N, 8.41.
4.2.14. 2-(4-Bromobenzylthio)-5-(2,3-
dihydrobenzo[b][1,4]dioxin-6-yl)-1,3,4-oxadiazole (6n)
Yellow crystal, yield: 65.9%, mp: 143 °C. 1H NMR (500 MHz,
CDCl3) d: 4.28–4.31 (m, 4H), 4.53 (s, 2H), 6.95 (d, J = 8.3 Hz, 1H),
7.20–7.25 (m, 1H), 7.35–7.43 (m, 2H), 7.53–7.54 (m, 1H), 7.68–
7.71 (d, J = 9.1 Hz; 1H), 7.75 (s, 1H). MS (ESI): 404.98
(C17H14BrN2O3S, [M+H]+). Anal. Calcd for C17H13BrN2O3S: C, 50.38;
H, 3.23; N, 6.91. Found: C, 50.24; H, 3.47; N, 6.74.
4.2.7. 2-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-5-(4-
fluorobenzylthio)-1,3,4-oxadiazole (6g)
White crystal, yield: 63.4%, mp: 118 °C. 1H NMR (500 MHz,
CDCl3) d: 4.29–4.31 (m, 4H), 4.47 (s, 2H), 6.94 (d, J = 8.3 Hz, 1H),
7.28 (d, J = 7.8 Hz, 1H), 7.41–7.44 (m, 2H), 7.46–7.49 (m, 2H),
7.50 (m, 1H). MS (ESI): 345.06 (C17H14FN2O3S, [M+H]+). Anal. Calcd
for C17H13FN2O3S: C, 59.29; H, 3.81; N, 8.13. Found: C, 59.36; H,
3.57; N, 8.31.
4.2.15. 2-(2-Chlorobenzylthio)-5-(2,3-
dihydrobenzo[b][1,4]dioxin-6-yl)-1,3,4-oxadiazole (6o)
White powder, yield: 60.1%, mp: 108 °C. 1H NMR (500 MHz,
CDCl3) d: 4.28–4.32 (m, 4H), 4.45 (s, 2H), 6.94 (d, J = 8.4 Hz, 1H),
7.08–7.12 (d, J = 8.3 Hz, 2H), 7.32 (m, 1H), 7.46–7.49 (m, 2H). MS
(ESI): 361.03 (C17H14ClN2O3S, [M+H]+). Anal. Calcd for
4.2.8. 2-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-5-(3-
nitrobenzylthio)-1,3,4-oxadiazole (6h)
White solid, yield: 54.7%, mp: 107–108 °C. 1H NMR (500 MHz,
CDCl3) d: 4.28–4.33 (m, 4H), 4.56 (s, 2H), 6.93–6.96 (m, 1H),
7.45–7.49 (m, 2H), 7.53 (d, J = 13.4 Hz, 1H), 7.86 (d, J = 12.8 Hz,
2H), 8.16 (d, J = 13.7 Hz, 1H), 8.34 (d, J = 13.6 Hz, 1H). MS (ESI):
372.06 (C17H14N3O5S, [M+H]+). Anal. Calcd for C17H13N3O5S: C,
54.98; H, 3.53; N, 11.31. Found: C, 54.66; H, 3.41; N, 11.62.
C17H13ClN2O3S: C, 56.59; H, 3.63; N, 7.76. Found: C, 56.69; H,
3.42; N, 7.58.
4.2.16. 2-(3-Chlorobenzylthio)-5-(2,3-
dihydrobenzo[b][1,4]dioxin-6-yl)-1,3,4-oxadiazole (6p)
Light yellow crystals, yield: 55.9%, mp: 122–123 °C. 1H NMR
(500 MHz, CDCl3) d: 4.28–4.32 (m, 4H), 4.50 (s, 2H), 6.93 (d,
J = 8.4 Hz, 1H), 7.23–7.25 (m, 2H), 7.32 (m, 1H), 7.46–7.49 (m, 2H).
MS (ESI): 361.03 (C17H14ClN2O3S, [M+H]+). Anal. Calcd for
4.2.9. 2-(4-Chlorobenzylthio)-5-(2,3-
dihydrobenzo[b][1,4]dioxin-6-yl)-1,3,4-oxadiazole (6i)
White powder, yield: 50.7%, mp: 124 °C. 1H NMR (500 MHz,
CDCl3) d: 4.28–4.32 (m, 4H), 4.45 (s, 2H), 6.94 (d, J = 8.4 Hz, 1H),
7.30 (d, J = 8.4 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H), 7.46–7.49 (m, 2H).
MS (ESI): 361.03 (C17H14ClN2O3S, [M+H]+). Anal. Calcd for C17H13
ClN2O3S: C, 56.59; H, 3.63; N, 7.76. Found: C, 56.37; H, 3.52; N, 7.98.
C17H13ClN2O3S: C, 56.59; H, 3.63; N, 7.76. Found: C, 56.38; H, 3.92;
N, 7.68.
4.2.17. 2-(2,6-Difluorobenzylthio)-5-(2,3-
4.2.10. 2-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-5-(4-
iodobenzylthio)-1,3,4-oxadiazole (6j)
dihydrobenzo[b][1,4]dioxin-6-yl)-1,3,4-oxadiazole (6q)
Yellow crystal, yield: 54.8%, mp: 121 °C. 1H NMR (500 MHz,
CDCl3) d: 4.28–4.31 (m, 4H), 4.52 (s, 2H), 6.95 (d, J = 8.3 Hz, 1H),
7.30–7.25 (m, 2H), 7.35–7.43 (m, 1H), 7.53–7.54 (m, 1H), 7.68–
7.71 (d, J = 9.2 Hz, 1H). MS (ESI): 363.05 (C17H13F2N2O3S, [M+H]+).
Anal. Calcd for C17H12F2N2O3S: C, 56.35; H, 3.34; N, 7.73. Found:
C, 56.23; H, 3.12; N, 7.93.
Light yellow solid, yield: 88.3%, mp: 124 °C. 1H NMR (500 MHz,
CDCl3) d: 4.28–4.31 (m, 4H), 4.43 (s, 2H), 6.94 (d, J = 8.6 Hz, 1H),
6.97–7.02 (d, J = 8.1 Hz, 2H), 7.40–7.47 (m, 2H), 7.50–7.56 (m,
2H). MS (ESI): 452.97 (C17H14IN2O3S, [M+H]+). Anal. Calcd for
C17H13IN2O3S: C, 45.15; H, 2.90; N, 6.19. Found: C, 45.04; H, 2.57;
N, 6.48.