BULLETIN OF THE
Article Synthesis of Potential Antiproliferative 3-Allylseleno-6-Alkylsulfonylpyridazines KOREAN CHEMICAL SOCIETY
J = 7.4 Hz, 3H, CH3, propyl). 13C NMR (CDCl3) δ
164.34, 159.48, 132.93, 118.87 (pyridazine), 129.80,
123.05, 28.87 (allyl), 54.06, 16.00, 12.95 (propyl).
J = 16.8 Hz, 1H, =CH2, allyl), 5.13 (d, J = 9.9 Hz, 1H,
=CH2, allyl), 4.10 (d, J = 7.2 Hz, 2H, SeCH2), 3.57 (t,
J = 7.9 Hz, 2H, SO2CH2, pentyl), 1.85–1.77 (m, 2H, CH2,
pentyl), 1.46–1.26 (m, 4H, CH2x2, pentyl), 0.90 (t,
J = 7.1 Hz, 3H, CH3, pentyl). 13C NMR (CDCl3) δ 164.29,
159.45, 132.96, 118.94 (pyridazine), 129.87, 123.12, 28.92
(allyl), 52.41, 30.41, 22.08, 21.75, 13.69 (pentyl). FT-IR
(NaCl) cm−1 3060, 3026 (aromatic), 2924, 2850 (CH2)
1601, 1372 (C–N), 1154 (SO2), 1028 (SO), 699 (C–Se).
HRMS (FAB, M + H) Calcd for 335.0332, found
335.0323.
3-Allylseleno-6-n-hexylsulfonylpyridazine (8f ): Yield:
38%, m.p.: 83–85ꢀC. 1H NMR (CDCl3) δ 7.84 (d,
J = 8.8 Hz, 1H, pyridazine), 7.66 (d, J = 8.8 Hz, 1H, pyri-
dazine), 6.13–6.00 (m, 1H, CH, allyl), 5.34 (d,
J = 16.9 Hz, 1H, =CH2, allyl), 5.12 (d, J = 9.9 Hz, 1H,
=CH2, allyl), 4.08 (d, J = 6.0 Hz, 2H, SeCH2), 3.55 (t,
J = 7.9 Hz, 2H, SO2CH2, hexyl), 1.74–1.85 (m, 2H, CH2,
hexyl), 1.38–1.48 (m, 2H, CH2, hexyl), 1.25–1.30 (m, 4H,
CH2x2, hexyl), 0.87 (t, J = 7.0 Hz, 3H, CH3, hexyl). 13C
NMR (CDCl3) δ 164.29, 159.55, 132.94, 118.83 (pyrida-
zine), 129.77, 123.03, 28.86 (allyl), 52.43, 31.04, 27.93,
22.19, 21.97, 13.78 (hexyl). FT-IR (NaCl) cm−1 3060,
3026 (aromatic), 2924, 2850 (CH2) 1601, 1372 (C–N),
1154 (SO2), 1028 (SO), 701 (C–Se). HRMS (FAB, M + H)
Calcd for 349.0489, found 349.0485.
3-Allylseleno-6-methylsulfonylpyridazine (8a): Yield:
32%, m.p.: 86–88ꢀC. 1H NMR (CDCl3) δ 7.86 (d,
J = 8.8 Hz, 1H, pyridazine), 7.70 (d, J = 8.8 Hz, 1H, pyri-
dazine), 6.16-6.02 (m, 1H, CH, allyl), 5.36 (d, J = 16.9 Hz,
1H, =CH2, allyl), 5.15 (d, J = 9.9 Hz, 1H, =CH2, allyl),
4.10 (d, J = 7.3 Hz, 2H, SeCH2), 3.42 (s, 3H, SO2CH3,
methyl). 13C NMR (CDCl3) δ 164.60, 160.16, 132.93,
118.97 (pyridazine), 129.99, 122.23, 28.92 (allyl), 40.38
(methyl). FT-IR (NaCl) cm−1 3060, 3026 (aromatic), 2924,
2849 (CH2) 1601, 1372 (C–N), 1154 (SO2), 1028 (SO),
700 (C–Se). HRMS (FAB, M + H) Calcd for 278.9706,
found 278.9704.
3-Allylseleno-6-ethylsulfonylpyridazine (8b): Yield:
16%, m.p.: 90–94ꢀC. 1H NMR (CDCl3) δ 7.85 (d,
J = 8.8 Hz, 1H, pyridazine), 7.67 (d, J = 8.8 Hz, 1H, pyri-
dazine), 6.13–5.99 (m, 1H, CH, allyl), 5.33 (d,
J = 16.9 Hz, 1H, =CH2, allyl), 5.12 (d, J = 9.9 Hz, 1H,
=CH2, allyl), 4.08 (d, J = 7.3 Hz, 2H, SeCH2), 3.59 (q,
J = 7.4 Hz, 2H, SO2CH2, ethyl), 1.37 (t, J = 7.4 Hz, 3H,
CH3, ethyl). 13C NMR (CDCl3) δ 164.43, 159.04, 132.95,
118.91 (pyridazine), 129.83, 123.24, 28.90 (allyl), 47.00,
6.89 (ethyl). HRMS (FAB, M + H) Calcd for 292.9863,
found 292.9850.
3-Allylseleno-6-n-propylsulfonylpyridazine (8c): Yield:
1
12%, Oil. H NMR (CDCl3) δ 7.86 (d, J = 8.8 Hz, 1H,
Results and Discussion
pyridazine), 7.69 (d, J = 8.8 Hz, 1H, pyridazine),
6.14–6.00 (m, 1H, CH, allyl), 5.34 (d, J = 16.8 Hz, 1H,
=CH2, allyl), 5.12 (d, J = 9.9 Hz, 1H, =CH2, allyl), 4.08
(d, J = 7.2 Hz, 2H, SeCH2), 3.54 (t, J = 7.9 Hz, 2H,
SO2CH2, propyl), 1.88–1.76 (m, 2H, CH2, propyl), 1.07 (t,
J = 7.4 Hz, 3H, CH3, propyl). 13C NMR (CDCl3) δ
164.34, 159.47, 132.94, 118.91 (pyridazine), 129.83,
123.24, 28.83 (allyl), 54.10, 15.98, 12.92 (propyl). FT-IR
(NaCl) cm−1 3060, 3026 (aromatic), 2923, 2849 (CH2)
1601, 1373 (C–N), 1154 (SO2), 1028 (SO), 697 (C–Se).
HRMS (FAB, M + H) Calcd for 307.0019, found
307.0023.
As shown in Scheme 1, condensation of dichloropyridazine
1 with various thioles, such as ethanethiol, propanethiol,
butanethiol, pentanethiol, and hexanethiol, at room
3-Allylseleno-6-n-butylsulfonylpyridazine (8d): Yield:
1
18%, Oil. H NMR (CDCl3) δ 7.86 (d, J = 8.8 Hz, 1H,
pyridazine), 7.67 (d, J = 8.8 Hz, 1H, pyridazine),
6.13–5.99 (m, 1H, CH, allyl), 5.33 (d, J = 16.8 Hz, 1H,
=CH2, allyl), 5.12 (d, J = 9.9 Hz, 1H, =CH2, allyl), 4.08
(d, J = 7.3 Hz, 2H, SeCH2), 3.55 (t, J = 8.0 Hz, 2H,
SO2CH2, butyl), 1.83–1.73 (m, 2H, CH2, butyl), 1.52–1.40
(m, 2H, CH2, butyl), 0.93 (t, J = 7.4 Hz, 3H, CH3, butyl).
13C NMR (CDCl3) δ 164.36, 159.43, 132.94, 118.85 (pyri-
dazine), 129.84, 123.12, 28.85 (allyl), 52.22, 23.99, 21.56,
13.43 (butyl). HRMS (FAB, M + H) Calcd for 321.0176,
found 321.0178.
3-Allylseleno-6-n-pentylsulfonylpyridazine (8e): Yield:
36%, m.p.: 52–55ꢀC. 1H NMR (CDCl3) δ 7.86 (d,
J = 8.8 Hz, 1H, pyridazine), 7.69 (d, J = 8.8 Hz, 1H, pyri-
dazine), 6.16–5.99 (m, 1H, CH, allyl), 5.36 (d,
Scheme 1. Synthesis of target 3-allylselenyl-6-alkylsulfonyl
(or sulfinyl) pyridazine derivatives (7c, and 8a–8f)
Bull. Korean Chem. Soc. 2017, Vol. 38, 1327–1332
© 2017 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim