654
M. A. Al-Omar and A. E.-G.E. Amr
Arch. Pharm. Chem. Life Sci. 2010, 10, 648–656
(KBr, n, cmꢁ1): 3366 (OH), 1700 (C O), 1600 (C N); 1H-NMR
1H-NMR (DMSO-d6, 270 MHz) d (ppm): 6.84 (s, 2H, pyri-H),
–
–
–
–
(DMSO-d6, 270 MHz) d (ppm): 6.82 (s, 2H, Pyri-H), 7.15–798 (m,
OH, exchangeable
11.38 (s, 2H, 2 OH, exchangeable with D2O), 13.05
6H, Ar-H þ benzylic-H), 11.24 (s, 2H,
2
(s, 1H, NH, exchangeable with D2O); 13C-NMR (DMSO-d6,
67.5 MHz) d (ppm): 93.86, 127.76, 132.98, 134.50, 137.56,
147.75, 159.46, 163.89, 196.15; EIMS: m/z (%) 493 (Mþ, 18)
and at 281 (100, base peak). Elemental analysis
for C15H5Cl4N5O4S (493.11): Calcd.: C, 36.54; H, 1.02; Cl,
28.76; N, 14.20; S, 6.50. Found: C, 36.47; H, 1.00; Cl, 28.70;
N, 14.06; S, 6.44.
with D2O); 13C-NMR (DMSO-d6, 67.5 MHz) d (ppm): 86.90,
126.76, 127.98, 128.34, 132,00, 134.55, 142.86, 145.00, 148.01,
148.65, 159.5, 196.15; EIMS: m/z (%) 338 (Mþ, 16), and at 130 (100,
base peak). Elemental analysis for C16H10N4O3S (338.34): Calcd.:
C, 56.80; H, 2.98; N, 16.56; S, 9.48. Found: C, 56.75; H, 2.92; N,
16.50; S, 9.42.
General procedure for the synthesis of sulfonyl compounds
12a and 12b
Method B
A mixture of 6 (0.25 g, 1 mmol) and benzaldehyde (0.106 g,
1 mmol) in 40 mL, a mixture of AcOH/Ac2O (1:3) was refluxed
for 5 h, allowed to cool, then poured onto water the solid formed
was collected by filtration and crystallized to yield compound 7
in 82% yield, as identified by its m.p., mixed m.p. and Rf value on
TLC by comparison with authentic sample from method A.
A mixture of hydrazide 11 (0.2 g, 1 mmol) and the aryl halides,
namely, benzene sulfonyl chloride or p-toluene sulfonyl chloride
(2 mmol) in absolute ethanol (20 mL) was refluxed for 8 h. The
formed precipitate was filtered off, dried and crystallized
from acetic acid/water to give compounds 12a and 12b,
respectively.
5-(2,6-Dihydroxypyridin-4-yl)-1,3,4-oxadiazole-2(3H)-
thione 8
N0-(6-Chloro-4-(2-(phenylsulfonyl)hydrazinecarbonyl)
pyridin-2-yl)benzene-sulfono-hydrazide 12a
To a solution of 1 (0.17g, 1 mmol) in hot alcoholic potassium
hydroxide (0.15 g, 50 mL), carbon disulphide (30 mL) was
added. The reaction mixture was heated in water bath for
6 h, the excess carbon disulphide evaporated under reduced
pressure, cooled and treated with acetic acid (5 mL). The result-
ing solid was collected by filtration, dried and crystallized from
Yield (78%), m.p. 1868C; IR (KBr, n, cmꢁ1): 3412 (OH), 3335–3228
1
–
(NH), 1680 (C O), 1368, 1160 (SO ); H-NMR (DMSO-d , 270 MHz) d
–
2
6
(ppm): 6.94, 7.15 (2s, 2H, pyri-H), 7.35–7.88 (m, 10H, Ar-H), 8.13,
8.25, 9.54, 10.86 (4s, 4H, 4 NH, exchangeable with D2O), 11.42 (s,
2H, 2 OH, exchangeable with D2O); EIMS: m/z (%) 482 (Mþ, 18) and
at 310 (100, base peak). Elemental analysis for C18H16ClN5O5S2
(481.93): Calcd.: C, 44.86; H, 3.35; Cl, 7.36; N, 14.53; S, 13.31.
Found: C, 44.80; H, 3.28; Cl, 7.29; N, 14.48; S, 13.26.
acetic acid to give compound 8. Yield (82%), m.p. 1788C; IR (KBr,
1
n, cmꢁ1): 3415 (OH), 3345 (NH), 1605 (C N), 1165 (C S); H-NMR
–
–
–
–
(DMSO-d6, 270 MHz) d (ppm): 6.84 (s, 2H, pyri-H), 8.56 (s, 1H, NH,
exchangeable with D2O), 11.25 (s, 2H, 2 OH, exchangeable
with D2O); EIMS: m/z (%) 210 (Mþ – 1, 100 and as base peak).
Elemental analysis for C7H5N3O3S (211.20): Calcd.: C, 39.81; H,
2.39; N, 19.90; S, 15.18. Found: C, 39.75; H, 2.34; N, 19.84; S,
15.08.
N0-(6-Chloro-4-(2-tosylhydrazinecarbonyl)pyridin-2-yl)-4-
methylbenzene-sulfono-hydrazide 12b
Yield (72%), m.p. 2328C; IR (KBr, n, cmꢁ1): 3398 (OH), 3342–3232
1
–
(NH), 1685 (C O), 1370, 1166 (SO ); H-NMR (DMSO-d , 270 MHz) d
–
2
6
(ppm): 2.28 (s, 6H, 2 CH3), 6.90, 7.18 (2s, 2H, pyri-H), 7.42–7.86 (m,
8H, Ar-H), 8.10, 8.22, 9.62, 10.82 (4s, 4H, 4 NH, exchangeable
with D2O), 11.38 (s, 2H, 2 OH, exchangeable with D2O); 13C-NMR
(DMSO-d6, 67.5 MHz) d (ppm): 21.05, 104.20, 117.82, 127.85,
128.78, 132.68, 136.98, 145.18, 149.65, 159.32, 164.52; EIMS:
m/z (%) 510 (Mþ, 28) and at 155 (100, base peak). Elemental
analysis for C20H20ClN5O5S2 (509.99): Calcd.: C, 47.10; H, 3.95;
Cl, 6.95; N, 13.73; S, 12.57. Found: C, 47.00; H, 3.90; Cl, 6.90; N,
13.67; S, 12.50.
4-Amino-3-(2,6-dihydroxypyridin-4-yl)-1H-1,2,4-triazole-
5(4H)-thione 9
A mixture of compound 8 (0.2 g, 1 mmol) and hydrazine
hydrate (0.4 g, 8 mmol) in absolute ethanol (30 mL) was heated
under reflux for 6 h. The reaction mixture was evaporated
under reduced pressure to dryness, washed with n-hexane
and solidified with diethyl ether. The obtained solid was filtered
off, dried and crystallized from ethanol to give N-aminotriazole
derivative 9. Yield (68%), m.p. 2428C; IR (KBr, n, cmꢁ1): 3396 (OH),
1
3298–2204 (NH , NH), 1608 (C N), 1158 (C S); H-NMR (DMSO-
–
–
–
–
General procedure for the synthesis of compounds 13–15
A mixture of compound 11 (0.2 g, 1 mmol) and diethylmalonate,
pentane-2,4-dione or ethyl 3-oxobutaneoate (2 mmol) in glacial
acetic acid for 6–8 h. After cooling, the formed precipitate was
filtered off, dried and crystallized from acetic acid to give the
corresponding compounds 13–15, respectively.
2
d6, 270 MHz) d (ppm): 5.05 (s, 2H, NH2 exchangeable with D2O),
6.78 (s, 2H, pyri-H), 11.18 (s, 2H, 2 OH, exchangeable with D2O),
12.98 (s, 1H, NH, exchangeable with D2O); 13C-NMR (DMSO-d6,
67.5 MHz) d (ppm): 94.05, 139.56, 147.25, 159.56, 194.15; EIMS:
m/z (%) 225 (Mþ, 8) and at 115 (100, base peak). Elemental
analysis for C7H7N5O2S (225.23): Calcd.: C, 37.33; H, 3.13; N,
31.09; S, 14.24. Found: C, 37.24; H, 3.04; N, 30.98; S, 14.17.
1-(6-Chloro-4-(3,5-dioxopyrazolidine-1-carbonyl)pyridin-2-
yl)pyrazolidine-3,5-dione 13
Yield (78%), m.p. 2568C; IR (KBr, n, cmꢁ1): 3410 (OH), 3265 (NH),
4,5,6,7-Tetrachloro-2-(3-(2,6-dihydroxypyridin-4-yl)-5-
1686 (C O); 1H-NMR (DMSO-d6, 270 MHz) d (ppm): 3.25 (s, 4H,
thioxo-1H-1,2,4-triazol-4(5H)-yl)isoindoline-1,3-dione 10
Compound 10 was synthesized by using the same procedure
of synthesis of derivative 2 but using compound 9 as
–
–
cyclic CH2), 7.34, 7.87 (2s, 2H, pyri-H), 9.86, 9.92 (2s, 2H, 2 NH,
exchangeable with D2O); 13C-NMR (DMSO-d6, 67.5 MHz) d (ppm):
45.65, 46.48, 112.30, 118.85, 145.75, 149.88, 152.68, 164.84,
167.92, 169.65, 171.85; EIMS: m/z (%) 337 (Mþ, 8) and at 238
a
starting material. Yield (75%), m.p. 2658C; IR (KBr,
n, cmꢁ1): 3415 (OH), 3312 (NH), 1605 (C N), 1160 (C S);
–
–
–
–
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