Synthesis and biological evaluation of some novel urea and thiourea derivatives
3H, CH3), 2.42 (s, 3H, CH3), 6.48–7.87 (m, 8H, ArH),
stirred and refluxed for 10 h, acetone was removed under
reduced pressure, and the solid mass dissolved in water and
acidified with 2 N HCl. The crude product was purified by
recrystallization from ethanol as needles.
8.55 (s, 1H, NH), 9.28 (s, 1H, NH).
3-Substituted-2-[p-(3,7-dimethyl-4-oxo-4H-
isoxazolo[4,5-d]pyridazine-5-yl)benzene-
sulfonylimino]-1,3-thiazolines (12a–d)
10a: IR (KBr, mmax, cm-1) 1,658 (CO), 1,666 (CO),
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3,295 (NH); H NMR (DMSO-d6) d: 1.11, 1.49, 3.54
(3 m, 11H, cyclohexyl H), d 2.38 (s, 3H, CH3), 2.86 (s,
3H, CH3), 7.82–8.04 (m, 4H, Ar–H), 8.23 (s, 1H, NH),
8.98 (s, 1H, NH).
A solution of the corresponding thiourea derivative 11
(10 mmol) in absolute ethanol (25 ml) was refluxed with
the a-bromoacetophenone (1.99 g, 10 mmol) and sodium
acetate (20 mmol) for 2 h. The reaction mixture was then
cooled and poured into water; the precipitated thiazoline
was recrystallized from ethanol as needles.
10b: IR (KBr, mmax, cm-1) 1,658 (CO), 1,663 (CO),
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3,295 (NH); H NMR (DMSO-d6) d: 2.28 (s, 3H, CH3),
2.38 (s, 3H, CH3), 7.19–8.15 (m, 5H, C6H5), 8.98 (s, 1H,
NH), 9.62 (s, 1H, NH).
10c: IR (KBr, mmax, cm-1) 1,659 (CO), 1,665 (CO),
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12a: IR (KBr, mmax, cm-1) 1,659 (CO), 3,312 (NH); H
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3,282 (NH); H NMR (DMSO-d6) d: 2.30 (s, 3H, CH3),
2.41 (s, 3H, CH3), 7.47–7.99 (m, 4H, Ar–H), 8.68 (s, 1H,
NMR (DMSO-d6) d: 2.29 (s, 3H, CH3), 2.33 (s, 3H,
CH3), 3.41 (s, 3H, NCH3), 7.40–7.89 (m, 9H, Ar–H).
NH) 0.9.45 (s, 1H, NH).
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12b: IR (KBr, mmax, cm-1) 1,656 (CO), 3,320 (NH); H
NMR (DMSO-d6) d: 2.35 (s, 3H, CH3), 2.36 (s, 3H,
CH3), 6.85–7.99 (m, 14H, C6H5).
p-(3,7-Dimethyl-4-oxo-4H-isoxazolo [4,5-
d]pyridazine-5-yl)benzenesulfonylthioureas (11)
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12c: IR (KBr, mmax, cm-1) 1,661 (CO), 3,324 (NH); H
NMR (DMSO-d6) d: 2.31 (s, 3H, CH3), 2.38 (s, 3H,
CH3), 6.49–7.78 (m, 12H, ArH).
A mixture of pyridazine derivative 7 (3.2 g, 10 mmol) and
anhydrous K2CO3 (3.2 g, 10 mmol) in dry acetone (25 ml)
was stirred and treated with the appropriate isothiocyanate
(12 mmol). After the mixture was stirred and refluxed for
10 h, acetone was removed under reduced pressure, and the
solid mass dissolved in water and acidified with 2 N HCl.
The crude product was purified by recrystallization from
ethanol as needles.
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12d: IR (KBr, mmax, cm-1) 1,659 (CO), 3,318 (NH). H
NMR (DMSO-d6) d: 2.29 (s, 3H, CH3), 2.34 (s, 3H,
CH3), 7.37–8.05 (m, 12H, ArH).
3-Substituted-2-[p-(3,7-dimethyl-4-oxo-4H-
isoxazolo[4,5-d]pyridazine-5-yl)benzene-
sufonylimino]-4-oxothiazolidines (13a–e)
11a: IR (KBr, mmax, cm-1) 1,662 (CO), 1,124 (CS),
3,308 (NH); H NMR (DMSO-d6) d: 2.29 (s, 3H, CH3),
2.38 (s, 3H, CH3), 3.33 (s, 3H, NCH3), 7.84–8.00 (m,
A mixture of 11 (10 mmol), ethyl bromoacetate (1.67 g,
10 mmol) and sodium acetate (20 mmol) in absolute ethanol
(30 ml) was refluxed for 2 h. The reaction mixture was then
filtered while hot, concentrated and allowed to cool. The
product obtained was recrystallized from ethanol as needles.
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4H, Ar–H), 8.54 (s, 1H, NH), 9.22 (s, 1H, NH).
11b: IR (KBr, mmax, cm-1) 1,658 (CO), 1,120 (CS),
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3,322 (NH); H NMR (DMSO-d6) d: 2.42 (s, 3H, CH3),
2.54 (s, 3H, CH3), 6.81–7.89 (m, 9H, C6H5), 8.66 (s, 1H,
13a: IR (KBr, mmax, cm-1) 1,657 (CO), 1,710 (CO),
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3,321 (NH); H NMR (DMSO-d6) d: 2.27 (s, 3H, CH3),
2.31 (s, 3H, CH3), 3.32 (s, 3H, NCH3), 7.43–7.86 (m,
NH), 10.22 (s, 1H, NH).
11c: IR (KBr, mmax, cm-1) 1,660 (CO), 1,132 (CS), 3,328
(NH); lH NMR (DMSO-d6) d: 2.37 (s, 3H, CH3), 2.46 (s,
3H, CH3), 6.76–8.01 (m, 8H, ArH), 8.78 (s, 1H, NH),
9.58 (s, 1H, NH).
4H, Ar–H).
13b: IR (KBr, mmax, cm-1) 1,658 (CO), 1,714 (CO),
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3,326 (NH); H NMR (DMSO-d6) d: 2.29 (s, 3H, CH3),
2.34 (s, 3H, CH3), 6.75–7.94 (m, 9H, C6H5).
11d: IR (KBr, mmax, cm-1) 1,656 (CO), 1,134 (CS),
13c: IR (KBr, mmax, cm-1) 1,663 (CO), 1,708 (CO),
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3,320 (NH). H NMR (DMSO-d6) d: 2.35 (s, 3H, CH3),
2.43 (s, 3H, CH3), 6.76–8.11 (m, 8H, ArH), 8.55 (s, 1H,
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3,328 (NH); H NMR (DMSO-d6) d: 2.32 (s, 3H, CH3),
2.36 (s, 3H, CH3), 6.47–7.87 (m, 8H, ArH).
NH), 9.28 (s, 1H, NH).
13d: IR (KBr, mmax, cm-1) 1,660 (CO), 1,711 (CO),
11e: IR (KBr, mmax, cm-1) 1,660 (CO), 1,128 (CS), 3,325
(NH). lH NMR (DMSO-d6) d: 2.27 (s, 3H, CH3), 2.35 (s,
3H, CH3), 6.68–7.88 (m, 9H, ArH), 8.55 (s, 1H, NH),
9.28 (s, 1H, NH).
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3,328 (NH). H NMR (DMSO-d6) d: 2.31 (s, 3H, CH3),
2.38 (s, 3H, CH3), 7.42–8.09 (m, 8H, ArH).
13e: IR (KBr, mmax, cm-1) 1,664 (CO), 1,675 (CO),
1,711 (CO), 3,323 (NH). lH NMR (DMSO-d6) d: 2.29 (s,
3H, CH3), 2.37 (s, 3H, CH3), 6.65–7.88 (m, 9H, ArH).
11f: IR (KBr, mmax, cm-1) 1,660 (CO), 1,138 (CS), 3,320
(NH). lH NMR (DMSO-d6) d: 2.28 (s, 3H, CH3), 2.34 (s,
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