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Molecules 2011, 16
and then diluted with cold water (30 mL). The resultant crude product thus precipitated was collected
by filtration, washed with water, dried and crystallized from dioxane to afford 9.
Method B: The same reactants of method A were heated in microwave at 500 w and 140 °C for
15 min. The reaction mixture was treated in a similar manner to method A to obtain compound 9.
Compound 9 was obtained as white crystals in 57% yield (Method A) and 79% yield (Method B), m.p.
1
150–151 °C. H-NMR: 2.30 (s, 3H, CH3), 6.25 (s, 1H, pyridine-H), 7.30–8.20 (m, 16H, Ar-H);
13C-NMR: 19.8 (CH3), 106.3, 118.3, 119.4, 126.7, 127.1, 128.8, 130.3, 133.8, 134.9, 137.1, 145.0,
155.7, 158.3, 160.0 (sp2 C), 163.4 (CO), 166.0 (CO). IRν: 3144 (CH), 2950 (CH), 1739 (CO). MS: M+
m/z: 492 (2%). Anal. Calcd for C29H20N2O4S (492.55): C (70.72%), H (4.09%), N (5.69%), S (6.51%).
Found: C (70.80%), H (4.30%), N (5.80%), S (6.70%)
3.7. 2-[(1,2-Disubstituted)oxoethylthio]-6-hydroxy-4-methylpyridine-3-carboxamides 10a-c
Method A: 1.84 g (0.01 mol) of 2 was dissolved in a warm ethanolic potassium hydroxide solution
[prepared by dissolving 0.56 g (0.01 mol) of potassium hydroxide in 50 mL of ethanol]. Then the
proper α-haloketone (0.01 mol) was added. The mixture refluxed for 10 minutes; the mixture then
stirred at room temperature overnight, then cooled and poured into water. The formed solid product
was filtered off and crystallized from ethanol.
Method B: The same reactants of method A were heated in microwave at 500 w and 90 °C for
5 min. The reaction mixture was treated in a similar manner to method A to obtain compounds 10a-c.
2-[6-Hydroxy-4-methyl-2-((2-oxopropyl)thio)]pyridine-3-carboxamide (10a). Obtained as white
1
crystals in 25% yield (Method A) and 55% (Method B); m.p. 241–242 °C. H-NMR: 2.00 (s, 3H,
CH3), 2.50 (s, 3H, CH3), 4.30 (s, 2H, CH2), 6.15 (pyridine-H), 7.65 (s, 2H, NH2, D2O exchangeable),
13
11.75 (s, 1H, OH, D2O exchangeable); C-NMR: 19.3 (CH3), 28.1 (CH3), 48.3 (CH2), 112.1, 116.2,
146.7, 155.2, 156.0 (sp2 C), 168.4 (CO), 179.3 (CO); IRν: 3295–3446 (broad, NH, OH), 1732, 1678
(2 CO); MS: M+ m/z: 240 (37%). Anal. Calcd for C10H12N2O3S (240.28): C (49.99%), H (5.03%),
N (11.66%), S (13.34%). Found: C (50.10%), H (4.90%), N (11.30%), S (13.60%).
2-(2,4-Dioxopentan-3-ylthio)-6-hydroxy-4-methylpyridine-3-carboxamide (10b). Obtained as white
crystals in 31% yield (Method A) and 45% yield (Method B); m.p. 311–312 °C. 1H-NMR: 2.20 (s, 3H,
CH3), 2.65 (s, 6H, 2CH3), 4.80 (s, 1H, CH), 6.20 (s, 1H, pyridine-H), 7.60 (s, 2H, NH2, D2O
13
exchangeable), 12.00 (s, 1H, OH, D2O exchangeable); C-NMR: 19.1 (CH3), 28.5 (CH3), 78.5 (CH),
111.4, 116.8, 146.1, 155.5, 156.4 (sp2 C), 168.0 (CO), 185.3 (CO); IRν: 3288–3433 (broad, NH, OH),
1705, 1678 (2 CO). MS: M+ m/z: 282 (12%). Anal. Calcd for C12H14N2O4S (282.32): C (51.05%),
H (5.00%), N (9.92%), S (11.36%). Found: C (51.20%), H (4.90%), N (10.00%), S (11.00%).
2-[6-Hydroxy-4-methyl-2-((2-oxo-2-phenylethyl)thio)]pyridine-3-carboxamide (10c). Obtained as
white crystals in 41% yield (Method A) and 63% yield (Method B); m.p. 276–277 °C. 1H-NMR: 2.10
(s, 3H, CH3), 4.95 (s, 2H, CH2), 6.25 (s, 1H, pyridine-H), 7.30 (s, 2H, NH2, D2O exchangeable),
13
7.56–7.94 (m, 5H, Ar-H), 11.95 (s, 1H, OH, D2O exchangeable); C-NMR: 20.1 (CH3), 38.5 (CH2),
112.5, 116.1, 128.5, 128.9, 134.2, 136.0, 146.4, 155.2, 156.8 (sp2 C), 168.3 (CO), 189.0 (CO); IRν:
3471(NH, OH), 1712, 1666 (2 CO). MS: M+ m/z: 302 (21.6%). Anal. Calcd for C15H14N2O3S