The reaction of ethoxymethylenacetylacetanilide (1) with cyanothioacetamide (2a) in the presence of
N-methylmorpholine in absolute ethanol at 25°C gave 3-cyano-6-methyl-5-phenylcarbamoylpyridine-2(1H)-
thione (3) as indicated by the spectral data. The IR spectra of thione 3 has bands for stretching vibrations of a
conjugated nitrile group in the vicinity of 2220 cm-1, imino groups at 3200-3320 cm-1, and carbonyl group in the
1
vicinity of 1640 cm-1. The H NMR spectra show characteristic signals for protons of the methyl group at
2.54 ppm, phenyl group and pyridine C(4)H at 7.34-7.64 and 8.30 ppm, and NH protons of the carbamoyl
fragment and pyridine ring at 10.30 and 14.27 ppm, respectively.
Alkylation of thione 3 by halides 4a-f in DMF in the presence of an equimolar amount of KOH
proceeds regioselectively, leading to the corresponding alkylthiopyridines 5a-f. The use of aroylmethyl halides
(6a) and hetaroylmethyl halides (6b) in the alkylation of thione 3 in the presence of a two-fold excess of KOH
leads to 3-amino-2-aroyl- (7a) and 3-amino-2-hetaroyl-6-methyl-5-phenylcarbamoylthieno[2,3-b]pyridines (7b).
The reaction of 1 with cyanoselenoacetamide 2b in the presence of base in absolute ethanol in an argon
atmosphere did not yield 3-cyano-6-methyl-5-phenylcarbamoylpyridine-2(1H)-selenone (8) as a pure compound,
probably due to the strong tendency of selenone 8 to undergo oxidation [11]. However, 2-alkylselenopyridines
9a-c were obtained upon introducing alkyl halides 4a,d,f into the reaction mixture. The structure of these
products suggests the intermediate formation of selenone 8.
The structures of 3, 5a-f, 7a,b, and 9a-c are in accord with their physico-chemical characteristics
(Table 1).
EXPERIMENTAL
1
The IR spectra were taken on an IKS-29 spectrometer for vaseline mulls. The H NMR spectra were
registered on a Bruker WP-100SY spectrometer at 100 MHz, Bruker AM-300 spectrometer for 5e at 300.13
MHz, and Gemini-200 spectrometer for 5f, 7a,b at 199.975 MHz for solutions in DMSO-d6 with TMS as the
internal standard. The reaction course and purity of the products were monitored by thin-layer chromatography
on Silufol-254 plates with 3:5 acetone–heptane as the eluent and iodine vapor as the developer.
3-Cyano-6-methyl-5-phenylcarbamoylpyridine-2(1H)-thione (3). A mixture of ethoxyethylene 1
(10 g, 42.9 mmol), cyanothioacetamide 2a (4.29 g, 42.9 mmol), and N-methylmorpholine (4.8 ml, 42.9 mmol)
was stirred in absolute ethanol at 25°C for 2 h. The precipitate formed was filtered off and washed with absolute
ethanol and hexane to give thione 3 (Table 1).
2-Alkylthio-3-cyano-6-methyl-5-phenylcarbamoylpyridines (5a-f). A sample of 10% aqueous KOH
(2 ml, 3.7 mmol) was added with stirring to a suspension of thione 3 (1 g, 3.7 mmol) in DMF (10 ml). After
5 min, the corresponding alkyl halide 4a-f (3.7 mmol) was added, and the mixture was stirred for 4 h. The
precipitate formed was filtered off and washed with ethanol and hexane to give 5a-f (Table 1)
3-Amino-2-aroyl- (7a) and 3-amino-2-hetaroyl-6-methyl-5-phenylcarbamoylthieno[2,3-b]pyridines
(7b). A sample of 10% aqueous KOH (2 ml, 3.7 mmol) was added with stirring to a suspension of thione 3 (1 g,
3.7 mmol) in DMF (10 ml). After 5 min, the corresponding aroyl halide (6a) or hetaroyl halide (6b) (3.7 mmol)
was added. After 0.5 h, another 10% aqueous KOH (2 ml) was added and the mixture was stirred for an
additional 4 h. The precipitate formed was filtered off and washed with ethanol and hexane (Table 1).
4-Alkylseleno-3-cyano-6-methyl-5-phenylcarbamoylpyridines (9a-c). A mixture of ethoxyethylene 1
(2 g, 8.57 mmol), cyanoselenacetamide 2b (1.3 g, 8.57 mmol), and N-methylmorpholine (0.96 ml, 8.57 mmol) in
absolute ethanol was stirred for 2 h in an argon atmosphere at 25°C. Then, the corresponding alkyl halide 4a,d,f
(8.57 mmol) was added and the mixture was stirred for 4 h. The precipitate formed was separated and washed
with ethanol and hexane to give 9a-c (Table 1).
This work was carried out with the financial support of the Russian Fund for Basic Research
(Project No. 99-03-32965).
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