CYCLOACYLATION OF N-PHENYL-3-OXOBUTANETHIOAMIDE
287
of butanethioamide I in the presence of K2CO3 with
3-aryl-2-propenoylchloride II at the NH group giving
intermediate A, or from preliminary formation of carb-
anion C which should be obviously acylated at the site of
the highest nucleophilicity (C2) transforming into an
intermediate product D whose intramolecular cyclization
affords 4H-thiopyran-4-ones IVaIVc (Scheme 4).
and the precipitated reaction product IIIaIIId was
filtered off, dried in air, and recrystallized from ethanol.
Yields and melting points of compounds IIIaIIId, IVa
IVc, and V are given in Table 1.
5-Acetyl-1,4-diphenyl-6-(methylsulfanyl)-3,4-
dihydro-2H-pyridin-2-one (VI) and 2-aroyl-3-
methyl-4,7-diphenyl-4,5-dihydro-6H-thieno[2,3-b]-
pyridin-6-ones (IXa and IXb). To a solution of 0.323 g
(1 mmol) of 1,4-diphenyl-6-thioxopiperidin-2-one IIIa and
0.056 g (1 mmol) of KOH in 4 ml of ethanol was added
at 20°C a solution of 1.5 mmol of methyl iodide (1 mmol
of 1-bromomethyl 1-phenyl ketone), The mixture was kept
30 min at 40°C, 10 min at 78°C, cooled, diluted with cold
water (10 ml), the precipitated reaction product VI or
IXa and IXb was filtered off, dried in air, and recrystallized
from ethanol (compound VI) or from acetic acid
(compounds IXa and IXb).
In all likelihood in the intermediate A containing an
electron-withdrawing group (Ar = m-NO2C6H4) the
electron density on the carbon atom C3 of the 3-aryl-2-
propenoyl substituent is reduced to such extent that the
attack of the C3 atom with a thioxo group becomes
possible, and it results in the intramolecular cyclization of
intermediate A into 1,3-thiazin-4-one V. When the
electrophilicity of the C3 carbon in intermediate A is
insufficient for the reaction with the thioxo group (Ar =
C6H5, p-CH3OC6H4, 2-thienyl) intermediate A transforms
into carbanion B which then converts into 6-thioxo-
piperidin-2-ones IIIaIIId.
Azo coupling of 6-thioxopiperidin-2-one IIIa with
p-chlorobenzenediazonium chloride. To a solution of
0.18 g (0.557 mmol) 6-thioxopiperidin-2-one IIIa in ml
of ethanol was added 0.7 ml of water and 0.36 g of finely
powdered anhydrous sodium acetate.At cooling with ice
and water was added within 45 min while vigorous
stirring a water solution of p-chlorobenzenediazonium
chloride prepared from 0.52 g of p-chloroaniline, 0.28 g
of sodium nitrite, 1.8 ml of concn..HCl, and 2.7 ml of
water. The reaction mixture was stirred for 1 h, then
a yellow precipitate was filtered off, washed with cold
water (3´5 ml), dried in air, and recrystallized from
2-propanol. The sample of reaction product VII thus
obtained mixed with compound of analogous structure
that we had prepared formerly [1] by azo coupling of
3-oxo-N-phenylbutanethioamide with p-chlorobenzene-
diazonium chloride melted without melting point de-
pression. The filtrate was acidified with 3 ml of concn.
HCl, kept for 5 h at 10°C, and the precipitated cinnamic
acid VIII was filtered off, dried, and recrystallized from
2-propanol.
EXPERIMENTAL
NMR spectra from solutions of compounds in CDCl3
were registerd on a spectrometer Varian-300 at operating
frequencies 300 (1H) and 75 MHz (13C), internal
reference TMS. IR spectra were recorded on a spectro-
photometer UR-20 from samples pelletized with KBr.
The purity and homogeneity of compounds was checked
by TLC on Silufol UV-254 plates, eluent petroleum ether
(bp 4080°C)chloroformacetone, 5:3:2.
4-Aryl-5-acetyl-1-phenyl-6-thioxopiperidin-2-
ones IIIaIIId, 2-aryl-5-acetyl-6-phenyl-amino-2,3-
dihydro-4H-thiopyran-4-ones IVaIVc, and 2-aceto-
nylidene-6-(m-nitro-phenyl)-3-phenyl-5,6-dihydro-
4H-1,3-thiazin-4-one (V). To a solution of 5.79 g
(0.03 mol) of 3-oxobutanoic acid N-phenylthioamide (I)
in 15 ml of anhydrous acetone containing 7.59 g
(0.055 mol) of dispersed dry K2CO3 was added while
vigorous stirring at 20°C a solution of 0.03 mol of 3-aryl-
2-propenoylchloride IIaIId in 10 ml of acetone. The
stirring was continued for 2 h at 20°C, 0.5 h at 50°C, and
0.5 h at 56°C. On cooling the reaction mixture was filtered
to separate potassium hydrogen carbonate and chloride.
The filtrate was evaporated, the crystalline precipitate
was ground with 10 ml of 10% aqueous NaOH. 4H-
Thiopyran-4-one IVaIVc [1,3-thiazin-4-one (V)]
insoluble in the alkaline solution was filtered off, dried in
air, and recrystallized from a mixture ethanolwater, 2:1.
The alkaline filtrate containing 6-thioxopiperidin-2-one
IIIaIIId was acidified with 20% water solution of HCl,
3-Methyl-4,7-diphenyl-4,5-dihydro-1H,6H-
pyrazolo[3,4-b]pyridin-6-one (X). To a dispersion of
0.323 g (1 mmol) of 6-thioxopiperidin-2-one IIIa in 2 ml
of glacial acetic acid was added 0.08 ml of hydrazine
hydrate, the mixture was stirred for 24 h at 20°C and 8 h
at 50°C till the precipitate of the initial compound
completely disappeared and hydrogen sulfide evolution
ceased. The solution obtained was neutralized by adding
3 g of potassium hydrogen carbonate, the separated
precipitate was filtered off, dried, and recrystallized from
a mixture hexane2-propanol, 3:2.
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 2 2005