272
BARANOVSKII et al.
5-benzyl-5-methylthiazol-4(5H)-ones XVII–XXIV
(Scheme 2).
(400 MHz) using tetramethylsilane as internal
reference. The purity of the products was checked by
TLC on Silufol UV-254 plates using methanol–acetone
(5:2) as eluent.
The yields of N-(5-benzil-5-methyl-4-oxo-4,5-dihyd-
rothiazol-2-yl)acetamides IX–XVI were 65–80%, and
their transformation into aminothiazoles XVII–XXIV
was quantitative. The yields, melting points, elemental
2-Methyl-3-phenyl-2-thiocyanatopropanamide (І).
Benzenediazonium tetrafluoroborate, 20 g, was added
in portions over a period of 1 h to a mixture of 6.8 g of
methacrylamide, 2.8 g of copper(ІІ) tetrafluoroborate
hexahydrate, and 11.7 g of potassium thiocyanate in
250 ml of a 1:4 water–DMSO mixture under stirring at
–20°C. When nitrogen no longer evolved (1.5 h), the
mixture was diluted with 150 ml of water and
extracted with diethyl ether (200 ml). The extract was
washed with water, dried over anhydrous calcium
chloride, and evaporated, and the solid residue was
recrystallized from methanol. Yield 14.9 g (85%). The
reaction in aqueous acetone (1:2.5) was performed in a
similar way. Following an analogous procedure, we
obtained compounds II–VIIІ.
1
analyses, and H NMR spectra of compounds IX–
XXIV are collected in Tables 1 and 2.
In the IR spectra of IX–XVI we observed absorp-
tion bands due to stretching vibrations of two car-
bonyl groups (1690–1740 cm–1); unlike initial 3-aryl-
2-methyl-2-thiocyanatopropanamides I–VIII, no band
typical of thiocyanato group (2152–2164 cm–1) was
1
present. The H NMR spectra of IX–XVI contained
signals from aromatic protons in the region δ 7.48–
6.81 ppm (as multiplets for unsymmetrical substitution
in the benzene ring or as singlets or doublets for para-
substitution). Protons in the methyl and NH groups of
the acetamide fragment resonated as singlets at δ 2.12–
2.10 and 12.62–12.37 ppm, respectively. The 5-methyl
group gave a singlet at δ 1.575–1.46 ppm, and signals
from methylene protons in the benzyl fragments
appeared as singlets or doublets in the region δ 3.36–
2.88 ppm.
N-(5-Benzyl-5-methyl-4-oxo-4,5-dihydrothiazol-
2-yl)acetamide (IX). A solution of 2 g of compound І
in 15 ml of acetic anhydride was heated for 6 h under
reflux. The mixture was concentrated under reduced
pressure to a volume of 5 ml and cooled to –20°S, and
the colorless crystals were filtered off and purified by
recrystallization from methanol. Yield 1.9 g (80%).
Thus 3-aryl-2-methyl-2-thiocyanatopropanamides I–
VIII are convenient starting compounds for the
synthesis of difficultly accessible 5-benzylthiazol-4
(5H)-ones which attract interest as potential
biologically active substances [9, 10].
Compounds X–XVI were synthesized in a similar
way.
2-Amino-5-benzyl-5-methylthiazol-4(5H)-one
(XVII). Compound IX, 1.5 g, was dissolved in 8 ml of
ethanol, a solution of 0.9 g of potassium hydroxide in
1.5 ml of water was added, and the mixture was heated
for 4 h under reflux. The mixture was cooled and
extracted with 15 ml of diethyl ether. The extract was
washed with water, dried over anhydrous calcium
EXPERIMENTAL
The IR spectra were recorded on IKS-29 and
Specord M80 spectrometers from samples dispersed in
mineral oil. The 1H NMR spectra were measured from
solutions in DMSO-d6 on a Varian Mercury instrument
Scheme 2.
O
C
CH3
O
CH3
S
O
CH3
S
OH−
Ac2O
NH2
N
N
N
Δ
S
−Ac, Δ
R
R
R
NH
NH2
O
CH3
I−VIII
IX−XVI
XVII−XXIV
IX, XVII, R = H; X, XVIII, R = 2-Me; XI, XIX, R = 3-Me; XII, XX, R = 4-Me; XIII, XXI, R = 2-MeO; XIV, XXII, R = 4-
MrO; XV, XXIII, R = 4-Br; XVI, XXIV, R = 2,5-Cl2.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 2 2009