Modification of 2-amino-4-phenylthiazole under microwave irradiation

Full text of DOI:10.1134/S1070363209030311

ISSN 1070-3632, Russian Journal of General Chemistry, 2009, Vol. 79, No. 3, pp. 515–516. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © D.P. Khrustalev, 2009, published in Zhurnal Obshchei Khimii, 2009, Vol. 79, No. 3, pp. 525–526.
LETTERS
TO THE EDITOR
Modification of 2-Amino-4-phenylthiazole
under Microwave Irradiation
D. P. Khrustalev
Institute of Organic Synthesis and Coal Chemistry of Kazakhstan,
ul. Alikhanova 1, Karaganda, 100000 Kazakhstan
e-mail: khrustalev@bk.ru
Received July 18, 2008
DOI: 10.1134/S1070363209030311
The high scientific interest attracted by the
derivatives of 2-amino-4-phenylthiazole is due to the
broad spectrum of biological activity exhibited by
these compounds. For instance, in this series substances
were found possessing antipyretic, antioxidative,
analgesic, and some other types of biological activity
[1–3]. The main disadvantage in the synthesis of 2-
amino-4-phenylthiazole derivatives is the long reaction
time [3]. We have studied the possibility of synthesis
of 5-amino-containing 2-amino-4-phenyl-thiazole
under the conditions of microwave irradiation.
Ph
Ph
N
N
Br2, dioxane
NH2
NH2
Br
S
I
S
II
Product II was a tar-like brown mass. It was used in
further transformations without the additional
purification.
2-Amino-5-morpholyl-4-phenylthiazole III and
1,2-N,N-bis(2-amino-4-phenylthiazolyl)hydrazine IV
were prepared by treating compound II with an excess
of morpholine or hydrazine under the conditions of
microwave irradiation.
The starting substance, 2-amino-5-bromo-4-phenyl-
thiazole, was obtained by bromination of 2-amino-4-
phenylthiazole I with the molecular bromine in
dioxane.
Ph
Ph
Ph
Ph
N
N
N
N
microwave
microwave
H
C NH
N
C
NH2
N
NH2
Br
S
S
S
S
O
H2N
NH2
III
II
IV
The only product of the reaction of 2-amino-5-
10 ml of dioxane. The solution obtained was treated
with a solution of 0.29 ml of bromine in 5 ml of
dioxane in the course of 30 min. After the addition was
complete the reaction mixture was stirred for 30 min,
and dioxane was removed in a vacuum of a water-jet
pump. The compound obtained was used without the
additional purification.
bromo-4-phenylthiazole with hydrazine hydrate under
the conditions of the microwave irradiation is the
product of symmetric alkylation of hydrazine, 1,2-bis
(2-amino-4-phenylthiazolyl)hydrazine.
2-Amino-4-phenylthiazole was synthesized under
the conditions of the microwave irradiation according
to the procedure [4].
Synthesis of 2-amino-5-N-morpholyl-4- phenyl-
thiazole (III). 2-Amino-5-bromo-4-phenylthiazole
(II), 1.50 g, was treated with 10 ml of morpholine, and
Synthesis of 2-amino-5-bromo-4-phenylthiazole
(II). 2-Amino-4-phenylthiazole, 1 g, was dissolved in
515

516
KHRUSTALEV
the resulting mixture was exposed to the microwave
irradiation (70 W, 10 min). Morpholine was distilled
off in a vacuum, and the residue was treated with
chloroform. The solution obtained was washed with
the saturated solution of sodium hydrogen carbonate,
with the saturated solution of sodium chloride, and
dried over sodium sulfate. The solvent was removed in
a vacuum of a water-jet pump, and the residue was
purified by column chromatography on silica gel,
elution with 2:1 hexane–ethyl acetate. mp 205°C with
decomposition, yield 37%. IR spectrum (KBr), ν, cm–1:
3383, 3279, 3241, 2964, 2909, 2857, 2819, 1626,
(33), 60(40), 77(55), 89(100), 104(50), 121(45), 133
(40), 165(50), 176(47), [M]+ 382(15). Found, %: C
56.79, H 4.45. C18H10N6S2. Calculated, %: C 56.82, H
4.24.
IR spectra were recoded on
a
NICOLET
AVATAR-320 Fourier spectrometer in KBr pellets. 1H
NMR spectra were taken on a Bruker DRX-500 (500
MHz) spectrometer in DMSO-d6 against internal TMS.
Mass spectra were measured on a MX-1321 device
with the direct injection system and the ionizing
electron energy 70 eV. Melting points were measured
on a Boetius installation. Experiments were carried out
in a LG MS2022H microwave stove.
1
1531, 1326, 1042, 848, 693. H NMR spectrum
(DMSO-d6) δ, ppm: 2.72–2.75 t (4H, CH2N), 3.71-
3.73 t (4H, CH2O), 6.8 s (2H, NH2), 7.20-7.23 t (2H,
Ph), 8.1 d (2H, Ph). Found, %: C 59.68, H 5.77.
C13H15N3OS. Calculated, %: C 59.74, H 5.79.
REFERENCES
1. Geronikaki, D., Chatziopoulos, and C., Soloupis, G,
Molecules, 2003, no. 8, p. 472.
1,2-Bis(2-amino-4-phenylthiazolyl)hydrazine (IV).
This compound was prepared under the conditions
analogous to the previous synthesis, mp 105–107°C,
yield 45%. IR spectrum (KBr) ν, cm–1: 3443, 3375,
3230, 3172, 2857, 1623, 1508, 1336, 1069, 850, 695.
1H NMR spectrum (DMSO-d6), δ, ppm: 7.3 m (3H,
Ph), 7.7 m (2H, Ph). Mass spectrum, [m/z, (I, %)]: 51
2. Sondhi, S.M., Singh, N, and Lahoti, A.M., Bioorganic
and Medicinal Chemistry, 2005, no. 13, p. 4291.
3. Lu, H.L., Li, Z., and Anthonsen, T., Molecules, 2005,
no 5, p. 1056.
4. Khrustalev, D.P., Suleimenova, A.A., and Fazylov, S.D.,
Zh. Prikl. Khim., 2008, vol. 81, no. 5, p. 863.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 3 2009