Some transformations of 2-amino-4-phenyl-1,3-thiazole

Article abstract of DOI:10.1023/B:RJAC.0000038813.35580.37

Reactions of 2-amino-4-phenyl-1,3-thiazole with aromatic aldehydes, phenyl isocyanate, and carboxylic acid chlorides were studied.

Full text of DOI:10.1023/B:RJAC.0000038813.35580.37

Russian Journal of Applied Chemistry, Vol. 77, No. 5, 2004, pp. 787 789. Translated from Zhurnal Prikladnoi Khimii, Vol. 77, No. 5,
2004, pp. 791 793.
Original Russian Text Copyright
2004 by Sadigova, Magerramov, Allakhverdiev, Vekilova.
ORGANIC SYNTHESIS
AND INDUSTRIAL ORGANIC CHEMISTRY
Some Transformations of 2-Amino-4-phenyl-1,3-thiazole
S. E. Sadigova, A. M. Magerramov, M. A. Allakhverdiev, and T. M. Vekilova
Baku State University, Baku, Azerbaijan
Received December 4, 2003; in final form, March 2004
Abstract Reactions of 2-amino-4-phenyl-1,3-thiazole with aromatic aldehydes, phenyl isocyanate, and
carboxylic acid chlorides were studied.
Various thiazoles exhibit antimicrobial, antihelmin-
tic, antiparasitic, and antipyretic properties [1 3].
Thiazole derivatives are widely used as antioxidants
[4], vulcanization accelerators [5], and photochromic
compounds [6]. Thiazoles and azomethines derived
from them are important analytical reagents [7]. Thia-
zoles are also used for preparing various heterocycles
[8], cyclizing terpenes [9], and concentrating some
transition metals. In many cases, the triazoles used
contain aryl and basic (amino) groups.
where R = H (IV), OH (V).
It is known thart condensation of various amines
with aldehydes yields Schiff bases. We have studied
for the first time the reactions of I with benzaldehyde
and salicylaldehyde and obtained the corresponding
Schiff bases IV and V.
2-(2-Hydroxybenzylidenimino)-4-phenyl-1,3-thia-
zole V is hydrogenated under mild conditions with
sodium borohydride to give 2-(2-hydroxybenzyl-
amino)-4-phenyl-1,3-thiazole VI. Treatment of VI
with HCl gives the corresponding hydrochloride:
In this context, it seemed appropriate to prepare a
thiazole containing simultaneously aryl and amino
groups, 2-amino-4-phenyl-1,3-thiazole I, and its deriv-
atives.
Ph
N
V + NaBH4
Ph
NHCH2C6H4OH-2
VI
S
Compound I was prepared according to [10] in
two steps: bromination of acetophenone followed by
the reaction of the resulting -bromoacetophenone
with thiourea; the yield of the target product was 90%:
N
HCl
NHCH2C6H4OH-2 HCl.
VII
S
Br , AlCl
With the aim to synthesize potentially physiologi-
cally active derivatives of thiazole I, we prepared its
hydrochloride VIII, which, in contrast to the free
base, is readily soluble in water; acylation of I gave
amide hydrochlorides IX and X:
2
3
PhCOCH3
PhCOCH2Br
N
_
HBr
Ph
NH C(S)NH
2
2
.
NH2
S
I
N
Reaction of thiazole I with phenyl isocyanate gave
urea derivative II; hydrogen substitution with bromine
in I yielded 2-amino-5-bromo-4-phenylthiazole III:
Ph
I + HCl
NH2 HCl,
S
VIII
N
Ph
PhN=C=O
N
Ph
NHCNHPh
O
I + RCOCl
NHCOR HCl,
S
II
S
IX, X
Br , AcOH
2
N
Ph
Br
I
_
where R = Me (IX), Ph (X).
HBr
S
NH2
The IR spectra of Schiff bases IV and V are similar
to that of thiazole I. However, there is a new absorp-
tion band at about 3450 cm in the spectra of IV and
V, characterizing an intramolecular hydrogen bond
between the phenolic hydroxyl and N=CH fragment.
III
N
Ph
1
1-CH(O)-2-RC H
6
4
N CH C6H4R 2,
IV, V
S
H O
2
1070-4272/04/7705-0787 2004 MAIK Nauka/Interperiodica

788
SADIGOVA et al.
Yields, melting points, and elemental analyses of 2-amino-4-aryl-1,3-thiazole I and its derivatives II X
Found, %
Calculated, %
Com-
pound
Yield,
%
mp,
C
Formula
C
H
N
S
C
H
N
S
I
II
70
91
65
71
80
70
93
85
90
87
148 150 61.21
209 65.16
155 156 42.58
160 161 72.61
4.73
4.28
2.44
4.73
4.13
5.14
4.57
4.11
4.26
4.03
15.51
14.08
10.68
10.75
9.74
9.86
8.92
13.45
10.78
8.72
18.42 C9H8N2S
61.34
65.06
42.37
72.70
68.55
68.06
4.58
4.44
2.76
4.58
4.31
5.00
4.74
4.27
4.35
4.14
15.89 18.19
14.23 10.86
10.98 12.57
10.60 12.12
9.99 11.44
9.92 11.36
8.79 10.06
13.17 15.07
11.00 12.59
8.84 10.12
10.92 C16H13N3OS
12.73 C9H7N2SBr
12.02 C16H12N2S
11.28 C16H12N2OS
11.49 C16H14N2OS
10.26 C16H15N2OSCl 60.28
15.22 C9H9N2SCl 50.82
III
IV
V
VI
VII
VIII
IX
X
143
155
177
68.76
67.93
60.35
176 177 50.99
168
195
51.99
60.48
12.74 C11H11N2OSCl 51.87
10.95 C16H13N2OSCl 60.66
No bands characteristic of NH stretching vibrations
were revealed. The bands at about 3300 cm in the
IR spectrum of VI characterize the intramolecular
hydrogen bond HN HO.
ysis was performed on Silufol UV-254 plates. A 1 : 1
(by volume) mixture of isopropyl alcohol and heptane
was used as eluent. The plates were developed with
iodine vapor.
2
1
2-(Phenylaminocarbonylamino)-4-phenyl-1,3-
thiazole II. A 2.4-g (0.02-mol) portion of phenyl iso-
cyanate was added dropwise with stirring to a solution
of 3.4 g (0.02 mol) of I in 20 ml of anhydrous tolu-
ene. The stirring was continued for 24 h at 60 C.
Then the mixture was cooled to room temperature,
and the colorless crystalline precipitate was filtered
off and recrystallized from acetone.
The UV spectrum of V dramatically differs from
that of its hydrogenated analog VI. The absorption
bands at 208 and 278 nm in V belong to conjugated
aromatic rings, and the long-wave band at 385 nm is
due to the
* transition in the conjugated azo-
methine fragment C=N. In the spectrum of VI, this
band is absent. The lack of conjugation between the
benzene rings results in this case in the presence of
two bands at 260 and 282 nm, assignable to the
monosubstituted benzene and phenolic rings, respec-
tively, instead of a single band at 278 nm.
2-Amino-4-phenyl-5-bromo-1,3-thiazole III.
A solution of 3.2 g (0.02 mol) of bromine in 10 ml of
acetic acid was added at 20 C to a solution of 3.4 g
(0.02 mol) of I in 20 ml of glacial acetic acid, and the
mixture was stirred at 20 C for 30 min. Then 100 ml
of water was added. The yellowish precipitate that
formed in 2 h was filtered off and recrystallized from
ethanol.
1
In the H NMR spectrum of V, the phenolic hy-
droxyl proton gives a signal at about 3.25 ppm, and
the N=CH proton, at 7.85 7.90 ppm. In the hydroxy-
phenyl moiety, the four nonequivalent protons give
a multiplet at 7.2 7.5 ppm.
2-Benzylidenamino-2-phenyl-1,3-thiazole IV.
A 8.8-g (0.05-mol) portion of I was added to 5.3 g
(0.05 mol) of benzaldehyde, and the mixture was vig-
orously stirred for 3 min. Then the mixture was trans-
ferred into a beaker, 15 ml of ethanol was added, and
the mixture was cooled. The colorless crystalline pre-
cipitate that formed in several minutes was filtered off.
The yields and melting points of I X are listed in
the table. The purity of I X was confirmed by TLC,
and the compositions and structures were proved by
elemental analysis and by IR, UV, and H NMR spec-
troscopy.
1
EXPERIMENTAL
2-(2-Hydroxybenzylidenamino)-4-phenyl-1,3-thi-
azole V. A 8.8-g (0.05-mol) portion of I was added
to 6.1 g (0.05 mol) of salicylaldehyde, and the mixture
was vigorously stirred for 30 min. In so doing, the
mixture spontaneously warmed up to 40 C. Then the
mixture was transferred into a beaker, 15 ml of ethan-
ol was added, and the mixture was cooled with ice.
The crystalline precipitate that formed was filtered off.
The IR spectra of I X were taken on a Specord IR-
75 spectrophotometer. Samples were prepared as thin
films or mulls in mineral oil. The spectra were re-
1
corded in the range 700 3700 cm using KBr, NaCl,
1
and LiF prisms. The H NMR spectra were taken on a
Varian VXR-400S spectrometer (400 MHz, solutions
in DMSO-d , internal reference TMS). The TLC anal-
6
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 77 No. 5 2004

SOME TRANSFORMATIONS OF 2-AMINO-4-PHENYL-1,3-THIAZOLE
789
2-(2-Hydroxybenzylamino)-4-phenyl-1,3-thiazole
VI. A 30-ml portion of ethanol was added to 5.6 g
(0.02 mol) of V, and the mixture was stirred to obtain
a suspension. Then sodium borohydride was added,
and the mixture was stirred for an additional 30 min.
After that, 100 ml of water was added, and the mix-
ture was acidified to pH 7.5. The colorless crystalline
precipitate that formed was filtered off and recrystal-
lized from benzene.
ing as bioactive substances, antioxidants, and analyt-
ical reagents.
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2-Amino-4-phenyl-1,3-thiazole hydrochloride
VIII. Dry HCl was passed through a solution of 8.2 g
(0.05 mol) of I in 30 ml of isopropyl alcohol, cooled
to 0 C. The colorless crystalline precipitate that
formed was filtered off and washed three times with
anhydrous diethyl ether. The resulting hydrochloride
was recrystallized from ethanol.
Compound VII was prepared similarly.
2-Acetylamino-4-phenyl-1,3-thiazole hydrochlo-
ride IX. Freshly distilled acetyl chloride (1.5 g,
0.02 mol) was added dropwise to a solution of 3.4 g
(0.02 mol) of I in 10 ml of anhydrous toluene, cooled
to 0 5 C. The colorless crystalline precipitate that
formed was filtered off and recrystallized from ace-
tone.
Compound X was prepared similarly.
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CONCLUSION
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naya Literatura, 1949, coll. 2, pp. 40 41.
2-Amino-4-phenyl-1,3-thiazole was synthesized in
a high yield and converted into various derivatives
(azomethines, halides, amides), which may be promis-
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 77 No. 5 2004