Microwave-assisted synthesis of 2-aryl(hetaryl)-5-phenylamino-1,3,4- thiadiazoles from 5-substituted tetrazoles

Full text of DOI:10.1134/S1070428009040307

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 4, pp. 631–632. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © Yu.A. Efimova, G.G. Karabanovich, T.V. Artamonova, G.I. Koldobskii, 2009, published in Zhurnal Organicheskoi Khimii, 2009,
Vol. 45, No. 4, pp. 644–645.
SHORT
COMMUNICATIONS
Microwave-Assisted Synthesis of 2-Aryl(hetaryl)-5-phenylamino-
1,3,4-thiadiazoles from 5-Substituted Tetrazoles
Yu. A. Efimova, G. G. Karabanovich, T. V. Artamonova, and G. I. Koldobskii
St. Petersburg State Institute of Technology, Moskovskii pr. 26, St. Petersburg, 190013 Russia
e-mail: koldobsk@tu.spb.ru
Received December 9, 2008
DOI: 10.1134/S1070428009040307
In the recent years 2-aryl-5-arylamino-1,3,4-thia-
diazoles have attracted considerable attention due to
their intrinsic high biological activity [1]. Compounds
of the 2-aryl-5-arylamino-1,3,4-thiadiazole series were
found to exhibit antimicrobial [2], antituberculous [3],
and antiphlogistic properties [4], as well as to inhibit
development of some cancer diseases [5]. However,
the lack of convenient methods for the preparation of
2,5-disubstituted 1,3,4-thiadiazoles strongly restricts
their potential application in medical practice. Known
and widely used methods of synthesis of 2,5-disub-
stituted 1,3,4-thiadiazoles often include a number of
steps and are insufficiently effective [1, 6]. On the
other hand, as early as 1961 Huisgen et al. [7] reported
a simple one-step procedure for the synthesis of
2-phenyl-5-phenylamino-1,3,4-thiadiazole from
5-phenyl-1H-tetrazole and phenyl isothiocyanate.
shorten the reaction time by a factor of 4. No reaction
occurred when a mixture of 5-(pyridin-2-yl)-1H-tetra-
zole and phenyl isothiocyanate was heated for 2 h at
170°C. Under conditions of microwave irradiation, the
corresponding 1,3,4-thiadiazole (Ig) was formed in
50% yield in 0.5 h (170°C, 70 W). Our results are very
important, for they open new prospects in using micro-
wave irradiation in the chemistry of tetrazoles.
The yields of 1,3,4-thiadiazoles Ia–Ig obtained by
MW-assisted reactions and by conventional heating are
listed below, %: Ia, 77, 88; Ib, 82, 85; Ic, 64, 64; Id,
74, 43; Ie, 69, 74; If, 80, 80; Ig, 50, 0.
5-(4-Dimethylaminophenyl)-N-phenyl-1,3,4-thia-
diazol-2-amine (Ia). A mixture of 0.5 g (2.6 mmol) of
5-(4-dimethylaminophenyl)-1H-tetrazole and 5 ml
(42.2 mmol) of phenyl isothiocyanate was stirred for
0.5 h at 170°C under microwave irradiation (70 W).
The mixture was cooled to 20°C, 40 ml of hexane was
added, and the precipitate was filtered off, washed
with hexane (2×20 ml), and dried in air. Yield 77%,
mp 221–222°C (from acetonitrile) [10]. IR spectrum,
ν, cm–1: 3244, 3190, 3137, 3052, 2999, 2906, 2858,
2811, 1608, 1568, 1532, 1501, 1452, 1421, 1363,
1312, 1271, 1234, 1192, 1095, 1066, 1014, 975, 947,
While continuing our studies on the synthesis and
chemical transformations of tetrazoles under condi-
tions of microwave irradiation (MW) [8, 9], we ex-
amined microwave-assisted reactions of 5-aryl(hetaryl)-
tetrazoles with phenyl isothiocyanate and obtained the
corresponding 2-aryl(hetaryl)-5-phenylamino-1,3,4-
thiadiazoles Ia–Ig in good yields. Comparison of our
results with those obtained in conventional thermal
reactions showed that microwave irradiation strongly
affects the reaction rate and makes it possible to
1
869, 812, 745, 693, 652, 611. H NMR spectrum, δ,
ppm: 3.05 s (6H, NCH3), 6.82 d (2H, Harom), 7.04 m
(1H, Harom), 7.38 m (2H, Harom), 7.70–7.74 m (4H,
Harom), 9.37 s (1H, NH).
PhN=C=S, MW
170°C, 0.5 h
HN
N
N
N
2-Aryl(hetaryl)-5-phenylamino-1,3,4-thiadiazoles
Ib–Ig were synthesized in a similar way.
N
R
R
NHPh
N
S
5-(4-Methoxyphenyl)-N-phenyl-1,3,4-thiadi-
azol-2-amine (Ib). Yield 82%, mp 201°C (from
ethanol) [11]. H NMR spectrum (DMSO-d6), δ, ppm:
Ia–Ig
1
R = 4-Me2NC6H4 (a), 4-MeOC6H4 (b), 4-MeC6H4 (c), Ph (d),
4-ClC6H4 (e), 4-O2NC6H4 (f), pyridin-2-yl (g).
3.81 s (3H, OCH3), 6.99–7.06 m (3H, Harom), 7.32–
631

EFIMOVA et al.
632
7.36 t (2H, Harom), 7.63 d (2H, Harom), 7.77 d (2H,
Harom), 10.44 s (1H, NH).
N 21.62; S 12.39. C13H10N4S. Calculated, %: C 61.41;
H 3.94; N 22.05; S 12.60.
5-(4-Methylphenyl)-N-phenyl-1,3,4-thiadiazol-2-
amine (Ic). Yield 64%, mp 224°C (from acetonitrile)
[11]. H NMR spectrum, δ, ppm: 2.41 s (3H, CH3),
The IR spectra were recorded from samples pre-
pared as KBr pellets on a Shimadzu FTIR-8400s
spectrometer. The H NMR spectra were measured on
1
1
7.07 t (1H, Harom), 7.32–7.40 m (4H, Harom), 7.73–
7.80 m (4H, Harom), 9.53 s (1H, NH).
a Bruker WM-400 instrument at 400 MHz from solu-
tions in acetone-d6. Microwave-assisted reactions were
carried our in a Milestone P/N 44072 microwave oven.
The purity of the products was checked by TLC on
Silufol plates using acetone–hexane (1:2) as eluent.
The procedure for the thermal reactions was the same
as under microwave irradiation.
N,5-Diphenyl-1,3,4-thiadiazol-2-amine (Id).
Yield 74%, mp 203°C (from ethyl acetate) [7]. 1H NMR
spectrum, δ, ppm: 7.02–7.06 t (1H, Harom), 7.33–
7.38 m (2H, Harom), 7.48 m (3H, Harom), 7.72 d (2H,
Harom), 7.87 d (2H, Harom), 9.55 s (1H, NH).
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 08-03-00342a).
5-(4-Chlorophenyl)-N-phenyl-1,3,4-thiadiazol-2-
amine (Ie). Yield 69%, mp 223°C (from ethyl
acetate) [1]. H NMR spectrum, δ, ppm: 7.09 t (1H,
1
H
arom), 7.36–7.42 m (2H, Harom), 7.56 d (2H, Harom),
REFERENCES
7.73 d (2H, Harom), 7.92 d (2H, Harom), 9.62 s (1H, NH).
5-(4-Nitrophenyl)-N-phenyl-1,3,4-thiadiazol-2-
amine (If). Yield 80%, mp 258–260°C (from ethanol)
[1]. H NMR spectrum, δ, ppm: 7.12 t (1H, Harom),
7.37–7.43 t (2H, Harom), 7.76 d (2H, Harom), 8.19 d (2H,
Harom), 8.39 d (2H, Harom), 9.84 s (1H, NH).
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1
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 4 2009