Tetrazoles: LVI. Synthesis of 5-substituted tetrazoles under microwave activation in the presence of heterogeneous catalyst (Zinc oxide)

Article abstract of DOI:10.1134/S1070428011050125

Reactions of aromatic and heteroaromatic nitriles with sodium azide in the presence of zinc oxide under the conditions of microwave activation provide 5-aryl(hetaryl)tetrazoles in high yields. Pleiades Publishing, Ltd., 2011.

Full text of DOI:10.1134/S1070428011050125

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 5, pp. 728−730. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © L.V. Myznikov, Yu.A. Efimova, T.V. Artamonova, G.I. Koldobskii, 2011, published in Zhurnal Organicheskoi Khimii, 2011, Vol. 47,
No. 5, pp. 723−725.
Tetrazoles: LVI. Synthesis of 5-Substituted
Tetrazoles under Microwave Activation in the Presence
of Heterogeneous Catalyst (Zinc Oxide)
L. V. Myznikov, Yu. A. Efimova, T. V. Artamonova, and G. I. Koldobskii†
St. Petersburg State Technological Institute, St. Petersburg, 190013 Russia
e-mail: postleo@mail.ru
Received July 7, 2010
Abstract—Reactions of aromatic and heteroaromatic nitriles with sodium azide in the presence of zinc oxide
under the conditions of microwave activation provide 5-aryl(hetaryl)tetrazoles in high yields.
DOI: 10.1134/S1070428011050125
The significant interest in tetrazole chemistry in the
last decades has been due to the wide application of these
compounds in versatile fields. They found application in
pharmaceutics as lipophilic spacers and substitutes of
carboxylic acids, as components of explosives, as ligands
in the coordination chemistry, and also as precursors in
the preparation of diverse heterocyclic compounds [2–5].
Recently a great attention is attracted by the search
for and application of safe heterogeneous catalysts which
may be used in the synthesis many times thus reducing
the amount of toxic wastes.
Zinc oxide is known to be used as catalyst of the
Friedel–Krafts reaction [7], in Beckmann rearrange-
ment [8], sulfonation [9], and in the synthesis of cyclic
urea derivatives from diamines [10]. The zinc oxide was
reported to be used in the composition of catalysts for
alcohols dehydration [11]. Kantam et al. [12] showed
that nanocrystalline ZnO was an efficient heterogeneous
catalyst of [1+3]-cycloaddition of sodium azide to ni-
triles leading to the formation of 5-substituted tetrazoles.
However the preparation of tetrazoles in the presence of
zinc oxide required a prolonged heating. The presumed
mechanism of this reaction was discussed in [13, 14].
The search for new and refinement of the known
methods of the synthesis of 5-substituted tetrazoles is
one of the most important problems of the chemistry of
these compounds. As a rule the 5-substituted tetrazoles
are obtained by the reaction of azides with nitriles in the
presence of catalysts. The formerly described methods
possess some disadvantages like the application of strong
Lewis acids, expensive and toxic metals, the formation of
explosive derivatives of hydrazoic acid. Besides these re-
actions proceed under fairly severe conditions and require
long heating. Sufficiently simple and safe method was
developed in [6]. The tetrazoles were obtained in water
medium in the presence of zinc salts. The drawbacks of
this method were the low reaction rate and the necessity
to heat the reaction mixture at 170°С in a pressure reactor
in the case of nitriles of low reactivity.
We studied the reactions of nitriles of diverse struc-
tures with sodium azide in the presence of heterogeneous
catalyst, commercial ZnO, under the conditions of mi-
crowave activation (MWA). We selected as investigation
objects aliphatic, aromatic, and heteroaromatic nitriles in
order to determine the limits of the application of ZnO
in [1+3]-cycloaddition under the MWA conditions. The
solvent is known to affect significantly the course of such
reactions. It proved that reactions carried out in DMF both
at the thermal heating and in MWA conditions required
–
*
†
–––––––––––––––––
For Communication LV, see [1].
Deceased.
7
28

TETRAZOLES: LVI.
729
for the completion no less than 24 h. We showed that in
a microwave reactor at 120–130°C in the presence of ZnO
in DMSO 5-aryltetrazoles with electron-acceptor sub-
stituents in the phenyl ring Ib–If and 5-hetaryltetrazoles
Ig–Ii formed in high yields. The comparison of data ob-
tained in the reaction at the thermal heating and at MWA
shows that MWAmakes it possible to obtain tetrazoles in
higher yields than in the unactivated process within the
same time (see the table). The low yield of 5-phenyltet-
razoles may be ascribed to the volatility of benzonitrile.
We failed to isolate the target products in attempts to
carry out the synthesis of 5-substituted tetrazoles along
this procedure from aliphatic nitriles. The phthalodinitrile
gave exclusively the product of monoaddition Ic whereas
at the catalysis with zinc salts о-di(tetrazol-5-yl)benzene
was obtained [6, 13, 14].
Yield of 5-substituted tetrazoles Iа–Ii in DMСО (130°С) under
the conditions of thermal heating and MWA
Yield, %
Compound
Time, h
no.
thermal heating
16
MWA
39
Iа
Ibа
12
4
16
67
20
44
26
41
53
54
37
74
73
62
66
90
64
73
Ic
0.25
Id
Ieа
If
Ig
Ih
Ii
1
4
4
2
2
1
а
1
20°С.
of 0.67 g (5 mmol) of 4-methoxybenzonitrile in 6 ml of
DMSO was added 0.49 g (7.5 mmol) of sodium azide and
0.4 g (5 mmol) of zinc oxide, and the reaction mixture
was stirred in the microwave reactor at 130°С (70 W)
for 12 h. Then zinc oxide was filtered off, the filtrate
was evaporated in a vacuum, the product obtained was
dissolved in 10 ml of cold water. The mixture was treated
with concn. HCl till pH 2, the separated precipitate
was filtered off, washed with water, and dried in air.
Yield 0.34 g (39%), mp 226–228°С (ethyl acetate) [15].
H
N
MBA, ZnO
N
N
RCN + NaN3
R
_
20 130o
1
°
C, DMSO
N
_
Iа Ii
R = MeOC H (а), Ph (b), 2-CNC H (c), 3-BrC H (d),
6
4
6
4
6
4
4
4
-BrC H (e), 4-ClC H (f), 2-pyridyl (g), 3-pyridyl (h),
-pyridyl (i).
6 4 6 4
–
1
The catalyst can be easily regenerated and repeatedly
used without notable reduction in the activity.
IR spectrum, ν, cm : 3438, 3143, 3075, 3015, 2985,
2923, 2842, 2726, 2557, 2482, 1616, 1585, 1501, 1468,
1
9
443, 1407, 1300, 1182, 1163, 1120, 1056, 1034, 1020,
92, 834, 807, 800, 752, 698, 636, 612, 522. Н NMR
Thus the method of preparation of 5-substituted
tetrazoles in the presence of zinc oxide can be consider-
ably improved if the reaction is carried out in DMSO
medium under the conditions of microwave activation.
This method may be regarded as one of the most safe
procedures for preparation of tetrazoles.
1
spectrum, δ, ppm (DMSO-d ): 3.82 s (3Н, СН ), 7.14 d
6
3
(2Нароm.), 7.95 d (2Нarom).
Tetrazoles Ib–Ii were similarly obtained, tetrazoles
Ib, Ie were prepared at heating to 120°С.
-Phenyltetrazole (Ib), mp 215°С (ethyl acetate)
5
EXPERIMENTAL
–1
[16]. IR spectrum, ν, cm : 3432, 3129, 3078, 3055, 2980,
2
1
1
917, 2849, 2794, 2702, 2608, 2544, 2481, 2458, 1609,
564, 1486, 1467, 1409, 1288, 1257, 1164, 1101, 1085,
057, 1036, 1016, 994, 959, 926, 791, 784, 725, 704, 689.
IR spectra were recorded on a spectrophotometer
Shimadzu FTIR-8400s from pellets with KBr, Н NMR
spectra were registered on a spectrometer Bruker WM-
00. Reactions under MWA conditions were carried out
1
1
Н NMR spectrum, δ, ppm (acetone-d ): 7.36 m (3Нarom),
6
4
8
.15 m (2Нarom).
in a reactor Milestone P/N 44072. The purity and homo-
geneity of compounds obtained was checked by TLC on
Sorbfil plates, eluent ethyl acetate–tetrachloromethane,
5
-(2-Cyanophenyl)tetrazole (Ic), mp 223–224°С
–
1
(
ethanol) [17]. IR spectrum, ν, cm : 3746, 3422, 3131,
3
2
2
1
1
079, 3060, 3014, 2993, 2979, 2957, 2917, 2876, 2834,
751, 2721, 2689, 2674, 2644, 2618, 2545, 2503, 2467,
229, 1857, 1722, 1625, 1608, 1581, 1569, 1492, 1481,
454, 1407, 1384, 1279, 1242, 1200, 1167, 1098, 1066,
042, 1013, 1000, 970, 864, 783, 757, 745, 723, 707, 666,
555, 518, 501. Н NMR spectrum, δ, ppm (DMSO-d ):
2
: 3.
The reactions of nitriles with sodium azide were
performed by the same procedure both at the thermal
heating and under MWA conditions.
1
5
-(4-Methoxyphenyl)tetrazole (Iа). To a solution
6
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 5 2011

730
MYZNIKOV et al.
7
.77 t (1Нarom), 7.92 t (1Нarom), 8.07 t (2Нarom).
ACKNOWLEDGMENTS
5
-(3-Bromophenyl)tetrazole (Id), mp 150°С (aque-
–
1
The study was carried out under the financial support
of the Russian Foundation of Basic Research (grant no.
8-03-00342а).
ous ethanol) [15]. IR spectrum, ν, cm : 3430, 3123,
060, 2963, 2917, 2852, 2753, 2619, 1633, 1574, 1469,
444, 1402, 1251, 1241, 1156, 1092, 1073, 1011, 1003,
95, 888, 790, 746, 738, 675, 653. Н NMR spectrum, δ,
ppm (DMSO-d ): 7.55 t (1Нarom), 7.78 d (1Нarom), 8.03 d
3
1
9
0
1
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–
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2
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8
(
(
1
6
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5
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–1
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631, 1529, 1441, 1389, 1354, 1292, 1251, 1238, 1201,
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6
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 5 2011