Synthesis and characterization of new polynuclear bis-5-oxy-1H-tetrazoles

Article abstract of DOI:10.1134/S1070428009010229

Different bis-phenols reacted with cyanogen bromide in the presence of triethylamine as base to give the corresponding bis-cyanates which were treated with sodium azide in acetone as solvent to produce new bis(5-oxy-1H-tetrazole) derivatives. One more bis-tetrazole derivative was synthesized by reaction of 5-(4-aminophenoxy)-1H-tetrazole with adipoyl chloride. The prepared compounds were characterized by usual spectroscopic techniques.

Full text of DOI:10.1134/S1070428009010229

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 1, pp. 154–157. © Pleiades Publishing, Ltd., 2009.
Published in Russian in Zhurnal Organicheskoi Khimii, 2009, Vol. 45, No. 1, pp. 156–159.
Synthesis and Characterization of New Polynuclear
Bis-5-oxy-1H-tetrazoles*
Y. Mansoori, R. Sarvari, M. R. Zamanloo, and G. H. Imanzadeh
Department of Applied Chemistry, College of Science, University of Mohaghegh Ardabili, Ardabil, 56199-11367 Iran
phone: +(98451)5514702; fax: +(98451)5514701; e-mail: ya_mansoori @yahoo,com
Received April 25, 2007
Abstract—Different bis-phenols reacted with cyanogen bromide in the presence of triethylamine as base to
give the corresponding bis-cyanates which were treated with sodium azide in acetone as solvent to produce new
bis(5-oxy-1H-tetrazole) derivatives. One more bis-tetrazole derivative was synthesized by reaction of
5-(4-aminophenoxy)-1H-tetrazole with adipoyl chloride. The prepared compounds were characterized by usual
spectroscopic techniques.
DOI: 10.1134/S1070428009010229
Tetrazoles constitute a very important class of com-
pounds for medicinal chemistry. Substituted tetrazoles
were found to exhibit a wide spectrum of neurological
activity which, depending on the substitution pattern,
ranges from strong stimulation of the nervous system
to depressant action. 5-Substituted-1H-tetrazoles may
serve as nonclassical isosters for the carboxylic acid
moiety (RCOOH) in the design of anticancer, antimi-
crobial, antihypertensive, and antiallergic agents. The
term nonclassical isosterism (used interchangeably
with the term bioisosterism) refers to the concept im-
plying that functional groups having similar physico-
chemical properties may be interchangeable, resulting
in similar biological properties [1].
zoles show strong stimulating effect on the central
nervous system, while 2,5-disubstituted tetrazoles do
not [2]. On the other hand, most azides (important
precursors of many classes of compounds such as
amines, aziridines, ureas, oxadiazoles, and others) are
carcinogenic [3–5].
Dabbagh and co-workers used tetrazoles in many
chemical reactions. They reported on the equilibrium
between 5-substituted 1- and 2-acyltetrazoles, their
thermal decomposition, and conversion into imidoyl
azides, isoureas, and oxadiazoles [6–8]. Also, the syn-
thesis of new azo dyes containing an aryloxytetrazole
fragment was described [9], While studying the reac-
tivity of polynuclear tetrazoles toward different elec-
trophiles, Filichev et al. [10] synthesized new mono-
and bis-3-substituted thymidine derivatives containing
a 1,5-bis(tetrazol-5-yl)-3-oxapentane fragment as
linker. Such compounds attract interest as inhibitors of
DNA chain extension and antisense agents. Syntheses
of nonfused methylene-bridged polynuclear triazole-
and tetrazole-containing systems were also reported by
Verkhozina et al. [11]. Bronisz [12] described the first
coordination polymer based on 1,2-bis(2H-tetrazol-2-
The main difficulty in studies on tetrazole com-
pounds is related to possible equilibrium between
1H-tetrazole, 2H-tetrazole, and imidoyl azide (open-
chain isomer of 1H-tetrazole) tautomers in solution
(Scheme 1). The composition of the tautomer mixture
depends on the 5-substituent, solvent polarity, and
other factors. Generally, each isomer is characterized
by its own specific chemical and pharmaceutical
behavior. For example, some 1,5-disubstituted tetra-
Scheme 1.
N
N
O
NH
N
N
N
R
R
NH
N
H
N
R
OH
R
N3
Carboxylic acid
1H-Tetrazole
2H-Tetrazole
Imidoyl azide
* The text was submitted by the authors in English.
154

SYNTHESIS AND CHARACTERIZATION OF NEW POLYNUCLEAR
155
Scheme 2.
H
H
Pyridine
reflux, 2 h
O
O
N
N
O
N
N
+
N
N
N
N
N
N
Cl
Cl
R
R
R
R
R
R
n
metal ions. Efficient filtering materials based on these
complexones have been developed recently for thor-
ough purification of biological fluids from heavy
metals and radionuclides [13].
yl)ethane (ebtz, A). The ligand was synthesized by
alkylation of 1H-tetrazole. The author showed that the
coordination geometry of Zn(II) in [Zn(ebtz)3](ClO4)2
is not simply propagated in the network because of the
presence of elastic linkage in ebtz enabling the coor-
dinated ligand molecule to adopt a syn conformation in
contrast to anti conformation of the free ligand mole-
cule in the solid state [12].
Furthermore, bis-tetrazole compounds can react
with dicarboxylic acid chlorides (Huisgen reaction) or
bis-isocyanates to give polymers containing 1,3,4-oxa-
diazole units. These polymeric compounds, displaying
tough mechanical properties and excellent heat resist-
ance, are advanced materials for high-performance ap-
plications, e.g., in electronic devices [14] (Scheme 2).
N
N
N
N
N
N
N
N
A
In the present work, we synthesized new bis(5-oxy-
1H-tetrazole) derivatives I–VIII (Scheme 3). Different
bis-phenols reacted with cyanogen bromide in the
presence of triethylamine as base in acetone at 0–5°C
to give the corresponding bis-cyanates. Treatment of
the latter with sodium azide afforded (after acidifica-
tion) the desired bis-tetrazoles I–VIII in 20–75% yield
Zubarev et al. [13] have recently reported on the
synthesis of a series of podand (polydentate ligand)
systems containing two to four 2-(tetrazol-5-yl)ethyl
fragments in one molecule. The molecular structure
and physicochemical properties of these tetrazole
podands enabled their high complexing ability toward
Scheme 3.
H
H
(1) 2NaN3, acetone
(2) H+, H2O
O
O
N
N
Et3N, acetone
X
HO
X
OH
+
2BrCN
NCO
X
OCN
N
N
N
N
N
N
I–VIII
Me
Me
Cl
I, X =
; II, X =
VI, X =
; III, X =
; IV, X =
; V, X =
;
Me
S
; VII, X =
; VIII, X =
.
Scheme 4.
O
H
N
O
N
Cl
4
+
N
Cl
N
N
NH2
O
H
N
H
N
N
N
O
O
N
PhH, reflux, 4 h
N
N
N
H
O
O
N
H
IX
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 1 2009

MANSOORI et al.
Yields, melting points, and IR, 1H NMR, and mass spectra of bis-tetrazoles I–IXa
156
Comp. Yield, Decomposition
1H NMR spectrum (DMSO-d6),
δ, ppm
IR spectrum (KBr), ν, cm–1
no.
%
point, °C
I
50
241–242
7.50 s
3100 w, 2920 m, 2600 s, 2450 m, 1613 s, 1497 s,
1179 s
II
20
40
35
75
46
30
60
16
179–180
212–214
b110–111b
197–199
174–175
226–228
176–178
205–207
7.30–6.80 m
3025 m, 2893 m, 2745 m, 2648 m, 2480 w, 1595 s,
1484 s, 1418 s, 1242 s, 1137 s, 1074 s
III
IV
V
7.80–7.00 m (3H), 2.20 s (3H)
3028 m, 2889 m, 2745 m, 2630 m, 1593 s, 1490 s,
1412 s, 1171 s, 1062 s
9.70–8.50 br.s, 7.45–7.10 m (2H), 3053 m, 2727 m, 2630 m, 2498 m, 1611 s, 1569 s,
7.80 d (1H, J = 7.8 Hz)
1509 m, 1430 s, 1286 m, 1045 m, 857 w
7.20 s (8H), 1.50 s (6H)
3034 w, 2969 m, 2867 m, 2741 m, 2628 m, 1585 s,
1497 s, 1407 s, 1168 s, 1043 s
VI
VII
VIII
IX
11.40 s (2H), 7.60 s (4H)
8.20–7.30 m
3022 m, 2890 m, 2733 m, 2624 m, 2452 w, 1617 s,
1569 s, 1484 s, 1192 s, 1052 s, 839 s
3047 m, 2896 m, 2739 m, 2624 m, 2450 w, 1589 s,
1502 s, 1388 s, 1249 s, 1171 m, 1050 s
15.00–11.00 br (2H), 9.5–7.8 m 3239 m, 3044 m, 2889 m, 2738 m, 2638 m, 1569 s,
(6H) 1508 s, 1448 s, 1206 s, 1056 s, 954 s
10.10 s (2H), 9.00 br.s, 7.20 d 3264 s, 3059 s, 2914 s, 2727 s, 2613 s, 2468 m,
(4H, J = 8.2 Hz), 7.70 d (4H, J = 1648 s, 1623 s, 1539 s, 1503 s, 1406 s, 1183 m,
8.2 Hz), 2.65–2.0 m (4H), 1.95– 1044 m
1.20 m (4H)
a
Mass spectrum, m/z: II, 246; III, 260; V, 264; VII, 296.
mp 94–95°C.
b
(see table). In addition, bis-tetrazole IX was synthe-
sized by the reaction of 5-(4-aminophenoxy)-1H-tetra-
zole with adipoyl dichloride (Scheme 4). In this case,
two equivalents of the amine was used, one of which
acted as base to bind liberated hydrogen chloride. The
yields, melting points, and spectral parameters of com-
pounds I–IX are given in table.
EXPERIMENTAL
The 1H NMR spectra were recorded on a Joel JNM-
EX 90A spectrometer. The IR spectra were measured
in KBr on a Buck Infrared Spectrophotometer Model
500. The mass spectra (electron impact, 70 eV) were
obtained on a Shimadzu QP-5050 mass spectrometer
coupled with a Shimadzu GC-17A gas chromatograph.
Typical procedure for the preparation of bis-
tetrazole compounds I–VIII. A 100-ml two-necked
round-bottom flask equipped with a magnetic stirrer
was charged with a solution of 4.3 mmol of the
corresponding bis-phenol and 9 mmol of cyanogen
bromide in 10 ml of anhydrous acetone. The solution
was cooled to 0–5°C, and a solution of 0.91 g
(9 mmol) of triethylamine in 5 ml of anhydrous ace-
tone was added dropwise. Triethylamine hydrobromide
gradually separated as a white solid. The mixture was
stirred for an additional 30 min and filtered, and the
filtrate was added to a suspension of 0.96 g
(14.7 mmol) of sodium azide in 5 ml of anhydrous
acetone at room temperature. The mixture was stirred
for 90 min on heating under reflux, 10 ml of water was
Unlike the initial bis-phenols, the IR spectra of bis-
tetrazoles I–IX lacked absorption bands assignable to
stretching vibrations of hydroxy groups (3600 cm–1),
while a complex absorption pattern was observed in
the region 3000–2480 cm–1, and C=N absorption bands
were present at 1610–1590 cm–1. No OH signal was
1
observed in the H NMR spectra of I–IX, and the NH
signal usually appeared in the region δ 10–20 ppm,
though it was strongly broadened in most cases. The
mass spectra of compounds II, III, V, and VII con-
tained the corresponding molecular ion peaks.
The synthesized compounds can be used for the
preparation of new thermally stable polymers contain-
ing 1,3,4-oxadiazole units via Huisgen reaction. This
part of the study is now under implementation.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 1 2009

SYNTHESIS AND CHARACTERIZATION OF NEW POLYNUCLEAR
157
4. Dabbagh, H.A. and Ghaelee, S., J. Org. Chem., 1996,
added, and the mixture was concentrated under re-
duced pressure, cooled in an ice bath, and acidified by
dropwise addition of concentrated hydrochloric acid.
The precipitate of bis-tetrazole I–VIII was filtered off,
washed with cold water, and recrystallized from ethyl
acetate–hexane (see table).
vol. 61, p. 3439.
5. Butler, R.N., Advances in Heterocyclic Chemistry, Kat-
ritzky, A.R. and Boulton, A.J., Amsterdam: Elsevier,
1977, vol. 21, p. 323.
6. Dabbagh, H.A. and Lwowski, W., J. Org Chem., 2000,
vol. 66, p. 7284.
N,N′-Bis[4-(1H-tetrazol-5-yloxy)phenyl]adip-
amide (IX). Adipoyl chloride, 0.99 g (5.47 mmol) was
added dropwise under stirring to a suspension of 3.87 g
(21.85 mmol) of 5-(4-aminophenoxy)-1H-tetrazole in
anhydrous benzene (preliminarily dried with metallic
sodium). The mixture was stirred for 4 h on heating
under reflux, the solvent was removed under reduced
pressure, the residue was poured into water, and the
mixture was acidified to pH 1 with concentrated hy-
drochloric acid and stirred for 2 h at room temperature.
The brown precipitate was filtered and washed with
cold water. Yield 1.58 g (16%).
7. Dabbagh, H.A. and Mansoori, Y., Russ. J. Org. Chem.,
2001, vol. 37, p. 1771.
8. Dabbagh, H.A., Mansoori, Y., Jafari, M., and Rosta-
mi, M., J. Chem. Res., Synop., 2000, p. 442.
9. Dabbagh, H.A. and Mansoori, Y., Dyes Pigments, 2002,
vol. 54, p. 37.
10. Filichev, V.V., Jasko, M.V., Malin, A.A., Zuba-
rev, V.Yu., and Ostrovskii, V.A., Tetrahedron Lett.,
2002, vol. 43, p. 1901.
11. Verkhozina, O.N., Kizhnyaev, V.N., Vereshchagin, L.I.,
Rokhin, A.V., and Smirnov, A.I., Russ. J. Org. Chem.,
2003, vol. 39, p. 1792.
12. Bronisz, R., Inorg. Chim. Acta, 2002, vol. 340, p. 215.
REFERENCES
13. Zubarev, V.Yu., Bezklubnaya, E.V., Pyartman, A.K.,
Trifonov, R.E., and Ostrovskii, V.A., Chem. Heterocycl.
Compd. (Engl. transl.), 2003, vol. 39, p. 1317.
1. Herr, R.J., Bioorg. Med. Chem., 2002, vol. 10, p. 3379.
2. Stone, W.E., Pharmacology, 1970, vol. 3, p. 367.
14. Ding, J., Day, M., Robertson, G., and Roovers, J.,
3. Dabbagh, H.A. and Lwowski, W., J. Org. Chem., 1989,
Macromolecules, 2002, vol. 35, p. 3474.
vol. 54, p. 3952.
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