Tetrazoles: XLVII. A route to tetrazole-containing dendrimers

Article abstract of DOI:10.1007/s11178-005-0013-5

The reaction of 5-methylsulfonyl-1-phenyltetrazole with pentaerythritol in acetonitrile in the presence of sodium hydroxide gave tetrakis(1-phenyltetrazol- 5-yloxymethyl)methane. Sulfur-containing analog of the latter was obtained by alkylation of 1-pheny

Full text of DOI:10.1007/s11178-005-0013-5

Russian Journal of Organic Chemistry, Vol. 40, No. 9, 2004, pp. 1318–1321. Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 9, 2004,
pp. 1366–1368.
Original Russian Text Copyright © 2004 by Artamonova, Zatsepina, Koldobskii.
Tetrazoles: XLVII.* A Route
to Tetrazole-Containing Dendrimers
T. V. Artamonova, M. V. Zatsepina, and G. I. Koldobskii
St. Petersburg State Institute of Technology, Moskovskii pr. 26, St. Petersburg, 190013 Russia
e-mail: koldobsk@tu.spb.ru
Received February 12, 2004
Abstract—The reaction of 5-methylsulfonyl-1-phenyltetrazole with pentaerythritol in acetonitrile in the
presence of sodium hydroxide gave tetrakis(1-phenyltetrazol-5-yloxymethyl)methane. Sulfur-containing analog
of the latter was obtained by alkylation of 1-phenyl-4,5-dihydrotetrazole-5-thione with 1,3-dibromo-2,2-bis-
(
bromomethyl)propane. Nitration of the resulting polytetrazoles afforded the corresponding tetrakis(p-nitro-
phenyl) derivatives which can be used in the synthesis of tetrazole-containing dendrimers according to the
divergent scheme.
Obviously increasing interest in dendrimers
originates from the possibility of their use as new
polymeric materials, highly efficient catalysts, and
medicines [2–4]. Important factors stimulating deve-
lopment of the chemistry of dendrimers are beauty and
structural complexity of these compounds. The number
of various dendrimers continuously grows. Numerous
nitrogen-, silicon-, and sulfur-containing dendrimers
and those incorporating aromatic and heterocyclic
fragments have been reported. However, no published
data on tetrazole-containing dendrimers are available,
though there are grounds to believe [5] that such com-
pounds may be useful for the development of mem-
branes for ultrafiltration, new sorbents, and medicines
with a broad spectrum of activity.
work) of a dendrimer, followed by successive addition
of new structural fragments. In terms of the selected
scheme, we developed procedures for the preparation
of previously unknown heterocyclic systems including
more than two tetrazole rings. The resulting structures
can be used as frameworks in the synthesis of tetra-
zole-containing dendrimers.
Heterocyclic systems including more than two
tetrazole rings can be obtained by several methods
some of which were widely used in the recent years.
Examples are 1,3-dipolar cycloaddition of hydrazoic
acid salts to polynitriles [6–8] and reaction of 1-aryl-
5
-methylsulfonyltetrazoles with polyfunctional O-nu-
cleophiles [9–11]. The latter procedure was applied in
the present work. By reaction of 5-methylsulfonyl-1-
phenyltetrazole with pentaerythritol in acetonitrile in
the presence of sodium hydroxide at 18–20°C we
obtained 84% of tetrakis(1-phenyltetrazol-5-yloxy-
methyl)methane (I) (Scheme 1). Sulfur-containing
Two possible ways of building up dendrimer
structures are known. Among these, we selected an ap-
proach which is referred to as the divergent scheme. It
implies stepwise synthesis of the central part (frame-
Scheme 1.
N
N
N
N
N
N
Ph
SO Me
N
N
2
O
O
O
O
NaOH, MeCN
N
Ph
Ph
Ph
Ph
+
C(CH OH)
2 4
N
N
N
N
N
N
N
N
N
N
N
I
*
For communication XLVI, see [1].
1
070-4280/04/4009-1318 © 2004 MAIK “Nauka/Interperiodica”

TETRAZOLES: XLVII.
1319
Scheme 2.
N
N
N
N
N
N
N
N
Ph
S
N
N
S
S
S
S
NaOH, DMF
Ph
Ph
Ph
Ph
N
+
C(CH Br)4
2
N
NH
N
N
N
N
N
N
N
II
Scheme 3.
N
N
N
N
N
N
N
N
N
N
SO2
SO2
KMnO , CH Cl –10% AcOH, Bu NBr
4
2
2
4
Ph
Ph
Ph
Ph
II
SO2
SO2
N
N
N
N
N
N
III
analog of I, which can also be used as framework for
the synthesis of tetrazole-containing dendrimers, was
prepared by alkylation of 1-phenyl-4,5-dihydrotetra-
zole-5-thione with 1,3-dibromo-2,2-bis(bromomethyl)-
propane in DMF at 110°C (Scheme 2). It should be
noted that our numerous attempts to perform this
reaction under milder conditions using such solvents as
alcohol and acetonitrile, as well as in the two-phase
system chloroform–aqueous sodium hydroxide in the
presence of tetrabutylammonium bromide, were unsuc-
cessful. Obviously, the reason is the specific steric
structure of the alkylating agent. This is consistent
with the available data on the alkylation of 1-phenyl-
catalysis. The oxidation product was tetrasulfone III
which was isolated in 51% yield (Scheme 3).
The next step toward tetrazole-containing den-
drimers according to the divergent scheme was nitra-
tion of tetrazoles I and II. Treatment of these com-
pounds with a mixture of sulfuric and nitric acids gave
the corresponding tetranitro derivatives IV and V
(
Scheme 4). As follows from the NMR spectra, the
nitration occurs at the para position of the phenyl sub-
stituent. Nucleophilic replacement of the nitro group in
tetrazoles IV and V by the action of various alkoxide
ions can be regarded as the most evident route to tetra-
zole-containing dendrimers in terms of the divergent
scheme. It should be noted that nitrotetrazoles VI and
VII obtained by nitration of the corresponding di-
tetrazoles (Scheme 5) can be used as dendrons for
building up dendrimers according to the convergent
scheme.
4
,5-dihydrotetrazole-5-thione with sterically unhin-
dered reagents [9, 12].
Like other 1-aryl-5-alkylsulfanyltetrazoles [9, 12],
tetrazole II was smoothly oxidized with potassium
permanganate under conditions of phase-transfer
Scheme 4.
N
N
N
N
N
N
N
N
X
X
X
X
HNO , H SO
3
2
4
4-O NC H
C H NO -4
C H NO -4
6 4 2
2
6
4
6
4
2
I, II
4
-O NC H
2
6
4
N
N
N
N
N
N
N
N
IV, V
IV, X = O; V, X = S.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 9 2004

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320
ARTAMONOVA et al.
Scheme 5.
Ph
S
(CH2)n
S
Ph
4-O NC H
S
(CH )
S
C H NO -4
6 4 2
2
6
4
2 n
HNO , H SO
N
N
3
2
4
N
N
N
N
N
N
N
N
N
N
N
N
N
N
VI, VII
VI, n = 1; VII, n = 2.
EXPERIMENTAL
The IR spectra were recorded in KBr on a UR-20
spectrometer. The NMR spectra were obtained on
a Bruker AC-200 spectrometer from solutions in
DMSO-d6.
acetic acid, 5 ml of methylene chloride, and 5 ml of
water. The mixture was stirred for 20 h at 35°C, 5 ml
of ethanol was added, the precipitate of manganese
dioxide was filtered off and washed with 10 ml of
methylene chloride, and the organic phase was
separated, washed with 10 ml of water, dried over
magnesium sulfate, and evaporated under reduced
pressure. Yield 0.54 g (51%), mp 169–171°C (from
Bis(1-phenyltetrazol-5-ylsulfanyl)methane and
,2-bis(1-phenyltetrazol-5-ylsulfanyl)ethane were syn-
thesized by the procedure reported in [9].
1
–
1
methanol). IR spectrum, ν, cm : 920, 1020, 1080,
1
3
7
160, 1250, 1350, 1400, 1470, 1510, 1600, 2940,
Tetrakis(1-phenyltetrazol-5-yloxymethyl)-
methane (I). A mixture of 4 mmol of 5-methylsul-
fonyl-1-phenyltetrazole, 1 mmol of pentaerythritol,
1
080. H NMR spectrum, δ, ppm: 4.20 s (8H, CH ),
2
.70 s (20H, H ). Found, %: C 43.79; H 2.96;
arom
N 24.63. C H N O S . Calculated, %: C 43.81;
3
3
28 16
8 4
4
mmol of NaOH, and 10 ml of acetonitrile was stirred
H 3.01; N 24.78.
for 5 h at 20°C. The mixture was diluted with 50 ml
of water, and the precipitate was filtered off, washed
with 20 ml of water, and dried in air. Yield 0.8 g
Tetrakis[1-(4-nitrophenyl)tetrazol-5-yloxy-
methyl]methane (IV). Compound II, 0.66 mmol, was
dissolved in 3 ml of 94% sulfuric acid, the solution
was cooled to 5°C, and 1.8 ml of 98% nitric acid was
added dropwise with stirring. The mixture was stirred
for 30 min at 5°C and for 1 h at 18–20°C and was
poured onto 50 g of finely crushed ice. The precipitate
was filtered off, washed with 20 ml of water, and
dried in air. Yield 0.8 g (70%), mp 245–246°C (from
(
84%), mp 199°C (from aqueous DMF, 1:1). IR spec-
–1
trum, ν, cm : 900, 960, 1019, 1050, 1070, 1100, 1130,
1
2
5
294, 1360, 1389, 1457, 1505, 1560, 1596, 2370,
1
380, 2900, 2980, 3100. H NMR spectrum, δ, ppm:
.20 s (8H, CH ), 7.50–7.70 m (20H, H ). Found, %:
2
arom
C 55.72; H 4.11; N 31.63. C H N O . Calculated, %:
3
3
28 16
4
C 55.62; H 3.94; N 31.46.
–
1
DMSO). IR spectrum, ν, cm : 920, 1012, 1040, 1059,
Tetrakis(1-phenyltetrazol-5-ylsulfanylmethyl)-
methane (II). A mixture of 3 mmol of 1-phenyl-4,5-
dihydrotetrazole-5-thione, 0.7 mmol of 1,3-dibromo-
,2-bis(bromomethyl)propane, 3 mmol of NaOH, and
ml of DMF was stirred for 5 h at 110°C. The mixture
1
112, 1189, 1308, 1354, 1420, 1468, 1504, 1529, 1567,
1
1614, 2361, 3140, 3150. H NMR spectrum, δ, ppm:
5
.10 s (8H, CH ), 7.90 d (8H, H
), 8.30 d
arom
2
2
5
(
8H, Harom). Found, %: C 44.30; H 2.83; N 31.37.
C H N O . Calculated, %: C 44.39; H 2.69; N 31.39.
3
3
24 20 12
was cooled to 18°C, 50 ml of a 5% aqueous solution of
sodium hydroxide was added, and the precipitate was
filtered off, washed with 20 ml of water, and dried in
air. Yield 0.35 g (66%), mp 158°C (from 2-propanol).
Tetrazoles V–VII were synthesized in a similar
way.
Tetrakis[1-(4-nitrophenyl)tetrazol-5-ylsulfanyl-
methyl]methane (V). Yield 72%, mp 154–155°C
–
1
IR spectrum, ν, cm : 900, 990, 1014, 1050, 1080,
–
1
1
1
089, 1180, 1190, 1240, 1279, 1387, 1420, 1458,
(from acetonitrile). IR spectrum, ν, cm : 980, 1006,
1
498, 1595, 2350, 2360, 2970, 3000, 3100. H NMR
1028, 1055, 1080, 1114, 1176, 1215, 1244, 1279, 1313,
spectrum, δ, ppm: 4.00 s (8H, CH ), 7.70 s (20H,
1344, 1385, 1398, 1433, 1494, 1533, 1595, 1610,
2
1
H
). Found, %: C 51.04; H 3.61; N 28.77.
3080. H NMR spectrum, δ, ppm: 3.90 s (8H, CH ),
arom
2
C H N S . Calculated, %: C 51.03; H 3.61; N 28.86.
8.00 d (8H, Harom), 8.50 d (8H, Harom). Found, %:
C 41.39; H 2.79; N 29.37. C H N O S . Calculated,
33
28 16 4
3
3
24 20
8 4
Tetrakis(1-phenyltetrazol-5-ylsulfonylmethyl)-
methane (III). Potassium permanganate, 6 mmol, was
added to a mixture of 1.3 mmol of compound II,
%
: C 41.42; H 2.51; N 29.29.
Bis[1-(4-nitrophenyl)tetrazol-5-ylsulfanyl]-
methane (VI). Yield 74%, mp 195–198°C (from
0
.13 mmol of tetrabutylammonium bromide, 1 ml of
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 9 2004

TETRAZOLES: XLVII.
1321
–
1
acetonitrile). IR spectrum, ν, cm : 990, 1020, 1040,
3. Newkome, G.R., Moorefield, C.N., and Vogtle, F.,
Dendrimers and Dendrons: Concepts, Synthesis,
Application, Weinheim: Wiley, 2001.
1
1
3
090, 1180, 1230, 1260, 1280, 1350, 1390, 1440,
500, 1540, 1600, 1620, 1680, 2870, 2940, 2970,
1
4
5
6
. Moorefield, C.N. and Newkome, G.R., C.R. Acad. Sci.,
003, vol. 6, p. 715.
. Kizhnyaev, V.N. and Vereshchagin, L.I., Usp. Khim.
003, vol. 72, p. 159.
. Zubarev, V.Yu., Gurskaya, G.V., Zavodnik, V.E., and
Ostrovskii, V.A., Khim. Geterotsikl. Soedin., 1997,
p. 1494.
030, 3100, 3130. H NMR spectrum, δ, ppm: 5.31 s
2
(
2H, CH ), 7.90 d (4H, H ), 8.50 d (4H, H ).
2 arom arom
Found, %: C 39.41; H 2.25; N 39.30. C H N O S .
1
5
10 10
4 2
2
Calculated, %: C 39.30; H 2.18; N 30.52.
,2-Bis[1-(4-nitrophenyl)tetrazol-5-ylsulfanyl]-
ethane (VII). Yield 97%, mp 189–190°C (from DMF).
1
–
1
IR spectrum, ν, cm : 990, 1020, 1040, 1070, 1090,
7
8
. Zubarev, V.Yu. and Ostrovskii, V.A., Khim. Geterotsikl.
Soedin., 2000, p. 867.
. Zubarev, V.Yu., Bezklubnaya, E.V., Pyartman, A.K.,
Trifonov, R.E., and Ostrovskii, V.A., Khim. Geterotsikl.
Soedin., 2003, p. 1496.
1
1
3
120, 1150, 1200, 1250, 1290, 1350, 1390, 1410,
440, 1500, 1540, 1600, 1620, 2880, 2940, 2970,
1
020, 3100, 3140. H NMR spectrum, δ, ppm: 3.82 s
(
4H, CH ), 7.90 d (4H, H ), 8.50 d (4H, H ).
2 arom arom
Found, %: C 40.56; H 2.31; N 29.51. C H N O S .
Calculated, %: C 40.68; H 2.54; N 29.66.
1
6
12 10
4
2
9. Gol’tsberg, M.A. and Koldobskii, G.I., Russ. J. Org.
Chem., 1996, vol. 32, p. 1194.
1
0. Gol’tsberg, M.A. and Koldobskii, G.I., Khim. Getero-
tsikl. Soedin., 1996, p. 1515.
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