Tetrazoles: LII. Synthesis of functionally substituted tetrazoles from benzene-1,3,5-tricarboxylic acid derivatives

Article abstract of DOI:10.1134/S1070428008040180

N,N′,N′-Triarylbenzene-1,3-5-tricarboximidoyl chlorides reacted with sodium azide under conditions of phase-transfer catalysis to give functionally substituted tetrazoles whose subsequent functionalization led to complex heterocyclic structures which may

Full text of DOI:10.1134/S1070428008040180

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 4, pp. 577–581. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © M.V. Zatsepina, T.V. Artamonova, G.I. Koldobskii, 2008, published in Zhurnal Organicheskoi Khimii, 2008, Vol. 44, No. 4,
pp. 582–586.
Tetrazoles: LII.* Synthesis of Functionally Substituted Tetrazoles
from Benzene-1,3,5-tricarboxylic Acid Derivatives
M. V. Zatsepina, 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 September 14, 2007
Abstract—N,N′,N″-Triarylbenzene-1,3,5-tricarboximidoyl chlorides reacted with sodium azide under condi-
tions of phase-transfer catalysis to give functionally substituted tetrazoles whose subsequent functionalization
led to complex heterocyclic structures which may be regarded as first-generation tetrazole-containing
dendrimers.
DOI: 10.1134/S1070428008040180
In continuation of our studies on the synthesis and
properties of functionally substituted tetrazoles [1–5],
we have developed an approach to complex hetero-
cyclic structures including three and more tetrazole
rings; these structures could be used for the preparation
of tetrazole-containing dendrimers. Analysis of pos-
sible ways for solving this problem led us to select
benzene-1,3,5-tricarboxylic acid derivatives which
were successfully used in the synthesis of various
functionally substituted tetrazoles. In the first step of
our study we showed that acylation of 2-(1-phenyl-1H-
tetrazol-5-yloxy)ethan-1-ol with benzene-1,3,5-tricar-
bonyl trichloride in the presence of pyridine gives tris-
[2-(1-phenyl-1H-tetrazol-5-yloxy)ethyl] benzene-
1,3,5-tricarboxylate (I) (Scheme 1).
We then tried to obtain functionally substituted
tetrazoles from the corresponding N,N′,N″-triarylben-
zene-1,3,5-tricarboxamides via sequential transforma-
tion of these compounds into imidoyl chlorides and
treatment of the latter with sodium azide under con-
ditions of phase-transfer catalysis. As a result, we
isolated a number of heterocyclic structures IIa–IIe
containing three tetrazole ring (Scheme 2). The oxida-
tion of compound IIc with sodium dichromate in
sulfuric acid smoothly afforded tricarboxylic acid III
(Scheme 3) which was then converted into the corre-
sponding N-aryl triamides Va and Vb (Scheme 4).
Using amide Vb as starting compound we obtained
complex heterocyclic system VI which includes six
tetrazole rings (Scheme 5).
Scheme 1.
N
N
N
O
Cl
O
O
N
O
OH
Pyridine
O
+
N
O
O
O
O
N
N
N
N
N
N
N
N
N
Cl
Cl
O
O
N
N
O
O
I
* For communication LI, see [1].
577

ZATSEPINA et al.
578
Scheme 2.
N
N
R
N
R
N
N
Cl
N
R
R
Bu4NBr, CHCl3–H2O
+
NaN3
Cl
N
N
N
N
Cl
R
N
N
N
N
N
R
IIa–IIe
R = MeO (a), EtO (b), Me (c), H (d), Br (e).
Scheme 3.
O
HO
N
N
N
N
O
OH
Na2Cr2O7, H2SO4
IIc
N
N
N
N
N
N
N
N
O
OH
III
1
Thus the use of benzene-1,3,5-tricarboxylic acid as
base structural unit opens the way to tetrazole-con-
taining dendrimers of the first generation.
3209, 3263. H NMR spectrum, δ, ppm: 3.97 s (9H,
CH3), 7.14 d (6H, Harom), 8.06 d (6H, Harom), 8.99 s
(3H, Harom), 10.80 s (3H, NH). Found, %: C 67.92;
H 5.31; N 7.88. C30H27N3O6. Calculated, %: C 68.56;
H 5.18; N 8.00.
EXPERIMENTAL
N,N′,N″-Tris(4-ethoxyphenyl)benzene-1,3,5-tri-
carboxamide. Yield 87%, mp 272–273°C (from
DMF–MeCN, 1:2). IR spectrum, ν, cm–1: 826, 922,
1045, 1115, 1174, 1242, 1303, 1394, 1412, 1477, 1511,
1595, 1606, 2872, 2933, 2977, 3071, 3132, 3272.
1H NMR spectrum, δ, ppm: 1.51 t (9H, CH3), 4.20 q
(6H, CH2), 7.12 d (6H, Harom), 8.09 d (6H, Harom),
9.05 s (3H, Harom), 10.94 s (3H, NH). Found, %:
C 69.59; H 5.97; N 7.26. C33H33N3O6. Calculated, %:
C 69.83; H 5.86; N 7.40.
The IR spectra were recorded on a Shimadzu FTIR-
8400s spectrometer from samples prepared as KBr
1
pellets. The H and 13C NMR spectra were measured
on a Bruker WM-400 spectrometer in DMSO-d6 unless
otherwise stated.
2-(1-Phenyl-1H-tetrazol-5-yloxy)ethan-1-ol was
synthesized according to the procedure described in
[6]. N,N′,N″-Triarylbenzene-1,3,5-tricarboxamides
were prepared as reported [7] and were converted into
the corresponding imidoyl chlorides by treatment with
thionyl chloride at 75–80°C over a period of 2 h [8].
N,N′,N″-Tris(4-methylphenyl)benzene-1,3,5-tri-
carboxamide. Yield 90%, mp 297–298°C (from
DMF–H2O, 5:1). IR spectrum, ν, cm–1: 811, 913,
1010, 1071, 1262, 1299, 1322, 1404, 1448, 1514,
1536, 1606, 1646, 2866, 2920, 3056, 3119, 3193,
N,N′,N″-Tris(4-methoxyphenyl)benzene-1,3,5-
tricarboxamide. Yield 91%, mp 281–282°C (from
DMF–MeCN, 1:2). IR spectrum, ν, cm–1: 828, 911,
1032, 1109, 1176, 1245, 1301, 1325, 1412, 1462, 1511,
1595, 1606, 1648, 2834, 2932, 2953, 3064, 3131,
1
3235. H NMR spectrum, δ, ppm: 2.30 s (9H, CH3),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 4 2008

TETRAZOLES: LII.
579
Scheme 4.
R
H
O
O
Cl
N
N
N
N
N
N
N
N
N
O
NH
R
Cl
O
4-RC6H4NH2
N
N
N
N
N
N
pyridine
SOCl2
III
N
N
N
N
N
N
N
N
N
N
H
O
N
Cl
O
R
IV
Va, Vb
R = MeO (a), Me (b).
Scheme 5.
Me
N
N
N
N
N
N
N
N
N
Me
N
N
N
N
N
(1) SOCl2
(2) NaN3, Bu4NBr, CHCl3–H2O
N
N
Vb
N
N
N
N
N
N
N
N
Me
VI
7.20 d (6H, Harom), 7.88 d (6H, Harom), 8.86 s (3H,
Harom), 10.76 s (3H, NH). Found, %: C 75.64; H 5.94;
N 8.81. C30H27N3O3. Calculated, %: C 75.45; H 5.70;
N 8.80.
N,N′,N″-Tris(4-bromophenyl)benzene-1,3,5-tri-
carboxamide. Yield 89%, mp 285–286°C (from
DMF–H2O, 5:1). IR spectrum, ν, cm–1: 819, 1011,
1073, 1174, 1258, 1292, 1317, 1394, 1487, 1517, 1536,
1
1595, 1649, 3056, 3116, 3235, 3263. H NMR spec-
N,N′,N″-Triphenylbenzene-1,3,5-tricarboxamide.
Yield 96%, mp 326–327°C (from DMFA–H2O, 5:1)
[7]. IR spectrum, ν, cm–1: 690, 753, 1257, 1320, 1444,
trum, δ, ppm: 7.55 d (6H, Harom), 7.78 d (6H, Harom),
8.69 s (3H, Harom), 10.74 s (3H, NH). Found, %:
C 48.51; H 2.73; N 6.32. C27H18Br3N3O3. Calculated,
%: C 48.25; H 2.70; N 6.25.
1
1497, 1544, 1599, 1650, 3064, 3285. H NMR spec-
trum, δ, ppm: 7.13–7.81 m (15H, Harom), 7.68 s (3H,
H
arom), 10.57 s (3H, NH). Found, %: C 74.51; H 4.88;
Tris[2-(1-phenyl-1H-tetrazol-5-yloxy)ethyl] ben-
zene-1,3,5-tricarboxylate (I). Benzene-1,3,5-tricar-
bonyl trichloride, 1.39 mmol, was slowly added to
N 9.77. C27H21N3O3. Calculated, %: C 74.47; H 4.86;
N 9.65.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 4 2008

ZATSEPINA et al.
580
a solution of 4.85 mmol of 2-(1-phenyl-1H-tetrazol-5-
yloxy)ethan-1-ol in 5 ml of pyridine under stirring at
30–35°C. The mixture was stirred for 3 h at 20°C,
diluted with 100 ml of water, and stirred for 15 min,
and the precipitate was filtered off, washed with water
(50 ml), and dried in air. Yield 0.72 g (67%), mp 54–
56°C (from EtOAc–EtOH, 2:1). IR spectrum, ν, cm–1:
759, 905, 930, 1021, 1029, 1100, 1133, 1231, 1297,
1329, 1400, 1450, 1505, 1563, 1596, 1730, 2890,
EtOAc, 3:1). IR spectrum, ν, cm–1: 762, 788, 900,
1018, 1074, 1113, 1264, 1442, 1497, 1517, 1596,
1
3055, 3067. H NMR spectrum, δ, ppm: 7.39–7.62 m
(15H, Harom), 7.88 s (3H, Harom). Found, %: C 63.57;
H 3.54; N 33.35. C27H18N12. Calculated, %: C 63.52;
H 3.55; N 32.92.
Compounds IIc and IIe were synthesized in a simi-
lar way.
1,3,5-Tris[1-(4-methylphenyl)-1H-tetrazol-5-yl]-
benzene (IIc). Yield 71%, mp 267–268°C (from
DMF–MeCN, 2:1). IR spectrum, ν, cm–1: 816, 896,
1002, 1015, 1066, 1105, 1270, 1423, 1446, 1489, 1515,
1
2961, 3071, 3078. H NMR spectrum, δ, ppm: 5.32 t
(6H, CH2), 5.49 t (6H, CH2), 7.95–8.22 m (15H,
Harom), 9.25 s (3H, Harom). Found, %: C 56.06; H 4.12;
N 21.92. C36H30N12O9. Calculated, %: C 55.81; H 3.90;
N 21.70.
1
2867, 2921, 3057, 3077. H NMR spectrum, δ, ppm:
2.60 s (9H, CH3), 7.55 s (12H, Harom), 8.22 s (3H,
1,3,5-Tris[1-(4-methoxyphenyl)-1H-tetrazol-5-
yl]benzene (IIa). A solution of 5.95 mmol of N,N′,N″-
tris(4-methoxyphenyl)benzene-1,3,5-tricarboximidoyl
trichloride in 30 ml of chloroform was slowly added to
a mixture of 20.81 mmol of sodium azide, 0.5 mmol of
tetrabutylammonium bromide, and 25 ml of water. The
mixture was stirred for 8 h at 20°C, and the organic
phase was separated, washed with water (30 ml), dried
over magnesium sulfate, and evaporated under reduced
pressure. Yield 2.0 g (89%), mp 255–256°C (from
MeCN–EtOH, 2:1). IR spectrum, ν, cm–1: 837, 897,
1025, 1046, 1064, 1104, 1172, 1255, 1304, 1423,
1449, 1514, 1590, 1607, 2840, 2935, 2963, 3007,
H
arom). Found, %: C 64.97; H 4.11; N 30.51.
C30H24N12. Calculated, %: C 65.21; H 4.38; N 30.42.
1,3,5-Tris[1-(4-bromophenyl)-1H-tetrazol-5-yl]-
benzene (IId). Yield 79%, mp 299–300°C (decomp.,
from DMF). IR spectrum, ν, cm–1: 833, 894, 1000,
1009, 1071, 1099, 1270, 1404, 1446, 1486, 1511, 1587,
1
3059, 3068, 3090. H NMR spectrum, δ, ppm: 7.71 d
(6H, Harom), 7.97 d (6H, Harom), 8.29 s (3H, Harom).
Found, %: C 43.30; H 2.15; N 22.78. C27H15Br3N12.
Calculated, %: C 43.40; H 2.02; N 22.49.
4,4′,4″-[Benzene-1,3,5-triyltris(1H-tetrazol-5,1-
diyl)]tribenzoic acid (III). Sulfuric acid (94%), 8 ml,
was slowly added to a mixture of 4.16 mmol of tetra-
zole IIc, 24.97 mmol of sodium dichromate, and 8 ml
of water under stirring at 18–20°C. The mixture was
stirred for 3 h at 110°C, cooled to 18–20°C, and
poured into 100 ml of an ice–water mixture. The pre-
cipitate was filtered off, washed with 5% sulfuric acid
(3×30 ml) and water (3×30 ml), and dissolved in
50 ml of 5% aqueous sodium hydroxide. The solution
was filtered and acidified with concentrated hydro-
chloric acid to pH 2, and the precipitate was filtered
off, washed with water (3×30 ml), and dried at 50°C.
Yield 1.8 g (67%), mp >300°C (from DMF–EtOH,
1:1). IR spectrum, ν, cm–1: 772, 785, 865, 1000, 1013,
1039, 1062, 1105, 1174, 1271, 1385, 1416, 1446, 1513,
1
3081. H NMR spectrum, δ, ppm: 3.96 s (9H, CH3),
7.29 d (6H, Harom), 7.62 d (6H, Harom), 8.23 s
(3H, Harom). Found, %: C 59.71; H 4.11; N 28.23.
C30H24N12O3. Calculated, %: C 60.00; H 4.03; N 27.99.
Compound IIb was synthesized in a similar way.
1,3,5-Tris[1-(4-ethoxyphenyl)-1H-tetrazol-5-yl]-
benzene (IIb). Yield (85%), mp 192–193°C (from
MeCN–EtOH, 1:1). IR spectrum, ν, cm–1: 838, 899,
920, 1047, 1109, 1172, 1257, 1305, 1393, 1423, 1442,
1475, 1514, 1589, 1608, 2897, 2935, 2980, 3078.
1H NMR spectrum, δ, ppm: 1.35 t (9H, CH3), 4.10 q
(6H, CH2), 7.04 d (6H, Harom), 7.34 d (6H, Harom), 7.91 s
(3H, Harom). Found, %: C 61.42; H 4.31; N 25.91.
C33H30N12O3. Calculated, %: C 61.67; H 4.70; N 26.15.
1
1570, 1605, 1641, 1712, 3076. H NMR spectrum, δ,
ppm: 7.31 s (3H, Harom), 7.32 d (6H, Harom), 7.86 d (6H,
H
131.2, 132.1, 133.9, 137.0, 152.3, 166.7. Found, %:
C 55.64; H 3.01; N 25.86. C30H18N12O6. Calculated, %:
C 56.08; H 2.82; N 26.16.
1,3,5-Tris(1-phenyl-1H-tetrazol-5-yl)benzene
(IId). A solution of 5.95 mmol of N,N′,N″-triphenyl-
benzene-1,3,5-tricarboximidoyl chloride in 30 ml of
chloroform was slowly added at 20°C to a mixture of
20.81 mmol of sodium azide, 0.5 mmol of tetrabutyl-
ammonium bromide, and 25 ml of water. The mixture
was stirred for 8 h at 20°C, and the precipitate was
filtered off, washed with water (100 ml), and dried at
50°C. Yield 2.2 g (73%), mp 264–265°C (from MeCN–
arom). 13C NMR spectrum, δC, ppm: 125.7, 126.1,
4,4′,4″-[Benzene-1,3,5-triyltris(1H-tetrazol-5,1-
diyl)]tribenzoyl trichloride (IV). A mixture of
0.78 mmol of compound III, 3 ml of thionyl chloride,
and one drop of DMF was stirred for 2 h at 75–80°C.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 4 2008

TETRAZOLES: LII.
581
Excess thionyl chloride was removed under reduced
pressure, and the residue was treated with petroleum
ether (3×20 ml). Yield 0.48 g (89%). Trichloride IV
thus obtained was brought into further syntheses with-
out additional purification.
a mixture of 1.35 mmol of sodium azide, 0.5 mmol of
tetrabutylammonium bromide, and 25 ml of water. The
mixture was stirred for 8 h at 20°C, and the organic
phase was separated, washed with water (30 ml), dried
over magnesium sulfate, and evaporated under reduced
pressure. Yield 0.23 g (61%), mp 187–189°C (from
DMF–EtOAc, 2:1). IR spectrum, ν, cm–1: 752, 820,
848, 897, 1000, 1061, 1101, 1138, 1179, 1268, 1435,
1475, 1514, 1613, 2855, 2923, 3048, 3070, 3075.
1H NMR spectrum (acetone-d6), δ, ppm: 2.41 s (9H,
CH3), 7.42 d (6H, Harom), 7.50 d (6H, Harom), 7.61 d
(6H, Harom), 7.80 d (6H, Harom), 8.10 s (3H, Harom).
Found, %: C 62.51; H 3.72; N 34.41. C51H36N24. Cal-
culated, %: C 62.19; H 3.68; N 34.13.
4,4′,4″-[Benzene-1,3,5-triyltris(1H-tetrazol-5,1-
diyl)]tris[N-(4-methoxyphenyl)benzamide] (Va).
Trichloride IV, 0.62 mmol, was slowly added to a so-
lution of 2.17 mmol of 4-methoxyaniline in 5 ml of
pyridine under stirring at 30–35°C. The mixture was
stirred for 3 h at 20°C, 100 ml of 5% hydrochloric acid
was added, the mixture was stirred for 15 min, and the
precipitate was filtered off, washed with water (50 ml),
and dried at 50°C. Yield 0.22 g (59%), mp 197–200°C
(from DMF–EtOH, 2:1). IR spectrum, ν, cm–1: 761,
828, 896, 1030, 1104, 1176, 1247, 1322, 1414, 1441,
1512, 1534, 1599, 1607, 1656, 2836, 2935, 3002, 3072,
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 08-03-00342).
1
3301. H NMR spectrum, δ, ppm: 3.73 s (9H, CH3),
REFERENCES
6.92 d (6H, Harom), 7.59 d (6H, Harom), 7.65 d (6H,
H
arom), 8.04 d (9H, Harom), 10.31 s (3H, NH). Found,
1. Myznikov, L.V., Roh, J., Artamonova, T.V., Hrabalek, A.,
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%: C 63.68; H 4.11; N 21.32. C51H39N15O6. Calculated,
%: C 63.94; H 4.10; N 21.93.
4,4′,4″-[Benzene-1,3,5-triyltris(1H-tetrazol-5,1-
diyl)]tris[N-(4-methylphenyl)benzamide] (Vb) was
synthesized in a similar way. Yield 0.36 g (64%),
mp 193–195°C (from DMF–EtOH, 2:1). IR spectrum,
ν, cm–1: 760, 813, 857, 895, 1000, 1012, 1102, 1261,
1298, 1321, 1405, 1444, 1514, 1606, 1652, 2855, 2921,
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1
2950, 2950, 3031, 3193, 3307. H NMR spectrum, δ,
ppm: 2.89 s (9H, CH3), 7.72 d (6H, Harom), 7.97 d (6H,
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(3H, NH). Found, %: C 66.94; H 4.09; N 23.15.
C51H39N15O3. Calculated, %: C 67.32; H 4.32; N 23.09.
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diyl-4,1-phenylene)]tris[1-(4-methylphenyl)-1H-tet-
razole] (VI). Tris-imidoyl chloride prepared from
amide Vb, 0.38 mmol, was dissolved in 30 ml of
chloroform, and the solution was slowly added to
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 4 2008