Synthesis of some symmetrically substituted compounds derived from 1,3-bis(6-azauracil-1-yl)benzene and 1,3,5-tris(6-azauracil-1-yl)benzene [1]

Article abstract of DOI:10.1002/jhet.5570390219

The 3,5-bis(5 -carboxy-6-azauracil-1-yl)aniline (7) and 1,3,5-tris(5-carboxy-6-azauracil-l-yl)benzene (10) were prepared from 3-amino-5-nitroacetanilide (1) via intermediates 2-6. A series of other substituted 6-azauracil derivatives 9, 11-14 were also pr

Full text of DOI:10.1002/jhet.5570390219

Mar-Apr 2002
Synthesis of Some Symmetrically Substituted Compounds
Derived from 1,3-Bis(6-Azauracil-1-yl)benzene and 1,3,5-
Tris(6-Azauracil-1-yl)benzene [1]
357
Petr Bílek and Jan Slouka*
Dept. of Organic Chemistry, Palacky University, Tr.Svobody 8, 771 46 Olomouc, Czech Republic
Received August 2, 2001
The 3,5-bis(5-carboxy-6-azauracil-1-yl)aniline (7) and 1,3,5-tris(5-carboxy-6-azauracil-1-yl)benzene
(10) were prepared from 3-amino-5-nitroacetanilide (1) via intermediates 2-6. A series of other substituted
6-azauracil derivatives 9, 11-14 were also prepared.
J. Heterocyclic Chem., 39, 357 (2002).
Double 6-azauracil derivatives with two 6-azauracil
wash the ferric hydroxide precipitate thoroughly since a lot
of the desired amino derivative can be adsorbed on the
huge surface of the hydroxide.
The second 6-azauracil nucleus was built in similar way
as the first one. For the cyclization of hydrazone 5 to the
N-[3,5-bis(6-azauracil)phenyl]acetamide (6), the alkaline
cyclization in a solution of sodium carbonate at a room
temperature was used. In this way, we received the desired
derivative 6 in a very good yield.
The protecting acetyl group was removed by acidic
hydrolysis in hydrochloric acid. During this step, the
nitrile groups were hydrolyzed to carboxyl groups. The
desired amine 7 was isolated from the reaction mixture as
the hydrochloride salt.
The third 6-azauracil nucleus was built in the same way
as the second one via a hydrazone 8 that was again
cyclized in alkaline solution of sodium carbonate to the
desired triple 6-azauracil derivative 9. The last nitrile
group of derivative 9 was hydrolyzed in a mixture of acetic
acid and hydrochloric acid resulting in symmetrical tris
carboxylic acid 10.
During the synthesis of desired amino compounds 7 or
triple 6-azauracil derivative 9, other synthetic ways were
also studied. One of them began with the acetyl derivative
3 that was hydrolyzed by boiling in hydrochloric acid to
the amino acid 11. This amino derivative was used for the
preparation of the double 6-azauracil derivative 13 via
hydrazone 12. The cyclization of hydrazone proceeded
again by reflux of its pyridine solution. However, further
reduction of nitro group of derivative 13 to the desired
amino derivative failed due to isolation problems of the
amino compound from the reaction mixture.
The other possible alternative way lead through diamino
derivative 14, which was prepared by acidic hydrolysis of
amino derivative 4. The further step should have employed
the double diazotation and further coupling with ethyl
cyanoacetylcarbamate to get the double hydrazono deriva-
tive. Unfortunately, the procedure failed.
nuclei bonded on the benzene ring in a meta orientation,
relative to each other, might be interesting from the point
of view of their possible interactions with various sub-
strates. Thanks to the free rotation of heterocycles around
the heterocycle-benzene bond they can assume various
conformations with various distances of bonding hydrogen
atoms. Some derivatives of that type have been prepared
earlier [2-5]. However, these derivatives were either
unsubstituted on benzene ring [2-4] or some vicinal
amino-, hydroxy- and hydrazino derivatives where both 6-
azauracil rings were connected by C atom in position 5 of
the 6-azauracil ring.
The main topic of this communication is the synthesis of
1,3-di-6-azauracil derivatives of benzene, where both 6-
azauracil rings are connected by N atom in position 1 of 6-
azauracil ring that contain a amino group at the 5 position
of benzene. Thus generating a symmetric compound with
respect to both 6-azauracil rings. The main attention was
dedicated to the synthesis of the symmetrical 1,3,5-tris(6-
azauracil-1-yl)benzene derivative 10. Such compound has
never been described before.
As a starting material for the preparation of above
described compounds we chose 3-amino-5-nitroac-
etanilide (1), which was prepared from 3,5-dinitroaniline
by acetylation followed by the reduction of one nitro group
using (NH ) S.
4 2
Diazotization of 1 and further coupling of the formed
diazonium salt with ethyl cyanoacetylcarbamate afforded
the corresponding hydrazone 2 in a good yield. The hydra-
zone 2 was then cyclized thermally by boiling in dry pyri-
dine to the 1-(3-acetylamino-5-nitrophenyl)-6-azauracil-5-
carbonitrile (3). The reaction is very sensitive to the pres-
ence of moisture in the pyridine, which can cause
hydrolytic splitting of the formed triazine ring. The traces
of side product were removed by thorough washing of
crude triazine 3 with acetic acid. In the next step, the nitro
group of 3 was reduced to the corresponding amino deriv-
ative 4. For the reduction, we used ferrous hydroxide,
which is heavily employed for such type of synthesis in
our laboratory. It is very convenient to prepare and is
selective to nitro group only. However, it was necessary to
Due to the free rotation of 6-azauracil nuclei around sin-
gle benzene-6-azauracil bond, all double 6-azauracil deriv-
atives (6-8, 13) and both triple 6-azauracil derivatives
(9,10) can assume various space conformations with

358
P. Bílek and J. Slouka
Vol. 39
-1
changing distance of 6-azauracil hydrogen atoms so they
could bind into various substrates.
ment. Wave numbers are in cm . Elemental analyses were per-
formed by using an EA 1108 Elemental Analyser (Fison
Instrument). NMR spectra were measured on a Bruker AMX-360
(360 MHz) and Varian Unity+ 300 (300 MHz) spectrometers in
EXPERIMENTAL
DMSO-d solutions; the chemical shifts δ are reported in ppm.
6
3-Amino-5-nitroacetanilide (1).
The melting points were determined on a Boetius stage and are
not corrected. The infrared spectra were measured using KBr disc
technique and scanned on an ATI Unicam Genesis FTIR instru-
Ethanolic solution of (NH ) S was prepared in advance in this
4 2
manner: A solution of 54 ml of 26% ammonia in 100 ml of 96%

Mar-Apr 2002
Synthesis of Some Symmetrically Substituted Compounds
359
ethanol was saturated under cooling with 10.5 g (0.3 mol) of sul-
phane. Resulting solution contains 0.14 g (2.05 mmoles) of
2244, 1750, 1730, 1674, 1622, 1533, 1462, 1426, 1334, 1285,
1221, 1231, 1167, 1096, 1020, 895, 797, 750, 720, 689, 573, 548,
435.
(NH ) S in 1 ml.
4 2
A solution of 1.86 g (10 mmoles) of 3,5-dinitroaniline in 7 ml
of acetanhydride was heated for 1 hour at 105 °C on an oil bath.
Then, the resulting solution was poured into 370 ml of ice water.
The precipitated solid was collected by suction and washed with
water. Crude N-3,5-dinitrophenylacetamide was dissolved in 60
ml of ethanol and the solution was allowed to reflux. Into the
Anal. Calcd. for C H N O •H O (333.3): C, 43.11; H, 2.99;
N, 25.15. Found: C, 42.90; H, 2.56; N, 25.35.
12
8
6
5
2
2-(3-Acetamino-5-aminophenyl)-3,5-dioxo-2,3,4,5-tetrahydro-
1,2,4-triazin-6-carbonitrile (4).
A solution of 2.225 g (8 mmoles) of FeSO •7H O in 8 ml of
4
2
boiling solution, 15 portions of (NH ) S (prepared as described
above) was added in course of 75 minutes (each portion = 1 ml of
water was added to the warm solution of 2.525 g (8 mmoles) of
Ba(OH) •8H O in 18 ml of warm water. The mixture of precipi-
4 2
2
2
(NH ) S solution). Then, the reaction mixture was allowed to
tated Fe(OH) and BaSO was added in small portions to the
4 2
2 4
reflux for 30 minutes then cooled and filtered. The filtrate was
taken down on a boiling water bath. The residue was mixed with
6 ml of 36% HCl and 50 ml of water and the mixture was filtered.
The filtrate was neutralized using 10% NaOH solution. The next
day, the precipitated solid was collected by suction, washed with
water and in air. Double recrystallization from water afforded
orange solid with overall yield 70 %, mp 205-206 °C (ref. 204-
205 °C [6]).
solution of 332 mg (1 mmol) of nitro triazine 3 and 2 ml of 25%
ammonia in 30 ml of water. The reaction mixture was then heated
for 5 minutes at 60 °C and then on a boiling water bath for 60
minutes with continuous stirring. Hot reaction mixture was then
filtered and the precipitate was washed thoroughly with a warm
1% ammonia solution. Combined filtrates were then taken down
in vacuo. The residue was mixed with little warm water, ammo-
nia and charcoal and resulting solution was filtered. The filtrate
was then acidified with 98% acetic acid. The next day the precip-
itated solid was collected by suction, washed with water and
Anal. Calcd. for C H N O (195.8): C, 49.23; H, 4.62; N,
8
9 3 3
21.54. Found: C, 49.26; H, 4.18; N, 21.29.
dried in air to give 249 mg (75 %) of aminotriazine 4. mp 229-
Ethyl 3-Acetamino-5-nitrophenylhydrazonocyanoacetylcarba-
mate (2).
1
230 °C (water); H-nmr: δ 2.05 (s, 3H, COCH ); 5.50 (br, 2H,
3
NH ); 6.39 (t, 1H, J=1.9, H ); 6.90 (t, 1H, J=1.9, H ); 6.97 (t, 1H,
2
4
6
A solution of 80 mg of NaNO (1.15 mmol) in 3 ml of ice-cold
J=1.9, H ); 9.88 (s, 1H, NH); 12.95 (br, 1H, NH); ir: 3395, 2791,
2
2
water was added drop wise at 0-5 °C to a pre-cooled solution of
196 mg of amine 1 (1 mmol) in a mixture of 2.5 ml of 98% acetic
acid, 3 ml of 36% hydrochloric acid and 15 ml of water. Reaction
mixture was then left to stand in an ice bath for another 20 min-
utes. Then, the solution of diazonium salt was added drop wise to
a cooled solution that was prepared in this manner: 500 mg (3
mmoles) of ethyl cyanoacetylcarbamate was dissolved in 230 ml
of hot water and, after cooling to 0 °C, 10 g of sodium acetate
was added. The reaction mixture was left to stand at 0-5 °C. The
next day, the precipitated solid was collected by suction, thor-
oughly washed with water and dried in air to give 353.6 mg (97
2244, 1709, 1684, 1620, 1599, 1554, 1486, 1444, 1371, 1298,
1155, 996, 849, 577, 553.
Anal. Calcd. for C H N O •H O (334.3): C, 43.12; H, 3.02;
12
8
6
5
2
N, 25.14. Found: C, 43.32; H, 3.41; N, 24.99.
Ethyl 3-(3,5-Dioxo-2,3,4,5-tetrahydro-6-cyano-1,2,4-triazin-2-
yl)-5-acetaminophenylhydrazonocyanoacetylcarbamate (5).
A solution of 30 mg (0.45 mmol) of NaNO in 1 ml of ice-cold
2
water was added drop wise at 0-5 °C to a pre-cooled solution of
100 mg (0.32 mmol) of aminotriazine 4 in a mixture of 4 ml of
98% acetic acid, 0.5 ml of 36% hydrochloric acid and 0.5 ml of
water. Reaction mixture was then left to stand in an ice bath for
another 20 minutes. Then, the solution of diazonium salt was
added drop wise to a cooled solution that was prepared in this
manner: 144 mg (1.1 mmol) of ethyl cyanoacetylcarbamate was
dissolved in 60 ml of hot water and, after cooling to 0 °C, 4 g of
sodium acetate was added. The reaction mixture was left to stand
at 0-5 °C. The next day, the precipitated solid was collected by
suction, thoroughly washed with water and dried in air to give
1
%) of hydrazone 2; mp 218-220 °C (ethanol); H-nmr: δ 1.32 (t,
3H, J=7.3, CH ); 2.15 (s, 3H, COCH ); 4.24 (q, 2H, J=7.3, CH );
3
3
2
8.25 (m, 2H, J=2.1, H +H ); 8.33 (t, 1H, J=2.1, H ); 10.53 (s, 1H,
2
4
6
NH); 10.88 (s, 1H, NH); 12.47 (s, 1H, NH); ir: 3334, 3223, 3098,
2990, 2223, 2191, 1765, 1681, 1607, 1541, 1488, 1447, 1371,
1348, 1296, 1266, 1235, 1215, 1159, 1131, 1025, 989, 920, 879,
779, 745, 674, 643, 574, 538.
Anal. Calcd. for C
H N O (362.2): C, 46.41; H, 3.87; N,
14 14 6 6
137 mg (91 %) of hydrazone 5; mp 235 °C (decomp.) (ethanol);
23.21. Found: C, 46.81; H, 3.90; N, 23.49.
1
H-nmr: δ 1.30 (t, 3H, J=7.0, CH ); 4.23 (q, 2H, J=7.0, CH );
3
2
2-(3-Acetamino-5-nitrophenyl)-3,5-dioxo-2,3,4,5-tetrahydro-
1,2,4-triazin-6-carbonitrile (3).
2.12 (s, 3H, COCH ); 7.56 (t, 1H, J=2.0, H ); 7.61 (t, 1H, J=2.0,
3
4
H ); 7.97 (t, 1H, J=2.0, H ); 10.31 (s, 1H, NH); 10.51 (s, 1H,
2
6
A solution of 362 mg (1 mmol) of hydrazone 2 in 30 ml of dry
pyridine was refluxed for 20 hours and then taken down in vacuo.
The residue was mixed with little water and a few drops of 36%
HCl to adjust pH. The solid was collected with suction and mixed
with 5 ml of 98% acetic acid. The mixture was refluxed for 5
minutes and filtered. The filtrate contains pure hydrazonecyano-
acetamide derivative arose by hydrolytic splitting of triazine 3.
The filtration cake of pure triazine 3 was washed with water and
NH); 12.39 (br, 1H, NH); 12.72 (br, 1H, NH); ir: 3353, 2988,
2215, 1779, 1712, 1674, 1618, 1554, 1481, 1415, 1324, 1279,
1195, 1153, 1023, 918, 868, 692, 603, 563, 535, 464.
Anal. Calcd. for C
H N O •3H O (507.2): C, 42.60; H,
18 15 9 6 2
4.14; N, 24.85. Found: C, 42.78; H, 4.12; N, 24.74.
3,5-Bis(3,5-dioxo-2,3,4,5-tetrahydro-6-cyano-1,2,4-triazin-2-
yl)acetanilide (6).
dried in air to give 246 mg (75 %) of triazine 3; mp 284 °C
A mixture of 100 mg (0,2 mmol) of hydrazone 5 and 72 mg
1
(decomp.) (ethanol); H-nmr: δ 2.17 (s, 3H, COCH ); 8.08 (t, 1H,
(0.68 mmol) of Na CO in 15 ml of water was left to stand for 10
3
2 3
J=2.0, H ); 8.21 (t, 1H, J=2.0, H ); 8.67 (t, 1H, J=2.0, H ); 10.73
(s, 1H, NH); 13.23 (br, 1H, NH); ir: 3370, 3122, 2990, 2813,
days with intermittent stirring. Then, after addition of little char-
coal, the mixture was filtered and filtrate was acidified with 12%
2
4
6

360
P. Bílek and J. Slouka
Vol. 39
HCl to pH=1. The next day, the precipitated solid was collected
by suction, washed with water and dried in air to give 75 mg (88
%) of double triazine 6. mp >360 °C (water/ethanol); H-nmr: δ
A solution of 107 mg (0.2 mmol) of triazine 9 in a mixture of 8
ml of 98% acetic acid and 8 ml of 36 % HCl was refluxed for 5
hours and then taken down on a boiling water bath. The solid was
mixed with little water, collected by suction, washed with water
and dried in air to give 108 mg (91 %) of triple triazino car-
1
2.11 (s, 3H, COCH ); 7.42 (t, 1H, J=2.0, H ); 7.92 (t, 1H, J=2.0,
3
4
H ); 7.94 (t, 1H, J=2.0, H ); 10.47 (s, 1H, NH); 12.69 (br, 1H,
6
2
1
NH); 13.08 (br, 1H, NH); ir: 3493, 3382, 2979, 2786, 2244, 1720,
1613, 1557, 1475, 1424, 1307, 1159, 1076, 1016, 978, 880, 807,
739, 667, 585, 566, 476.
boxylic acid 10; mp 297-298 °C (ethanol/water); H-nmr: 7.80 (s,
3H, H +H +H ); ir: 3575, 3465, 3345, 3240, 1734, 1691, 1617,
2
4
6
1443, 1291, 1158, 1028, 812, 623.
Anal. Calcd. for C H N O •H O (425.3): C, 45.18; H, 2.61;
Anal. Calcd. for C H N O •3H O (597.4): C, 36.19; H,
16
9
9
5
2
18
9
9
12
2
N, 29.64. Found: C, 45.47; H, 3.02; N, 29.34.
2.53; N, 21.10. Found: C, 36.20; H, 2.37; N, 20.99
3,5-Bis(3,5-dioxo-2,3,4,5-tetrahydro-6-carboxy-1,2,4-triazin-2-
yl)-aniline (7).
2-(3-Amino-5-nitrophenyl)-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-
triazin-6-carboxylic Acid (11).
A solution of 106 mg (0.25 mmol) of triazine 6 in 10 ml of
20% HCl was refluxed for 4 hours. Upon cooling, needles of
hydrochloride precipitated from reaction mixture. The next day,
the precipitate was collected by suction and dried in air to give 93
mg (81 %) of amine 7 hydrochloride; mp >360 °C (10% HCl);
A mixture of 400 mg (1.2 mmol) of triazine 3 and 20 ml of
20% HCl was refluxed for 5 hours. After the addition of little
charcoal, the mixture was filtered and the filtrate was taken down
on a boiling water bath. The residue was mixed with 15 ml of
20% Na CO solution and filtered. The filtrate was acidified with
2
3
1
H-nmr: δ 6.75 (d, 2H, J=1.9, H +H ); 6.77 (t, 2H, J=1.9, H );
9% HCl. The next day, the precipitated solid was collected by
suction, thoroughly washed with water and dried in air to give
2
6
4
12.55 (br, 2H, 2xNH); ir: 3448, 3082, 2833, 1729, 1618, 1553,
1410, 1311, 1154, 1055, 930, 870, 817, 740, 657, 588, 570, 460.
Anal. Calcd. for C H N O •HCl•H O (457.75): C, 36.74; H,
1
326 mg (83 %) of acid 11. mp 235 °C (decomp.) (water); H-nmr:
δ 6.21 (br, 2H, NH ); 7.16 (t, 1H, J=2.1, H ); 7.47 (t, 1H, J=2.1,
14
9
7
8
2
2
2
3.02; N, 21.42. Found: C, 36.44; H, 2.64; N, 21.42.
H ); 7.53 (t, 1H, J=2.1, H ); 12.59 (br, 1H, NH); ir: 3425, 3356,
4
6
3230, 3037, 2807, 1720, 1704, 1637, 1537, 1401, 1358, 1300,
1157, 805, 768, 637, 574.
Ethyl 3,5-Bis(3,5-dioxo-2,3,4,5-tetrahydro-6-carboxy-1,2,4-tri-
azin-2-yl) phenylhydrazonocyanoacetylcarbamate (8).
Anal. Calcd. for C H N O •2H O (329.2): C, 36.48; H, 3.37;
10
7
5
6
2
A solution of 25 mg (0.3 mmol) of NaNO in 2 ml of ice-cold
2
N, 21.28. Found: C, 36.75; H, 2.98; N, 21.37.
water was added drop wise at 0-5 °C to a pre-cooled solution of
139 mg (0.25 mmol) of amine 7 in 3 ml of 36% hydrochloric acid
and 5 ml of water. Reaction mixture was then left to stand in an ice
bath for another 30 minutes. Then, the solution of diazonium salt
was added drop wise to a cooled solution that was prepared in this
manner: 100 mg (0.7 mmol) of ethyl cyanoacetylcarbamate was
dissolved in 100 ml of hot water and, after cooling to 0 °C, 4 g of
sodium acetate was added. The reaction mixture was left to stand
at 0-5 °C. The next day, the precipitated solid was collected by
suction, thoroughly washed with water and dried in air to give 139
Ethyl 3-Nitro-5-(3,5-dioxo-2,3,4,5-tetrahydro-6-carboxy-1,2,4-
triazin-2-yl)phenylhydrazonocyanacetylcarbamate (12).
A solution of 160 mg (2.32 mmoles) of NaNO in 5 ml ice-
2
cold water was added drop wise at 0-5 °C to a pre-cooled solu-
tion of 660 mg (2 mmoles) of amine 11 in a mixture of 10 ml of
36% hydrochloric acid and 30 ml of water. Reaction mixture
was then left to stand in an ice bath for another 30 minutes.
Then, the solution of diazonium salt was added drop wise to a
cooled solution that was prepared in this manner: 900 mg (5.4
mmoles) of ethyl cyanoacetylcarbamate was dissolved in 250
ml of hot water and, after cooling to 0 °C, 20 g of sodium
acetate was added. The reaction mixture was left to stand at
0-5 °C. The next day, 15 ml of 36% HCl was added to the solu-
tion of hydrazone and the precipitated solid was collected by
suction, washed thoroughly with water and dried in air to give
541 mg (57 %) of hydrazone 12. mp 226-228 °C (decomp.)
1
mg (98 %) of hydrazone 8; mp >360 °C (ethanol); H-nmr: δ 1.23
(t, 3H, J=7.2, CH ); 4.13 (q, 2H, J=7.2, CH ); 7.31 (t, 1H, J=1.8,
3
2
H ); 7.60 (d, 2H, J=1.8, H +H ); 9.38 (br, 1H, NH); ir: 3442,
4
2
6
3082, 2988, 2799, 2219, 1777, 1705, 1614, 1444, 1414, 1371,
1304, 1279, 1176, 1155, 1017, 962, 892, 821, 735, 634, 564.
Anal. Calcd. for C
H
N
O
(570.4): C, 42.12; H, 2.47; N,
20 14 10 11
24.56. Found: C, 42.45; H, 2.80; N, 24.49.
1
(ethanol); H-nmr: δ 1.32 (t, 3H, J=7.1, CH ); 4.26 (q, 2H,
2-[3,5-Bis(3,5-dioxo-2,3,4,5-tetrahydro-6-carboxy-1,2,4-triazin-
2-yl)phenyl]-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-car-
bonitrile (9).
3
J=7.1, CH ); 8.21 (t, 1H, J=2.0, H ); 8.32 (t, 1H, J=2.0, H );
2
2
4
8.73 (t, 1H, J=2.0, H ); 11.03 (s, 1H, NH); 12.68 (s, 1H, NH);
6
ir: 3559, 3417, 3096, 2220, 1771, 1716, 1709, 1626, 1541,
1498, 1472, 1466, 1405, 1353, 1317, 1279, 1239, 1215, 1184,
1150, 1094, 1024, 922, 668, 571.
A mixture of 114 mg (0.2 mmol) of hydrazone 8 and 106 mg (1
mmol) of Na CO in 20 ml of water was left to stand for 10 days
2
3
with intermittent stirring. Then, after addition of little charcoal, the
mixture was filtered and filtrate was acidified with 12% HCl to
pH=1. The next day, the precipitated solid was collected by suc-
tion, washed with water and dried in air to give 79 mg (75 %) of
Anal. Calcd. for C
H N O •H O (478.3): C, 40.17; H, 2.93;
10 12 8 9 2
N, 23.43. Found: C, 39.75; H, 2.64; N, 23.71.
2-[3-Nitro-5-(3,5-dioxo-2,3,4,5-tetrahydro-6-cyano-1,2,4-tri-
azin-2-yl)phenyl]-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-
carboxylic Acid (13).
1
triple triazine 9; mp >360 (water/ethanol); H-nmr: δ 7.78 (d, 2H,
J=2.0, H +H ); 7.85 (t, 1H, J=2.0, H ); ir: 3444, 3209, 2242, 1724,
2
6
4
1612, 1560, 1440, 1408, 1305, 1152, 1029, 818, 739, 626, 567.
Anal. Calcd. for C H N •H O (532.4): C, 39.86; H,
1.86; N, 25.83. Found: C, 39.58; H, 2.02; N, 25.97.
A solution of 160mg (0.33 mmol) of hydrazone 12 in 40 ml
of dry pyridine was refluxed for 21 hours and then taken down
in vacuo. The residue was mixed with little water and a few
drops of 36% HCl to adjust pH. The solid was collected with
suction, washed with water and dried in air to give 123 mg
O
18
8
10 10
2
1,3,5-Tris(3,5-dioxo-2,3,4,5-tetrahydro-6-carboxy-1,2,4-triazin-
2-yl)benzene (10).

Mar-Apr 2002
Synthesis of Some Symmetrically Substituted Compounds
361
(87 %) of double triazine 13; mp 205 °C (decomp.) (water);
Acknowledgement.
1
H-nmr: δ 8.21 (t, 1H, J=2.0, H ); 8.47 (t, 1H, J=2.0, H ); 8.59
4
2
This research was supported by grant No. CEZ: J 14-98;
N 70000008 of Grant agency of the Czech Republic and by grant
(t, 1H, J=2.0, H ); 12.73 (br, 1H, NH); 13.95 (br, 1H, NH); ir:
6
3012, 2795, 2244, 1715, 1627, 1540, 1409, 1357, 1303, 1182,
1151, 1094, 891, 748, 568.
ˇ
ˇ
MSM 15310008 of MSMT CR.
REFERENCES AND NOTES
Corresponding author, Fax: ++420-68-5634405,
Anal. Calcd. for C H N O •H O (432.2): C, 38.89; H, 1.85;
14
6
8
8
2
N, 25.93. Found: C, 38.90; H, 1.76; N, 25.55.
2-(3,5-Diaminophenyl)-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-tri-
azin-6-carboxylic Acid (14).
*
e-mail: WIEDERMANNOVA@PRFNW.UPOL.CZ
[1] Part 3 of "Polycyclic Heterocycles with Acidic N-H
Group" series. For previous paper see I. Wiedermannova and J.
Slouka, J. Heterocyclic Chem. 38, 1465 (2001).
[2] J. Slouka, Collect. Czech. Chem. Commun., 55, 2967
(1990).
[3] J. Slouka, V. Bekarek and J. Hlavac, Collect. Czech.
Chem. Commun., 59, 2741 (1994).
[4] J. Hlavac, J. Slouka, J. Heterocyclic Chem., 34, 917
(1997).
A solution of 108 mg (0.25 mmol) of amine 4 in 10 ml of 20%
HCl was refluxed for 4 hours. Then, after the addition of little
charcoal, the mixture was filtered. After standing overnight at 0-
5 °C, the solid precipitated from the solution. The solid was col-
lected with suction, washed with ether and dried in air to give 68
mg (82 %) of diamine 14 dihydrochloride; mp >360 °C (20%
1
HCl); H-nmr: δ 6.71 (t, 1H, J=1.8, H ); 6.80 (d, 2H, J=1.8,
4
H +H ); 12.55 (br, 1H, NH); ir: 3456, 2963, 2795, 2569, 1720,
2
6
1644, 1562, 1518, 1405, 1339, 13002, 1213, 1157, 1069, 855,
732, 670, 648, 592, 540.
[5] J. Hlavac, J. Slouka, P. Hradil and K. Lemr, J.
Heterocyclic Chem., 37, 115 (2000).
Anal. Calcd. for C H N O •2HCl (336.1): C, 35.73; H, 3.30;
N, 20.83. Found: C, 35.42; H, 3.44; N, 20.98.
[6] Ciba-Geigy AG, German Patent 2,256,313 (1973); Chem.
Abstr. 79, 54860 (1974).
10
9 5 4