Diphenylmethyl and tetrahydropyranyl protecting groups in the synthesis of 3-substituted 5-amino- and 5-hydrazino-1,2,4-triazoles

Article abstract of DOI:10.1134/S107036320712016X

The use of hydrazine as reagent in nucleophilic substitution and reduction in the 1,2,4-triazole series in combination with introduction of labile protecting groups makes it possible to synthesize 5-hydrazino-3-nitro-1H-1,2,4- triazole and 3-chloro-5-hydr

Full text of DOI:10.1134/S107036320712016X

ISSN 1070-3632, Russian Journal of General Chemistry, 2007, Vol. 77, No. 12, pp. 2179 2185.
Pleiades Publishing, Ltd., 2007.
Original Russian Text
pp. 2034 2040.
V.V. Tolstyakov, I.V. Tselinskii, N.A. Dreving, 2007, published in Zhurnal Obshchei Khimii, 2007, Vol. 77, No. 12,
Diphenylmethyl and Tetrahydropyranyl Protecting
Groups in the Synthesis of 3-Substituted 5-Amino-
and 5-Hydrazino-1,2,4-triazoles
V. V. Tolstyakov, I. V. Tselinskii, and N. A. Dreving
St. Petersburg State Institute of Technology (Technical University),
Moskovskii pr. 26, St. Petersburg, 190013 Russia
e-mail: tolstyakov@hotmail.com
Received July 12, 2007
Abstract The use of hydrazine as reagent in nucleophilic substitution and reduction in the 1,2,4-triazole
series in combination with introduction of labile protecting groups makes it possible to synthesize 5-hydrazino-
3-nitro-1H-1,2,4-triazole and 3-chloro-5-hydrazino-1H-1,2,4-triazol-5-ylhydrazine which were difficultly
accessible previously, as well as to extend the series of 3-substituted 5-amino-1H-1,2,4-triazoles.
DOI: 10.1134/S107036320712016X
3-Substututed 5-amino-1H-1,2,4-triazoles (R =
Alk, Ar) can be successfully synthesized via cycliza-
tion of acylated aminoguanidines. However, 5-amino-
1,2,4-triazoles having a phenoxy, phenylsulfanyl,
azolyl, or some other substituent in the 3-position can
be prepared only from N-cyano iminocarbonates. In
particular, 5-amino-3-phenoxy-1H-1,2,4-triazole was
obtained in such a way [1, 2]. 5-Amino-3-phenylsul-
fanyl-1H-1,2,4-triazole was synthesized by arylation
of 5-amino-2H-1,2,4-triazole-3(4H)-thione [3].
We now propose an alternative procedure for the
synthesis of such compounds, which is based on
nucleophilic replacement of the halogen atom in 5-
halo-3-nitro-1,2,4-triazoles with preliminary protec-
tion of the N1H group to avoid its deprotonation in
basic medium (which sharply reduces the nucleophi-
licity of the substrate). This is achieved by introduc-
tion of a readily removable diphenylmethyl substit-
uent and subsequent reduction and deprotection
[scheme (1)].
CHPh2
CHPh2
CHPh2
N
N
N
N
N2H4
NuH
N
H2SO4
N
NH
N
O2N
Br
benzene
DMF
K2CO3
O2N
Nu
i-PrOH
(1)
H2N
Nu
Nu
NH2
N
N
N
N
I
II V
VI IX
X XIII
II, VI, X, Nu = PhO; III, VII, XI, Nu = PhS; IV, VIII, XII, Nu = 1H-imidazol-1-yl; V, IX, XIII, Nu = 5-amino-1,2,4-
triazol-1-yl.
The syntheses of a series of 1-diphenylmethyl-3-
nitro-5-R-1,2,4-triazoles II V were reported by us
previously [4]. The nitro group therein is smoothly
reduced with hydrazine hydrate in propan-2-ol to
produce the corresponding amines without using
Raney nickel catalyst. In this case, removal of the
diphenylmethyl protecting group by treatment with
96% sulfuric acid in benzene [4] is quite admissible.
It seems obvious that the bromine atom in 5-bromo-
1-diphenylmethyl-3-nitro-1H-1,2,4-triazole (I) can be
replaced in a selective fashion by hydrazine and that
the subsequent deprotection of the N1 atom could
produce 5-hydrazino-3-nitro-1H-1,2,4-triazole. Ho-
wever, when the reaction was carried out in propan-2-
ol with excess 98% hydrazine hydrate (2.5 h under
reflux), we isolated 5-amino-1-diphenylmethyl-3-
2179

2180
TOLSTYAKOV et al.
nitro-1H-1,2,4-triazole (XIV), and increase in the re-
action time to 6 h resulted in the formation of 3,5-
diamino-1-diphenylmethyl-1H-1,2,4-triazole
[scheme (2)].
(XV)
CHPh2
CHPh2
CHPh2
N
N
H2SO4
N
N2H4
N
N
N
benzene
i-PrOH
O2N
Br
O2N
NH2
H2N
NH2
(2)
N
N
N
I
XIV
XV
Analogous result was obtained in the reaction of
1-diphenylmethyl-5-methylsulfonyl-3-nitro-1H-1,2,4-
triazole with excess hydrazine hydrate at room tem-
perature in a shorter time.
with hydrazine [6] to give a mixture of the expected
substitution product (1-methyl-3-nitro-1H-1,2,4-tri-
azol-5-ylhydrazine, 70%) and minor reduction product
(5-amino-1-methyl-3-nitro-1H-1,2,4-triazole, 30%).
We succeeded in partially lowering the contribution of
the redox reaction by (1) converting hydrazine into
hydrazinium acetate (whose ability to transfer an elec-
tron is much weaker) and (2) using a smaller excess
of the reagent (molar ratio hydrazine substrate 3:1).
Under these conditions we obtained the desired
1-diphenylmethyl-3-nitro-1,2,4-triazol-5-ylhydrazine
(XVI) [scheme (3)].
The ability of hydrazine to act not only as nucleo-
phile but also as reducing agent became apparent
while attempting to perform nucleophilic substitution
in 1,2,4-triazoles having reducible groups. As shown
in [5], the reaction of 4-amino-3,5-bis(methylsulfanyl)-
4H-1,2,4-triazole with hydrazine hydrate leads to
4-amino-5-methylsulfanyl-2H-1,2,4-triazole-3(4H)-
thione; 1-methyl-3,5-dinitro-1H-1,2,4-triazole reacted
CHPh2
CHPh2
N
N
N
N
+ CH3COO N2H5+
O2N
NHNH2
O2N
Br
(3)
N
N
I
XVI
The result of the reaction of compound XVI with
hydrazine hydrate confirmed the assumption that the
hydrazino group in 1,2,4-triazoles having electron-
withdrawing substituents can be reduced to amino
group with excess hydrazine [scheme (4)].
sulfuric acid benzene, but treatment with trifluoro-
acetic acid in the presence of phenol is more advan-
tageous due to smaller loss of the product during
isolation [scheme (5)].
CHPh2
CHPh2
N
N
N
N
2
+ N2H4
O2N
NHNH2
O2N
NHNH2
N
N
XVI
XVI
(1) trifluoroacetic acid
phenol
CHPh2
N
NH
N
(5)
N
(4)
(2) HCl
+ N2 + 2NH3
O2N
NHNH2 HCl
O2N
NH2
N
N
XVII
XIV
Removal of the diphenylmethyl protecting group
from compound XVI can be performed in the system
Obviously, the ability of 1,2,4-triazole heteroring
to capture an electron from hydrazine molecule and
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 77 No. 12 2007

DIPHENYLMETHYL AND TETRAHYDROPYRANYL PROTECTING
hence the probability of redox reaction should de-
2181
crease when less electron-withdrawing substituents
are present in the 1,2,4-triazole ring. 3,5-Dichloro-1-
(tetrahydropyran-2-yl)-1H-1,2,4-triazole (XVIII) and
3,5-dibromo-1-(tetrahydropyran-2-yl)-1H-1,2,4-tri-
azole (XIX) were synthesized by reaction of the cor-
responding dihalotriazoles with 3,4-dihydro-2H-pyran
[8]. Compounds XVIII and XIX reacted with excess
hydrazine hydrate in ethanol at 95 100 C, following
exclusively the nucleophilic halogen replacement path
[scheme (6)].
O
N
N
Hlg
N
NHNH2
N
XX, XXI
HCl
NH
N
(CH2)4OH
1 min
~
~
~
Hlg
N
H
C
H
N
XXII, XXII
NH
N
HCl
1 h
O
O
N
N
N
N
(6)
(7)
+ N2H4 H2O
Hlg
NHNH2 HCl
XXIV, XXV
N
Hlg
NHNH2
Hlg
Hlg
N
N
XVIII, XIX
XX, XXI
XX, XXII, XXIV, Hlg = Cl; XXI, XXIII, XXV, Hlg = Br.
XVIII, XX, Hlg = Cl; XIX, XXI, Hlg = Br.
The yields, melting points, and elemental analyses
of compounds VI XXV are given in Table 1. The
structure of compounds XVII, XXIV, and XXV was
confirmed by the 13C NMR spectra, the other prod-
ucts were characterized by 1H NMR spectroscopy
(Table 2). The mass spectra of VII, XIV XVII, XXI,
and XXIII XXV are presented in Table 3.
Elimination of the tetrahydropyranyl group from
molecules XX and XXI required more severe condi-
tions (heating in an acidic aqueous solution at the
boiling point for 1 h) than those reported in [7].
Presumably, hydrolysis of the tetrahydropyran ring is
accompanied by formation of Schiff bases XXII and
XXIII via reaction at the hydrazino group. This reac-
tion occurs within 1 2 min after dissolution of com-
pounds XX and XXI in a hot 20% aqueous solution
of hydrochloric acid; Schiff bases XXII and XXIII
separate from the mixture, and they can be isolated in
almost quantitative yield. Prolonged heating leads ini-
tially to dissolution of XXII and XXIII, and (after
heating for 1 h), hydrazino derivatives XXIV and
XXV precipitate as the corresponding hydrochlorides
[scheme (7)].
EXPERIMENTAL
1
The H NMR spectra were recorded on a Bruker
AM-200 instrument (200 MHz) using DMSO-d6 as
solvent. The 13C NMR spectra were measured on a
Bruker DPX-300 spectrometer at 75 MHz from solu-
tions in D2O. The progress of reactions was monitored
by TLC on Silufol UV-254 plates (carbon tetrachlo-
ride propan-2-ol, 4:1; detection under UV light).
Table 1. Yields, melting points, and elemental analyses of substituted triazoles VI XXV
Found, %
Calculated, %
H
Comp.
no.
Yield,
%
mp,
C
Formula
C
H
N
C
N
VI
72.0
89.1
68.2
58.6
58.4
60.3
58.5
169
73.69
71.06
68.15
61.14
55.18
50.09
39.35
29.12
61.16
68.35
4.92
4.96
5.13
5.02
4.21
4.43
4.20
4.09
4.79
5.36
16.24
15.73
25.83
34.12
31.17
28.64
55.14
66.86
23.50
26.78
C21H18N4O (342.4)
C21H18N4S (358.5)
73.67
70.36
68.34
61.43
54.54
49.98
40.00
28.92
61.01
67.90
5.30
5.06
5.10
4.85
4.58
4.19
4.03
3.64
4.44
5.70
16.36
15.63
26.56
33.71
31.80
29.14
55.97
67.44
23.72
26.40
VII
VIII
IX
X
XI
XII
XIII
XIV
XV
123
199
205
120
145
263
281
210
195
C18H16N6
C17H16N8
C8H8N4O
C8H8N4S
C5H6N6
(316.4)
(332.4)
(176.2)
(192.2)
(150.1)
(166.1)
79.2
C4H6N8
74.5, 80.1, 95.1a
63.4
C15H13N5O2 (295.3)
C15H15N5 (265.3)
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 77 No. 12 2007

2182
TOLSTYAKOV et al.
Found, %
Table 1. (Contd.)
Calculated, %
H
Comp.
no.
Yield,
%
mp,
C
Formula
C
H
N
C
N
XVI
40.6
36.6
77.6
81.3
72.6
95.6
92.4
94.2
35.3
40.5
191
215
80
117
125
110
184
185
215
226
57.76
13.08
38.41
27.22
38.52
31.71
39.24
31.83
14.49
10.80
4.37
3.34
4.23
2.83
5.43
5.84
5.45
5.08
2.75
2.07
26.85
46.38
19.05
13.29
32.11
26.82
32.03
26.83
40.90
33.27
C15H14N6O2 (310.3)
C2H5ClN6O2 (180.6)
C7H9Cl2N3O (222.1)
C7H9Br2N3O (311.0)
C7H12ClN5O (217.7)
C7H12BrN5O (262.1)
C7H12ClN5O (217.7)
C7H12BrN5O (262.1)
C2H5Cl2N5 (170)
C2H5BrClN5 (214.5)
58.06
13.30
37.86
27.04
38.36
32.08
38.63
32.08
14.13
11.20
4.55
2.79
4.08
2.92
5.56
4.61
5.56
4.61
2.96
2.35
27.08
46.55
18.92
13.51
32.18
26.72
32.18
26.72
41.20
32.66
XVII
XVIII
XIX
XX
XXI
XXII
XXIII
XXIV
XXV
a
Methods a, b, and c, respectively.
1
Table 2. H NMR spectra of substituted triazoles VI XVI and XVIII XXIII and 13C NMR spectra of triazoles XVII and
XVI XXVa
Comp.
no.
,
C, ppm
VI
VII
5.23 s (2H), 6.62 s (1H), 7.19 7.42 m (15H)
4.20 s (2H), 6.87 s (1H), 7.09 7.43 m (15H)
VIII
IX
X
5.54 s (2H), 6.42 s (1H), 7.10 s (1H), 7.17 7.46 m (11H), 7.83 s (1H)
5.46 s (2H), 7.17 7.47 m (12H), 7.61 s (1H), 7.81 s (1H)
5.96 s (2H), 7.01 7.17 m (3H), 7.24 7.38 m (2H), 11.34 s (1H)
6.01 s (2H), 7.19 7.38 m (5H), 12.09 s (1H)
XI
XII
6.24 s (2H), 6.97 s (1H), 7.47 s (1H), 8.01 s (1H), 11.90 s (1H)
6.22 s (2H), 6.96 s (2H), 7.36 s (1H), 11.97 s (1H)
6.96 s (1H), 7.21 7.44 m (12H)
XIII
XIV
XV
6.21 s (2H), 6.52 s (1H), 7.14 7.42 m (12H)
XVI
XVII
XVIII
XIX
XX
4.42 m (2H), 7.02 s (1H), 7.21 7.43 m (10H), 8.37 s (1H)
155.93, 160.27
1.53 2.25 m (6H), 3.61 3.75 m (1H), 3.86 3.98 m (1H), 5.49 5.60 m (1H)
1.53 2.23 m (6H), 3.61 3.73 m (1H), 3.87 3.98 m (1H), 5.46 5.56 m (1H)
1.49 2.16 m (6H), 3.58 3.71 m (1H), 3.84 3.94 m (1H), 4.03 4.49 m (2H), 5.23 5.34 m (1H), 7.92 8.14 m
(1H)
XXI
1.36 2.09 m (6H), 3.50 3.65 m (1H), 3.75 3.87 m (1H), 4.16 4.66 m (2H), 5.22 5.37 m (1H), 7.88 8.22 m
(1H)
XXII
Isomer mixture (ratio 1: 4.3):
1.37 1.51 m (4H), 2.13 2.31 m (2H), 3.32 3.51 m (2H), 4.03 4.42 m (1H), 6.58 s (1H), 10.43 s (1H), 12.91 s
(1H) and 1.37 1.51 m (4H), 2.13 2.31 m (2H), 3.32 3.51 m (2H), 4.03 4.42 m (1H), 7.26 s (1H), 10.82 s
(1H), 12.75 s (1H)
XXIII
Isomer mixture (1: 4.5):
1.38 1.55 m (4H), 2.14 2.29 m (2H), 3.37 3.57 m (2H), 4.03 4.72 m (1H), 6.59 s (1H), 10.49 s (1H), 13.16 s
(1H) and 1.38 1.55 m (4H), 2.14 2.29 m (2H), 3.37 3.57 m (2H), 4.03 4.72 m (1H), 7.28 s (1H), 10.91 s
(1H), 12.99 s (1H)
XXIV
XXV
146.275, 158.037
131.858, 159.107
a
The spectra of VI XVI and XVIII XXIII were recorded in DMSO-d , and those of XVII, XVI, and XXV, in D O.
6
2
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DIPHENYLMETHYL AND TETRAHYDROPYRANYL PROTECTING
2183
Table 3. Mass spectra of substituted triazoles VII, XIV XVII, XXI, and XXIII XXV
Comp.
no.
m/z (Irel, %)
VII
XIX
XV
XVI
XVII
XXI
XXIII
XXIV
XXV
358 [M+] (18), 167 (100), 152 (20), 136 (4), 121 (3), 109 (8), 77 (13)
295 [M+] (2), 167 (100), 152 (17), 115 (4), 77 (5), 45 (5)
265 [M+] (10), 250 (2), 167 (100), 152 (20), 128 (2), 77 (5), 43 (14)
310 [M+] (2), 263 (5), 233 (5), 167 (100), 152 (24), 139 (5), 115 (7), 77 (12), 53 (21)
144 [M+] (36), 127 (58), 114 (1), 98 (11), 68 (36), 53 (40), 36 (100)
261 [M+] (18), 214 (5), 179 (80), 106 (6), 85 (95), 67 (40), 57 (55), 41 (100)
263 [M+] (7), 216 (5), 205 (7), 190 (11), 177 (12), 162 (30), 148 (9), 100 (30), 85 (100), 67 (22), 53 (85), 41 (93)
133 [M+] (78), 117 (7), 103 (10), 88 (29), 76 (10), 68 (20), 62 (59), 53 (78), 43 (85), 36 (100)
177 [M+] (25), 161 (2), 147 (2), 133 (9), 106 (25), 93 (3), 81 (12), 68 (40), 53 (80), 43 (85), 36 (100)
Compounds XVIII and XIX were synthesized ac-
12 h at 20 C. During that time, the organic phase was
replaced twice (a solution of diphenylmethanol in
benzene was separated by decanting, and a fresh por-
tion of benzene was added). When the reaction was
complete, the organic layer was separated, and the
residue was poured into 20 ml of water on cooling.
The mixture was neutralized with an aqueous solution
of potassium hydroxide and extracted with ethyl
acetate (4 25 ml). The extract was dried over MgSO4,
the solvent was distilled off, and the residue was re-
crystallized from aqueous ethanol (1:1).
cording to the procedure described in [7]. The data for
compounds X, XI, XVIII, and XXIV were in agree-
ment with those given in [1 3, 8, 9].
1-Diphenylmethyl-5-phenoxy-1H-1,2,4-triazol-5-
amine (VI). A solution of 1.58 g of triazole II and
20 ml of 98% hydrazine hydrate in 50 ml of propan-2-
ol was heated for 1 h under reflux. The mixture was
cooled and poured into 200 ml of water, and the
precipitate was filtered off and recrystallized from
ethanol.
3-Phenylsulfanyl-1H-1,2,4-triazol-5-amine (XI)
was obtained from 0.68 g of triazole VII using 20 ml
of benzene and 4 ml of 96% sulfuric acid according to
the procedure described above for compound X.
1-Diphenylmethyl-5-phenylsulfanyl-1H-1,2,4-
triazol-5-amine (VII). A solution of 1.44 g of triazole
III and 20 ml of 98% hydrazine hydrate in 50 ml of
propan-2-ol was heated for 2 h under reflux. The
product was isolated and purified as described above
for compound VI.
3-(1H-Imidazol-1-yl)-1H-1,2,4-triazol-5-amine
(XII) was synthesized from 0.55 g of triazole VIII
using 20 ml of benzene and 4 ml of 96% sulfuric acid,
following the procedure described above for com-
pound X. The reaction time was 14 h, and the benzene
layer was replaced four times. When the reaction was
complete, the organic layer was separated, the residue
was diluted with 10 ml of water on cooling and neutra-
lized with aqueous potassium hydroxide. The mixture
was poured onto a Petri dish and allowed to evaporate
to dryness on exposure to air. The dry residue was
extracted with propan-2-ol in a Soxhlet apparatus. The
extract was evaporated, and the residue was recrystal-
lized from ethanol.
5-(1H-Imidazol-1-yl)-1-diphenylmethyl-1H-
1,2,4-triazol-3-amine (VIII) was synthesized from
1.14 g of triazole IV and 15 ml of 98% hydrazine
hydrate in 40 ml of propan-2-ol as described above for
compound VI. After heating, the mixture was evap-
orated to dryness on a rotary evaporator under re-
duced pressure, and the residue was recrystallized
from ethanol.
5-(5-Amino-1H-1,2,4-triazol-1-yl)-1-diphenyl-
methyl-1H-1,2,4-triazol-3-amine (IX) was syn-
thesized from 1.72 g of triazole V and 25 ml of 98%
hydrazine hydrate in 50 ml of propan-2-ol as de-
scribed above for compound VI; reaction time 4 h.
When the reaction was complete, the solvent was
distilled off to dryness under reduced pressure on a
rotary evaporator, and the residue was recrystallized
from aqueous ethanol (1:1).
3-(5-Amino-1H-1,2,4-triazol-1-yl)-1H-1,2,4-tri-
azol-5-amine (XIII) was obtained from 0.715 g of
triazole IX using 20 ml of benzene and 5 ml of 96%
sulfuric acid. The procedure was the same as de-
scribed above for the synthesis of compound XII. The
product was recrystallized from water.
3-Phenoxy-1H-1,2,4-triazol-5-amine (X). A mix-
ture of 0.38 g of compound VI, 15 ml of benzene, and
3 ml of 96% sulfuric acid was vigorously stirred for
1-Diphenylmethyl-3-nitro-1H-1,2,4-triazol-5-
amine (XIV). a. A solution of 4 g of compound I and
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2184
TOLSTYAKOV et al.
10 ml of 98% hydrazine hydrate in 60 ml of propan-2-
ol was heated for 2.5 h under reflux. After cooling,
the precipitate was filtered off and recrystallized from
ethanol.
The mixture was heated to the boiling point and was
maintained boiling for 2 h. It was then cooled, diluted
with 50 ml of ethyl acetate, washed with 50 ml of a
5% aqueous solution of sodium hydrogen carbonate,
and evaporated. The product was recrystallized twice
from propan-2-ol.
b. A mixture of 0.36 g of 1-diphenylmethyl-5-
methylsulfonyl-3-nitro-1,2,4-triazole [4], 5 ml of 98%
hydrazine hydrate, and 18 ml of propan-2-ol was stir-
red for 3 h at 18 20 C.
3,5-Dibromo-1-(tetrahydropyran-2-yl)-1H-1,2,4-
triazole (XIX) was synthesized in a similar way from
17 g of 3,5-dibromo-1,2,4-triazole and 15 g of 3,4-
dihydro-2H-pyran in 100 ml of ethyl acetate in the
presence of 0.3 g of p-toluenesulfonic acid.
c. Compound XVI, 0.1 g, was dissolved in 12 ml
of ethanol, 0.6 ml of 98% hydrazine hydrate was
added, and the mixture was kept for 60 h at 20 C and
evaporated to dryness. The residue was recrystallized
from ethanol.
3-Chloro-1-(tetrahydropyran-2-yl)-1H-1,2,4-
triazol-5-ylhydrazine (XX). A mixture of 6.9 g of
triazole XIII and 25 ml of 98% hydrazine hydrate in
150 ml of ethanol was heated for 3 h under reflux.
The mixture was evaporated to dryness, and the res-
idue was recrystallized from toluene.
1-Diphenylmethyl-1H-1,2,4-triazole-3,5-diamine
(XV). A mixture of 4 g of compound I and 10 ml of
98% hydrazine hydrate in 60 ml of propan-2-ol was
heated for 6 h under reflux. It was then cooled and
poured into 150 ml of water, and the precipitate was
filtered off and recrystallized from aqueous ethanol
(1:1).
3-Bromo-1-(tetrahydropyran-2-yl)-1H-1,2,4-
triazol-5-ylhydrazine (XXI) was synthesized in a
similar way from 15 g of compound XIX and 30 ml
of 98% hydrazine hydrate in 150 ml of ethanol. The
product was purified by recrystallization from toluene.
1-(1-Diphenylmethyl-3-nitro-1H-1,2,4-triazol-5-
yl)hydrazine (XVI). Hydrazinium acetate, 7.5 g, was
added to a solution of 10 g of triazole I in 150 ml of
propan-2-ol, and the mixture was heated for 3 h under
reflux. The mixture was cooled, and the precipitate
was filtered off, washed with water, and recrystallized
twice from methanol.
1-(3-Chloro-1H-1,2,4-triazol-5-yl)-2-(5-hy-
droxypentylidene)hydrazine (XXII). Compound XX,
3 g, was dissolved in 10 ml of 20% hydrochloric acid
on heating to 95 100 C. After 1 2 min, compound
XXII separated. The mixture was cooled, and the
precipitate was filtered off and recrystallized twice
from water.
3-Nitro-1H-1,2,4-triazol-5-ylhydrazine (XVII).
a. A mixture of 0.85 g of compound XVI, 0.51 g of
phenol, and 15 ml of trifluoroacetic acid was heated
for 3 h at 60 65 C. It was then evaporated to dryness,
the residue was kept for 20 h in a vacuum desiccator
and dissolved in 50 ml of benzene, and the solution
was extracted into 20% hydrochloric acid (2 10 ml).
The acid solution was concentrated until crystals of
XVII hydrochloride separated. The product was fil-
tered off and dried in air.
1-(3-Bromo-1H-1,2,4-triazol-5-yl)-2-(5-hydroxy-
pentylidene)hydrazine (XXIII) was synthesized in a
similar way from 3 g of compound XXI.
5-Chloro-1H-1,2,4-triazol-3-ylhydrazine hy-
drochloride (XXIV). A mixture of 3 g of compound
XX and 75 ml of 10% hydrochloric acid was heated
for 1 h at the boiling point in an open vessel. During
that time, the volume of the mixture decreased to
30 ml. The mixture was cooled, and the precipitate
was filtered off and recrystallized from 10% hydro-
chloric acid.
b. Compound XVI, 0.85 g, was treated with 3 ml
of 96% sulfuric acid in 80 ml of benzene as described
above for triazole XII. The benzene layer was sep-
arated, and 5 10 ml of ethanol was added dropwise
to the solution of compound XVII in sulfuric acid on
cooling to 5 to 0 C until XVII sulfate separated. The
product was filtered off, washed in succession with
diethyl ether and ethanol, dried in a vacuum desic-
cator, and recrystallized from 1,4-dioxane.
5-Bromo-1H-1,2,4-triazol-3-ylhydrazine hy-
drochloride (XXV) was synthesized in a similar way
from 3 g of compound XXI.
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