Synthesis of 1-Alkyl-5-amino-1,2,4-triazoles Based on Nucleophilic Substitution and Reduction Reactions

Article abstract of DOI:10.1134/S1070428018100160

A series of 1-alkyl-5-amino-1H-1,2,4-triazoles were synthesized starting from 3,5-dibromo-1H- 1,2,4-triazole by alkylation and subsequent nucleophilic substitution of the 5-bromine atom by azido group, reduction of the latter to amino group, and hydrodebromination.

Full text of DOI:10.1134/S1070428018100160

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2018, Vol. 54, No. 10, pp. 1537–1548. © Pleiades Publishing, Ltd., 2018.
Original Russian Text © V.V. Tolstyakov, 2018, published in Zhurnal Organicheskoi Khimii, 2018, Vol. 54, No. 10, pp. 1525–1534.
Synthesis of 1-Alkyl-5-amino-1,2,4-triazoles
Based on Nucleophilic Substitution and Reduction Reactions
V. V. Tolstyakova
a St. Petersburg State Institute of Technology, Moskovskii pr. 26, St. Petersburg, 190013 Russia
e-mail: tolstyakov@hotmail.com
Received November 15, 2017
Abstract—A series of 1-alkyl-5-amino-1H-1,2,4-triazoles were synthesized starting from 3,5-dibromo-1H-
1,2,4-triazole by alkylation and subsequent nucleophilic substitution of the 5-bromine atom by azido group,
reduction of the latter to amino group, and hydrodebromination.
DOI: 10.1134/S1070428018100160
There are a few published data on the use of
1-alkyl-5-amino-1H-1,2,4-triazoles in pharmacology
and agriculture; nevertheless, the available data
(mainly those reported during the past two decades)
indicate a certain potential of these compounds and
the necessity of further research in this field. Com-
pounds containing an 1-alkyl-5-amino-1H-1,2,4-tri-
azole fragment were proposed as medications for the
treatment of ischemia (HMG-CoA-reductase inhibi-
tors) [1], type II diabetes, and obesity (JNK inhibitors)
[2], as well as analgesics, antidepressants (fatty acid
hydrolase inhibitors) [3], antiulcer agents (H2-hista-
mine receptor blockers) [4], selective herbicides [5],
and photoactivated pesticides [6].
Herein, a general method of synthesis of 1-alkyl-5-
amino-1H-1,2,4-triazoles 5a–5g is proposed, which is
based on the alkylation of 3,5-dibromo-1H-1,2,4-tri-
azole (1), nucleophilic substitution of the 5-bromine
atom in 2a–2g by azido group, reduction of the latter
to amino group, and subsequent hydrodebromination
of 3-bromo derivatives 4a–4g (Scheme 1). This
scheme is analogous to that proposed in [12] for the
synthesis of 1-alkyl-5-[alkyl(dialkyl)amino]-1H-1,2,4-
triazoles, but the amino group was introduced through
azido due to insufficient nucleophilicity of the amine
rather than directly as in [12]. The proposed procedure
is advantageous since it utilizes accessible starting
compound and reagents and ensures high selectivity
and fairly high yields in all stages (Table 1).
Compound 1 is usually prepared by direct halo-
genation of commercially available 1H-1,2,4-triazole;
the product is obtained with high yield and sufficient
purity, and the procedure is easily scalable [13, 14].
The alkylation of triazole 1 (a) was reported in
a number of publications [12, 14–17]; the reacton is
characterized by high yields and selectivity. The
alkylating agents were dimethyl sulfate (for 2a), alkyl
halides (2b, 2c, 2e–2g), and 3,4-dihydro-2H-pyran
Up to now, only two synthetic approaches to 1-alkyl-
5-amino-1H-1,2,4-triazoles have been known. These
are direct alkylation of 3(5)-amino-1H-1,2,4-triazole
[4, 6, 7] and cyclization of formic acid or its syn-
thetic analogs with 1-alkylhydrazines [1, 8–11].
A significant drawback of the first approach is the lack
of selectivity: direct alkylation of 3(5)-amino-1H-1,2,4-
triazole usually gives mixtures of 2–4 regioisomers.
The second approach utilizes 1-alkylhydrazines many
of which are difficultly accessible compounds.
Scheme 1.
Br
Br
Br
Br
N2H4
Raney Ni
N
N
N
N
N
AlkX
NaN3
[H]
N
N
N
N
N
a
b
c
d
Br
Br
N3
H2N
H2N
N
N
N
N
N
H
Alk
Alk
Alk
Alk
1
2a–2g
3a–3g
4a–4g
5a–5g
Alk = Me (a), iso-C5H11 (b), PhCH2 (c), tetrahydropyran-2-yl (d), HOCH2CH2 (e), 2,4-Cl2C6H3CH2 (f), 4-MeOC6H4CH2 (g).
1537

TOLSTYAKOV
1538
Table 1. Yieldsa of the akylation (a), nucleophilic substitu-
tion of bromine by azido group (b), reduction of the azido
group to amino (c), and reductive debromination (g) in the
synthesis of compounds 5a–5g
formation of compounds 2 into 3 can also be accom-
plished through intermediate 5-hydrazino derivative 6.
Using compound 2a as an example, it was shown that
nucleophilic substitution of bromine by hydrazino
group and subsequent nitrosation afforded azide 3a in
a fairly high yield (Scheme 2).
Yield, %
Comp.
no.
Overall
yield, %
a
b
c
d
The reduction of the 5-azido group in 3a–3g to
amino (reaction c) was successfully accomplished
using sodium tetrahydridoborate in ethanol or sodium
sulfite in water. The first procedure is more general
due to the solubility factor. The reduction according to
Staudinger with the use of triphenylphosphine to
obtain intermediate phosphazene 7 (Scheme 3) was
less successful, presumably due to difficulties in the
separation of the hydrolysis products.
5a
5b
5c
5d
5e
5f
88
89
88
95
61
86
74
90
87
74
74
94
78
83
85
74
83
83
87
83
86
61
71
78
79
78
88
80
41
41
42
46
39
49
42
5g
a
The best yield from a series of experiments is given.
Hydrodehalogenation in the series of 1,2,4-triazoles
was described in [12, 18–20]. As a rule, it is achieved
by hydrogenation over Pd/C in the presence of a base.
Dimethyl hydrogen phosphite was also used for selec-
tive reductive debromination [19]. In this work, com-
pounds 4a–4g were hydrodebrominated (reaction d) by
treatment with hydrazine hydrate (as a source of
hydrogen) in the presence of Raney nickel [21].
Despite known disadvantages related to safety and
toxicity, this system can be regarded as an accessible
alternative which demonstrated high selectivity. For
example, in the synthesis of compound 5f, the chlorine
atoms in the benzyl substituent remained intact.
(2d). Triazole 1 was either preliminarily converted to
sodium salt or used in the neutral form which was
activated under acidic or basic conditions. The alkyla-
tion of 1 with isopentyl bromide and benzyl chloride
was carried out under different conditions, but there
were no appreciable differences in the yield and purity
of compounds 2b and 2c thus obtained.
The nucleophilic substitution of bromine by azido
group (b) was also highly selective. However, in some
cases, the reactions were accompanied by formation of
tars, and reduced yields were obtained under harsh
conditions. Compounds 2a–2c and 2f were converted
to 3a–3c and 3f in DMFA at 90–95°C (6–9 h) with
high yields, whereas the yields of 3d, 3e, and 3g under
the same conditions were 39–58%, and the products
required additional purification. The yields were im-
proved by lowering the temperature to 50–65°C and
replacing DMF by DMSO, but in this case significant
increase of the reaction time was necessary. The trans-
EXPERIMENTAL
1
The H and 13C NMR spectra were recorded on
Varian DPX-300 (300.1 and 75.5 MHz, respectively)
and Bruker Avance-III-400 spectrometers (400 MHz
1
for H) using DMSO-d6 as solvent and tetramethyl-
silane as internal standard. The IR spectra were meas-
Scheme 2.
Br
Br
Br
N
N
N
N2H4·H2O, i-PrOH
NaNO2, HCl, H2O
93%
H2N
N
N
N
Br
N
N3
83%
N
N
N
H
Me
Me
Me
2a
6
3a
Scheme 3.
Br
Br
Br
N
N
N
Ph3P, PhMe
78%
H2SO4, H2O
Ph3P
N
N
N
N3
N
H2N
50%
N
N
N
Me
Me
Me
3a
7
4a
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 10 2018

SYNTHESIS OF 1-ALKYL-5-AMINO-1,2,4-TRIAZOLES
1539
ured in KBr on a Shimadzu FTIR-8400 spectrometer.
The mass spectra (electron impact, 70 eV) were
obtained on a Finnigan MAT INCOS 50 quadrupole
mass spectrometer with direct sample admission into
the ion source.
itate was filtered off, and the solvent was distilled off
from the filtrate. The residue was dissolved in 150 mL
of ethyl acetate, the solution was washed with
10% aqueous sodium hydroxide (2×10 mL) and dried
over magnesium sulfate, and the solvent was distilled
off. Yield 25.5 g (85%), mp 6–7°C (from hexane). IR
spectrum, ν, cm–1: 2959, 2936, 1464, 1433, 1420,
1389, 1369, 1263, 1171, 1134, 1059, 989, 745, 702.
3,5-Dibromo-1-methyl-1H-1,2,4-triazole (2a).
A solution of 1.4 g (36 mmol) of sodium hydroxide in
13 mL of water was added to a solution of 8.0 g
(36 mmol) of 3,5-dibromo-1H-1,2,4-triazole (1) in
100 mL of acetone. The two-phase system thus formed
was stirred at 20°C until it became homogeneous, and
4.6 g (36 mmol) of dimethyl sulfate was added drop-
wise at such a rate that the temperature of the mixture
did not exceed 40°C. The mixture was then refluxed
for 2 h. The reaction was assumed to be complete
when the mixture became weakly acidic and sodium
methyl sulfate precipitated. The mixture was filtered,
and the solvent was distilled off from the filtrate under
reduced pressure. The residue was washed with water,
and the precipitate was filtered off and recrystallized
from hexane. Yield 7.8 g (88%), mp 64–65°C [22].
IR spectrum, ν, cm–1: 2951, 1717, 1699, 1464, 1418,
1391, 1354, 1275, 1250, 1115, 1016, 989, 712, 700.
1H NMR spectrum, δ, ppm: 3.87 s (3H, CH3).
13C NMR spectrum, δC, ppm: 37.4 (CH3), 131.3 (C3),
139.1 (C5). Mass spectrum, m/z (Irel, %): 243 (51.1)
[M]+, 241 (100) [M]+, 239 (48.9) [M]+, 229 (21.3), 227
(48.3), 225 (24.2), 218 (1.2), 200 (6.1), 198 (12.3), 196
(5.1), 162 (14.5), 160 (13.1), 136 (33.4), 134 (34.9),
122 (30.6), 120 (31.3), 119 (6.3), 117 (7.4), 108 (14.6),
107 (7.7), 106 (16.2), 105 (8.9), 93 (15.9), 91 (18.9),
81 (40.9), 79 (32.5), 52 (12.7), 43 (33.8), 41 (12.2), 40
(13.3), 39 (9.1), 38 (18.5), 29 (53.2), 28 (10.7), 27
(16.3), 26 (8.2), 15 (60.3), 12 (7.4).
3
1H NMR spectrum, δ, ppm: 0.90 d (6H, CH3, J =
6.5 Hz), 1.47–1.59 m (1H, CH), 1.66 d.d (2H, CH2,
3
3J = 7.0, 14.5 Hz), 4.14 t (2H, CH2, J = 14.5 Hz).
13C NMR spectrum, δC, ppm: 22.4 (2C, CH3), 25.3
(CH), 37.8 (CH2), 48.5 (1-CH2), 130.7 (C3), 139.5
(C5). Mass spectrum, m/z (Irel, %): 300 (5.4) [M]+, 299
(13.4) [M]+, 298 (10.7) [M]+, 297 (27.6) [M]+, 296
(6.4) [M]+, 295 (14.8) [M]+, 294 (0.7) [M]+, 291 (0.5),
286 (0.5), 285 (2.0), 284 (3.5), 283 (2.7), 282 (7.3),
281 (0.9), 280 (4.0), 271 (0.5), 270 (1.2), 269 (1.0),
268 (2.7), 267 (1.0), 266 (1.9), 264 (0.5), 257 (2.3),
256 (3.2), 255 (5.0), 254 (5.5), 253 (3.0), 252 (2.7),
243 (44.4), 242 (13.7), 241 (85.5), 240 (20.4), 239
(42.2), 238 (9.2), 230 (45.5), 229 (44.2), 228 (84.3),
227 (80.2), 226 (40.8), 225 (37.3), 219 (14.8), 218
(98.3), 216 (100), 70 (7.0), 55 (7.8). Found, %:
C 28.54; H 3.84; N 14.63. C7H11Br2N3. Calculated, %:
C 28.31; H 3.73; N 14.15. M 296.99.
1-Benzyl-3,5-dibromo-1H-1,2,4-triazole (2c).
a. Potassium carbonate, 16.6 g (0.12 mol), was added
to a solution of 25.0 g (0.11 mol) of triazole 1 in
400 mL of acetone. The suspension was stirred for
15 min at 20°C, 12.7 g (0.10 mol) of benzyl chloride
was added, and the mixture was refluxed for 8 h with
stirring. The solvent was distilled off, and the light
yellow oily residue was treated with 200 mL of water.
The mixture was stirred for 5 min, and crystals
precipitated and were filtered off and recrystallized
from hexane. Yield 22.3 g (64%).
3,5-Dibromo-1-(3-methylbutyl)-1H-1,2,4-triazole
(2b). a. A solution of 1.72 g (43 mmol) of sodium
hydroxide in 2 mL of water was added with stirring to
a solution of 10.0 g (43 mmol) of triazole 1 in 100 mL
of DMF, and 6.49 g (43 mmol) of isopentyl bromide
was then added. The mixture was stirred for 13 h on
a boiling water bath, cooled, and poured into 1 L of
water. The yellow oily material was separated using
a separatory funnel (bottom layer), additionally
washed with water, and dried for 3 days in a vacuum
desiccator over phosphoric anhydride. The product
was used in further syntheses without additional puri-
fication. Yield 11.5 g (89%).
b. Benzyl chloride, 12.6 g (0.1 mol), was added to
a suspension of 25.0 g (0.1 mol) of triazole 1 sodium
salt in 150 mL of acetonitrile, and the mixture was
refluxed for 10 h with stirring. The mixture was
cooled, the inorganic precipitate was filtered off, the
filtrate was evaporated, and the residue was recrys-
tallized from hexane. Yield 28.0 g (88%), mp 65–
66°C; published data: mp 62–64°C [14], 64–66°C
[15]. IR spectrum, ν, cm–1: 1674, 1497, 1452, 1435,
1418, 1360, 1259, 1205, 1184, 1159, 1082, 1061, 989,
1
912, 787, 731, 700, 656, 592. H NMR spectrum, δ,
b. Triazole 1 sodium salt, 25.0 g (0.1 mol), was
dispersed in 150 mL of acetonitrile, 15.1 g (0.1 mol) of
isopentyl bromide was added, and the mixture was
refluxed for 10 h. The mixture was cooled, the precip-
ppm: 5.41 s (2H, CH2), 7.27–7.43 m (5H, Harom).
13C NMR spectrum, δC, ppm: 53.4 (CH2), 128.2
(Carom), 128.8 (Carom), 129.3 (Carom), 131.3 (C3), 135.0
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 10 2018

TOLSTYAKOV
1540
(Carom), 139.9 (C5). Mass spectrum, m/z (Irel, %): 319
(2.2) [M]+, 317 (4.8) [M]+, 315 (2.2) [M]+, 93 (5.3), 92
(9.9), 91 (100), 89 (7.3), 77 (9.5), 65 (49.6), 64 (5.4),
63 (16.9), 52 (6.4), 51 (23.0), 50 (10.4), 41 (5.7), 39
(30.2), 38 (9.8), 27 (5.3).
C4H5Br2N3O. Calculated, %: C 17.73; H 1.86;
N 15.51. M 270.91.
3,5-Dibromo-1-(2,4-dichlorobenzyl)-1H-1,2,4-
triazole (2f). 2,4-Dichlorobenzyl chloride, 15.8 g
(81 mmol), was added to a suspension of 21.0 g
(84 mmol) of triazole 1 sodium salt in 150 mL of
acetonitrile, and the mixture was refluxed for 10.5 h
with stirring. The mixture was cooled and diluted with
800 mL of water, and the precipitate was filtered off,
dried, and recrystallized from propan-2-ol. Yield
27.0 g (86%), mp 127–128°C. IR spectrum, ν, cm–1:
1591, 1564, 1460, 1425, 1414, 1387, 1364, 1348,
1302, 1256, 1109, 1097, 1074, 1047, 989, 866, 839,
814, 785, 733, 702, 683, 650, 552. 1H NMR spectrum,
3,5-Dibromo-1-(tetrahydro-2H-pyran-2-yl)-1H-
1,2,4-triazole (2d). Triazole 1, 85.0 g (0.38 mol), was
dissolved in 500 mL of ethyl acetate, 2–3 drops of
trifluoroacetic acid were added, the mixture was heated
to 50°C, and 75.0 g (0.87 mol) of 3,4-dihydro-2H-
pyran was added over a period of 2.5 h. The mixture
was refluxed for 1 h with stirring and evaporated, and
the residue was recrystallized from toluene. Yield
111.5 g (95%), mp 116–117°C [15]. IR spectrum, ν,
cm–1: 2951, 2901, 2869, 2361, 1448, 1418, 1364, 1310,
1289, 1240, 1204, 1184, 1082, 1055, 1042, 1001, 982,
939, 912, 880, 847, 820, 793, 700, 563. 1H NMR spec-
trum, δ, ppm: 1.43–1.60 m (2H), 1.61–1.79 m (1H),
1.84–2.04 m (2H), 2.04–2.20 m (1H), 3.54–3.76 m
(1H), 3.91 d.d (1H, 3J = 3.2, 2J = 8.7 Hz), 5.54 d.d (1H,
3J = 2.5, 9.2 Hz). 13C NMR spectrum, δC, ppm: 21.7
(CH2), 24.7 (CH2), 28.7 (CH2), 67.3 (CH2O), 84.6
(OCH), 132.0 (C3), 140.0 (C5). Mass spectrum, m/z
(Irel, %): 86 (5.8), 85 (100), 67 (10.8), 57 (11.1), 55
(8.4), 43 (8.9), 41 (18.9), 39 (6.5), 29 (17.8), 27 (8.7).
3
δ, ppm: 5.46 s (2H, CH2), 7.33 d (1H, Harom, J =
3
4
8.3 Hz), 7.47 d.d (1H, Harom, J = 8.9, J = 2.0 Hz),
7.66 d (1H, Harom, 4J = 1.9 Hz). 13C NMR spectrum, δC,
ppm: 50.8 (CH2), 128.4 (Carom), 129.7 (Carom), 131.4
(Carom), 132.1 (C3), 132.7 (Carom), 134.1 (Carom), 134.7
(Carom), 140.2 (C5). Mass spectrum, m/z (Irel, %): 385
(0.4) [M]+, 354 (7.0), 353 (3.9), 352 (35.4), 351 (5.4),
350 (49.5), 349 (2.2), 348 (22.7), 198 (5.2), 163 (11.0),
162 (5.5), 161 (65.9), 160 (7.5), 159 (100), 125 (5.9),
124 (6.6), 123 (17.4), 93 (6.3), 91 (6.3), 89 (16.1), 75
(5.9), 73 (5.1), 63 (8.6). Found, %: C 27.76; H 1.44;
N 10.63. C9H5Br2Cl2N3. Calculated, %: C 28.01;
H 1.31; N 10.89. M 385.87.
2-(3,5-Dibromo-1H-1,2,4-triazol-1-yl)ethanol
(2e). 2-Chloroethanol, 8.1 g (85 mmol), was added to
a suspension of 21.2 g (85 mmol) of triazole 1 sodium
salt in 100 mL of acetonitrile, and the mixture was
refluxed for 5.5 h with stirring. An additional portion
of 2-chloroethanol, 5.5 g (68 mmol), was added, and
the mixture was refluxed for 5.5 h more. After cooling,
the inorganic precipitate was filtered off, the filtrate
was evaporated, and the residue was recrystallized
from toluene. Yield 14.0 g (61%), mp 94–95°C. IR
spectrum, ν, cm–1: 3308 (OH), 1468, 1452, 1429, 1387,
1364, 1271, 1092, 1074, 997, 966, 870, 704, 660, 525.
3,5-Dibromo-1-(4-methoxybenzyl)-1H-1,2,4-
triazole (2g). 4-Methoxybenzyl chloride, 29.3 g
(0.187 mol), was added to a suspension of 46.6 g
(0.187 mol) of triazole 1 sodium salt in 350 mL of
acetonitrile, and the mixture was refluxed for 9 h with
stirring. The mixture was filtered while hot, the filtrate
was evaporated, and the residue was recrystallized
from hexane. Yield 48.0 g (74%), mp 73–74°C; pub-
lished data [23]: mp 75.7°C. IR spectrum, ν, cm–1:
1612, 1585, 1514, 1456, 1433, 1412, 1356, 1317,
1304, 1263, 1244, 1177, 1110, 1061, 1020, 988, 835,
3
1H NMR spectrum, δ, ppm: 3.75 q (2H, CH2, J =
1
5.4 Hz), 4.19 t (2H, CH2, 3J = 5.3 Hz), 4.98 t (1H, OH,
3J = 5.6 Hz). 13C NMR spectrum, δC, ppm: 52.9 (CH2),
59.4 (CH2OH), 131.8 (C3), 139.5 (C5). Mass spectrum,
m/z (Irel, %): 273 (12.9) [M]+, 272 (2.1) [M]+, 271
(29.8) [M]+, 269 (15.6) [M]+, 243 (16.7), 242 (7.3),
241 (32.2), 240 (14.4), 239 (15.4), 238 (6.2), 231 (1.7),
230 (46.8), 228 (100), 227 (5.8), 226 (52.3), 162
(58.6), 160 (60.3), 135 (27.1), 133 (34.2), 120 (5.2),
108 (20.2), 106 (20.8), 93 (9.8), 91 (6.1), 81 (10.3),
79 (8.0), 55 (17.9), 53 (7.1), 45 (10.1), 44 (11.7),
43 (15.6), 42 (6.2), 31 (56.6), 29 (24.5), 28 (13.0),
27 (15.8). Found, %: C 17.48; H 1.75; N 15.82.
824, 766, 698, 559, 517. H NMR spectrum, δ, ppm:
3.75 s (3H, OCH3), 5.32 s (2H, CH2), 6.94 d (2H,
3
3
Harom, J = 8.5 Hz), 7.25 d (2H, Harom, J = 8.0 Hz).
13C NMR spectrum, δC, ppm: 53.0 (CH2), 55.6
(OCH3), 114.7 (Carom), 126.9 (Carom), 130.0 (Carom),
131.0 (C3), 138.6 (Carom), 139.8 (C5), 159.7 (Carom).
Mass spectrum, m/z (Irel, %): 350 (1.0) [M]+, 349 (8.2)
[M]+, 348 (2.0) [M]+, 347 (16.8) [M]+, 346 (1.1) [M]+,
345 (8.7) [M]+, 305 (2.4), 304 (1.0), 303 (9.8), 302
(0.8), 301 (7.4), 122 (20.9), 121 (100), 106 (7.3), 91
(12.2), 89 (6.7), 78 (21.9), 77 (14.8), 63 (5.5), 52 (5.2),
51 (5.6), 28 (5.3), 18 (9.1), 15 (5.2).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 10 2018

SYNTHESIS OF 1-ALKYL-5-AMINO-1,2,4-TRIAZOLES
1541
5-Azido-3-bromo-1-methyl-1H-1,2,4-triazole
(3a). a. A solution of 24.0 g (0.1 mol) of triazole 2a
and 8.5 g (0.13 mol) of sodium azide in 125 mL of
DMF was stirred for 8.5 h at 95–100°C. The mixture
was cooled, poured into 600 mL of water, and ex-
tracted with ethyl acetate (5×125 mL). The combined
extracts were washed with water (2×20 mL) and dried
over magnesium sulfate, the solvent was distilled off,
and the residue was recrystallized from hexane. Yield
18.2 g (90%).
218 (7.0), 217 (7.5), 216 (6.9), 215 (5.3), 178 (5.1),
176 (6.7), 164 (9.8), 162 (10.6), 152 (6.9), 138 (8.4),
133 (9.1), 131 (5.6), 98 (5.0), 97 (20.7), 71 (5.6), 70
(5.8), 69 (5.9), 68 (15.1), 57 (7.8), 55 (17.8), 53 (8.7),
44 (6.6), 43 (100). Found, %: C 32.39; H 4.25;
N 32.73. C7H11BrN6. Calculated, %: C 32.45; H 4.28;
N 32.43. M 259.11.
5-Azido-1-benzyl-3-bromo-1H-1,2,4-triazole (3c).
A mixture of 25.3 g (0.08 mol) of triazole 2c and 6.8 g
(0.10 mol) of sodium azide in 160 mL of DMF was
stirred for 14 h at 90–95°C. The mixture was cooled
and poured into 1 L of water, and the precipitate was
filtered off. An additional amount of the product
(2.5 g) was isolated from the filtrate by extraction with
ethyl acetate (4×50 mL). The combined extracts were
washed with water (2×20 mL) in a separatory funnel
and dried over magnesium sulfate, and the solvent was
distilled off on a rotary evaporator under reduced
pressure. Both portions of the product were combined
and recrystallized from hexane. Yield 16.6 g (74%),
mp 65–66°C. IR spectrum, ν, cm–1: 2152 (N3), 1518,
1491, 1497, 1481, 1454, 1400, 1321, 1279, 1258,
1194, 1094, 1026, 991, 814, 770, 719, 696, 669, 560,
b. A solution of 3.0 g (43 mmol) of sodium nitrite in
9 mL of water was added dropwise to a mixture of
8.3 g (43 mmol) of compound 6 in 80 mL of con-
centrated aqueous HCl and 30 mL of water, cooled to
5–6°C. The mixture was stirred for 1 h at that tempera-
ture, diluted with water to a volume of 400 mL, and
extracted with ethyl acetate (4×150 mL). The com-
bined extracts were washed with water (2×10 mL) and
dried over magnesium sulfate, the solvent was distilled
off under reduced pressure on a rotary evaporator, and
the residue was recrystallized from hexane. Yield 8.2 g
(93%), mp 54–55°C. IR spectrum, ν, cm–1: 2291, 2160
(N3), 1545, 1485, 1410, 1292, 1244, 1072, 995, 847,
1
1
714, 677, 513, 525. H NMR spectrum, δ, ppm: 3.59 s
556, 525. H NMR spectrum, δ, ppm: 5.11 s (2H,
(3H, CH3). 13C NMR spectrum, δ, ppm: 34.8 (CH3),
136.7 (C3), 150.1 (C5). Mass spectrum, m/z (Irel, %):
204 (0.6) [M]+, 202 (0.6) [M]+, 53 (7.6), 43 (100), 42
(16.5), 40 (13.2), 39 (6.2), 38 (15.6), 32 (5.4), 29
(100.9), 28 (100.1), 27 (99.2), 26 (91.4), 25 (12.5), 24
(48.5), 18 (101.4), 18 (101.8), 17 (71.8), 16 (98.9), 14
(101.8), 13 (58.1), 12 (85.9). Found, %: C 17.99;
H 1.45; N 40.96. C3H3BrN6. Calculated, %: C 17.75;
H 1.49; N 41.40. M 203.00.
CH2), 7.27–7.41 m (5H, Harom). 13C NMR spectrum,
δC, ppm: 51.2 (CH2), 128.3 (Carom), 128.7 (Carom),
129.2 (Carom), 135.3 (Carom), 137.4 (C3), 150.2 (C5).
Mass spectrum, m/z (Irel, %): 280 (1.6) [M]+, 278 (1.7)
[M]+, 251 (0.7), 249 (0.5), 171 (10.0), 92 (7.8), 91
(100), 65 (16.6), 51 (5.3), 39 (9.6). Found, %: C 38.35;
H 2.68; N 30.10. C9H7BrN6. Calculated, %: C 38.73;
H 2.53; N 30.11. M 279.10.
5-Azido-3-bromo-1-(tetrahydro-2H-pyran-2-yl)-
1H-1,2,4-triazole (3d). A suspension of 2.0 g
(6.4 mmol) of triazole 2d and 0.6 g (9.2 mmol) of
sodium azide in 10 mL of DMSO was stirred for 30 h
at 50°C. The mixture was cooled and poured into
90 mL of water, and the precipitate was filtered off.
An additional amount of the product (0.1 g) was
isolated from the filtrate by extraction with ethyl
acetate (4×15 mL). The combined extracts were
washed with water (2×20 mL) and dried over magne-
sium sulfate, the solvent was distilled off on a rotary
evaporator under reduced pressure, and the residue was
combined with the main portion and recrystallized
from hexane. Yield 1.3 g (74%), mp 75–76°C. IR spec-
trum, ν, cm–1: 2959, 2953, 2858, 2172, 2156 (N3),
1522, 1508, 1487, 1375, 1290, 1276, 1256, 1232,
1207, 1182, 1142, 1086, 1076, 939, 916, 885, 845,
5-Azido-3-bromo-1-(3-methylbutyl)-1H-1,2,4-
triazole (3b). A solution of 5.3 g (18 mmol) of triazole
2b and 1.5 g (23 mmol) of sodium azide in 40 mL of
DMF was stirred for 12.5 h at 95–100°C. The mixture
was cooled, poured into 300 mL of water, and ex-
tracted with ethyl acetate (4×50 mL). The combined
extracts were washed with water (2×20 mL), dried
over magnesium sulfate, and evaporated on a rotary
evaporator under reduced pressure. Yield 4.0 g (87%),
mp –7°C (from hexane). IR spectrum, ν, cm–1: 2959,
2156 (N3), 1522, 1485, 1281, 1259, 1198, 1074, 991,
714. 1H NMR spectrum, δ, ppm: 0.88 d (6H, CH3, 3J =
6.5 Hz), 1.44–1.55 m (1H, CH), 1.59 d.d (2H, CH2,
3
3J = 6.9, 14.25 Hz), 3.89 t (2H, CH2, J = 7.2 Hz).
13C NMR spectrum, δC, ppm: 23.6 (2C, CH3), 26.4
(CH), 38.7 (CH2), 47.5 (1-CH2), 138.1 (C3), 150.9
(C5). Mass spectrum, m/z (Irel, %): 260 (1.4) [M]+, 258
(0.9) [M]+, 236 (0.9), 234 (2.6), 232 (3.2), 219 (1.9),
1
816, 770, 716, 594, 544, 527. H NMR spectrum, δ,
ppm: 1.44–1.59 m (2H), 1.58–1.74 m (1H), 1.74–
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 10 2018

TOLSTYAKOV
1542
1.91 m (1H), 1.91–2.16 m (2H), 3.53–3.67 m (1H),
134.1 (Carom), 134.5 (Carom), 137.7 (C3), 150.6 (C5).
Mass spectrum, m/z (Irel, %): 350 (0.9) [M]+, 348 (2.3)
[M]+, 346 (1.7) [M]+, 313 (1.7), 311 (1.3), 239 (5.8),
163 (10.3), 161 (63.3), 160 (7.3), 159 (100), 133
(18.5), 131 (15.2), 125 (5.8), 124 (7.3), 123 (16.1), 89
(17.1), 63 (7.7). Found, %: C 31.47; H 1.90; N 24.24.
C9H5BrCl2N6. Calculated, %: C 31.06; H 1.45;
N 24.15. M 347.99.
2
3
3.91 d (1H, J = 11.6 Hz), 5.25 d.d (1H, J = 2.7,
9.4 Hz). 13C NMR spectrum, δC, ppm: 21.8 (CH2), 24.7
(CH2), 28.8 (CH2), 67.3 (CH2O), 82.8 (OCH), 137.7
(C3), 150.5 (C5). Mass spectrum, m/z (Irel, %): 275
(0.5) [M]+, 274 (2.4) [M]+, 272 (2.4) [M]+, 133 (6.0),
131 (6.4), 86 (5.8), 85 (100), 84 (20.2), 67 (11.3), 57
(11.3), 55 (8.1), 43 (8.7), 41 (18.3), 39 (6.4), 29 (18.5),
28 (7.2), 27 (9.3). Found, %: C 30.77; H 3.05;
N 30.94. C7H9BrN6O. Calculated, %: C 30.79; H 3.32;
N 30.77. M 273.09.
5-Azido-3-bromo-1-(4-methoxybenzyl)-1H-1,2,4-
triazole (3g). A suspension of 4.3 g (11 mmol) of
triazole 2g and 0.96 g (15 mmol) of sodium azide in
30 mL of DMSO was stirred for 40 h at 65°C. The
mixture was cooled and poured into 300 mL of water,
and the precipitate was filtered off, dried, and recrys-
tallized from hexane. Yield 3.3 g (83%), mp 84–85°C.
IR spectrum, ν, cm–1: 2164 (N3), 1614, 1585, 1514,
1479, 1425, 1394, 1321, 1306, 1275, 1248, 1178, 1117,
1080, 1028, 989, 820, 762, 735, 712, 691, 669, 635,
2-(5-Azido-3-bromo-1H-1,2,4-triazol-1-yl)-
ethanol (3e). A suspension of 10.9 g (40 mmol) of
compound 2e and 3.5 g (54 mmol) of sodium azide in
60 mL of DMSO was stirred for 30 h at 65°C. The
mixture was cooled, poured into 250 mL of water, and
extracted with ethyl acetate (6×100 mL). The com-
bined extracts were washed with 10 mL of water and
dried over magnesium sulfate, the solvent was distilled
off on a rotary evaporator under reduced pressure, and
the residue was recrystallized from toluene. Yield
8.77 g (94%), mp 74–75°C. IR spectrum, ν, cm–1: 3369
(OH), 2158 (N3), 1533, 1477, 1456, 1431, 1412, 1362,
1281, 1261, 1238, 1186, 1107, 1069, 997, 962, 868,
1
556, 519. H NMR spectrum, δ, ppm: 3.74 s (3H,
3
OCH3), 5.04 s (2H, CH2), 6.93 d (2H, Harom, J =
3
8.7 Hz), 7.24 d (2H, Harom, J = 8.6 Hz). 13C NMR
spectrum, δC, ppm: 50.8 (CH2), 55.6 (OCH3), 114.6
(Carom), 127.2 (Carom), 130.0 (Carom), 137.2 (C3), 149.9
(C5), 159.7 (Carom). Mass spectrum, m/z (Irel, %): 311
(0.7) [M]+, 310 (5.9) [M]+, 309 (0.8) [M]+, 308 (5.9)
[M]+, 279 (0.5), 267 (0.6), 265 (0.5), 122 (9.2), 121
(100), 78 (8.8). Found, %: C 38.54; H 2.88; N 27.20.
C10H9BrN6O. Calculated, %: C 38.85; H 2.93;
N 27.19. M 309.12.
1
714, 656, 621, 577, 525. H NMR spectrum, δ, ppm:
3
3.68 q (2H, CH2, J = 5.4 Hz), 3.92 t (2H, CH2,
3
13
3J = 5.4 Hz), 4.91 t (1H, OH, J = 5.6 Hz). C NMR
spectrum, δC, ppm: 50.9 (CH2), 59.1 (CH2OH), 137.0
(C3), 150.6 (C5). Mass spectrum, m/z (Irel, %): 235
(0.8) [M]+, 234 (11.2) [M]+, 232 (12.0) [M]+, 133
(22.0), 131 (20.2), 81 (5.3), 79 (5.3), 68 (5.3), 53 (7.7),
45 (100), 43 (12.7), 42 (7.3), 31 (19.5), 29 (13.9), 28
(5.4), 27 (11.7). Found, %: C 20.97; H 2.48; N 36.51.
C4H5BrN6O. Calculated, %: C 20.62; H 2.16; N 36.06.
M 233.03.
3-Bromo-1-methyl-1H-1,2,4-triazol-5-amine (4a).
a. Triazole 3a, 3.0 g (14.7 mmol), was added to a solu-
tion of 10.0 g (79 mmol) of sodium sulfite in 100 mL
of water, and the mixture was stirred for 30 min at 95–
100°C. The mixture was cooled and extracted with
ethyl acetate (3×75 mL), the combined extracts were
dried over magnesium sulfate, the solvent was distilled
off, and the residue was recrystallized from toluene.
Yield 2.2 g (85%).
5-Azido-3-bromo-1-(2,4-dichlorobenzyl)-1H-
1,2,4-triazole (3f). A mixture of 26.2 g (68 mmol) of
triazole 2f and 5.7 g (88 mmol) of sodium azide in
150 mL of DMF was stirred for 12 h at 90–95°C. The
mixture was cooled and poured into 1 L of water, and
the precipitate was filtered off, dried, and recrystal-
lized from toluene–hexane (1:1). Yield 18.5 g (78%),
mp 120–121°C. IR spectrum, ν, cm–1: 2152 (N3), 1589,
1560, 1518, 1479, 1439, 1427, 1404, 1393, 1360,
1304, 1275, 1252, 1204, 1186, 1103, 1086, 1053, 991,
870, 856, 820, 766, 723, 714, 683, 669, 658, 567, 557,
b. Sodium tetrahydridoborate, 0.1 g (26 mmol), was
added in portions over a period of 15 min to a solution
of 0.55 g (2.7 mmol) of triazole 3a in 10 mL of pro-
pan-2-ol, allowing the mixture to warm up. The mix-
ture was then heated to the boiling point, cooled, and
filtered, the filtrate was evaporated, and the residue
was recrystallized from toluene. Yield 0.40 g (83%).
1
525. H NMR spectrum, δ, ppm: 5.19 s (2H, CH2),
c. A mixture of 0.7 g (1.6 mmol) of phosphazene 7
and 100 mL of 3% aqueous sulfuric acid was refluxed
for 3 h. The mixture was cooled, the precipitate of
triphenylphosphine oxide was filtered off, and the
filtrate was neutralized to pH 7 with 10% aqueous
3
7.37 d (1H, Harom, J = 8.3 Hz), 7.44 d.d (1H, Harom
,
3J = 8.3, J = 1.9 Hz), 7.63 d (1H, Harom, J = 1.9 Hz).
13C NMR spectrum, δC, ppm: 48.5 (CH2), 128.2
(Carom), 129.5 (Carom), 131.6 (Carom), 132.7 (Carom),
4
4
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 10 2018

SYNTHESIS OF 1-ALKYL-5-AMINO-1,2,4-TRIAZOLES
1543
sodium hydroxide and extracted with ethyl acetate
(3×75 mL). The combined extracts were washed with
water (2×20 mL) and dried over magnesium sulfate,
the solvent was distilled off, and the residue was
recrystallized from toluene. Yield 0.14 g (50%),
mp 140–141°C. IR spectrum, ν, cm–1: 3315 (NH2),
3169, 1653 (NH2), 1578, 1512, 1429, 1304, 1259,
100 mL of water and 20 mL of ethanol was refluxed
for 40 min. The mixture was cooled to 0°C, and the
precipitate was filtered off, dried, and recrystallized
from toluene. Yield 1.0 g (83%), mp 194–195°C. IR
spectrum, ν, cm–1: 3292 (NH2), 3148, 1661 (NH2),
1570, 1504, 1456, 1447, 1366, 1296, 1240, 1138,
1
1105, 1003, 787, 756, 702, 683, 660, 608. H NMR
1
1236, 1101, 1001, 876, 812, 739, 673, 656. H NMR
spectrum, δ, ppm: 5.09 s (2H, CH2), 6.71 br.s (2H,
NH2), 7.21–7.39 m (5H, Harom). 13C NMR spectrum,
δC, ppm: 49.8 (CH2), 128.0 (Carom), 128.1 (Carom),
129.0 (Carom), 136.6 (C3), 136.9 (Carom), 156.9 (C5).
Mass spectrum, m/z (Irel, %): 255 (2.1) [M]+, 254 (20.0)
[M]+, 253 (2.3) [M]+, 252 (20.5) [M]+, 108 (7.4), 106
(9.2), 92 (13.5), 91 (100), 89 (6.1), 77 (5.3), 65 (18.4),
53 (7.0), 51 (5.7), 39 (6.8). Found, %: C 42.53; H 3.45;
N 22.41. C9H9BrN4. Calculated, %: C 42.71; H 3.58;
N 22.14. M 253.10.
spectrum, δ, ppm: 3.48 s (3H, CH3), 6.47 br.s (2H,
13
NH2). C NMR spectrum, δC, ppm: 33.9 (CH3), 135.7
(C3), 156.9 (C5). Mass spectrum, m/z (Irel, %): 179
(4.2) [M]+, 178 (97.0) [M]+, 176 (100) [M]+, 136
(30.7), 135 (6.0), 134 (32.7), 108 (16.8), 106 (17.2), 68
(5.0), 55 (7.0), 53 (17.0), 43 (28.0), 42 (6.9), 30 (6.9),
27 (5.1), 15 (24.0), 13 (5.3), 12 (10.0). Found, %:
C 20.32; H 2.62; N 31.51. C3H5BrN4. Calculated, %:
C 20.36; H 2.85; N 31.65. M 177.00.
3-Bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-
1,2,4-triazol-5-amine (4d). Sodium tetrahydrido-
borate, 0.45 g (12 mmol), was added over a period of
30 min to a solution of 4.64 g (17 mmol) of triazole 3d
in 125 mL of ethanol, allowing the mixture to warm up
to 30°C. The mixture was stirred for 2 h and filtered,
the solvent was distilled off from the filtrate, and the
residue was crystallized from toluene. Yield 3.48 g
(83%), mp 145–146°C. IR spectrum, ν, cm–1: 3381
(NH2), 3300, 3161, 2949, 2978, 2360, 2341, 1647
(NH2), 1566, 1504, 1472, 1441, 1373, 1360, 1292,
1281, 1263, 1204, 1188, 1096, 1047, 1028, 1018, 989,
3-Bromo-1-(3-methylbutyl)-1H-1,2,4-triazol-
5-amine (4b). Sodium tetrahydridoborate, 1.13 g
(0.03 mol), was added over a period of 30 min to
a solution of 8.1 g (0.03 mol) of triazole 3b in 130 mL
of propan-2-ol, allowing the mixture to warm up. The
mixture was then heated to the boiling point and
cooled, the precipitate was filtered off, the solvent was
distilled off from the filtrate, and the residue was
extracted with ethyl acetate (3×75 mL). The combined
extracts were washed with water (2×20 mL) and dried
over magnesium sulfate, the solvent was distilled off,
and the residue was recrystallized from toluene–
hexane (1:1). Yield 5.4 g (74%), mp 119–120°C. IR
spectrum, ν, cm–1: 3331 (NH2), 3080, 2954, 2934,
2870, 2763, 2341, 1657 (NH2), 1582, 1504, 1458,
1387, 1370, 1300, 1248, 1171, 1096, 1074, 991, 737,
706, 660. 1H NMR spectrum, δ, ppm: 0.91 d (6H, CH3,
3J = 6.2 Hz), 1.46–1.63 m (3H, CH, CH2), 3.89 t (2H,
CH2, 3J = 7.0 Hz), 6.47 br.s (2H, NH2). 13C NMR spec-
trum, δC, ppm: 22.6 (2C, CH3), 25.4 (CH), 37.6 (CH2),
44.8 (1-CH2), 135.8 (C3), 156.3 (C5). Mass spectrum,
m/z (Irel, %): 235 (1.2) [M]+, 234 (11.4) [M]+, 232
(11.8) [M]+, 219 (0.7), 218 (0.5), 217 (1.2), 191 (0.6),
190 (0.6), 189 (0.7), 178 (21.0), 177 (8.2), 176 (22.7),
175 (7.1), 165 (9.6), 164 (40.5), 163 (10.4), 162 (41.6),
153 (7.8), 135 (6.3), 133 (6.0), 108 (9.8), 106 (9.3), 98
(5.0), 97 (100), 70 (5.6), 68 (9.6), 57 (5.4), 55 (20.2),
53 (9.1), 43 (33.6), 42 (11.5), 41 (29.6), 39 (11.0), 29
(10.8), 27 (12.0). Found, %: C 35.78; H 6.09; N 24.62.
C7H13BrN4. Calculated, %: C 36.07; H 5.62; N 24.03.
M 233.11.
1
926, 891, 868, 849, 812, 758, 731, 658, 619. H NMR
spectrum, δ, ppm: 1.42–1.66 m (3H), 1.77 m (1H),
1.84–2.13 m (2H), 3.53–3.68 m (1H), 3.87 d (1H, 2J =
12.5 Hz), 5.23 d.d (1H, 3J = 2.5, 9.6 Hz), 6.70 br.s (2H,
NH2). 13C NMR spectrum, δC, ppm: 22.6 (CH2), 24.9
(CH2), 29.1 (CH2), 67.0 (CH2O), 81.7 (OCH), 137.1
(C3), 156.8 (C5). Mass spectrum, m/z (Irel, %): 248
(2.9) [M]+, 246 (3.0) [M]+, 165 (16.1), 164 (10.6), 163
(18.0), 162 (10.5), 108 (8.7), 106 (8.5), 86 (5.4), 85
(100), 84 (40.7), 68 (7.2), 67 (18.4), 57 (23.5), 56
(5.0), 55 (15.6), 53 (13.0), 43 (22.5), 42 (6.9), 41
(34.6), 39 (11.5), 29 (31.3), 28 (6.4), 27 (15.2). Found,
%: C 34.46; H 4.15; N 22.60. C7H11BrN4O. Calculated,
%: C 34.03; H 4.49; N 22.67. M 247.09.
2-(5-Amino-3-bromo-1H-1,2,4-triazol-1-yl)-
ethanol (4e). Sodium tetrahydridoborate, 0.9 g
(23 mmol), was added over a period of 10 min to a so-
lution of 7.6 g (33 mmol) of compound 3e in 120 mL
of ethanol, allowing the mixture to warm up to 30°C.
The mixture was stirred for 2 h and filtered, the solvent
was distilled off from the filtrate, and the residue was
crystallized from ethyl acetate. Yield 5.89 g (87%),
1-Benzyl-3-bromo-1H-1,2,4-triazol-5-amine (4c).
A solution of 1.33 g (4.8 mmol) of triazole 3c and
10.0 g (79 mmol) of sodium sulfite in a mixture of
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 10 2018

TOLSTYAKOV
1544
mp 153–154°C. IR spectrum, ν, cm–1: 3425 (OH),
3366 (NH2), 3296, 3173, 1645 (NH2), 1583, 1568,
1508, 1433, 1381, 1364, 1342, 1306, 1244, 1096,
1070, 1036, 1003, 997, 964, 874, 862, 731, 650, 561,
523, 502. 1H NMR spectrum, δ, ppm: 3.66 q (2H, CH2,
spectrum, ν, cm–1: 3317 (NH2), 3173, 2932, 1653
(NH2), 1616, 1589, 1566, 1508, 1445, 1421, 1356,
1308, 1288, 1246, 1178, 1101, 1032, 1001, 835, 804,
766, 745, 714, 694, 663, 554, 507. 1H NMR spectrum,
δ, ppm: 3.75 s (3H, OCH3), 4.99 s (2H, CH2), 6.64 br.s
(2H, NH2), 6.89 d (2H, Harom, 3J = 8.6 Hz), 7.20 d (2H,
3
3J = 5.6 Hz), 3.88 t (2H, CH2, J = 5.7 Hz), 4.85 t
13
3
13
(1H, OH, 3J = 5.3 Hz), 6.33 br.s (2H, NH2). C NMR
Harom, J = 8.6 Hz). C NMR spectrum, δC, ppm: 49.2
spectrum, δC, ppm: 50.4 (CH2), 60.9 (CH2OH), 137.0
(C3), 158.3 (C5). Mass spectrum, m/z (Irel, %): 209
(1.8) [M]+, 208 (33.7) [M]+, 206 (32.5) [M]+, 178
(5.3), 177 (11.5), 176 (4.0), 175 (12.8), 165 (9.7),
164 (96.3), 162 (100), 135 (25.8), 133 (28.5), 108
(15.1), 106 (15.6), 97 (48.1), 68 (24.0), 57 (8.0), 55
(8.0), 53 (16.5), 45 (11.0), 43 (24.2), 42 (7.2), 31
(24.7), 30 (7.4), 29 (11.2), 27 (8.8). Found, %:
C 23.35; H 3.29; N 27.40. C4H7BrN4O. Calculated, %:
C 23.21; H 3.41; N 27.06. M 207.03.
(CH2), 55.6 (OCH3), 114.4 (Carom), 128.8 (Carom), 129.6
(Carom), 136.4 (C3), 156.6 (C5), 159.3 (Carom). Mass
spectrum, m/z (Irel, %): 285 (2.7) [M]+, 284 (19.9) [M]+,
283 (2.5) [M]+, 282 (19.6) [M]+, 269 (0.9), 267 (1.1),
122 (18.2), 121 (100), 108 (5.0), 106 (7.0), 91 (9.8), 89
(5.1), 78 (12.3), 77 (10.9). Found, %: C 42.13; H 3.50;
N 19.61. C10H11BrN4O. Calculated, %: C 42.42;
H 3.92; N 19.79. M 283.12.
1-Methyl-1H-1,2,4-triazol-5-amine (5a). Hydra-
zine hydrate (98%), 10 mL (0.5 mol), was added to
a mixture of 1.31 g (7.4 mmol) of compound 4a and
0.3 g (7.4 mmol) of sodium hydroxide in 20 mL of
ethanol, and 0.3 g of Raney nickel was then added.
The mixture was heated to 60°C and stirred at that
temperature until hydrazine hydrate was consumed
completely (vigorous reaction ceased). Two additional
portions of hydrazine hydrate, 10 mL (0.5 mol) each,
were then added in a similar way. When the reaction
was complete (overall reaction time 3.5 h), the catalyst
was filtered off, the solvent was distilled off from the
filtrate, and the residue was crystallized from toluene.
Yield 0.44 g (61%), mp 183–184°C; published data:
mp 183°C [24], 185°C [8]. IR spectrum, ν, cm–1: 3308
(NH2), 3113, 1670 (NH2), 1578, 1533, 1448, 1420,
1296, 1259, 1202, 1094, 1007, 980, 866, 787, 739,
3-Bromo-1-(2,4-dichlorobenzyl)-1H-1,2,4-triazol-
5-amine (4f). Sodium tetrahydridoborate, 1.13 g
(30 mmol), was added over a period of 15 min to
a solution of 10.7 g (30 mmol) of triazole 3f in 200 mL
of propan-2-ol, heated to 60°C. The mixture was then
heated to 80°C, cooled, and evaporated to dryness, and
the residue was crystallized from toluene. Yield 8.0 g
(83%), mp 160–161°C. IR spectrum, ν, cm–1: 3314
(NH2), 3157, 3055, 1653 (NH2), 1574, 1501, 1475,
1445, 1393, 1298, 1254, 1242, 1134, 1103, 1053, 999,
1
878, 858, 812, 679, 654, 569. H NMR spectrum, δ,
ppm: 5.15 s (2H, CH2), 6.77 br.s (2H, NH2), 6.98 d
3
3
(1H, Harom, J = 8.4 Hz), 7.41 d.d (1H, Harom, J = 8.3,
4J = 2.1 Hz), 7.60 d (1H, Harom, 4J = 2.1 Hz). 13C NMR
spectrum, δC, ppm: 47.4 (CH2), 128.1 (Carom), 129.4
(Carom), 130.8 (Carom), 133.3 (Carom), 133.4 (Carom),
133.6 (Carom), 137.1 (C3), 157.3 (C5). Mass spectrum,
m/z (Irel, %): 326 (1.1) [M]+, 324 (5.9) [M]+, 323 (1.4)
[M]+, 322 (12.4) [M]+, 320 (8.0) [M]+, 291 (0.6), 290
(1.0), 289 (7.3), 288 (3.6), 287 (29.9), 285 (25.0), 163
(10.9), 161 (63.4), 159 (100), 125 (6.2), 124 (5.7), 123
(14.9), 108 (11.3), 106 (11.1), 89 (11.2), 53 (10.8), 42
(5.7), 28 (6.2). Found, %: C 34.05; H 1.78; N 17.28.
C9H7BrCl2N4. Calculated, %: C 33.57; H 2.19;
N 17.40. M 321.99.
1
677, 646. H NMR spectrum, δ, ppm: 3.50 s (3H,
CH3), 6.03 br.s (2H, NH2), 7.21 s (1H, 3-H). 13C NMR
spectrum, δC, ppm: 33.6 (CH3), 148.4 (C3), 155.7
(C5). Mass spectrum, m/z (Irel, %): 99 (4.2) [M]+, 98
(100) [M]+, 97 (13.5), 70 (1.7), 56 (22.1), 55 (5.7),
54 (2.1), 53 (2.6), 43 (42.4), 42 (5.8), 28 (39.3), 27
(6.5), 15 (11.6).
1-(3-Methylbutyl)-1H-1,2,4-triazol-5-amine (5b).
Hydrazine hydrate (98%), 10 mL (0.5 mol), was added
to a mixture of 1.30 g (5.6 mmol) of compound 4b and
0.22 g (5.5 mmol) of sodium hydroxide in 20 mL of
ethanol, and 0.3 g of Raney nickel was then added.
The mixture was heated to 60°C and stirred at that
temperature until hydrazine hydrate was consumed
completely (vigorous reaction ceased). Two additional
portions of hydrazine hydrate, 10 mL (0.5 mol) each,
were then added in a similar way. When the reaction
was complete (overall reaction time 3.5 h), the catalyst
was filtered off, the solvent was distilled off from the
3-Bromo-1-(4-methoxybenzyl)-1H-1,2,4-triazol-
5-amine (4g). Sodium tetrahydridoborate, 0.146 g
(3.9 mmol), was added over a period of 15 min at 30°C
to a solution of 1.7 g (5.5 mmol) of triazole 3g in
50 mL of ethanol. The mixture was heated to 45°C,
stirred for 10 min at that temperature, and diluted with
50 mL of water, and ethanol was distilled off. After
cooling, the precipitate was filtered off. Yield 1.34 g
(86%), mp 137–138°C (from toluene–hexane, 1:4). IR
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 10 2018

SYNTHESIS OF 1-ALKYL-5-AMINO-1,2,4-TRIAZOLES
1545
filtrate, and the residue was crystallized from water.
Yield 0.61 g (71%), mp 104–105°C. IR spectrum, ν,
cm–1: 3294 (NH2), 3244, 3107, 2959, 2740, 2677,
2525, 1672 (NH2), 1564, 1495, 1474, 1456, 1412,
1385, 1369, 1337, 1279, 1223, 1177, 1159, 1126, 1042,
1013, 953, 903, 883, 851, 812, 770, 756, 719, 637,
590. 1H NMR spectrum, δ, ppm: 0.91 d (6H, CH3, 3J =
5.4 Hz), 1.47–1.61 m (3H, CH, CH2), 3.83 t (2H, CH2,
3J = 7.0 Hz), 6.06 br.s (2H, NH2), 7.25 s (1H, 3-H).
13C NMR spectrum, δC, ppm: 22.7 (2C, CH3), 25.4
(CH), 37.8 (CH2), 44.4 (1-CH2), 148.3 (C3), 155.1
(C5). Mass spectrum, m/z (Irel, %): 154 (11.0) [M]+, 139
(2.0), 97 (52.3), 84 (72.4), 70 (43.1). Found, %:
C 54.11; H 9.34; N 36.63. C7H14N4. Calculated, %:
C 54.52; H 9.15; N 36.33. M 154.21.
was distilled off from the filtrate, and the residue was
crystallized from toluene. Yield 1.41 g (79%), mp 149–
150°C. IR spectrum, ν, cm–1: 3319 (NH2), 3134, 2943,
2773, 2721, 1801, 1668 (NH2), 1570, 1521, 1456,
1440, 1379, 1294, 1281, 1261, 1209, 1186, 1161,
1086, 1063, 1042, 1007, 972, 937, 914, 881, 845, 829,
1
810, 745, 723, 654, 557. H NMR spectrum, δ, ppm:
1.41–1.66 m (3H), 1.71–1.81 m (1H), 1.89–2.00 m
(1H), 2.03–2.17 m (1H), 3.44–3.71 m (1H), 3.86 d.d
3
2
3
(1H, J = 4.8, J = 7.8 Hz), 5.24 d.d (1H, J = 2.4,
9.7 Hz), 6.31 br.s (2H, NH2), 7.33 s (1H, 3-H).
13C NMR spectrum, δC, ppm: 22.7 (CH2), 25.0 (CH2),
29.3 (CH2), 66.9 (CH2O), 81.7 (OCH), 148.8 (C3),
155.8 (C5). Mass spectrum, m/z (Irel, %): 169 (0.9)
[M]+, 168 (14.1) [M]+, 85 (100), 84 (50.5), 67 (14.2),
57 (17.4), 55 (12.5), 43 (17.5), 42 (5.4), 41 (22.4), 39
(6.6), 29 (17.0), 28 (12.2), 27 (7.9). Found, %:
C 49.92; H 7.10; N 33.36. C7H12N4O. Calculated, %:
C 49.99; H 7.19; N 33.31. M 168.20.
1-Benzyl-1H-1,2,4-triazol-5-amine (5c). Hydra-
zine hydrate (98%), 10 mL (0.5 mol), was added to
a mixture of 1.165 g (4.6 mmol) of triazole 4c and
0.184 g (4.6 mmol) of sodium hydroxide in 20 mL of
ethanol, and 0.5 g of Raney nickel was then added.
The mixture was heated to 60°C and stirred at that
temperature until hydrazine hydrate was consumed
completely (vigorous reaction ceased). Two additional
portions of hydrazine hydrate, 10 mL (0.5 mol) each,
were then added in a similar way. When the reaction
was complete (overall reaction time 3.5 h), the catalyst
was filtered off, the solvent was distilled off from the
filtrate, and the residue was crystallized from toluene.
Yield 0.62 g (78%), mp 127–128°C [6]. IR spectrum,
ν, cm–1: 3427, 3312 (NH2), 3119, 1796, 1649 (NH2),
1570, 1522, 1497, 1452, 1431, 1360, 1310, 1283,
1254, 1205, 1113, 1078, 1059, 1028, 974, 903, 743,
708, 652, 581. 1H NMR spectrum, δ, ppm: 5.10 s (2H,
CH2), 6.27 br.s (2H, NH2), 7.17–7.37 m (5H, Harom),
7.31 s (1H, 3-H). 13C NMR spectrum, δC, ppm: 49.4
(CH2), 127.8 (Carom), 128.9 (Carom), 137.5 (Carom), 148.9
(C3), 155.7 (C5). Mass spectrum, m/z (Irel, %): 175
(5.7) [M]+, 174 (46.9) [M]+, 173 (4.2), 132 (2.1), 131
(0.6), 92 (8.4), 91 (100), 65 (10.9), 28 (6.7).
2-(5-Amino-1H-1,2,4-triazol-1-yl)ethanol (5e).
Hydrazine hydrate (98%), 8 mL (0.4 mol), was added
to a mixture of 0.93 g (4.5 mmol) of triazole 4e and
0.18 g (4.5 mmol) of sodium hydroxide in 10 mL of
ethanol, and 0.3 g of Raney nickel was then added.
The mixture was stirred at 60°C until hydrazine
hydrate was consumed completely (vigorous reaction
ceased). Two additional portions of hydrazine hydrate,
8 mL (0.4 mol) each, were then added in a similar way.
When the reaction was complete (overall reaction time
3.5 h), the catalyst was filtered off, the solvent was
distilled off from the filtrate, 5 mL of water and 50 mL
of toluene were added to the residue, and toluene–
water azeotrope was distilled off. The azeotropic
drying procedure was repeated until complete drying.
The residue was treated with hot ethyl acetate (3×
50 mL), the combine extracts were evaporated, and the
residue was recrystallized from toluene. Yield 0.45 g
(78%), mp 104–105°C. IR spectrum, ν, cm–1: 3375,
3204 (NH2), 3053, 2849, 2932, 2710, 2586, 1747,
1653 (NH2), 1566, 1529, 1468, 1447, 1383, 1367,
1285, 1269, 1244, 1209, 1140, 1067, 1024, 984, 961,
876, 860, 822, 735, 664, 646, 548. 1H NMR spectrum,
δ, ppm: 3.65 t (2H, CH2, 3J = 5.7 Hz), 3.90 t (2H, CH2,
3J = 5.9 Hz), 4.91 br.s (1H, OH), 6.05 br.s (2H, NH2),
1-(Tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-
5-amine (5d). Hydrazine hydrate (98%), 12 mL
(0.6 mol), was added to a mixture of 2.61 g
(10.56 mmol) of triazole 4d and 0.42 g (10.5 mmol) of
sodium hydroxide in 40 mL of ethanol, and 0.5 g of
Raney nickel was then added. The mixture was heated
to 60°C and stirred at that temperature until hydrazine
hydrate was consumed completely (vigorous reaction
ceased). Two additional portions of hydrazine hydrate,
12 mL (0.6 mol) each, were then added in a similar
way. When the reaction was complete (overall reaction
time 3.5 h), the catalyst was filtered off, the solvent
13
7.32 s (1H, 3-H). C NMR spectrum, δC, ppm: 48.7
(CH2), 59.9 (CH2OH), 148.5 (C3), 155.9 (C5). Mass
spectrum, m/z (Irel, %): 129 (3.9) [M]+, 128 (47.7)
[M]+, 99 (0.5), 98 (13.5), 97 (35.7), 86 (0.5), 85 (16.2),
84 (100), 71 (5.1), 70 (14.3), 57 (10.0), 55 (36.3),
43 (40.9), 42 (11.2), 31 (16.9), 29 (11.5), 28 (35.2),
27 (9.1). Found, %: C 37.78; H 6.25; N 43.68.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 10 2018

TOLSTYAKOV
1546
C4H8N4O. Calculated, %: C 37.49; H 6.29; N 43.73.
M 128.13.
precipitate was filtered off. An additional amount of
the product was isolated from the filtrate by extraction
with ethyl acetate (2×25 mL). The combined extracts
were evaporated, and the residue was combined with
the main portion of the product and recrystallized from
toluene. Yield 0.755 g (80%), mp 144–145°C. IR spec-
trum, ν, cm–1: 3327 (NH2), 3142, 3113, 1661 (NH2),
1616, 1574, 1522, 1448, 1425, 1352, 1279, 1263,
1250, 1209, 1178, 1126, 1061, 1034, 978, 843, 789,
756, 741, 719, 689, 679, 640, 554. 1H NMR spectrum,
δ, ppm: 3.72 s (3H, OCH3), 5.03 s (2H, CH2), 6.29 br.s
1-(2,4-Dichlorobenzyl)-1H-1,2,4-triazol-5-amine
(5f). Hydrazine hydrate (98%), 12 mL (0.6 mol), was
added to a mixture of 1.84 g (5.74 mmol) of triazole 4f
and 0.23 g (5.75 mmol) of sodium hydroxide in 45 mL
of ethanol, and 0.3 g of Raney nickel was then added.
The mixture was stirred at 60°C until hydrazine
hydrate was consumed completely (vigorous reaction
ceased). An additional portion of hydrazine hydrate,
12 mL (0.6 mol), was then added in a similar way.
When the reaction was complete (overall reaction time
4 h), the catalyst was filtered off, ethanol was distilled
off from the filtrate, the residue was cooled, and the
precipitate was filtered off and recrystallized from
toluene. Yield 1.23 g (88%), mp 142–143°C. IR spec-
trum, ν, cm–1: 3450 (NH2), 3283, 3076, 2928, 1825,
1638 (NH2), 1589, 1560, 1522, 1468, 1435, 1418,
1385, 1352, 1290, 1252, 1205, 1150, 1121, 1097,
1069, 1051, 976, 957, 928, 918, 866, 837, 816, 806,
(2H, NH2), 6.89 d (2H, Harom, 3J = 8.7 Hz), 7.17 d (2H,
3
H
arom, J = 8.6 Hz), 7.33 s (1H, C3). 13C NMR spec-
trum, δC, ppm: 48.8 (CH2), 55.5 (CH3O), 114.3 (Carom),
129.4 (Carom), 129.5 (Carom), 148.9 (C3), 155.5 (C5),
159.1 (Carom). Mass spectrum, m/z (Irel, %): 205 (2.1)
[M]+, 204 (16.8) [M]+, 122 (9.7), 121 (100), 78 (7.2),
77 (6.0), 28 (6.9). Found, %: C 59.23; H 5.72;
N 27.09. C10H12N4O. Calculated, %: C 58.81; H 5.92;
N 27.43. M 204.23.
1
(3-Bromo-1-methyl-1H-1,2,4-triazol-5-yl)hydra-
zine (6). A mixture of 17.5 g (0.073 mol) of triazole 2a
and 36.5 mL (0.73 mol) of 98% hydrazine hydrate in
150 mL of propan-2-ol was refluxed for 5.5 h with
stirring. The mixture was cooled, the precipitate was
filtered off, and the filtrate was evaporated to a volume
of 15 mL to isolate an additional amount of the product
which was combined with the main portion and recrys-
tallized from toluene. Yield 11.6 g (83%), mp 196–
197°C. IR spectrum, ν, cm–1: 3325 (NH), 3256, 2924,
1634 (NH), 1582, 1521, 1456, 1437, 1429, 1331, 1294,
1246, 1227, 1132, 1024, 999, 947, 866, 731, 681, 608,
733, 723, 685, 650, 550, 503. H NMR spectrum, δ,
ppm: 5.18 s (2H, CH2), 6.41 br.s (2H, NH2), 6.79 d
3
3
(1H, Harom, J = 8.4 Hz), 7.42 d.d (1H, Harom, J = 8.3,
4J = 2.2 Hz), 7.42 s (1H, 3-H), 7.65 d (1H, Harom, J =
4
2.2 Hz). 13C NMR spectrum, δC, ppm: 47.1 (CH2),
128.0 (Carom), 129.3 (Carom), 130.2 (Carom), 133.2
(Carom), 133.3 (Carom), 134.2 (Carom), 149.6 (C3), 156.3
(C5). Mass spectrum, m/z (Irel, %): 246 (1.2) [M]+, 245
(0.9) [M]+, 244 (7.8) [M]+, 243 (1.6) [M]+, 242 (11.8)
[M]+, 210 (2.1), 209 (19.4), 208 (6.9), 207 (59.3), 205
(0.9), 163 (11.1), 162 (5.3), 161 (66.6), 160 (7.9), 159
(100), 125 (9.5), 124 (8.5), 123 (21.2), 99 (6.6), 89
(29.8), 75 (13.1), 74 (8.6), 73 (9.1), 63 (17.3), 62 (8.8),
55 (6.3), 54 (9.5), 53 (6.8), 50 (5.7), 43 (20.5), 42
(11.4), 39 (5.9), 28 (22.8), 27 (8.1). Found, %:
C 44.20; H 3.34; N 23.17. C9H8Cl2N4. Calculated, %:
C 44.47; H 3.32; N 23.05. M 243.09.
1
567, 557. H NMR spectrum, δ, ppm: 3.51 s (3H,
CH3), 4.52 br.s (2H, NH2, overlapped by the signal
of water present in the solvent), 7.84 s (1H, NH).
13C NMR spectrum, δC, ppm: 34.3 (CH3), 135.5 (C3),
159.5 (C5). Mass spectrum, m/z (Irel, %): 193 (61.3)
[M]+, 191 (64.2) [M]+, 178 (4.8), 177 (8.2), 176 (8.2),
175 (10.0), 174 (2.9), 164 (3.1), 163 (4.1), 161 (9.1),
159 (8.2), 136 (5.3), 135 (9.4), 134 (6.3), 133 (11.4),
112 (70.4), 108 (16.0), 106 (16.1), 95 (13.0), 83 (43.0),
82 (47.8), 81 (8.6), 80 (5.7), 78 (6.9), 68 (5.9), 56
(7.6), 55 (18.1), 53 (30.6), 43 (100), 42 (32.7), 41
(7.9), 40 (7.3), 31 (18.6), 30 (37.6), 29 (18.8), 28
(11.8), 27 (7.5), 17 (5.7), 16 (8.9), 15 (39.4). Found,
%: C 19.07; H 3.11; N 36.87. C3H6BrN5. Calculated,
%: C 18.77; H 3.15; N 36.47. M 192.02.
1-(4-Methoxybenzyl)-1H-1,2,4-triazol-5-amine
(5g). Hydrazine hydrate (98%), 12 mL (0.6 mol), was
added to a mixture of 1.31 g (4.63 mmol) of triazole 4g
and 0.185 g (4.63 mmol) of sodium hydroxide in
25 mL of ethanol, and 0.3 g of Raney nickel was then
added. The mixture was stirred at 60°C until hydrazine
hydrate was consumed completely (vigorous reaction
ceased). An additional portion of hydrazine hydrate,
12 mL (0.6 mol), was then added in a similar way.
When the reaction was complete (overall reaction time
4 h), the catalyst was filtered off, ethanol was distilled
off from the filtrate, 20% aqueous HCl was added to
the residue until pH 7, the mixture was cooled, and the
3-Bromo-1-methyl-N-(triphenyl-λ5-phosphanyli-
dene)-1H-1,2,4-triazol-5-amine (7). A solution of
1.29 g (5 mmol) of triphenylphosphine in 10 mL of
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 10 2018

SYNTHESIS OF 1-ALKYL-5-AMINO-1,2,4-TRIAZOLES
1547
6. Er-Rhaimini, A. and Mornet, R., J. Heterocycl. Chem.,
toluene was added to a solution of 1.0 g (5 mmol) of
triazole 3a in 30 mL of toluene. When the reaction was
complete (it was accompanied by evolution of heat and
gas), the mixture was cooled, and the precipitate was
filtered off. Yield 1.7 g (78%), mp 187–188°C (from
toluene). IR spectrum, ν, cm–1: 1591, 1577, 1541,
1481, 1452, 1433, 1414, 1387, 1329, 1298, 1244,
1209, 1190, 1183, 1113, 1051, 1026, 988, 851, 808,
750, 741, 719, 692, 654, 573, 529, 519. 1H NMR spec-
trum, δ, ppm: 3.64 s (3H, CH3), 7.56–7.79 m (15H,
1992, vol. 29, p. 1561.
7. Barascut, J.L., Claramunt, R.M., and Elguero, J., Bull.
Soc. Chim. Fr., 1973, p. 1849.
8. Chipen, G.I. and Grinshtein, V.Ya., Izv. Akad. Nauk Latv.
SSR, Ser. Khim., 1962, no. 2, p. 263.
9. Chipen, G.I. and Grinshtein, V.Ya., Zh. Obshch. Khim.,
1962, vol. 32, p. 3811.
10. Kroeger, C.-F., Etzold, G., and Beyer, H., Justus Liebigs
Ann. Chem., 1963, p. 156.
11. Baba, M., Kamimura, S., and Nemugaki, S., JPN Patent
no. 2005343867, 2005.
H
arom). 13C NMR spectrum, δC, ppm: 33.4 (CH3), 128.0
(Carom), 129.0 (Carom), 129.3 (Carom), 129.4 (Carom),
132.9 (Carom), 133.0 (Carom), 133.1 (Carom), 134.8 (C3),
158.5 (C5). Mass spectrum, m/z (Irel, %): 440 (1.5)
[M]+, 439 (19.7) [M]+, 438 (95.7) [M]+, 437 (100)
[M]+, 436 (94.3) [M]+, 435 (77.1), 432 (0.7), 361 (6.6),
359 (7.6), 357 (5.8), 328 (6.4), 303 (7.2), 289 (7.2),
288 (35.4), 283 (5.8), 281 (6.2), 262 (15.0), 261 (10.6),
185 (18.3), 184 (14.7), 183 (87.6), 152 (9.5), 108
(13.8), 107 (9.0), 77 (9.3), 43 (9.2), 32 (6.3), 28 (19.2),
18 (38.6), 17 (6.9), 16 (5.4), 14 (7.2). Found, %:
C 57.75; H 4.04; N 13.08. C21H18BrN4P. Calculated,
%: C 57.68; H 4.15; N 12.81. M 437.27.
12. Szommer, T., Lukacs, A., Kovacs, J., Szabo, J., Hoff-
mann, G., Schmitt, H., and Gerencser, J., Mol. Diversity,
2012, p. 81.
13. Grinshtein, V.Ya. and Strazdin’, A.A., Chem. Hetero-
cycl. Compd., 1969, vol. 5, p. 844.
14. Zumbrunn, A., Synthesis, 1998, p. 1357.
15. Bradshaw, J.S., Nielsen, R.B., Tse, P.-K., Arena, G.,
Wilson, B.E., Dalley, N.K., Lamb, J.D., Christen-
sen, J.J., and Izatt, R.M., J. Heterocycl. Chem., 1986,
vol. 23, p. 361.
16. Khaliullin, F.A. and Klen, E.E., Russ. J. Org. Chem.,
2009, vol. 45, p. 135.
17. Gregory, V., Pasteris, R.J., and Hanagan, M.A., US
Patent no. 8449898, 2013.
18. Witkowski, J.T. and Robins, R.K., J. Org. Chem., 1970,
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 17-03-00566-a).
vol. 35, p. 2635.
19. Libnow, S., Wille, S., Christiansen, A., Hein, M.,
Reinke, H., Kockerling, M., and Miethchen, R.,
Synthesis, 2006, p. 496.
REFERENCES
1. Hobson, A., Akiti, O., Deshmukh, S., and Harper, S., Org.
Process Res. Dev., 2010, vol. 14, p. 441.
20. Aiwale, S.T. and Dallavalle, S., Synthesis, 2012, vol. 44,
p. 3055.
2. Huang, L., Liu, S., Lunney, E.A., and Planken, S.P., Int.
Patent Appl. no. WO 2007/125405.
21. Alonso, F., Beletskaya, I.P., and Yus, M., Chem. Rev.,
2002, vol. 102, p. 4009.
22. Miethchen, R., Seipt, H.-U., and Kroger, C.-F.,
3. Fay, L.K., Johnson, D.S., and Kesten, S.R., US Patent
no. 8044052, 2011.
Z. Chem., 1969, vol. 9, p. 300.
4. Jones, D.F. and Oldham, K., EU Patent Appl.
no. EP 0060696, 1982.
5. Braun, R., Kohn, A., Almsick, A., Ahrens, H., Dorner-
Rieping, S., Willms, L., Hauser-Hahn, I., Heinemann, I.,
Gatzweiler, E., and Rosinger, C.H., US Patent
no. 8481749, 2013.
23. Flohr, A., Groebke Zbinden, K., Kuhn, B., Lerner, C.,
Rudolph, M., and Schaffhauser, H., Int. Patent Appl.
no. WO 2013178572, 2013.
24. Kroeger, C.-F., Schoknecht, G., and Beyer, H., Chem.
Ber., 1964, vol. 97, p. 396.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 10 2018