The curtius reaction in the synthesis of noncondensed polynuclear azoles

Article abstract of DOI:10.1007/s10593-011-0781-5

Polynuclear noncondensed systems in which the azole rings are bound by urethane or carbamide fragments have been synthesized by the reaction of azole carboxylic acid azides with heterocyclic alcohols.

Full text of DOI:10.1007/s10593-011-0781-5

Chemistry of Heterocyclic Compounds, Vol. 47, No. 4, July 2011 (Russian original Vol. 47, No. 4, April, 2011)
THE CURTIUS REACTION IN THE SYNTHESIS OF
NONCONDENSED POLYNUCLEAR AZOLES
L. I. Vereshchagin1, T. V. Golobokova1,
F. A. Pokatilov1, A. G. Proidakov1, O. N. Verkhozina1,
A. I. Smirnov1, and V. N. Kizhnyaev1*
Polynuclear noncondensed systems in which the azole rings are bound by urethane or carbamide frag-
ments have been synthesized by the reaction of azole carboxylic acid azides with heterocyclic alcohols.
Keywords: azolylurethanes, heterocyclic ureas, heterocyclic alcohols, isocyanates, Curtius rearrange-
ment.
With the aim to synthesize noncondensed polynuclear azole containing systems we have previously [1,
2] used methods of adding heterocycles to the core structure having an active substituent in the form of an azide,
nitrile, or chloromethyl group, halogen, or acetylenic bond. The methods allow us to connect a number of
heterocycles separated by a methylene group or by other fragments.
In this study continuing our work on the synthesis of polynuclear heterocyclic structures we have exam-
ined the possible use of the Curtius rearrangement of heterocyclic acid azides to isocyanates and their
subsequent reaction with azole-containing alcohols to yield polynuclear structures in which the azole rings are
separated by carbamide or urethane fragments.
It is known that acyl and aroyl azides undergo the Curtius rearrangement upon heating to give alkyl and
aryl isocyanates. The latters subsequently react with compounds having an active hydrogen atom, e.g. alcohols,
amines, etc to give urethanes, ureas, and other compounds [3, 4]. However the behavior of triazoles and tetrazo-
les, unsubstituted at the nitrogen atom, and of other heterocyclic alcohols has remained unclear to this time.
In order to assess the reactivity of the azole-containing alcohols 1a–d and glycol 2 with isocyanates we
have carried out their reaction with benzoyl azide (Scheme 1). Since isocyanates are readily formed from acyl
azides upon heating in an anhydrous medium [3, 4] their initial separation was not necessary. Reactions of
compounds 1a–d, 2 with benzoyl azide were carried out on heating in absolute dioxane. It was found that
alcohols 1a–d and glycol 2 react without particular complications with the phenyl isocyanate formed during the
Curtius rearrangement to yield the N-phenylurethanes 3a–d and 4 (Table 1).
____________
*To whom correspondence should be addressed; e-mail: kizhnyaev@chem.isu.ru.
Institute for Oil and Coal Chemical Synthesis, Irkutsk State University, 1 K. Marx Street, Irkutsk 664003,
Russia.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 557–565, April, 2011. Original
article submitted June 24, 2010.
0009-3122/11/4704-0456©2011 Springer Science+Business Media, Inc.
456

In the case of the alcohols 1b,c there might have been expected a reaction at the active hydrogen atom of
the tetrazole and triazole ring, all the more so since reaction of isocyanates with NH-unsubstituted compounds is
known [3]. However, the reaction does not occur for phenyl isocyanate and 1,2,3-triazoles and tetrazoles. The
result of the reaction of phenyl isocyanate with the azoles 1b,c unsubstituted at the nitrogen atom is possibly due to
the weak nucleophilicity of the azole ring. The 5-aminotetrazole hydrate gave diphenylurea and this is likely
formed by participation of the water of hydration in the reaction. A similar effect has been seen in the reaction of
isocyanates with nitrophenols and with other compounds having acceptor substituents in the molecule [3]. It is
most probably for this reason that phenyl isocyanate does not react with the amino group of the 5-aminotetrazole.
Scheme 1
R
CH2OH
R
CH2OCONHPh
PhCON3
R1
R1
N
N
N
N
N
N
1a–d
3a–d
HOH2C
CH2OH
PhNHOCOH2C
CH2OCONHPh
PhCON3
N
N
N
N
O
O
4
2
1, 3 a–c R = H, a R1 = Bn, b R1 = 1,2,4-triazol-3-yl, c R1 = tetrazol-5-ylmethyl;
d R1 = Bn, 1d R = CH2OH, 3d R = CH2OCONHPh
In order to assess the reactivity of heterocyclic acid azides we have carried out the reaction of 2-phenyl-
1,2,3-triazole-4-carboxylic acid azide (5a) with the alcohols 1a,b and 2. In dioxane solution at 70–95ºC
compound 5a undergoes a rearrangement to the corresponding isocyanate which gives a set of noncondensed
triazole rings (6a,b and 7) linked by a urethane group (Scheme 2) when the alcohols indicated above are used.
Bistriazoles, connected via a carbamide fragment, were obtained: compound 8a in the process of rear-
rangement of the triazolocarboxylic acid azide 5 in the presence of small amounts of water in the reaction
medium and compound 8b through diazotization of the triazolocarbohydrazide N-oxide 9. In the latter case the
expected acyl azide could not be separated (Scheme 3).
Scheme 2
O
O
N3
N
O
H
CH2
1a,b
N
N
N
N
N
N
N
N
R1
N
Ph
Ph
5a
6a,b
2
O
O
N
H
N
H
O
N
CH2
N
CH2
N
N
O
N
N
N
N
N
O
7
Ph
Ph
6 a R1 = Bn; b R1 =
NH
N
457

Scheme 3
H
N
CO
H2O
N
N
5a
N
Ph
8a
2
O
O
H
Me
Me
Me
N
CO
OEt
NH2
N
+
+
+
N
N
N
H
N
N
N
N
N
–
N
–
O
–
O
Ph
O
Ph
Ph
2
12
9
8b
H
N
Me
O
CO
Me
OH
N
N
Ph
N
N
N
Ph
N
2
8c
11e
(PhO)2PON3
O
Me
H
N
Me
CO
OH
N
N
N
N
N
Ph
N
Ph
8d
2
11d
Experimentally, it was easier to prepare the azides indicated above by reaction of the acid chlorides
10a–c with sodium azide under phase transfer synthetic conditions (Scheme 4). Compounds 10a–c were
themselves prepared by treating acids 11a–c with phosphorus pentachloride.
Scheme 4
O
O
O
Cl
O
OH
N3
NaN3
N
N
N
N
N
N
N
N
N
Ph
Ph
11a
Ph
10a
5a
O
O
O
O
O
NaN3
PCl5
N3
Cl
Cl
OH
N3
HO
Bn
N
N
N
N
N
N
Bn
Bn
N
N
N
10b
11b
5b
O
O
O
O
O
O
NaN3
N3
Cl
OH
N3
HO
Bu
Cl
N
N
N
N
N
N
N
Bu
Bu
N
N
11c
10c
5c
458

TABLE 1. Characteristics of Compounds 1, 3–10
Found, %
Calculated, %
Com-
pound
Empirical formula
Mp, °C
Yield, %
С
H
N
1b
1c
3a
3b
3c
3d
4
C5H6N6O
C5H7N7O
36.51
36.14
3.83
3.61
50.12
50.60
182–184
130–131
108–110
115–118
78–81
85–90
105–110
92–94
175–176
218–220
229–231
222–225
196
76
78
60
58
64
94
92
66
55
67
48
40
72
74
72
72
86
79
33.71
33.14
3.47
3.86
53.92
54.14
C17H16N4O2
C12H11N7O2
C12H12N8O2
C25H23N5O4
C18H16N4O5
C9H6N6O
66.18
66.23
5.39
5.19
18.65
18.18
49.65
50.52
4.28
3.85
34.87
34.38
48.48
48.00
4.19
4.00
36.52
37.33
64.78
65.64
6.13
5.03
14.66
15.31
59.32
58.69
4.72
4.34
14.73
15.21
5a
6a
6b
7
49.02
50.46
3.04
2.80
38.80
39.25
C19H17N7O2
C14H12N10O2
C22H18N10O5
C17H14N8O
C19H18N8O3
C19H18N8O
C19H18N8O
C10H11N5O2
C11H7Cl2N3O2
C8H9Cl2N3O2
61.02
60.80
4.40
4.53
26.26
26.13
47.90
47.72
3.15
3.40
40.92
39.77
51.80
52.58
3.72
3.58
26.91
27.88
8a
8b
8с
8d
9
58.65
58.95
4.17
4.04
32.51
32.36
56.31
56.15
5.02
4.43
27.30
27.58
60.73
60.96
4.75
4.81
29.81
29.94
260
60.82
60.96
4.91
4.81
29.93
29.94
255
51.81
51.50
4.65
4.72
29.75
30.04
175–177
41
10b
10c
47.72
46.47
2.51
2.46
15.07
14.78
23.82
23.30
4.49
4.46
21.50
20.38
53
However, this method was not applicable to the synthesis of certain azolocarboxylic acid azides since
the starting acid chlorides could not be prepared in satisfactory yield. Thus attempts to prepare the tetrazol-5-yl
acetic acid chloride by treating the corresponding acid with thionyl chloride or phosphorus pentachloride
resulted in tarring of the reaction product. Hence to prepare bistriazoles linked by a carbamide fragment we used
the reaction of the triazolocarboxylic acids 11e,d with diphenylphosphoryl azide in dioxane in the presence of
triethylamine and excess water (Scheme 3). Most likely, the reaction occurs via intermediate formation of
acylazide groups, then an isocyanate with successive reaction with water, followed by decomposition of the
carbamic acid formed to the amine. Treatment of the amine produced with isocyanate gives the disubstituted
urea 8c,d.
The IR spectra of the carboxylic acid azides 5a–c show strong absorption bands for carbonyl (1690–
1700 cm–1) and for the azide group (2170–2200 cm–1).
The 1H NMR spectra of the ureas 8b–d show signals for the NH group protons at 8.80–9.20 and phenyl
substituents at 7.20–7.95 ppm and the IR spectra show absorptions for NH at 3235–3328 and 1715–1725 cm–1
for a carbonyl group.
459

The urethanes obtained (3a–d, 4, 6a,b and 7) show characteristic IR absorption bands at 3293–3345,
1688–1751, and 1125–1259 cm–1 for the NH group, carbonyl group, and ether respectively. The 13C NMR
spectra show signals at 150–163 for the carbonyl group and 51–63 ppm for the oxymethyl group.
EXPERIMENTAL
IR spectra were obtained on an Infralum FT-801 instrument for KBr tablets or as a thin layer in vaseline
1
13
oil. H and C NMR spectra were taken on a Varian VXR-500s instrument (500 and 126 MHz respectively)
1
((13C–{1H}) with decoupling from the protons) using acetone-d6 for the H spectra or DMSO-d6 for the 13C
spectra. The residual signals for the undeuterated methyl groups were used as internal standard: 39.5 ppm for
1
13C and 2.10 ppm for H respectively. Elemental analysis was performed on a FLASH EA 1112 Series CHN
analyzer. Monitoring of the course of the reaction was carried out by TLC on Silufol plates. The eluent mixture
was ethyl acetate and hexane in the volume ratio (2:3).
1-Benzyl-1,2,3-triazole-4,5-dicarboxylic acid [5], 1-butyl-1,2,3-triazole-4,5-dicarboxylic acid [5], 3-
azido-1,2,4-triazole [6], 4-carboxy-5-methyl-2-phenyl-1,2,3-triazole [7], 4-carboxy-5-methyl-1-phenyl-1,2,3-
triazole [8], 5-ethoxycarbonyl-4-methyl-2-phenyl-1,2,3-triazole-1-oxide [9], diphenylphosphoryl azide [10], 5-
azidomethyltetrazole [11], 4,5-(dihydroxymethyl)furazan [12], 2-phenyl-1,2,3-triazole-4-carboxylic acid [13], 1-
benzyl-4,5-(dihydroxymethyl)-1,2,3-triazole [14], and 1-benzyl-4-hydroxymethyl-1,2,3-triazole [14] were
prepared by the known method.
4-Hydroxymethyl-1-(1,2,4-triazol-3-yl)-1,2,3-triazole (1b). A solution of 3-azido-1,2,4-triazole (3.2 g,
29 mmol) and propargyl alcohol (1.4 g, 25 mmol) in ethanol (5 ml) was held at solvent reflux temperature for
10 h. Solvent was removed and the residue was crystallized from alcohol.
5-Hydroxymethyl-1-(tetrazol-5-ylmethyl)-1,2,3-triazole (1c) was prepared similarly from 5-azido-
methyltetrazole (10.5 g, 85 mmol) and propargyl alcohol (4.4 g, 79 mmol).
2-Phenyl-1,2,3-triazole-4-carboxylic Acid Chloride (10a). 2-Phenyl-1,2,3-triazole-4-carboxylic acid
(11a) (10 g, 53 mmol) was added portionwise with stirring at room temperature to a suspension of PCl5 (22.5 g,
108 mmol) in benzene (150 ml). After solution of the acid the reaction mixture was stirred for a further 2 h.
Solvent was evaporated and the phosphoryl chloride formed was distilled off in vacuo using a water pump. The
residue was recrystallized from hexane.
1-Benzyl-1,2,3-triazole-4,5-dicarboxylic acid dichloride (10b) was prepared similarly from 1-benzyl-
1,2,3-triazole-4,5-dicarboxylic acid (11b) (11.6 g, 47 mmol) and PCl5 (21.3 g, 102 mmol). The 1-butyl-1,2,3-
triazole-4,5-dicarboxylic acid dichloride (10c) was prepared from 1-butyl-1,2,3-triazole-4,5-dicarboxylic acid
(11c) (3.8 g, 18 mmol) and PCl5 (8.3 g, 40 mmol).
2-Phenyl-1,2,3-triazole-4-carboxylic Acid Azide (5a). Compound 10a (5 g, 24 mmol) was added por-
tionwise to a vigorously stirred mixture of sodium azide (2.4 g, 37 mmol) in water (25 ml), benzyltriethylam-
monium chloride (0.2 g), and ether (35 ml) at room temperature. The reaction product was stirred for 2 h, the
organic layer separated, and the aqueous washed with ether. The combined ether extracts were dried over
calcium chloride and the solvent was evaporated off.
1-Benzyl-1,2,3-triazole-4,5-dicarboxylic acid diazide (5b) in ether (10 ml) was obtained similarly
from compound 10b (3 g, 11 mmol) and sodium azide (1.6 g, 25 mmol). In the pure state the azide undergoes
rearrangement with evolution of nitrogen at room temperature.
1-Butyl-1,2,3-triazole-4,5-dicarboxylic acid diazide (5c) in ether (10 ml) was prepared from com-
pound 10c (4.4 g, 18 mmol) and sodium azide (2.6 g, 40 mmol).
1-Benzyl-4-[(N-phenylcarbamoyl)oxymethyl]-1,2,3-triazole (3a). A solution of alcohol 1a (0.5 g,
3 mmol) and benzoyl azide (0.5 g, 3.4 mmol) in dioxane (10 ml) was stirred at solvent reflux temperature for
2.5–3.0 h. Solvent was evaporated and the viscous mass was washed with benzene. The precipitate obtained was
crystallized from ethanol.
Compounds 3b–d, 4, 6a,b, and 7 were prepared similarly.
460

TABLE 2. Spectroscopic Parameters* for Compounds 1, 3–10
IR spectra,
Compound
13С NMR spectra, , ppm
, сm–1
1
2
3
1b
3635–3615
(OH)
54.8 (СН2ОН); 114.0 (С, vic. triazole); 145.0 (ipso-C, sym.
triazole); 148.6 (ipso-C, vic. triazole); 148.7 (C, sym. triazole)
1c
3a
3645–3625
(OH)
42.5 (СН2); 54.2 (СН2ОН); 122.9 (С, vic. triazole); 147.7
(ipso-C, vic. triazole); 157.8 (С, tetrazole)
3295 (NH),
1246 (–O–),
1697 (C=O)
52.0 (СН2, Bn); 56.6 (СН2О); 117.5 (С, vic. triazole); 117.6
(2o-C, Ph); 122.5 (p-C, Ph); 127.0 (p-C, Bn); 128.1 (2m-C, Ph);
128.8 (2o-C, Bn); 129.0 (2m-C, Bn); 134.0 (ipso-C, Bn); 138.0
(ipso-C, Ph); 144.7 (ipso-C, vic. triazole); 152.3 (С=О)
3b
3c
3d
3442 (NH),
1125 (–O–),
1751 (C=O)
54.5 (СН2О); 117.0 (С, vic. triazole); 119.6 (2o-C, Ph); 124.1
(p-C, Ph); 129.8 (2m-C, Ph); 137.4 (ipso-C, sym. triazole);
140.8 (ipso-C, Ph); 153.0 (С=О); 166.2 (ipso-C, vic. triazole);
176.5 (C, sym. triazole)
3330 (NH),
1227 (–O–),
1721 (C=O)
54.8 (СН2О); 58.1 (СН2); 118.6 (С, vic. triazole); 119.9 (2o-C,
Ph); 124.5 (p-C, Ph); 129.2 (2m-C, Ph); 139.8 (ipso-C, Ph);
143.8 (ipso-C, vic. triazole); 154.5 (С=О); 159.3 (ipso-C,
tetrazole)
3445–3300
(NH)
51.5, 55.0 (2СН2О); 60.7 (СН2, Вn); 119.9 (4o-C, Ph);
122.5 (4m-C, Ph); 123.5 (2p-C, Ph); 127.0 (p-C, Bn); 127.8
(2o-C, Bn); 128.6, 142.3 (2ipso-C, vic. triazole); 129.3
(2m-C, Bn); 133.3 (ipso-C, Вn); 134.5, 139.5 (2ipso-C, Ph);
150.6, 155.0 (2С=О)
4
3293 (NH),
1259 (–O–),
1701 (C=O)
56.0 (2СН2О); 124.5 (2p-C, Ph); 129.5 (4o-C, Ph);
130.4 (4m-C, Ph); 139.5 (2ipso-C, Ph); 153.5 (2С=О);
153.8 (2ipso-C, oxadiazole)
5a
5b
5c
6a
2158 (N3),
1688 (C=O)
117.1 (2o-C, Ph); 126.8 (C, vic. triazole); 127.7 (p-C, Ph); 128.0
(2m-C, Ph); 137.2 (ipso-C, Ph); 142.5 (ipso-C, vic. triazole);
153.0 (С=О)
2192 (N3),
1698 (C=O)
52.2 (СН2, Bn); 112.4, 128.7 (2ipso-C, vic. triazole); 128.2
(p-C, Bn); 128.8 (2o-C, Bn); 129.1 (2m-C, Bn);
131.5 (ipso-C, Bn); 158.9, 161.3 (2С=О)
2197 (N3),
1694 (C=O)
13.4 (СН3); 18.7 (СН2СН2СН2СН3); 31.1 (СН2СН2СН2СН3);
49.8 (СН2СН2СН2СН3); 113.6, 127.3 (2ipso-C, vic. triazole);
161.4, 162.8 (2С=О)
3324 (NH),
1213 (–O–),
1725 (C=O)
53.5 (СН2, Bn); 62.9 (СН2О); 118.2 (2o-C, Ph); 118.9 (С,
vic. triazole С–С); 126.5 (p-C, Ph); 127.0 (p-C, Bn); 128.3
(2o-C, Bn); 128.9 (2m-C, Ph); 129.4 (2m-C, Bn); 131.4 (С,
vic. triazole С-N); 134.0 (ipso-C, Ph); 134.5 (ipso-C, Bn); 143.3
(ipso-C, vic. triazole С–С); 147.6 (ipso-C, vic. triazole С–N);
154.5 (С=О)
6b
3315 (NH),
1230 (–O–),
1730 (C=O)
55.0 (СН2О); 118.4 (2o-C, Ph); 127.1 (p-C, Ph); 129.6 (2m-C,
Ph); 135.2 (ipso-C, Ph); 126.8 (С, vic. triazole N–C), 149.1
(2ipso-C, vic. triazole N–C); 145.4 (С, vic. triazole C–N), 147.0
(ipso-C, vic. triazole C–N); 138.6 (C, sym. triazole) 174.7
(ipso-C, sym. triazole); 150.6 (С=О)
7
3335 (NH),
1215 (–O–),
1722 (C=O)
55.0 (2СН2О); 118.0 (4o-C, Ph); 126.8 (2С, vic. triazole);
128.3 (2p-C, Ph); 129.4 (4m-C, Ph); 135.0 (2ipso-C, Ph);
145.4 (2ipso-C, vic. triazole); 150.6 (2С=О); 157.0 (2ipso-C,
oxadiazole)
8a
3280 (NH),
1720 (C=O)
118.6 (4o-C, Ph); 126.5 (2С, vic. triazole); 128.2 (2p-C, Ph);
129.8 (4m-C, Ph); 134.2 (2ipso-C, Ph); 145.5 (2ipso-C,
vic. triazole); 150.2 (С=О)
8b
3270 (NH),
1725 (C=O)
–
8с
3260 (NH),
1715 (C=O)
–
8d
3280 (NH),
1720 (C=O)
–
461

TABLE 2 (continued).
1
2
3
9
3235 (NH),
1668 (C=O)
–
10b
10c
1757 (COCl)
53.8 (СН2, Bn); 127.9 (2o-C, Bn); 127.0 (p-C, Bn); 128.7
(2m-C, Bn); 135.9 (ipso-C, Bn); 143.6, 160.4 (2ipso-C,
vic. triazole); 160.5, 162.9 (2С=О)
1730 (COCl)
13.4 (СН3); 18.8 (СН2СН2СН2СН3); 32.6 (СН2СН2СН2СН3);
47.8 (СН2СН2СН2СН3); 145.3, 156.7 (2ipso-C, vic. triazole);
165.0, 155.4 (2С=О)
_______
* 1H NMR spectra, , ppm: 8b – 2.09 (6H, s, 2CH3); 7.36–8.23 (10H, m,
2Ph); 16.9 and 13.5 (2H, br s, 2NH); 8d – 2.02 (6H, s, 2CH3); 7.28–8.28
(10H, m, 2Ph); 15.5 and 12.8 (2H, br s, 2NH); 8c – 2.02 (6H, s, 2CH3);
7.33–7.55 (10H, m, 2Ph); 15.5 and 12.08 (2H, br s, 2NH).
1-(1,2,4-Triazol-3-yl)-4-[(N-phenylcarbamoyl)oxymethyl]-1,2,3-triazole (3b) from alcohol 1b (0.5 g,
3 mmol) and benzoyl azide (0.5 g, 3.4 mmol) in dioxane (10 ml).
1-[(Tetrazol-5-yl)methyl]-4-[(N-phenylcarbamoyl)oxymethyl]-1,2,3-triazole (3c) from alcohol 1c
(0.5 g, 2.8 mmol) and benzoyl azide (0.5 g, 3.4 mmol) in dioxane (10 ml).
1-Benzyl-4,5-bis[(N-phenylcarbamoyl)oxymethyl]-1,2,3-triazole (3d) from alcohol 1d (0.5 g,
2.3 mmol) and benzoyl azide (0.7 g, 4.8 mmol) in dioxane (10 ml).
3,4-Bis[(N-phenylcarbamoyl)oxymethyl]-1,2,5-oxadiazole (4) from 3,4-dihydroxymethyl-1,2,5-
oxadiazole (0.5 g, 3.8 mmol) and benzoyl azide (1.2 g, 8.2 mmol) in dioxane (10 ml).
(1-Benzyl-4-[N-(2-phenyl-1,2,3-triazol-4-yl)carbamoyl]oxymethyl-1,2,3-triazole (6a) from alcohol
1a (0.5 g, 2.6 mmol) and azide 5a (0.7 g, 3.3 mmol) in dioxane (10 ml).
1-(1,2,4-Triazol-3-yl)-4-[N-(2-phenyl-1,2,3-triazol-4-yl)carbamoyl]oxymethyl-1,2,3-triazole
(6b)
from alcohol 1b (0.5 g, 3 mmol) and azide 5a (0.8 g, 3.7 mmol) in dioxane (10 ml).
3,4-Bis[N-(2-phenyl-1,2,3-triazol-4-yl)carbamoyl]oxymethyl-1,2,5-oxadiazole (7) from 3,4-dihyd-
roxymethyl-1,2,5-oxadiazole (2) (0.3 g, 2.3 mmol) and azide 5a (1 g, 4.7 mmol) in dioxane (10 ml).
4-Methyl-1-oxido-2-phenyl-1,2,3-triazole-5-carboxylic Acid Hydrazide (9). Hydrazine hydrate (1 g,
20 mmol) was added to a solution of ethyl 4-methyl-2-phenyl-1-oxido-1,2,3-triazole-5-carboxylate (12) (2.2 g,
9 mmol) in alcohol (10 ml), stirred under reflux for 3 h, and left overnight. Solvent was evaporated and the
residue was crystallized from alcohol.
Bis-(2-phenyl-1,2,3-triazol-4-yl)urea (8a). Water (3ml) was added to a solution of the azide 5a (0.5 g,
2.3 mmol) in dioxane (5 ml) and stirred at the solvent reflux temperature for 3 h. Solvent was evaporated and the
oily residue was washed with benzene.
N,N’-Bis(4-methyl-2-phenyl-1,2,3-triazol-5-yl)urea (8d). A solution of the triazolylcarboxylic acid
11d (4 g, 20 mmol), diphenylphosphoryl azide (5.5 g, 20 mmol), and triethylamine (2.3 g, 23 mmol) in dioxane
(20 ml) and benzene (15 ml) was stirred at room temperature for 0.5 h. A solution of water (3.6 ml) and propyl
alcohol (7.5 ml) was added with heating on a boiling water bath. Heating was continued until the starting acid
spot had disappeared by TLC. The reaction product was treated with ether, the aqueous layer separated, the ether
layer dried over magnesium sulfate, and the solvent was removed in vacuo. The light yellow, oily residue was
separated by column chromatography on silica gel using benzene–chloroform–ethyl acetate (4:1:3) as eluent.
N,N’-Bis(4-methyl-3-phenyl-1,2,3-triazol-5-yl)urea (8c) was prepared similarly from the triazole 11e.
N,N’-Bis(4-methyl-1-oxido-2-phenyl-1,2,3-triazol-5-yl)urea (8b). A solution of sodium nitrite (0.6 g,
9 mmol) in water (2 ml) was added dropwise with vigorous stirring to a solution of the hydrazide 9 (7 g,
30 mmol) in iced water (12 ml), conc. HCl (0.9 ml), and ether (20 ml) at 0–2ºC and the temperature was
maintained below 7ºC. After the starting hydrazide had disappeared from the reaction mixture (TLC on Silufol)
462

the ether layer was separated and the aqueous layer was treated with ether. The combined ether extracts were
dried over magnesium sulfate, the solvent was evaporated, and the residue was recrystallized from alcohol.
REFERENCES
1.
2.
L. I. Vereshchagin, O. N. Verkhozina, A. G. Proidakov, A. I. Smirnov, and V. N. Kizhnyaev, Khim.
Geterotsikl. Soedin., 1432 (2008). [Chem. Heterocycl. Comp., 44, 1158 (2008)].
L. I. Vereshchagin, O. N. Verkhozina, F. A. Pokatilov, A. G. Proidakov, and V. N. Kizhnyaev, Khim.
Geterotsikl. Soedin., 255 (2010). [Chem. Heterocycl. Comp., 46, 206 (2010)].
A. A. Blagonravova and G. A. Levkovich, Usp. Khim., 24, 93 (1955).
P. A. S Smith in Organic Reactions [Russian translation] Vol. 3, Inostr. Lit., Moscow (1951), p. 322.
R. Wiley and K. F. Hussung, J. Org. Chem., 21, 190 (1956).
3.
4.
5.
6.
G. I. Tsypin, T. F. Sharamet, T. A. Kravchenko, and M. S. Pevzner, Khim. Geterotsikl. Soedin., 262
(1980). [Chem. Heterocycl. Comp., 16, 199 (1980)].
7.
8.
9.
T. Ajello and S. Cusmano, Gazz. Chim. Ital., 70, 770 (1940).
P. Ramart-Lucas, I. Hoch, and M. Crumez, Bull. Soc. Chim., 447 (1949).
L. P. Kirillova, V. M. Shul’gina, M. A. Shafeev, and A. A. Al’mukhamedov, Zh. Org. Khim., 32, 1087
(1996).
10.
11.
T. Shiori and S. Ymada, Chem. Pharm. Bull., 22, 849 (1974).
O. N. Verkhozina, V. N. Kizhnyaev, L. I. Vereshchagin, A. G. Rokhin, and A. I. Smirnov, Zh. Org.
Khim., 39, 1863 (2003).
12.
I. V. Vigalok, A. V. Ostrovskaya, and N. V. Svetlakov, Russian Patent 435240; Byul. Izobr., No 51
(25), 801 (1974).
13.
14.
J. L. Riebsomer and G. Sumrel, J. Org. Chem., 19, 807 (1948).
L. G. Tikhonova, E. S. Serebryakova, A. V. Maksikova, L. I. Vereshchagin, and G. V. Chernyshova, Zh.
Org. Khim., 17, 1401 (1981).

463