Synthesis of polynuclear azoles linked through carbamate and urea bridges

Article abstract of DOI:10.1134/S1070428012040185

Polynuclear azoles linked through carbamate and urea fragments were synthesized by reactions of the corresponding azolecarboxylic acid azides with heterocyclic alcohols and amines. Pleiades Publishing, Ltd., 2012.

Full text of DOI:10.1134/S1070428012040185

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 4, pp. 566–574. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © T.V. Golobokova, F.A. Pokatilov, A.G. Proidakov, M.V. Kazantseva, G.G. Shevchenko, L.I. Vereshchagin, V.N. Kizhnyaev, 2012,
published in Zhurnal Organicheskoi Khimii, 2012, Vol. 48, No. 4, pp. 568–576.
Synthesis of Polynuclear Azoles Linked through Carbamate
and Urea Bridges
T. V. Golobokova, F. A. Pokatilov, A. G. Proidakov, M. V. Kazantseva, G. G. Shevchenko,
L. I. Vereshchagin, and V. N. Kizhnyaev
Irkutsk State University, ul. K.Marksa 1, Irkutsk, 664033 Russia
e-mail: kizhnyaev@chem.isu.ru
Received May 23, 2011
Abstract—Polynuclear azoles linked through carbamate and urea fragments were synthesized by reactions of
the corresponding azolecarboxylic acid azides with heterocyclic alcohols and amines.
DOI: 10.1134/S1070428012040185
We previously showed [1–3] a general possibility
of synthesizing nonfused polynuclear triazole-, tetra-
zole-, and 1,3,4-oxadiazole-containing systems linked
by various bridging moieties. Such systems were con-
structed by attachment of a heteroring to a base mole-
cule possessing a reactive substituent like azide, cyano,
or chloromethyl group, halogen atom, or acetylenic
bond. In continuation of studies in this field we
examined a synthetic approach to polynuclear azole
blocks in which the heterorings are linked through
carbamate or urea fragments. For this purpose, hetero-
cyclic carboxylic acid azides were subjected to thermal
rearrangement into the corresponding isocyanates,
followed by reaction of the latter with azolyl-sub-
stituted alcohols and amines, which afforded mono-
and bis-azolyl-substituted carbamates and ureas.
Scheme 1.
O
Δ
N
Ph
·
–N2
Ph
N3
O
III
IV
R
R
OH
OH
O
O
IV
IV
IV
IV
NHPh
RNH2
N
N
N
N
O
RNH
NHPh
R'
R'
N
N
Ia–Id
Va–Vd
IIa, IIb
VIa, VIb
HO
O
O
O
PhNH
NHPh
N
N
N
N
O
O
N
NH2
N
N
H
NHPh
O
O
Ie
Ve
IId
VId
O
H2N
HN
N
IV
NHPh
N
N
N
Ph
Ph
N
N
IIc
VIc
I, R = H, R′ = PhCH2 (a), tetrazol-5-ylmethyl (b), 1,2,4-triazol-3-yl (c); R = HOCH2, R′ = PhCH2 (d); II, VI, R = 1H-1,2,4-triazol-3-
yl (a), 4H-1,2,4-triazol-4-yl (b); V, R = H, R′ = PhCH2 (a), tetrazol-5-ylmethyl (b), 1H-1,2,4-triazol-3-yl (c); R = PhNHC(O)OCH2,
R′ = PhCH2 (d).
566

SYNTHESIS OF POLYNUCLEAR AZOLES
567
Scheme 2.
O
N
N
Δ
O
·
N
N
Ph
Ph
N
–N2
N
N
N3
VIIa
5
O
5'
N
5'
4'
N
O
4
R
IIa, IIb
Ia, Ic
N
4'
N
Ph
O
N
R
Ph
N
N
N
N
N
N
N
H
H
H
IXa, IXb
VIIIa, VIIIb
H
5'
NCO
O
N
N
4'
Ph
4
N
N
Ph
5'
N
O
IIc
Id
O
4
3
O
N
N
N
N
N
N
4'
Ph
Ph
N
N
5
4'
N
N
N
H
N
H
O
N
N
Ph
N
N
O
H
Ph
5'
Ph
IXc
VIIIc
N
N
N
5'
O
O
IId
N
N
N
4'
Ph
Ph
N
N
N
N
H
N
H
N
N
N
H
H
IXd
VIe
VIII, R = PhCH2 (a), 1H-1,2,4-triazol-3-yl (b); IX, R = 1H-1,2,4-triazol-3-yl (a), 4H-1,2,4-triazol-4-yl (b).
It is known that acyl azides undergo thermal rear-
rangement with formation of alkyl or aryl isocyanates
which readily react with NH and OH nucleophiles
(alcohols, amines) to produce the corresponding carba-
mates, ureas, and other compounds [4, 5]. However,
there are no published data on analogous reactions
with alcohols and amines of the triazole and tetrazole
series, including those unsubstituted at the nitrogen.
Preliminarily, the reactivity of azole-containing
alcohols Ia–Ic, diols Id and Ie, and amines IIa–IId
toward isocyanates (Scheme 1) was estimated in the
reaction with benzoyl azide (III) on heating in an an-
hydrous solvent. Taking into account facile generation
of isocyanates from acyl azides on heating, there was
no necessity of their isolation. Thus phenyl isocyanate
(IV) generated in situ from azide III reacted with com-
pounds I and II to give the corresponding azolylmethyl
phenylcarbamates Va–Ve and N-azolyl-N′-phenyl-
ureas VIa–VId.
The reactions of alcohols Ib and Ic and amine IIa
with phenyl isocyanate were expected to involve the
pyrrole-type nitrogen atom in the triazole or tetrazole
ring, the more so isocyanates are postulated to react
with compounds having an NH group [4]. However, in
our case neither 1,2,4-triazole nor tetrazole ring par-
ticipated in the reaction with phenyl isocyanate, pre-
sumably due to weak nucleophilicity of the heteroring.
Analogous reactions were performed with triazole-
carbonyl azides VIIa and VIIb and tetrazol-2-ylacetyl
azide (VIIc). Azides VIIa–VIIc were converted into
the corresponding isocyanates by heating at 70–95°C
in dioxane or toluene, and subsequent reactions with
alcohols Ia and Ic, diol Ie, and amines IIa–IId led to
the formation of nonfused polynuclear azole systems
VIIIa–VIIIc and IXa–IXh in which the heterorings
were linked through carabamate or urea fragments,
respectively (Schemes 2, 3).
The reactivity of amino group in an azole ring
having a free NH proton considerably depends on its
position in the ring and on the nature of the heteroring.
The presence of an electron-withdrawing substituent
hampers the rearrangement [5], so that we failed to
obtain products of isocyanate addition to 5-aminotetra-
zole, ethyl 4-amino-3-phenyl-1,2,3-triazole-5-carbox-
ylate, and ethyl 3-amino-1,2,4-triazole-5-carboxylate.
Removal of the carboxy group from the latter made it
possible to obtain disubstituted ureas VIa, IXa, IXe,
and IXg from aminotriazole IIa. The reaction of VIIa
with 5-aminotetrazole hydrate gave N,N′-bis(2-phenyl-
2H-1,2,3-triazol-4-yl)urea (VIe), presumably due to
participation of hydrate water present in the initial
aminotetrazole. 2-Aminopyridine reacted with isocya-
nates fairly readily to produce N,N′-disubstituted ureas
VId, IXd, and IXh.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 4 2012

GOLOBOKOVA et al.
568
Scheme 3.
Ph
H
N
N
H
N
N
IIc
N
N
Ph
N
N
N
O
Ph
IXf
O
H
NCO
N
N
N
N
H
N
N
Δ
IIa
IId
N
N
N
N
NH
N3
N
Ph
–N2
N
N
N
N
Ph
Ph
O
N
N
IXg
VIIc
H
N
N
H
N
N
N
Ph
N
O
IXh
O
O
Me
H
H
N
Me
Me
N3
N3
N
Δ
IIa
N
Ph
N
NH
–N2
N
N
N
N
N
O
N
N
Ph
Ph
N
N
VIIb
IXe
Scheme 4.
NH
NCO
N
NH
N
N
N
o-C6H4(NH2)2
PhNH2
N
N
N
Ph
NHPh
N
H
N
N
O
O
N
Ph
Ph
N
N
NH2
XVa
XVb
NH2
H
N
H
N
H
NCO
NHPh
N
N
N
o-C6H4(NH2)2
PhNH2
N
Ph
Ph
N
N
N
O
O
N
N
Ph
N
XVc
XVd
The reactions of azides VIIa and VIIc with aniline
afforded N-phenylureas XVa and XVc, respectively.
o-Phenylenediamine gave rise to N-(2-aminophenyl)-
N′-(5-phenyltetrazol-2-ylmethyl)- and N-(2-amino-
phenyl)-N′-(2-phenyl-2H-1,2,3-triazol-4-yl)ureas XVb
and XVd instead of expected bis-addition products
(Scheme 4). Presumably, the reason is poor solubility
of compounds XVb and XVd which are therefore
removed from the reaction zone.
in the presence of triethylamine and excess water
(Scheme 6). This reaction is likely to involve inter-
mediate formation of acyl azide which is converted
into isocyanate, the latter reacts with water to give
carbamic acid derivative whose decomposition yields
triazolylamine. Its reaction with isocyanate leads to
urea XIVa or XIVb. Diazotization of triazolecarbo-
hydrazide N-oxide XVI gave symmetric urea XI
(Scheme 7).
Initial azides VIIa–VIIc were synthesized by treat-
ment of the corresponding carboxylic acid chlorides
XIIa–XIIc with sodium azide under phase-transfer
conditions (Scheme 5).
Scheme 5.
O
O
NaN3
Ht
Cl
Ht
N3
Bis-triazolyl ureas XIVa and XIVb were synthe-
sized via rearrangement of the corresponding acyl
azides in reactions of triazolecarboxylic acids XIIIa
and XIIIb with diphenoxyphosphoryl azide in dioxane
XIIa–XIIc
VIIa–VIIc
Ht = 2-Phenyl-2H-1,2,3-triazol-4-yl (a), 5-methyl-1-phenyl-
1H-1,2,3-triazol-4-yl (b), 5-phenyltetrazol-2-ylmethyl (c).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 4 2012

SYNTHESIS OF POLYNUCLEAR AZOLES
569
Scheme 6.
Me
Me
Me
COOH
H
H
N
N
(PhO)2P(O)N3
N
N
N
N
N
O
N
N
N
N
Ph
Ph
Ph
XIIIa
XIVa
Me
Me
Me
COOH
H
H
N
N
(PhO)2P(O)N3
Ph
N
Ph
N
N
N
Ph
N
O
N
N
N
N
XIIIb
XIVb
Scheme 7.
O
NH2
NH
Me
Me
Me
COOH
Me
H
N
H
N
N
N
N
N
N
N
N
O–
O–
O
N
N
N
N
N
–O
O–
Ph
Ph
Ph
Ph
XVI
XI
The structure of the newly synthesized compounds
was confirmed by their NMR and IR spectra and ele-
mental analyses. The IR spectra of carboxylic acid
azides VIIa–VIIc contained strong absorption bands
typical of stretching vibrations of carbonyl (1700–
1690 cm–1) and azido groups (2200–2170 cm–1). Ureas
XI, XIVa, and XIVb displayed in the 1H NMR spectra
signals from protons in the phenyl rings (δ 7.30–
7.95 ppm) and methyl (δ 2.27–2.37 ppm) and NH
groups (δ 9.20–8.90 ppm); IR absorption bands in the
regions 3328–3235 and 1649–1590 cm–1 correspond to
stretching vibrations of the NH and carbonyl groups.
In the IR spectra of carbamates Va–Ve and VIIIa–
VIIIc we observed absorption bands at 3322–3328
(NH), 1259–1227 (C–O), and 1720–1650 cm–1 (C=O);
signals in their 13C NMR spectra at δC 151–153 and
54–57 ppm were assigned, respectively, to the carbon-
yl carbon atom and CH2O group.
VXR-500s spectrometer at 500 and 126 MHz, respec-
tively, from solutions in acetone-d6 (1H) or DMSO-d6
(13C), using the residual proton and carbon signals of
the solvent as reference. The elemental compositions
were determined on a FLASH EA 1112 Series CHN
analyzer. The progress of reactions was monitored by
TLC on Silufol plates using ethyl acetate–hexane (2:3
by volume) as eluent.
Benzoyl azide [6], 5-methyl-2-phenyl-2H-1,2,3-tri-
azole-4-carboxylic acid [7], ethyl 5-methyl-2-phenyl-
2H-1,2,3-triazole-4-carboxylate 3-oxide [8], diphe-
noxyphosphoryl azide [9], 5-azidomethyltetrazole [1],
1,2,5-oxadiazole-3,4-diyldimethanol [10], 1-benzyl-5-
hydroxymethyl-1H-1,2,3-triazole [11], 1H-1,2,4-tri-
azol-3-amine [12], 1,2,4-triazol-4-amine [13], 1-ben-
zyl-1H-1,2,3-triazole-4,5-dicarboxylic acid, 1-butyl-
1H-1,2,3-triazole-4,5-dicarboxylic acid [14], 5-methyl-
1-phenyl-1H-1,2,3-triazole-4-carboxylic acid [15],
3-azido-1,2,4-triazole [16], and 1,4-diphenyl-1H-1,2,3-
triazol-5-amine [17] were synthesized by known
methods.
Thus we have demonstrated the possibility for syn-
thesizing symmetrically and unsymmetrically substi-
tuted ureas and carbamates by reactions of azole-
carboxylic acid azides with heterocyclic alcohols and
amines.
[1-(1H-1,2,4-Triazol-3-yl)-1H-1,2,3-triazol-4-yl]-
methanol (Ic). A solution of 3.2 g (30 mmol) of
3-azido-1,2,4-triazole and 1.4 g (25 mmol) of prop-2-
yn-1-ol in 5 ml of ethanol was heated for 10 h under
reflux. The solvent was removed under reduced pres-
sure. Yield 3.24 g (78%), mp 130–131°C (from EtOH).
IR spectrum: ν 3635–3615 cm–1 (OH). 13C NMR spec-
trum, δC, ppm: 54.8 (CH2OH), 114.0 (C5), 145.0 (C3′),
EXPERIMENTAL
The IR spectra were recorded in KBr or mineral oil
1
on an Infralum FT-801 instrument. The H and
13C–{1H} NMR spectra were measured on a Varian
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 4 2012

GOLOBOKOVA et al.
570
148.6 (C4), 148.7 (C5′). Found, %: C 36.51; H 3.83;
N 50.12. C5H6N6O. Calculated, %: C 36.15; H 3.64;
N 50.58.
air. Yield 3.4 g (66%). IR spectrum, ν, cm–1: 2158 (N3),
1688 (C=O). 13C NMR spectrum, δC, ppm: 117.1 (Co),
127.7 (Cp), 126.8 (C5), 128.0 (Cm), 137.2 (Ci), 142.5
(C4), 153.0 (C=O). Found, %: C 49.02; H 3.04;
N 38.80. C9H6N6O. Calculated, %: C 50.46; H 2.80;
N 39.25.
[1-(Tetrazol-5-ylmethyl)-1H-1,2,3-triazol-4-yl]-
methanol (Ib) was synthesized in a similar way from
10.5 g (84 mmol) of 5-azidomethyltetrazole and 4.4 g
(80 mmol) of prop-2-yn-1-ol. Yield 11 g (76%),
mp 182–184°C (from EtOH). IR spectrum: ν 3645–
3625 cm–1 (OH). 13C NMR spectrum, δC, ppm: 42.5
(CH2), 54.2 (CH2OH), 122.9 (C5), 147.7 (C4), 157.8
(C5′). Found, %: C 33.71; H 3.47; N 53.92. C5H7N7O.
Calculated, %: C 33.14; H 3.86; N 54.14.
Compounds VIIb and VIIc were synthesized
in a similar way.
5-Methyl-1-phenyl-1H-1,2,3-triazole-4-carbonyl
azide (VIIb) was obtained from 4.9 g (22 mmol) of
XIIb and 3.2 g (49 mmol) of sodium azide in 50 ml of
water using 0.3 g of BTEAC. Yield 4.6 g (92%),
mp 88–89°C. IR spectrum, ν, cm–1: 2193 (N3), 1694
(C=O). Found, %: C 52.78; H 3.59; N 36.45.
C10H8N6O. Calculated, %: C 52.63; H 3.50; N 36.84.
2-Phenyl-2H-1,2,3-triazole-4-carbonyl chloride
(XIIa). 2-Phenyl-2H-1,2,3-triazole-4-carboxylic acid,
10 g (53 mmol), was added in portions under stirring at
room temperature to a suspension of 22.5 g
(108 mmol) of PCl5 in 150 ml of benzene. After
dissolution of the acid, the mixture was stirred for 2 h
and evaporated under reduced pressure (water-jet
pump). Yield 8.6 g (78%), mp 92–94°C (from hexane).
Found, %: C 51.72; H 3.05; N 21.40. C9H6ClN3O.
Calculated, %: C 52.04; H 2.89; N 20.40.
(5-Phenyltetrazol-2-yl)acetyl azide (VIIc) was
obtained from 5 g (24 mmol) of XIIc and 3.12 g
(48 mmol) of sodium azide in 50 ml of water. Yield
4.34 g (79%), mp 95°C. IR spectrum, ν, cm–1: 2192
(N3), 1698 (C=O). Found, %: C 47.39; H 3.15;
N 42.53. C9H7N7O. Calculated, %: C 47.16; H 3.05;
N 42.79.
5-Methyl-1-phenyl-1H-1,2,3-triazole-4-carbonyl
chloride (XIIb). Acid XIIIb, 5 g (25 mmol), was
added in portions under stirring at room temperature to
a mixture of 6.25 g (30 mmol) of PCl5 in 50 ml of
benzene. After dissolution of the acid, the mixture was
stirred for 3 h and evaporated under reduced pressure
(water-jet pump). Yield 5.1 g (92%), mp 136–138°C
(from hexane). Found, %: C 54.31; H 3.83; N 18.46.
C10H8ClN3O. Calculated, %: C 54.17; H 3.61; N 18.96.
5-Methyl-2-phenyl-2H-1,2,3-triazole-4-carbohy-
drazide 3-oxide (XVI). Hydrazine hydrate, 1 g
(20 mmol), was added to a solution of 2.2 g (9 mmol)
of ethyl 5-methyl-2-phenyl-2H-1,2,3-triazole-4-car-
boxylate 3-oxide in 10 ml of alcohol. The mixture was
heated for 3 h under reflux and left overnight, and the
solvent was removed. Yield 1.7 g (72%), mp 175–
177°C (from EtOH). IR spectrum, ν, cm–1: 3235 (NH),
1668 (C=O). Found, %: C 51.81; H 4.65; N 29.75.
C10H11N5O2. Calculated, %: C 51.50; H 4.72; N 30.04.
(5-Phenyltetrazol-2-yl)acetyl chloride (XIIc) was
synthesized in a similar way from 5 g (25 mmol) of
5-phenyltetrazol-2-ylacetic acid and 6.2 g (30 mmol)
of PCl5 in 50 ml of benzene. After removal of phos-
phoryl chloride, the residue was evacuated over a peri-
od of 5 h. Yield 5.3 g (79%), oily liquid. Found, %:
C 49.51; H 2.97; N 25.61. C9H7ClN4O. Calculated, %:
C 48.53; H 3.14; N 25.16.
1-Benzyl-1H-1,2,3-triazol-4-ylmethyl phenylcar-
bamate (Va). A solution of 0.5 g (2.6 mmol) of
triazole Ia and 0.5 g (3.4 mmol) of benzoyl azide (III)
in 10 ml of dioxane was stirred for 2.5–3 h on heating
under reflux. The solvent was removed, and the oily
residue was treated with benzene. Yield 0.5 g (60%),
mp 108–110°C (from EtOH). IR spectrum, ν, cm–1:
3295 (NH), 1697 (C=O), 1246 (C–O). 13C NMR spec-
trum, δC, ppm: 52.0 (PhCH2), 56.6 (CH2O), 117.5 (C5),
117.6 (Co), 122.5 (Cp), 127.0 (Cp, Bzl), 128.1 (Cm),
128.8 (Co, Bzl), 129.0 (Cm, Bzl), 134.0 (Ci, Bzl), 138.0
(Ci), 144.7 (C4), 152.3 (C=O). Found, %: C 66.18;
H 5.39; N 18.65. C17H16N4O2. Calculated, %: C 66.23;
H 5.19; N 18.18.
2-Phenyl-2H-1,2,3-triazole-4-carbonyl azide
(VIIa). Acid chloride XIIa, 5 g (24 mmol), was added
in portions under vigorous stirring at room temperature
to a mixture of 2.4 g (37 mmol) of sodium azide, 25 ml
of water, 0.2 g of benzyltriethylammonium chloride
(BTEAC), and 35 ml of diethyl ether. The mixture was
stirred for 3 h until XIIa disappeared (TLC), the
organic phase was separated, and the aqueous phase
was extracted with diethyl ether (5×35 ml). The ex-
tracts were combined with the organic phase, dried
over anhydrous CaCl2, and evaporated by purging with
Compounds Vb–Ve and VIIIa–VIIIc were synthe-
sized in a similar way.
1-(Tetrazol-5-ylmethyl)-1H-1,2,3-triazol-4-yl-
methyl phenylcarbamate (Vb) was synthesized from
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SYNTHESIS OF POLYNUCLEAR AZOLES
571
0.5 g of (2.7 mmol) of Ib and 0.5 g (3.4 mmol) of III
in 10 ml of dioxane. Yield 0.5 g (64%), mp 78–81°C.
IR spectrum, ν, cm–1: 3442 (NH), 1751 (C=O), 1125
(C–O). 13C NMR spectrum, δC, ppm: 54.8 (CH2O),
58.1 (CH2), 118.6 (C5), 119.9 (Co), 124.5 (Cp), 129.2
(Cm), 139.8 (Ci), 143.8 (C4), 154.5 (C=O), 159.3 (C5′).
Found, %: C 48.48; H 4.19; N 36.52. C12H12N8O2. Cal-
culated, %: C 48.00; H 4.00; N 37.33.
C 61.02; H 4.40; N 26.26. C19H17N7O2. Calculated, %:
C 60.80; H 4.53; N 26.13.
1-(1H-1,2,4-Triazol-3-yl)-1H-1,2,3-triazol-4-yl-
methyl 2-phenyl-2H-1,2,3-triazol-4-ylcarbamate
(VIIIb) was synthesized from 0.5 g (3 mmol) of Ic and
0.8 g (3.7 mmol) of VIIa in 10 ml of dioxane. Yield
0.6 g (67%), mp 218–220°C. IR spectrum, ν, cm–1:
3315 (NH), 1730 (C=O), 1230 (C–O). 13C NMR spec-
trum, δC, ppm: 55.0 (CH2O), 116.8 (C5′), 118.4 (Co),
127.1 (Cp), 129.6 (Cm), 131.4 (C5), 135.2 (Ci), 147.0
(C4′), 147.7 (C3″), 149.1 (C4), 148.6 (C5″), 150.6
(C=O). Found, %: C 47.90; H 3.15; N 40.92.
C14H12N10O2. Calculated, %: C 47.73; H 3.43; N 39.76.
1-(1H-1,2,4-Triazol-3-yl)-1H-1,2,3-triazol-4-yl-
methyl phenylcarbamate (Vc) was synthesized from
0.5 g (3 mmol) of Ic and 0.5 g (3.4 mmol) of III in
10 ml of dioxane. Yield 0.5 g (58%), mp 115–118°C.
IR spectrum, ν, cm–1: 3330 (NH), 1721 (C=O), 1227
(C–O). 13C NMR spectrum, δC, ppm: 52.7 (CH2O),
117.6 (Co), 121.5 (C5), 121.7 (Cp), 133.2 (Ci), 139.1
(C3′), 145.3 (C5′), 145.5 (C4), 153.3 (C=O). Found, %:
C 49.65; H 4.28; N 34.87. C12H11N7O2. Calculated, %:
C 50.52; H 3.85; N 34.38.
1,2,5-Oxadiazole-3,4-diylbismethylene bis-
(2-phenyl-2H-1,2,3-triazol-4-ylcarbamate (VIIIc)
was synthesized from 0.5 g (3.8 mmol) of Ie and 1.8 g
(8.4 mmol) of VIIa in 10 ml of dioxane. Yield 0.9 g
(48%), mp 229–231°C. IR spectrum, ν, cm–1: 3335
(NH), 1722 (C=O), 1215 (C–O). 13C NMR spectrum,
δC, ppm: 55.0 (CH2O), 118.0 (Co), 126.8 (C5′), 128.3
(Cp), 129.4 (Cm), 135.0 (Ci), 145.4 (C4′), 150.6 (C=O),
157.0 (C3, C4). Found, %: C 51.80; H 3.72; N 26.91.
C22H18N10O5. Calculated, %: C 52.58; H 3.58; N 27.88.
1-Benzyl-1H-1,2,3-triazole-4,5-diylbismethylene
bis(phenylcarbamate) (Vd) was synthesized from
0.5 g (2.3 mmol) of diol Id and 0.7 g (4.8 mmol) of III
in 10 ml of dioxane. Yield 0.9 g (94%), mp 85–95°C.
IR spectrum: ν 3445–3300 cm–1 (NH). 13C NMR spec-
trum, δC, ppm: 55.0 and 51.5 (CH2O), 60.7 (PhCH2),
119.9 (Co), 122.5 (Cm), 123.5 (Cp), 127.0 (Cp, Bzl),
127.8 (Co, Bzl), 129.3 (Cm, Bzl), 133.3 (Ci, Bzl), 134.5
and 139.5 (Ci), 142.3 and 128.6 (C4, C5), 150.6 and
155.0 (C=O). Found, %: C 64.78; H 6.13; N 14.66.
C25H23N5O4. Calculated, %: C 65.64; H 5.03; N 15.31.
N,N′-Bis(5-methyl-2-phenyl-2H-1,2,3-triazol-5-
yl)urea (XIVa). A solution of 4 g (20 mmol) of acid
XIIIa, 5.5 g (20 mmol) of diphenoxyphosphoryl azide,
and 2.3 g (23 mmol) of triethylamine in a mixture of
20 ml of dioxane and 15 ml of benzene was stirred for
0.5 h at room temperature. The mixture was heated on
a water bath, a mixture of 3.6 ml (200 mmol) of water
and 7.5 ml (125 mmol) of propyl alcohol was added,
and the mixture was heated until initial acid XIIIa
disappeared (TLC). The mixture was extracted with
diethyl ether, the extract was dried over magnesium
sulfate, the solvent was removed under reduced pres-
sure, and the residue, light yellow oily substance, was
purified by column chromatography on silica gel.
Yield 5.4 g (72%), mp 255°C. IR spectrum, ν, cm–1:
3280 (NH), 1720 (C=O). 1H NMR spectrum, δ, ppm:
2.30 s (6H, CH3), 7.95 m (10H, Ph), 8.80 br.s (2H,
NH). Found, %: C 60.82; H 4.91; N 29.93. C19H18N8O.
Calculated, %: C 60.96; H 4.81; N 29.94.
1,2,5-Oxadiazole-3,4-diylbismethylene bis(phen-
ylcarbamate) (Ve) was synthesized from 0.5 g
(3.8 mmol) of Ie and 1.2 g (8.2 mmol) of III in 10 ml
of dioxane. Yield 1.3 g (92%), mp 105–110°C. IR
spectrum, ν, cm–1: 3293 (NH), 1701 (C=O), 1259
(C–O). 13C NMR spectrum, δC, ppm: 56.0 (CH2O),
124.5 (Cp), 129.5 (Co), 130.4 (Cm), 139.5 (Ci), 153.5
(C=O), 153.8 (C3, C4). Found, %: C 59.32; H 4.72;
N 14.73. C18H16N4O5. Calculated, %: C 58.69; H 4.34;
N 15.21.
1-Benzyl-1H-1,2,3-triazol-4-ylmethyl 2-phenyl-
2H-1,2,3-triazol-4-ylcarbamate (VIIIa) was synthe-
sized from 0.5 g (2.6 mmol) of Ia and 0.7 g (3.3 mmol)
of VIIa in 10 ml of dioxane. Yield 0.5 g (55%),
mp 175–176°C. IR spectrum, ν, cm–1: 3324 (NH), 1725
(C=O), 1213 (C–O). 13C NMR spectrum, δC, ppm: 53.5
(PhCH2), 62.9 (CH2O), 118.2 (Co), 118.9 (C5), 126.5
(Cp), 127.0 (Cp, Bzl), 128.3 (Co, Bzl), 128.9 (Cm),
129.4 (Cm, Bzl), 131.4 (C5′), 134.0 (Ci), 134.5 (Ci, Bzl),
143.3 (C4), 147.6 (C4′), 154.5 (C=O). Found, %:
N,N′-Bis(5-methyl-1-phenyl-1H-1,2,3-triazol-4-
yl)urea (XIVb) was synthesized in a similar way from
acid XIIIb. Yield 5.5 g (74%), mp 260°C. IR spec-
trum, ν, cm–1: 3260 (NH), 1715 (C=O). 1H NMR spec-
trum, δ, ppm: 2.30 s (6H, CH3), 7.20–7.93 m (10H,
Ph), 9.20 br.s (2H, NH). Found, %: C 60.73; H 4.75;
N 29.81. C19H18N8O. Calculated, %: C 60.96; H 4.81;
N 29.94.
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GOLOBOKOVA et al.
572
N-Phenyl-N′-(pyridn-2-yl)urea (VId) was synthe-
N,N′-Bis(5-methyl-3-oxido-2-phenyl-2H-1,2,3-
sized from 0.32 g (3.4 mmol) of IId and 0.5 g
(3.4 mmol) of III in 10 ml of anhydrous toluene. Yield
0.53 g (73%), mp 183–185°C (from EtOH). IR spec-
trum, ν, cm–1: 3219 (NH), 1689 (C=O). 13C NMR
spectrum, δC, ppm: 116.7 (Co), 122.7 (Cp), 129.6 (Cm),
138.7 (Ci), 151.7 (C2), 154.9 (C=O). Found, %:
C 68.37; H 5.06; N 19.44. C12H11N3O. Calculated, %:
C 67.60; H 5.16; N 19.71.
triazol-4-yl)urea (XI). A solution of 0.6 g (9 mmol) of
sodium nitrite in 2 ml of water was added dropwise
under vigorous stirring to a solution of 7 g (30 mmol)
of hydrazide XVI in a mixture of 12 ml of ice water,
0.9 ml of concentrated hydrochloric acid, and 20 ml of
diethyl ether, cooled to 0–2°C; during the addition, the
temperature was maintained below 7°C. When the
initial hydrazide disappeared (TLC), the ether layer
was separated, and the aqueous phase was extracted
with diethyl ether. The combined extracts were dried
over anhydrous magnesium sulfate and evaporated.
Yield 8.7 g (72%), mp 196°C (from EtOH). IR spec-
trum, ν, cm–1: 3270 (NH), 1725 (C=O). 1H NMR spec-
trum, δ, ppm: 3.15 s (6H, CH3), 7.20–7.42 m (10H,
Ph), 8.90 br.s (2H, NH). Found, %: C 56.31; H 5.02;
N 27.30. C19H18N8O3. Calculated, %: C 56.15; H 4.43;
N 27.58.
Bis(2-phenyl-2H-1,2,3-triazol-4-yl)urea (VIe)
was obtained from 0.5 g (2.3 mmol) of azide VIIa in
5 ml of dioxane and 2 mmol of tetrazole-5-amine
hydrate. The solvent was evaporated, and the viscous
residue was washed with benzene. Yield 0.31 g (40%),
mp 222–225°C (from EtOH). IR spectrum, ν, cm–1:
3280 (NH), 1720 (C=O). 13C NMR spectrum, δC, ppm:
118.6 (Co), 126.5 (C5), 128.2 (Cp), 129.8 (Cm), 134.2
(Ci), 150.2 (C=O). Found, %: C 58.65; H 4.17;
N 32.51. C17H14N8O. Calculated, %: C 58.95; H 4.04;
N 32.36.
N-Phenyl-N′-(1H-1,2,4-triazol-3-yl)urea (VIa).
A solution of 0.3 g (3.6 mmol) of amine IIa and 0.6 g
(4 mmol) of azide III in 10 ml of anhydrous toluene
was stirred for 1.5–2 h at 70–95°C until gaseous
products no longer evolved and a solid separated. The
precipitate was filtered off. Yield 0.64 g (87%),
mp 135–138°C (from EtOH). IR spectrum, ν, cm–1:
3441 (N–H, triazole), 3138 (NH), 1730 (C=O).
13C NMR spectrum, δC, ppm: 118.3 (Co), 122.3 (Cp),
129.2 (Cm), 139.2 (Ci), 146.7 (C3), 155.2 (C5), 158.1
(C=O). Found, %: C 53.06; H 4.17; N 33.62.
C9H9N5O. Calculated, %: C 53.20; H 4.43; N 34.48.
N-(2-Phenyl-2H-1,2,3-triazol-4-yl)-N′-(1H-1,2,4-
triazol-3-yl)urea (IXa) was synthesized from 0.2 g
(2.3 mmol) of IIa and 0.5 g (2.3 mmol) of VIIa in
10 ml of anhydrous toluene. Yield 0.51 g (82%),
mp 193–198°C (from EtOH). IR spectrum, ν, cm–1:
3445 (NH, triazole), 3256 (NH), 1734 (C=O).
13C NMR spectrum, δC, ppm: 116.7 (Co), 128.9 (Cp),
129.3 (Cm), 147.5 (C4′), 132.9 (C5′), 134.9 (Ci), 148.7
(C3), 154.7 (C=O), 155.3 (C5). Found, %: C 48.19;
H 3.59; N 40.95. C11H10N8O. Calculated, %: C 48.89;
H 3.73; N 41.46.
Compounds VIb–VIe, IXa–IXh, and XVa–XVd
N-(2-Phenyl-2H-1,2,3-triazol-4-yl)-N′-(4H-1,2,4-
triazol-4-yl)urea (IXb) was synthesized from 0.2 g
(2.3 mmol) of IIb and 0.5 g (2.3 mmol) of VIIa in
10 ml of anhydrous toluene. Yield 0.45 g (73%),
mp 235°C (from EtOH). IR spectrum, ν, cm–1: 3121
(NH), 1697 (C=O). 13C NMR spectrum, δC, ppm: 117.1
(Co), 127.4 (Cp), 129.4 (Cm), 130.1 (C5′), 138.4 (Ci),
143.1 (C4′), 144.0 (C3, C5), 152.8 (C=O). Found, %:
C 48.53; H 3.51; N 41.02. C11H10N8O. Calculated, %:
C 48.89; H 3.73; N 41.46.
were synthesized in a similar way.
N-Phenyl-N′-(4H-1,2,4-triazol-4-yl)urea (VIb)
was synthesized from 0.3 g (3.6 mmol) of IIb and
0.6 g (4 mmol) of III in 10 ml of anhydrous toluene.
Yield 0.46 g (63%), mp 210°C (from EtOH). IR spec-
trum, ν, cm–1: 3256 (NH), 1682 (C=O). 13C NMR
spectrum, δC, ppm: 118.1 (Co), 122.1 (Cp), 128.1 (Cm),
138.0 (Ci), 143.9 (C3, C5), 153.1 (C=O). Found, %:
C 52.80; H 4.27; N 33.70. C9H9N5O. Calculated, %:
C 53.20; H 4.43; N 34.48.
N-(1,4-Diphenyl-1H-1,2,3-triazol-5-yl)-
N′-(2-phenyl-2H-1,2,3-triazol-4-yl)urea (IXc) was
synthesized from 0.54 g (2.3 mmol) of IIc and 0.5 g
(2.3 mmol) of VIIa in 10 ml of anhydrous toluene.
Yield 0.76 g (74%), mp 78°C (from EtOH). IR spec-
trum, ν, cm–1: 3055 (NH), 1707 (C=O). 13C NMR
spectrum, δC, ppm: 147.5, 122.2, 127.9 (C4, C4′, C5),
132.9 (C5′), 150.6 (C=O). Found, %: C 65.23; H 4.16;
N 26.34. C23H18N8O. Calculated, %: C 65.40; H 4.26;
N 26.50.
N-(1,5-Diphenyl-1H-1,2,3-triazol-4-yl)-N′-phen-
ylurea (VIc) was synthesized from 0.5 g (2.1 mmol)
of IIc and 0.4 g (2.7 mmol) of III in 10 ml of anhy-
drous dioxane. Yield 0.65 g (88%), mp 155°C (from
EtOH). IR spectrum, ν, cm–1: 3331 (NH), 1601 (C=O).
13C NMR spectrum, δC, ppm: 119.2 (Co), 121.5 and
124.6 (C4, C5), 123.0 (Cp), 129.2 (Cm), 138.5 (Ci),
153.5 (C=O). Found, %: C 70.94; H 5.50; N 19.80.
C21H17N5O. Calculated, %: C 70.98; H 4.78; N 19.71.
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SYNTHESIS OF POLYNUCLEAR AZOLES
573
N-(2-Phenyl-2H-1,2,3-triazol-4-yl)-N′-(pyridin-2-
yl)urea (IXd) was synthesized from 0.11 g (1.0 mmol)
of IId and 0.22 g (1.0 mmol) of VIIa in 10 ml of
anhydrous toluene. Yield 0.16 g (57%), mp 230°C
(from EtOH). IR spectrum, ν, cm–1: 3213 (NH), 1705
(C=O). 13C NMR spectrum, δC, ppm: 98.4 (C5′), 118.7
(Co), 128.9 (Cp), 129.3 (Cm), 135.2 (Ci), 145.5 (C4′),
151.5 (C2), 155.5 (C=O). Found, %: C 59.58; H 4.06;
N 30.60. C14H12N6O. Calculated, %: C 60.00; H 4.20;
N 30.00.
N-Phenyl-N′-(5-phenyltetrazol-2-ylmethyl)urea
(XVa) was synthesized from 0.2 g (2.2 mmol) of
aniline and 0.5 g (2.2 mmol) of VIIc in 10 ml of anhy-
drous toluene. Yield 0.40 g (62%), mp 174°C (from
EtOH). IR spectrum, ν, cm–1: 3275 (NH), 1672 (C=O).
13C NMR spectrum, δC, ppm: 54.4 (CH2), 118.4 (Co),
122.5 (Cp), 123.7 (Ci′), 126.5 (Co′), 128.0 (Cm), 129.3
(Cm′), 130.4 (Cp′), 137.2 (Ci), 162.1 (C=O), 185.3 (C5′),
Found, %: C 60.74; H 4.91; N 28.72. C15H14N6O.
Calculated, %: C 61.21; H 4.76; N 28.57.
N-(5-Methyl-1-phenyl-1H-1,2,3-triazol-4-yl)-
N′-(1H-1,2,4-triazol-3-yl)urea (IXe) was synthesized
from 0.18 g (2.1 mmol) of IIa and 0.5 g (2.2 mmol) of
VIIb in 10 ml of anhydrous toluene. Yield 0.34 g
(56%), mp 254°C (from EtOH). IR spectrum, ν, cm–1:
3456 (N1′–H), 3195 (NH), 1706 (C=O). 13C NMR
spectrum, δC, ppm: 113.5, 151.5 (C4, C5), 116.4 (Co),
126.6 (Cp), 128.2 (Cm), 143.3 (Ci), 148.7 (C3′), 152.6
(C=O), 155.3 (C5′). Found, %: C 50.73; H 3.95;
N 39.26. C12H12N8O. Calculated, %: C 50.70; H 4.25;
N 39.42.
N-(2-Aminophenyl)-N′-(5-phenyltetrazol-2-yl-
methyl)urea (XVb) was synthesized from 0.12 g
(1 mmol) of o-phenylenediamine and 0.5 g (2.2 mmol)
of VIIc in 10 ml of anhydrous toluene. Yield 0.16 g
(53%), mp 107°C (from EtOH). IR spectrum, ν, cm–1:
3246 (NH), 1732 (C=O). Found, %: C 58.16; H 4.71;
N 31.75. C15H15N7O. Calculated, %: C 58.25; H 4.85;
N 31.21.
N-Phenyl-N′-(2-phenyl-2H-1,2,3-triazol-4-yl)-
urea (XVc) was synthesized from 0.2 g (2.2 mmol) of
aniline and 0.5 g (2.2 mmol) of VIIa in 10 ml of anhy-
drous toluene. Yield 0.45 g (73%), mp 145–148°C
(from EtOH). IR spectrum, ν, cm–1: 3281 (NH), 1657
(C=O). 13C NMR spectrum, δC, ppm: 98.5 (C5′), 118.7
(Co′), 120.6 (Cp), 121.5 (Co), 128.9 (Cm), 128.9 (Cp′),
129.4 (Cm′), 135.2 (Ci′), 140.8 (Ci), 145.6 (C4′), 154.1
(C=O). Found, %: C 65.30; H 4.55; N 25.68.
C15H13N5O. Calculated, %: C 64.51; H 4.66; N 25.08
N-(1,4-Diphenyl-1H-1,2,3-triazol-5-yl)-
N′-(5-phenyltetrazol-2-ylmethyl)urea (IXf) was syn-
thesized from 0.52 g (2.2 mmol) of IIc and 0.5 g
(2.2 mmol) of VIIc in 10 ml of anhydrous toluene.
Yield 0.52 g (55%), mp 78°C (from EtOH). IR spec-
trum, ν, cm–1: 3286 (NH), 1721 (C=O). 13C NMR
spectrum, δC, ppm: 57.8 (CH2), 122.5 and 128.1 (C4,
C5), 140.4 (C=O), 185.6 (C5′). Found, %: C 63.93;
H 4.91; N 28.26. C23H9N9O. Calculated, %: C 63.15;
H 4.38; N 28.82.
N-(2-Aminophenyl)-N′-(2-phenyl-2H-1,2,3-tri-
azol-4-yl)urea (XVd) was synthesized from 0.13 g
(1.2 mmol) of o-phenylenediamine and 0.5 g
(2.3 mmol) of VIIa in 10 ml of anhydrous toluene.
Yield 0.19 g (54%), mp 178°C (from EtOH). IR spec-
trum, ν, cm–1: 3387 (NH2), 3250 (NH), 1678 (C=O).
13C NMR spectrum, δC, ppm: 98.5 (C5′), 118.7 (Co),
128.9 (Cp), 129.4 (Cm), 135.2 (Ci), 145.6 (C4′), 153.0
(C=O). Found, %: C 60.61; H 4.51; N 28.06.
C15H14N6O. Calculated, %: C 61.22; H 4.76; N 28.57.
N-(5-Phenyltetrazol-2-ylmethyl)-N′-(1H-1,2,4-
triazol-3-yl)urea (IXg) was synthesized from 0.2 g
(2.3 mmol) of IIa and 0.5 g (2.2 mmol) of VIIc in
10 ml of anhydrous toluene. Yield 0.31 g (50%),
mp 232°C (from EtOH). IR spectrum, ν, cm–1: 3410
(N1′–H), 3260 (NH), 1703 (C=O). 13C NMR spectrum,
δC, ppm: 53.7 (CH2), 125.5 (Co), 125.7 (Ci), 128.5
(Cm), 130.5 (Cp), 150.5 (C3′), 162.4 (C=O), 163.3 (C5′),
183.6 (C5). Found, %: C 46.52; H 3.91; N 44.40.
C11H11N9O. Calculated, %: C 46.31; H 3.85; N 44.21.
REFERENCES
N-(5-Phenyltetrazol-2-ylmethyl)-N′-(pyridin-2-
yl)urea (IXh) was synthesized from 0.2 g (2 mmol) of
IId and 0.5 g (2.2 mmol) of VIIc in 10 ml of anhy-
drous toluene. Yield 0.36 g (61%), viscous material. IR
spectrum, ν, cm–1: 3415, 3259 (NH), 1710 (C=O).
13C NMR spectrum, δC, ppm: 54.3 (CH2), 148.2 (C2′),
156.8 (C=O), 185.7 (C5). Found, %: C 56.01; H 4.63;
N 33.78. C14H13N7O. Calculated, %: C 56.94; H 4.40;
N 33.22.
1. Verkhozina, O.N., Kizhnyaev, V.N., Vereshchagin, L.I.,
Rokhin, A.V., and Smirnov, A.I., Russ. J. Org. Chem.,
2003, vol. 39, p. 1792.
2. Vereshchagin, L.I., Petrov, A.V., Proidakov, A.G., Poka-
tilov, F.A., Smirnov, A.I., and Kizhnyaev, V.N., Russ. J.
Org. Chem., 2006, vol. 42, p. 912.
3. Vereshchagin, L.I., Petrov, A.V., Kizhnyaev, V.N., Poka-
tilov, F.A., and Smirnov, A.I., Russ. J. Org. Chem., 2006,
vol. 42, p. 1049.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 4 2012

GOLOBOKOVA et al.
574
10. Vigalok, I.V., Ostrovskaya, A.V., and Svetlakov, N.V.,
USSR Inventor’s Certificate no. 435240, 1973; Byull.
Izobret., 1974, no, 51.
11. Maksikova, A.V., Serebryakova, E.S., Tikhonova, L.G.,
and Vereshchagin, L.I., Khim. Geterotsikl. Soedin.,
1980, p. 1688.
4. Blagonravova, A.A. and Levkovich, G.A., Usp. Khim.,
1955, vol. 24, p. 93.
5. Smith, P.A.S., Organic Reactions, Adams, R., Ed., New
York: Wiley, 1946. Translated under the title Organiche-
skie reaktsii, Moscow: Inostrannaya Literatura, 1951,
vol. 3, p. 322.
12. Allen, C. and Bell, A., Org. Synth., 1946, vol. 26, p. 11.
13. Herbst, R. and Garrison, J., J. Org. Chem., 1953,
6. Houben, J., Die Methoden der organischen Chemie,
Leipzig: Georg Thieme, 1925, vol. 2, 3rd ed. Translated
under the title Metody organicheskoi khimii, Moscow:
Goskhimizdat, 1941, vol. II, part 1, p. 194.
vol. 18, p. 872.
14. Wiley, R. and Hussung, K.F., J. Org. Chem., 1956,
vol. 21, p. 190.
7. Ajello, T. and Cusmano, S., Gazz. Chim. Ital., 1940,
vol. 70, p. 770.
15. Raap, R. and Howard, J., Can. J. Chem., 1969, vol. 47,
p. 813.
8. Kirillova, L.P., Shul’gina, V.M., Shafeev, M.A., Al’mu-
khamedov, A.A., and Vereshchagin, L.I., Russ. J. Org.
Chem., 1996, vol. 32, p. 1051.
16. Heitke, B.T. and McCarty, C., J. Org. Chem., 1974,
vol. 39, p. 1522.
9. Shioiri, T. and Yamada, S., Chem. Pharm. Bull., 1974,
17. Lieber, E., Chao, T.S., and Ramachandra Rao, C.N.,
vol. 22, p. 849.
Org. Synth., 1957, vol. 37, p. 26.
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