Synthesis of polynuclear azoles linked by ether tethers

Article abstract of DOI:10.1134/S1070428013010223

Alkylation of NH-triazoles and tetrazoles and cycloaddition of organic and inorganic azides to propargyl ethers bearing a cyano group gave a number of polynuclear heterocyclic systems bridged by ether tethers.

Full text of DOI:10.1134/S1070428013010223

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 1, pp. 130–137. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © T.V. Golobokova, F.A. Pokatilov, A.G. Proidakov, L.I. Vereshchagin, V.N. Kizhnyaev, 2013, published in Zhurnal Organicheskoi
Khimii, 2013, Vol. 49, No. 1, pp. 135–141.
Dedicated to Full Member of the Russian Academy of Sciences
G.A. Tolstikov on his 80th anniversary
Synthesis of Polynuclear Azoles Linked by Ether Tethers
T. V. Golobokova, F. A. Pokatilov, A. G. Proidakov, L. I. Vereshchagin, and V. N. Kizhnyaev
Irkutsk State University, ul. K. Marksa 1, Irkutsk, 664003 Russia
e-mail: Kizhnyaev@chem.isu.ru
Received April 24, 2012
Abstract—Alkylation of NH-triazoles and tetrazoles and cycloaddition of organic and inorganic azides to
propargyl ethers bearing a cyano group gave a number of polynuclear heterocyclic systems bridged by ether
tethers.
DOI: 10.1134/S1070428013010223
We previously [1–4] synthesized non-fused poly-
nuclear triazole- and tetrazole-containing systems
bridged by methylene, carbamate, and urea fragments.
In continuation of studies in this field, in the present
work we examined a synthetic approach to polynuclear
blocks in which azole rings are linked through ether
tethers. For this purpose, we used 1,3-dipolar cyclo-
addition of organic and inorganic azides to ethers con-
taining cyano groups and in some cases triple carbon–
carbon bond.
ethyl) ether contained signals at δ 7.9–8.1, 7.3–7.6, and
8.4–8.7 ppm. Signals from the bridging methylene
groups were located at δ 5.5–6.4 (NCH2O), 4.1–4.6
(NCH2CH2O), and 3.7–4.2 ppm (NCH2CH2O).
N1-Substituted isomers of the triazole series were
1
identified on the basis of the H NMR data. The pres-
ence of two different signals from the CH protons in
the triazole rings of Ia–Id indicated formation of just
N1-substituted structures; the CH protons in N2- and
N4-substituted isomers are equivalent due to symmetric
structure of the azole ring. Tetrazoles Ie and If were
assigned the structure of N1-isomers on the basis of
published data [5].
A classical version of synthesis of bis-azolyl ethers
is based on reaction of potassium triazolate or tetra-
zolate with dihaloalkanes. The alkylation of triazoles
and tetrazole with bis(chloromethyl) and bis(2-chloro-
ethyl) ethers resulted in the formation of mixtures of
regioisomeric bis-triazoles and bis-tetrazoles Ia–If,
which were difficult to separate (Scheme 1). By
column chromatography we succeeded in isolating
N1- and N2-substituted isomers, the major products
(~85%) being those alkylated at N1.
The above approach to bis-azolyl ethers is not free
from disadvantages. In particular, the yields did not
exceed 54%, and only N-substituted derivatives can be
obtained in such a way. However, the most interesting
are compounds possessing unsubstituted NH group
which ensures their subsequent modifications and de-
termines some specificity of their physical properties.
1
In the H NMR spectra of Ia, Ic, and If we ob-
Therefore, we tried another approach to polynuclear
azoles. It is based on the transformation of terminal
functional groups in initial ethers into heterocyclic
structures. Appropriate initial compounds are nitriles II
served signals from protons in the azole rings at δ 7.8–
8.4, 7.6–8.2, and 8.6–9.2 ppm, respectively. The spec-
tra of azoles Ib, Id, and Ie derived from bis(2-chloro-
Scheme 1.
H
Y
N
Y
N
N
X
X
X
KOH, DMF, 74–100°C
N
Cl
O
Cl
N
N
+
( )n ( )n
O
Y
( )n
( )n
Ia–If
X = N, Y = CH, n = 1 (a), 2 (b); X = CH, Y = N, n = 1 (c), 2 (d); X = Y = N, n = 2 (e), 1 (f).
130

SYNTHESIS OF POLYNUCLEAR AZOLES LINKED BY ETHER TETHERS
131
Scheme 2.
N
N
NH
NH
HN
NH4N3, DMF, 90–100°C
NC
O
CN
CN
N
N
N
O
N
N
II
VII
N
N
NH4N3, DMF, 90–100°C
O
NC
O
N
O
O
HN
N
N
III
VIII
Ph
N
Ph
N
PhC CH, PhMe, 100°C
≡
O
N3
N3
N
N
N
N
O
IV
IX
Ph
Ph
PhCH2N3, PhMe, 100°C
N
N
N
HC
CH
O
N
N
O
N
VI
X
Ph
N
Ph
N
NH4N3, DMF
90–100°C
PhC
PhMe, 100°C
≡
CH
4
N
5
HN
O
N3
CN
N
N
CN
N
5'
N
N
N
O
O
V
XI
XII
triazol-4-yl)ethyl] ether (X). 3-(2-Azidoethoxy)pro-
panenitrile (V) reacted with phenylacetylene at the
azido group, yielding 3-[2-(4-phenyl-1H-1,2,3-triazol-
1-yl)ethoxy]propanenitrile (XI), and heating of the
latter with ammonium azide led to the formation of
ether XII containing both triazole and tetrazole rings.
and III, bis-azide IV, azido nitrile V, and dipropargyl
ether (VI) (Scheme 2). Dinitriles II and III were
heated with ammonium azide to obtain tetrazolyl-sub-
stituted ethers VII and VIII, respectively. Bis(2-azido-
ethyl) ether (IV) reacted with phenylacetylene to give
bis[2-(4-phenyl-1H-1,2,3-triazol-1-yl)ethyl] ether (IX).
Addition of two benzyl azide molecules to bis(prop-2-
yn-1-yl) ether (VI) afforded bis[2-(1-benzyl-1H-1,2,3-
Acetylenic cyanoethyl ethers XIIIa and XIIIb
occupy a specific place in the series of dipolarophiles.
Scheme 3.
NH4N3, DMF
90–100°C
N
OH
R
R
N
KOH, 20°C
N
+
CN
CN
H2C
N
R
O
O
XIV
PhCH2N3
H
HC
HC
HC
XIIIa, XIIIb
R'N3
PhMe, 100°C
PhMe, 100°C
N
R
R
N
5'
CH2=CHCN
KOH, 20°C
NH4N3, DMF
CN 90–100°C
N
5
OH
O
N
O
4
R'
R'
R'
N
N
N
H
N
N
N
XVIIa, XVIIb
N
N
N
XVIa, XVIb
XVa–XVc
XIII, R = H (a), Ph (b); XV, R = H, R′ = PhCH2 (a), 1,2,4-triazol-3-yl (b); R = Ph, R′ = 1,2,4-triazol-3-yl (c);
XVI, XVII: R′ = PhCH2 (a), 1,2,4-triazol-3-yl (b).
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GOLOBOKOVA et al.
132
Scheme 4.
NC
CN
O
OH
OH
O
O
NaOH, H2O, 60°C
HO
O
CN
+
CN
H2C
OH
NC
OH
OH
O
O
NC
CN
XVIII
N
N
NH
HN
N
N
N
N
N
O
O
HN
H
N
NH4N3, DMF, 105°C
O
N
N
N
O
N
H
N
H
N
O
O
N
N
N
N
N
N
N
XX
N
N
NH
HN
N
N
NC
CN
CN
N
N
O
O
O
O
OH
OH
CH2=CHCN
NH4N3, DMF
105°C
NaOH, H2O, 60°C
O
O
O
O
HO
OH
NC
HN
NH
N
N
N
N
N
N
XIX
XXI
They were used as starting compounds to obtain bis-
azoles with different heterocycles via the known
cyanoethylation of acetylenic alcohols [6]. The pres-
ence of an ether moiety, triple carbon–carbon bond,
and cyano group in a single molecule makes it possible
to synthesize polynuclear structures with various com-
binations of triazole and tetrazole rings and extends
their synthetic potential.
nium azide at the cyano group gave bis-azoles XVIIa
and XVIIb.
Following the second version, cyanoethyl ether
XIIIa reacted with ammonium azide to give tetrazole
derivative XIV, and reaction of the latter at the
acetylenic bond with benzyl azide produced tetrazole–
triazole system XVII. However, the initial reaction
with ammonium azide to obtain compound XIV is
impractical, for the acetylenic ether fragment in XIIIa
decomposes under fairly severe conditions, and the
yield of XIV does not exceed 20%.
We also used as dipolarophiles poly(cyanoethyl)
ethers prepared by cyanoethylation of sorbitol and
pentaerythritol (Scheme 4). These polyols are soluble
in water, and they readily reacted with acrylonitrile to
produce the corresponding poly(cyanoethyl) ethers
XVIII and XIX. Compounds XVIII and XIX were
isolated as powders, and their reaction with ammonium
azide in dimethylformamide at 100–105°C afforded
polytetrazolyl-substituted branched ethers XX and
XXI. The products were colorless powders soluble in
aqueous alkali, highly donor solvents, aqueous–organ-
ic mixtures (acetone, acetonitrile–water), and aqueous
solutions of strong mineral acids and some inorganic
Prop-2-yn-1-ol and 1-phenylprop-2-yn-1-ol reacted
with acrylonitrile under solvent-free conditions
(Scheme 3). It is advisable to add acrylonitrile to
a mixture of acetylenic alcohol and alkali. The reverse
order of addition of the reactants favors formation of
a considerable amount of acrylonitrile polymerization
products. We examined two versions of synthesis of
non-fused polycyclic azole systems. The first of these
included cycloaddition of organic azides, namely
benzyl azide and 3-azido-1,2,4-triazole, to the triple
C≡C bond of cyanoethyl ethers XIIIa and XIIIb with
formation of 1,2,3-triazole derivatives XVa–XVc.
Compounds XVa and XVb were also synthesized in-
dependently by cyanoethylation of triazolylmethanols
XVIa and XVIb. The subsequent reaction of triazole-
containing cyanoethyl ethers XVa–XVc with ammo-
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SYNTHESIS OF POLYNUCLEAR AZOLES LINKED BY ETHER TETHERS
133
salts (thiocyanates, iodides, perchlorates). The struc-
ture of the isolated compounds was proved by their
NMR and IR spectra and elemental analyses.
1,1′-[Oxybis(ethane-2,1-diyl)]di(1H-1,2,4-tri-
azole) (Ib) was synthesized in a similar way from
4.0 g (58 mmol) of 1,2,4-triazole and 4.1 g (29 mmol)
of bis(2-chloroethyl) ether. Yield 4.6 g (38%),
mp 74.5–75°C. IR spectrum, ν, cm–1: 3100 (C–H, Ht),
1100–1155 (C–O–C). 1H NMR spectrum, δ, ppm: 3.9 t
(2H, CH2O, J = 13 Hz), 4.5 t (2H, CH2, J = 14 Hz),
7.68 d (1H, 3-H, J = 1.6 Hz), 7.91 d (1H, 5-H, J =
1.6 Hz). Found, %: C 46.32; H 6.15; N 40.03.
C8H12N6O. Calculated, %: C 46.15; H 5.81; N 40.36.
EXPERIMENTAL
The IR spectra were obtained on an Infralum FT-
801 spectrometer from samples dispersed in mineral
oil or pelleted with KBr. The 1H and 13C NMR spectra
were recorded on a Varian VXR-500s spectrometer
from solutions in acetone-d6 (1H, 500 MHz) or
DMSO-d6 (13C, 126 MHz) using the residual proton
and carbon signals of the solvent as reference (δ 2.1,
2.6 ppm; δC 29.5, 39.5 ppm); the 13C NMR spectra
were recorded without decoupling from protons. The
elemental compositions were determined on a FLASH
EA 1112 Series CHN analyzer. The progress of reac-
tions was monitored by TLC on Silufol UV-254 plates
using ethyl acetate–hexane (3:2) as eluent; spots were
visualized by treatment with iodine vapor.
1,1′-[Oxybis(methylene)]di(1H-1,2,3-triazole)
(Ic). Powdered 85% potassium hydroxide, 16.8 g
(0.3 mol), was dispersed in 75 ml of DMF, 20.7 g
(0.3 mol) of 1,2,3-triazole was added dropwise at 35–
40°C, the mixture was stirred until it became homo-
geneous, 5 g of anhydrous magnesium sulfate was
added, and 11.5 g (0.1 mol) of bis(chloromethyl) ether
was added dropwise, maintaining the temperature
below 40°C. When the exothermic reaction was over,
the mixture was heated for 5–7 h at 95–100°C, cooled,
and filtered, the filtrate was evaporated under reduced
pressure, and the residue was recrystallized from
alcohol. Yield 7.4 g (41%), mp 46–47°C. IR spectrum,
ν, cm–1: 3135 (C–H, Ht), 1070–1075 (C–O–C).
1H NMR spectrum, δ, ppm: 5.5 s (2H, CH2), 7.7 d (1H,
5-H, J = 1.0 Hz), 8.1 d (1H, 4-H, J = 1.0 Hz). Found,
%: C 39.70; H 4.41; N 46.21. C6H8N6O. Calculated,
%: C 40.00; H 4.48; N 46.65.
The N1-substituted isomers of Ia–If were isolated
by column chromatography on Al2O3 of activity grade
II; eluent diethyl ether–petroleum ether, 1:1.
Bis(2-azidoethyl) ether (IV) [6], 2-azidoethanol [7],
bis(prop-2-yn-1-yl) ether (VI) [8], 3-azido-1,2,4-tri-
azole [9], (1-benzyl-1,2,3-triazol-4-yl)- and [1-(1,2,4-
triazol-3-yl)-1,2,3-triazol-4-yl]methanols XVIa and
XVIb [10], 2,2′-oxydiacetonitrile (II) [11], and
3,3′-[ethane-1,2-diylbis(oxy)]dipropanenitrile (III)
[12] were synthesized by known methods; their prop-
erties were consistent with published data.
Compounds Id–If were synthesized in a similar
way.
1,1′-[Oxybis(ethane-2,1-diyl)]di(1H-1,2,3-tri-
azole) (Id) was synthesized from 10.35 g (0.15 mol) of
1,2,3-triazole and 7 g (0.05 mol) of bis(2-chloroethyl)
ether. Yield 2.4 g (23%); distillation of the product was
accompanied by decomposition. IR spectrum, ν, cm–1:
1,1′-[Oxybis(methylene)]di(1H-1,2,4-triazole)
(Ia). Potassium carbonate, 4.9 g (36 mmol), was
dispersed in 25 ml of DMF, 5 g (73 mmol) of 1,2,4-tri-
azole was added under stirring, the mixture was stirred
for 15–20 min, and 4.1 g (36 mmol) of bis(chloro-
methyl) ether in 10 ml of DMF was added. The mix-
ture was heated for 1.5 h at 70°C and for 4 h at 100°C.
It was then cooled and filtered, the filtrate was evap-
orated under reduced pressure, the residue was treated
with ethyl acetate and neutralized with an aqueous so-
lution of sodium hydrogen carbonate, the organic layer
was separated and dried over calcined magnesium sul-
fate, the solvent was removed by purging with warm
air, and the residue was recrystallized from alcohol.
Yield 3.5 g (54%), mp 74.5–75°C. IR spectrum, ν,
1
3140 (C–H, Ht), 1070–1075 (C–O–C). H NMR spec-
trum, δ, ppm: 3.9 t (2H, CH2O, J = 13 Hz), 4.5 t (2H,
CH2, J = 14 Hz), 7.3 d (1H, 5-H, J = 1.0 Hz), 7.5 d
(1H, 4-H, J = 1.0 Hz). Found, %: C 46.83; H 5.82;
N 39.90. C8H12N6O. Calculated, %: C 46.15; H 5.81;
N 40.36.
1,1′-[Oxybis(ethane-2,1-diyl)]di(1H-tetrazole)
(Ie) was synthesized from 2.1 g (0.03 mol) of tetrazole
and 2.1 g (0.014 mol) of bis(2-chloroethyl) ether. Yield
1.2 g (40%), mp 106°C. IR spectrum, ν, cm–1: 3145
1
1
cm–1: 3090 (C–H, Ht), 1155–1100 (C–O–C). H NMR
(C–H, Ht), 1100–1075 (C–O–C). H NMR spectrum,
δ, ppm: 4.0 t (2H, CH2O, J = 13 Hz), 4.6 t (2H, CH2,
J = 14 Hz), 8.4 s (1H, 5-H). Found, %: C 34.51;
H 5.00; N 53.82. C6H10N8O. Calculated, %: C 34.28;
H 4.80; N 53.31.
spectrum, δ, ppm: 5.5 s (2H, CH2), 7.5 d (1H, 3-H, J =
1.6 Hz), 8.4 d (1H, 5-H, J = 1.6 Hz). Found, %:
C 39.87; H 4.53; N 46.21. C6H8N6O. Calculated, %:
C 40.00; H 4.48; N 46.65.
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GOLOBOKOVA et al.
134
was removed by purging with warm air. Yield 1.8 g
1,1′-[Oxybis(methylene)]di(1H-tetrazole) (If) was
(15%), mp 200–205°C (from ethanol). 13C NMR spec-
trum, δC, ppm: 24.7 t (5-CH2, JCH = 144 Hz), 67.6 t
(OCH2, JCH = 147 Hz), 68.0 t (CH2CH2, JCH = 142 Hz),
161.2 s (C5). Found, %: C 37.87; H 6.09; N 44.57.
C8H14N8O2. Calculated, %: C 37.79; H 5.55; N 44.07.
synthesized from 2.1 g (0.03 mol) of tetrazole and
1.7 g (0.015 mol) of bis(chloromethyl) ether. Yield
1.1 g (40%), mp 97.5°C. IR spectrum, ν, cm–1: 3090
1
(C–H, Ht), 1050–1100 (C–O–C). H NMR spectrum,
δ, ppm: 6.1 s (2H, CH2), 9.2 s (1H, 5-H). Found, %:
C 26.61; H 3.65; N 61.24. C4H6N8O. Calculated, %:
C 26.38; H 3.32; N 61.52.
1,1′-[Oxybis(ethane-2,1-diyl)]bis(4-phenyl-1H-
1,2,3-triazole) (IX). A solution of 4.2 g (27 mmol) of
diazide IV and 5 g (49 mmol) of phenylacetylene in
25 ml of toluene was stirred for 5 h at 100°C. The mix-
ture was evaporated, and the viscous oily residue was
crystallized from ethanol. Yield 7 g (72%), mp 171–
172°C. 13C NMR spectrum δC, ppm: 49.1 t (2C, 1-CH2,
JCH = 143 Hz), 69.3 t (2C, CH2O, JCH = 140 Hz),
119.3 d (2C, C5, JCH = 196 Hz), 129.0 s (Ci); 125.7,
128.4, 128.7 d (5C, Co, Cm, Cp, JCH = 162 Hz), 144.8 s
(2C, C4). Found, %: C 65.91; H 5.85; N 23.97.
C20H20N6O. Calculated, %: C 66.65; H 5.59; N 23.32.
3-(2-Azidoethoxy)propanenitrile (V). Acrylo-
nitrile, 5.8 g (0.11 mol), was added dropwise under
vigorous stirring to a mixture of 10 g (0.14 mol) of
2-azidoethanol and 2 g of 45% aqueous KOH, main-
taining the temperature below 35°C. The mixture was
then stirred for 4 h at room temperature and left
overnight. It was neutralized with aqueous HCl, dried
over CaCl2, and filtered, and the filtrate was distilled
under reduced pressure. Yield 11 g (71%), bp 140°C
(2 mm). IR spectrum, ν, cm–1: 2210 (C≡N), 2100 (N3),
1210 (C–O–C). Found, %: C 42.31; H 5.85; N 39.75.
C5H8N4O. Calculated, %: C 42.85; H 5.75; N 39.98.
Compounds X and XI were synthesized in a similar
way.
5,5′-[Oxybis(methylene)]di(1H-tetrazole) (VII).
A solution of 23 g (0.2 mol) of bis(chloromethyl) ether
and 16.6 g (0.1 mol) of potassium iodide in 80 ml of
ethanol was added dropwise to a solution of 29.4 g
(0.6 mol) of sodium cyanide in 30 ml of water. The
mixture was stirred for 48 h at 80°C and treated with
100 ml of ethyl acetate, the precipitate was filtered off.
the filtrate was dried over calcined MgSO4, the solvent
was distilled off, and 50 ml of DMF, 13 g (0.2 mol) of
NaN3, and 10.7 g (0.2 mol) of NH4Cl were added to
the residue under stirring. The mixture was stirred for
10 h at 90–100°C and evaporated under reduced pres-
sure, the residue was treated with ethyl acetate, the
aqueous phase was separated, acidified with concen-
trated hydrochloric acid to pH 2, and extracted with
ethyl acetate (4×15 ml), the extracts were dried over
MgSO4, and the solvent was removed by purging with
warm air. Yield 4.2 g (12%), mp 106°C (from ethanol).
IR spectrum, ν, cm–1: 1590 (Ht), 1210 (C–O–C).
Found, %: C 26.98; H 3.35; N 60.58. C4H6N8O. Cal-
culated, %: C 26.38; H 3.32; N 61.52.
4,4′-[Oxybis(methylene)]bis(1-benzyl-1H-1,2,3-
triazole) (X) was synthesized from 1.88 g (0.02 mol)
of dipropargyl ether (VI) in 15 ml of toluene and
4.76 g (0.04 mol) of benzyl azide. When the reaction
was complete (TLC), the mixture was evaporated, the
residue was dissolved in diethyl ether, and the solution
was passed through a column charged with aluminum
oxide. Yield 7 g (98%), mp 119–120°C. IR spectrum,
ν, cm–1: 1600 (Ph), 1580 (Ht), 1200–1100 (C–O–C).
1H NMR spectrum, δ, ppm: 5.54 t (2H, CH2), 7.30
(5H, Harom), 8.01 (5-H). Found, %: C 67.00; H 5.85;
N 23.08. C20H20N6O. Calculated, %: C 66.65; H 5.59;
N 23.32.
3-[2-(4-Phenyl-1,2,3-triazol-1-yl)ethoxy]propane-
nitrile (XI) was synthesized from 2.8 g (0.02 mol) of
azide V and 2.55 g (0.025 mol) of phenylacetylene in
15 ml of toluene. Yield 3.3 g (70%), mp 77°C. IR
spectrum, ν, cm–1: 2210 (C≡N), 1600 (Ph), 1210
(C–O–C). 13C NMR spectrum, δC, ppm: 18.4 t (1C,
CH2CN, JCH = 138 Hz), 49.4 t (1C, 1-CH2, JCH
=
148 Hz), 63.8 t (1C, OCH2, JCH = 149 Hz), 68.6 t (1C,
OCH2, JCH = 145 Hz), 119.1 s (1C, C≡N), 117.1 d (1C,
C5, JCH = 196 Hz), 129.1 s (1C, Ci); 124.9, 127.8,
128.3 d (5C, Co, Cm, Cp, JCH = 162 Hz), 144.8 s (1C,
C4). Found, %: C 64.37; H 5.85; N 23.75. C13H14N4O.
Calculated, %: C 64.45; H 5.82; N 23.13.
5,5′-[Ethane-1,2-diylbis(oxyethane-2,1-diyl)]di-
(1H-tetrazole) (VIII). A mixture of 8 g (0.047 mol) of
compound III, 7.7 g (0.12 mol) of NaN3, and 6.4 g
(0.12 mol) of NH4Cl in 50 ml of DMF was stirred for
10 h at 90–100°C. The mixture was then evaporated
under reduced pressure, the residue was treated with
water, acidified with concentrated hydrochloric acid to
pH 2, and extracted with ethyl acetate (5×15 ml),
the extracts were dried over MgSO4, and the solvent
5-{2-[2-(4-Phenyl-1H-1,2,3-triazol-1-yl)ethoxy]-
ethyl}-1H-tetrazole (XII) was synthesized as de-
scribed above for compound VIII from 1 g
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SYNTHESIS OF POLYNUCLEAR AZOLES LINKED BY ETHER TETHERS
135
(0.015 mol) of NaN3 and 0.8 g (0.015 mol) NH4Cl in
15 ml of DMF and 2.5 g (0.01 mol) of XI. Yield 1.1 g
(39%), mp 172–175°C. IR spectrum, ν, cm–1: 1590
(Ph), 1450–1440 (Ht), 1210–1170 (C–O–C). 13C NMR
spectrum, δC, ppm: 24.9 t (1C, 5′-CH2, JCH = 139 Hz),
48.5 t (1C, 1-CH2, JCH = 141 Hz), 68.1 t (1C, OCH2,
JCH = 145 Hz), 69.1 t (1C, CH2O, JCH = 149 Hz),
119.1 d (1C, C5, JCH = 190 Hz), 129.1 s (1C, Ci);
125.8, 128.4, 128.6 d (5C, Co, Cm, Cp, JCH = 161 Hz),
144.8 s (C4), 161.3 s (C5′). Found, %: C 53.98; H 5.56;
N 34.81. C13H15N7O. Calculated, %: C 54.73; H 5.30;
N 34.37.
9.2 g (83%), mp 101–102°C. IR spectrum, ν, cm–1:
1600 (Ph), 1580 (Ht), 1200–1100 (C–O–C). Found, %:
C 64.73; H 5.45; N 24.91. C13H14N4O. Calculated, %:
C 64.45; H 5.82; N 23.12.
b. Compound XVa was synthesized as described
above for XIIIa from 2 g (0.01 mol) of XVIa and
0.79 g (0.015 mol) of acrylonitrile using 0.5 g of 40%
aqueous KOH in 5 ml of dioxane. Yield 0.9 g (36%),
mp 100–102°C. The product showed no depression of
the melting point on mixing with a sample prepared as
described in a.
3-{[(1,2,4-Triazol-3-yl)-1,2,3-triazol-4-yl]me-
thoxy}propanenitrile (XVb). a. The procedure was
analogous to the synthesis of XVa (a); from 1.5 g
(0.013 mol) of 3-azido-1,2,4-triazole and 1.5 g
(0.013 mol) of ether XIIIa in 10 ml of toluene we ob-
tained 1.7 g (60%) of XVb with mp 162°C. 13C NMR
spectrum, δC, ppm: 16.7 t (CH2CN, JCH = 139 Hz),
3-[(1-Phenylprop-2-yn-1-yl)oxy]propanenitrile
(XIIIa) was synthesized as described above for com-
pound V from 14.3 g (0.25 mol) of propargyl alcohol
and 13.2 g (0.25 mol) of acrylonitrile. Yield 20 g
(73%), bp 130°C (20 mm). 13C NMR spectrum, δC,
ppm: 17.2 t (CH2CN, JCH = 136 Hz), 56.7 t (CH2,
JCH = 148 Hz), 63.2 t (OCH2, JCH = 147 Hz), 75.7 d
(HC≡C, JCH = 252 Hz), 78.5 d (HC≡C, JCH = 46 Hz),
117.9 s (CN). Found, %: C 66.53; H 6.25; N 13.03.
C6H7NO. Calculated, %: C 66.04; H 6.47; N 12.84.
61.8 t (CH2O, JCH = 149 Hz), 64.0 t (OCH2, JCH
=
145 Hz), 118.9 s (CN), 122.7 d (C5, JCH = 196 Hz),
143.6 s (C3″), 145.8 d (C5″, JCH = 217 Hz), 153.5 s (C4).
Found, %: C 44.03; H 4.22; N 44.56. C8H9N7O. Cal-
culated, %: C 43.83; H 4.14; N 44.73.
3-[(1-Phenylprop-2-yn-1-yl)oxy]propanenitrile
(XIIIb) was synthesized as described above for com-
pound V from 4.5 g (34 mmol) of 1-phenylprop-2-yn-
1-ol and 1.8 g (34 mmol) of acrylonitrile using 1 g of
40% aqueous KOH. Yield 2.1 g (33%), bp 175–177°C
b. As described above for compound V, from 1.5 g
(0.009 mol) of XVIb and 0.47 g (0.009 mol) of acrylo-
nitrile using 0.3 g of 40% aqueous KOH in 5 ml of
dioxane we obtained 0.8 g (42%) of XVb with
mp 160–162°C. The product showed no depression of
the melting point on mixing with a sample prepared as
described in a.
13
(2 mm). C NMR spectrum, δC, ppm: 16.7 t (CH2CN,
JCH = 137 Hz), 61.3 t (OCH2, JCH = 147 Hz), 69.2 d
(CHO, JCH = 144 Hz), 77.0 d (HC≡C, JCH = 252 Hz),
79.8 d (HC≡C, JCH = 47 Hz), 117.6 s (CN); 125.8,
127.0, 127.7 (CHarom, JCH = 163 Hz); 136.3 s
(1C, Carom).
3-{Phenyl[1-(1,2,4-triazol-3-yl)-1,2,3-triazol-4-
yl]methoxy}propanenitrile (XVc) was synthesized as
described above for compound IX from 1.5 g
(8.1 mmol) of XIIIb and 1.03 g (9.4 mmol) of 3-azido-
1,2,4-triazole in 10 ml of toluene. Yield 0.8 g (31%),
mp 168–170°C. 13C NMR spectrum, δC, ppm: 118.2 s
(CN), 17.2 t (CH2CN, JCH = 136 Hz), 62.4 t (OCH2,
5-[2-(Prop-2-yn-1-yloxy)ethyl]-1H-tetrazole
(XIV) was synthesized from 1.95 g (0.03 mol) of
NaN3, 1.6 g (0.03 mol) of NH4Cl, and 3 g (0.027 mol)
of compound XIIIa in 15 ml of DMF. Yield 0.8 g
(20%), mp 91–92°C. IR spectrum, ν, cm–1: 1464–1440
(Ht), 1210–1150 (C–O–C). 13C NMR spectrum, δC,
ppm: 25.4 t (5-CH2, JCH = 137 Hz), 58.1 t (≡CCH2O,
JCH = 144 Hz), 68.4 t (OCH2, JCH = 147 Hz), 75.5 d
(HC≡, JCH = 252 Hz), 81.5 d (HC≡C, JCH = 47 Hz),
158.7 s (C5). Found, %: C 48.78; H 5.65; N 37.21.
C6H8N4O. Calculated, %: C 47.36; H 5.30; N 36.82.
J
CH = 147 Hz), 74.3 d (CHPhO, JCH = 145 Hz), 153.5 s
(C4), 120.9 d (C5, JCH = 201 Hz), 147.3 s (C3″), 144.2 d
(C5″, JCH = 214 Hz), 138.5 s (Ph); 126.0, 127.5, 127.1
(CH, Ph, JCH = 164 Hz).
5-{2-[(1-Benzyl-1H-1,2,3-triazol-4-yl)methoxy]-
ethyl}-1H-tetrazole (XVIIa). a. A solution of 4 g
(0.026 mol) of compound XIV and 4 g (0.03 mol) of
benzyl azide in 20 ml of toluene was heated for 15 h at
100–105°C until the initial acetylenic compound dis-
appeared (TLC). The solvent was distilled off under
reduced pressure. Yield 5 g (67%), mp 143°C (from
ethanol). IR spectrum, ν, cm–1: 1465–1440 (Ht), 1250–
1120 (C–O–C). 13C NMR spectrum, δC, ppm: 24.9 t
3-[(1-Benzyl-1,2,3-triazol-4-yl)methoxy]propane-
nitrile (XVa). a. A mixture of 5 g (0.045 mol) of ether
XIIIa and 6.6 g (0.05 mol) of benzyl azide in 15 ml of
toluene was stirred for 6 h at 105°C until the initial
azide disappeared (TLC). The precipitate was filtered
off, recrystallized from water, and dried in air. Yield
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 1 2013

GOLOBOKOVA et al.
(1C, 5′-CH2, JCH = 137 Hz), 55.2 t (1C, CH2Ph, JCH
136
=
a similar way from 5.7 g (0.043 mol) of pentaerythritol
and 10 g (0.18 mol) of acrylonitrile. Yield 27.4 g
(84%), mp 43°C. 13C NMR spectrum, δC, ppm: 20.7 t
(4C, CH2CN, JCH = 143 Hz), 48.8 s [C(CH2)4], 61.3 t
140 Hz), 63.2 t (1C, 4-CH2, JCH = 139 Hz), 65.0 t
(1C, OCH2, JCH = 145 Hz), 69.1 t (1C, CH2O, JCH
149 Hz), 126.5 d (1C, C5, JCH = 192 Hz), 133.8 s (1C,
=
Ci); 128.4, 129.3, 129.1 d (5C, Co, Cm, Cp, JCH
=
(4C, CH2O, JCH = 146 Hz), 71.9 t (4C, CH2O, JCH =
160 Hz), 145.9 s (1C, C4), 161.1 s (1C, C5′). Found, %:
C 54.21; H 5.92; N 34.47. C13H15N7O. Calculated, %:
C 54.73; H 5.30; N 34.37.
144 Hz), 118.1 s (4C, C≡N). Found, %: C 59.40;
H 6.81; N 15.88. C17H24N4O4. Calculated, %: C 58.61;
H 6.94; N 16.08.
b. As described above for compound VIII, from
3.4 g (0.052 mol) of NaN3, 2.6 g (0.05 mol) of NH4Cl,
and 9.6 g (0.04 mol) of XVa in 25 ml of DMF we
obtained 4.6 g (41%) of XVIIa with mp 143°C. The
product showed no depression of the melting point on
mixing with a sample prepared as described in a.
1,2,3,4,5,6-Hexakis[2-(1H-tetrazol-5-yl)ethoxy]-
hexane (XX). A suspension of 7.5 g (0.12 mol) of
NaN3 and 5 g (0.09 mol) of NH4Cl in 30 ml of DMF
was added at room temperature to a solution of 5 g
(0.001 mol) of compound XVIII in 25 ml of DMF, and
the mixture was stirred for 24 h at 105°C. The mixture
was cooled to 20–25°C, the solvent was distilled off
under reduced pressure, and 50 ml of 0.1 N aqueous
HCl was added to the residue until pH 2. The precip-
itate was filtered off, repeatedly washed with water
until neutral washings, and dried in air. Yield 7.2 g
(97%), mp 150°C. 13C NMR spectrum, δC, ppm: 21.9 t
5-(2-{[1-(1H-1,2,4-triazol-3-yl)-1H-1,2,3-triazol-
4-yl]methoxy}ethyl)-1H-tetrazole (XVIIb) was syn-
thesized as described above for compound VIII from
2.5 g (0.011 mol) of XVb, 1.4 g (0.022 mol) of NaN3,
and 1.2 g (0.022 mol) of NH4Cl in 15 ml of DMF.
Yield 2.4 g (84%), mp 158–158°C. IR spectrum, ν,
cm–1: 1465–1440 (Ht), 1245–1110 (C–O–C). 13C NMR
spectrum, δC, ppm: 24.7 t (5′-CH2, JCH = 139 Hz),
(4C, 5-CH2, JCH = 137 Hz), 22.3 t (2C, 5-CH2, JCH
=
137 Hz), 63.8 t (4C, OCH2, JCH = 147 Hz), 64.7 t (2C,
OCH2, JCH = 147 Hz), 68.7 t (2C, CH2), 76.5–77.8
(overlapping signals, 4C, CH), 152.5–152.8 br.s (C5).
Found, %: C 38.10; H 5.01; N 43.38. C24H38N24O6.
Calculated, %: C 37.99; N 5.05; N 44.31.
63.0 t (4-CH2, JCH = 135 Hz), 65.1 t (OCH2, JCH
=
147 Hz), 126.8 d (C5, JCH = 191 Hz), 143.0 s (C4),
148.1 d (C5″, JCH = 220 Hz), 149.7 s (C3″), 161.3 s
(C5′). Found, %: C 36.89; H 3.48; N 53.95. C8H10N10O.
Calculated, %: C 36.64; H 3.84; N 53.41.
1,3-Bis[2-(1H-tetrazol-5-yl)ethoxymethyl]-2,2-
bis[2-(1H-tetrazol-5-yl)ethoxymethyl]propane
(XXI) was synthesized in a similar way from 5 g of
(0.014 mol) tetranitrile XIX, 7.5 g (0.12 mol) of NaN3,
and 5 g (0.09 mol) of NH4Cl in 25 ml of DMF. Yield
6.1 g (84%), mp 143°C. 13C NMR spectrum, δC, ppm:
20.7 (5-CH2, JCH = 135 Hz), 48.5 s [C(CH2)4], 63.1 t
(OCH2, JCH = 144 Hz), 71.6 t (OCH2, JCH = 143 Hz),
152.5 s (C5). Found, %: C 38.10; H 5.01; N 42.51.
C17H28N16O4. Calculated, %: C 39.23; N 5.42; N 43.06.
1,2,3,4,5,6-Hexakis(2-cyanoethoxy)hexane
(XVIII). A solution of 0.3 g of sodium hydroxide in
1 ml of water was added under stirring over a period of
10 min to a solution of 5 g (0.027 mol) of sorbitol and
10 g (0.18 mol) of acrylonitrile in 5 ml of water, and
the mixture was stirred for 5 h at 60°C. The mixture
was cooled to room temperature, poured into 25 ml of
water under stirring, and neutralized with 0.1 N aque-
ous HCl. The solvent was distilled off under reduced
pressure, the residue was extracted with ethyl acetate
(4×20 ml), the extracts were combined and dried over
calcined MgSO4, the solvent was removed on a rotary
evaporator, and the viscous oily residue was dried
under reduced pressure. Yield 8.5 g (90%). 13C NMR
spectrum, δC, ppm: 21.0 t (4C, CH2CN, JCH = 137 Hz),
21.9 t (2C, CH2CN, JCH = 137 Hz), 61.8 t (4C, OCH2,
This study was performed under financial support
by the Ministry of Education and Science of the
Russian Federation.
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