Epichlorohydrin as a Precursor of Functionally Substituted 1,2,3-Triazoles and Tetrazoles

Article abstract of DOI:10.1134/S1070428019020106

Different procedures for azidation of epichlorohydrin and 2-(oxiran-2-ylmethyl)-5-phenyltetrazole in aqueous medium are considered. The synthetic potential of 1-azido-3-chloropropan-2-ol is demonstrated by its reactions with NH-unsubstituted azoles and 1.

Full text of DOI:10.1134/S1070428019020106

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2019, Vol. 55, No. 2, pp. 186–192. © Pleiades Publishing, Ltd., 2019.
Russian Text © T.V. Golobokova, A.G. Proidakov, L.I. Vereshchagin, V.N. Kizhnyaev, 2019, published in Zhurnal Organicheskoi Khimii, 2019, Vol. 55,
No. 2, pp. 234–241.
Epichlorohydrin as a Precursor of Functionally Substituted
1,2,3-Triazoles and Tetrazoles
T. V. Golobokovaa,*, A. G. Proidakova, L. I. Vereshchagina, and V. N. Kizhnyaeva
a Irkutsk State University, ul. K. Marksa 1, Irkutsk, 664003 Russia
*e-mail: t.golobokova@rambler.ru
Received May 8, 2018; revised May 14, 2018; accepted October 13, 2018
Abstract—Different procedures for azidation of epichlorohydrin and 2-(oxiran-2-ylmethyl)-5-phenyltetrazole
in aqueous medium are considered. The synthetic potential of 1-azido-3-chloropropan-2-ol is demonstrated by
its reactions with NH-unsubstituted azoles and 1.3-dipolar cycloaddition to ethynyl dipolarophiles.
Keywords: epichlorohydrin, 1,3-dipolar cycloaddition, NH-unsubstituted azoles, alkylation, nucleophilic
substitution, azidation, oxirane, 1,2,3-triazole, tetrazole, sodium azide
DOI: 10.1134/S1070428019020106
1,2-Azidoalcohols are most commonly synthesized
by nucleophilic substitution in the parent oxirane ring
under the action of azidating agents (NaN3, NH4N3,
etc.) in various conditions [1–4].
To find a safer approach to 1-azido-3-chloropropan-
2-ol (1), we have accomplished six different azidation
procedures for epichlorohydrin and revealed the main
regularities of this process (Scheme 1).
As the starting epoxy compound we took
epichlorohydrin. Azidation of the latter opens the way
to a polyfunctional 1-azido-3-chloropropan-2-ol, a
promising synthetic precursor for novel heterocyclic
carbinols. The azide anion can attack both the ring α-
and β-carbon atom, and, a result, a mixture of isomeric
products is formed. Moreover, the reaction can be
complicated by a concurrent nucleophilic substitution
of chlorine to give 1,3-diazidopropan-2-ol. In the
present research we established general regularities of
azidation of epichlorohydrin and 2-(oxiran-2-ylmethyl)-
5-phenyltetrazole.
It was found that in an alkaline medium (Table 1,
entries no. 1, 3, 4, and 6), the azide anion adds to the
least substituted β-carbon atom in epichlorohydrin,
after which the chloride ion in the intermediate 1-azido-
3-chloropropan-2-ol is substituted by the second N3
group to form diazide 2. Varying the epichlorohydrin–
sodium azide ratio did not have any effect on the
reaction direction.
In an acidic nedium (Table 1, entry no. 2), the
nucleophile selectively attacks the least substituted β-
carbon atom of the oxirane ring to a form
azidochlorohydrin 1 as a single product. When the
initial pH of the reaction mixture was 7.3 (Table 1,
entry no. 5), a mixture of products 1 and 2 formed in
yields of 75 and 25%, respectively.
We earlier reported [5] the synthesis of 1-azido-3-
chloropropan-2-ol in the reaction of epichlorohydrin with
triethylammonium hydrazoate in diethyl ether; the salt was
not preliminarily isolated because of its high hygro-
scopicity and instability. The yield of the target product in
this reaction is high (95%), but the necessity of working
with the toxic hydrazoic acid limits its practical use.
The composition and structure of the synthesized
compounds were established by NMR and IR
spectroscopy and confirmed by elemental analysis. The
Scheme 1.
OH
CH2Cl
OH
-
N3
Table 1
Cl
N3
N3
N3
+
NaN3
O
pH > 7
2
1
186

EPICHLOROHYDRIN AS A PRECURSOR OF FUNCTIONALLY SUBSTITUTED
Table 1. Azidation of epichlorohydrin with NaN3 in water
187
Products, %
1,3-diazidopropan-2-ol 1-azido-3-chloropropan-2-ol
Entry
no.
Reaction conditions
pН
Yield, %
1
2
Water, 25°С
Water, 25°С
9.7
5.6
37
63
100
–
–
100
Water, 60°С,
epichlorohydrin : azide = 1 : 1
3
4
9.7
9.7
32
18
100
100
–
–
Water, 60°С,
epichlorohydrin : azide = 1 : 2
5
6
Water, 0–5°С, Mg(ClO4)2
Water, TEBAC, 80°С
7.3
9.7
40
79
25
75
–
100
1Н NMR spectra of the intermediate chlorohydrin 1
display characteristic nonequivalent proton signals of
the N3CH2–СH(OH)–CH2Cl fragment at 3.44 and 3.40
and 4.00, 3.63, and 3.57 ppm, and its 13C NMR
spectrum contains signals at 71.2, 46.7, and 54.2 ppm
from –CH–, Cl–CH2–, and –CH2–N3, respectively. The
IR spectrum of compound 1 contains stretching vib-
ration bands of the ОН (3380 cm–1), С–Сl (783 cm–1),
The composition and structure of the synthesized
compounds were established by NMR and IR
spectroscopy and confirmed by elemental analysis.
1
The Н NMR spectrum of compound 4a displays
characteristic nonequivalent proton signals of the
N3CH2–СH(OH)–CH2– fragment at 3.81 and 3.87,
4.57, 4.87, and 4.95 ppm, respectively. The IR
spectrum of compound 4a contains characteristic
stretching vibration bands of the OH (3386 cm–1) and
13
and –N3 groups (2145 cm–1). The C NMR spectrum
1
of a symmetric product 2 contains equivalent CH2 carbon
signals at 54.5 ppm, and the proton signals of these
groups in the 1Н NMR spectrum appear at 3.33 ppm.
N3 groups (2156 cm–1). The Н NMR spectrum of
product 4b contains nonequivalent proton signals of
the НО–CH2–СH(N3)–CH2– fragment at 3.52 and
3.58, 4.63, and 4.84 ppm, respectively. The ratio of
isomers 4a and 4b was estimated from the intensities
of the nonequivalent proton signals of the –СН2–ОН
and –СН2–N3 functional fragments.
Optimization of the described procedures allowed
us to extend them to 2-(oxiran-2-ylmethyl)-5-
phenyltetrazole (3) (Scheme 2).
The azidation of compound 3 with sodium azide in
different conditions (Table 2) was found to involve
competitive attack of the azide anion on both the β-
(least substituted) and α-carbon atom of the parent
epoxide ring to form a mixture of 1-azido-3-(5-
phenyltetrazol-2-yl)propan-2-ol (4a) and 2-azido-3-(5-
phenyltetrazol-2-yl)propan-1-ol (4b).
1-Azido-3-chloropropan-2-ol (1) can be considered
as a bifunctional precursor, because transforming of its
terminal groups opens the way to heterocyclic bi- and
polynuclear carbinols of different structures.
First, the azide functionality renders azidochloro-
hydrin 1 active in 1,3-dipolar cycloaddition to acetylenic
dipolarophiles 5а–5d leading to 1,2,3-triazolyl-sub-
stituted chloropropan-2-ols 6а–6d (Scheme 3).
It was found that compound 4b is the main product
both in an acidic (Table 2, entry no. 2) and in an
alkaline medum (Table 2, entry nos 1, 3). When the
initial pH of the reaction mixture is 7.3 (Table 2, entry
no. 4), selective formation of isomer 4a is observed.
The reactions were performed in toluene (or
ethanol) for 4–12 h at different temperatures, depen-
ding on the reactivity of the acetylenic component. It
Scheme 2.
Ph
Ph
Ph
HO
N3
N
Table 2
N
N
N3
OH
NaN3
O
+
+
N
N
N
N
N
N
N
N
N
4b
3
4a
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GOLOBOKOVA et al.
188
Scheme 3.
R'
R''
R'
R``
OH
OH
HO
N3
N3
+
Cl
N3
R'
R''
+
N
N
N
N
N
N
5a_5d
6a_6d
1
R' = Ph, R'' = H (5a, 6a); R' = R'' = COOH (5b, 6b); R' = C(O)Ph, R''= Ph (5c, 6c); R' = CH2OC(O)Ph, R'' = H (5d, 6d).
Scheme 4.
Water/toluene
NaOH
R
R
OH
N
N
H
TEBAC
+
Cl
N3
N3
N
N
K2CO3
DMF
130-140oC
N
N
N
N
OH
7a, 7b
1
8a, 8b
H
N
N
N
N
N
(8b).
N3
(7b)
; R=
R = Ph (7a, 8a); R=
N
N
N
OH
was found that the 1,3-dipolar cycloaddition reactions
of 1-azido-3-chloropropan-2-ol (1) to ethynyl ketone
5c and acetylenedicarboxylic acid 5b proceed in
milder conditions and within a shorter time.
acetylenedicarboxylic acid 5b gave a single isomer of
1,4,5-trisubstituted 1,2,3-triazole 6b. In the reaction of
azidochlorohydrin 1 with dipolarophiles 5c, no
isomeric products were detected: the 1Н NMR
spectrum of product 6c showed no splitting of signals
of the phenyl substituent in the 1,2,3-triazole ring, and
the 1Н NMR spectrum of compound 6d displayed only
one 1.2.3-triazole proton signals (7.5 ppm).
The reaction of an unsymmetric ethynyl derivative
5а with azidochlorohydrin 1 gave a mixture of 1,5- and
1,4-disubstituted 1,2,3-triazoles 6а with the
predominance of the 1,4 isomer (≈70%). The
conclusion on the formation of the two isomers is
based on the evidence in [6], which shows that the
ortho-proton signals of the phenyl ring in the 1,4
Second, the presence of a chlorine substituent in 1-
azido-3-chloropropan-2-ol (1) allows its use as an
alkylating agent in reactions with NH-unsubstituted
azoles. To accomplish such reactions, one has first
prepared corresponding azole salts [7]. Regardless of a
common reaction route, the alkylation conditions of
NH-unsubstituted azoles with various haloalkyl
reagents are not standard. In particular, the alkylation
of 5-phenyltetrazole 7а with compound 1 in the
presence of trimethylamine was unsuccessful: no target
product 8а ormed. Using stronger bases (for example,
KOH) resulted in tarring of the reaction mixture.
1
isomer are shifted downfield. The Н NMR spectrum
of compound 6а displays a double set of signals of the
ortho-, para-, and meta protons of the phenyl ring:
7.89, 7.41, and 7.30 ppm for the 1,4 isomer and 7.71,
7.61, and 7.50 ppm for the 1,5 isomer. The
cycloaddition of 1-azido-3-chloro-propan-2-ol (1) to
Table 2. Azidation of 2-(oxiran-2-ylmethyl)-5-phenyltetra-
zole with NaN3 in water
Product, %
Entry
The best results not only with 5-phenyltetrazole 7а,
but also with bistetrazole 7b were obtained under
phase-transfer conditions: water–toluene, NaOH in the
presence of catalytic quantities of TEBAC (Scheme 4).
Reaction conditions
pН
no.
4b
95
80
4a
5
1
2
Water, 25°С
Water, 25°С
9.7
5.6
20
No less successful was the alkylation of NH-
unsubstituted tetrazoles 7а and 7b with azido-
chlorohydrin 1 in DMF in the presence of K2CO3 at
130–140°С to form target products 8а and 8b.
Water, 60°С, epoxide : azide =
3
4
9.7
60
–
40
1 : 1
Water, 0–5°С, Mg(ClO4)2 7.3
100
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EPICHLOROHYDRIN AS A PRECURSOR OF FUNCTIONALLY SUBSTITUTED
189
The alkylation of 5-phenyltetrazole 7а provides an
Procedure 5. Epichlorohydrin, 2 g (0.02 mol), was
added to a cold (0–5°С) solution of 2.9 g (0.013 mol)
of Mg(ClO4)2 and 2 g (0.0308 mol) of NaN3 in 50 mL
of water. The reaction mixture was left to stand at 0–5°С
for 20–24 h. After the reaction was complete, the
precipitate was filtered off. The filtrate was extracted
with ether (4 × 15 mL). The combined ether extracts
were dried over CaCl2. The ether was distilled off, and
the remaining product was distilled at reduced pressure.
Yield 1.3 g (40%), bp 78–80°С (4 mmHg). IR
spectrum (thin film), ν, cm–1: 3258 (ОН), 2145 (-N3),
N1- and N2-isomer mixture with the predominance of
1
2.5-disubstituted product 8а (≈80%). The Н NMR
spectrum of compound 8а shows two triplets in the
methylene proton region, assignable to the nonequi-
valent protons of the N1–CH2 (4.50–4.63 ppm) and
N2–CH2 groups (4.87 and 4.95 ppm). The reaction of
bistetrazole 7b with azidochlorohydrin 1 resulted in
the preferential formation of the N2N2-isomer (≈95%).
1
The Н NMR spectrum of product 8b contains two
complex multiplets at 4.86–4.89 and 4.68–4.70 ppm
for the N2N2 and N2N1 isomers, respectively. The
signals were assigned, taking account of the regularity
observed in the tetrazole series and consisting in that the
methylene proton signals of the N2-isomers are downfield
from those of the N1-isomers [8, 9]. Indirect evidence
for the formation of a mixture of the N2N2- and N2N1-
isomers of compound 8b is provided by the splitting of
the phenyl proton signals. The symmetric N2N2-isomer
gives a strong singlet at 8.3 ppm, while the N2N1-
isomer gives two doublets at 8.12 and 8.33 ppm.
1
784 (C-Cl). Н NMR spectrum (acetone-d6), δ, ppm
(nJ, Hz): 3.63 d and 3.57 d (1Н' or 1Н'', 2J = 11.2, 3J =
5.6 and 2J 11.2, 3J 5.2, СН2–Сl); 3.44 d and 3.40 d (1Н'
or 1Н'', 2J 10.5, 3J 4.0 and 2J 10.5, 3J 4.5, СН2–N3); 4.0
3
m (1Н, СН); 4.86 d (1Н, J 4.8, ОН). 13C NMR
spectrum (acetone-d6), δ, ppm: 54.2 (СН2–N3); 71.2
(СН), 46.7 (CH2–Cl).
1,3-Diazidopropan-2-ol (2). Procedure 1.
Epichlorohydrin, 2 g (0.02 mol), was added in portions
to a solution of 3.9 g (0.06 mol) of NaN3 in 45 mL of
water at 25°С. The initial pH of the mixture was 9.7.
The mixture was stirred at 25°С until reaction
completion and then extracted with ether (4 × 15 mL).
The ether extracts were combined and dried over
CaCl2. The ether was distilled off, and the remaining
product was distilled at reduced pressure. Yield 1 g
(37%), bp 93–95°С (2 mmHg).
EXPERIMENTAL
The IR spectra were obtained on an Infralum FT-
801 Fourier spectrometer in thin films of mineral oil.
1
The Н and 13С NMR spectra were measured on a
Bruker 400-DPX spectrometer (400.13 and 101.61 МHz,
respectively) with proton decoupling in acetone-d6
(1Н, 13С) or DMSO-d6 (1Н, 13С), using residual proton
signals of the solvents as internal standards: δ 29.5
and 39.5 for 13С and 2.1 and 2.6 ppm for 1Н,
respectively. Elemental analysis was performed on a
Thermo Flash EA 1112 CHN analyzer. Reaction
progress was monitored by TLC on Silufol UV-254
plates, eluent hexane−ether (1 : 3), developer iodine
vapor.
Procedure 3. Sodiun azide, 1.3 g (0.02 mol), was
added to an emulsion of 2 g (0.02 mol) of
epichlorohydrin in 45 mL of water. The reaction
mixture was vigorously stirred at 60°С. After the
reaction was complete, the reaction mixture was
extracted with ether (4 × 15 mL). The ether extracts were
combined and dried over CaCl2. The ether was
distilled off, and the remaining product was distilled at
reduced pressure. Yield 0.5 g (18%), bp 93–95°С
(2 mmHg).
2-(Oxiran-2-ylmethyl)-5-phenyltetrazole
synthesized as described in [10].
3
was
Procedure 4. Sodiun azide, 2.8 g (0.04 mol), was
added to an emulsion of 2 g (0.02 mol) of epichloro-
hydrin in 45 mL of water. The reaction mixture was
vigorously stirred at 60°С. After the reaction was
complete, the reaction mixture was extracted with
ether (4 × 15 mL). The ether extracts were combined
and dried over CaCl2. The ether was distilled off, and
the remaining product was distilled at reduced
pressure. Yield 0.9 g (32%), bp 93–95°С (2 mmHg).
1-Azido-3-chloropropan-2-ol (1). Procedure 2.
Epichlorohydrin, 2 g (0.02 mol), was added in portions
to a solution of 3.9 g (0.06 mol) of NaN3 in 20 mL of
water and 25 mL of glacial acetic acid at 25°С. The
initial pH of the mixture was 5.4. The reaction mixture
was stirred at 25°С, after which it was extracted with
ether (4 × 15 mL). The combined ether extracts were
washed with 10% NaOH and dried over CaCl2. The
ether was removed by distillation, and the remaining
product was distilled at reduced pressure. Yield 1.7 g
(63%), bp 80–82°С (5 mmHg).
Procedure 6. Epichlorohydrin, 5 g (0.054 mol), in
20 mL of water and 0.1 g of TEBAC were added to a
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GOLOBOKOVA et al.
190
solution of 4.5 g (0.069 mol) in 25 mL of water at
25°С. The reaction mixture was stirred at 80°С. After
the reaction as complete, the organic layer was
separated, and the aqueous layer was extracted with
ether (4 × 15 mL). The organic fractions were com-
bined and dried over CaCl2. The solvents were distilled
off, and the reaming product was distilled at reduced
pressure. Yield 6 g (79%), bp 93–95°С (4 mmHg). IR
spectrum (thin film), ν, cm–1: 3234 (ОН), 2138 (N3).
1Н NMR spectrum (acetone-d6), δ, ppm (nJ, Hz): 3.33
(СmetaPh); 128.5 (СparaPh). Found, %: C 48.72; H 4.96;
N 40.71. C10H11N7O2. Calculated, %: C 48.98; H 4.52;
N 39.98.
Procedure 2. Epoxide 3, 1 g (0.005 mol), was
added in portions to a solution of 1.6 g (0.025 mol) of
NaN3 in 15 mL of water and 25 mL of glacial acetic
acid at 25°С. The initial pH of the mixture was 5.4.
The reaction mixture was stirred at 25°С, after which it
was extracted with ether (4 × 15 mL). The combined
ether extracts were washed with 10% NaOH and dried
over CaCl2. The ether was distilled off, and the
remaining product was recrystallized from ethyl
acetate. Yield 0.48 g (40%), mp 54–60°С (ethyl
acetate).
3
d (2Н, J 5.2, СН2–N3); 3.96 m (1Н, СН); 4.86 d (1Н,
13
3J 4.8, ОН). C NMR spectrum (acetone-d6), δ, ppm:
54.5 (СН2–N3); 70.6 (СН).
1-Azido-3-(5-phenyltetrazol-2-yl)propan-2-ol
(4a). Procedure 4. Epoxide 3, 0.5 g (0.0025 mol), was
added to a cold (0–5°С) solution of 0.3 g (0.0014 mol)
of Mg(ClO4)2 and 0.23 g (0.0035 mol) of NaN3 in
5 mL of water. The reaction mixture was left to stand
at 0–5°С for 20–24 h. After the reaction was complete,
the precipitate was filtered off. The filtrate was
extracted with ether (4 × 15 mL). The combined ether
extracts were dried over CaCl2. The ether was distilled
off. Yield 0.21 g (35%), mp 64–67°С (ethyl acetate).
IR spectrum (thin film), ν, cm–1: 3386 (OH), 2156
Procedure 3. Sodium azide, 0.3 g (0.005 mol), was
added to a suspension of 0.5 g (0.0025 mol) of epoxide
3 in 10 mL of water. The reaction mixture was stirred
at 60°С until reaction completion and then extracted
with ether (4 × 15 mL). The ether extracts were
combined and dried over CaCl2. The ether was
distilled off, and the remaining product was
recrystallized from ethyl acetate. Yield 0.3 g (50%),
mp 56–64°С (ethyl acetate).
1
(N3). Н NMR spectrum (acetone-d6), δ, ppm (nJ, Hz):
1-Chloro-3(4-phenyl-1.2.3-triazol-1-yl)propan-2-
ol (6а). A solution of 1 g (0.0098 mol) of acetylene 5а
and 1.2 g (0.0098 mol) of azide 1 in 20 mL of toluene
was heated at 100–105°С for 14 h until the starting
acetylene was consumed completely (by TLC). The
solvent was removed on a rotary evaporator, and the
residue was recrystallized from ethyl acetate. Yield 1 g
(43 %), mp 115–117°С. IR spectrum (thin film), ν, cm–1:
2
3
2
4.87 d and 4.95 d (1Н' or 1Н'', J 13.6, J 7.6 and J
3
13.6, J 4.4, СН2-tetrazole); 3.81 d and 3.87 d (1Н' or
2
3
2
3
1Н'', J 4.8, J 4.0 and J 4.8, J 2.4, СН2–N3); 4.57 m
(1Н, СН); 5.02 s (1Н, ОН). 13C NMR spectrum
(acetone-d6), δ, ppm: 69.9 (СН); 54.6 (CH2–N3); 57.0
(СН2–tetrazole); 165.6 (tetrazole С); 131.1 (СipsoPh);
129.8 (СorthoPh); 127.3 (СmetaPh); 128.5 (СparaPh).
Found, %: C 48.72; H 4.96; N 40.71. C10H11N7O2.
Calculated, %: C 48.98; H 4.52; N 39.98.
1
3256 (OH), 3154 (triazole СН), 786 (C-Cl). Н NMR
spectrum (DMSO-d6), δ, ppm (nJ, Hz): 4.70 d and 4.58
d (1Н' or 1Н'', 2J 12.0, 3J 4.0 and 2J 12.0, 3J 8.0, СН2–
triazole, 1,4-isomer); 4.61 d and 4.56 d (1Н' or 1Н'', 2J
8.0, 3J 4.0 and 2J 8.0, 3J 4.0, СН2–triazole, 1.5-isomer);
2-Azido-3-(5-phenyltetrazol-2-yl)propan-1-ol (4b).
Procedure 1. Epoxide 3, 1 g (0.005 mol), was added in
portions to a solution of 1 g (0.025 mol) of NaN3 in
15 mL of water at 25°С. The initial pH of the mixture
was 9.68. The reaction mixture was stirred at 25°С,
after which it was extracted with ether (4 × 15 mL). The
ether was distilled off, and the remaining product was
recrystallized from ethyl acetate. Yield 0.9 g (75%),
mp 54–56°С (ethyl acetate). IR spectrum (thin film), ν,
cm–1: 3297 (OH), 2142 (N3). 1Н NMR spectrum
(acetone-d6), δ, ppm (nJ, Hz): 4.84 m (1Н' or 1Н'', СН2–
tetrazole); 3.52 d and 3.58 d (1Н' or 1Н'', 2J 4.8, 3J 4.0
2
3
2
3.71 d and 3.65 d (1Н' or 1Н'', J 12.0, J 8.0 and J
12.5, 3J 7.8, СН2–Сl, 1,4-isomer); 7.89 m (1Н,
СorthoНPh, 1.5-isomer); 7.41 m (1Н, СmetaНPh, 1.5-
isomer); 7.30 m (1Н, СparaНPh, 1.5-isomer); 7.71 m
(1Н, СorthoНPh, 1,4-isomer); 7.61 m (1Н, СmetaНPh, 1,4-
isomer); 7.50 m (1Н, СparaНPh, 1,4-isomer); 5.74 d
(1Н, 3J 5.6, ОН); 4.32 m (1Н, СН). 13C NMR
spectrum (DMSO-d6), δ, ppm: 123.5 (triazole СН);
146.2 (triazole С–Ph); 70.8 (СН); 47.1 (CH2–Cl); 54.1
(СН2–triazole); 132.1 (СipsoPh); 129.9 (СorthoPh); 127.4
(СmetaPh); 129.6 (СparaPh). Found, %: C 54.73; H 5.21;
N 17.96. C11H12ClN3O. Calculated, %: C 55.59; H
5.09; N 17.68.
2
3
and J 4.8, J 2.4, СН2OH); 4.63 m (1Н, СН); 5.51 s
(1Н, ОН). 13C NMR spectrum (acetone-d6), δ, ppm:
56.9 (СН); 63.4 (CH2ОН); 63.0 (СН2–tetrazole); 163.5
(tetrazole С); 130.9 (СipsoPh); 129.5 (СorthoPh); 127.1
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EPICHLOROHYDRIN AS A PRECURSOR OF FUNCTIONALLY SUBSTITUTED
191
1-(3-Chloro-2-hydroxypropyl)-1.2.3-triazole-4,5-
dicarboxylic acid (6b) was prepared in a similar way
from 2 g (0.017 mol) of acetylene 5b and 2.8 g
(0.021 mol) of azide 1 in 20 mL of ethanol at 50°С.
Yield 1.5 g (36 %), mp 65–67°С (ethanol). IR
spectrum (thin film), ν, cm–1: 3278 (OH), 1758
1-Azido-3-(5-phenyltetrazol-2-yl)-propan-2-ol
(8а). Procedure 1. To 1 g (0.007 mol) of 5-
phenyltetrazole in 15 mL of water, 0.4 g (0.011 mol) of
KOH was added. The mixture was stirred until
homogeneous, and 1.2
g
(0.01 mol) of
azidochlorohydrin 1 in 15 mL of toluene and a
catalytic amount of TEBAC were added. The reaction
mixture was stirred at 80°С for 10 h and then separated
into layers. The inorganic layer was extracted with
ether (4 × 15 mL). The ether extracts were combined with
the organic layer and dried over CaCl2. The solvents were
distilled off, and the remaining product was recrystal-
lized from ethyl acetate. Yield 1 g (58%), mp 58–60°С
(ethyl acetate). IR spectrum (thin film), ν, cm–1: 3257
1
(СООН), 780 (C–Cl). Н NMR spectrum (DMSO-d6),
δ, ppm (nJ, Hz): 5.03 d and 4.98 d (1Н' or 1Н'', 2J 16.0,
2
3
3J 4.0 and J 12.0, J 11.6, СН2–triazole); 3.76 m and
3.73 m (1Н' or 1Н''); 4.40 m (1Н, СН). 13C NMR
spectrum (DMSO-d6), δ, ppm: 165.8 and 158.4
(2СООН); 70.4 (СН); 47.1 (CH2–Cl); 57.6 (СН2–
triazole); 139.4 and 133.6 (triazole 2С). Found, %: C
33.04; H 2.98; N 16.31. C7H8ClN3O5. Calculated, %: C
33.68; H 3.23; N 16.83.
1
(OH), 2106 (N3). Н NMR spectrum (acetone-d6), δ,
ppm (nJ, Hz): 4.87 d and 4.95 d (1Н' or 1Н'', 2J 13.6, 3J
7.6 and 2J 13.6, 3J 4.4, СН2–tetrazole, N2-isomer); 4.50–
4.63 m (1Н' or 1Н'', СН2–tetrazole, N1-isomer); 3.81 d
and 3.87 d (1Н' or 1Н'', 2J 4.8, 3J 4.0 and 2J 4.8, 3J 2.4,
СН2–N3); 4.57 m (1Н, СН); 5.02 s (1Н, ОН). 13C
NMR spectrum (acetone-d6), δ, ppm: 69.9 (СН); 54.6
(CH2–N3); 57.0 (СН2–tetrazole); 165.6 (tetrazole С);
131.1 (СipsoPh); 129.8 (СorthoPh); 127.3 (СmetaPh);
128.5 (СparaPh). Found, %: C 48.12; H 5.06; N 40.52.
C10H11N7O2. Calculated, %: C 48.98; H 4.52; N 39.98.
[1-(3-Chloro-2-hydroxypropyl)-5-phenyl-1,2,3-
triazol-4-yl](phenyl)methanone (6c) was prepared in
a similar way from 2 g (0.009 mol) of acetylene 5c and
1.7 g (0.012 mol) of azide 1 in 20 mL of ethanol at
50°С. Yield 2.58 g (89%), mp 174–176°С (ethanol). IR
spectrum (thin film), ν, cm–1: 3302 (OH), 1684 (СО),
1
769 (C–Cl). Н NMR spectrum (DMSO-d6), δ, ppm
2
(nJ, Hz): 4.58 d and 4.39 d (1Н' or 1Н'', J 13.0, 3J 8.0
2
3
and J 13.0, J 7.6, СН2–triazole); 3.74 d and 3.66 d
2
3
2
3
(1Н' or 1Н'', J 13.0, J 8.0 and J 13.0, J 8.0, СН2–
Cl); 3.91 m (1Н, СН); 5.00 br.s (1Н, ОН) 7.4–8.1 m
(10Н, Ph). 13C NMR spectrum (DMSO-d6), δ, ppm:
69.4 (СН); 47.1 (CH2–Cl); 54.8 (СН2–triazole); 134.9
and 129.6 (triazole 2С). Found, %: C 32.85; H 4.51; N
12.79. C18H16ClN3O2. Calculated, %: C 63.25; H 4.72;
N 12.29.
1-Azido-3-(5-{4-[2-(3-azido-2-hydroxypropyl)-
tetrazol-5-yl]phenyl}tetrazol-2-yl)propan-2-ol (8b)
was prepared in a similar way from 1 g (0.0046 mol)
of bistetrazole 7b, 1.34 g (0.011 mol) of azidochloro-
hydrin 1, 0.44 g (0.011 mol) of KOH, and a catalytic
amount of TEBAC. Yield 1.2 g (63%), mp 95–98°С
(ethyl acetate). IR spectrum (thin film), ν, cm–1: 3262
[1-(3-Chloro-2-hydroxypropyl)-1.2.3-triazol-4-
yl]methylbenzylcarboxylate (6d) was prepared in a
similar way from 0.9 g (0.005 mol) of acetylene 5d
and 1 g (0.007 mol) of azide 1. Yield 0.9 g (67%), mp
127°С. IR spectrum (thin film), ν, cm–1: 3235 (OH),
1734 (СОО), 778 (C–Cl). 1Н NMR spectrum (DMSO-
1
(OH), 2117 (N3). Н NMR spectrum (acetone-d6), δ,
ppm (nJ, Hz): 4.86–4.89 m (2Н, СН2–tetrazole, N2N2-
isomer); 4.68–4.70 m (2Н, СН2–tetrazole, N1N2-
2
3
isomer); 3.81 d and 3.87 d (1Н' or 1Н'', J 4.8, J 4.0
2
3
and J 4.8, J 2.4, СН2–N3); 4.82 m (1Н, СН); 5.16 s
(1Н, ОН); 8.3 s (4Н, Ph, N2N2-isomer), 8.12 d (2Н, 3J
7.8, 2СНPh, N2N1-isomer); 8.33 d (2Н, 3J 7.8, 2СНPh,
N2N1-isomer). 13C NMR spectrum (acetone-d6), δ, ppm:
72.3 (СН); 54.0 (CH2–N3); 55.1 (СН2–tetrazole); 162.0
(tetrazole С). Found, %: C 39.26; H 2.53; N 46.11.
C14H16N14O2. Calculated, %: C 40.78; H 3.91; N
47.55.
2
d6), δ, ppm (nJ, Hz): 4.56 d and 4.95 d (1Н' or 1Н'', J
3
2
3
13.6, J 3.6 and J 13.6, J 7.6, СН2–triazole); 3.62 d
2
3
2
3
and 3.59 d (1Н' or 1Н'', J 11.0, J 4.8 and J 11.0, J
5.2, СН2–Cl); 4.13 m (1Н, СН); 5.80 d (1Н, J 5.6,
3
ОН); 5.41 s (2Н, СН2–О); 7.95 m (1Н, СorthoНPh);
7.51 m (1Н, СmetaНPh); 7.63 m (1Н, СparaНPh). 13C
NMR spectrum (DMSO-d6), δ, ppm: 69.1 (СН); 46.5
(CH2–Cl); 57.8 (СН2–triazole); 141.6 (triazole С–
СН2); 125.1 (triazole СН); 52.6 (CH2–О), 165.4
(СОО); 131.9 (СipsoPh); 132.5 (СorthoPh); 128.3
(СmetaPh); 134.1 (СparaPh). Found, %: C 52.37; H 5.06;
N 13.92. C13H14ClN3O3. Calculated, %: C 52.80; H
4.77; N 14.21.
1-Azido-3-(5-phenyltetrazol-2-yl)propan-2-ol
(8а). Procedure 2. To 1 g (0.0068 mol) of 5-phenyl-
tetrazole in 30 mL of DMF, 0.55 g (0.004 mol) of
K2СО3 was added. The mixture was heated to 50°С,
0.8 g (0.0068 mol) of azidochlorohydrin 1 was added
with stirring. The reaction mixture was stirred at 130°С
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 2 2019

GOLOBOKOVA et al.
192
2. Vyvyan, J.R., Meyer, J.A., and Meyer, K.D., J. Org.
Chem., 2003, vol. 68, p. 9144. doi 10.1021/jo035112y
3. Wang, Zh., Cui, Y-T., Xu, Zh-B., and Qu, J.,
J. Org. Chem., 2008, vol. 73, p. 2270. doi 10.1021/
jo702401t
and then cooled and filtered. The filtrate was poured
into cold water, and the precipitate that formed was
filtered off, and recrystallized from ethyl acetate. Yield
1.4 g (87%), mp 59–60°С (ethyl acetate).
1-Azido-3-(5-{4-[2-(3-azido-2-hydroxypropyl)tet-
razol-5-yl]phenyl}tetrazol-2-yl)propan-2-ol (8b) was
prepared in a similar way from 1 g (0.0046 mol) of
bistetrazole 7b, 1.1 g (0.0092 mol) of azidochloro-
hydrin 1, and 1.9 g (0.01 mol) of K2СО3. Yield 0.9 g
(23%), mp 110°С (ethyl acetate).
4. Fringuelli, F., Pizzo, F., Tortoioli, S., and Vaccaro, L.,
J. Org. Chem., 2003, vol. 68, p. 8248. doi 10.1021/
jo0348266
5. Golobokova, T.V., Projdakova, A.G., Vereshchagin, L.I.,
and Kizhnyaev, V.N., Russ. J. Org. Chem., 2015, vol. 51,
p. 1308. doi 10.1134/S1070428015090171
6. Alonso, G., Garcia-Lopez, M.T., Garcia-Munoz, G.,
Madronero, R., and Rico, M., J. Heterocycl. Chem.,
1970, vol. 7, p. 1269. doi 10.1002/jhet.5570070606
7. Verhozina, O.N., Kizhnyaev, V.N., Vereshchagin, L.I.,
Rohin, A.V., and Smirnov, A.I., Russ. J. Org. Chem.,
2003, vol. 39, p. 1792. doi 10.1023/
B:RUJO.0000019746.10504.f3
FUNDING
The work was funded by the Ministry of Education
and Science of the Russian Federation in the
framework of the basic part of the State order for
scientific research (project no. 4.5183.2017/8.9).
8. Koldobskii, G.I., Ostrovskii, V.A., and Poplavskii, V.S.,
Chem. Heterocycl. Comp., 1981, vol. 17, p. 965. doi
10.1007/BF00503523
CONFLICT OF INTEREST
The authors declare no conflict of interest.
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 2 2019