Reaction of 2-(ethoxymethylidene)-3-oxo carboxylic acid esters with tetrazol-5-amine

Article abstract of DOI:10.1134/S1070428015070179

2-(Ethoxymethylidene)-3-oxo carboxylic acid esters reacted with tetrazol-5-amine to give ethyl 4-alkyl-2-azidopyrimidine-5-carboxylates capable of undergoing subsequent nucleophilic substitution of hydrogen on C⁶ or azido group. The reaction of ethyl 2-benzoyl-3-ethoxyprop-2-enoate with tetrazol-5-amine was accompanied by partial decomposition to afford a mixture of ethyl 3-oxo-3-phenylpropanoate and ethyl 7-(1-ethoxy-1,3-dioxo-3-phenylpropan-2-yl)-5-phenyl-4,7-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate. Ethyl 7-hydroxytetrazolo[1,5-a]pyrimidine-6-carboxylate was formed as a result of cyclization of diethyl 2-(ethoxymethylidene)propanedioate with tetrazol-5-amine.

Full text of DOI:10.1134/S1070428015070179

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2015, Vol. 51, No. 7, pp. 992–1002. © Pleiades Publishing, Ltd., 2015.
Original Russian Text © M.V. Goryaeva, Ya.V. Burgart, M.A. Ezhikova, M.I. Kodess, V.I. Saloutin, 2015, published in Zhurnal Organicheskoi Khimii, 2015,
Vol. 51, No. 7, pp. 1010–1020.
Reaction of 2-(Ethoxymethylidene)-3-oxo Carboxylic Acid Esters
with Tetrazol-5-amine
M. V. Goryaeva, Ya. V. Burgart, M. A. Ezhikova, M. I. Kodess, and V. I. Saloutin
Postovskii Institute of Organic Synthesis, Ural Branch, Russian Academy of Sciences,
ul. S. Kovalevskoi/Akademicheskaya 22/20, Yekaterinburg, 620990 Russia
e-mail: pmv@ios.uran.ru
Received March 28, 2015
Abstract—2-(Ethoxymethylidene)-3-oxo carboxylic acid esters reacted with tetrazol-5-amine to give ethyl
4-alkyl-2-azidopyrimidine-5-carboxylates capable of undergoing subsequent nucleophilic substitution of hydro-
gen on C6 or azido group. The reaction of ethyl 2-benzoyl-3-ethoxyprop-2-enoate with tetrazol-5-amine was
accompanied by partial decomposition to afford a mixture of ethyl 3-oxo-3-phenylpropanoate and ethyl
7-(1-ethoxy-1,3-dioxo-3-phenylpropan-2-yl)-5-phenyl-4,7-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate.
Ethyl 7-hydroxytetrazolo[1,5-a]pyrimidine-6-carboxylate was formed as a result of cyclization of diethyl
2-(ethoxymethylidene)propanedioate with tetrazol-5-amine.
DOI: 10.1134/S1070428015070179
2-(Ethoxymethylidene)-3-oxo carboxylic acid
esters are generally recognized as building blocks for
the synthesis of various open-chain and heterocyclic
compounds, including those used in medical practice
[1]. 2-(Ethoxymethylidene)-3-oxo carboxylic acid
esters can be converted into pyrimidine and azolo-
pyrimidine systems structurally related to nucleobases
and therefore exhibiting a broad spectrum of biological
activity [2–5].
with tetrazol-5-amines. However, such reactions could
give rise to functionalized tetrazolo[1,5-a]pyrimidines
as promising candidates for biological screening; in
particular, compounds possessing antitumor [13], anti-
viral [14], antimicrobial, and antioxidant activity [15]
have been found among tetrazolo[1,5-a]pyrimidine
derivatives. Known tetrazolo[1,5-a]pyrimidines were
prepared by cyclization of tetrazol-5-amine with
1,3-dicarbonyl compounds or their derivatives [16].
A convenient synthetic approach to the tetrazolo-
[1,5-a]pyrimidine skeleton is based on the three-com-
ponent Biginelli condensation of 3-oxo esters with al-
dehydes and tetrazol-5-amine [17, 18] or its two-com-
ponent modifications utilizing 2-benzylidene-3-oxo
esters and tetrazol-5-amine [19, 20].
Reactions of nonfluorinated 2-(ethoxymethylidene)-
3-oxo carboxylic acid esters with aminoazoles were
reported to produce either open-chain 2-[(azolyl-
amino)methylidene]-3-oxo derivatives [6] or imme-
diately azolo[1,5-a]pyrimidines [7–9], depending on
the reactant structure and conditions. Unlike nonfluori-
nated analogs, polyfluorinated 2-(ethoxymethylidene)-
3-oxo carboxylates react with aminoazoles to afford
stable dihydroazolo[1,5-a]pyrimidines with a geminal
amino hydroxy fragment neighboring to the poly-
fluoroalkyl group [10, 11]. Due to specific features of
3-amino-1H-pyrazol-5-ol, reactions of that binucleo-
phile with 2-(ethoxymethylidene)-3-oxo-3-polyfluoro-
alkylpropanoates lead to the formation of dihydro-
pyrazolo[1,5-a]pyrimidines and pyrazolo[3,4-b]-
pyridines [12].
We anticipated that the use of tetrazol-5-amine as
binucleophile in reactions with 2-(ethoxymethylidene)-
3-oxo carboxylates could change the traditional cy-
clization pathways due to its low basicity (pKb 12.18
[21]) relative to other aminoazoles and the ability to
undergo azido–tetrazole isomerism [22, 23].
We examined the reactions of 2-(ethoxymethyli-
dene)-3-oxo carboxylates 1a–1d and diethyl
2-(ethoxymethylidene)propanedioate (1e) with tetra-
zol-5-amine. Heating of 1a–1c with tetrazol-5-amine
in boiling ethanol resulted in the formation of an insep-
arable mixture of products, whereas the reaction in
We have found no published data on reactions of
2-(ethoxymethylidene)-3-oxo carboxylic acid esters
992

REACTION OF 2-(ETHOXYMETHYLIDENE)-3-OXO CARBOXYLIC ACID ESTERS
993
Scheme 1.
O
O
R
R
OH
N
O
O
N
N
N
N
i
H
EtO
N
O
+
OEt
N
N
R
N
NH2
–EtOH
N
N
H
N
NH
OEt
OEt
1a–1c
N
H
A
B
O
R
O
R
N
EtO
N
EtO
N
–H2O
N
N
N
N
N3
C
2a–2c
EtO
O
EtO
O
EtO
N
O
EtO
O
N
N
N
Me
Me
iii
ii
1c
+
2c
N
NH2
N
N
N
N
NH
N
HN
H
N
N
N3
N3
N3
N
3
3A
R = CF3 (a), H(CF2)2 (b), Me (c); i: 2,2,2-trifluoroethanol, reflux, 32–38 h; ii: 22°C, 12 days; iii: EtOH, 22°C, 9 days.
1,4-dioxane, even on prolonged heating (32 h under
reflux) was characterized by incomplete conversion
and low selectivity. However, by heating the reactants
in boiling 2,2,2-trifluoroethanol we obtained 2-azido-
pyrimidines 2a–2c instead of expected tetrazolyl-
aminomethylidene derivatives A or tetrazolo[1,5-a]-
pyrimidines like B and C (Scheme 1).
thesized from ester 1c and tetrazol-5-amine in ethanol
at room temperature (Scheme 1). 2-Azidopyrimidine
2c was detected by TLC in the reaction mixture as
intermediate.
1
According to the H NMR and IR data, five struc-
tures 3A–3E are possible for compound 3 due to
azido–tetrazole isomerism without taking into account
annular amino–imine transformations involving the
Presumably, initial condensation of 1a–1c with
tetrazol-5-amine yields intermediate tetrazolylamino-
methylidene derivative A which undergo intramolec-
ular cyclization via regioselective addition of the endo-
cyclic NH group to the ketone carbonyl carbon atom;
dihydrotetrazolo[1,5-a]pyrimidines B thus formed lose
water molecule, yielding tetrazolo[1,5-a]pyrimidines
C. Azido–tetrazole isomerization [24] of the latter
through opening of the tetrazole ring at the N1–N8
leads to 2-azidopyrimidines 2a–2c (Scheme 1).
The azide structure of 2a–2c follows from the pres-
ence of an absorption band at 2144–2146 cm–1 in the
IR spectra, which is typical of stretching vibrations of
azido group [25]. The NMR spectra of 2a–2c in
chloroform-d also indicated the presence of only one
azide isomer (6-H, δ 9.03–9.13 ppm; C2, δC 163.39–
163.89 ppm) [22].
13
NH group. On the basis of the C NMR spectra, in-
1
cluding two-dimensional H–13C HSQC and HMBC
experiments, compound 3 was assigned the structure of
ethyl 7-{[2-azido-5-(ethoxycarbonyl)pyrimidin-4-yl]-
methyl}-5-methyl-4,7-dihydrotetrazolo[1,5-a]pyrimi-
dine-6-carboxylate (3B). The C3a signal in the 13C
NMR spectrum of 3 was observed at δC 149.71 ppm,
which is typical of the fusion carbon atom in 4,7-di-
hydrotetrazolopyrimidines [20], and the C2′ atom in the
second heterocycle resonated in a weaker field, at
δC 163.41 ppm, as in the spectra of 2-azidopyrimidines
2a–2c. The difference in the chemical shifts of C3a and
C2′ is determined by different hybridizations of the
neighboring nitrogen atom. These data allowed us to
rule out bis-azido tautomer 3A.
Structure 3B is confirmed by the 2D HMBC cross
peaks between the NH proton (δ 10.7 ppm), on the one
hand, and 5-CH3 (δC 19.42 ppm), C6 (δC 97.77 ppm),
and C3a nuclei (δC 149.71 ppm) of the tetrazolopyrimi-
dine fragment, on the other, as well as between 6′-H
Unlike 4-polyfluoroalkyl-substituted pyrimidines
2a and 2b, 2-azido-4-methylpyrimidine 2c was un-
stable, and it transformed into compound 3 on storage
in air (without a solvent). Compound 3 was also syn-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 7 2015

GORYAEVA et al.
994
EtO
N
O
N
EtO
O
N
EtO
O
EtO
O
EtO
N
O
N
EtO
O
N
5'
6
Me
Me
Me
N
7
4'
6'
5
HN
1'N
N3' 8N
1 N
4NH
HN
3a
2'
2N
N
N3
N
N3
N3
N3
N3
3A
3B
3C
EtO
O
EtO
HN
O
N
EtO
N
O
N
EtO
HN
O
Me
Me
N
N
N
N
N
N
N
N3
N3
N
N
3D
3E
(δ 9.02 ppm) and C5' and C2′ (δC 120.17 and
163.41 ppm, respectively) of the azidopyrimidine frag-
ment. Nonequivalent protons in the methylene bridge
(δC 41.01 ppm) displayed long-range couplings with
carbon nuclei in both tetrazolopyrimidine (C7,
δC 55.28 ppm; C6, δC 97.77 ppm) and azidopyrimidine
fragments (C5′, δC 120.17 ppm; C4′, δC 169.09 ppm).
Correlations were also observed between 7-H and C4′,
C3a, and C5. The signals at δC 163.69 and 164.71 ppm
were assigned to the carbonyl carbon atoms on the
basis of HMBC cross peaks with the OCH2 protons.
Compound 3 can be formed as a result of nucleo-
philic addition of the methyl group of one molecule 2c
to the electrophilic C6H atom of the other molecule,
followed by azido–tetrazole isomerization of interme-
diate 3A (Scheme 1).
When the reactions of fluorinated esters 1a and 1b
with tetrazol-5-amine were carried out in boiling
1,4-dioxane in the presence of a catalytic amount of
sodium acetate, the products were ethyl 2-amino-4-
polyfluoroalkylpyrimidine-5-carboxylates 4a and 4b
(Scheme 2). The reaction with 1a was accompanied by
side formation of ethyl 2-(1H-tetrazol-5-ylamino)-4-
(trifluoromethyl)pyrimidine-5-carboxylate (5). Pre-
sumably, these reactions involve intermediate forma-
tion of 2-azidopyrimidines 2a and 2b which undergo
thermal decomposition with elimination of nitrogen to
give nitrenes [26], and the latter abstract hydrogen
from other substrates, e.g., tetrazol-5-amine, eventually
leading to 4a and 4b. Compound 4a and 4b were also
synthesized by cyclization of esters 1a and 1b with
guanidine carbonate involving the (ethoxymethyli-
dene)acyl fragment on heating in boiling 1,4-dioxane
in the presence of sodium acetate. Compound 4a is
active against herpes viruses (HSV-1); it was synthe-
sized previously by cyclization of ethyl 2-(dimethyl-
aminomethylidene)-4,4,4-trifluoro-3-oxobutanoate
with guanidine [27]. 2-(Tetrazolylamino)pyrimidine 5
is the product of nucleophilic substitution of the azido
group (which is a good nucleofuge) [28] in interme-
diate 2-azidopyrimidine 2a by aminotetrazole residue.
In fact, 2-(1H-tetrazol-5-ylamino)pyrimidine 5 was ob-
tained in a good yield by reaction of 2a with tetrazol-5-
amine (Scheme 2).
Enamine–imine tautomerism is possible for amino-
pyrimidine derivatives. However, compounds 4a, 4b,
Scheme 2.
O
R
O
R
O
CF3
i
N
1a, 1b
+
EtO
N
EtO
N
EtO
N
N
–HN3
–N2
N
N
N
N3
N
NH2
N
N
H
H
2a, 2b
4a, 4b
5
ii
iii
2a
1a, 1b
R = CF3 (a), H(CF2)2 (b); i: tetrazol-5-amine, NaOAc, 1,4-dioxane, ∆, 16–18 h; ii: guanidinium carbonate, NaOAc,
DMF, 80°C, 24–26 h; iii: tetrazol-5-amine, Et3N, 1,4-dioxane, ∆, 40 h.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 7 2015

REACTION OF 2-(ETHOXYMETHYLIDENE)-3-OXO CARBOXYLIC ACID ESTERS
995
N7
N4
and 5 in crystal and in solution exist as a single
C10
C9
N5
enamine tautomer. The IR spectra of 4a and 4b con-
tained a doublet absorption band at 3372–3379/3336–
3337 cm–1 due to symmetric and antisymmetric
stretching vibrations of the NH2 group, and a two-
proton singlet at δ 7.95–8.04 ppm (NH2) was observed
O1
O1D C8 C3
O2D
C4
N2
C1
C10D
C9D
C5
N3
N6
C2
1
in their H NMR spectra. The structure of 5 was con-
O2
F2
N1
firmed by X-ray analysis (see figure).
C7
The reaction of 1a with tetrazol-5-amine in the
presence of triethylamine in boiling ethanol has
demonstrated once more the importance of the condi-
tions. In this case, only a small amount of 2a was
formed (8%), while the major products were com-
pounds 6 and 7 resulting from acid decomposition
(Scheme 3). Ester 6 was isolated in the pure state, and
trifluoroacetamide 7 was detected in the reaction mix-
ture by GC/MS (m/z 181 [M]+). Presumably, 5-amino-
tetrazolate anion generated by the action of base (tri-
ethylamine) reacts with 1a both at the ethoxymethyli-
dene group and ketone carbonyl group to give unstable
intermediate D which decomposes into 6 and 7.
F1
F3
Structure of the molecule of ethyl 2-(1H-tetrazol-5-ylamino)-
4-(trifluoromethyl)pyrimidine-5-carboxylate (5) according to
the X-ray diffraction data.
methylidene-substituted ester 9, and tetrazolopyrimi-
dine 10 (Scheme 4).
Ethyl 2-benzoyl-3-(1H-tetrazol-5-ylamino)prop-2-
enoate (9) exists as a mixture of Z and E isomers
stabilized by intramolecular hydrogen bond, as report-
ed previously for 2-R-aminomethylidene-3-oxo esters
[31]. The structure of 10 was determined on the basis
of the 1H and 13C NMR and 2D 1H–13C HSQC/HMBC
spectra (CDCl3). The 1H NMR data showed that mole-
cule 10 contains two ethoxycarbonyl groups, two
Ethyl 2-benzoyl-3-ethoxyprop-2-enoate (1d) react-
ed with tetrazol-5-amine in boiling ethanol to produce
a complex mixture of products. By column chromatog-
raphy we isolated only ethyl benzoylacetate (8) which
was likely to be formed as a result of decomposition of
initial ester 1d. The transformation of 2-(alkoxy-
methylidene)-3-oxo esters into the corresponding
3-oxo esters in reactions with nitrogen nucleophiles via
transfer of the alkoxymethylidene group to the amine
has been reported in [29, 30]. Heating of the same
reactants in 2,2,2-trifluoroethanol also led to the
formation of a mixture of products, from which we
succeeded in isolating ester 8, tetrazolylamino-
phenyl substituents, two sp3-carbon atoms (CH, 3J2′,7
=
2.8 Hz), and an NH group (δ 10.48 ppm). Carbon
atoms linked to hydrogens were unambiguously as-
signed using 2D HSQC experiment. The most informa-
tive cross peaks in the 2D HMBC spectrum were as
follows: 2′-H was coupled with C1′, C3′, C6, and C7;
7-H was coupled with C5, C6, C9, and C1′; and NH was
coupled with C6, C3a, and Ci. The carbonyl carbon
signals were identified by long-range couplings with
Scheme 3.
2a
–H2O
F3C
H
N
N
O
N
F3C
OH
N
N
N
i
H
NH
H
N
N
O
1a
N
H
N
N
H
–EtOH
N
O
N
OEt
N
EtO
D
H
H
N
H
N
O
CF3
N
N
+
N
N
N
OEt
NH
O
N
N
6
7
i: Tetrazol-5-amine, EtOH, Et3N, ∆.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 7 2015

GORYAEVA et al.
996
Scheme 4.
H
N
4
N3
N2
N
Ph
N
OEt
5
3a
O
O
O
O
N
i
6
+
+
9
N
N
N
O
Ph
OEt
Ph
OEt
N
H
8
EtOC(O)
H
7
1
2'
1'
3'
Ph
O
EtO
EtOC(O)
C(O)Ph
1d
8
9
10
Ph
Ph
EtOC(O)
EtOC(O)
EtOC(O)
N
8
N
N
9
10
N
–H2O
N
N
N
H
N3
C(O)Ph
E
F
i: Tetrazol-5-amine, 2,2,2-trifluoroethanol, ∆, 48 h.
the OCH2 (C9, C1′) and o-H protons (C3′). Compound
10 was isolated as a single diastereoisomer, but relative
configuration of its chiral centers was not determined
dine-6-carboxylate (12) (Scheme 5). The optimal con-
ditions for the formation of 12 were prolonged heating
in boiling ethanol in the presence of triethylamine. If
no triethylamine was added, the transformation of 1e
into 11 was not complete even after refluxing in
ethanol for 48 h. Compound 11 underwent cyclization
into 12 on prolonged heating in the absence of a base.
Presumably, heterocycle 10 is formed through inter-
mediate tetrazolopyrimidine E (Scheme 5). The mass
spectrum of amino derivative 9 (m/z 269 [M ‒ H2O]+)
suggests the possibility for the formation of hetero-
cyclic structure E which can take up ester 8 molecule
at the CH electrophilic center. The reaction is accom-
panied by tetrazole rearrangement through interme-
diate 2-azidopyrimidine F whose cyclization yields
fused heterocycle 10. The tetrazole structure of 10 is
stabilized due to increased electron density on the N8
fusion atom in the partly hydrogenated pyrimidine
fragment. The same also applies to the tetrazolopyrimi-
dine moiety of 3.
Compound 12 is potentially tautomeric: keto–enol,
lactim–lactam, and azido–tetrazole transformations are
possible, so that hydroxy tautomer 12A, oxo form 12B,
azide structures 12E–12G, and/or regioisomeric tetra-
zolo[1,5-a]pyrimidines 12C and 12D (resulting from
the tetrazole rearrangement of 12A) may be assumed.
The structure of 12 was determined on the basis of the
1
1
IR and H and 13C NMR spectra and 2D H–13C and
2D H–15N HMBC experiments. The IR spectrum of
1
As expected, the reaction of diethyl 2-(ethoxy-
methylidene)propanedioate (1e) with tetrazol-5-amine
afforded 2-(1H-tetrazol-5-ylaminomethylidene)pro-
panedioate (11) which underwent cyclization during
the process to ethyl 7-hydroxytetrazolo[1,5-a]pyrimi-
12 lacked absorption in the region 2100–2200 cm–1,
which ruled out azido tautomers 12E–12G in crystal.
The presence of only one absorption band at 1715 cm–1
is rather consistent with the structures of enol tauto-
mers 12A and 12C having one ester carbonyl group.
Scheme 5.
ii, 36 h
N
O
O
OH
N
N
OEt
N
i, 12 h
EtOC(O)
N
N
+
EtO
EtO
OEt
N
N
N
O
H
N
H
EtO
11
O
1e
12
i, 48 h
i: Tetrazol-5-amine, Et3N, EtOH, ∆; ii: EtOH, ∆.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 7 2015

REACTION OF 2-(ETHOXYMETHYLIDENE)-3-OXO CARBOXYLIC ACID ESTERS
997
O
OH
7
H
HO
N
N1
N2
N
N
O
N
8
N
EtOC(O)
EtOC(O)
6
N
N
N
N
N
N
N
N
N
N
4
N
5
EtOC(O)
N3
3a
EtOC(O)
N
H
12A
12B
12C
12D
OH
N
O
N
O
EtOC(O)
EtOC(O)
EtOC(O)
NH
N3
N
N
N3
N
H
N3
12E
12F
12G
The sets of signals observed in the 1H and 13C NMR
spectra of 12 in DMSO-d6 also corresponded to
a single tetrazole tautomer 12A or 12C. The two
downfield signals of C7 and C3a (δC 153.48 and
structure 12C, allowed us to exclude the latter and
finally choose regioisomer 12A.
Despite structural similarity, heterocycles 2a–
2c and 12 are differently prone to azido–tetrazole
isomerism. Electron-withdrawing substituents in the
heterocycle favor opening of the fused tetrazole ring
due to reduced electron density on the fusion nitrogen
atom [24]. Obviously, the presence of an ethoxycar-
bonyl group on C6 and of a polyfluoroalkyl substituent
on C7 in molecules 2a and 2b should considerably
destabilize the fused tetrazole ring, so that the tetra-
zole–azide equilibrium should be displaced almost
completely toward the azido isomer. On the other
hand, compound 2c with an electron-donating methyl
group on C7 also exists solely as the azido tautomer, in
contrast to tetrazolopyrimidine 12 having a hydroxy
group in the same position.
13
158.63 ppm) in the C NMR spectrum were indistin-
guishable in the HMBC spectrum since both these dis-
played couplings with 5-H through three bonds (3JCH).
However, the 3JCH value for the C3a fusion atom should
be larger than that for C7 [32, 33]. By measuring these
constants in the proton-coupled 13C NMR spectrum
3
(3JC3a
= 16.6, JC7–5-H = 7.6 Hz) we unambiguously
–5-H
assigned the signal at δC 158.63 ppm to C3a.
The structure of 12 was finally proved by a series
1
of 2D H–15N HMBC experiments with variation of
the pulse delay. The spectrum revealed correlations of
5-H (δ 8.7 ppm) with three 15N nuclei (δN 210.6, 247.4,
306.3 ppm), which were assigned to N4, N8, and N3,
respectively, taking into account published data
[22, 34]. The absence of a correlation between 5-H and
N8 (δN 350–400 ppm), which should be observed for
The preference of the azide structure of 2c, as well
as of analogs 2a and 2b, may be rationalized assuming
formation of unstable zwitterionic structure T′ with the
Scheme 6.
O
R
O–
R
O–
R
N
N
N
N
EtO
N
EtO
N
EtO
N
N
R = AlkF, Me
N
N
N
N
N
N
N
T
T'
Az
O
R
O
R
EtO
N
EtO
N
N
N
N
N
N
N
N
N
Az'
Az"
H
O
OH
O
O
N
N
N
EtO
N
EtO
N
N
R = OH
N
N
N
N
T
T"
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 7 2015

GORYAEVA et al.
998
positively charged fusion nitrogen atom (Scheme 6)
and negative charge localized on the ester carbonyl
oxygen atom. In this case, the electron density on N8 is
considerably reduced despite electron-donating effect
of the neighboring methyl group. Opening of the
tetrazole ring in T′ leads to thermodynamically more
stable azide tautomer which can be represented by
a number of resonance structures (Az–Az″). Structure
T′ for compound 12 is hardly probable due to keto–
enol tautomerism (tautomers T and T″; Scheme 6).
and tetrazol-5-amine monohydrate (Sigma–Aldrich)
were commercial products.
2-Azidopyrimidines 2a–2c (general procedure).
A mixture of 3 mmol of ester 1a–1c and 0.31 g
(3 mmol) of tetrazol-5-amine in 20 mL of 2,2,2-tri-
fluoroethanol was heated for 32–38 h under reflux.
When the reaction was complete (TLC), the mixture
was evaporated to dryness under reduced pressure, and
the residue was purified by column chromatography
using chloroform as eluent.
Thus, the reactions of 2-(ethoxymethylidene)-3-oxo
carboxylates 1a–1d with tetrazol-5-amine differ from
known cyclizations with other aminoazoles [7–12];
these reactions involve formation of tetrazolopyrimi-
dines only as intermediates due to facile isomerization
of the tetrazole ring to azido group. 2-Azidopyrimi-
dines thus obtained are promising reagents for the
synthesis of biologically active pyrimidine derivatives
by cross coupling at the CH electrophilic center and/or
nucleophilic substitution of the azido group.
Ethyl 2-azido-4-(trifluoromethyl)pyrimidine-5-
carboxylate (2a). Yield 0.54 g (69%), yellow oily
material. IR spectrum (ATR), ν, cm–1: 2988 (C–H),
2144 (N3), 1731 (C=O), 1581, 1551 (C=C–C=N),
1
1195–1084 (C–F). H NMR spectrum (500 MHz,
CDCl3), δ, ppm: 1.41 t (3H, CH3, J = 7.1 Hz), 4.44 q
13
(2H, OCH2, J = 7.1 Hz), 9.13 s (1H, 6-H). C NMR
spectrum (126 MHz, CDCl3), δC, ppm: 13.81 (CH3),
1
62.90 (OCH2), 119.57 q (CF3, JCF = 276.6 Hz),
3
2
119.67 q (C5, JCF = 0.9 Hz), 155.79 q (C4, JCF
=
37.8 Hz), 162.54 (C=O), 162.97 (C6), 163.89 q (C2,
4JCF = 1.2 Hz). 19F NMR spectrum (470 MHz, CDCl3):
δF 95.34 ppm, s (CF3). Mass spectrum, m/z (Irel, %):
261 (20) [M]+, 233 (37), 216 (33), 188 (22), 162 (17),
148 (6), 133 (10), 120 (17), 106 (11), 92 (34), 69
(81), 53 (28), 29 (100). Found, %: C 36.83; H 2.31;
N 26.81. C8H6F3N5O2. Calculated, %: C 36.79; H 2.32;
N 26.82.
EXPERIMENTAL
The diffuse reflectance infrared Fourier transform
(DRIFT) spectra were recorded on a Perkin Elmer
Spectrum One spectrometer, and the attenuated total
reflectance (ATR) spectra were measured on a Nicolet
6700 instrument in the range from 400 to 4000 cm–1.
The NMR spectra were obtained on Bruker DRX-400
and Bruker Avance-500 spectrometers using tetra-
Ethyl 2-azido-4-(1,1,2,2-tetrafluoroethyl)pyrimi-
dine-5-carboxylate (2b). Yield 0.53 g (60%), yellow
oily material. IR spectrum (ATR), ν, cm–1: 2989,
2940 (C–H), 2146 (N3), 1732 (C=O), 1581, 1547
13
methylsilane (1H, C) and C6F6 (19F) as reference. All
1
13
signals in the H and C NMR spectra were assigned
1
using two-dimensional H–13C HSQC and HMBC
1
(C=C–C=N), 1130–1102 (C–F). H NMR spectrum
techniques. The mass spectra of 2a–2c and 4b were
recorded on a Thermo Scientific Trace GC Ultra DSQ
II GC/MS instrument (TR-5ms column, 30 m×
0.25 mm×0.25 μm), and the mass spectra of 3, 5, and
9‒12 were obtained on a Shimadzu GCMS-QP2010
Ultra instrument. The elemental compositions were
determined using a Perkin Elmer PE 2400 Series II
analyzer. Silica gel Merck 60 (0.063–0.200 mm) was
used for column chromatography. The melting points
were measured in open capillaries on a Stuart SMP3
melting point apparatus.
(400 MHz, CDCl3), δ, ppm: 1.41 t (3H, CH3, J =
7.1 Hz), 4.44 q (2H, OCH2, J = 7.1 Hz), 6.61 t.t (1H,
HCF2, JHF = 52.9, 5.7 Hz), 9.03 s (1H, 6-H). 13C NMR
spectrum (126 MHz, CDCl3), δC, ppm: 13.89 (CH3),
63.02 (OCH2), 109.38 t.t (CF2H, JCF = 252.0, 31.3 Hz),
112.19 t.t (CF2, JCF = 255.1, 26.7 Hz), 121.07 (C5),
2
158.17 t (C4, JCF = 28.4 Hz), 162.17 (C6), 163.31
4
(C=O), 163.39 t (C2, JCF = 1.5 Hz). 19F NMR spec-
trum (375 MHz, CDCl3), δC, ppm: 23.76 d.m (2F,
CF2H, JFH = 52.9 Hz), 44.54 m (2F, CF2). Mass spec-
trum, m/z (Irel, %): 293 (20) [M]+, 265 (17), 248 (36),
220 (23), 209 (14), 171 (9), 142 (26), 120 (21), 101
(64), 92 (46), 53 (34), 51 (58), 29 (100). Found, %:
C 36.81; H 2.40; N 23.85. C9H7F4N5O2. Calculated, %:
C 36.87; H 2.41; N 23.89.
Ethyl 2-(ethoxymethylidene)-3-oxo-3-(polyfluoro-
alkyl)propanoates 1a and 1b [31], ethyl 2-(ethoxy-
methylidene)-3-oxobutanoate (1c) [35], and ethyl
2-benzoyl-3-ethoxyprop-2-enoate (1d) [36] were syn-
thesized according to known procedures. Diethyl
(ethoxymethylidene)propanedioate (1e) (Alfa Aesar)
Ethyl 2-azido-4-methylpyrimidine-5-carboxylate
(2c). Yield 0.29 g (46%), yellow oily material. IR spec-
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REACTION OF 2-(ETHOXYMETHYLIDENE)-3-OXO CARBOXYLIC ACID ESTERS
999
trum (ATR), ν, cm–1: 2984 (C–H), 2144 (N3), 1725
(C=O), 1576, 1544 (C=C–C=N). H NMR spectrum
washed with diethyl ether, and recrystallized from
ethanol. The filtrates were used to isolate compound 5.
1
(500 MHz, CDCl3), δ, ppm: 1.41 t (3H, CH3, J =
7.1 Hz), 2.80 s (Me), 4.40 q (2H, OCH2, J = 7.1 Hz),
9.03 s (1H, 6-H). 13C NMR spectrum (126 MHz,
CDCl3), δC, ppm: 14.16 (CH3), 24.42 (4-CH3), 61.48
(OCH2), 119.30 (C5), 161.31 (C6), 163.49 (C2), 164.21
(C=O), 171.87 (C4). Mass spectrum, m/z (Irel, %): 207
(53) [M]+, 162 (31), 134 (43), 109 (60), 67 (100),
53 (57), 43 (91), 29 (89). Found, %: C 46.34; H 4.22;
N 33.83. C8H9N5O2. Calculated, %: C 46.38; H 4.38;
N 33.80.
b. A mixture of 3 mmol of ester 1a and 1b, 0.27 g
(3 mmol) of guanidine carbonate, and 0.40 g (3 mmol)
of sodium acetate in 15 mL of DMF was stirred for
24–26 h at 80°C. When the reaction was complete
(TLC), the mixture was poured into 200 mL of cold
water, and the precipitate was filtered off and recrys-
tallized from ethanol.
Ethyl 2-amino-4-(trifluoromethyl)pyrimidine-5-
carboxylate (4a). Yield 0.27 g (38%) (a), 0.42 g
(60%) (b); yellow powder, mp 178–179°C; published
1
Ethyl 7-{[2-azido-5-(ethoxycarbonyl)pyrimidin-
4-yl]methyl}-5-methyl-4,7-dihydrotetrazolo[1,5-a]-
pyrimidine-6-carboxylate (3). a. A mixture of 0.56 g
(3 mmol) of compound 1c and 0.31 g (3 mmol) of
tetrazol-5-amine in 20 mL of ethanol was stirred for
9 days at room temperature. When the reaction was
complete (TLC), the mixture was evaporated to
dryness under reduced pressure, and the residue was
washed with diethyl ether and recrystallized from
hexane.
data [27]: mp 175–177°C. The H NMR spectrum of
4a was identical to that reported in [27].
Ethyl 2-amino-4-(1,1,2,2-tetrafluoroethyl)pyrim-
idine-5-carboxylate (4b). Yield 0.35 g (44%) (a),
0.55 g (68%) (b); yellow powder, mp 141–142°C. IR
spectrum (DRIFT), ν, cm–1: 3372, 3336, 3212 (NH,
NH2), 1716 (C=O), 1666, 1590, 1543 (C=C–C=N),
1
1179–1069 (C–F). H NMR spectrum (500 MHz,
CDCl3), δ, ppm: 1.39 t (3H, CH3, J = 7.2 Hz), 4.37 q
(2H, OCH2, J = 7.2 Hz), 5.80 br.s (2H, NH2), 6.68 t.t
(1H, HCF2, JHF = 53.4, 5.8 Hz), 8.83 s (1H, 6-H).
13C NMR spectrum (126 MHz, CDCl3), δC, ppm: 14.01
(CH3), 62.08 (OCH2), 109.71 t.t (CF2H, JCF = 251.6,
30.8 Hz), 112.52 t.t (CF2, JCF = 254.4, 26.1 Hz), 114.99
(C5), 158.24 t (C4, 2JCF = 26.9 Hz), 162.32 (C6), 162.80
(C2), 164.14 (C=O). 19F NMR spectrum (470 MHz,
CDCl3), δF, ppm: 23.46 d.m (2F, CF2H, JFH = 53.4 Hz),
43.43 m (2F, CF2). Mass spectrum, m/z (Irel, %): 267
(16) [M]+, 239 (13), 222 (100), 202 (11), 171 (11), 120
(10), 101 (4), 93 (7), 68 (7), 53 (6), 29 (5). Found, %:
C 40.52; H 3.41; N 15.75. C9H9F4N3O2. Calculated, %:
C 40.46; H 3.40; N 15.73.
b. Oily compound 2c, 0.30 g, 0.7 mmol, solidified
on storage in air for 12 days at room temperature. The
solid material was washed with diethyl ether and
recrystallized from hexane. Yield 0.60 g (48%) (a),
0.26 g (86%) (b); yellow powder, mp 145–146°C. IR
spectrum (DRIFT), ν, cm–1: 3325 (N–H), 2982 (C–H),
2137 (N3), 1705 (C=O), 1577, 1541 (C=C–C=N).
1H NMR spectrum (500 MHz, CDCl3), δ, ppm: 1.37 m
(6H, OCH2CH3), 2.55 s (3H, 5-Me), 3.47 d.d (1H,
CH2, J = 13.4, 3.9 Hz), 4.16 d.d (1H, CH2, J = 13.4,
7.0 Hz), 4.26 q (2H, OCH2, J = 7.2 Hz), 4.24–4.35 m
(2H, OCH′), 6.34 d.d (1H, 7-H, J = 7.0, 3.9 Hz),
2
13
9.02 s (1H, 6′-H), 10.72 s (1H, NH). C NMR spec-
Ethyl 2-(1H-tetrazol-5-ylamino)-4-(trifluoro-
methyl)pyrimidine-5-carboxylate (5). a. The filtrates
obtained after the isolation and purification of com-
pound 4a were combined and evaporated. The residue
was washed with diethyl ether and recrystallized from
ethanol.
trum (126 MHz, CDCl3), δC, ppm: 14.10 (CH3), 14.24
(CH3), 19.42 (5-CH3), 41.01 (CH2), 55.28 (C7), 60.73
(OCH2), 61.84 (OCH′ ), 97.77 (C6), 120.17 (C5′),
2
147.83 (C5), 149.71 (C3a), 161.79 (C6′), 163.41 (C2′),
163.69 and 164.71 (C=O), 169.09 (C4′). Mass spec-
trum, m/z (Irel, %): 207 (69) [M/2]+, 179 (3), 162 (27),
134 (48), 109 (53), 80 (45), 67 (73), 43 (100). Found,
%: C 46.35; H 4.39; N 33.76. C16H18N10O4. Calculated,
%: C 46.38; H 4.38; N 33.80.
b. A mixture of 0.13 g (0.5 mmol) of 2-azido-
pyrimidine 2a, 0.05 g (0.5 mmol) of tetrazol-5-amine,
and three drops of triethylamine in 15 mL of 1,4-di-
oxane was heated for 5 days under reflux. When the
reaction was complete (TLC), the mixture was poured
into 200 mL of cold water, and the precipitate was
filtered off and recrystallized from ethanol. Yield
0.14 g (15%) (a), 0.13 g (89%) (b); white powder,
mp 216–218°C. IR spectrum (DRIFT), ν, cm–1: 3252,
3170 (NH), 2967, 2931 (C–H), 1744 (C=O), 1629,
Compounds 4a and 4b (general procedure).
a. A mixture of 3 mmol of ester 1a or 1b, 0.31 g
(3 mmol) of tetrazol-5-amine, and 0.20 g (1.5 mmol)
of sodium acetate in 25 mL of 1,4-dioxane was heated
for 16–18 h under reflux. When the reaction was com-
plete (TLC), the mixture was poured into 100 mL of
cold water. The precipitate was filtered off, dried,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 7 2015

GORYAEVA et al.
1000
1
1583, 1551 (C=C–C=N), 1205–1142 (C–F). H NMR
spectrum (400 MHz, DMSO-d6), δ, ppm: 1.33 t (3H,
CH3, J = 7.1 Hz), 4.36 q (2H, OCH2, J = 7.1 Hz), 9.12
s (1H, 6-H), 12.50 br.s (1H, NH), 15.81 br.s (1H, 1′-H).
13C NMR spectrum (126 MHz, DMSO-d6), δC, ppm:
13.71 (CH3), 61.98 (OCH2), 115.89 (C5), 119.85 q
(CF3, 1JCF = 276.4 Hz), 150.78 br.s (C5′), 154.00 q (C4,
2JCF = 36.4 Hz), 158.36 (C2), 162.37 (C6), 162.53
CH3, J = 7.1 Hz), 4.09 q (2H, OCH2, J = 7.1 Hz),
5.53 d (1H, 2-H, J = 13.5 Hz), 7.78 d.d (1H, 3-H, J =
13.5, 11.0 Hz), 10.74 d (1H, NH, J = 11.0 Hz),
13
16.13 br.s (1H, NH). C NMR spectrum (126 MHz,
DMSO-d6), δC, ppm: 14.33 (CH3), 59.04 (OCH2),
96.45 (C2), 141.97 (C3), 156.11 br.s (C5′), 167.10
(C=O). Found, %: C 39.22; H 4.97; N 37.99.
C6H9N5O2. Calculated, %: C 39.34; H 4.95; N 38.22.
19
(C=O). F NMR spectrum (375 MHz, DMSO-d6): δF
Compounds 9 and 10. A mixture of 0.65 g
(3 mmol) of ethyl 2-benzoyl-3-ethoxyprop-2-enoate
(1d) and 0.31 g (3 mmol) of tetrazol-5-amine in 25 mL
of 2,2,2-trifluoroethanol was heated for 48 h under
reflux. When the reaction was complete (TLC), the
mixture was evaporated under reduced pressure, and
the residue was purified by column chromatography
using chloroform as eluent. The first fraction contained
ethyl 3-oxo-3-phenylpropanoate (8), and next fractions
contained compounds 9 and 10. The fraction contain-
ing ester 9 was evaporated under reduced pressure, and
the residue was washed with diethyl ether. The fraction
containing tetrazolopyrimidine 10 was evaporated to
dryness under reduced pressure, and the residue was
recrystallized from acetonitrile.
97.20 ppm, s (CF3). Mass spectrum, m/z (Irel, %): 303
(8) [M]+, 275 (3), 258 (16), 247 (22), 220 (100), 192
(34), 152 (22), 124 (18), 77 (22), 69 (14), 53 (14), 45
(8). Found, %: C 35.62; H 2.60; N 32.25. C9H8F3N7O2.
Calculated, %: C 35.65; H 2.66; N 32.34.
X-Ray diffraction data for compound 5. Single
crystals of 5 were grown by crystallization from
acetone–ethanol (2 :1). Monoclinic crystal system,
space group P21/c; C9H8F3N7O2; M 393.23; unit cell
parameters: a = 13.6445(10), b = 8.2009(16), c =
12.3719(17) Å; β = 116.625(11)°; V = 1237.6(3) Å3;
Z = 4; dcalc = 1.627 g/cm3; μ(MoKα) = 0.133 mm–1;
F(000) = 616. Total of 8453 reflection intensities were
measured on an Xcalibur 3 diffractometer at 295(2) K
(MoKα radiation, graphite monochromator, CCD detec-
tor, ω/2θ scanning); 2256 reflections were independent
(Rint = 0.0987), and 1940 reflections were character-
ized by Fo > 4σ(Fo). The structure was solved by the
direct method, followed by Fourier difference syn-
theses, using SHELXL-97 software package [37] and
was refined by the least-squares procedure in aniso-
tropic approximation for all non-hydrogen atoms using
SHELXL-97 [37]; final divergence factors R1 =
0.0596, wR2 = 0.1645; goodness of fit 1.004 [for
reflections with I > 2σ(I)]; number of variables 227.
The complete set of crystallographic data was depos-
ited to the Cambridge Crystallographic Data Centre
(entry no. CCDC 918900) and is available at http://
www.ccdc.cam.ac.uk/conts/retrieving.html.
Ethyl 2-benzoyl-3-(1H-tetrazol-5-ylamino)prop-
2-enoate (9). Yield 0.07 g (8%), white powder,
mp 122–124°C. IR spectrum (DRIFT), ν, cm–1: 3493,
3007 (N–H, O–H), 3056, 3031, 2980 (C–H), 1663
1
(C=O), 1612, 1584 (C=C). H NMR spectrum
(500 MHz, DMSO-d6), δ, ppm: E isomer (60%): 0.97 t
(3H, CH3, J = 7.1 Hz), 3.97 q (2H, OCH2, J = 7.1 Hz),
7.39–7.58 m (5H, Ph), 8.73 d (1H, 3-H, J = 13.6 Hz),
11.86 d (1H, NH, J = 13.6 Hz); Z isomer (40%): 0.92 t
(3H, CH3, J = 7.2 Hz), 4.03 q (2H, OCH2, J = 7.2 Hz),
7.39–7.58 m (1H, Ph), 8.41 d (1H, 3-H, J = 13.8 Hz),
10.67 d (1H, NH, J = 13.8 Hz). 13C NMR spectrum
(126 MHz, DMSO-d6), δC, ppm, E isomer: 13.78
(CH3), 59.37 (OCH2), 101.28 (C2), 127.16 (Co), 127.58
(Cm), 130.31 (Cp), 141.49 (Ci), 152.18 (C3), 159.25
(C5′), 166.59 and 195.22 (C=O); Z isomer: 13.63
(CH3), 59.36 (OCH2), 101.76 (C2), 127.86 (Co), 128.07
(Cm), 130.99 (Cp), 140.74 (Ci), 151.95 (C3), 159.44
(C5′), 166.87 and 192.37 (C=O). Mass spectrum, m/z
(Irel, %): 269 (7) [M ‒ H2O]+, 241 (1), 213 (2), 196 (2),
129 (6), 105 (62), 77 (24), 45 (100). Found, %:
C 54.30; H 4.55; N 24.40. C13H13N5O3. Calculated, %:
C 54.35; H 4.56; N 24.38.
Ethyl 3-(1H-tetrazol-5-ylamino)prop-2-enoate
(6). A mixture of 0.72 g (3 mmol) of ethyl 3-oxo-4,4,4-
trifluoro-2-(ethoxymethylidene)butanoate (1a), 0.31 g
(3 mmol) of tetrazol-5-amine, and three drops of
triethylamine in 25 mL of ethanol was heated for 4 h
under reflux. When the reaction was complete (TLC),
the mixture was evaporated to dryness under reduced
pressure, and the precipitate was washed with diethyl
ether and recrystallized from ethanol. Yield 0.24 g
(44%), white powder, mp 173–174°C. IR spectrum
(DRIFT), ν, cm–1: 3170, 3047 (N‒H), 3047, 2967
(C–H), 1692 (C=O), 1624, 1558 (C=C, C=N). 1H NMR
spectrum (400 MHz, DMSO-d6), δ, ppm: 1.21 t (3H,
Ethyl 7-(1-ethoxy-1,3-dioxo-3-phenylpropan-2-
yl)-5-phenyl-4,7-dihydrotetrazolo[1,5-a]pyrimidine-
6-carboxylate (10). Yield 0.18 g (26%), white powder,
mp 109–111°C. IR spectrum (DRIFT), ν, cm–1: 3202,
3151 (O–H), 3073, 3034, 2980 (C–H), 1747, 1674
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 7 2015

REACTION OF 2-(ETHOXYMETHYLIDENE)-3-OXO CARBOXYLIC ACID ESTERS
1001
1
(C=O), 1637, 1568 (C=C). H NMR spectrum
13.0 Hz), 11.01 d (1H, NH, J = 13.0 Hz). 13C NMR
spectrum (126 MHz, DMSO-d6), δC, ppm: 14.02 (CH3),
14.13 (CH3), 60.05 (OCH2), 60.34 (OCH2), 98.43 (C2),
148.70 (CH), 155.57 br.s (C5′), 164.02 and 166.05
(C=O). Mass spectrum, m/z (Irel, %): 255 (12) [M]+,
227 (8), 210 (21), 198 (76), 152 (100), 124 (62), 85
(13), 53 (86). Found, %: C 42.27; H 5.12; N 27.38.
C9H13N5O4. Calculated, %: C 42.35; H 5.13; N 27.44.
(500 MHz, CDCl3), δ, ppm: 0.88 t (3H, CH3, J =
7.2 Hz), 1.15 t (3H, CH′, J = 7.2 Hz), 3.97 d.q and
4.01 d.q (1H each, OCH2, J = 10.7, 7.2 Hz), 4.11 q
(2H, OCH′, J = 7.2 Hz), 5.28 d (1H, 2′-H, J = 2.8 Hz),
3
2
6.47 d (1H, 7-H, J = 2.8 Hz), 7.39 m (2H, o-H), 7.45–
7.53 m (3H, m-H, p-H), 7.55 m (2H, m′-H), 7.63 m
(1H, p′-H), 8.18 m (2H, o′-H), 10.48 s (1H, NH).
13C NMR spectrum (126 MHz, CDCl3), δC, ppm: 13.42
Ethyl 7-hydroxytetrazolo[1,5-a]pyrimidine-6-
carboxylate (12). Yield 0.19 g (30%) (a), 0.48 g
(76%) (b), 0.10 g (95%) (c); white powder, mp 236–
238°C. IR spectrum (DRIFT), ν, cm–1: 3419 (O–H),
(CH′), 13.89 (CH3), 55.74 (C7), 59.03 (C2′), 60.79
3
(OCH′ ), 61.69 (OCH2), 95.60 (C6), 128.05 (Co),
2
128.55 (Cm), 128.98 (Co′, Cm′), 130.40 (Cp), 133.73
(Cp′), 134.53 (Ci), 135.62 (Cm′), 149.74 (C3a), 150.39
(C5), 165.66 (C=O), 167.53 (C1′), 192.91 (C3′). Mass
spectrum, m/z (Irel, %): 269 (10) [M ‒ 192]+, 241 (1),
213 (2), 192 (8) [PhC(O)CH2CO2Et]+, 129 (4), 105
(100), 77 (30). Found, %: C 62.18; H 5.00; N 15.11.
C24H23N5O5. Calculated, %: C 62.46; H 5.02; N 15.18.
1
1715 (C=O), 1633, 1534 (C=C–C=N). H NMR spec-
trum (500 MHz, DMSO-d6), δ, ppm: 1.28 t (3H, CH3,
J = 7.1 Hz), 3.36 s (OH, H2Osolv), 4.21 q (2H, OCH2,
J = 7.1 Hz), 8.71 s (1H, 5-H). 13C NMR spectrum
(126 MHz, DMSO-d6), δC, ppm: 14.39 q.t (CH3, J =
126.6, 2.6 Hz), 59.14 t.q (OCH2, J = 147.1, 4.5 Hz),
3
98.15 d (C6, J = 6.2 Hz), 153.48 d (C7, JC7–5-H
=
Compounds 11 and 12. a. A mixture of 0.65 g
(3 mmol) of diethyl 2-(ethoxymethylidene)propanedi-
oate (1e), 0.31 g (3 mmol) of tetrazol-5-amine, and
three drops of triethylamine in 25 mL of ethanol was
heated for 12 h under reflux. When the reaction was
complete (TLC), the mixture was evaporated to dry-
ness under reduced pressure, the residue was ground
with chloroform, and the precipitate of 11 was filtered
off and recrystallized from ethanol. The filtrate was
evaporated, and the residue (compound 12) was recrys-
tallized from acetonitrile.
7.6 Hz), 158.63 d (C3a, JC3a–5-H = 16.6 Hz), 160.08 d
(C5, J = 177.6 Hz), 165.39 q (C=O, J = 3.2 Hz). Mass
spectrum, m/z (Irel, %): 209 (9) [M]+, 192 (30), 165
(40), 137 (70), 124 (28), 109 (36), 95 (22), 81 (28), 69
(46), 53 (100), 44 (38), 43 (33). Found, %: C 39.99;
H 3.39; N 33.30. C7H7N5O3. Calculated, %: C 40.20;
H 3.37; N 33.48.
3
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 13-03-00617), by the Program of the Ural Branch,
Russian Academy of Sciences (project no. 15-21-3-9),
and by the Program for State Support of Leading
Scientific Schools (project no. 3656.2014.3).
b. A mixture of 0.65 g (3 mmol) of diethyl
2-(ethoxymethylidene)propanedioate (1e), 0.31 g
(3 mmol) of tetrazol-5-amine, and three drops of tri-
ethylamine in 25 mL of ethanol was heated for 48 h
under reflux. When the reaction was complete (TLC),
the mixture was evaporated to dryness under reduced
pressure, and the residue was recrystallized from
ethanol to obtain compound 12.
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