Synthesis of Alkyl 5-aryl-7-methyl-1,5-dihydrotetrazolo-[1,5-a]pyrimidine- 6-carboxylates

Article abstract of DOI:10.1134/S1070428010050180

Alkyl 5-aryl-7-methyl-1,5-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylates were obtained by melting acetoacetic acid esters with 5-aminotetrazole and aromatic aldehyde. Pleiades Publishing, Ltd., 2010.

Full text of DOI:10.1134/S1070428010050180

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 5, pp. 699−705. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © V.L. Gein, I.N. Vladimirov, O.V. Fedorova, A.A. Kurbatova, N.V. Nosova, I.V. Krylova, M.I. Vakhrin, 2010, published in
Zhurnal Organicheskoi Khimii, 2010, Vol. 46, No. 5, pp. 707−712.
Synthesis of Alkyl 5-Aryl-7-methyl-1,5-dihydrotetrazolo-
[1,5-a]pyrimidine-6-carboxylates
V. L. Geina, I. N. Vladimirova, O. V. Fedorovab,A. A. Kurbatovaa,
N. V. Nosovaa, I. V. Krylovaa, and M. I. Vakhrina
a Perm State Pharmaceutical Academy, Perm, 614990 Russia
e-mail: geinvl48@mail.ru
b Postovskii Institute of Organic Synthesis, Ural Division, Russian Academy of Sciences, Yekaterinburg
Received May 26, 2009
Abstract—Alkyl 5-aryl-7-methyl-1,5-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylates were obtained by
melting acetoacetic acid esters with 5-aminotetrazole and aromatic aldehyde.
DOI: 10.1134/S1070428010050180
Aiming at the preparation of new alkyl 1,5-dihydro-
tetrazolo[1,5-a]pyrimidine-6-carboxylates, at estimation
of the effect of the substituent in the ester group on the
course of the reaction and at the establishment of the
spatial arrangement of compounds obtained we investigat-
ed the reaction of various acetoacetic acid esters with
the mixture of 5-amino-tetrazole and aromatic aldehydes.
It was established formerly that the reaction of keto-
acid esters with a mixture of an aromatic aldehyde and
a 5-aminotetrazole or 3-amino-1,2,4-triazole resulted in
the formation of fused heterocyclic systems [1]. For
instance, methyl pyruvates reacted with a mixture of
an aromatic aldehyde and a 5-aminotetrazole [2, 3] or
3-amino-1,2,4-triazole [4] to give methyl 5-aryl-6-acyl-
7-methoxycarbonyl-1,5-dihydrotetrazolo[1,5-a]pyrimi-
dine-6-carboxylates and methyl 5-aryl-6-acyl-7-methoxy-
carbonyl-1,5-dihydrotriazolo[1,5-a]pyrimidine-6-carboxy-
lates respectively.
The study showed that at the melting of equimolar
amounts of the initial reagents at 130–170°C over 20–
30 min a single product was obtained, alkyl 5-aryl-7-
Scheme 1.
O
NH2
O
O
R1
HN
O
R1
+
+
R2CHO
N
NH
O
N
R2
N N
N
N
N
Iа_Il, IIа_IIi, IIIа_IIIj, IVа_IVe,
Vа_Vd, VIа, VIb
I, R1 = Me, R2 = Ph (a), 4-Me-C6H4 (b), 4-OH-3-OCH3C6H3 (c), 4-OH-3-OC2H5C6H3 (d), 4-(C2H5)2NC6H4 (e), 4-ClC6H4 (f),
4-NO2C6H4 (g), 3-NO2C6H4 (h), 4-(CH3)2NC6H4 (i), 3-OCH3C6H4 (j); II, R1 = Et, R2 = Ph (a), 3-CH3OC6H4 (b), 4-C2H5OC6H4
(c), 4-(i-Pr)-C6H4 (d), 4-C2H5C6H4 (e), 4-OH-3-OCH3C6H3 (f), 4-OH-3-OC2H5C6H3 (g), 3-FC6H4 (h), 4-(CH3)2NC6H4 (i); III, R1
= i-Pr, R2 = Ph (a), 3-FC6H4 (b), 4-FC6H4 (c), 4-OHC6H4 (d), 4-CH3OC6H4 (e), 3,4-(CH3O)2C6H3 (f), 4-OH-3-OC2H5C6H3 (g),
4-(t-Bu)C6H4 (h), 3-OCH3C6H4 (i), 3-NO2C6H4(j); IV, R1 = i-Bu, R2 = Ph (a), 4-BrC6H4 (b), 4-NO2C6H4 (c), 4-CH3OC6H4 (d),
4-ClC6H4 (e); V, R1 = t-Bu, R2 = Ph (a), 4-Me-C6H4 (b), 3,4-(CH3O)2C6H3 (c), 2-NO2C6H4 (d); VI, R1 = Bz, R2 = 4-NO2C6H4 (a),
4-OH-3-OC2H5C6H3 (b).
699

GEIN et al.
700
methyl-1,5-dihydrotetrazolo[1,5-a]-pyrimidinecarboxy-
late Ia–Ij, IIa–IIi, IIIa–IIIj, IVa–IVe, Va–Vd, VIa,
VIb.
crystal was grown by slow crystallization from ethanol
(cf. the figure). The results of the XRD analysis
completely confirmed the assumed structure.
Compounds obtained are colorless or colored crystal-
line substances soluble in DMSO, DMF, at heating in the
glacial acetic acid, dioxane, sparingly soluble in alcohol,
insoluble in water, ether, and chloroform.
The bicyclic fragment of the molecule is flat. The
double bonds are localized, no significant conjugation is
observed.All bond distances and bond angles have values
common for the corresponding atoms.
The character of substituents in aromatic aldehydes
affected the yield of the products. For instance, the
reaction with aldehydes with any substituents in the para-
position proceeds with a better yield whereas at the
presence of a substituent in the meta- or ortho-position
the duration of the reaction increased and the yield
decreased. The yield is also affected by the presence in
the aldehyde of electron-donor or electron-acceptor
substituents: the former substituents reduce the yields.
The character of substituents in the esters does not notably
affect the yield of the formed products.
The 1H NMR spectra of compounds obtained alongside
the signals of the alkoxy groups contain a group of signals
of the aromatic protons as a multiplet at 6.50–6.90 ppm,
a singlet of C5H proton in the region 6.50–6.70 ppm,
a signal of NH proton at 11.00–11.40 ppm, and singlets
of methyl groups in the region 2.25–2.45 ppm. In the IR
spectra absorption bands are observed belonging to the
stretching vibrations of NH group in the region 3200–
3450 cm–1, to ester groups in the range 1650–1750 cm–1,
and to the stretching vibrations of the C=C bond at 1660–
1700 cm–1.
EXPERIMENTAL
IR spectra were recorded on a spectrophotometer
Specord UR-20 from mulls in mineral oil. H NMR
spectra were registered on a spectrometer Bruker DRX
500 (500.13 MHz) in DMSO-d6, internal reference TMS.
1
XRD investigation of compound IIIh was performed
on an automatic diffractometer Xcalibur 3 equipped with
CCD detector [MoKα radiation, λ 0.71073 A, graphite
°
monochromator, 293 (2) K]. The structure was solved
by the direct method and refined by the full-matrix least-
squares method first in isotropic, then in anisotropic
approximation by F2 for all nonhydrogen atoms applying
programs SHELXS97, SHELXL97 [5]. All hydrogen
atoms were revealed in the difference synthesis, but in
further calculations the geometrically computed positions
were used in the rider model. Final refinement of the
hydrogen atoms was performed in the isotropic
approximation.
Methyl 7-methyl-5-phenyl-1,5-dihydrotetrazolo-
[1,5-a]pyrimidine-6-carboxylate (Ia). A mixture of
0.01 mol (1.20 g) of methyl acetoacetate, 0.01 mol (1.05
g) of 5-aminotetrazole monohydrate, and 0.01 mol (1.06
g) of benzaldehyde was melted at heating on a metal
bath at 130–170°C till the end of gas evolution, then the
reaction mixture was cooled, treated with ethanol, the
precipitate was filtered off and recrystallized from
isopropyl alcohol. Yield 1.82 g (67%), mp 201–203°C.
IR spectrum, ν, cm–1: 3263 (NH), 1735 (COOCH3), 1670
For investigation by the XRD method of the structure
of isopropyl 5-(4-tert-butylphenyl)-7-methyl-1,5-dihydro-
tetrazolo[1,5-a]-pyrimidinecarboxylate (IIIh) a single
C
1
(C=C). H NMR spectrum, δ, ppm: 2.40 s (3H, CH3),
3.50 s (3H, COOCH3), 6.60 s (1H, C5H), 7.30 m (5H,
C6H5), 11.15 s (1H, NH). Found, %: C 57.63; H 4.90;
N 26.01. C13H13N5O2. Calculated, %: C 57.56; H 4.83;
N 25.82.
Compounds Ib–Ij were similarly obtained.
Methyl 7-methyl-5-(4-methylphenyl)-1,5-di-
hydrotetrazolo[1,5-a]pyrimidine-6-carboxylate (Ib).
Yield 1.54 g (54%), mp 194–196°C. IR spectrum, ν,
cm–1: 2368 (NH), 1712 (COOCH3), 1684 (C=C).
1H NMR spectrum, δ, ppm: 2.40 s (3H, CH3), 2.50 s
The structure of isopropyl 5-(4-tert-butylphenyl)-7-methyl-
1,5-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate (IIIh)
according to XRD investigation.
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SYNTHESIS OF ALKYL 5-ARYL-7-METHYL-1,5-DIHYDROTETRAZOLO-...
701
6.70 s (1H, C5H), 7.40 m (4H, C6H4), 11.25 s (1H, NH).
Found, %: C 49.42; H 3.80; N 26.62. C13H12N6O4.
Calculated, %: C 49.37; H 3.82; N 26.57.
(3H, CH3C6H4), 3.50 s (3H, COOCH3), 6.60 s (1H,
C5H), 7.102 d (4H, C6H4), 11.30 C (1H, NH). Found, %:
C 58.72; H 5.25; N 24.73. C14H15N5O2. Calculated, %:
C 58.94; H 5.30; N 24.55.
Methyl 7-methyl-5-(3-nitrophenyl)-1,5-dihydro-
tetrazolo[1,5-a]pyrimidine-6-carboxylate (Ih). Yield
2.03 g (64%), mp 130–132°C. IR spectrum, ν, cm–1: 3176
Methyl 5-(4-hydroxy-3-methoxyphenyl)-7-
methyl-1,5-dihydrotetrazolo[1,5-a]pyrimidine-6-
carboxylate (Ic). Yield 1.04 g (33%), mp 225–226°C.
IR spectrum, ν, cm–1: 3440 (OH), 3376 (NH), 1696
1
(NH), 1772 (COOCH3), 1688 (C=C). H NMR spec-
trum, δ, ppm: 2.45 s (3H, CH3), 3.55 s (3H, COOCH3),
6.95 s (1H, C5H), 7.95 m (4H, C6H4), 11.30 s (1H, NH).
Found, %: C 49.42; H 3.80; N 26.62. C13H12N6O4.
Calculated, %: C 49.37; H 3.82; N 26.57.
1
(COOCH3), 1672 (C=C). H NMR spectrum, δ, ppm:
2.40 s (3H, CH3), 3.50 s (3H,COOCH3), 3.75 s (6H,
CH3OC6H3OH), 6.55 s (1H, C5H), 6.70 m (3H, C6H3),
9.10 s (1H, CH3OC6H3OH), 11.20 s (1H, NH). Found,
%: C 53.06; H 4.83; N 22.03. C14H15N5O4. Calculated,
%: C 52.99; H 4.76; N 22.07.
Methyl 5-(4-dimethylaminophenyl)-7-methyl-
1,5-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxy-
late (Ii). Yield 1.63 g (52%), mp 234–236°C. IR spectrum,
ν, cm–1: 3352 (NH), 1616 (COOCH3), 1588 (C=C).
1H NMR spectrum, δ, ppm: 2.40 s (3H, CH3), 2.80 s
[6H, N(CH3)2], 3.60 s (3H, COOCH3), 6.50 s (1H, C5H),
6.85 m (4H, C6H4), 11.05 s (1H, NH). Found, %: C 57.51;
H 5.69; N 25.81. C15H18N6O2. Calculated, %: C 57.31;
H 5.77; N 26.74.
Methyl 5-(4-hydroxy-3-ethoxyphenyl)-7-methyl-
1,5-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxy-
late (Id). Yield 1.01 g (31%), mp 232–234°C. IR
spectrum, ν, cm–1: 3368 (OH), 3256 (NH), 1696
1
(COOCH3), 1674 (C=C). H NMR spectrum, δ, ppm:
1.30 t (3H, CH3CH2OC6H3OH), 2.50 s (3H, CH3), 3.50 s
(3H, COOCH3), 4.00 m (2H, CH3CH2OC6H3OH),
6.60 s (1H, C5H), 6.70 m (3H, C6H3), 9.00 s (1H,
C6H4OH), 11.30 C (1H, NH). Found, %: C 54.50;
H 5.20; N 21.05. C15H17N5O4. Calculated, %: C 54.38;
H 5.17; N 21.14.
Methyl 7-methyl-5-(3-methoxyphenyl)-1,5-
dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate
(Ij). Yield 1.86 g (62%), mp 200–202°C. IR spectrum, ν,
cm–1: 3376 (NH), 1676 (COOCH3), 1620 (C=C).
1H NMR spectrum, δ, ppm: 2.45 s (3H, CH3), 3.55 s
(3H, COOCH3), 3.75 s (3H, C6H4OCH3), 6.60 s (1H,
C5H), 7.05 m (4H, C6H4), 11.20 s (1H, NH). Found, %:
C 57.91; H 5.13; N 22.88. C14H15N5O3. Calculated, %:
C 57.81; H 5.02; N 23.24.
Methyl 5-(4-diethylaminophenyl)-7-methyl-1,5-
dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate
(Ie). Yield 1.38 g (40%), mp 235–237°C. IR spectrum,
ν, cm–1: 3264 (NH), 1808 (COOCH3), 1672 (C=C).
1H NMR spectrum, δ, ppm: 1.05 m [6H, (CH3CH2)2N],
2.45 s (3H, CH3), 3.30 m [4H, (CH3CH2)2N], 3.55 s (3H,
COOCH3), 6.52 s (1H, C5H), 6.80 m (4H, C6H4), 11.15 s
(1H, NH). Found, %: C 59.71; H 6.50; N 24.30.
C17H22N6O2. Calculated, %: C 59.63; H 6.48; N 24.54.
Ethyl 7-methyl-5-phenyl-1,5-dihydrotetrazolo-
[1,5-a]pyrimidine-6-carboxylate (IIa). A mixture of
0.01 mol (1.36 g) of ethyl acetoacetate, 0.01 mol (1.05 g)
of 5-aminotetrazole monohydrate, and 0.01 mol (1.06 g)
of benzaldehyde was melted at heating on a metal bath
at 130–170°C till the end of gas evolution, then the
reaction mixture was cooled, treated with ethanol, the
precipitate was filtered off and recrystallized from
isopropyl alcohol. Yield 2.02 g (71%), mp 196–198°C.
IR spectrum, ν, cm–1: 3784 (NH), 1572 (COOC2H5),
Methyl 7-methyl-5-(4-chlorophenyl)-1,5-di-
hydrotetrazolo[1,5-a]pyrimidine-6-carboxylate (If).
Yield 1.89 g (62%), mp 121–123°C. IR spectrum, ν,
cm–1: 3263 (NH), 1745 (COOCH3), 1682 (C=C).
1H NMR spectrum, δ, ppm: 2.45 s (3H, CH3), 3.55 s
(3H, COOCH3), 6.70 s (1H, C5H), 7.40 m (4H, C6H4),
11.25 s (1H, NH). Found, %: C 51.12; H 4.02; Cl 12.03;
N 22.85. C13H12ClN5O2. Calculated, %: C 51.07; H 3.96;
Cl 11.96; N 22.91.
1
1516 (C=C). H NMR spectrum, δ, ppm: 1.10 t (3H,
COOCH2CH3), 2.45 s (3H, CH3), 3.90 m (2H,
COOCH2CH3), 6.55 s (1H, C5H), 7.20 m (5H, C6H5),
11.55 s (1H, NH). Found, %: C 57.23; H 4.51; N 22.01.
C14H15N5O2. Calculated, %: C 58.94; H 5.30; N 24.55.
Methyl 7-methyl-5-(4-nitrophenyl)-1,5-dihydro-
tetrazolo[1,5-a]pyrimidine-6-carboxylate (Ig). Yield
2.27 g (72%), mp 234–237°C. IR spectrum, ν, cm–1: 3263
Compounds IIb–IIi were similarly obtained.
Ethyl 7-methyl-5-(3-methoxyphenyl)-1,5-di-
hydrotetrazolo[1,5-a]pyrimidine-6-carboxylate
(IIb). Yield 1.98 g (63%), mp 160–162°C. IR spectrum,
1
(NH), 1745 (COOCH3), 1682 (C=C). H NMR spec-
trum, δ, ppm: 2.45 s (3H, CH3), 3.55 s (3H, COOCH3),
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GEIN et al.
702
trum, ν, cm–1: 3408 (OH), 3288 (NH), 1712 (COOC2H5),
ν, cm–1: 3112 (NH), 1672 (COOC2H5), 1656 (C=C).
1H NMR spectrum, δ, ppm: 1.05 t (3H, COOCH2CH3),
2.45 s (3H, CH3), 3.75 s (3H, C6H4OCH3), 4.00 m (2H,
COOCH2CH3), 6.60 s (1H, C5H), 7.10 m (4H, C6H4),
11.25 s (1H, NH). Found, %: C 57.23; H 4.51; N 22.01.
C15H17N5O3. Calculated, %: C 57.13; H 5.43; N 22.21.
1
1688 (C=C). H NMR spectrum, δ, ppm: 1.05 t (3H,
COOCH2CH3), 1.30 t (3H, CH3CH2OC6H3OH), 2.45 s
(3H, CH3), 3.95 s (3H, CH3CH2OC6H3OH), 4.00 m (2H,
COOCH2CH3), 6.53 s (1H, C5H), 6.70 m (3H, C6H3),
9.07 s (1H, OH), 11.20 s (1H, NH). Found, %: C 55.73;
H 5.60; N 20.32. C16H19N5O4. Calculated, %: C 55.64;
H 5.55; N 20.28.
Ethyl 7-methyl-5-(4-ethoxyphenyl)-1,5-dihydro-
tetrazolo[1,5-a]pyrimidine-6-carboxylate (IIc). Yield
1.91 g (58%), mp 115–116°C. IR spectrum, ν, cm–1: 3313
Ethyl 7-methyl-5-(3-fluorophenyl)-1,5-di-
hydrotetrazolo[1,5-a]pyrimidine-6-carboxylate
(IIh). Yield 1.64 g (54%), mp 190–192°C. IR spectrum,
ν, cm–1: 3688 (NH), 1712 (COOC2H5), 1680 (C=C).
1H NMR spectrum, δ, ppm: 1.05 t (3H, COOCH2CH3),
2.45 s (3H, CH3), 4.00 m (2H, COOCH2CH3), 6.65 s
(1H, C5H), 7.30 m (4H, C6H4), 11.25 s (1H, NH). Found,
%: C 55.73; H 5.60; F 6.28; N 20.32. C14H14FN5O2.
Calculated, %: C 55.44; H 4.65; F 6.26; N 23.09.
1
(NH), 1704 (COOC2H5), 1684 (C=C). H NMR
spectrum, δ, ppm: 1.05 t (3H, COOCH2CH3), 1.30 t (3H,
CH3CH2OC6H4), 2.45 s (3H, CH3), 3.90 m (2H,
CH3CH2OC6H4), 4.00 m (2H, COOCH2CH3), 6.60 s
(1H, C5H), 7.05 m (4H, C6H4), 11.25 s (1H, NH). Found,
%: C 58.23; H 5.91; N 22.09. C16H19N5O3. Calculated,
%: C 58.35; H 5.81; N 21.26.
Ethyl 5-(4-isopropylphenyl)-7-methyl-1,5-di-
hydrotetrazolo[1,5-a]pyrimidine-6-carboxylate
(IId). Yield 1.47 g (45%), mp 208–209°C. IR spectrum,
ν, cm–1: 3368 (NH), 1704 (COOC2H5), 1680 (C=C).
1H NMR spectrum, δ, ppm: 1.05 t (3H, COOCH2CH3),
1.15 m [6H, CH(CH3)2], 2.45 s (3H, CH3), 2.85 m [1H,
CH(CH3)2], 4.00 m (2H, COOCH2CH3), 6.75 s (1H,
C5H), 7.02 m (4H, C6H4), 11.25 s (1H, NH). Found, %:
C 62.54; H 6.50; N 21.48. C17H21N5O2. Calculated, %:
C 62.37; H 6.47; N 21.39.
Ethyl 5-(4-dimethylaminophenyl)-7-methyl-1,5-
dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate
(IIi). Yield 1.60 g (49%), mp 184–186°C. IR spectrum,
ν, cm–1: 3693 (NH), 1708 (COOC2H5), 1600 (C=C).
1H NMR spectrum, δ, ppm: 1.05 m [6H, (CH3)2N], 1.10 t
(3H, COOCH2CH3), 2.45 s (3H, CH3), 4.00 m (2H,
COOCH2CH3), 6.65 s (1H, C5H), 7.00 m (4H, C6H4),
11.00 s (1H, NH). Found, %: C 58.62; H 6.21; N 25.71.
C16H20N6O2. Calculated, %: C 58.52; H 6.14; N 25.59.
Ethyl 7-methyl-5-(4-ethylphenyl)-1,5-dihydro-
tetrazolo[1,5-a]pyrimidine-6-carboxylate (IIe). Yield
1.30 g (42%), mp 206–208°C. IR spectrum, ν, cm–1: 3368
Isopropyl 7-methyl-5-phenyl-1,5-dihydro-
tetrazolo[1,5-a]pyrimidine-6-carboxylate (IIIa).
A mixture of 0.01 mol (1.44 g) of isopropyl acetoacetate,
0.01 mol (1.05 g) of 5-aminotetrazole monohydrate, and
0.01 mol (1.06 g) of benzaldehyde was melted at heating
on a metal bath at 130–170°C till the end of gas evolution,
then the reaction mixture was cooled, treated with ethanol,
the precipitate was filtered off and recrystallized from
ethanol. Yield 2.15 g (72%), mp 219–220°C. IR spectrum,
ν, cm–1: 3263 (NH), 1755 [COOCH(CH3)2], 1672
(C=C). 1H NMR spectrum, δ, ppm: 1.00 m [6H,
COOCH(CH3)2], 2.45 s (3H, CH3), 4.85 m [1H,
COOCH(CH3)2], 6.70 s (1H, C5H), 7.35 m (5H, C6H5),
11.30 s (1H, NH). Found, %: C 60.21; H 5.73; N 23.41.
C15H17N5O2. Calculated, %: C 60.19; H 5.72; N 23.40.
1
(NH), 1704 (COOC2H5), 1676 (C=C). H NMR
spectrum, δ, ppm: 1.05 t (3H, COOCH2CH3), 1.15 t (3H,
CH3CH2C6H4), 2.45 s (3H, CH3), 4.00 m (2H,
COOCH2CH3), 6.70 s (1H, C5H), 7.20 m (4H, C6H4),
11.25 s (1H, NH). Found, %: C 61.41; H 6.10; N 22.43.
C16H19N5O2. Calculated, %: C 61.33; H 6.11; N 22.53.
Ethyl 5-(4-hydroxy-3-methoxyphenyl)-7-methyl-
1,5-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxy-
late (IIf). Yield 1.52 g (46%), mp 205–207°C. IR spec-
trum, ν, cm–1: 3472 (OH), 3304 (NH), 1704 (COOC2H5),
1
1648 (C=C). H NMR spectrum, δ, ppm: 1.05 t (3H,
COOCH2CH3), 2.45 s (3H, CH3), 3.75 s (3H,
CH3OC6H3OH), 4.00 m (2H, COOCH2CH3), 6.55 s
(1H, C5H), 6.75 m (3H, C6H3), 9.15 s (1H, OH), 11.20 s
(1H, NH). Found, %: C 54.42; H 5.23; N 19.59.
C15H17N5O4. Calculated, %: C 54.38; H 5.17; N 19.32.
Compounds IIIb–IIIj were similarly obtained.
Isopropyl 7-methyl-5-(3-fluorophenyl)-1,5-
dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate
(IIIb). Yield 2.00 g (63%), mp 209–210°C. IR spectrum,
ν, cm–1: 3260 (NH), 1772 [COOCH(CH3)2], 1677
(C=C). 1H NMR spectrum, δ, ppm: 1.00 m [6H,
COOCH(CH3)2], 2.45 s (3H, CH3), 4.80 m [1H,
Ethyl 5-(4-hydroxy-3-ethoxyphenyl)-7-methyl-
1,5-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxy-
late (IIg). Yield 1.14 g (33%), mp 233–234°C. IR spec-
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SYNTHESIS OF ALKYL 5-ARYL-7-METHYL-1,5-DIHYDROTETRAZOLO-...
703
1
COOCH(CH3)2], 6.70 s (1H, C5H), 7.30 m (4H, C6H4),
11.30 s (1H, NH). Found, %: C 56.92; H 5.03; F 6.02;
N 22.15. C15H16FN5O2. Calculated, %: C 56.78; H 5.08;
F 5.99; N 22.07.
[COOCH(CH3)2], 1656 (C=C). H NMR spectrum, δ,
ppm: 1.00 m [6H, COOCH(CH3)2], 1.15 t (3H,
CH3CH2OC6H3OH), 2.45 s (3H, CH3), 4.00 m (2H,
CH3CH2OC6H3OH), 4.80 m [1H, COOCH(CH3)2],
6.50 s (1H, C5H), 6.80 m (3H, C6H3), 9.00 s (1H, OH),
11.15 s (1H, NH). Found, %: C 56.78; H 5.81; N 19.55.
C17H21N5O4. Calculated, %: C 56.82; H 5.89; N 19.49.
Isopropyl 7-methyl-5-(4-fluorophenyl)-1,5-
dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate
(IIIc). Yield 2.12 g (67%), mp 227–229°C. IR spectrum,
ν, cm–1: 3266 (NH), 1763 [COOCH(CH3)2], 1683
Isopropyl 5-(4-tert-butylphenyl)-7-methyl-1,5-
dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate
(IIIh). Yield 1.84 g (52%), mp 223–225°C. IR spectrum,
ν, cm–1: 3263 (NH), 1755 [COOCH(CH3)2], 1672
1
(C=C). H NMR spectrum, δ, ppm: 1.00 m [6H,
COOCH(CH3)2], 2.45 s (3H, CH3), 4.80 m [1H,
COOCH(CH3)2], 6.70 s (1H, C5H), 7.30 d (4H, C6H4),
11.40 s (1H, NH). Found, %: C 56.83; H 5.03; F 6.04;
N 22.25. C15H16FN5O2. Calculated, %: C 56.78; H 5.08;
F 5.99; N 22.07.
1
(C=C). H NMR spectrum, δ, ppm: 1.00 s (9H, t-Bu),
1.05 m [6H, COOCH(CH3)2], 2.55 s (3H, CH3), 4.75 m
[1H, COOCH(CH3)2], 6.70 s (1H, C5H), 7.35 m (4H,
C6H4), 11.30 s (1H, NH). Found, %: C 65.11; H 7.23;
N 20.41. C19H25N5O2. Calculated, %: C 64.20; H 7.09;
N 19.70.
Isopropyl 5-(4-hydroxyphenyl)-7-methyl-1,5-
dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate
(IIId). Yield 1.84 g (59%), mp 253–255°C. IR spectrum,
ν, cm–1: 3472 (OH), 3304 (NH), 1704 [COOCH(CH3)2],
Isopropyl 7-methyl-5-(3-methoxyphenyl)-1,5-
dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate
(IIIi). Yield 2.00 g (61%), mp 193–194°C. IR spectrum,
ν, cm–1: 3168 (NH), 1676 [COOCH(CH3)2], 1672
1
1652 (C=C). H NMR spectrum, δ, ppm: 1.00 m [6H,
COOCH(CH3)2], 2.45 s (3H, CH3), 4.80 m [1H,
COOCH(CH3)2], 6.50 s (1H, C5H), 6.90 m (4H, C6H4),
9.55 s (1H, C6H4OH), 11.25 s (1H, NH). Found, %:
C 57.16; H 5.53; N 22.20. C15H17FN5O3. Calculated, %:
C 57.13; H 5.43; N 22.21.
1
(C=C). H NMR spectrum, δ, ppm: 1.00 m [6H,
COOCH(CH3)2], 2.45 s (3H, CH3), 3.85 s (3H,
CH3OC6H4), 4.80 m [1H, COOCH(CH3)2], 6.50 s (1H,
C5H), 6.80 m (4H, C6H4), 11.15 s (1H, NH). Found, %:
C 58.42; H 5.86; N 22.11. C16H19N5O3. Calculated, %:
C 58.35; H 5.81; N 21.26.
Isopropyl 5-(4-methoxyphenyl)-7-methyl-1,5-
dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate
(IIIe). Yield 1.35 g (41%), mp 217–218°C. IR spectrum,
ν, cm–1: 3112 (NH), 1672 [COOCH(CH3)2], 1656
Isopropyl 7-methyl-5-(3-nitrophenyl)-1,5-di-
hydrotetrazolo[1,5-a]pyrimidine-6-carboxylate
(IIIj). Yield 2.55 g (72%), mp 260–261°C. IR spectrum,
ν, cm–1: 3208 (NH), 1704 [COOCH(CH3)2], 1676
(C=C). 1H NMR spectrum, δ, ppm: 1.00 m [6H,
COOCH(CH3)2], 2.45 s (3H, CH3), 4.80 m [1H,
COOCH(CH3)2], 6.90 s (1H, C5H), 8.00 m (4H, C6H4),
11.50 s (1H, NH). Found, %: C 55.42; H 4.73; N 24.51.
C15H16N6O4. Calculated, %: C 52.32; H 4.68; N 24.41.
1
(C=C). H NMR spectrum, δ, ppm: 1.00 m [6H,
COOCH(CH3)2], 2.45 s (3H, CH3), 3.75 s [3H,
CH3OC6H4], 4.8 m [1H, COOCH(CH3)2], 6.60 s (1H,
C5H), 7.10 m (4H, C6H4), 11.25 s (1H, NH). Found, %:
C 58.40; H 5.80; N 22.26. C16H19N5O3. Calculated, %:
C 58.35; H 5.81; N 21.26.
Isopropyl 5-(3,4-dimethoxyphenyl)-7-methyl-
1,5-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxy-
late (IIIf). Yield 1.07 g (31%), mp 231–233°C. IR
spectrum, ν, cm–1: 3211 (NH), 1689 [COOCH(CH3)2],
Isobutyl 7-methyl-5-phenyl-1,5-dihydrotetr-
azolo[1,5-a]pyrimidine-6-carboxylate (IVa).
A mixture of 0.01 mol (1.58 g) of isobutyl acetoacetate,
0.01 mol (1.05 g) of 5-aminotetrazole monohydrate, and
0.01 mol (1.06 g) of benzaldehyde was melted at heating
on a metal bath at 130–170°C till the end of gas evolution,
then the reaction mixture was cooled, treated with ethanol,
the precipitate was filtered off and recrystallized from
ethanol. Yield 2.25 g (72%), mp 192–194°C. IR spectrum,
ν, cm–1: 3632 (NH), 1700 [COOCH2CH(CH3)2], 1676
1
1676 (C=C). H NMR spectrum, δ, ppm: 1.00 m [6H,
COOCH(CH3)2], 2.45 s (3H, CH3), 3.70 s, 3.75 s [6H,
(CH3O)2C6H3], 4.80 m [1H, COOCH(CH3)2], 6.60 s
(1H, C5H), 6.85 m (3H, C6H3), 11.20 s (1H, NH). Found,
%: C 56.79; H 5.80; N 19.53. C17H21N5O4. Calculated,
%: C 56.82; H 5.89; N 19.49.
Isopropyl 5-(4-hydroxy-3-ethoxyphenyl)-7-
methyl-1,5-dihydrotetrazolo[1,5-a]pyrimidine-6-
carboxylate (IIIg). Yield 1.24 g (36%), mp 217–219°C.
IR spectrum, ν, cm–1: 3354 (OH), 3202 (NH), 1676
1
(C=C). H NMR spectrum, δ, ppm: 0.80 m [6H,
COOCH2CH(CH3)2], 1.70 m [1H, OOCH2CH(CH3)2],
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 5 2010

GEIN et al.
704
2.50 s (3H, CH3), 3.75 m [2H, COOCH2CH(CH3)2],
6.70 s (1H, C5H), 7.35 m (5H, C6H5), 11.40 c (1H, NH).
Found, %: C 61.35; H 6.35; N 22.01. C16H19N5O2.
Calculated, %: C 61.33; H 6.11; N 22.35.
A mixture of 0.01 mol (1.58 g) of tert-butyl acetoacetate,
0.01 mol (1.05 g) of 5-aminotetrazole monohydrate, and
0.01 mol (1.06 g) of benzaldehyde was melted at heating
on a metal bath at 130–170°C till the end of gas evolution,
then the reaction mixture was cooled, treated with ethanol,
the precipitate was filtered off and recrystallized from
isopropyl alcohol. Yield 1.09 g (35%), mp 204–205°C.
IR spectrum, ν, cm–1: 3176 (NH), 1872 [COOC(CH3)3],
Compounds IVb–IVe were similarly obtained.
Isobutyl 5-(4-bromophenyl)-7-methyl-1,5-
dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate
(IVb). Yield 3.09 g (79%), mp 208–210°C. IR spectrum,
ν, cm–1: 3712 (NH), 1700 [COOCH2CH(CH3)2], 1676
1
1644 (C=C). H NMR spectrum, δ, ppm: 1.20 m [9H,
COOC(CH3)3], 2.45 s (3H, CH3), 6.50 s (1H, C5H),
7.25 m (5H, C6H5), 11.00 s (1H, NH). Found, %: C 62.35;
H 6.13; N 22.40. C16H19N5O2. Calculated, %: C 61.33;
H 6.11; N 22.35.
1
(C=C). H NMR spectrum, δ, ppm: 0.70 m [6H,
COOCH2CH(CH3)2], 1.75 m [1H, COOCH2CH(CH3)2],
2.45 s (3H, CH3), 3.75 m [2H, COOCH2CH(CH3)2],
6.70 s (1H, C5H), 7.65 m (4H, C6H4), 11.35 s (1H, NH).
Found, %: C 49.03; H 4.83; N 17.65. C16H18BrN5O2.
Calculated, %: C 48.99; H 4.63; N 17.85.
Compounds Vb–Vd were similarly obtained.
tert-Butyl 7-methyl-5-(4-methylphenyl)-1,5-
dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate
(Vb). Yield 1.37 g (42%), mp 220–229°C. IR spectrum,
ν, cm–1: 3214 (NH), 1756 [COOC(CH3)3], 1713 (C=C).
1H NMR spectrum, δ, ppm: 1.20 m [9H, COOC(CH3)3],
2.25 s (3H, CH3), 6.40 s (1H, C5H), 7.15 m (4H, C6H4),
11.00 s (1H, NH). Found, %: C 62.62; H 6.17; N 20.40.
C16H19N5O2. Calculated, %: C 62.37; H 6.47; N 21.39.
Isobutyl 7-methyl-5-(4-nitrophenyl)-1,5-dihydro-
tetrazolo[1,5-a]pyrimidine-6-carboxylate (IVc). Yield
2.86 g (80%), mp 200–202°C. IR spectrum, ν, cm–1: 1658
(C=C), 1714 [COOCH2CH(CH3)2], 3392 (NH).
1H NMR spectrum, δ, ppm: 0.75
m
[6H,
COOCH2CH(CH3)2], 1.65 m [1H, COOCH2CH(CH3)2],
2.35 s (3H, CH3), 3.75 m [2H, COOCH2CH(CH3)2],
6.80 s (1H, C5H), 7.85 m (4H, C6H4), 11.35 s (1H, NH).
Found, %: C 52.08; H 5.09; N 23.65. C16H18N6O4.
Calculated, %: C 53.63; H 5.06; N 23.45.
tert-Butyl 5-(3,4-dimethoxyphenyl)-7-methyl-1,5-
dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate
(Vc). Yield 1.94 g (52%), mp 235–237°C. IR spectrum,
ν, cm–1: 3513 (NH), 1804 [COOC(CH3)3], 1690 (C=C).
1H NMR spectrum, δ, ppm: 1.20 m [9H, COOC(CH3)3],
2.30 s (3H, CH3), 3.75 d [6H, (CH3O)2C6H3], 6.40 s
(1H, C5H), 7.15 m (3H, C6H3), 11.00 s (1H, NH). Found,
%: C 58.62; H 6.17; N 17.43. C18H23N5O4. Calculated,
%: C 57.90; H 6.21; N 17.40.
Isobutyl 7-methyl-5-(4-methoxyphenyl)-1,5-
dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate
(IVd). Yield 1.85 g (54%), mp 155–157°C. IR spectrum,
ν, cm–1: 3215 (NH), 1694 [COOCH2CH(CH3)2], 1656
1
(C=C). H NMR spectrum, δ, ppm: 0.70 m [6H,
COOCH2CH(CH3)2], 1.70 m [1H, COOCH2CH(CH3)2],
2.45 s (3H, CH3), 3.75 m [2H, COOCH2CH(CH3)2], 3.85
s (3H, CH3OC6H4), 6.65 s (1H, C5H), 7.00 m (4H, C6H4),
11.10 s (1H, NH). Found, %: C 60.01; H 6.20; N 20.65.
C17H21N5O3. Calculated, %: C 59.46; H 6.16; N 20.40.
tert-Butyl 5-(2-nitrophenyl)-7-methyl-1,5-
dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate
(Vd). Yield 1.94 g (52%), mp 235–237°C. IR spectrum,
ν, cm–1: 3513 (NH), 1804 [COOC(CH3)3], 1690 (C=C).
1H NMR spectrum, δ, ppm: 1.20 m [9H, COOC(CH3)3],
2.40 s (3H, CH3), 6.85 s (1H, C5H), 7.85 m (4H, C6H4),
11.00 s (1H, NH). Found, %: C 54.62; H 5.17; N 24.43.
C16H18N6O4. Calculated, %: C 53.45; H 5.06; N 23.45.
Isobutyl 5-(4-chlorophenyl)-7-methyl-1,5-
dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate
(IVe). Yield 2.39 g (69%), mp 198–200°C. IR spectrum,
ν, cm–1: 3192 (NH), 1686 [COOCH2CH(CH3)2], 1636
1
(C=C). H NMR spectrum, δ, ppm: 0.70 m [6H,
Benzyl 7-methyl-5-(4-nitrophenyl)-1,5-dihydro-
tetrazolo[1,5-a]pyrimidine-6-carboxylate (VIa). Yield
1.64 g (42%), mp 251–253°C. IR spectrum, ν, cm–1: 3784
COOCH2CH(CH3)2], 1.70 m [1H, COOCH2CH(CH3)2],
2.45 s (3H, CH3), 3.75 m [2H, COOCH2CH(CH3)2],
6.65 s (1H, C5H), 7.30 m (4H, C6H4), 11.20 s (1H, NH).
Found, %: C 52.08; H 5.09; Cl 10.11; N 23.65.
C16H18ClN5O4. Calculated, %: C 55.25; H 5.22; Cl 10.19;
N 20.14.
1
(NH), 1708 (COOCH2C6H5), 1676 (C=C). H NMR
spectrum, δ, ppm: 2.35 s (3H, CH3), 4.90 d (2H,
COOCH2C6H5), 6.45 s (1H, C5H), 7.00 m (5H,
COOCH2C6H5), 7.80 m (4H, C6H4), 11.30 s (1H, NH).
Found, %: C 59.05; H 4.20; N 21.81. C19H16N6O4.
tert-Butyl 7-methyl-5-phenyl-1,5-dihydro-
tetrazolo[1,5-a]pyrimidine-6-carboxylate (Va).
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SYNTHESIS OF ALKYL 5-ARYL-7-METHYL-1,5-DIHYDROTETRAZOLO-...
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Calculated, %: C 58.46; H 4.11; N 21.42.
REFERENCES
Benzyl 5-(4-hydroxy-3-methoxyphenyl)-7-
methyl-1,5-dihydrotetrazolo[1,5-a]pyrimidine-6-
carboxylate (VIb). Yield 1.37 g (35%), mp 232–234°C.
IR spectrum, ν, cm–1: 3176 (NH), 1684 (COOC2H5),
1. Zhidovinova, M.S., Fedorova, O.V., Rusinov, G.L., and
Ovchinnikova, I.G., Izv. Akad. Nauk, Ser. Khim., 2003,
p. 1677.
2. Gein, V.L., Gein, L.F., and Tsyplyakova, E.P., Zh. Org. Khim.,
2003, vol. 39, p. 797.
1
1632 (C=C). H NMR spectrum, δ, ppm: 2.50 s (3H,
CH3), 3.75 s (3H, CH3OC6H3OH), 4.95 d (2H,
COOCH2C6H5), 6.55 m (5H, COOCH2C6H5), 6.65 s
(1H, C5H), 7.20 m (4H, C6H4), 9.00 s (1H, OH), 11.30 s
(1H, NH). Found, %: C 59.05; H 4.20; N 21.81.
C20H19N5O4. Calculated, %: C 61.06; H 4.87; N 17.80.
3. Gein, V.L., Gein, L.F., Tsyplyakova, E.P., and Panova, O.S.,
Zh. Org. Khim., 2007, vol. 43, p. 1386.
4. Gein, V.L., Gein, L.F., and Tsyplyakova, E.P., Khim.
Geterotsikl. Soedin., 2003, p. 949.
5. Sheldrick, G.M., Acta Cryst. A, 2008, vol. 64, p. 112.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 5 2010