Reactions of methyl 4-hetaryl-2,4-dioxobutanoates with a mixture of aminoazole and aromatic (heteroaromatic) aldehyde

Full text of DOI:10.1007/s11178-008-3031-2

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 3, pp. 478–480. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © V.L. Gein, E.P. Tsyplyakova, G.A. Stashina, V.A. Bakulev, 2008, published in Zhurnal Organicheskoi Khimii, 2008, Vol. 44, No. 3,
pp. 478–480.
SHORT
COMMUNICATIONS
Reactions of Methyl 4-Hetaryl-2,4-dioxobutanoates
with a Mixture of Aminoazole and Aromatic
(Heteroaromatic) Aldehyde
V. L. Geina, E. P. Tsyplyakovaa, G. A. Stashinab, and V. A. Bakulevc
a Perm State Pharmaceutical Academy, ul. Lenina 48, Perm, 614990 Russia
e-mail: perm@pfa.ru
b Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia
c Ural State Technical University, Yekaterinburg, Russia
Received July 3, 2007
DOI: 10.1134/S1070428008030317
We previously described methods of synthesis of
methyl 6-acyl-7-aryl-4,7-dihydrotetrazolo[1,5-a]pyri-
midine-5-carboxylates and methyl 6-acyl-7-aryl-4,7-
dihydrotriazolo[1,5-a]pyrimidine-5-carboxylates by
reactions of methyl acylpyruvates with a mixture of
an aromatic aldehyde and 5-aminotetrazole [1] or
3-amino-1,2,4-triazole [2], respectively. With a view to
further study how the structure of heterocyclic amine
affects the direction of these reactions in the present
work we examined reactions of methyl 4-(2-thienyl)-
and 4-(2-furyl)-2,4-dioxobutanoates with mixtures of
aromatic (heteroaromatic) aldehydes and 5-amino-1-
methyltetrazole, 3,5-diamino-1,2,4-tetrazole, and ethyl
5-amino-1H-imidazole-4-carboxylate.
bands due to vibrations of the ketone carbonyl group
(1607–1620 cm–1), lactam carbonyl group (1701–
1755 cm–1), and enol OH group (3250–3269 cm–1).
The product structure indicates that replacement of
hydrogen at N1 in the 5-aminotetrazole molecule by
methyl group prevents formation of fused tetrazolo-
[1,5-a]pyrimidine system.
Fusion of methyl 4-phenyl-2,4-dioxobutanoate with
3,5-diamino-1,2,4-triazole, and benzaldehyde at 125–
150°C gave methyl 2-amino-6-benzoyl-7-phenyl-4,7-
dihydro[1,2,4]triazolo[1,5-a]pyrimidine-5-carboxylate
(II) which was isolated as a weakly colored crystalline
substance soluble in organic solvents and insoluble in
1
water. Compound II displayed in the H NMR spec-
By heating for a short time a mixture of methyl
4-(2-thienyl)- or 4-(2-furyl)-2,4-dioxobutanoate,
5-amino-1-methyltetrazole, and thiophene-2-carbalde-
hyde, benzaldehyde, or pyridine-3-carbaldehyde in
acetic acid we obtained the corresponding 5-aryl-
(hetaryl)-4-hetaroyl-3-hydroxy-1-(1-methyltetrazol-5-
yl)-2,5-dihydro-1H-pyrrol-2-ones Ia–Ic (Scheme 1).
Compounds Ia–Ic are colorless or slightly colored crys-
talline substances, which are readily soluble in DMF
and DMSO, soluble in ethanol and acetic acid on heat-
ing, and insoluble in water. They give rise to a positive
color test (cherry color) with an alcoholic solution of
trum a two-proton doublet at δ 5.30 ppm from the pri-
mary amino group, a three-proton singlet at δ 3.20 ppm
from the ester methyl group, a singlet at δ 6.21 ppm
from the 7-H proton, a multiplet centered at δ 7.33 ppm
from protons in the phenyl rings, and a singlet at
δ 10.80 ppm from the NH proton in position 4. The IR
spectrum of II was consistent with the assumed struc-
ture. Presumably, triazolopyrimidine II is formed ac-
cording to the mechanism proposed previously for
methyl 6-acyl-7-aryl-4,7-dihydrotriazolo[1,5-a]pyrimi-
dine-5-carboxylates [2].
1
Analogous reaction of methyl 4-phenyl-2,4-dioxo-
butanoate with ethyl 5-amino-1H-imidazole-4-carbox-
ylate and benzaldehyde at 120–150°C led to the forma-
tion of ethyl 5-(4-benzoyl-3-hydroxy-2-oxo-5-phenyl-
2,5-dihydro-1H-pyrrol-1-yl)-1H-imidazole-4-carbox-
FeCl3. The H NMR spectra of Ia–Ic contain signals
from aromatic protons, hydroxy proton, CH proton in
the 5-position of the pyrrole ring (δ 6.13–6.48 ppm),
and protons in the methyl group (δ 4.27–4.33 ppm, s).
In the IR spectra of Ia–Ic we observed absorption
478

REACTIONS OF METHYL 4-HETARYL-2,4-DIOXOBUTANOATES
479
Scheme 1.
N
N
R'
N
O
N
N
NH2
N
N
N
Me
N
R
Me
O
OH
Ia–Ic
O
N
N
H
N
OH
N
N
O
MeO
Ph
H2N
NH2
N
NH2
OMe
+
R'CHO
N
R
O
O
Ph
II
COOEt
NH2
EtO
N
O
O
N
OH
Ph
N
N
H
O
NH
Ph
III
I, R = 2-thienyl (a), 2-furyl (b, c); R′ = 2-thienyl (a), Ph (b), 3-pyridyl (c).
1
3250 (OH). H NMR spectrum, δ, ppm: 6.48 s (1H,
5-H), 6.80 m (6H, Harom), 4.33 s (3H, CH3), 10.80 s
(1H, OH). Found, %: C 47.99, 48.01; H 3.00, 2.98;
N 18.80, 18.82. C15H11N5S2O3. Calculated, %: C 48.25;
H 2.94; N 18.76.
ylate (III). Compound III is a weakly colored crys-
talline substance which is insoluble in water and sol-
uble in organic solvents on heating. It gives a positive
color test (cherry color) with an alcoholic solution of
FeCl3, which is typical of pyrrolediones. The 1H NMR
spectrum of III contained signals from protons in the
ethoxy group and aromatic rings, a singlet from the
5-H proton in the pyrrole ring (δ 6.38 ppm), a singlet
from 2-H in the imidazole ring (δ 8.55 ppm), and
singlets from the NH and OH protons at δ 12.80 and
11.02 ppm, respectively. Presumably, the nucleophilic-
ity and basicity of the NH nitrogen atom in ethyl
5-amino-1H-imidazole-4-carboxylate is considerably
reduced due to enhanced aromaticity of the imidazole
system and electron-withdrawing effect of the ester
fragment.
4-(2-Furoyl)-3-hydroxy-1-(1-methyltetrazol-5-
yl)-5-phenyl-2,5-dihydro-1H-pyrrol-2-one (Ib) was
synthesized in a similar way. Yield 0.96 g (27%),
mp 266–268°C. IR spectrum, ν, cm–1: 1614 (C=O),
1701 (C=O, lactam), 3266 (OH). 1H NMR spectrum, δ,
ppm: 6.13 s (1H, 5-H), 6.53 m (8H, Harom), 4.27 s (3H,
CH3), 10.95 s (1H, OH). Found, %: C 59.79, 5976;
H 3.90, 3.88; N 17.62, 17.57. C17H13N5O4. Calculated,
%: C 59.82; H 3.81; N 17.59.
4-(2-Furoyl)-3-hydroxy-1-(1-methyltetrazol-5-
yl)-5-(pyridin-3-yl)-2,5-dihydro-1H-pyrrol-2-one
(Ic) was synthesized in a similar way. Yield 0.62 g
(15%), mp 223–225°C. IR spectrum, ν, cm–1: 1614
(C=O), 1701 (C=O, lactam), 3266 (OH). 1H NMR spec-
trum, δ, ppm: 6.20 s (1H, 5-H), 6.55 m (7H, Harom),
4.30 s (3H, CH3), 10.78 s (1H, OH). Found, %:
C 54.48, 54.50; H 3.38, 3.41; N 23.76, 23.80.
C16H12N6O4. Calculated, %: C 54.54; H 3.40; N 23.86.
3-Hydroxy-1-(1-methyltetrazol-5-yl)-4-(2-theno-
yl)-5-(2-thienyl)-2,5-dihydro-1H-pyrrol-2-one (Ia).
Thiophene-2-carbaldehyde, 0.01 mol, and an equi-
molar amount of 1-methyltetrazol-5-amine were dis-
solved on heating in 10 ml of acetic acid, 0.01 mol of
methyl 4-(2-thienyl)-2,4-dioxobutanoate was added,
and the mixture was heated to the boiling point and
kept at room temperature until a solid separated. The
precipitate was filtered off and recrystallized from
acetic acid. Yield 0.63 g (16%), mp 242–244°C. IR
spectrum, ν, cm–1: 1620 (C=O), 1710 (C=O, lactam);
Methyl 2-amino-6-benzoyl-7-phenyl-4,7-dihydro-
[1,2,4]triazolo[1,5-a]pyrimidine-5-carboxylate (II).
A mixture of 0.01 mol of methyl 4-phenyl-2,4-dioxo-
butanoate, 0.01 mol of benzaldehyde, and 0.01 mol of
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 3 2008

GEIN et al.
480
1
3H-1,2,4-triazole-3,5-diamine was heated on a metal
bath at 125–150°C until gaseous products no longer
evolved. The melt was cooled and treated with ethanol,
and the precipitate was filtered off and recrystallized
from ethanol and acetic acid. Yield 1.19 g (34%),
mp 223–224°C. IR spectrum, ν, cm–1: 1680 (C=O),
(OH), 3200 (NH). H NMR spectrum, δ, ppm: 1.35 t
(3H, CH3), 4.37 q (2H, OCH2), 6.38 s (1H, 5′-H),
8.55 s (1H, 2-H), 7.64 m (10H, Harom), 11.02 s (1H,
OH), 12.80 s (1H, NH). Found, %: C 66.20, 66.22;
H 4.60, 4.62; N 10.17, 10.12. C23H19N3O5. Calculated,
%: C 66.18; H 4.55; N 10.07.
1
1715 (C=O, ester), 3210 (NH, NH2). H NMR spec-
The IR spectra were recorded on a UR-20 spec-
trometer from samples dispersed in mineral oil. The
1H NMR spectra were measured on a Bruker DRX-500
instrument at 500.13 MHz in DMSO-d6.
trum, δ, ppm: 3.20 s (3H, OCH3), 5.30 d (2H, NH2),
6.21 s (1H, 7-H), 7.33 m (10H, H), 10.80 s (1H, NH).
Found, %: C 61.69, 61.75; H 4.60, 4.63; N 20.15,
20.10. C18H16N5O3. Calculated, %: C 61.71; H 4.57;
N 20.05.
REFERENCES
5-(4-Benzoyl-3-hydroxy-2-oxo-5-phenyl-2,5-di-
hydro-1H-pyrrol-1-yl)-1H-imidazole-4-carboxylate
(III) was synthesized in a similar way. Yield 1.29 g
(31%), mp 210–212°C. IR spectrum, ν, cm–1: 1610
(C=O), 1705 (C=O, lactam), 1715 (C=O, ester), 3250
1. Gein, V.L., Gein, L.F., and Tsyplyakova, E.P., Khim.
Geterotsikl. Soedin., 2003, p. 949.
2. Gein, V.L., Gein, L.F., Tsyplyakova, E.P., and Rozo-
va, E.A., Russ. J. Org. Chem., 2003, vol. 39, p. 753.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 3 2008