Reactions of ethyl 1-Benzylidene-7a-hydroxy-4-phenyl-6-oxo-oxooctahydro-1H- indene-5-carboxylate and ethyl 5-Benzylidene-4a-hydroxy-1-phenyl-3- oxodecahydronaphthalene-2-carboxylate with 1,2,4-Triazol-3-amine. Synthesis of substituted triazoloquinazolines

Full text of DOI:10.1134/S107042801204029X

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 4, pp. 613–615. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © T.V. Gulai, A.G. Golikov, 2012, published in Zhurnal Organicheskoi Khimii, 2012, Vol. 48, No. 4, pp. 614–615.
SHORT
COMMUNICATIONS
Reactions of Ethyl 1-Benzylidene-7a-hydroxy-4-phenyl-6-oxo-
octahydro-1H-indene-5-carboxylate and Ethyl 5-Benzylidene-
4a-hydroxy-1-phenyl-3-oxodecahydronaphthalene-2-carboxylate
with 1,2,4-Triazol-3-amine. Synthesis of Substituted
Triazoloquinazolines
T. V. Gulai and A. G. Golikov
Chernyshevskii Saratov State University, ul. Astrakhanskaya 83, Saratov, 410012 Russia
e-mail: tania912@mail.ru
Received December 26, 2011
DOI: 10.1134/S107042801204029X
Due to the presence of several reaction centers,
hydroxy oxo derivatives of octahydroindene and deca-
hydronaphthalene may be used as intermediate prod-
ucts in the synthesis of various complex systems. The
1,3-dicarbonyl fragment in their molecules is capable
of being involved in heterocyclizations with difunc-
tional nucleophiles. Reactions of such compounds with
hydrazine and hydroxylamine were studied in suf-
ficient detail [1]. However, only a few data are avail-
able on reactions of their analogs, hydroxyoxocyclo-
hexanecarboxylates, with 3-amino-1,2,4-triazole [2];
the product structure was thoroughly studied using 2D
NMR spectroscopy.
formation of systems with different modes of ring
fusion and different positions of heteroatoms.
By heating equimolar amounts of the reactants at
140–160°C under solvent-free conditions we obtained
previously unknown fused triazoloquinazoline deriva-
tives: 9-benzylidene-6-phenyl-7,8,9,10-tetrahydro-6H-
cyclopenta[g][1,2,4]triazolo[3,4-b]- and -[4,3-a]quin-
azolin-5-ols IIIa and IIIb and 10-benzylidene-6-
phenyl-6,7,8,9,10,11-hexahydrobenzo[g][1,2,4]tri-
azolo[3,4-b]- and -[4,3-a]quinazolin-5-ols IVa and
1
IVb (Scheme 1). The H NMR spectra of the product
mixtures contained double sets of signals from ben-
zylic [6-H, δ 4.68 (IIIa), 4.62 (IIIb), 4.47 (IVa),
4.41 ppm (IVb)] and vinylic protons [9-CH, δ 6.18
(IIIa), 6.35 ppm (IIIb); 10-CH, δ 6.48 (IVa),
6.62 ppm (IVb)]. Signals were assigned to the linear
and angular isomers with account taken of magnetic
anisotropy of the triazole ring.
In the present communication we report on the
reactions of ethyl 1-benzylidene-7a-hydroxy-6-oxo-4-
phenyloctahydro-1H-indene-5-carboxylate (I) and
ethyl 5-benzylidene-4a-hydroxy-3-oxo-1-phenyldeca-
hydronaphthalene-2-carboxylate (II) with 3-amino-
1,2,4-triazole. The presence of several reaction
centers in the substrate and reagent could give rise to
We succeeded in identifying only signals from
major isomers IIIa and IVa in the 13C NMR spectra of
Scheme 1.
Ph
O
O
Ph
6
OH
5
Ph
6
OH
5
3
OEt
N
N4
N
N
Δ
2
N
( )n
( )n
( )n
+
+
1
N
NH2
N
N3
N2
N
N
9 (10)
9 (10)
H
HO
1
Ph
Ph
Ph
I, II
IIIa, IVa
IIIb, IVb
I, III, n = 1; II, IV, n = 2.
613

GULAI, GOLIKOV
614
Scheme 2.
Ph
O
O
Ph
O
Ph
O
N
N
N
Path a
OEt
OEt
NH
OH
HN
OEt
( )n
( )n
( )n
+
N
–H2O
H2N
N
N
N
H
N
HO
HO
HO
N
N
Ph
Ph
Ph
H
Ph
Ph
Ph
OH
EtO
EtO
O–
N
OH
N
N
( )n
( )n
( )n
N
N
–EtOH
–H2O
N
N
N
N
N
N
H
HO
HO
Ph
Ph
Ph
IIIa, IVa
N
Ph
O
Ph
OEt HN
N
N
N
Path b
OEt
N
( )n
( )n
OH H
+
H2N
N
O
O
H
HO
Ph
HO
Ph
Ph
OH
N
Ph
OH
Ph
OH
N
N
N
N
( )n
( )n
( )n
–EtOH
–2H2O
H
N
N
N
N
O–
OH
HO
HO
Ph
Ph
Ph
N
N
N
IIIb, IVb
the product mixtures. The spectra contained, respec-
tively, four and five signals from sp3-carbon atoms,
which indicated that the heterocyclization was accom-
panied by dehydration.
and 0.22 g (2.6 mmol) of 3-amino-1,2,4-triazole was
heated for 60 min at 140–160°C. The crystalline prod-
uct was washed with water and ethanol. Overall yield
0.67 g (66%), light-yellow crystals, mp 242–260°C
1
(decomp.). H NMR spectrum, δ, ppm: 4.68 s and
A probable scheme of formation of isomeric line-
arly and angularly fused triazoloquinazoline deriva-
tives involves initial nucleophilic attack by the primary
amino group of aminotriazole at the ketone (path a) or
ester carbonyl group (path b) in the substrate. The sub-
sequent attack by the pyridine-type nitrogen atom in
the triazole fragment on the other carbonyl carbon
atom leads to the corresponding intramolecular cy-
clization products (Scheme 2).
4.62 s (1H, 6-H), 5.79 br.s (5-OH), 6.18 s and 6.35 s
(1H, 9-CH), 7.14–7.42 m (10H, Harom), 8.14 s and
8.16 s (1H, 3-H). 13C NMR spectrum, δC, ppm: 26.82
(C7), 29.90 (C8), 32.05 (C10), 43.21 (C6), 152.48 (C3).
Found, %: C 76.01; H 5.44; N 14.48. C25H20N4O.
Calculated, %: C 76.51; H 5.14; N 14.28.
10-Benzylidene-6-phenyl-6,7,8,9,10,11-hexahy-
drobenzo[g][1,2,4]triazolo[3,4-b]quinazolin-5-ol
(IVa) and 10-benzylidene-6-phenyl-6,7,8,9,10,11-
hexahydrobenzo[g][1,2,4]triazolo[4,3-a]quinazolin-
5-ol (IVb) were synthesized in a similar way. Yield
63%, mp 227–237°C (decomp.). 1H NMR spectrum, δ,
ppm: 4.47 s and 4.41 s (1H, 6-H), 5.65 br.s (5-OH),
6.48 s and 6.62 s (10-CH), 7.13–7.34 m (10H, Harom),
8.09 s and 8.11 s (1H, 1-H). 13C NMR spectrum, δC,
ppm: 22.76 (C8), 27.29 (C7), 29.11 (C9), 29.23 (C11),
46.67 (C6), 152.24 (C3). Found, %: C 76.53; H 5.75;
N 13.92. C26H22N4O. Calculated, %: C 76.83; H 5.46;
N 13.78.
Heterocyclic systems III and IV consist of four
fused rings, and they can be regarded as structural
analogs of tetracycline antibiotics. Therefore, we plan
to separate the obtained mixtures of isomers with
a view to examine their biological activity.
9-Benzylidene-6-phenyl-7,8,9,10-tetrahydro-6H-
cyclopenta[g][1,2,4]triazolo[3,4-b]quinazolin-5-ol
(IIIa) and 9-benzylidene-6-phenyl-7,8,9,10-tetra-
hydro-6H-cyclopenta[g][1,2,4]triazolo[4,3-a]quinaz-
olin-5-ol (IIIb). A mixture of 1 g (2.6 mmol) of ester I
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 4 2012

REACTIONS OF ETHYL 1-BENZYLIDENE-7a-HYDROXY-4-PHENYL-6-OXOOCTAHYDRO-...
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1
The H and 13C NMR spectra were recorded on
REFERENCES
1
a Varian spectrometer at 400 MHz (for H) using
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Vyssh. Uchebn. Zaved., Ser. Khim. Khim. Tekhnol., 2006,
vol. 49, p. 123.
DMSO-d6 as solvent and TMS as internal reference.
The progress of reactions and the purity of products
were monitored by TLC on Silufol UV-254 plates
[C6H14–(i-Pr)2O–CHCl3, 3:1:1]; spots were visualized
by treatment with iodine vapor or water.
2. Poplevina, N.V., Kuznetsova, A.A., and Kriven’ko, A.P.,
Khim. Geterotsikl. Soedin., 2010, p. 1420.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 4 2012