Mendeleev
Communications
Mendeleev Commun., 2010, 20, 170–171
Synthesis of [1,2,4]triazolo[1,5-a]quinazolines from
7-methyl-5-phenyl-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine
Dmitrii Yu. Sidorenko* and Valerii D. Orlov
V. N. Karazin Kharkov National University, 61077 Kharkov, Ukraine. Fax: +3 057 707 5292;
e-mail: dmitriy.yu.sidorenko@univer.kharkov.ua, orlov@univer.kharkov.ua
DOI: 10.1016/j.mencom.2010.05.016
Tetrahydro- and dihydrotriazolo[1,5-a]quinazolines were prepared by reaction of 7-methyl-5-phenyl-4,7-dihydro[1,2,4]triazolo-
[1,5-a]pyrimidine with chalcone.
During our recent studying of dihydroazolopyrimidines1,2 we
have found3–5 that under basic catalysis C(6)-positioned carbon
atom can act as a nucleophilic centre and add to α,β-unsaturated
ketones to form Michael adducts. Under the same conditions,
[1,2,4]triazolo[1,5-a]dihydropyrimidines3,4 and some other azolo-
azines4,5 bearing the methyl group at the 5-position of six-mem-
bered heterocycle undergo deprotonation at this methyl group
and produce azoloquinazolines as a result of intramolecular cycliza-
tion. Interestingly, 5-methyl-4,7-dihydrotetrazolo[5,1-a]pyrimi-
dines do not react with aldehydes (other type of electrophiles)
at C(5)-Me group.5
In summary, 7-methyl-4,7-dihydro[1,2,4]triazolo[1,5-a]pyri-
midines in the reaction with α,β-enones undergo similar cycliza-
tion like their 5-methyl analogues.
The authors are grateful to Dr. V. I. Musatov and Dr. Ya. I. Sakho
1
for H NMR experiments and to Dr. V. V. Vashenko for registra-
tion of mass spectra.
This work was supported by the Foundation of Fundamental
Researches of Ukraine (grant no. F 25.3/032 of 03.09.07).
†
1
Melting points were determined on a Kofler apparatus. The H NMR
In the present study we have performed a similar reaction of
chalcone with dihydroazolopyrimidine bearing methyl group
at the 7-position (Scheme 1). The required 7-methyl-5-phenyl-
4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine 2 was prepared from
3-aminotriazole 1 and 1-phenylbut-2-en-1-one as described pre-
viously.†,1,2
spectra were recorded at 200 MHz on a Varian Mercury VX-200 spectro-
meter with TMS as an internal standard in [2H6]DMSO. Mass spectra
were taken on a Finnigan MAT 4651P instrument (EI, 70 eV). TLC was
used to monitor the reactions and control the purity of products on Silufol
UV-254; eluents acetone–hexane (1:1), chloroform–hexane (1:1) and
pure chloroform; visualized under UV light or in iodine camera.
7-Methyl-5-phenyl-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine 2. A solu-
tion of aminotriazole 1 (0.1 mol) and 1-phenylbut-2-en-1-one (1 mol) in
20 ml of n-butanol was refluxed for 30–90 min. After cooling, crystals of
triazolopyrimidine 2 were filtered off, washed with methanol and dried.
Yield, 72%. White solid, mp 186–188 °C. IR (KBr, nmax/cm–1): 1680
(C=C–NH), 1614 (C=C). 1H NMR, d: 1.9 (d, 3H, Me, J 8.2 Hz), 4.6 (dd,
1H, CH, J 8.2 Hz, J 6.0 Hz), 6.2 (d, 1H, CH, J 6.0 Hz), 6.8–7.8 (m, 5H,
Ar), 7.9 (s, 1H, CH-triazole), 10.0 (br. s, 1H, NH). MS (EI), m/z (%):
212 (100, M+), 197(18), 171(46), 135(30), 130(26). Found (%): C, 68.12;
H, 5.54; N, 26.12. Calc. for C12H12N4 (%): C, 67.90; H, 5.70; N, 26.40.
Reaction of compound 2 with chalcone in methanol in the
presence of sodium methoxide at 40–50 °C4,5 resulted in a
mixture of two cyclocondensation products 3 and 4, which were
separated by crystallization from propan-2-ol.‡ According to
the elemental and spectral analyses, they have structures of tetra-
1
hydro (3) and dihydro (4) triazoloquinazolines. The H NMR
spectrum of tetrahydrotriazoloquinazoline 3 contained the fol-
lowing characteristic signals: ABX system of protons at 2.8, 3.1,
4.4 ppm (J 14.1, 8.0 and 6.0 Hz), and the AB system of protons
at 5.3 and 6.6 ppm (J 6.0 Hz), assigned to =C(9)H and C(9a)H
protons. The spectrum of dihydrotriazoloquinazoline 4 con-
tained AB system of =C(9)H and C(9a)H protons at 5.4 and
6.6 ppm (J 6.2 Hz), while the signal of =C(7)H overlapped with
aromatic protons in the broad multiplet in the range of 6.9–8.3 ppm.
‡
5,6,8-Triphenyl-4,6,7,9a-tetrahydro[1,2,4]triazolo[1,5-a]quinazoline 3
and 5,6,8-triphenyl-4,9a-dihydro[1,2,4]triazolo[1,5-a]quinazoline 4.
A solution of triazolopyrimidine 2 (0.01 mol) and chalcone (0.01 mol) in
10 ml of methanol containing 0.015 mol of sodium methoxide was refluxed
for 5 min, cooled and filtered. The crystals were washed with methanol
to give 77% of the crude material. Recrystallization from propan-2-ol or
propan-2-ol–DMF (10:1) mixture gave crystals which were washed with
acetone to afford tetrahydrotriazoloquinazoline 3, yield 30%. The mother
liquor was concentrated and recrystallised in the same manner to give
18% of dihydrotriazoloquinazoline 4.
For 3: white solid, mp 238–240 °C. IR (KBr, nmax/cm–1): 1668
(C=C–NH), 1608 (C=C). 1H NMR, d: 2.8 (dd, 1H, CHAHB–CHX, J 14.1 Hz,
J 6.0 Hz), 3.1 (dd, 1H, CHAHB–CHX, J 14.1 Hz, J 8.0 Hz), 4.4 (dd, 1H,
CHAHB–CHX, J 8.0 Hz, J 6.0 Hz), 5.3 (d, 1H, CHA–CHB, J 6.0 Hz), 6.6 (d,
1H, CHA–CHB, J 6.0 Hz), 6.8–8.2 (m, 16H, Ar + CH-triazole), 10 (s, 1H,
NH). MS (EI), m/z (%): 402 (100, M+), 325 (58), 320 (24). Found (%):
C, 80.51; H, 5.54; N, 13.89. Calc. for C27H22N4 (%): C, 80.57; H, 5.51;
N, 13.92.
Me
O
N
N
N
NH
N
Ph
Me
Ph
NH2
N
N
Ph
H
1
2
Ph
O
N
N
N
N
N
Ph
N
Ph
Ph
Ph
For 4: white solid, mp 161–163 °C. IR (KBr, nmax/cm–1): 1589 (C=C),
1592, 1598 (C=C). 1H NMR, d: 5.4 (d, 1H, CHA–CHB, J 6.2 Hz), 6.6 (d,
1H, CHA–CHB, J 6.2 Hz), 6.9–8.3 (m, 17H, Ar + CH-triazole), 10.6 (s,
1H, NH). MS, m/z (%): 400 (M+, 100), 323 (67). Found (%): C, 80.95;
H, 5.08; N, 14.01. Calc. for C27H20N4 (%): C, 80.98; H, 5.03; N, 13.99.
N
Ph
N
Ph
H
H
3
4
Scheme 1
– 170 –
© 2010 Mendeleev Communications. All rights reserved.
Sidorenko, Dmitrii Yu.
