Benzannulation of 5-methyl-7-phenyl-4,7-dihydrotetrazolo[1,5-a]pyrimidine with chalcones and their synthetic equivalents as a method for the synthesis of tetrazolo[5,1-b]quinazolines

Article abstract of DOI:10.1007/s11172-008-0270-x

Derivatives of tetrahydrotetrazolo[5,1-b]quinazolines were synthesized by the reactions of 5-methyl-7-phenyl-4,7-dihydrotetrazolo[1,5-a]pyrimidine with α,β-unsaturated carbonyl compounds and their synthetic equivalents in methanol in the presence of sodium methoxide. The spontaneous or specifically target oxidation of these derivatives gives rise to aromatic tetrazoloquinazolines. The reaction pathways and mechanisms were discussed. The structures of the resulting compounds were confirmed by IR and ¹H NMR spectroscopy, mass spectrometry, and elemental analysis.

Full text of DOI:10.1007/s11172-008-0270-x

Russian Chemical Bulletin, International Edition, Vol. 57, No. 9, pp. 2005—2010, September, 2008
2005
Benzannulation of 5ꢀmethylꢀ7ꢀphenylꢀ4,7ꢀdihydrotetrazolo[1,5ꢀa]pyrimidine
with chalcones and their synthetic equivalents
as a method for the synthesis of tetrazolo[5,1ꢀb]quinazolines
D. Yu. Sidorenko and V. D. Orlov
V. N. Karazin Kharkov National University,
4 pl. Svobodi, 61077 Kharkov, Ukraine.
Eꢀmail: dmitriy.yu.sidorenko@univer.kharkov.ua; orlov@univer.kharkov.ua
Derivatives of tetrahydrotetrazolo[5,1ꢀb]quinazolines were synthesized by the reactions
of 5ꢀmethylꢀ7ꢀphenylꢀ4,7ꢀdihydrotetrazolo[1,5ꢀa]pyrimidine with α,βꢀunsaturated carbonyl
compounds and their synthetic equivalents in methanol in the presence of sodium methoxide.
The spontaneous or specifically target oxidation of these derivatives gives rise to aromatic
tetrazoloquinazolines. The reaction pathways and mechanisms were discussed. The structures
of the resulting compounds were confirmed by IR and 1H NMR spectroscopy, mass spectromeꢀ
try, and elemental analysis.
Key words: partially hydrogenated tetrazolo[5,1ꢀb]quinazolines, synthesis, cyclocondensaꢀ
tion, heteroaromatization, chalcones.
Scheme 1
Fused azoloazine systems have attracted attention due
primarily to the fact that they are widespread among natuꢀ
ral biologically active compounds.1 For the past several
years, we have developed methods for the synthesis of these
compounds and studied their chemical transformations,
the emphasis being given to partially hydrogenated strucꢀ
tures.2—5
Using arylꢀsubstituted 4,7ꢀdihydroꢀ1,2,4ꢀtriazolo[1,5ꢀa]ꢀ
pyrimidines as examples, it was shown3—5 that the reacꢀ
tions of this class of compounds with α,βꢀunsaturated carꢀ
bonyl compounds and their synthetic equivalents afford
Michael βꢀadducts at position 6 of the bicyclic moiety.
The reaction with the use of 5ꢀmethylꢀsubstituted triazolꢀ
opyrimidine as the substrate is accompanied by the inꢀ
tramolecular cyclocondensation giving rise to tetrahydroꢀ
azoloquinazoline systems.3—5 The degree of hydrogenation
can be varied using different oxidizing agents, thus preparꢀ
ing both dihydro derivatives and their aromatic products5
(Scheme 1).
It is unusal that that the Me group at position 5 of the
dihydropyrimidine ring is involved in the condensation
step of this reaction. It should be noted that this fact reꢀ
mained unexplained.3—5 Since data on the analogous reꢀ
actions with other azoloazine systems are lacking in
the literature, the aim of the present study was to examine
whether this reaction can proceed with 5ꢀmethylꢀ7ꢀpheꢀ
nylꢀ4,7ꢀdihydrotetrazolo[1,5ꢀa]pyrimidine (1), whose
synthesis has been described earlier.6
er for triazolopyrimidine derivatives (by refluxing the comꢀ
ponents in MeOH in the presence of sodium methoxide).4
In our case, this reaction afforded an unidentified mixture
Initially, the reaction of compound 1 with chalcones
2a—g was carried out under the conditions described earliꢀ
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1971—1976, September, 2008.
1066ꢀ5285/08/5709ꢀ2005 © 2008 Springer Science+Business Media, Inc.

2006
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 9, September, 2008
Sidorenko and Orlov
of products and was accompanied by partial resinification.
Most likely, this is associated with the higher πꢀaccepting
ability of the tetrazole ring, which facilitates the side oxiꢀ
dation reactions. In addition, tetrazole derivatives can unꢀ
dergo the Dimroth rearrangement (Scheme 2) giving rise
to isomeric compounds as impurities.7,8
3a—e in moderate and good yields. However, under these
conditions, substantial amounts of fully aromatic comꢀ
pounds 6a—f were isolated as byꢀproducts as well. The
synthesis under inert atmosphere (argon) in the oxygenꢀ
free solvent, which was preliminarily prepared by refluxing
the solvent in an inert gas flow, produced tetrahydro comꢀ
pounds 3a—f in substantially higher yield (compounds
3b—d were obtained as virtually the only reaction prodꢀ
ucts). To the contrary, compounds 6a—e were prepared
as the only products by refluxing the reaction mixtures
in air over a long period of time.
Scheme 2
The electronic character of the substituent in the chalꢀ
cone component is of importance for the final composiꢀ
tion of the reaction products. For example, the reaction of
tetrazolopyrimidine 1 with chalcone 2a performed under
inert atmosphere for 30 min afforded a mixture of tetrahyꢀ
drotetrazoloquinazoline 3a and its aromatization product
6a in a ratio of 60 : 40 (the reaction performed in air gave
these compounds in a ratio of 30 : 70). Under analogous
conditions, the reactions of chalcones containing elecꢀ
tronꢀreleasing substituents (dimethylamino (2d), methoxy
Moderate heating (30—40 °C) of solutions of comꢀ
pounds 1 and 2a—e in MeOH in the presence of sodium
methoxide as the catalyst (Scheme 3) proved to be the
method of choice for the synthesis of target compounds
Scheme 3
Ar = 4ꢀRC6H4, R = H (a), Me (b), OMe (c), NMe2 (d), Cl (e), Br (f), NO2 (g)

Tetrazolo[5,1ꢀb]quinazolines
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 9, September, 2008
2007
(2c), or methyl (2b) groups) gave rise to the products in
the following ratios: 3d : 6d , = 95 : 5, 3c : 6c = 90 : 10, and
3b : 6b = 80 : 20 (in air, the ratios were 40 : 60, 35 : 65, and
50 : 50, respectively). The presence of the electronꢀwithꢀ
drawing substituents Cl or Br (2e or 2f, respectively) leads
to an increase in the percentage of the fully aromatic products
(25 : 75) (without inert atmosphere, the ratio was 10 : 90).
In the case of chalcone 2g containing the nitro group, only
aromatized tetrazoloquinazoline 6g was isolated (even unꢀ
der argon). In other words, the stronger the electronꢀwithꢀ
drawing properties of the substituent R in the chalcone
molecule, the higher the rate of dehydrogenation (oxidaꢀ
tion), the higher the yield of aromatic compounds 6, and
the lower the yield of tetrahydrotetrazoloquinazolines 3.
The ratio of products 3 to 6 was estimated based on the
1H NMR spectra (the presence of characteristic signals)
and liquid chromatography data. Products 3 and 6 were
separated by fractional crystallization from acetone, PriOH,
or their mixture (1 : 1) under inert atmosphere. In most
cases, both groups of compounds (3and 6) were isolated in the
individual state. The presence of intermediate partially arꢀ
omatic products 4 and 5 was confirmed by GLCꢀmass
spectrometry of the substances precipitated from the reaction
mixtures. However, attempts to isolate these intermediates
in the pure form in amounts sufficient for further investiꢀ
gations failed. According to the GLCꢀmass spectrometric
data (an acetonitrile—water mixture, gradient elution),
heating of the reaction mixture containing tetrazolopyriꢀ
midine 1 and chalcone 2a under argon for 20 min resulted
in the formation of four products with molecular masses of
404 (59%), 402 (1%), 402 (2%), and 400 (38%). The startꢀ
ing compounds 1 and 2a were not detected in this mixture.
Unlike the reaction of chalcone 2a, the reactions of its
acetylene analog 7 or 2,3ꢀdibromoꢀ1,3ꢀdiphenylpropanꢀ
1ꢀone (8) with tetrazolopyrimidine 1 in methanol in
the presence of MeONa (a threefold excess of sodium
methoxide was used in the reaction with 8) afforded excluꢀ
sively aromatic product 6a regardless of whether the reacꢀ
tion was performed under inert atmosphere or in air.
Apparently, the reaction of 1 with 7 proceeds by analoꢀ
gy with chalcone through the βꢀaddition and cycloconꢀ
densation. As mentioned above, dihydro product 5a is unꢀ
stable and undergoes fast cyclization to give 6a. The first
step of the reaction of 1 with 8 would be expected to inꢀ
volve dehydrobromination.9,10 The resulting βꢀbromoꢀ
chalcone (2ꢀbromoꢀ1,3ꢀdiphenylpropꢀ1ꢀenꢀ3ꢀone) behaves
analogously to chalcones 2. Thus, the reaction involves
the βꢀaddition and cyclocondensation followed by dehyꢀ
drobromination and dehydrogenation. Moreover, the presꢀ
ence of the bromine atom leads to an increase in the elecꢀ
trophilicity of the βꢀC center of the chalcone molecule,
i.e., results in an increase in the reaction rate. In our opinꢀ
ion, the formation of intermediate propinone 7 under such
mild conditions, which was hypothesized in the study,5 is
hardly probable.
We also performed the target aromatization of comꢀ
pounds 3a—f under the conditions described in the study5
(NBS in PriOH, sodium nitrite and bromine in AcOH). As
a result, we isolated the corresponding aromatic products
6a—f.
The structures of compounds 3a—f and 6a—g were
1
determined by H NMR and IR spectroscopy and mass
spectrometry.
The EI mass spectra of tetrahydrotetrazoloquinazoꢀ
lines 3a—f have the molecular ion peak [M + 1]+ and the
peak [M – 27]+ (extrusion of a nitrogen molecule). The IR
spectra of 3a—f show characteristic stretching bands of the
exocyclic C=C and C=N bonds, whereas the stretching
bands of the C=O group are absent. It is difficult to sepaꢀ
rate the stretching bands of the N—H group because the
latter group is associated and appears as a broadened band
at 3680—3300 cm–1. The 1H NMR spectra are most charꢀ
acteristic for these compounds. These spectra show the
proton signal of the NH group of the pyrimidine ring at
δ 9.8—10.6, which appears as a broadened singlet, an AMX
system of the protons at positions 7 and 8 of the cycloꢀ
hexadiene fragment, as three doublets of doublets (someꢀ
times partially degenerate) at δ 2.5—4.0, a singlet of
the proton at position 9, a weakly split doublet of the proꢀ
ton at position 5 (allylic coupling with one of the protons
of the AMX system), and a multiplet of aromatic protons.
Since compounds 3a—f contain two chiral centers, it could
be expected that the reaction will afford a mixture of diaꢀ
stereomers. However, no doubling of the signals is obꢀ
served in the 1H NMR spectra of these compounds. Hence, it
can be said with confidence that the reaction is diasteꢀ
reoselective.
The mass spectra of fully aromatic products 6a—g have
the molecular ion peak and the peak [M – 28]+. In the
1H NMR spectra, all signals are observed in the region of
aromatic proton resonance, and it is difficult to separate
the characteristic signals.
In our experiments, we varied the ratios of the reagents
and the catalyst and performed the reactions under inert
atmosphere and in air. As mentioned above, this was reꢀ
flected in the ratio of aromatic to partially hydrogenated
products. However, we failed to stop the reaction in the step
giving rise to the β adduct. In all cases, the cyclocondensaꢀ
tion proceeds at high rate. This is surprising taking into
account that the carbonyl group of the dihydrochalcone
fragment of the intermediate β adduct, in our opinion,
should be characterized by moderate activity typical of
aromatic ketones. At the same time, attempts to perform
condensation of the methyl group in compound 1 with
reactive carbonyl compounds, such as phenylglyoxal,
4ꢀnitroꢀ and 4ꢀbromobenzaldehydes, and cinnamaldeꢀ
hyde, failed. Consequently, the cyclocondensation is deꢀ
termined primarily by the intramolecular factor, e.g.,
the spatial proximity of the methyl and carbonyl groups in
the βꢀadduct molecule.

2008
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 9, September, 2008
Sidorenko and Orlov
Scheme 4
5ꢀMethylꢀ7ꢀphenylꢀ4,7ꢀdihydrotetrazolo[1,5ꢀa]pyrimidine
(1).6 A mixture of 5ꢀaminotetrazole (0.85 g, 0.01 mol) and benzꢀ
ylideneacetone (1.46 g, 0.01 mol) in amyl alcohol was refluxed
under argon for 4 h. The solvent was concentrated in vacuo,
the resinous precipitate was washed with PriOH, and white crysꢀ
tals of product 1 were filtered off. The yield was 1.5 g (75%),
m.p. 164—166 °C (cf. lit. data6: m.p. 164—166 °C).
The activation of the methyl groups in azines is the
classical situation. The reaction under study is unusual in
that the methyl group of the partially hydrogenated pyrimꢀ
idine system is involved in this reaction, the activation of
this group being unexpected. In our opinion, this can be
attributed to the fact that tetrazolopyrimidine 1 exists in
solution as an equilibrium imineꢀenamine tautomeric mixꢀ
ture with the enamine tautomer predominating.6 In alkaꢀ
line media, these compounds undergo deprotonation and
their reactions with chalcones afford exclusively the anꢀ
ionic forms A, B, and C in both steps (Scheme 4), which is
also facilitated by the electronꢀwithdrawing effect of the
tetrazole ring. These forms are responsible for the lability
of the hydrogen atoms involved in cyclocondensation and
the fact that it is impossible to isolate the intermediate
Michael adducts.
6,8,9ꢀTriphenylꢀ4,7,8,9ꢀtetrahydrotetrazolo[5,1ꢀb]quinazolꢀ
ine (3a) and its aromatization product (6a). A. A solution of
benzylideneacetophenone (2a) (0.4 g, 0.002 mol) and 5ꢀmethylꢀ
7ꢀphenylꢀ4,7ꢀdihydrotetrazolo[1,5ꢀa]pyrimidine (1) (0.4 g,
0.002 mol) in oxygenꢀfree MeOH (10 mL), to which sodium
(25 mg) was added in advance, was heated under argon to
~30—40 °C for 15 min. The precipitate that formed was filtered
off and successively washed with MeOH and Me2CO. The reꢀ
sulting mixture consisting of 6,8,9ꢀtriphenyltetrahydrotetrazoꢀ
lo[5,1ꢀb]quinazoline (3a, 60%) and 6,8,9ꢀtriphenylꢀ4,7,8,9ꢀtetꢀ
razolo[5,1ꢀb]quinazoline (6a, 40%) was separated by crystallizaꢀ
tion from PriOH. The yield of the crude product was 75%.
Compound 3a. The yield was 0.4 g (50%), a white crystalline
compound, m.p. >300 °C. Found (%): C, 77.47; H, 5.19;
N, 17.43. C26H21N5. Calculated (%): C, 77.40; H, 5.25; N, 17.36.
IR, ν/cm–1: 1668 (C=C—NH), 1608 (C=C). 1H NMR (400 MHz,
DMSOꢀd6—CCl4), δ: 2.65 dd, 1 H, CHAHM, J = 16.0 Hz,
J = 3.3 Hz); 3.30 dd, 1 H, CHAHM, J = 5.0 Hz, J = 16.0 Hz);
3.71 dd, 1 H, CHX, J = 3.3 Hz, J = 5.0 Hz); 6.50 (s, 1 H, CH);
6.62 (d, 1 H, CH, J = 2.5 Hz); 6.81—7.15 (m, 15 H, Ar—H);
10.62 (br.s, 1 H, NH). MS, m/z (Irel (%)): 404 [M + H]+ (100),
402 [M – H]+ (23), 376 [(M – N2) + H]+ (84).
The formation of the ionic forms is additionally supꢀ
ported by the fact that the reaction mixtures turned bright
yellow after the addition of sodium methoxide to a soluꢀ
tion of the starting tetrazolopyrimidine 1 (before the addiꢀ
tion of chalcones 2a—g).
Experimental
The progress of the reactions was monitored and the purity of
the reaction products was checked by TLC on Silufol UVꢀ254
plates using 1 : 1 acetone—hexane or chloroform—hexane mixꢀ
tures and pure chloroform as the eluents.
The 1H NMR spectra were measured on Varian VXꢀ200
Mercury and Bruker DRXꢀ400 instruments operating at 200
and 400 MHz, respectively, with the use of DMSOꢀd6 or
a DMSOꢀd6—CCl4 mixture as the solvent and Me4Si as the inꢀ
ternal standard. The IR spectra were recorded on Specord Mꢀ82
and Specord IRꢀ75 spectrophotometers in KBr pellets.
The EI mass spectra were obtained on Hewlett—Packard
LC/MSD 1100 and Finnigan MAT 4651P mass spectrometers
at 70 eV.
Compound 6a. The yield was 0.17 g (21.5%), a yellow crystalꢀ
line compound, m.p. 188—190 °C Found (%): C, 78.34; H, 4.26;
N, 17.48. C26H17N5. Calculated (%): C, 78.18; H, 4.29; N, 17.53.
1
IR, ν/cm–1: 1575 (C=N), 1594 (C=C). H NMR (400 MHz,
DMSOꢀd6—CCl4), δ: 6.68—7.65 (m, 17 H, Ar—H). MS, m/z
(Irel (%)): 400 [M]+ (100), 372 [M – N2]+ (98).
Compounds 3b—f and 6b—g were synthesized analogously.
8ꢀ(4ꢀMethylphenyl)ꢀ6,9ꢀdiphenylꢀ4,7,8,9ꢀtetrahydrotetrazoꢀ
lo[5,1ꢀb]quinazoline (3b) and its aromatization product 6b. The
yield of the crude product (80 : 20) was 78%.
Compound 3b. The yield was 0.4 g (45%), a white crystalline
compound, m.p. >300 °C. Found (%): C, 77.45; H, 5.64;
N, 16.52. C27H23N5. Calculated (%): C, 77.67; H, 5.55; N, 16.77.
The yields of the target compounds are given for the pure
products (after separation).

Tetrazolo[5,1ꢀb]quinazolines
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 9, September, 2008
2009
IR, ν/cm–1: 1669 (C=C—NH), 1608 (C=C). 1H NMR
(200 MHz, DMSOꢀd6), δ: 2.24 (s, 3 H, Me); 2.61 dd, 1 H,
CHAHM, J = 15.7 Hz, J = 3.4 Hz); 3.23 dd, 1 H, CHAHM,
J = 5.1 Hz, J = 15.7 Hz); 3.62 dd, 1 H, CHX, J= 3.4 Hz, J = 5.1 Hz);
6.46 (s, 1 H, CH); 6.63 (d, 1 H, CH, J = 1.7 Hz); 6.78—7.35
(m, 14 H, Ar—H); 10.10 (br.s, 1 H, NH). MS, m/z (Irel (%)): 418
[M + H]+ (100), 416 [M – H]+ (15), 391 [(M – N2) + H]+ (93).
Compound 6b. The yield was 0.1 g (12%), a yellow crystalline
compound, m.p. 189—191 °C. Found (%): C, 78.49; H, 4.56;
N, 16.88. C27H19N5. Calculated (%): C, 78.43; H, 4.63; N, 16.94.
J = 5.2 Hz, J = 15.8 Hz); 3.61 dd, 1 H, CHX, J = 3.5 Hz,
J = 5.5 Hz); 6.62 (s, 1 H, CH); 6.74 (d, 1 H, CH, J = 1.6 Hz);
6.88—7.50 (m, 14 H, Ar—H); 9.94 (br.s, 1 H, NH). MS,
m/z (Irel (%)): 439 [M + H]+ (98), 436 [M – H]+ (19), 411
[(M – N2) + H]+ (82).
Compound 6e. The yield was 0.35 g (40%), a yellow crystalꢀ
line compound, m.p. 188—190 °C. Found (%): C, 72.06; H, 3.68;
Cl, 8.13; N, 16.11. C26H16ClN5. Calculated (%): C, 71.97;
H, 3.72; Cl, 8.17; N, 16.14. IR, ν/cm–1: 1580 (C=N), 1598 (C=C).
1H NMR (400 MHz, DMSOꢀd6—CCl4), δ: 6.78 (s, 1 H, 7ꢀCH);
6.80—7.45 (m, 15 H, Ar—H). MS, m/z (Irel (%)): 434 [M]+ (92),
408 [M – N2]+ (100).
1
IR, ν/cm–1: 1578 (C=N), 1599 (C=C). H NMR (200 MHz,
DMSOꢀd6), δ: 2.31 (s, 3 H, Me); 6.65—7.54 (m, 15 H, Ar—H);
6.69 (s, 1 H, 7ꢀCH). MS, m/z (Irel (%)): 413 [M]+ (100), 385
[M – N2]+ (94).
8ꢀ(4ꢀMethoxyphenyl)ꢀ6,9ꢀdiphenylꢀ4,7,8,9ꢀtetrahydrotetraꢀ
zolo[5,1ꢀb]quinazoline (3c) and its aromatization product 6c. The
yield of the crude product (90 : 10) was 68%.
8ꢀ(4ꢀBromophenyl)ꢀ6,9ꢀdiphenylꢀ4,7,8,9ꢀtetrahydrotetrazoꢀ
lo[5,1ꢀb]quinazoline (3f) and its aromatization product 6f. The
yield of the crude product (25 : 75) was 74%.
Compound 3f. The yield was 0.15 g (15.5%), a white crystalꢀ
line compound, m.p. >300 °C. Found (%): C, 64.68; H, 4.24; Br,
16.53; N, 14.51. C26H20BrN5. Calculated (%): C, 64.74; H, 4.18;
Br, 16.56; N, 14.52. IR, ν/cm–1: 1670 (C=C—NH), 1610 (C=C).
1H NMR (400 MHz, DMSOꢀd6—CCl4), δ: 2.70 dd, 1 H,
CHAHM, J = 15.4 Hz, J = 3.7 Hz); 3.30 dd, 1 H, CHAHM,
J = 5.2 Hz, J = 15.4 Hz); 3.81 dd, 1 H, CHX, J = 3.7 Hz,
J = 5.2 Hz); 6.40 (s, 1 H, CH); 6.62 (d, 1 H, CH, J = 1.9 Hz);
6.90—7.50 (m, 14 H, Ar—H); 10.50 (br.s, 1 H, NH). MS, m/z
(Irel (%)): 483 [M + H]+ (50), 481 [M + H]+ (52), 479 [M – H]+
(35), 453 [(M – N2) + H]+ (48), 455 [(M – N2) + H]+ (47).
Compound 6f. The yield was 0.36 g (37.6%), a yellow crystalꢀ
line compound, m.p. 188—190 °C. Found (%): C, 65.24; H, 3.41;
Br, 16.53; N, 14.61. C26H16BrN5. Calculated (%): C, 65.28;
H, 3.37; Br, 16.70; N, 14.64. IR, ν/cm–1: 1574 (C=N), 1596 (C=C).
1H NMR (400 MHz, DMSOꢀd6—CCl4), δ: 6.65—7.50 (m, 16 H,
Ar—H). MS, m/z (Irel (%)): 477 [M]+ (50), 479 [M]+ (50), 449
[M – N2]+ (47), 451 [M – N2]+ (45).
Compound 3c. The yield was 0.5 g (50%), a white crystalline
compound, m.p. >300 °C. Found (%): C, 74.45; H, 5.24;
N, 16.27. C27H23N5O. Calculated (%): C, 74.80; H, 5.35;
N, 16.16. IR, ν/cm–1: 1670 (C=C—NH), 1612 (C=C). 1H NMR
(200 MHz, DMSOꢀd6), δ: 2.64 dd, 1 H, CHAHM, J = 15.8 Hz,
J = 3.4 Hz); 3.25 dd, 1 H, CHAHM, J = 5.2 Hz, J = 15.8 Hz);
3.61 (s, 3 H, OMe); 3.75 dd, 1 H, CHX, J = 3.4 Hz, J = 5.2 Hz);
6.52 (s, 1 H, CH); 6.58 (d, 1 H, CH, J = 2.4 Hz); 6.82—7.45
(m, 14 H, Ar—H); 10.21 (br.s, 1 H, NH). MS, m/z (Irel (%)): 434
[M + H]+ (100), 432 [M – H]+ (17), 406 [(M — N2) + H]+ (89).
Compound 6c. The yield was 0.07 g (5%), a yellow crystalline
compound, m.p. 185—187 °C. Found (%): C, 75.54; H, 4.36;
N, 16.38. C27H19N5O. Calculated (%): C, 75.51; H, 4.46; N, 16.31.
1
IR, ν/cm–1: 1580 (C=N), 1601 (C=C). H NMR (200 MHz,
DMSOꢀd6), δ: 3,58 (s, 3 H, OMe); 6.65—7.52 (m, 16 H, Ar—H).
MS, m/z (Irel (%)): 429 [M]+ (100), 401 [M – N2]+ (87).
8ꢀ(4ꢀDimethylaminophenyl)ꢀ6,9ꢀdiphenylꢀ4,7,8,9ꢀtetrahyꢀ
drotetrazolo[5,1ꢀb]quinazoline (3d) and its aromatization prodꢀ
uct 6d. The yield of the crude product (95 : 5) was 70%.
8ꢀ(4ꢀNitrophenyl)ꢀ6,9ꢀdiphenyltetrazolo[5,1ꢀb]quinazoline
(6g). The yield was 0.45 g (50%), a yellow crystalline compound,
m.p. 195—197 °C. Found (%): C, 70.24; H, 3.61; N, 18.68.
C26H16N6O2. Calculated (%): C, 70.26; H, 3.63; N, 18.91.
Compound 3d. The yield was 0.7 g (75%), a yellow crystalline
compound, m.p. >300 °C. Found (%): C, 75.38; H, 5.74;
N, 18.52. C28H26N6. Calculated (%): C, 75.31; H, 5.87; N, 18.82.
IR, ν/cm–1: 1667 (C=C—NH), 1610 (C=C). 1H NMR (200
MHz, DMSOꢀd6), δ: 2.62 (s, 6 H, NMe2); 2.58 dd, 1 H, CHAHM,
J = 16.0 Hz, J = 3.6 Hz); 3.15 dd, 1 H, CHAHM, J = 5.1 Hz,
J = 16.0 Hz); 3.56 dd, 1 H, CHX, J = 3.6 Hz, J = 5.1 Hz); 6.55
(s, 1 H, CH); 6.67 (d, 1 H, CH, J = 1.7 Hz); 6.82—7.40 (m, 14 H,
Ar—H); 10.32 (br.s, 1 H, NH). MS, m/z (Irel (%)): 447.5 [M + H]+
(100), 445 [M – H]+ (12), 419.5 [(M – N2) + H]+ (98).
1
IR, ν/cm–1: 1576 (C=N), 1596 (C=C). H NMR (200 MHz,
DMSOꢀd6), δ: 6.65—7.52 (m, 16 H, Ar—H). MS, m/z (Irel (%)):
445 [M]+ (100), 417 [M – N2]+ (96).
Compound 6a. B. A solution of dibromobenzylideneacetopheꢀ
none (0.6 g, 0.002 mol) and 5ꢀmethylꢀ7ꢀphenylꢀ4,7ꢀdihydrotetꢀ
razolo[1,5ꢀa]pyrimidine (0.4 g, 0.002 mol) in oxygenꢀfree MeOH
(10 mL), to which sodium (50 mg) was added in advance, was
heated to ~30—40 °C using a reflux condenser under argon
for 15 min. The precipitate that formed was filtered off, succesꢀ
sively washed with MeOH and Me2CO, and crystallized from
PriOH. The yield was 68%, a yellow crystalline compound, m.p.
186—190 °C. The spectroscopic data are identical to those deꢀ
scribed above (method A).
Compound 6d. The yield was 0.05 g (5%), a yellow crystalline
compound, m.p. 185—186 °C. Found (%): C, 75.84; H, 5.09;
N, 18.86. C28H22N6. Calculated (%): C, 76.00; H, 5.01; N, 18.99.
1
IR, ν/cm–1: 1582 (C=N), 1598 (C=C). H NMR (200 MHz,
DMSOꢀd6), δ: 2.65 (s, 6 H, NMe2); 6.65—7.54 (m, 16 H, Ar—H).
MS, m/z (Irel (%)): 443 [M]+ (100), 415 [M – N2]+ (74).
8ꢀ(4ꢀChlorophenyl)ꢀ6,9ꢀdiphenylꢀ4,7,8,9ꢀtetrahydrotetrazoꢀ
lo[5,1ꢀb]quinazoline (3e) and its aromatization product 6e. The
yield of the crude product (25 : 75) was 80%.
Compound 3e. The yield was 0.14 g (16%), a white crystalline
compound, m.p. >300 °C. Found (%): C, 71.38; H, 4.74;
Cl, 8.23; N, 15.82. C26H20ClN5. Calculated (%): C, 71.31; H, 4.60;
Cl, 8.10; N, 15.99. IR, ν/cm–1: 1668 (C=C—NH), 1607 (C=C).
1H NMR (400 MHz, DMSOꢀd6—CCl4), δ: 2.68 dd, 1 H,
CHAHM, J = 15.8 Hz, J = 3.5 Hz); 3.22 dd, 1 H, CHAHM,
C. A solution of 1,3ꢀdiphenylpropynone (0.4 g, 0.002 mol)
and 5ꢀmethylꢀ7ꢀphenylꢀ4,7ꢀdihydrotetrazolo[1,5ꢀa]pyrimidine
(0.4 g, 0.002 mol) in oxygenꢀfree MeOH (10 mL), to which
sodium (25 mg) was added in advance, was heated to ~30—40 °C
using a reflux condenser under argon for 15 min. The precipitate
that formed was filtered off, successively washed with MeOH
and Me2CO, and crystallized from PriOH. The yield was 55%,
a yellow crystalline compound, m.p. 187—189 °C. The spectroꢀ
scopic data are identical to those described above (method A).
Fully aromatic tetrazolo[5,1ꢀb]quinazolines 6a—f (general
procedures).

2010
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 9, September, 2008
Sidorenko and Orlov
1. A mixture of 8ꢀarylꢀ6,9ꢀdiphenylꢀ4,7,8,9ꢀtetrahydrotetrꢀ
azolo[5,1ꢀb]quinazoline 3a—f (0.5 mmol) and NBS (0.15 g,
1 mmol) was dissolved in PriOH (10 mL) and refluxed for 30 min.
The crystals of 6a—f that formed were filtered off and recrystalꢀ
lized from PriOH. The yields were 75—85%.
2. A mixture of 8ꢀarylꢀ6,9ꢀdiphenylꢀ4,7,8,9ꢀtetrahydrotetꢀ
razolo[5,1ꢀb]quinazoline 3a—f (0.6 mmol) and sodium nitrite
(0.06 g, 0.7 mmol) was dissolved in AcOH (5 mL) and refluxed
for 1 h. Products 6a—f were precipitated with water and recrysꢀ
tallized from PriOH. The yields were 60—76%.
3. A mixture of 8ꢀarylꢀ6,9ꢀdiphenylꢀ4,7,8,9ꢀtetrahydrotetrꢀ
azolo[5,1ꢀb]quinazoline 3a—f (0.5 mmol) and bromine (0.06 mL,
1 mmol) was dissolved in AcOH (5 mL). The reaction mixture
was refluxed for 1 h and treated with an excess of a concentrated
aqueous sodium hydroxide solution. Products 6a—f that precipiꢀ
tated were filtered off and recrystallized from PriOH. The yields
were 75—85%.
on Aromatic Unsaturated Ketones], Folio, Kharkov, 1998,
148 pp. (in Russian).
3. V. Lipson, S. Desenko, O. Zhikol, A. Kaganovsky, I. Igꢀ
natenko, N. Vorobyova, D. Sidorenko, Int. Conf. "Chemistry
of NitrogenꢀContaining Heterocycles" (CNCHꢀ2003), Kharkꢀ
ov, 2003, p. 20.
4. V. V. Lipson, I. V. Ignatenko, S. M. Desenko, S. V. Shishkiꢀ
na, O. V. Shishkin, S. A. Komykhov, N. V. Logvinenko,
V. D. Orlov, H. Meier, J. Heterocycl. Chem., 2003, 40, 1081.
5. V. V. Lipson, S. M. Desenko, I. V. Ignatenko, O. V. Shishkin,
S. V. Shishkina, Izv. Akad. Nauk, Ser. Khim., 2006, 335 [Russ.
Chem. Bull., Int. Ed., 2006, 55, 345].
6. S. M. Desenko, E. S. Gladkov, S. A. Komykhov, O. V.
Shishkin, V. D. Orlov, Khim. Geterotsikl. Soedin., 2001, 811
[Chem. Heterocycl. Compd., 2001, 37, 811 (Engl. Transl.)].
7. N. N. Kolos, B. V. Paponov, V. D. Orlov, Khim. Geterotsikl.
Soedin., 2003, 310 [Chem. Heterocycl. Compd., 2003, 39, 310
(Engl. Transl.)].
This study was financially supported by the Ukrainian
Foundation for Fundamental Research (Grant No. DFFD
F25.3/032, Contract No. F25/728ꢀ2007, September 3,
2007).
8. N. N. Kolos, B. V. Paponov, V. D. Orlov, M. I. Lvovskaja,
A. O. Doroshenko, O. V. Shishkin, J. Mol. Struct., 2006, 114.
9. Organic Syntheses, Ed. H. Gilman, 2nd ed., John Wiley and
Sons, New York—London, 1944, Coll. Vol. 1.
10. N. N. Kolos, V. D. Orlov, E. Yu. Yur´eva, E. V. Zhidkova,
Khim. Geterotsikl. Soedin., 1993, 1409 [Chem. Heterocycl.
Compd., 1993, 29, 1210 (Engl. Transl.)].
References
1. Kh. M. Shakhidoyatov, in Azotistye geterotsikly i alkaloidy
[Nitrogen Heterocycles and Alkaloids], Eds V. G. Kartsev, G. A.
Tolstikov, IridiumꢀPress, Moscow, 2001, 186 (in Russian).
2. V. D. Orlov, S. M. Desenko, Azageterotsikly na osnove aroꢀ
maticheskikh nepredel´nykh ketonov [Azaheterocycles Based
Received July 25, 2007;
in revised form June 16, 2008