SYNTHESIS OF SOME 1,2,4-TRIAZOLOQUINAZOLINES BASED ON 4-QUINAZOLYLTHIOSEMICARBAZIDES

Article abstract of DOI:10.1135/cccc19940222

The paper describes the cyclization reactions of substituted 1-(4'-quinazolyl)-4-phenylthiosemicarbazides (Ia - Ie).The thermal intramolecular cyclization gives 2H-1,2,4-triazolo<4,3-c>quinazoline-3-thiones (IIa - IId).Heating of I with HgO gives 3-anilino-1,2,4-triazolo<4,3-c>quinazolines (IIIa - IIIe).The IR ans 1H NMR spectra of the compounds synthesized are presented.

Full text of DOI:10.1135/cccc19940222

222
Spirkova, Stankovsky, Dandarova:
SYNTHESIS OF SOME 1,2,4-TRIAZOLO[4,3-c]QUINAZOLINES
BASED ON 4-QUINAZOLYLTHIOSEMICARBAZIDES
Katarina SPIRKOVA, Stefan STANKOVSKY and Miloslava DANDAROVA
Department of Organic Chemistry,
Slovak Technical University, 812 37 Bratislava, The Slovak Republic
Received November 17, 1992
Accepted June 14, 1993
The paper describes the cyclization reactions of substituted 1-(4′-quinazolyl)-4-phenylthiosemicarb-
azides (Ia – Ie). The thermal intramolecular cyclization gives 2H-1,2,4-triazolo[4,3-c]quinazoline-3-
thiones (IIa – IId). Heating of I with HgO gives 3-anilino-1,2,4-triazolo[4,3-c]quinazolines (IIIa – IIIe).
1
The IR and H NMR spectra of the compounds synthesized are presented.
Derivatives of triazole and quinazoline exhibit a number of interesting biological ef-
fects1,2. With the aim of combining these properties, we described3 – 5 syntheses of
series of 1,2,4-triazolo[4,3-c]quinazolines substituted in both the pyrimidine and benzene
nuclei.
In order to extend the spectrum of these compounds, the present communication
describes syntheses of some 1,2,4-triazolo[4,3-c]quinazoline-3-thiones II and 3-anilino
derivatives III.
The syntheses of both types of compounds started from the chosen 1-(4′-quinazolyl)-
4-phenylthiosemicarbazides Ia – Ie obtained by the reaction of the corresponding 4-hy-
drazinoquinazolines with phenyl isothiocyanate. Similar thiosemicarbazides with a
methyl or aryl group in 2-position are described in ref.6 where also their antituberculo-
static properties are mentioned.
The final thiones IIa – IIe were obtained by the method described by Marckwald7 for
quinoline derivatives. The heating of thiosemicarbazides at their melting points without
solvent results in the condensation with simultaneous splitting off of aniline. Two simi-
lar compounds, viz. 5-phenyl- and 5-(4-pyridyl)-1,2,4-triazolo[4,3-c]quinazoline-3-
thiones were described in the above-mentioned communication6 and their structure was
confirmed by independent synthesis – the reaction of corresponding 4-hydrazinoquina-
zolines with carbon disulfide. The heating of the thiosemicarbazides Ia – Ie with the
yellow mercury(II) oxide gave products identified as the corresponding 2H-3-anilino-
1,2,4-triazolo[4,3-c]quinazolines IIIa – IIIe. Their formation can be described in the
following way: in actual fact, the dehydrosulfurization takes place with the imidoyl-
thiourea – one of the tautomeric forms of thiosemicarbazide I.
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223
The treatment with HgO gives the corresponding imidoylcarbodiimide with exo-
cyclic C=N bond. Such compounds are little stable and easily cyclize, giving (in a
6π-electrocyclic reaction) the above-mentioned triazole skeleton condensed to quina-
zoline. Similar cyclizations were described also for other imidoylheterocumulenes8,9
.
The IR spectra of these compounds show skeletal vibrations as well as the absorption
bands at 3 300 cm−1 characteristic of secondary amines. The corresponding charac-
1
teristic peak appears in H NMR at 8.9 ppm. Interesting is the position of the H-10
proton at 8.2 ppm (i.e. outside the aromatic multiplet at 6.6 – 7.7). A similar phenome-
non is observed also with other quinazoline derivatives having an extended conjugated
system, e.g. with compounds Ia – Ie.
Collect. Czech. Chem. Commun. (Vol. 59) (1994)

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Spirkova, Stankovsky, Dandarova:
Calculated/Found
TABLE I
Characteristic data of synthesized compounds I – III
Formula
(M.w.)
M.p., °C
Yield, %
Compound
% C
% H
5.12
% N
% S
7.76
Ia
C20H21ClN6S
(412.9)85
228 – 229
58.17
20.35
57.92
219 – 221
54.78
223 – 225
61.03
212 – 215
68.27
207 – 209
61.19
124 – 126
52.40
130 – 133
48.33
147 – 149
57.38
223 – 226
65.61
252 – 253
63.27
248 – 250
59.78
253 – 255
65.69
234 – 236
74.98
287 – 290
66.42
5.08
55.00
4.53
61.27
4.79
68.54
4.91
61.38
4.07
52.58
4.35
48.51
3.63
57.50
4.28
65.73
4.01
63.40
4.89
59.92
4.44
65.88
4.72
75.19
4.77
66.66
4.01
20.19
4.61
20.17
4.93
19.87
4.97
18.03
4.21
19.37
4.41
21.72
3.76
21.63
4.32
21.03
4.14
19.02
5.05
22.00
4.50
21.83
4.83
21.39
4.88
19.78
4.06
20.98
7.90
20.25
7.84
20.00
6.39
18.16
8.23
19.52
7.33
21.89
9.86
21.75
9.83
21.17
7.91
19.16
10.82
Ib
C
19H19ClN6OS
(414.9)84
7.72
6.54
8.31
7.45
10.02
9.96
8.08
10.96
–
Ic
C25H24ClN7S
(490.1)92
Id
C
C
C
C
22H19N5S
(385.5)87
Ie
22H18N6O2S
(430.5)89
IIa
IIb
IIc
IId
IIIa
IIIb
IIIc
IIId
IIIe
14H14ClN5S
(319.8)69
13H12ClN5OS
(321.9)98
C19H17ClN6S
(396.9)64
C
C
C
C
16H12N4S
(292.4)79
20H19ClN6
(378.9)65
22.18
–
19H17ClN6O
(380.9)44
22.06
–
–
25H22ClN7
(455.8)64
21.51
–
–
C22H17N5
(351.4)44
22H16N6O2
(396.4)51
19.92
–
–
C
21.20
–
–
Collect. Czech. Chem. Commun. (Vol. 59) (1994)

Short Communication
225
TABLE II
Spectral properties of synthesized compounds I – III
IR spectra, cm−1
Compound
1H NMR, δ ppm
ν(NH) ν(C=N)
ν(C−N)
NH
H-5, resp. H-10
8.28 d
H-Ar
H-Het
Ia
Ib
Ic
Id
Ie
3 338
3 280
3 210
1 615
1 620
1 616
1 620
1 620
1 380
10.13 bs
9.86 s
7.00 – 7.57 m 3.62 m
1.57 m
9.66 s
3 350
3 295
3 190
1 370
1 388
1 385
10.22 bs
9.87 s
8.29 d
7.00 – 7.56 m 3.65 m
9.67 s
3 331
3 294
3 111
10.20 bs
9.87 s
8.29 d
7.00 – 7.58 m 3.81 m
3.24 m
9.70 s
3 360
3 350
3 320
10.27 bs
9.87 s
–
–
6.90 – 8.70 m 2.65 sc
7.20 – 8.60 m 2.65 sc
9.70 s
3 336
3 296
3 272
1 388
10.62 bs
10.20 bs
1 510a
1 310b
IIa
IIb
IIc
–
–
–
1 628
1 635
1 628
1 384
1 380
1 381
10.50 bs
10.00 bs
9.91 bs
–
–
–
6.90 – 8.40 m 1.54 m
3.50 m
6.44 – 8.30 m 3.71 m
3.78 m
6.20 – 8.10 m 3.40 m
3.85 m
IId
–
1 630
1 620
1 361
1 350
10.01 bs
8.86 bs
–
7.20 – 8.60 m 2.60 sc
IIIa
3 304
8.15 m
6.65 – 7.76 m 3.70 m
1.58 m
IIIb
IIIc
3 315
3 280
1 612
1 624
1 365
1 360
8.88 bs
8.88 bs
8.16 m
8.18 m
6.70 – 7.76 m 3.68 m
6.60 – 7.70 m 3.85 m
3.34 m
IIId
IIIe
3 416
3 364
1 616
1 620
1 388
8.89 bs
9.04 bs
8.25 m
8.31 m
6.50 – 7.75 m 2.58 sc
7.10 – 7.75 m 2.59 sc
1 384
1 570a
1 345b
a ν(as) NO2; b ν(s) NO2; c (CH3).
Collect. Czech. Chem. Commun. (Vol. 59) (1994)

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Spirkova, Stankovsky, Dandarova:
EXPERIMENTAL
The IR absorption spectra of synthesized compounds were measured with a Specord M 80 apparatus
1
(Zeiss, Jena) using the KBr technique. The H NMR spectra were measured with a BS 587 A Tesla
spectrometer at the working frequency of 80 MHz using hexadeuteriodimethyl sulfoxide as solvent
and tetramethylsilane as internal reference.
5
The syntheses of starting 4-hydrazinoquinazolines are described elsewhere3 –
.
Substituted 1-(4′-Quinazolyl)-4-phenylthiosemicarbazides Ia – Ie
The respective substituted 4-hydrazinoquinazoline (0.01 mol) was suspended in 100 ml ethanol at
boiling temperature, and a solution of 1.4 g (0.01 mol) phenyl isothiocyanate in 20 ml ethanol was
added through the condenser. After 1 h refluxing, the solution was cooled, and the precipitated crys-
talline solid was collected by filtration and recrystallized from ethanol. Characterization of com-
pounds is given in Tables I and II.
Substituted 2H-1,2,4-Triazolo[4,3-c]quinazoline-3-thiones IIa – IId
The respective substituted 1-(4′-quinazolyl)-4-phenylthiosemicarbazide (0.01 mol) was heated at its
melting temperature without solvent on an oil bath. The obtained melt was dissolved in dioxane,
boiled with charcoal, filtered, and left to stand. The precipitated crystalline solid was purified by
recrystallization from hexane. Characterization of compounds is given in Tables I and II.
Substituted 3-Anilino-1,2,4-triazolo[4,3-c]quinazolines IIIa – IIIe
A mixture of the respective substituted 1-(4′-quinazolyl)-4-phenylthiosemicarbazide (0.01 mol), 4.4 g
yellow HgO, and 20 ml dry dichloroethane was stirred at boiling temperature 1 h, whereafter another
portion of 2.2 g HgO was added and the stirring was continued for another 5 h. The colloidal HgS
precipitated on cooling was separated by filtration, the filtrate was boiled with charcoal, filtered, and
evaporated in vacuum until dry. The evaporation residue was recrystallized from ethyl acetate. Char-
acterization of compounds is given in Tables I and II.
REFERENCES
1. Charusia M. R., Sharma S. K.: Heterocycles 14, 1761 (1980).
2. Susse M., Johne S.: Z. Chem. 21, 431 (1981).
3. Stankovsky S., Sokyrova M.: Collect. Czech. Chem. Commun. 49, 1795 (1984).
4. Stankovsky S., Boulmokh A.: Chem. Papers 43, 433 (1989).
5. Spirkova K., Stankovsky S.: Collect. Czech. Chem. Commun. 56, 1719 (1991).
6. Vereshchagina N. N., Postovskii I. I., Merkalov S. L.: Khim. Geterotsikl. Soedin. 1, 1154 (1965).
7. Marckwald W., Meyer E.: Ber. Dtsch. Chem. Ges. 33, 1885 (1900).
8. Augart K. D., Kresze G., Schonberger N.: Justus Liebigs Ann. Chem. 720, 1457 (1973).
9. Blatter H. M., Lukaszewski H.: Tetrahedron Lett. 1964, 855.
Translated by J. Panchartek.
Collect. Czech. Chem. Commun. (Vol. 59) (1994)