Studies on quinazolines, Part IV: Fused mesoionic heterocycles from 3-amino-2-aryl-4(3H)-quinazolinethiones

Article abstract of DOI:10.1002/hc.10172

The 3-amino-4(3H)-quinazolinethiones 2a-c react with phenyl isothiocyanate in DMF, giving N,N-disubstituted thioureas 3a-c. When 2a-c are treated with phenyl isothiocyanate in dry acetonitrile in the presence of triethylamine, the mesoionic compounds 4a-c are isolated. The methiodide 5a reacts with carbon nucleophiles such as malononitrile and/or ethyl cyanoacetate in the presence of triethylamine to give the corresponding 1,2,4-triazoles 6a,b. On the other hand, compounds 2a-c react with CS₂-K₂CO₃ combination to furnish 1,3,4-thiadiazolo[3,2-c]-4-quinazolinium-2-mercaptides 7a-c. Treatment of the methiodide 8a with malononitrile in the presence of potassium t-butoxide provides a mixture of 2-[2-(2-nitrophenyl)-3H-quinazolin-4-ylidene]malononitrile 9 (24%) and 2-amino-5-(2-nirophenyl)pyrazolo[1,5-c]quinazoline-1-carbonitrile 10 (40%). The reaction between Schiff bases 11 derived from 2a and phenacyl bromide yields 2-benzoyl-1,3,4-thiadiazino[3,2-c]quinazolin-5-ium bromide derivatives 12a,b.

Full text of DOI:10.1002/hc.10172

Heteroatom Chemistry
Volume 14, Number 7, 2003
Studies on Quinazolines, Part IV: Fused
Mesoionic Heterocycles from
3-Amino-2-aryl-4(3H)-quinazolinethiones
A. A. F. Wasfy
Chemistry Department, Faculty of Science, Benha University, Benha, Egypt
Received 8 January 2003; revised 17 March 2003
INTRODUCTION
ABSTRACT: The 3-amino-4(3H)-quinazolinethiones
2a–c react with phenyl isothiocyanate in DMF, giving
N,N-disubstituted thioureas 3a–c. When 2a–c are
treated with phenyl isothiocyanate in dry acetoni-
trile in the presence of triethylamine, the mesoionic
compounds 4a–c are isolated. The methiodide 5a
reacts with carbon nucleophiles such as malonon-
itrile and/or ethyl cyanoacetate in the presence of
triethylamine to give the corresponding 1,2,4-triazoles
6a,b. On the other hand, compounds 2a–c react
with CS2–K2CO3 combination to furnish 1,3,4-
thiadiazolo[3,2-c]-4-quinazolinium-2-mercaptides
7a–c. Treatment of the methiodide 8a with mal-
ononitrile in the presence of potassium t-butoxide
The preparative use of 3-amino-4(3H)-quinazo-
linone derivatives as useful precursors for the
synthesis of five- and six-membered heterocycles
annelated to quinazolines was reported [1] from
this laboratory. Aryl-substituted and heteroaryl-
fused five-membered ring mesoionic heterocycles
possess anti-inflammatory activity [2,3]. In addi-
tion, the chemistry of fused ring mesoionic sys-
tems has not been studied as extensively as mono-
cyclic mesoionic systems [4–6]. In continuation of
our studies on quinazolines [7,8], we thought it
worthwhile to exploit the potential of 3-amino-
4(3H)-quinazolinethione as starting material for the
synthesis of some highly functionalized fused five-
membered mesoionic heterocycles hitherto unre-
ported.
provides
a
mixture of 2-[2-(2-nitrophenyl)-3H-
(24%) and
quinazolin-4-ylidene]malononitrile 9
2-amino-5-(2-nirophenyl)pyrazolo[1,5-c]quinazoline-
1-carbonitrile 10 (40%). The reaction between Schiff
bases 11 derived from 2a and phenacyl bromide yields
2-benzoyl-1,3,4-thiadiazino[3,2-c]quinazolin-5-ium
The general strategy for the synthesis of 3-amino-
4(3H)-quinazolinethione derivatives [9]
2 was
hydrazinolysis of appropriately substituted 4H-3,1-
benzothiazinethiones [10] 1, readily available from
direct thiation of the corresponding 3,1-benzoxazin-
4-one derivatives [11]. Now we report in this paper
a facile synthesis of [1,2,4]triazolo[1,5-c]quinazo-
line derivatives. It is based on the reaction of
anhydro-5-methyl-2-mercapto[1,3,4]thiadiazolo-
[3,2-c]quinazolin-4-ium hydroxide or its methiodide
with n-butylamine or aniline [12]. The formation of
these compounds seems to be strongly dependent on
the nature of the substituent on the quinazoline ring.
Thus, the 3-amino-2-(2-nitrophenyl)-, 2-(4-
tolyl)- or 2-(2-naphthyl)-4(3H)-quinazolinethiones
(2a–c) react with phenyl isothiocyanate at re-
flux temperature in dimethylformamide for 5 h,
ꢀ
C
bromide derivatives 12a,b.
2003 Wiley Periodicals,
Inc. Heteroatom Chem 14:581–586, 2003; Published on-
line in Wiley InterScience (www.interscience.wiley.com).
DOI 10.1002/hc.10172
See A. A. F. Wasfy, Heteroatom Chem. 2003, 14, #, for Part III
of this series.
Correspondence to: A. A. F. Wasfy; e-mail: wasfy588@hotmail.
com.
c
ꢀ
2003 Wiley Periodicals, Inc.
581

582 Wasfy
giving 1-phenyl-3-(2-aryl-4-thioxo-4H-quinazolin-3-
yl)thioureas (3a–c). However, when 2a–c are treated
with phenyl isothiocyanate in dry acetonitrile in the
presence of triethylamine at reflux temperature for
24 h, the mesoionic compounds 4a–c are isolated
as crystalline solids in moderate yields. Compounds
4a–c react with methyl iodide to form 2-methylthio-
5-aryl-1-phenyl[1,2,4]triazolo[1,5-c]quinazolinium
iodides (5a–c) that are obtained as stable crys-
talline solids in excellent yields. When compounds
5a–c are heated at slightly above their melting
points, they are transformed into the mesoionic
compounds 4a–c in near quantitative yields. Com-
pound 5a reacts with carbon nucleophiles such
as malononitrile and ethyl cyanoacetate in the
presence of base to furnish 2-carboethoxy-3-[2-(5-
methylthio-4-phenyl-4H-[1,2,4]triazol-3-yl)phenyla-
mino]-3-(2-nitrophenyl)acrylonitrile (6a) and 2-
{[2-(5-methylthio-4-phenyl-4H-[1,2,4]triazol-3-yl)-
phenylamino]-2-(4-tolyl)methylene}malononitrile
(6b) as crystalline solids in good yields.
Moreover, we previously reported [1] the prepara-
tive use of Schiff bases as open-chain precursors
of functionalized 1,3-thiazolidine-4-one derivatives.
We have now utilized the potential of this type of
starting materials for the synthesis of some new
annelated 1,3,4-thiadiazine derivatives of mesoionic
character. Thus, the N-aminoheterocycle 2a reacts
with aromatic aldehydes, namely benzaldehyde or p-
chlorobenzaldehyde, in the presence of hydrochloric
acid to give 3-(arylideneamino)-2-(2-nitrophenyl)-
3H-quinazoline-4-thiones (11a,b) in good yields.
Aldimines 11a,b reacted with phenacyl bromide
in methanol or ethanol at reflux temperature for
24 h to afford the corresponding 2-benzoyl-3-phenyl-
or 3-(4-chlorophenyl)-6-(2-nitrophenyl)-2H,3H,4H-
1,3,4-thiadiazino[3,2-c]quinazolin-5-ium bromides
(12a,b) as crystalline solids in moderate to good
yields.
The structural assignments of all the compounds
(Schemes 1 and 2) were based on elemental analyses
1
and characteristic IR, H NMR, and mass spectral
It was anticipated that treatment of 2a–c with
carbon disulfide in the presence of a base will
lead to highly reactive isothiocyanate intermedi-
ates via dithiocarbamates, and these would in
turn immediately cyclize to 5-aryl-2-mercapto-1,3,4-
thiadiazolo[3,2-c]quinazolin-4-ium (7a–c). Upon re-
action with methyl iodide in acetone at room tem-
perature, compounds 7a–c undergo S-methylation
to give the corresponding 5-aryl-2-methylthio-1,3,4-
thiadiazolo[3,2-c]quinazolin-4-ium iodide (8a–c). To
be certain that the structural assignments are the
same as that of the methiodides 5a–c prepared
from 3-amino-2-aryl-4(3H)-quinazolinethiones (2a–
c), phenyl isothiocyanate, and methyl iodide, the
same compounds were obtained by unequivo-
cal synthesis involving amination of 8a–c with
aniline [12]. This reaction is similar to that
reported for the conversion of monocyclic 2-
methylthio-1,3,4-thiadiazolium into 2-methylthio-
1,3,4-triazolium [13].
data.
EXPERIMENTAL
Melting points were measured in open capillary
tubes and are uncorrected. IR spectra in KBr were
On the other hand, compound 8a reacts
with malononitrile in the presence of potassium t-
butoxide to furnish a mixture of 2-[2-(2-nitrophenyl)-
3H-quinazolin-4-ylidene]malononitrile (9) and 2-
amino-5-(2-nitrophenyl)pyrazolo[1,5-c]quinazoline-
1-carbonitrile (10, 40%). This latter compound
can be obtained as the only reaction product in
good yield (55%) from 8a, malononitrile, and
triethylamine as base.
Schiff bases have been shown to be highly use-
ful as synthetic intermediates in preparative hetero-
cyclic chemistry. Condensations of homophthalic an-
hydrides with Schiff bases have been the key steps for
synthesizing isoquinolines and indole alkaloids [14].
SCHEME 1

Studies on Quinazolines, Part IV 583
3-Amino-2-(2-nitrophenyl)-, 2-(4-Tolyl)-, or 2-(2-
Naphthyl)-4-(3H)-quinazolinethiones (2a–c)
A solution of thiones 1a–c (0.065 mol) and hy-
drazine hydrate (6.3 ml, 0.13 mol) in ethanol (180 ml)
was refluxed for 5 h. The solid product separated
on cooling was recrystallized from ethanol to give
2a–c.
2a: Yield 14.1 g (73%), mp 169–171◦C (lit. [9] mp
171◦C); IR (cm−1): 3295 and 3182 (NH2), 1620 (C N),
1325 (C S). Found: C, 56.44; H, 3.41; N, 18.62%.
Calcd for C14H10N4O2S: C, 56.37; H, 3.38; N, 18.78%.
2b: Yield 12.4 g (71%), mp 174–176◦C (lit. [9]
mp 175◦C); IR (cm−1): 3340 and 3300 (NH2), 1615
(C N), 1340 (C S). Found: C, 67.42; H, 4.88; N,
15.66%. Calcd for C15H13N3S: C, 67.39; H, 4.90; N,
15.72%.
2c: Yield 14.2 g (72%), mp 170–172◦C (lit. [9]
mp 172◦C); IR (cm−1): 3325 and 3280 (NH2), 1610
(C N), 1318 (C S). Found: C, 72.41; H, 4.21; N,
13.75%. Calcd for C18H13N3S: C, 71.26; H, 4.32; N,
13.85%.
1-Phenyl-3-[2-(2-nitrophenyl)-, 2-(4-Tolyl)-,
or 2-(2-Naphthyl)-4-thioxo-4H-quinazolin-
3-yl]thioureas (3a–c)
SCHEME 2
To a solution of 2a–c (0.004 mol) in dry dimethyl-
formamide (25 ml), phenyl isothiocyanate (0.96 ml,
0.008 mol) was added. The deep red solution was
refluxed for 4 h. After cooling at room tempera-
ture, the mixture was poured into ice/water (25
ml) and the precipitated solid crude recrystallized
from ethanol to yield products 3a–c as crystalline
solids.
recorded on a Shimadzu 470 spectrophotometer and
1H NMR spectra were recorded on a JOEL Fx 90 Q9
MHz (Fourier transform NMR spectrometer) using
TMS as internal reference (chemical shifts δ, ppm).
Mass spectra were recorded on an HP model MS
5988 spectrometer.
3a: Yield 0.93 g (54%), mp 193–195◦C, yellow
plates; IR (cm−1): 3340–3210 (NH), 1600 (C C), 1550
(C N), 1325 (C S); 1H NMR (Me2SO-d6): δ = 7.41–
8.52 (m, 13H, Ar H), 9.20–10.22 (br s, 2H, 2 × NH).
Found: C, 58.40; H, 3.30; N, 16.28%. Calcd for
C21H15N5O2S2: C, 58.18; H, 3.49; N, 16.16%.
2-(2-Nitrophenyl)-, 2-(4-Tolyl)-, or 2-(2-Naphth-
yl)-4H-3,1-benzothiazine-4-thiones (1a–c)
These were prepared from appropriately substi-
tuted 3,1-benzoxazin-4-ones (0.07 mol) and phos-
phorus pentasulphide (0.14 mol) according to liter-
ature [10]. Recrystallization from ethanol furnished
1a–c.
3b: Yield 0.84 g (52%), mp 198–200◦C, yellow
plates; IR (cm−1): 3320–3195 (NH), 1600 (C C), 1570
1
1a: Yield 10.5 g (50%), mp 146–148◦C (lit. [10] mp
147◦C); IR (cm−1): 1618 (C N), 1329 (C S). Found:
C, 55.77; H, 2.60; N, 9.52%. Calcd for C14H8N2O2S2:
C, 55.98; H, 2.68; N, 9.33%.
(C N), 1365 (C S); H NMR (Me2SO-d6): δ = 2.36
(s, 3H, ArCH3), 7.32–8.61 (m, 13H, Ar H), 9.42–
10.38 (br s, 2H, 2 × NH). Found: C, 65.72; H, 4.70;
N, 13.75%. Calcd for C22H18N4S2: C, 65.64; H, 4.51;
N, 13.92%.
1b: Yield 6.6 g (35%), mp 158–160◦C (lit. [10] mp
160◦C); IR (cm−1): 1613 (C N), 1320 (C S). Found:
C, 66.98; H, 4.32; N, 5.28%. Calcd for C15H11NS2: C,
66.88; H, 4.12; N, 5.20%.
3c: Yield 0.96 g (55%), mp 188–190◦C, yel-
low plates; IR (cm−1): 3350–3240 (NH), 1610
(C C), 1570 (C N), 1375 (C S); 1H NMR (Me2SO-
d6): δ = 7.28–8.42 (m, 16H, Ar H), 9.55–10.38 (br
s, 2H, 2 × NH). Found: C, 68.22; H, 4.32; N,
12.91%. Calcd for C25H18N4S2: C, 68.47; H, 4.10; N,
12.77%.
1c: Yield 10.6 g (50%), mp 156–158◦C (lit. [10] mp
157◦C); IR (cm−1): 1595 (C N), 1335 (C S). Found:
C, 70.84; H, 3.82; N, 4.62%. Calcd for C18H11NS2: C,
70.79; H, 3.63; N, 4.59%.

584 Wasfy
(25), 336 (14), 310 (6), 219 (68), 142 (100). Found: C,
54.22; H, 3.82; N, 10.77%. Calcd for C23H19IN4S: C,
54.12; H, 3.75; N, 10.98%.
2,3-Dihydro-5-(2-nitrophenyl)-, 5-(4-Tolyl)-,
or 5-(2-Naphthyl)-1-phenyl-2-thioxo-
[1,2,4]triazolo[1,5-c]quinazolinium (4a–c)
5c: Yield 3.8 g (87%), mp 285–287◦C, yellow
prisms; IR (cm−1): 1628 (C C), 1598 (C N); 1H
NMR (CDCl3 + CF3CO2H): δ = 2.98 (s, 3H, SCH3),
7.35–8.60 (m, 16H, Ar H); MS (70 eV): m/z (%) =
406 (M+ + 2-ICH3, 10), 405 (12), 404 (M+-ICH3, 18),
403 (15), 372 (6), 346 (17), 255 (48), 142 (100). Found:
C, 57.32; H, 3.61; N, 10.18%. Calcd for C26H19IN4S:
C, 57.15; H, 3.50; N, 10.25%.
To a solution of N-aminoheterocycles 2a–c (0.015
mol) in dry acetonitrile (50 ml), phenyl isothio-
cyanate (3.6 ml, 0.03 mol) and triethylamine (4.2 ml,
0.03 mol) were added. The mixture was heated at re-
flux for 25 h. After cooling at room temperature, the
crude product was separated and recrystallized from
chloroform to afford products 4a–c.
4a: Yield 3.7 g (63%), mp 283–285◦C, yellow nee-
dles; IR (cm−1): 1620 (C N), 1355 (polarized C S);
1H NMR (Me2SO-d6): δ = 7.25–8.81 (m, 13H, Ar H);
MS (70 eV): m/z (%) = 399 (M+, 76), 398 (50), 367
(15), 250 (100). Found: C, 63.28; H, 3.33; N, 17.62%.
Calcd for C21H13N5O2S: C, 63.15; H, 3.28; N, 17.53%.
4b: Yield 3.3 g (61%), mp 290–292◦C, pale yellow
needles; IR (cm−1): 2940 (alkyl-H), 1615 (C N), 1362
Thermolysis of Methiodides 5a–c; Alternative
Preparation of 4a–c
The dry iodides 5a–c (0.002 mol) were heated at a
temperature slightly above their melting points un-
der reduced pressure for 40 min. After cooling, the
residues were recrystallized from chloroform to yield
compounds identified to be 4a–c by melting point
and mixed melting point determinations.
1
(polarized C S); H NMR (Me2SO-d6): δ = 2.55 (s,
3H, ArCH3), 7.33–8.74 (m, 13H, Ar H); MS (70 eV):
m/z (%) = 368 (M+, 33), 367 (31), 366 (12), 336 (13),
219 (100). Found: C, 71.62; H, 4.21; N, 15.10%. Calcd
for C22H16N4S: C, 71.72; H, 4.38; N, 15.21%.
4c: Yield 3.5 g (59%), mp 275–277◦C, yellow nee-
dles; IR (cm−1): 1621 (C N), 1358 (polarized C S);
1H NMR (Me2SO-d6): δ = 7.28–8.76 (m, 16H, Ar H);
MS (70 eV): m/z (%) = 406 (M+ + 2, 8), 405 (10), 404
(M+, 22), 403 (24), 372 (17), 255 (100). Found: C,
74.18; H, 3.72; N, 13.99%. Calcd for C25H16N4S: C,
74.23; H, 3.99; N, 13.85%.
2-Carboethoxy-3-[2-(5-methylthio-4-phenyl-
4H-[1,2,4]-triazol-3-yl)phenylamino]-3-
(2-nitrophenyl)acrylonitrile (6a) and
2-{[2-(5-Methylthio-4-phenyl-4H-[1,2,4]triazol-
3-yl)phenylamino]-2-(4-tolyl)-
methylene}malononitrile (6b)
To a well stirred solution of compound 5a (1.1 g,
0.002 mol) in dry acetonitrile (25 ml), the nitriles
(0.0022 mol), namely, malononitrile (0.15 g) and/or
ethyl cyanoacetate (0.23 ml) and triethylamine (0.6
ml, 0.004 mol) were added. The reaction mixture was
refluxed for 24 h. After cooling to room tempera-
ture, the precipitated solid was separated by filtra-
tion and recrystallized from chloroform–ethanol to
furnish 6a,b.
2-Methylthio-5-(2-nitrophenyl)-, 5-(4-Tolyl)-,
or 5-(2-Naphthyl)-1-phenyl-[1,2,4]triazolo-
[1,5-c]quinazolinium Iodides (5a–c)
To a solution of 4a–c (0.008 mol) in dichloromethane
(50 ml), methyl iodide (1 ml, 0.016 mol) was added.
After 20 min, a yellow precipitated solid separates.
The mixture was refluxed for an additional 20 min.
After cooling, the precipitate was collected by filtra-
tion and recrystallized from chloroform to furnish
methiodides 5a–c as crystalline solids.
6a: Yield 0.63 g (66%), mp 254–256◦C, yellow
prisms; IR (cm−1): 3345 (NH), 2215 (C N), 1618
1
(C C), 1588 (C N); H NMR (CDCl3 + CF3CO2H):
δ = 2.88 (s, 3H, SCH3), 7.12–8.24 (m, 13H, Ar H),
9.66 (br s, 1H, NH); MS (70 eV): m/z (%) = 479 (M+,
55), 452 (10), 414 (100). Found: C, 62.71; H, 3.62; N,
20.32%. Calcd for C25H17N7O2S: C, 62.62; H, 3.57; N,
20.45%.
5a: Yield 3.9 g (91%), mp 290–292◦C, yellow
prisms; IR (cm−1): 1624 (C C), 1590 (C N); 1H
NMR (CDCl3 + CF3CO2H): δ = 2.95 (s, 3H, SCH3),
7.14–8.34 (m, 13H, Ar H); MS (70 eV): m/z (%) =
399 (M+-ICH3, 28), 398 (24), 367 (12), 250 (65), 142
(100). Found: C, 48.60; H, 2.72; N, 12.75%. Calcd for
C22H16IN5O2S: C, 48.81; H, 2.98; N, 12.94%.
6b: Yield 0.61 g (58%), mp 262–264◦C, yellow
needles; IR (cm−1): 3310 (NH), 2210 (C N), 1718 (CO
ester), 1616 (C C), 1588 (C N); 1H NMR (CDCl3 +
CF3CO2H): δ = 1.26 (t, 3H, CH3), 2.96 (s, 3H, SCH3),
4.45 (q, 2H, CH2), 7.17–8.42 (m, 13H, Ar H), 9.87 (br
s, 1H, NH); MS (70 eV): m/z (%) = 526 (M+, 30), 453
(25), 414 (100). Found: C, 61.71; H, 4.30; N, 15.84%.
Calcd for C27H22N6O4S: C, 61.59; H, 4.21; N, 15.96%.
5b: Yield 3.5 g (88%), mp 310–312◦C, yellow
prisms; IR (cm−1): 2920 (alkyl-H), 1620 (C C), 1600
1
(C N); H NMR (CDCl3 + CF3CO2H): δ = 2.52 (s,
3H, ArCH3), 2.94 (s, 3H, SCH3), 7.28–8.72 (m, 13H,
Ar H); MS (70 eV): m/z (%) = 368 (M+-ICH3, 30), 367

Studies on Quinazolines, Part IV 585
Calcd for C16H11IN4O2S2: C, 39.84; H, 2.30; N,
11.63%.
5-(2-Nitrophenyl)-, 5-(4-Tolyl)-, or
5-(2-Naphthyl)-2-mercapto-1,3,4-
thiadiazolo[3,2-c]quinazolin-4-ium (7a–c)
8b: Yield 4.1 g (77%), mp 202–204◦C, yellow nee-
dles; IR (cm−1): 2936 (alkyl-H), 1618 (C C), 1602
3-Amino-4-thioquinazolones 2a–c (0.018 mol) were
first suspended in DMF (10 ml). Carbon disulfide was
added when most of the materials had dissolved af-
ter stirring for few minutes at room temperature.
Anhydrous potassium carbonate (4.1 g, 0.03 mol)
was then added to each with continuous stirring
for 30 min at room temperature, after which yel-
low solids separated from the reaction mixture. Af-
ter 4 h, the mixture was poured onto crushed ice and
acidified with acetic acid. The yellow solids were col-
lected, washed with water and then with alcohol, and
then dried. The crude product was finally crystallized
from chloroform–ethanol to furnish 7a–c.
1
(C N); H NMR (CDCl3 + CF3CO2H): δ = 2.42 (s,
3H, ArCH3), 2.97 (s, 3H, SCH3), 7.16–8.61 (m, 8H,
Ar H); MS (70 eV): m/z (%) = 311 (M+ + 2-ICH3, 16),
310 (11), 309 (M+-ICH3, 19), 308 (14), 277 (22), 219
(64), 142 (100). Found: C, 45.27; H, 3.08; N, 9.22%.
Calcd for C17H14IN3S2: C, 45.24; H, 3.13; N, 9.31%.
8c: Yield 4.5 g (78%), mp 210–212◦C, orange–
yellow needles; IR (cm−1): 1628 (C C), 1610 (C N);
1H NMR (CDCl3+ CF3CO2H): δ = 2.99 (s, 3H, SCH3),
7.21–8.42 (m, 11H, Ar H); MS (70 eV): m/z (%) = 347
(M+ + 2-ICH3, 12), 346 (14), 345 (M+-ICH3, 20), 344
(14), 313 (18), 287 (8), 255 (54), 142 (100). Found: C,
49.48; H, 2.71; N, 8.45%. Calcd for C20H14IN3S2: C,
49.29; H, 2.90; N, 8.62%.
7a: Yield 4.8 g (79%), mp 208–210◦C, yellow nee-
dles; IR (cm−1): 1620 (C C), 1604 (C N), 1340 (po-
larized C S); 1H NMR (Me2SO-d6): δ = 7.12–8.42 (m,
8H, Ar H); MS (70 eV): m/z (%) = 340 (M+, 28), 339
(18), 308 (16), 250 (100). Found: C, 52.82; H, 2.22; N,
16.24%. Calcd for C15H8N4O2S2: C, 52.93; H, 2.37; N,
16.46%.
Independent Synthesis of 5a–c
To a solution of 8a–c (0.002 mol) in toluene (20 ml),
aniline (0.23 ml, 0.0025 mol) was added. The reac-
tion mixture was refluxed for 24 h. After cooling
to room temperature, the mixture was kept at 0◦C
overnight. The precipitated solid was collected by fil-
tration and recrystallized from chloroform to yield
a product identified as 5a–c by melting point and
mixed melting point determinations.
7b: Yield 4.1 g (75%), mp 214–216◦C, yellow nee-
dles; IR (cm−1): 2910 (alkyl-H), 1609 (C N), 1355
1
(polarized C S); H NMR (Me2SO-d6): δ = 2.46 (s,
3H, ArCH3), 7.26–8.45 (m, 8H, Ar H); MS (70 eV):
m/z (%) = 309 (M+, 30), 308 (26), 277 (16), 219
(100). Found: C, 62.40; H, 3.41; N, 13.22%. Calcd for
C16H11N3S2: C, 62.11; H, 3.58; N, 13.58%.
Reaction of 8a with Malononitrile
7c: Yield 4.7 g (77%), mp 222–224◦C, yellow nee-
dles; IR (cm−1): 1626 (C C), 1600 (C N), 1336 (po-
larized C S); 1H NMR (Me2SO-d6): δ = 7.33–8.51 (m,
11H, Ar H); MS (70 eV): m/z (%) = 347 (M+ + 2,
12), 346 (8), 345 (M+, 24), 344 (20), 313 (19), 255
(100). Found: C, 66.18; H, 3.32; N, 12.26%. Calcd for
C19H11N3S2: C, 66.06; H, 3.21; N, 12.16%.
Procedure A. To a stirred solution of malonon-
itrile (0.53 g, 0.008 mol) in dry acetonitrile (20
ml), potassium t-butoxide (0.9 g, 0.008 mol) was
added under nitrogen. The resultant solution was
stirred for 20 min at room temperature and a so-
lution of 8a (1.93 g, 0.004 mol) in dry acetonitrile
(20 ml) was added. The reaction mixture was re-
fluxed for 3 h. After cooling to room temperature,
the precipitated solid was collected by filtration,
washed with cooled ethanol (15 ml), and treated
with hot chloroform–benzene [1:1 (w:w)] (30 ml).
The insoluble material was separated by filtration
and recrystallized from ethanol to give 9. The fil-
trate was kept at 0◦C overnight and the precipitated
solid was found to be the 2-amino-5-(2-nitrophenyl)-
pyrazolo[1,5-c]quinazoline-1-carbonitrile (10).
2-Methylthio-5-(2-nitrophenyl)-, 5-(4-Tolyl)-,
or 5-(2-Naphthyl)-1,3,4-thiadiazolo-
[3,2-c]quinazolin-4-ium Iodide (8a–c)
A suspension of the mesoionic compounds 7a–
c (0.012 mol) in acetone (50 ml) containing
iodomethane (1.5 ml, 0.024 mol) was left overnight
at room temperature with occasional swirling. Mild
reflux for 30 min followed by evaporation under wa-
ter pump gave a crude methiodide that recrystallized
from chloroform–ethanol to afford 8a–c.
9: Yield 0.3 g (24%), mp 220–222◦C, yellow
prisms; IR (cm−1): 3260–3140 (NH), 2215–2190
8a: Yield 4.6 g (80%), mp 191–193◦C, orange–
yellow needles; IR (cm−1): 1625 (C C), 1604 (C N);
1H NMR (CDCl3+ CF3CO2H): δ = 2.98 (s, 3H,
SCH3), 7.21–8.44 (m, 8H, Ar H); MS (70 eV):
m/z (%) = 340 (M+-ICH3, 24), 339 (19), 308 (14),
250 (100). Found: C, 39.92; H, 2.45; N, 11.71%.
(C N), 1623 (C C), 1600 (C N); H NMR (CDCl3):
1
δ = 7.34–8.62 (m, 8H, Ar H), 10.81 (br s, 1H, NH);
MS (70 eV): m/z (%) = 316 (M+ + 1, 11), 315 (M+,
65), 314 (22), 289 (32), 288 (4), 251 (100). Found: C,
64.92; H, 2.91; N, 22.42%. Calcd for C17H9N5O2: C,
64.76; H, 2.88; N, 22.21%.

586 Wasfy
10: Yield 0.5 g (40%), mp 241–243◦C, yellow nee-
methanol (25 ml) and the reaction mixture refluxed
for 24 h. The solution was cooled to room tem-
perature, diethyl ether (20 ml) was added, and the
mixture was left at 0◦C overnight. The precipitated
solid was filtered off, dried, and recrystallized from
methanol to furnish 12a,b.
dles; IR (cm−1): 3325 and 3222 (NH2), 2218 (C N),
1630 (C C), 1588 (C N); MS (70 eV): m/z (%) =
330 (M+, 19), 316 (21), 315 (62), 289 (14), 250
(100). Found: C, 61.64; H, 3.28; N, 25.31%. Calcd for
C17H10N6O2: C, 61.82; H, 3.05; N, 25.44%.
12a: Yield 0.7 g (60%), mp 193–195◦C, pale yel-
low; IR (cm−1): 3345 (NH), 1685 (CO), 1600 (C N);
1H NMR (CDCl3): δ = 4.53 (q, 1H, H-3), 6.85 (d,
1H, J = 6.7, H-2), 7.42–8.40 (m, 18H, Ar H), 9.60
(d, 1H, J = 5.6, H-4); MS (70 eV): m/z (%) = 506
(M+−Br, 20), 505 (10), 298 (38), 250 (60), 208 (28),
105 (55), 103 (100). Found: C, 59.32; H, 3.45; N,
9.48%. Calcd for C29H21BrN4O3S: C, 59.49; H, 3.62; N,
9.57%.
Procedure B. To a well stirred solution of mal-
ononitrile (0.15 g, 0.0023 mol) in dry acetonitrile
(15 ml), triethylamine (0.32 ml, 0.0023 mol) and 8a
(0.97 g, 0.002 mol) were added. The reaction mixture
was refluxed for 24 h. After cooling to room tem-
perature, the precipitated solid was collected by fil-
tration and recrystallized from chloroform–benzene
[1:1 (w:w)] to give yellow needles as product in 55%
yield (identified as 10) by melting point and mixed
melting point determinations.
12b: Yield 0.68 g (55%), mp 175–177◦C, pale yel-
low; IR (cm−1): 3362 (NH), 1680 (CO), 1605 (C N);
1H NMR (CDCl3): δ = 4.58 (q, 1H, H-3), 6.77 (d, 1H,
J = 6.7, H-2), 7.33–8.52 (m, 17H, Ar H), 9.64 (d, 1H,
J = 5.6, H-4); MS (70 eV): m/z (%) = 540 (M+−Br,
22), 539 (14), 298 (31), 250 (43), 242 (10), 137
(14), 105 (100). Found: C, 56.28; H, 3.48; N, 9.22%.
Calcd for C29H20BrClN4O3S: C, 56.19; H, 3.25; N,
9.04%.
3-(Arylideneamino)-2-(2-nitrophenyl)-
3H-quinazoline-4-thiones (11a,b)
Aromatic aldehydes (0.0041 mol), namely, benzalde-
hyde (0.41 ml) and/or p-chlorobenzaldehyde (0.58
g) and a catalylic amount of hydrochloric acid were
added to a solution of the N-aminothioquinazolone
2a (1.2 g, 0.004 mol) in methanol (30 ml). The resul-
tant solution was heated at reflux temperature for 45
min after which it was cooled. The precipitated solid
was filtered off, washed with cold methanol, dried,
and crystallized from methanol to furnish 11a,b.
11a: Yield 1.4 g (91%), mp 203–205◦C, yellow
plates; IR (cm−1): 1625 (C C), 1598 (C N), 1410
(C S); 1H NMR (CDCl3): δ = 7.48–8.33 (m, 13H,
Ar H), 10.84 (s, 1H, ylidene H); MS (70 eV): m/z
(%) = 386 (M+, 42), 283 (100), 282 (20), 103 (10),
25. Found: C, 65.38; H, 3.81; N, 14.32%. Calcd for
C21H14N4O2S: C, 65.27; H, 3.65; N, 14.50%.
REFERENCES
[1] Yassin, F. A.; Eissa, A. M. F.; Wasfy, A. A. F. Indian J
Chem 1994, 33B, 1193.
[2] Kamitani, T.; Saito, Y.; Teraji, T. Japanese Patent
7,232,072, 1973; Chem Abstr 1973, 78, 4257.
[3] Kamitani, T.; Saito, Y.; Teraji, T. Japanese Patent
7,232,073, 1973; Chem Abstr 1973, 78, 4259.
[4] Ohta, M.; Kato, H. In Nonbenzenoid Aromatics;
Snyder, J. P. (Ed.); Academic Press: New York, 1969;
Ch. 4.
[5] Talukdar, P. B.; Sengupta, S. K.; Datta, A. K. Indian J
Chem 1976, 14B, 176.
[6] Newton, C. J.; Ramsden, C. A. Tetrahedron 1982, 38,
2965.
[7] Wasfy, A. A. F.; Yassin, F. A.; Eissa, A. M. F. Indian J
Chem 1995, 34B, 537.
[8] Wasfy, A. A. F. Phosphorus Sulfur Silicon 2002, 177,
1349.
[9] Legrand, L.; Lozac’h, N. Bull Soc Chim Fr 1961, 1400.
[10] Legrand, L. Bull Soc Chim Fr 1960, 337.
[11] Bain, D. I.; Smalley, R. K. J Chem Soc C 1968,
1593.
11b: Yield 1.4 g (86%), mp 187–189◦C, yellow
plates; IR (cm−1): 1629 (C C), 1608 (C N), 1420
(C S); 1H NMR (CDCl3): δ = 7.35–8.41 (m, 12H,
Ar H), 10.92 (s, 1H, ylidene H); MS (70 eV): m/z
(%) = 422 (M+ + 2, 10), 420 (M+, 28), 283 (100), 282
(38), 250 (36), 102 (42). Found: C, 59.82; H, 3.22; N,
13.54%. Calcd for C21H13N4O2S: C, 59.93; H, 3.11; N,
13.31%.
[12] Talukdar, P. B.; Sengupta, S. K.; Datta, A. K. Indian J
Chem 1977, 15B, 1110.
[13] Talukdar, P. B.; Sengupta, S. K.; Datta, A. K. Indian J
Chem 1973, 11B, 753.
[14] Govindachari, T. R.; Chinnasamy, P.; Rajeswari, S.;
Chandrasekaran, S.; Premila, S. M.; Natarajan, S.;
Nagarajan, K.; Pai, B. R. Heterocycles 1984, 22,
585.
2-Benzoyl-3-phenyl- or 3-(4-Chlorophenyl)-6-
(2-nitrophenyl)-2H,3H,4H-1,3,4-thiadiazino-
[3,2-c]quinazolin-5-ium Bromides (12a,b)
Phenacyl bromide (0.4 g, 0.002 mol) was added to
a solution of the aldimine 11a,b (0.002 mol) in hot