Studies on quinazolines. Part III. Synthesis of some fused-ring cationic and mesoionic derivatives of the 1,3-thiazolo[3,2-c]quinazoline ring system

Article abstract of DOI:10.1080/10426500390221078

4-Allylthio-2-arylquinazolines 4a-c undergo cyclization by action of bromine to furnish 5-aryl-3-bromomethyl-2,3-dihydrothiazolo[3,2-c]quinazolin-4- ium bromide 5a-c. Compounds 5a-c undergo ring opening by action of water under acid catalysis to afford th

Full text of DOI:10.1080/10426500390221078

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Studies on Quinazolines. Part III. Synthesis of Some
Fused-Ring Cationic and Mesoionic Derivatives of the
1,3-Thiazolo[3,2-c]quinazoline Ring System
A.A. F. Wasfy a
a Benha University , Benha, Egypt
Published online: 23 Aug 2006.
To cite this article: A.A. F. Wasfy (2003) Studies on Quinazolines. Part III. Synthesis of Some Fused-Ring Cationic and
Mesoionic Derivatives of the 1,3-Thiazolo[3,2-c]quinazoline Ring System, Phosphorus, Sulfur, and Silicon and the Related
Elements, 178:9, 1901-1910, DOI: 10.1080/10426500390221078
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Phosphorus, Sulfur, and Silicon, 178:1901–1910, 2003
ꢀC
Copyright Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500390221078
STUDIES ON QUINAZOLINES. PART III. SYNTHESIS
OF SOME FUSED-RING CATIONIC AND MESOIONIC
DERIVATIVES OF THE
1,3-THIAZOLO[3,2-c]QUINAZOLINE RING SYSTEM
A. A. F. Wasfy
Benha University, Benha, Egypt
(Received October 2, 2002; accepted February 25, 2003)
4-Allylthio-2-arylquinazolines 4a–c undergo cyclization by action
of bromine to furnish 5-aryl-3-bromomethyl-2,3-dihydrothiazolo[3,2-
c]quinazolin-4-ium bromide 5a–c. Compounds 5a–c undergo ring
opening by action of water under acid catalysis to afford the
corresponding dibromide derivatives 6a–c. Bromination of 3-allyl-2-
aryl-4(3H)quinazolinethiones 7a–c leads to 5-aryl-2-bromomethyl-2,3-
dihydrothiazolo[3,2-c]quinazolin-4-ium bromides 8a–c. However, 5-
aryl-1,3-thiazolo[3,2-c]quinazolinium-3-olate 10a–c were prepared by
the cyclodehydration of the corresponding thioglycolic acids 9a–c with
Ac2O.
Keywords: Annelated quinazoline derivatives; fused cationic and
mesoionic heterocycles; 1,3-thiazolo[3,2-c]quinazoline derivatives
We previously reported1 the synthesis of bridgehead nitrogen hetero-
cycles of neutral character which contain the quinazoline moiety, e.g., 3-
oxo-2H-imidazo[1,2-c]- and 4-oxo-2H,3H-pyrimido[1,2-c]quinazolines.
In this context we communicate here the synthesis of some new cationic
or mesoionic annelated derivatives of the thiazolo[3,2-c]quinazoline
ring system based on quinazoline-4(3H)-thione. In continuation of our
ꢀ
studies on phenomena of a thione
thiol tautomeric equilibrium in
ꢁ
heterocyclic diazines, in particular, in the quinazoline-4(3H)-thione1
and pyrimidine-2(1H)-thione2 series, we have now investigated for the
first time the behavior of the quinazoline-4(3H)-thione derivatives 3a–c
toward unsaturated alkylating reagents under different reaction con-
ditions in order to obtain more precise information about the course of
the reaction. We also have prepared the S- and N-unsaturated alkyl
Address correspondence to A. A. F. Wasfy, Chemistry Department, Faculty of Science,
Benha University, Benha, Egypt.
1901

1902
A. A. F. Wasfy
derivatives with the aim of using them as starting material for the
synthesis of the title compounds.
Accordingly, three representative members of quinazoline-4(3H)-
thiones3 3 (R = benzyl, 2-chlorophenyl, 2-naphthyl) were selected
for the present investigation and these were conveniently pre-
pared by heating of the corresponding 4H-3,1-benzothiazine-4-thiones4
2, readily available from direct thionation of 3,1-benzoxazin-4-one
derivatives5 1, with formamide at 150◦C. Now we report in this
paper the synthesis of otherwise not available cationic derivatives
of the thiazolo[3,2-c]quinazoline ring system. It has been briefly
mentioned,6,7 that thiazolo[3,2-c]quinazolinum cations are interme-
diates in the preparation of 2-(o-aminophenyl)-thiazoles from 2-(4-
quinazolinylthio)acetophenones and perchloric acid or phosphoryl
chloride.
It is worth mentioning that the rational approach for the prepara-
tion of thiazolo[3,2-c]quinazolinium cations is based on the cyclization of
S- and N-allyl derivatives 4a–c and 7a–c of quinazoline-4(3H)-thiones
3a–c. In this type of compounds the allylic side-chain can provide
a secondary carbenium ion at a carbon center appropriately located
for an attack at N-3 or at the exocyclic sulfur to form the thiazole
ring.
As alkylation in other heterocyclic thioureas with an exocyclic thiono
function proceeds at the sulfur atom, similarly, 4-(allylthio)-2-benzyl-,
2-(2-chlorophenyl)- or 2-(2-naphthyl)quinazolines (4a–c) are obtained
in excellent yields from 2-benzyl-, 2-(2-chlorophenyl)- or 2-(2-naphthyl)-
4(3H)-quinazolinethiones (3a–c) and allyl bromide in the presence
of triethylamine. Compounds 4a–c undergo ring closure by action of
bromine in glacial acetic acid at room temperature to furnish the
corresponding 3-(bromomethyl)-5-benzyl, 5-(2-chlorophenyl)- or 5-(2-
naphthyl)-2,3-dihydrothiazolo[3,2-c]-quinazolin-4-ium bromide (5a–c)
in good yield. The conversion of 4a–c to 5a–c presumably involves initial
formation of a bromonium ion. Subsequent cyclization by intramolecu-
lar nucleophilic attack of the N-3 of the quinazoline ring would give
the corresponding 2,3-dihydrothiazolo[3,2-c]quinazolinium bromide
5a–c.
Compounds 5a–c undergo ring opening of the thiazole moi-
ety by action of water under acid catalysis to furnish the cor-
responding 2-benzyl-, 2-(2-chlorophenyl)-, or 2-(2-naphthyl)-4-[(2,3-
dibromopropyl)thio]quinazolines (6a–c) in moderate yields. The
formation of 6a–c proceeds via initial nucleophilic attack of wa-
ter at position 3 of the 2,3-dihydrothiazole ring followed by nucle-
ophilic attack of the bromide anion on the open-chain bromohydrine to
give 6a–c. Unfortunately, attempts to prepare the N-allyl derivatives

Studies on Quinazolines. Part III
1903
7a–c, by direct allylation of quinazoline-4(3H)-thiones 3a–c, is im-
peded by the preferencial reactivity of the sulfur atom with the
alkylating reagent. Therefore, we have prepared the regioisomers of
5a–c, 3-allyl-2-benzyl-, 2-(2-chlorophenyl)- and 2-(2-naphthyl)-4(3H)-
quinazolinethiones (7a–c) in good yields by the reaction of 2-benzyl-,
2-(2-chlorophenyl)- and 2-(2-naphthyl)-4H-3,1-benzothiazine-4-thiones
(2a–c) with allylamine. In agreement with the previously reported
results,8 bromination of 7a–c in acetic acid solution at room tem-
perature gave 2-(bromomethyl)-5-benzyl-, 5-(2-chlorophenyl)- and 5-(2-
naphthyl)-2,3-dihydrothiazolo[3,2-c]quinazolin-4-ium bromides (8a–c)
in good yields.
A variety of monocyclic mesoionic compounds are known,9 but
derivatives containing fused mesoionic rings are less common, espe-
cially those with the second ring being heteroaromatic.10 We have
now attempted to synthesize some fused-ring mesoionic systems
based on 4(3H)-quinzolinethiones. Our approach to the prepara-
tion of mesoionic 5-benzyl-, 5-(2-chlorophenyl)-, and 5-(2-naphthyl)-
1,3-thiazolo[3,2-c]quinazolinium-3-olates (10a–c) is based on the
cyclization of 2-benzyl-, 2-(2-chlorophenyl- and 2-(2-naphthyl)-4-
(carboxymethylthio)quinazolines (9a–c).
Thus, the condensation of 2-benzyl-, 2-(2-chlorophenyl)- and 2-(2-
naphthyl)-4(3H)-quinazolinethiones (3a–c) with bromoacetic acid un-
der basic condition readily gave the corresponding carboxymethylthio
derivatives 9a–c in fair yields, and these were smoothly converted into
the corresponding mesoionic compounds 10a–c by treatment with acetic
anhydride in the presence or absence of triethylamine.
The structural assignments of all the compounds (Scheme 1) were
based on elemental analyses and characteristic IR and 1H NMR
spectral data.
EXPERIMENTAL
Melting points were taken in open capillary tubes and are uncorrected.
IR spectra in KBr were recorded on a Shimadzu 470 spectrophotometer
and 1H NMR spectra were recorded on a JEOL Fx 90 Q9 MHz (Fourier
transform NMR spectrometer) using TMS as internal reference (chem-
ical shifts are expressed as δ, ppm). Mass spectra were recorded on an
HP Model MS 5988 spectrometer.
2-Benzyl-, 2-chlorophenyl- and 2-naphthyl-4H-3,1-benzothiazine-4-
thiones (2a–c) were prepared from 1a–c (0.07 mmol) and phosphorus
pentasulfide (0.14 mmol) according to the literature.4 Recrystallization
from benzene furnished 2a–c.

1904
A. A. F. Wasfy
SCHEME 1
2a: yield 5.6 g (30%), m.p. 147–149◦C (lit.4 m.p. 148◦C); IR
(cm−1): 2910 (alkyl-H), 1620 (C N), 1325 (C S). Found: C, 66.92;
H, 4.38; N, 5.42%. Calcd for C15H11NS2: C, 66.88; H, 4.12; N,
5.20%.

Studies on Quinazolines. Part III
1905
2b: yield 8.7 g (43%), m.p. 144–146◦C (lit.4 m.p. 145◦C); IR (cm−1):
1615 (C N), 1310 (C S). Found: C, 58.30; H, 2.82; N, 4.91%. Calcd for
C14H8CINS2: C, 58.02; H, 2.78; N, 4.83%.
2c: yield 10.6 g (50%), m.p. 155–157◦C (lit.4 m.p. 157◦C); IR (cm−1):
1610 (C N), 1295 (C S). Found: C, 70.84; H, 3.82; N, 4.62%. Calcd for
C18H11NS2: C, 70.79; H, 3.63; N, 4.59%.
2-Benzyl-, 2-chlorophenyl- and 2-naphthyl-4(3H )-
quinazolinethiones (3a–c)
A mixture of 2a–c (0.024 mmol) and formamide (1.2 ml, 0.03 mmol) was
heated in an oil bath at 150◦C for 4 h. The resulting solid product was
cooled and crystallized from ethanol to furnish 3a–c.
3a: yield 3.6 g (59%), m.p. 220–222◦C (lit.3 m.p. 221◦C); IR (cm−1):
3300–3240 (NH), 2960 (alkyl-H), 2560 (SH), 1625 (C C), 1260 (C S);
1H NMR (CDCl3): δ = 3.36 (s, 2H, CH2Ph), 7.11–8.74 (m, 9H, Ar-H and
quinazoline ring), 9.52 (s, 1H, NHC S, ratio 55.8), 11.14 (s, 1H, SH,
ratio 44.2). Found: C, 71.48; H, 4.82; N, 11.22%. Calcd for C15H12N2S:
C, 71.40; H, 4.79; N, 11.10%.
3b: yield 3.7 g (57%), m.p. 204–206◦C (lit.3 m.p. 206◦C); IR (cm−1):
3340–3210 (NH), 2550 (SH), 1615 (C C), 1255 (C S). Found: C, 61.71;
H, 3.39; N, 10.20%. Calcd for C14H9CIN2S: C, 61.65; H, 3.33; N, 10.27%.
3c: yield 3.8 g (55%), m.p. 219–220◦C (lit.3 m.p. 219.5◦C); IR (cm−1):
3280–3170 (NH), 2570 (SH), 1618 (C C), 1250 (C S). Found: C, 74.87;
H, 4.22; N, 9.94%. Calcd for C18H12N2S: C, 74.97; H, 4.19; N, 9.71%.
4-Allylthio-2-benzyl-, 2-(2-chlorophenyl)-
and 2-(2-naphthyl)quinazolines (4a–c)
To a solution of the appropriate thione 3a–c (8 mmol) in benzene (50 ml),
triethylamine (1.2 ml, 8.6 mmol) and allyl bromide (0.7 ml, 8.3 mmol)
were added; after 4 h of heating under reflux, triethylammonium
bromide was deposited. After cooling, the salt was separated by filtra-
tion and the filterate concentrated to dryness to afford a crude product
which was recrystallized from ethanol to give 4a–c.
4a: yield 2.1 g (90%), m.p. 71–73◦C, yellow needles; IR (cm−1): 2920,
1539, 1480, 1447, 1340, 1313, 990, 927, 860, 770, 765; 1H NMR (CDCl3):
δ = 3.32 (s, 2H, CH2Ph), 4.10 (d, 2H, J = 7.1 Hz, SCH2), 5.18–5.74 (m,
2H, CH CH2), 5.90–6.55 (m, 1H, CH CH2), 7.28–8.60 (m, 9H, Ar-H);
MS (70 eV): m/z (%) = 293 (M+ +1) (18), 292(M+) (38), 291 (100). Found:
C, 73.81; H, 5.34; N, 9.62%. Calcd for C18H16N2S: C, 73.94; H, 5.52; N,
9.58%.

1906
A. A. F. Wasfy
4b: yield 2.2 g (88%), m.p. 64–66◦C, yellow needles; IR (cm−1): 1590,
1584, 1475, 1360, 1340, 1200, 1080, 1019, 960, 817, 760, 710; 1H
NMR (CDCl3): δ = 4.22 (d, 2H, J = 7.1 Hz, SCH2), 5.10–5.66 (m, 2H,
CH CH2), 5.80–6.44 (m, 1H, CH CH2), 7.42–8.34 (m, 8H, Ar-H); MS
(70 eV): m/z (%) = 314 (M+ + 2) (17), 313 (40), 312 (M+) (36), 311 (100).
Found: C, 65.20; H, 4.24; N, 8.88%. Calcd for C17H13ClN2S: C, 65.27; H,
4.19; N, 8.96%.
4c: yield 2.3 g (87%), m.p. 85–87◦C, yellow needles; IR (cm−1): 1620,
1558, 1530, 1480, 1382, 1300, 1250, 1107, 990, 907, 830, 790, 755;
1H NMR (CDCl3): δ = 4.20 (d, 2H, J = 7.1 Hz, SCH2), 5.12–5.62 (m,
2H, CH CH2), 5.92–6.66 (m, 1H, CH CH2), 7.44–8.42 (m, 11H, Ar-H);
MS (70 eV): m/z (%) = 329 (M+ + 1) (11), 328 (M+) (36), 327 (100). Found:
C, 76.74; H, 4.68; N, 8.64%. Calcd for C21H16N2S: C, 76.80; H, 4.91; N,
8.53%.
3-Bromomethyl-5-benzyl-, 5-(2-chlorophenyl)- and 5-(2-
naphthyl)-2,3-dihydrothiazolo[3,2-c]quinazolin-4-ium
Bromide 5a–c
A solution of bromine (1 g, 6.3 mmol) in acetic acid (20 ml) was added
dropwise to a well-stirred solution of the appropriate quinazoline 4a–c
(6 mmol) in the same solvent (20 ml) at room temperature. When the
addition was completed, the yellow precipitate which gradually sepa-
rated during the reaction, was filtered off, washed several times with
diethyl ether and crystallized from ethanol to furnish 5a–c.
5a: yield 1.7 g (64%), m.p. 192–194◦C, colorless needles; IR (cm−1):
2940, 1610, 1590; 1576, 1559, 1489, 1425, 1400, 1342, 1290, 1170, 1050,
960, 886, 850, 718, 660; 1H NMR (CDCl3 + CF3CO2H): δ = 3.25–3.65 (m,
with interference, 4H, CH2Br and CH2Ph), 4.04–4.84 (m, 2H, SCH2),
6.25–6.85 (m, 1H, CHCH2Br), 7.40–8.50 (m, 9H, Ar-H); MS (70 eV): m/z
(%) = 373 (M+ + 2) (6), 371 (M+) (8), 219(100). Found: C, 47.94; H, 3.67;
N, 6.28%. Calcd for C18H16Br2N2S: C, 47.81; H, 3.57; N, 6.19%.
5b: yield 1.7 g (62%), m.p. 176–178◦C, yellow needles; IR (cm−1):
2935, 1610, 1590; 1560, 1500, 1440, 1400, 1309, 1290, 1140, 1082, 1012,
950, 880, 760, 685; 1H NMR (CDCl3 + CF3CO2H): δ = 3.35–3.68 (m, 2H,
CH2Br), 3.95–5.04 (m, 2H, SCH2), 6.40–6.90 (m, 1H, CHCH2Br), 7.28–
8.45 (m, 8H, Ar-H); MS (70 eV): m/z (%) = 393 (M+ + 2) (4), 391 (M+) (5),
239 (100). Found: C, 43.42; H, 2.88; N, 5.66%. Calcd for C17H13Br2ClN2S:
C, 43.20; H, 2.77; N, 5.93%.
5c: yield 1.7 g (60%), m.p. 223–225◦C, yellow needles; IR (cm−1):
2960, 1625, 1560; 1546, 1480, 1410, 1370, 1340, 1248, 1170, 1040, 990,
830, 790, 730, 625; 1H NMR (CDCl3 + CF3CO2H): δ = 3.32–3.70 (m,
2H, CH2Br), 3.90–4.89 (m, 2H, SCH2), 6.30–6.78 (m, 1H, CHCH2Br),

Studies on Quinazolines. Part III
1907
7.22–8.32 (m, 11H, Ar-H); MS (70 eV): m/z (%) = 409 (M++2) (8),
407 (M+) (5), 255 (100). Found: C, 51.94; H, 3.60; N, 5.88%. Calcd for
C21H16Br2N2S: C, 51.66; H, 3.30; N, 5.74%.
2-Benzyl-, 2-(2-chlorophenyl)- and 2-(2-naphthyl)-
4-[(2,3-dibromopropyl)thio]quinazolines (6a–c)
A solution of the appropriate bromide 5a–c (2.5 mmol) in acetic
acid/water (60 ml, 2:1, V/V) was stirred at room temperature for 6 h.
The solution was poured into ice and the resultant precipitated solid
was separated by filtration, washed with water, and recrystallized from
acetone to give 6a–c.
6a: yield 0.47 g (42%), m.p. 114–116◦C, colorless needles; IR (cm−1):
2950, 1618, 1558; 1544, 1480, 1442, 1344, 1318, 1255, 1190, 1030, 994,
860, 840, 772, 658; 1H NMR (CDCl3): δ = 3.34 (s, 2H, CH2Ph), 3.75–4.45
(m, 4H, CH2CHBrCH2Br), 4.58–5.12 (m, 1H, CHBr), 7.35–8.65 (m, 9H,
Ar-H); MS (70 eV): m/z (%) = 452 (M+ + 2) (7), 450 (M+) (4), 219 (100).
Found: C, 47.94; H, 3.78; N, 6.49%. Calcd for C18H16Br2N2S: C, 47.81;
H, 3.57; N, 6.19%.
6b: yield 0.47 g (40%), m.p. 128–130◦C, colorless needles; IR (cm−1):
2935, 1618, 1585, 1565, 1542, 1530, 1450, 1401, 1342, 1318, 1250, 1170,
1082, 1030, 871, 792, 735, 700; 1H NMR (CDCl3): δ = 3.82–4.28 (m, 4H,
CH2CHBrCH2Br), 4.45–4.95 (m, 1H, CHBr), 7.27–8.54 (m, 8H, Ar-H);
MS (70 eV): m/z (%) = 474 (M+ + 4) (4), 472 (M+ + 2) (8), 470 (M+) (5),
239 (100). Found: C, 43.42; H, 2.93; N, 5.79%. Calcd for C17H13Br2ClN2S:
C, 43.20; H, 2.77; N, 5.93%.
6c: yield 0.53 g (44%), m.p. 134–136◦C, colorless needles; IR (cm−1):
2970, 1625, 1560; 1540, 1501, 1456, 1349, 1262, 1160, 1020, 840, 780,
1
718, 685; H NMR (CDCl3): δ = 3.66–4.37 (m, 4H, CH2CHBrCH2Br),
4.45–4.82 (m, 1H, CHBr), 7.39–8.66 (m, 11H, Ar-H); MS (70 eV): m/z
(%) = 488 (M+ + 2) (10), 486 (M+) (7), 255 (100). Found: C, 51.88; H,
3.60; N, 5.89%. Calcd for C21H16Br2N2S: C, 51.66; H, 3.30; N, 5.74%.
3-Allyl-2-benzyl-, 2-(2-chlorophenyl)- and
2-(2-naphthyl)-4(3H )-quinazolinethiones (7a–c)
To a suspension of the appropriate 1,3-benzothiazine-4(H)-thione 2a–c
(8 mmol) in ethanol (50 ml), allylamine (0.7 ml, 9.4 mmol) was added.
The reaction mixture was refluxed for 2 h. After cooling at 0◦C the yellow
precipitated solid was collected by filtration and the crude product was
recrystallized from ethanol to give 7a–c.
7a: yield 1.8 g (77%), m.p. 110–112◦C, yellow needles; IR (cm−1): 2965,
1
1575, 1520; 1470, 1350, 1330, 1210, 940, 910, 850, 760, 650; H NMR

1908
A. A. F. Wasfy
(CDCl3): δ = 3.38 (s, 2H, CH2Ph), 4.70–5.60 (m, 4H, CH2 CH CH2),
5.90–6.50 (m, 1H, CH CH2), 7.18–8.22 (m, 9H, Ar-H); MS (70 eV): m/z
(%) = 292 (M+) (25), 219 (100). Found: C, 73.80; H, 5.58; N, 9.46%. Calcd
for C18H16N2S: C, 73.94; H, 5.52; N, 9.58%.
7b: yield 2 g (80%), m.p. 115–117◦C, yellow needles; IR (cm−1): 1620,
1560, 1540; 1480, 1420, 1338, 1080, 1000, 990, 880, 790, 730, 690;
1H NMR (CDCl3): δ = 4.72–5.58 (m, 4H, CH2 CH CH2), 5.75–6.45 (m,
1H, CH CH2), 7.25–8.18 (m, 8H, Ar-H); MS (70 eV): m/z (%) = 314
(M+ + 2) (22), 312 (M+) (40), 297 (100). Found: C, 65.27; H, 4.25; N,
8.84%. Calcd for C17H13ClN2S: C, 65.27; H, 4.91; N, 8.96%.
7c: yield 2 g (77%), m.p. 127–129◦C, yellow needles; IR (cm−1): 1618,
1570, 1557; 1470, 1365, 1342, 1210, 1118, 1030, 950, 912, 810, 762, 724,
1
620; H NMR (CDCl3): δ = 4.75–5.52 (m, 4H, CH2 CH CH2), 5.70–
6.50 (m, 1H, CH CH2), 7.30–8.10 (m, 11H, Ar-H); MS (70 eV): m/z (%)
= 329 (M+ + 1) (12), 328 (M+) (41), 327 (100). Found: C, 76.77; H, 4.67;
N, 8.66%. Calcd for C21H16N2S: C, 76.80; H, 4.91; N, 8.53%.
2-Bromomethyl-5-benzyl-, 5-(2-chlorophenyl)- and
5-(2-naphthyl)-2,3-dihydrothiazolo[3,2-c]quinazolin-
4-ium bromides (8a–c)
A solution of bromine (0.9 g, 5.6 mmol) in acetic acid (15 ml) was
added dropwise to a well-stirred solution of the appropriate thione 7a–c
(5 mmol) in the same solvent (25 ml) at room temperature. The reac-
tion mixture was stirred at room temperature for 3 h and the yellow
solid which gradually separated during the reaction was collected by
filtration, washed with water, and recrystallized from methanol to give
8a–c.
8a: yield 1.5 g (67%), m.p. 238–240◦C, colorless needles; IR (cm−1):
2954, 1618, 1590; 1560, 1480, 1350, 1300, 1245, 1029, 966, 825, 788,
727, 628; 1H NMR (CDCl3 + CF3CO2H): δ = 3.36 (s, 2H, CH2Ph), 3.68–
4.18 (m, 2H, CH2Br), 4.95–5.70 (m, 3H, N+ CH2 CH), 7.38–8.54 (m,
9H, Ar-H); MS (70 eV): m/z (%) = 373 (M+ + 2) (6), 371 (M+) (7), 219
(100). Found: C, 47.90; H, 3.68; N, 6.25%. Calcd for C18H16Br2N2S: C,
47.81; H, 3.57; N, 6.19%.
8b: yield 1.48 g (63%), m.p. 281–283◦C, colorless needles; IR (cm−1):
2940, 1625, 1590, 1560, 1480, 1405, 1345, 1305, 1094, 1025, 826, 770,
728, 709; 1H NMR (CDCl3 + CF3CO2H): δ = 3.78–4.26 (m, 2H, CH2Br),
5.14–5.77 (m, 3H, N+ CH2 CH), 7.40–8.56 (m, 8H, Ar-H); MS (70 eV):
m/z (%) = 393 (M+ + 2) (8), 391 (M+) (4), 239 (100). Found: C, 43.47; H,
2.84; N, 5.69%. Calcd for C17H13Br2ClN2S: C, 43.20; H, 2.77; N, 5.93%.
8c: yield 1.58 g (65%), m.p. 225–227◦C, colorless needles; IR (cm−1):
2928, 1615, 1557; 1522, 1478, 1404, 1346, 1255, 1178, 1020, 960, 842,

Studies on Quinazolines. Part III
1909
775, 740, 620; 1H NMR (CDCl3 + CF3CO2H): δ = 3.75–4.15 (m, 2H,
CH2Br), 4.90–5.80 (m, 3H, N+ CH2 CH), 7.43–8.70 (m, 11H, Ar-H);
MS (70 eV): m/z (%) = 409 (M++2) (6), 407 (M+) (7), 255 (100). Found:
C, 51.90; H, 3.62; N, 5.84%. Calcd for C21H16Br2N2S: C, 51.66; H, 3.30;
N, 5.74%.
4-Carboxymethylthio-2-benzyl-, 2-(2-chlorophenyl)-
and 2-(2-naphthyl)quinazolines (9a–c)
Thiones 3a–c (4.5 mmol) and bromoacetic acid (0.63 g, 4.5 mmol) in
anhydrous benzene (50 ml) were treated with Et3N (0.64 ml, 4.6 mmol)
and stirred overnight at room temperature. The solution was filtered
to remove all Et3N.HBr, and the benzene was evaporated in vacuo.
The products 9a–c were finally obtained as small yellow needles by
recrystallization from ethanol.
9a: yield 1 g (72%), m.p. 176–178◦C; IR (cm−1) (br) 3500–3400, 1710,
1
1620, 1542, 1464, 1420, 1320, 1090, 980, 920, 845, 770, 690; H NMR
(Me2SO-d6): δ = 3.41 (s, 2H, CH2Ph), 4.46 (s, 2H, SCH2CO), 7.40–8.55
(m, 9H, Ar-H); MS (70 eV): m/z (%) = 310 (M+) (18), 266 (22), 219 (100).
Found: C, 65.55; H, 4.29; N, 9.22%. Calcd for C17H14N2O2S: C, 65.79;
H, 4.55; N, 9.03%.
9b: yield 1 g (70%), m.p. 161–163◦C; IR (cm−1) (br) 3540–3425, 1715,
1618, 1590, 1572, 1470, 1365, 1320, 1210, 1180, 1002, 980, 828, 750,
680; 1H NMR (Me2SO-d6): δ = 4.37 (s, 2H, SCH2CO), 7.35–8.62 (m, 8H,
Ar-H); MS (70 eV): m/z (%) = 330 (M+) (22), 286 (42), 239 (100). Found:
C, 58.33; H, 3.53; N, 8.62%. Calcd for C16H11ClN2O2S: C, 58.10; H, 3.35;
N, 8.47%.
9c: yield 1 g (68%), m.p. 182–184◦C; IR (cm−1) (br) 3560–3414, 1705,
1628, 1590, 1530, 1490, 1381, 1310, 1270, 1100, 982, 910, 840, 780, 750,
1
690; H NMR (Me2SO-d6): δ = 4.40 (s, 2H, CH2), 7.28–8.48 (m, 11H,
Ar-H); MS (70 eV): m/z (%) = 346 (M+) (25), 302 (19), 255 (100). Found:
C, 69.44; H, 4.32; N, 8.22%. Calcd for C20H14N2O2S: C, 69.35; H, 4.10;
N, 8.10%.
Mesoionic Ring Formation: 5-Benzyl-, 5-(2-chlorophenyl)-
and 5-(2-naphthyl)-1,3-thiazolo[3,2-c]quinazolinium-
3-olate (10a–c)
The thioglycolic acids 9a–c (2 mmol) were added to a mixture of Ac2O
(3 ml) and Et3N (3 ml). After the mixture was stirred for 15 min, an-
hydrous ether was added (20 ml). The dark red solids of 10a–c recrys-
tallized from chloroform/cyclohexane, giving dark red needles.

1910
A. A. F. Wasfy
10a: yield 0.38 g (65%), m.p. 286–288◦C; IR (cm−1): 1648s (polarized
CO), 1620, 1602, 1562, 1545, 1489, 1420, 1347, 1338, 1310, 1245, 1170,
1
1040, 990, 835, 791, 730, 622; H NMR (Me2SO-d6): δ = 3.51 (s, 2H,
CH2Ph), 7.30–8.66 (m, 10H, Ar-H); MS (70 eV): m/z (%) = 292 (M+) (22),
219 (100). Found: C, 69.62; H, 4.22; N, 9.61%. Calcd for C17H12N2OS:
C, 69.84; H, 4.14; N, 9.58%.
10b: yield 0.39 g (63%), m.p. 269–271◦C; IR (cm−1): 1654s (polarized
CO), 1625, 1598, 1582, 1557, 1471, 1360, 1340, 1206, 1088, 1016, 961,
1
822, 769, 720; H NMR (Me2SO-d6): δ = 7.22–8.64 (m, 9H, Ar-H); MS
(70 eV): m/z (%) = 314 (M+ + 2) (6), 312 (M+) (12), 239 (100). Found: C,
61.62; H, 2.82; N, 8.76%. Calcd for C16H9ClN2OS: C, 61.44; H, 2.90; N,
8.96%.
10c: yield 0.38 g (58%), m.p. 292–294◦C; IR (cm−1): 1659s (polarized
CO), 1619, 1597, 1552, 1529, 1352, 1304, 1207, 1185, 1145, 991, 975,
1
835, 816, 769, 719, 645; H NMR (Me2SO-d6): δ = 7.45–8.62 (m, 12H,
Ar-H); MS (70 eV): m/z (%) = 330 (M+ + 2) (8), 328 (M+) (14), 255 (100).
Found: C, 73.30; H, 3.78; N, 8.64%. Calcd for C20H12N2OS: C, 73.15; H,
3.68; N, 8.53%.
REFERENCES
[1] A. A. F. Wasfy, Phosphorus, Sulfur and Silicon, 177, 1349 (2002).
[2] A. A. F. Wasfy, M. S. Amine, and A. M. F. Eissa, Heterocyclic Communications, 2,
375 (1996).
[3] L. Legrand and N. Lozac’h, Bull. Soc. Chim. France, 618 (1961).
[4] L. Legrand, Bull. Soc. Chim. France, 337 (1960).
[5] D. I. Bain and R. K. Smalley, J. Chem. Soc. (C), 1593 (1968).
[6] H. Singh, S. K. Aggarwal, and N. Malhotra, Heterocycles, 22, 353 (1984).
[7] H. Singh and K. Deep, Tetrahedron, 40, 4937 (1984).
[8] P. Molina, M. Alajarin, and M. J. Perez de Vega, Synth. Commun., 933 (1983).
[9] a) M. Ohta and H. Kato, Non-Benzenoid Aromatics, edited by J. P. Snyder (Academic
Press, New York, 1966), p. 117; b) W. D. Ollis and C. A. Ramsden, Adv. Heterocyclic
Chem., 19, 3 (1976).
[10] a) D. Mackay and L. L. Wong, Can. J. Chem., 53, 1973 (1975); b) P. N. Preston and
K. Turnbull, J. Chem. Soc. Perkin I, 1229 (1977).