Dapson in heterocyclic chemistry, part II: Antimicrobial and antitumor activities of some novel sulfone biscompounds containing biologically active thioureido, carbamothioate, quinazoline, imidazolidine, and thiazole moieties

Article abstract of DOI:10.1080/10426500802505424

The reaction of 4,4′-diisothiocyanato-1,1-diphenylsulfone 2 with aromatic amines and phenol derivatives afforded the corresponding thioureio derivatives 3-9, respectively. Also, the reaction of 2 with catechol gave the corresponding carbamothioate derivat

Full text of DOI:10.1080/10426500802505424

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Phosphorus, Sulfur, and Silicon
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Dapson in Heterocyclic
Chemistry, Part II:
Antimicrobial and Antitumor
Activities of Some Novel
Sulfone Biscompounds
Containing Biologically Active
Thioureido, Carbamothioate,
Quinazoline, Imidazolidine,
and Thiazole Moieties
M. M. Ghorab a , M. A. A. Radwan b , N. M. H. Taha c
, N. E. Amin a , M. A. Shehab b & I. M. I. Faker b
a Department of Drug Radiation Research , National
Center for Radiation Research and Technology
(NCRRT) , Nasr City, Cairo, Egypt
b Applied Organic Chemistry Department , National
Research Center , Cairo, Egypt
c Organic Chemistry Department, Faculty of Science
for Girls , Al-Azhar Universty , Cairo, Egypt
Published online: 03 Nov 2008.
To cite this article: M. M. Ghorab , M. A. A. Radwan , N. M. H. Taha , N. E. Amin ,
M. A. Shehab & I. M. I. Faker (2008) Dapson in Heterocyclic Chemistry, Part II:
Antimicrobial and Antitumor Activities of Some Novel Sulfone Biscompounds
Containing Biologically Active Thioureido, Carbamothioate, Quinazoline,
Imidazolidine, and Thiazole Moieties, Phosphorus, Sulfur, and Silicon and the Related
Elements, 183:12, 2906-2917

To link to this article: http://dx.doi.org/10.1080/10426500802505424
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Phosphorus, Sulfur, and Silicon, 183:2906–2917, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802505424
Dapson in Heterocyclic Chemistry, Part II: Antimicrobial
and Antitumor Activities of Some Novel Sulfone
Biscompounds Containing Biologically Active Thioureido,
Carbamothioate, Quinazoline, Imidazolidine, and
Thiazole Moieties
M. M. Ghorab,1 M. A. A. Radwan,2 N. M. H. Taha,3
N. E. Amin,1 M. A. Shehab,2 and I. M. I. Faker2
1Department of Drug Radiation Research, National Center for
Radiation Research and Technology (NCRRT), Nasr City, Cairo, Egypt
2Applied Organic Chemistry Department National Research Center,
Cairo, Egypt
3Organic Chemistry Department, Faculty of Science for Girls,
Al- Azhar Universty, Cairo, Egypt
The reaction of 4,4ꢀ-diisothiocyanato-1,1-diphenylsulfone 2 with aromatic amines
and phenol derivatives afforded the corresponding thioureio derivatives 3–9, re-
spectively. Also, the reaction of 2 with catechol gave the corresponding carbamoth-
ioate derivative 11. Quinazoline derivatives 14 and 15 were obtained in good yield
via reaction of 2 with anthranlic acid derivatives. Imidazolidine biscompounds
16 and 17 were readily synthesized from the reaction of 2 with N-(4-substituted-
phenyl)cyanothioformanilides. The structure of the products was confirmed from
elemental analysis as well as spectral data. Most of the synthesized compounds
showed remarkable antimicrobial activity compared with chloramphenicol and
Grisofluvine as positive controls. Compound 6 was almost as active an antitumor
agent as the reference drug Doxorubicin.
Keywords Antimicrobial and antitumor agents; biscompounds bearing thioureido,
quinazoline, and imidazolidine
INTRODUCTION
A large number of sulfone derivatives have been found to exhibit a wide
variety of pharmacological activities.1–8 In addition the bisheterocyclic
compounds quinazoline and imidazolidine derivatives are well known
as antifungal9–11 and antitumor12–17 agents. In view of these findings,
Received 30 September 2007; accepted 11 December 2007.
Address correspondence to M. M. Ghorab, Department of Drug Radiation Research,
National Center for Radiation Research and Technology (NCRRT), P.O. Box 29, Nasr
City, Cairo, Egypt. E-mail: mmsghorab@yahoo.com
2906

Sulfone Biscompounds
2907
we undertook the synthesis of a new series of bisheterocyclic sulfone
compounds incorporating the above-mentioned biologically active moi-
eties in one molecule and evaluated their antimicrobial and antitumor
activities.
RESULTS AND DISCUSSION
Several compounds were designed with the aim of exploring their an-
timicrobial and antitumor properties (Schemes 1–5). Treatment of dap-
son 1 wtih thiophosgene at room temperature in the presence of dilute
HCl furnished the diisothiocyanate 2 in high yield.
Treatment of diisothiocyanate 2 with aromatic amines (1:2 mol)
in dioxan afforded the novel thioureido derivatives 3–6, respectively
(Scheme 1).
SCHEME 1
The structure of compounds 3–6 was confirmed by analytical and
–1
–1
spectral data. IR spectrum of compound 3 revealed bands at 3368 cm
–1
–1
(NH), 2940 cm (CH aliph.), 1314, 1148 cm (SO2), and 1280 cm
1
(C S). H-NMR spectrum of (3 in DMSO-d6) exhibited signals at 2.23
[s, 6H, 2CH3], 7.05–7.5 [m, 16H, Ar-H], 8.4, and 9.2 [2s, 4H, 4NH]. The
–1
IR spectrum of compound 4 revealed bands at 3152, 3140 cm (NH,
–1
–1
NH2), 1356, 1178 cm (SO2), and 1258 cm (C=S). Mass spectrum of
compound 4 showed a molecular ion peak m/z at 548 (M+, 0.84%), with
a base peak at 150 (100%), and other significant peaks appeared at 550
(M+2, 0.63%), 551 (M+3, 0.88), 524 (0.8%), 480 (0.2%), 367 (0.10%),
313 (0.14%), 266 (1.05%), 208 (1.13%), 140 (0.48%), 90 (3.78%), and
76 (1.53%). IR spectrum of compound 5 revealed bands at 3460, 3358,
–1
–1
–1
3250 cm (NH), 2934 cm (CH aliph.), 1314, 1144 cm (SO2), and
–1
1
1288 cm (C=S). H-NMR spectrum of (5 in DMSO-d6) showed sig-
nals at 3.8 [s, 6H, 2OCH3], 6.6–8.0 [m, 16H, Ar-H], 8.2, and 8.7 [2s,

2908
M. M. Ghorab et al.
4H, 4NH]. Mass spectrum of 5 exhibited a molecular ion peak m/z at
578 (M+, 29.03%), with a base peak at 52 (100%), and other signifi-
cant peaks appeared at 562 (41.94%), 506 (32.26%), 438 (29.03%), 375
(29.03%), 269 (61.29%), 199 (41.94%), 134 (61.29%), and 77 (32.26%).
–1
The IR spectrum of compound 6 exhibited bands at 3450, 3370 cm
–1
–1
(NH), 1310, 1146 cm (SO2), and 1290 cm (C S). Mass spectrum
of 6 revealed a molecular ion peak m/z at 676 (M+, 7.05%), with a
base peak at 458 (100%), and other significant peaks appeared at 677
(M+1, 20.63%), 678 (M+2, 11.51%), 675 (M-1, 8.17%), 640 (19.12%),
591 (7.96%), 533 (37.98%), 510 (17.71%), 486 (27.03%), 433 (78.39%),
416 (50.69%), 381 (87.72%), 297 (28.20%), 193 (40.17%), 145 (37.66%),
and 77 (5.01%).
Our investigation was extended to include the reactivity of di- isoth-
iocyanate 2 toward binucleophiles such as 1,2-phenylenediamine, 2-
aminophenol, and/or 2-aminothiophenol. Thus, diisothiocyanate 2 was
reacted with 1,2-phenylenediamine or 2-aminophenol and/or 2-amino-
thiophenol (1:2 mol) in dimethylformamide catalyzed with triethy-
lamine to produce biscompounds 7–9, respectively (Scheme 2).
SCHEME 2
Compound 10 was discarded on the basis of analytical and spec-
tral data. The IR spectrum of compound 7 showed bands at 3402 and
–1
3250 cm (NH, NH2). Mass spectrum of compound 7 showed a molec-
ular ion peak m/z at 548 (M+, 4.70%), with a base peak at 236 (100%),
and other significant peaks appeared at 550 (M+2, 17.38%), 552 (M+4,
35.51%), 423 (15.22%), 383 (21.01%), 313 (78.81%), 248 (28.71%), 191
(31.52%), 140 (44.57%), 108 (88.84%), and 78 (48.74%). IR spectrum
–1
–1
of 8 revealed bands at 3380 cm (OH), 3238, 3200 cm (NH), 1340,
–1 –1
1148 cm (SO2), and 1274 cm (C S). Mass spectrum of compound

Sulfone Biscompounds
2909
8 showed a molecular ion peak m/z at 550 (M+, 1.80%), with a base
peak at 147 (100%), and other significant peaks appeared at 552 (M+2,
3.87%), 509 (1.82%), 385 (1.66%), 313 (18.95%), 193 (9.55%), 95 (8.72%),
and 72 (7.88%). IR spectrum of compound 9 revealed bands at 3324,
–1
–1
–1
3200 cm (NH), 1320, 1144 cm (SO2), and 1288 cm (C S). Mass
spectrum of compound 9 showed a molecular ion peak m/z at 582 (M+,
0.8%), with a base peak at m/z 167 (100%), and other significant peaks
appeared at 580 (M-2, 0.20%), 552 (0.31%), 523 (0.93%), 424 (0.35%),
368 (1.45%), 288 (0.72%), 257 (28.98%), 108 (8.57%), and 76 (3.48%).
We also investigated the reactivity of diisothiocyanate 2 toward aro-
matic hydroxy compounds. Thus, catechol as binucleophile was reacted
with diisothiocyanate 2 in dioxan/triethylamine to produce 4,4ꢀ-bis(3-
(2-hydroxyphenyl)-2-carbamothioate)-1,1-diphenylsulfone 11 (Sch-
eme 3).
SCHEME 3
Structure 12 was eliminated on the basis of analytical and spectral
–1
data. The IR spectrum of compound 11 exhibited bands at 3568 cm
–1
–1
(OH), 3448 cm (NH), 1380, and 1150 cm (SO2). Mass spectrum of
compound 11 revealed a molecular ion peak m/z at 551 (M-1, 27.54%),
with a base peak at 313 (100%), and other significant peaks ap-
peared at 550 (M-2, 12.00%), 549 (M-3, 18.48%), 548 (M-4, 8.85%),
537 (25.83%), 388 (80.17%), 285 (45.17%), 236 (83.23%), 114 (48.38%),
and 55 (42.35%).
Cyclocondensation of 1 mol of diisothiocyanate 2 with 2 mol of an-
thranilic acid derivatives in dioxane/TEA furnished the novel bisquina-
zolinone derivatives 14 and 15, respectively. Analytical and spectral
data were compatible with the structure of quinazoline derivatives 14
and 15 (Scheme 4).
–1
The IR spectrum of compound 14 revealed bands at 3372 cm
–1
–1
–1
(NH), 1676 cm (C O), 1606 cm (C N), 1382, 1124 cm (SO2),

2910
M. M. Ghorab et al.
SCHEME 4
and 1262 cm–1 (C=S). Mass spectrum of compound 14 showed a molec-
ular ion peak m/z at 570 (M+, 1.81%), with a base peak at 408 (100%),
and other significant peaks appeared at 435 (4.25%), 377 (31.05%), 252
(28.42%), 234 (10.01%), 118 (84.40%), 108 (9.23%), and 78 (8.25%). The
–1
IR spectrum of compound 15 revealed bands at 3366 cm (NH), 3084
cm–1 (CH arom.), 1702 cm–1 (C O), 1610 cm–1 (C N), 1374, 1148 cm
–1
–1
(SO2), and 1292 cm (C S). Mass spectrum of compound 15 exhibited
a molecular ion peak m/z at 708 (M+, 0.11%), with a base peak at 88
(100%), and other significant peaks appeared at 710 (M+2, 0.28%),
677 (0.28%), 651 (0.28%), 551 (5.38%), 439 (2.51%), 256 (11.82%), 187
(41.28%), 149 (11.40%), 111 (9.18%), and 73 (17.81).
This investigation was extended to cover the behavior of di-
isothiocyanate 2 towards cyanothioformanilides. Thus, compound 2
reacted with N-phenylcyanothioformanilides (1:2 mol) where 2 mol
were consumed and yielded 4,4ꢀ-bis(5-imino-1-(4-tolyl)-2,4-dithioxo-
imidazolidine-3-yl)-1,1-diphenyl sulfone 16 and 4,4ꢀ-bis(5-imino-1-(4-
methoxyphenyl)-2,4-dithioxo-imidazolidine-3-yl)-1,1-diphenylsulfone
17, respectively (Scheme 5).
The structure of 16 and 17 was confirmed by analytical and spectral
–1
data. The IR spectrum of compound 16 showed bands at 3448 cm
(NH), 2924 cm–1 (CH aliph.), 1592 cm–1 (C N), 1384, 1156 cm–1 (SO2),
and 1304 cm–1 (C S). 1H-NMR spectrum of compound (16 in DMSO-d6)
exhibited signals at 2.3 [s, 6H, 2CH3], 6.6–8.0 [m, 16H, Ar-H], 8.3, and
8.4 [2s, 4H, 4NH]. Mass spectrum of compound 16 showed a molecular
ion peak m/z at 683 (M-1, 0.55%), with a base peak at 91 (100%),

Sulfone Biscompounds
2911
SCHEME 5
and other significant peaks appeared at 551 (0.55%), 523 (0.84%), 370
(2.14%), 313 (3.18%), 224 (4.28%), 196 (1.08%), 128 (2.46%), and 76
–1
–1
(54.10%). The IR spectrum of compound 17 revealed bands at 3398 cm
(NH), 2924 cm (CH aliph.), 1386, 1154 cm (SO2), and 1252 cm
–1
–1
(C S). 1H-NMR spectrum of (17 in DMSO-d6) showed signals at 3.8 [s,
6H, 2OCH3], 7.1–8.2 [m, 16H, Ar-H], 9.9 [s, 2H, 2NH]. Mass spectrum
of compound 17 showed a molecular ion peak m/z at 716 (M+, 4.00%),
with a base peak at 165 (100%), and other significant peaks appeared
at 486 (4.27%), 461 (5.87%), 326 (8.80%), 241 (16.80%), 215 (3.47%),
144 (21.80%), 104 (12.27%), and 77 (18.40%).
Finally, the thiazole derivative 18 was prepared by reaction of di-
isothiocyanate 2 with malononitrile and sulfur in the presence of tri-
ethylamine (Scheme 6).
SCHEME 6
–1
IR spectrum of compound 18 showed bands at 3320, 3200 cm
(NH2), 2198 cm–1 (C N), 1390, 1148 cm–1 (SO2), and 1280 cm–1 (C S).
Mass spectrum of compound 18 showed a molecular ion peak m/z at 527
(M-1, 8.35%), with a base peak at 86 (100%), and other significant peaks
appeared at 415 (2.73%), 354 (5.49%), 295 (10.35%), 281 (37.31%), 257
(9.07%), 207 (4.75%), 192 (40.82%), 134 (9.0%), 101 (41.97%), and 77
(43.14%).
Antimicrobial Activity
Some of the newly synthesized compounds were screened for their an-
timicrobial activity using the diffusion agar technique.18 The tested
compounds were dissolved in N, N-dimethylformamide (DMF), which

2912
M. M. Ghorab et al.
TABLE I Antibacterial Activity of Some Synthesized Compounds
Salmonella
E. coli
Staphylococcus
typhi
Bacillus
aureus
subtillus
Compound No.
1
2.5
5
1
2.5
5
1
2.5
5
1
2.5
5
2
3
5
6
++ ++
++
++
++
++
+
+
++
0
+
++
+
+
+
+
0
+
+
+
0
++ ++
+
++
+
++
+
+
+
+
+
0
++
++
++
+
0
+
+
+
0
++
+
0
+
++ ++
++
++
+
+
+
++
++
0
++
+
+
+
0
++
+
16
DMF
+
++
0
0
0
0
0
0
0
Chloramphenicol ++ + + + + + + + + + + + + + + + ++ ++ + + + ++ + + + + + +
Well diameter 1 cm (100 mL of each conc. was tested.
Inhibition values = 0.1–0.5 cm beyond control = +
Inhibition values = 0.6–0.1 cm beyond control = ++
Inhibition values = 1.1–1.5 cm beyond control = + + +
Inhibition values =>1 cm beyond control = + + ++, 0 = not detected.
showed no inhibition zones. Tables I and II lists the screening results of
the tested compounds against the Gram-negative bacteria Escherichia
coli and Salmonella typhi, Gram-positive bacteria Staphylococcus au-
reus and Bacillus subtillus, and pathogenic fungi Aspergillus niger and
Aspergillus flavus. The reference antibiotic chloramphenicol and fungi-
cide Grisofluvine were used as positive controls for comparison. The
fungi cultures were maintained on Czapek’s Dox agar media.
Most of the synthesized compounds showed remarkable activity to-
ward the tested microorganisms but were less active than the standard
chloramphenicol and Grisofluvine.
TABLE II Antifungal Activity of Some Synthesized Compounds
Aspergillus niger
Aspergillus vlavu
Compound No.
1
2.5
5
1
2.5
5
2
3
5
6
+
++
+
++
++
+
+
0
+
+
+
+
0
0
+
+
+
+
+
++
+
++
++
0
0
++
+
++
++
0
16
DMF
0
0
+
0
0
0
Grisofluvine
+ + +
+ + +
+ + +
+ + +
+ + +
+ + +
Well diameter 1 cm (100 mL of each conc. was tested
Inhibition values = 0.1–0.5 cm beyond control = +
Inhibition values = 0.6–0.1 cm beyond control = ++
Inhibition values = 1.1–1.5 cm beyond control = + + +
Inhibition values =>1 cm beyond control = + + ++, 0 = not detected.

Sulfone Biscompounds
2913
Antitumor Activity
Reagents
1. RPMI 1640 medium (sigma).
2. Ehrlich Ascites Carcinoma cells (EAC) suspension (2.5 × 105 mL).
3. Trypan blue dye: A stock solution was prepared by dissolving 1 g of
the dye in distilled water (100 mL). The working solution was then
prepared by diluting 1 mL of the stock solution with 9 mL of distilled
water. The stain was used then for staining the dead EAC cells.
4. The compounds tested were (2–15).
Procedure
1. EAC cells were obtained by needle aspiration of the ascetic fluid
from preinoculated mice under aseptic conditions.19
2. The cells were tested for viability and contamination by staining a
certain cell volume of this fluid by an equal volume of the working
solution of trypan blue dye.20,21
3. The ascetic fluid was diluted with saline (1:10) to contain 2.5 × 106
mL cells on a hemocytometer.
In a set of sterile test tubes 0.1 mL of tumor cells suspension, 0.8 mL
RPMI 1640 media and 0.1 mL of each tested compound (corresponding
to 100, 50 and 25 µg/mL) were mixed. The test tubes were incubated
at 37◦C for 2 hr. A trypan blue exclusion test20,21 was carried out to
calculate the presence of nonviable cells. Compounds producing more
than 70% non viable cells are considered active.21
No. of non viable
Total No. of cells
% of non-viable cells =
× 100
The relationship between the surviving fraction and drug concen-
tration was plotted to obtain the survival curve of EAC cell. The re-
sponse parameter calculated was the IC50 value, which corresponds
to the compound concentration causing 50% mortality in net cells
(Table III).
From these results, it was found that the biscompound bearing bro-
mophenylthioureido diphenylsulfone 6 exhibited higher activity than
the positive control Doxorubicin against EAC cell; the nonviable cell
about 100%, 95%, 85% at a concentration (100, 50, and 25 µg /mL); and
IC50 of 0.5 µg/mL.

2914
M. M. Ghorab et al.
TABLE III In Vitro Antitumor Activity of Some Newly Synthesized
Compounds
Non-viable cells (%)
Concentration (µg/mL)
Compound No.
100
50
25
IC50
2
3
4
5
6
8
15
0
0
10
20
100
0
0
0
0
10
95
0
0
0
0
0
85
0
>100a
<100a
<100a
<100a
0.5
>100
>100
52
100
100
0
55
0
20
Doxorubicin
aIC50 >100 µg/mL is considered to be inactive.
EXPERIMENTAL
Melting points were uncorrected. IR spectra were recorded (KBr) on a
Perkin Elmer 1650 spectrophotometer. 1H-NMR spectra were recorded
on a varian Gemini spectrometer 300 (300 MHz) using DMSO-d6 as a
solvent, and TMS as internal standard chemical shifts were expressed
as δ ppm units. Mass spectra were recorded on a gas chromatography
GC-MS qp 100 Ex (schimadzu instrument) at 70 ev. Microanalytical
data were obtained from the Microanalytical Data Unit at the Cairo
University.
4,4ꢀ-Bis(3-(4-tolyl)-2-thioureido)-1,1ꢀ-diphenylsulfone (3),
4,4ꢀ-Bis(3-(4-aminophenyl)-2-thioureido)-1,1ꢀ-diphenylsulfone
(4), 4,4ꢀ-Bis(3-(3-anisyl)-2-thioureido)-1,1ꢀ-diphenylsulfone (5),
and 4,4ꢀ-Bis(3-(4-bromo-phenyl)-2-thioureido)-1,1ꢀ-
diphenylsulfone (6)
A mixture of 2 (0.01 mol) and aromatic amines (0.02 mol) in dioxan
(30 mL) containing triethylamine (0.5 mL) was refluxed until the clear
solution was obtained (6 hr). The solid residue was collected by filtra-
tion, washed with cold water, and recrystallized from ethanol to give
(3–6), (Table 4).

Sulfone Biscompounds
2915
TABLE IV Physical and Analytical Data of the Synthesized
Compounds
Analyses % Required/Found
Compound
No.
m.p
(◦C)
Yield
%
Mol. Formula
(Mol. Wt)
C
H
N
S
2
145
88
79
81
77
69
72
80
82
85
75
78
84
82
78
C14H8N2O2S3 (332)
50.60 2.40 8.43
50.40 2.60 8.60
61.53 4.76 10.25
61.70 4.90 10.50
56.93 4.37 15.32
57.20 4.20 15.60
58.13 4.49 9.68
58.40 4.20 9.50
28.91
29.20
17.58
17.90
17.51
17.20
16.60
16.90
14.20
14.50
17.51
17.80
17.45
17.30
18.68
18.50
17.39
17.70
16.84
16.50
13.56
13.70
23.39
23.60
22.34
22.60
30.30
30.50
3
170–172
>300
C
28H26N4O2S3 (546)
26H24N6O2S3 (548)
28H26N4O4S3 (578)
4
C
C
5
60–62
6
158–159
>300
C
26H20Br2N4O2S3 (676) 46.15 2.95 8.28
46.50 3.30 8.60
7
C26H24N6O2S3 (548)
C26H22N4O4S3 (550)
C26H22N4O2S5 (582)
C26H20N2O6S3 (552)
C28H18N4O4S3 (570)
56.93 4.37 15.32
57.20 4.60 15.20
56.73 4.00 10.18
56.50 4.30 10.10
60.70 3.50 10.90
60.90 3.20 11.20
56.52 3.62 5.07
56.20 3.90 5.30
58.94 3.15 9.82
59.30 3.40 9.70
8
135–137
93–95
9
11
14
15
16
17
18
260–262
>300
>300
C
28H14Cl4N4O4S3 (708) 47.46 1.98 7.91
47.30 1.80 8.20
105–107
125–127
>300
C32H24N6O2S5 (684)
C32H24N6O4S5 (716)
C20H12N6O2S5 (528)
56.14 3.50 12.28
56.40 3.40 12.50
53.63 3.35 11.73
53.30 3.20 11.40
45.45 2.27 15.90
45.10 2.10 16.20
4,4ꢀ-Bis(3-(2-aminophenyl)-2-thioureido)-1,1ꢀ-diphenylsulfone
(7), 4,4ꢀ-Bis(3-(2-hydroxyphenyl)-2-thioureido)-1,1ꢀ-
diphenylsulfone (8), and 4,4ꢀ-Bis(3-(2-mercaptophenyl)-2-
thioureido)-1,1ꢀ-diphenylsulfone (9)
A mixture of 2 (0.01 mol) and 1,2-phenylenediamine, 2-amino-phenol,
and/or 2-aminothiophenol (0.02 mol) in dimethylformamide (10 mL)
containing, triethylamine (0.5 mL) was refluxed for 8 hr. The reaction
mixture was poured into cold water, and the solid product was collected
by filtration and recrystallized from dioxan to give (7–9) (Table IV).

2916
M. M. Ghorab et al.
4,4ꢀ-Bis(3-(2-hydroxyphenyl)-2-carbamothioate)-1,1ꢀ-
diphenylsulfone (11)
To a mixture of 2 (0.01 mol), catechol (0.02 mol) in dioxan (30 mL)
containing a few drops of triethylamine. The reaction mixture was re-
fluxed for 24 h. After cooling the obtained solid was recrystallized from
ethanol, to give (11) (Table IV).
4,4ꢀ-Bis(2,3-dihydro-2-thioxo-4-oxo-1H-quinazolin-3-yl)-1,1ꢀ-
diphe-nylsulfone (14) and 4,4ꢀ-Bis(6,8-dichloro-2,3-dihydro-2-
thioxo-4-oxo-1H-quinazolin-3-yl)-1,1ꢀ-diphenylsulfone (15)
To a stirred suspension of 2 (0.01 mol), anthranilic acid derivatives (0.02
mol) in dioxan (20 mL) containing triethylamine (0.5 mL) was added.
The reaction mixture was heated under reflux for 30 min, filtered while
hot, and then cooled. The solid obtained was collected by filtration and
recrystallized from dioxan to give (14) and (15) (Table IV).
4,4ꢀ-Bis(5-imino-1-(4-tolyl)-2,4-dithioxo-imidazolidine-3-yl)-
1,1ꢀ-diphenylsulfone (16) and 4,4ꢀ-Bis(5-imino-1-
(4-methoxyphenyl)-2,4-dithioxo-imidazolidine-3-yl)-1,1ꢀ-
diphenylsulfone (17)
A solution of 2 (0.01 mol) and N-(4-substituted phenyl) cyanothiofor-
manilide (0.02 mol) in tetrahydrofuram (20 mL) containing (0.5 mL)
triethylamine was refluxed for 3 hr. The solid that formed when heated
was collected and washed with dioxan to give 16, 17 (Table IV).
4,4ꢀ-Bis(4-amino-5-cyano-2-thioxo-3H-thiazol-3-yl)-1,1ꢀ-
diphenyl-sulfone (18)
To a stirred solution of malononitrile (0.01 mole), finely divided sulfur
(0.01 mol), and triethylamine (0.5 mL) in absolute ethanol (30 mL),
the diisothiocyanate 2 (0.01 mole) was added. The reaction mixture
was heated under reflux for 1 hr. The obtained product was filtered,
washed with ethanol, dried, and recrystallized from dioxan to give (18)
(Table IV).
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