Utility of N-[4-(N-substituted sulfamoyl)phenyl] cyanothioformamides in the synthesis of heterocyclic compounds

Article abstract of DOI:10.1002/jccs.200400051

The novel cyanothioformamides 2a-d were prepared by treatment of isothiocyanatosulfonamides 1a-d with potassium cyanide at room temperature. Cyclocondensation of compounds 2b,c with phenyl isocyanate as electrophile furnished the corresponding imidazolidines 3a,b. The reactivity of compound 3a towards some nitrogen nucleophiles was investigated. Thus, the thiosemicarbazone 4 and imidazo[4,5-b]quinoxaline 6 were synthesized by condensation of compound 3a with thiosemicarbazide and o-phenylenediamine, respectively. Treatment of 3a with hydrochloric acid afforded compound 7. Our investigation was extended to include the reactivity of cyanothioformamide 2 towards o-aminophenol, anthranilic acid, and o-phenylenediamine and yielded the corresponding heterocycles 9, 11 and 13 derivatives, respectively. Structures of the synthesized compounds were established by their elemental analysis and spectral data.

Full text of DOI:10.1002/jccs.200400051

Journal of the Chinese Chemical Society, 2004, 51, 327-333
327
Utility of N-[4-(N-Substituted Sulfamoyl)phenyl] cyanothioformamides in
the Synthesis of Heterocyclic Compounds
Mohamed S. A. El-Gabya*, Ahmed M. Sh. El-Shariefb,
Ahmed A. Atallaa and Abu-Bakr A. A. M. El-Adasya
aChemistry Department, Faculty of Science, Al-Azhar University at Assiut, Assiut 71524, Egypt
bChemistry Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo, Egypt
The novel cyanothioformamides 2a-d were prepared by treatment of isothiocyanatosulfonamides 1a-d
with potassium cyanide at room temperature. Cyclocondensation of compounds 2b,c with phenyl isocyanate
as electrophile furnished the corresponding imidazolidines 3a,b. The reactivity of compound 3a towards
some nitrogen nucleophiles was investigated. Thus, the thiosemicarbazone 4 and imidazo[4,5-b]quinoxaline
6 were synthesized by condensation of compound 3a with thiosemicarbazide and o-phenylenediamine, re-
spectively. Treatment of 3a with hydrochloric acid afforded compound 7. Our investigation was extended to
include the reactivity of cyanothioformamide 2 towards o-aminophenol, anthranilic acid, and o-phenylenedi-
amine and yielded the corresponding heterocycles 9, 11 and 13 derivatives, respectively. Structures of the syn-
thesized compounds were established by their elemental analysis and spectral data.
Keywords: Sulfonamide; Cyanothioformamide; Imidazole; Benzoazole derivatives.
INTRODUCTION
Sulfonamides have been reported to exhibit antimicro-
peak was observed at m/z 302 (M+-OH; rel. intensity = 0.5)
and base peak at m/z 227. Cyclocondensation of compounds
2b,c with phenyl isocyanate as electrophile in THF contain-
ing triethylamine at room temperature yielded the imidazo-
lidinone derivatives 3a,b, Scheme I. The structures of com-
pounds 3a,b were confirmed by their spectroscopic analysis.
The IR spectrum of compound 3a showed a band of the C=O
group at 1784 cm-1 in addition to two NH and SO2 function
groups. In the 1H NMR spectrum of 3a measured in DMSO-
d6, the following signals were observed: 7.00 (t, 1H, CH-py-
rimidine), 7.20, 8.30 (2 hump, two NH), 8.50 (d, 2H, two
CH-pyrimidine) in addition to aromatic protons at 7.50-8.00
(m, 9H, Ar-H).
bial,1,2 antifungal,3 insulin releasing,4 carbonic anhydrase in-
hibitory,5 antiinflammatory,6 and antitumor7 properties.
Some active sulfonamides as antibacterials are also known
for their immunmodifying effects.8 In view of these facts and
as a continuation of our research program on the chemistry of
cyanothioformamides,9-15 we report herein on the synthesis
of novel cyanothioformamide 2a-d, imidazolidines 3a,b,
imidazo[4,5-b]quinoxaline 6, benzoazole 9a,b & 13, and
quinazoline 11 derivatives containing sulfonamido moieties.
RESULTS AND DISCUSSION
Scheme I
S
O
Potassium cyanide was reacted with isothiocyanato-
sulfonamides 1a-d in ethanol (60%) at room temperature and
furnished the novel cyanothioformamides 2a-d, and their
structures were established on the basis of analytical and
spectral data. The infrared spectra of the cyanothioform-
amides 2 contain characteristic bands for NH, CºN and SO2
O
KCN
CN
RHN
S
N
H
RHN
RHN
S
NCS
O
O
2a-d
1a-d
2b,c
PhNCO
CSCl2, Ref. [18]
NH2
O
S
R
O
1
N
O
O
function groups. In the H NMR spectrum of compound 2b
N
Ph
HN
S
N
N
recorded in DMSO-d6 showed in addition to the signals of the
phenyl and pyrimidinyl ring protons, an exchangeable sulfa-
moyl proton (SO2NH) and thiocarbamoyl proton (CSNH)
signals. Also, in the mass spectrum of 2b a molecular ion
O
1 and 2a; R= H
b; R= 2-Pyrimidinyl
NH
S
3a,b
c; R= 2-(4-Methylpyrimidinyl)
d; R= 2-Thiazolyl
3a; R= H
3b; R= CH3

328 J. Chin. Chem. Soc., Vol. 51, No. 2, 2004
El-Gaby et al.
The reactivity of imidazolidine 3a towards some nitro-
gen nucleophiles was investigated. Thus, thiosemicarbazone
4 was produced by treatment of compound 3a with thio-
semicarbazide under reflux in absolute ethanol, via elimina-
tion of hydrogen sulfide (lead acetate paper test). Also, com-
pound 3a was subjected to react with two molecules of p-
toludine and yielded the corresponding diimine derivative 5,
through elimination of hydrogen sulfide and ammonia. In the
same manner, compound 3a treated with vicinal diamine as
4,5-dimethyl-1,2-phenylenediamine and afforded the novel
imidazo[4,5-b]quinoxaline 6. Conversion of imino group in
3a into carbonyl group was achieved via treatment with hy-
drochloric acid at room temperature, Scheme II.
DMF/TEA and produced the benzoxazoles 9a,b. Quinazoline
11 was synthesized by interaction of compound 2b with
anthranilic acid in ethanol containing triethylamine under re-
flux. The formation of compound 11 was assumed to proceed
via thiourea 10 formation followed by loss of water molecule,
Scheme III. Also, quinazoline 11 was synthesized by treat-
ment of isothiocyanate 1b with anthranilic acid according to
a procedure reported by El-Gaby16 (mp, mmp and TLC). 2-
Mercapto benzimidazole 12 was produced by reaction of
compound 2a with o-phenylenediamine as binucleophile.
The formation of 12 was proceeded to take place through
elimination of hydrogen cyanide and sulfanilamide mole-
cules. Compound 12 was prepared from the interaction of
o-phenylenediamine with carbon disulfide in alcoholic potas-
sium hydroxide.17 On the other hand, cyclocondensation of
compounds 2b-d with o-phenylenediamine furnished the cor-
responding 2-anilino derivatives 13a-c on the basis of analyt-
ical and spectral data. Formation of 13 was assumed to pro-
ceed via the elimination of hydrogen cyanide and hydrogen
sulfide (lead acetate paper test). Also, compounds 13 were
produced by an independent synthetic route via treatment of
1b-d with o-phenylenediamine under reflux in absolute etha-
nol catalyzed by triethylamine, Scheme III. Hydrogen sulfide
was evolved when compound 2a was treated with ortho chlo-
roaniline under reflux in absolute ethanol/TEA and produced
compound 14. The infrared spectrum of compound 14 re-
vealed the presence of a characteristic band for CºN at 2206
cm-1. On the other hand thioureas 15a,b were obtained by
treatment of compound 2b with ortho chloroaniline, via elim-
ination of hydrogen cyanide, Scheme III. Also, refluxing of
compound 1b with ortho chloroaniline in dioxane furnished
the thiourea 15a and ortho methylaniline, respectively (mp,
mmp and TLC).
Scheme II
S
O
O
S
N
N
H2NNH-C-NH2
N
Ph
N
H
N
O
NH
H2N-C-HN-N
S
4
NH2
CH3
O
O
S
N
N
N
Ph
N
H
N
O
N
CH3
H3C
N
5
3a
H3C
H3C
NH2
O
O
S
N
N
NH2
N
Ph
N
H
N
O
N
N
CH3
H3C
6
O
O
S
N
N
HCl
EXPERIMENTAL
N
Ph
N
H
N
S
O
O
All melting points are uncorrected and were determined
7
on a digital Gallen-Kamp MFB-595 instrument. IR spectra
1
This investigation was extended to study the reactivity
(KBr) were measured on a Shimadzu 440 spectrometer. H
of cyanothioformamide 2 towards some oxygen and nitrogen
nucleophiles. Thus, treatment of compounds 2b,c with cate-
chol under reflux in absolute ethanol and triethylamine fur-
nished the novel 1,3-benzodioxole derivatives 8a,b. The for-
mation of 8 was proceeded via elimination of hydrogen cya-
nide and hydrogen sulfide, Scheme III. In a similar manner,
ortho aminophenol was reacted with compounds 2b,c in
NMR spectra were obtained in dimethyl sulfoxide on a
Varian Gemini 200 (200 MHz) spectrometer using TMS as an
internal standard; chemical shifts are reported as d units.
Mass spectra were obtained on a GC MS-QP 1000 Ex mass
spectrometer at 70 eV. Elemental analyses were carried out at
the Microanalytical Center of Cairo University. Physical and
analytical data for the synthesized compounds are given in

Cyanothioformamides in Heterocyclic Synthesis
J. Chin. Chem. Soc., Vol. 51, No. 2, 2004 329
Scheme III
X
R
X
O
S
OH
O
S
N
2b,c
N
H
N
H
N
-HCN
O
X= NH2
-H2S
X= OH
-H2S
R
N
R
N
Cl
O
O
N
H
O
S
N
H2N
S
N
O
S
N
O
N
N
H
N
H
O
O
N
H
N
H
NC
O
O
14
8a,b
9a,b
O
COOH
NH2
Cl
OH
S
O
S
N
NH2
2b
-HCN
N
H
N
H
N
H
N
2a
2b
O
10
2
-H2O
X
COOH
NH2
O
O
S
N
NH2
N
N
H
1b
N
O
S
N
H
11
X
N
O
S
S
NH2
N
H
N
H
N
H
2a
N
O
O
-HCN
H
N
H
N
15a,b
1b
S
NH2
O
NH2
NH2
S
X
O
- H2N
N
S
NH2
NH2
O
H2N
H2N
CS2
KOH
N
H
SH
12
8,9 a; R= H
b; R= CH3
13 a; R= 2-pyrimidinyl
NH2
2b-d
O
-HCN
H
H
N
b; R= 2-(4-methylpyrimidinyl)
c; R= 2-thiazolyl
N
S
NHR
O
15 a; X= Cl
b; X= CH3
S
NH2
NH2
-H2S
N
O
S
1b-d
N
H
N
H
NHR
O
13a-c
Table 1. The spectral data are collected in Table 2.
thiocyanate 118 (0.01 mole) in ethanol (50 mL; 60%) was
stirred at room temperature for 8 h. The reaction mixture was
then poured into ice/HCl, and the obtained product was col-
lected, washed with water, and recrystallized from the proper
solvent to give 2.
N-[4-(N-substituted sulfamoyl)phenyl]cyanothioform-
amides (2a-d)
General procedure
A mixture of potassium cyanide (0.01 mole) and iso-
Mass spectrum of compound 2a exhibited a molecular

330 J. Chin. Chem. Soc., Vol. 51, No. 2, 2004
El-Gaby et al.
Table 1. Melting Point, Yield, and Analytical Data of the Synthesized Compounds
Compd.
No.
M.P
(°C)
Solvent
cryst.
Color
Yield
(%)
Formula
Elemental analyses Calcd./Found
(Mol. Wt.)
C
H
N
2a
2b
2c
2d
3a
3b
4
160-2
220-1
203-2
195-6
150-1
130-2
120-1
190-2
170-1
220-2
190-2
218-9
160-1
175-6
>300
CHCl3/
pet.ether
CHCl3/
pet.ether
CHCl3/
pet.ether
CHCl3/
pet.ether
Ethanol
Orange
Orange
Orange
Orange
Orange
Yellow
Orange
Yellow
Yellow
Red
78
75
70
59
72
60
68
64
62
75
80
79
75
80
84
65
74
69
58
81
77
66
C8H7N3O2S2
(241.29)
39.82
39.80
45.13
45.20
46.84
46.70
40.73
40.60
52.04
52.10
53.09
53.10
48.48
48.40
65.88
65.70
61.94
61.80
51.93
51.80
55.28
55.10
56.24
56.30
55.58
55.60
56.68
56.70
52.54
52.60
55.98
55.90
55.73
55.80
56.83
56.70
51.74
51.70
50.23
50.30
48.63
48.70
54.12
54.30
2.92
2.90
2.84
2.80
3.33
3.40
2.49
2.50
3.22
3.20
3.56
3.60
3.46
3.50
4.52
4.60
4.04
4.10
2.98
2.80
3.55
3.70
3.69
3.20
3.57
3.50
3.96
3.90
3.18
3.20
4.03
4.10
3.85
3.70
4.24
4.30
3.53
3.50
3.31
3.30
3.36
3.30
4.29
4.40
17.41
17.30
21.93
21.90
21.01
21.10
17.27
17.30
19.17
19.20
18.57
18.50
25.44
25.50
16.30
16.40
18.73
18.60
15.94
15.80
15.17
15.10
14.65
14.50
19.06
19.10
18.36
18.40
17.02
17.10
18.65
18.70
22.94
22.80
22.09
22.10
18.85
18.80
16.74
16.70
16.68
16.70
17.53
17.40
C12H9N5O2S2
(319.37)
C13H11N5O2S2
(333.39)
C11H8N4O2S3
(324.40)
C19H14N6O3S2
(438.49)
Ethanol
Ethanol
Benzene
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Dioxane
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
C20H16N6O3S2
(452.52)
C20H17N9O3S2
(495.54)
5
C33H27N7O3S
(601.69)
6
C27H21N7O3S
(523.58)
7
C19H13N5O4S2
(439.47)
8a
8b
9a
9b
11
12
13a
13b
13c
14
15a
15b
Orange
Yellow
Yellow
Yellow
Orange
Golden
Yellow
Yellow
Yellow
Yellow
Yellow
Yellow
C17H13N4O4S
(369.37)
C18H15N4O4S
(383.40)
C17H13N5O3S
(367.39)
C18H15N5O3S
(381.42)
C18H13N5O3S2
(411.46)
301-3
170-2
254-5
165-6
220-1
162-4
200-2
C7H6N2S
(150.20)
C17H14N6O2S
(366.40)
C18H16N6O2S
(380.43)
C16H13N5O2S2
(371.44)
C14H11ClN4O2S
(334.79)
C17H14ClN5O2S2
(419.91)
C18H17N5O2S2
(399.50)

Cyanothioformamides in Heterocyclic Synthesis
J. Chin. Chem. Soc., Vol. 51, No. 2, 2004 331
Table. 2. Spectroscopic Data of the Synthesized Compounds
Compd.
No.
IR (KBr, cm-1)
1H NMR (ppm, d) (DMSO-d6)
2a
3361, 3267, 3200 (NH, NH2), 2211 (CºN), 1336,
1157 (SO2).
7.40 (s, 2H, SO2NH2), 7.72 (s, 1H, NH), 7.93, 8.03 (2d, 4H,
Ar-H, J = 8.60 Hz).
2b
3400, 3274 (NH), 2119 (CºN), 1383, 1161 (SO2).
7.04 (t, 1H, CH-pyrimidine, J = 4.8 Hz), 7.57, 7.61 (2s, 2H,
two NH), 8.01-8.09 (m, 4H, Ar-H), 8.50 (d, 2H, two CH-
pyrimidine, J = 4.8 Hz).
2c
3450, 3267 (NH), 2115 (CºN), 1371, 1137 (SO2).
2.31 (s, 3H, CH3), 6.88, 8.31 (2d, 2H, two CH-pyrimidine, J
= 4.8 Hz), 7.55-8.07 (m, 6H, Ar-H and two NH).
2d
3a
3420, 3267 (NH), 2110 (CºN), 1371, 1147 (SO2).
3300, 3132 (NH), 1784 (C=O), 1319, 1157 (SO2).
7.00 (t, 1H, CH-pyrimidine, J = 4.6 Hz), 7.50, 8.30 (2 hump,
two NH), 7.50-8.00 (m, 9H, Ar-H), 8.50 (d, 2H, two CH-
pyrimidine, J = 4.6 Hz).
3b
4
3466, 3200 (NH), 1732 (C=O), 1371, 1147 (SO2).
2.48 (s, 3H, CH3), 7.01, 8.13 (2d, 2H, two CH-pyrimidine, J
= 4.7 Hz), 7.20-7.90 (m, 11H, Ar-H and NH).
3450, 3317, 3240 (NH, NH2), 1728 (C=O), 1581
(C=N), 1334, 1157 (SO2).
3.68 (s, 2H, NH2), 7.02 (d, 1H, CH-pyrimidine, J = 4.8 Hz),
7.39-7.91(m, 9H, Ar-H), 8.5 (d, 2H, CH-pyrimidine, J = 4.8
Hz), 10.0 (s, 1H, NH), 11.60 (hump, 1H, NH).
2.24, 2.28 (2s, 6H, 2CH3), 6.58 (t, 1H, CH-pyrimidine, J =
4.5 Hz), 6.98-7.89 (m, 17H, Ar-H), 8.47 (d, 2H, two CH-
pyrimidine, J = 4.5Hz), 11.20 (hump, 1H, NH).
2.27, 2.30 (2s, 6H, 2CH3), 6.55 (d, 1H, CH-pyrimidine, J =
4.7 Hz), 8.49 (d, 2H, two CH-pyrimidine, J = 4.7 Hz), 6.99-
7.90 (m, 12H, Ar-H and NH).
5
6
7
3355 (NH), 1720 (C=O), 1589 (C=N), 1334, 1157
(SO2).
3390 (NH), 1743 (C=O), 1581 (C=N), 1342, 1164
(SO2).
3150 (NH), 1780, 1743 (C=O), 1326, 1164 (SO2).
7.06 (t, 1H, CH-pyrimidine, J = 4.8 Hz), 7.46-8.22 (m, 9H,
Ar-H), 8.54 (d, 2H, two CH-pyrimidine, J = 4.8 Hz), 11.80
(hump, 1H, NH).
8a
8b
3450 (NH), 1620 (C=N), 1338, 1161 (SO2).
3340 (NH), 1596 (C=N), 1342, 1157 (SO2).
2.31 (s, 3H, CH3), 6.57, 8.31 (2d, 2H, two CH-pyrimidine, J
= 4.6 Hz), 7.61-7.95 (m, 8H, Ar-H), 11.35 (s, 1H, NH).
9a
9b
3371, 3309 (NH), 1643 (C=N), 1326, 1149 (SO2).
3332, 3124 (NH), 1640 (C=N), 1342, 1157 (SO2).
2.31 (s, 3H, CH3), 6.88, 8.33 (2d, 2H, two CH-pyrimidine, J
= 4.6 Hz), 7.25-7.99 (m, 8H, Ar-H), 11.02, 11.35 (2s, 2H,
two NH).
11
3446, 3249 (NH), 1664 (C=O), 1620 (C=N), 1338,
1143 (SO2).
12
3193 (NH), 1620 (C=N).
13a
3355, 3200 (NH), 1630 (C=N), 1326, 1149 (SO2).
6.56 (t, 1H, CH-pyrimidine, J = 4.8 Hz), 7.11-7.65 (m, 8H,
Ar-H), 8.51 (d, 2H, two CH-pyrimidine, J = 4.8 Hz), 7.83,
8.20 (two hump, 2H, two NH), 12.14 (s, 1H, NH).
2.33 (s, 3H, CH3), 6.87-7.92 (m, 9H, Ar-H and NH), 6.54,
8.31 (2d, 2H, two CH-pyrimidine, J = 4.6 Hz), 6.90, 12.49
(2s, 2H, two NH).
13b
3200, 3109 (NH), 1596 (C=N), 1342, 1157 (SO2).
13c
14
3295 (NH), 1620 (C=N), 1340, 1141 (SO2).
3340, 3255, 3111 (NH), 2206 (CºN), 1658 (C=N),
1326, 1157 (SO2).
7.24-8.01 (m, 10H, Ar-H + SO2NH2), 11.62 (s, 1H, NH).
15a
15b
3363, 3112 (NH), 1342, 1157 (SO2).
3425, 3359 (NH), 1647 (C=N), 1326, 1152 (SO2).
2.27 (s, 3H, CH3), 6.56 (d, 1H, CH-pyrimidine, J = 4.6 Hz),
8.50 (d, 2H, two CH-pyrimidine, J = 4.6 Hz), 6.98-8.00 (m,
8H, Ar-H), 5.98, 11.00 (two hump, 2H, two NH), 9.64 (s,
1H, NH).

332 J. Chin. Chem. Soc., Vol. 51, No. 2, 2004
El-Gaby et al.
ion peak at m/z 241 (0.2%) together with a base peak at m/z
213.84 (100%); other significant peaks were observed m/z at:
197 (22%), 149 (13%), 133 (56.9%) and 75 (6.3%).
Also, mass spectrum of compound 2b exhibited a mo-
lecular ion peak at m/z 302 (M-OH; rel. int. 0.5) and base
peak at m/z 227 (100%); other significant peaks were ob-
served at m/z: 195 (2.1%), 161 (0.7%), 134 (26%) and 76
(4.5%).
2-[4-(N-3-R-pyrimidin-2-yl)sulfamoyl]phenylimino-1,3-
benzodioxoles (8a,b)
General procedure
A mixture of compound 2b or 2c (0.01 mole) and
catechol (0.01 mole) in absolute ethanol (30 mL) and a few
drops of triethylamine was refluxed for 48 h. then allowed to
cool. The solid product was collected and recrystallized from
the proper solvent to give 8.
1-Phenyl-3-[4-(N-(3-R-pyrimidin-2-yl)sulfamoyl]phenyl-5-
imino-4-thioxo-2-imidazolidinones (3a,b)
2-[4-(N-(3-R-pyrimidin-2-yl)sulfamoyl]anilinobenzoxazoles
(9a,b)
General procedure
General procedure
A mixture of cyanothioformamide 2b or 2c (0.01
mole), phenyl isocyanate (0.01 mole) and triethylamine (0.5
mL) in dry tetrahydrofuran (20 mL) was stirred at room tem-
perature for 24 h. The obtained product was collected,
washed with ether, and recrystallized from the proper solvent
to give 3.
A mixture of compound 2b or 2c (0.01 mole) and o-
aminophenol (0.01 mole) and triethylamine (0.5 mL) in
dimethylformamide (10 mL) was heated under reflux for 12
h., then allowed to cool and poured into cold water (50 mL).
The solid product was collected and recrystallized from the
proper solvent to give 9.
1-Phenyl-3-[4-(N-pyrimidin-2-yl)sulfamoyl]phenyl-5-
imino-4-thiosemicarbazone-2-imidazolidinone (4)
A mixture of compound 3a (0.01 mole) and thio-
semicarbazide (0.01 mole) in absolute ethanol (30 mL) was
refluxed for 24 h, then allowed to cool and poured into cold
water (50 mL). The solid product was collected and recrys-
tallized from the proper solvent to give 4.
3-[4-(N-pyrimidin-2-yl)sulfamoyl]phenyl-2-thioxo-quin-
azolin-4-ones (11a,b)
A mixture of compound 2b (0.01 mole), anthranilic
acid (0.01 mole) in ethanol (30 mL) and a few drops of tri-
ethylamine (0.5 mL) was refluxed for 3 h. The solid product
which was produced on heating was collected and recrys-
tallized from the proper solvent to give 11.
1-Phenyl-3-[4-(N-pyrimidin-2-yl)sulfamoyl]phenyl-4,5-bis-
[p-tolylimino]-2-imidazolidinone (5)
2-Mercaptobenzimidazole (12)
A mixture of compound 1a (0.01 mole), o-phenylene-
diamine (0.01 mole) and triethylamine (0.5 mL) in absolute
ethanol (30 mL) was refluxed for 24 h. The solid that was ob-
tained was recrystallized from the proper solvent to give 12.
A mixture of compound 3a (0.01 mole), 4-methyl ani-
line (0.02 mole) and triethylamine (0.5 mL) in absolute etha-
nol (30 mL) was heated under reflux 12 h, then allowed to
cool and poured into crushed ice and acidified with HCl. The
solid product was collected and recrystallized from the
proper solvent to give 5.
2-[4-(N-substituted sulfamoyl)]anilinobenzimidazoles
(13a-c)
Method A: The experimental procedure used for the
synthesis of 12 was carried out except for the use of 2b-d in-
stead of 2a.
6,7-Dimethyl-1-phenyl-3-[4-(N-pyrimidin-2-yl)sulfamoyl]-
phenyl-1H-imidazo-[4,5-b]quinoxaline-2-one (6)
A mixture of compound 3a (0.01 mole) and 4,5-di-
methyl-1,2-phenylenediamine (0.01 mole) in ethanol (30
mL) was heated under reflux for 48 h; the obtained product
was recrystallized from the proper solvent to give 6.
Method B: A mixture of compound 1 (0.01 mole) with
o-phenylenediamine (0.01 mole) in absolute ethanol (30 mL)
and triethylamine (0.5 mL) was heated under reflux for 48 h.
The obtained product was recrystallized from the proper sol-
vent.
1-Phenyl-3-[4-(N-pyrimidin-2-yl)sulfamoyl]phenyl-4-
thioxo-2,5-imidazolidinedione (7)
N-(2-Chlorophenyl)-2-cyano-N¢-(4-sulfamoylphenyl)acet-
amidine (14)
To a mixture of compound 3a (0.01 mole) in boiling
ethanol (20 mL), conc HCl (5 mL) was added. The solid prod-
uct was recrystallized from the proper solvent to give 7.
A mixture of compound 1a (0.01 mole), o-chloro-
aniline (0.01 mole) and triethylamine (0.5 mL) in absolute

Cyanothioformamides in Heterocyclic Synthesis
J. Chin. Chem. Soc., Vol. 51, No. 2, 2004 333
Koboldt, C. M.; Logusch, E. W.; Morton, M. B.; Perkins, W.
E.; Reinhard, E. J.; Seibert, K.; Veenhuizen, A. W.; Zhang,
Y.; Reitz, D. B. J. Med. Chem. 1995, 38, 4570.
7. Yoshino, H.; Veda, N.; Niijima, J.; Sugumi, H.; Kotake, Y.;
Koyanagi, N.; Yoshimatsu, K.; Asada, M.; Watanabe, T.;
Nagasu, T.; Tsukahara, K.; Lijima, A.; Kitoh, K. J. Med.
Chem. 1992, 35, 2496.
ethanol (30 mL) was heated under reflux for 8 h., then al-
lowed to cool and poured into cold water (50 mL). The solid
product was collected and recrystallized from the proper sol-
vent to give 14.
N1-[4-(N-pyrimidin-2-yl)sulfamoyl)phenyl-N3-(2-substi-
tuted phenyl)thioureas (15a,b)
8. Labro, M. T. L. Drugs 1993, 45, 319.
General procedure
9. El-Sharief, A. M. Sh.; Ammar, Y. A.; Mohamed, Y. A.;
El-Gaby, M. S. A. Phosphorus, Sulfur and Silicon 1999,
148, 117.
10. El-Sharief, A. M. Sh.; Ammar, Y. A.; Mohamed, Y. A.;
El-Gaby, M. S. A. Phosphorus, Sulfur and Silicon 1999,
149, 215.
11. El-Sharief, A. M. Sh.; Atalla, A. A.; Hussein, A. M.;
El-Gaby M. S. A.; Hassan, A. A. Phosphorus, Sulfur and Sil-
icon 2000, 160, 141.
A mixture of 1b (0.01 mole), 2-substituted aniline (0.01
mole) and triethylamine (0.5 mL) in absolute ethanol (30 mL)
was heated under reflux for 7 h, then allowed to cool and
poured into cold water (50 mL). The solid product was col-
lected and recrystallized from the proper solvent to give 15.
Received April 30, 2003.
12. El-Sharief, A. M. Sh.; Hussein, A. M.; El-Gaby, M. S. A.;
Atalla, A. A.; Ahmed, A. A. Phosphorus, Sulfur and Silicon
2001, 170, 47.
13. El-Sharief, A. M. Sh.; Ammar, Y. A.; Mohamed, Y. A.;
El-Gaby, M. S.A. Heteroatom. Chem. 2002, 13 (4), 291.
14. El-Sharief, A. M. Sh.; Ammar, Y. A.; El-Gaby, M. S. A.;
Zahran, M. A.; Khames, A. A. Afinidad 2003, LX(503), 47.
15. El-Gaby, M. S. A.; Ammar, Y. A.; El-Sharief, A. M. Sh.;
Zahran, M. A.; Khames, A. A Heteroatom Chem. 2002, 13
(7), 611.
16. El-Gaby, M. S. A. Phosphorus, Sulfur and Silicon 2000,
156, 157.
17. Van Allan, J. A.; Deacon., B. D. Org. Synth. Coll. 1963, IV,
569.
REFERENCES
1. El-Gaby, M. S. A.; Atalla, A. A.; Gaber, A. M.; Abd
Al-Wahab, K. A. IL Farmaco 2000, 55, 596.
2. El-Gaby, M. S. A.; Micky, J. A.; Taha, N. M.; El-Sharief, M.
A. M. Sh. Acta Chim. Slov. 2002, 49, 159.
3. El-Gaby, M. S. A.; Gaber, A. M.; Atalla A. A.; Abd
Al-Wahab, K. A. IL Farmaco 2002, 57, 613.
4. Maren, T. H. Annu. Rev. Pharmacol. Toxicol. 1976, 16, 309.
5. Supuran, C. T.; Scozzafava, A.; Jurca, B. C.; Iies, M. A. Eur.
J. Med. Chem. 1998, 33, 83.
18. Uher, M.; Floch, L.; Jendrichovsky, J. Collection Czech.
Chem. Commun. 1974, 39, 182.
6. Li, J. J.; Anderson, D.; Burton, E. G.; Cogburn, J. N.; Collins,
J. T.; Garland, D. J.; Huang, S. A.; H. C.; Isakson, P. C.;