Structural study and biological evaluation of some novel 1,2,4-triazole, thiazole, and bisthiazole derivatives bearing a sulfonamide moiety

Article abstract of DOI:10.1080/10426500802417323

The starting material 1,2,4-triazole derivative (3) was used to synthesize some novel condensed triazoles. Thus, treatment of compound (3) with phenyl isocyanate in refluxing pyridine furnished the novel [1,2,4]triazolo[4,3-b][1,2, 4]triazole derivative (5). Also, cyclization of compound (3) with phenyl isothiocyanate afforded the [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivative (7). Hydrazone derivative (9d) was allowed to react with some halogenated reagents such as chloroacetone, ethyl chloroacetate, and chloroacetonitrile to furnish thiazole derivatives (12), (13), and (15), respectively. In a similar manner, bishydrazone (17) was used to prepare the novel bisthiazoles (18) and (19). Some of the synthesized compounds were evaluated for their antibacterial activity.

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Phosphorus, Sulfur, and Silicon
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Structural Study and Biological
Evaluation of Some Novel
1,2,4-Triazole, Thiazole, and
Bisthiazole Derivatives Bearing
a Sulfonamide Moiety
Abdullah G. M. Al-Sehemi a
a Chemistry Department, King Khalid University,
Teachers College at Abha, Kingdom of Saudia Arabia
Published online: 22 Jul 2009.
To cite this article: Abdullah G. M. Al-Sehemi (2009) Structural Study and Biological
Evaluation of Some Novel 1,2,4-Triazole, Thiazole, and Bisthiazole Derivatives Bearing
a Sulfonamide Moiety, Phosphorus, Sulfur, and Silicon and the Related Elements,
184:8, 1991-2003, DOI: 10.1080/10426500802417323
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Phosphorus, Sulfur, and Silicon, 184:1991–2003, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802417323
Structural Study and Biological Evaluation of Some
Novel 1,2,4-Triazole, Thiazole, and Bisthiazole Derivatives
Bearing a Sulfonamide Moiety
Abdullah G. M. Al-Sehemi
Chemistry Department, King Khalid University, Teachers College at
Abha, Kingdom of Saudia Arabia
The starting material 1,2,4-triazole derivative (3) was used to synthesize some novel
condensed triazoles. Thus, treatment of compound (3) with phenyl isocyanate in
refluxing pyridine furnished the novel [1,2,4]triazolo[4,3-b][1,2,4]triazole deriva-
tive (5). Also, cyclization of compound (3) with phenyl isothiocyanate afforded
the [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivative (7). Hydrazone derivative (9d)
was allowed to react with some halogenated reagents such as chloroacetone, ethyl
chloroacetate, and chloroacetonitrile to furnish thiazole derivatives (12), (13), and
(15), respectively. In a similar manner, bishydrazone (17) was used to prepare the
novel bisthiazoles (18) and (19). Some of the synthesized compounds were evaluated
for their antibacterial activity.
Keywords Bisthiazole; hydrazone; thiazole; thiocarbohydrazide; 1,2,4-triazole
INTRODUCTION
Recently some new triazoles have been synthesized as possible an-
tibacterial, antimicrobial, antiviral, and antifungal agents.1–4 Also, a
number of thiazoles have been reported to exhibit antitubercular, anti-
malarial, CNS depressant, and analgesic5–8 properties and antimicro-
bial activity against both Gram-positive and Gram-negative bacteria.9
Furthermore, sulfonamide and azo-sulfonamide derivatives have been
found to be biologically versatile anticancer,10 antimalarial,11 and anti-
tubercular drugs.12–14 In continuation of our interest in organic sulfur
heterocycles,15–19 moiety was designed and their biological effects were
evaluated in a specific program aimed at the synthesis of some new
Received 9 March 2008; accepted 13 August 2008.
Address correspondence to Abdullah G. M. Al-Sehemi, Chemistry Department, King
Khalid University, Teachers College at Abha, Box 249, Kingdom of Saudia Arabia. E-mail:
agmasq@gmail.com
1991

1992
A. G. M. Al-Sehemi
1,2,4-triazole, thiazole, and bisthiazole derivatives containing the sul-
fonamido moiety for evaluated their biological effects.
RESULTS AND DISCUSSION
When the sulfanilamide (1a) was allowed to react with the succinic
anhydride under reflux in ethanol in the presence of triethylamine,
the corresponding succinamic acid derivative (2) was obtained. Its IR
spectrum showed bands at 3330–2750 cm−1 (broad-COOH), 3320, 3280
cm−1 (NH, NH2), 1750, 1690 cm−1 (2 C=O), and its 1H NMR spec-
trum revealed signals at 2.4–2.7 (m, 4H, CH2CH2), 7.2 (s, 2H, NH2),
12.1 (br, 1H, OH). 3-(4-Amino-5-mercapto-4H-[1,2,4]triazol-3-yl)-N-(4-
sulfamoyl-phenyl)-propionamide 3 was prepared in a good yield (84%)
by fusion of N-(4-sulfamoyl-phenyl)-succinamic acid (2) with thiocarbo-
hydrazide. The IR spectrum of 3 exhibited the absence of broad band
characteristic for the carboxylic group and the presence of 3390, 3260,
3220 cm−1 (NH, NH2). The mass spectrum of 3 showed a molecular
ion peak m/z at 342 (M+; 13.03), 343 (M+1, 33.45%) together with
a base peak at 56 (100%), and other significant peaks appeared at
254 (13.03%), 185 (41.55%), 133 (41.20%), 125 (88.87%), 101 (58.15%),
68 (44.01%). The reaction of 3 with phenyl isocyanate in refluxing
pyridine gave a product that formulated as the [1,2,4]triazolo[4,3-
b][1,2,4]triazole derivative 5. Its mass spectrum revealed a molecular
ion peak m/z 427 (M+; 7.45%), with a base peak at 158 (100%), and
other significant peaks appeared at 408 (10.41%), 373 (0.88%), 329
(12.66%), 254 (80.34%), 217 (18.80%), 108 (34.04%), 92 (88.78%), 76
(4.08%). The formation of the triazolotriazole derivative is assumed to
proceed through the urea intermediate (4) followed by elimination of
hydrogen sulfide,20 as depicted in Scheme 1.
On the other hand, interaction of 3 with phenyl isothiocyanate gave
the corresponding 6-anilino-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole
derivative 7 via intermediate 6 followed by elimination of hydrogen
sulfide. Its IR spectrum showed bands at 3344, 3300, 3280 cm−1 (NH,
NH2).
For obtaining the thiazole derivatives, diazotization of sulfanil-
amide(1a) and its derivatives (1b–c) followed by coupling with cyan-
othioacetamide in the presence of sodium acetate in ethanol at 5◦C
furnished the hydrazone form (9a–d) rather than the azo form on the
1
1
basis of HNMR spectra (Scheme 2). The H NMR spectrum of com-
pound (9a) recorded in dimethylsulfoxide revealed a signal at δ = 11.71
ppm, which is attributed to hydrazone NH functional group.

Novel 1,2,4-Triazole, Thiazole, and Bisthiazole Derivatives
1993
SCHEME 1
Due to the possibility of existence in both tautomeric forms, that is, as
azo(A)-hydrazo(H) tautomerization, molecular models of possible tau-
tomeric forms were calculated in the gas phase, using semi-empirical
AM1, PM3, and MNDO methods using HyperChem 7.5 software. The

1994
A. G. M. Al-Sehemi
SCHEME 2
initial geometries of the molecules were built using standard parame-
ters and then optimized using the Polak–Ribiere geometrical optimiza-
tion. The heat of formation and relative stabilities of the two tautomeric
forms 9 and 10 are listed in Table I.
All semi-empirical calculations lead to the same result that the A-
form has more heat of formation value than the H-form. The negative
TABLE I Heat of Formation (ꢀ H◦f ) and Relative Stabilities (ꢀꢀ Hf◦
kcal.mol−1) of Tautomeric Forms of 9 and 10
Method
ꢀ H◦f
ꢀꢀ H◦f
10
9
MNDO
AM1
PM3
222.8
52.0
86.5
224.5
59.6
89.6
−1.7
−7.6
−3.1
ꢀꢀ H◦f = ꢀ Hf◦(H) – ꢀ H◦f (A).

Novel 1,2,4-Triazole, Thiazole, and Bisthiazole Derivatives
1995
FIGURE 1 Optimized geometries of H-form (9) and A-form (10).
sign of the ꢀꢀ H◦f indicates that the H-form is more stable by all
computational methods.
The equilibrium geometries have been calculated also by ab initio
calculations in the gas phase at 6-31G* basis set level, which were
carried out using HyperChem 7.5 software. The optimized structure
information is shown in Figure 1 along with the relative energies of
9 and 10. For all calculations, the most stable tautomer corresponds
to the H-form structure 9. This, however, is in agreement with the
experiment data.
The reactivity of the thiocarbamoyl functional group in compound
(9d) towards some halogenated reagents was studied. Thus, cycloalky-
lation of compound (9d) with chloroacetone in refluxing ethanol in the
presence of fused sodium acetate yielded the corresponding thiazole
derivative (12). The structure of the thiazole derivative (12) was es-
tablished by its analytical and spectral data. The infrared spectrum of
compound (12) exhibited absorption bands characteristic for NH (3326,
3103 cm−1) and C ≡ N (2221 cm−1). Also, the 1H NMR spectrum of com-
pound (12) in DMSO-d6 showed the presence H-thiazole at δ = 5.04
ppm in addition to NH proton at δ = 11.98 ppm, besides other signals
due to methyl and aromatic protons. The formation of compound (12)
is assumed to proceed via initial alkylation to form intermediate (11)
followed by intramolecular cyclization21,22 by elimination of a water
molecule. Cyclization of compound (9d), also with ethyl chloroacetate
at reflux temperature in ethanol in the presence of fused sodium ac-
etate, afforded thiazole derivative (13) via alkylation of thiocarbamoyl
functional group and elimination of ethanol molecule. In addition, cy-
clocondensation of compound (9d) with chloroacetonitrile in ethanol
in the presence of triethylamine under reflux furnished aminothiazole

1996
A. G. M. Al-Sehemi
SCHEME 3
derivative (15). The formation of thiazole (15) is assumed to proceed
through initial alkylation to form (14) followed by intramolecular nu-
cleophilic cyclization and tautomerization (Scheme 3).
It was of interest to incorporate the moiety of thiazole rings into
the well-known antimicrobial diphenyl sulfides.23,24 We have syn-
thesized some heterocycle compounds containing diphenyl sulfone

Novel 1,2,4-Triazole, Thiazole, and Bisthiazole Derivatives
1997
SCHEME 4
and thiazole moieties for their useful biological application. 4,4ꢀ-
Diaminodiphenylsulfone (16) was diazotized and coupled with cyan-
othioacetamide to form bishydrazone derivative (17). Treatment of
bishydrazone (17) with chloroacetone under reflux in ethanol furnished
bisthiazole derivative (18). Finally, condensation of bishydrazone (17)
with chloroacetonitrile in dioxane in the presence of triethylamine at
reflux temperature produced the bisthiazole derivative (19) (Scheme 4).
ANTIMICROBIAL SCREENING
The synthesized compounds were evaluated for antibacterial activity
using the agar diffusion technique.25 A 1 mg/mL solution in dimethyl-
formamide was used. All the prepared compounds were tested for an-
tibacterial activity against the following: Staphylococcus aureus (NCTC
7447), Bacillus subtilis (NCTC 10400), Sarcina sp. (NCTC 1117),

1998
A. G. M. Al-Sehemi
TABLE II Antibacterial Property of the Synthesized Compounds
Gram positive
Gram negative
Staphylococcus
aureus
Bacillus
subtilis
Escherichia
coli
Serratia
marcescens
Compd.
No.
Sarcina Sp.
(NCTC 7447) (NCTC 10400) (NCTC 1117) (NCTC 10416) (IMRU 70)
7a
7b
7c
7d
9
11
13
15
18
19
++
+
++
++
+
+
+ + +
+
+
++
+
++
++
+
+
++
++
++
+
++
+
+
+
++
++
+ + +
++
+
++
+
+
+
+
+
++
+
++
++
+
+
+ + +
+
+
++
+
+
+
++
+ + ++
+
+
Standard + + ++
+ + ++
+ + ++
+ + ++
+ = Less active (2–5 mm).
++ = Moderately active (6–14 mm).
+ + + = Highly activity (15–20 mm).
Escherichia coli (NCTC 10416), and Serratia marcescens (IMRU 70).
Dimethylformamide showed no inhibition zone. The agar media were
incubated with different microorganism cultures; after 24 h of incu-
bation at 30◦C for bacteria, the diameter of inhibition zone (mm) was
measured. Ampicillin in a concentration 25 µg mL−1 was used as ref-
erence for antibacterial activity. The minimal inhibitory concentration
(MIC) of some of the tested compounds was measured by a twofold serial
method.26 Most of the synthesized compounds exhibited antibacterial
activity towards all the microorganisms used (Table II).
EXPERIMENTAL
Melting points are uncorrected. IR spectra were recorded (KBr) on a
Perkin Elmer 1650 spectrophotometer. 1H NMR spectra were recorded
on Varian Gemini spectrometer 200 (200 MHz) using DMSO-d6 as a
solvent and TMS as internal standard. Chemical shifts are expressed
as δ ppm units. Microanalytical data were obtained from the Microana-
lytical Data unit at Cairo University. Physical data for the synthesized
compounds are given in Table III. The spectral data are collected in
Table IV.

Novel 1,2,4-Triazole, Thiazole, and Bisthiazole Derivatives
1999
TABLE III Physical Data for the Synthesized Compounds
Required (found)
Compd.
No.
Mp
Yield (%)
(Color)
Solvent
Cryst.
Mol. Formula
(M.wt)
(◦C)
C
H
N
2
208–210
258–260
229–230
298–300
157–159
160–162
180–182
272–274
170–172
130 dec.
165–167
240–242
220–222
>300
81
(colorless)
84
(colorless)
73
(colorless)
78
(colorless)
79
(Yellow)
74
(Yellow)
70
(Orange)
87
(Yellow)
68
(Yellow)
75
(Yellow)
77
(Yellow)
84
(Orange)
76
EtOH
C10H12N2O5S
(272)
44.12
4.41
10.29
(44.40) (4.60) (10.40)
38.60 4.09 24.56
(38.30) (4.30) (24.80)
50.59 3.98 22.95
(50.80) (3.70) (23.30)
48.76 3.84 22.12
(48.60) (3.60) (22.40)
38.16 3.18 24.74
(38.00) (3.10) (24.60)
42.85 3.30 23.08
(42.70) (3.20) (22.90)
44.44 3.70 22.21
(44.30) (3.75) (22.10)
43.21 3.07 27.15
(43.30) (2.95) (27.00)
48.11 3.26 24.55
(48.00) (3.20) (24.50)
44.88 2.74 24.44
(44.80) (2.80) (24.30)
45.00 3.00 28.00
(44.90) (2.90) (28.00)
45.96 2.98 23.83
(45.80) (2.90) (23.70)
52.75 3.30 20.51
(52.40) (3.50) (20.30)
48.18 2.92 25.55
(48.10) (2.80) (25.40)
3
EtOH
C
11H14N6O3S2
(342)
5
Dioxane
Dioxane
EtOH
C
18H17N7O4S
(427)
7
C
18H17N7O3S2
(443)
9a
9b
9c
9d
12
13
15
17
18
19
C9H9N5O2S2
(283)
EtOH
C
13H12N6O3S2
(364)
EtOH
C
C
C
C
C
C
C
14H14N6O3S2
(378)
13H11N7O2S2
(361)
16H13N7O2S2
(399)
15H11N7O3S2
(401)
15H12N8O2S2
(400)
18H14N8O2S3
(470)
24H18N8O2S3
(546)
EtOH
Dioxane
Dioxane
Dioxane
Benzene
Dioxane
Dioxane
(Orange)
64
(Orange)
C
22H16N10O2S3
(548)
N-(4-Sulfamoyl-phenyl)-succinamic acid (2)
A mixture of sulfanilamide 1 (0.01 mol; 1.72 g) and succinic anhydride
(0.01 mol; 1.00 g) in ethanol (30 mL) containing 3 drops of triethylamine
was refluxed for 3 h. The solid obtained was recrystallized from ethanol
to give 2.
3-(4-Amino-5-mercapto-4H-[1,2,4]triazol-3-yl)-N-
(4-sulfamoyl-phenyl)-propion-amide (3)
A mixture of 2 (0.01 mol; 2.72 g) and thiocarbohydrazide (0.01 mol;
1.09 g) was fused at 220◦C in an oil bath for 15 min. After cooling, the
reaction mixture was triturated with ethanol (30 mL) to give 3.

2000
A. G. M. Al-Sehemi
TABLE IV Spectroscopic Data for the Synthesized Compounds
1HNMR (ppm, δ)
Compd. No.
IR (KBr, cm−1
)
(DMSO-d6)
2
3330–2750(br-COOH), 3320, 3280
(NH,NH2), 2940 (CH-aliph),
1750, 1690 (2C=O)
2.7(m, 4H, 2× CH2), 7.2(s, 2H,
NH2), 7.4–7.9(m, 4H, Ar-H),
10.2(s, 1H, NH), 12.1(br, 1H,
COOH)
3
3390, 3260, 3220 (NH, NH2), 2940
(CH-aliph.), 1700 (C=O), 1620
(C=N)
2.8 (m, 4H, 2 CH2), 7.3–7.6 (m, 4H,
Ar-H), 7.8 (br, 4H, 2 NH2), 8.3 (s,
2H, 2 NH)
5
3300, 3260 (NH, NH2), 1708, 1658
(2C=O), 1594 (C=N)
7
3344, 3300, 3280 (NH, NH2), 1664
(C=O), 1594 (C=N)
2.7 (m, 4H, 2CH2), 7.2–7.9 (m, 11H,
Ar-H+ NH2), 10.3 (s, 2H, 2NH)
7.31 (s, 2H, SO2NH2), 7.81 (m, 4H,
Ar-H), 9.43 (s, 1H, NH), 9.85 (s,
1H, SH), 11.7 (s, 1H,
9a
3362, 3292, 3218 (NH/NH2), 2220
(C ≡ N), 1598 (N=N), 1330, 1154
(SO2)
hydrazone-H)
9b
3420, 3330, 3160 (NH/NH2), 2212
(C ≡ N), 1614 (C=N), 1596
(N=N), 1338, 1160 (SO2)
2.30 (s, 3H, CH3), 3.90 (br, 2H,
NH2), 6.14 (s, 1H, isooxazole-H),
7.61–7.92 (m, 5H, Ar-H and
SO2NH), 11.46 (s, 1H,
hydrazone-H)
9c
9d
3400, 3310, 3200 (NH/NH2), 2214
(C ≡ N), 1624 (C=N), 1590
(N=N), 1396, 1148 (SO2)
1.78, 1.95 (2s, 6H, 2CH3), 7.56–7.87
(m, Ar-H and SO2NH), 9.5 (s, 1H,
NH), 9.80 (s, 1H, SH), 11.80 (s,
1H, hydrazone-H)
7.03 (t, 1H, pyrimidine-H),
7.83–7.96 (m, 5H, Ar-H and
SO2NH), 8.50 (d, 2H,
pyrimidine-H), 9.48 (s, 1H, NH),
9.86 (s, 1H, SH), 11.80 (s, 1H,
hydrazone-H)
3360, 3232, 3190 (NH/NH2), 2212
(C ≡ N), 1616 (C=N), 1598
(N=N), 1330, 1164 (SO2)
12
13
3326, 3103 (2 NH), 2977
(CH-aliph), 2221 (C ≡ N), 1627
(C=N), 1594 (N=N), 1344, 1140
(SO2)
3224, 3108 (2 NH), 2224 (C ≡ N),
1737 (C=O), 1580 (N=N), 1339,
1157 (SO2)
2.10 (s, 3H, CH3), 5.04 (s, 1H,
thiazole-H), 7.47–8.04 (m, 8H,
Ar-H and SO2NH), 11.98 (s, 1H,
hydrazone-H)
4.80 (s, 2H, CH2), 7.03 (t, 1H,
pyrimidine-H), 7.58–8.03 (m, 5H,
Ar-H and SO2NH), 8.52 (d, 2H,
pyrimidine-H), 12.01 (s, 1H,
hydrazone-H)
15
3329, 3229, 3111 (NH/NH2), 2226
(C ≡ N), 1579 (N=N), 1343, 1158
(SO2)
4.40 (br, 2H, NH2), 5.21 (s, 1H,
thiazole-H), 7.03 (t, 1H,
pyrimidine-H), 7.53–8.00 (m, 5H,
Ar-H and SO2NH), 8.50 (d, 2H,
pyrimidine-H), 11.80 (s, 1H,
hydrazone-H)
(Continued on next page)

Novel 1,2,4-Triazole, Thiazole, and Bisthiazole Derivatives
2001
TABLE IV Spectroscopic Data for the Synthesized Compounds
(Continued)
1HNMR (ppm, δ)
Compd. No.
IR (KBr, cm−1
)
(DMSO-d6)
17
3390, 3300, 3200 (NH/NH2), 2210
(C ≡ N), 1596 (N=N), 1298, 1148
(SO2)
7.85–7.97 (m, 8H, Ar-H), 9.50, 9.81
(2s, 4H, 2NH2), 11.80 (s, 2H,
hydrazone-H)
18
19
3351, 3104 (2 NH), 2219 (C ≡ N),
2.19, 2.29 (2s, 6H, 2CH3), 4.21
(s,2H, thiazole-H), 7.38–8.10 (m,
8H, Ar-H), 12.10 (s, 2H,
1593 (N=N), 1358, 1148 (SO2)
hydrazone-H)
3352, 3223 (2 NH), 2195 (C ≡ N),
1593 (N=N), 1348, 1148 (SO2)
4.20 (s, 2H, thiazole-H), 6.60 (s, 4H,
2NH2), 7.67–7.98 (m, 8H, Ar-H),
12.01 (s, 2H,hydrazone-H)
3-(6-Oxo-7-phenyl-6,7-dihydro-5H-[1,2,4]triazolo-[4,3-b][1,2,4]
triazol-3-yl)-N-(4-sulfamoyl-phenyl)-propionamide (5) and
3-(6-Phenylamino-[1,2,4]triazolo[3,4-b] [1,3,4]thiadiazol-3-yl)-
N-(4-sulfamoyl-phenyl)-propionamide (7)
A solution of 3 (0.01 mol) and phenyl isocyanate and/or phenyl isoth-
iocyanate (0.01 mol) in dry pyridine (30 mL) was refluxed until the
evolution of H2S had ceased (12 h). The reaction mixture was poured
into ice cold water (100 mL), and the solid product that formed was
filtered off and recrystallized from ethanol to give compounds 5 and 7,
respectively.
2-Cyano-2-[(4-sulfamoylphenyl)-hydrazono]thioacetamide
(9a–d) and 2-cyano-2 -[(4-{4-[N-(cyanothiocarbamoyl-
methylene)-hydrazino]-benzenesulfonyl}-phenyl)-hydrazono]
thioacetamide (17)
Sulfanilamide 1 or sulfone 16 (0.01 mole) was dissolved in a mixture
of concentrated HCl (5 mL) and water (5 mL) and cooled to 0◦C in
an ice bath. A cold aqueous solution of sodium nitrite (0.01 mole) was
then added. The diazonium salt so obtained was filtered into a cooled
mixture of sodium acetate (3 g) and cyanothioacetamide (0.01 mole)
in ethanol (50 mL). The resulting solid was washed with water and
recrystallized from the proper solvent to give 9 and 17, respectively.

2002
A. G. M. Al-Sehemi
4-{N-[Cyano-(4-methylthiazol-2-yl)-methylene]-hydrazino}-N-
pyrimidin-2-yl-benzenesulfonamide (12) and Bisthiazole
Derivatives (18)
A mixture of compound 9d or 17 (0.01 mole), chloroacetone (0.01 mole),
and sodium acetate (2 g) in ethanol (40 mL) was heated under reflux
for 2 h, then allowed to cool and poured into water (50 mL). The solid
product was collected and recrystallized from the proper solvent to give
12 and 18, respectively.
4-{N-[Cyano-(4-oxo-4,5-dihydrothiazol-2-yl)-methylene]
hydrazine}-N-pyrimidin- 2-yl-benzenesulfonamide (13)
A mixture of compound 9d (0.01 mole), ethyl chloroacetate (0.01 mole),
and sodium acetate (3 g) in ethanol (30 mL) was heated under reflux
for 1 h. The solid product that was produced upon heating was collected
and recrystallized to give 13.
4-{N-[4-Aminothiazol-2-yl)-cyano-methylene]hydrazine}-N-
pyrimidin-2-yl-benz-enesulfonamide (15) and Bisthiazole
Derivative (19)
A mixture of compound 9d or 17 (0.01 mole), chloroacetonitrile (0.01
mole), and triethylamine (0.5 mL) in ethanol (30 mL) was heated un-
der reflux for 24 h, then allowed to cool and poured into cold water
(40 mL). The solid product was collected and recrystallized from the
proper solvent to give 15 and 19.
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