Dapson in heterocyclic chemistry, part III: Synthesis, antimicrobial, and antitumor activities of some new bisheterocyclic compounds containing biologically active diphenylsulfone moiety

Article abstract of DOI:10.1080/10426500802505440

The key intermediate diisothiocyanate 2 was allowed to react with 5-amino-3-methyl-pyrazole-4-carbonitrile 3, ethyl 5-amino-1-phenyl-pyrazole-4- carboxylate 6, 2-amino-tetrahydrobenzo[b]thiophene-3-car-bonitrile 9, ethyl-2-amino-tetra-hydrobenzo[b]thiophe

Full text of DOI:10.1080/10426500802505440

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Phosphorus, Sulfur, and Silicon
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Dapson in Heterocyclic
Chemistry, Part III: Synthesis,
Antimicrobial, and Antitumor
Activities of Some New
Bisheterocyclic Compounds
Containing Biologically Active
Diphenylsulfone Moiety
M. M. Ghorab a , N. E. Amin a , M. S. A. El Gaby b
N. M. H. Taha c , M. A. Shehab d & I. M. I. Faker d
,
a Department of Drug Radiation Research , National
Center for Radiation Research and Technology
(NCRRT) , Nasr City, Cairo, Egypt
b Organic Chemistry Department, Faculty of Science
for Boys , Al-Azhar Universty , Asute, Cairo, Egypt
c Organic Chemistry Department, Faculty of Science
for Girls , Al-Azhar Universty , Cairo, Egypt
d Applied Organic Chemistry Department , National
Research Center , Cairo, Egypt
Published online: 03 Nov 2008.
To cite this article: M. M. Ghorab , N. E. Amin , M. S. A. El Gaby , N. M. H. Taha , M.
A. Shehab & I. M. I. Faker (2008) Dapson in Heterocyclic Chemistry, Part III: Synthesis,
Antimicrobial, and Antitumor Activities of Some New Bisheterocyclic Compounds
Containing Biologically Active Diphenylsulfone Moiety, Phosphorus, Sulfur, and Silicon
and the Related Elements, 183:12, 2918-2928, DOI: 10.1080/10426500802505440
To link to this article: http://dx.doi.org/10.1080/10426500802505440

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Phosphorus, Sulfur, and Silicon, 183:2918–2928, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802505440
Dapson in Heterocyclic Chemistry, Part III: Synthesis,
Antimicrobial, and Antitumor Activities of Some New
Bisheterocyclic Compounds Containing Biologically
Active Diphenylsulfone Moiety
M. M. Ghorab,1 N. E. Amin,1 M. S. A. El Gaby,2
N. M. H. Taha,3 M. A. Shehab,4 and I. M. I. Faker4
1Department of Drug Radiation Research, National Center for
Radiation Research and Technology (NCRRT), Nasr City, Cairo, Egypt
2Organic Chemistry Department, Faculty of Science for Boys,
Al-Azhar Universty, Asute, Cairo, Egypt
3Organic Chemistry Department, Faculty of Science for Girls,
Al-Azhar Universty, Cairo, Egypt
4Applied Organic Chemistry Department National Research Center,
Cairo, Egypt
The key intermediate diisothiocyanate 2 was allowed to react with 5-amino-
3-methyl-pyrazole-4-carbonitrile 3, ethyl 5-amino-1-phenyl-pyrazole-4-carboxylate
6, 2-amino-tetrahydrobenzo[b]thiophene-3-car-bonitrile 9, ethyl-2-amino-tetra-
hydrobenzo[b]thiophene-3-carboxylate 12, and/or 1,2,4-triazole 15 to give the corre-
sponding biscompounds 4, 5, 7, 8, 10, 11, 13, 14, and 16, respectively. The structure
of the synthesized compounds was elucidated by elemental analyses and spectral
data. Some of the prepared compounds were tested for their antimicrobial and
antitumor activities.
Keywords Antimicrobial and antitumor activities; biscompounds having diphenylsul-
fone moiety
INTRODUCTION
Diphenylsulfone and bisheterocyclic compounds are reported to have
a broad spectrum of biological activities. Some are endowed with
antifungal,1 antitumor,2 or radioprotective3 properties. Some pyra-
zolopyrimidine, benzothienopyrimidine, and 1,2,4-triazole derivatives
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
2918

Bisheterocyclics Containing Diphenylsulfone
2919
also have various biological properties such as antimicrobial,4−7
anticancer,8,10 antifungal,11−14 and insecticidal.15
In addition many investigators have reported that sulfur-containing
compounds have a radioprotective capacity, since a free SH group that
acts as –OH scavenger or H-donating agent reacts with primary le-
sions, thus leading to a chemical restitution of the damaged site.16
Based on the preceding, a symbiotic approach was utilized via a com-
bination of the sulfone, bisheterocyclic compounds in one structural
formula aiming to produce new compounds with possible antimicrobial
and antitumor activities.
RESULTS AND DISCUSSION
Treatment of dapson1 with thiophosgene at room temperature in the
presence ofdilute hydrochloric acid furnished the corresponding di-
isothiocyanate deriviative 2.
The reactivity of diisothiocyanate
2 toward heterocyclic or-
thoaminocarbonitrile and ortho-aminoester was discussed. Thus, when
diisothiocyanate 2 (1 mol) was reacted with 5-amino-3-methyl-pyrazole-
4-carbo-nitrile 3 (2 mol) in ethanol containing triethylamine, the cyclic
compound 4 was isolated while hot. The pyrazole derivative 5 was ob-
tained from the mother liquor of the reaction mixture. The proposed
structures were based on correct elemental analyses and spectral data
(Scheme 1).
SCHEME 1
The IR spectrum of 4 showed bands at 3470, 3374, 3270 cm−1 (NH),
3076 cm−1 (CH arom.), 1374, 1150 cm−1 (SO2), and 1290 cm−1 (C=S).
Mass spectrum of compound 4 revealed a molecular ion peak m/z at

2920
M. M. Ghorab et al.
576 (M+, 2.83%), with a base peak at 108 (100%), and other significant
peaks appeared at 577 (M+1, 4.72%), 578 (M+2, 1.83%), 552 (8.52%),
393 (2.30%), 332 (25.35%), 290 (87.37%), 248 (31.35%), 140 (60.24%),
92 (28.29%), and 76 (6.47%). The IR spectrum of compound 5 revealed
bands at 3296 cm−1 (NH), 2216 cm−1 (C N), 1590 cm−1 (C N), 1312,
1
1148 cm−1 (SO2), and 1250 cm−1 (C=S). H-NMR spectrum of com-
pound (5 in DMSO-d6) showed signals at 2.4 [s, 6H, 2CH3], 6.2, 6.6, 7.5
[3s, 6H, 6NH], 7.6, and 7.8 [2d, 8H, Ar-H, AB system]. Mass spectrum
of compound 5 exhibited a molecular ion peak m/z at 576 (M+, 36%),
with a base peak at 65 (100%), and other significant peaks appeared at
575 (M-1, 40%), 490 (72%), 399 (32%), 354 (48%), 263 (48%), 218 (56%),
131 (48%), and 90 (92%).
Also, interaction of isothiocyanate 2 (1 mol), with ethyl-5-amino-
1-phenylpyrazol-4-carboxylate 6 (2 mol) in dimethylformamide con-
taining triethylamine gave the corresponding the pyrazolopyrimidine
derivative 7 while hot, while pyrazole derivative 8 was isolated from
the cooled filtered product of the reaction mixture (Scheme 2).
The IR spectrum of compound 7 exhibited bands at 3464 cm−1 (NH),
1640 cm−1 (C O), 1588 cm−1 (C=N), 1310, 1150 (SO2), and 1224 cm−1
(C S). Mass spectrum of 7 showed a molecular ion peak m/z at 702 (M+,
0.78%), with a base peak at 73 (100%), and other significant peaks
appeared at 635 (1.14%), 579 (2.65%), 537 (4.68%), 383 (8.40%), 331
(5.14%), 256 (23.64%), 149 (37.88%), 128 (33.71%), and 97 (37.18%).
The IR spectrum of compound 8 exhibited bands at 3396, 3268, 3198
cm−1 (NH), 2990, 2946 cm−1 (CH aliph.), 1750, 1684 cm−1 (C O), 1624,
1
1600 cm−1 (C N), 1382, 1148 cm−1 (SO2), and 1260 cm−1 (C S). H–
NMR spectrum of compound (8 in DMSO-d6) showed signals at 1.3
[t, 6H, 2CH3], 4.2 [q, 4H, 2CH2], 6.4 [s, 2H, 2CH pyrazole], 7.3–7.7
SCHEME 2

Bisheterocyclics Containing Diphenylsulfone
2921
SCHEME 3
[m, 18H, Ar-H], and 7.8 [s, 4H, 4NH]. Mass spectrum of compound 8
revealed a molecular ion peak m/z at 794 (M+, 0.7%), with a base peak
at 184 (100%), and other significant peaks appeared at 615 (0.7%), 528
(0.14%), 439 (0.9%), 396 (0.17%), 307 (0.36%), 231 (90.59%), and 77
(52.94%).
In a similar manner, 1 mol of diisothiocyanate 2 was reacted with
2 mol of 2-amino-tetrahydrobenzo[b]thiophene-3-carbonitrile 9 to give
the corresponding bisthienopyrimidine derivative 10 while hot, while
the benzothiophene 11 was obtained from the filtered product of the
reaction mixture (Scheme 3).
The IR spectrum of compound 10 revealed bands at 3430, 3352
cm−1 (NH), 2932 cm−1 (CH aliph.), 1626, 1592 cm−1 (C N), 1374, 1148
cm−1 (SO2), and 1250 cm−1 (C S). Mass spectrum of compound 10
showed a molecular ion peak m/z at 688 (M+, 1.48%), with a base
peak at 232 (100%), and other significant peaks appeared at 691 (M+3,
1.2%), 618 (1.41%), 575 (2.88%), 533 (8.80%), 445 (4.50%), 396 (5.24%),
265 (20.44%), 204 (95.83%), and 118 (17.00%). The IR spectrum of
compound 11 revealed bands at 3434, 3334, 3222 cm−1 (NH), 2938,
2838 cm−1 (CH aliph.), 2196 cm−1 (C N), 1376, 1148 cm−1 (SO2), and
1284 cm−1 (C S). 1H-NMR spectrum of (11 in DMSO-d6) exhibited sig-
nals at 1.6 [m, 8H, 4CH2], 2.3, 2.4 [m, 8H, 4CH2], 6.6–8.0 [m, 8H, Ar-H],
11.4, and 11.6 [2s, 4H, 4NH]. Mass spectrum of compound 11 revealed
a molecular ion peak m/z at 688 (M+, 36.36%), with a base peak at
239 (100%), and other significant peaks appeared at 658 (50.00%), 550
(54.53%), 480 (68.18%), 444 (45.45%), 347 (59.09%), 194 (63.64%), 122
(68.18%), and 77 (68.18%).
In addition, the corresponding benzothienopyrimidine 13 was
obtained while hot via the reaction of 2 with ethyl-2-amino-
tetrahydrobenzo[b]-thiophene-3-carboxylate 12 (1:2 mol), while the

2922
M. M. Ghorab et al.
SCHEME 4
benzothiophene derivative 14 was isolated from the filtered product
of the reaction mixture (Scheme 4).
The IR spectrum of 13 revealed bands at 3450 cm−1 (NH), 3094 cm−1
(CH arom.), 2980 cm−1 (CH aliph.), 1636 cm−1 (C=O), 1314, 1146 cm−1
(SO2), and 1248 cm−1 (C S). Mass spectrum of compound 13 exhib-
ited a molecular ion peak m/z at 690 (M+, 0.3%), with a base peak at
66 (100%), and other significant peaks appeared at 689 (M-1, 0.83%),
552 (0.38%), 524 (0.70%), 423 (0.32%), 290 (8.15%), 225 (8.18%), 179
(24.82%), 101 (18.88%), and 75 (44.57%). The IR spectrum of 14 exhib-
ited bands at 3404, 3300 cm−1 (NH), 2986, 2938 cm−1 (CH aliph.), 1648
1
cm−1 (C=O), 1384, 1152 cm−1 (SO2), 1294 cm−1 (C S). H-NMR spec-
trum of (14 in DMSO-d6) revealed signals at 1.3 [t, 6H, 2CH3 ester],
1.7 [m, 8H, 4CH2 cyclo], 2.4, 2.6 [m, 8H, 4CH2 cyclo], 4.2 [q, 4H, 2CH2
ester], and 6.6–8.0 [m, 12H, Ar-H + 4NH]. Mass spectrum of compound
14 exhibited a molecular ion peak m/z at 782 (M+, 1.56%), with a base
peak at 55 (100%), and other significant peaks appeared at 738 (2.54%),
684 (2.54%), 599 (2.73%), 480 (2.73%), 366 (3.52%), 271 (4.30%), 233
(2.15%), 179 (38.48%), 151 (3.32%), and 78 (2.34%).
Finally, interaction of compound 2 with 1,2,4-triazole derivative 15
yielded the novel condensed bisheterocyclic compound 16 (Scheme 5).
SCHEME 5

Bisheterocyclics Containing Diphenylsulfone
2923
The IR spectrum of compound 16 revealed bands at 3450, 3354, 3210
cm−1 (NH, NH2), 1626, 1594 cm−1 (C=N), 1364, 1146 cm−1 (SO2), and
1292 cm−1 (C S). Mass spectrum of compound 16 showed a molecular
ion peak m/z at 608 (M-NH2, 0.38%), with a base peak at 341 (100%),
and other significant peaks appeared at 578 (3.27%), 552 (5.33%), 538
(2.12%), 423 (1.57%), 324 (47.10%), 248 (44.10%), 140 (22.22%), 108
(27.40%), and 90 (2.75%).
Antimicrobial Activity
Some of the newly synthesized compounds were screened for their an-
timicrobial activity using the diffusion agar technique.17 The tested
compounds were dissolved in N, N-dimethylformamide (DMF), which
showed no inhibition zones. Tables I and II list 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 the pathogenic fungi Aspergillus niger
and Aspergillus flavus. The reference antibiotic chloramphenicol and
fungicide Grisofluvine were used as positive controls for comparison.
The fungi cultures were maintained on Czapek’s Dox agar media.
Most of the tested compounds showed a remarkable activity toward
the tested microorganisms and were less active than the standard chlo-
ramphenicol and Grisofluvine.
TABLE I Antibacterial Activity of Some Synthesized Compounds
Salmonella
typhi
Staphylococcus
aureus
Bacillus
subtillus
E. coli
Compound
No.
1
2.5
5
1
2.5
5
1
2.5
5
1
2.5
5
2
4
8
++ ++
++
0
+
0
+
+
0
+
0
+
+
+
0
0
++ ++
+
+
0
++
+
++
+
0
0
0
0
0
+
+
+
+
++
+
+
+
11
14
16
DMF
++ ++
++ ++
++ ++
++
++
++
0
++
+
++ ++ ++ ++ ++ ++
++
++
++
0
+
+
+
0
+
+
0
+
+
++
+
++
++
++ ++ ++
0
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.

2924
M. M. Ghorab et al.
TABLE II Antifungal Activity of Some Synthesized Compounds
Aspergillus niger
Aspergillus vlavus
Compound No.
1
2.5
5
1
2.5
5
2
4
8
11
14
16
DMF
+
+
+
++
+
++
++
+
+
+
++
+
+
++
+
+
+
+
+
+
+
0
+
+
+
+
+
+
++
+
++
++
0
+
++
++
+
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.
In-Vitro 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 (2–16).
Procedure
1. EAC cells were obtained by needle aspiration of the ascetic fluid
from preinoculated mice under aseptic conditions.18
2. The cells were tested for viability and contamination by staining a
certain cell volume of this fluid with an equal volume of the working
solution of trypan blue dye.19,20
3. The ascetic fluid was diluted with saline (1:10) to contain 2.5 ×
106 mL cells on a hemocytometer.
4. 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 (correspond-
ing to 100, 50, and 25 µg/mL) were mixed. The test tubes were incu-
bated at 37◦C for 2 hr. Trypan blue exclusion test19,20 was carried out

Bisheterocyclics Containing Diphenylsulfone
2925
TABLE III In Vitro Antitumor Activity of Some Newly Synthesized
Compounds
Non-viable cells (%)
Concentration (µg/mL)
Compound No.
100
50
25
IC50
2
4
7
10
13
16
0
20
0
10
30
0
0
10
0
0
10
0
0
0
>100a
>100 a
>100 a
>100 a
>100a
>100a
52
0
0
0
0
Doxorubicin
100
55
20
aIC50 >100 µg/mL is considered to be inactive.
to calculate the presence of nonviable cells. Compounds producing
more than 70% non viable cells are considered active.20
No. of non viable
Total No. of cells
% of non-viable cells =
× 100
The relationship between the surviving fraction and drug concentra-
tion was plotted to obtain the survival curve of EAC cell. The response
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 all tested compounds showed
no activity against EAC cells.
EXPERIMENTAL
Melting points were 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 were expressed
as δ ppm units. Mass spectra were recorded on a gas chromatography
GC-MS 9p 100 Ex (schiumadzu instrument) at 70 ev. Microanalytical
data were obtained from the Microanalytical Data Unit at the Cairo
University.

2926
M. M. Ghorab et al.
TABLE IV Physicochemical Data of the Synthesized Compounds
Mol.
Formula
Elemental analyses%
Required/Found
m.p.
(◦C)
Yield
[%]
Comound
No.
(Mol. Wt)
C
H
N
S
2
4
5
7
145–147 88
238–240 52 C24H20N10O2S3 (576) 50.00 50.30 3.47 3.10 24.30 24.60 16.66 16.40
>300 39 C24H20N10O2S3 (576) 50.00 50.30 3.47 3.70 24.30 24.10 16.66 16.30
270–272 61
88–90 34
253–255 46
126–128 41
173–175 35
C14H8N2O2S3 (332) 50.60 50.40 2.40 2.10 8.43 8.10 28.91 29.20
C34H22N8O4S3 (702) 58.12 58.40 3.13 3.50 15.96 16.20 13.68 13.40
C38H34N8O6S3 (794) 57.43 57.10 4.28 4.50 14.11 14.30 12.09 12.30
C32H28N6O2S5 (688) 55.81 55.50 4.06 4.30 12.20 12.40 23.25 23.50
C32H28N6O2S5 (688) 55.81 55.50 4.06 4.30 12.20 12.50 23.25 23.60
C32H26N4O4S5 (690) 55.65 55.40 3.77 3.40 8.12 8.40 23.19 23.15
C36H38N4O6S5 (782) 55.24 55.50 4.86 4.50 7.16 7.50 20.46 20.10
8
10
11
13
14
16
98–100
48
165–167 81 C18H20N14O2S5 (624) 34.61 34.80 3.20 2.90 31.41 31.60 25.64 25.40
4,4ꢀ-Bis(6,7-dihydro-3-methyl-4-oxo-6-thioxo-1H,5H-pyrazolo
[3,4-pyrimidin-5-yl]-1,1ꢀ-diphenylsulfone (4) and 4,4ꢀ-bis
(3-(4-cyano- 3-methyl-1H-pyrazol-5-yl)thioureido)-1,1ꢀ-
diphenylsulfone (5)
A
mixture of 2 (0.01 mole) and 5-amino-3-methyl-pyrazole-4-
carbonitrile 3 (0.02 mole) in ethanol (20 mL) containing 3 drops of
triethylamine was refluxed for 30 minutes. The reaction mixture was
filtered while hote to give compound 4, while, the pyrazole derivative 5
was isolated from the mother liquer of the reaction mixture (Table IV).
4,4ꢀ-Bis(6,7-dihydro-1-phenyl-4-oxo-6-thioxo-1H,5H-
pyrazolo[3,4-d]-pyrimidin-5-yl)-1,1ꢀ-diphenylsulfone (7) and
4,4ꢀ-bis(3-(4-ethyloxy-1-phenyl-1H-pyrazol-5-yl)thioureido)-
1,1ꢀ-diphenylsulfone (8)
A mixture of 2 (0.01 mole) and ethyl-5-amino-1-phenylpyrazole-4-
carboxylate 6 (0.02 mole) in dioxane (20 mL) containing triethylamine
(0.5 mL) was refluxed for 1 hr. The reaction mixture was filtered while
hot to give 7, while pyrazole derivative 8 was isolated from the filtered
of the reaction mixture and recrystallized from ethanol (Table IV).
4,4ꢀ-Bis(4-imino-2-thioxo-3,4,5,6,7,8-hexahydro-1H-
benzo[4,5]thieno-[2,3-d]pyrimidin-3-yl]-1,1ꢀdiphenylsulfone
(10) and 4,4ꢀ-bis(3-(3-cyano-4,5,6,7-tetrahydrobenzo[b]
thiophen-2-yl)-2-thioureido)-1,1ꢀ-diphenylsulfone (11)
A
mixture of
2 (0.01 mole) and 2-amino-tetrahydrobenzo[b]-
thiophene-3-carbonitrile 9 (0.02 mole) in ethanol (30 mL) containing

Bisheterocyclics Containing Diphenylsulfone
2927
triet-hylamine (0.5 mL) was refluxed for 1 hr. The cyclic compound
10 was obtained on hot and recrystallized from dioxane, while the
benzothio-phene 11 was isolated from the filtered of the reaction mix-
ture and recry-stallized from ethanol (Table IV).
4,4ꢀ-Bis(4-oxo-2-thioxo-3,4,5,6,7,8-hexahydro-1H-
benzo[4,5]thieno-[2,3-d]pyrimidin-3-yl]-1,1ꢀdiphenylsulfone
(13) and 4,4ꢀ-bis(3-(3-ethyloxy-4,5,6,7-tetrahydrobenzo[b]
thiophen-2-yl)-2-thioureido)-1,1ꢀ-diphenylsulfone (14)
A mixture of 2 (0.01 mole) and ethyl 2-amino-tetrahydrobenzo[b]-
thiophene-3-carboxylate 12 (0.02 mole) in dioxan (20 mL) containing
triethylamine (0.5 mL) was refluxed for 1 hr. The cyclic compound 13
was obtained on hot and recrystallized from dimethylformamide, while
the benzothiophene derivative 14 was isolated from the filtered of the
reaction mixture and recrystallized from ethanol (Table IV).
4,4ꢀ-Bis(1-(5-mercapto-4-amino-4H-1,2,4-triazolo-3-yl)
thiosemicarbazid-4-yl)-1,1ꢀ-diphenylsulfone (16)
A mixture of 2 (0.01 mol) and 1,2,4-triazole 15 (0.02 mol) in dimethyl-
formamide (20 mL) containing triethylamine (0.5 mL) was refluxed for
2 hr. The solid product was collected and recrystallized from dioxan to
give (16) (Table IV).
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