Synthesis and antimicrobial activity of some new heterocycles based on 3-methyl-1-phenyl-5-benzene sulfonamido pyrazole

Article abstract of DOI:10.1080/10426500210238

Treatment of 3-methyl 1-phenyl-5-amino pyrazole 1 with 4-acetyl benzene sulfonyl chloride in pyridine gave the sulfonamide 2. Condensation of 2 with aromatic aldehydes, semicarbazide, and thiosemicarbazide furnished the α, β-unsaturated ketones 3a-c, the

Full text of DOI:10.1080/10426500210238

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Synthesis and Antimicrobial Activity of some New
Heterocycles Based on 3-Methyl-1-Phenyl-5-Benzene
Sulfonamido Pyrazole
T. I. El-Emary a , N. Al-Muaikel a & O. S. Moustafa b
a Al Jouf Teachers College, P.O Box 269, Al Jouf, Saudi Arabia
b Department of Chemistry, Faculty of Science, Assiut University, Assiut, 71516, Egypt
Version of record first published: 27 Oct 2010.
To cite this article: T. I. El-Emary , N. Al-Muaikel & O. S. Moustafa (2002): Synthesis and Antimicrobial Activity of some New
Heterocycles Based on 3-Methyl-1-Phenyl-5-Benzene Sulfonamido Pyrazole, Phosphorus, Sulfur, and Silicon and the Related
Elements, 177:1, 195-210
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Phosphorus, Sulfur and Silicon, 2002, 177:195–210
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SYNTHESIS AND ANTIMICROBIAL ACTIVITY
OF SOME NEW HETEROCYCLES BASED
ON 3-METHYL-1-PHENYL-5-BENZENE
SULFONAMIDO PYRAZOLE
T. I. El-Emary,a N. Al-Muaikel,a and O. S. Moustafab
Al Jouf Teachers College, P.O Box 269, Al Jouf-Saudi Arabiaa
and Department of Chemistry, Faculty of Science,
71516 Assiut University, Assiut, Egyptb
(Received April 19 2001.)
Treatment of 3-methyl 1-phenyl-5-amino pyrazole 1 with 4-acetyl ben-
zene sulfonyl chloride in pyridine gave the sulfonamide 2. Condensation
of 2 with aromatic aldehydes, semicarbazide, and thiosemicarbazide
furnished the , -unsaturated ketones 3a–c, the semicarbazone 4a and
the thiosemicarbazone 4b respectively. Reaction of 3a–c with hydrazine
hydrate, phenyl hydrazine, hydroxylamine, thiourea afforded the pyra-
zoles 5a–f, isoxazoles 6a–c, and pyrimidinethiones 7a–c. Reaction of
3a–c with malononitrile in ethanol containing piperidine provided the
pyran derivatives 8a–c, while, when the reaction was carried out in boil-
ing acetic acid in presence of ammonium acetate, the pyridine deriva-
tives 9a–c were formed. When 4a reacted with thionyl chloride and
with selenium dioxide, 1,2,3-thiadiazole and 1,2,3-selenadiazole 10,
11 were formed respectively. Allowing 4b to react with -halocarbonyl
compounds such as phenacyl bromide, chloroacetone, 2-bromomethyl
propionate, chloroacetic acid, and bromo diethylmalonate afforded the
thiazolines 12a,b and thiazolidinones 13a–c respectively.
Keywords: Benzene sulfonamide; pyrazole
INTRODUCTION
The sulfonamides have been widely studied for their chemotherpeutic
activity, their important role as antibacterial, insulin releasing, car-
bonic anhydrase inhibitory, antithyroid, antimalarial and antileprotic
7
agents is recognized.1
Recently, certain sulfonamides have been reported as showing in-
teresting antiinflammatory8,9 and antitumor10 12 activity. Some active
Address correspondence to T. I. El-Emary, Al Jouf Teachers College, P.O. Box 269,
Al Jouf-Saudi Arabia.
195

196
T. I. El-Emary et al.
sulfonamides as antibacterials are also known for their immunodifying
effects.13
Pyrazole nucleus has received much attention during the last
decades due to outstanding biological activities as antianxiety,14 an-
tipyretic, analgesic, antiinflammatory drugs,15,16 and the antibacterial
22
and antifungal properties.17
These observations encouraged us to continue our previous work5,22
to synthesize new hetrocycles containing benzene sulfonamide moiety
based on pyrazole ring, hoping to get compounds with enhanced po-
tency. Some of the synthesized compounds were screened in vitro for
antimicrobial activities.
DISCUSSION
The reaction of 3-methyl-1-phenyl-5-amino pyrazole 1 with 4-acetyl
benzene sulfonyl chloride led to the formation of 3-methyl-1-phenyl-
5-(40-acetyl)benzene sulfonamido pyrazole 2 (Scheme 1). Both the el-
emental and spectral data of compound 2 are in consistent. The
1H NMR spectrum of 2, showed signals at 2.35 (s, 3H, CH3), 3.15
(s, 3H, COCH3), 7.1–8.4 (m, 10H, aromatic protons and pyrazole pro-
ton), and at 8.6 (s, 1H, SO2NH); the IR spectrum displayed absorption
bands at 3250, 1690, 1360, and 1145 cm 1, which is characteristic for
NH, CO and SO2asym, SO2sym groups.
The potency of the acetyl group of compound 2 was examined
and used to synthesize new , -unsaturated ketones 3a–c, semicar-
bazone 4a, and thiosemicarbazone 4b based on 3-methyl-1-phenyl-5-
benzenesulfonamido pyrazole. Thus, the condensation of compound 2
with aromatic aldehydes, such as benzaldehyde, 4-chlorobenzaldehyde,
and 4-nitrobenzaldehyde, using 10% aqueous sodium hydroxide
produced the , -unsaturated ketons 3a–c (Scheme 1). As well, the
interaction of compound 2 with semicarbazide and with thiosemi-
carbazide afforded the semicarbazone and the thiosemicarbazone
derivatives 4a,b respectively. The structure of 3a–c and 4a,b were
confirmed on the light of elemental and spectral data. Thus, for
example, the 1H NMR of compound 3a, revealed signals at 2.50
(s, 3H, CH3), 6.9–8.5 (m, 17H, Ar H, pyrazole-H, ethylenic-H) and
8.7 (s, 1H, SO2NH). The IR spectrum showed absorption bands at
1
3320, 1720, 1370, and 1150 cm
assigned for NH, CO, SO2asym,
and SO2sym groups. The 1H NMR of compound 4a showed signals
at 2.45 (s, 3H, CH3), 2.55 (s, 3H, CH3), 7.1–8.5 (m, 10H, Ar H,
pyrazole-H), 8.7 (s, 1H, SO2NH), 9.1 (s, 1H, NH), 11.2 (s, 2H, NH2).
The IR spectrum revealed absorption bands at 3420–3270, 1365, 1140

Sulfonamidestes
197
SCHEME 1
1
cm
for (NH+ NH2), for SO2asym and SO2sym groups. Compounds
3a–c and 4a,b were used as key intermediates in approach to syn-
thesize a variety of heterocycles bearing sulfonamide moieties; thus,
allowing compounds 3a–c to interact with hydrazine hydrate, phenyl

198
T. I. El-Emary et al.
SCHEME 2

Sulfonamidestes
199
hydrazine, hydroxyl amine, and thiourea, the pyrazoles 5a–f, isoxa-
zoles 6a–c, and pyrimidinethiones 7a–c were produced (Scheme 2).
As well, reaction of 3a–c with malononitrile in ethanol containing
piperidine provided the pyran derivatives 8a–c, while when the
reaction was carried out in the presence of ammonium acetate, the
pyridine derivatives 9a–c were formed (Scheme 2). The structures of
the pyran derivatives 8a–c and the pyridine derivatives 9a–c have
been investigated on the basis of elemental and spectral data, thus, for
example the 1H NMR of compound 8a revealed the following signals at
2.5 (s, 3H, CH3), 4.5 (s, 2H, NH2), 5.0 (s, 1H, CH pyran), 7.2–8.3 (m,
15H, Ar H, pyrazol-H), 8.6 (s, 1H, SO2NH). The IR spectrum showed
1
absorption band at 3420–3350, 3200, 2210 cm for NH2, NH, and
1
CN groups. On the other hand, the H NMR of compound 9a revealed
the following signals at 2.45 (s, 3H, CH3), 6.7 (s, 2H, NH2), 7.0–8.6
(m, 15H, Ar H, Pyrazole-H), 8.8 (s, 1H, SO2NH). The IR spectrum
1
explore absorption bands at 3400–3290, 3250, 2220 cm for NH2,
NH, and CN groups. Since 1,2,3-thiadiazole and 1,2,3-selenadiazoles
26
are known by their antibacterial properties,5,23
new members of
these classes were synthesized by converting the semicarbazone 4a
by oxidative cyclization with thionyl chloride or selenium dioxide to
give the 1,2,3-thiadiazole 10 and 1,2,3-selenadiazole 11 respectively
(Scheme 3). The formation of the thiadiazole and selenadiazole 10, 11
were confirmed by elemental analyses as well as by spectral data, thus
the IR spectra are characterized by the absence of the carbonyl and
amino bands of the semicarbazone 3, while other bands were observed
SCHEME 3

200
T. I. El-Emary et al.
and could be assigned to
(750 cm 1) for compound 10 and
c-s
c-se-N
(840 cm 1) for compound 11.
The importance of compound 4b as an interesting intermediate
prompted us to explore its utility in the synthesis of new thiazolidine
and thiazolidinone derivatives, thus allowing the thiosemicarbazone
4b to react with some -halocarbonyl compounds, namely phenacyl
bromide, chloroacetone, 2-bromo methylpropionate, chloroacetic acid,
and bromodimethyl malonate, in refluxing ethanol in the presence of
sodium acetate, thiazoline, and thiazolidinone derivatives 12a,b and
13a–c were produced respectively. These reactions were assumed to
proceed via S-alkylation followed by dehydration or loss of an alcohol
molecule (Scheme 4).
SCHEME 4
ANTIMICROBIAL ACTIVITY
Fourteen compounds (2, 3a,b, 4a,b, 5b, 5d, 5f, 7b, 8b, 9b, 10, 12a,
13b) were tested for their antimicrobial activity using gram positive
and gram negative bacteria: Bacillus cereus, Staphylococcus areus,
Escherichia coli, and Micrococous leutea. They were tested by fil-
ter paper disc method27,28 at Assiut University by the aid of Prof.
A. Moharam.
The result of the antimicrobial tests are summarized in Table I.
All of the tested compounds were found to possess moderate to strong

Sulfonamidestes
201
TABLE I Antimicrobial Screen of the Synthesized Compoundsa
Compd.
no.
Bacellus
cereus
Staphylococus
aureus
Escherichia
coli
Micrococcous
leutea
b
2
3a
12
12
13
11
13
11
12
12
12
10
11
12
13
13
—
12
11
12
11
12
11
11
11
12
—
—
11
12
12
—
11
11
11
—
—
—
11
—
10
—
—
—
11
10
—
—
—
11
—
10
—
—
—
—
—
—
—
11
10
—
3b
4a
4b
5b
5d
5f
7b
8b
9b
10
12a
13b
DMF
5
aInhibition zones are measured in mm. The concentration used is 4 10 M. Control
discs were performed with DMF (dimethylformamide) and no zones of inhibition were
observed.
b— = resistant.
antimicrobial activity towards B. cereus. Also, all tested compounds
except 8b showed moderate antimicrobial activity against S. areus.
Compounds 2, 3a, 3b, 5d, 7b, 12a, 13b showed modreat activity
against E. coli while the rest of the tested compounds showed resis-
tant. Only four compounds, 3b, 4b, 12a, 13b, showed moderate activity
against M. leutea, while the rest of the tested compounds showed no
effect.
EXPERIMENTAL
All m.p.s are uncorrected and were determined on a Mel-Temp II ap-
paratus. IR spectra were recorded on a Pye-Unicam SP3-100 spec-
trophotometer ( max. in cm 1) using the KBr wafer technique, and
1H NMR spectra were recorded on a 90 MHz Varian EM-390 NMR spec-
trophotometer in suitable solvents using TMS as an internal standard
(chemical shifts in values). Elemental analyses were determined on a
Perkin-Elmer 240 C microanalyser.
5-Amino-3-methyl-1-phenyl-pyrazole (1)
This compound was prepared according to the literature.29

202
T. I. El-Emary et al.
3-Methyl-1-phenyl-5(4-acetyl)sulfonamidophenyl)-
pyrazole (2)
4-Acetyl benzene sulphonyl chloride (0.01 mol) was added portionwise
with shaking to 1 (0.01 mol) and dissolved in pyridine (25 ml). The
reaction mixture was heated on a water bath for 2 h and then cooled
and poured into ice water. The mixture was slightly acidifed with diluted
HCl, and the precipitated solid was collected by filteration, washed with
water, dried, and crystallized from, the proper solvent (cf. Tables II
and III).
3-Methyl-1-phenyl-5(4(arylidine
acetophenon-1-yl)sulfonamidophenyl)pyrazole (3a--c)
General Procedure
To a well stirred mixture of 2 (0.01 mol) and aromatic aldehydes,
namely bezaldehyde, 4-chlorobenzaldehyde and 4-nitro benzaldehyde
(0.01 mol) in ethanol (40 ml) an aqueous sodium hydoxide (10 ml, 10%),
was added and the mixture was stirred at room temperature for 5–6 h.
The precipitated solid was filtered washed with water, and crystallized
from the proper solvent (cf. Tables II and III).
Condensation of 2 with semicarbazide: Formation
of 3-methyl-1-phenyl-5(4-(acetyl semicarbazone-1-yl)
benzene sulfonamido)pyrazole (4a)
A mixture of semicarbazide hydrochloride (0.01 mol) and sodium ac-
etate (0.0 mol) dissolved in water (15 ml) was added to a solution of 2
(0.01 mol) and dissoved in ethanol (30 ml). The reaction mixture was
heated under reflux for 2 h, evaporated to one half of its volume, and
then poured into ice water. The solid pricipitate was filtered, washed
with water, dried, and crystallized from the proper solvent (cf. Tables II
and III).
Condensation of 2 with thiosemicarbazide: Formation
of 3-methyl-1-phenyl-5(4-(acetyl thiosemicarbazone-1-yl)
benzene sulfonamido)pyrazole (4b)
A mixture of 2 (0.01 mol) and thiosemicarbazide (0.01) in ethanol
(30 ml) was heated under reflux for 2 h. The solid product was collected
by filteration after cooling, washed with water, dried, and crystallized
from the proper solvent (cf. Tables II and III).

Sulfonamidestes
203
S%
TABLE II Physical and Analytical Data of the Synthesized Compounds
Elemental analyses
required/found
Compd.
no.
M.P. ( C)
(solvent)
Yield
(%)
Mol. formula
(mol. wt)
C%
H%
N%
2
135–137
(ethanol)
192–193
(ethanol)
210–212
(ethanol)
235–237
(ethanol)
260–262
(dioxan-water)
(2:1)
78
62
57
51
58
C18H17N3O3S
(355.4)
C25H21N3O3S
(443.5)
60.83 4.82 11.83
61.23 4.91 11.62
9.02
9.37
7.23
7.45
6.71
6.38
6.56
6.32
7.77
7.65
3a
3b
3c
4a
67.70 4.77
68.15 4.83
9.48
9.28
8.79
9.10
C
25H20N3O3SCl 62.83 4.22
(477.9) 63.12 4.11
C25H20N4O5S
(488.5)
C19H20N6O3S
(412.5)
61.46 4.13 11.47
61.77 4.12 11.28
55.32 4.89 20.38
55.65 5.10 20.58
4b
5a
275–277
(dioxan-water)
(3:1)
248–250
(dioxan-water)
(2:1)
63
52
C
19H20N6O2S2
(428.5)
53.25 4.70 19.62 14.96
53.68 4.60 19.33 15.30
C
25H21N5O2S
(455.5)
65.92 4.65 15.38
66.36 4.87 15.15
7.04
6.88
5b
5c
5d
5e
5f
218–220
(ethanol)
256–258
(ethanol)
222–224
(ethanol)
286–288
(ethanol)
234–235
(dioxan-water)
(2:1)
61
48
54
42
47
C
31H25N5O2S
(531.6)
70.04 4.74 13.18
70.43 4.48 13.45
6.03
5.88
6.54
6.23
5.66
5.52
6.41
6.21
5.56
5.32
C25H20N5O2SCl 61.28 4.11 14.30
(489.97) 62.56 4.12 14.35
31H24N5O2SCl 65.77 4.27 12.37
C
(565.99)
25H20N6O4S
(500.5)
66.15 4.37 12.12
59.99 4.03 16.80
60.42 4.13 16.62
64.57 4.20 14.58
64.82 4.11 14.11
C
C31H24N6O4S
(576.6)
6a
6b
6c
7a
7b
7c
8a
186–188
(benzene)
202–204
(ethanol)
236–238
(ethanol)
177–178
(ethanol)
184–186
(ethanol)
220–222
(ethanol)
250–252
(CHCl3-pet. ether)
(3:1)
41
37
C
25H20N4O3S
(456.5)
65.77 4.42 12.28
66.12 4.23 12.08
7.02
6.76
6.53
6.18
6.39
6.11
C25H19N4O3SCl 61.16 3.90 11.42
(490.9)
25H19N5O5S
(501.5)
61.48 3.80 11.12
59.87 3.82 13.97
60.22 3.93 13.63
62.25 4.62 13.96 12.78
62.55 4.87 13.77 12.54
C
62
53
C
26H23N5O2S2
(501.6)
C26H22N5O2S2Cl 58.25 4.14 13.07 11.96
(536.1)
26H22N6O4S2
(546.6)
58.64 4.10 12.88 11.62
57.13 4.06 15.38 11.73
57.53 4.23 15.11 11.43
65.99 4.55 13.75
66.37 4.77 13.66
C
51
C28H23N5O3S
(509.6)
6.29
5.89
(Continued on next page)

204
T. I. El-Emary et al.
TABLE II Physical and Analytical Data of the Synthesized Compounds
(Continued)
Elemental analyses
required/found
Compd.
no.
M.P. ( C)
(solvent)
Yield
(%)
Mol. formula
(mol. wt)
C%
H%
N%
S%
8b
8c
294–296
(dioxan)
>300
(dioxan)
>300
(acetic acid)
>300
(acetic acid)
>300
(acetic acid)
248–250
(ethanol)
217–218
(acetic acid)
277–279
(dioxan)
284–286
(ethanol)
288–290
(dioxan)
266–268
(acetone-water)
(3:1)
43
37
54
42
33
41
28
63
55
52
58
C28H22N5O3SCl 61.83 4.08 12.88
5.89
5.55
5.78
5.56
6.33
6.11
5.93
5.87
5.81
5.77
(543.9)
C28H22N6O5S
(554.6)
62.23 4.16 12.67
60.63 4.00 15.16
60.96 4.23 14.87
66.38 4.38 16.59
66.76 4.57 16.44
9a
C
28H22N6O2S
(506.6)
9b
C28H21N6O2SCl 62.16 3.91 15.54
(540.99)
C28H21N7O4S
(551.6)
62.48 4.12 15.34
60.96 3.84 17.78
61.33 3.63 17.61
9c
10
C
18H15N5O2S2
(397.5)
54.38 3.80 17.62 16.13
54.78 3.81 17.54 16.22
11
C
18H15N5O2SSe 48.64 3.40 15.76
(444.4) 48.87 3.48 15.37
7.21
6.97
12a
12b
13a
13b
C27H24N6O2S2
(528.6)
C22H22N6O2S2
(466.6)
61.35 4.58 15.90 12.13
61.74 4.66 15.65 12.14
56.63 4.75 18.02 13.74
56.78 4.68 17.85 13.43
54.75 4.60 17.42 13.29
54.87 4.76 17.13 13.11
53.82 4.30 17.92 13.68
53.87 4.76 17.63 13.27
C
22H22N6O3S2
(482.6)
C21H20N6O3S2
(468.6)
13c
217–218
(ethanol)
49
C
24H24N6O5S2
(540.6)
53.32 4.48 15.55 11.86
53.78 4.41 15.23 11.65
Reaction of 3a--c with hydrazine hydrate and phenyl
hydrazine: Formation of 3-methyl-1-phenyl-5(4(5-aryl-
1-H(phenyl)-2-pyrazoline-3-yl)benzene sulfonamido)
pyrazoles (5a--f)
General Procedure
A mixture of 3a–c and hydrazine hydrate (excess, 1 ml, 80%) or
phenyl hydrazine (0.006 mol) was heated gently without solvent for
15 min, then ethanol (25 ml) was added and the reaction mixture was
heated under reflux for 6–8 h. After cooling, the product was collected by
filteration, washed with water, dried, and crystallized from the proper
solvent (cf. Tables II and III).

205

206

207

208
T. I. El-Emary et al.
Reaction of 3a--c with hydroxyl amine: Formation of
3-methyl-1-phenyl-5-(4-(5-aryl isoxazol-3-yl)benzen
sulfonamido)pyrazoles (6a--c)
General Procedure
To a solution of 3a–c (0.005 mol) in ethanol (25 ml), an aqueous solu-
tion (10 ml, containing hydroxyl amine hydrochloride (0.006 mol), and
sodium acetate (0.008 mol) was added. The reaction mixture was then
heated under reflux for 3–5 h. After cooling, the product was filtered
off, washed with water, dried, and crystallized from the proper solvent
(cf. Tables II and III).
Reaction of 3a--c with thiourea: Formation of
3-methyl-1-phenyl-5-(4-(6-aryl-pyrimidine-2-thione-4-yl)
benzene sulfonamido)pyrazoles (7a--c)
General Procedure
Equimolar amounts (0.005 mol) of 3a–c and thiourea were dissolved
in ethanol (25 ml). To this solution, alcoholic KOH (5 ml, 25%) was
added and the reaction mixture was heated under reflux for 6–8 h.
The reaction mixture was cooled, poured into water, and neutralized
with HCl. The product was filtered off, washed with water, dried, and
crystallized from the proper solvent (cf. Tables II and III).
Reaction of 3a--c with malononitrile in ethanol/
piperidine: Formation of 3-methyl-1-phenyl-5-(4-
(2-amino-4-aryl-3-cyano pyran-6-yl) benzene
sulfonamido)pyrazole (8a--c)
General Procedure
A mixture of 3a–c (0.005 mol) and malononitrile (0.005 mol) in
ethanol (25 ml) containing piperidine (few drops) was heated under
reflux for 4–7 h. After cooling, the product was filtered off, washed
with water, dried, and crystallized from the proper solvent (cf. Tables II
and III).
Reaction of 3a--c with malononitrile in acetic
acid/ammonium acetate: Formation of 3-methyl-1-
phenyl-5-(4-(2-amino-4-aryl-3-cyanopyridin-6-yl)benzene
sulfonamido) pyrazoles (9a--c)
General Procedure
A mixture of 3a–c (0.005 mol), malononitrile (0.005 mol), and ammo-
nium acetate (0.01 mol) in acetic acid (20 ml) was heated under reflux

Sulfonamidestes
209
for 6–8 h. After cooling, the reaction mixture was poured into cold water,
the product was filtered off, washed with water, dried, and crystallized
from the proper solvent (cf. Tables II and III).
Reaction of the semicarbazone 4a with thionyl chloride:
Formation of 3-methyl-1-phenyl-5-(4-(1,2,3-thiadiazole-
4-yl) benzene sulfonamido) pyrazole (10)
Thionyl chloride (10 ml) was gradually added to the semicarbazone
derivative 4a (0.005 mol) at ice bath temperature. The reaction mix-
ture was removed from the ice bath and heated on a water bath for
3 h. Chloroform (50 ml) was then added and the reaction mixture was
decomposed with ice-cold saturated sodium carbonate solution and sep-
arated. The organic layer was washed with water and dried. After evap-
oration of the solvent, the residue was recrystallized from the proper
solvent (cf. Tables II and III).
Reaction of the semicarbazone 4a with selenium
dioxide: Formation of 3-methyl-1-phenyl-5-(4(4-(1,2,3-
selenadiazole-4-yl) benzene sulfonamido) pyrazole (11)
To a boiling stirred solution of the semicarbazone 4a (0.005 mol) in
acetic acid (20 ml), selenium dioxide (0.005 mol) was added portion-
wise. The reaction mixture was filtered twice while hot. The cold fil-
trate was poured into ice water and the precipitate was filtered, washed
with water, dried, and crystallized from the proper solvent (cf. Tables II
and III).
Reaction of the thiosemicarbazone 4b with
-halocarbonyl compounds and -haloesters: Formation
of the thiazolidines 12a,b and the thiazolidinones
(13a--c)
General Procedure
A mixture of 4b (0.005 mol), -halocarbonyl compounds or
-haloesters (0.005 mol), namely, phenacyl bromide, chloroace-
tone,
-bromo methylpropionate, chloroacetic acid, and bromo
diethylmalonate, and sodium acetate (0.01 mol) in ethanol (30 ml)
was heated under reflux for 6–8 h. After cooling, the precipitate was
filtered, washed with water, dried, and crystallized from the proper
solvent (cf. Tables II and III).

210
T. I. El-Emary et al.
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