Synthesis and antimicrobial studies of pyrazolyl oxadiazoles and thiadiazoles

Article abstract of DOI:10.1002/jhet.645

A new class of bis heterocycles sulfone linked pyrazolyl oxadiazoles thiadiazoles were prepared from E-phenylsulfonylethenesulfonylacetic acid and studied their antimicrobial activities.

Full text of DOI:10.1002/jhet.645

September 2011
Synthesis and Antimicrobial Studies of Pyrazolyl Oxadiazoles
and Thiadiazoles
1197
Venkatapuram Padmavathi,* Sanapalli Nagi Reddy, Guda Dinneswara Reddy,
Bhumireddy Chinnachennaiahgari Venkatesh, and Adivireddy Padmaja
Department of Chemistry, Sri Venkateswara University, Tirupati 517 502, India
*E-mail: vkpuram2001@yahoo.com
Received April 13, 2010
DOI 10.1002/jhet.645
Published online 12 May 2011 in Wiley Online Library (wileyonlinelibrary.com).
A new class of bis heterocycles—sulfone linked pyrazolyl oxadiazoles thiadiazoles were prepared
from E-phenylsulfonylethenesulfonylacetic acid and studied their antimicrobial activities.
J. Heterocyclic Chem., 48, 1197 (2011).
INTRODUCTION
multifunctional synthetic intermediate E-phenylsulfonyl
ethenesulfonyl acetic acid (1) is prepared as per the lit-
erature procedure [21]. The compound 1 is treated with
different aromatic acid hydrazides in the presence
of phosphorus oxychloride to get 2-(((E)-2-(phenylsulfo-
nyl)vinylsulfonyl)methyl)-5-aryl-1,3,4-oxadiazole (2). Inter-
coversion of 2 to 2-(((E)-2-(phenylsulfonyl)vinylsulfonyl)
methyl)-5-aryl-1,3,4-thiadiazole (3) is effected by the reac-
Pyrazole and its derivatives represent one of the most
active classes of compounds possessing a wide spectrum
of biological activities. During the past years, considerable
evidence has been accumulated to demonstrate the efficacy
of pyrazole derivatives including antibacterial [1], antifun-
gal [2,3], herbicidal [4], insecticidal [5], and other biologi-
cal activities [6,7]. Some commercial pesticides have been
developed viz., fripronil (MB46030) [8], ET-751 [9] and
pyrazolate (A-544) [10]. 1,3,4-Oxadiazole is associated
with potent pharmacological activity due to the presence
of toxophoric AN¼¼CAOA linkage [11]. The 1,3,4-oxa-
diazole derivatives have been found to exhibit diverse bio-
logical activities such as antimicrobial [12], anti-HIV [12],
antitubercular [13], antimalarial [14], analgesic [15], anti-
inflammatory [16], anticonvulsant [17], and hypoglycemic
[18]. 1,3,4-Thiadiazoles are known to possess antibacterial
and antifungal properties similar to those of well-known
sulphonamide drugs [19]. Thus, the 1,3,4-thiadiazoles ex-
hibit a broad spectrum of biological activities possibly due
to the presence of the toxophoric N¼¼CAS moiety [20].
Prompted by these observations and in continuation of our
search for bioactive molecules, we herein report the syn-
thesis of novel bis heterocycles, emphasizing in particular
on the strategy of combining two chemically different but
pharmacologically compatible heterocycles in one frame
to study their antibacterial and antifungal activities.
1
tion of 2 with thiourea. The H-NMR spectra of 2a and
3a showed two doublets at d 7.84, 8.04 and 7.81, 8.06
ppm for HB and HA. The coupling constant value J ¼
14.7 Hz indicates that they are in trans geometry. In addi-
tion, a singlet is observed at d 5.43 in 2a and at 5.52 ppm
in 3a for methylene protons. The olefin functionality in 2
and 3 is used to develop pyrazoline ring. Thus the 1,3-
dipolar cycloaddition of etherial diazomethane to 2 and 3
in the presence of triethylamine gave 2-((40,50-dihydro-30-
(phenylsulfonyl)-10H-pyrazol-40-ylsulfonyl) methyl)-5-aryl-
1,3,4-oxadiazole (4) and 2-((40,50-dihydro-30-(phenylsul-
fonyl)-10H-pyrazol-40-ylsulfonyl)methyl)-5-aryl-1,3,4-thia-
1
diazole (5), respectively (Tables 1 and 2). The H-NMR
spectra of 4a and 5a displayed AMX splitting pattern for
pyrazoline ring protons. Thus three double doublets
observed at d 4.53, 4.10, 3.66 in 4a and at 4.61, 4.22,
3.72 ppm in 5a are assigned to HA, HM and HX, respec-
tively. The coupling constant values JAM ¼ 12.5, 12.8,
JAX ¼ 5.8, 6.1, JMX ¼ 10.3, 10.7 Hz indicates that HA,
HM are cis, HA, HX are trans and HM, HX are geminal.
Apart from these, a singlet is observed at d 4.52 in 4a and
at 4.55 ppm in 5a due to methylene protons.
RESULTS AND DISCUSSION
The compounds
4
and
5
are subjected to
The synthetic pathway followed for the preparation of
the title compounds is as shown in Scheme 1. The
aromatization to get 2-((30-(phenylsulfonyl)-10H-pyrazol-
40-ylsulfonyl)methyl)-5-aryl-1,3,4-oxadiazole (6) and 2-
C
V
2011 HeteroCorporation

Scheme 1
Table 1
Physical and analytical data of compounds 2–7.
Analysis % calcd./found
H
Compound
Mp (ꢀC)
146–148
Yield (%)
69
Molecular formula
C17H14N2O5S2
C
N
2a
52.30
52.38
53.45
53.37
48.06
48.15
50.23
50.16
51.41
51.49
46.31
46.25
49.99
49.87
51.11
51.02
46.30
46.39
48.20
48.31
49.33
49.42
44.76
44.66
50.22
50.13
51.34
51.45
46.50
46.61
48.42
48.51
49.55
49.62
44.95
45.04
3.61
3.65
3.99
3.94
3.08
3.13
3.47
3.51
3.83
3.86
2.97
3.01
3.73
3.68
4.06
4.00
3.24
3.28
3.60
3.65
3.92
3.98
3.13
3.08
3.28
3.22
3.63
3.57
2.82
2.86
3.16
3.20
3.50
3.56
2.72
2.65
7.17
7.25
2b
2c
3a
3b
3c
4a
4b
4c
5a
5b
5c
6a
6b
6c
7a
7b
7c
129–131
152–154
164–166
171–173
182–184
157–159
163–165
172–174
171–173
182–184
197–199
165–167
169–171
185–187
183–185
196–198
210–212
64
72
66
62
65
79
75
83
77
76
80
75
69
76
72
68
74
C18H16N2O5S2
C17H13ClN2O5S2
C17H14N2O4S3
C18H16N2O4S3
C17H13ClN2O4S3
C18H16N4O5S2
C19H18N4O5S2
C18H15ClN4O5S2
C18H16N4O4S3
C19H18N4O4S3
C18H15ClN4O4S3
C18H14N4O5S2
C19H16N4O5S2
C18H13ClN4O5S2
C18H14N4O4S3
C19H16N4O4S3
C18H13ClN4O4S3
6.93
7.02
6.59
6.64
6.89
6.79
6.66
6.74
6.35
6.28
12.95
12.84
12.55
12.66
12.00
12.14
12.49
12.35
12.11
12.21
11.60
11.71
13.02
13.15
12.60
12.70
12.05
12.14
12.55
12.43
12.17
12.08
11.65
11.74

September 2011 Synthesis and Antimicrobial Studies of Pyrazolyl Oxadiazoles and Thiadiazoles
1199
Table 2
activity. However the remaining compounds displayed
significant antifungal activity.
IR data of compounds 2–7.
IR (KBr) cmꢁ1
CONCLUSION
Compound
SO2
C¼C
C¼N
NH
–
A new class of pyrazolyl oxadiazoles and thiadiazoles
are prepared adopting simple and well-versed methodolo-
gies. Preliminary antimicrobial studies of these compounds
showed that the bis heterocycles, pyrazole in combination
with thiadiazole exhibited excellent antimicrobial activity.
2a
2b
2c
3a
3b
3c
4a
4b
4c
5a
5b
5c
6a
6b
6c
7a
7b
7c
1136
1141
1144
1138
1143
1146
1131
1143
1135
1140
1138
1145
1132
1137
1141
1134
1139
1143
1318
1321
1325
1317
1320
1323
1336
1340
1338
1333
1335
1337
1332
1336
1339
1335
1332
1338
1630
1626
1631
1635
1632
1623
1589
1594
1608
1583
1597
1603
1586
1594
1609
1585
1598
1606
1582
1595
1607
1585
1593
1605
–
–
3345
3340
3336
3332
3348
3341
3325
3342
3346
3340
3343
3347
EXPERIMENTAL
–
–
–
–
–
–
–
–
–
–
Melting points were determined in open capillaries on a
Mel-Temp apparatus and are uncorrected. The purity of the
compounds was checked by TLC (silica gel H, BDH, ethyl ac-
etate/hexane, 1:3). The IR spectra were recorded on a Thermo
Nicolet IR 200 FT-IR spectrometer as KBr pellets and the
wave numbers were given in cmꢁ1. The H-NMR spectra were
1
recorded in CDCl3/DMSO-d6 on a Bruker spectrospin operat-
ing at 400 MHz. The 13C-NMR spectra were recorded in
CDCl3/DMSO-d6 on a Bruker spectrospin operating at 100
MHz. All chemical shifts are reported in d (ppm) using TMS
as an internal standard. The microanalyses were performed on
a Perkin-Elmer 240C elemental analyzer. The starting com-
pound E-phenylsulfonylethenesulfonylacetic acid (1) was pre-
pared by the literature procedure [21].
2-(((E)-2-(Phenylsulfonyl)vinylsulfonyl)methyl)-5-aryl-1,3,4-
oxadiazole (2): General procedure. To the compound E-phe-
nylsulfonylethenesulfonylacetic acid (1) (5 mmol), benzoic
acid hydrazide (5 mmol) and POCl3 (4 mL) were added and
heated under reflux for 5–6 h. The excess POCl3 was removed
under reduced pressure and the residue was poured onto
crushed ice. The resulting precipitate was filtered, washed with
saturated sodium bicarbonate solution and then with water,
dried and recrystallized from ethanol.
2-(((E)-2-(Phenylsulfonyl)vinylsulfonyl)methyl-5-aryl-1,3,4-
thiadiazole (3): General procedure. In a sealed test tube, the
compound 2 (5 mmol), thiourea (20 mmol) dissolved in tetra-
hydrofuran (5 mL) was taken. The contents were heated at
120–150ꢀC in an oil bath for 22–26 h. After the reaction was
completed, it was extracted with dichloromethane. The organic
layer was washed with water, brine solution and dried over an-
hydrous Na2SO4. The resultant solid was recrystallized from
methanol.
2-((40,50-Dihydro-30-(phenylsulfonyl)-10H-pyrazol-40-ylsul-
fonyl)methyl)-5-aryl-1,3,4-oxadiazole (4)/2-((40,50-Dihydro-
30-(phenylsulfonyl)-10H-pyrazol-40-ylsulfonyl)methyl)-5-aryl-
1,3,4-thiadiazole (5): General procedure. To a cooled solu-
tion of 2/3 (2.5 mmol) in dichloromethane (10 mL), an ethe-
real solution of diazomethane (20 mL, 0.4 M) and triethyl-
amine (0.06 g) were added. The reaction mixture was kept at
ꢁ20 to ꢁ15ꢀC for 40–48 h. The solvent was removed under
reduced pressure. The resultant solid was purified by column
chromatography (hexane-ethyl acetate, 4:1).
((30-(phenylsulfonyl)-10H-pyrazol-40-ylsulfonyl)methyl)-
5-aryl-1,3,4-thiadiazole (7). The H-NMR spectra of 6a
1
and 7a displayed two singlets at d 7.21, 5.44 and 7.25,
5.47 ppm due to pyrazole ring and methylene protons. A
broad singlet is observed at d 6.52 in 6a and at 6.55 ppm
in 7a due to NH which disappeared on deuteration. The
structures of all the compounds 2–7 are further ascer-
tained by 13C-NMR spectra (Table 3).
ANTIMICROBIAL STUDIES
The bis heterocycles 6 and 7 are screened for their
antibacterial and antifungal activity. For antibacterial
studies, microorganisms employed are Staphylococcus
aureus, Bacillus subtilis, (Gram-positive) and Esche-
richia coli, Klebsiella pneumoniae (Gram-negative). For
antifungal, Fusarium solani, Curvularia lunata, and As-
pergillus niger are used as microorganisms. Chloram-
phenicol and Ketoconazole are used as standard drugs
for antibacterial and antifungal studies, respectively. The
results of the compounds of preliminary antimicrobial
testing are shown in Tables 4 and 5. Among the
screened samples, the compounds 7a and 7c showed
excellent antibacterial activity against Gram-positive
bacteria (35–38 mm) and good activity against Gram-
negative bacteria (26–32 mm). On the other hand, the
compound 6 exhibited least activity against both bacte-
ria. The compound having thiadiazole unit in combina-
tion with pyrazole with chloro substituent on the phenyl
ring (7c) accounted for significant antimicrobial activity.
The compounds 7a and 7c showed maximum antifungal
2-((30-Phenylsulfonyl)-10H-pyrazol-40-ylsulfonyl)methyl)-5-
aryl-1,3,4-oxadiazole (6)/2-((30-Phenylsulfonyl)-10H-pyrazol-
40-ylsulfonyl)methyl)-5-aryl-1,3,4-thiadiazole (7): General
procedure. A solution of 4/5 (1 mmole) and chloranil (1
mmole) in xylene (10 mL) was refluxed for 24–32 h. Then,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1200
V. Padmavathi, S. N. Reddy, G. D. Reddy, B. C. Venkatesh, and A. Padmaja
Vol 48
Table 3
1H and 13C NMR data of compounds 2–7.
Compound
1H NMR (d, ppm)
13C NMR (d, ppm)
2a
2b
2c
3a
3b
3c
4a
5.43 (s, 2H, SO2ACH2), 7.84 (d, 1H, HB, J ¼ 14.7 Hz), 8.04
(d, 1H, HA, J ¼ 14.7 Hz), 7.58–7.84 (m, 10H, ArAH)
50.5 (SO2ACH2), 130.1 (CAHB), 145.1 (CAHA), 156.6 &
165.2 (C¼N), 121.1, 126.2, 128.1, 129.0, 129.8, 130.2,
131.4, 139.1 (aromatic carbons)
21.6 (ArACH3), 50.8 (SO2ACH2), 130.8 (CAHB), 144.8
(CAHA), 156.6 & 165.4 (C¼N), 121.3, 126.1, 128.2,
129.2, 129.8, 130.6, 131.5, 138.7 (aromatic carbons)
50.3 (SO2ACH2), 130.3 (CAHB), 143.7 (CAHA), 157.5 &
165.1 (C¼N), 122.1, 128.7, 128.9, 130.2, 130.4, 135.5,
137.7, 139.4 (aromatic carbons)
2.34 (s, 3H, ArACH3), 5.40 (s, 2H, SO2ACH2), 7.87
(d, 1H, HB, J ¼ 14.6 Hz), 8.06 (d, 1H, HA, J ¼ 14.6 Hz),
7.67–8.16 (m, 9H, ArAH)
5.56 (s, 2H, SO2ACH2), 7.86 (d, 1H, HB, J ¼ 14.8 Hz), 8.08
(d, 1H, HA, J ¼ 14.8 Hz), 7.62–7.97 (m, 9H, ArAH)
5.52 (s, 2H, SO2ACH2), 7.81 (d, 1H, HB, J ¼ 14.7 Hz), 8.06
(d, 1H, HA, J ¼ 14.7 Hz), 7.58–7.97 (m, 10H, ArAH)
51.0 (SO2ACH2), 131.5 (CAHB), 145.3 (CAHA), 156.8 &
165.7 (C¼N), 121.2, 126.1, 127.2, 129.3, 130.2, 130.4,
131.6, 138.2 (aromatic carbons)
2.29 (s, 3H, ArACH3), 5.46 (s, 2H, SO2ACH2), 7.84
(d, 1H, HB, J ¼ 14.5 Hz), 8.05 (d, 1H, HA, J ¼ 14.8 Hz),
7.59–7.98 (m, 9H, ArAH)
21.8 (ArACH3), 51.3 (SO2ACH2), 130.2 (CAHB), 145.2
(CAHA), 156.8 & 164.6 (C¼N), 121.5, 126.3, 128.4,
129.5, 130.3, 130.4, 131.6, 138.5 (aromatic carbons)
51.8 (SO2ACH2), 130.6 (CAHB), 145.4 (CAHA), 156.5 &
165.3 (C¼N), 121.5, 126.3, 128.6, 129.5, 130.3, 130.7,
131.8, 138.6 (aromatic carbons)
51.4 (SO2ACH2), 48.5 (C-40), 58.9 (C-50), 149.3 (C-30),
157.9 (C-5), 164.8 (C-2), 121.8, 127.5, 128.4, 129.8,
130.2, 137.1, 139.5, 140.2 (aromatic carbons)
5.54 (s, 2H, SO2ACH2), 7.85 (d, 1H, HB, J ¼ 14.9 Hz), 8.09
(d, 1H, HA, J ¼ 14.9 Hz), 7.64–7.98 (m, 9H, ArAH)
4.52 (s, 2H, SO2ACH2), 3.66 (dd, 1H, HX, JAX ¼ 5.8 Hz,
JMX ¼ 10.3 Hz), 4.10 (dd, 1H, HM, JAM ¼ 12.5 Hz), 4.53
(dd, 1H, HA), 7.22–7.95 (m, 10H, ArAH), 8.85 (bs, 1H,
NH)
4b
4c
5a
5b
5c
2.33 (s, 3H, ArACH3), 4.49 (s, 2H, SO2ACH2), 3.59 (dd, 1H,
HX, JAX ¼ 5.5 Hz, JMX ¼ 10.5 Hz), 4.12 (dd, 1H, HM,
JAM ¼ 12.2 Hz), 4.51 (dd, 1H, HA), 7.18–7.89 (m, 9H,
ArAH), 8.97 (bs, 1H, NH)
4.57 (s, 2H, SO2ACH2), 3.65 (dd, 1H, HX, JAX ¼ 5.3 Hz,
JMX ¼ 10.2 Hz), 4.14 (dd, 1H, HM, JAM ¼ 12.4 Hz), 4.56
(dd, 1H, HA), 7.24–7.98 (m, 9H, ArAH), 9.13 (bs, 1H,
NH)
21.7 (ArACH3), 53.2 (SO2ACH2), 47.9 (C-40), 57.8
(C-50), 151.3 (C-30), 159.9 (C-5), 163.4 (C-2), 121.5,
127.3, 129.1, 131.1, 132.8, 139.1, 140.4, 141.3
(aromatic carbons)
52.8 (SO2ACH2), 47.4 (C-40), 58.6 (C-50), 148.6 (C-30),
158.5 (C-5), 162.9 (C-2), 121.6, 128.3, 129.5, 131.2,
132.7, 138.6, 139.8, 140.7 (aromatic carbons)
4.55 (s, 2H, SO2ACH2), 3.72 (dd, 1H, HX, JAX ¼ 6.1 Hz,
JMX ¼ 10.7 Hz), 4.22 (dd, 1H, HM, JAM ¼ 12.8 Hz), 4.61
(dd, 1H, HA), 7.26–7.93 (m, 10H, ArAH), 8.85 (bs, 1H,
NH)
51.8 (SO2ACH2), 48.9 (C-40), 59.3 (C-50), 147.4 (C-30),
156.8 (C-5), 167.5 (C-2), 122.5, 128.6, 126.3, 131.5,
133.4, 137.2, 140.5, 141.4 (aromatic carbons)
2.35 (s, 3H, ArACH3), 4.53 (s, 2H, SO2ACH2), 3.64 (dd, 1H,
HX, JAX ¼ 6.3 Hz, JMX ¼ 10.6 Hz), 4.16 (dd, 1H, HM,
JAM ¼ 12.6 Hz), 4.55 (dd, 1H, HA), 7.28–7.92 (m, 9H,
ArAH), 8.81 (bs, 1H, NH)
4.62 (s, 2H, SO2ACH2), 3.71 (dd, 1H, HX, JAX ¼ 6.2 Hz,
JMX ¼ 10.5 Hz), 4.18 (dd, 1H, HM, JAM ¼ 12.7 Hz), 4.58
(dd, 1H, HA), 7.24–7.98 (m, 9H, ArAH), 8.92 (bs, 1H,
NH)
22.3 (ArACH3), 53.6 (SO2ACH2), 46.4 (C-40), 58.1
(C-50), 149.5 (C-30), 163.2 (C-5), 165.4 (C-2), 123.5,
127.6, 129.7, 130.6, 131.7, 138.7, 139.6, 140.8
(aromatic carbons)
51.3 (SO2ACH2), 48.3 (C-40), 57.5 (C-50), 149.7 (C-30),
159.4 (C-5), 163.4 (C-2), 122.5, 129.2, 130.2, 131.6,
132.8, 137.9, 140.2, 141.5 (aromatic carbons)
6a
6b
5.44 (s, 2H, SO2ACH2), 6.52 (bs, 1H, NH), 6.84–7.78
(m, 11H, C5 AH, ArAH)
51.5 (SO2ACH2), 48.9 (C-40), 58.3 (C-50), 148.2 (C-30),
158.6 (C-5), 165.5 (C-2), 121.4, 127.6, 128.8, 129.9,
130.4, 137.6, 139.8, 140.6 (aromatic carbons)
21.9 (ArACH3), 53.5 (SO2ACH2), 47.7 (C-40), 57.6
(C-50), 151.9 (C-30), 160.3 (C-5), 163.6 (C-2), 121.8,
127.8, 129.6, 131.5, 132.5, 139.6, 140.6, 141.1
(aromatic carbons)
0
2.32 (s, 3H, ArACH3), 5.52 (s 2H, SO2ACH2), 6.54
0
(bs, 1H, NH), 6.86–7.76 (m, 10H, C5 AH, ArAH)
6c
7a
7b
5.56 (s, 2H, SO2ACH2), 6.72 (bs, 1H, NH), 6.87–7.78
(m, 10H, C5 AH, ArAH)
52.9 (SO2ACH2), 47.8 (C-40), 58.9 (C-50), 149.7 (C-30),
159.8 (C-5), 162.5 (C-2), 121.2, 128.7, 129.9, 131.8,
132.5, 138.2, 139.6, 141.4 (aromatic Carbons)
51.2 (SO2ACH2), 48.3 (C-40), 59.2 (C-50), 147.5 (C-30),
158.4 (C-5), 164.2 (C-2), 122.4, 128.3, 126.1, 131.2,
133.3, 137.8, 140.3, 141.1 (aromatic carbons)
22.8 (ArACH3), 53.9 (SO2ACH2), 47.7 (C-40), 58.6
(C-50), 150.7 (C-30), 158.8 (C-5), 165.9 (C-2), 123.2,
127.4, 129.6, 130.3, 131.2, 138.5, 139.3, 140.7
(aromatic carbons)
0
5.47 (s, 2H, SO2ACH2), 6.55 (bs, 1H, NH), 6.86–7.74
0
(m, 11H, C5 AH, ArAH)
2.34 (s, 3H, ArACH3), 5.43 (s, 2H, SO2ACH2), 6.57
0
(bs, 1H, NH), 6.87–7.76 (m, 10H, C5 AH, ArAH)
7c
5.52 (s, 2H, SO2ACH2), 6.58 (bs, 1H, NH), 6.89–7.78
(m, 10H, C5 AH, ArAH)
51.9 (SO2ACH2), 48.2 (C-40), 57.8 (C-50), 149.7 (C-30),
157.6 (C-5), 163.7 (C-2), 122.9, 129.6, 130.5, 131.4,
132.6, 137.3, 140.8, 141.7 (aromatic carbons)
0
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

September 2011 Synthesis and Antimicrobial Studies of Pyrazolyl Oxadiazoles and Thiadiazoles
1201
Table 4
The in vitro antibacterial activity of 6–7.
Zone of inhibition (mm)
Gram (þ)ve
Gram (ꢁ)ve
K. pneumoniae
Compound
Concentration (lg/mL)
S. aureus
B. subtilis
E. coli
6a
100
200
100
200
100
200
100
200
100
200
100
200
100
200
14
17
12
14
16
19
32
36
25
29
35
38
35
39
16
18
11
12
14
16
33
35
26
30
33
36
38
41
09
11
–
–
09
–
6b
10
10
12
25
28
19
22
29
32
40
44
–
6c
11
13
24
26
17
19
27
31
42
45
7a
7b
7c
Chloramphenicol
Table 5
[3] Pulido, M. L.; Fenyes, J. G.; Eur. Pat. Appl. EP 467,708;
Chem Abstr 1992, 116, 146150j.
The in vitro antifungal activity of 6–7.
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J Heterocycl Chem 1990, 27, 807.
Zone of inhibition (mm)
F. solani C. lunata A. niger
Concentration
(lg/mL)
[5] Naoto, M.; Kazue, N.; Tomotoshi, I.; Hiroaki, F.; Kenichi,
M.; Hirotaka, T.; Yoriko, O.; Masahiro, T. Eur. Pat. Appl. EP 361,827
(1990), p 120.
Compound
6a
100
200
100
200
100
200
100
200
100
200
100
200
100
200
20
23
18
20
24
26
30
33
28
33
32
35
38
42
22
24
19
20
22
25
27
29
30
31
34
37
41
44
18
20
16
18
19
21
22
25
23
25
26
29
36
39
[6] Pande, A.; Saxena, V. K. Indian J Chem 1987, 26B, 390.
[7] Kopp, M.; Lancelot, J. C.; Dallemagne, P.; Rault, S. J Het-
erocycl Chem 2001, 38, 1045.
6b
[8] Colliot, F.; Kukorowski, K. A.; Hawkins, D. W.; Roberts,
D. A. Brighton Crop Prot Conf Pests Dis 1992, 1, 29.
[9] Miura, Y.; Ohnishi, M.; Mabuchi, T.; Yanai, I. Brighton
Crop Prot Conf Weeds 1993, 1, 35.
6c
7a
7b
7c
[10] Konotsune, T.; Kawakubo, K.; Honma, T. Jpn. Pat.
8,035,035 (1980); Chem Abstr 1980, 93, 20750.
[11] Rigo, B.; Couturier, D. J Heterocycl Chem 1985, 22, 287.
[12] El-Emam, A. A.; Al-Deeb, O. A.; Al-Omar, M.; Lehmann,
J. Bioorg Med Chem 2004, 12, 5107.
Ketoconazole
[13] Kucukguzel, S. G.; Oruc, E. E.; Rollas, S.; Sahin, F.;
Ozbek, A. Eur J Med Chem 2002, 37, 197.
[14] Kagthara, P. R.; Shah, N. S.; Doshi, R. K.; Parekh, H. H.
Indian J Chem 1999, 38B, 572.
the reaction mixture was treated with a 5% NaOH solution.
The organic layer was separated and repeatedly washed with
water. It was dried over anhydrous Na2SO4, and the solvent
was removed on a rotary evaporator. The resultant solid was
purified by recrystallization from 2-propanol.
[15] Akhter, M.; Husain, A.; Azad, B.; Ajmal, M. Eur J Med
Chem 2009, 44, 2372.
[16] Unangast, P. C.; Shrum, G. P.; Conner, D. T.; Dyer, C. D.;
Schrier, D. J. J Med Chem 1992, 35, 3691.
[17] Khan, M. S. Y.; Khan, R. M.; Drabu, S. Indian J Heterocycl
Chem 2001, 11, 119.
Acknowledgments. The authors are grateful to Council of Sci-
entific and Industrial Research (CSIR), New Delhi, for financial
assistance under major research project.
[18] O’Neal, J. B.; Rosen, H.; Russell, P. B.; Adams, A. C.;
Blumenthal, A. J Med Chem 1962, 5, 617.
¨
[19] Sandstrom, J. Adv Heterocycl Chem 1968, 9, 165.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet