Antifungal activities of N-arylbenzenesulfonamides against phytopathogens and control efficacy on wheat leaf rust and cabbage club root diseases.

Article abstract of DOI:10.1271/bbb.66.2677

A set of N-arylbenzenesulfonamides with various substituents at the arylamine and benzenesulfonyl positions were prepared, and their antifungal properties were measured in vitro against such plant pathogenic fungi as Pythium ultimum, Phytophthora capsici, Rhizoctonia solani, and Botrytis cinerea. Compounds 3, 4, 8, 9, 10, 14, 16, 18, 20, 21, 24 and 27 had antifungal activity over a broad spectrum of the phytopathogenic fungi tested, where 50% of inhibition (ED50) was in the range of 3-15 microg/ml. Based on the in vitro activity, six derivatives (3, 4, 10, 18, 21 and 27) were selected and tested further for their fungicidal efficacy in vivo. The fungicidal efficacy of 10, 21 and 27 had a disease control value of over 85% at 50 microg/ml against wheat leaf rust, while that of 4 was selective against cabbage club root disease.

Full text of DOI:10.1271/bbb.66.2677

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Antifungal Activities of N-Arylbenzenesulfonamides
against Phytopathogens and Control Efficacy on
Wheat Leaf Rust and Cabbage Club Root Diseases
Jae Gon KANGa, Jong Hyun HURa, Sung Jun CHOIa, Gyung Ja CHOIb, Kwang Yun CHOb,
Leonid N. TENc, Ki Hun PARKa & Kyu Young KANGa
a Department of Agricultural Chemistry, Division of Applied Life Science, Gyeongsang
National University Chinju 660-701, Korea
b Screening Division, Korea Research Institute of Chemical Technology Yusong-Gu, Taejon
305-600, Korea
c National University of Uzbekistan, VUZ Gorodok Tashkent 700179, Uzbekistan
Published online: 22 May 2014.
To cite this article: Jae Gon KANG, Jong Hyun HUR, Sung Jun CHOI, Gyung Ja CHOI, Kwang Yun CHO, Leonid N. TEN,
Ki Hun PARK & Kyu Young KANG (2002) Antifungal Activities of N-Arylbenzenesulfonamides against Phytopathogens and
Control Efficacy on Wheat Leaf Rust and Cabbage Club Root Diseases, Bioscience, Biotechnology, and Biochemistry, 66:12,
2677-2682, DOI: 10.1271/bbb.66.2677
To link to this article: http://dx.doi.org/10.1271/bbb.66.2677
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Biosci. Biotechnol. Biochem., 66 (12), 2677–2682, 2002
Note
Antifungal Activities of
N-Arylbenzenesulfonamides against Phytopathogens
and Control E‹cacy on Wheat Leaf Rust and Cabbage Club Root Diseases
2
Jae Gon KANG,1 Jong Hyun HUR,1 Sung Jun CHOI,1 Gyung Ja CHOI,2 Kwang Yun CHO
,
†
1,
Leonid N. TEN,3 Ki Hun PARK,1 and Kyu Young KANG
1Department of Agricultural Chemistry, Division of Applied Life Science, Gyeongsang National University,
Chinju 660-701, Korea
2Screening Division, Korea Research Institute of Chemical Technology, Yusong-Gu, Taejon 305-600, Korea
3National University of Uzbekistan, VUZ Gorodok, Tashkent 700179, Uzbekistan
Received April 15, 2002; Accepted July 25, 2002
A set of
N
-arylbenzenesulfonamides with various
It is well known that the chemotherapeutic bacteri-
al activity of sulfonamide6–8) is due to inhibiting the
substituents at the arylamine and benzenesulfonyl posi-
tions were prepared, and their antifungal properties
were measured in vitro against such plant pathogenic
synthesis of dihydrofolic acid from p-aminobenzoic
acid, pteridine, and glutamic acid by means of di-
hydropteroate synthase, because of their competitive
fungi as Pythium ultimum
, Phytophthora capsici,
Rhizoctonia solani, and Botrytis cinerea. Compounds 3,
4, 8, 9, 10, 14, 16, 18, 20, 21, 24 and 27 had antifungal
activity over a broad spectrum of the phytopathogenic
fungi tested, where 50
range of 3–15 g ml. Based on the in vitro activity, six
derivatives (3, 4, 10, 18, 21 and 27) were selected and
tested further for their fungicidal e‹cacy in vivo. The
fungicidal e‹cacy of 10, 21 and 27 had a disease control
value of over 85
while that of 4 was selective against cabbage club root
disease.
antagonism against
here the synthesis of various
p
-aminobenzoic acid.9) We report
N
-arylbenzenesul-
fonamides and the selection of a potential fungicide
for several plant pathogens in vitro and in vivo. The
requisite substrates, 1–30, were easily prepared by
treating of commercially available benzenesul-
fonylchloride derivatives with each corresponding
arylamine under basic conditions in THF.10)
% of inhibition (ED50) was in the
m
W
% at 50 mg ml against wheat leaf rust,
The sulfonamide derivatives described in the
present work were examined in vitro for their an-
tifungal activities against the four plant pathogenic
W
fungi, P. ultimum, P. capsici, R. solani, and B.
Key words:
N
-arylbenzenesulfonamide; fungicidal ac-
cinerea. The results are summarized in Table 1. In the
design of a fungicide, the sulfonamide moiety located
between the aromatic rings, and substituents (H,
CH3, F, CF3, Cl and NO2) in the benzenesulfonyl and
arylamine moieties were considered as a key func-
tions to aŠord antifungal activity. For example, com-
pound 11 had only one diŠerent substituent from
compound 17 (CH3 to NO2) in the benzenesulfonyl
moiety, the ED50 value of compound 11 being 10–
tivity; wheat leaf rust; cabbage club root
The development of fungicides has been attracting
considerable attention because millions of dollars
worth of crops are damaged by fungal diseases.1) In
the previous paper, we described the isolation and
antifungal activities of the simple sulfonamide,
N-
butylbenzenesulfonamide, from a Pseudomonas sp.2)
Although it had relatively low antifungal activity, it
showed a broad action spectrum for potential appli-
cation as the lead compound for a new fungicide. A
new sulfonamide fungicide has recently been devel-
oped for controlling club root disease.3–5) Substantial
eŠort by our laboratories has been directed to the
synthesis of a large number of sulfonamides in order
to construct our own compound library of new an-
tifungal agents against several plant pathogenic fungi
25
mg ml, while that of 17 was over 150 mg ml
W W
against all the fungi tested. Table 1 also shows that
such as Pythium ultimum, Phytophthora capsici,
Rhizoctonia solani and Botrytis cinerea
.
Fig. 1. Synthesis of
N-Arylbenzenesulfonamide.
†
To whom correspondence should be addressed. Fax: +82-55-757-0178; E-mail: kykang
＠
nongae.gsnu.ac.kr
Abbreviations: RB, rice blast; RSB, rice sheath blight; TGM, tomato gray mould; TLB, tomato late blight; WLR, wheat leaf rust; BPM,
barley powdery mildew; CCR, cabbage club root

2678
J. G. KANG et al.
Table 2. Fungicidal Activities of the Sulfonamide Derivatives
Table 1. Antifungal Activities of Sulfonamides
against Six Phytopathogenic Fungia,b
ED50 (ppm)a
Group Compound
R2
Compound
RB
RSB
TGM TLB WLR BPM
P.u.b P.c. R.s. B.c.
3
4
10
18
21
27
0
3
8
0
0
7
0
0
0
0
0
2
0
0
2
0
2
3
0
0
7
0
44
25
0
9
95
0
87
87
0
2
0
0
0
4
I
1
2
3
4
5
6
H
75.4
6.9
11.7
5.4
66.6 68.9 239.2
10.3 42.3 65.7
14.6 24.1 14.8
9.0 14.4 28.0
p
p
o
o
-NO2
-CF3
-Cl,
-CF3,
p
-NO2
p
p
-NO2 19.31 18.5 28.5 33.1
m
-CF3,
-F
13.5
5.6 16.8 10.7
a
All activities were measured at 50 mg ml against RB (rice blast, Mag-
W
II
7
8
9
10
11
12
H
29.0
17.3
11.8
13.1
22.3 22.5 69
19.3 16.8 35.5
naporthe grisea), RSB (rice sheath blight, Corticium sasaki), TGM
(tomato gray mould, Botrytis cinerea), TLB (tomato late blight,
Phytophthora capsici), WLR (wheat leaf rust, Puccinia recondita) and
BPM (barley powdery mildew, Erysiphe graminis).
p
p
o
o
-NO2
-CF3
-Cl, p-NO2
14.1
11.8
20.7 13.0
34.3 17.5
8.6
8.0 12.1
9.5
b
-CF3,
p
-NO2 24.6
-CF3, p-F 12.6
9.9
7.9
The control value
(
z)
was calculated by the following equation:
100 [(disease severity of untreated plants„disease severity of treated
plants) disease severity of untreated plants].
×
m
W
III
IV
V
13
14
15
16
17
18
H
n.dc 110.0 53.9 352
7.2
16.0
10.5
p
p
o
o
-NO2
-CF3
-Cl, p-NO2
18.4 n.d
71.8
21.5 22.2 18.4
9.4 27.0 34.7
Table 3. Disease Control E‹cacy (
tives and Flusulfamide on Cabbage Club Root (CCR) Caused by
Plasmodiophora brassicae
z
) of Sulfonamide Deriva-
-CF3,
p
p
-NO2 146
874
n.d 409
m
-CF3,
-F
11.4
2.8 18.5 12.1
Concentration ( mg ml)
W
19
20
21
22
23
24
H
21.3
12.3
4.3
48.4 33.7 72.4
Compound
p
p
o
o
-NO2
-CF3
-Cl,
27.7 n.d
n.d
19
56
167
500
12.2 15.4 13.6
16.4 30.3 152.7
79.9 124.3 143.4
3
4
10
18
21
27
0
17
0
0
17
0
0
83
25
8
25
0
0
82
50
17a
33
0
0
95
67
p
-NO2
5.5
-CF3, p-NO2 34.8
m
-CF3,
p
-F
9.4
14.5 15.4
9.7
a
25
26
27
28
29
30
H
17.9
5.7
7.3
7.2
47.4 26.6 68.0
14.7 65.7 85.3
75
92
62
p
p
o
o
-NO2
-CF3
-Cl, p-NO2
Flusulfamideb
0
17
42
12.1
6.0
6.2
7.0 34.8 63.6
a
-CF3,
p
-NO2 155.4 232.8 26.2 n.d
-CF3, p-F 10.1 60.8 6.0 3.5
Phytotoxicity.
Commercial fungicide for CCR.
b
m
a
b
c
ED50
growth.
P.u.: Pythium ultimum, P.c.: Phytophthora capsici, R.s.: Rhizoctonia
z
: Concentration required to cause 50 inhibition of fungal
(85–90
z control) against wheat leaf rust and to a
lesser extent against tomato late blight. Compound 4
solani, B.c.: Botrytis cinerea
.
n.d: not detected.
showed highly selective activity (80
z
control) against
cabbage club root disease. Compound 4 had rela-
tively stronger fungicidal activity than that of the
commercial fungicide, ‰usulfamide,3–5) as shown in
Table 3 which is inconsistent with the published
data.5) This discrepancy in the fungicidal e‹cacy
toward cabbage club root disease between compound
most of the
N
-arylbenzenesulfonamides had low in
vitro activity against Botrytis cinerea, but that a set
of
at the benzylamine position showed ED50 values of
3–15 g ml. It is also apparent that the compounds
with a
had strong inhibition in vitro against P. ultimum
capsici R. solani, and B. cinerea
N-arylbenzenesulfonamides with m-CF3 and p-F
m
4 and ‰usulfamide might be explained by a diŠerence
W
5)
p
-CF3 substituent at the benzylamine position
P.
in the application methods. Shimotori et al
.
have
,
applied the test compounds to soil by thoroughly
mixing with a dustable powder (DP) before seedling
transplantation, whereas we treated the compounds
in a solution on the surface of the soil after trans-
planting. The manufacturer of ‰usulfamide recom-
mends mixing the chemical (DP) thoroughly with the
soil to maximize its e‹cacy because of its strong ad-
sorption and little movement characteristic in the
soil. In summary, after testing many of the sul-
fonamide collections with a structural relationship,
,
.
We thus chose six compounds (3, 4, 10, 18, 21 and
27) based on their in vitro antifungal activity and
tested them further in vivo. These compounds (3, 4,
10, 18, 21 and 27) were examined for their fungicidal
activities against seven plant diseases, namely four
obligate pathogens (TLB, WLR, BPM and CCR) and
three nonobligate pathogens (RB, RSB and TGM), at
500, 250 and 50
of the 50 g ml treatment being given in Table 2.
These compounds exhibited fungicidal activities with
a selective spectrum of plant pathogens at 50 g ml.
Compounds 10, 21 and 27 showed selective activity
mg ml, the disease control value (z)
W
m
we discovered that
zenesulfonamide (4) had a distinctly diŠerent eŠect
on CCR, while -4-tri‰uoromethylphenylnitroben-
zenesulfonamides including 21 and 27, had a selective
N-2-chloro-4-nitrophenylben-
W
m
N
W

Antifungal Activities of
N
-Arylbenzenesulfonamide
2679
eŠect on WLR. These results could provide a useful
guide to the development of potential new selective
fungicides.
termined as the percentage of infected leaf area 5
days after the inoculation. The rice sheath blight as-
say used treated rice seedlings at the third-leaf stage
that were inoculated by adding 7-day-old wheat-rice
bran (200 ml of wheat bran and 100 ml of rice bran in
a 1-l Erlenmeyer ‰ask) cultures of C. sasaki to soil.
±
Experimental
Apparatus. 1H- and 13C-NMR spectra were ob-
tained with a Bruker AM 500 spectrometer (1H-NMR
at 500 MHz and 13C-NMR at 125 MHz). Melting
point (mp) data were determined with Thomas-
Hoover capillary apparatus and are uncorrected.
Elemental analyses were performed with a LECO
Micro-carbon Hydrogen Determinator.
After incubating for 4 days in the dark at 25
29C
under 100
z
RH, the inoculated plants were kept in a
±
growth chamber for 4 days at 25
29C under 100z
RH with 12 h of daylight per day, and the disease
severity was then assessed. The tomato late blight as-
say used treated tomato seedlings at the second-leaf
stage that were inoculated with P. infestans by
spraying with a zoospore suspension (108 zoospore l)
W
In vitro mycelial growth inhibition assay. Each
compound dissolved in methanol or dimethyl sul-
phoxide (DMSO) was tested for its in vitro antifungal
activity against four plant pathogenic fungi. Each
released from a sporangial suspension of the fungus.
The tomato gray mould assay was conducted on
tomato seedlings at the second-leaf stage that were
inoculated by spraying a spore suspension (109 spores
serially diluted compound was incorporated in 1 5
l) of B. cinerea. The inoculated tomato plants were
W
W
strength potato dextrose agar (PDA) plates at 0 to
9 z
kept in the dark at 25 C under 100 RH, and the
200
m
g ml, and a 5-mm agar plug of the four
disease severity was assessed 3–4 days after inocula-
tion. Wheat leaf rust was assayed with treated wheat
seedlings at the ˆrst-leaf stage that had been inoculat-
ed with P. recondita by spraying with a spore suspen-
W
phytopathogenic fungi, P. ultimum, P. capsici, R.
solani and B. cinerea, was placed at the center of the
plate. Three replicate plates of each concentration
for each fungus were incubated at 25
9
C for each test-
sion (0.67 g spores l, containing 250 mg l of Tween
W
W
ed fungus. After incubating for 2–6 days, the radial
growth was measured, and the ED50 value for the
mycelial growth inhibition was calculated by a probit
analysis.11)
20) of the fungus. The seedlings were incubated in a
moist chamber for 1 day at 20 C and then trans-
9
ferred to an incubation room. The disease severity
was determined by rating the infected leaf area 7 days
after the inoculation. To assay cabbage club root,
cabbage seedlings were transplanted after the soil had
been inoculated with a P. brassicae spore suspension
In vivo assay. Six compounds based on their in
vitro activity were selected and tested further in vivo
for antifungal activity against the following diseases:
RB (Magnaporthe grisea (Hebert) Barr); RSB (Cor-
ticium sasaki Matsu); TGM (Botrytis cinerea); TLB
(2
×
106 spores ml), and then 10 ml of each sample
W
solution was applied to assess the disease-suppression
activity. The disease severity was assessed 35 days af-
ter inoculation. The development of barley powdery
mildew was assayed for treated barley seedlings at the
ˆrst-leaf stage that had been inoculated with E.
graminis. f. sp. hordei by dusting with the dry inocu-
lum from diseased plants. The inoculated barley
(
Phytophthora infestans); WLR (Puccinia recondita
Rob ex Desm); BPM (Erysiphe graminis DC f. sp.
hordei Marchal) and CCR (Plasmodiophora brassi-
cae). Rice (Oryza sativa L, Nakdong), tomato
(
Lycopersicon esculentum Mill, cv Seokwang),
wheat (Triticum aestivum L, cv Chokwang), barley
9
seedlings were incubated for 7 days at 20 C in an in-
(
(
Hordeum sativum Pers, cv Dongbori) and cabbage
Brassica campestris L, cv Manhui) were used as
cubation room, and the disease severity was then de-
termined.
hosts. All the plants except cabbage were grown in
vinyl pots (4.5 cm diameter) in a greenhouse at
Typical isolation procedure for sulfonamides
N-phenylbenzenesulfonamide ( ). To a solution of
NaH (60 in oil; 194 mg, 5.1 mmol) in 10 ml of dry
1–30.
±
25
5
9
C for 1–4 weeks. The potted plant seedlings
1
were sprayed with the test compound dissolved
in water+methanol (95+5) containing Tween 20
z
THF was added a solution of aniline (189 mg,
2.0 mmol) in THF (3 ml), and the solution was
(250 mg l) as a wetting agent and allowed to stand
W
for 24 h.12)
stirred for 10 min at 0
fonyl chloride (300 mg, 1.7 mmol) was added to this
reaction mixture at 0 C, before the reaction mixture
9C. A solution of benzenesul-
To assess the development of rice blast, treated rice
seedlings at the second-leaf stage were inoculated
9
with M. grisea by spraying with a spore suspension
was warmed to room temperature and stirred over-
night. The mixture was then quenched with sat.
NaHCO3 and extracted with ethylacetate. The com-
bined organic layer was washed with brine, dried
with anhydrous sodium sulfate, ˆltered, and evapo-
rated in vacuo. Chromatography on silica gel with
8
×
(5 10 spores l) of the fungus. After incubating the
W
±
29C under
seedlings in the dark for 1 day at 25
100 RH, they were transferred to a growth cham-
ber maintained at 25
12 h of daylight per day. The disease severity was de-
z
±
29C under 70–80z RH and

2680
J. G. KANG et al.
hexane-EtOAc provided solid 1 (339 mg, 86
z
), mp
N-phenyl-4-methylbenzenesulfonamide
(7). Mp
99–101
9C.
d
H (CDCl3, 500 MHz): 7.09 (3H, m), 7.22
100–102 C; H (CDCl3, 500 MHz): 2.31 (3H, s), 7.05
9 d
＝
＝
(2H, dd,
J
8.0 and 7.5 Hz), 7.42 (2H, dd,
J
8.0
7.5 and 7.5 Hz), 7.79
8.5 and 1.0 Hz); dC (CDCl3, 125 MHz):
122.1, 125.9, 127.6, 129.4, 129.7, 133.4, 136.8,
139.7. Anal. Found: C, 61.57; H, 4.93; N, 6.17
Calcd. for C12H11NO2S: C, 61.78; H, 4.75; N,
6.00
(1H, m), 7.11 (2H, m), 7.18 (4H, m), 7.70 (2H, m);
dC (CDCl3, 125 MHz): 21.9, 121.8, 125.5, 127.7,
129.7, 130.1, 136.5, 137.2, 144.3. Anal. Found: C,
＝
J
and 8.0 Hz), 7.52 (1H, dd,
(2H, dd,
J
＝
63.35; H, 5.46; N, 5.59
z. Calcd. for C13 H13NO2S:
z.
C, 63.13; H, 5.30; N, 5.66z.
z.
N-4-nitrophenyl-4-methylbenzenesulfonamide (
Mp 101–103 C; dH (DMSO-d6, 500 MHz): 2.13 (3H,
s), 7.10 (2H, d,
8).
9
＝
＝
N-4-nitrophenylbenzenesulfonamide (
2
). Mp 116–
J
9.1 Hz), 7.17 (2H, d,
J
8.2 Hz),
＝
8.3 Hz), 7.91 (2H, d, J 9.2 Hz); dC
＝
＝
118
9
C; dH (CDCl3, 400 MHz): 7.25 (2H, d,
J
7.55 (2H, d,
J
＝
9.0 Hz), 7.52 (2H, dd,
J
8.3 and 7.6 Hz), 7.61 (1H,
(DMSO-d6, 125 MHz): 21.8, 118.8, 126.2, 127.6,
130.9, 137.0, 143.4, 144.9, 145.1. Anal. Found: C,
53.61; H, 4.32; N, 9.41
C, 53.42; H, 4.14; N, 9.58
＝
＝
9.0 Hz);
m), 7.92 (2H, d,
J
8.6 Hz), 8.12 (2H, d,
J
dC (CDCl3, 100 MHz): 118.6, 125.4, 127.2, 129.5,
133.9, 138.3, 142.6, 143.9. Anal. Found: C, 52.01;
z
. Calcd. for C13H12 N2O4S:
z
.
H, 3.74; N, 10.19
z. Calcd. for C12H10 N2O4S: C,
51.79; H, 3.62; N, 10.07
z
.
N-4-tri‰uorometylphenyl-4-methylbenzenesul-
fonamide ( ). Mp 131–133 C); dH
C (lit.5) 132–135
(CD3OD, 500 MHz): 2.38 (3H, s), 7.27 (2H, d,
9
9
9
N-4-tri‰uoromethylphenylbenzenesulfonamide
. Mp 89–91 C; H (CDCl3, 500 MHz): 7.20 (2H, d,
8.5 Hz), 7.48 (4H, m), 7.58 (1H, m), 7.86 (2H,
＝
＝
＝
J
(
3
)
9
d
J
8.5 Hz), 7.32 (2H, d,
J
8.0 Hz), 7.51 (2H, d,
C (CD3OD, 125 MHz): 21.8,
265.3 Hz), 127.3 (m), 127.7,
128.6, 131.2, 138.4, 143.3, 145.9. Anal. Found: C,
53.51; H, 3.94; N, 4.35 . Calcd. for C14H12F3NO2S:
C, 53.33; H, 3.84; N, 4.44
＝
J
8.5 Hz), 7.73 (2H, m);
＝
121.0, 126.0 (q, J
d
＝
dd,
J
8.5 and 1.0 Hz);
d
C (CDCl3, 125 MHz): 119.9,
228.8 Hz), 126.65, 126.71, 127.2, 129.4,
133.5, 138.8, 139.8. Anal. Found: C, 51.67; H, 3.48;
N, 4.79 . Calcd. for C13H10F3NO2S: C, 51.82; H,
3.35; N, 4.65
＝
J
124.1 (q,
z
z
z
.
z.
N-2-chloro-4-nitrophenyl-4-methylbenzenesul-
fonamide (10). Mp 162–164.3 C);
C (lit.5) 161–163
dH (CDCl3, 500 MHz): 2.40 (3H, s), 7.29 (2H, d,
N-2-chloro-4-nitrophenylbenzenesulfonamide (
Mp 162.3–163 C); dH (CDCl3,
C (lit.5) 162.5–163.5
500 MHz): 7.24 (2H, m), 7.54 (2H, d,
4
).
9
9
9
9
＝
＝
＝
J
J
8.4 Hz),
8.0 and 8.0 Hz), 8.13 (1H, d,
7.9 Hz), 8.43 (1H, dd, 8.2 and 1.2 Hz), 8.72
J
8.1 Hz), 7.76 (3H, m), 8.08 (1H, dd,
9.1
＝
2.5 Hz); dC (CDCl3,
＝
7.72 (1H, dd,
J
and 2.5 Hz), 8.20 (1H, d, J
J
＝
(1H, d,
J
＝
125 MHz): 22.0, 119.2, 123.6, 123.9, 125.6, 127.7,
＝
J
1.2 Hz); dC (CDCl3, 125 MHz): 119.5,
130.5, 135.7, 139.9, 144.0, 145.7. Anal. Found:
123.88, 123.92, 125.6, 127.6, 130.0, 134.5, 138.8,
139.8, 144.1. Anal. Found: C, 46.31; H, 2.87; N,
8.86
N, 8.96
C, 47.86; H, 3.47; N, 8.79
z
.
Calcd. for
C13H11ClN2O4S: C, 47.78; H, 3.39; N, 8.57
z
.
z. Calcd. for C12H9ClN2O4S: C, 46.09; H, 2.90;
z
.
N-2-tri‰uoromethyl-4-nitrophenyl-4-methylben-
zenesulfonamide (11). Mp 108–110
9C; dH (CDCl3,
N-2-tri‰uoromethyl-4-nitrophenylbenzenesul-
500 MHz): 2.40 (3H, s), 7.29 (2H, d,
J
＝
8.5 Hz),
＝
＝
fonamide (
5
). Mp 120.9–121.1
9
C; dH (CD3OD,
7.75 (2H, d,
J
＝
8.5 Hz), 7.97 (1H, d,
J
9.0), 8.33
＝
＝
500 MHz): 7.55 (2H, m), 7.64 (1H, m), 7.88 (3H, m),
(1H, dd,
J
9.0 and 2.5 Hz), 8.40 (1H, d,
2.5 Hz); dC (CDCl3, 125 MHz): 21.6, 119.4 (q,
J
J
8.42 (2H, m); dC (CD3OD, 125 MHz): 123.7 (m),
＝
＝
123.8 (q,
J
275 Hz), 124.9, 127.0, 128.4, 129.1,
25 Hz), 120.9, 122.6 (q,
127.5, 127.4, 130.2, 135.0, 140.4, 143.2, 145.5. Anal.
Found: C, 46.89; H, 3.29; N, 7.89 . Calcd. for
C14H11F3N2O4S: C, 46.67; H, 3.08; N, 7.77
J
262.5 Hz), 123.0 (m),
130.5, 134.7, 141.3, 141.9, 145.6. Anal. Found: C,
45.31; H, 2.54; N, 7.96 . Calcd. for C13H9F3N2O4S:
C, 45.09; H, 2.62; N, 8.09
z
z
z.
z.
N-3-tri‰uoromethyl-4-‰uoro-phenylbenzenesul-
fonamide ). Mp 132–132.6 C; dH (CD3OD,
500 MHz): 7.20 (1H, m), 7.35 (2H, m), 7.50 (2H, m),
N-3-tri‰uoromethyl-4-‰uorophenyl-4-methylbenz-
(6
9
enesulfonamide (12). Mp 97.3–98.59C; dH (CDCl3,
500 MHz): 2.40 (3H, s), 7.07 (1H, m), 7.28 (4H, m),
＝
7.59 (1H, m), 7.75 (2H, d,
125 MHz):119.3 (d, 25 Hz), 119.9 (m), 121.5,
262.5 Hz), 128.6, 128.9, 130.7, 134.7,
J
8.0 Hz); dC (CD3OD,
7.66 (2H, m); dC (CDCl3, 125 MHz): 21.5, 117.9
J
＝
(d, J 25 Hz), 119.1 (m), 120.8 (m), 122.0 (q, J
＝ ＝
＝
124.1 (q,
136.0, 141.0, 158.4 (d,
Found: C, 49.09; H, 2.71; N, 4.61
C13H9F4NO2S: C, 48.90; H, 2.84; N, 4.39
J
275.0 Hz), 127.3, 127.5 (m), 130.0, 132.8 (d,
＝
＝
＝
z
J
262.5 Hz). Anal.
. Calcd. for
J
12.5 Hz), 135.4, 144.7, 157.2 (d,
Anal. Found: C, 50.62; H, 3.48; N, 4.43
for C14H11F4NO2S: C, 50.45; H, 3.33; N, 4.20z.
J
250 Hz).
z
. Calcd.
z.

Antifungal Activities of
N
-Arylbenzenesulfonamide
2681
N-phenyl-2-nitrobenzenesulfonamide
117–119 C; dH (CDCl3, 500 MHz): 7.18 (3H, m),
7.27 (2H, m), 7.56 (1H, m), 7.68 (1H, m), 7.83 (2H,
m); C (CDCl3, 125 MHz): 123.3, 125.3, 126.6, 129.5,
131.9, 132.3, 132.5, 133.9, 135.5, 148.8. Anal.
Found: C, 51.81; H, 3.57; N, 10.31 . Calcd. for
C12H10N2O4S: C, 51.79; H, 3.62; N, 10.07
(
13). Mp
N-phenyl-3-nitrobenzenesulfonamide
(
19). Mp
9
118–1209C; dH (CD3OD, 500 MHz): 7.09 (3H, m),
＝
8.0 and 8.0 Hz), 8.07
7.23 (2H, m), 7.73 (1H, dd,
J
d
(1H, m), 8.40 (1H, m), 8.53 (1H, m); dC (DMSO-d6,
100 MHz): 122.9, 129.6, 130.0, 131.3, 131.4, 131.9,
132.7, 134.0, 139.3, 148.0. Anal. Found: C, 51.96;
z
z.
H, 3.74; N, 10.32
z. Calcd. for C12H10N2O4S: C,
51.79; H, 3.62; N, 10.07
z
.
N-4-nitrophenyl-2-nitrobenzenesulfonamide (14).
Mp 178.5–179.5
(lit.5) 179–180); dH (CDCl3,
500 MHz): 7.39 (2H, m), 7.68 (1H, m), 7.75 (1H, m),
9
C
N-4-nitrophenyl-3-nitrobenzenesulfonamide (20).
Mp 183.5–184.9 C; dH (CD3OD, 500 MHz): 7.34
9
＝
＝
8.0 and
7.89 (1H, m), 8.00 (1H, m), 8.17 (2H, m);
d
C (CDCl3,
(2H, d,
J
9.0 Hz), 7.81 (1H, dd,
J
＝
125 MHz): 121.1, 125.4, 125.8, 126.4, 131.7, 133.0,
134.7, 141.6, 145.2, 148.3. Anal. Found: C, 44.79;
8.0 Hz), 8.12 (2H, d,
J
J
9.0 Hz), 8.23 (1H, d,
＝
＝
8.0 Hz), 8.67 (1H, s); dC
J
8.0 Hz), 8.44 (1H, d,
H, 3.01; N, 13.24
z
. Calcd. for C12 H9N3O6S: C,
(DMSO-d6, 125 MHz): 123.4, 125.4, 130.17, 132.4,
44.58; H, 2.81; N, 13.00
z
.
133.4, 134.5, 138.3, 139.2, 148.5, 149.2. Anal.
Found: C, 44.79; H, 2.94; N, 13.24
z. Calcd. for
N-4-tri‰uoromethyphenyl-2-nitrobenzenesulfona-
mide (15). Mp 128–130 C; dH (CDCl3, 500 MHz):
8.3 Hz), 7.54 (2H, d, 8.4 Hz),
8.1 and 8.1 Hz), 8.13 (1H, m), 8.43
C (CDCl3, 125 MHz): 120.5,
260.0 Hz), 127.0 (m), 127.1,
127.9, 130.8, 132.7, 138.8, 140.9, 148.5. Anal.
Found: C, 45.32; H, 2.84; N, 8.31 . Calcd. for
C13H9F3N2O4S: C, 45.09; H, 2.62; N, 8.09
z
C12H9N3O6S: C, 44.58; H, 2.81; N, 13.00 .
9
7.23 (2H, d,
7.72 (1H, dd,
J
＝
＝
J
＝
N-4-tri‰uoromethylphenyl-3-nitrobenzenesulfona-
mide (21). Mp 94–96 C; dH (CDCl3, 500 MHz): 7.24
J
9
＝
＝
(1H, m), 8.72 (1H, m);
122.5, 123.8 (q,
d
(2H, d,
(1H, dd,
J
J
8.4 Hz), 7.54 (2H, d,
J
8.4 Hz), 7.72
＝
8.1 and 8.1 Hz), 8.13 (1H, m), 8.43 (1H,
＝
J
m), 8.72 (1H, m); dC (CDCl3, 125 MHz): 120.5,
122.5, 123.7 (q, 270.4 Hz), 127.1 (m), 127.8 (m),
128.1, 130.8, 132.7, 138.8, 140.9, 148.5. Anal.
Found: C, 45.31; H, 2.81; N, 8.34 . Calcd. for
C13H9F3N2O4S: C, 45.09; H, 2.62; N, 8.09
z
J
＝
z
.
z
N-2-chloro-4-nitrophenyl-2-nitrobenzenesulfona-
mide (16). Mp 166–1689C; dH (DMSO-d6, 500 MHz):
z
.
7.55 (1H, d,
J
＝
9.0 Hz), 7.89 (2H, m), 8.01 (2H, m),
N-2-chloro-4-nitrophenyl-3-nitrobenzenesulfona-
8.18 (1H, dd,
J
9.0 and 2.5 Hz), 8.30 (1H, d,
mide (22). Mp 178–180
9
C (lit.5) 179–180
9
C; dH
9.2 Hz), 7.69
9.2
2.7 Hz), 8.25 (1H, m),
＝
＝
＝
(CD3OD, 500 MHz): 7.38 (1H, d, J
J
2.5 Hz); dC (DMSO-d6, 125 MHz): 123.6, 125.0,
125.5, 126.4, 128.8, 130.2, 132.9, 133.1, 135.1,
(1H, dd, J 8.0 and 8.0 Hz), 7.83 (1H, dd, J
＝ ＝
＝
and 2.8 Hz), 8.10 (1H, d, J
140.9, 144.8, 147.7. Anal. Found: C, 40.51; H, 2.41;
N, 11.93
z
. Calcd. for C12 H8ClN3O6S: C, 40.29; H,
8.29 (1H, m), 8.72 (1H, m); dC (CD3OD, 125 MHz):
120.7, 123.0, 124.2, 126.5, 126.7, 128.0, 131.5,
133.9, 140.3, 148.7, 149.9, 154.4. Anal. Found:
2.25; N, 11.75
z
.
N-2-tri‰uoromethyl-4-nitrophenyl-2-nitrobenz-
enesulfonamide (17). Mp 160–164 C; dH (CD3OD,
500 MHz): 7.34 (1H, d, 9.5 Hz), 7.61 (3H, m),
8.04 (2H, m), 8.29 (1H, d,
125 MHz): 122.8, 122.9 (m), 124.5 (m), 125.3, 125.4
(q, 275 Hz), 128.8, 131.3, 133.1, 133.8, 138.1,
139.6, 150.3, 155.4. Anal. Found: C, 40.14; H, 2.21;
N, 10.95 . Calcd. for C13H8FN3O6S: C, 39.90; H,
2.06; N, 10.74
C, 40.51; H, 2.36; N, 11.97
z
. Calcd. for
9
C12H8ClN3O6S: C, 40.29; H, 2.25; N, 11.75
z.
J
＝
＝
J
2.5 Hz); dC (CD3OD,
N-2-tri‰uoromethyl-4-nitrophenyl-3-nitrobenzene-
sulfonamide (23). Mp 234–236 C; dH (CD3OD,
400 MHz): 7.82 (1H, dd, 8.3 and 8.3 Hz), 7.87
8.5 Hz), 8.29 (1H, m), 8.45 (1H, s), 8.49
(2H, m), 8.67 (1H, m); dC (CD3OD, 100 MHz):
9
J
＝
J
＝
＝
J
(1H, d,
z
＝
255 Hz), 125.1 (m),
z
.
123.2, 123.69 (m), 123.7 (q,
J
128.8, 128.83, 129.2, 132.2, 133.8, 141.2, 143.5,
N-3-tri‰uoromethyl-4-‰uorophenyl-2-nitrobenz-
enesulfonamide (18). Mp 117–118.9 C; dH (CDCl3,
9.2 and 9.2 Hz), 7.43
(2H, m), 7.64 (1H, m), 7.75 (1H, m), 7.83 (1H,
146.2, 149.8. Anal. Found: C, 40.21; H, 2.26; N,
9
10.98
2.06; N, 10.74z.
z. Calcd. for C13H8F3N3O6S: C, 39.90; H,
＝
500 MHz): 7.14 (1H, dd,
J
＝
＝
8.0
dd,
J
7.8 and 1.3 Hz), 7.90 (1H, dd,
J
N-3-tri‰uoromethyl-4-‰uorophenyl-3-nitroben-
zenesulfonamide (24). Mp 130–132 C; dH (CDCl3,
9.3 and 9.3 Hz), 7.34
8.1 and 8.1 Hz), 8.03 (1H,
8.1 Hz), 8.45 (1H, m), 8.66 (1H, m); dC
and 1.1 Hz); dC (CDCl3, 125 MHz): 118.5, (d,
9
＝
＝
＝
400 MHz): 7.16 (1H, dd, J
J
22.0 Hz), 120.0 (m), 122.2 (q,
J
275.0 Hz),
＝
＝
(2H, m), 7.72 (1H, dd, J
122.9 (m), 126.0, 129.6 (d,
J
8.8 Hz), 132.09, 132.1
＝
z
＝
J
(m), 132.2, 133.2, 134.9, 148.1, 158.2 (d,
J
237.5).
d,
(CDCl3, 100 MHz): 118.4 (d,
122.4, 122.7 (m), 128.0, 128.3 (d, J
＝
＝
Anal. Found: C, 43.04; H, 2.38; N, 7.91
. Calcd.
J
22.2 Hz), 121.8 (m),
7.8 Hz), 130.7,
for C13H8F4N2O4S: C, 42.86; H, 2.21; N, 7.69
z
.

2682
J. G. KANG et al.
＝
＝
262.5 Hz), 128.6,
131.5 (m), 131.8 (q,
J
260.8 Hz), 132.6, 140.7,
and 12.5 Hz), 121.5, 124.5 (q,
128.9 (d,
＝
141.0, 147.7, 158.4 (d, J
J
＝
＝
＝
12.5 Hz), 130.7, 136.0 (d, J
148.4, 157.7 (d,
J
250 Hz). Anal. Found: C, 42.68;
J
12.5 Hz),
262.5 Hz). Anal. Found:
C, 43.05; H, 2.36; N, 7.91z. Calcd. for C13H8F4-
H, 2.39; N, 7.84
z
. Calcd. for C13H8F4N2O4S: C,
42.86; H, 2.21; N, 7.69
z.
N2O4S: C, 42.86; H, 2.21; N, 7.69
z
.
N-phenyl-4-nitrobenzenesulfonamide
166–168 C; dH (CD3OD, 500 MHz): 7.11 (3H, m),
(25). Mp
9
Acknowledgment
7.24 (2H, m), 7.98 (2H, m), 8.33 (2H, m); dC
(CD3OD, 125 MHz): 123.2, 125.6, 126.8, 130.0,
130.8, 138.7, 147.1, 152.0. Anal. Found: C, 51.98;
This research was conducted under the grant-aid
from Province of Gyeongsangnam-do, Republic of
Korea.
H, 3.75; N, 10.29
z. Calcd. for C12H10 N2O4S: C,
51.79; H, 3.62; N, 10.07
z
.
References
N-4-nitrophenyl-4-nitrobenzenesulfonamide (26).
Mp 172–173.9
9
C (lit.5) 171.5–173
9
C); dH (CD3-
1) Farr, D. F., Billis, G. F., Chamuris, G. P., and
Rossman, A. Y., Fungi on plant products in the Unit-
ed States. American Phytopathological Society, St.
Paul, Minn (1989).
＝
＝
COCD3, 500 MHz): 7.51 (2H, d,
J
J
9.0 Hz), 8.19
9.0 Hz), 8.42
＝
9.0 Hz), 8.21 (2H, d,
(2H, d,
(2H, d,
J
＝
J
9.0 Hz); dC (CD3COCD3, 125 MHz):
2) Kim, K. K., Kang, J. G., Moon, S. S., and Kang, K.
120.7, 125.7, 126.5, 130.0, 144.5, 145.4, 146.0,
152.0. Anal. Found: C, 44.76; H, 2.94; N, 13.27
Calcd. for C12H9N3O6S: C, 44.58; H, 2.81; N,
13.00
Y., Isolation and identiˆcation of antifungal
N-butyl-
z
.
benzenesulphonamide produced by Pseudomonas sp.
AB2. J. Antibiotics, 53, 131–136 (2000).
z.
3) Mitsui Toatsui Chemicals, EU. Patent 0199433 (Nov.
23, 1988).
4) Worthing, C. R., and Hance, R. J., Flusulfamide. In
``The pesticide manual'' 9th ed., The British Crop
Protection Council, UK, pp. 425 (1991).
N-4-tri‰uoromethylphenyl-4-nitrobenzenesulfona-
mide 27). Mp 151.1–152.4 C; dH (CD3OD,
500 MHz): 7.31 (2H, d, 8.5 Hz), 7.54 (2H, d,
(
9
＝
J
J
5) Shimotori, H., Yanagida, H., Enomoto, Y.,
Igarashi, K., Yoshinari, M., and Umemoto, M.,
Evaluation of benzenesulfonanilide derivatives for
the control of crucifers clubroot. J. Pesticide Sci., 21,
31–35 (1996).
＝
＝
＝
＝
9.0 Hz), 8.34 (2H, d,
J
J
J
8.5 Hz), 8.07 (2H, d,
9.0 Hz); C (CD3OD, 125 MHz): 121.6, 125.85 (q,
262.5 Hz), 125.9, 127.95 (q,
d
＝
J
37.5 Hz), 128.0
(m), 130.0, 142.4, 146.8, 152.2. Anal. Found: C,
45.34; H, 2.76; N, 8.32 . Calcd. for C13H9F3N2O4S:
C, 45.09; H, 2.62; N, 8.09
z
6) De Benedetti, P. G., In ``Progress in drug research'',
z.
ed. Jucker, E., Birkha
(1991).
7) Zani, F., and Vicini, P., Antimicrobial activity of
some 1,2-benzisothiazoles having benzenesul-
ä user Verlag, Basel, pp. 361–417
N-2-chloro-4-nitrophenyl-4-nitrobenzenesulfona-
mide (28). Mp 193–195.4
9
C (lit.5) 195.5–196.5
9
C); dH
a
fonamide moiety. Arch. Pharm. Pharm. Med.
Chem., 331, 219–223 (1998).
＝
J
(DMSO-d6, 400 MHz): 7.23 (1H, d,
9.3 Hz), 7.80
＝
9.3 and 3.0 Hz), 8.00 (3H, m), 8.25 (2H,
(1H, dd,
J
8) Mandell, G. L., and Petri Jr., W. A., Antimicrobial
agents: sulfonamides, trimethoprim-sulfamethoxa-
zole, quinolones, and agents for urinary tract infec-
tions. In ``The pharmacological basis of therapeu-
tics'' 9th ed., ed. Hardman, J. G., New York,
Mcgraw-Hill, pp. 716–722 (1995).
m); dC (DMSO-d6, 100 MHz): 117.2, 123.4, 123.9,
124.6, 124.8, 127.4, 135.7, 148.2, 151.5, 154.1. Anal.
Found: C, 40.52; H, 2.43; N, 11.97
z
. Calcd. for
C12H8ClN3O6S: C, 40.29; H, 2.25; N, 11.75
z
.
N-2-tri‰uoromethyl-4-nitrophenyl-4-nitroben-
zenesulfonamide (29). Mp 128–130 C; dH (CD3OD,
500 MHz): 7.51 (1H, d, 9.3 Hz), 8.04 (1H, dd,
9.3 and 2.8 Hz), 8.09 (2H, m), 8.27 (2H, m); dC
(CD3OD, 125 MHz): 121.8, 122.3 (m), 124.6 (m),
125.1, 125.5 (q, 270.5 Hz), 128.7, 129.2, 138.7,
150.8, 152.6, 156.6. Anal. Found: C, 40.08; H, 2.15;
N, 10.94 . Calcd. for C13H8F3N3O6S: C, 39.90; H,
2.06; N, 10.74
9) Eliopoulos, G. M., and Moellering Jr., R. C.,
Antibiotics. In ``Laboratory medicine'' 3th ed., ed.
Lorian, V., Williams & Willkins, Baltimore, chapter
13 (1991).
10) Greene, T. E., and Wuts, P. G. M., In ``Protective
groups in organic synthesis'' 2nd ed., John Wiley &
Sons, New York, pp. 379–381 (1991).
11) Kang, J. G., Kim, K. K., and Kang, K. Y., An-
tagonism and structural identiˆcation of antifungal
compound from Chaetomium cochliodes against
9
J
＝
＝
J
J
＝
z
z
.
phytopathogenic fungi. Agric. Chem. Biotechnol.
42, 146–150 (1999).
,
N-3-tri‰uoromethyl-4-‰uorophenyl-4-nitroben-
zenesulfonamide (30). Mp 115–116 C; dH (CD3OD,
9.5 and 9.5 Hz), 7.39
(2H, m), 7.98 (2H, m), 8.36 (2H, m); dC (CD3OD,
9
12) Kim, J. C., Choi, G. J., Park, J. H., Kim, H. T., and
Cho, K. Y., Activity against plant pathogenic fungi
of phomalactone isolated from Nigrospora sphaerica.
Pest Manag. Sci., 57, 554–559 (2001).
＝
J
500 MHz): 7.24 (1H, dd,
＝
＝
37.5
125 MHz): 119.4 (d,
J
25 Hz), 120.1 (dq,
J