Controlled synthesis of N, N-dimethylarylsulfonamide derivatives as nematicidal agents

Article abstract of DOI:10.1080/10286020.2019.1694513

Gramine can be intelligently and efficiently supplied with N, N-dimethylamino group and then reacted with the corresponding sulfonyl chlorides to synthesize N, N-dimethylarylsulfonamides. We herein designed and controlled synthesis of N, N-dimethylarylsulfonamide derivatives, and first reported the results of the nematicidal activity of 15 title compounds 3a-o against Meloidogyne incongnita in vitro, respectively. Among all of the title derivatives, compounds 3a, 3c, 3k, and 3o exhibited potent nematicidal activity with median lethal concentration (LC₅₀) values ranging from 0.22 to 0.26 mg/L. Most noteworthy, N, N-dimethyl-4-methoxyphenylsulfonamide (3c) and N, N-dimethyl-8-quinolinesulfonamide (3o) showed the best promising and pronounced nematicidal activity, with LC₅₀ values of 0.2381 and 0.2259 mg/L, respectively.

Full text of DOI:10.1080/10286020.2019.1694513

Journal of Asian Natural Products Research
ISSN: 1028-6020 (Print) 1477-2213 (Online) Journal homepage: https://www.tandfonline.com/loi/ganp20
Controlled synthesis of N, N-
dimethylarylsulfonamide derivatives as
nematicidal agents
Gen-Qiang Chen, Yan-Fei Xia, Jin-Ming Yang, Zhi-Ping Che, Di Sun, Shen Li,
Yue-E Tian, Sheng-Ming Liu, Jia Jiang & Xiao-Min Lin
To cite this article: Gen-Qiang Chen, Yan-Fei Xia, Jin-Ming Yang, Zhi-Ping Che, Di Sun, Shen
Li, Yue-E Tian, Sheng-Ming Liu, Jia Jiang & Xiao-Min Lin (2019): Controlled synthesis of N, N-
dimethylarylsulfonamide derivatives as nematicidal agents, Journal of Asian Natural Products
Research, DOI: 10.1080/10286020.2019.1694513
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JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
https://doi.org/10.1080/10286020.2019.1694513
Controlled synthesis of N, N-dimethylarylsulfonamide
derivatives as nematicidal agents
Gen-Qiang Chen, Yan-Fei Xia, Jin-Ming Yang, Zhi-Ping Che, Di Sun, Shen Li,
Yue-E Tian, Sheng-Ming Liu, Jia Jiang and Xiao-Min Lin
Laboratory of Pharmaceutical Design & Synthesis, Department of Plant Protection, College of
Forestry, Henan University of Science and Technology, Luoyang 471003, China
ABSTRACT
ARTICLE HISTORY
Gramine can be intelligently and efficiently supplied with N, N-
dimethylamino group and then reacted with the corresponding
sulfonyl chlorides to synthesize N, N-dimethylarylsulfonamides. We
herein designed and controlled synthesis of N, N-dimethylarylsul-
fonamide derivatives, and first reported the results of the nemati-
cidal activity of 15 title compounds 3a-o against Meloidogyne
incongnita in vitro, respectively. Among all of the title derivatives,
compounds 3a, 3c, 3k, and 3o exhibited potent nematicidal activ-
ity with median lethal concentration (LC ) values ranging from
Received 20 May 2019
Accepted 13 November 2019
KEYWORDS
Gramine; N; N-
dimethylarylsulfonamides;
nematicidal activity;
Meloidogyne incongnita
50
0
.22 to 0.26 mg/L. Most noteworthy, N, N-dimethyl-4-methoxyphe-
nylsulfonamide (3c) and N, N-dimethyl-8-quinolinesulfonamide
3o) showed the best promising and pronounced nematicidal
(
activity, with LC50 values of 0.2381 and 0.2259 mg/L, respectively.
1. Introduction
Plant-parasitic nematode is one of the most important plant pathogen, which is
responsible for serious losses every year. Globally, the annual crops losses caused by
nematodes were as high as 14%, resulting in economic losses of $80–100 billion [1].
Southern root-knot nematode (Meloidogyne incongnita (Kofold & White) Chitwood),
a typical parasitic pest, is widely distributed in the world [2]. Moreover, at present,
CONTACT Zhi-Ping Che
zhipingche@163.com
ß 2019 Informa UK Limited, trading as Taylor & Francis Group

2
G.-Q. CHEN ET AL.
Figure 1. Structures of cyazofamid, compounds I and II, gramine (1), and design of N, N-dimethy-
larylsulfonamide derivatives (3).
there are only a few commercial nematicides left in use, and their repeated applica-
tions over the years have led to the development of resistance [3–6]. Therefore, to
prevent southern root-knot nematode and overcome the problems of resistance devel-
opment and environmental pollution, the research and development of efficacious
nematicidal agents has received much attention internationally in recent years [7–11].
To the best of our knowledge, sulfonamides (SAs) show a variety of biological
activities including nematicidal activity [12,13], anti-oomycete activity [1], anticon-
vulsant activity [14], antibacterial activity [15], antifungal activity [16], cardiac
myosin activator [17], and 5-HT receptor antagonists [18]. In addition, SAs are
6
widely used as pharmaceuticals in pesticide. For example, cyazofamid, whose struc-
tural formula is shown in Figure 1, containing N, N-dimethylsulfonamide group,
is an imidazole fungicide for use on food crops. As shown in Figure 1, Dupont
patents protect the nematicidal activity of compounds I and II in 2010 and 2012,
respectively [12,13]. Furthermore, compound I displayed the promising nematicidal
activity at a concentration of 250 mg/L in vivo. Especially, compound II exhibited
the best promising nematicidal activity, the mortality rate was higher than 50%
against the southern root-knot nematode, M. incongnita, in vivo at a concentration
of 50 mg/L.
Generally, there are two ways to synthesize N, N-dimethylarylsulfonamides. The first
kind is usually prepare the intermediate of SAs, and then the SAs reacts with iodome-
thane to form N, N-dimethylarylsulfonamides [17]. The second is the direct reaction of
sulfonyl chlorides with dimethylamine to prepare N, N-dimethylarylsulfonamides. Of
course, this process can also be assisted by ultrasonic irradiation [18,19]. It is well-known
that the traditional procedure for the synthesis of N, N-dimethylarylsulfonamides often
requires rigorous reaction conditions, and generally gives lower to moderate yields.
Interestingly, gramine (1, 3-(dimethylaminomethyl)indole; Figure 1), a commercial nat-
ural metabolite, can be intelligently and efficiently supplied with N, N-dimethylamino

JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
3
group, and then reacted with the corresponding sulfonyl chlorides to synthesize N, N-
dimethylarylsulfonamides.
Inspired by the above-mentioned interesting results, and the aim in our continuing
endeavor to find more active nematicidal hits [7,8], we herein designed and con-
trolled synthesis of N, N-dimethylarylsulfonamide derivatives (3, Figure 1), and first
report the results of the nematicidal activity of 15 N, N-dimethylarylsulfonamide
derivatives against M. incongnita in vitro, respectively. Additionally, their structur-
e–activity relationship (SAR) studies were also described.
2. Results and discussion
2.1. Chemistry
To find out the most compatible reaction conditions for synthesizing N, N-dimethy-
larylsulfonamide derivatives, a wide range of reaction parameters were tested by alter-
ing the base as well as the temperature and the solvent in a test reaction of gramine
(1) with benzenesulfonyl chloride (2a) (Scheme 1).
As outlined in Table 1, the reaction catalyzed by benzyltriethylaminiumꢀchloride
(
2
TEBA) was found to be sluggish (entries 1–3). When 1.0 mmol of 1 and 1.2 mmol of
ꢁ
a reacted at 25 C in the presence of 1.8 mmol of sodium hydroxide (NaOH) in a
dry dichloromethane (CH Cl ) solution, N, N-dimethylphenylsulfonamide (3a) was
2
2
ꢁ
ꢁ
not obtained (entry 1). When the temperature was lowered to 0 C or –15 C, 3a was
obtained in a trace or 29% yields even if the reaction time was prolonged to 24 h,
respectively (entries 1 and 2). To our delight, this process proves that the reaction we
originally designed can be achieved. Subsequently, the effect of different bases, tem-
peratures, and solvents to the yield were also investigated. When the molar ratio
ꢁ
between 2a and 1 was 2, the reaction was stirred at 25 C for 24 h in the presence of
3
.0 mmol of potassium carbonate (K CO ) in different solvents, the corresponding
2 3
yields of 3a were 0%, trace, and 63%, respectively (entries 4–6). It was preliminarily
proved that the different solvents had a greater influence on the yield of 3a, and the
solvent acetonitrile (CH CN) (entry 6) was found to greatly enhance the reaction
3
rate. Meanwhile, when 1.0 mmol of 1 and 2.0 mmol of 2a reacted at reflux for 24 h in
the presence of 4.5 mmol of triethylamine (Et N) in different solvents, the corre-
3
sponding yields of 3a were 32%, 51%, and 78%, respectively (entries 7–9). It was fur-
ther proved that the base and the solvent were the two main factors affecting the
yield of 3a. Subsequently, the effect of molar ratio between 1, 2a, and base to the
yield of 3a was also investigated (entries 10–12). When 1.0 mmol of 1 and 1.2 mmol
Scheme 1. Model reaction.

4
G.-Q. CHEN ET AL.
Table 1. Optimization of the reaction conditions.
Amount of (mmol)
ꢁ
Entry
1
2a
Base (mmol)
T ( C)
t (h)
Solvent
Yield of 3a (%)
a
1
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.2
1.2
1.2
2.0
2.0
2.0
2.0
2.0
2.0
1.2
1.2
1.5
NaOH (1.8)
NaOH (1.8)
NaOH (1.8)
25
0
24
24
24
24
24
24
24
24
24
24
24
24
CH
2
CH
2
CH
2
CH
3
CH
2
CH
3
CH
3
CH
2
CH
3
CH
3
CH
3
CH
3
Cl
Cl
Cl
2
2
2
0
a
2
Trace
29
0
Trace
63
32
51
78
75
a
3
–15
25
25
25
56
40
80
25
25
25
4
5
6
7
8
9
K
K
K
2
CO
2
CO
2
CO
3
3
3
(3.0)
(3.0)
(3.0)
COCH
Cl
3
2
CN
COCH
Et
Et
Et
Et
Et
Et
3
N (4.5)
3
N (4.5)
3
N (4.5)
3
N (3.0)
3
N (1.5)
3
N (1.5)
3
Cl
2
CN
CN
CN
CN
1
1
1
a
0
1
2
73
79
Catalyzed by TEBA (0.1 mmol).
ꢁ
of 2a reacted at 25 C for 24 h in the presence of 3.0 mmol of Et N in a dry CH CN
3
3
solution, 3a was obtained in a 75% yield (entry 10). When the amount of Et N was
3
reduced by half, 3a was obtained in a 73% yield (entry 11). When 1.0 mmol of 1 and
ꢁ
1
.5 mmol of 2a reacted at 25 C for 24 h in the presence of 1.5 mmol of Et N in a dry
3
CH CN solution, 3a was obtained in a 79% yield (entry 12). Based on the amount of
3
2
a, base, temperatures, and solvents screened, evidently, the optimized reaction condi-
ꢁ
tion was the reaction of 1.0 mmol of 1 with 1.5 mmol of 2a at 25 C for 24 h in the
presence of 1.5 mmol of Et N in a dry CH CN solution.
3
3
Based upon the above findings, subsequently, a wide range of arylsulfonyl chlorides
(
2, R ¼ (p-Me)Ph, (p-OMe)Ph, (p-tert-butyl)Ph, (2,4,6-trimethyl)Ph, (2,4,6-
triisopropyl)Ph, (p-F)Ph, (p-Br)Ph, (o-NO )Ph, (m-NO )Ph, (p-NO )Ph, (p-Cl, m-
2
2
2
NO )Ph, 2-thienyl, 1-naphthyl, or 8-quinolyl), and gramine (1) were investigated to
2
explore the scope of the reaction. As outlined in Table 2, N, N-dimethylarylsulfona-
mide derivatives (3b-o) were prepared in 76%–98% yields for 24 h. The steric and
electronic effects of substituents of 2a to the reaction were not very obvious.
Compared with the traditional methods, the main advantage of the present procedure
is milder conditions and better yields.
2
.2. Biological activities
Fifteen N, N-dimethylarylsulfonamide derivatives 3a-o and emamectin benzoate (used
as a positive control) were screened in vitro for their nematicidal activities against M.
incongnita. As shown in Table 3, among all of the title derivatives, compounds 3a, 3c,
3
k, and 3o exhibited potent nematicidal activity with median lethal concentration
(
LC ) values ranging from 0.22 to 0.26 mg/L. Most noteworthy, N, N-dimethyl-4-
5
0
methoxyphenylsulfonamide (3c) and N, N-dimethyl-8-quinolinesulfonamide (3o)
showed the best promising and pronounced nematicidal activity, with LC50 values of
0.2381 and 0.2259 mg/L, respectively.
Meanwhile, some interesting results of the SARs of 3a-o were also observed. (1)
Among N, N-dimethylarylsulfonamide derivatives (3a-d), compounds 3a and 3c
exhibited the most potent nematicidal activity, but when the 4-methyl or the 4-tert-
butyl group was introduced on the phenyl ring of 3a, the nematicidal activity of the

JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
5
Table 2. Synthesis of N, N-dimethylarylsulfonamide derivatives (3b-o).
a
Entry
1
Gramine (1)
Arylsulfonyl chlorides (2)
N,N-Dimethylarylsulfonamides (3)
Yield (%)
1
2b
3b
88
2
3
4
1
1
1
2c
2d
2e
3c
3d
3e
98
86
89
5
1
2f
3f
76
6
7
8
1
1
1
2g
2h
2i
3g
3h
3i
82
89
83
9
1
2j
3j
96
1
1
0
1
1
1
2k
2l
3k
3l
86
84
1
1
2
3
1
1
2m
2n
3m
3n
87
90
1
4
1
2o
3o
82
a
Isolated yields.

6
G.-Q. CHEN ET AL.
Table 3. Nematicidal activity of N, N-dimethylarylsulfonamide derivatives 3a-o against
M. incongnita.
Compounds
Toxicity regression equation
Correlation coefficient
LC50 (mg/L)
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
y ¼ 10.6256 þ 9.3290x
y ¼ 7.5499 þ 5.7516x
y ¼ 10.3300 þ 8.5530x
y ¼ 7.3212 þ 4.5467x
y ¼ 7.2335 þ 4.8446x
y ¼ 7.2476 þ 4.7251x
y ¼ 7.5218 þ 4.7958x
y ¼ 7.8832 þ 5.2788x
y ¼ 7.4962 þ 4.8661x
y ¼ 8.9788 þ 7.0711x
y ¼ 10.1810 þ 8.8113x
y ¼ 6.5731 þ 3.4350x
y ¼ 7.6271 þ 4.7300x
y ¼ 7.6170 þ 4.8484x
y ¼ 9.9566 þ 7.6712x
y ¼ 7.0620 þ 2.0687x
0.9961
0.9968
0.9861
0.9805
0.9824
0.9959
0.9970
0.9967
0.9813
0.9827
0.9915
0.9777
0.9946
0.9841
0.9861
0.9750
0.2494
0.3603
0.2381
0.3087
0.3459
0.3344
0.2980
0.2843
0.3069
0.2737
0.2582
0.3484
0.2783
0.2886
0.2259
0.1008
Emamectin benzoate
corresponding compounds were reduced sharply (3a vs. 3b and 3d). Interestingly,
when the 4-methoxy group was introduced on the phenyl ring of 3a, the nematicidal
activity of the corresponding compound was enhanced (3a vs. 3c). The LC50 values
of 3a-d against M. incongnita were 0.2494, 0.3603, 0.2381, and 0.3087 mg/L, respect-
ively. (2) When R ¼ 2,4,6-trimethylphenyl or R ¼ 2,4,6-triisopropylphenyl, the nemati-
cidal activity was decreased dramatically compared with 3a (3a vs. 3e and 3f). (3) N,
N-Dimethylphenylsulfonamide (3a) displayed potent nematicidal activity with LC50
value of 0.2494 mg/L, but when the chloro or the bromo atom was introduced on the
phenyl ring of 3a, the nematicidal activity of the corresponding compounds was
decreased significantly (3a vs. 3g and 3 h). (4) We found that the R ¼ nitrophenylsul-
fonyl, and the nitro group at different positions of the benzene ring, could lead to
derivatives with different nematicidal activity (3k vs. 3j and 3i). For example, the
LC50 values of 3i-k against M. incongnita were 0.3069, 0.2737, and 0.2582 mg/L,
respectively. (5) It is interesting that the R ¼ 4-chloro-3-nitrophenylsulfonyl as a two-
electron-withdrawing substituent (such as NO and Cl) could result in weaker compound
2
3l relative to those containing phenylsulfonyl as a one-electron-withdrawing substituent
(e.g. 3g-k, the LC50 values ranging from 0.2582 to 0.3069 mg/L). (6) The introduction of
the sulfonyl containing heterocyclic ring moieties can significantly improve the nemati-
cidal activity. As compared to 2-thiophenesulfonyl and 1-naphthalensulyonyl derivatives,
8-quinolinesulfonyl derivative displayed the best promising and pronounced nematicidal
activity (3m and 3n vs. 3o). For example, the LC50 values of 3m-o against M. incongnita
were 0.2783, 0.2886, and 0.2259 mg/L, respectively.
3. Experimental
3.1. General experimental procedures
Melting points were taken on a X-6 microscopic melting point apparatus (Beijing
Tech instrument Co., Ltd., Beijing, China) and are uncorrected. Nuclear magnetic res-
onance (NMR) spectra were recorded on a Bruker Avance DMX 400 MHz instrument
1
(
Bruker Daltonik, Bremen, Germany) in CDCl3 ( H at 400 MHz) using TMS

JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
7
(
(
tetramethylsilane) as the internal standard. Electrospray ion trap mass spectrometry
ESI-TRAP-MS) was carried out with a Bruker ESI-TRAP Esquire 6000 plus mass
spectrometry instrument (Bruker, Germany). Gramine and arylsulfonyl chloride were
purchased from Aladdin Chemistry Co., Ltd. (Shanghai, China). Ethyl acetate,
CH Cl , and petroleum ether were purchased from Beichen Fangzheng Reagent
2
2
Factory (Tianjin, China). Analytical thin-layer chromatography (TLC) was performed
with silica gel plate using silica gel 60 GF254 (Qingdao Haiyang Chemical Co., Ltd.,
Shandong, China). Silica gel column chromatography was performed with silica gel
200–300 mesh (Qingdao Haiyang Chemical Co., Ltd., Shandong, China).
3
.2. Preparation of N, N-dimethylarylsulfonamide derivatives (3a-o)
To a solution of gramine (1, 1.0 mmol) and arylsulfonyl chloride (2, 1.5 mmol) in dry
ꢁ
CH CN (10 ml) at 25 C, a solution of Et N (1.5 mmol) in dry CH CN (5 ml) was added
3
3
3
drop wise for 10 min [20–24]. After reaction for 24 h, the reaction solution was concen-
trated under reduced pressure to give crude product. The crude product was dissolved
in CH Cl (15 ml) and diluted with water (15 ml) and extracted with CH Cl (30 ml ꢂ
2
2
2
2
3). Subsequently, the combined organic phase was washed by saturated aq. brine
(
30 ml), dried over anhydrous Na SO , concentrated in vacuo, and purified by silica gel
2 4
column chromatography to obtain the target compounds in 76%–98% yields. The data
for 3a-o are shown as follows.
3
.2.1. Data for N, N-dimethylphenylsulfonamide (3a)
1
Yield ¼ 79%, Yellow oily liquid. H NMR (400 MHz, CDCl ) d: 7.77–7.80 (m, 2 H),
3
þ
7
.53–7.63 (m, 3 H), 2.71 (s, 6 H). HRESIMS: m/z 186.0585 [M þ H] (calcd for
C H NO S, 186.0583).
8
12
2
3
.2.2. Data for N, N-dimethyl-4-methylphenylsulfonamide (3 b)
ꢁ
1
Yield ¼ 88%, Pale yellow solid, m.p. 79–80 C. H NMR (400 MHz, CDCl ) d: 7.67
3
(
d, J ¼ 8.0 Hz, 2 H), 7.34 (d, J ¼ 8.0 Hz, 2 H), 2.69 (s, 6 H), 2.44 (s, 3 H). HRESIMS: m/
þ
z 200.0745 [M þ H] (calcd for C H NO S, 200.0740).
9
14
2
3
.2.3. Data for N, N-dimethyl-4-methoxyphenylsulfonamide (3c)
ꢁ
1
Yield ¼ 98%, Brown solid, m.p. 73–74 C. H NMR (400 MHz, CDCl ) d: 7.70–7.73
3
(
[
m, 2 H), 6.99–7.03 (m, 2 H), 3.88 (s, 3 H), 2.68 (s, 6 H). HRESIMS: m/z 216.0690
M þ H] (calcd for C H NO S, 216.0689).
þ
9
14
3
3
.2.4. Data for N, N-dimethyl-4-tert-butylphenylsulfonamide (3d)
ꢁ
1
Yield ¼ 86%, White solid, m.p. 118–119 C. H NMR (400 MHz, CDCl ) d: 7.68–7.71
3
(
[
m, 2 H), 7.52–7.56 (m, 2 H), 2.71 (s, 6 H), 1.35 (s, 9 H). HRESIMS: m/z 242.1211
M þ H] (calcd for C H NO S, 242.1209).
þ
1
2
20
2

8
G.-Q. CHEN ET AL.
3
.2.5. Data for N, N-dimethyl-2,4,6-trimethylsulfonamide (3e)
1
Yield ¼ 89%, Yellow oily liquid. H NMR (400 MHz, CDCl ) d: 6.94–6.95 (m, 2 H),
3
þ
2
.73 (s, 6 H), 2.61 (s, 6 H), 2.30 (s, 3 H). HRESIMS: m/z 228.1055 [M þ H] (calcd for
C H NO S, 228.1053).
1
1
18
2
3
.2.6. Data for N, N-dimethyl-2,4,6-triisopropylsulfonamide (3f)
ꢁ
1
Yield ¼ 76%, Pale yellow solid, m.p. 122–123 C. H NMR (400 MHz, CDCl ) d: 7.16
3
(s, 2 H), 4.14–4.20 (m, 2 H), 2.86–2.93 (m, 1 H), 2.75 (s, 6 H), 1.23–1.26 (m, 18 H).
þ
HRESIMS: m/z 312.1995 [M þ H] (calcd for C H NO S, 312.1992).
17
30
2
3
.2.7. Data for N, N-dimethyl-4-fluorophenylsulfonamide (3 g)
ꢁ
1
Yield ¼ 82%, Brown solid, m.p. 75–76 C. H NMR (400 MHz, CDCl ) d: 7.77–7.82
3
þ
(
m, 2 H), 7.20–7.27 (m, 2 H), 2.71 (s, 6 H). HRESIMS: m/z 204.0490 [M þ H] (calcd
for C H FNO S, 204.0489).
8
11
2
3
.2.8. Data for N, N-dimethyl-4-bromophenylsulfonamide (3 h)
ꢁ
1
Yield ¼ 89%, White solid, m.p. 91–92 C. H NMR (400 MHz, CDCl ) d: 7.67–7.70
3
þ
(
m, 2 H), 7.62–7.65 (m, 2 H), 2.71 (s, 6 H). HRESIMS: m/z 263.9693 [M þ H] (calcd
for C H BrNO S, 263.9688).
8
11
2
3
.2.9. Data for N, N-dimethyl-2-nitrophenylsulfonamide (3i)
1
Yield ¼ 83%, Yellow oily liquid. H NMR (400 MHz, CDCl ) d: 7.94–7.99 (m, 1 H),
3
7.67–7.74 (m, 2 H), 7.60–7.63 (m, 1 H), 2.91 (s, 6 H). HRESIMS: m/z 231.0435
þ
[
M þ H] (calcd for C H N O S, 231.0434).
8
11 2 4
3
.2.10. Data for N, N-dimethyl-3-nitrophenylsulfonamide (3j)
ꢁ
1
Yield ¼ 96%, Pale yellow solid, m.p. 121–122 C. H NMR (400 MHz, CDCl ) d: 8.62
3
(
(
t, J ¼ 2.0 Hz, 1 H), 8.46–8.48 (m, 1 H), 8.10–8.13 (m, 1 H), 7.77–7.81 (m, 1 H), 2.79
þ
s, 6 H). HRESIMS: m/z 231.0431 [M þ H] (calcd for C H N O S, 231.0434).
8
11 2 4
3
.2.11. Data for N, N-dimethyl-4-nitrophenylsulfonamide (3k)
ꢁ
1
Yield ¼ 86%, Pale yellow solid, m.p. 175–176 C. H NMR (400 MHz, CDCl ) d:
3
8.38–8.42 (m, 2 H), 7.96–7.99 (m, 2 H), 2.78 (s, 6 H). HRESIMS: m/z 231.0437
þ
[
M þ H] (calcd for C H N O S, 231.0434).
8
11 2 4
3
.2.12. Data for N, N-dimethyl-4-chloro-3-nitrophenylsulfonamide (3 l)
ꢁ
1
Yield ¼ 84%, Violet solid, m.p. 102–103 C. H NMR (400 MHz, CDCl ) d: 8.25 (d,
3
J ¼ 2.0 Hz, 1 H), 7.92 (dd, J ¼ 8.4 Hz, 2.0 Hz, 1 H), 7.77 (d, J ¼ 8.4 Hz, 1 H), 2.80 (s,
þ
6
H). HRESIMS: m/z 265.0048 [M þ H] (calcd for C H ClN O S, 265.0044).
8
10
2 4
3
.2.13. Data for N, N-dimethyl-2-thiophenesulfonamide (3 m)
ꢁ
1
Yield ¼ 87%, Brown solid, m.p. 67–68 C. H NMR (400 MHz, CDCl ) d: 7.63 (dd,
3
J¼ 5.2 Hz, 1.2 Hz, 1 H), 7.56 (dd, J¼ 3.6Hz, 1.2 Hz, 1H), 7.17 (dd, J¼ 5.2 Hz, 4.0 Hz,
1
H), 2.75 (s, 6 H). HRESIMS: m/z 192.0148 [M þ H]þ (calcd for
C H NO S , 192.0147).
6
10
2 2

JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
9
3
.2.14. Data for N, N-dimethyl-1-naphthalenesulfonamide (3n)
1
Yield ¼ 90%, Yellow oily liquid. H NMR (400 MHz, CDCl ) d: 8.76–8.79 (m, 1 H), 8.21
3
(
2
dd, J¼ 7.2Hz, 1.2Hz, 1H), 8.06–8.09 (m, 1 H), 7.92–7.94 (m, 1 H), 7.53–7.67 (m, 3 H),
þ
.82 (s, 6H). HRESIMS: m/z 236.0745 [M þ H] (calcd for C H NO S, 236.0740).
12
14
2
3
.2.15. Data for N, N-dimethyl-8-quinolinesulfonamide (3o)
ꢁ
1
Yield ¼ 82%, Pale yellow solid, m.p. 130–131 C. H NMR (400 MHz, CDCl ) d:
3
9
.08–9.10 (m, 1 H), 8.47–8.50 (m, 1 H), 8.26 (dd, J ¼ 8.0 Hz, 1.6 Hz, 1 H), 8.05 (dd,
J ¼ 8.0 Hz, 1.2 Hz, 1 H), 7.61–7.65(m, 1 H), 7.54 (q, J ¼ 4.4 Hz, 1 H), 2.99 (s, 6 H).
þ
HRESIMS: m/z 237.0689 [M þ H] (calcd for C H N O S, 237.0692).
11
13 2 2
3
.3. Nematicidal activity of compounds 3a-o against M. incongnita
Fifteen N, N-dimethylarylsulfonamide derivatives (3a-o) were screened in vitro for their
nematicidal activity against M. incongnita. The ranges of compounds 3a-o and emamec-
tin benzoate (used as a positive control) concentrations for the assays were defined in
preliminary experiments. Dimethyl sulfoxide solution of compounds 3a-o and emamec-
tin benzoate, and the final concentrations of active ingredients (a.i.) in medium were the
following: for compounds 3a-o 0.20, 0.25, 0.30, 0.35, and 0.40 mg/L, for emamectin
benzoate 0.050, 0.075, 0.100, 0.125, and 0.150 mg/L. Then 50 sterilized nematodes
(
second-stage juveniles (J ) of M. incongnita) were transferred to a 60-mm-diameter
2
watch-glass with 2 ml of the above solutions, and placed the watch-glass in Petri dishes
ꢁ
and kept in an incubator at 25 C for 12 h. The blank control group was prepared in
the same way but lacked the tested compound. Three replicates in each trial were made
and the independent experiment was repeated three times. The activities of five concen-
trations of the tested compounds were monitored under a microscope by recording the
death rate of the tested nematodes. Nematodes that did not move when prodded with a
needle were considered to be dead. The method for determining nematicidal activity
was based on as described in our previous article [25]. The LC50 values of compounds
3a-o and emamectin benzoate were calculated using the probit method.
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
This work was financially supported by the National Natural Science Foundation of China
(grant no. U1604105) and the Natural Science Foundation of Henan Province (grant no.
1
82300410043, 182300410016, and 152300410082).
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