Construction and Characterization of 3,7-Dichloro-N-(2,6-Diethylphenyl)-N-(2-Propoxyethyl)Quinolone-8-Carboxamide: A Potential Novel Pesticide Compound

Article abstract of DOI:10.1007/s10593-021-02866-x

[Figure not available: see fulltext.] A novel compound, 3,7-dichloro-N-(2,6-diethylphenyl)-N-(2-propoxyethyl)quinoline-8-carboxamide was synthesized by splicing together a chloro-substituted quinoline moiety found in quinclorac (a selective herbicide) and a substituted amide moiety found in pretilachlor (another selective herbicide) using the active substructure splicing method. The chemical structure of this compound was characterized by ¹H, ¹³C NMR, FTIR, high-resolution mass spectra and X-ray diffraction analysis. Pesticide potency (herbicidal and fungicidal activity) of this compound was evaluated. This compound displayed excellent control efficiency against Echinochloa crusgalli and also showed good fungicidal in vitro activity against Phytophthora capsici, Phytophthora sojae, and Phytophthora infestans.

Full text of DOI:10.1007/s10593-021-02866-x

DOI 10.1007/s10593-021-02866-x
Chemistry of Heterocyclic Compounds 2021, 57(1), 49–54
Construction and characterization of 3,7-dichloro-
N-(2,6-diethylphenyl)-N-(2-propoxyethyl)quinolone-8-carboxamide:
a potential novel pesticide compound
Xi-Le Deng1, Chun-Hui Zhu2, Xiao-Mao Zhou1, Lian-Yang Bai1*
1 Hunan Provincial Key Laboratory for Biology and Control of Weeds,
Hunan Agricultural Biotechnology Research Institute,
Hunan Academy of Agricultural Sciences,
2 Yuanda Road, Changsha 410125, China; е-mail: dengxile@hunaas.cn
2 Institute of Plant Protection, Hunan Academy of Agricultural Science,
2 Yuanda Road, Changsha 410125, China; е-mail: zhuchunhuizhb@hunaas.cn
Published in Khimiya Geterotsiklicheskikh Soedinenii,
Submitted March 19, 2020
2021, 57(1), 49–54
Accepted after revision June 10, 2020
A novel compound, 3,7-dichloro-N-(2,6-diethylphenyl)-N-(2-propoxyethyl)quinoline-8-carboxamide was synthesized by splicing
together a chloro-substituted quinoline moiety found in quinclorac (a selective herbicide) and a substituted amide moiety found in
pretilachlor (another selective herbicide) using the active substructure splicing method. The chemical structure of this compound was
1
characterized by H, 13C NMR, FTIR, high-resolution mass spectra and X-ray diffraction analysis. Pesticide potency (herbicidal and
fungicidal activity) of this compound was evaluated. This compound displayed excellent control efficiency against Echinochloa crus-
galli and also showed good fungicidal in vitro activity against Phytophthora capsici, Phytophthora sojae, and Phytophthora infestans.
Keywords: pretilachlor, quinclorac, active substructure splicing, fungicidal activity, herbicide activity.
Infesting weeds are a major global challenge, because
crop–weed competition can adversely impact production of
globally important agricultural crops (e.g., rice (Oryza
sativa), soybean (Glycine max), and wheat (Triticum
aestivum)).1–3 Currently, weeds are commonly controlled
via herbicide application, which often presents an efficient
and efficacious method to reduce unwanted crop weed
populations.4–8 However, due to the overuse of herbicidal
products, weed resistance has emerged, leading to a gradual
decrease in product efficacy and subsequent need to
increase herbicide usage.9–13 Therefore, it is important to
identify and try new herbicides with high biological
activity.
Quinclorac (3,4-dichloro-8-quinolinecarboxylic acid,
CAS no. 84087-01-4) (Scheme 1) is a persistent quinoline
herbicide first discovered in the 1980s by BASF.14
Quinclorac acts a lipase inhibitor and contains a core
chemical structure made up of a chloro-substituted
quinoline group and a carboxyl moiety.15 As a highly
efficient and selective auxin-type herbicide, quinclorac is
typically applied to control Echinochloa crus-galli and
other common weeds (e.g., Monochoria vaginalis,
Digitaria sanguinalis, Setaria viridis, Sesbania exaltata,
and Oenanthe javanica),16–20 although prolonged overuse
of this product has led to the emergence of resistance in
Echinochloa crus-galli.21 Quinclorac still represents the
primary herbicide product recommended for use on
Echinochloa crus-galli around rice paddies, due to its
highly efficient weed control and low phototoxicity to rice
plants.22,23
Pretilachlor (Scheme 1) (2-chloro-N-(2,6-diethylphenyl)-
N-(2-propoxyethyl)acetamide, CAS no. 51218-49-6) is a
chloroacetanilide herbicide, first identified in 1970s by
Ciba-Geigy A.-G.24 The core chemical structure of this
product is primarily made up of diethyl-substituted phenyl
and chloroacetanilide moieties. Pretilachlor is a broad-
spectrum herbicide commonly applied to control various
plant pests, such as Echinochloa crus-galli and Mono-
0009-3122/21/57(1)-0049©2021 Springer Science+Business Media, LLC
49

Chemistry of Heterocyclic Compounds 2021, 57(1), 49–54
Scheme 1
from separate pesticide products can be used in novel
pesticide designs, and also highlights how herbicide
structures can be applied to develop and screen potential
novel fungicide products.
Methodology used in the synthesis of compound 1 is
shown in Scheme 2. Using 2,6-diethylaniline (2) as the
starting material, amide 3 was obtained via condensation
with propoxyacetyl chloride in 61% yield. Then, secondary
amine 4 was produced by reducing amide 3 with LiAlH4 as
a reduction reagent40 in 90% yield. Acylchlorination41 of
quinclorac (5) then allowed us to afford 3,7-dichloro-
quinoline-8-carbonyl chloride 6. Finally, chloride 6 was
amidated using imine 4 to obtain the target compound 1 in
67% yield.
The chemical structure of compound 1 was characte-
1
choria vaginalis.25,26 Pretilachlor is often used as a
selective pre- and post-emergence herbicide in rice crop
protection, inhibiting the influx of weeds throughout plant
growth.27,28 To date, the primary mechanisms of the
herbicide action of pretilachlor are still not absolutely clear.
However, it was found that interferences in protein and
carbohydrate synthesis were observed in rice and broad
bean (Vicia faba) treated by pretilachlor.29,30 Although this
herbicide can decrease biomass production in treated rice
and interfere with the abilities of rice plants to assimilate
nutrients, it can be safely used on paddy fields if used
alongside a herbicide safener (fenclorim) to reduce the
phytotoxicity.31–33
Active substructure splicing is one of the most common
methods used for pesticide design.34–37 Hence, the
compound of interest in this study, 3,7-dichloro-N-(2,6-
diethylphenyl)-N-(2-propoxyethyl)quinoline-8-carboxamide
(1), was synthesized using this technique (Scheme 1). We
aimed to create a highly efficient pesticide compound by
combining chemical moieties from the herbicides
quinclorac and pretilachlor: a chloro-substituted quinoline
group and N-alkylarylamine, respectively, joined by an
amide bond.
rized using H and 13C NMR, FTIR, and high-resolution
1
mass spectroscopy. The H NMR spectra of compound 1
clearly showed the signals of quinoline protons appearing
as four doublets in the chemical shift range of 7.63–8.87 ppm,
and the protons of diethyl-substituted phenyl ring were
observed as a multiplet at 7.23–7.28 ppm and a triplet at
1
7.33 ppm. Moreover, H NMR signals of methyl groups
were observed as triplets at 0.71, 1.34, and 1.39 ppm and
those of methylene groups – as several multiplets in the
range of 1.32–3.58 ppm. Meanwhile, the 13C NMR
spectrum, which also matched the proposed structure
showed resonances of quinoline and phenyl rings at 126.9–
150.6 ppm in the aromatic region, and the resonances of the
alkyl group at 10.4–72.8 ppm in unsubstituted and sub-
stituted aliphatic regions. Notably, a singlet at 166.3 ppm
corresponding to the carbonyl carbon atom was found in its
characteristic region. Finally, the FTIR and HRMS data
well matched with the expected values for the calculated
brutto formula.
Compound 1 crystallized in the P21/c space group of the
monoclinical crystal system. The molecular structure is
visualized in Figure 1, and selected molecular structure
parameters, including bond lengths and bond angles, are
listed in Table S1 of the Supplementary information file.
The view of the crystal packing along the b crystallo-
graphic axis is shown in Figure S1 of the Supplementary
information file.
The herbicidal activity of compound 1 was evaluated
under greenhouse conditions. In addition, as this compound
contained both a quinoline moiety and an amide group,
which were also found in commercial fungicides, such as
ethoxyquin and fluopicolide, and might possess fungicidal
activity,38,39 this latter activity of compound 1 was tested as
well. This research provides an in depth characterization of
a potentially novel herbicide, emphasizes how moieties
The main bond lengths and bond angles of the quinoline
ring and phenyl ring in the crystal structure of compound 1
are similar to those reported in the literature for compounds
with similar structural motifs.42–46 The molecule of
Scheme 2
50

Chemistry of Heterocyclic Compounds 2021, 57(1), 49–54
Table 1. Interatomic distances (d) and bond angles (<)
of hydrogen bonding interactions in the crystal structure
of compound 1
d(D–H),
d(H···A), d(D···A),
<(DHA),
deg
D–H···A*
Å
Å
Å
C(22)–H(22)···O(1)
C(19)–H(19)···O(2)
C(19)–H(19)···N(2)
0.97
0.97
0.97
2.58
2.50
2.51
3.519(5)
3.385(5)
2.942(6)
162
152
187
* Symmetry transformations used to generate the equivalent atoms:
x, y, –1 + z.
Table 2. Herbicidal activity of compound 1
toward Zinnia elegans, Abutilon theophrasti, Setaria glauca,
and Echinochloa crus-galli after 15-day treatment
under greenhouse conditions*
Weed destruction, %
Com-
Dose,
pounds g a.i./hm2
Z.
A.
S.
E.
elegans theophrasti
glauca
crus-galli
125
NT**
NT
NT
NT
NT
45.7 ± 4.0
1
250
500
125
250
500
45.6 ± 3.7 75.9 ± 2.6
Figure 1. Molecular structure of compound 1 with atoms repre-
sented as thermal vibration ellipsoids of 50% probability.
30.2 ± 6.0 40.8 ± 5.6
100
NT
NT
96.5 ± 1.8
35.9 ± 3.6
65.5 ± 1.9
NT
NT
NT
NT
compound 1 is comprised of four distinct moieties (a
disubstituted phenyl ring, a chlorine-substituted quinoline
ring, an amide moiety, and a 2-propoxyethyl moiety). The
bond lengths of the amide moiety C(1)–C(10), C(10)–N(2),
and N(2)–C(11) were found to have values 1.506(6), 1.346(5),
and 1.455(5) Å, respectively. The valence angles of
C(1)–C(10)–N(2) and C(10)–N(2)–C(11) were 119.0(3)°
and 119.4(3)°. The bond length of C(10)–O(1) in the amide
group was 1.241(5) Å, which is similar to what is generally
reported for C=O bond, indicating that C(10)–O(1) has a fully
double bond character.36,42,47–49 The dihedral angle between
the mean planes of phenyl ring and quinoline ring is 8.294(1)°,
indicating the two rings are nearly coplanar in the
synthesized compound.
In the whole structure, each molecule with CH2 carbon
atoms, C(19) and C(22), was found to participate in
C–H···O hydrogen bonding interactions (symmetry code:
x, y, –1 + z) (Table 1), which ultimately formed a three-
dimensional network of molecules. The C···O distances
between H-bond donor (D) and acceptor (A) atoms were
3.519(5) Å for C(22)–H(22)···O(1). In addition, weak
intramolecular C–H···O and C–H···N hydrogen bonds also
helped to stabilize the crystal structure.
The herbicidal activity of compound 1 was evaluated in
an experimental greenhouse using four plant weeds: Zinnia
elegans, Abutilon theophrasti, Setaria glauca, and Echinochloa
crus-galli (Table 2). At 500 g a.i./hm2, compound 1
demonstrated control efficiencies of 30.2 and 40.8%
against Z. elegans and A. theophrasti, respectively. This was
significantly better than herbicidal potency of quinclorac
(5) (which demonstrated control efficiencies of 10.1 and
20.3%, respectively). At doses of 125 and 250 g a.i./hm2,
both compound 1 and quinclorac (5) were found to be
nontoxic to Z. elegans and A. theophrasti. Furthermore,
compound 1 was found to be more efficacious against
S. glauca (100%), than quinclorac (5) (60%) at 500 g a.i./hm2.
Also, compound 1 demonstrated higher herbicidal activity
Quinclorac
(5)
10.1 ± 3.7 20.3 ± 4.8 60.8 ± 6.1 90.7 ± 2.4
* The statistical analyses were carried out via the SPSS 22.0 software
package, and all the mean values within each column are significantly
different from each other at P < 0.05.
** NT – herbicidal activity was not tested.
against E. crus-galli (96.5%, 500 g a.i./hm2) than quinclorac
(5) (90.7%, 500 g a.i./hm2), which is specifically active
against E. crus-galli. Finally, we found that at decreased
concentrations compound
1 always displays higher
herbicidal activity than quinclorac (5) against E. crus-galli.
The result indicated that the combination of the chloro-
substituted quinoline group derived from quinclorac (5)
and the N-alkylarylamine moiety derived from pretilachlor
could enhance herbicide activity.
As compound 1 contains both a quinoline moiety and an
amide group that might be a core structure possessing
fungicidal activity, we hypothesized that this compound
might also have fungicidal activity. Therefore, its
fungicidal activity against four plant pathogens (Phyto-
phthora capsici, Phytophthora sojae, Peronophthora
litchii, and Phytophthora infestans) was tested in vitro
(Table 3). At 50 mg/l concentration, compared to the
fungicidal activity of cyazofamid (a commercial fungicide),
compound 1 was still found to demonstrate good fungicidal
activity against P. capsici, P. sojae, and P. infestans and
moderate fungicidal activity against P. litchii. To further
investigate the fungicidal activities of compound 1, the
EC50 values of compound 1 and cyazofamid toward
P. capsici, P. sojae, and P. infestans were compared
(Tables 4). Although compound 1 displayed relatively
weaker fungicidal activity than cyazofamid, it exhibited
potential fungicidal activities against P. capsici, P. sojae,
and P. infestans. What is more, the fungicidal activity of
compound 1 against P. capsici (EC50 0.8062 mg/l) is much
51

Chemistry of Heterocyclic Compounds 2021, 57(1), 49–54
tively) in CDCl3, internal standard TMS (1H) or solvent
signal (13C, δ 77.0 ppm). High-resolution ESI mass spectra
were recorded on an Agilent Technologies 6230 TOF LC/MS
system. The melting point was determined using a Hanon
MP100 automatic melting point apparatus with an open
capillary tube.
Methods for preparing 3,7-dichloro-N-(2,6-diethyl-
phenyl)-N-(2-propoxyethyl)quinoline-8-carboxamide (1)
are described in literature50–52 and used here with indicated
modifications. The commercially available 2,6-diethyl-
aniline, THF, and Et3N were used without further
purification.
Table 3. In vitro fungicidal activity of compound 1
compared to that of the fungicide cyazofamid, for the plant
pathogens Phytophthora capsici, Phytophthora sojae, Peronophthora
litchi, and Phytophthora infestans at 50 mg/l*
Inhibition rate, %
Compounds
P. capsici
92.7 ± 1.2
100
P. sojae
87.8 ± 0.7
100
P. litchii
53.5 ± 0.5
95
P. infestans
84.0 ± 2.0
100
1
Cyazofamid
* The statistical analyses were carried out via the SPSS 22.0 software
package, and all the mean values within each column are significantly
different from each other at P < 0.05.
N-(2,6-Diethylphenyl)-2-propoxyacetamide
(3).
Table 4. Median effective concentrations (EC50 values)
of compound 1 compared to cyazofamid for the plant pathogen
Phytophthora capsici, Phytophthora sojae, and Phytophthora
infestans characterized in in vitro bioassays
2,6-Diethylaniline (2) (0.75 g, 5.00 mmol) and Et3N
(0.76 g, 7.50 mmol, 1.04 ml) were dissolved in anhydrous
THF (20 ml), and then propoxyacetyl chloride (0.68 g,
5 mmol) in anhydrous THF (15 ml) was added. The
reaction mixture was stirred for 8 h at room temperature
until the starting material disappeared (as indicated by
TLC). The solvent was evaporated under reduced pressure
(20 mm Hg) at 40°C. The obtained residue was dissolved
in EtOAc (30 ml), washed with 10% brine (3×60 ml). The
organic layer was then separated from the aqueous layer,
and dried by anhydrous MgSO4. The solvent was removed
under reduced pressure (20 mm Hg) at 35°C. The residue
was further purified using silica gel (eluent petroleum ether –
EC50,
mg/l
95% confidence
interval
Compounds
y = a + bx*
Phytophthora capsici
0.6612–0.9831
0.8062
0.1495
y = 5.1061 + 1.1347x
y = 6.1342 + 1.3741x
1
Cyazofamid
0.1151–0.1941
Phytophthora sojae
1.1596–2.2081
1.6002
0.3258
y = 4.8128 + 0.9171x
y = 5.6285 + 1.2906x
1
Cyazofamid
0.2858–0.3716
1
EtOAc, 5:1). Yield 0.76 g (61%), white solid. H NMR
Phytophthora infestans
2.1278–3.1583
spectrum, δ, ppm (J, Hz): 1.02 (3H, t, J = 7.4,
OCH2CH2CH3); 1.23 (6H, t, J = 7.5, 2ArCH2CH3); 1.69–
1.77 (2H, m, OCH2CH2CH3,); 2.64 (4H, q, J = 7.4,
2ArCH2CH3); 3.62 (2H, t, J = 6.5, OCH2CH2CH3); 4.16
(2H, s, OCH2CO); 7.14 (2H, d, J = 7.6, H Ar); 7.26 (1H,
dd, J = 8.4, J = 6.7, H Ar); 10.0 (1H, s, NH). 13C NMR
spectrum, δ, ppm: 10.5; 14.4; 22.9; 24.9; 70.4; 73.6; 126.4;
128.0; 131.9; 141.4; 169.0 (C=O). Found, m/z: 205.1809
[M+H]+. C15H23NO2. Calculated, m/z: 205.1802.
2.5923
0.5847
y = 4.5151 + 1.1722x
y = 5.3055 + 1.3106x
1
Cyazofamid
0.4909–0.6964
* The equation to calculate EC50 values, where y – dependent variable;
a – longitudinal intercept; b – slope; x – independent variable.
better than that against P. sojae (EC50 1.6002 mg/l) and
P. infestans (EC50 2.5923 mg/l). These results indicated
that compound 1 can potentially be used to design novel
fungicides, and further study on structure–activity
relationship of compound 1 is underway.
2,6-Diethyl-N-(2-propoxyethyl)aniline (4).53 N-(2,6-Di-
ethylphenyl)-2-propoxyacetamide (3) (1.25 g, 5.00 mmol)
was dissolved in anhydrous THF (20 ml) under a nitrogen
atmosphere of 2 Mpa. The reaction mixture was then
cooled at 0°C in an ice water bath, and 2.50 M LiAlH4
solution in THF (4.55 g, 4.40 ml, 12 mmol) was added.
The reaction mixture was subsequently warmed to room
temperature and stirred for 8 h at room temperature until
the starting material disappeared (as indicated by TLC).
The mixture was quenched with H2O (10 ml), and the
solvent was evaporated under reduced pressure (20 mmHg) at
40°C. The residue was extracted with EtOAc (2×30 ml), and
the extract was washed with 10% brine (3×60 ml). The
organic layer was then dried over anhydrous MgSO4, and
the solvent was subsequently evaporated under reduced
pressure (20 mmHg) at 35°C. The crude material was then
purified by flash chromatography on silica gel (eluent
petroleum ether – EtOAc, 6:1). Yield 1.06 g (90%),
In this study, 3,7-dichloro-N-(2,6-diethylphenyl)-N-(2-prop-
oxyethyl)quinoline-8-carboxamide was synthesized by
combining a chloro-substituted quinoline group derived
from quinclorac with a substituted amide moiety derived
from pretilachlor using the active substructure splicing
method. The chemical structure of the synthesized
compound was subsequently characterized using standard
spectroscopic methods and X-ray crystallography. The
product displayed excellent control efficiency against the
weed plant E. crus-galli which was better than that of
quinclorac, as well as good fungicidal activity in vitro
against three fungal species (P. capsici, P. sojae, and
P. infestans). This research provides a foundation for the
design of a novel herbicide product, using chemical
moieties derived from known herbicides and highlights the
potential for use of herbicidal compounds in the synthesis
and screening of new fungicide products.
1
colorless liquid. H NMR spectrum, δ, ppm (J, Hz): 1.03
(3H, t, J = 7.4, OCH2CH2CH3); 1.23 (6H, t, J = 7.6,
2ArCH2CH3); 1.70–1.77 (2H, m, OCH2CH2CH3); 2.63
(4H, q, J = 7.5, 2ArCH2CH3); 3.35 (2H, t, J = 7.4, NCH2);
3.46 (2H, t, J = 6.5, OCH2CH2CH3); 3.64 (2H, t, J = 7.5,
OCH2); 7.16 (2H, d, J = 7.5, H Ar); 7.25 (1H, dd, J = 8.3,
J = 6.8, H Ar); 7.91 (1H, s, NH).
Experimental
The IR spectra were obtained on a PerkinElmer
1
Spectrum 100 FTIR spectrometer in KBr pellets. H and
13C NMR spectra were obtained on a Bruker Avance
AV-400-WB spectrometer (400 and 100 MHz, respec-
52

Chemistry of Heterocyclic Compounds 2021, 57(1), 49–54
3,7-Dichloroquinoline-8-carbonyl
chloride
(6).
individual weed species) before herbicide treatment. Active
ingredients (compound 1 and quinclorac (5)) were
suspended or emulsified in H2O and applied using a
tracked crop sprayer (Engineer Research Ltd., UK).
Z. elegans and A. theophrasti were used when in the 2 leaf
stage, while S. glauca and E. crus-galli were grown to 2–3 leaf
stages before the treatment. Compound 1 and quinclorac (5)
were applied at doses of 500, 250, and 125 g a.i./hm2.
Following the treatment, the weeds were naturally dried
and kept at 10–25 or 20–35°C (depending on the species)
in a greenhouse. The plants were gathered and their reactions
to the individual treatments were evaluated 15 days after
the treatment. Toxicological evaluations were based on a
percentage scale, where 100% was defined as no weed
emergence or the complete destruction of the above ground
parts and 0% was defined as no damage or normal weed
growth. Each experiment was replicated three times.
Fungicidal activity assay. The in vitro fungicidal
activity of compound 1 was tested using the mycelium
growth rate method.58–60 Plant pathogen species used were
P. capsici, P. sojae, P. litchii, and P. infestans. To prepare
10 mg/ml solution, compound 1 (10 mg) was weighed and
dissolved in DMSO (1 ml). This solution was then mixed
with boiling hot potato dextrose agar (PDA) (199 ml).
Medium containing compound 1 (used for initial screening)
in 50 mg/l concentration was poured into sterile Petri
dishes (diameter 9 cm). After all the dishes were cooled
down to 60–70°C, 0.5 cm diameter mycelia disks were
inoculated onto the center of the Petri dishes for 3–8 days
(representing the exposure period) and then incubated at
25°C. DMSO was used as the negative control. Hypha
diameter was measured using the cross bracketing method.
The commercial fungicide cyazofamid was used as the
positive control. Each experiment was replicated for three
times. The in vitro inhibition rate of compound 1 against
fungi was calculated as (C – T)/(C – 0.5)×100% where C
represents the average diameter of fungal hypha on
untreated PDA (in cm), and T represents the average
diameter of fungal hypha on PDA treated with the test
compound (in cm). The test concentrations used for calcu-
lating EC50 values were 10, 5, 2.5, 1.25, and 0.625 mg/l
respectively. The EC50 values were calculated using log-
probit analysis.
Quinclorac (5) (0.80 g, 3.31 mmol) was dissolved in SOCl2
(50 ml) and refluxed for 10 h (76°C). The reaction mixture
was distilled under reduced pressure to obtain crude
3,7-dichloroquinoline-8-carbonyl chloride (6) which was
subsequently used in the next step without further purification.
3,7-Dichloro-N-(2,6-diethylphenyl)-N-(2-propoxyethyl)-
quinoline-8-carboxamide (1). N-(2,6-Diethylphenyl)-2-prop-
oxyacetamide (4) (0.59 g, 2.50 mmol), dissolved in
anhydrous THF (15 ml), was added dropwise to a solution
of 3,7-dichloroquinoline-8-carbonyl chloride (6) (0.61 g,
2.50 mmol) and Et3N (0.76 g, 7.50 mmol, 1.04 ml) in THF
(15 ml). The reaction mixture was stirred for 8 h at room
temperature (25°C) until the reaction had completed as
monitored by TLC. The solvent was then evaporated, and
the residue was taken up in EtOAc (30 ml), washed with
10% aqueous HCl solution (2 × 50 ml), NaHCO3 solution
(2×50 ml, 1 M), and, finally, 10% brine (3×60 ml). The
organic layer was dried over anhydrous MgSO4. The
solvent was then evaporated under reduced pressure
(20 mmHg) at 40°C. The crude product was purified on
silica gel (eluent petroleum ether – EtOAc, 7:1). Yield 0.77 g
(67%), white solid, mp 293–294°C. IR spectrum, ν, cm–1:
1786 (C=O), 1589 (C=N), 1472 (C=N), 1308 (C–N), 1165,
1138 (C–O), 1097, 1064, 923, 893 (C–H), 806, 642, 481.
1H NMR spectrum, δ, ppm (J, Hz): 0.71 (3H, t, J = 7.4,
OCH2CH2CH3); 1.32–1.41 (2H, m, OCH2CH2CH3); 1.34
(3H, t, J = 7.4, ArCH2CH3); 1.39 (3H, t, J = 7.4,
ArCH2CH3); 2.72–2.81 (1H, m, ArCH2CH3); 2.84–2.93
(1H, m, ArCH2CH3); 2.97–3.09 (3H, m, NCH2,
ArCH2CH3); 3.20–3.26 (1H, m, NCH2); 3.28–3.36 (2H, m,
OCH2CH2CH3); 3.41–3.48 (1H, m, OCH2); 3.51–3.58 (1H,
m, OCH2); 7.23–7.28 (2H, m, H Ar); 7.33 (1H, t, J = 7.5,
H Ar); 7.63 (1H, d, J = 8.8, H quinoline); 7.75 (1H, d, J = 8.8,
H quinoline); 8.16 (1H, d, J = 2.4, H quinoline); 8.87 (1H,
d, J = 2.4, H quinoline). 13C NMR spectrum, δ, ppm: 10.4;
18.5; 18.9; 22.7; 50.3; 67.4; 72.8; 126.9; 128.0; 128.5;
128.7; 129.1; 129.4; 129.5; 132.2; 133.9; 135.4; 136.7;
136.8; 138.0; 143.8; 150.6; 166.3 (C=O). Found, m/z:
459.1610 [M+H]+. C25H28Cl2N2O2. Calculated, m/z: 459.1601.
X-ray structural investigation of compound 1. A color-
less single crystal of compound 1 was obtained by
recrystallization from a dilute EtOH solution. X-ray single
crystal structure data were collected using a Rigaku
SuperNova dual wavelength diffractometer, equipped with
an AtlasS2 CCD area detector; MoKα radiation (λ 1.54184 Å)
at 100.01(10) K. Data was processed using the SHELXL
program, the crystal structure was solved by the direct
method using Olex254 and ShelXT55 structure solution
programs and refined by the least squares method using the
Statistical analyses. All the statistical analyses were
carried out using the SPSS 22.0 software package (IBM,
NY, USA). Data were represented by the standard devia-
tions (values ± SD) and analyzed for statistical significance
by means of ordinary one-way analysis of variance, and
P < 0.05 was considered to indicate the statistically
significant difference.
ShelXL
refinement
package.56
The
complete
crystallographic information on compound 1 has been
deposited at the Cambridge Crystallographic Data Center
(deposit CCDC 1878381).
Supplementary information file containing 1H and
13C NMR and mass spectra as well as X-ray data of
compound 1 is available at the journal website at
http://link.springer.com/journal/10593.
Herbicidal activity assay.57 Four weed species were
used in the herbicide bioassays: Z. elegans, A. theophrasti,
S. glauca, and E. crus-galli. Weeds were grown in paper
flowerpots (diameter 7 cm) that contained loamy sand
(substrate: ~3.0% humus). The seeds of the test weeds were
sown separately, according to the species. The test weeds
were grown to heights of 3–15 cm (depending on
This work was performed with funding from National
Key Research Development Program of China (2018YFD
0201106), National Natural Science Foundation of China
(No. 31772182 and 31701803), and China Agriculture
Research System (CARS-16-E19).
53

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