Synthesis and Herbicidal Activity of α-(Substituted Phenoxybutyryloxy or Valeryloxy)alkylphosphonates and 2-(Substituted Phenoxybutyryloxy)alkyl-5,5-dimethyl-1,3,2-dioxaphosphinan-2-one

Article abstract of DOI:10.1021/acs.jafc.6b02032

On the basis of our work on the modification of alkylphosphonates 1, a series of α-(substituted phenoxybutyryloxy or valeryloxy)alkylphosphonates (4-5) and 2-(substituted phenoxybutyryloxy)alkyl-5,5-dimethyl-1,3,2-dioxaphosphinan-2-one (6) were designed and synthesized. The bioassay results indicated that 14 of title compounds 4 exhibited significant postemergence herbicidal activity against velvetleaf, common amaranth, and false daisy at 150 g ai/ha. Compounds 5 were inactive against all tested weeds. Compounds 6 exhibited moderate to good inhibitory effect against the tested dicotyledonous weeds. Structure-activity relationship (SAR) analyses showed that the length of the carbon chain as linking bridge had a great effect on the herbicidal activity. Broad-spectrum tests of compounds 4-1, 4-2, 4-9, 4-30, and 4-36 were carried out at 75 g ai/ha. Especially, 4-1 exhibited 100% inhibition activity against the tested dicotyledonous weeds, which was higher than that of glyphosate.

Full text of DOI:10.1021/acs.jafc.6b02032

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Article
Synthesis and Herbicidal Activity of #-(Substituted Phenoxybutyryloxy
or Valeryloxy)alkylphosphonates and 2-(Substituted
Phenoxybutyryloxy)alkyl-5,5-dimethyl-1,3,2-dioxaphosphinan-2-one
Wei Wang, Shasha Zhang, Yuan Zhou, Hao Peng, Hongwu He, and Xingtao Lu
J. Agric. Food Chem., Just Accepted Manuscript • DOI: 10.1021/acs.jafc.6b02032 • Publication Date (Web): 17 Aug 2016
Downloaded from http://pubs.acs.org on August 21, 2016
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Synthesis and Herbicidal Activity of αꢀ(Substituted Phenoxybutyryloxy or
Valeryloxy)alkylphosphonates and 2ꢀ(Substituted Phenoxybutyryloxy)alkylꢀ
5,5ꢀdimethylꢀ1,3,2ꢀdioxaphosphinanꢀ2ꢀone
Wei Wang†,‡, Shaꢀsha Zhang†, Yuan Zhou†, Hao Peng†,*, Hongꢀwu He†,*, Xingꢀtao Lu§
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†College of Chemistry, Central China Normal University; Key Laboratory of Pesticide &
Chemical Biology, Ministry of Education, 152 Luoyu Road, Wuhan, 430079, P. R. China.
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‡Xi’an Modern Chemistry Research Institute, Xi’an 710000, China
§Tai’an Academy of Agricultural Sciences, Tai’an 271000, China
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*Corresponding author: (Tel: +86ꢀ27ꢀ67867958; Fax: +86ꢀ27ꢀ67867960; Eꢀmail:
he1208@mail.ccnu.edu.cn; penghao@mail.ccnu.edu.cn)
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ABSTRACT: Based on our work on the modification of alkylphosphonates 1, a series of αꢀ
(substituted phenoxybutyryloxy or valeryloxy)alkylphosphonates (4ꢀ5) and 2ꢀ(substituted
phenoxybutyryloxy)alkylꢀ5,5ꢀdimethylꢀ1,3,2ꢀdioxaphosphinanꢀ2ꢀone (6) was designed and
synthesized. The bioassay results indicated that fourteen of title compounds 4 exhibited
significant postꢀemergence herbicidal activity against velvetleaf, common amaranth and false
daisy at 150 g ai/ha. Compounds 5 were inactive against all the tested weeds. Compounds 6
exhibited moderate to good inhibitory effect against the tested dicotyledonous weeds. Structureꢀ
activity relationship (SAR) analyses showed that the length of the carbon chain as linking bridge
had a great effect on the herbicidal activity. Broad spectrum test of compounds 4ꢀ1, 4ꢀ2, 4ꢀ9, 4ꢀ
30 and 4ꢀ36 were carried out at 75 g ai/ha. Especially, 4ꢀ1 exhibited 100% inhibition activity
against the tested dicotyledonous weeds, which was higher than that of glyphosate.
KEYWORDS: synthesis; herbicide; structureꢀactivity relationship; phosphonate; modification;
crop selectivity
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INTRODUCTION
Alkylphosphonate derivatives have attracted more and more interest due to their potential
biological activity, and they are intensely used in agricultural and pharmaceutical chemistry.1ꢀ5
For the purpose of developing novel herbicides against new targets, we have ever synthesized
series of alkylphosphonates 1 (Figure 1), and some of them displayed excellent herbicidal or
fungicidal activities.6 Among alkylphosphonates 1, clacyfos, as a selective postꢀemergence
herbicide, displayed outstanding herbicidal activity on the broadꢀleaved weeds.6 Based on the
structure of compounds 1, compounds 2 have been designed and synthesized by the introduction
of some heterocycles such as furanic and pyridinic groups into the R3 group of the general
structure 1. Among the compounds 2, compound HWS showed the most effective activity
against broadleaved weeds at 50 g ai/ha. Furthermore, compounds 3 have been designed and
synthesized by the introduction of a cyclophosphonate moiety into the phosphonate part of
structure 1. The compounds 3ꢀ2 and 3ꢀ3 showed high activity with an inhibition effect of 70−100
% at 75 g ai/ha against all the tested broadleaf weeds and against tested dicotyledons, such as
velvetleaf, leaf mustard, and false daisy, which indicated that they could be developed as a
selective postꢀemergence herbicides. 7
The structural skeleton of 1 was used as the lead compound. An acetoxy (CH2COO) group
served as the linker and connected the phosphonate and phenoxy moieties in 1. To explore the
relationship between the length of the linking bridge and the herbicidal activity, compounds 4
and 5, as shown in the Figure 1, were designed and synthesized by replacing the acetoxy group
with a butyryloxy group and a valeryloxy group, respectively. As a comparison, compounds 6
were designed by introducing a cyclophosphonate moiety into the phosphonate part of lead
compound 1. In this work, we report the syntheses and characterization of novel
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alkylphosphonates 4, 5 and 6, and they are evaluated for their herbicidal activities and safety to
some crops.
MATERIALS AND METHODS
Chemicals
Chemicals and reagents were obtained from commercial sources Sinopharm Chemical
Reagent Co., Ltd. (SCRC, Shanghai, China) and used as received. FTꢀIR spectra were measured
on a PerkinꢀElmer FTꢀIR spectrometer (PerkinElmer, Mass., USA). NMR spectra were obtained
using Varian XLꢀ400 (Varian, Calif., USA) or Varian XLꢀ600 (Varian, Calif., USA)
spectrometer using CDCl3 as solvents and TMS as an internal standard. Chemical shifts (δ) were
expressed in parts per million downfield from the internal standard. The mass spectra were
recorded using a Finnigen TRACE spectrometer (Applied Biosystems, Mass., USA) and
API2000LC/MS (Applied Biosystems, Mass., USA). Elemental analysis was carried out using a
Vario EL III elemental analyzer (Elementar, Hanau, Germany).
Synthesis Procedures
Synthesis of Compounds 8aꢀf.
Compounds 8aꢀf were prepared according to our earlier reported method with minor
modifications.8ꢀ12 To a solution of appropriate phosphite 7 (1.0 equiv) and aldehydes (1.0 equiv)
in chloroform (10 mL), triethylamine (0.5 equiv) was added at 0oC to afford compounds 8aꢀf.
Synthesis of Compounds 10 and 11aꢀg
The intermediate 10 was prepared according to procedures reported in the literature.13 The
intermediate 10 (4.0 mmol) was dissolved in thionyl chloride (3 mL). Then N,Nꢀ
dimethylformamide (5% mol) was added and the reaction mixture was allowed to heat at reflux
for 5ꢀ6 h. Thionyl chloride was removed under reduced pressure to afford light yellow oils 11aꢀg
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with yields of 85ꢀ90%.
Synthesis of Compounds 18aꢀb.
Following the procedure described for 8aꢀf, compounds 18aꢀb were obtained with yields of
60ꢀ90%. Compounds 18aꢀb have been reported in the literature.7
Synthesis of Compounds 16.
The intermediate 16 was prepared according to procedures reported in the literature. 14ꢀ15 The
substituted 3ꢀphenoxypropanol 12 was obtained from substituted phenol and 1ꢀchloroꢀ3ꢀ
hydroxypropane according to the methods given in the literature.8 To a stirred solution of
substituted 3ꢀphenoxypropanol 12 (1.0 equiv) and triethylamine (1.2 equiv) in dichloromethane
o
(DCM, 10mL), cooled to 0ꢀ5 C, methanesulfonyl chloride (1.2 equiv) in DCM (5 mL) was
added dropwise. The reaction mixture was allowed to heat at 30ꢀ35oC for 3ꢀ5 h. The solution was
filtered and the filtration was evaporated under reduced pressure to afford crude product 13, and
then, a solution of sodium ethoxide (1.0 equiv) in ethanol (10 mL) was added to the crude and
allowed to heat at reflux for 2 h. Then diethyl malonate (1.0 equiv) was added dropwise over 60
min period. The resulting mixture was refluxed for 5ꢀ8 h at 70ꢀ80 oC, and filtered, the filtration
was evaporated under reduced pressure to afford crude product 14 without further purification
(Figure 3). The intermediate 14 was added to aqueous NaOH (2M, 80 mL). The resulting
mixture was allowed to stir for 18 h at 30ꢀ35oC, and then acidified by 5% HCl. The acid 15 was
precipitated, filtered off, and subsequently washed with H2O, then dissolved into
dimethylformamide (10 mL) and refluxed for 8 h at 110ꢀ120 oC and cooled to 25ꢀ30oC. Then ice
water (30 mL) was added to the mixture, and the precipitate was filtered off. A colorless crystal
16 was obtained with a yield of 90ꢀ96% (Figure 3). 14ꢀ15
Synthesis of Compounds 17aꢀc.
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Following the procedure described for 11aꢀg, the substituted phenoxyvaleryloxy chlorides
17aꢀc were afforded as light yellow oils with yields of 71ꢀ84%.
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Synthesis of Compounds 4ꢀ1−4ꢀ42.
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To a solution of intermediate 8aꢀf (1.0 equiv) and triethylamine (1.1 equiv) in chloroform (20
o
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mL), cooled to 0ꢀ5 C, a solution of substituted phenoxybutanoyl chlorides 11aꢀg (1.1 equiv) in
o
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chloroform (15 mL) was added dropwise. The mixture was allowed to stir at 25ꢀ30 C for 3ꢀ5 h,
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and then at 40ꢀ45 oC for 1ꢀ2 h. The chloroform layer was washed with 5% HCl, saturated sodium
bicarbonate, and brine, dried, and concentrated. The residue was purified by flash
chromatography (2:1, petroleum ether/acetone) to afford title compounds 4ꢀ1−4ꢀ42.
Synthesis of Compounds 5ꢀ1ꢀ5ꢀ6.
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Following the procedure described for 4ꢀ1ꢀ4ꢀ42, compounds 5ꢀ1ꢀ5ꢀ6 were obtained.
Synthesis of Compounds 6ꢀ1ꢀ6ꢀ6.
Following the procedure described for 4ꢀ1ꢀ4ꢀ42, compounds 6ꢀ1ꢀ6ꢀ6 were obtained.
RESULTS AND DISCUSSION
Synthesis
The intermediates 8ꢀ18 were prepared according to procedures reported in the literature.9ꢀ12
The ethyl substituted phenoxybutanoate 9 were synthesized by the reaction of substituted
phenols and ethyl 4ꢀbromobutanoate with potassium carbonate as the catalyst. Substituted
phenoxybutanoic acids 10 were prepared by hydrolyzing the corresponding intermediates 9 in
the presence of sodium hydrate as a base.
In triethylamine or pyridine, with chloroform as solvent, the target compounds 4 and 5 were
synthesized from the reaction of intermediates 8 with substituted phenoxybutanoyl chlorides 11
and substituted phenoxyvaleryloxy chlorides 17, respectively (Figure 2 and 3). In triethylamine
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or pyridine, with chloroform as solvent, the target compounds 6 were synthesized from the
reaction of intermediates 18 and substituted phenoxybutanoyl chlorides 11 (Figure 4). The
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structures of the target compounds 4, 5 and 6 were characterized by H NMR, 13C NMR, 31P
NMR, IR, MS and elemental analysis. The target compounds 4, 5 and 6 exhibit some
characteristic peaks at δ = 3.60ꢀ3.84 (m or dd, 6H, 2×PꢀOꢀCH3) and δ = 5.28ꢀ6.31 (d or t or m,
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1H, PꢀCH) in the H NMR. A typical carbon resonance at δC 168.56ꢀ173.72 in the 13C NMR
spectra of 4 also confirms the presence of a carbonꢀoxygen double bond. The typical phosphorus
resonance in the 31P NMR spectra of 4, 5 and 6 reveals the presence of a phosphorus center
coupled to an adjacent CH at δP 16.16ꢀ23.28, 20.09ꢀ24.07 and 9.98ꢀ15.58, respectively.
Greenhouse Herbicidal Activity and Crop Selectivity
All the title compounds were tested at 150 g ai/ha for postꢀemergence herbicidal activity on
barnyard grass (Echinochloa crusgalli), green bristlegrass (Setaira viridis), crab grass (Digitaria
sanguinalis), velvetleaf (Abutilon theophrasti), slender amaranth (Amaranthus retroflexus) and
false daisy (Eclipta prostrata). Clacyfos was selected as a control. As shown by the data in Table
1, we see that all of compounds 4 with 2ꢀNO2 or 4ꢀNO2 substitution on the phenoxybenzene ring
were inactive against all of the tested weeds, while other compounds 4 exhibited weak to
excellent activity against dicotyledonous weeds and were almost inactive against the tested
monocotyledonous weeds. Compounds 4ꢀ1−4ꢀ3, 4ꢀ8−4ꢀ9, 4ꢀ15, 4ꢀ19, 4ꢀ22, 4ꢀ24, 4ꢀ30, 4ꢀ31 and
4ꢀ36−4ꢀ38 exhibited significant herbicidal activity against velvetleaf, slender amaranth and false
daisy. It is worthwhile to note that compounds 4ꢀ1, 4ꢀ2, 4ꢀ9, 4ꢀ22 and 4ꢀ30 displayed remarkable
herbicidal activity on the tested broadꢀleaved weeds with an 85ꢀ100% inhibition, which was
equal to that of clacyfos against the tested dicotyledons with an 85ꢀ100% inhibition at 150 g
ai/ha. Especially, the herbicidal activity of compounds 4ꢀ1 and 4ꢀ9 against velvetleaf, leaf
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mustard and false daisy were 100% inhibition effect at 150 g ai/ha. All of the compounds 5 were
inactive against all of tested plants at 150 g ai/ha, no matter what the substitution groups (R, X
and Y) were. As shown by the data in Table 2, all of title compounds 6 displayed outstanding
herbicidal activity against dicotyledonous weeds equal to clacyfos. Interestingly, the herbicidal
activity of compounds 6 against monocotyledonous weeds with values of 10ꢀ30% inhibition at
the same rate were better than those of compounds 4 and that of clacyfos with values of zero at
150 g ai/ha.
Comparing the data shown in Table 1, title compounds 4 with 2,4ꢀCl2 or 4ꢀClꢀ2ꢀCH3 as X and
Y (such as 4ꢀ1, 4ꢀ2, 4ꢀ8, 4ꢀ9, 4ꢀ19, 4ꢀ20, 4ꢀ22, 4ꢀ23, 4ꢀ29, 4ꢀ30, 4ꢀ36 and 4ꢀ37) exhibited
significant herbicidal activity (more than 80% inhibition) against the tested dicotyledons for
postꢀemergence treatment at 150 g ai/ha, regardless of different substituents in the R1 moiety
(such as CH3, CH2CH3, nꢀPr and Ph) and R moiety (such as CH3 and CH2CH3). The 2,4ꢀCl2 or 4ꢀ
Clꢀ2ꢀCH3 substitution on the phenoxybenzene ring was the most promotive followed by 4ꢀCl or
4ꢀClꢀ3ꢀCH3. The nitro group substitution on the phenoxybenzene ring resulted in inactive against
all of the tested weeds, no matter what other groups served as R1 and R moieties.
Bioassay results indicated that compounds 5 showed no herbicidal activity against all tested
plants at 150 g ai/ha in postꢀemergence treatment, regardless of the different substituents R, R1
and X, Y. As shown by the data in Table 2, all of the compounds 6 exhibited 60ꢀ85% inhibition
against dicotyledonous weeds at 150 g ai/ha in postꢀemergence treatment, no matter what the
different of substituents R, R1 and X, Y. However, compounds 6 exhibited a 10ꢀ30% herbicidal
inhibition against all of the tested monocotyledons, which is better than that of clacyfos without
activity against the tested monocotyledons.
The SAR analysis of compounds 4 implied that the carbon chain with three carbon atoms
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between carbonyl and phenoxy moiety seemed to have a favorable effect on herbicidal activity,
in this case substituents X and Y on the phenoxyꢀbenzene ring still greatly affected the activity.
Compounds 4 with 2,4ꢀCl2 or 4ꢀClꢀ2ꢀCH3 as X and Y especially exhibit much higher herbicidal
activity. However, compounds 5 with a fourꢀmember carbon chain as linking bridge resulted in a
loss of activity against all of the tested weeds even 2,4ꢀCl2 or 4ꢀClꢀ2ꢀCH3 as X and Y on the
phenoxyꢀbenzene ring.
It was found that 4ꢀ1, 4ꢀ2, 4ꢀ9, 4ꢀ30 and 4ꢀ36 displayed much higher herbicidal activity than
that of other compounds at 150 g ai/ha, so these compounds were chosen for a broad spectrum
test to confirm their activity and potential application. They were tested at the rates of 75 and 150
g ai/ha for postꢀemergence herbicidal activity against velvetleaf, false daisy, field mustard,
tomato, leaf mustard, glory, common vetch, goosefoot, ball cabbage, common amaranth, radish,
monarch redstem and sheathed monochoria herb. As shown by the data in Table 3, the herbicidal
activities and spectra of 4ꢀ1, 4ꢀ2, 4ꢀ9, 4ꢀ30 and 4ꢀ36 were comparable with that of glyphosate.
The title compound 4ꢀ1 showed especially higher herbicidal activity than glyphosate against
velvetleaf, field mustard, leaf mustard, glory, common vetch, goosefoot, ball cabbage, common
amaranth radish, monarch redstem and sheathed monochoria herb at 75 g ai/ha.
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Furthermore, the crop selectivity of 4ꢀ1, 4ꢀ2, 4ꢀ9, 4ꢀ20, 4ꢀ22 and 4ꢀ23 were also tested. As
shown by the data in Table 4, the compounds were harmless to wheat and maize by postꢀ
emergence application at 450 g ai/ha, which indicated that these compounds could be developed
as potential herbicides used in wheat and maize fields.
In summary, three series of novel αꢀ(substituted phenoxybutyryloxy or
valeryloxy)alkylphosphonates 4ꢀ5 and 2ꢀ(substituted phenoxybutyryloxy)alkylꢀ5,5ꢀdimethylꢀ
1,3,2ꢀdioxaphosphinanꢀ2ꢀone derivatives 6 were designed and synthesized based on the
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structural modification of 1, and their postꢀemergence herbicidal activity against six species of
weeds were evaluated. Structureꢀactivity relationship (SAR) analyses indicated that a threeꢀ
member carbon chain as linking bridge in the modified structure had a favorable effect on
herbicidal activity against the tested dicotyledons, and the herbicidal activity of compound could
be further increased by a reasonable combination of X, Y and R in the parent structure 4. The
title compounds 5 with a fourꢀmember carbon chain showed no activity against all of the tested
weeds. Compounds 6 containing a phosphorusꢀheterocyclic ring showed lower herbicidal
activity against the tested dicotyledons compared with those of compounds 4. Title compound 4ꢀ
1 was found to possess high activity and a broad spectrum against all of the tested broadleaf
weeds with a 70ꢀ100% inhibition effect at 75 g ai/ha; furthermore, it is very safe for wheat and
maize at 450 g ai/ha. These findings demonstrate that 4ꢀ1 could be as a potential selective postꢀ
emergence herbicide for further development.
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ASSOCIATED CONTENT
Supporting Information
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Structures were characterized and confirmed by H NMR, C NMR, P NMR, IR, MS and
elemental analysis. The physicochemical properties and spectroscopic data of all title compounds
are provided. Bioassay methods for greenhouse herbicidal activity and crop selectivity are
provided. This material is available free of charge via the Internet at http://pubs.acs.org.
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ACKNOWLEDGMENT
This research was supported in part by the Natural Science Foundation of Hubei Province of
China (No. 2014CFA111), and the National Natural Science Foundation of China (No.
21172090 and 21472062).
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inexpensive precursors for stereodefined chloroꢀsubstituted olefins and unsymmetrical
disubstituted acetylenes. J. Org. Chem. 2000, 65, 3733–3737.
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246
(12) He, H. W.; Wang, T.; Yuan, J. L. Synthesis and herbicidal activities of methylꢀ1ꢀ(2,4ꢀ
dichloroꢀphenoxyacetoxy)alkylphosphonatemonosalts. J. Organomet. Chem. 2005, 690,
2608ꢀ2613.
247
248
(13)
Xie, Q. L.; Zheng, J. Y. Synthesis and structure of tricyclohexyistannane
aromatoxyacetares. Chin. J. Org. Chem. 1991, 11, 82ꢀ87.
249
250
(14) Wen, R. Chapter 2: Alkylation Reaction. In Organic Reactions for Drug Synthesis, 3;
Chemical Industry Press: Beijing, China, 2002; 44ꢀ51.
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252
(15) Huang, X.; Wang, Y., G.; Chen, Z. C. Chapter 5: Alcohol and Phenol. In New Organic
Synthetic Chemistry, 1; Chemical Industry Press: Beijing, China, 2002; 196ꢀ203.
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254
255
256
257
258
259
260
FIGURE CAPTIONS
Table 1. Herbicidal activity of compounds 4ꢀ1ꢀ4ꢀ42.
Table 2. Herbicidal activity of compounds 6ꢀ1ꢀ6ꢀ6.
Table 3. Broad spectra bioassay of compounds 4ꢀ1, 4ꢀ2, 4ꢀ9, 4ꢀ30 and 4ꢀ36.
Table 4. Crop selectivity of compounds 4ꢀ1, 4ꢀ2, 4ꢀ9, 4ꢀ20, 4ꢀ22 and 4ꢀ23
Figure 1. Chemical modification of lead structure 1.
Figure 2. Synthetic route of αꢀ(substituted phenoxybutyryloxy)alkylphosphonates 4ꢀ1ꢀ4ꢀ42.
Figure 3. Synthetic route of αꢀ(substituted phenoxyvaleryloxy)alkylphosphonates 5ꢀ1ꢀ5ꢀ6.
261
262
Figure 4. Synthetic route of 2ꢀ(substituted phenoxybutyryloxy)alkylꢀ5,5ꢀdimethylꢀ1,3,2ꢀ
dioxaphosphinanꢀ2ꢀone 6ꢀ1ꢀ6ꢀ6.
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Table 1. Herbicidal activity of compounds 4ꢀ1ꢀ4ꢀ42.
postꢀemergence, 150 g ai/ha
Compd. R1
R
X
Y
ECa
SVa
DSa
ATa
BJa
EPa
Me Me
Me Me
Me Me
Me Me
2ꢀCl
2ꢀMe
4ꢀCl
4ꢀCl
4ꢀCl
H
0
0
0
0
0
30
30
0
100
95
100
98
100
100
70
4ꢀ1
4ꢀ2
0
30
30
0
70
70
4ꢀ3
3ꢀMe
2ꢀCl
4ꢀCl
4ꢀCl
4ꢀCl
H
0
60
60
40
4ꢀ7
Me
Me
Me
Me
Me
Me
Me
Me
Et
Et
Et
Et
Pr
Pr
Pr
Pr
30
40
50
0
0
100
100
70
100
100
60
75
4ꢀ8
2ꢀMe
4ꢀCl
30
30
0
30
20
0
100
60
4ꢀ9
4ꢀ10
4ꢀ13
4ꢀ15
4ꢀ19
4ꢀ20
4ꢀ21
4ꢀ22
4ꢀ23
4ꢀ24
4ꢀ27
4ꢀ29
4ꢀ30
4ꢀ31
3ꢀMe
4ꢀCl
4ꢀCl
H
70
60
60
30
40
0
30
20
0
30
20
0
75
70
70
2ꢀCl
4ꢀCl
4ꢀCl
4ꢀCl
4ꢀCl
4ꢀCl
H
100
100
30
100
80
80
2ꢀMe
3ꢀMe
2ꢀCl
50
0
0
0
60
50
Me Ph
Me Ph
Me Ph
Me Ph
30
0
0
0
85
100
80
100
60
2ꢀMe
4ꢀCl
0
0
95
50
0
50
0
40
0
75
70
75
3ꢀMe
2ꢀCl
4ꢀCl
4ꢀCl
4ꢀCl
H
60
40
40
Et
Et
Et
Me
Me
Me
0
0
0
85
80
60
2ꢀMe
4ꢀCl
50
40
30
50
30
50
100
100
90
90
85
70
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Et
Et
Et
Et
Et
Me
Ph
3ꢀMe
2ꢀCl
4ꢀCl
4ꢀCl
4ꢀCl
H
0
0
0
0
20
0
60
100
100
100
80
60
80
80
80
70
85
60
80
70
70
60
90
4ꢀ34
4ꢀ36
4ꢀ37
4ꢀ38
4ꢀ41
30
40
50
30
0
Ph
2ꢀMe
4ꢀCl
0
Ph
60
30
0
50
20
0
Ph
3ꢀMe
4ꢀCl
100
Clacyfos
264
265
aEC for Echinochloa crusgalli; SV for Setaira viridis; DS for Digitaria sanguinalis; AT for
Abutilon theophrasti; BJ for Brassica juncea; EP for Eclipta prostrate.
266
267
268
n.b.: Compounds 4ꢀ4, 4ꢀ5, 4ꢀ6, 4ꢀ11, 4ꢀ12, 4ꢀ14, 4ꢀ16, 4ꢀ17, 4ꢀ18, 4ꢀ25, 4ꢀ26, 4ꢀ28, 4ꢀ32, 4ꢀ33,
4ꢀ35, 4ꢀ39, 4ꢀ40 and 4ꢀ42 with no herbicidal activity against all the tested weeds were not listed
in the Table 1.
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Table 2. Herbicidal activity of compounds 6ꢀ1ꢀ6ꢀ6.
postꢀemergence, 150 g ai/ha
Compd.
R
X
Y
ECa
SVa
DSa
ATa
BJa
EPa
Me
Me
Me
Ph
2ꢀCl
2ꢀMe
4ꢀCl
2ꢀCl
2ꢀMe
4ꢀCl
4ꢀCl
4ꢀCl
H
30
30
30
30
10
20
0
30
30
30
30
10
20
0
30
30
30
20
10
20
0
85
85
85
80
70
75
75
50
85
80
80
60
90
80
75
90
6ꢀ1
6ꢀ2
6ꢀ3
6ꢀ4
6ꢀ5
6ꢀ6
80
4ꢀCl
4ꢀCl
H
75
Ph
80
Ph
75
100
Clacyfos
270
271
aEC for Echinochloa crusgalli; SV for Setaira viridis; DS for Digitaria sanguinalis; AT for
Abutilon theophrasti; BJ for Brassica juncea; EP for Eclipta prostrate.
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Table 3. Broad spectra bioassay of compounds 4ꢀ1, 4ꢀ2, 4ꢀ9, 4ꢀ30 and 4ꢀ36.
Rate
Postꢀemergence
Compd.
g ai/ha ATa ECa BCa SLa BJa PCa VSa CAa BOa ARa RSa ABa MKa
150
75
100 100 90 90 95 100 100 90
100 70 70 80 90 100 100 80
95 100 80 80 100 100 75
80 60 80 70 80 100 75
100 100 70 70 100 100 70
85 100 95 100 100
4ꢀ1
4ꢀ2
80
90
80 100 100
85 100 90
150
75
75
70
60
50
80
80
90
90
85
150
75
75
70
70
50
90
80
60 100 100
50 100 90
4ꢀ9
80
100 90
70 70
100 80
60
60 60 90 100 60
150
75
60 70 100 100 70
60 50 70 80 60
80
60
70
60
75
70
50
30
50
0
50
40
4ꢀ30
150
75
80 95 85 100 80
60 70 85 100 70
80
70
80
80
80
70
90
80
70 100
70 90
4ꢀ36
\
\
150
75
100 100 80 85 80 60 95
80 90 70 85 30 60 95
90
70
80
70
90
90
65 100 100
60 100 100
glyphosate
273
274
275
276
277
aAT for Abutilon theophrasti; EC for Eclipta prostrata; BC for Brassica chinensis L.; SL for
Solanum lycopersicum; BJ for Brassica juncea; PC for Pharbitis nil (L.) Choisy; VS for Vicia
sativa L.; CA for Chenopodium album; BO for Brassica oleracea; AR for Amaranthus
retroflexus; RS for Raphanus sativus L.; AB for Ammannia baccifera L.; MK for Monochoria
vaginalis (BL.) Kunth
278
279
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Table 4. Crop selectivity of compounds 4ꢀ1, 4ꢀ2, 4ꢀ9, 4ꢀ20, 4ꢀ22 and 4ꢀ23
Crops (percent inhibition, 450 g ai/ha）a
Compd.
R
R1
X
Y
wheat
rice
maize cotton soybean rape
Me
Me
Me
Me
Me
Me
Me
Me
Et
2ꢀCl
4ꢀCl
0
0
0
0
0
0
31ꢀ50
31ꢀ50
0
0
0
0
0
0
0
11ꢀ30
11ꢀ30
11ꢀ30
11ꢀ30
11ꢀ30
11ꢀ30
11ꢀ30
11ꢀ30
11ꢀ30
11ꢀ30
11ꢀ30
11ꢀ30
31ꢀ50
31ꢀ50
0
4ꢀ1
4ꢀ2
2ꢀMe 4ꢀCl
2ꢀMe 4ꢀCl
2ꢀMe 4ꢀCl
4ꢀ9
Pr
31ꢀ50
11ꢀ30
31ꢀ50
31ꢀ50
11ꢀ30
31ꢀ50
4ꢀ20
4ꢀ22
4ꢀ23
Ph
Ph
2ꢀCl
4ꢀCl
2ꢀMe 4ꢀCl
281
a>10%, not safe to crops; 0ꢀ10%, safe to crops.
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Figure 1. Chemical modification of lead structure 1.
283
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Figure 2. Synthetic route of αꢀ(substituted phenoxybutyryloxy)alkylphosphonates 4ꢀ1ꢀ4ꢀ42.
285
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Figure 3. Synthetic route of αꢀ(substituted phenoxybutyryloxy)alkylphosphonates 5ꢀ1ꢀ5ꢀ6.
287
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Figure 4. Synthetic route of 2ꢀ(substituted phenoxybutyryloxy)alkylꢀ5,5ꢀdimethylꢀ1,3,2ꢀ
dioxaphosphinanꢀ2ꢀone 6ꢀ1ꢀ6ꢀ6.
290
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TABLE OF CONTENTS GRAPHICS
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