Synthesis and Herbicidal Activity of Novel Sulfonylureas Containing Thiadiazol Moiety

Thirteen novel sulfonylureas containing thiadiazole moiety were synthesized in a two-step reaction. Their structures were determined using IR, ^1H NMR, HRFTMS, and elemental analysis. Herbicidal activities of these compounds were determined in the green house bio-assay. The results show that four compounds among them exhibit some activity toward four tested herbs.

Metsulfuron-methyl Molecularly Imprinted Stir Bar Sorptive Extraction Coupled with High Performance Liquid Chromatography for Trace Sulfonylurea Herbicides Analysis in Complex Samples

Metsulfuron-methyl molecularly imprinted polymer（MIP）-coated stir bar was prepared for sorptive extraction of sulfonylurea herbicides in complex samples.The MIP-coating was about 21.3 μm thickness with the relative standard deviation（RSD） of 4.4%（n=10）.It was homogeneous and porous with good thermal stability and chemical stability.The extraction capability of the MIP-coating was 2.8 times over that of the non-imprinted polymer（NIP）-coating in hexane.The MIP-coating exhibited selective adsorption ability to the template and its analogues.The extraction conditions,including extraction solvent,desorption solvent,extraction time,desorption time and stirring speed,were optimized.A method for the determination of six sulfonylurea herbicides by MIP-coated stir bar sorptive extraction coupled with high performance liquid chromatography（HPLC） was developed.The linear range was 10―200 μg/L and the detection limits were within a range of 2.0―3.3 μg/L.It was also applied to the analysis of sulfonylurea herbicides in spiked river water,soil and rice samples.

Development and molecular analysis of a novel acetohydroxyacid synthase rapeseed mutant with high resistance to sulfonylurea herbicides

With the increasing promotion of simplified rapeseed cultivation in recent years,the development of cultivars with high resistance to herbicides is urgently needed.We previously developed M342,which shows sulfonylurea herbicide resistance,by targeting acetohydroxyacid synthase(AHAS),a key enzyme in branched-chain amino acid synthesis.In the present study,we used a progeny line derived from M342 for an additional round of ethyl methane sulfonate mutagenesis,yielding the novel mutant DS3,which harbored two mutations in AHAS genes and showed high sulfonylurea resistance.One mutation was the substitution Trp574 Leu,as in M342,according to Arabidopsis protein sequencing.The other site was a newly recognized substitution,Pro197 Leu.A KASP marker targeting Pro197 Leu was developed and reliably predicted the response to sulfonylurea herbicides in the F2 population.The combination of Trp574 Leu and Pro197 Leu in DS3 produced a synergistic effect that greatly increased herbicide resistance.Analysis of the protein structures of AHAS1 and AHAS3 in wild-type and single-gene mutant plants revealed three-dimensional protein conformational changes that could account for differences in herbicide resistance characteristics including toxicity tolerance,AHAS enzyme activity,and AHAS gene expression.

Rapid Residue Analysis of Sulfonylurea Herbicides in Surface Water: Methodology and Residue Findings in eastern Tiaoxi River of China

A new method combining QuEChERS (quick, easy, cheap, effective, rugged and safe) and DLLME (dispersive liquid–liquid microextraction) for the simultaneous determination of residues of ten sulfonylurea herbicide in water using UPLC-MS/MS was developed and validated. Analytes were extracted and purified with QuEChERS and concentrated in chlorobenzene by applying the DLLME procedure. Several extraction parameters were tested, such as volume, extractive solvent by the QuEChERS method and subsequently used for DLLME, selection of extractive solvent and its volume, was tested. The developed method was validated on the basis of international guidelines. Mean recoveries ranged from 81.2 to 104.9%. Repeatability and reproducibility were lower than 10%. Limits of detection (LODs) and quantification (LOQs) were below 0.074 μg/L and 0.244 μg/L, respectively. Decision limit (CCα) and detection capability (CCβ) were calculated and CCβ ranged from 0.101 μg/L (pyrazosulfuron-ethyl) to 0.260 μg/L (nicosulfuron). Finally, when the method was applied to real samples, traces of three compounds were found in 42 samples and only thifensulfuon-methyl was detected above the LOQ in three samples at 0.17-0.20 μg/L.

Precise base editing of non-allelic acetolactate synthase genes confers sulfonylurea herbicide resistance in maize

Single-nucleotide polymorphisms contribute to phenotypic diversity in maize. Creation and functional annotation of point mutations has been limited by the low efficiency of conventional methods based on random mutation. An efficient tool for generating targeted single-base mutations is desirable for both functional genomics and precise genetic improvement. The objective of this study was to test the efficiency of targeted C-to-T base editing of two non-allelic acetolactate synthase(ALS) in generating sulfonylurea herbicide-resistant mutants. A CRISPR/Cas9 nickase-cytidine deaminase fused with uracil DNA glycosylase inhibitor(UGI) was employed to achieve targeted conversion of cytosine to thymine in ZmALS1 and ZmALS2. Both protoplasts and recovered mutant plants showed the activity of the cytosine base editor, with an in vivo efficiency of up to 13.8%. Transgene-free edited plants harboring a homozygous ZmALS1 mutation or a ZmALS1 and ZmALS2 double mutation were tested for their resistance at a dose of up to 15-fold the recommended limit of chlorsulfuron, a sulfonylurea herbicide widely used in agriculture. Targeted base editing of C-to-T per se and a phenotype verified in the generated mutants demonstrates the power of base editing in precise maize breeding.

2D-and 3D-QSBR Study on the Relationship between the Structure and Biodegradation Property of Sulfonylurea Herbicides

Using DFT method, 10 sulfonylurea herbicides were computed at the B3LYP/6- 31G＊ level. Based on linear solvation energy theory, the corresponding linear solvation energy relationship （LSER） equation （R2 -- 0.759） to the half-life time （T1/2） of biodegradation was obtained with the structural and thermodynamic parameters as theoretical descriptors. Furthermore, CoMSIA method was also applied to establish 3D models which reveal the fields influencing these properties. The relationship between the properties and the structure was obtained. And the related coefficient of the model is 0.952. Results showed the electronic property is important to affect the biodegradation of these compounds by analysis of the 2D and 3D models.

Synthesis and Herbicidal Activity of Novel 5-Substituted Benzenesulfonylureas

Sulfonylurea herbicides have been widely used because of their low application rates, good crop sdeetivities and low mammalian toxicities. However, some sulfonylureas might persist unfavourably in the environment with residual problems. In order to look for ecologically safer and environmentally benign sulfonylureas, and on keeping the pyrimidine ring being monosubstitated, 15 novd C5-monosubstituted benzenesulfonylurea compounds were synthesized. The structures of all the compounds synthesized were confirmed by demental analysis and ^1H NMR. Preliminary herbicidal activities of these new sulfonylurea compounds were determined by ALS screening （ in vitro） and pot bioassay experiments（ in vivo）. The herbicidal results show that some novel sulfonylureas are comparable to commercial Foramsulfuron and Monosulfuron.

Synthesis and Herbicidal Activity of Novel Sulfonylurea Derivatives

Sulfonylurea herbicides have been applied worldwide in agriculture. Some sulfonylurea residues might exist in soil longer than that people expected. However, flupyrsulfuron-methyl-sodium which was firstly reported as a new 5-substituted sulfonylurea herbicide has less than one month residual life. Therefore, 5-substituted benzenesulfonylureas are potential molecules to regulate its residual situation. In order to develop new sulfonylurea derivatives, the substituent on the critical 5-posotion of the benzene ring was optimized. On the basis of our former work on sulfonylureas which contains a characteristic mono-substituted pyrimidine moiety, twenty-six new sulfonylurea deriva- tives were synthesized and their structures were confirmed by 1H NMR, 31p NMR and elemental analysis. The greenhouse bioassay tests show that some title compounds exhibit potent herbicidal activity.

Synthesis and herbicidal activities of pyridyl sulfonylureas:More convenient preparation process of phenyl pyrimidylcarbamates

Four 4-monosubstituted pyrimidine pyridyl sulfonylureas were synthesized from pyridinesulfonamide and phenyl pyrimidylcarbamate and screened for herbicidal activities. We also reported a convenient preparation process of phenyl pyrimidylcarbamates from pyrimidineamine and phenyl chloroformate.

Synthesis and Characterization of Novel Sulfonylurea Derivatives

On the basis of study on the mechanism of action of sulfonylurea herbicides, nine sulfonylurea derivatives of iso-{xazolidinone} were designed and synthesized. The structures of these compounds were confirmed by means of IR, MS, NMR and elemental analysis. The results of preliminary active tests indicate that the compounds have some herbicidal activity. The structure-activity relationship was also studied.

Design, synthesis and bioactivity of novel herbicides targeted ALS (Ⅶ): Quantitative structure-activity relationships of herbicidal sulfonylureas

The quantitative relationship between the structures of 20 sulfonylureas and their herbicidal activities against rape was analyzed using physicochemical parameters and regression analysis. The results showed that the electronic properties of the molecules are the dominant factor to the activity and there is apparently an optimum electronic property (∑σ or pKa) for the molecules to fit the receptor. Combined with the previous QSAR results for herbicidal triazolopyrimidine-2-sulfonamides, we can conclude that the structure-activity relationships of these two sets of compounds are identical, which suggested that these two sets of compounds acted on the same target site.

Controllable Effect of Structural Modification of Sulfonylurea Herbicides on Soil Degradation

The study of soil degradation behaviors of sulfonylurea herbicides in relation to their different structural attributes is utmost important for us to comprehend the development of new eco-friendly herbicides. It is postulated that the structural modification of the chemical structures could influence their degradation rates in soil. Nine devised structures were synthesized to study their herbicidal activity as well as their soil degradation behaviors respectively. The novel compounds I-3-I-7 were characterized by UV, ^1H NMR and ^13C NMR, MS and EA. Bioassays indicated that most of target compounds displayed superior herbicidal activities in comparison with Chlorsulfuron. Soil degradation results further confirmed our previous assumption that the introduction of electron-donating substituents at 54 position of the benzene ring distinctly increased their degradation rates, among which dimethylamino and diethylamino groups can adjust the degradation rate to a more favorable status.

Synthesis and Crystal Structure of 2-[(4-Methoxy- 6-methylthio-2-pyrimidinyl)aminocarbonyl- aminosulfonyl] Benzoic Acid Methyl Ester

The title compound 2-[(4-methoxy-6-methylthio-2-pyrimidinyl)aminocarbonyl- aminosulfonyl]benzoic acid methyl ester (C15H16N4O6S2, Mr = 412.44) was obtained by the reaction of (4-methoxy-6-methylthio-2-pyrimidinyl)amine with 2-methoxylcarbonylbenzene-sulfonylisocya- nate. The crystal is of monoclinic, space group P21/c with a =11.169(3), b = 9.508(3), c = 17.690(5) ? b = 91.593(5), Z = 4, V = 1877.9(10) 3, Dc = 1.459 g/cm3, F(000) = 856, m(MoKa) = 0.324 mm-1, R = 0.0690 and wR = 0.1368 for 3301 observed reflections (I > 2s(I)). The N(1)H…N(3) and N(2)H…O(4) hydrogen bonds can be observed. In the molecule the phenyl plane(I), pyrimi- din-2-yl-urea bridge plane(Ⅱ) and ester plane(Ⅲ) form three conjugated systems.

Synthesis,Crystal Structure and Herbicidal Activity of O,O'-Diethyl-N-[2-(5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yloxy)-benzoxyl]-1-amino-benzyl phosphonate

The crystal structure of the title compound （C25H28N5O5P,Mr=509.49） has been determined by single-crystal X-ray diffraction.The crystal is of monoclinic,space group P21/c with a=13.0726（4）,b=13.4513（4）,c=15.103（1）,β=93.650（1）°,V=2650.29（14）3,Z=4,Dc= 1.277 g/cm3,F（000）=1072,μ（MoKα）=0.147 mm-1,the final R=0.0748 and wR=0.1956 for 3186 observed reflections （I 〉 2σ（I））.The fused triazolopyrimidine system ring is coplanar,the dihedral angles between the triazolopyrimidine and C（1）-C（3）-C（5） phenyl,the triazolopyrimidine and C（17）-C（19）-C（21） phenyl,and the two phenyl rings are 66.87,58.79 and 80.11o,respectively.Intramolecular N（5）-H（5A）…O（3） and intermolecular C（2）-H（2）…N（4）,C（18）-H（18）…O（3）,C（19）-H（19）…O（2） and C（24）-H（24C）…N（4） hydrogen bonds together with C-H…π interactions contribute to the stability of the structure and result in a three-dimensional framework.The preliminary bioassay indicates that the title compound exhibits moderate herbicidal activity against dicotyledonous plants （Brassica campestris L） at the concentration of 100 mg/L.

Design, Synthesis and Herbicidal Activity of Novel Sulfonylureas Containing Tetrahydrophthalimide Substructure

To develop novel sulfonylurea herbicides, a series of chlorsulfuron derivatives was designed and synthesized through introducing tetrahydrophthalimide substructure taken from protoporphyrinogen IX oxidase（PPO） inhibitors onto the critical 5-position of the classical benzene ring. The structures of title compounds were confirmed by infrared spectroscopy, ultraviolet spectroscopy, 1H and 13C NMR spectrometry, mass spectrometry and elemental analysis. In addition, the crystal structure of compound I1-5 was further determined by X-ray diffraction analysis. Bioassay results showed that individual compounds exhibited good herbicidal activities, especially compound I1-8, which displayed 100% inhibition rate against Echinochloa crusgalli at 150 g/ha（1 ha=104 m2） with the method of foliage spray in the pot experiment.

Synthesis and Crystal Structure of N-(1,3,4-Thiadiazol-2-yl)-1-[1-(6-chloropyridin-3-yl)methy]-5-methyl-1H-[1,2,3]triazol-4-carboxamide

The crystal structure of the title compound （C12H10ClN7OS, Mr= 335.78） has been determined by single-crystal X-ray diffraction. The crystal is of triclinic, space group Pi with a = 8.4093（11）, b = 9.4430（12）, c = 11.1454（14） A, α = 95.508（2）, β = 111.366（2）, γ = 115.259（2）°, V = 711.42（16） A3, Z = 2, Dc = 1.568 g/cm3, F（000） = 344, μ（MoKα） = 0.428 mm-1, the final R = 0.0476 and wR = 0.1243 for 2353 observed reflections （I 〉 2o（/））. The dihedral angles between the pyridine and triazole, thiazole and triazole, and pyridine and thiazole rings are 69.2（1）, 9.2（1） and 72.7（1）°, respectively. Intramolecular C（8）--H（8B）...O（1） and N（5）-H（5A）..-N（4） as well as intermolecular C（5）-H（5）...S（1）, C（3）-H（3）.,.N（6） and N（5）-H（5A）...N（1） hydrogen bonds together with weak C-H...Ir hydrogen-bonding and π-π stacking interactions contribute to the stability of the structure. There is also evidence for significant electron delocalization in the triazolyl system.

Synthesis and Herbicidal Activity of Novel Sulfonylureas Containing 1,2,4-Triazolinone Moiety

A series of new sulfonylureas incorporating 1,2,4-triazolinone moiety was synthesized, which were further bio-assayed for the herbicidal activity against four herbs, representative of monocotyledons and dicotyledons. Some of them exhibited high potency to inhibit the growth of dicotyledons（Bassica napus and Arnaranthus retroflexus） in the pot experiment. Compounds 9a and 9b also displayed an excellent herbicidal activity against Bassica napus at a concentration of 15 g/hectare, which were comparable with commercial triasulfuron.

Gas-phase Smiles Rearrangement of Sulfonylurea Herbicides in Electrospray Ionization Mass Spectrometry

In the negative ion mode of electrospray ionization tandem mass spectrometry （ES1-MS/MS） of four sulfonyl- urea herbicides, Smiles rearrangements were observed in rimsulfuron and nicosulfuron. In the case of rimsulfuron, two competitive gas-phase Smiles rearrangements initiated by nitrogen anion and oxygen anion respectively were witnessed. The ion-neutral complex was proposed as the reactive intermediate in the course of this unimoleeular dissociation reaction of the oxygen attack Smiles rearrangement route. The density functional theory （DFT） was carried out to elucidate the mechanism as well as to show the possible transition states and the intermediates.

Non-hydrolytic Sol-gel Methodology to Prepare a Molecularly Imprinted, Organic-silica Hybrid-based Stir Bar for Recognition of Sulfonylurea Herbicides

Based on a molecularly imprinted organic-silica hybrid-based stir bar, a pre-treatment methodology was devel- oped for enrichment of nicosulfuron in aqueous samples. The molecularly imprinted organic-silica hybrid-based coating on the outer surface of a glass stir bar was prepared by in-situ polymerization using nicosulfuron as a template molecule, a-methacrylic acid as a functional monomer, methacryloxypropytrimethoxysilane as a cross-linker in the mixture of acetonitrile and trichloromethane （V/V, 7.5 ： 1）. To achieve the selective extraction of the target analyte from aqueous samples, several main parameters, including extraction time, pH value and contents of inor- ganic salt in the sample matrix were investigated. Evidence was also presented by the scanning electronic micro- scopic images of the imprinted and non-imprinted stir bars. Then, the extraction efficiency of the stir bar was tested with separate experiments and competitive sorption experiments. These results showed that using six sulfonylureas as substrates the molecularly imprinted organic-silica hybrid-based stir bar gave high selectivity for the template, nicosulfuron compared to the non-imprinted organic-silica hybrid-based stir bar. This sorption extraction was cou- pled to liquid chromatography ultraviolet detection allowing the determination of nicosulfuron from tap water. The method showed good recoveries and precision, 96.0% （RSD 2.7%, n=3） for tap water spiked with 0.125 nmol （25.00 mL sample）, suggesting that the stir bar can be successfully applied to the pre-concentration of nicosulfuron in real aqueous samples.

Synthesis and Herbicidal Activity of Derivatives of Toxin III from Phoma herbarbum

[Objective] In order to improve the herbicidal activity of toxins III（methyl2-methyl-3,5-dinitrobenzoate） from Phoma herbarbum, its structure was optimized by derivatization. [Method] Sixteen novel title compounds were synthesized by nitration and acylation with o-toluic acid as a starting material. Their structures were confirmed by IR and1 H NMR. [Result] The herbicidal activity screening showed that the inhibition rate of J-L-59 against E. crusgalli roots was 93.7% at 100 μg/ml. The fresh weight efficacy of J-L-59 against A. theophrasti and A. retroflexus was 100%at 1 000 g a.i./hm^2 , and the ED50 value for A. retroflexus was 94.06 g a.i./hm^2 .[Conclusion] J-L-59 has higher herbicidal activity.