2-[2-(烷氧羰基苯氧羰基)苯氧基]-4,6-二甲氧基嘧啶类化合物的合成及其除草活性研究

为了寻找高效、安全、经济的除草活性化合物, 设计并合成了9个新的2-[2-(烷氧羰基苯氧羰基)苯氧基]-4,6-二甲氧基嘧啶类化合物, 其化学结构经IR, ¹H NMR, LC/MS和元素分析确证. 初步生物活性测定结果表明, 该类化合物在有效成份2250 g/ha剂量时, 对苘麻(Abutilon theophrasti)、稗草(Echinochloa crus-galli)、狗尾草(Setaria viridis)等都具有良好的除草活性, 抑制率达90％以上. 其中5b, 5e, 5h在187.5 g/ha剂量时, 仍具有良好的除草活性, 抑制率达90％以上.     

Design,Synthesis, and Herbicidal Evaluation of Novel Uracil Derivatives Containing 1,3,4‐Thiadiazolyl Moiety

Uracil derivatives, such as commercial herbicides butafenacil and benzfendizone, have been identified as inhibitors of protoporphyrinogen oxidase (Protox, EC 1.3.3.4), one of the most important action targets of herbicides. In order to search for novel Protox inhibitors with high efficacy, broad‐spectrum activity, and safety to crops, commercially herbicide butafenacil was used as lead compound for further optimization; a series of title compounds 8a , 8b , 8c , 8d , 8e , 8f , 8g , 8h , 8i , 8j , 8k , 8l , 8m , 8n were designed and synthesized by introducing 1,3,4‐thiadiazole moiety into the uracil skeleton. The preliminary bioassays (in vitro) indicated that most of the target compounds displayed better inhibition against Echinochloa crus‐galli than Brassica campestris. The greenhouse bioassay results indicated that most of the compounds tested exhibited good‐to‐excellent herbicidal activities against B. campestris, A. retroflexus, E. crusgalli, and D. sanguinalis in pre‐emergence treatment at a dose of 1500 g/ha, for example, compound 8d showed 100% inhibition against the four plants tested in pre‐emergence treatment at a dose of 1500 g/ha. So, these types of skeletons can be used as valuable lead compounds for the development of a pre‐emergent herbicide.     

In Silico Structure-Guided Optimization and Molecular Simulation Studies of 3-Phenoxy-4-(3-trifluoromethylphenyl)pyridazines as Potent Phytoene Desaturase Inhibitors

A series of novel 3-phenoxy-4-(3-trifluoromethylphenyl)pyridazines 2–5 were designed, based on the structure of our previous lead compound 1 through the in silico structure-guided optimization approach. The results showed that some of these new compounds showed a good herbicidal activity at the rate of 750 g ai/ha by both pre- and post-emergence applications, especially compound 2a, which displayed a comparable pre-emergence herbicidal activity to diflufenican at 300–750 g ai/ha, and a higher post-emergence herbicidal activity than diflufenican at the rates of 300–750 g ai/ha. Additionally, 2a was safe to wheat by both pre- and post-emergence applications at 300 g ai/ha, showing the compound’s potential for weed control in wheat fields. Our molecular simulation studies revealed the important factors involved in the interaction between 2a and Synechococcus PDS. This work provided a lead compound for weed control in wheat fields.     

Synthesis and biological activity of novel phenyltriazolinone derivatives

Phenyltriazolinones are one of the most important classes of herbicides targeting the protoporphyrinogen oxidase enzyme. A series of triazolinone derivatives containing a strobilurin pharmacophore were designed and synthesized with the aim of discovering new phenyltriazolinone analogues with high activity. The herbicidal activity of the synthesized compounds was assayed and some of the test compounds displayed moderate herbicidal activity at 150 g ai/ha.     

Synthesis and Herbicidal Activities of 3‐(4‐Chloro‐2‐fluoro‐5‐substituted phenyl)benzo[d][1,2,3]triazin‐4(3H)‐one Derivatives

A series of 3‐phenyl benzo[d][1,2,3]triazin‐4(3H)‐one derivatives were synthesized through the condensation of phenol E and alkyl (alkenyl, alkynyl) chlorides (bromides, iodide) or alkyl chloroacetates or N‐alkyl chloroacetamides using K₂CO₃ as the acid acceptor in N,N‐dimethylformamide. Phenol E was prepared from starting material, 5‐amino‐2‐chloro‐4‐fluorophenyl ethyl carbonate, in four steps involving in amidation, reduction, diazotization, and deprotecting‐group reaction. The herbicidal activities of the title compounds were tested against two dicotyledonous plants and two monocotyledonous plants, in which some of them exhibited high herbicidal activities against two dicotyledonous plants in preemergence and postemergence treatments. Moreover, when the dosage was decreased to 180 and 90 g/ha, compounds F1 , F8 , and F9 showed highly selective inhibitory activities against amaranth pigweed, alfalfa, asteraceae, field sowthistle, morning glory, purslane, and velvetleaf in postemergence treatment but had no herbicidal efficacy on rape except F1 , suggesting that it be possible to find a kind of herbicides to inhibit dicotyledonous weeds in the field of dicotyledonous crops with the same genus as aforementioned weeds.     

Design,synthesis and herbicidal activity of novel cyclic phosphonates with diaryl ethers containing pyrimidine

Abstract

Thirteen novel cyclic phosphates were rationally designed and synthesized by introducing diary ethers containing pyrimidine. All the target compounds were characterized by ¹H, ¹³C, ³¹P NMR and HRMS. The test of herbicidal activity indicated that most of the compounds showed good herbicidal activities against Amaranthus retroflexus. The compounds IA-2 (1-(5,5-dimethyl-2-oxido-1,3,2-dioxaphosphinan-2-yl)propyl-2-((4,6-dimethoxypyrimidin-2-yl)oxy)benzoate) and IA-3 ((5,5-dimethyl-2-oxido-1,3,2-dioxaphosphinan-2-yl)(phenyl)methyl-2-((4,6-dimethoxypyrimidin-2-yl)oxy)benzoate) exhibited remarkable post-emergency herbicidal activity against the tested monocotyledonous weed at the dosage of 112.5?g ai/ha.     

Synthesis and biological activity of novel 2-methyl-4-trifluoromethyl-thiazole-5-carboxamide derivatives

Nine novel 2-methyl-4-trifluoromethylthiazole-5-carboxamide derivatives were designed and synthesized utilizing ethyl 4,4,4-trifluoroacetoacetate as a starting material. Subsequently, the biological activity of the compounds was evaluated in the greenhouse. Results indicated that all of the compounds have some fungicidal and insecticidal activity but no herbicidal activity. Compound 1 has fungicidal activity with 90% control of tomato late blight at 375 g ai/ha, while two compounds 2F and 2H show insecticidal activity with 80 and 100% control, respectively, against potato leafhopper at 600 g ai/ha.     

Synthesis and Biological Activity of Ethyl 4‐Alkyl‐2‐(2‐(substituted phenoxy)acetamido)thiazole‐5‐carboxylate

A series of novel ethyl 4‐(methyl or trifluoromethyl)‐2‐(2‐(substituted phenoxy)acetamido)thiazole‐5‐carboxylates 7a , 7b , 7c , 7d , 7e and 8f , 8g , 8h , 8i , 8j , 8k , 8l , 8m , 8n , 8o , 8p , 8q , 8r were synthesized, and their structures were confirmed by IR, ¹H‐NMR, MS spectra and elemental analysis. The results of preliminary bioassays show that some of the title compounds exhibit moderate to good herbicidal activities. Compared with the fluorine free compounds 7a , 7b , and 7e , the compounds bearing fluorine 8g , 8j , and 8q showed higher herbicidal activities with 70–100% inhibition against Capsella bursa‐pastoris, Amaranthus restroflexus, and Eclipta prostrata at the dosage of 150 g/ha, which indicated that the trifluoromethyl on the thiazole ring was beneficial for the herbicidal activity. Furthermore, compounds 8f , 8g , 8h , 8i , 8j , 8k , 8l , 8m , 8n , 8o , 8p , 8q , 8r were tested for fungicidal activity against Pseudoperonospora cubensis at 500 µg/mL. Compounds 8f and 8q showed the best fungicidal activity with more than 80% inhibition.     

Synthesis and Biological Activity of 1‐(Substituted phenoxyacetoxy)‐1‐(pyridin‐2‐yl or thien‐2‐yl)methylphosphonates

A series of novel O,O‐dimethyl 1‐(substituted phenoxyacetoxy)‐1‐(pyridin‐2‐yl or thien‐2‐yl)methylphosphonates 6a , 6b , 6c , 6d , 6e , 6f , 6g , 6h , 6i , 6j , 6k , 6l , 6m , 6n and 7a , 7b , 7c , 7d were synthesized. Their structures were confirmed by IR, ¹H NMR, mass spectroscopy, and elemental analyses. The results of preliminary bioassays show that some of the title compounds exhibit moderate to good herbicidal and fungicidal activities. For example, the title compounds 6a , 6c , 6l , 6m , and 7d possess 90–100% inhibition against most of the tested plants at the dosage of 1500 g ai/ha, whereas the title compounds 6b , 6g , 6h and 6n possess 92–100% inhibition against Fusarium oxysporum, Phyricularia grisea, Botrytis cinereapers, Gibberella zeae, Sclerotinia sclerotiorum, and Cercospora beticola at the concentration of 50 mg/L.     

Synthesis and Herbicidal Activity of Novel N‐(2‐Fluoro‐5(3‐methyl‐2,6‐dioxo‐4‐(trifluoromethyl)‐2,3‐dihydro‐pyrimidin‐1(6H)‐yl)phenyl)‐2‐phenoxyacetamide Derivatives

Thirteen novel N‐(2‐fluoro‐5‐(3‐methyl‐2,6‐dioxo‐4‐(trifluoromethyl)‐2,3‐dihydropyrimidin‐1(6H)‐yl)phenyl)‐2‐phenoxy)acetamides were designed and synthesized utilizing 4‐fluoro‐aniline and ethyl 3‐amino‐4,4,4‐trifluoro‐but‐2‐enoate as starting materials. The chemical structures of all compounds were confirmed by ¹H NMR, IR, mass spectrum and elemental analyses. Subsequently, the herbicidal activities of the as‐prepared compounds were evaluated in the greenhouse. Bioassay results indicated that most of compounds had better herbicidal activities against dicotyledonous weeds. Among all the tested compounds, compounds 4a – 4i showed good herbicidal activities at both pre‐emergence and post‐emergence treatment against two or three kinds of dicotyledonous weeds, such as Abutilon theophrasti Medic, Amaranthus ascendens L, and Chenopodium album L at the dosage of 75 g ai/ha.     

Synthesis, Herbicidal Activity, and Structure-Bioactivity Relationship of Pyridyl-Containing 2-Phenyliminothiazolidines

Summary. A series of novel 2-phenyliminothiazolidine derivatives were designed and synthesized. All title compounds were characterized by ¹H NMR and, in some cases, by ¹³C NMR, IR, and HRMS. Their agricultural bioactivities were evaluated and some of these compounds exhibited efficient herbicidal activities against Echinochloa crusgalli, Sorghum vulgare, Digitaria sanguinalis, Eclipta prostrasta, Cucumis sativus, and Brassica campestris at 50 μg/cm³. Analysis of the quantitative structure-activity relationship (QSAR) showed that the electronic parameter was the main factor to affect herbicidal activities.     

新型4,4-二甲基异噁唑-3-酮衍生物的合成及生物活性研究

以Baylis-Hillman加成物为起始原料,设计并合成了5个结构新颖的4,4-二甲基异唑-3-酮衍生物。所合成的化合物经IR、1HNMR和元素分析确证。生物活性测试结果表明,所合成的目标产物在2000gai/ha的剂量下均具有较好的除草活性。中间体1-(2,4-二氯苯基)-2-溴甲基丙烯酸乙酯具有杀虫活性,在600gai/ha的剂量下对朱砂叶螨防效为100%。     

Synthesis and biological activity of ethyl 2-(5-methyl-3-arylisoxazole-4-carboxamido)-4-alkylthiazole-5-carboxylate

A series of novel ethyl 2-(5-methyl-3-arylisoxazole-4-carboxamido)-4-alkylthiazole-5-carboxylates I-1-6 were synthesized. The structures of all target compounds were characterized by ¹H NMR, ¹³C NMR, IR, MS and elemental analyses. Their fungicidal and herbicidal activities were evaluated. The results of preliminary bioassays show that the title compounds I-4 possess 20–50% inhibition against most of the tested plants at the dosage of 150 g ai/ha, while the title compounds I-1-5 possess 32–58% inhibition against FusaHum graminearum, Thanatephorus cucumeris, Botrytis cinereapers and Fusarium oxysporum in vitro at the concentration of 100 mg/L.     

Design,Synthesis and Herbicidal Activities of Tetrahydroisoindoline‐1,3‐dione Derivatives Containing Alkoxycarbonyl Substituted 2‐Benzoxazolinone

Several different alkoxycarbonyl‐substituted 2‐benzoxazolinone moieties have been incorporated into a tetrahydroisoindoline‐1,3‐dione scaffold to provide 25 compounds ( 1a – 1u and 2a – 2d ). The structures of these compounds were confirmed by ¹H and ¹³C NMR, HRMS and X‐ray single‐crystal diffraction. Some of these compounds ( 1g , 1h , 1j , 1k ) exhibited excellent herbicidal activities against Abutilon theophrasti, Amaranthus retroflexus and Echinochloa crus‐galli at a rate of 375 g AI·ha^?1. Among them, compounds 1h and 1j displayed the best post‐emergence herbicidal effect against Abutilon theophrasti with ED₅₀ values of 1.8 and 5.3 g AI·ha^?1, respectively, which are superior to that of the commercial acifluorfen (44.3 g AI·ha^?1). Field trials demonstrated that compound 1h exhibited similar herbicidal activity to a high concentration atrazine, and found to be safer for maize than atrazine. The results of this study therefore show that compound 1h could potentially be used as a post‐emergence herbicide for maize fields.     

N-杂环甲基2-(4-杂芳氧基苯氧基)丙酰胺的合成及除草活性

以2-(4-羟基苯氧)丙酸为原料,设计合成了16个新的手性N-杂环甲基2-(4-杂芳氧基苯氧基)丙酰胺化合物,其化学结构经核磁共振、色谱-质谱、红外光谱及元素分析确证.初步生物活性测定结果表明,合成的化合物在2.25×103g/ha剂量时对单子叶杂草马唐(Digitaria sanguinalis)、稗草(Echinochloa crus-galli)及狗尾草(Setaria viridis)等均具有90%以上的活性;进一步活性及作物安全性测试表明,化合物(R)-(+)-N-[(6-氯吡啶-3-基)甲基]-2-[4-(3-氯-5-三氟甲基吡啶-2-基氧基)苯氧基]丙酰胺(2b)的除草活性高于噁唑酰草胺,且对水稻茎叶处理安全,同时对水稻田主要杂草千金子的活性远高于氰氟草酯;化合物的除草活性与立体构型有关,R构型为活性构型.     

具有除草活性的吡唑啉并四嗪酮衍生物的设计、合成与定量构效关系的研究

设计合成了一系列未见文献报道的4-乙氧羰基-1,7-二氢-1-取代苯基-5-(未)取代吡唑啉[5,1-d][1,2,3,5]四嗪-7-酮衍生物, 其结构均经过¹H NMR、IR和元素分析表征. 生测结果显示, 与已报道的化合物相比, 它们表现出较好的除草活性. 定量的结构与活性关系研究表明, 它们的除草活性与取代基的立体效应参数和疏水性参数呈现很好的相关性, 相关系数r大于0.8. 当作用对象为油菜时, 化合物的活性可能主要与取代基R¹的摩尔分子折射和取代基R²的疏水性参数有关. 当取代基R¹的摩尔分子折射参数为1.452时, 相应化合物可能具有对油菜最高的除草活性; 当作用对象为稗草时, 化合物的活性主要与取代基R²疏水性参数和Taft (Es)参数有关.     

Design,Synthesis, and Bioactivity Evaluation of Novel 3‐(Substituted Phenoxy)‐6‐Methyl‐4‐(3‐Trifluoromethylphenyl) Pyridazine Derivatives

Using 3‐(4‐cyano phenoxy)‐6‐methyl‐4‐(3‐trifluoromethylphenyl) pyridazine (compound A ) as a leading compound, a total of 24 novel 3‐(substituted phenoxy)‐6‐methyl‐4‐(3‐trifluoromethylphenyl) pyridazine derivatives containing two electron‐withdrawing groups on the benzene ring (acylamine and oxime ether) were synthesized. Their herbicidal, insecticidal activities were bioassayed, and the herbicidal activity of compound CD-2 against Brassica campestris was 97.6% at 300 g/ha, which was better than the commercial herbicide diflufenican at the this concentration and is equal to the activity of the leading compound A . Compound CD-4 , CD-5 , CJ-3 , and CJ-5 displayed excellent insecticidal activity against Aphis laburni Kaltenbach (>95%). The results show that the oxime ether substitutions exhibit better bleaching and herbicidal activity than the acylamine ones. The bleaching and herbicidal activity of para‐position substitutions is better than the meta‐position ones. It seems that the para‐position on the benzene ring of oxime ether pyridazine derivatives is one of the key active sites that affect their herbicidal activities.     

Synthesis and Herbicidal Activity of Novel 4‐Acyl‐2,5‐disubstituted‐3‐hydroxypyrazoles and 4‐Arylcarbonyl‐3‐substitutedisoxazol‐5‐ones

Two series of novel 4‐acyl‐2,5‐disubstituted‐3‐hydroxypyrazoles 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h and 4‐arylcarbonyl‐3‐substitutedisoxazol‐5‐ones 7a , 7b , 7c , 7d , 7e , 7f , 7g , 7h , 7i were synthesized by the Scotton–Baumann reaction of 2,5‐disubstituted‐2,4‐dihydro‐pyrazol‐3‐ones 1 or 3‐substituted‐4H‐isoxazol‐5‐ones 6 and various acyl chlorides, followed by the Fries rearrangement in the presence of calcium hydroxide and calcium oxide as the catalyst. Their structures were confirmed by IR, ¹H NMR, mass spectroscopy, and elemental analyses. ¹H NMR indicated that compounds 3 existed in enol forms and compounds 7 in keto configurations. The results of preliminary bioassays showed that some of the title compounds 3 and 7 exhibited moderate to good herbicidal activities against Brassica campestris L. at the concentration of 100 mg/L. Isoxazole compounds 7 showed better herbicidal activity against B. campestris L. than pyrazole compounds 3 did at the concentration of 100 mg/L. Moreover, most of the isoxazole compounds displayed higher herbicidal activity against B. campestris L. than Echinochloa crus‐galli. However, these compounds showed weak herbicidal activities at the concentration of 10 mg/L.     

Synthesis and Herbicidal Activity of 3-Acetyl-4-hydroxy-2,1-benzothiazine Derivatives

In order to develop a novel herbicide containing the 2,1-benzothiazine motif, a series of 3-acetyl-4- hydroxy-2,1-benzothiazine derivatives was synthesized. All the target compounds were confirmed by 1H NMR,13C NMR, and high-resolution mass spectrometry(HRMS).In addition,the crystal structure of compoimd T27 was detemiined by single crystal X-ray diflraction. The bioassay results showed that some of the 3-acetyl-4-hydroxy- 2,1-benzothiazine derivatives(T13, T15, T22, and T24) showed good herbicidal activity at a dosage of 100 pg/mL. Among them,compounds T22 and T24 showed promising post-emergent herbicidal activities against Brassica campestris and Amaranthus retroflexus even at a dosage of 375 g/ha(1ha=104 m^2) in the greeiiliouse test. Studies on the structure-activity relationship demonstrated that the type of acetyl group played an important role in the herbicidal activity, and that the introduction of a phenoxyacetyl group at the 3-position of 2,1-beiizothiazine was beneficial in improving the herbicidal activity. The present study also indicated that 3-phenoxyacetyl-4-hydroxy-2,1-benzothiazine could be a potential lead compound for fiirther development of novel 2,1 -benzothiazine-containing herbicides.     

Synthesis and Herbicidal Activity of Novel Pyrimidinyl Derivatives Containing an α-Amino Phosphonate Moiety

In order to find novel pyrimidinyl carboxylic acid analogs with high activity and low toxicity, a series of novel pyrimidinyl derivatives containing an α-amino phosphonate moiety 5 was synthesized by the condensation of 4-(4,6-dimethoxypyrimidin-2-yloxy)phenoxyacetic 3a or propionic acids 3b with dialkyl α-amino substitutedbenzyl phosphonates 4. Their structures were characterized by spectroscopic data (IR, ¹H NMR, ³¹P NMR, MS) and elemental analyses. The results of preliminary herbicidal activities (in vitro) showed that most of these compounds exhibited higher herbicidal activities against dicotyledonous weeds (Brassica campestris L) than monocotyledonous weeds (Echinochloa crus-galli). Further bioassays (in vivo) indicated that some of compounds 5 possessed selective herbicidal activity against amaranth pigweed (A. retroflexus) in post-emergence treatment.

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