WO2008104101A1

WO2008104101A1 - 1-(3-methyl-4-fluoro) phenyl-1-methylcyclopropane compounds and use thereof

Info

Publication number: WO2008104101A1
Application number: PCT/CN2007/000641
Authority: WO
Inventors: Bin Li; Dong Xiang; Naiguo Si; Hongfei Wu; Jing Yuan; Ruixiu Yang; Zhinian Li
Original assignee: Sinochem Corporation; Shenyang Research Institute Of Chemical Industry
Priority date: 2007-02-28
Filing date: 2007-02-28
Publication date: 2008-09-04

Abstract

1-(3-methyl-4-fluoro) phenyl-1-methylcyclopropane compounds of formula (I) and use thereof are disclosed, wherein: X is N or CH; W is O or NH; B1 bond and adjacent phenyl are of cis- or trans- form; B2 bond and B1 bond are of cis- or trans- form. Said compounds of formula (I) possess activities for controlling fungi and pests and can be used for preventing plant diseases and insect pests.

Description

1- (3-甲基 -4-氟）苯基 -1-甲基环丙垸类化合物及其应用 1-(3-methyl-4-fluoro)phenyl-1-methylcyclopropene compound and application thereof

技术领域 Technical field

本发明属于杀菌、杀虫剂领域，涉及一种 1- (3-甲基 -4-氟）苯基 -1-甲基环丙烷类化合物及其应用。背景技术 The invention belongs to the field of bactericidal and insecticides, and relates to a 1-(3-methyl-4-fluoro)phenyl-1-methylcyclopropane compound and application thereof. Background technique

由于杀菌剂或杀虫剂在使用一段时间后，病害或害虫会对其产生抗性，因此，需要不断发明新型的和改进的具杀菌或杀虫活性的化合物和组合物。 Since fungicides or insecticides are resistant to diseases or pests after a period of use, it is necessary to continuously invent new and improved compounds and compositions having bactericidal or insecticidal activity.

某些具有杀菌活性的 1- (单卤取代或 2， 4-或 2， 6-二卤取代）苯基 _1-甲基环丙烷类化合物的制备已有报道（WO0187826Al )。但如本发明所示的 1- (3-甲基 -4-氟）苯基 -1-甲基环丙垸类化合物的制备及其杀菌、杀虫活性未见公幵。发明内容 The preparation of certain bactericidal 1- (monohalo-substituted or 2,4- or 2,6-dihalo-substituted) phenyl 1-1-methylcyclopropane compounds has been reported (WO0187826 Al). However, the preparation of the 1-(3-methyl-4-fluoro)phenyl-1-methylcyclopropene compound as shown in the present invention and its bactericidal and insecticidal activity are not disclosed. Summary of the invention

本发明的目的在于提供一种在很小的剂量下就可以控制多种病虫害的 1- (3-甲基 -4-氟）苯基 -1-甲基环丙烷类化合物，它可应用于农业上以防治作物的病害和虫害。 The object of the present invention is to provide a 1-(3-methyl-4-fluoro)phenyl-1-methylcyclopropane compound which can control various pests and diseases at a small dose, which can be applied to agriculture. To control crop diseases and pests.

本发明的技术方案如下： The technical solution of the present invention is as follows:

本发明提供了一种 1- (3-甲基 -4-氟）苯基 -1-甲基环丙垸类化合物，如通式 I所示： The present invention provides a 1-(3-methyl-4-fluoro)phenyl-1-methylcyclopropene compound as shown in Formula I:

其中：

among them:

X为 N或 CH; X is N or CH;

W为 0或 NH; W is 0 or NH;

B1键与邻近的苯环为反式或顺式； B2键与 B1键为反式或顺式。 The B1 bond is trans or cis to the adjacent benzene ring; the B2 bond and the B1 bond are trans or cis.

本发明中较为优选的化合物为通式 I中： A more preferred compound in the present invention is in the formula I:

X为 N或 CH; X is N or CH;

W为 0或 NH; W is 0 or NH;

B1键与邻近的苯环为反式或顺式; B2键与 B1键为反式。 The B1 bond is trans or cis to the adjacent benzene ring; the B2 bond and the B1 bond are trans.

本发明中更为优选的化合物为通式 I中： More preferred compounds of the invention are of formula I:

X为 N; W为 NH; X is N; W is NH;

B l键与邻近的苯环为反式； B2键与 B 1键为反式。 The B l bond is trans to the adjacent benzene ring; the B 2 bond and the B 1 bond are trans.

本发明的通式化合物 I可由如下方法制备： The compound of the formula I of the present invention can be produced by the following method:

IV IV

原料 II (参考下列文献制备：徐克勋主编《精细有机化工原料及中间体手册》， P.3-199,化学工业出版社出版）与 ΠΙ (参考下列文献制备： Smissman E. E. et al. J. Org. Chem. 1964, 29, 3161 ) , 在碱的存在下如氢氧化钠、氢氧化钾、甲醇钠、叔丁醇钠或叔丁醇钾等，溶于适宜的溶剂如二氯甲烷、氯仿、四氯化碳、己烷、苯、甲苯、甲醇、乙醇、乙酸乙酯、乙腈、 THF、二氧六环、 DMF或二甲基亚砜等，温度为 -10 °C到沸点下反应 0.5-48小时制得中间体羧酸盐，羧酸盐经适宜的酸如硫酸、盐酸或醋酸等酸化后，在酸性条件下脱羧制得化合物 IV。 Raw material II (Refer to the following literature preparation: Xu Kexun's "Handbook of Fine Organic Chemicals and Intermediates", P.3-199, published by Chemical Industry Press) and ΠΙ (Refer to the following literature: Smissman EE et al. J. Org. Chem. 1964, 29, 3161 ), in the presence of a base such as sodium hydroxide, potassium hydroxide, sodium methoxide, sodium t-butoxide or potassium t-butoxide, dissolved in a suitable solvent such as dichloromethane, chloroform, tetra Carbon chloride, hexane, benzene, toluene, methanol, ethanol, ethyl acetate, acetonitrile, THF, dioxane, DMF or dimethyl sulfoxide, etc., the temperature is -10 ° C to the boiling point of the reaction 0.5-48 The intermediate carboxylate is obtained in an hour, and the carboxylate is acidified by a suitable acid such as sulfuric acid, hydrochloric acid or acetic acid, and then decarboxylated under acidic conditions to obtain a compound IV.

化合物 IV与三甲基氧化锍卤化物（可由市场上购买到， H表示卤，选自碘、溴或氯)，在碱的存在下如氢氧化钠、氢氧化钾、甲醇钠、叔丁醇钠或叔丁醇钾等，溶于适宜的溶剂如二氯甲烷、氯仿、四氯化碳、己烷、苯、甲苯、乙酸乙酯、乙腈、 THF、二氧六环、 Compound IV and trimethylsulfoxonium halide (commercially available, H for halogen, selected from iodine, bromine or chlorine), in the presence of a base such as sodium hydroxide, potassium hydroxide, sodium methoxide, tert-butanol Sodium or potassium t-butoxide, etc., soluble in a suitable solvent such as dichloromethane, chloroform, carbon tetrachloride, hexane, benzene, toluene, ethyl acetate, acetonitrile, THF, dioxane,

沸点下反应 0.5-48小时制得化合物 1-1。溶剂可为二氯甲烷、氯仿、四氯化碳、己垸、苯、甲苯、甲醇、乙醇、乙酸乙酯、乙腈、 THF、二氧六环、 DMF或二甲基亚砜等。加入酸类物质，如硫酸、盐酸或醋酸等对反应有利。

The compound 1-1 was obtained by reacting at the boiling point for 0.5 to 48 hours. The solvent may be dichloromethane, chloroform, carbon tetrachloride, hexane, benzene, toluene, methanol, ethanol, ethyl acetate, acetonitrile, THF, dioxane, DMF or dimethyl sulfoxide. The addition of an acid such as sulfuric acid, hydrochloric acid or acetic acid is advantageous for the reaction.

1-1 1-2 1-1 1-2

化合物 1-1 在适宜的溶剂中，与甲胺水溶液，温度为 -10°C到沸点下反应 0.5-48 小时制得化合物 1-2。溶剂可为二氯甲烷、氯仿、四氯化碳、己烷、苯、甲苯、甲醇、乙醇、乙酸乙酯、乙腈、 THF、二氧六环、 DMF或二甲基亚砜等。 Compound 1-1 is obtained by reacting with a methylamine aqueous solution at a temperature of -10 ° C to a boiling point for 0.5 to 48 hours in a suitable solvent. The solvent may be dichloromethane, chloroform, carbon tetrachloride, hexane, benzene, toluene, methanol, ethanol, ethyl acetate, acetonitrile, THF, dioxane, DMF or dimethyl sulfoxide.

本发明的通式化合物 1-1也可由如下方法制备： The compound of the formula 1-1 of the present invention can also be produced by the following method:

V VII V VII

化合物 V与羟胺盐酸盐（可由市场上购买得到），在碱的存在下如碳酸钠、碳酸钾、氢氧化钠、氢氧化钾、甲醇钠、叔丁醇钠、叔丁醇钾或三乙胺等，溶于适宜的溶剂如二氯甲烷、氯仿、四氯化碳、己烷、苯、甲苯、甲醇、乙醇、乙酸乙酯、乙腈、 THF、二氧六环、 DMF或二甲基亚砜等，温度为 -1^{Λ ¾} ' 0.5-48小时制得化合物 VII。 ' . ' Compound V and hydroxylamine hydrochloride (commercially available), in the presence of a base such as sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, sodium methoxide, sodium t-butoxide, potassium t-butoxide or triethyl b. Amine, etc., soluble in a suitable solvent such as dichloromethane, chloroform, carbon tetrachloride, hexane, benzene, toluene, methanol, ethanol, ethyl acetate, acetonitrile, THF, dioxane, DMF or dimethyl Compound VII is obtained by sulfone or the like at a temperature of -1 ^{Λ 3⁄4} ' for 0.5 to 48 hours. ' . '

VII VIII . 1-1 化合物 VII与 VIII (可 ώ市场上购买到），在碱的存在下如碳酸钠、碳酸钾、氢

VII VIII . 1-1 Compounds VII and VIII (available commercially), in the presence of a base such as sodium carbonate, potassium carbonate, hydrogen

'氧化钠、氢氧化钾、甲醇钠、叔丁醇钠、叔丁醇钾或三乙胺等，.溶于适宜的溶剂如二氯甲 iL完、氯仿、四氯化碳、己烷、苯、申苯、乙酸乙酯、乙腈、 THF、二氧六环、 DMF 或二甲基亚砜等，温度为 -10,°C到沸点下反应 0.5- 小时制得化合物 1-1。根 IS反应条件的差异或起始原料的不同，化合物 V、 VII、化合物 1-1和化合物 1-2 均有可能存在立体异构现象。例如 B1键与邻近的苯环可以为反式或顺式； B2键与 B1键可以为反式或顺式。通过选择适当的起始原料或控制反应条件，可以得到一种异构体过量的产物或单一异构体。也可以通过对粗产物进行常规手段的分离，例如通过柱色谱、重结晶等方法，得到单一异构体。这些异构体的结构可通过 X-射线单晶衍射，核磁共振等常规分析方法确定。 'Sodium oxide, potassium hydroxide, sodium methoxide, sodium t-butoxide, potassium t-butoxide or triethylamine, etc., soluble in suitable solvents such as dichloromethane, chloroform, carbon tetrachloride, hexane, benzene The compound 1-1 is obtained by reacting benzene, ethyl acetate, acetonitrile, THF, dioxane, DMF or dimethyl sulfoxide at a temperature of -10, ° C to the boiling point for 0.5-hour. Stereoisomerism may exist in compounds V, VII, compound 1-1 and compound 1-2 depending on the difference in the reaction conditions of the roots or the starting materials. For example, the B1 bond and the adjacent benzene ring may be trans or cis; the B2 bond and the B1 bond may be trans or cis. An isomer excess product or a single isomer can be obtained by selecting an appropriate starting material or controlling the reaction conditions. The single isomer can also be obtained by conventional means of separation of the crude product, for example by column chromatography, recrystallization, and the like. The structure of these isomers can be determined by conventional analytical methods such as X-ray single crystal diffraction, nuclear magnetic resonance, and the like.

表 1列出了部分通式 I化合物的结构和物理性质。分通式 I化合物的结构及物理性质 Table 1 lists the structural and physical properties of some of the compounds of formula I. Structure and physical properties of compounds of the general formula I

本发明的通式 I化合物具有高杀菌活性。现已发现，通式 I化合物对病菌如稻瘟病、霜霉病、白粉病等有较好的防治效果，尤其对水稻中的重要病害稻瘟病具有意想不到的高活性。因此，本发明还包括通式 I化合物用于防治植物病害的用途。 The compounds of the formula I according to the invention have a high bactericidal activity. It has been found that the compound of the formula I has a good control effect against pathogenic bacteria such as rice blast, downy mildew, powdery mildew, and the like, and has an unexpectedly high activity especially for rice rickets which are important diseases in rice. Accordingly, the present invention also encompasses the use of a compound of formula I for controlling plant diseases.

本发明的通式 I化合物具有意想不到的高杀虫活性。对害虫如朱砂叶螨和蚕豆蚜有很好的防治效果。因此，本发明还包括通式 I化合物用于防治虫害的用途。 The compounds of formula I of the present invention have unexpectedly high insecticidal activity. It has a good control effect on pests such as cinnabar leafhopper and broad bean mites. Accordingly, the present invention also encompasses the use of a compound of formula I for controlling pests.

由于本发明的通式 I化合物中含氟的苯环上同时含有甲基，根据已知的有机化学和环境化学知识，可以预期这类化合物与现有技术中含卤苯环类化合物相比，具有更好的环境相容性。 Since the fluorine-containing benzene ring of the compound of the formula I of the present invention contains a methyl group at the same time, according to known knowledge of organic chemistry and environmental chemistry, it is expected that such a compound is compared with the halogen-containing benzene ring compound of the prior art. Has better environmental compatibility.

本发明还包括以通式 I化合物作为活性组分的杀菌、杀虫组合物。该组合物中活性组分的重量百分含量在 1-99%之间。组合物中还包括农业上可接受的载体。 . 本发明的组合物可以制剂的形式施用。通式 I化合物作为活性组分溶解或分散于载体中或配制成制剂以便作为杀菌或杀虫剂使用时更易于分散。例如：这些化学制剂可被制成可湿性粉剂或乳油。在这些组合物中，至少加入一种液体或固体载体，并且当需要时可以加入适当的表面活性剂。 The present invention also encompasses a bactericidal, insecticidal composition having a compound of the formula I as an active ingredient. The active ingredient in the composition is present in an amount between 1 and 99% by weight. Also included in the composition are agriculturally acceptable carriers. The composition of the invention may be administered in the form of a formulation. The compound of the formula I is dissolved or dispersed as an active ingredient in a carrier or formulated to be more easily dispersed when used as a bactericidal or insecticide. For example, these chemicals can be formulated as wettable powders or emulsifiable concentrates. In these compositions, at least one liquid or solid carrier is added, and a suitable surfactant may be added as needed.

本发明的技术方案还包括防治病害的方法：将本发明的杀菌组合物施于所述的病害生长介质上，如施于需要控制病害的植物上。通常选择的较为适宜有效量为每公顷. 5克到 5000克，.优选有效量为每公顷 10克到 500克。 . ·. The technical solution of the present invention also includes a method of controlling a disease by applying the bactericidal composition of the present invention to the disease growth medium, such as to a plant in need of controlling the disease. A more suitable effective amount is usually selected from 5 g to 5000 g per hectare. The preferred effective amount is from 10 g to 500 g per hectare. .

本发明的技术方案还包括防治虫害的方法：将本发明的杀虫组合物施于所述的害虫或其生长介质上，如施于需要控制虫害的植物上。通常选择的较为适宜有效量为每公顷 10克到 10000克，优选有效量为每公顷 100克到 5000克。, The technical solution of the present invention further includes a method for controlling pests: applying the pesticidal composition of the present invention to the pest The insect or its growth medium, such as applied to plants that need to control pests. A more suitable effective amount is usually selected from 10 grams to 10,000 grams per hectare, preferably from 100 grams to 5000 grams per hectare. ,

对于某些应用，可在本发明的杀菌、杀虫组合物中加入一种或多种其它的杀菌剂、杀虫剂、除草剂、植物生长调节剂或肥料等，由此可产生附加的优点或效果。 For some applications, one or more other fungicides, insecticides, herbicides, plant growth regulators or fertilizers, etc. may be added to the bactericidal, pesticidal compositions of the present invention, thereby providing additional advantages Or effect.

应明确的是，在本发明的权利要求所限定的范围内，可进行各种变换和改动。附图说明 It is to be understood that various changes and modifications may be made within the scope of the appended claims. DRAWINGS

图 1为化合物 1B的分子结构图。具体实施方式 Figure 1 is a molecular structure diagram of Compound 1B. detailed description

下列合成实例、生测试验结果可用来进一步说明本发明，但不意味着限制本发明。合成实例 The following synthetic examples, bioassay results can be used to further illustrate the invention, but are not meant to limit the invention. Synthesis example

1、中间体反式 4- (3-甲基 -4-氟苯基） -戊 -3-烯 -2-酮的合成： 1. Synthesis of intermediate trans 4-(3-methyl-4-fluorophenyl)-pent-3-en-2-one:

在 2000毫升的反应瓶中加入 3-甲基 -4-氟苯乙酮（109.4克， 0.72摩尔），反式 3 一乙氧基一 2—丁烯酸乙酯（115克， 0.72摩尔）和 750毫升无水二甲基甲酰胺。室温搅拌下分批加入叔丁醇钾（89克， 0.79摩尔）。 8小时后将反应液倒入 1000毫升水中，用 2x200毫升乙酸乙酯萃取除去未反应的原料，水相用 6N的盐酸酸化至 pH=2，过滤收集生成的黄色固体，分别用水和石油醚洗涤，得到中间体酸。将中间体酸投入 1000毫升的反应瓶中，加入 500毫升 1N的盐酸，升温至 50°C脱羧，至无气体放出。反应液冷至.室温后用 3 x200毫升乙酸乙酯萃取，有机相经水、饱和食盐水洗涤后，用无水硫酸镁干燥，浓缩后得到 100克棕色油状物，主产物含量 95% (HPLC: 流动相为水：乙腈 =30： 70。以下与此相同），收率 69%。经核磁验证其结构为反式 4- (3- 甲基 -4-氟苯基） -戊 -3-烯 -2-酮。核磁数据如下： ' In a 2000 ml reaction flask was added 3-methyl-4-fluoroacetophenone (109.4 g, 0.72 mol), trans 3-ethoxy-2-carbenoate (115 g, 0.72 mol) and 750 ml of anhydrous dimethylformamide. Potassium tert-butoxide (89 g, 0.79 mol) was added portionwise with stirring at room temperature. After 8 hours, the reaction solution was poured into 1000 ml of water, and the unreacted raw materials were extracted with 2×200 ml of ethyl acetate. The aqueous phase was acidified to pH=2 with 6N hydrochloric acid, and the resulting yellow solid was collected by filtration and washed with water and petroleum ether respectively. , the intermediate acid is obtained. The intermediate acid was placed in a 1000 ml reaction flask, and 500 ml of 1 N hydrochloric acid was added thereto, and the mixture was heated to 50 ° C to decarboxylate until no gas evolved. After the reaction mixture was cooled to room temperature, the mixture was extracted with EtOAc EtOAc EtOAc. : The mobile phase was water: acetonitrile = 30: 70. The same as below), the yield was 69%. The structure was verified to be trans-4-(3-methyl-4-fluorophenyl)-pent-3-en-2-one by nuclear magnetic resonance. The nuclear magnetic data is as follows: '

Ή NMR (300MHz, CDC1₃): 7.845-7.819(m, 2H), 7.098-7.039(t, 1H), 2.583(s, 3H), 2.333(s, 3H)。 NMR NMR (300 MHz, CDC1 ₃ ): 7.845-7.819 (m, 2H), 7.098-7.039 (t, 1H), 2.583 (s, 3H), 2.333 (s, 3H).

2、中间体反式和顺式 l-(2-(4-氟 -3-甲基苯基) -2-甲基环丙基)乙酮的合成：

2. Synthesis of intermediate trans and cis-l-(2-(4-fluoro-3-methylphenyl)-2-methylcyclopropyl)ethanone:

在 1000毫升的反应瓶中加入三甲基氧化锍碘化物（101.5克， 0.461摩尔）、叔丁醇钾（51.8克， 0.461摩尔）和 400毫升二甲基甲酰胺，室温下搅拌 1小时，然后快速加入反式 4- G-甲基 -4-氟苯基） -戊 -3善 2-酮 (88.5克， 0.461摩尔）和 100毫升二甲基甲酰胺形成的溶液，室温反应 8小时。将反应液倒入 200毫升的冰水中，用 3x200毫升乙酸乙酯萃取，合并有机相，经水、饱和食盐水洗涤后，用无水硫酸续干燥，浓缩后得 105克深棕色油状物，其中极性较弱（HPLC: 保留时间较长。以下与此相同）与极性较强 2个主产物的比例为 85 ： 15。总含量为 51%, 收率 56%。通过柱色谱分离（淋洗液：乙酸乙酯：石油醚 =1 ： 40)得 41.5克极性较弱（TLC: Rf值较大。以下与此相同）的油状物，经核磁验证其结构为反式 1-(2-(4-氟 -3-甲基苯基) -2- 甲基环丙基)乙酮；同时还得到 5.2 克极性较强油状物，经核磁验证其结构为顺式 1-(2-(4-氟 -3-甲基苯基) -2-甲基环丙基)乙酮。核磁数据如下： + In a 1000 ml reaction flask, trimethylsulfoxonium iodide (101.5 g, 0.461 mol), potassium t-butoxide (51.8 g, 0.461 mol) and 400 ml of dimethylformamide were added, and stirred at room temperature for 1 hour, then A solution of trans 4-G-methyl-4-fluorophenyl)-pent-3-y-2-one (88.5 g, 0.461 mol) and 100 ml of dimethylformamide was quickly added and allowed to react at room temperature for 8 hours. The reaction mixture was poured into 200 ml of ice water, and extracted with EtOAc (3 mL, EtOAc). The polarity is weak (HPLC: longer retention time, the same as below) and the ratio of the two main products with a strong polarity is 85:15. The total content was 51% and the yield was 56%. By column chromatography (eluent: ethyl acetate: petroleum ether = 1: 40), 41.5 g of an oil having a weak polarity (TLC: Rf value, the same as the above) was obtained, and its structure was verified by nuclear magnetic resonance. Trans-1-(2-(4-fluoro-3-methylphenyl)-2-methylcyclopropyl)ethanone; also obtained 5.2 g of a more polar oil, which was verified by nuclear magnetic resonance. Formula 1-(2-(4-Fluoro-3-methylphenyl)-2-methylcyclopropyl)ethanone. The nuclear magnetic data is as follows:

反式 1-(2-(4-氟 -3-甲基苯基) -2-甲基环丙基)乙酮： 1H NMR (300MHz, CDC1₃): 7.108-7.043(m, 2H)， 6.959-6.900(1, 1H), 2.346(s,3H), 2.266(s, 3H), 2.246-2.219(m, 1H)， l,584(m, 1H), 1.380-1.342(m, 4H)。 Trans 1-(2-(4-Fluoro-3-methylphenyl)-2-methylcyclopropyl)ethanone: 1H NMR (300MHz, CDC1 ₃ ): 7.108-7.043 (m, 2H), 6.959 - 6.900 (1, 1H), 2.346 (s, 3H), 2.266 (s, 3H), 2.246-2.219 (m, 1H), l, 584 (m, 1H), 1.380-1.342 (m, 4H).

顺式 l-(2-(4-氟 -3-甲基苯基) -2-甲基环丙基)乙酮： 1H NMR (300MHz, CDC1₃): 7.032-7.008(m, 2H), 6.908-6.876(t, 1H), 2.248-2.191(m, 4H), 2.048(s, 3H), 1.869-1.837(m_; 1H)， 1.466(s, 3H), 1.167-1.126(m, 1H)。. Cis-l-(2-(4-Fluoro-3-methylphenyl)-2-methylcyclopropyl)ethanone: 1H NMR (300MHz, CDC1 ₃ ): 7.032-7.008 (m, 2H), 6.908 -6.876(t, 1H), 2.248-2.191(m, 4H), 2.048(s, 3H), 1.869-1.837 (m _; 1H), 1.466 (s, 3H), 1.167-1.126 (m, 1H). .

3、化合物 1A和 IB的合成： 3. Synthesis of compound 1A and IB:

1A IB 1A IB

在 1Q0O 毫升的反应瓶中加入反式 1-(2-(4-氟 -3-甲基苯基) -2-甲基环丙基)乙酮 (26.8克， 0.130摩尔），反式 2-甲氧亚胺棊- 2-(2- (胺氧甲基)苯基)乙酸甲酯（34克， L Add trans-(2-(4-fluoro-3-methylphenyl)-2-methylcyclopropyl)ethanone (26.8 g, 0.130 mol) in a 1Q0 mL flask, trans 2- Methoxyimine 棊 2-(2-(Aminooxymethyl)phenyl)acetic acid methyl ester (34 g, L

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Tl79000/.00ZN3/X3d I0W0I/800Z OAV 乙酸乙酯萃取，有机相经水和饱和食盐水洗涤后，用无水硫酸镁干燥，浓缩后得 4.4克浅黄色油状物， HPLC分析主产物含量为 95%, 收率 91 %。通过柱色谱提纯（淋洗液：乙酸乙酯：石油醚 =1 ： 4)得 4.2克白色固体，熔点： 96〜99°C, 经核磁验证其结构为化合物 2A。核磁数据如下： Tl79000/.00ZN3/X3d I0W0I/800Z OAV The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate, and evaporated. Purification by column chromatography (eluent: ethyl acetate: petroleum ether = 1 : 4) afforded white crystals (yield: The nuclear magnetic data is as follows:

化合物 2A: ^]HNMR (300MHz, CDC1₃): 7.472-7.25(m, 1H), 7.413-7.352(m, 2H), 7.198-7.175(m, 1H), 7.078-7.012(m, 2H), 6.951-6.890(t, 1H), 6.785-6.713(d, 1H), 4.992(s, 2H), 3.959(s, 3H), 2.918-2.901(d, 3H), 2.254-2.248(d, 3H), 1.980(s, 3H), 1.725-1.656(m, 1H), 1.356-1.301(m, 1H), 1.169(s, 3H), 1.156-1.089(m, 1H)。 Compound 2A: ^] HNMR (300MHz, CDC1 ₃ ): 7.472-7.25 (m, 1H), 7.413-7.352 (m, 2H), 7.198-7.175 (m, 1H), 7.078-7.012 (m, 2H), 6.951- 6.890(t, 1H), 6.785-6.713(d, 1H), 4.992(s, 2H), 3.959(s, 3H), 2.918-2.901(d, 3H), 2.254-2.248(d, 3H), 1.980( s, 3H), 1.725-1.656 (m, 1H), 1.356-1.301 (m, 1H), 1.169 (s, 3H), 1.156-1.089 (m, 1H).

5、化合物 2B的合成： 5. Synthesis of Compound 2B:

在 100毫升的反应瓶中加入化合物 IB (2.3克， 0.0054摩尔）， 15毫升甲醇和 2.5 毫升 40%甲胺水溶液，在室温下搅拌 6小时后，将反应液倾入 25毫升水中，用 3x20 毫升乙酸乙酯萃取，有机相经水和饱和食盐水洗涤后，用无水硫酸缓干燥，浓缩后得 2.1克浅黄色油状物， HPLC分析主产物含量为 95%，收率 87%。通过柱色谱提纯（淋洗液：乙酸乙酯：石油醚 = 1 ： 4)得 1.9克白色固体，熔点： 96〜98°C，经核磁验证其结构为化合物 2B。核磁数据如下：

Compound IB (2.3 g, 0.0054 mol), 15 ml of methanol and 2.5 ml of 40% aqueous methylamine solution were added to a 100 ml reaction flask. After stirring at room temperature for 6 hours, the reaction solution was poured into 25 ml of water, using 3 x 20 ml. The organic layer was washed with water and a saturated aqueous solution of sodium chloride, and then evaporated to dryness. Purification by column chromatography (eluent: ethyl acetate: petroleum ether = 1 : 4) afforded 1.9 g of white solid, m.p. The nuclear magnetic data is as follows:

化合物 2B : ^]H NMR (300MHz, CDC1₃): 7.470(m, 1H), 7.384-7.353(m, 2H), 7.211-7.085(m, 3H), 6.815-6.784(t, 1H), 6.632-6.701 (d, 1H), 5.018(s, 2H), 3.873(s, 3H), 2.800-2.783(d, 3H), 2.07 l(s, 3H), 2.071-2.047(m, 1H), 1.834(s, 3H), 1.194(s, 3H), 1.205-1.167(m, 1H), 0.960-0.920(m, lH)c Compound 2B: ^] H NMR (300MHz, CDC1 ₃ ): 7.470 (m, 1H), 7.384-7.353 (m, 2H), 7.211-7.085 (m, 3H), 6.815-6.784(t, 1H), 6.632-6.701 (d, 1H), 5.018(s, 2H), 3.873(s, 3H), 2.800-2.783(d, 3H), 2.07 l(s, 3H), 2.071-2.047(m, 1H), 1.834(s, 3H), 1.194(s, 3H), 1.205-1.167(m, 1H), 0.960-0.920(m, lH)c

6、化合物 3A和 3B的合成： 6. Synthesis of compounds 3A and 3B:

〇〇

3A 3B 3A 3B

在 100毫升的反应瓶中加入顺式 l-(2-(4-氟 -3-甲基苯基) -2-甲基环丙基)乙酮（3.0克， 0.0145摩尔），反式 2-甲氧亚胺基 -2- (2- (胺氧甲基)苯基)乙酸甲酯（4.0克， 0.0170摩尔)， 50毫升无水甲醇和 2滴冰醋酸，室温下搅拌 6小时。将反应液倾入 50毫升水中，用 3x20 毫升乙酸乙酯萃取，有机相经水和饱和食盐水洗涤后，用无水硫酸镁干燥，浓缩后得 5.5 克浅黄色油状物， HPLC分析其中极性较弱与极性较强 2个主产物的比例为 85： 15, 总含量为 85%，收率 76%。通过柱色谱分离（淋洗液：乙酸乙酯：石油醚 =1 ： 40)得到 4.0克极性较弱的油状物，室温放置后得到白色固体，熔点： 58〜62°C，经核磁验证其结构为 3A; 同时还得到 0.7克油状物， HPLC分析其中化合物 3A与极性较强化合物的比例为 40 : 60， 1H MR分析混合物中极性较强化合物结构为化合物 3B。核磁数据如下： ' 化合物 3A_: 1HNMR (300MHz, CDC1₃): 7.347-7.317(m, 2H), 7.233 -7.203 (m, 1H), 7.141-7.112(m, 1H), 7.055-6.95 l(m, 2H), 6.859-6.799(t, 1H), 4.836-4.815(q, 2H), 3.999(s, 3H), 3.802(s, 3H)， 2.210-2.204(d, 3H), 1.796-1.748(m, 1H), 1.576-1.539(m, 1H), 1.418(s, 3H), 1.329(s, 3H), 1.000-0.914(m, 1H) Add cis-l-(2-(4-fluoro-3-methylphenyl)-2-methylcyclopropyl)ethanone (3.0 g, 0.0145 mol) in a 100 ml reaction vial, trans 2- Methyl methoxyimino-2-(2-(aminooxymethyl)phenyl)acetate (4.0 g, 0.0170 mol), 50 ml of anhydrous methanol and 2 ml of glacial acetic acid were stirred at room temperature for 6 hours. The reaction mixture was poured into 50 ml of water and extracted with 3×20 ml of ethyl acetate. The organic phase was washed with water and brine, and dried over anhydrous magnesium sulfate. The ratio of the two main products, which is weaker and more polar, is 85: 15, the total content is 85%, and the yield is 76%. By column chromatography (eluent: ethyl acetate: petroleum ether = 1 : 40), 4.0 g of a weakly oily oil was obtained, which was stood at room temperature to give a white solid, melting point: 58 to 62 ° C, which was verified by NMR. The structure was 3A; at the same time, 0.7 g of an oil was obtained, and the ratio of the compound 3A to the more polar compound was 40:60 by HPLC analysis. The structure of the compound having a relatively strong polarity in the 1H MR analysis mixture was the compound 3B. The nuclear magnetic data are as follows: 'Compound 3A _: 1H NMR (300MHz, CDC1 ₃ ): 7.347-7.317(m, 2H), 7.233 -7.203 (m, 1H), 7.141-7.112(m, 1H), 7.055-6.95 l(m, 2H), 6.859-6.799(t, 1H), 4.836-4.815(q, 2H), 3.999(s, 3H), 3.802(s, 3H), 2.210-2.204(d, 3H), 1.796-1.748(m, 1H), 1.576-1.539(m, 1H), 1.418(s, 3H), 1.329(s, 3H), 1.000-0.914(m, 1H)

化合物 3B_: 】H NMR (300MHz, CDC1₃): 7.477-7.320(m, 3H), 7.240-7.187(m, 1H), 7.050-6.933(m, 2H), 6.870-6.800(m, 1H), 5.058-5.029(q, 2H), 4.050(s, 3H), 3.840(s, 3H), 2.391-2.358(m, 1H), 2.194-2.189(m, 3H), 1.413(s, 3H), 1.364-1.326(m, 1H), 1.069-1.0Ql(m, 4H)。 ' Compound 3B _: H NMR (300MHz, CDC1 ₃ ): 7.477-7.320 (m, 3H), 7.240-7.187 (m, 1H), 7.050-6.933 (m, 2H), 6.870-6.800 (m, 1H), 5.058 -5.029(q, 2H), 4.050(s, 3H), 3.840(s, 3H), 2.391-2.358(m, 1H), 2.194-2.189(m, 3H), 1.413(s, 3H), 1.364-1.326 (m, 1H), 1.069-1.0Ql (m, 4H). '

7、化合物 4A的合成： 7. Synthesis of Compound 4A:

在 50毫升的反应瓶中加入化合物 3A ( 1.0克， 0.0023摩尔）， 10毫升甲醇和 2 毫升 40%甲胺水溶液，在室温下搅拌 6小时后，将反应液倾入 50毫升水中，用 3x20 . 毫升乙酸乙酯萃取，有机相经水和饱和食盐水洗涤后，用无水硫酸镁干燥，浓缩后得 0.9克浅黄色油状物， HPLC分析主产物含量为 9⁷%，收率 87%。通过柱色谱提纯（淋冼液：，乙酸乙酯石油醚 = 1 ： 4) 得到 0.7克白色固体，. 熔点： 114〜118°C，经如下核磁验证其结构为化合物' 4A。 . ：化合物 4A_: Ή MR (300MHz, CDC1₃): 7.375-7.295(m, 2H), 7.247-7.205(m, 1H)_; 7.165-7.122(m, 1H), 7.061-7.03 l(m, 1H), 6.995-6.942(m, 1H), 6.868-6.799(m, 1H)_; 6.644-6.62S(d, 1H), 4.829-4.807(q, 2H), 3.911 (s, 3H), 2.865-2.847(d, 3H), 2.216-2.210(d, 3H)_; 1.791-1.743(m, IH), 1.585-1.568(m, 1H), 1.420(s, 3H), 1.330(s, 3H), 0.958-0.913(m, 1H)Compound 3A (1.0 g, 0.0023 mol), 10 ml of methanol and 2 ml of 40% aqueous methylamine solution were added to a 50 ml reaction flask, and after stirring at room temperature for 6 hours, the reaction solution was poured into 50 ml of water, using 3x20. ml of ethyl acetate was extracted, the organic phase was washed with water and saturated brine, dried over anhydrous magnesium sulfate to give 0.9 g pale yellow oil was concentrated, HPLC analysis of the main product content of ^97%, yield 87%. Purification by column chromatography (dipping solution: ethyl acetate petroleum ether = 1 : 4) yielded 0.7 g of white solid, m.p.: 114~118 ° C. . : Compound 4A _: Ή MR (300MHz, CDC1 ₃ ): 7.375-7.295(m, 2H), 7.247-7.205(m, 1H) _; 7.165-7.122(m, 1H), 7.061-7.03 l(m, 1H), 6.995 -6.942(m, 1H), 6.868-6.799(m, 1H) _; 6.644-6.62S(d, 1H), 4.829-4.807(q, 2H), 3.911 (s, 3H), 2.865-2.847(d, 3H ), 2.216-2.210(d, 3H) _; 1.791-1.743(m, IH), 1.585-1.568(m, 1H), 1.420(s, 3H), 1.330(s, 3H), 0.958-0.913(m, 1H )

8、化合物 4A和 4B混合物的合成： 8. Synthesis of a mixture of compounds 4A and 4B:

40%3A+60%3B 4A+4B 40%3A+60%3B 4A+4B

在 50毫升的反应瓶中加入 40%3A+60%3B的混合物， 5毫升甲醇和 0.6毫升 40% 甲胺水溶液，在室温下搅拌 6小时后，将反应液倾入 10毫升水中，用 3 x 10毫升乙酸乙酯萃取，有机相经水和饱和食盐水洗涤后，用无水硫酸镁干燥，浓缩后得 0.4克浅黄色油状物， HPLC分析极性较弱与极性较强 2个主产物总含量为 95%，收率 76 %。通过柱色谱分离（淋洗液：乙酸乙酯：石油醚 = 1 ： 4) 得 0.3克油状物， HPLC分析其中化合物 4A和极性较强化合物的比例为 40 ： 60，核磁分析混合物中极性较强化合物结构为化合物 4B。核磁数据如下： In a 50 ml reaction flask, a mixture of 40% 3A + 60% 3B, 5 ml of methanol and 0.6 ml of 40% aqueous methylamine solution were added. After stirring at room temperature for 6 hours, the reaction solution was poured into 10 ml of water, using 3 x The organic phase was washed with water and brine, dried over anhydrous magnesium sulfate and evaporated The total content was 95% and the yield was 76%. Separation by column chromatography (eluent: ethyl acetate: petroleum ether = 1 : 4) afforded 0.3 g of oil, which was analyzed by HPLC. The ratio of compound 4A to the more polar compound was 40: 60. The stronger compound structure is compound 4B. The nuclear magnetic data is as follows:

化合物 4B : 1H NMR (300MHz, CDC1₃): 7.467-7.296(m, 3H), 7.248-7.178(m, IH), 7.062-6.933(m, 2H), 6.869-6.746(m, 2H), 5.030-5.004(q, 2H), 3.961(s, 3H), 2.896-2.880(d 3H), 2.375-2.348(m, IH), 2.216-2.190(q, 3H), 1.418(s, 3H), 1.360-1.329(m, IH), 1.026-1.009(m, 4H) ₀ Compound 4B: 1H NMR (300MHz, CDC1 ₃ ): 7.467-7.296 (m, 3H), 7.248-7.178 (m, IH), 7.062-6.933 (m, 2H), 6.869-6.746 (m, 2H), 5.030- 5.004(q, 2H), 3.961(s, 3H), 2.896-2.880(d 3H), 2.375-2.348(m, IH), 2.216-2.190(q, 3H), 1.418(s, 3H), 1.360-1.329 (m, IH), 1.026-1.009(m, 4H) ₀

9、中间体反式 l-(2-(4-氟 -3-甲基苯基)- 2-甲基环丙基)乙酮肟的合成- 9. Synthesis of intermediate trans-l-(2-(4-fluoro-3-methylphenyl)-2-methylcyclopropyl)ethanone oxime -

在 100毫升的反应瓶中加入反式 1-(2-(4-氟 -3-甲基苯基) -2-甲基环丙基)乙酮（3.1 克， 0.015摩尔），羟胺盐酸盐（5.3克， 0.075摩尔），三乙胺（6.1克， 0.060摩尔) 和 30毫升甲醇，升温回流搅拌反应 3小时。将反应液倾入 50毫升水中，用 3 x50毫升乙酸乙酯萃取，有机相经水和饱和食盐水洗涤后，用无水硫酸镁干燥，浓缩后得 3.1克浅黄色油状物，收率 94 %，经如下核磁验证其结构¾反式 1-(2- (4-氟- 3-甲基苯基) -2-甲基环丙基)乙酮肟。 . lH NMR (300MHz, CDC1₃) : 7.108-7.044(m, 2H), 6.955 -6.869 (t, IH), 2.268(s, 3 H), In a 100 ml reaction flask was added trans 1-(2-(4-fluoro-3-methylphenyl)-2-methylcyclopropyl)ethanone (3.1 g, 0.015 mol), hydroxylamine hydrochloride (5.3 g, 0.075 mol), triethylamine (6.1 g, 0.060 mol) and 30 ml of methanol. The reaction mixture was poured into 50 ml of water and extracted with EtOAc EtOAc EtOAc. The structure of 3⁄4 trans-(2-(4-fluoro-3-methylphenyl)-2-methylcyclopropyl)ethanone oxime was verified by the following NMR. lH NMR (300MHz, CDC1 ₃ ): 7.108-7.044(m, 2H), 6.955 -6.869 (t, IH), 2.268(s, 3 H),

I f) 2.086(s, 3H), 1.794-1.745(m, IH), 1.293-1.230(m, 4H), 1.196-1.150(m, 1H)。 I f) 2.086 (s, 3H), 1.794-1.745 (m, IH), 1.293-1.230 (m, 4H), 1.196-1.150 (m, 1H).

10、化合物 5A的合成： 10. Synthesis of Compound 5A:

在 50毫升的反应瓶中加入反式 l-(2-(4-氟 -3-甲基苯基) -2-甲基环丙基)乙酮肟（1.0 克， 0.0045摩尔）， 10毫升二甲基甲酰胺和叔丁醇钠（0.43克， 0.0045摩尔），窒温下搅拌反应 1小时，加入反式 2-(2- (溴甲基)苯基) -3-甲氧基丙烯酸甲酯（1.3克， 0.0045 摩尔），室温下反应 3小时。将反应液倾入 50毫升水中，用 3x50毫升乙酸乙酯萃取，有机相经水和饱和食盐水洗涤后，用无水硫酸镁干燥，浓缩后得 1.5克浅黄色油状物， HPLC分析主产物的含量 52.5%, 收率 42%。通过柱色谱提纯（淋洗液：乙酸乙酯：石油醚 = 1 ： 10)得 0.5克油状物，含量 72.5%，经如下核磁验证其结构为化合物 5A。 In a 50 ml reaction flask was added trans-l-(2-(4-fluoro-3-methylphenyl)-2-methylcyclopropyl)ethanone oxime (1.0 g, 0.0045 mol), 10 ml two Methylformamide and sodium tert-butoxide (0.43 g, 0.0045 mol) were stirred at room temperature for 1 hour, and trans-methyl 2-(2-(bromomethyl)phenyl)-3-methoxyacrylate was added. (1.3 g, 0.0045 mol), reacted at room temperature for 3 hours. The reaction mixture was poured into 50 ml of water and extracted with EtOAc EtOAc. The content was 52.5%, and the yield was 42%. Purification by column chromatography (eluent: ethyl acetate: petroleum ether = 1 : 10) yielded 0.5 g of oily substance (yield: 72.5%).

化合物 5A: ¾ NMR (300MHz, CDC1₃): 7.486-7.455(m, IH), 7.330-7.272(m, 2H), 7.165-7.134(m, IH), 7.083-7.030(m, 2H), 6.944-6.882(t, IH), 5.023(s,2H), 3.824(s, 3H), 3.686(s, 3H), 2.260-2.255(D, 3H), 2.026(s, 3H), 1.888(s, IH), 1.888-1.704(m, IH), 1.360-1.324(m, IH), 1.209(s, 3H), 1.140-1.097(m, 1H)。 Compound 5A: _3⁄4 NMR (300MHz, CDC1 ₃ ): 7.486-7.455 (m, IH), 7.330-7.272 (m, 2H), 7.165-7.134 (m, IH), 7.083-7.030 (m, 2H), 6.944- 6.882(t, IH), 5.023(s,2H), 3.824(s, 3H), 3.686(s, 3H), 2.260-2.255(D, 3H), 2.026(s, 3H), 1.888(s, IH) , 1.888-1.704(m, IH), 1.360-1.324(m, IH), 1.209(s, 3H), 1.140-1.097(m, 1H).

11、中间体顺式 l-(2-(4-氟 -3-甲基苯基) -2-甲基环丙基)乙酮肟的合成- 11. Synthesis of intermediate cis l-(2-(4-fluoro-3-methylphenyl)-2-methylcyclopropyl)ethanone oxime -

在 100毫升的反应瓶中加入顺式 1-(2-(4-氟 -3-甲基苯基) -2-甲基环丙基)乙酮（1.0 克， 0.005摩尔），羟胺盐酸盐（1.8克， 0.025摩尔），三乙胺（2.0克， 0.020摩尔）和 10毫升甲醇，升温回流反应 3小时。将反应液倾入 50毫升水中，用 3^50毫升乙酸乙酯萃取，有机相经水和饱和食盐水洗涤后，用无水硫酸镁干燥，浓缩后得 1.0克浅黄色油状物，收率 94%，经如下核磁验证其结构为顺式 1-(2-(4-氟 -3-甲基苯基) -2- 甲基环丙基)乙酮肟。

Add cis-(2-(4-fluoro-3-methylphenyl)-2-methylcyclopropyl)ethanone (1.0 g, 0.005 mol) in a 100 ml reaction vial, hydroxylamine hydrochloride (1.8 g, 0.025 mol), triethylamine (2.0 g, 0.020 mol) and 10 ml of methanol. The reaction mixture was poured into 50 ml of water, EtOAc (EtOAc m. %, the structure was verified to be cis 1-(2-(4-fluoro-3-methylphenyl)-2-methylcyclopropyl)ethanone oxime by the following NMR.

Ή NMR (300MHz, CDC1₃): 7.058-6.999(m, 2H), 6.870-6.841(t, IH), 2.218(s, 3H), 1.845-1.798(m, IH), 1.566-1.529(m, IH), 1.402(s, 3H), 1.003-0.957(m, 1H)。 NMR NMR (300MHz, CDC1 ₃ ): 7.058-6.999(m, 2H), 6.870-6.841(t, IH), 2.218(s, 3H), 1.845-1.798(m, IH), 1.566-1.529(m, IH ), 1.402(s, 3H), 1.003-0.957 (m, 1H).

12、化合物 5B的合成： 12. Synthesis of Compound 5B:

n

n

5B 5B

在 50毫升的反应瓶中加入顺式 1-(2-(4-氟 -3-甲基苯基) -2-甲基环丙基)乙酮肟 (0.8 克， 0.0036摩尔）， 10毫升二甲基甲酰胺和叔丁醇钠（0.35克， 0.0036摩尔），室温下搅拌反应 1小时，加入反式 2-(2- (溴甲基)苯基) -3-甲氧基丙烯酸甲酯（1.0克， 0.0036 摩尔），室温下反应 3小时。将反应液倾入 50毫升水中，用 3x50毫升乙酸乙酯萃取，有机相经水和饱和食盐水洗涤后，用无水硫酸镁干燥，浓缩后得 1.4克浅黄色油状物， HPLC分析主产物的含量 75%, 收率 65 %。通过柱色谱提纯（淋洗液：乙酸乙酯：石油醚 = 1 ： 20) 得到 0.8克白色固体，熔点： 112~115°C，经如下核磁验证其结构为化合物 5B。 Add cis 1-(2-(4-fluoro-3-methylphenyl)-2-methylcyclopropyl)ethanone oxime (0.8 g, 0.0036 mol) in a 50 ml reaction vial, 10 ml two Methylformamide and sodium tert-butoxide (0.35 g, 0.0036 mol) were stirred at room temperature for 1 hour, and trans-methyl 2-(2-(bromomethyl)phenyl)-3-methoxyacrylate ( 1.0 g, 0.0036 mol), reacted at room temperature for 3 hours. The reaction mixture was poured into 50 ml of water and extracted with EtOAc EtOAc. The content is 75%, and the yield is 65%. Purification by column chromatography (eluent: ethyl acetate: petroleum ether = 1 : 20) afforded 0.8 g of white solid, m.p.: 112-115 ° C.

化合物 5B: 1H NMR (300MHz, CDC1₃): 7.371-7.163(m, 3H), 7.115-6.977(m, 3H), 6.878-6.817(t, 1H), 4.886-4.847(q, 2H), 3.770(s, 3H), 3.648(s, 3H), 2.213(s, 3H), 1.802-1.776(m, 1H), 1.603-1.567(m, 1H)， 1.429(s, 3H), 1.365(s, 3H), 1.304(s, 1H), 0.971-0.927(m， 1H)。 Compound 5B: 1H NMR (300MHz, CDC1 ₃ ): 7.371-7.163 (m, 3H), 7.115-6.977 (m, 3H), 6.878-6.817 (t, 1H), 4.886-4.847 (q, 2H), 3.770 ( s, 3H), 3.648(s, 3H), 2.213(s, 3H), 1.802-1.776(m, 1H), 1.603-1.567(m, 1H), 1.429(s, 3H), 1.365(s, 3H) , 1.304 (s, 1H), 0.971-0.927 (m, 1H).

生测实例 Biometric example

杀菌活性的测定 Determination of bactericidal activity

1. 对稻瘟病的离体杀菌活性的测定： 1. Determination of in vitro bactericidal activity against rice blast:

供试菌种：稻瘟病（P ton' gn ), 培养基为 AEA培养基。 Test species: rice blast (P ton' gn ), the medium is AEA medium.

将熔好的培养基冷却至 60°C〜70°C, 按所设浓度加入定量药剂，制成含有不同药量的含毒培养基，待其充分冷却后，接种直径为 0.5cm的稻瘟病菌菌片,放置培养箱中培养。在培养箱中培养 10天后进行调查，调査时分别测量每个处理的菌落生长直径，并计算抑菌率。结果见表 2。 The molten medium is cooled to 60 ° C to 70 ° C, and the quantitative agent is added according to the set concentration to prepare a toxic medium containing different doses, and after being sufficiently cooled, the rice blast with a diameter of 0.5 cm is inoculated. The bacteria tablets are placed in an incubator for cultivation. The culture was carried out for 10 days in an incubator, and the growth diameter of each treated colony was measured and the inhibition rate was calculated. The results are shown in Table 2.

表 2: 部分通式 I化合物对稻瘟病的离体杀菌活性 Table 2: In vitro bactericidal activity of some compounds of formula I against rice blast

4A 77 45 6

40%4A+60%4B 92 79 44 40%4A+60%4B 92 79 44

5A 95 62 25 5A 95 62 25

5B 75 58 11 5B 75 58 11

按以上方法，选取化合物 2A和已知化合物 KCCWO0187826A1中的化合物 3.20) 进行了稻瘟病的离体杀菌活性的平行测定。结果见表 3。 The parallel determination of the in vitro bactericidal activity of rice blast was carried out by the above method, selecting compound 2A and compound 3.20) in the known compound KCCWO0187826A1. The results are shown in Table 3.

表 3 : 化合物 2A与已知化合物 KC*对稻瘟病的离体杀菌活性平行比较 Table 3: Parallel comparison of compound 2A with known compounds KC* for in vitro bactericidal activity against rice blast

其化合物 KC的结构式如下: The structural formula of its compound KC is as follows:

KC KC

2. 对黄瓜霜霉病的杀菌活性的测定 - 选择生长整齐一致的盆栽黄瓜幼苗剪去生长点保留二片真叶，按照设计浓度进行喷雾处理。处理后的试验材料在第二天接种黄瓜霜霉病孢子悬浮液，然后放置人工气候室（温度：昼 25Ό、夜 20Ό，相对湿度： 95〜100%)培养，保湿培养 6天后调查防治效果，按发病程度分 6级记载，以病指计算防效。结果见表 4。 2. Determination of bactericidal activity against cucumber downy mildew - Select potted cucumber seedlings with uniform growth and cut off the growth points to retain two true leaves, sprayed according to the designed concentration. The treated test material was inoculated with the cucumber downy mildew spore suspension on the next day, and then placed in an artificial climate chamber (temperature: 昼25Ό, night 20Ό, relative humidity: 95~100%), and the control effect was investigated after 6 days of moisturizing culture. According to the degree of disease, it is recorded at 6 levels, and the disease index is used to calculate the control effect. The results are shown in Table 4.

表 4: 部分通式 I化合物对黄瓜霜霉病保护试验结果 Table 4: Test results of partial compound I compound against cucumber downy mildew

3. 对小麦白粉病的杀菌活性的测定：

3. Determination of bactericidal activity against wheat powdery mildew:

盆栽小麦于温室中培养至二叶期，选取长势整齐一致的小麦幼苗，使用作物喷雾机进行叶片喷雾处理。 24 小时后对小麦叶片接种白粉病原菌孢子粉，然后将幼苗放置温室中进行常规水肥管理并保持一定湿度，在空白对照充分发病后，进行防治效果调査，按照叶片发病情况分级记载，计算病情指数以及防治效果。 The potted wheat was cultivated in the greenhouse until the second leaf stage, and the wheat seedlings with uniform growth were selected, and the leaf spray treatment was carried out using a crop sprayer. After 24 hours, the wheat leaves were inoculated with powdery pathogen spore powder, and then the seedlings were placed in the greenhouse for routine water and fertilizer management and maintained at a certain humidity. After the blank control was fully ill, the control effect was investigated, and the disease index was calculated according to the leaf incidence. And control effects.

表 5: 部分通式 I化合物对小麦白粉病保护试验结果 Table 5: Results of the protective test of some compounds of formula I on wheat powdery mildew

杀虫活性的测定： Determination of insecticidal activity:

1. 对朱砂叶螨的杀虫活性的测定： 1. Determination of the insecticidal activity of Tetranychus cinnafolia:

待测化合物原药用丙酮溶解，用含有 0.1%吐温 80的水稀释至所需的浓度。将盆栽菜豆苗保留一片叶，保证每叶片背面侵染有雌成螨 30〜40头，用 Airbrush喷雾处理，每处理喷液量 0.5mL，每处理 3次重复。处理后放入 24°C，相对湿度 60%〜70%，每日光照 14小时的室内培养， 48小时后调査存活虫数，计算死亡率。 . The test compound was dissolved in the original pharmaceutically acceptable acetone and diluted to the desired concentration with water containing 0.1% Tween 80. The potted bean sprouts were kept in a leaf, and the back of each leaf was infested with 30 to 40 heads of female cockroaches, and sprayed with Airbrush. The amount of liquid sprayed per treatment was 0.5 mL, and the treatment was repeated 3 times. After the treatment, the indoor culture was carried out at 24 ° C, relative humidity 60% to 70%, daily light for 14 hours, and the number of living animals was investigated after 48 hours, and the mortality was calculated. .

2. 对蚕豆蚜的杀虫活性的测定： 2. Determination of the insecticidal activity of broad bean meal:

待测化合物原药用丙酮溶解，用含有 0.1%吐温 80的水稀释至所需的浓度。将花生叶用 Airbrush喷雾处理，每叶正反面喷雾，喷液量为 0.25 ml，阴干后每处理接入 25〜35头试虫，每处理 3'次重复。处理后放入 20°C，相对湿度 60%〜70%，无光照的室内培养， 48 小时后调查存活虫数，计算死亡率。 The test compound was dissolved in the original pharmaceutically acceptable acetone and diluted to the desired concentration with water containing 0.1% Tween 80. The flowers are sprayed with Airbrush spray, and the spray is applied to the front and back of each leaf. The spray volume is 0.25 ml. After the dry operation, 25 to 35 test insects are added per treatment, and each treatment is repeated 3 times. After the treatment, 20 ° C, relative humidity 60% ~ 70%, indoor culture without light, 48 hours later, the number of surviving insects was investigated, and the mortality was calculated.

'部分通式 I化合物的杀虫活性测试结果见表 6。 The results of the insecticidal activity test of the compound of the formula I are shown in Table 6.

表 6: 化合物 2A的杀虫活性 Table 6: Insecticidal activity of compound 2A

ppm Ppm

600 150 600 150

' 朱砂叶螨 90 70 '朱砂叶螨 90 70

蚕豆蚜 100 90 Broad bean meal 100 90

Claims

权利要求书 Claims

X为 N或 CH; X is N or CH;

W为 0或 NH; W is 0 or NH;

2、按照权利要求 1所述的化合物，其特征在于：通式 I中 2. A compound according to claim 1 wherein:

X为 N或 CH; X is N or CH;

W为 0或 NH; W is 0 or NH;

B1键与邻近的苯环为反式或顺式； B2键与 B1键为反式。 The B1 bond is trans or cis to the adjacent benzene ring; the B2 bond and the B1 bond are trans.

3、按照权利要求 2所述的化合物，其特征在于：通式 I中 3. A compound according to claim 2, characterized by:

X为 N; X is N;

W为丽； W is Li;

B1键与邻近的苯环为反式； B2键与 B1键为反式。 ' The B1 bond is trans to the adjacent benzene ring; the B2 bond and the B1 bond are trans. '

. 4、权利要求 1所述的通式 I化合物用于控制植物病害的用途。 · 5、权利要求 1所述的通式 I化合物用于控制虫害的用途。 4. Use of a compound of formula I according to claim 1 for the control of plant diseases. 5. Use of a compound of formula I according to claim 1 for controlling pests.

• 6、一种杀菌、杀虫组合物，其特征在于：含有如通式 I化合物的活性组分和农业上可接受的载体，组合物中活性组分的重量百分含量为 1-99%。 6. A bactericidal, insecticidal composition, characterized by: an active ingredient comprising a compound of formula I and an agriculturally acceptable carrier, the active ingredient being present in the composition in an amount of from 1 to 99% by weight .

7、一种防治植物病害的方法，其特征在于：将权利要求 6所述的组合物以每公顷 5克到 5000克的有效剂量施于需要控制病害的植物上。 . A method for controlling plant diseases, characterized in that the composition of claim 6 is applied to plants in need of disease control at an effective dose of from 5 g to 5000 g per hectare. .

8、权利要求 7.所述的方法，其特征在于：所述组合物施于需要控制病害的植物上的有效剂量为每公顷 10克到 500克。 8. The method of claim 7, wherein: the effective amount of said composition applied to the plant to be controlled for the disease is from 10 grams to 500 grams per hectare.

9、一种防治虫害的方法，其特征在于：将权利要求 6.所述的组合物以每公顷 10 克到 10000克的有效剂量施于需要控制的害虫或其生长的介质上。 A method for controlling pests, characterized in that the composition of claim 6. is applied to a pest to be controlled or a medium for growth thereof at an effective dose of from 10 g to 10,000 g per hectare.

10、权利要求 9所述的方法，其特征在于：所述组合物施于需要控制的害虫或其生长的介质上的有效剂量为每公顷 100克到 5000克。 10. The method of claim 9 wherein: the effective amount of said composition applied to the pest to be controlled or the medium in which it is grown is from 100 grams to 5000 grams per hectare.