CN109320505B - Preparation and application of halobutenolactone compounds with insecticidal activity - Google Patents

Abstract

The invention relates to a preparation method and application of halogenated butenolide compounds with insecticidal activity, and relates to nitrogen-containing ring-opening compounds with a formula (A), wherein R is ₁ ，R ₂ ，R ₃ And X are each as defined in the specification. The invention discloses a preparation method and application of a novel pesticide, wherein the compound and derivatives thereof have the following effects on homoptera, lepidoptera and other agricultural and forestry pests: aphids, plant hoppers, whiteflies, leafhoppers, thrips, cotton bollworms, cabbage caterpillars, diamond back moths, prodenia lituras, armyworms and the like have high insecticidal activity.

Description

Preparation and use of halobutenolactone compounds with insecticidal activity

technical field

The present invention relates to a novel butenolactone neonicotinoid insecticide, a preparation method and application thereof.

technical background

Neonicotinoids act on insect nicotinic acetylcholine receptors (nAChRs), and have quickly become green pesticides with the characteristics of high efficiency, low toxicity, broad spectrum, high selectivity, low residue, and safety to mammals and various aquatic organisms. Classic representative. The traditional neonicotinoids represented by imidacloprid (Group 4A agonists cover imidacloprid, acetamiprid, clothianidin, dinotefuran, nitenpyram, thiacloprid and thiamethoxam) are registered in more than 120 countries, worldwide Sales of more than 2 billion US dollars, market share of more than 25% (European patents 247477, 296453, 685477, 235725, 235725, 315826, 192060, 244777, 0386565, 580553, and 1031566, Japanese patents 62292765, 8259568, and 291171 7242633). However, in recent years, the toxicity of traditional neonicotinoid insecticides to honeybees has been reported in many countries and regions, and it is recognized as an important reason for the sharp decline in the number and population of honeybees. Since 2017, Canada, France and other countries plan to phase out traditional neonicotinoid pesticides such as imidacloprid in all agricultural products within three years. The development of neonicotinoid insecticides with novel structures and safety against pollinators such as bees is an urgent task and a great challenge for researchers.

SUMMARY OF THE INVENTION

The purpose of the present invention is to provide a class of halobutenoic acid lactone compounds for efficiently controlling pests and a preparation method thereof.

Another object of the present invention is to provide protection of growing and harvested crops from attack and infestation by insects.

A first aspect of the present invention provides a compound having the structure represented by formula (A):

The compound is characterized in that wherein R ₁ is selected from: pyridyl, thiazolyl, pyrimidinyl, tetrahydrofuranyl, oxazolyl or its halide.

The compound is characterized in that wherein R ₂ and R ₃ are C _1-6 alkyl, C _3-4 cycloalkyl or halogenated C _1-6 alkyl.

The compound is characterized in that X is chlorine or bromine.

Described a kind of insecticide composition, it comprises:

(a) 1-99.99% by weight of the compound of any one of claims 1-4;

(b) Pesticidally acceptable carriers and/or excipients.

The pesticide composition is characterized in that the pesticide composition is used for killing or preventing pests selected from the following: Coleoptera, Lepidoptera, Hemiptera, Orthoptera, Isoptera , or Diptera, preferably Isoptera or Lepidoptera.

Detailed ways

Through long-term and in-depth research, the inventors found that mucic halogen acid and alcohol can react under acidic conditions to build a butenolactone skeleton structure, and then react with a heterocyclic substituted secondary amine to synthesize a new type of butenoic acid. Ester neonicotinoid compounds. Such compounds have completely novel molecular structures and have high activity against aphids and rice planthoppers. On this basis, the inventors have completed the present invention.

The preparation method of the compound of the present invention

In a specific embodiment of the present invention, the synthetic method of the compound of formula (A) is as follows:

Insecticidal activity of the active substances according to the invention

The term "active substance of the invention" or "active compound of the invention" refers to a compound of the invention which has a high insecticidal activity.

The active substance of the present invention can be used to control and eliminate a wide range of agricultural and forestry plant pests, stored grain pests, public health pests, and pests that endanger animal health. In the present specification, "insecticide" is a general term for substances having the effect of controlling all the pests mentioned above. Examples of pests include, but are not limited to: Coleopteran insects: Sitophilus zeamais, Tribolium castaneum, Potato lady beetle (Henosepilachnavigintioctomaculata), Henosepilachna sparsa, Tap beetle (Agriotesfuscicollis), red-footed beetle (Anomala cupripes), four-striped beetle (Popillia quadriguttata), potato beetle (Monolepta hieroglyphica), pine beetle (Monochamus alternatus), rice root elephant (Echinocnemus squameus), Paulownia beetle ( Basiprionotabisignata), Anoplophorachinensis, Apripona germari, Scolytus schevy, or Agriotes fuscicollis. Lepidoptera: Lymantria dispar, Malacosoma neustria testacea, Diaphania perspectalis, Clania variegata, Cnidocampa flauescens, Dendrolimus punctatus ), Orgyia gonostigma, Paranthrene tabaniformis, Spodoptera litura, Chilo suppressalis, Ostrinianubilalis, Ephestia cautella, Cotton roll Moth (Adoxophyes orana), Chestnut Shrimp (laspyresia splendana), Small Cutworm (Agrotis fucosa), Galleria mellonella, Diamondback Moth (Plutellaxylostella), Phyllocnistis citrella, or Oriental Armyworm ( Mythimnaseparata). Homoptera: Nephotettix cincticeps, Nilaparvatalugens, Pseudococcus comstocki, Unaspis yanonensis, Myzus persicae, Aphis gossydii , radish aphid (Lipaphis erysimipseudobrassicae), pear bug (Stephanitis nashi), or whitefly (Bemisia tabaci). Orthoptera: Blattella germanica, Periplaneta american, Gryllotalpa africana, or Locus migratoria. Isoptera: Invasive red fire ants (Solenopsis invicta), or domestic termites (Coptotermes formosanus). Diptera: Muscadomestica, Aedes aegypti, Delia platura, Culex sp., or Anopheles sinensis.

The compounds involved in the invention are especially effective against piercing-sucking and filing-sucking mouthpart pests such as aphids, leafhoppers, planthoppers, thrips, whiteflies and other agricultural and forestry pests.

Pesticidal compositions containing the active substances of the present invention

The active substances of the present invention can be prepared into insecticidal compositions by conventional methods. The active compounds can be formulated into the customary formulations such as solutions, emulsions, suspensions, powders, foams, pastes, granules; aerosols, natural and synthetic materials impregnated with active substances, in polymeric Microcapsules in cigarettes, for seed coating formulations, and formulations for use with combustion devices - such as smoking cartridges, smoking pots and smoking trays, as well as ULV Cold and Hot Mist ( Warmmist) formulation.

These formulations can be produced by known methods, for example, by mixing the active compounds with extenders, which are liquid or liquefied gas or solid diluents or carriers, optionally with surfactants, ie emulsifiers and/or Dispersants and/or foam formers. For example, when water is used as an extender, organic solvents can also be used as auxiliaries.

Essentially suitable as diluents or carriers are liquid solvents such as: aromatic hydrocarbons such as xylene, toluene or alkylnaphthalene; chlorinated aromatic or chlorinated aliphatic hydrocarbons such as chlorobenzene, vinyl chloride or Dichloromethane; aliphatic hydrocarbons, such as cyclohexane or paraffins, such as mineral oil fractions; alcohols, such as ethanol or ethylene glycol and their ethers and lipids; ketones, such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone; or unusual polar solvents such as dimethylformamide and dimethylsulfoxide, and water. A diluent or carrier for liquefied gas refers to a liquid that will become a gas at normal temperature and pressure, such as aerosol propellants such as halogenated hydrocarbons and butane, propane, nitrogen and carbon dioxide.

The solid carrier may be ground-natural minerals, such as kaolin, clay, talc, quartz, activated clay, montmorillonite, or diatomaceous earth, and ground-synthetic minerals, such as highly dispersed silicic acid, alumina, and silicates . Solid carriers for granules are ground and graded natural limestones such as calcite, marble, pumice, sepiolite and dolomite, as well as granules synthesized from inorganic and organic coarse powders, and organic materials such as sawdust, coconut shells, Particles of corn cobs and tobacco stems, etc.

Nonionic and anionic emulsifiers can be used as emulsifiers and/or foam formers. For example, polyoxyethylene-fatty acid esters, polyoxyethylene-fatty alcohol ethers, such as alkyl aryl polyglycol ethers, alkyl sulfonates, alkyl sulfates, aryl sulfonates and white protein hydrolysate. Dispersants include, for example, lignin sulfite waste liquor and methyl cellulose.

Furthermore, the active compounds of the present invention may also be present in their commercial formulations in admixture with synergists in dosage forms for use prepared from these formulations. A synergist is a compound that enhances the action of an active compound. Since the active compound itself is active, it is not necessary to add a synergist.

These formulations generally contain 0.001-99.99% by weight of the pesticidal composition, preferably 0.01-99.9% by weight, more preferably 0.05-90% by weight of the active compound of the invention. The concentration of active compound in the dosage forms prepared for use from commercial formulations can vary widely. The concentration of active compound in the dosage form used may be from 0.0000001 to 100% (g/v), preferably between 0.0001 and 1%.

Example

The present invention will be further described below in conjunction with specific embodiments. It should be understood that these examples are only used to illustrate the present invention and not to limit the scope of the present invention. In the following examples, the experimental methods without specific conditions are usually in accordance with conventional conditions, or in accordance with the conditions suggested by the manufacturer. Percentages and parts are by weight unless otherwise indicated.

Example 1. Synthesis of A series chlorobutenolactone neonicotinoid compounds (1) Synthesis of intermediate 3,4-dichloro-5-methoxy-2(5H)-furanone

2.0g (11.9mmol) of mucic acid and 30mL of methanol were added to a 100mL flask, 0.5mL of concentrated sulfuric acid was added, the constant temperature was 70°C with magnetic stirring and reflux, and the reaction was followed by TLC. After the reaction, 1.3g anhydrous potassium carbonate was added and stirred for 0.5h, and suction filtered. , and spin-dried under reduced pressure to obtain the crude product, and the crude product was separated by column chromatography (V petroleum ether: V dichloromethane=1:1) to obtain a pale yellow oily liquid with a yield of 60%. ¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm): 5.79 (s, 1H, O-CH-O), 3.61 (s, 3H, O-CH ₃ ).

Synthesis of intermediate 3,4-dichloro-5-ethoxy-2(5H)-furanone: ¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm): 5.84 (s, 1H, O-CH-O ), 3.88 (ddq, J=42.6, 9.4, 7.1 Hz, 2H, O-CH ₂ -), 1.35 (t, J=7.1 Hz, 3H, O-CH ₃ ).

Synthesis of intermediate 3,4-dichloro-5-fluoroethoxy-2(5H)-furanone: ¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm): 5.92 (s, 1H, O-CH- O), 4.70(m, 2H, O-CH ₂ -), 4.06(m, 2H, F-CH ₂ -).

(2) Synthesis of target compounds

3-Chloro-4-((3-methylamino-6-chloro)methylpyridine)-5-methoxy-2(5H)-furanone (A01)

0.45g (2.5mmol) intermediate 5-methoxy-3,4-dichloro-2(5H)-furanone and 0.58g (3.75mmol) intermediate 3-(methylamino)methanone were respectively added to the 100mL flask Base-6-chloropyridine, use 3 mL of freshly distilled DMF to dissolve, add 0.35 g of anhydrous potassium carbonate to the dissolved mixed solution, stir at room temperature, follow the reaction by TLC, and add 50 mL of ice to the crude product after the reaction is complete Water, a solid was precipitated immediately, suction filtration under reduced pressure, and the solid obtained by suction filtration was dissolved in 30 mL of dichloromethane, then washed with dilute hydrochloric acid, saturated sodium bicarbonate solution, and water, dried with anhydrous sodium sulfate, and suction filtered. , spin dry, and column chromatography separates V (petroleum ether): V (ethyl acetate) = 1:1 to obtain a light yellow oily liquid with a yield of 63%.

¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm): 8.34 (d, J=2.3 Hz, 1H, Py-H), 7.65 (dd, J=8.2, 2.5 Hz, 1H, Py-H), 7.41 ( d, J=8.2Hz, 1H, Py-H), 5.75 (s, 1H, O-CH-O), 4.88–4.65 (m, 2H, Py-CH ₂ -N), 3.56 (s, 3H, N) -CH ₃ ), 3.11 (s, 3H, O-CH ₃ ). ¹³ C NMR (100 MHz, CDCl ₃ ) δ 167.70, 155.15, 151.40, 148.73, 137.99, 130.59, 124.82, 97.97, 87.69, 55.74, 52.33, 38.15.

3-Chloro-4-((3-ethylamino-6-chloro)methylpyridine)-5-methoxy-2(5H)-furanone (A02)

¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm): 8.32 (d, J=2.2 Hz, 1H, Py-H), 7.63 (dd, J=8.4, 2.0 Hz, 1H, Py-H), 7.39 ( d, J=8.2Hz, 1H, Py-H), 5.73 (s, 1H, O-CH-O), 4.88–4.51 (m, 2H, Py-CH ₂ -N), 3.55 (s, 3H, CH ₃ -O), 3.51-3.44 (m, 2H, N _- CH2-), 1.25 (t, J=7.0 Hz, 3H, _CH3- ).

3-Chloro-4-((3-propylamino-6-chloro)methylpyridine)-5-methoxy-2(5H)-furanone (A03)

¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm): 8.31 (d, J=2.4 Hz, 1H, Py-H), 7.61 (dd, J=8.3, 2.5 Hz, 1H, Py-H), 7.39 ( d, J=8.2Hz, 1H, Py-H), 5.71 (s, 1H, O-CH-O), 4.85–4.58 (m, 2H, Py-CH ₂ -N), 3.54 (s, 3H, O _-CH3 ), 3.45-3.30 (m, 2H, N-CH2-), 1.67 (q, J=7.6Hz, 2H, _{-CH2- )} , 0.93 (t, J=7.4Hz, 3H, _CH3 -).

3-Chloro-4-((3-isopropylamino-6-chloro)methylpyridine)-5-methoxy-2(5H)-furanone (A04)

¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm): 8.39 (d, J=2.4 Hz, 1H, Py-H), 7.82 (dd, J=8.3, 2.3 Hz, 1H, Py-H), 7.33 ( s,1H,Py-H),6.85(s,1H,O-CH-O),4.56(s,2H,Py- _CH2 -N),3.84(s,3H, _CH3 -O),3.54( d, J=33.3 Hz, 2H, N _- CH2-), 1.18 (d, J=6.7 Hz, 6H, _-CH3 -N- _CH3- ).

3-Chloro-4-((3-cyclopropylamino-6-chloro)methylpyridine)-5-methoxy-2(5H)-furanone (A05)

¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm): 8.36 (d, J=2.4 Hz, 1H, Py-H), 7.62 (dd, J=8.2, 2.3 Hz, 1H, Py-H), 7.39 ( d, J＝8.2Hz, 1H, Py-H), 5.89(s, 1H, O-CH-O), 5.21(d, J＝16.0Hz, 1H, Py-CH-N), 4.46(s, 1H , Py-CH-N), 3.56 (s, 3H, O-CH ₃ ), 2.90 (ddd, J=6.9, 4.9, 2.2 Hz, 1H, N-CH-), 1.00 (m, 4H, -CH ₂ -CH ₂ -).

3-Chloro-4-((3-butylamino-6-chloro)methylpyridine)-5-methoxy-2(5H)-furanone (A06) ¹ H NMR (400MHz, CDCl ₃ )δ(ppm) ): 8.31(d, J＝2.4Hz, 1H, Py-H), 7.61(dd, J＝8.3, 2.4Hz, 1H, Py-H), 7.39(d, J＝7.4Hz, 1H, Py-H ), 5.71(s, 1H, O-CH-O), 4.58(d, J＝38.9Hz, 2H, Py-CH ₂ -N), 3.54(s, 3H, CH ₃ -O), 3.46–3.31( m, 2H, -CH ₂ -N), 1.71–1.57 (m, 2H, -CH ₂ -), 1.40–1.31 (m, 2H, -CH ₂ -), 0.95 (d, J=7.3Hz, 3H, _CH3- ).

3-Chloro-4-((3-methylamino-6-chloro)methylpyridine)-5-ethoxy-2(5H)-furanone (A07) ¹ H NMR (400MHz, CDCl ₃ )δ(ppm) ): 8.34(d, J＝2.4Hz, 1H, Py-H), 7.65(dd, J＝8.3, 2.4Hz, 1H, Py-H), 7.41(d, J＝8.2Hz, 1H, Py-H ), 5.79(s, 1H, O-CH-O), 4.76(s, 2H, O-CH ₂ -), 3.95(dd, J=9.4, 7.1Hz, 1H, Py-CH ₂ -), 3.73( dq, J=9.3, 7.0 Hz, 1H, Py _- CH2-), 3.12 (s, 3H, N- _CH3- ), 1.26 (t, J=7.0 Hz, 3H, _CH3- ). 3-Chloro-4-((3-ethylamino-6-chloro)methylpyridine)-5-ethoxy-2(5H)-furanone (A08)

¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm): 8.33 (d, J=2.4 Hz, 1H, Py-H), 7.65 (dd, J=8.3, 2.2 Hz, 1H, Py-H), 7.39 ( d, J=8.2Hz, 1H, Py-H), 5.78 (s, 1H, O-CH-O), 4.70 (d, J=3.3Hz, 2H, O-CH ₂ -), 3.95 (dd, J = 9.4, 7.1 Hz, 1H, Py-CH ₂ ), 3.71 (m, 1H, Py-CH ₂ ), 3.51 (m, 2H, N-CH ₂ ), 1.28 (m, 6H, CH ₃ -, CH ₃ -).

3-Chloro-4-((3-propylamino-6-chloro)methylpyridine)-5-ethoxy-2(5H)-furanone (A09)

¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm): 8.32 (d, J=2.5 Hz, 1H, Py-H), 7.64 (dd, J=8.2, 2.5 Hz, 1H, Py-H), 7.39 ( d, J=8.2Hz, 1H, Py-H), 5.77 (s, 1H, O-CH-O), 4.81–4.58 (m, 2H, Py-CH ₂ -H), 3.95 (dd, J=9.4 , 7.1Hz, 1H, O-CH ₂ -), 3.35 (d, J=8.1Hz, 1H, O-CH ₂ -), 1.68 (d, J=7.7Hz, 2H, N-CH ₂ -), 1.30 -1.14 (m, 3H, _CH3- ), 0.92 (t, J=7.4 Hz, 3H, _CH3- ).

3-Chloro-4-((3-isopropylamino-6-chloro)methylpyridine)-5-ethoxy-2(5H)-furanone (A10)

¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm): 8.41 (m, 1H, Py-H), 7.82 (dd, J=8.3, 2.5 Hz, 1H, Py-H), 7.32 (s, 1H, Py -H), 6.83 (s, 1H, O-CH-O), 4.56 (s, 2H, Py-CH ₂ -N), 4.31 (q, J=7.1 Hz, 2H, O-CH ₂ ), 4.11 ( m, 1H, N-CH-), 1.35 (q, J=6.9 Hz, 3H, _CH3- ), 1.17 (s, 6H, _CH3- , _CH3 ).

3-Chloro-4-((3-cyclopropylamino-6-chloro)methylpyridine)-5-ethoxy-2(5H)-furanone (A11)

¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm): 8.32 (dd, J=2.6, 0.8 Hz, 1H, Py-H), 7.63 (dd, J=8.3, 2.5 Hz, 1H, Py-H), 7.35(dd, J=8.3, 0.7Hz, 1H, Py-H), 5.95(s, 1H, O-CH-O), 5.15(d, J=16.1Hz, 1H, Py-CH ₂ -), 4.46 (d, J=16.1 Hz, 1H, Py-CH ₂ -), 3.95–3.84 (m, 1H, O-CH ₂ -), 3.72 (dq, J=9.4, 7.1 Hz, 1H, O-CH ₂ - ), 2.94-2.87 (m, 1H, N-CH ₂ ), 1.25-1.18 (m, 4H, -CH ₂ -CH ₂ -), 1.00-0.67 (m, 3H, CH ₃ -).

3-Chloro-4-((3-butylamino-6-chloro)methylpyridine)-5-ethoxy-2(5H)-furanone (A12) ¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm) ): 8.32(d, J＝2.4Hz, 1H, Py-H), 7.63(d, J＝2.1Hz, 1H, Py-H), 7.39(d, J＝8.2Hz, 1H, Py-H), 5.76 (s, 1H, O-CH-O), 4.82–4.57 (m, 2H, Py-CH ₂ -), 4.00–3.88 (m, 1H, O-CH ₂ -), 3.70 (dd, J=9.3 , 7.1Hz, 1H, O-CH ₂ -), 3.51–3.30 (m, 1H, N-CH-), 1.66 (dd, J=15.6, 8.2Hz, 3H, CH ₃ -), 1.29–1.18 (m , 4H, -CH ₂ -CH ₂ -), 0.95 (t, J=7.4 Hz, 3H, CH ₃ -).

3-Chloro-4-((3-methylamino-6-chloro)methylpyridine)-5-fluoroethoxy-2(5H)-furanone (A13)

¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm): 8.34 (d, J=2.5 Hz, 1H, Py-H), 7.64 (dd, J=8.2, 2.5 Hz, 1H, Py-H), 7.40 ( d, J=8.2Hz, 1H, Py-H), 5.88 (s, 1H, O-CH-O), 4.79 (s, 2H, Py-CH ₂ -), 4.66 (m, 1H, F-CH ₂ ), 4.53 (m, 1H, F-CH ₂ ), 4.12 (m, 2H, O-CH ₂ -), 3.15 (s, 3H, N-CH ₃ -).

3-Chloro-4-((3-ethylamino-6-chloro)methylpyridine)-5-fluoroethoxy-2(5H)-furanone (A14)

¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm): 8.32 (d, J=2.4 Hz, 1H, Py-H), 7.64 (dd, J=8.3, 2.4 Hz, 1H, Py-H), 7.38 ( d, J=8.2Hz, 1H, Py-H), 5.85 (s, 1H, O-CH-O), 4.74 (q, J=16.4Hz, 2H, Py-CH ₂ -N), 4.67–4.60 ( m, 1H, F-CH ₂ ), 4.57-4.47 (m, 1H, F-CH ₂ ), 4.13 (d, J=7.2Hz, 1H, O-CH ₂ -), 4.00 (q, J=2.2, 1.6 Hz, 1H, O-CH2-), 3.61-3.45 (m, 2H, N- _{CH2 )} , 1.27 (td, J=7.1, 3.5 Hz, 3H, _CH3- ). 3-Chloro-4-((3-propylamino-6-chloro)methylpyridine)-5-fluoroethoxy-2(5H)-furanone (A15)

¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm): 8.32 (d, J=2.5 Hz, 1H, Py-H), 7.63 (dd, J=8.3, 2.4 Hz, 1H, Py-H), 7.39 ( d, J=8.3Hz, 1H, Py-H), 5.83 (s, 1H, O-CH-O), 4.82 (d, J=16.4Hz, 1H, F-CH ₂ -), 4.73–4.58 (m , 2H, Py-CH ₂ -N), 4.51 (td, J=3.8, 1.9Hz, 1H, F-CH ₂ ), 4.10 (m, 2H, O-CH ₂ ), 3.41 (m, 2H, N- _CH2 ), 1.69 (q, J=7.4Hz, 2H, _-CH2- ), 0.93 (t, J=7.4Hz, 3H, _CH3- ).

3-Chloro-4-((3-cyclopropylamino-6-chloro)methylpyridine)-5-fluoroethoxy-2(5H)-furanone (A16)

¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm): 8.36 (d, J=2.5 Hz, 1H, Py-H), 7.64 (dd, J=8.3, 2.5 Hz, 1H, Py-H), 7.38 ( d, J=8.2Hz, 1H, Py-H), 6.03 (s, 1H, O-CH-O), 5.20 (d, J=16.1Hz, 1H, F-CH ₂ -), 4.62 (m, 1H ,F-CH ₂ -),4.51(m,2H,Py-CH ₂ -N),4.12(m,1H,O-CH ₂ -),4.01(m,1H,O-CH ₂ -),3.95( m, 1H, N-CH-), 1.01 (m, 4H, _{-CH2 -} CH2-).

Example 2. Synthesis of B series bromobutenolactone neonicotinoid compounds (1) Synthesis of intermediate 3,4-dibromo-5-methoxy-2(5H)-furanone

Add 3.0g (11.7mmol) mucobromic acid and 30mL methanol to a 100mL flask, add 0.5mL concentrated sulfuric acid, stir at a constant temperature of 70°C with magnetic stirring and reflux, follow the reaction by TLC, add 1.2g anhydrous potassium carbonate after the reaction, stir for 0.5h, and filter with suction , and spin-dried under reduced pressure to obtain the crude product, and the crude product was separated by column chromatography (V petroleum ether: V dichloromethane=1:1) to obtain a white solid with a yield of 92%. ¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm): 5.80 (s, 1H, O-CH-O), 3.60 (s, 3H, O-CH ₃ ).

Synthesis of intermediate 3,4-dibromo-5-ethoxy-2(5H)-furanone: ¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm): 5.84 (s, 1H, O-CH-O ), 4.05–3.73 (m, 2H, O-CH ₂ ), 1.35 (t, J=7.1 Hz, 3H, CH ₃ -).

Synthesis of intermediate 3,4-dibromo-5-fluoroethoxy-2(5H)-furanone: ¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm): 5.92 (s, 1H, O-CH- O), 4.70(m, 2H, F-CH ₂ -), 4.10(m, 2H, O-CH ₂ -).

(2) Synthesis of target compounds

3-Bromo-4-((3-methylamino-6-chloro)methylpyridine)-5-methoxy-2(5H)-furanone (B01)

0.50g (1.85mol) of intermediate 5-methoxy-3,4-dibromo-2(5H)-furanone and 0.44g (2.78mmol) of intermediate 3-(methylamino)methane were respectively added to the 100mL flask Base-6-chloropyridine, use 3 mL of freshly distilled DMF to dissolve, add 0.30 g of anhydrous potassium carbonate to the dissolved mixed solution, stir at room temperature, follow the reaction by TLC, add 50 mL of ice to the crude product after the reaction is complete Water, a solid precipitated immediately, filtered under reduced pressure, and the solid obtained by suction filtration was dissolved in 30 mL of dichloromethane, then washed with dilute hydrochloric acid, saturated sodium bicarbonate solution, and clean water, dried with anhydrous sodium sulfate, and filtered with suction. , spin-dried, and separated by column chromatography V (petroleum ether): V (ethyl acetate) = 1:1 to obtain a light yellow solid with a yield of 83%. ¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm): 8.44 (m, 1H, Py-H), 7.69-7.61 (m, 1H, Py-H), 7.40 (d, J=8.2 Hz, 1H, Py -H), 5.77(s, 1H, O-CH-O), 4.97–4.66(m, 2H, Py-CH ₂ -N), 3.55(s, 3H, O-CH ₃ -), 3.12(s, 3H,N- _CH3 ).

3-Bromo-4-((3-ethylamino-6-chloro)methylpyridine)-5-methoxy-2(5H)-furanone (B02) ¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm) ): 8.32(s, 1H, Py-H), 7.63(d, J＝7.7Hz, 1H, Py-H), 7.39(d, J＝8.1Hz, 1H, Py-H), 5.76(s, 1H , O-CH-O), 4.66(m, 2H, Py-CH ₂ -N), 3.54(s, 3H, O-CH ₃ ), 3.51(d, J=8.1Hz, 2H, N-CH ₂ - ), 1.25 (t, J=6.8 Hz, 3H, CH ₃ -). 3-Bromo-4-((3-propylamino-6-chloro)methylpyridine)-5-methoxy-2(5H)-furanone (B03) ¹ H NMR (400MHz, CDCl ₃ )δ(ppm) ): 8.31(d, J＝2.4Hz, 1H, Py-H), 7.61(dd, J＝8.2, 2.5Hz, 1H, Py-H), 7.39(d, J＝8.2Hz, 1H, Py-H ), 5.74(s, 1H, O-CH-O), 4.85(d, J＝16.4Hz, 1H, Py-CH ₂ -N), 4.61(m, 1H, Py-CH ₂ -N), 3.54( s, 3H, O-CH ₃ ), 3.39 (qq, J=12.2, 6.2, 4.4 Hz, 2H, N-CH ₂ ), 1.68 (p, J=7.5 Hz, 2H, -CH ₂ -), 0.93 ( t, J=7.3 Hz, 3H, CH ₃ -).

3-Bromo-4-((3-isopropylamino-6-chloro)methylpyridine)-5-methoxy-2(5H)-furanone (B04)

¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm): 8.38 (d, J=2.5 Hz, 1H, Py-H), 7.80 (dd, J=8.3, 2.4 Hz, 1H, Py-H), 7.31 ( d, J=8.3Hz, 1H, Py-H), 7.06 (s, 1H, O-CH-O), 4.55 (s, 2H, Py-CH ₂ -N), 4.10 (m, 1H, N-CH -), 3.84 (s, 3H, O- _CH3 ), 1.32-1.18 (m, 4H, _{-CH2 -} CH2-). 3-Bromo-4-((3-cyclopropylamino-6-chloro)methylpyridine)-5-methoxy-2(5H)-furanone (B05)

¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm): 8.35 (d, J=2.5 Hz, 1H, Py-H), 7.62 (dd, J=8.3, 2.5 Hz, 1H, Py-H), 7.38 ( d, J＝8.2Hz, 1H, Py-H), 5.91(s, 1H, O-CH-O), 5.32(d, J＝16.1Hz, 1H, Py-CH ₂ -N), 4.44(d, J=16.0Hz, 1H, Py-CH ₂ -N), 3.56 (s, 3H, O-CH ₃ ), 2.89 (m, 1H, N-CH-), 0.92 (m, 4H, -CH ₂ -CH _2- ).

3-Bromo-4-((3-butylamino-6-chloro)methylpyridine)-5-methoxy-2(5H)-furanone (B06) ¹ H NMR (400MHz, CDCl ₃ )δ(ppm) ): 8.30(d, J＝2.4Hz, 1H, Py-H), 7.61(dd, J＝8.3, 2.6Hz, 1H, Py-H), 7.38(d, J＝8.2Hz, 1H, Py-H ), 5.73(s, 1H, O-CH-O), 4.86(d, J＝16.5Hz, 1H, Py-CH ₂ -N), 4.61(m, 1H, Py-CH ₂ -N), 3.53( s, 3H, O-CH ₃ ), 3.42 (td, J=13.2, 11.9, 6.1 Hz, 2H, N-CH ₂ -), 1.63 (qd, J=8.5, 8.0, 6.4 Hz, 2H, -CH ₂ -), 1.34 (m, 2H, _-CH2- ), 0.94 (t, J=7.4Hz, 3H, _CH3- ). 3-Bromo-4-((3-methylamino-6-chloro)methylpyridine)-5-ethoxy-2(5H)-furanone (B07) ¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm) ): 8.34(d, J＝2.4Hz, 1H, Py-H), 7.65(dd, J＝8.3, 2.2Hz, 1H, Py-H), 7.41(d, J＝8.2Hz, 1H, Py-H ), 5.82(s, 1H, O-CH-O), 4.81(s, 2H, Py-CH ₂ -N), 3.90(m, 1H, O-CH ₂ -), 3.74(dq, J=9.3, 7.0 Hz, 1H, O-CH ₂ -), 3.13 (s, 3H, N-CH ₃ ), 1.26 (t, J=7.0 Hz, 3H, CH ₃ -).

3-Bromo-4-((3-ethylamino-6-chloro)methylpyridine)-5-ethoxy-2(5H)-furanone (B08) ¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm) ): 8.33(d, J＝2.4Hz, 1H, Py-H), 7.65(dd, J＝8.3, 2.4Hz, 1H, Py-H), 7.39(d, J＝8.3Hz, 1H, Py-H ), 5.80(s, 1H, O-CH-O), 4.77(m, 2H, Py-CH ₂ -), 3.95(dq, J=9.4, 7.1Hz, 1H, O-CH ₂ -), 3.74( q,J=7.0Hz,1H,O- _CH2 -),3.58(dd,J=14.7,7.2Hz,1H,N- _CH2 -),3.45(dq,J=14.2,7.0Hz,1H,N _-CH2- ), 1.29-1.23 (m, 6H, _CH3- , _CH3- ).

3-Bromo-4-((3-propylamino-6-chloro)methylpyridine)-5-ethoxy-2(5H)-furanone (B09)

¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm): 8.35 (m, 1H, Py-H), 7.67-7.62 (m, 1H, Py-H), 7.39 (dd, J=8.2, 0.6 Hz, 1H ,Py-H),5.79(s,1H,O-CH-O),4.77(m,2H,Py- _CH2 -N),3.94(dq,J=9.4,7.1Hz,1H,O- _CH2 -), 3.70 (dq, J=9.4, 7.1 Hz, 1H, O-CH ₂ -), 3.33 (m, 2H, N-CH ₂ -), 1.66 (m, 2H, -CH ₂ -), 1.23 ( t, J=7.1 Hz, 3H, _CH3- ), 0.92 (t, J=7.2 Hz, 3H, _CH3- ).

3-Bromo-4-((3-isopropylamino-6-chloro)methylpyridine)-5-ethoxy-2(5H)-furanone (B10)

¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm): 8.37 (d, J=2.5 Hz, 1H, Py-H), 7.79 (dd, J=8.3, 2.5 Hz, 1H, Py-H), 7.30 ( d, J=8.4Hz, 1H, Py-H), 7.04 (s, 1H, O-CH-O), 4.55 (s, 2H, Py-CH ₂ -N), 4.30 (q, J=7.2Hz, 2H, O-CH ₂ -), 4.14 (m, 1H, N-CH-), 1.34 (q, J=7.1 Hz, 3H, CH ₃ -), 1.18 (d, J=6.7 Hz, 6H, CH ₃ -, CH ₃ -).

3-Bromo-4-((3-cyclopropylamino-6-chloro)methylpyridine)-5-ethoxy-2(5H)-furanone (B11)

¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm): 8.34 (d, J=2.5 Hz, 1H, Py-H), 7.64 (dd, J=8.3, 2.5 Hz, 1H, Py-H), 7.37 ( d, J＝8.2Hz, 1H, Py-H), 5.97(s, 1H, O-CH-O), 5.29(d, J＝16.1Hz, 1H, Py-CH ₂ -N), 4.46(d, J=16.1 Hz, 1H, Py-CH ₂ -N), 3.95 (m, 1H, O-CH ₂ -), 3.77 (m, 1H, O-CH ₂ -), 2.93 (m, 1H, N-CH -), 1.27 (m, 3H, CH ₃ -), 0.987 (m, 2H, -CH ₂ -), 0.81 (m, 2H, -CH ₂ -).

3-Bromo-4-((3-butylamino-6-chloro)methylpyridine)-5-ethoxy-2(5H)-furanone (B12) ¹ H NMR (400MHz, CDCl ₃ )δ(ppm) ): 8.31(m, 1H, Py-H), 7.63(dd, J=8.3, 2.5Hz, 1H, Py-H), 7.43(m, 1H, Py-H), 5.78(s, 1H, O- CH-O), 4.77 (m, 2H, Py-CH ₂ -N), 3.94 (dd, J=9.4, 7.1Hz, 1H, O-CH ₂ -), 3.73 (m, 1H, O-CH ₂ - ), 3.45(m, 2H, N-CH ₂ -), 1.65(m, 2H, -CH ₂ -), 1.31(m, 5H, -CH ₂ -, CH ₃ -), 0.95(t, J=7.3 Hz, 3H, CH ₃ -). 3-Bromo-4-((3-methylamino-6-chloro)methylpyridine)-5-fluoroethoxy-2(5H)-furanone (B13)

¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm): 8.34 (d, J=2.4 Hz, 1H, Py-H), 7.65 (dd, J=8.3, 2.3 Hz, 1H, Py-H), 7.41 ( d, J=8.2Hz, 1H, Py-H), 5.90 (s, 1H, O-CH-O), 4.84 (s, 2H, Py-CH ₂ -N), 4.70–4.62 (m, 1H, F _-CH2 ), 4.53 (dd, J=5.1, 2.2Hz, 1H, F- _CH2 ), 4.18-3.93 (m, 2H, O- _CH2 ), 3.16 (s, 3H, N- _CH3 ).

3-Bromo-4-((3-ethylamino-6-chloro)methylpyridine)-5-fluoroethoxy-2(5H)-furanone (B14)

¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm): 8.35 (m, 1H, Py-H), 7.63 (dd, J=8.3, 2.0 Hz, 1H, Py-H), 7.39 (d, J=8.2 Hz, 1H, Py-H), 5.87 (s, 1H, O-CH-O), 4.88–4.69 (m, 2H, Py-CH ₂ -N), 4.67–4.58 (m, 1H, F-CH ₂ -), 4.52 (p, J=3.0, 2.5Hz, 1H, F-CH _2- ), 4.21–4.06 (m, 1H, O-CH ₂ ), 4.04–3.92 (m, 1H, O-CH ₂ - ), 3.54 (dt, J=14.7, 7.3 Hz, 2H, N-CH ₂ -), 1.30-1.26 (m, 3H, CH ₃ -).

3-Bromo-4-((3-propylamino-6-chloro)methylpyridine)-5-fluoroethoxy-2(5H)-furanone (B15)

¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm): 8.31 (d, J=2.5 Hz, 1H, Py-H), 7.62 (dd, J=8.3, 2.5 Hz, 1H, Py-H), 7.39 ( d, J=8.2Hz, 1H, Py-H), 5.85(s, 1H, O-CH-O), 4.87(d, J=16.5Hz, 1H, Py-CH ₂ -N), 4.67(d, J=16.4Hz, 1H, Py-CH ₂ -N), 4.64-4.59 (m, 1H, F-CH ₂ ), 4.51 (d, J=1.1Hz, 1H, F-CH ₂ ), 4.08 (s, 1H, O-CH ₂ ), 3.99 (d, J=2.6 Hz, 1H, O-CH ₂ ), 3.44 (q, J=6.6, 5.9 Hz, 2H, N-CH ₂ ), 1.68 (d, J= 3.2Hz, 2H, _CH2 ), 0.93 (t, J=7.3Hz, 3H, _CH3 ). 3-Bromo-4-((3-isopropylamino-6-chloro)methylpyridine)-5-fluoroethoxy-2(5H)-furanone (B16)

¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm): 8.37 (d, J=2.4 Hz, 1H, Py-H), 7.76 (dd, J=8.3, 2.3 Hz, 1H, Py-H), 7.12 ( s, 1H, Py-H), 4.70 (m, 1H, O-CH-O), 4.62–4.58 (m, 1H, F-CH ₂ -), 4.55 (s, 2H, Py-CH ₂ -N) , 4.53–4.49 (m, 1H, F-CH ₂ -), 4.48–4.44 (m, 1H, O-CH ₂ -), 4.13 (q, J=6.6Hz, 1H, O-CH ₂ -), 1.19 (dd, J=6.8, 4.8 Hz, 6H, _CH3- , _CH3- ).

3-Bromo-4-((3-cyclopropylamino-6-chloro)methylpyridine)-5-fluoroethoxy-2(5H)-furanone (B17)

¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm): 8.35 (d, J=2.5 Hz, 1H, Py-H), 7.63 (dd, J=8.3, 2.6 Hz, 1H, Py-H), 7.37 ( d, J=8.2Hz, 1H, Py-H), 6.05 (s, 1H, O-CH-O), 5.30 (d, J=16.1Hz, 1H, Py-CH ₂ -N), 4.64 (dd, J=5.3, 2.7Hz, 1H, F-CH ₂ -), 4.54–4.52 (m, 1H, Py-CH ₂ -N), 4.47 (s, 1H, F-CH ₂ -), 4.17–4.04 (m ,1H,O- _CH2 -),3.99-3.94(m,1H,O- _CH2 -),3.01-2.94(m,1H,N- _CH2 -),1.37-1.26(m,1H,-CH _2- ), 1.00 (d, J=7.5Hz, 1H, CH2-), 0.90-0.83 (m, 2H, _{-CH2- )} .

3-Bromo-4-((3-butylamino-6-chloro)methylpyridine)-5-fluoroethoxy-2(5H)-furanone (B18)

¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm): 8.34-8.29 (m, 1H, Py-H), 7.62 (dd, J=8.3, 2.6 Hz, 1H, Py-H), 7.39 (dd, J =8.3,0.7Hz,1H,Py-H),5.85(s,1H,O-CH-O),4.87(d,J=16.5Hz,1H,Py- _CH2 -N),4.70–4.63(m , 1H, Py-CH ₂ -N), 4.61(s, 1H, F-CH ₂ -), 4.51(d, J＝1.0Hz, 1H, F-CH ₂ -), 4.19–4.05(m, 1H, O-CH ₂ -), 3.99 (d, J=2.7Hz, 1H, O-CH ₂ -), 3.53–3.43 (m, 2H, N-CH ₂ -), 1.69–1.60 (m, 2H, -CH _2- ), 1.35-1.29 (m, 2H, _-CH2- ), 0.94 (t, J=7.3 Hz, 3H, _CH3- ).

Example 3. Test of insecticidal activity of the compounds of the present invention

(1) Biological activity test of rice planthopper - spray method

3-4 rice seedlings with 2 leaves and 1 heart (about 3.5 cm in length) were fixed in a 6 cm petri dish with quartz sand, and the mid-third instar nymphs of the rice planthopper were anesthetized with carbon dioxide. The above-mentioned rice seedlings were placed under the Potter spray tower, and at the same time, the Tween water with the highest concentration of organic solvent was used as a blank control. After spraying, cover it with a transparent glass cup, place it at 23-28°C, and illuminate for 15 hours, and investigate the results two days later. Touching with a brush, all the test worms with weak growth, slow action, and significantly less feeding are judged to be dead.

(2) Aphid biological activity test - spray method

An appropriate amount of aphids of the same size were placed on the broad bean seedling plants with a height of 2-3 cm, and after 24 hours in the insect breeding room, the above-mentioned broad bean seedlings were placed under the Potter spray tower for treatment, and the Tween water of the highest concentration organic solvent was used as a blank control. Placed at 20-23 °C for observation of indoor culture, and the results were observed after 2 days. Touching with a brush, all the test worms with weak growth, slow action, and significantly less feeding are judged to be dead.

Table 1 Synthetic Compound Biological Activity

Example 4. Preparation of Insecticide Compositions Containing Compounds of the Invention

(a) Oily suspension

Prepare the following components in proportion: 25% (weight percentage, the same below) any one of compounds A1-A16 or B1-B18; 5% polyoxyethylene sorbitan hexaoleate; 70% higher aliphatic hydrocarbon oil. The components are ground together in a sand mill until the solids fall below about 5 microns. The resulting viscous suspension can be used directly, but also after emulsification in water.

(b) Aqueous suspension

Prepare the following components in proportions: 25% of any of compounds A1-A16 or B1-B18; 3% hydrate attapulgit; 10% calcium lignosulfonate; 0.5% sodium dihydrogen phosphate; 61.5 %water. The components are ground together in a ball mill until the solids drop below about 10 microns. The aqueous suspension can be used directly.

(c) Bait

The following components are prepared in proportions: 0.1-10% any of compounds A1-A16 or B1-B18; 80% wheat flour; 19.9-10% molasses. The components are thoroughly mixed to form the bait shape as desired. Edible baits can be dispersed into hygienic pest-infested premises, such as domestic or industrial premises, such as kitchens, hospitals or shops, or outdoor areas, to control the pests by oral ingestion.

All documents mentioned herein are incorporated by reference in this application as if each document were individually incorporated by reference. In addition, it should be understood that after reading the above teaching content of the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the appended claims of the present application.

Claims (4)

1.A compound having a structure represented by formula (A):

，

wherein R is ₁ Is a pyridyl halide, R ₂ Is C _1-6 Alkyl or C _3-4 Cycloalkyl radical, R ₃ Is halo C _1-6 Alkyl, X is chlorine or bromine.

2. A pesticide composition comprising:

(a) 1-99.99% by weight of a compound of claim 1;

(b) an agriculturally pharmaceutically acceptable excipient.

3. The pesticidal composition of claim 2, wherein the pesticidal composition is used to kill: insects of the order homoptera.

4. A method of combating pests which comprises applying a compound as claimed in claim 1 or a pesticidal composition as claimed in any one of claims 2 to 3 to a plant suffering from pests or to the environment surrounding said plant.