Substituted benzo [d] oxazole compound as well as preparation method and application thereof

Abstract

The invention discloses a substituted benzo [d] oxazole compound as shown in a general formula (I) as well as a preparation method and application of the substituted benzo [d] oxazole compound. The compound has a benzo [d] oxazole-pyridine skeleton structure, in which: R is selected from C-Cbranched alkyl sulfinyl or C-Ccycloalkyl sulfinyl, preferably isopropyl sulfinyl; r is C-Calkyl; and R is C-Ccycloalkyl. According to the method, a platform preparation route is adopted, a sulfoxide center construction step is placed at the synthesis end, and the system temperature is maintained at 0-10 DEG C (preferably 1-3 hours) by accurately regulating and controlling the dosage (1.05-1.2 equivalents) of an oxidant and controlling the dropping speed, so that the generation (the content lt is 0.5%) of a sulfone byproduct is effectively inhibited, and the stereoselectivity control of the chiral center is realized. A biological activity test result shows that the compound has excellent insecticidal activity on agricultural pests such as brown planthopper, the LC value of the compound can be as low as 1.85 mg / L, the physicochemical property of the compound is suitable for preparation processing, and the compound can be widely applied to prevention and control of the agricultural pests.

Description

Technical Field

[0001] This invention belongs to the field of agricultural chemicals and organic synthesis technology, specifically focusing on a class of substituted benzo[d]oxazole compounds and their preparation methods, enantiomeric control methods, pesticide compositions and applications. Background Technology

[0002] Derivatives containing benzo[d]oxazole and pyridine rings show broad application prospects in the field of modern agrochemicals. However, in the existing synthesis process of such compounds containing sulfoxide groups, there have long been technical bottlenecks such as poor oxidation selectivity and the easy generation of sulfone byproducts (often >5.0%) that are difficult to separate, resulting in high industrialization costs and limited product purity. Summary of the Invention

[0003] This invention aims to provide a compound of general formula (I) and its preparation method. By optimizing the oxidation process, this invention effectively suppresses the formation of sulfone byproducts (content <0.5%).

[0004] To achieve the above objectives, the present invention adopts the following technical solution:

[0005] Provide a compound of general formula (I), wherein R¹ is selected from C3-C6 branched alkyl sulfinyl or C3-C6 cycloalkyl sulfinyl; R² is selected from C1-C6 alkyl; and R³ is selected from C3-C7 cycloalkyl.

[0006] A preparation method is provided, comprising the following steps: subjecting a thioether intermediate to terminal selective oxidation or asymmetric oxidation under the action of an oxidant.

[0007] The oxidant is selected from: hydrogen peroxide, aqueous solution of hydrogen peroxide (preferably 30%–50%), urea peroxide, sodium percarbonate, peracetic acid, perpropionic acid, perphthalic acid, m-chloroperoxybenzoic acid, or potassium peroxymonosulfate.

[0008] The catalyst is selected from: sodium tungstate, potassium tungstate, tungstic acid, phosphotungstic acid, sodium molybdate, molybdate, methyl rhenium trioxide, vanadium pentoxide, or tetraisopropyl titanate.

[0009] The technical advantages of this invention are as follows: by strictly controlling the oxidant equivalent (1.05-1.2 eq) and the dropping rate (maintaining temperature at 0-10°C and dropping time at 1-3 hours), highly selective synthesis of sulfoxide is achieved, significantly reducing the difficulty of purification. Attached Figure Description Figure 1 This is a schematic diagram of the structure of general formula (I) of the present invention. Figure 2 This is a schematic diagram of the structure of compound P1-01 in Example 1 of the present invention. Detailed Implementation

[0010] General synthesis process description: In a reaction vessel, dissolve the thioether intermediate in a solvent (such as acetonitrile, dichloromethane, or ethyl acetate) and add 1 mol%–5 mol% of catalyst. Cool the system to 0–10°C. Slowly add the calculated amount of oxidant using a constant-pressure dropping funnel or micropump. The dropping rate must be strictly controlled to ensure that the exothermic reaction does not cause the system temperature to exceed 10°C. For experiments on a 50 mmol scale, the dropping time is recommended to be between 60–180 minutes. After the dropping is complete, maintain this temperature and continue stirring the reaction for 2–4 hours.

[0011] Example 1: Preparation of compound P1-01 Figure 2 Schematic diagram of the structure of compound P1-01

[0012] 2-Amino-4-(isopropylthio)phenol was subjected to a condensation-ring-closure reaction with the corresponding 3-ethylsulfonyl-5-cyclopropylpyridine-2-carboxylic acid to obtain a thioether intermediate.

[0013] Detailed oxidation procedure: Dissolve the obtained thioether intermediate (50 mmol) in 200 mL of acetonitrile, and add 0.16 g of Na₂WO₄·2H₂O. Cool to 5°C. Slowly add 30% H₂O₂ (approximately 6.0 g, 1.05 eq) dropwise over 120 minutes. Observe the internal temperature during the addition, maintaining it at 2–8°C. After the addition is complete, maintain the reaction at 5°C for 3 hours.

[0014] Results: The purity of the obtained P1-01 (5-isopropylsulfinyl-2-(3-ethylsulfonyl-5-cyclopropylpyridin-2-yl)benzo[d]oxazole) was ≥95%, and the content of sulfone impurities was determined to be 0.32%. HRMS (ESI-TOF): m / z [M+H]⁺419.10.

[0015] Example 2: Parallel Tests of Oxidizing Agents Following the method of Example 1, the oxidants were replaced with equivalent amounts of m-chloroperoxybenzoic acid (mCPBA), urea peroxide, and potassium persulfate, respectively. Experimental results showed that each oxidant could be successfully converted into the target sulfoxide, and the sulfoxide impurity content could be controlled below 0.8% under controlled dropping at 0-10°C.

[0016] Example 3: Parallel Tests of Catalyst Following the method of Example 1, the catalysts were replaced with sodium molybdate, vanadium pentoxide, and methyl rhenium trioxide, respectively. Experimental results showed that when sodium molybdate was used as the catalyst, the reaction induction period was slightly longer, but the sulfoxide selectivity of the final product was comparable to that of Example 1.

[0017] Example 4: Bioactivity Assay The insecticidal activity of the compound of this invention against brown planthopper (Nilaparvata lugens) was determined using the conventional leaf-dipping method. Compound P1-01 was prepared into a series of concentrations in acetone. Rice leaves were soaked in the solution and then dried. Third-instar nymphs of brown planthoppers were then introduced into the solution, and the mortality rate was recorded after 48 hours. The results showed that compound P1-01 had an LC50 of [missing information - likely a specific concentration]. 50 The concentration was 1.85 mg / L, demonstrating excellent insecticidal activity.

Claims

1. A compound of general formula (I) or a racemic mixture, enantiomer, or single enantiomer thereof, or a pesticide-acceptable salt or solvate thereof:

2. Wherein, R¹ is selected from C3-C6 branched alkyl sulfinyl or C3-C6 cycloalkyl sulfinyl; R² is selected from C1-C6 alkyl; R³ is selected from C3-C7 cycloalkyl.

3. The compound according to claim 1, characterized in that: R¹ is -S(O)-CH(CH3)2; R² is selected from methyl, ethyl, n-propyl or isopropyl; R³ is selected from cyclopropyl, cyclobutyl or cyclopentyl.

4. The compound according to claim 1, characterized in that, R² represents ethyl, and R³ represents cyclopropyl.

5. The compound according to claim 1, wherein it is 5-isopropylsulfinyl-2-(3-ethylsulfonyl-5-cyclopropylpyridin-2-yl)benzo[d]oxazole.

6. The compound according to claim 1, characterized in that, The pesticide-acceptable salts are selected from hydrochloride, sulfate, phosphate, methanesulfonate, sodium salt, potassium salt, calcium salt, or magnesium salt.

7. A method for preparing the compound according to any one of claims 1 to 5, characterized in that, Includes any of the following paths: Path (1): a) Condensate 2-amino-4-(thioether corresponding to R¹)phenol with 3-(R²-sulfonyl)-5-R³-pyridine-2-carboxylic acid or its active derivative to obtain an amide intermediate; b) The amide intermediate obtained in step a) is subjected to a ring-closing reaction in the presence of a dehydrating ring-closing agent to form a benzo[d]oxazolium thioether intermediate; c) The thioether intermediate obtained in step b) is subjected to terminal selective oxidation or asymmetric oxidation under the action of an oxidant to obtain the compound of general formula (I).

8. Path (2): A 2-aminophenol derivative containing a sulfoxide group at the 5-position is directly condensed and cyclically closed with 3-(R²-sulfonyl)-5-R³-pyridine-2-carboxylic acid or its active derivative to obtain the compound of general formula (I).

9. Figure 1. Schematic diagram of general formula (I).

10. The method according to claim 6, characterized in that, The oxidant mentioned in step c) of path (1) is selected from: hydrogen peroxide, aqueous hydrogen peroxide solution, urea peroxide, sodium percarbonate, peracetic acid, perpropionic acid, perphthalic acid, m-chloroperoxybenzoic acid or potassium persulfate; preferably a 30%–50% aqueous hydrogen peroxide solution; the molar ratio of the oxidant to the sulfide intermediate is controlled between 1.0:1.05 and 1.0:1.2, and the reaction temperature is controlled between 0–10°C.

11. The method according to claim 6 or 7, characterized in that, In step c) of path (1), a catalyst containing a metal element is used, wherein the catalyst is selected from: sodium tungstate, potassium tungstate, tungstic acid, phosphotungstic acid, sodium molybdate, molybdate, methyl rhenium trioxide, vanadium pentoxide or tetraisopropyl titanate; or a chiral catalytic system is used for asymmetric oxidation, wherein the chiral catalytic system is selected from: titanium / tartrate ester system, vanadium / chiral Schiff base system or chiral metal Salen complex system.

12. The method according to claim 7 or 8, characterized in that, In step c), the reaction temperature of the system is kept constant at 0-10°C by controlling the dropping rate of the oxidant, and the dropping time is controlled at 1-3 hours.

13. A pesticide composition, characterized in that, The active ingredient comprises an effective amount of any one of claims 1 to 5, and an agriculturally acceptable carrier and / or adjuvant.

14. The use of the compound of any one of claims 1 to 5 or the pesticide composition of claim 10 in the control of agricultural pests.

15. A method for controlling agricultural pests, characterized in that, Apply the compound of any one of claims 1 to 5 or the pesticide composition of claim 10 to the pest or its growth medium.

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