A preparation method of a dual-oxazolidine compound

Abstract

The application provides a preparation method of a dual-phenyl-oxazolyl acid compound, and a specific synthesis route is as follows: wherein the definition of R1 is as defined in the description. The dual-phenyl-oxazolyl acid compound is prepared through one-step reaction, the production cost is reduced, and the method has a good industrial application prospect.

Description

Technical Field

[0001] This invention belongs to the field of pesticide compound synthesis, specifically relating to a method for preparing a bisbenzazole acid compound. Background Technology

[0002] Ethyl bis(oxazolyl)ate, as an important herbicide safener, has become a key adjuvant in modern agricultural production. By enhancing crop tolerance to specific herbicides, it effectively improves crop safety while ensuring weed control.

[0003] Currently, there are many methods for synthesizing ethyl bis(benzoxazole) acid, but they all suffer from the problem of long synthesis routes. For example, the synthesis route disclosed by the applicant in patent CN107652245 uses benzophenone as a starting material to synthesize ethyl bis(benzoxazole) acid in three steps. The synthesis route is as follows:

[0004] .

[0005] The applicant disclosed a synthetic route in patent CN117903074, which uses stilbene as a starting material to synthesize ethyl bis(benzyl)oxazolate in two steps. The synthetic route is as follows:

[0006] .

[0007] The above-mentioned synthetic route involves numerous steps and is costly. The applicant ingeniously utilizes dichlorodiphenylmethane and 2-(hydroxyimino)propionic acid or its ester to synthesize bisphenyloxazole acid compounds in a one-step process, improving reaction yield and reducing production costs. Based on this, the present invention was completed. Summary of the Invention

[0008] To address the drawbacks of existing technologies for synthesizing bisbenzazole acid compounds, such as long synthesis routes and high production costs, this invention provides a one-step method for preparing bisbenzazole acid compounds. Specifically, it involves reacting a compound of formula II with a compound of formula III in the presence of a base and a catalyst to prepare a compound of formula I. The synthetic route is as follows:

[0009] ,

[0010] R1 is selected from hydrogen or C1-C6 alkyl, preferably hydrogen, methyl, or ethyl.

[0011] Beneficial effects

[0012] This invention provides a one-step method for preparing bisbenzoxazole acid compounds, which improves reaction yield, reduces production costs, and uses mild reaction conditions, making it more suitable for industrial production. Detailed Implementation

[0013] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. Unless otherwise expressly stated, throughout the specification and claims, the term "comprising" or its variations such as "including" or "comprising of," etc., will be understood to include the stated components or steps, without excluding other substances or steps.

[0014] Furthermore, to better illustrate the present invention, numerous specific details are provided in the following detailed embodiments.

[0015] Those skilled in the art will understand that the present invention can be practiced even without certain specific details. In some embodiments, materials, methods, and means well known to those skilled in the art are not described in detail in order to highlight the spirit of the invention.

[0016] In this invention, C1-C6 alkyl refers to straight-chain or branched alkyl groups containing 1-6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, etc., but is not limited thereto.

[0017] This invention provides a method for preparing a compound of formula I, comprising the step of reacting a compound of formula II with a compound of formula III in the presence of a base and a catalyst to prepare the compound of formula I; the synthetic route is as follows:

[0018] ,

[0019] R1 is selected from hydrogen or C1-C6 alkyl, preferably hydrogen, methyl, or ethyl.

[0020] In the above preparation method, the alkali is an organic alkali or an inorganic alkali. The organic alkali includes triethylamine, pyridine, sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc., and the inorganic alkali includes one or more of sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, sodium hydride, and potassium hydride. Preferably, the alkali is one or more of sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, and potassium hydride.

[0021] In the above preparation method, the catalyst is selected from one or more of palladium, palladium acetate, palladium propionate, palladium benzoate, palladium trifluoroacetate, palladium dichloride, palladium dibromide, palladium sulfate, tris(dibenzylacetone)dipalladium, bis(dibenzylacetone)dipalladium, palladium acetylacetonate, nickel, nickel nitrate, nickel dibromide, nickel difluoride, nickel sulfate, nickel dichloride, nickel acetate, cuprous chloride, cuprous bromide, cuprous iodide, and cuprous cyanide.

[0022] Preferably, the reaction in the preparation method of the present invention is carried out in a solvent selected from one or more of acetonitrile, benzene, toluene, tetrahydrofuran, 1,4-dioxane, petroleum ether, n-hexane, cyclohexane, pyridine, DMF, acetone, butanone, methyl isobutyl ketone, cyclohexanone, ethyl acetate, butyl acetate, isopropyl acetate, and DMSO.

[0023] Preferably, the reaction temperature of the preparation method of the present invention is 40-100℃, and the reaction time is 1-5h.

[0024] I. Preparation Examples

[0025] In this specification, if there are any differences between chemical names and chemical structures, the structure is preferred. Generally, the compounds of this invention can be prepared by the methods described herein, unless further specified. The raw materials, reagents, etc., used to prepare the compounds of this invention are commercially available or can be prepared by methods conventional in the art.

[0026] Example 1 Synthesis of Bisbenoxazolic Acid

[0027]

[0028] Take 250 ml of toluene, add 5.67 g of 2-(hydroxyimino)propionic acid, 11.85 g of dichlorodiphenylmethane, 3.0 g of sodium hydride, and 0.006 g of nickel chloride. React at 80 °C for 2 h. After the reaction is complete, add hydrochloric acid aqueous solution, take the organic layer and concentrate to obtain 13.20 g of bis(benzoxazole) acid, with a yield of 98.8%.

[0029] Example 2 Synthesis of Bisbenoxazol Acid

[0030] Take 250 ml of toluene, add 5.67 g of 2-(hydroxyimino)propionic acid, 11.85 g of dichlorodiphenylmethane, 17.28 g of potassium carbonate, and 0.006 g of nickel chloride. React at 80 °C for 2 h. After the reaction is complete, add hydrochloric acid solution, take the organic layer, concentrate, and recrystallize from methanol to obtain 11.01 g of bis(benzoxazole) acid, with a yield of 82.4%.

[0031] Example 3 Synthesis of methyl bis(benzoxazole) acid

[0032]

[0033] Take 200 ml of acetonitrile, add 6.44 g of methyl 2-(hydroxyimino)propionate, 11.85 g of dichlorodiphenylmethane, 6.0 g of sodium hydroxide, and 0.01 g of palladium chloride. React at 40 °C for 3 h. After the reaction is complete, add dichloroethane, then add water and concentrate the organic layer to obtain 13.84 g of methyl bis(benzoxazole) acid, with a yield of 98.4%.

[0034] Example 4 Synthesis of methyl bis(benzoxazole) acid

[0035] Take 200 ml of acetonitrile, add 6.44 g of methyl 2-(hydroxyimino)propionate, 11.85 g of dichlorodiphenylmethane, 15.18 g of triethylamine, and 0.01 g of palladium chloride. React at 40 °C for 3 h. After the reaction is complete, add dichloroethane, then add water and concentrate the organic layer to obtain 11.20 g of methyl bis(benzoxazole) acid, with a yield of 79.6%.

[0036] Example 5 Synthesis of ethyl 2-(hydroxyimino)propionate

[0037]

[0038] Take 150 ml of methanol, add 5.81 g of ethyl pyruvate, 5.21 g of hydroxylamine hydrochloride and 10.12 g of triethylamine, react at 60 °C for 3 h, add dichloroethane after the reaction is complete, then add water and take the organic layer to concentrate to obtain 6.50 g of ethyl 2-(hydroxyimino)propionate, with a yield of 99.2%.

[0039] Example 6 Synthesis of ethyl bis(benzoxazole) acid

[0040]

[0041] Take 200 ml of 1,4-dioxane, add 7.21 g of ethyl 2-(hydroxyimino)propionate, 11.85 g of dichlorodiphenylmethane, 22.5 g of sodium methoxide methanol solution (30% by mass), and 0.009 g of cuprous cyanide. React at 60 °C for 3 h. After the reaction is complete, add dichloroethane, then add water and concentrate the organic layer to obtain 14.53 g of ethyl bis(benzoxazole) acid, with a yield of 98.4%.

[0042] 1H NMR (300MHz, DMSO) δ7.26-7.45(m,10H), δ4.20-4.28(q,2H), δ3.91(s,2H), δ1.22-1.27(t,3H).

[0043] Example 7 Synthesis of ethyl bis(benzoxazole) acid

[0044] Take 200 ml of 1,4-dioxane, add 7.21 g of ethyl 2-(hydroxyimino)propionate, 11.85 g of dichlorodiphenylmethane, and 22.5 g of sodium methoxide methanol solution (30% by mass). React at 60 °C for 3 h. After the reaction is complete, add dichloroethane, then add water, collect the organic layer for concentration, and purify by preparative liquid chromatography to obtain 4.27 g of ethyl bis(benzoxazole) acid, with a yield of 28.9%.

[0045] The preferred embodiments of the present invention have been described in detail above; however, the present invention is not limited thereto. Within the scope of the inventive concept, various simple modifications can be made to the technical solutions of the present invention, including combinations of various technical features in any other suitable manner. These simple modifications and combinations should also be considered as the content disclosed in the present invention and are all within the protection scope of the present invention.

Claims

1. A method for preparing a compound of formula I, characterized in that, The synthetic route includes the step of reacting compound II with compound III in the presence of a base and a catalyst to prepare compound I; the synthetic route is as follows: ， R1 is selected from hydrogen or C1-C6 alkyl, preferably hydrogen, methyl, or ethyl.

2. The preparation method according to claim 1, characterized in that, The alkali is an organic or inorganic alkali. The organic alkali includes triethylamine, pyridine, sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc., and the inorganic alkali includes one or more of sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, sodium hydride, and potassium hydride. Preferably, the alkali is one or more of sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, and potassium hydride.

3. The preparation method according to claim 1 or 2, characterized in that, The catalyst is selected from one or more of palladium, palladium acetate, palladium propionate, palladium benzoate, palladium trifluoroacetate, palladium dichloride, palladium dibromide, palladium sulfate, tris(dibenzylacetone)dipalladium, bis(dibenzylacetone)dipalladium, palladium acetylacetonate, nickel, nickel nitrate, nickel dibromide, nickel difluoride, nickel sulfate, nickel dichloride, nickel acetate, cuprous chloride, cuprous bromide, cuprous iodide, and cuprous cyanide.

4. The preparation method according to any one of claims 1-3, characterized in that, The reaction is carried out in a solvent selected from one or more of the following: acetonitrile, benzene, toluene, tetrahydrofuran, 1,4-dioxane, petroleum ether, n-hexane, cyclohexane, pyridine, DMF, acetone, butanone, methyl isobutyl ketone, cyclohexanone, ethyl acetate, butyl acetate, isopropyl acetate, and DMSO.

5. The preparation method according to any one of claims 1-4, characterized in that, The reaction temperature is 40-100℃, and the reaction time is 1-5h.

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