Preparation method and intermediate of tembotrione

Abstract

The invention provides a method for preparing tembotrions, which is characterized by comprising any one of the following steps. # imgabs0 #

Description

Preparation method and intermediate of tembotrione Technical Field

[0001] The present invention relates to a novel process and a novel intermediate compound for preparing the herbicide tembotrione. Background Art

[0002] Cyclosulfuron is a triketone herbicide with the advantages of high efficiency, low toxicity, low residue and broad spectrum. Therefore, its market has been expanding since it was launched on the market.

[0003] As a method for preparing tembotrione, the original patent document DE19846792A1 discloses the following method:

[0004] The raw material dichlorotoluene used in the above method has poor selectivity during the reaction, resulting in a large number of impurities and a low yield.

[0005] The following routes are currently widely reported and adopted (see, for example, Chinese patent application No. 200510030163.5):

[0006] However, the above method has a total of 11 steps, which is too many. The FC reaction of acetyl chloride is highly irritating, and the post-treatment produces a large amount of wastewater containing the catalyst aluminum chloride. The subsequent sodium hypochlorite haloform reaction is also carried out in the aqueous phase. During the reaction, haloform is generated and a large amount of wastewater containing sodium chloride is produced, which causes serious pollution. In addition, after the acetyl group is attached to the molecule through the FC reaction, the methyl group needs to be cut off through the chloroform reaction. This is unreasonable from the perspective of raw material economy and has problems such as high cost and low efficiency.

[0007] Summary of the Invention

[0008] The present invention aims to provide a novel method and a novel intermediate compound for preparing tembotrione.

[0009] The novel method and novel intermediate of the present invention can prepare tembotrione in fewer steps than the above-mentioned existing process route, thereby saving costs and improving production efficiency.

[0010] Specifically, the present invention relates to:

[0011] (1) A method for preparing tembotrione, characterized in that it comprises any one of the following steps:

[0012] (2) The method according to (1) above, wherein steps (v) and (v′) are respectively the following steps:

[0013] (3) The method for preparing tembotrione according to (1) or (2) above, further comprising any one or two or more intermediate preparation steps of (i) to (iv) as shown below:

[0014] (4) According to the method described in (3) above, steps (i) to (iv) are each independently the following steps:

[0015] In step (iii'), the bromination reagent is bromine, N-bromosuccinimide, or a combination of hydrogen bromide and hydrogen peroxide, preferably bromine; in step (iv'), CF3CH2OM is CF3CH2ONa or CF3CH2OK.

[0016] (5) The method according to any one of (1) to (4) above, comprising the following intermediate preparation steps:

[0017] (6) According to the method described in (5) above, the intermediate preparation steps are as follows:

[0018] In the formula, the bromination reagent is bromine, N-bromosuccinimide, or a combination of hydrogen bromide and hydrogen peroxide, preferably bromine; CF3CH2OM is CF3CH2ONa or CF3CH2OK.

[0019] (7) The method according to (5) or (6) above, further comprising the following steps:

[0020] The step (vi') is carried out in a stepwise manner by isolating the intermediate ester compound, or in a one-pot manner without isolating the intermediate ester compound.

[0021] (8) The method according to (7) above, wherein steps (vi) and (vi′) are respectively the following steps:

[0022] The step (vi′-1) is carried out in a stepwise manner by isolating the intermediate ester compound, or in a one-pot manner without isolating the intermediate ester compound.

[0023] (9) A compound represented by the following formula (A):

[0024] Wherein, R1 and R2 are any of the following:

[0025] R1 is CF3-CH2-O-CH2-, and R2 is CH3-SO2-;

[0026] R1 is Br-CH2-, and R2 is CH3-SO2-;

[0027] R1 is CH3-, and R2 is CH3-SO2-;

[0028] R1 is CH3-, and R2 is CH3-S-.

[0029] (10) A method for preparing tembotrione, characterized in that the compound described in (9) above is used as an intermediate.

[0030] (11) Use of the compound according to (9) above as an intermediate for the preparation of tembotrione. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 is a diagram of the compound of formula (VI) prepared in Example 1 1 HNMR spectrum.

[0032] Figure 2 is a diagram of the compound of formula (VI) prepared in Example 1 13 CNMR spectrum.

[0033] Figure 3 is a diagram of the compound of formula (I) prepared in Example 2 1 HNMR spectrum.

[0034] Figure 4 is a diagram of the compound of formula (I) prepared in Example 2 13 CNMR spectrum.

[0035] Figure 5 is a graph showing the compound of formula (II) prepared in Example 3. 1 HNMR spectrum.

[0036] Figure 6 is a graph showing the compound of formula (II) prepared in Example 3. 13 CNMR spectrum.

[0037] FIG7 is a graph showing the compound of formula (III) prepared in Example 4. 1 HNMR spectrum.

[0038] FIG8 is a graph showing the compound of formula (III) prepared in Example 4. 13 CNMR spectrum.

[0039] Figure 9 is a graph showing the compound of formula (IV) prepared in Example 5. 1 HNMR spectrum.

[0040] FIG10 is a graph showing the compound of formula (IV) prepared in Example 5. 13 CNMR spectrum.

[0041] Figure 11 is a diagram of the compound of formula (V) prepared in Example 6 1 HNMR spectrum.

[0042] Figure 12 is a graph showing the compound of formula (V) prepared in Example 6. 13 CNMR spectrum.

[0043] Figure 13 is a graph showing the compound of formula (VIII) prepared in Example 9. 1 HNMR spectrum.

[0044] Figure 14 is a graph showing the structure of the compound of formula (VIII) prepared in Example 9. 13 CNMR spectrum.

[0045] Figure 15 is a diagram of the tembotrione compound prepared in Example 10. 1 HNMR spectrum.

[0046] Figure 16 is a diagram of the tembotrione compound prepared in Example 10. 13 CNMR spectrum. DETAILED DESCRIPTION

[0047] One aspect of the present invention provides a novel compound represented by the following formula (A):

[0048] Wherein, R1 and R2 are any of the following:

[0049] R1 is CF3-CH2-O-CH2-, and R2 is CH3-SO2-;

[0050] R1 is Br-CH2-, and R2 is CH3-SO2-;

[0051] R1 is CH3-, and R2 is CH3-SO2-;

[0052] R1 is CH3-, and R2 is CH3-S-.

[0053] The compounds represented by formula (A) specifically include compounds of the following formulas (I)-(IV):

[0054] The compound of formula (I) of the present invention can be prepared by the following route:

[0055] In a specific embodiment, the above route uses the compound of formula (VI) and bromine as raw materials and is carried out as follows, but is not limited thereto.

[0056] In a more specific embodiment, the above reaction is performed as follows, but not limited thereto: bromine is added dropwise to the compound of formula (VI), and after completion of the reaction, the reaction is quenched with an alkaline solution, washed with an alkaline solution and then with water, and separated to obtain the compound of formula (I). Specific examples of the alkaline solution include, but are not limited to, aqueous NaOH solution.

[0057] In a more specific embodiment, the above reaction is carried out at a temperature of about 10-30°C.

[0058] In a more specific embodiment, dichloromethane or 1,2-dichloroethane is used as a solvent in the above reaction.

[0059] The compound of formula (VI) as a raw material can be prepared by the following reaction according to the known method described in, for example, patent document CN106631941A:

[0060] The compound of formula (II) of the present invention can be prepared by the following route:

[0061] In a specific embodiment, the above route uses hydrogen peroxide as an oxidant and is carried out as follows, but is not limited thereto.

[0062] In a more specific embodiment, the above reaction can be performed as follows but is not limited thereto: the compound of formula (I) is mixed with a solvent and an optional catalyst, the temperature is increased, hydrogen peroxide is added dropwise to the mixture, and after the reaction is completed, the temperature is reduced, the mixture is filtered, washed with water, and dried to obtain a compound of formula (II).

[0063] In a more specific embodiment, tungstate, metatungstate, vanadate, or metavanadate is used as a catalyst in the above reaction, and the salts include sodium salt, potassium salt, and ammonium salt. Preferably, sodium tungstate dihydrate is used as the catalyst.

[0064] In a more specific embodiment, glacial acetic acid or formic acid is used as a solvent in the above reaction.

[0065] In a more specific embodiment, the temperature in the above reaction is raised to 40-100°C, preferably to 70-90°C.

[0066] In a more specific embodiment, the molar ratio of the compound of formula (I) to hydrogen peroxide in the above reaction is about 1-5, preferably 2-3.

[0067] The compound of formula (III) of the present invention can be prepared by the following route:

[0068] In a specific embodiment, the above route uses the compound of formula (II) and a bromination reagent as raw materials and is carried out as follows, but is not limited thereto.

[0069] In a more specific embodiment, the above reaction can be carried out as follows, but is not limited thereto: a compound of formula (II) is mixed with a solvent and an optional initiator, the temperature is raised, and a bromination reagent is added dropwise to the mixture. After completion of the reaction, the reaction is quenched with an alkaline solution, washed sequentially with an alkaline solution and water, and the solvent is evaporated and the resulting solid is dried to obtain a compound of formula (III). Specific examples of the alkaline solution include, but are not limited to, aqueous NaOH solution.

[0070] In a more specific embodiment, bromine, N-bromosuccinimide, or a combination of hydrogen bromide and hydrogen peroxide is used as the brominating agent in the above reaction, preferably bromine is used as the brominating agent.

[0071] In a more specific embodiment, benzoyl peroxide (BPO) and azobisisobutyronitrile (AIBN) are used as initiators in the above reaction.

[0072] In a more specific embodiment, dichloromethane, dichloroethane or carbon tetrachloride is used as solvent in the above reaction.

[0073] In a more specific embodiment, the temperature in the above reaction is raised to 40-100°C, preferably to 50-80°C.

[0074] The compound of formula (IV) of the present invention can be prepared by the following route:

[0075] In a specific embodiment, the above route uses the compound of formula (III) and sodium trifluoroethoxide or potassium trifluoroethoxide as raw materials and is carried out as follows, but is not limited thereto.

[0076] In the above formula, CF3CH2OM is CF3CH2ONa or CF3CH2OK.

[0077] In a more specific embodiment, the above reaction can be carried out as follows, but is not limited thereto: the compound of formula (III) and sodium trifluoroethoxide or potassium trifluoroethoxide are dissolved in a solvent, and the solution of the compound of formula (III) is added dropwise to the sodium trifluoroethoxide or potassium trifluoroethoxide solution. After completion of the reaction, water is added to quench the reaction, the layers are separated, the organic layer is washed with saturated brine, the solvent is evaporated, the mixture is recrystallized from methanol or ethanol, and dried to obtain the compound of formula (IV).

[0078] In a more specific embodiment, tetrahydrofuran, 1,4-dioxane, or diethyl ether is used as a solvent in the above reaction, and anhydrous tetrahydrofuran is preferably used as a solvent.

[0079] In a more specific embodiment, when the solution of the compound of formula (III) is added dropwise to a solution of sodium trifluoroethoxide or potassium trifluoroethoxide, the temperature of the reactants is controlled not to exceed -5 to 15°C during the addition.

[0080] In a more specific embodiment, sodium or potassium trifluoroethoxide is prepared by reacting sodium or potassium hydride, sodium or potassium methoxide, sodium or potassium hydroxide, and trifluoroethanol.

[0081] The compound of formula (IV) of the present invention can be prepared into a carboxylic acid compound of formula (V) by, but not limited to, the following carbonyl insertion reaction:

[0082] In a more specific embodiment, the reaction (v-1) can be carried out as follows, but is not limited thereto: a compound of formula (IV), water, an acid-binding agent, a catalyst, a ligand, and a first solvent are added to an autoclave, the mixture is evacuated, the atmosphere is replaced with nitrogen, CO is introduced, and the reaction is carried out at 80-120°C, preferably 80-90°C, for 10-20 hours. The mixture is filtered, the first solvent is evaporated, and a second solvent is added to dissolve the mixture. The pH is adjusted to 2-3, a white solid is precipitated, and the mixture is filtered to obtain a compound of formula (V).

[0083] In a more specific embodiment, in the above reaction, a noble metal catalyst such as palladium, rhodium, ruthenium, copper, or cobalt is used as the catalyst.

[0084] In a more specific embodiment, a palladium catalyst is used, specific examples of which include but are not limited to palladium chloride (PdCl2), palladium carbonate (PdCO3), palladium acetate [Pd(OAc)2], palladium / carbon (Pd / C), palladium trifluoroacetate [Pd(OTFA)2], bis(dibenzylideneacetonepalladium) [Pd(dba)2], etc., preferably palladium chloride (PdCl2).

[0085] In a more specific embodiment, a phosphorus ligand or a salt thereof is used as a catalyst ligand in the above reaction, preferably 1,3-(bisdiphenylphosphino)propane, 1,4-bis(diphenylphosphino)butane or bis[(4-N,N-dimethylamino)phenyl]di-tert-butylphosphine.

[0086] In a more specific embodiment, the acid binding agent used in the above reaction is triethylamine, potassium carbonate, sodium carbonate, cesium carbonate (CsCO3), potassium phosphate, N,N-dimethylacetamide (DMAC), N,N-diisopropylethylamine (DIPEA), 1,8-diazabicycloundec-7-ene (DBU), triethylenediamine (DABCO), etc.

[0087] In a more specific embodiment, the first solvent used in the above reaction is a solvent selected from aromatic hydrocarbons, sulfoxides, ethers, and amides, preferably one or more of toluene, 1,4-dioxane, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, dimethyl sulfoxide (DMSO), tetrahydrofuran (THF), and N,N-dimethylformamide (DMF).

[0088] In a more specific embodiment, the pressure of CO introduced into the above reaction is about 1-4 MPa.

[0089] In a more specific embodiment, in the above reaction, after the first solvent is evaporated, an alcohol solvent such as methanol or ethanol is added as a second solvent for dissolution.

[0090] In other embodiments, the compound of formula (IV) of the present invention can be directly prepared into an ester compound of formula (VIII) by, but not limited to, the following carbonyl insertion reaction.

[0091] The carboxylic acid compound of formula (V) and the ester compound of formula (VIII) are important intermediates for the preparation of tembotrione. Tembotrione can be prepared by the following route, referring to the known methods disclosed in, for example, patent document DE19846792A1. When preparing tembotrione by rearrangement of the ester compound of formula (VIII), a cyanide catalyst is preferably used, and acetone cyanohydrin is particularly preferably used as the catalyst.

[0092] In a more specific embodiment, the method for carrying out the reaction (v′-1) is the same as the method for carrying out the reaction (v-1) described above, except that no water is added to the reactants.

[0093] After the intermediate ester compound of formula (VIII) is prepared from the compound of formula (IV), the intermediate ester compound can be separated first and tembotrione can be prepared step by step, or tembotrione can be directly prepared by a one-pot process without separating the intermediate ester compound.

[0094] In the above reactions (v-1) and (v′-1), the method of inserting carbonyl groups by CO is listed, but the present invention is not limited to this. The embodiments of preparing the intermediate acid compound represented by formula (V) from the compound of formula (IV) by other methods, or directly preparing the intermediate ester compound of formula (VIII) are all included in the scope of the present invention.

[0095] Another aspect of the present invention provides a novel method for preparing tembotrione, comprising using any one or more compounds of formula (I) to formula (IV) as intermediates. Regardless of whether these intermediate compounds are isolated during the preparation process, using these intermediates in a single form or as an unisolated mixture to prepare tembotrione falls within the scope of the novel method of the present invention.

[0096] In another aspect, the present invention provides a novel method for preparing tembotrione, which comprises any one of the following steps:

[0097] Wherein, route (v) represents the preparation of the carboxylic acid compound of formula (V) from the compound of formula (IV), and route (v') represents the direct preparation of the ester compound of formula (VIII) from the compound of formula (IV).

[0098] In a more specific embodiment, the steps (v) and (v') are respectively the following steps, and the more specific embodiments of these steps are as described above.

[0099] The novel method for preparing tembotrione of the present invention may further include any one or two or more intermediate preparation steps of the following (i) to (iv):

[0100] In a specific embodiment, the above (i) to (iv) may be steps (i') to (v') as shown below, and more specific embodiments of these steps are as described above.

[0101] In a more specific embodiment, the novel method of the present invention comprises the following steps:

[0102] In a more specific embodiment, the novel method of the present invention comprises the following steps:

[0103] In the formula, the bromination reagent is bromine, N-bromosuccinimide, or a combination of hydrogen bromide and hydrogen peroxide, preferably bromine; CF3CH2OM is CF3CH2ONa or CF3CH2OK.

[0104] In another aspect, the present invention provides the use of the compounds of formula (I) to (IV) as intermediates for the preparation of tembotrione.

[0105] Example

[0106] Example 1 Preparation of the compound of formula (VI)

[0107] At 20°C, 1165g of 5.1% hydrochloric acid was added to a four-necked flask, and 100g of 3-chloro-2-methylaniline was added dropwise. After the addition was complete, 251.41g of a 20% aqueous solution of NaNO2 was further added dropwise at 0°C, with the temperature controlled not to exceed -5 to 10°C during the addition, and the mixture was stirred to obtain a diazonium salt solution. 273g of a 20% aqueous solution of CH3SNa and 26.62g of a 32% aqueous solution of NaOH were weighed and placed in another four-necked flask. The diazonium salt solution was added dropwise to this flask, and the reaction was monitored by high performance liquid chromatography. After the reaction was completed, the pH was adjusted to 2 to 3 with hydrochloric acid, and the organic layer was collected and distilled to obtain the compound of formula (VI).

[0108] HPLC conditions: Kromasil C18 reverse phase column, mobile phase: acetonitrile: water (pH adjusted to 3.7-4.1 with formic acid) = 80:20 (V:V), flow rate 1.0 mL / min, column temperature 30°C, detection wavelength 210 nm, injection volume 5 μL.

[0109] Compound of formula (VI) 1 The HNMR (CDCl3) spectrum is shown in Figure 1. 13 The CNMR (CDCl3) spectrum is shown in Figure 2.

[0110] Example 2 Preparation of the compound of formula (I)

[0111] 100.75 g of the compound of formula (VI) and 400 g of dichloromethane were placed in a four-necked round-bottom flask, and 98.4 g of bromine was added dropwise at about 10° C. After completion of the reaction, as monitored by high-performance liquid chromatography, the reaction was quenched with 30 mL of a 32% NaOH solution. The organic phase was separated and washed twice with 70 mL of a 32% aqueous NaOH solution, then twice with 70 mL of water. The layers were separated, and the solvent was removed by rotary evaporation of the organic layer to obtain the compound of formula (I).

[0112] HPLC conditions: except that the detection wavelength was 254 nm, the others were the same as those in Example 1.

[0113] Compounds of formula (I) 1 The HNMR (CDCl3) spectrum is shown in Figure 3. 13 The CNMR (CDCl3) spectrum is shown in Figure 4.

[0114] Example 3 Preparation of the compound of formula (II)

[0115] 146 g of the compound of formula (I), 1.91 g of sodium tungstate dihydrate, and 600 mL of glacial acetic acid were added to a four-necked flask, the temperature was raised to 80°C, and 224 g of 23% hydrogen peroxide was added dropwise. After the reaction was completed as monitored by HPLC, the reaction was stopped, the temperature was lowered, and the mixture was filtered. The filter cake was washed twice with water and then dried at 60°C to obtain the compound of formula (II). Melting point: 138-140°C.

[0116] HPLC conditions: same as in Example 1.

[0117] Compound of formula (II) 1 The HNMR (CDCl3) spectrum is shown in Figure 5. 13 The CNMR (CDCl3) spectrum is shown in Figure 6.

[0118] Example 4 Preparation of the compound of formula (III)

[0119] Method 1: Add 84 g of compound (II), 3.58 g of benzoyl peroxide, and 500 mL of 1,2-dichloroethane to a four-necked round-bottom flask, heat to 60°C, and add 52.8 g of bromine dropwise. After the bromine addition is complete, monitor the reaction by HPLC. After completion, quench the reaction with 50 mL of 32% aqueous NaOH solution. The organic phase is separated and washed twice with 50 mL of 32% aqueous NaOH solution and twice with 50 mL of water. The solvent is removed by rotary evaporation at 50°C, and the resulting solid is dried at 60°C to yield compound (III). Melting point: 148-150°C.

[0120] Method 2: 84 g of the compound of formula (II), 3.58 g of benzoyl peroxide, 64.1 g of N-bromosuccinimide and 500 mL of carbon tetrachloride were added to a four-necked round-bottom flask, the temperature was raised to 60°C, and after completion of the reaction monitored by high performance liquid chromatography, the reaction was filtered, and the filtrate was rotary evaporated at 50°C to remove the solvent. The residue was recrystallized with 150 mL of ethanol, filtered, and the filter cake was dried at 60°C to obtain a compound of formula (III).

[0121] HPLC conditions: same as in Example 1.

[0122] Compound of formula (III) 1 The HNMR (CDCl3) spectrum is shown in Figure 7. 13 The CNMR (CDCl3) spectrum is shown in Figure 8.

[0123] Example 5 Preparation of the compound of formula (IV)

[0124] Dissolve 9.2 g of 60% sodium hydride in 80 mL of anhydrous tetrahydrofuran at -5 to 5°C. Add a solution of 24 g of trifluoroethanol in 20 mL of anhydrous tetrahydrofuran dropwise to this solution. After the addition is complete, add a solution of 83 g of the compound of formula (III) in 400 mL of anhydrous tetrahydrofuran dropwise, maintaining the temperature at no more than 15°C. After the addition is complete, stir and monitor the reaction by HPLC. After completion, quench with water. Separate the liquids, wash the organic phase twice with 40 mL of saturated brine, remove the solvent by rotary evaporation, and recrystallize the residue with 120 g of methanol or ethanol. Filter and dry the filter cake at 60°C to obtain the compound of formula (IV). Melting point: 80-82°C.

[0125] HPLC conditions: Kromasil C18 reverse phase column, mobile phase: acetonitrile: water (added with 0.1% formic acid) = 60:40 (v:v), flow rate 1.0 mL / min, column temperature 30°C, detection wavelength 210 nm, injection volume 5 μL.

[0126] Compound of formula (IV) 1The HNMR (DMSO) spectrum is shown in Figure 9. 13 The CNMR (DMSO) spectrum is shown in Figure 10.

[0127] Example 6 Preparation of carboxylic acid compound of formula (V) 1

[0128] To an autoclave were added 40 g of the compound of formula (IV), 20 g of water, 26.49 g of triethylamine, 0.4 g of PdCl2 catalyst, 4.65 g of the ligand 1,4-bis(diphenylphosphino)butane, and 400 g of the solvent 1,4-dioxane. The mixture was evacuated, replaced with nitrogen, and CO was introduced at a pressure of approximately 1 to 4 MPa. The reaction was allowed to proceed at 80°C for approximately 12 hours. After completion of the reaction, the reaction was monitored by high-performance liquid chromatography, filtered, the solvent dioxane was removed by rotary evaporation, methanol was added for dissolution, and the pH was adjusted to 2 to 3. A white solid precipitated and filtered. The filter cake was washed with water, slurried, and then filtered to obtain the compound of formula (V) with a yield of 81.13% and a melting point of 155-157°C.

[0129] HPLC conditions: same as in Example 5.

[0130] Compounds of formula (V) 1 The HNMR (DMSO) spectrum is shown in Figure 11. 13 The CNMR (DMSO) spectrum is shown in Figure 12.

[0131] Example 7 Preparation of carboxylic acid compound of formula (V) 2

[0132] To an autoclave were added 40 g of the compound of formula (IV), 20 g of water, 26.49 g of triethylamine, 0.4 g of PdCl2 catalyst, 3.95 g of the ligand 1,3-bis(diphenylphosphino)propane, and 400 g of tetrahydrofuran solvent. The mixture was evacuated, replaced with nitrogen, and CO was introduced at a pressure of approximately 1 to 4 MPa. The reaction was allowed to proceed at 80°C for approximately 12 h. After completion of the reaction, the reaction was monitored by high-performance liquid chromatography, filtered, and the tetrahydrofuran solvent was removed by rotary evaporation. Methanol was added for dissolution, and the acid was adjusted to a pH of 2 to 3. A white solid precipitated, which was filtered. The filter cake was washed with water, slurried, and then filtered to obtain the compound of formula (V) with a yield of 67.57% and a melting point of 155-157°C.

[0133] Example 8 Preparation of Tembotrione 1

[0134] Dissolve 1.5 g of the compound of formula (V) in 20 mL of 1,4-dioxane, add 1.03 g of thionyl chloride dropwise at 5°C, and heat to 55°C for reaction. After completion of the reaction, monitor by high-performance liquid chromatography, and remove the solvent by rotary evaporation to obtain the compound of formula (VII). Separately, dissolve 0.5 g of 1,3-cyclohexane in 15 mL of dioxane, add 0.44 g of triethylamine, and add dropwise to the compound of formula (VII) prepared above under an ice bath. After the addition is complete, stir at room temperature for approximately 2 hours. After completion of the reaction, monitor by high-performance liquid chromatography, and remove the solvent by rotary evaporation to obtain a solution of the compound of formula (VIII).

[0135] To the solution of the compound of formula (VIII) obtained above was added 0.1 mL of acetone cyanohydrin, and the reaction was carried out at 60° C. for 4 h. After completion of the reaction, the reaction was monitored by high performance liquid chromatography, and the mixture was filtered. The solvent was removed from the filtrate by rotary evaporation, and water was added. The pH was adjusted to 2-3 with hydrochloric acid. The obtained solid was filtered and dried to obtain tampronone in a yield of 76.59%.

[0136] HPLC conditions: same as in Example 5.

[0137] Example 9 Direct preparation of ester intermediate of formula (VIII)

[0138] Method 1: To an autoclave were added 94.73 g of the compound of formula (IV), 29.41 g of 1,3-cyclohexanedione, 27.83 g of triethylamine, 3 g of bis[(4-N,N-dimethylamino)phenyl]di-tert-butylphosphine palladium dichloride, and 250 g of dioxane as solvent. The atmosphere was replaced with nitrogen three times, and 1-4 MPa of CO was introduced. The temperature was raised and the reaction was continued at 85°C for approximately 3 h. After completion of the reaction, the temperature was cooled to room temperature, the pressure was released, the autoclave was opened, the reaction solution was poured out, and the reaction mixture was filtered. The filter cake was washed with 10 g of dioxane, and the mother liquor was evaporated to remove the solvent. 80 g of ethanol was added to the dried mother liquor, and the mixture was heated to 70°C for dissolution. The mixture was slowly cooled to crystallize, filtered, and the solid was dried at 70°C to obtain the ester compound (VIII) in an 80% yield.

[0139] Method 2: The solvent was replaced with 300 g of ethylene glycol diethyl ether. Other steps were the same as those in Method 1 to obtain the ester compound (VIII) with a yield of 71.63%.

[0140] HPLC conditions: same as in Example 5.

[0141] Compound of formula (VIII) 1 The HNMR (DMSO) spectrum is shown in Figure 13. 13 The CNMR (DMSO) spectrum is shown in Figure 14.

[0142] Example 10 Preparation of Tembotrione 2 (One-pot method)

[0143] To the autoclave were added 56.84 g of the compound of formula (IV), 37.95 g of triethylamine, 0.4 g of PdCl2 catalyst, 3.98 g of the ligand 1,4-bis(diphenylphosphino)butane, and 300 g of the solvent 1,4-dioxane. The autoclave was evacuated and replaced with nitrogen three times. CO was introduced at a pressure of about 1 to 4 MPa. The reaction was carried out at 80 to 85 ° C for about 8 h, then the temperature was lowered to 70 ° C, 2 g of acetone cyanohydrin was added, and the reaction was continued for 5 h. After the reaction is completed as monitored by high performance liquid chromatography, the reaction mixture is cooled to room temperature, the pressure is released, the reactor is opened, filtered, triethylamine hydrobromide is removed, the solvent dioxane is removed by rotary evaporation, methanol and water are added to dissolve, the pH is adjusted to 8-9 with sodium hydroxide solution, the reaction mixture is heated to 50°C and stirred, the insoluble matter is filtered out, the acid is adjusted to pH 2-3, a white solid is precipitated, the solution is cooled to room temperature and stirred in an ice bath for 0.5h, filtered, washed with water, filtered, and dried at 60°C to obtain a yellow-white powdery solid cyclosulfonone with a yield of 64.67% and a melting point of 120-122°C.

[0144] The obtained tembotrione 1 The HNMR (DMSO) spectrum is shown in Figure 15. 13 The CNMR (DMSO) spectrum is shown in Figure 16.

[0145] Example 11

[0146] To an autoclave were added 56.84 g of the compound of formula (IV), 21.84 g of 1,3-cyclohexanedione, 37.95 g of triethylamine, 0.5 g of PdCl2 catalyst, 4 g of the ligand 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl or 4,5-bisdiphenylphosphino-9,9-dimethylxanthene, and 290 g of the solvent 1,4-dioxane. The autoclave was evacuated and replaced with nitrogen three times. 1-4 MPa of CO was introduced and the reaction was continued at 85°C for approximately 10 hours. The yield was less than 10%, which was unsatisfactory.

Claims

1. A method for preparing tembotrione, characterized in that: Include any of the following steps:

2. The method according to claim 1, wherein the steps (v) and (v′) are respectively the following steps:

3. The method according to claim 2, wherein the reaction of step (v-1) or (v′-1) is carried out in the presence of a noble metal catalyst and a phosphorus ligand or a salt thereof, wherein the noble metal is selected from palladium, rhodium, ruthenium, copper, cobalt, preferably a palladium catalyst, more preferably palladium chloride (PdCl 2 ), palladium carbonate (PdCO 3 ), palladium acetate [Pd(OAc) 2 ], palladium / carbon (Pd / C), palladium trifluoroacetate [Pd(OTFA) 2 ], bis(dibenzylideneacetonepalladium) [Pd(dba) 2 ]; The phosphorus ligand or its salt is preferably 1,3-(bisdiphenylphosphino)propane, 1,4-bis(diphenylphosphino)butane or bis[(4-N,N-dimethylamino)phenyl]di-tert-butylphosphine.

4. The method according to claim 3, wherein the reaction solvent is one or more selected from toluene, 1,4-dioxane, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, dimethyl sulfoxide (DMSO), tetrahydrofuran (THF), and N,N-dimethylformamide (DMF).

5. The method according to any one of claims 1 to 3, further comprising any one or two or more intermediate preparation steps as shown below (i) to (iv):

6. The method according to claim 4, wherein steps (i) to (iv) are independently the following steps: In step (iii'), the bromination reagent is bromine, N-bromosuccinimide, or a combination of hydrogen bromide and hydrogen peroxide, preferably bromine; In step (iv'), CF3CH2OM is CF3CH2ONa or CF3CH2OK.

7. [Corrected 26.12.2023 in accordance with Rule 26] A process according to any one of claims 1 to 6, comprising the following steps of preparing an intermediate:

8. The method according to claim 7, wherein the intermediate preparation steps are as follows: In the formula, the bromination reagent is bromine, N-bromosuccinimide, or a combination of hydrogen bromide and hydrogen peroxide, preferably bromine; CF3CH2OM is CF3CH2ONa or CF3CH2OK.

9. The method according to claim 7 or 8, further comprising the steps of: The step (vi') is carried out in a stepwise manner by isolating the intermediate ester compound, or in a one-pot manner without isolating the intermediate ester compound.

10. The method according to claim 9, wherein steps (vi) and (vi′) are respectively the following steps: The step (vi′-1) is carried out in a stepwise manner by isolating the intermediate ester compound, or in a one-pot manner without isolating the intermediate ester compound.

11. A compound represented by the following formula (A): Wherein, R1 and R2 are any of the following: R1 is CF3-CH2-O-CH2-, and R2 is CH3-SO2-; R1 is Br-CH2-, and R2 is CH3-SO2-; R1 is CH3-, and R2 is CH3-SO2-; R1 is CH3-, and R2 is CH3-S-.

12. The method for preparing the compound of formula (A) according to claim 11, comprising any one or two or more steps of (i) to (iv) as shown below: Preferably, steps (i) to (iv) are independently the following steps: In step (iii'), the bromination reagent is bromine, N-bromosuccinimide, or a combination of hydrogen bromide and hydrogen peroxide, preferably bromine; In step (iv'), CF3CH2OM is CF3CH2ONa or CF3CH2OK.

13. A method for preparing tembotrione, characterized in that: The compound according to claim 11 is used as an intermediate.

14. Use of the compound according to claim 11 as an intermediate for the preparation of tembotrione.

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