Preparation method of chlorantraniliprole or cyantraniliprole

Abstract

The present invention provides a method for preparing chlorantraniliprole or cyantraniliprole, which comprises the following steps: in the presence of an additive and a solvent, 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carbonyl chloride is subjected to a coupling reaction with an anthranilamide of formula (I) to obtain chlorantraniliprole or cyantraniliprole of formula (II), wherein R is Cl or CN, the solvent is selected from acetonitrile, 1,2-dioxane, tetrahydrofuran and a combination thereof, the additive is selected from N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone and a combination thereof, the coupling reaction temperature is from 20°C to the reflux temperature of the solvent, and the reaction system does not contain alkaline substances. #imgabs0#

Description

Technical Field

[0001] The invention relates to a preparation method of chlorantraniliprole or cyantraniliprole. Background Art

[0002] Chlorantraniliprole and cyantraniliprole are highly effective and selective nicotinic acid receptor inhibitor insecticides. The nicotinic acid receptor is a channel protein that controls the release of intracellular calcium ions. Chlorantraniliprole and cyantraniliprole directly bind to and activate the nicotinic acid receptors in insects, causing the uncontrolled release of calcium ions stored in smooth and striated muscle cells until they are exhausted, thereby damaging the insect's muscle movement regulation, causing insect paralysis and even death.

[0003] WO03 / 015519A1 discloses a method for preparing chlorantraniliprole or cyantraniliprole, which comprises: reacting 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid with aminobenzamide in the presence of methylsulfonyl chloride and pyridine to obtain chlorantraniliprole or cyantraniliprole in a yield of 58% to 65%.

[0004] However, there is still a need to develop alternative methods for preparing chlorantraniliprole or cyantraniliprole in order to achieve the goals of environmental protection, cost saving, high yield, high purity and / or simple operation. Summary of the invention

[0005] To this end, after in-depth research, the inventors of the present invention first proposed a method for preparing chlorantraniliprole or cyantraniliprole, which comprises the following steps:

[0006] In the presence of an additive and a solvent, 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carbonyl chloride is subjected to a coupling reaction with anthranilamide of formula (I) to obtain chlorantraniliprole or cyanantraniliprole of formula (II)

[0007]

[0008] Wherein, R is Cl or CN,

[0009] The solvent is selected from acetonitrile, 1,2-dioxane, tetrahydrofuran and a combination thereof,

[0010] The additive is selected from N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone and a combination thereof, and

[0011] The temperature of the coupling reaction is from about 20°C to the reflux temperature of the solvent.

[0012] In the prior art, it has long been advocated that alkaline substances must be used as acid-binding agents to neutralize hydrochloric acid, a byproduct produced in the coupling reaction, and to form salts with the reactants, thereby improving the yield of the coupling reaction.

[0013] Compared with the prior art, the present invention no longer requires the use of alkaline compounds (such as pyridines), and for the first time, chlorantraniliprole and cyantraniliprole can be obtained with high yield, high purity and low cost by using a small amount of specific additives.

[0014] The present invention also provides a method for preparing chlorantraniliprole or cyantraniliprole, which comprises the following steps:

[0015] i) subjecting 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid to a chlorination reaction with a chlorinating agent in the presence of a solvent to obtain a reaction solution containing 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carbonyl chloride, wherein the solvent is selected from acetonitrile, 1,2-dioxane, tetrahydrofuran, and a combination thereof,

[0016] ii) in the presence of the additive and the solvent, the reaction solution containing 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carbonyl chloride is subjected to an in-situ coupling reaction with anthranilamide of formula (I) to obtain chlorantraniliprole or cyantraniliprole of formula (II)

[0017]

[0018] Wherein, R is Cl or CN,

[0019] The additive is selected from N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone and a combination thereof, and

[0020] The temperature of the coupling reaction is from about 20°C to the reflux temperature of the solvent.

[0021] As mentioned above, compared with the prior art, the present invention no longer requires the use of alkaline compounds (such as pyridines), and for the first time, chlorantraniliprole and cyantraniliprole can be obtained with high yield, high purity and low cost by using a small amount of specific additives. Moreover, according to the present invention, after the chlorination reaction of step i), the reaction mixture of step i) does not need to be subjected to additional separation and purification, but the coupling reaction of step ii) is directly carried out in situ, which is simple to operate and cost-saving. DETAILED DESCRIPTION

[0022] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which the invention belongs. In the event of any inconsistency, the definitions provided in this application shall prevail.

[0023] Unless otherwise indicated, the numerical ranges listed herein are intended to include the endpoints of the range, and all values ​​and all sub-ranges within that range.

[0024] The materials, contents, methods, devices, and examples herein are illustrative and should not be construed as limiting unless otherwise specified.

[0025] The terms "comprising", "including" and "having" used herein all mean that other components or other steps that do not affect the final effect may be included. These terms cover the meanings of "consisting of" and "consisting essentially of". The products and methods according to the present invention may contain or include the essential technical features described in this disclosure, as well as additional and / or optional components, ingredients, steps or other restrictive features described herein; or may be composed of the essential technical features described in this disclosure, as well as additional and / or optional components, ingredients, steps or other restrictive features described herein; or may be composed essentially of the essential technical features described in this disclosure, as well as additional and / or optional components, ingredients, steps or other restrictive features described herein.

[0026] Unless explicitly stated otherwise, all materials and reagents used in this disclosure are commercially available.

[0027] Unless otherwise stated or clearly contradicted, all operations performed herein may be performed at room temperature and pressure.

[0028] As used herein, the term "about" means that the numerical value it defines may have a deviation within the range of ±10% of the numerical value, for example, the term "about 55° C." means the range of "55±5.5° C.".

[0029] As used herein, the term "normal pressure" refers to about 1 atmosphere (about 1013.25 hPa).

[0030] As used herein, the term "room temperature" refers to about 20 to about 25°C, preferably about 25°C.

[0031] Examples of the present disclosure will be described in detail below.

[0032] Preparation method of chlorantraniliprole or cyantraniliprole

[0033] In one aspect, the present invention provides a method for preparing chlorantraniliprole or cyantraniliprole, comprising the following steps:

[0034] In the presence of an additive and a solvent, 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carbonyl chloride is subjected to a coupling reaction with anthranilamide of formula (I) to obtain chlorantraniliprole or cyanantraniliprole of formula (II)

[0035]

[0036] Wherein, R is Cl or CN,

[0037] The solvent is selected from acetonitrile, 1,2-dioxane, tetrahydrofuran and a combination thereof,

[0038] The additive is selected from N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone and a combination thereof, and

[0039] The temperature of the coupling reaction is from about 20°C to the reflux temperature of the solvent.

[0040] In some examples, 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carbonyl chloride is added to the reaction system in the form of a solution dissolved in a solvent. The solvent is the same or different from the solvent of the coupling reaction, preferably the same, so as to facilitate operation and purification of the product.

[0041] In some examples, 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carbonyl chloride was added directly to the reaction system.

[0042] In some examples, the solvent for the coupling reaction is acetonitrile. Acetonitrile helps to improve the yield and / or purity of the product chlorantraniliprole or cyantraniliprole.

[0043] In some examples, the solvent is acetonitrile, and the reaction temperature is about 20 to about 80°C, preferably about 35 to about 75°C, more preferably about 50 to about 60°C, and most preferably about 55°C.

[0044] Unless otherwise stated or clearly contradictory, the preferences, reaction conditions and operating conditions described below for the coupling reaction or "step ii)" apply to this embodiment.

[0045] On the other hand, the present invention provides a method for preparing chlorantraniliprole or cyantraniliprole, comprising the following steps:

[0046] i) subjecting 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid to a chlorination reaction with a chlorinating agent in the presence of a solvent to obtain a reaction solution containing 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carbonyl chloride, wherein the solvent is selected from acetonitrile, 1,2-dioxane, tetrahydrofuran, and a combination thereof,

[0047] ii) in the presence of the additive and the solvent, the reaction solution containing 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carbonyl chloride is subjected to an in-situ coupling reaction with anthranilamide of formula (I) (hereinafter referred to as "anthranilic acid amide") to obtain chlorantraniliprole or cyantraniliprole of formula (II)

[0048]

[0049] Wherein, R is Cl or CN,

[0050] The additive is selected from N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone and a combination thereof, and

[0051] The temperature of the coupling reaction is from about 20°C to the reflux temperature of the solvent.

[0052] When R is Cl, formula (II) is the structural formula of chlorantraniliprole, that is, formula (II-A); when R is CN, formula (II) is the structural formula of cyantraniliprole, that is, formula (II-B).

[0053]

[0054] The inventors of the present invention have discovered for the first time that the yield of the product chlorantraniliprole or cyantraniliprole can be unexpectedly increased by adding a specific additive in the coupling reaction.

[0055] In the present invention, in-situ reaction means that the reaction solution obtained in step i) is only subjected to distillation to remove excess solvent without additional separation and purification, and can be directly used in step ii).

[0056] The reaction raw materials 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid and o-aminobenzamide are both in solid form. Therefore, these reaction raw materials are dissolved by a solvent so that the coupling reaction and the optional chlorination reaction are all carried out in the liquid phase to improve the solubility and conversion rate of the reaction raw materials.

[0057] In step ii) and step i), the same or different solvents may be used, preferably the same solvent is used, so as to simplify separation and purification and improve the purity of the final product.

[0058] In step ii) and the optional step i), the reaction is carried out at 20°C to the reflux temperature of the solvent for convenient operation, thereby improving the reaction rate, selectivity and / or yield.

[0059] In some embodiments, the chlorinating agent is thionyl chloride or a compound of the general formula XS(O) 2 Cl compounds, X is C 1-C 4 Alkyl, C 1 -C 2 haloalkyl, or optionally substituted by 1-3 groups selected from halogen, C 1 -C 3 Preferably, the chlorinating agent is one or more of thionyl chloride, methanesulfonyl chloride, propanesulfonyl chloride, benzenesulfonyl chloride and p-toluenesulfonyl chloride. More preferably, thionyl chloride, which is cheap and environmentally friendly, is used as the chlorinating agent.

[0060] In some examples, in step i), the molar ratio of the chlorinating agent to 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid is from about 1:1 to about 1.3:1.

[0061] In some examples, in step i), the solvent and the chlorinating agent are added sequentially to 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid, or the chlorinating agent and the solvent are added sequentially to 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid, or the chlorinating agent and the solvent are added simultaneously to 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid.

[0062] In some examples, in step i), the chlorination reaction is carried out under stirring.

[0063] In some examples, in step i), the weight of the solvent is about 2 to about 10 times, preferably about 4 to about 8 times, and more preferably about 6 to about 7 times, the weight of 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid.

[0064] In some examples, in step i), the solvent is acetonitrile, and the reaction temperature is about 20 to about 80°C, preferably about 35 to about 75°C, more preferably about 50 to about 60°C, and most preferably about 55°C.

[0065] In some examples, in step i), the reaction time is about 1 hour to about 5 hours, preferably about 3 hours to about 4 hours.

[0066] In some examples, step i) is performed under normal pressure.

[0067] In some examples, step ii) is performed under normal pressure.

[0068] In some examples, before performing step ii), the process further comprises distilling the reaction solution containing 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carbonyl chloride under reduced pressure.

[0069] In some examples, before performing step ii), reduced pressure distillation is performed at a temperature from the reaction temperature of step i) to about 10° C. lower than the reaction temperature of step i) and an internal pressure of 10 hPa to 500 hPa to remove the solvent.

[0070] In some examples, before performing step ii), reduced pressure distillation is performed at an internal temperature of about 55° C. and an internal pressure of about 80 hPa to remove acetonitrile as a solvent.

[0071] In some examples, in step ii), the reaction system comprises a basic substance.

[0072] In some examples, the alkaline substance includes inorganic substances such as carbonates or bicarbonates of alkali metals or alkaline earth metals; and organic substances such as tertiary amines, especially pyridine and its derivatives, such as pyridine, 2-methylpyridine, 3-methylpyridine and 2,6-lutidine.

[0073] In some examples, in step ii), the reaction system does not contain alkaline substances.

[0074] According to the present invention, a basic substance is no longer necessary for the coupling reaction, and the presence or absence of the basic substance has no significant effect on the result of the coupling reaction (eg, product yield and / or product purity).

[0075] In some examples, in step ii), the solvent and the additive are added to the anthranilamide in sequence, or the additive and the solvent are added to the anthranilamide in sequence, or the solvent and the additive are added to the anthranilamide at the same time.

[0076] In some examples, in step ii), the coupling reaction is performed under stirring.

[0077] In some examples, in step ii), a reaction solution containing 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carbonyl chloride is added, preferably dropwise, to a mixture of the anthranilamide of formula (I), the solvent and the additive.

[0078] In some examples, in step ii), the additive is N,N-dimethylformamide or N,N-dimethylacetamide.

[0079] In some examples, in step i) and step ii), the solvent is acetonitrile. Acetonitrile helps to improve the yield and / or purity of the product chlorantraniliprole or cyantraniliprole.

[0080] In some examples, in step ii), the solvent is acetonitrile, and the reaction temperature is about 20-about 80°C, preferably about 35-about 75°C, more preferably about 50-about 60°C, and most preferably about 55°C.

[0081] In some examples, the molar ratio of o-aminobenzamide of formula (I) to 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid is from about 0.9:1 to about 1.1:1, preferably from about 1:1 to about 1.05:1, such as about 1:1, about 1.01:1, about 1.02:1, about 1.03:1, about 1.04:1 or about 1.05:1, more preferably from about 1.02:1 to about 1.03:1, and most preferably about 1.03: 1. At such a molar ratio, the expensive raw material 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid can be reacted completely without wasting o-aminobenzamide of formula (I), thereby achieving a good balance between economic cost and yield.

[0082] In some examples, in step ii), the amount of the additive is about 10% to about 50% by weight of 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid, preferably about 10% to about 30% by weight, such as about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45% and about 50% by weight. Within the amount range of such additives, the reaction yield can be effectively improved without increasing the difficulty of purifying the product due to the introduction of too much additives.

[0083] In some examples, in step ii), the weight of the solvent is about 2 to about 10 times, preferably about 4 to about 8 times, more preferably about 6 to about 7 times, of the weight of 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid.

[0084] In some examples, in step ii), the reaction time is about 0.5 hour to about 2 hours, preferably about 1 hour.

[0085] In some examples, after step ii), a post-treatment step iii) is further included: isolating and purifying chlorantraniliprole or cyantraniliprole.

[0086] In some examples, after performing step ii), the post-treatment step iii) includes: allowing the reaction system to naturally cool to room temperature, dripping water in an amount of about 0.2 to about 1.5 times the weight of the solvent in the coupling reaction of step ii), and then filtering and drying. Adding water to the reaction solution helps the product to precipitate. The amount of water added dropwise is about 0.2 times to about 1.5 times, preferably about 0.5 times to about 0.7 times or about 0.8 times to about 1.2 times, such as about 0.2 times, about 0.29 times, about 0.33 times, about 0.36 times, about 0.42 times, about 0.5 times, about 0.57 times, about 0.64 times, about 0.66, about 0.7 times, about 0.71 times, about 0.75 times, about 0.8 times, about 0.83 times, about 0.86 times, about 1 times, about 1.14 times, about 1.2 times, about 1.33 times or about 1.5 times the weight of the solvent in the coupling reaction of step ii). When the amount of water added dropwise to the reaction system is within the above range, a good balance can be achieved between product yield and purity.

[0087] In some examples, in step iii), the temperature of the water added dropwise to the reaction system is room temperature, for example, about 20 to about 25°C.

[0088] In some examples, in step iii), the water added dropwise to the reaction system is tap water or deionized water.

[0089] When the product of formula (II) is chlorantraniliprole (II-A), after performing step ii), the weight of water added dropwise to the reaction system is preferably about 0.2 times to about 1.0 times the weight of the solvent in the coupling reaction of step ii), preferably about 0.5 times to about 0.7 times.

[0090] When the product of formula (II) is cyantraniliprole (II-B), after performing step ii), the weight of water added dropwise to the reaction system is preferably about 0.2 to about 1.5 times the weight of the solvent in the coupling reaction of step ii), preferably about 0.8 to about 1.2 times.

[0091] In some embodiments, the present invention provides a method for preparing chlorantraniliprole, comprising the following steps:

[0092] i) subjecting 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid and thionyl chloride in a molar ratio of about 1:1 to 1:1.3 to a chlorination reaction in the presence of acetonitrile at a temperature of about 50 to about 60° C. to obtain a reaction solution containing 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carbonyl chloride, wherein the weight of acetonitrile is about 4 to 5 times the weight of 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid, and distilling under reduced pressure, and

[0093] ii) in the presence of acetonitrile and DMF or DMAc and at a temperature of about 50 to about 60° C., subjecting a reaction solution containing 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carbonyl chloride to an in situ coupling reaction with anthranilamide of formula (IA) to obtain chlorantraniliprole of formula (II-A), wherein the molar ratio of anthranilamide to 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid is from about 1:1 to about 1.05:1, the weight of acetonitrile is about 4 to 5 times the weight of 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid, and the weight of DMF or DMAc is about 10 to about 50% by weight of the weight of 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid.

[0094] and iii) allowing the reaction system to cool naturally to room temperature, and adding dropwise into the reaction system water in an amount of about 0.2 to about 1.0 times, preferably about 0.5 to about 0.7 times, the weight of the acetonitrile in step ii).

[0095] Then filter and dry.

[0096] In some embodiments, the present invention provides a method for preparing cyantraniliprole, comprising the following steps:

[0097] i) subjecting 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid and thionyl chloride in a molar ratio of about 1:1 to 1:1.3 to a chlorination reaction in the presence of acetonitrile at a temperature of about 50 to about 60° C. to obtain a reaction solution containing 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carbonyl chloride, wherein the weight of acetonitrile is about 4 to 5 times the weight of 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid, and distilling under reduced pressure, and

[0098] ii) in the presence of acetonitrile and DMF or DMAc and at a temperature of about 50 to about 60° C., subjecting a reaction solution containing 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carbonyl chloride to an in situ coupling reaction with anthranilamide of formula (IB) to obtain cyantraniliprole of formula (II-B), wherein the molar ratio of anthranilamide to 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid is from about 1:1 to about 1.05:1, the weight of acetonitrile is about 4 to 5 times the weight of 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid, and the weight of DMF or DMAc is about 10 to about 50% by weight of the weight of 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid.

[0099]

[0100] iii) allowing the reaction system to cool naturally to room temperature, and adding dropwise water in an amount of about 0.2 to about 1.5 times, preferably about 0.8 to about 1.2 times, the weight of the acetonitrile in step ii).

[0101] of water, then filtered and dried.

[0102] It should be pointed out that the following examples are only used to illustrate the present invention, but are not intended to limit the present invention.

[0103] In the following examples, high performance liquid chromatography was used to measure the relative content of each component in the final product.

[0104] Synthesis Example 1 (Example 2-12): Preparation of Chlorantraniliprole ("Compound II-A")

[0105]

[0106]

[0107] Step i) Add 20g (0.0661mol, 1.0eq) 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid, 80g acetonitrile and 10.2g (0.0859mol, 1.3eq) thionyl chloride to a three-necked flask, heat to an internal temperature of 55°C for reaction, and react until the reaction liquid is clear, about 3 to 4h. Distill under reduced pressure at about 80 hPa to remove excess acetonitrile, and distill under reduced pressure at an internal temperature of 55°C to obtain 60g of brown liquid.

[0108] Step ii) Add 13.8g (0.0694mol, 1.05eq) of o-aminobenzamide of formula (IA), 120g of acetonitrile and 2g of DMAc to a four-necked flask, heat to an internal temperature of 55°C, and stir for 20min. Add the brown liquid obtained in step i) dropwise to the four-necked flask at a temperature of 55-60°C, and continue the addition for about 1.0h. After the addition is completed, maintain the internal temperature at 55°C for 1h. Cool naturally to room temperature and add 80g of water (water temperature 25°C). After the addition is completed, stir at 25°C for 2h. Filter, rinse the filter cake with 160g of water, and vacuum dry the filter cake at 70°C to obtain 30.3g of white solid chlorfenapyr (compound II-A).

[0109] As shown in Table 1, the coupling reaction conditions were changed and the reaction results were recorded.

[0110]

[0111]

[0112] In Table 1, the column "Reaction solution (215 nm)" indicates the reaction solution after the coupling reaction is completed and before water is added for crystallization; 215 nm represents the liquid phase detection wavelength. The column "Product content" indicates the content of each component in the precipitated product after water is added for crystallization. Unless otherwise specified or clearly contradictory, the yield, purity (i.e., product content) and absolute yield mentioned below refer to the yield, purity and absolute yield after water is added for crystallization.

[0113] As can be seen from Table 1, in Examples 1-1, 1-2 and 1-4, when the nitrogen-containing polar aprotic solvent N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAc) or N-methylpyrrolidone (NMP) is used as an additive, the yield of chlorantraniliprole is higher than 94%, and the absolute yield is higher than 91.5%. In Examples 1-3 and 1-5, when the sulfur-containing polar aprotic solvent dimethyl sulfoxide (DMSO) or sulfolane (TMSO) is used as an additive, the yield and absolute yield of chlorantraniliprole are significantly reduced.

[0114] In Examples 2-4 and 2-5, a relatively large amount of N,N-dimethylacetamide (DMAc) is used as both a solvent and an additive, which can significantly improve the yield of chlorantraniliprole, but DMAc is not easy to remove, and the product chlorantraniliprole contains too much residual DMAc, which affects the purity of the product. In Example 2-6, when the amount of DMAc used is 50% by weight of 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid (KA), the residual DMAc content in the product chlorantraniliprole is reduced to 0.21%.

[0115] In Example 2-7 and Example 2-8, the reaction raw material chlorantraniliprole is slightly in excess relative to 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid (KA), and the yield of chlorantraniliprole to 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid (KA) when the equivalent ratio is 1.03:1 (94.5%, the yield before crystallization by adding water) is significantly higher than the yield when the equivalent ratio is 1.02:1 (89.1%, the yield before crystallization by adding water).

[0116] In Example 2-7, after the coupling reaction, water was not added to the reaction solution, but the reaction solution was directly cooled to 0°C and then filtered. The yield was only 87.8%, which proved that adding an appropriate amount of water to the reaction solution can significantly improve the final yield of the product.

[0117] In Example 2-12, Example 2-13, Example 2-14 and Example 2-15, after the coupling reaction is completed, water with a weight of 0.63 times, 0.57 times, 0.64 times and 0.71 times the weight of acetonitrile in the coupling reaction is added to the reaction system respectively, and the yield of chlorantraniliprole is higher than 93%, the absolute yield is higher than 91.5%, and the purity is higher than 96%. In particular, in Example 2-14, water with a weight of 0.64 times the weight of acetonitrile in the coupling reaction is added to the reaction system, and the yield of chlorantraniliprole is as high as 95.4%, the absolute yield is as high as 93.11%, and the purity is as high as 97.6%, proving that the mass ratio of water:acetonitrile of 0.64:1 is more helpful to improve the yield and purity of chlorantraniliprole.

[0118] In Example 2-14, Example 2-18, Example 2-19 and Example 2-20, different coupling reaction temperatures were used: 55°C, 15°C, 35°C and 75°C, and the absolute yields of chlorantraniliprole were 93.11%, 90.99%, 92.24% and 92.53%, respectively. It can be seen that 35-75°C is a better reaction temperature range, and about 55°C is the optimal reaction temperature.

[0119] In Examples 2-13, 2-16 and 2-17, different coupling reaction temperatures were used: 55°C, 30°C and 75°C, and the absolute yields of chlorantraniliprole were 92.91%, 88.81% and 89.94%, respectively. It can be seen that about 55°C is a better reaction temperature.

[0120] In Example 2-17 and Example 2-20, the coupling reaction temperature was 75°C, the weight of water added to the reaction system was 0.57 times and 0.64 times the weight of acetonitrile in the coupling reaction, respectively, the yields of chlorantraniliprole were 93.2% and 95.1%, respectively, and the absolute yields were 89.94% and 92.53, respectively, demonstrating that a mass ratio of water:acetonitrile of 0.64:1 is more helpful in improving the yield and purity of chlorantraniliprole.

[0121] In Example 2-14, Example 4-2, Example 4-3 and Example 4-4, the amount of additive DMAc used was 10%, 20%, 30% and 50% of the weight of 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid (KA), respectively, and the yields of chlorfenapyr were all higher than 95%, and the absolute yields were all higher than 92.5%.

[0122] It is proved that the preferred dosage of the additive is 10 wt %-50 wt % of the weight of 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid (KA), preferably 10 wt % to 30 wt %, 30 wt % is the optimal dosage of the additive taking into account both yield and purity, and 10 wt % is the dosage of the additive taking into account both yield, purity and cost-effectiveness.

[0123] In Example 4-1, without using additives, the yield of chlorantraniliprole decreased to 93.1%, and the absolute yield decreased to 89.75%. Compared with Examples 1-3 and 1-5, Example 4-1 proves that not all polar aprotic solvents are helpful to improve the yield of the coupling reaction, and further proves that the significant improvement of the product yield by the nitrogen-containing polar aprotic solvent selected in the present invention is unexpected.

[0124] In Example 4-5, DMAc was used as both a solvent and an additive, and 2.5% of DMF by weight of 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid (KA) was used as an additive. The yield of chlorantraniliprole was as high as 98.7%. However, too much DMAc remained in chlorantraniliprole, resulting in a purity of chlorantraniliprole of only 94.3%.

[0125] Synthesis Example 2 (Example 3-4): Preparation of cyantraniliprole (Compound II-B)

[0126]

[0127] Step i) Add 20g (0.0661mol, 1.0eq) 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid, 80g acetonitrile and 10.2g (0.0859mol, 1.3eq) thionyl chloride to a three-necked flask, heat to an internal temperature of 55°C for reaction, and react until the reaction liquid is clear, about 3 to 4h. Distill under reduced pressure at about 80 hPa to remove excess acetonitrile, and distill under reduced pressure at an internal temperature of 55°C to obtain 50g of brown liquid.

[0128] Step ii) Add 12.5g (0.0661mol, 1.0eq) of o-aminobenzamide of formula (IB), 140g of acetonitrile and 2g of DMAc to a four-necked flask, heat to an internal temperature of 55°C, and stir for 20min. Add the brown liquid obtained in step i) dropwise to the four-necked flask at a temperature of 55-60°C for about 1.0h. After the addition is completed, maintain the internal temperature at 55°C for 1h. Cool naturally to room temperature and add 100g of water (water temperature 25°C). After the addition is completed, stir at 25°C for 2h. Filter, rinse the filter cake with 100g of water, and vacuum dry the filter cake at 70°C to obtain 28.6g of off-white solid cyantraniliprole (compound II-B).

[0129] As shown in Table 2, the coupling reaction conditions were changed and the reaction results were recorded.

[0130]

[0131] As can be seen from Table 2, compared with Example 3-1, Example 3-4, compared with Example 3-2, and compared with Example 3-6, the use of the additive DMAc in the coupling reaction can improve the yield and absolute yield of cyantraniliprole.

[0132] In Example 3-4, Example 3-5, Example 3-6 and Example 3-7, the weight of water added to the reaction system was 0.71 times, 0.86 times, 1 times and 1.14 times the weight of acetonitrile in the coupling reaction, respectively. It was found that 1 times and 1.14 times the amount of water were more helpful in improving the yield and purity of cyantraniliprole.

[0133] Compared with Example 3-6 in Example 3-8, and compared with Example 3-7 in Example 3-9, when DMF was added as an additive in addition to DMAc, the yield and purity of cyantraniliprole were reduced.

[0134] In addition to those described herein, various modifications of the present invention will be apparent to those skilled in the art based on the foregoing description. Such modifications are also intended to fall within the scope of the appended claims. Each reference cited in this application (including all patents, patent applications, journal articles, books and any other disclosures) is incorporated herein by reference in its entirety.

Claims

1. A method for preparing chlorantraniliprole or cyantraniliprole, comprising the following steps: In the presence of an additive and a solvent, 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carbonyl chloride is subjected to a coupling reaction with anthranilamide of formula (I) to obtain chlorantraniliprole or cyanantraniliprole of formula (II) Wherein, R is Cl or CN, The solvent is selected from acetonitrile, 1,2-dioxane, tetrahydrofuran and a combination thereof, 3-Bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carbonyl chloride is prepared from 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid. The additive is selected from N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone and a combination thereof, and the amount of the additive is 10 wt % to 50 wt % of 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid, and The temperature of the coupling reaction is from 20°C to the reflux temperature of the solvent.

2. A method for preparing chlorantraniliprole or cyantraniliprole, comprising the following steps: i) subjecting 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid to a chlorination reaction with a chlorinating agent in the presence of a solvent to obtain a reaction solution containing 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carbonyl chloride, wherein the solvent is selected from acetonitrile, 1,2-dioxane, tetrahydrofuran, and a combination thereof, ii) in the presence of the additive and the solvent, the reaction solution containing 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carbonyl chloride is subjected to an in-situ coupling reaction with anthranilamide of formula (I) to obtain chlorantraniliprole or cyantraniliprole of formula (II) Wherein, R is Cl or CN, The additive is selected from N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone and a combination thereof, and the amount of the additive is 10 wt % to 50 wt % of 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid, and The temperature of the coupling reaction is from 20°C to the reflux temperature of the solvent.

3. The method according to claim 1 or 2, wherein: The additive is N,N-dimethylformamide or N,N-dimethylacetamide.

4. The method according to claim 2, wherein: In step i) and step ii), the solvent is acetonitrile, and The reaction temperatures of step i) and step ii) are the same or different and are independently 20-80°C.

5. The method according to claim 4, wherein: The reaction temperatures of step i) and step ii) are the same or different and are independently 35-75°C.

6. The method according to claim 4, wherein: The reaction temperatures of step i) and step ii) are the same or different and are independently 50-60°C.

7. The method according to claim 4, wherein: The reaction temperature of step i) and step ii) is the same and independently of each other is 55°C.

8. The method according to claim 2, wherein: In step ii), the molar ratio of the anthranilamide of formula (I) to 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid is 0.9:1 to 1.1:

1.

9. The method according to claim 8, wherein: In step ii), the molar ratio of the anthranilamide of formula (I) to 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid is 1:1 to 1.05:

1.

10. The method according to claim 8, wherein: In step ii), the molar ratio of the anthranilamide of formula (I) to 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid is 1.02:1 to 1.03:

1.

11. The method according to claim 1 or 2, wherein: The additive is used in an amount of 10 to 30 weight % of 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid.

12. The method according to claim 2, wherein: In step ii), the weight of the solvent is 2 to 10 times the weight of 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid.

13. The method according to claim 12, wherein: In step ii), the weight of the solvent is 4 to 8 times the weight of 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid.

14. The method according to claim 12, wherein: In step ii), the weight of the solvent is 6 to 7 times the weight of 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carboxylic acid.

15. The method according to claim 2, wherein: Before carrying out step ii), the method further comprises distilling the reaction solution containing 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carbonyl chloride obtained in step i) under reduced pressure.

16. The method according to claim 2, wherein: After step ii), a post-treatment step iii) is also included: isolating and purifying the product chlorantraniliprole or cyantraniliprole.

17. The method according to claim 16, wherein the post-processing step iii) comprises: The reaction system is allowed to cool to room temperature naturally, water is added dropwise to the reaction system in an amount of 0.2 to 1.5 times the weight of the solvent in the coupling reaction of step ii), filtered, and dried.

18. The method according to claim 17, wherein: Add water dropwise to the reaction system in an amount of 0.5 to 0.7 times the weight of the solvent in the coupling reaction of step ii).

19. The method according to claim 17, wherein: Add water dropwise to the reaction system in an amount of 0.8 to 1.2 times the weight of the solvent in the coupling reaction of step ii).

20. The method according to claim 2, wherein: In step ii), a reaction solution containing 3-bromo-1-(3-chloro-2-pyridine)-1H-pyrazole-5-carbonyl chloride is added dropwise to a mixture of the anthranilamide of formula (I), the solvent and the additive.

Images