阅读说明：本技术 一种二卤代均三嗪的合成方法 (Synthesis method of dihalogenated s-triazine ) 是由 李成金 张忠根 司亮 陈勇强 于 2020-12-28 设计创作，主要内容包括：本发明公开了一种二卤代均三嗪的合成方法,包括以下步骤：将取代腈类化合物与卤代腈化合物溶解在一定溶剂中,加入一定的催化剂,在一定温度下通入卤代氢一定时间；反应得到二卤代均三嗪。本发明提出了一种合成二卤代均三嗪的新反应路线,以取代腈类化合物和卤代腈化合物为原料,采用一步反应制得二卤代均三嗪,节省了反应的步骤和过程,工艺简便,成本低,产品收率高,达到99％以上,并且合成过程中避免使用格氏反应这种危险工艺,降低生产风险,同时避免了污染环境的问题。(The invention discloses a synthesis method of dihalogenated s-triazine, which comprises the following steps: dissolving substituted nitrile compound and halogenated nitrile compound in a certain solvent, adding a certain catalyst, and introducing halogenated hydrogen for a certain time at a certain temperature; the reaction gives dihalo-s-triazine. The invention provides a new reaction route for synthesizing dihalogenated s-triazine, which takes substituted nitrile compounds and halogenated nitrile compounds as raw materials, prepares the dihalogenated s-triazine by one-step reaction, saves the steps and the process of the reaction, has simple and convenient process, low cost and high product yield which is more than 99 percent, avoids the dangerous process of Grignard reaction in the synthesis process, reduces the production risk and avoids the problem of environmental pollution at the same time.)

1. A synthesis method of dihalogenated s-triazine, which is characterized by comprising the following steps: the method comprises the following steps:

dissolving substituted nitrile compounds shown in a formula (1) and halogenated nitrile compounds shown in a formula (2) in a solvent, adding a catalyst, and introducing hydrogen halide for reaction to obtain dihalogenated s-triazine;

in the formula, R is C₁-C₆Alkyl radical, C₂-C₆Alkenyl radical, C₂-C₆Alkynyl, C₃-C₆Cycloalkyl radical, C₆-C₁₀Aryl, benzyl, phenoxy, C₅-C₁₀Bicyclic radical, C₃-C₁₀Heterocyclyl or C₃-C₆Trialkylsilyl and X is halogen.

2. The method of claim 1A synthesis method of dihalogenated s-triazine, which is characterized by comprising the following steps: said R is formed by at least one group R_aSubstituted, R_aIs halogen, nitro, C₁-C₄Alkyl radical, C₂-C₄Alkenyl radical, C₂-C₄Alkynyl, C₃-C₆Cycloalkyl radical, C₁-C₄Haloalkyl, C₂-C₄Haloalkenyl, C₂-C₄Haloalkynyl group, C₃-C₆Halocycloalkyl radical, C₁-C₆Alkoxy radical, C₁-C₄Alkylamino radical, C₁-C₄Haloalkoxy, C₁-C₄Alkylthio radical, C₁-C₄Alkylsulfinyl radical, C₁-C₄Alkylsulfonyl radical, C₂-C₆Alkoxycarbonyl, C₂-C₆Alkylcarbonyl group, C₃-C₆(alkyl) Cycloalkylamino, C₂-C₆Alkylamino carbonyl, C₁-C₆Alkoxycarbonylamino group, C₂-C₈Dialkylamino group, C₃-C₆Cycloalkylamino, C₃-C₈Dialkylaminocarbonyl group, C₃-C₆Trialkylsilyl, phenyl, phenoxy, benzyl or halophenyl, and X is fluorine, chlorine, bromine or iodine.

3. A method of synthesizing dihalo-s-triazine according to claim 1, wherein: r is straight chain C₁-C₆Alkyl, straight chain C₂-C₆Alkenyl, straight-chain C₂-C₆Alkynyl, C₃-C₆Cycloalkyl, straight chain C₆-C₁₀Aryl, benzyl, phenoxy, C₅-C₁₀Bicyclic radical, C₃-C₁₀Heterocyclyl or C₃-C₆Linear trialkylsilyl groups.

4. A method of synthesizing a dihalo-s-triazine according to claim 3, wherein: said R is formed by at least one group R_bSubstituted, R_bIs halogen, nitro, thiocyano, amino, C₁-C₄Alkyl radical, C₂-C₄Alkenyl radical, C₂-C₄Alkynyl, C₃-C₆Cycloalkyl radical, C₁-C₄Haloalkyl, C₂-C₄Haloalkenyl, C₂-C₄Haloalkynyl group, C₃-C₆Halocycloalkyl radical, C₁-C₆Alkoxy radical, C₁-C₄Alkylamino radical, C₁-C₄Haloalkoxy, C₁-C₄Alkylthio radical, C₁-C₄Alkylsulfinyl radical, C₁-C₄Alkylsulfonyl radical, C₂-C₆Alkoxycarbonyl, C₂-C₆Alkylcarbonyl group, C₃-C₆(alkyl) Cycloalkylamino, C₂-C₆Alkylamino carbonyl, C₁-C₆Alkoxycarbonylamino group, C₂-C₈Dialkylamino group, C₃-C₆Cycloalkylamino, C₃-C₈Dialkylaminocarbonyl group, C₃-C₆Trialkylsilyl, phenyl, phenoxy, benzyl or halophenyl, and X is fluorine or bromine.

5. A method of synthesizing dihalo-s-triazine according to claim 1, wherein: r is methyl, and X is chlorine.

6. A method of synthesizing dihalo-s-triazine according to claim 1, wherein: the molar ratio of the substituted nitrile compound to the halogenated nitrile compound is 10: 1 to 1: 10.

7. a method of synthesizing dihalo-s-triazine according to claim 1, wherein: the solvent is one or more than two of diethyl ether, diisopropyl ether, methyl tert-butyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, tetrahydropyran, dichloromethane, 1-dichloroethane, 1, 2-dichloropropane, 1-dichloroethylene, 1, 2-dichloroethylene, trichloromethane, 1, 2-trichloropropane, trichloroethylene, tetrachloroethylene, tetrachloromethane, tetrachloroethane, chlorobenzene, dichlorobenzene, acetonitrile, pyridine, benzene, toluene, xylene, isopropylbenzene, tert-butyl benzene, styrene, acetone and ether, and the hydrogen halide is HF, HCl, HBr or HI.

8. A method of synthesizing dihalo-s-triazine according to claim 1, wherein: the catalyst is Lewis acid catalyst, and is selected from one or more than two of aluminum trichloride, aluminum tribromide, aluminum triiodide, boron trichloride, boron trifluoride, antimony pentachloride, ferric trichloride, ferric tribromide, stannic chloride, titanium dichloride, titanium tetrachloride, tellurium tetrachloride, bismuth trichloride, bismuth trifluoride and zinc chloride.

9. A method of synthesizing dihalo-s-triazine according to claim 1, wherein: the reaction temperature is-50-150 ℃, and the reaction pressure is 0.1-50 MPa.

10. A method of synthesizing dihalo-s-triazine according to claim 9, wherein: the reaction temperature is-10-25 deg.C, and the reaction pressure is 0.1-5 MPa.

Technical Field

The invention belongs to the field of organic synthesis, and particularly relates to a synthesis method of dihalogenated s-triazine.

Background

Triazine compounds have wide application in the fields of medicines, pesticides, dyes and the like, wherein s-triazine compounds such as cyanuric chloride are important intermediates of pesticides, dyes and medicines; monoalkyl dihalogenated s-triazines, especially methyldichloro-s-triazine, are core intermediates of the pesticide herbicide tribenuron-methyl.

The traditional synthesis method of the alkyl dihalogenated s-triazine intermediate mainly comprises the following reaction routes: 1) US5095113 discloses a process for preparing methyl s-triazine by condensation reaction of sodium dicyandiamide and acetyl chloride, which is highly polluting and has high raw material price. 2) WO2008/76883 and US6107301 disclose a process for the preparation of methyl s-triazine by reacting cyanuric chloride with a methyl grignard reagent (such as methyl magnesium chloride or methyl magnesium bromide), respectively, which is safe since it requires the use of a grignard reagent; 3) US2832779 discloses a method for preparing phenyl dichloros-triazine by ring closure of benzonitrile and dicyandiamide, followed by reaction with chlorinating agents such as phosphorus oxychloride and phosphorus pentachloride, which causes environmental pollution due to the use of phosphorus oxychloride and phosphorus trichloride; 4) US4220765 discloses a process for the preparation of phenyl dichloros-triazine by condensation of benzyl trichloride with cyanogen chloride at relatively high temperatures and in low yields by fractional distillation and recrystallization; 5) US2019/131535 discloses a condensation process of benzeneboronic acid with cyanuric chloride, which uses noble metal palladium, and is more expensive and less widely applicable.

Disclosure of Invention

Aiming at the problems, the invention researches and designs a synthesis method of dihalogenated s-triazine to solve the defects of high cost, low yield and environmental pollution of the synthesis of dihalogenated s-triazine by the traditional method. The technical means adopted by the invention are as follows:

a method for synthesizing dihalo-s-triazine, comprising the following steps:

dissolving a substituted nitrile compound RCN and a halogenated nitrile compound XCN in a solvent, adding a catalyst, and introducing hydrogen halide for reaction to obtain dihalogenated s-triazine, wherein the reaction formula is as follows:

wherein R is C₁-C₆Alkyl radical, C₂-C₆Alkenyl radical, C₂-C₆Alkynyl, C₃-C₆Cycloalkyl radical, C₆-C₁₀Aryl, benzyl, phenoxy, C₅-C₁₀Bicyclic radical, C₃-C₁₀Heterocyclyl or C₃-C₆Trialkylsilyl and X is halogen.

Preferably, said R is represented by at least one group R_aSubstituted, R_aIs halogen, nitro, C₁-C₄Alkyl radical, C₂-C₄Alkenyl radical, C₂-C₄Alkynyl, C₃-C₆Cycloalkyl radical, C₁-C₄Haloalkyl, C₂-C₄Haloalkenyl, C₂-C₄Haloalkynyl group, C₃-C₆Halocycloalkyl radical, C₁-C₆Alkoxy radical, C₁-C₄Alkylamino radical, C₁-C₄Haloalkoxy, C₁-C₄Alkylthio radical, C₁-C₄Alkylsulfinyl radical, C₁-C₄Alkylsulfonyl radical, C₂-C₆Alkoxycarbonyl, C₂-C₆Alkylcarbonyl group, C₃-C₆(alkyl) Cycloalkylamino, C₂-C₆Alkylamino carbonyl, C₁-C₆Alkoxycarbonylamino group, C₂-C₈Dialkylamino group, C₃-C₆Cycloalkylamino, C₃-C₈Dialkylaminocarbonyl group, C₃-C₆Trialkylsilyl, phenyl, phenoxy, benzyl or halophenyl, and X is fluorine, chlorine, bromine or iodine.

Preferably, R is a straight chain C₁-C₆Alkyl, straight chain C₂-C₆Alkenyl, straight-chain C₂-C₆Alkynyl, C₃-C₆Cycloalkyl, straight chain C₆-C₁₀Aryl, benzyl, phenoxy, C₅-C₁₀Bicyclic radical, C₃-C₁₀Heterocyclyl or C₃-C₆Linear trialkylsilyl groups.

Preferably, said R is represented by at least one radicalGroup R_bSubstituted, R_bIs halogen, nitro, thiocyano, amino, C₁-C₄Alkyl radical, C₂-C₄Alkenyl radical, C₂-C₄Alkynyl, C₃-C₆Cycloalkyl radical, C₁-C₄Haloalkyl, C₂-C₄Haloalkenyl, C₂-C₄Haloalkynyl group, C₃-C₆Halocycloalkyl radical, C₁-C₆Alkoxy radical, C₁-C₄Alkylamino radical, C₁-C₄Haloalkoxy, C₁-C₄Alkylthio radical, C₁-C₄Alkylsulfinyl radical, C₁-C₄Alkylsulfonyl radical, C₂-C₆Alkoxycarbonyl, C₂-C₆Alkylcarbonyl group, C₃-C₆(alkyl) Cycloalkylamino, C₂-C₆Alkylamino carbonyl, C₁-C₆Alkoxycarbonylamino group, C₂-C₈Dialkylamino group, C₃-C₆Cycloalkylamino, C₃-C₈Dialkylaminocarbonyl group, C₃-C₆Trialkylsilyl, phenyl, phenoxy, benzyl or halophenyl, and X is fluorine or bromine.

Preferably, R is methyl and X is chlorine.

Preferably, the molar ratio of the substituted nitrile compound to the halogenated nitrile compound is 10: 1 to 1: 10.

preferably, the solvent is one or more of diethyl ether, diisopropyl ether, methyl tert-butyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, tetrahydropyran, dichloromethane, 1-dichloroethane, 1, 2-dichloropropane, 1-dichloroethylene, 1, 2-dichloroethylene, trichloromethane, 1, 2-trichloropropane, trichloroethylene, tetrachloroethylene, tetrachloromethane, tetrachloroethane, chlorobenzene, dichlorobenzene, acetonitrile, pyridine, benzene, toluene, xylene, cumene, tert-butyl benzene, styrene, acetone, and ether.

Preferably, the catalyst is a lewis acid catalyst.

Preferably, the catalyst is one or more of aluminum trichloride, aluminum tribromide, aluminum triiodide, boron trichloride, boron trifluoride, antimony pentachloride, iron trichloride, iron tribromide, tin tetrachloride, titanium dichloride, titanium tetrachloride, tellurium tetrachloride, bismuth trichloride, bismuth trifluoride and zinc chloride.

Preferably, the hydrogen halide is HF, HCl, HBr, HI.

Preferably, the reaction temperature is-50 ℃ to 150 ℃, and the reaction pressure is 0.1MPa to 50 MPa.

Preferably, the reaction temperature is-10 ℃ to 25 ℃, and the reaction pressure is 0.1MPa to 5 MPa.

In the definitions of the compounds given above, the terms used in the collection generally represent the following substituents:

halogen: fluorine, chlorine, bromine, iodine, etc.;

alkyl groups: a linear or branched alkyl group such as methyl, ethyl, propyl, isopropyl or tert-butyl;

cycloalkyl groups: substituted or unsubstituted cyclic alkyl groups, such as cyclopropyl, cyclopentyl or cyclohexyl. Substituents such as methyl, halogen, and the like;

halogenated alkyl groups: straight-chain or branched alkyl groups in which the hydrogen atoms may be partially or fully substituted by halogen, for example, chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, etc.;

alkoxy groups: a linear or branched alkyl group attached to the structure via an oxygen atom linkage;

haloalkoxy groups: straight-chain or branched alkoxy groups, in which the hydrogen atoms may be partially or completely replaced by halogen. For example, chloromethoxy, dichloromethoxy, trichloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, trifluoroethoxy and the like;

alkylamino group: one or two straight or branched chain alkyl groups attached to the structure via a nitrogen atom;

haloalkylamino group: a substituent formed by substituting a part or all of hydrogen atoms on the alkylamino group with halogen;

alkylthio group: a linear or branched alkyl group attached to the structure via a sulfur atom bond;

haloalkylthio: straight-chain or branched alkylthio groups in which the hydrogen atoms may be partially or fully substituted by halogen atoms. For example, chloromethylthio, dichloromethylthio, trichloromethylthio, fluoromethylthio, difluoromethylthio, trifluoromethylthio, chlorofluoromethylthio and the like.

Compared with the prior art, the synthesis method of dihalogenated s-triazine has the following beneficial effects: the invention provides a new reaction route for synthesizing dihalogenated s-triazine, which takes substituted nitrile compounds and halogenated nitrile compounds as raw materials, prepares the dihalogenated s-triazine by one-step reaction, saves the steps and the process of the reaction, has simple and convenient process, low cost and high product yield which is more than 99 percent, avoids the dangerous process of Grignard reaction in the synthesis process, reduces the production risk and avoids the problem of environmental pollution at the same time.

Detailed Description

Example 1:

preparation of 2-methyl-4, 6-dichloro-1, 3, 5-s-triazine:

adding 80 g of dichloromethane into a four-mouth bottle with a stirrer, cooling to 5 ℃, then adding 31 g of cyanogen chloride and 0.5 g of catalyst aluminum trichloride, continuously cooling to-5 ℃, and then dropwise adding 10.5 g of acetonitrile for ring-closure reaction under the condition of introducing hydrogen chloride. After the reaction is carried out for 8 hours under the pressure of 0.1MPa, a solid product begins to be separated out. And continuously reacting for 4 hours, taking a liquid sample, and analyzing the acetonitrile-free raw material to obtain the 2-methyl-4, 6-dichloro-1, 3, 5-s-triazine reactant in one step. The reaction was then filtered at low room temperature to give the crude product. The crude product was washed with ice 40 g dichloromethane to give 45 g wet product. Wherein the purity of the 2-methyl-4, 6-dichloro-1, 3, 5-s-triazine is more than or equal to 99.0 percent, and the weight yield is more than or equal to 99 percent.

Example 2:

preparation of 2-methyl-4, 6-dibromo-1, 3, 5-s-triazine:

adding 80 g of dichloromethane into a four-mouth bottle with a stirrer, cooling to 5 ℃, then adding 62.0 g of cyanogen bromide and 0.5 g of catalyst aluminum tribromide, continuously cooling to-5 ℃, and then dropwise adding 10.5 g of acetonitrile to carry out ring closure reaction under the condition of introducing hydrogen bromide. After the reaction is carried out for 8 hours under the pressure of 2MPa, a solid product begins to precipitate. And continuously reacting for 4 hours, taking a liquid sample, and analyzing the acetonitrile-free raw material to obtain the 2-methyl-4, 6-dibromo-1, 3, 5-s-triazine reactant in one step. The reaction was then filtered at low room temperature to give the crude product. The crude product was washed with ice 40 g dichloromethane to give 124.8 g wet product. The purity is more than or equal to 99.0 percent, and the weight yield is more than or equal to 99 percent.

Example 3:

preparation of 2-phenyl-4, 6-dichloro-1, 3, 5-s-triazine:

adding 80 g of dichloromethane into a four-mouth bottle with a stirrer, cooling to 5 ℃, then adding 31 g of cyanogen chloride and 0.5 g of catalyst aluminum trichloride, continuously cooling to-5 ℃, and then dropwise adding 25.5 g of benzonitrile to carry out a ring-closure reaction under the condition of introducing hydrogen chloride. And (3) reacting for 8 hours under the pressure of 5MPa under heat preservation, and then beginning to separate out a solid product. After 4 hours of reaction, taking a liquid sample to analyze the raw material without benzonitrile, and obtaining the reactant of 2-phenyl-4, 6-dichloro-1, 3, 5-s-triazine by one-step reaction. The reaction was then filtered at low room temperature to give the crude product. The crude product was washed with ice 40 g dichloromethane to give 56.3 g wet product. The purity is more than or equal to 99.0 percent, and the weight yield is more than or equal to 99 percent.

Example 4:

preparation of 2- (pyridin-3-yl) -4, 6-dichloro-1, 3, 5-s-triazine:

adding 80 g of dichloromethane into a four-mouth bottle with a stirrer, cooling to 5 ℃, then adding 31 g of cyanogen chloride and 0.5 g of catalyst aluminum trichloride, continuously cooling to-5 ℃, and then dropwise adding 26.2 g of nicotinonitrile under the condition of introducing hydrogen chloride for carrying out a ring-closure reaction. After the reaction is carried out for 8 hours under the pressure of 10MPa, a solid product begins to precipitate. The reaction is continued for 4 hours, and a liquid sample is taken for analysis of the smokeless nitrile raw material, so that the 2- (pyridine-3-yl) -4, 6-dichloro-1, 3, 5-s-triazine product is obtained by one-step reaction. The reaction was then filtered at low room temperature to give the crude product. The crude product was washed with ice 40 g dichloromethane to give 54 g wet product. The purity is more than or equal to 99.0 percent, and the weight yield is more than or equal to 99 percent.

The above-mentioned embodiments are merely illustrative of the preferred embodiments of the present invention, and do not limit the scope of the present invention, and various modifications and improvements of the technical solution of the present invention by those skilled in the art should fall within the protection scope defined by the claims of the present invention without departing from the spirit of the present invention.