Process for the preparation of polysubstituted 1,3,5-triazine derivatives

Abstract

The application provides a preparation method of a polysubstituted 1,3,5-triazine, and chemical formula 1 and biuret are reacted in a solvent under the action of a catalyst to generate an intermediate chemical formula 3, and the chemical formula 3 is reacted in a solvent under the action of an acid binding agent to generate chemical formula 4. Compared with the prior art, the two-step reaction is stable, the metal ion content is controlled in the ppb level, the application range is wide, and the method can be applied to multiple fields such as photoelectricity, chemical industry, medicine and agriculture.

Description

Technical Field

[0001] The present invention belongs to the field of organic synthesis, and in particular relates to a method for preparing polysubstituted 1,3,5-triazine derivatives. Background Art

[0002] Polysubstituted 1,3,5-triazine derivatives have a wide range of applications. For example, dichloro-substituted 1,3,5-triazine derivatives can be used to prepare electroplating solutions for high-purity metals, semiconductors, and polycrystalline silicon, and are expected to play a significant role in the microelectronics and new energy industries. In the field of OLEDs, OLEDs based on polysubstituted 1,3,5-triazine derivatives also achieve fast response, wide color gamut, and high contrast, making them promising for use in flexible displays, smartphones, and VR devices. Despite their promising prospects, polysubstituted 1,3,5-triazine derivatives still have some shortcomings in their practical preparation. For example, the prior art CN 108264490A discloses a method for preparing 1,3,5-triazine derivatives, obtained by reacting benzaldehyde with benzamidine hydrochloride. However, this method can only synthesize triphenyl-substituted 1,3,5-triazines and cannot prepare more basic halogenated triazines. The limited group modification limits the molecular structure design and performance improvement of triazine derivatives in the fields of medicine, new energy, and semiconductors. Prior art CN112300088A uses sodium hydride, which reacts violently with water and lower alcohols, causing combustion or explosion. It can spontaneously ignite in moist air and, in addition, release hydrogen gas, which can explode when exposed to water or moist air. Prior art document Product Subclass 3: 1,3,5-Triazines and Phosphorus Analogue mentions reacting biuret with ethyl formate in the presence of sodium ethoxide, followed by treatment with hydrogen chloride. Hydrogen chloride has a suffocating odor, is highly irritating to the upper respiratory tract, and readily dissolves in water to form hydrochloric acid, which is highly corrosive.

[0003] In summary, the synthesis methods of these molecules are relatively cumbersome, the reaction raw materials are dangerous, and it is difficult to achieve industrial production. Polysubstituted 1,3,5-triazine derivatives have certain toxicity and environmental pollution risks. How to control the waste emissions during their production and use has become a difficult problem. Their charge transfer performance is affected by factors such as molecular structure and crystal morphology, and further in-depth research and exploration is also needed. In short, polysubstituted 1,3,5-triazine derivatives have broad application prospects in OLED and high-purity fields, but it is necessary to overcome the shortcomings of their cumbersome synthesis methods and toxic pollution, and further in-depth research on their charge transfer performance is needed to provide better support for industrial production and practical applications. Summary of the Invention

[0004] The present invention provides a method for preparing polysubstituted 1,3,5-triazine derivatives, the reaction equation is:

[0005] ;

[0006] wherein R1 is selected from H, C1-C6 alkyl, C1-C4 alkoxy, halogen, C1-C4 alkyl substituted or unsubstituted C6-C 18 Aryl, C3-C 18 The heteroaryl group, R1 is connected to the benzene ring with a single bond or shares a pair of chemical bonds to form a condensed group;

[0007] X is selected from Br and Cl.

[0008] According to the above technical solution, the C6-C 18 Aryl is selected from benzene, biphenyl, terphenyl, naphthalene, anthracene; the C3-C 18 The heteroaryl group is selected from carbazolyl, carbazolylphenyl, phenylcarbazolyl, dibenzothiophene, and dibenzofuran.

[0009] According to the above technical solution, the preparation method comprises the following steps:

[0010] (I) Chemical formula 1 and biuret react in a solvent under the action of a catalyst to form an intermediate chemical formula 3;

[0011] (II) Chemical formula 3 reacts with a halogenating agent in a solvent under the action of an acid-binding agent to generate chemical formula 4.

[0012] As a preferred technical solution, the chemical formula 1 is selected from the compounds represented by the following structural formula:

[0013] 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 .

[0014] According to the above technical solution, the catalyst is selected from: copper acetate, copper oxide, copper dichloride, copper nitrate, copper acetylacetonate, and nickel acetate.

[0015] As a preferred technical solution, the catalyst is selected from copper acetate.

[0016] According to the above technical scheme, biuret, chemical formula 1, and the catalyst are added in a molar ratio of 1:(1-2):(0.1-0.5), heated under reflux in a solvent for reaction, and the reaction is monitored by liquid phase. The reaction is filtered, washed with water, recrystallized and filtered, and the resulting filter cake is vacuum dried to obtain the intermediate chemical formula 3.

[0017] According to the above technical solution, in the preparation method of Chemical Formula 1, the halogenating agent is selected from one of phosphorus oxychloride, phosphorus pentachloride, phosphorus trichloride, thionyl chloride, phosphorus oxybromide, and phosphorus pentabromide; and the acid binding agent is selected from one of triethylamine, diisopropylethylamine, pyridine, piperidine, quinoline, potassium carbonate, potassium hydroxide, potassium tert-butoxide, sodium carbonate, sodium acetate, sodium hydroxide, and sodium tert-butoxide.

[0018] As a preferred technical solution, the halogenating agent is selected from phosphorus oxychloride and phosphorus oxybromide, and the acid binding agent is selected from triethylamine, diisopropylethylamine, and pyridine.

[0019] According to the above technical scheme, the chemical formula 3, the halogenating agent, and the acid-binding agent are added in a molar ratio of 1:(2-4):(2-4). The reaction is heated under reflux in a solvent. After liquid phase monitoring, the reaction is cooled to room temperature, 5V water is added dropwise at room temperature, filtered, and purified by column chromatography to obtain the chemical formula 4.

[0020] According to the above technical solution, the solvent is selected from the group consisting of benzene, toluene, xylene, methanol, ethanol, acetonitrile, ether, dichloromethane, dichloroethane, carbon tetrachloride, tetrahydrofuran, N,N-dimethylformamide, and N,N-dimethylacetamide.

[0021] Overall, the preparation method of polysubstituted 1,3,5-triazine compounds provided by the present invention provides a more efficient synthesis method. The crude product can obtain a product purity of up to 95%, and a simple post-treatment process can increase the product purity to above 99.8%, while the metal ion content is controlled at the ppb level. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] In order to further illustrate the purity and structural identification of the product, the following figures are provided:

[0023] Figure 1 The mass spectrum of 2,4-dichloro-6-phenyl-1,3,5-triazine prepared in the present invention;

[0024] Figure 2 This is the NMR image of 2,4-dichloro-6-phenyl-1,3,5-triazine prepared in the present invention;

[0025] Figure 3 This is a liquid chromatogram of the crude 2,4-dichloro-6-phenyl-1,3,5-triazine prepared in Example 1;

[0026] Figure 4 This is a liquid chromatogram of the final product of 2,4-dichloro-6-phenyl-1,3,5-triazine prepared in Example 1;

[0027] Figure 5 This is a liquid chromatogram of the crude 2-(4-bromophenyl)-4-(naphthalen-2-yl)-6-phenyl-1,3,5-triazine prepared in Comparative Example 1;

[0028] Figure 6 This is the liquid chromatogram of 2-(4-bromophenyl)-4-(naphthalen-2-yl)-6-phenyl-1,3,5-triazine prepared in Comparative Example 1. Implementation Method

[0029] The embodiments of the present invention will be described in detail below with reference to the examples, but it will be understood by those skilled in the art that the following examples are merely illustrative of the present invention and should not be construed as limiting the scope of the invention. Where specific conditions are not specified in the examples, the methods were performed according to conventional conditions or the conditions recommended by the manufacturer. Where the manufacturers of the reagents or instruments are not specified, they are all conventional products that can be obtained commercially.

[0030] Example 1: 2,4-dichloro-6-phenyl-1,3,5-triazine

[0031]

[0032] In a reaction flask, 50 g of biuret, 61.77 g of benzaldehyde, 8.81 g of copper acetate, and 500 ml of toluene were added with stirring, and the temperature was raised to 110°C for reaction. The reaction was completed by liquid phase monitoring, filtered, washed with water, recrystallized with anhydrous ethanol, and filtered. The filter cake was vacuum dried to obtain 83.78 g of 2,4-dihydroxy-6-phenyl-1,3,5-triazine with a yield of 91.3%.

[0033] In a reaction flask, 50 g of 2,4-dihydroxy-6-phenyl-1,3,5-triazine and 500 ml of acetonitrile were added dropwise, and 121.57 g of phosphorus oxychloride was added dropwise. After the addition was complete, 138 ml of diisopropylethylamine was added dropwise. After the addition was complete, the temperature was raised to 85° C. and refluxed for 3 h. The reaction solution was cooled to room temperature, and 250 ml of water was added dropwise, with the temperature controlled at 20° C. during the addition. After the addition was complete, the solution was filtered and the filter cake was washed with alcohol to obtain a crude product with a purity of 98.2% as determined by liquid chromatography. The crude product was purified by column chromatography to obtain 51.8 g of 2,4-dichloro-6-phenyl-1,3,5-triazine as a white solid with a yield of 86.7%. The purity was determined by liquid chromatography to reach 99.99%. The metal ion content was determined by inductively coupled plasma spectrometry to be below 30 ppb. The target 2,4-dichloro-6-phenyl-1,3,5-triazine was identified by mass spectrometry and hydrogen nuclear magnetic resonance spectroscopy.

[0034] Example 2: 2,4-dichloro-6-(3,5-dichlorophenyl)-1,3,5-triazine

[0035]

[0036] In a reaction flask, 50 g of biuret, 101.87 g of 3,5-dichlorobenzaldehyde, 8.81 g of copper acetate, and 500 ml of toluene were added with stirring, and the temperature was raised to 110°C for reaction. The reaction was monitored by liquid phase. The reaction was completed, filtered, washed with water, recrystallized from anhydrous ethanol, and filtered. The filter cake was vacuum dried to obtain 111.65 g of 6-(3,5-dichlorophenyl)-1,3,5-triazine-2,4(1H,3H)dione with a yield of 89.2%.

[0037] In the reaction bottle, put 50g 89.12 g of phosphorus oxychloride was added dropwise to 500 ml of acetonitrile. After the addition was complete, 102 ml of diisopropylethylamine was added dropwise. After the addition was complete, the temperature was raised to 85°C and refluxed for 3 h. The reaction solution was cooled to room temperature and 250 ml of water was added dropwise with the temperature controlled at 20°C during the addition. After the addition was complete, the solution was filtered and the filter cake was washed with alcohol to obtain a crude product with a purity of 97.31% as determined by liquid chromatography. The crude product was purified by column chromatography to obtain 49.77 g of a white solid with a yield of 87.1%. The purity was determined by liquid chromatography to reach 99.98%. The metal ion content was determined to be below 30 ppb by inductively coupled plasma spectrometry. The target compound was identified as 2,4-dichloro-6-(3,5-dichlorophenyl)-1,3,5-triazine by mass spectrometry and hydrogen nuclear magnetic resonance.

[0038] Example 3: 2-(4-bromobiphenyl)-4,6-dichloro-1,3,5-triazine

[0039]

[0040] In a reaction flask, 50 g of biuret, 151.99 g of 4'-bromo-[1,1'-biphenyl]-4-carboxaldehyde, 8.81 g of copper acetate, and 500 ml of toluene were added with stirring. The temperature was raised to 110°C for reaction. The reaction was monitored by liquid phase monitoring until completion. The reaction was filtered, washed with water, recrystallized from anhydrous ethanol, and filtered. The filter cake was vacuum dried to obtain 144.24 g of 6-(3,5-dichlorophenyl)-1,3,5-triazine-2,4(1H,3H)dione with a yield of 86.4%.

[0041] In a reaction flask, add 50g 6-(4'-bromo-[1,1'-biphenyl]-4-yl)-1,3,5-triazine-2,4(1H,3H)-dione and 500ml acetonitrile, add 66.82g phosphorus oxychloride dropwise, add 61ml triethylamine dropwise after the addition is complete, heat to 85℃ and reflux for 3h, cool the reaction solution to room temperature, add 250ml water dropwise, control the temperature at 20℃ during the addition process, filter after the addition is complete, and wash the filter cake with alcohol to obtain The crude product was determined to have a purity of 96.72% by liquid chromatography. The crude product was purified by column chromatography to obtain 46.06 g of a white solid with a yield of 83.2%. The purity was determined to be 99.97% by liquid chromatography. The metal ion content was determined to be below 30 ppb by inductively coupled plasma spectrometry. The target 2-(4-bromobiphenyl)-4,6-dichloro-1,3,5-triazine was identified by mass spectrometry and hydrogen nuclear magnetic resonance.

[0042] Example 4: 2,4-dichloro-6-naphthalen-2-yl-1,3,5-triazine

[0043]

[0044] In a reaction flask, 50 g of biuret, 90.91 g of 2-naphthaldehyde, 8.81 g of copper acetate, and 500 ml of toluene were added with stirring, and the temperature was raised to 110° C. to react. The reaction was monitored by liquid phase. The mixture was filtered, washed with water, recrystallized from anhydrous ethanol, and filtered. The filter cake was vacuum dried to obtain 102.93 g of 6-naphthalene-2-yl-1,3,5-triazine-2,4(1H,3H)dione with a yield of 88.7%.

[0045] In a reaction flask, 50g of 6-naphthalene-2-yl-1,3,5-triazine-2,4 (1H, 3H) dione and 500ml of acetonitrile were added dropwise, and 96.13g of phosphorus oxychloride was added dropwise. After the addition was complete, 88ml of triethylamine was added dropwise. After the addition was complete, the temperature was raised to 85°C and the reaction was refluxed for 3h. The reaction solution was cooled to room temperature and 250ml of water was added dropwise. The temperature was controlled at 20°C during the addition. After the addition was complete, the solution was filtered and the filter cake was washed with alcohol to give a crude product. The purity was determined by liquid chromatography to be 96.15%. The crude product was purified by column chromatography to obtain 48.76g of a white solid with a yield of 84.5%. The purity was determined by liquid chromatography to reach 99.96%. The metal ion content was determined by inductively coupled plasma spectrometry to be below 30ppb. The target 2,4-dichloro-6-naphthalene-2-yl-1,3,5-triazine was identified by mass spectrometry and hydrogen spectrum of nuclear magnetic resonance.

[0046] Example 5: 4-(4,6-dichloro-1,3,5-triazine-2-yl)-N,N-diphenylaniline

[0047]

[0048] In a reaction flask, 50 g of biuret, 159.10 g of 4-diphenylaminobenzaldehyde, 8.81 g of copper acetate, and 500 ml of toluene were added with stirring. The temperature was raised to 110° C. for reaction. The reaction was monitored by liquid phase. The mixture was filtered, washed with water, recrystallized from anhydrous ethanol, and filtered. The filter cake was vacuum dried to obtain 145.37 g of 6-(4-(diphenylamino)phenyl)-1,3,5-triazine-2,4(1H,3H)-dione with a yield of 84.3%.

[0049] In the reaction bottle, put 50g 120.66 g of phosphorus oxybromide was added dropwise to 500 ml of acetonitrile. After the addition was complete, 35 ml of pyridine was added dropwise. After the addition was complete, the temperature was raised to 85°C and refluxed for 3 h. The reaction solution was cooled to room temperature and 250 ml of water was added dropwise with the temperature controlled at 20°C during the addition. After the addition was complete, the solution was filtered and the filter cake was washed with alcohol to obtain a crude product with a purity of 96.15% as determined by liquid chromatography. The crude product was purified by column chromatography to obtain 55.2 g of a white solid with a yield of 81.6%. The purity was determined by liquid chromatography to reach 99.93%. The metal ion content was determined to be below 30 ppb by inductively coupled plasma spectrometry. The target compound was identified as 4-(4,6-dichloro-1,3,5-triazin-2-yl)-N,N-diphenylaniline by mass spectrometry and proton nuclear magnetic resonance spectroscopy.

[0050] Example 6: 2,4-dichloro-6-(dibenzothiophen-3-yl)-1,3,5-triazine

[0051]

[0052] In a reaction flask, 50 g of biuret, 123.55 g of dibenzothiophene-3-carboxaldehyde, 8.81 g of copper acetate, and 500 ml of toluene were added with stirring. The temperature was raised to 110° C. for reaction. The reaction was monitored by liquid phase monitoring until completion. The product was filtered, washed with water, recrystallized with anhydrous ethanol, and filtered. The filter cake was vacuum dried to obtain 119.04 g of 6-(dibenzothiophene-3-yl)-1,3,5-triazine-2,4(1H,3H)-dione with a yield of 83.1%.

[0053] In the reaction bottle, put 50g 77.88 g of phosphorus oxychloride was added dropwise to 500 ml of acetonitrile. After the addition was complete, 42 ml of pyridine was added dropwise. After the addition was complete, the temperature was raised to 85°C and refluxed for 3 h. The reaction solution was cooled to room temperature and 250 ml of water was added dropwise with the temperature controlled at 20°C during the addition. After the addition was complete, the solution was filtered and the filter cake was washed with alcohol to obtain a crude product with a purity of 95.02% as determined by liquid chromatography. The crude product was purified by column chromatography to obtain 44.38 g of a white solid with a yield of 78.9%. The purity was determined by liquid chromatography to reach 99.86%. The metal ion content was determined by inductively coupled plasma spectrometry to be below 30 ppb. The target product was identified as 2,4-dichloro-6-(dibenzothiophen-3-yl)-1,3,5-triazine by mass spectrometry and hydrogen nuclear magnetic resonance.

[0054] Comparative Example 1 2,4-dichloro-6-naphth-2-yl-1,3,5-triazine

[0055]

[0056] Weigh 50g of biuret in 500ml of tetrahydrofuran, add 25.03g of sodium hydride in batches at 0℃, stir at 70℃ for 1 hour after addition, add 90.32g of methyl naphthoate, react at 90℃ for more than 24 hours, pour the reaction solution into water, adjust the pH to acidic with hydrochloric acid, filter, dry, crystallize with N,N-dimethylformamide, and dry to obtain 55.70g of 6-naphthyl-1,3,5-triazine-2,4-(1H,3H)-dione, with a yield of 48%.

[0057] In a reaction flask, 50g of 6-naphthyl-1,3,5-triazine-2,4-(1H,3H)-dione and 500ml of acetonitrile were added dropwise, and 96.13g of phosphorus oxychloride was added dropwise. After the addition was complete, 110ml of diisopropylethylamine was added dropwise. After the addition was complete, the temperature was raised to 85°C and the reaction was refluxed for 3h. The reaction solution was cooled to room temperature and 250ml of water was added dropwise, with the temperature controlled at 20°C during the addition. After the addition was complete, the solution was filtered and the filter cake was washed with alcohol to obtain a crude product. The purity of the product was 90.1% by liquid chromatography. The crude product was purified by column chromatography to obtain 33.64g of 2,4-dichloro-6-naphthyl-1,3,5-triazine with a yield of 58.3%. The purity of the product was 97.6% by liquid chromatography. The product was identified as the target 2,4-dichloro-6-naphthyl-1,3,5-triazine by mass spectrometry and hydrogen nuclear magnetic resonance.

[0058] The above implementation process shows that the reagents used in the prior art are relatively dangerous, and the yield is low when the substituent is sterically hindered. Many byproducts are produced, and these byproducts are difficult to remove, making subsequent processes difficult. However, the two-step reaction of the present invention is stable, maintaining a yield of over 75% even with sterically hindered substituents. The product is highly pure, reaching over 99.8% purity in a single purification step, and the metal ion content is controlled at the ppb level.

[0059] The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited thereto. Within the technical concept of the present invention, various simple variations of the technical solution of the present invention may be made, including combining the various technical features in any other appropriate manner. These simple variations and combinations should also be regarded as disclosed in the present invention and fall within the scope of protection of the present invention.

Claims

1. A method for preparing a polysubstituted 1,3,5-triazine, characterized in that: The reaction equation is: Wherein, R1 is selected from H, C1-C6 alkyl, C1-C4 alkoxy, halogen, C1-C4 alkyl substituted or unsubstituted C6-C 18 Aryl, C3-C 18 wherein R1 is a heteroaryl group, R1 is connected to the benzene ring with a single bond or shares a pair of chemical bonds to form a condensed group; X is selected from Cl, Br; The synthesis method comprises the following steps: (I) Chemical formula 1 and biuret react in a solvent under the action of a catalyst to form an intermediate chemical formula 3; (II) Chemical formula 3 reacts with a halogenating agent in a solvent under the action of an acid-binding agent to produce chemical formula 4; The catalyst is selected from copper acetate.

2. The method for preparing a polysubstituted 1,3,5-triazine according to claim 1, characterized in that: The molar ratio of the biuret, chemical formula 1, and the catalyst is 1:(1-2):(0.1-0.5).

3. The method for preparing a polysubstituted 1,3,5-triazine according to claim 1, characterized in that: The acid binding agent is selected from one of triethylamine, diisopropylethylamine, pyridine, potassium carbonate, potassium hydroxide, potassium tert-butoxide, sodium carbonate, sodium acetate, sodium hydroxide, and sodium tert-butoxide.

4. The method for preparing a polysubstituted 1,3,5-triazine according to claim 1, characterized in that: The halogenating agent is selected from the group consisting of phosphorus oxychloride, phosphorus pentachloride, phosphorus trichloride, thionyl chloride, phosphorus oxybromide, and phosphorus pentabromide.

5. The method for preparing a polysubstituted 1,3,5-triazine according to claim 1, characterized in that: The molar ratio of the chemical formula 3, the halogenating agent and the acid-binding agent is 1:(2-4):(2-4).

6. The method for preparing a polysubstituted 1,3,5-triazine according to claim 1, characterized in that: The chemical formula 1 is selected from:

7. A method for preparing a polysubstituted 1,3,5-triazine according to any one of claims 1 to 5, characterized in that: The solvent is selected from the group consisting of benzene, toluene, xylene, methanol, ethanol, acetonitrile, ether, dichloromethane, dichloroethane, carbon tetrachloride, tetrahydrofuran, N,N-dimethylformamide, and N,N-dimethylacetamide.

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