Synthesis method of 2, 4-dichloro-6-(4-methoxyphenyl)-s-triazine

Abstract

The invention discloses a synthesis method of 2, 4-dichloro-6-(4-methoxyphenyl)-s-triazine, which comprises the following steps: carrying out Friedel-Crafts reaction on anisole and cyanuric chloride as reaction raw materials in the presence of a catalyst to obtain 2, 4-dichloro-6-(4-methoxyphenyl)-s-triazine; wherein when the Friedel-Crafts reaction is carried out, grinding auxiliary liquid is added to grind the solid-phase raw material to carry out the solid-phase Friedel-Crafts reaction; the ball mill is adopted as reaction equipment, the grinding auxiliary liquid is added to grind the solid-phase raw material to perform the solid-phase Friedel-Crafts reaction, only a small amount of auxiliary liquid is needed to promote grinding, the problem of poor dissolvability of cyanuric chloride is effectively solved, and the method has the advantages that the reaction speed is high, the reaction equipment is simple, and the operation is simple and convenient; the monoarylation selectivity is high, and the yield is good; a large amount of organic solvent is not needed, and stirring is not needed.

Description

Technical Field

[0001] The invention relates to a synthesis method of an s-triazine ultraviolet absorber UV627 intermediate, in particular to a liquid-assisted solid-phase synthesis method of 2,4-dichloro-6-(4-methoxyphenyl)-triazine, and belongs to the field of synthesis of s-triazine ultraviolet absorber UV627 intermediate. Background Art

[0002] UV627 is an oil-soluble triazine absorber with good absorption in both ultraviolet A and B regions. It can not only be used in polymer materials, but also has been approved by the EU for use in daily chemicals such as sunscreen.

[0003] Similar to the synthesis of most triazine ultraviolet absorbers, the most economical synthesis route of UV627 is theoretically to use cyanuric chloride as raw material, and selectively react it with anisole in the presence of aluminum chloride to obtain 2,4-dichloro-6-(4-methoxyphenyl)-s-triazine; after separation and purification, it is reacted with m-diphenol to obtain 2,4-bis(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-s-triazine by Friedel-Crafts reaction, and then the phenolic hydroxyl group is selectively isooctylated to obtain UV627 ultraviolet absorber. Its synthesis route is as follows: Figure 1 shown; from Figure 1 It can be seen from the synthesis route that the synthesis of UV627 includes three steps: 1) cyanuric chloride undergoes a selective Friedel-Crafts reaction with anisole in the presence of a Lewis acid such as aluminum chloride to obtain 2,4-dichloro-6-(4-methoxyphenyl)-s-triazine; 2) after separation and purification, 2,4-dichloro-6-(4-methoxyphenyl)-s-triazine continues to undergo a double Friedel-Crafts reaction with resorcinol in the presence of aluminum chloride to obtain 2,4-bis(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-s-triazine; 3) the phenolic hydroxyl group is then selectively etherified with a halogenated isooctane in the presence of a base; wherein, the technology of step 2) and step 3) is mature and has been widely implemented in the industrial production of various triazine ultraviolet absorbers; however, for step 1), there is a problem of controlling the continuous side reactions of di-substitution and even tri-substitution, which is the difficulty in synthesizing UV627 from cyanuric chloride via the Friedel-Crafts route.

[0004] In order to improve the selectivity of cyanuric chloride and anisole to form 2,4-dichloro-6-(4-methoxyphenyl)-s-triazine, cyanuric chloride needs to be kept in a certain excess state relative to anisole. But cyanuric chloride has little solubility in most Friedel-Crafts reaction solvents, and needs to use a large amount of solvents to form solution, causing reaction to be difficult to practical application. If cyanuric chloride can not be dissolved completely, even if excessively fed relative to anisole, the cyanuric chloride actually participating in the reaction in the solution in the early stage of the reaction is still insufficient, i.e. anisole is relatively excessive, i.e. disubstituted or even trisubstituted by-products can be formed. In order to synthesize 2,4-dichloro-6-(4-methoxyphenyl)-s-triazine, the disclosed technical routes include a substitution reaction using a 4-methoxyphenyl Grignard reagent and cyanuric chloride, or a synthesis technology using a cross-coupling reaction of 4-methoxyphenylboric acid and cyanuric chloride under transition metal catalysis. However, the Grignard reagent requires anhydrous and oxygen-free operation, and the aryl boronic acid reagent is expensive, which leads to a high production cost of 2,4-dichloro-6-(4-methoxyphenyl)-s-triazine.

[0005] Chinese patent (CN111039883) discloses a scheme using a microchannel reactor, wherein cyanuric chloride is reacted with anisole in a solvent such as dichloroethane in the presence of aluminum chloride to obtain 2,4-dichloro-6-(4-methoxyphenyl)-s-triazine by Friedel-Crafts reaction. However, all materials including cyanuric chloride and aluminum chloride need to be completely dissolved at room temperature to form a solution, which still belongs to a solution reaction system. Compared with a solution reaction system, a solid phase reaction is not affected by the solubility of the reactants or products. Summary of the invention

[0006] The main purpose of the invention is to provide a method for synthesizing 2,4-dichloro-6-(4-methoxyphenyl)-s-triazine, which overcomes a series of problems existing in the synthesis of 2,4-dichloro-6-(4-methoxyphenyl)-s-triazine by a solution reaction system.

[0007] To achieve the above purpose, the main technical solutions adopted by the present invention include:

[0008] A method for synthesizing 2,4-dichloro-6-(4-methoxyphenyl)-s-triazine comprises the steps of using anisole and cyanuric chloride as reaction raw materials to carry out Friedel-Crafts reaction in the presence of a catalyst to obtain 2,4-dichloro-6-(4-methoxyphenyl)-s-triazine; wherein a grinding auxiliary liquid is added during the Friedel-Crafts reaction to grind the solid raw materials to carry out solid-phase Friedel-Crafts reaction.

[0009] In a preferred embodiment of the present invention, when performing solid phase Friedel-Crafts reaction, the weight of the added grinding auxiliary liquid is lower than the total weight of the reaction materials, which is most conducive to grinding and improves grinding and reaction efficiency.

[0010] In a preferred embodiment of the present invention, the grinding auxiliary liquid is a Friedel-Crafts reaction solvent, wherein the Friedel-Crafts reaction solvent includes but is not limited to chlorobenzene, chloroform, dichloroethane, dichloromethane or ethyl acetate and other commonly used Friedel-Crafts reaction solvents, and 1,2-dichloroethane is most preferred.

[0011] A preferred embodiment of the present invention, in order to solve the problem of poor solubility of cyanuric chloride, the present invention adopts a ball mill as a reaction equipment, and grinds the solid raw material by ball milling, and only a small amount of auxiliary liquid is needed to promote the grinding, which has the technical effects of fast reaction speed, high monoarylation selectivity, good yield, etc.; wherein, the ball mill rotation speed is preferably 100-400rpm, more preferably 300rpm.

[0012] In a preferred embodiment of the present invention, the solid-phase Friedel-Crafts reaction can be carried out by adding a grinding auxiliary liquid to grind the solid-phase raw material at room temperature, and the room temperature can be 15-25°C.

[0013] In a preferred embodiment of the present invention, the catalyst is preferably aluminum chloride; wherein, relative to the amount of anisole, the amount of aluminum chloride is 1.1-2.0 times the molar amount, preferably 1.1-1.5 times the molar amount, and most preferably 1.3-1.5 times the molar amount.

[0014] In a preferred embodiment of the present invention, the amount of cyanuric chloride used is 1.0-1.5 times the amount of anisole used, wherein the yield is best when the molar amount is 1.1-1.3 times.

[0015] Compared with the prior art of synthesizing 2,4-dichloro-6-(4-methoxyphenyl)-s-triazine in an existing solution reaction system, the method for synthesizing 2,4-dichloro-6-(4-methoxyphenyl)-s-triazine by liquid-assisted ball milling solid phase of the present invention mainly includes the following advantages: 1) it is not required to dissolve the cyanuric chloride raw material, does not require a large amount of organic solvent, and the amount of solvent used in the grinding auxiliary liquid is lower than the total weight of the reaction materials; 2) there is no stirring problem; 3) the reaction time is short; 4) the reaction equipment is simple and the operation is easy. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 A synthetic process route of a UV627 ultraviolet absorber in the prior art.

[0017] Figure 2 The invention discloses a synthetic process route for liquid-assisted ball milling solid-phase synthesis of 2,4-dichloro-6-(4-methoxyphenyl)-s-triazine. DETAILED DESCRIPTION

[0018] The present invention will be further described below in conjunction with specific embodiments, and the advantages and features of the present invention will become clearer as the description proceeds. However, it should be understood that the embodiments are exemplary only and do not constitute any limitation to the scope of the present invention. It should be understood by those skilled in the art that the details and forms of the technical solution of the present invention may be modified or replaced without departing from the spirit and scope of the present invention, but these modifications or replacements all fall within the protection scope of the present invention.

[0019] Example 1 Liquid-Assisted Ball Milling Solid Phase Synthesis of 2,4-Dichloro-6-(4-methoxyphenyl)-s-triazine

[0020] Place grinding balls in a 100mL ceramic ball mill, add anisole (10.8g, 100mmol), cyanuric chloride (20.2g, 110mmol), aluminum chloride 17.5g (130mmol), and 40g dichloroethane. Fix the reaction tank containing the materials on the ball mill; add water to the counterbalance tank to make the weight of the balance tank equal to that of the reaction tank. Open the outlet valve of the reaction tank and connect it to the inlet valve of the balance tank through an air duct so that the hydrogen chloride gas produced by the reaction is absorbed in the balance tank. Start the ball mill, set the speed to 300rpm, take samples and analyze every 30 minutes, and the reaction is completed after 2 hours. Pour the reaction material and the water in the balance tank into cold concentrated hydrochloric acid (50mL), stir and hydrolyze. Remove dichloroethane by rotary evaporation, filter with suction, and rinse the filter cake with water to obtain a crude product as a light yellow solid. The product was recrystallized from acetone to obtain 18.4 g of a white solid 2,4-dichloro-6-(4-methoxyphenyl)-s-triazine with a yield of 72%.

[0021] 1 HNMR (400MHz, CDCl 3 )δ (ppm): 3.91 (s, 3H), 6.97 (d, J = 8.8Hz, 2H), 8.44 (d, J = 8.8Hz, 2H). 13 CNMR (100MHz, CDCl 3 )δ(ppm):55.7,114.4,125.0,132.2,165.2,171.6,174.1.

[0022] Example 2 Liquid-Assisted Ball Milling Solid Phase Synthesis of 2,4-Dichloro-6-(4-methoxyphenyl)-s-triazine

[0023] Place grinding balls in a 100mL ceramic ball mill, add anisole (10.8g, 100mmol), cyanuric chloride (20.2g, 110mmol), aluminum chloride 17.5g (130mmol), and 40g dichloroethane. Fix the reaction tank containing the materials on the ball mill; add water to the counterbalance tank to make the weight of the balance tank equal to that of the reaction tank. Open the outlet valve of the reaction tank and connect it to the inlet valve of the balance tank through an air duct so that the hydrogen chloride gas produced by the reaction is absorbed in the balance tank. Start the ball mill, set the speed to 100rpm, take samples and analyze every 30 minutes, and the reaction is completed after 5 hours. Pour the reaction material and the water in the balance tank into cold concentrated hydrochloric acid (50mL), stir and hydrolyze. Remove dichloroethane by rotary evaporation, filter with suction, and rinse the filter cake with water to obtain a crude product as a light yellow solid. After recrystallization from acetone, 18.1 g of white solid 2,4-dichloro-6-(4-methoxyphenyl)-s-triazine was obtained with a yield of 71%. The product structure was identified as in Example 1.

[0024] Example 3 Liquid-Assisted Ball Milling Solid Phase Synthesis of 2,4-Dichloro-6-(4-methoxyphenyl)-s-triazine

[0025] Place grinding balls in a 100mL ceramic ball mill, add anisole (10.8g, 100mmol), cyanuric chloride (20.2g, 110mmol), aluminum chloride 17.5g (130mmol), and 40g dichloroethane. Fix the reaction tank containing the materials on the ball mill; add water to the counterbalance tank to make the weight of the balance tank equal to that of the reaction tank. Open the outlet valve of the reaction tank and connect it to the inlet valve of the balance tank through an air duct so that the hydrogen chloride gas produced by the reaction is absorbed in the balance tank. Start the ball mill, set the speed to 400rpm, take samples and analyze every 30 minutes, and the reaction is completed after 1.5 hours. Pour the reaction material and the water in the balance tank into cold concentrated hydrochloric acid (50mL), stir and hydrolyze. Remove dichloroethane by rotary evaporation, filter with suction, and rinse the filter cake with water to obtain a crude product as a light yellow solid. After recrystallization from acetone, 17.7 g of white solid 2,4-dichloro-6-(4-methoxyphenyl)-s-triazine was obtained with a yield of 69%. The product structure was identified as in Example 1.

[0026] Example 4 Liquid-Assisted Ball Milling Solid Phase Synthesis of 2,4-Dichloro-6-(4-methoxyphenyl)-s-triazine

[0027] Place grinding balls in a 100mL ceramic ball mill, add anisole (10.8g, 100mmol), cyanuric chloride (18.5g), aluminum chloride 17.5g, and ethylene dichloride 40g. Fix the reaction tank containing the materials on the ball mill; add water to the counterbalance tank to make the weight of the balance tank equal to that of the reaction tank. Open the outlet valve of the reaction tank and connect it to the inlet valve of the balance tank through an air duct so that the hydrogen chloride gas produced by the reaction is absorbed in the balance tank. Start the ball mill, set the speed to 300rpm, take samples and analyze every 30 minutes, and the reaction is completed after 2 hours. Pour the reaction material and the water in the balance tank into cold concentrated hydrochloric acid (50mL), stir and hydrolyze. Remove the ethylene dichloride by rotary evaporation, filter with suction, and rinse the filter cake with water to obtain a crude product as a light yellow solid. Recrystallization with acetone gave 14.5 g of white solid 2,4-dichloro-6-(4-methoxyphenyl)-s-triazine with a yield of 57%. The product structure was identified in Example 1.

[0028] Example 5 Liquid-Assisted Ball Milling Solid Phase Synthesis of 2,4-Dichloro-6-(4-methoxyphenyl)-s-triazine

[0029] Place grinding balls in a 100mL ceramic ball mill, add anisole (10.8g, 100mmol), cyanuric chloride (20.2g), aluminum chloride 14.5g, and ethylene dichloride 40g. Fix the reaction tank containing the materials on the ball mill; add water to the counterbalance tank to make the weight of the balance tank equal to that of the reaction tank. Open the outlet valve of the reaction tank and connect it to the inlet valve of the balance tank through an air duct so that the hydrogen chloride gas produced by the reaction is absorbed in the balance tank. Start the ball mill, set the speed to 300rpm, take samples and analyze every 30 minutes, and the reaction is completed after 2 hours. Pour the reaction material and the water in the balance tank into cold concentrated hydrochloric acid (50mL), stir and hydrolyze. Remove the ethylene dichloride by rotary evaporation, filter with suction, and rinse the filter cake with water to obtain a crude product as a light yellow solid. After recrystallization from acetone, 17.3 g of white solid 2,4-dichloro-6-(4-methoxyphenyl)-s-triazine was obtained with a yield of 68%. The product structure was identified as in Example 1.

[0030] Example 6 Liquid-Assisted Ball Milling Solid Phase Synthesis of 2,4-Dichloro-6-(4-methoxyphenyl)-s-triazine

[0031] Place grinding balls in a 100mL ceramic ball mill, add anisole (10.8g, 100mmol), cyanuric chloride (20.2g), aluminum chloride 20.0g, and ethylene dichloride 40g. Fix the reaction tank containing the materials on the ball mill; add water to the counterbalance tank to make the weight of the balance tank equal to that of the reaction tank. Open the outlet valve of the reaction tank and connect it to the inlet valve of the balance tank through an air duct so that the hydrogen chloride gas produced by the reaction is absorbed in the balance tank. Start the ball mill, set the speed to 300rpm, take samples and analyze every 30 minutes, and the reaction is completed after 2 hours. Pour the reaction material and the water in the balance tank into cold concentrated hydrochloric acid (50mL), stir and hydrolyze. Remove the ethylene dichloride by rotary evaporation, filter with suction, and rinse the filter cake with water to obtain a crude product as a light yellow solid. After recrystallization from acetone, 19.0 g of white solid 2,4-dichloro-6-(4-methoxyphenyl)-s-triazine was obtained with a yield of 74%. The product structure was identified as in Example 1.

[0032] Example 7 Liquid-Assisted Ball Milling Solid Phase Synthesis of 2,4-Dichloro-6-(4-methoxyphenyl)-s-triazine

[0033] Place grinding balls in a 100mL ceramic ball mill, add anisole (10.8g, 100mmol), cyanuric chloride (20.2g), aluminum chloride 26.0g, and ethylene dichloride 40g. Fix the reaction tank containing the materials on the ball mill; add water to the counterbalance tank to make the weight of the balance tank equal to that of the reaction tank. Open the outlet valve of the reaction tank and connect it to the inlet valve of the balance tank through an air duct so that the hydrogen chloride gas produced by the reaction is absorbed in the balance tank. Start the ball mill, set the speed to 300rpm, take samples and analyze every 30 minutes, and the reaction is completed after 2 hours. Pour the reaction material and the water in the balance tank into cold concentrated hydrochloric acid (50mL), stir and hydrolyze. Remove the ethylene dichloride by rotary evaporation, filter with suction, and rinse the filter cake with water to obtain a crude product as a light yellow solid. Recrystallization with acetone gave 16.1 g of white solid 2,4-dichloro-6-(4-methoxyphenyl)-s-triazine with a yield of 63%. The product structure was identified in Example 1.

[0034] Example 8 Liquid-Assisted Ball Milling Solid Phase Synthesis of 2,4-Dichloro-6-(4-Methoxyphenyl)-s-Triazine

[0035] Place grinding balls in a 100mL ceramic ball mill, add anisole (10.8g, 100mmol), cyanuric chloride (27.5g), aluminum chloride 17.5g, and ethylene dichloride 40g. Fix the reaction tank containing the materials on the ball mill; add water to the counterbalance tank to make the weight of the balance tank equal to that of the reaction tank. Open the outlet valve of the reaction tank and connect it to the inlet valve of the balance tank through an air duct so that the hydrogen chloride gas produced by the reaction is absorbed in the balance tank. Start the ball mill, set the speed to 300rpm, take samples and analyze every 30 minutes, and the reaction is completed after 2 hours. Pour the reaction material and the water in the balance tank into cold concentrated hydrochloric acid (50mL), stir and hydrolyze. Remove the ethylene dichloride by rotary evaporation, filter with suction, and rinse the filter cake with water to obtain a crude product as a light yellow solid. Recrystallization with acetone gave 17.5 g of white solid 2,4-dichloro-6-(4-methoxyphenyl)-s-triazine with a yield of 68%. The product structure was identified in Example 1.

[0036] Example 9 Liquid-Assisted Ball Milling Solid Phase Synthesis of 2,4-Dichloro-6-(4-Methoxyphenyl)-s-Triazine

[0037] Place grinding balls in a 100mL ceramic ball mill, add anisole (10.8g, 100mmol), cyanuric chloride (20.2g), aluminum chloride 17.5g, and ethylene dichloride 45g. Fix the reaction tank containing the materials on the ball mill; add water to the counterbalance tank to make the weight of the balance tank equal to that of the reaction tank. Open the outlet valve of the reaction tank and connect it to the inlet valve of the balance tank through an air duct so that the hydrogen chloride gas produced by the reaction is absorbed in the balance tank. Start the ball mill, set the speed to 300rpm, take samples and analyze every 30 minutes, and the reaction is completed after 2 hours. Pour the reaction material and the water in the balance tank into cold concentrated hydrochloric acid (50mL), stir and hydrolyze. Remove the ethylene dichloride by rotary evaporation, filter with suction, and rinse the filter cake with water to obtain a crude product as a light yellow solid. After recrystallization from acetone, 18.5 g of white solid 2,4-dichloro-6-(4-methoxyphenyl)-s-triazine was obtained with a yield of 72%. The product structure was identified as in Example 1.

[0038] Example 10 Liquid-Assisted Ball Milling Solid Phase Synthesis of 2,4-Dichloro-6-(4-Methoxyphenyl)-s-Triazine

[0039] Place grinding balls in a 100mL ceramic ball mill, add anisole (10.8g, 100mmol), cyanuric chloride (20.2g), aluminum chloride 17.5g, and ethylene dichloride 30g. Fix the reaction tank containing the materials on the ball mill; add water to the counterbalance tank to make the weight of the balance tank equal to that of the reaction tank. Open the outlet valve of the reaction tank and connect it to the inlet valve of the balance tank through an air duct so that the hydrogen chloride gas produced by the reaction is absorbed in the balance tank. Start the ball mill, set the speed to 300rpm, take samples and analyze every 30 minutes, and the reaction is completed after 5 hours. Pour the reaction material and the water in the balance tank into cold concentrated hydrochloric acid (50mL), stir and hydrolyze. Remove the ethylene dichloride by rotary evaporation, filter with suction, and rinse the filter cake with water to obtain a crude product as a light yellow solid. Recrystallization with acetone gave 18.0 g of white solid 2,4-dichloro-6-(4-methoxyphenyl)-s-triazine with a yield of 70%. The product structure was identified in Example 1.

[0040] Example 11 Liquid-Assisted Ball Milling Solid Phase Synthesis of 2,4-Dichloro-6-(4-methoxyphenyl)-s-triazine

[0041] Place grinding balls in a 100mL ceramic ball mill, add anisole (10.8g, 100mmol), cyanuric chloride (20.2g), aluminum chloride 17.5g, and ethylene dichloride 40g. Fix the reaction tank containing the materials on the ball mill; add water to the counterbalance tank to make the weight of the balance tank equal to that of the reaction tank. Open the outlet valve of the reaction tank and connect it to the inlet valve of the balance tank through an air duct so that the hydrogen chloride gas produced by the reaction is absorbed in the balance tank. Start the ball mill, set the speed to 300rpm, take samples and analyze every 30 minutes, and the reaction is completed after 3 hours. Pour the reaction material and the water in the balance tank into cold concentrated hydrochloric acid (50mL), stir and hydrolyze. Remove the ethylene dichloride by rotary evaporation, filter with suction, and rinse the filter cake with water to obtain a crude product as a light yellow solid. Recrystallization with acetone gave 16.0 g of white solid 2,4-dichloro-6-(4-methoxyphenyl)-s-triazine with a yield of 63%. The product structure was identified in Example 1.

[0042] Example 12 Liquid-Assisted Ball Milling Solid Phase Synthesis of 2,4-Dichloro-6-(4-methoxyphenyl)-s-triazine

[0043] Place grinding balls in a 100mL ceramic ball mill, add anisole (10.8g, 100mmol), cyanuric chloride (20.2g), aluminum chloride 17.5g, and chloroform 40g. Fix the reaction tank containing the material on the ball mill; add water to the counterbalance tank to make the weight of the balance tank equal to that of the reaction tank. Open the outlet valve of the reaction tank and connect it to the inlet valve of the balance tank through an air duct so that the hydrogen chloride gas produced by the reaction is absorbed in the balance tank. Start the ball mill, set the speed to 300rpm, take samples and analyze every 30 minutes, and the reaction is completed after 2 hours. Pour the reaction material and the water in the balance tank into cold concentrated hydrochloric acid (50mL), stir and hydrolyze. Remove dichloroethane by rotary evaporation, filter with suction, and rinse the filter cake with water to obtain a crude product as a light yellow solid. After recrystallization from acetone, 17.7 g of white solid 2,4-dichloro-6-(4-methoxyphenyl)-s-triazine was obtained with a yield of 69%. The product structure was identified as in Example 1.

[0044] Example 13 Liquid-Assisted Ball Milling Solid Phase Synthesis of 2,4-Dichloro-6-(4-Methoxyphenyl)-s-Triazine

[0045] Place grinding balls in a 100mL ceramic ball mill, add anisole (10.8g, 100mmol), cyanuric chloride (20.2g), aluminum chloride 17.5g, and chlorobenzene 40g. Fix the reaction tank containing the materials on the ball mill; add water to the counterbalance tank to make the weight of the balance tank equal to that of the reaction tank. Open the outlet valve of the reaction tank and connect it to the inlet valve of the balance tank through an air duct so that the hydrogen chloride gas produced by the reaction is absorbed in the balance tank. Start the ball mill, set the speed to 300rpm, take samples and analyze every 30 minutes, and the reaction is completed after 2 hours. Pour the reaction material and the water in the balance tank into cold concentrated hydrochloric acid (50mL), stir and hydrolyze. Remove dichloroethane by rotary evaporation, filter with suction, and rinse the filter cake with water to obtain a crude product as a light yellow solid. After recrystallization from acetone, 18.1 g of white solid 2,4-dichloro-6-(4-methoxyphenyl)-s-triazine was obtained with a yield of 71%. The product structure was identified as in Example 1.

[0046] Example 14 Liquid-Assisted Ball Milling Solid Phase Synthesis of 2,4-Dichloro-6-(4-methoxyphenyl)-s-triazine

[0047] Place grinding balls in a 100mL ceramic ball mill, add anisole (10.8g, 100mmol), cyanuric chloride (20.2g), aluminum chloride 17.5g, and ethyl acetate 40g. Fix the reaction tank containing the materials on the ball mill; add water to the counterbalance tank to make the weight of the balance tank equal to that of the reaction tank. Open the outlet valve of the reaction tank and connect it to the inlet valve of the balance tank through an air duct so that the hydrogen chloride gas produced by the reaction is absorbed in the balance tank. Start the ball mill, set the speed to 300rpm, take samples and analyze every 30 minutes, and the reaction is completed after 6 hours. Pour the reaction material and the water in the balance tank into cold concentrated hydrochloric acid (50mL), stir and hydrolyze. Remove dichloroethane by rotary evaporation, filter with suction, and rinse the filter cake with water to obtain a crude product as a light yellow solid. Recrystallization with acetone gave 12.9 g of white solid 2,4-dichloro-6-(4-methoxyphenyl)-s-triazine, with a yield of 50%. The product structure was identified in Example 1.

[0048] Table 1 Types of raw materials, dosage, ball milling speed and time, and product yields of Examples 2-14

[0049]

[0050] Comparative Example 1 Preparation of 2,4-dichloro-6-(4-methoxyphenyl)-triazine

[0051] The reaction was carried out according to the feed ratio of Example 7, the difference being that the reaction system of this comparative example is a solution reaction system.

[0052] Add 20.2g (110mmol) of cyanuric chloride and 500ml of dichloroethane to a 1-liter four-necked flask equipped with a mechanical stirrer, a thermometer and an isobaric dropping funnel, heat to 60°C and stir until basically dissolved; then cool to 0°C and add 20.0g (150mmol) of crushed aluminum chloride in 5 batches. After adding, stir for 10 minutes, then slowly add 10.8g (100mmol) of anisole / 50mL dichloroethane solution from the dropping funnel, keeping the internal temperature no more than 10°C. After adding, continue to stir the reaction and naturally rise to room temperature. Take samples every hour for analysis. After 15 hours, the reaction no longer proceeds. Pour the reaction material into cold dilute hydrochloric acid (10%, 100mL) and stir for hydrolysis. Separate the liquid, extract the water layer with 100mL of dichloroethane, combine the dichloroethane solutions, wash with water until neutral, dry over anhydrous sodium sulfate, remove the dissolved crude product as a light yellow solid. After recrystallization from acetone, 12.4 g of white solid 2,4-dichloro-6-(4-methoxyphenyl)-s-triazine was obtained with a yield of 48%.

[0053] Comparative Example 2 Preparation of 2,4-dichloro-6-(4-methoxyphenyl)-triazine

[0054] The reaction was carried out according to the feed ratio of Example 7, except that no auxiliary liquid solid grinding was added.

[0055] Place grinding balls in a 100mL ceramic ball mill, add anisole (10.8g, 100mmol), cyanuric chloride (20.2g, 110mmol) and aluminum chloride 20.0g (150mmol), fix the reaction tank containing the materials on the ball mill; add water to the counterbalance tank to make the weight of the balance tank equal to that of the reaction tank. Open the outlet valve of the reaction tank and connect it to the inlet valve of the balance tank through an air duct so that the hydrogen chloride gas produced by the reaction is absorbed in the balance tank. Start the ball mill, set the speed to 300rpm, take samples and analyze every 30 minutes, and find that the caking is serious and the mixing is uneven. Mix manually, then continue grinding, repeat several times, and the reaction is still not over after 4 hours. Pour the reaction material and the water in the balance tank into cold concentrated hydrochloric acid (50mL), stir and hydrolyze. Remove dichloroethane by rotary evaporation, filter with suction, rinse the filter cake with water, and drain. The filter cake was dissolved in 200 mL of dichloroethane, filtered, and insoluble matter was removed; the solvent was removed from the filtrate to obtain a crude product, which was then recrystallized with acetone to obtain 7.8 g of beige solid 2,4-dichloro-6-(4-methoxyphenyl)-triazine, with a yield of 30%.

Claims

1. A method for synthesizing 2,4-dichloro-6-(4-methoxyphenyl)-s-triazine, comprising carrying out a Friedel-Crafts reaction with anisole and cyanuric chloride as reaction raw materials in the presence of a catalyst; characterized in that: When performing the Friedel-Crafts reaction, a grinding auxiliary liquid is added to grind the solid phase raw material to perform the solid phase Friedel-Crafts reaction.

2. The synthesis method according to claim 1, characterized in that When carrying out solid phase Friedel-Crafts reaction, the weight of the milling auxiliary liquid added is lower than the total weight of the reaction materials.

3. The synthesis method according to claim 1, characterized in that The grinding auxiliary liquid is a Friedel-Crafts reaction solvent.

4. The synthesis method according to claim 3, characterized in that The Friedel-Crafts reaction solvent includes, but is not limited to, chlorobenzene, chloroform, dichloroethane, dichloromethane or ethyl acetate.

5. The synthesis method according to claim 1, characterized in that The solid raw materials are ground by ball milling.

6. The synthesis method according to claim 5, characterized in that The rotation speed of the ball mill is 100-400 rpm, preferably 300 rpm.

7. The synthesis method according to claim 1, characterized in that The solid phase Friedel-Crafts reaction is carried out at room temperature; wherein the room temperature is preferably 15-25°C.

8. The synthesis method according to claim 1, characterized in that The catalyst is aluminum chloride.

9. The synthesis method according to claim 1 or 8, characterized in that: The amount of the catalyst used is 1.1-2.0 times the molar amount of anisole, preferably 1.1-1.5 times the molar amount, and most preferably 1.3-1.5 times the molar amount.

10. The synthesis method according to claim 1, characterized in that The amount of cyanuric chloride used is 1.0-1.5 times the molar amount of anisole, preferably 1.1-1.3 times the molar amount.

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