Synthesis process of 2-chloro-4, 6-dimethyl pyrimidine

Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to a 2-chloro-4, 6-dimethyl pyrimidine synthesis process, which comprises: 1) mixing 2-hydroxy-4, 6-dimethyl pyrimidine, xylene and phosphorus oxychloride, heating to a temperature of 50-60 DEG C, dropwise adding N, N-diisopropylethylamine, heating to a temperature of 80-105 DEG C after the dropwise adding is completed, carrying out a reaction for 2-3 h, removing excess phosphorus oxychloride, cooling to a room temperature, and carrying out a reaction for 2-3 h to obtain a 2-chloro-4, 6-dimethyl pyrimidine intermediate; a reaction liquid crude product is obtained; and 2) dropwise adding the crude product of the reaction liquid into a supersaturated sodium bicarbonate aqueous solution at 5-15 DEG C, keeping the water temperature in the dropwise adding process, keeping the water temperature after dropwise adding, stirring for 15-35 minutes, filtering, standing and layering filtrate, drying an organic phase by anhydrous magnesium sulfate, removing xylene, and performing reduced pressure distillation to obtain the 2-chloro-4, 6-dimethyl pyrimidine. According to the method, the dosage of phosphorus oxychloride can be reduced, hydrolysis of the product is effectively avoided, the yield of the product is improved, and the method has no obvious amplification effect and is suitable for industrial production.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and specifically relates to a synthesis process of 2-chloro-4,6-dimethylpyrimidine. Background Art

[0002] 2-Chloro-4,6-dimethylpyrimidine is an important intermediate for medicine and pesticides. It can also be used to prepare a new type of energetic material with good thermal stability and high nitrogen content. At present, the commonly used synthesis methods of 2-chloro-4,6-dimethylpyrimidine are prepared by mixing 2-hydroxy-4,6-dimethylpyrimidine with a large amount of phosphorus oxychloride for reflux reaction. However, this synthesis method requires the use of more than eight times phosphorus oxychloride to participate in the reaction, and the reaction time is long. After the reaction scale is enlarged, the reaction time may need to be extended to more than 48 hours, which poses a great safety hazard. Moreover, the post-reaction treatment process is complicated. During the post-treatment process, 2-chloro-4,6-dimethylpyrimidine is easily hydrolyzed into the raw material 2-hydroxy-4,6-dimethylpyrimidine, resulting in a decrease in yield. Therefore, it is of great strategic significance to explore the synthesis process of 2-chloro-4,6-dimethylpyrimidine to make it more suitable for industrial production. Summary of the invention

[0003] The present invention aims to provide a 2-chloro-4,6-dimethylpyrimidine synthesis process to solve the problem of low yield in the existing 2-chloro-4,6-dimethylpyrimidine synthesis method.

[0004] In order to achieve the above object, the scheme of the present invention is: a 2-chloro-4,6-dimethylpyrimidine synthesis process, comprising the following steps:

[0005] S1, reaction stage: 2-hydroxy-4,6-dimethylpyrimidine, xylene and phosphorus oxychloride are mixed, the temperature is raised to 50-60°C, N,N-diisopropylethylamine is added dropwise, and after the addition is completed, the temperature is raised to 80-105°C for reaction for 2-3h, and the excess phosphorus oxychloride is removed and the temperature is cooled to room temperature to obtain a crude reaction solution;

[0006] S2, post-treatment stage: the crude reaction liquid is added dropwise to a supersaturated sodium bicarbonate aqueous solution. During the addition, the water temperature of the saturated sodium bicarbonate aqueous solution is maintained at 5-15°C. After the addition is completed, the water temperature is maintained and stirred for 15-35 minutes. After filtering, the filtrate is allowed to stand and separate. The organic phase is dried over anhydrous magnesium sulfate. After removing xylene from the organic phase, 2-chloro-4,6-dimethylpyrimidine is obtained by distillation under reduced pressure.

[0007] The working principle and beneficial effect of this scheme are as follows: In this scheme, N,N-diisopropylethylamine is an amine acid-binding agent with very high stability, which can react and combine the generated hydrogen chloride byproduct to generate N,N-diisopropylethylamine hydrochloride, which is conducive to the forward progress of the reaction. Moreover, since 2-chloro-4,6-dimethylpyrimidine spontaneously hydrolyzes in a strongly acidic or alkaline environment to regenerate 2-hydroxy-4,6-dimethylpyrimidine, in the post-treatment stage of this scheme, the crude reaction solution is added dropwise to a weakly alkaline supersaturated sodium bicarbonate aqueous solution to adjust the acidity and alkalinity of the crude reaction solution, thereby effectively avoiding the hydrolysis of 2-chloro-4,6-dimethylpyrimidine, thereby increasing the yield of 2-chloro-4,6-dimethylpyrimidine.

[0008] Compared with the existing preparation method of 2-hydroxy-4,6-dimethylpyrimidine and phosphorus oxychloride mixed reflux, this scheme has the following advantages: 1) This scheme greatly reduces the amount of phosphorus oxychloride used, improves reaction safety, and reduces environmental pollution; 2) This scheme greatly shortens the reaction time, has no obvious amplification effect, and is suitable for industrial production; 3) The post-reaction treatment process is optimized, the product hydrolysis rate is reduced, and the yield of 2-chloro-4,6-dimethylpyrimidine reaches more than 80%, and can reach up to 88.1%.

[0009] Optionally, in step S1, the molar ratio of 2-hydroxy-4,6-dimethylpyrimidine, phosphorus oxychloride and N,N-diisopropylethylamine is 1:(1.5-3):1.2.

[0010] Optionally, in step S1, the mass ratio of 2-hydroxy-4,6-dimethylpyrimidine to xylene is 1:1.5.

[0011] Optionally, in step S1, excess phosphorus oxychloride is removed by concentration under reduced pressure, and the vacuum degree during the removal of phosphorus oxychloride is 50-70 kPa.

[0012] Optionally, in step S2, xylene in the organic phase is removed by reduced pressure concentration, the vacuum degree during the xylene removal process is 3 to 5 kPa, and the temperature of the reduced pressure concentration of the organic phase is 65 to 90°C.

[0013] Optionally, in step S2, the reduced pressure distillation temperature of the organic phase after removing xylene is 90-100°C, and the vacuum degree is 200-800Pa.

[0014] Optionally, in step S2, after the filtrate is allowed to stand for stratification, the aqueous phase is washed with xylene, and the xylene used for washing the aqueous phase is combined with the organic phase.

[0015] Optionally, in step S1, the reaction is carried out under nitrogen protection. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 is the hydrogen nuclear magnetic resonance spectrum of the product in Example 1 of the present invention;

[0017] Figure 2 is a liquid chromatogram of the product in Example 1 of the present invention;

[0018] Figure 3 is a liquid chromatogram of the product in Example 2 of the present invention;

[0019] Figure 4 is a liquid chromatogram of the product in Example 3 of the present invention;

[0020] Figure 5 It is the liquid chromatogram of the product in Comparative Example 1 of the present invention;

[0021] Figure 6 It is the liquid chromatogram of the product in Comparative Example 2 of the present invention. DETAILED DESCRIPTION

[0022] The following describes the embodiments of the present invention through specific examples, and those skilled in the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and the details in this specification can also be modified or changed in various ways based on different viewpoints and applications without departing from the spirit of the present invention.

[0023] The present invention provides a 2-chloro-4,6-dimethylpyrimidine synthesis process, comprising the following steps:

[0024] S1, reaction stage: under nitrogen protection, 2-hydroxy-4,6-dimethylpyrimidine, xylene and phosphorus oxychloride are mixed, heated to 50-60°C, and N,N-diisopropylethylamine is added dropwise. After the addition is completed, the temperature is raised to 80-105°C for reaction for 2-3h, and the excess phosphorus oxychloride is removed and then cooled to room temperature to obtain a crude reaction solution. Among them, the molar ratio of 2-hydroxy-4,6-dimethylpyrimidine, phosphorus oxychloride and N,N-diisopropylethylamine is 1:(1.5-3):1.2; the mass ratio of 2-hydroxy-4,6-dimethylpyrimidine to xylene is 1:1.5. Moreover, the excess phosphorus oxychloride is removed by reduced pressure concentration, and the vacuum degree during the removal of phosphorus oxychloride is 50-70kPa, and the temperature is controlled at 80-85°C.

[0025] S2, post-treatment stage: the crude reaction liquid is added dropwise to a supersaturated sodium bicarbonate aqueous solution. During the addition process, the water temperature of the saturated sodium bicarbonate aqueous solution is maintained at 5 to 15°C. After the addition is completed, the water temperature is maintained and stirred for 15 to 35 minutes. After filtration, the filtrate is allowed to stand for stratification, and the organic phase is dried with anhydrous magnesium sulfate. After removing the xylene from the organic phase, 2-chloro-4,6-dimethylpyrimidine is obtained by vacuum distillation. The xylene in the organic phase is removed by vacuum concentration, and the vacuum degree during the removal of xylene is 3 to 5 kPa, and the temperature of the organic phase vacuum concentration is 65 to 90°C. The vacuum distillation temperature of the organic phase after removing the xylene is 90 to 100°C, and the vacuum degree is 200 to 800 Pa.

[0026] In addition, in the post-treatment stage, after the filtrate is allowed to stand for separation, the aqueous phase is washed with xylene, and the xylene used for washing the aqueous phase is combined with the organic phase to recover the product in the aqueous phase.

[0027] The following specific examples are given to explain the present invention in detail. It should also be understood that the following examples are only used to explain the present invention in detail and cannot be understood as limiting the scope of protection of the present invention. Some non-essential improvements and adjustments made by technicians in this field according to the above content of the present invention belong to the scope of protection of the present invention. The specific process parameters and the like in the following examples are only an example in a suitable range, that is, those skilled in the art can make a selection within a suitable range through the description of this article, and are not limited to the specific values ​​​​exemplified below. In addition, in the following examples and comparative examples, 2-hydroxy-4,6-dimethylpyrimidine is homemade, and reference patents WO2013004617 A1; TW201315731A prepare 2-hydroxy-4,6-dimethylpyrimidine (purity 97%) by acetylacetone and urea under acidic conditions. In addition, phosphorus oxychloride, xylene and sodium bicarbonate are all reagent grade.

[0028] Example 1

[0029] This embodiment provides a 2-chloro-4,6-dimethylpyrimidine synthesis process, comprising the following steps:

[0030] 1) Reaction stage: Under nitrogen protection, add 124.2g (1.0mol) 2-hydroxy-4,6-dimethylpyrimidine, 186.3g xylene and 230.1g (1.5mol) phosphorus oxychloride to a 1L reaction bottle equipped with a thermometer and an electric stirrer, start the electric stirrer, and stir the liquid in the reaction bottle. Subsequently, heat the reaction bottle, and the temperature of the liquid in the reaction bottle rises to 50-60°C and maintains it. Add 156.6g (1.2mol) N,N-diisopropylethylamine dropwise to the reaction bottle. After the addition is complete, the temperature of the liquid in the reaction bottle rises to 80-105°C. Keep the reaction warm for 2h, and detect that the reaction has reached the end point by TLC. The temperature of the liquid in the reaction flask is controlled to be maintained at 80-85°C, and the water pump is turned on to make the vacuum degree in the reaction flask 50-70kPa. The liquid in the reaction flask is concentrated under reduced pressure to remove excess phosphorus oxychloride (excess phosphorus oxychloride is about 50g). When almost no distillation is produced in the phosphorus oxychloride receiving bottle, it means that most of the phosphorus oxychloride in the liquid in the reaction flask has been removed. After most of the phosphorus oxychloride is removed, the liquid in the reaction flask is cooled to room temperature to obtain a crude reaction liquid.

[0031] 2) Post-treatment stage: under stirring conditions, the crude reaction liquid was added dropwise to a supersaturated sodium bicarbonate aqueous solution, which was prepared from 421.3 g of sodium bicarbonate and 844.5 g of water. During the addition, the water temperature of the saturated sodium bicarbonate aqueous solution was maintained at 5-15°C; after the addition was completed, the water temperature (5-15°C) was maintained and stirred for 15 minutes, and filtered. The filtrate obtained after filtration was allowed to stand for stratification to obtain an aqueous phase and an organic phase, and the aqueous phase was washed with 62.1 g of xylene, and the aqueous phase was washed with xylene and then combined with the organic phase. The organic phase was dried with anhydrous magnesium sulfate, and then filtered. After filtering, the temperature of the organic phase was controlled between 65 and 85°C, and the organic phase was concentrated under reduced pressure by a water pump. The vacuum degree during the reduced pressure concentration process was 3 to 5 kPa, so as to remove the xylene in the organic phase. When there was almost no distillation in the xylene receiving bottle, the organic phase was distilled under reduced pressure by a rotary vane vacuum pump. The vacuum degree during the reduced pressure distillation process was 200 to 800 Pa. The fractions between 90 and 95°C were collected to obtain 122.5 g of a colorless and transparent product. The nuclear magnetic resonance hydrogen spectrum of the product was as follows: Figure 1 As shown, it is shown that the product in this example is 2-chloro-4,6-dimethylpyrimidine. In addition, the yield of 2-chloro-4,6-dimethylpyrimidine in this example is 85.9%, and the liquid phase shows that its purity is 98.7% (as shown in FIG. Figure 2 shown).

[0032] Example 2

[0033] This embodiment provides a 2-chloro-4,6-dimethylpyrimidine synthesis process, comprising the following steps:

[0034] 1) Reaction stage: Under nitrogen protection, add 1.0kg (8.1mol) 2-hydroxy-4,6-dimethylpyrimidine and 1.5kg xylene to a 10L reactor, vacuum inhale 2.7kg (17.6mol) phosphorus oxychloride, heat the reactor, and raise the temperature of the liquid in the reactor to 50-60°C and maintain it, then drop 1.3kg (10.1mol) N,N-diisopropylethylamine into the reactor, and stir the liquid in the reactor during the dropwise addition. After the dropwise addition of N,N-diisopropylethylamine, the temperature of the liquid in the reactor rises to 80-105°C, and the reaction is kept warm for 3h. The reaction has reached the end point as detected by TLC. Subsequently, the temperature of the liquid in the kettle was controlled to be maintained at 80-85°C, and the water pump was turned on to make the vacuum degree in the kettle 50-70 kPa. The liquid in the kettle was concentrated under reduced pressure to remove excess phosphorus oxychloride (excess phosphorus oxychloride was about 1.28 kg). When almost no phosphorus oxychloride was distilled out of the phosphorus oxychloride receiving bottle, it represented that most of the phosphorus oxychloride in the liquid in the reaction bottle had been removed. After most of the phosphorus oxychloride was removed, the liquid in the kettle was cooled to room temperature to obtain a crude reaction liquid.

[0035] 2) Post-treatment stage: under stirring conditions, the crude reaction liquid is added dropwise to a 20L reactor containing a supersaturated sodium bicarbonate aqueous solution, which is prepared from 3.8kg of sodium bicarbonate and 7.6kg of water. During the addition, the temperature of the liquid in the reactor is maintained at 5-15°C; after the addition is completed, the water temperature (5-15°C) is maintained and stirred for 30 minutes, and filtered. The filtrate obtained after filtration is allowed to stand for stratification to obtain an aqueous phase and an organic phase. The aqueous phase is washed with 750g of xylene, and the aqueous phase is washed with xylene and then combined with the organic phase. The organic phase was dried with anhydrous magnesium sulfate, and then filtered. After filtering, the temperature of the organic phase was controlled between 75 and 90°C, and the organic phase was concentrated under reduced pressure by a water pump. The vacuum degree during the concentrated process was 3 to 5 kPa, so as to remove the xylene in the organic phase. When there was almost no distillation in the xylene receiving bottle, the organic phase was distilled under reduced pressure by a rotary vane vacuum pump. The vacuum degree during the distillation was 200 to 800 Pa. The fractions between 93 and 100°C were collected to obtain 931.1 g of colorless and transparent 2-chloro-4,6-dimethylpyrimidine with a yield of 81%. The liquid phase showed that its purity was 98.6% (such as Figure 3 shown).

[0036] Example 3

[0037] This embodiment provides a 2-chloro-4,6-dimethylpyrimidine synthesis process, comprising the following steps:

[0038] 1) Reaction stage: Under nitrogen protection, add 124.0g (1.0mol) 2-hydroxy-4,6-dimethylpyrimidine, 186.2g xylene and 459.9g (3.0mol) phosphorus oxychloride to a 1L reaction bottle equipped with a thermometer and an electric stirrer, start the electric stirrer, and stir the liquid in the reaction bottle. Subsequently, heat the reaction bottle, and the temperature of the liquid in the reaction bottle rises to 50-60°C and maintains it. Add 156.1g (1.2mol) N,N-diisopropylethylamine dropwise to the reaction bottle. After the addition is complete, the temperature of the liquid in the reaction bottle rises to 80-105°C. Keep the reaction warm for 2h, and detect that the reaction has reached the end point by TLC. The temperature of the liquid in the reaction flask is controlled to be maintained at 80-85°C, and the water pump is turned on to make the vacuum degree in the reaction flask 50-70kPa. The liquid in the reaction flask is concentrated under reduced pressure to remove excess phosphorus oxychloride (excess phosphorus oxychloride is about 263.7g). When almost no distillation is produced in the phosphorus oxychloride receiving bottle, it means that most of the phosphorus oxychloride in the liquid in the reaction flask has been removed. After most of the phosphorus oxychloride is removed, the liquid in the reaction flask is cooled to room temperature to obtain a crude reaction liquid.

[0039] 2) Post-treatment stage: under stirring conditions, the crude reaction liquid was added dropwise to a supersaturated sodium bicarbonate aqueous solution, which was prepared from 500.3 g of sodium bicarbonate and 899.8 g of water. During the addition, the water temperature of the saturated sodium bicarbonate aqueous solution was maintained at 5-15°C; after the addition was completed, the water temperature (5-15°C) was maintained and stirred for 15 minutes, and filtered. The filtrate obtained after filtration was allowed to stand for stratification to obtain an aqueous phase and an organic phase, and the aqueous phase was washed with 61.9 g of xylene, and the aqueous phase was washed with xylene and then combined with the organic phase. The organic phase was dried with anhydrous magnesium sulfate, and then filtered. After filtering, the temperature of the organic phase was controlled between 65 and 85°C, and the organic phase was concentrated under reduced pressure by a water pump. The vacuum degree during the reduced pressure concentration process was 3 to 5 kPa, so as to remove xylene in the organic phase. When there was almost no distillation in the xylene receiving bottle, the organic phase was distilled under reduced pressure by a rotary vane vacuum pump. The vacuum degree during the reduced pressure distillation process was 200 to 800 Pa. The fractions between 90 and 95°C were collected to obtain 125.7 g of colorless and transparent 2-chloro-4,6-dimethylpyrimidine, with a yield of 88.1%. The liquid phase showed that its purity was 98.1% (such as Figure 4 shown).

[0040] Comparative Example 1

[0041] This comparative example provides a 2-chloro-4,6-dimethylpyrimidine synthesis process, comprising the following steps:

[0042] 1) Reaction stage: Under nitrogen protection, add 124.0g (1.0mol) 2-hydroxy-4,6-dimethylpyrimidine, 185.8g xylene and 459.9g (3.0mol) phosphorus oxychloride to a 1L reaction bottle equipped with a thermometer and an electric stirrer, start the electric stirrer, and stir the liquid in the reaction bottle. Subsequently, heat the reaction bottle, the temperature of the liquid in the reaction bottle rises to 50-60°C and maintains, add 103.5g (1.2mol) triethylamine to the reaction bottle, after the addition is complete, the temperature of the liquid in the reaction bottle rises to 80-105°C, keep the reaction warm for 2h, and detect that the reaction has reached the end point by TLC. Control the temperature of the liquid in the reaction bottle to maintain at 80-85°C, turn on the water pump, so that the vacuum degree in the reaction bottle is 50-70kPa, and reduce the pressure and concentrate the liquid in the reaction bottle to remove excess phosphorus oxychloride (excess phosphorus oxychloride is about 263.5g). When almost no distillation is produced in the phosphorus oxychloride receiving bottle, it means that most of the phosphorus oxychloride in the liquid in the reaction bottle has been removed. After most of the phosphorus oxychloride is removed, the liquid in the reaction bottle is cooled to room temperature to obtain a crude reaction liquid.

[0043] 2) Post-treatment stage: under stirring conditions, the crude reaction liquid was added dropwise to a supersaturated sodium bicarbonate aqueous solution, which was prepared from 521.1 g of sodium bicarbonate and 923.1 g of water. During the addition, the water temperature of the saturated sodium bicarbonate aqueous solution was maintained at 5-15°C; after the addition was completed, the water temperature (5-15°C) was maintained and stirred for 15 minutes, and filtered. The filtrate obtained after filtration was allowed to stand for stratification to obtain an aqueous phase and an organic phase, and the aqueous phase was washed with 64.9 g of xylene, and the aqueous phase was washed with xylene and then combined with the organic phase. The organic phase was dried with anhydrous magnesium sulfate, and then filtered. After filtering, the temperature of the organic phase was controlled between 65 and 85°C, and the organic phase was concentrated under reduced pressure by a water pump. The vacuum degree during the concentrated process was 3 to 5 kPa, so as to remove the xylene in the organic phase. When there was almost no distillation in the xylene receiving bottle, the organic phase was distilled under reduced pressure by a rotary vane vacuum pump. The vacuum degree during the distillation was 200 to 800 Pa. The fraction between 90 and 95°C was collected to obtain 101.4 g of dark brown 2-chloro-4,6-dimethylpyrimidine with a yield of 71.1%. The liquid phase showed that its purity was 94.0% (such as Figure 5 shown).

[0044] Comparative Example 2

[0045] This comparative example provides a 2-chloro-4,6-dimethylpyrimidine synthesis process, comprising the following steps:

[0046] 1) Reaction stage: Under nitrogen protection, 124.2g (1.0mol) 2-hydroxy-4,6-dimethylpyrimidine, 184.2g xylene and 458.3g (3.0mol) phosphorus oxychloride were added to a 1L reaction bottle equipped with a thermometer and an electric stirrer, and the electric stirrer was started to stir the liquid in the reaction bottle. Subsequently, the reaction bottle was heated, and the temperature of the liquid in the reaction bottle rose to 80-105°C. The reaction was kept warm for 2h. TLC detection revealed that there was still unreacted 2-hydroxy-4,6-dimethylpyrimidine in the liquid in the reaction bottle. After continuing the reaction for 34h, unreacted 2-hydroxy-4,6-dimethylpyrimidine was still found. At this time, regardless of the unreacted 2-hydroxy-4,6-dimethylpyrimidine, the temperature of the liquid in the reaction bottle is controlled to be maintained at 80-85°C, the water pump is turned on to make the vacuum degree in the reaction bottle 50-70kPa, and the liquid in the reaction bottle is concentrated under reduced pressure to remove excess phosphorus oxychloride (excess phosphorus oxychloride is about 263.0g). When there is almost no distillation in the phosphorus oxychloride receiving bottle, it means that most of the phosphorus oxychloride in the liquid in the reaction bottle has been removed. After most of the phosphorus oxychloride is removed, the liquid in the reaction bottle is cooled to room temperature to obtain a crude reaction liquid.

[0047] 2) Post-treatment stage: under stirring conditions, the crude reaction liquid was added dropwise to a supersaturated sodium bicarbonate aqueous solution, which was prepared from 501.0 g of sodium bicarbonate and 894.4 g of water. During the addition, the water temperature of the saturated sodium bicarbonate aqueous solution was maintained at 5-15°C; after the addition was completed, the water temperature (5-15°C) was maintained and stirred for 15 minutes, and filtered. The filtrate obtained after filtration was allowed to stand for stratification to obtain an aqueous phase and an organic phase, and the aqueous phase was washed with 64.9 g of xylene, and the aqueous phase was washed with xylene and then combined with the organic phase. The organic phase was dried with anhydrous magnesium sulfate, and then filtered. After filtering, the temperature of the organic phase was controlled between 65 and 85°C, and the organic phase was concentrated under reduced pressure by a water pump. The vacuum degree during the concentrated process was 3 to 5 kPa, so as to remove xylene in the organic phase. When there was almost no distillation in the xylene receiving bottle, the organic phase was distilled under reduced pressure by a rotary vane vacuum pump. The vacuum degree during the distillation was 200 to 800 Pa. The fractions between 90 and 95°C were collected to obtain 75.2 g of colorless and transparent 2-chloro-4,6-dimethylpyrimidine, with a yield of 53.1%. The liquid phase showed that its purity was 98.1% (such as Figure 6 shown).

[0048] The above are only embodiments of the present invention. The invention is not limited to the fields involved in this implementation case. The common sense such as the known specific structures and characteristics in the scheme is not described in detail here. The ordinary technicians in the relevant field know all the common technical knowledge in the technical field to which the invention belongs before the application date or priority date, can obtain all the existing technologies in the field, and have the ability to apply the conventional experimental means before that date. The ordinary technicians in the relevant field can improve and implement this scheme in combination with their own abilities under the enlightenment given by this application. Some typical known structures or known methods should not become obstacles for ordinary technicians in the relevant field to implement this application. It should be pointed out that for those skilled in the art, without departing from the structure of the present invention, several deformations and improvements can be made, which should also be regarded as the protection scope of the present invention, which will not affect the effect of the implementation of the present invention and the practicality of the present invention. The protection scope required by this application shall be based on the content of its claims, and the specific implementation methods and other records in the specification can be used to explain the content of the claims.

Claims

1. A process for synthesizing 2-chloro-4,6-dimethylpyrimidine, characterized in that: The following steps are involved: S1, reaction stage: 2-hydroxy-4,6-dimethylpyrimidine, xylene and phosphorus oxychloride are mixed, the temperature is raised to 50-60°C, N,N-diisopropylethylamine is added dropwise, and after the addition is completed, the temperature is raised to 80-105°C for reaction for 2-3h, and the excess phosphorus oxychloride is removed and the temperature is cooled to room temperature to obtain a crude reaction solution; S2, post-treatment stage: the crude reaction liquid is added dropwise to a supersaturated sodium bicarbonate aqueous solution. During the addition, the water temperature of the saturated sodium bicarbonate aqueous solution is maintained at 5-15°C. After the addition is completed, the water temperature is maintained and stirred for 15-35 minutes. After filtering, the filtrate is allowed to stand and separate. The organic phase is dried over anhydrous magnesium sulfate. After removing xylene from the organic phase, 2-chloro-4,6-dimethylpyrimidine is obtained by distillation under reduced pressure.

2. The 2-chloro-4,6-dimethylpyrimidine synthesis process according to claim 1, characterized in that: In step S1, the molar ratio of 2-hydroxy-4,6-dimethylpyrimidine, phosphorus oxychloride and N,N-diisopropylethylamine is 1:(1.5-3):1.

2.

3. The 2-chloro-4,6-dimethylpyrimidine synthesis process according to claim 1, characterized in that: In step S1, the mass ratio of 2-hydroxy-4,6-dimethylpyrimidine to xylene is 1:1.

5.

4. The 2-chloro-4,6-dimethylpyrimidine synthesis process according to claim 1, characterized in that: In step S1, excess phosphorus oxychloride is removed by concentration under reduced pressure, and the vacuum degree during the phosphorus oxychloride removal process is 50-70 kPa.

5. The 2-chloro-4,6-dimethylpyrimidine synthesis process according to claim 1, characterized in that: In step S2, xylene in the organic phase is removed by reduced pressure concentration. The vacuum degree during the xylene removal process is 3-5 kPa, and the temperature of the reduced pressure concentration of the organic phase is 65-90°C.

6. The 2-chloro-4,6-dimethylpyrimidine synthesis process according to claim 1, characterized in that: In step S2, the reduced pressure distillation temperature of the organic phase after removing xylene is 90-100°C, and the vacuum degree is 200-800Pa.

7. The 2-chloro-4,6-dimethylpyrimidine synthesis process according to claim 1, characterized in that: In step S2, after the filtrate is allowed to stand for stratification, the aqueous phase is washed with xylene, and the xylene used for washing the aqueous phase is combined with the organic phase.

8. The 2-chloro-4,6-dimethylpyrimidine synthesis process according to claim 1, characterized in that: In step S1, the reaction is carried out under nitrogen protection.

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