A green and environmentally friendly catalytic synthesis method of N,2,3-trimethyl-2-isopropylbutyramide

Abstract

The invention discloses a catalytic synthesis method of green and environmentally friendly N,2,3-trimethyl-2-isopropylbutyramide, comprising the steps of: adding a catalyst and 2-isopropyl-2,3-dimethylbutyronitrile to a reactor and stirring fully, at 105-130°C, dropping an alkylating agent; after completion of the dropwise addition, the reaction temperature rises to 140-180°C, and the temperature is kept warm and stirred for no less than 10h, the reaction system drops to below 100°C, pure water is added to quench the reaction, and after the quenching ends, the system temperature drops to room temperature to obtain a crude product of N,2,3-trimethyl-2-isopropylbutyramide; the obtained crude product is extracted, washed, and crystallized by a mixed solvent to obtain a pure product of N,2,3-trimethyl-2-isopropylbutyramide. After the reaction of the present invention, the catalyst can be recycled after being treated by a certain method, which greatly reduces production costs, and also reduces pollution emissions, in line with the concept of green sustainable development.

Description

Technical Field

[0001] The invention relates to the technical field of cooling agent synthesis, and in particular to a green and environment-friendly catalytic synthesis method of N,2,3-trimethyl-2-isopropylbutyramide. Background Art

[0002] N,2,3-trimethyl-2-isopropylbutyramide is an important cooling agent, which is widely used in food, medicine, cosmetics and other fields. Its preparation method usually uses 2-isopropyl-2,3-dimethylbutyronitrile and dimethyl carbonate as raw materials under the action of acid catalyst.

[0003]

[0004] Mechanism: Nitriles are converted to N-alkylamides by using alkylating agents. In the presence of strong acids, dimethyl carbonate can generate stable carbocations, which can undergo Ritter reactions with nitriles to form amides.

[0005] Solutions of existing technologies: There are two main methods for synthesizing N,2,3-trimethyl-2-isopropylbutyramide. One method is to use polyphosphoric acid as a catalyst, DIPPN and dimethyl carbonate as raw materials, and react at high temperature. In addition, there is another method that uses a solid acid catalyst, DIPPN and dimethyl carbonate as raw materials, and reacts at a certain temperature.

[0006] Problems with the existing technology: However, there are some problems with the existing methods for synthesizing N,2,3-trimethyl-2-isopropylbutyramide. First, the polyphosphoric acid catalytic system cannot recycle the catalyst, and a large amount of phosphoric acid aqueous solution is produced that cannot be treated, resulting in excessive three wastes and high treatment costs. Secondly, the yield of the solid acid catalytic method is not high, the product post-processing is complicated, the purity of the obtained product is low, and the catalyst cannot be recycled and reused, resulting in a large amount of solid waste, which further increases the production cost. Summary of the invention

[0007] The present invention aims at the fact that the polyphosphoric acid system in the prior art generates a large amount of production wastewater during production, which is difficult to treat. This runs counter to the current green environmental protection, is not conducive to environmental friendliness, and also creates certain economic pressure on production enterprises to treat wastewater. The present invention provides a green and environmentally friendly catalytic synthesis method of N,2,3-trimethyl-2-isopropylbutyramide (WS-23). ​​After the reaction, the catalyst can be recycled after being treated by a certain method, which greatly reduces the production cost and also reduces pollution emissions, which is in line with the concept of green and sustainable development.

[0008] In order to achieve the above object, the present invention adopts the following technical solutions:

[0009] A green and environmentally friendly catalytic synthesis method of N,2,3-trimethyl-2-isopropylbutyramide comprises the following steps:

[0010] (1) Add the catalyst and 2-isopropyl-2,3-dimethylbutyronitrile into the reactor and stir thoroughly. Then, add the alkylating agent dropwise at 105-130°C.

[0011] (2) After the addition is complete, the reaction temperature is raised to 140-180°C, and the mixture is stirred for at least 10 hours. After the reaction is complete, the system temperature is lowered to room temperature to obtain a crude product of N,2,3-trimethyl-2-isopropylbutanamide;

[0012] (3) The obtained crude product is subjected to extraction, washing and mixed solvent crystallization to obtain pure N,2,3-trimethyl-2-isopropylbutyramide.

[0013] Preferably, the catalyst in step (1) is a composite catalyst prepared by mixing methanesulfonic acid and an additive in a mass ratio of 1:0.01-0.5;

[0014] The additive is a mixture of one or more of sulfuric acid, phosphoric acid, polyphosphoric acid, phosphorus pentachloride, phosphorus oxychloride, phosphorus pentoxide, thionyl chloride, sulfur dioxide, sulfur trioxide, sulfonyl chloride, chlorosulfonic acid, methylsulfonic anhydride, and methylsulfonyl chloride;

[0015] Preferably, the preparation method of the composite catalyst specifically comprises the following steps:

[0016] S1. Pump methane sulfonic acid into the reactor, open the condenser, and add additives while stirring in the reactor;

[0017] S2. Pass heat transfer oil and control the temperature in the kettle at 80±5℃. Stir for 1~2h. The system will become a colorless and transparent solution and the catalytic system reaction is completed.

[0018] Compared with the existing acid catalytic system, the composite catalytic system has the following advantages: the catalytic system can be used in an infinite cycle; compared with other catalytic systems that cannot be used and can only be treated as waste liquid, the cost of treating the three wastes is reduced. Compared with other catalysts, the catalytic system can significantly reduce the reaction time because the catalyst is pre-mixed to form a mixed anhydride, which can react well with DIPPN at the beginning of the reaction.

[0019] The composite acid catalyst used in the present invention has strong acidity and can catalyze the reaction of DIPPN and dimethyl carbonate under relatively mild conditions, thereby reducing the severity of the reaction conditions and improving the safety of the operation. In addition, because the catalytic effect of the catalytic system is good, the reaction efficiency is improved and the reaction time is greatly shortened from the existing 36-42 hours to 14-20 hours.

[0020] Preferably, the alkylating agent in step (1) is one of dimethyl carbonate, dimethyl sulfate and methanol.

[0021] Preferably, the molar ratio of the 2-isopropyl-2,3-dimethylbutyronitrile to the alkylating agent added in step (1) is 1:1-5.

[0022] Preferably, the crystallization method in step (3) specifically comprises the following steps:

[0023] S1. The decolorized organic phase is concentrated under reduced pressure, cooled with chilled water at 5-10°C / h for crystallization, and kept at -10-0°C with stirring for 1-5h;

[0024] S2, adding a certain proportion of mixed solvent, cooling at 2-5°C / h for crystallization, keeping warm at -15-0°C and stirring for 1-3h to obtain N,2,3-trimethyl-2-isopropylbutyramide wet product;

[0025] S3. The finished product is obtained after vacuum drying.

[0026] Preferably, the mixed solvent is an organic solvent and an alcohol solvent mixed in a volume ratio of 1:0.1-0.5.

[0027] Preferably, the organic solvent is selected from one or a combination of petroleum ether, n-heptane, cyclohexane, and n-hexane;

[0028] The alcohol solvent is selected from one or a combination of methanol, ethanol and isopropanol.

[0029] Extraction: Add pure water and petroleum ether to the crude product obtained in step (3), stir thoroughly, and allow to stand for separation, wherein the aqueous phase is extracted twice more with petroleum ether;

[0030] Washing: Combine the organic phases and perform alkali washing and water washing in sequence, and then use activated carbon for decolorization;

[0031] Mixed solvent crystallization: The decolorized organic phase is concentrated under reduced pressure to 1 / 4 of the original volume, cooled with chilled water at 5-10℃ / h for crystallization, and kept at -10-0℃ with stirring for 1-5h;

[0032] Then add a mixed solvent with a volume of 1 / 10 of the pre-crystallization solution, cool at 2-5°C / h for crystallization, keep warm at -15-0°C and stir for 1-3h, a large amount of white solid precipitates, and obtains N,2,3-trimethyl-2-isopropylbutyramide wet product. Use a small amount of cold methanol to wash the crystals to remove the residual mother liquor and impurities;

[0033] The wet product of N,2,3-trimethyl-2-isopropylbutyramide is dried, and the dried crystals are sieved through 100 meshes to obtain the finished crystalline product of N,2,3-trimethyl-2-isopropylbutyramide, and the crystal morphology is a needle-shaped or cubic crystal structure.

[0034] The reaction process of DIPPN and dimethyl carbonate in preparing WS-23 under the above catalyst system conditions conforms to the Ritter type reaction in the human name reaction, that is, in the pre-preparation process of the reaction catalyst system, part of the methane sulfonic acid (additive equivalent) is first mixed with one or more of the above additives to pre-prepare a mixed anhydride catalyst system, and then dimethyl carbonate generates a carbon cation under the strong acidic conditions formed by the methane sulfonic acid containing the mixed anhydride, and the cyanide nucleophilically attacks the carbon cation to obtain a cyanonium ion, and further resonance distributes the positive charge on the carbon atom with a smaller electronegativity. After the reaction is quenched, the water molecule captures the carbon cation and tautomerizes to obtain a stable amide derivative. The specific reaction mechanism process is shown as follows (taking sulfonyl chloride as an example):

[0035]

[0036] Compared with the prior art, the present invention has the following beneficial effects:

[0037] 1. Optimize reaction conditions: The present invention adopts a composite catalyst system, which can carry out reactions under relatively mild conditions, avoiding the problem of the prior art that reactions need to be carried out at high or low temperatures, reducing the difficulty and risk of operation, greatly reducing the reaction time, improving the kettle efficiency, and reducing production costs.

[0038] 2. Simplified operation process: The reaction process of the present invention is simple, no special equipment is required, and the post-treatment process is relatively simple, which avoids the need to use strong acid or strong base catalysts in the prior art, high equipment requirements, and complex post-treatment processes, thereby reducing production costs.

[0039] 3. Improve the yield and product quality: The yield of the present invention is high, and the target product can be obtained through simple operation steps, avoiding the problem in the prior art that multiple repeated experiments are required to obtain the ideal product, thereby improving production efficiency and product quality.

[0040] 4. The present invention obtains a needle-shaped or cubic crystal structure through a crystallization process. The needle-shaped crystal has a smaller cross-sectional area, so the contact area at the crystal contact point is significantly reduced, reducing the interaction force between crystals, especially under wet conditions, thereby reducing the possibility of agglomeration.

[0041] 5. Rod-shaped crystals have a higher surface energy due to their larger surface area, which increases the tendency to agglomerate in a wet environment. The needle-shaped crystal structure with lower surface energy obtained by this technical solution helps to reduce the interaction between crystals and reduce the tendency to agglomerate.

[0042] 6. This technical solution simplifies the process flow and reduces the complexity of operation, helps to reduce production costs, and improves the reliability and repeatability of the process. By optimizing solvent selection and crystallization conditions, higher product purity and yield are achieved.

[0043] 7. Since the needle shape has a lower tendency to agglomerate and better fluidity, it exhibits higher stability during storage and transportation. It helps to reduce product quality problems and reduced application performance caused by agglomeration. The needle-shaped crystal morphology makes WS-23 exhibit better solubility, dispersibility and taste in applications such as food, medicine and cosmetics. BRIEF DESCRIPTION OF THE DRAWINGS

[0044] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0045] Figure 1 is the gas chromatogram of Example 1 of the present invention;

[0046] Figure 2 is the gas chromatogram of Example 5 of the present invention;

[0047] Figure 3 is the gas chromatogram of Example 6 of the present invention;

[0048] Figure 4 It is the gas chromatogram of comparative example 1 of the present invention;

[0049] Figure 5 This is a physical comparison diagram of Example 1 of the present invention and Comparative Example 1 in a humid environment;

[0050] Figure 6 The XRD diffraction patterns of Example 1 and Comparative Examples 1-4 are shown in FIG.

[0051] Figure 7 This is a 5x microscope image of Example 1;

[0052] Figure 8 is an electron microscope image of Example 1;

[0053] Fig. 9 This is a 5x microscope image of Comparative Example 1. DETAILED DESCRIPTION

[0054] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention. Example 1

[0055] Phosphorus pentoxide (45 g) was added to methanesulfonic acid (400 g), and the temperature was raised to completely dissolve the phosphorus pentoxide. Then 2-isopropyl-2,3-dimethylbutyronitrile (100 g) was added, and dimethyl carbonate (161.8 g) was slowly added dropwise during the heating process. After the addition was completed, the mixture was kept warm and stirred at 140°C for 15 h. After the reaction was complete, the system temperature was lowered to room temperature, and pure water (1200 mL) and petroleum ether (200 mL) were added, and the mixture was fully stirred and allowed to stand for separation. The aqueous phase was extracted twice with petroleum ether (200 mL), and the combined organic phases were washed with 5% NaOH solution and deionized water in turn, and then decolorized with activated carbon. The decolorized organic phase was concentrated under reduced pressure to 1 / 4 of the original volume, and the temperature was lowered at 5°C / h for crystallization by opening chilled water, and the mixture was kept warm and stirred at -15°C for 3 h to obtain a pre-crystallization solution.

[0056] Then, methanol with a volume of 1 / 10 of the pre-crystallization solution was added, and the temperature was lowered at 2°C / h for crystallization, and the temperature was kept at -15°C and stirred for 1h, and a large amount of white solid was precipitated to obtain N,2,3-trimethyl-2-isopropylbutyramide wet product. The crystals were washed with 1wt% cold methanol to remove the residual mother liquor and impurities;

[0057] The wet product of N,2,3-trimethyl-2-isopropylbutyramide was dried in a vacuum drying oven at 40°C for 12 hours, and the dried crystals were sieved through 100 mesh to obtain the crystalline product of N,2,3-trimethyl-2-isopropylbutyramide (WS-23), which has a needle-like morphology. The product purity measured by GC is 99.3%, and the yield is 95.1%. Example 2

[0058] Add polyphosphoric acid (45 g) to methanesulfonic acid (400 g), then add 2-isopropyl-2,3-dimethylbutyronitrile (100 g), slowly drop dimethyl carbonate (161.8 g) during the heating process, and keep stirring at 140°C for 15 hours. After the reaction is complete, the system temperature is lowered to room temperature, pure water (1200 mL) and petroleum ether (200 mL) are added, stirred thoroughly, and allowed to stand for separation; the aqueous phase is extracted twice with petroleum ether (200 mL), the combined organic phases are washed with 5% NaOH solution and deionized water in turn, and then decolorized with activated carbon, and the decolorized organic phase is concentrated under reduced pressure to 1 / 4 of the original volume, cooled at 5°C / h with chilled water for crystallization, and kept stirring at -15°C for 3 hours to obtain a pre-crystallization solution;

[0059] Then add 1 / 10 volume of ethanol of the pre-crystallization solution, cool at 2°C / h for crystallization, keep warm at -15°C and stir for 1h, a large amount of white solid precipitates to obtain N,2,3-trimethyl-2-isopropylbutyramide wet product, wash the crystals with 1wt% cold methanol to remove residual mother liquor and impurities;

[0060] The wet product of N,2,3-trimethyl-2-isopropylbutyramide was dried in a vacuum drying oven at 40°C for 12 hours, and the dried crystals were sieved through 100 mesh to obtain the crystalline product of N,2,3-trimethyl-2-isopropylbutyramide (WS-23), which has a needle-like crystal morphology. The product purity measured by GC is 99.1%, and the yield is 89.7%. Example 3

[0061] Phosphorus pentachloride (45 g) was added to methanesulfonic acid (400 g), and then 2-isopropyl-2,3-dimethylbutyronitrile (100 g) was added. Dimethyl carbonate (161.8 g) was slowly added dropwise during the heating process. After the addition was completed, the mixture was kept warm and stirred at 140°C for 15 hours. After the reaction was complete, the system temperature was lowered to room temperature, and pure water (1200 mL) and n-hexane (200 mL) were added. The mixture was fully stirred and allowed to stand for separation. The aqueous phase was extracted twice with n-hexane (200 mL), and the combined organic phases were washed with 5% NaOH solution and deionized water in turn, and then decolorized with activated carbon. The decolorized organic phase was concentrated under reduced pressure to 1 / 4 of the original volume, cooled and crystallized at 5°C / h with chilled water, and kept warm and stirred at -15°C for 3 hours to obtain a pre-crystallization solution.

[0062] Then, 1 / 10 of the volume of the pre-crystallization solution of methanol was added, and the temperature was lowered at 2°C / h for crystallization, and the temperature was kept at -15°C and stirred for 1h, and a large amount of white solid was precipitated to obtain a wet product of N,2,3-trimethyl-2-isopropylbutyramide. The crystals were washed with 1wt% cold methanol to remove the residual mother liquor and impurities;

[0063] The wet product of N,2,3-trimethyl-2-isopropylbutyramide was dried in a vacuum drying oven at 40°C for 12 hours, and the dried crystals were sieved through 100 mesh to obtain the crystalline product of N,2,3-trimethyl-2-isopropylbutyramide (WS-23), which has a needle-like morphology. The product purity measured by GC is 99.3%, and the yield is 91.1%. Example 4

[0064] Phosphorus oxychloride (45 g) was added to methanesulfonic acid (400 g), and then 2-isopropyl-2,3-dimethylbutyronitrile (100 g) was added. Dimethyl carbonate (161.8 g) was slowly added dropwise during the heating process. After the addition was completed, the mixture was kept warm and stirred at 140°C for 15 h. After the reaction was complete, the system temperature was lowered to room temperature, and pure water (1200 mL) and n-hexane (200 mL) were added. The mixture was fully stirred and allowed to stand for separation. The aqueous phase was extracted twice with n-hexane (200 mL), and the combined organic phases were washed with 5% NaOH solution and deionized water in turn, and then decolorized with activated carbon. The decolorized organic phase was concentrated under reduced pressure to 1 / 4 of the original volume, cooled and crystallized at 5°C / h with chilled water, and kept warm and stirred at -15°C for 3 h to obtain a pre-crystallization solution.

[0065] A mixed solvent of ethanol with a volume of 1 / 10 of the pre-crystallization solution was added, and the temperature was lowered at 2°C / h for crystallization, and the mixture was kept at -15°C and stirred for 1h. A large amount of white solid was precipitated to obtain a wet product of N,2,3-trimethyl-2-isopropylbutyramide. The crystals were washed with 1wt% cold methanol to remove the residual mother liquor and impurities.

[0066] The wet product of N,2,3-trimethyl-2-isopropylbutyramide was dried in a vacuum drying oven at 40°C for 12 hours, and the dried crystals were sieved through 100 mesh to obtain the crystalline product of N,2,3-trimethyl-2-isopropylbutyramide (WS-23), which has a needle-like crystal morphology. The product purity measured by GC is 99.2%, and the yield is 90.5%. Example 5

[0067] Phosphorus pentoxide (20 g) was added to methanesulfonic acid (400 g), and the temperature was raised to completely dissolve the phosphorus pentoxide. Then 2-isopropyl-2,3-dimethylbutyronitrile (100 g) was added, and dimethyl carbonate (161.8 g) was slowly added dropwise during the heating process. After the addition was completed, the mixture was kept warm and stirred at 140°C for 15 h. After the reaction was complete, the system temperature was lowered to room temperature, and pure water (1200 mL) and cyclohexane (200 mL) were added, and the mixture was fully stirred and allowed to stand for separation. The aqueous phase was extracted twice with n-cyclohexane (200 mL), and the combined organic phases were washed with 5% NaOH solution and deionized water in turn, and then decolorized with activated carbon. The decolorized organic phase was concentrated under reduced pressure to 1 / 4 of the original volume, and the temperature was lowered at 5°C / h for crystallization by opening chilled water, and the mixture was kept warm and stirred at -15°C for 3 h to obtain a pre-crystallization solution.

[0068] Then, 1 / 10 of the volume of the pre-crystallization solution of methanol was added, and the temperature was lowered at 2°C / h for crystallization, and the temperature was kept at -15°C and stirred for 1h, and a large amount of white solid was precipitated to obtain a wet product of N,2,3-trimethyl-2-isopropylbutyramide. The crystals were washed with 1wt% cold methanol to remove the residual mother liquor and impurities;

[0069] The wet product of N,2,3-trimethyl-2-isopropylbutyramide was dried in a vacuum drying oven at 40°C for 12 hours, and the dried crystals were sieved through 100 mesh to obtain the crystalline product of N,2,3-trimethyl-2-isopropylbutyramide (WS-23), which has a needle-like morphology. The product purity measured by GC is 99.2%, and the yield is 85.1%. Example 6

[0070] Phosphorus pentoxide (45 g) and thionyl chloride (94 g) were added to methanesulfonic acid (400 g), and the temperature was raised to completely dissolve the phosphorus pentoxide. Then 2-isopropyl-2,3-dimethylbutyronitrile (100 g) was added, and dimethyl carbonate (161.8 g) was slowly added dropwise during the heating process. After the addition was completed, the system temperature was kept warm and stirred at 140°C for 15 hours. After the reaction was complete, the system temperature was lowered to room temperature, and pure water (1200 mL) and n-heptane (200 mL) were added, and the mixture was fully stirred and allowed to stand for separation. The aqueous phase was extracted twice with n-heptane (200 mL), and the combined organic phases were washed with 5% NaOH solution and deionized water in turn, and then decolorized with activated carbon. The decolorized organic phase was concentrated under reduced pressure to 1 / 4 of the original volume, and the temperature was lowered at 5°C / h for crystallization in chilled water, and the temperature was kept and stirred at -15°C for 3 hours to obtain a pre-crystallization solution.

[0071] Then, 1 / 10 of the volume of the pre-crystallization solution of methanol was added, and the temperature was lowered at 2°C / h for crystallization, and the temperature was kept at -15°C and stirred for 1h, and a large amount of white solid was precipitated to obtain a wet product of N,2,3-trimethyl-2-isopropylbutyramide. The crystals were washed with 1wt% cold methanol to remove the residual mother liquor and impurities;

[0072] The wet product of N,2,3-trimethyl-2-isopropylbutyramide was dried in a vacuum drying oven at 40°C for 12 hours, and the dried crystals were sieved through 100 mesh to obtain the crystalline product of N,2,3-trimethyl-2-isopropylbutyramide (WS-23), which has a needle-like morphology. The product purity measured by GC is 99.3%, and the yield is 93.1%. Example 7

[0073] Phosphorus pentoxide (45 g) and sulfur dioxide (94 g) were added to methanesulfonic acid (400 g), and the temperature was raised to completely dissolve the phosphorus pentoxide. Then 2-isopropyl-2,3-dimethylbutyronitrile (100 g) was added, and dimethyl carbonate (161.8 g) was slowly added dropwise during the heating process. After the addition was completed, the system temperature was kept warm and stirred at not less than 140°C for at least 10 hours. After the reaction was complete, the system temperature was lowered to room temperature, and pure water (1200 mL) and n-heptane (200 mL) were added, and the mixture was fully stirred and allowed to stand for separation. The aqueous phase was extracted twice with n-heptane (200 mL), and the combined organic phases were washed with 5% NaOH solution and deionized water in turn, and then decolorized with activated carbon. The decolorized organic phase was concentrated under reduced pressure to 1 / 4 of the original volume, and the temperature was lowered at 5°C / h for crystallization by opening chilled water, and the mixture was kept warm and stirred at -15°C for 3 hours to obtain a pre-crystallization solution.

[0074] Then add isopropanol (1 / 10 of the volume of the pre-crystallization solution), cool at 2°C / h for crystallization, keep warm at -15°C and stir for 1h, a large amount of white solid precipitates to obtain N,2,3-trimethyl-2-isopropylbutyramide wet product, wash the crystals with 1wt% cold methanol to remove residual mother liquor and impurities;

[0075] The wet product of N,2,3-trimethyl-2-isopropylbutyramide was dried in a vacuum drying oven at 40°C for 12 hours, and the dried crystals were sieved through 100 mesh to obtain the crystalline product of N,2,3-trimethyl-2-isopropylbutyramide (WS-23), which has a needle-like morphology. The product purity measured by GC is 99.4%, and the yield is 85.4%. Example 8

[0076] Phosphorus pentoxide (45 g) and methanesulfonic anhydride (94 g) were added to methanesulfonic acid (400 g), and the temperature was raised to completely dissolve the phosphorus pentoxide. Then 2-isopropyl-2,3-dimethylbutyronitrile (100 g) was added, and dimethyl carbonate (161.8 g) was slowly added dropwise during the heating process. After the addition was completed, the system temperature was kept warm and stirred at not less than 140°C for at least 10 hours. After the reaction was complete, the system temperature was lowered to room temperature, and pure water (1200 mL) and n-heptane (200 mL) were added, and the mixture was fully stirred and allowed to stand for separation. The aqueous phase was extracted twice with n-heptane (200 mL), and the combined organic phases were washed with 5% NaOH solution and deionized water in turn, and then decolorized with activated carbon. The decolorized organic phase was concentrated under reduced pressure to 1 / 4 of the original volume, and the temperature was lowered at 5°C / h for crystallization in chilled water, and the temperature was kept warm and stirred at -15°C for 3 hours to obtain a pre-crystallization solution.

[0077] Then add isopropanol (1 / 10 of the volume of the pre-crystallization solution), cool at 2°C / h for crystallization, keep warm at -15°C and stir for 1h, a large amount of white solid precipitates to obtain N,2,3-trimethyl-2-isopropylbutyramide wet product, wash the crystals with 1wt% cold methanol to remove residual mother liquor and impurities;

[0078] The wet product of N,2,3-trimethyl-2-isopropylbutyramide was dried in a vacuum drying oven at 40°C for 12 hours, and the dried crystals were sieved through 100 mesh to obtain the crystalline product of N,2,3-trimethyl-2-isopropylbutyramide (WS-23), which had a needle-like morphology. The product purity was 99.0% as measured by GC, and the yield was 81.1%. Example 9

[0079] Phosphorus pentoxide (45 g) and methylsulfonyl chloride (94 g) were added to methanesulfonic acid (400 g), and the temperature was raised to completely dissolve the phosphorus pentoxide. Then 2-isopropyl-2,3-dimethylbutyronitrile (100 g) was added, and dimethyl carbonate (161.8 g) was slowly added dropwise during the heating process. After the addition was completed, the system temperature was kept warm and stirred at not less than 140°C for at least 10 hours. After the reaction was complete, the system temperature was lowered to room temperature, and pure water (1200 mL) and n-heptane (200 mL) were added, and the mixture was fully stirred and allowed to stand for separation. The aqueous phase was extracted twice with n-heptane (200 mL), and the combined organic phases were washed with 5% NaOH solution and deionized water in turn, and then decolorized with activated carbon. The decolorized organic phase was concentrated under reduced pressure to 1 / 4 of the original volume, and the temperature was lowered at 5°C / h for crystallization in chilled water, and the mixture was kept warm and stirred at -15°C for 3 hours to obtain a pre-crystallization solution.

[0080] Then add isopropanol (1 / 10 of the volume of the pre-crystallization solution), cool at 2°C / h for crystallization, keep warm at -15°C and stir for 1h, a large amount of white solid precipitates to obtain N,2,3-trimethyl-2-isopropylbutyramide wet product, wash the crystals with 1wt% cold methanol to remove residual mother liquor and impurities;

[0081] The wet product of N,2,3-trimethyl-2-isopropylbutyramide was dried in a vacuum drying oven at 40°C for 12 hours, and the dried crystals were sieved through 100 mesh to obtain the crystalline product of N,2,3-trimethyl-2-isopropylbutyramide (WS-23), which has a needle-like crystal morphology. The product purity measured by GC was 99.1%, and the yield was 87.4%.

[0082] Comparative Example 1

[0083] This comparative example uses commercially available N,2,3-trimethyl-2-isopropylbutyramide (98%, Cas No. 51115-67-4, MDL No. MFCD00130070), and the purity of the product measured by GC is 98.3%.

[0084] Comparative Example 2

[0085] The difference between this comparative example and Example 1 is that no alcohol solvent is added, and the remaining steps are the same as Example 1. The purity of the product measured by GC is 99.3%, and the yield is 71.7%.

[0086] Comparative Example 3

[0087] The difference between this comparative example and Example 1 is that the second cooling and crystallization is not performed, and the remaining steps are the same as those in Example 1. The purity of the product measured by GC is 53.1%, and the yield is 42.5%.

[0088] Comparative Example 4

[0089] The difference between this comparative example and Example 1 is that no mixed solvent is added, and the remaining steps are the same as those in Example 1. The purity of the product measured by GC is 99.1%, and the yield is 72.8%.

[0090] Comparative Example 5

[0091] The difference between this comparative example and Example 2 is that the second cooling and crystallization is not performed, and the remaining steps are the same as those in Example 2. The purity of the product measured by GC is 55.4%, and the yield is 67.2%.

[0092] Compared with Comparative Example 1 (commercially available product), the product purity of Examples 1-9 is higher and the yield is also quite high, indicating that the N,2,3-trimethyl-2-isopropylbutyramide prepared by the synthesis method of the present invention has advantages in purity and yield. Comparative Examples 2 and 4 did not add alcohol solvents, resulting in a decrease in product purity and a lower yield than the corresponding examples, indicating that alcohol solvents help to improve the purity and yield of the product during the crystallization process. Comparative Examples 3 and 5 did not perform a second cooling crystallization, resulting in a significant decrease in product purity and a significant decrease in yield.

[0093] Figure 5 After being placed in a humid environment (relative humidity of 60% and room temperature) for 12 hours, the sample of Example 1 remained dispersed without agglomeration, while the commercially available WS-23 product of Comparative Example 1 showed obvious agglomeration. This indicates that the WS-23 crystals prepared in Example 1 have better moisture resistance and can maintain better dispersibility and stability in a humid environment.

[0094] Figure 1-4 is the gas chromatogram, Figure 6 It is an XRD diffraction diagram, which illustrates the difference in crystal structure between Example 1 and the comparative example.

[0095] Figure 7 and Fig. 9In the embodiment 1 and the comparative example 1, the crystal morphology is different. The crystal of the embodiment 1 shows a clear needle-like or cubic crystal structure, and the length is much larger than the diameter. This morphology is conducive to reducing the contact area and interaction between adjacent particles, thereby obtaining a smaller nano-sized crystal. In contrast, the crystal of the comparative example 1 shows a short rod or long rod crystal structure, and the agglomeration phenomenon is more serious.

[0096] Figure 8 This is an electron microscope image of Example 1, and it can also be seen that the product prepared in Example 1 has an obvious needle-like structure.

[0097] Compared with Comparative Example 1 (commercially available WS-23 product), the needle-shaped or cubic crystal product of Example 1 (self-made) has lower mass and smaller packing density than powder crystals or rod-shaped crystals at the same volume, which gives WS-23 a higher specific surface area, that is, a relatively large surface area to volume ratio, reduces the contact area and interaction between adjacent particles, and obtains smaller nano-sized crystals. Figure 7 The crystals in the WS-23 have a high specific surface area, that is, a relatively large surface area to volume ratio, which means that more active sites are exposed on the surface, which can effectively increase the contact rate of the cooling agent in the process of compounding with spices, thereby improving the compounding efficiency and the cooling sensation. The needle-shaped crystal structure also facilitates the transmission of electrons, protons and ions inside the crystal, making the cooling sensation of WS-23 more powerful in the mouth.

[0098] In summary, the WS-23 crystals prepared in Examples 1-9 have better moisture resistance, higher specific surface area, and better cooling burst impact, and have broad application prospects.

[0099] The above description is only a preferred specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can make equivalent replacements or changes according to the technical scheme and inventive concept of the present invention within the technical scope disclosed by the present invention, which should be covered by the protection scope of the present invention.

Claims

1. A green and environmentally friendly catalytic synthesis method of N,2,3-trimethyl-2-isopropylbutyramide, characterized in that: The steps include: (1) Add the catalyst and 2-isopropyl-2,3-dimethylbutyronitrile into the reactor and stir thoroughly. Then, add the alkylating agent dropwise at 105-130°C. (2) After the dropwise addition is completed, the temperature is raised to the reaction temperature, and the mixture is stirred at the temperature to obtain a crude product of N,2,3-trimethyl-2-isopropylbutyramide; (3) The obtained crude product is subjected to extraction, washing, and mixed solvent crystallization to obtain pure N,2,3-trimethyl-2-isopropylbutyramide; The catalyst in step (1) is a composite catalyst prepared by mixing methanesulfonic acid and an additive in a mass ratio of 1:0.05-0.35; The additive is a mixture of one or more of polyphosphoric acid, phosphorus pentachloride, phosphorus oxychloride, phosphorus pentoxide, thionyl chloride, sulfur dioxide, sulfonyl chloride, methylsulfonic anhydride, and methylsulfonyl chloride; The mixed solvent is an organic solvent and an alcohol solvent mixed in a volume ratio of 1:0.1-0.5; The organic solvent is selected from petroleum ether; The alcohol solvent is selected from one or a combination of methanol, ethanol and isopropanol; Extraction: Add pure water and petroleum ether to the crude product obtained in step (3), stir thoroughly, and allow to stand for separation, wherein the aqueous phase is extracted twice more with petroleum ether; Washing: Combine the organic phases and perform alkali washing and water washing in sequence, and then use activated carbon for decolorization; Mixed solvent crystallization: The decolorized organic phase is concentrated under reduced pressure to 1 / 4 of the original volume, cooled with chilled water at 5-10℃ / h for crystallization, and kept at -10-0℃ with stirring for 1-5h; Then add a mixed solvent with a volume of 1 / 10 of the pre-crystallization solution, cool at 2-5°C / h for crystallization, keep warm at -15-0°C and stir for 1-3h, a large amount of white solid precipitates, and obtains N,2,3-trimethyl-2-isopropylbutyramide wet product. Use a small amount of cold methanol to wash the crystals to remove the residual mother liquor and impurities; The wet product of N,2,3-trimethyl-2-isopropylbutyramide is dried, and the dried crystals are sieved through 100 meshes to obtain the finished crystalline product of N,2,3-trimethyl-2-isopropylbutyramide, and the crystal morphology is a needle-shaped or cubic crystal structure.

2. A green and environmentally friendly catalytic synthesis method of N,2,3-trimethyl-2-isopropylbutyramide according to claim 1, characterized in that: The specific preparation method of the composite catalyst specifically comprises the following steps: S1. Pump methane sulfonic acid into the reactor, open the condenser, and add additives while stirring in the reactor; S2. Pass heat transfer oil and control the temperature in the kettle at 80±5℃. Stir for 1~2h. The system will become a colorless and transparent solution and the catalytic system reaction is completed.

3. A green and environmentally friendly catalytic synthesis method of N,2,3-trimethyl-2-isopropylbutyramide according to claim 1, characterized in that: The alkylating agent in step (1) is selected from dimethyl carbonate, dimethyl sulfate and methanol.

4. A green and environmentally friendly catalytic synthesis method of N,2,3-trimethyl-2-isopropylbutyramide according to claim 1, characterized in that: The molar ratio of the amount of 2-isopropyl-2,3-dimethylbutyronitrile to the amount of the alkylating agent added in step (1) is 1:1-5.

5. A green and environmentally friendly catalytic synthesis method of N,2,3-trimethyl-2-isopropylbutanamide according to claim 1, characterized in that: The reaction temperature in step (2) is 140-180°C.

6. A green and environmentally friendly catalytic synthesis method of N,2,3-trimethyl-2-isopropylbutyramide according to claim 1, characterized in that: In step (2), the mixture is stirred at the temperature for not less than 10 hours.

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