A process for the preparation of N,2,3-trimethyl-2-isopropylbutanamide cooling agent

Abstract

This invention discloses a method for preparing N,2,3-trimethyl-2-isopropylbutyramide cooling agent. 2,2-Isopropylpropionitrile is synthesized from propionitrile and 2-bromopropane. The nitrile group is converted to an ester group via esterification catalyst, and then the ester group is amidated using an amination catalyst to obtain the final product. Impurities are removed with a purifying agent, and finally, high-purity product is obtained by recrystallization.

Description

Technical Field

[0001] This invention relates to the field of chemical synthesis technology, and more specifically to a method for preparing an N,2,3-trimethyl-2-isopropylbutyramide cooling agent. Background Technology

[0002] N,2,3-trimethyl-2-isopropylbutyramide is a high-quality cooling agent with high cooling activity and no side effects such as burning, numbness, or irritation. It is widely used as a cooling agent in confectionery, oral care, and pharmaceuticals.

[0003] There are many synthetic methods available today. A common one is to use propionitrile as a raw material and 1,2-dimethoxyethane (DME) as a solvent to react with bromoisopropane in the presence of sodium amide to synthesize DIPPN with a yield of 61.5%. Then, DIPPN is reacted with dimethyl carbonate (DMC) via a Ritter reaction under the catalysis of polyphosphoric acid (PPA) to synthesize WS-23 with a yield of 79.7%.

[0004] Another method involves using N-methylpropionamide and bromoisopropane as raw materials and organolithium as a catalyst to synthesize WS-23 in a tetrahydrofuran solution system in one step. This method avoids high pollution, complex procedures, and achieves high purity, but the yield is still not ideal and needs further improvement.

[0005] There is also a method that uses propionitrile and bromoisopropane as raw materials, 2,2-isopropylpropionitrile as an intermediate, and reacts with methanol in one step under the conditions of concentrated sulfuric acid or chlorosulfonic acid as a catalyst to obtain the product. The raw materials are simple and the process is not complicated, but the product contains many impurities and the generated polluting byproducts are more serious.

[0006] Solving these environmental, high-purity, and high-conversion problems is precisely the focus of this invention. Summary of the Invention

[0007] The technical problem to be solved by the present invention is to provide a method for preparing N,2,3-trimethyl-2-isopropylbutyramide cooling agent with low waste, low impurities and high conversion rate.

[0008] 1. To solve the above-mentioned technical problems, the technical solution provided by the present invention includes the following steps:

[0009] (1) Prepare 30 molar parts of sodium amino acid and 7.3 molar parts of liquid ammonia and place them in a container, then cool them to -60℃~40℃;

[0010] (2) Add a mixture of 10 parts propionitrile and 30 parts 2-bromopropane to the container and react at a constant temperature for 30 h;

[0011] (3) After the reaction is complete, allow it to heat up naturally until the liquid ammonia has completely evaporated. Add 10 parts of water to quench the reaction, then add 50 parts of water and mix thoroughly. Add 50 parts of ether to extract the aqueous phase and retain the organic phase.

[0012] (4) The organic phase was washed once with water and once with saturated NaCl solution, then dried with anhydrous sodium sulfate and filtered. The filtrate was collected and dried using an evaporator to obtain a pale yellow liquid precursor.

[0013] (5) Take 12-20 parts by molar weight of pale yellow liquid precursor, 60 parts of methanol, and 36-60 parts of esterification catalyst;

[0014] (6) Add the pale yellow liquid precursor, methanol and esterification catalyst to a high-pressure reactor, heat under reflux for 6 hours with stirring, and distill to recover excess methanol to obtain reactant A;

[0015] (7) After cooling reactant A, it was washed twice with sodium bicarbonate, extracted with saturated sodium chloride solution, and after standing, separation and drying, 2,3-dimethyl-2-isopropylbutyrate was obtained.

[0016] (8) Take 12-40 parts of 2,3-dimethyl-2-isopropylbutyrate, 60 parts of monomethylamine, 60 parts of methanol, and 10-20 parts of amination catalyst in molar amounts;

[0017] (9) Add 2,3-dimethyl-2-isopropylbutyrate, monomethylamine, methanol and amination catalyst to a high-pressure reactor and reflux for 8 hours under stirring.

[0018] (10) Distillation was used to recover excess methylamine and methanol to obtain crude product;

[0019] (11) Dissolve the crude product in diethyl ether, add 20-40 molar amounts of purification agent, stir well, filter, remove impurities and decolorize, and obtain a colorless, transparent, and clear solution;

[0020] (12) Add sodium hydroxide to the solution to adjust the pH to neutral, then wash once with water and once with saturated NaCl solution, and separate the organic phase.

[0021] (13) Provide a low temperature environment for the organic phase to recrystallize at around 0°C. After crystallization, filter and dry to obtain white needle-like crystals, which is the cooling agent product.

[0022] 2. Furthermore, the chemical composition of the esterification catalyst is trimethylsinium tetrafluoroboric acid;

[0023] 3. Further, the chemical composition of the amination catalyst is 1-butyl-3-methylimidazolium sulfate;

[0024] 4. Furthermore, the method for preparing the purifying agent is as follows:

[0025] (1) Take 100 parts of potassium sodium titanate and 100 parts of aluminum lactate;

[0026] (2) Crush the two solids into powder separately;

[0027] (3) The powdered raw material was ball-milled using 150 parts of ethanol as a carrier;

[0028] (4) Dry at room temperature to remove ethanol, then sieve through an 80-mesh sieve to obtain the purified powder;

[0029] The beneficial effects of this invention are as follows:

[0030] 1) The esterification catalyst used is trimethylsinium tetrafluoroboric acid. Fluorine and boron have excellent electron pair attraction ability and can accept electrons to form equilibrium centers. This property can attract electron pairs during the esterification reaction to promote the carboxyl group to detach from hydrogen and oxygen atoms to form ester groups, thereby promoting the reaction process and improving conversion efficiency.

[0031] 2) The trimethylsinium tetrafluoroboric acid cation formed in the solution system has extremely high acidity, which can provide hydrogen ions to promote the hydrolysis of nitrile groups to form carboxyl groups, and provide protonation reactions for alcohols and carboxyl groups to promote the formation of ester groups, thus efficiently improving the reaction conversion rate;

[0032] 3) Trimethylsinium tetrafluoroboric acid can form a protonated intermediate in the solution system, which can activate the nucleophilicity of hydroxyl groups, thereby promoting the reaction rate of esterification reaction, increasing the activity of alcohol raw materials and improving the conversion rate.

[0033] 4) The amination catalyst 1-butyl-3-methylimidazolium hydrosulfate used can form cations and anions in the system. The interaction between the cations and anions is relatively weak, and the charge separation is high. It provides an excellent environment for electron transfer in the system, promotes the activity of active groups in the raw materials, and promotes the reaction efficiency.

[0034] 5) The cations of 1-butyl-3-methylimidazolium hydrosulfate are connected by ether bridges, thus forming a cationic dimer conformation structure that is very stable. This structure has built-in voids that can restrict the size, shape, and charge of the molecules, control the selectivity of the reaction, and improve the conversion rate of the raw materials.

[0035] 6) Sodium and potassium titanate provide titanate and sodium and potassium ions in the system, which can combine with 1-butyl-3-methylimidazolium ions and tetrafluoroborate ions in the catalyst added in the previous step to form precipitates that are separated in the system, thus separating them from the organic system and removing the two ionic liquid catalysts.

[0036] 7) Aluminum lactate has a porous molecular structure and strong adsorption capacity. It can adsorb suspended particulate matter and colored impurities, which facilitates subsequent filtration and separation, making the liquid system transparent and clear.

[0037] 8) Aluminum lactate can complex with ionic liquids to form colloidal precipitates that stably adsorb particulate matter and increase the removal efficiency of esterification and amination catalysts in purification agents. Detailed Implementation

[0038] The present invention will be further described in detail below with reference to the embodiments.

[0039] Unless otherwise specified, the raw materials or chemical reagents used in the embodiments of this invention are obtained through conventional commercial channels.

[0040] Example 1

[0041] 1. Prepare the purification agent as follows:

[0042] (1) Take 100 parts of potassium sodium titanate and 100 parts of aluminum lactate;

[0043] (2) Crush the two solids into powder separately;

[0044] (3) The powdered raw material was ball-milled using 150 parts of ethanol as a carrier;

[0045] (4) Dry at room temperature to remove ethanol, then sieve through an 80-mesh sieve to obtain the purified powder;

[0046] 2. Prepare 30 molar amounts of sodium amide and 7.3 molar amounts of liquid ammonia in a container and cool to -50℃;

[0047] 3. Add a mixture of 10 parts propionitrile and 30 parts 2-bromopropane to the container and react at a constant temperature for 30 hours;

[0048] 4. After the reaction is complete, allow it to heat up naturally until the liquid ammonia has completely evaporated. Add 10 parts of water to quench the reaction, then add 50 parts of water and mix thoroughly. Add 50 parts of ether to extract the aqueous phase and retain the organic phase.

[0049] 5. The organic phase was washed once with water and once with saturated NaCl solution, then dried with anhydrous sodium sulfate and filtered. The filtrate was collected and dried using an evaporator to obtain a pale yellow liquid precursor.

[0050] 6. Take 16 parts by molar weight of the pale yellow liquid precursor, 60 parts of methanol, and 48 parts of trimethylstilbene tetrafluoroboric acid;

[0051] 7. Add the pale yellow liquid precursor, methanol, and trimethylsinium tetrafluoroboric acid to a high-pressure reactor, heat under reflux for 6 hours with stirring, and distill to recover excess methanol to obtain reactant A;

[0052] 8. After cooling reactant A, it was washed twice with sodium bicarbonate, extracted with saturated sodium chloride solution, and after standing, separation and drying, 2,3-dimethyl-2-isopropylbutyrate was obtained.

[0053] 9. Take 26 parts by molar amount of 2,3-dimethyl-2-isopropylbutyrate, 60 parts of monomethylamine, 60 parts of methanol, and 15 parts of 1-butyl-3-methylimidazolium sulfate;

[0054] 10. Add 2,3-dimethyl-2-isopropylbutyrate, monomethylamine, methanol, and 1-butyl-3-methylimidazolium sulfate to a high-pressure reactor and reflux for 8 hours under stirring.

[0055] 11. Excess methylamine and methanol are recovered by distillation to obtain the crude product;

[0056] 12. Dissolve the crude product in diethyl ether, add 30 parts by molar amount of purification agent, stir well, filter, remove impurities and decolorize, and obtain a colorless, transparent and clear solution;

[0057] 13. Add sodium hydroxide to the solution to adjust the pH to neutral, then wash once with water and once with saturated NaCl solution, and separate the organic phase.

[0058] 14. Provide a low-temperature environment for the organic phase to recrystallize at around 0°C. After crystallization, filter and dry to obtain white needle-like crystals, which is the cooling agent product.

[0059] Example 2

[0060] 1. Prepare the purification agent as follows:

[0061] (1) Take 100 parts of potassium sodium titanate and 100 parts of aluminum lactate;

[0062] (2) Crush the two solids into powder separately;

[0063] (3) The powdered raw material was ball-milled using 150 parts of ethanol as a carrier;

[0064] (4) Dry at room temperature to remove ethanol, then sieve through an 80-mesh sieve to obtain the purified powder;

[0065] 2. Prepare 30 molar amounts of sodium amide and 7.3 molar amounts of liquid ammonia in a container and cool to -50℃;

[0066] 3. Add a mixture of 10 parts propionitrile and 30 parts 2-bromopropane to the container and react at a constant temperature for 30 hours;

[0067] 4. After the reaction is complete, allow it to heat up naturally until the liquid ammonia has completely evaporated. Add 10 parts of water to quench the reaction, then add 50 parts of water and mix thoroughly. Add 50 parts of ether to extract the aqueous phase and retain the organic phase.

[0068] 5. The organic phase was washed once with water and once with saturated NaCl solution, then dried with anhydrous sodium sulfate and filtered. The filtrate was collected and dried using an evaporator to obtain a pale yellow liquid precursor.

[0069] 6. Take 12 parts by molar amount of the pale yellow liquid precursor, 60 parts by molar amount of methanol, and 36 parts by molar amount of trimethylstilbene tetrafluoroboric acid;

[0070] 7. Add the pale yellow liquid precursor, methanol, and trimethylsinium tetrafluoroboric acid to a high-pressure reactor, heat under reflux for 6 hours with stirring, and distill to recover excess methanol to obtain reactant A;

[0071] 8. After cooling reactant A, it was washed twice with sodium bicarbonate, extracted with saturated sodium chloride solution, and after standing, separation and drying, 2,3-dimethyl-2-isopropylbutyrate was obtained.

[0072] 9. Take 40 parts by molar amount of 2,3-dimethyl-2-isopropylbutyrate, 60 parts of monomethylamine, 60 parts of methanol, and 20 parts of 1-butyl-3-methylimidazolium sulfate;

[0073] 10. Add 2,3-dimethyl-2-isopropylbutyrate, monomethylamine, methanol, and 1-butyl-3-methylimidazolium sulfate to a high-pressure reactor and reflux for 8 hours under stirring.

[0074] 11. Excess methylamine and methanol are recovered by distillation to obtain the crude product;

[0075] 12. Dissolve the crude product in diethyl ether, add 40 parts by molar amount of purification agent, stir well, filter, remove impurities and decolorize, and obtain a colorless, transparent and clear solution;

[0076] 13. Add sodium hydroxide to the solution to adjust the pH to neutral, then wash once with water and once with saturated NaCl solution, and separate the organic phase.

[0077] 14. Provide a low-temperature environment for the organic phase to recrystallize at around 0°C. After crystallization, filter and dry to obtain white needle-like crystals, which is the cooling agent product.

[0078] Example 3

[0079] 1. Prepare the purification agent as follows:

[0080] (1) Take 100 parts of potassium sodium titanate and 100 parts of aluminum lactate;

[0081] (2) Crush the two solids into powder separately;

[0082] (3) The powdered raw material was ball-milled using 150 parts of ethanol as a carrier;

[0083] (4) Dry at room temperature to remove ethanol, then sieve through an 80-mesh sieve to obtain the purified powder;

[0084] 2. Prepare 30 molar amounts of sodium amide and 7.3 molar amounts of liquid ammonia in a container and cool to -50℃;

[0085] 3. Add a mixture of 10 parts propionitrile and 30 parts 2-bromopropane to the container and react at a constant temperature for 30 hours;

[0086] 4. After the reaction is complete, allow it to heat up naturally until the liquid ammonia has completely evaporated. Add 10 parts of water to quench the reaction, then add 50 parts of water and mix thoroughly. Add 50 parts of ether to extract the aqueous phase and retain the organic phase.

[0087] 5. The organic phase was washed once with water and once with saturated NaCl solution, then dried with anhydrous sodium sulfate and filtered. The filtrate was collected and dried using an evaporator to obtain a pale yellow liquid precursor.

[0088] 6. Take 20 parts by molar weight of the pale yellow liquid precursor, 60 parts of methanol, and 60 parts of trimethylstilbene tetrafluoroboric acid;

[0089] 7. Add the pale yellow liquid precursor, methanol, and trimethylsinium tetrafluoroboric acid to a high-pressure reactor, heat under reflux for 6 hours with stirring, and distill to recover excess methanol to obtain reactant A;

[0090] 8. After cooling reactant A, it was washed twice with sodium bicarbonate, extracted with saturated sodium chloride solution, and after standing, separation and drying, 2,3-dimethyl-2-isopropylbutyrate was obtained.

[0091] 9. Take 12 parts by molar amount of 2,3-dimethyl-2-isopropylbutyrate, 60 parts of monomethylamine, 60 parts of methanol, and 10 parts of 1-butyl-3-methylimidazolium sulfate;

[0092] 10. Add 2,3-dimethyl-2-isopropylbutyrate, monomethylamine, methanol, and 1-butyl-3-methylimidazolium sulfate to a high-pressure reactor and reflux for 8 hours under stirring.

[0093] 11. Excess methylamine and methanol are recovered by distillation to obtain the crude product;

[0094] 12. Dissolve the crude product in diethyl ether, add 20 parts by molar amount of purification agent, stir well, filter, remove impurities and decolorize, and obtain a colorless, transparent and clear solution;

[0095] 13. Add sodium hydroxide to the solution to adjust the pH to neutral, then wash once with water and once with saturated NaCl solution, and separate the organic phase.

[0096] 14. Provide a low-temperature environment for the organic phase to recrystallize at around 0°C. After crystallization, filter and dry to obtain white needle-like crystals, which is the cooling agent product.

[0097] Comparative Example 1

[0098] The difference between this comparative example and Example 1 is that the trimethylsuccinic acid in steps 6 and 7 is boron trichloride, and the rest of the implementation is the same as in Example 1.

[0099] Comparative Example 2

[0100] 1. Prepare the purification agent as follows:

[0101] (1) Take 100 parts of potassium sodium titanate and 100 parts of aluminum lactate;

[0102] (2) Crush the two solids into powder separately;

[0103] (3) The powdered raw material was ball-milled using 150 parts of ethanol as a carrier;

[0104] (4) Dry at room temperature to remove ethanol, then sieve through an 80-mesh sieve to obtain the purified powder;

[0105] 2. Prepare 30 molar amounts of sodium amide and 7.3 molar amounts of liquid ammonia in a container and cool to -50℃;

[0106] 3. Add a mixture of 10 parts propionitrile and 30 parts 2-bromopropane to the container and react at a constant temperature for 30 hours;

[0107] 4. After the reaction is complete, allow it to heat up naturally until the liquid ammonia has completely evaporated. Add 10 parts of water to quench the reaction, then add 50 parts of water and mix thoroughly. Add 50 parts of ether to extract the aqueous phase and retain the organic phase.

[0108] 5. The organic phase was washed once with water and once with saturated NaCl solution, then dried with anhydrous sodium sulfate and filtered. The filtrate was collected and dried using an evaporator to obtain a pale yellow liquid precursor.

[0109] 6. Take 16 parts by molar amount of the pale yellow liquid precursor, 60 parts by molar amount of methanol, and 20 parts by molar amount of trimethylstilbene tetrafluoroboric acid;

[0110] 7. Add the pale yellow liquid precursor, methanol, and trimethylsinium tetrafluoroboric acid to a high-pressure reactor, heat under reflux for 6 hours with stirring, and distill to recover excess methanol to obtain reactant A;

[0111] 8. After cooling reactant A, it was washed twice with sodium bicarbonate, extracted with saturated sodium chloride solution, and after standing, separation and drying, 2,3-dimethyl-2-isopropylbutyrate was obtained.

[0112] 9. Take 26 parts by molar amount of 2,3-dimethyl-2-isopropylbutyrate, 60 parts of monomethylamine, 60 parts of methanol, and 15 parts of 1-butyl-3-methylimidazolium sulfate;

[0113] 10. Add 2,3-dimethyl-2-isopropylbutyrate, monomethylamine, methanol, and 1-butyl-3-methylimidazolium sulfate to a high-pressure reactor and reflux for 8 hours under stirring.

[0114] 11. Excess methylamine and methanol are recovered by distillation to obtain the crude product;

[0115] 12. Dissolve the crude product in diethyl ether, add 30 parts by molar amount of purification agent, stir well, filter, remove impurities and decolorize, and obtain a colorless, transparent and clear solution;

[0116] 13. Add sodium hydroxide to the solution to adjust the pH to neutral, then wash once with water and once with saturated NaCl solution, and separate the organic phase.

[0117] 14. Provide a low-temperature environment for the organic phase to recrystallize at around 0°C. After crystallization, filter and dry to obtain white needle-like crystals, which is the cooling agent product.

[0118] Comparative Example 3

[0119] 1. Prepare the purification agent as follows:

[0120] (1) Take 100 parts of potassium sodium titanate and 100 parts of aluminum lactate;

[0121] (2) Crush the two solids into powder separately;

[0122] (3) The powdered raw material was ball-milled using 150 parts of ethanol as a carrier;

[0123] (4) Dry at room temperature to remove ethanol, then sieve through an 80-mesh sieve to obtain the purified powder;

[0124] 2. Prepare 30 molar amounts of sodium amide and 7.3 molar amounts of liquid ammonia in a container and cool to -50℃;

[0125] 3. Add a mixture of 10 parts propionitrile and 30 parts 2-bromopropane to the container and react at a constant temperature for 30 hours;

[0126] 4. After the reaction is complete, allow it to heat up naturally until the liquid ammonia has completely evaporated. Add 10 parts of water to quench the reaction, then add 50 parts of water and mix thoroughly. Add 50 parts of ether to extract the aqueous phase and retain the organic phase.

[0127] 5. The organic phase was washed once with water and once with saturated NaCl solution, then dried with anhydrous sodium sulfate and filtered. The filtrate was collected and dried using an evaporator to obtain a pale yellow liquid precursor.

[0128] 6. Take 16 parts by molar weight of the pale yellow liquid precursor, 60 parts of methanol, and 75 parts of trimethylstilbene tetrafluoroboric acid;

[0129] 7. Add the pale yellow liquid precursor, methanol, and trimethylsinium tetrafluoroboric acid to a high-pressure reactor, heat under reflux for 6 hours with stirring, and distill to recover excess methanol to obtain reactant A;

[0130] 8. After cooling reactant A, it was washed twice with sodium bicarbonate, extracted with saturated sodium chloride solution, and after standing, separation and drying, 2,3-dimethyl-2-isopropylbutyrate was obtained.

[0131] 9. Take 26 parts by molar amount of 2,3-dimethyl-2-isopropylbutyrate, 60 parts of monomethylamine, 60 parts of methanol, and 15 parts of 1-butyl-3-methylimidazolium sulfate;

[0132] 10. Add 2,3-dimethyl-2-isopropylbutyrate, monomethylamine, methanol, and 1-butyl-3-methylimidazolium sulfate to a high-pressure reactor and reflux for 8 hours under stirring.

[0133] 11. Excess methylamine and methanol are recovered by distillation to obtain the crude product;

[0134] 12. Dissolve the crude product in diethyl ether, add 30 parts by molar amount of purification agent, stir well, filter, remove impurities and decolorize, and obtain a colorless, transparent and clear solution;

[0135] 13. Add sodium hydroxide to the solution to adjust the pH to neutral, then wash once with water and once with saturated NaCl solution, and separate the organic phase.

[0136] Provide a low-temperature environment for the organic phase to recrystallize at around 0°C. After crystallization, filter and dry to obtain white needle-like crystals, which is the cooling agent product.

[0137] Comparative Example 4

[0138] 1. Prepare the purification agent as follows:

[0139] (1) Take 100 parts of potassium sodium titanate and 100 parts of aluminum lactate;

[0140] (2) Crush the two solids into powder separately;

[0141] (3) The powdered raw material was ball-milled using 150 parts of ethanol as a carrier;

[0142] (4) Dry at room temperature to remove ethanol, then sieve through an 80-mesh sieve to obtain the purified powder;

[0143] 2. Prepare 30 molar amounts of sodium amide and 7.3 molar amounts of liquid ammonia in a container and cool to -50℃;

[0144] 3. Add a mixture of 10 parts propionitrile and 30 parts 2-bromopropane to the container and react at a constant temperature for 30 hours;

[0145] 4. After the reaction is complete, allow it to heat up naturally until the liquid ammonia has completely evaporated. Add 10 parts of water to quench the reaction, then add 50 parts of water and mix thoroughly. Add 50 parts of ether to extract the aqueous phase and retain the organic phase.

[0146] 5. The organic phase was washed once with water and once with saturated NaCl solution, then dried with anhydrous sodium sulfate and filtered. The filtrate was collected and dried using an evaporator to obtain a pale yellow liquid precursor.

[0147] 6. Take 16 parts by molar amount of the pale yellow liquid precursor and 60 parts by molar amount of methanol;

[0148] 7. Add the pale yellow liquid precursor and methanol to a high-pressure reactor, heat under reflux for 6 hours with stirring, and distill to recover excess methanol to obtain reactant A;

[0149] 8. After cooling reactant A, it was washed twice with sodium bicarbonate, extracted with saturated sodium chloride solution, and after standing, separation and drying, 2,3-dimethyl-2-isopropylbutyrate was obtained.

[0150] 9. Take 26 parts by molar amount of 2,3-dimethyl-2-isopropylbutyrate, 60 parts of monomethylamine, 60 parts of methanol, and 15 parts of 1-butyl-3-methylimidazolium sulfate;

[0151] 10. Add 2,3-dimethyl-2-isopropylbutyrate, monomethylamine, methanol, and 1-butyl-3-methylimidazolium sulfate to a high-pressure reactor and reflux for 8 hours under stirring.

[0152] 11. Excess methylamine and methanol are recovered by distillation to obtain the crude product;

[0153] 12. Dissolve the crude product in diethyl ether, add 30 parts by molar amount of purification agent, stir well, filter, remove impurities and decolorize, and obtain a colorless, transparent and clear solution;

[0154] 13. Add sodium hydroxide to the solution to adjust the pH to neutral, then wash once with water and once with saturated NaCl solution, and separate the organic phase.

[0155] 14. Provide a low-temperature environment for the organic phase to recrystallize at around 0°C. After crystallization, filter and dry to obtain white needle-like crystals, which is the cooling agent product.

[0156] Comparative Example 5

[0157] The difference between this comparative example and Example 1 is that the 1-butyl-3-methylimidazolium sulfate in steps 9 and 10 is cuprous chloride, and the rest of the implementation is the same as in Example 1.

[0158] Comparative Example 6

[0159] 1. Prepare the purification agent as follows:

[0160] (1) Take 100 parts of potassium sodium titanate and 100 parts of aluminum lactate;

[0161] (2) Crush the two solids into powder separately;

[0162] (3) The powdered raw material was ball-milled using 150 parts of ethanol as a carrier;

[0163] (4) Dry at room temperature to remove ethanol, then sieve through an 80-mesh sieve to obtain the purified powder;

[0164] 2. Prepare 30 molar amounts of sodium amide and 7.3 molar amounts of liquid ammonia in a container and cool to -50℃;

[0165] 3. Add a mixture of 10 parts propionitrile and 30 parts 2-bromopropane to the container and react at a constant temperature for 30 hours;

[0166] 4. After the reaction is complete, allow it to heat up naturally until the liquid ammonia has completely evaporated. Add 10 parts of water to quench the reaction, then add 50 parts of water and mix thoroughly. Add 50 parts of ether to extract the aqueous phase and retain the organic phase.

[0167] 5. The organic phase was washed once with water and once with saturated NaCl solution, then dried with anhydrous sodium sulfate and filtered. The filtrate was collected and dried using an evaporator to obtain a pale yellow liquid precursor.

[0168] 6. Take 16 parts by molar weight of the pale yellow liquid precursor, 60 parts of methanol, and 48 parts of trimethylstilbene tetrafluoroboric acid;

[0169] 7. Add the pale yellow liquid precursor, methanol, and trimethylsinium tetrafluoroboric acid to a high-pressure reactor, heat under reflux for 6 hours with stirring, and distill to recover excess methanol to obtain reactant A;

[0170] 8. After cooling reactant A, it was washed twice with sodium bicarbonate, extracted with saturated sodium chloride solution, and after standing, separation and drying, 2,3-dimethyl-2-isopropylbutyrate was obtained.

[0171] 9. Take 26 parts by molar amount of 2,3-dimethyl-2-isopropylbutyrate, 60 parts of monomethylamine, 60 parts of methanol, and 5 parts of 1-butyl-3-methylimidazolium sulfate;

[0172] 10. Add 2,3-dimethyl-2-isopropylbutyrate, monomethylamine, methanol, and 1-butyl-3-methylimidazolium sulfate to a high-pressure reactor and reflux for 8 hours under stirring.

[0173] 11. Excess methylamine and methanol are recovered by distillation to obtain the crude product;

[0174] 12. Dissolve the crude product in diethyl ether, add 30 parts by molar amount of purification agent, stir well, filter, remove impurities and decolorize, and obtain a colorless, transparent and clear solution;

[0175] 13. Add sodium hydroxide to the solution to adjust the pH to neutral, then wash once with water and once with saturated NaCl solution, and separate the organic phase.

[0176] 14. Provide a low-temperature environment for the organic phase to recrystallize at around 0°C. After crystallization, filter and dry to obtain white needle-like crystals, which is the cooling agent product.

[0177] Comparative Example 6

[0178] 1. Prepare the purification agent as follows:

[0179] (1) Take 100 parts of potassium sodium titanate and 100 parts of aluminum lactate;

[0180] (2) Crush the two solids into powder separately;

[0181] (3) The powdered raw material was ball-milled using 150 parts of ethanol as a carrier;

[0182] (4) Dry at room temperature to remove ethanol, then sieve through an 80-mesh sieve to obtain the purified powder;

[0183] 2. Prepare 30 molar amounts of sodium amide and 7.3 molar amounts of liquid ammonia in a container and cool to -50℃;

[0184] 3. Add a mixture of 10 parts propionitrile and 30 parts 2-bromopropane to the container and react at a constant temperature for 30 hours;

[0185] 4. After the reaction is complete, allow it to heat up naturally until the liquid ammonia has completely evaporated. Add 10 parts of water to quench the reaction, then add 50 parts of water and mix thoroughly. Add 50 parts of ether to extract the aqueous phase and retain the organic phase.

[0186] 5. The organic phase was washed once with water and once with saturated NaCl solution, then dried with anhydrous sodium sulfate and filtered. The filtrate was collected and dried using an evaporator to obtain a pale yellow liquid precursor.

[0187] 6. Take 16 parts by molar weight of the pale yellow liquid precursor, 60 parts of methanol, and 48 parts of trimethylstilbene tetrafluoroboric acid;

[0188] 7. Add the pale yellow liquid precursor, methanol, and trimethylsinium tetrafluoroboric acid to a high-pressure reactor, heat under reflux for 6 hours with stirring, and distill to recover excess methanol to obtain reactant A;

[0189] 8. After cooling reactant A, it was washed twice with sodium bicarbonate, extracted with saturated sodium chloride solution, and after standing, separation and drying, 2,3-dimethyl-2-isopropylbutyrate was obtained.

[0190] 9. Take 26 parts by molar amount of 2,3-dimethyl-2-isopropylbutyrate, 60 parts of monomethylamine, 60 parts of methanol, and 25 parts of 1-butyl-3-methylimidazolium sulfate;

[0191] 10. Add 2,3-dimethyl-2-isopropylbutyrate, monomethylamine, methanol, and 1-butyl-3-methylimidazolium sulfate to a high-pressure reactor and reflux for 8 hours under stirring.

[0192] 11. Excess methylamine and methanol are recovered by distillation to obtain the crude product;

[0193] 12. Dissolve the crude product in diethyl ether, add 30 parts by molar amount of purification agent, stir well, filter, remove impurities and decolorize, and obtain a colorless, transparent and clear solution;

[0194] 13. Add sodium hydroxide to the solution to adjust the pH to neutral, then wash once with water and once with saturated NaCl solution, and separate the organic phase.

[0195] 14. Provide a low-temperature environment for the organic phase to recrystallize at around 0°C. After crystallization, filter and dry to obtain white needle-like crystals, which is the cooling agent product.

[0196] Comparative Example 8

[0197] 1. Prepare the purification agent as follows:

[0198] (1) Take 100 parts of potassium sodium titanate and 100 parts of aluminum lactate;

[0199] (2) Crush the two solids into powder separately;

[0200] (3) The powdered raw material was ball-milled using 150 parts of ethanol as a carrier;

[0201] (4) Dry at room temperature to remove ethanol, then sieve through an 80-mesh sieve to obtain the purified powder;

[0202] 2. Prepare 30 molar amounts of sodium amide and 7.3 molar amounts of liquid ammonia in a container and cool to -50℃;

[0203] 3. Add a mixture of 10 parts propionitrile and 30 parts 2-bromopropane to the container and react at a constant temperature for 30 hours;

[0204] 4. After the reaction is complete, allow it to heat up naturally until the liquid ammonia has completely evaporated. Add 10 parts of water to quench the reaction, then add 50 parts of water and mix thoroughly. Add 50 parts of ether to extract the aqueous phase and retain the organic phase.

[0205] 5. The organic phase was washed once with water and once with saturated NaCl solution, then dried with anhydrous sodium sulfate and filtered. The filtrate was collected and dried using an evaporator to obtain a pale yellow liquid precursor.

[0206] 6. Take 16 parts by molar weight of the pale yellow liquid precursor, 60 parts of methanol, and 48 parts of trimethylstilbene tetrafluoroboric acid;

[0207] 7. Add the pale yellow liquid precursor, methanol, and trimethylsinium tetrafluoroboric acid to a high-pressure reactor, heat under reflux for 6 hours with stirring, and distill to recover excess methanol to obtain reactant A;

[0208] 8. After cooling reactant A, it was washed twice with sodium bicarbonate, extracted with saturated sodium chloride solution, and after standing, separation and drying, 2,3-dimethyl-2-isopropylbutyrate was obtained.

[0209] 9. Take 26 parts by molar amount of 2,3-dimethyl-2-isopropylbutyrate, 60 parts by molar amount of monomethylamine and 60 parts by molar amount of methanol;

[0210] 10. Add 2,3-dimethyl-2-isopropylbutyrate, monomethylamine, and methanol to a high-pressure reactor and reflux for 8 hours under stirring.

[0211] 14. Excess methylamine and methanol are recovered by distillation to obtain the crude product;

[0212] 15. Dissolve the crude product in diethyl ether, add 30 parts by molar amount of purification agent, stir well, filter, remove impurities and decolorize, and obtain a colorless, transparent, and clear solution;

[0213] 16. Add sodium hydroxide to the solution to adjust the pH to neutral, then wash once with water and once with saturated NaCl solution, and separate the organic phase.

[0214] 17. Provide a low-temperature environment for the organic phase to recrystallize at around 0°C. After crystallization, filter and dry to obtain white needle-like crystals, which is the cooling agent product.

[0215] Comparative Example 9

[0216] The difference between this comparative example and Example 1 is that the potassium sodium titanate in step 1 is potassium sodium nitrate, and the rest of the implementation is the same as in Example 1;

[0217] Comparative Example 10

[0218] The difference between this comparative example and Example 1 is that the aluminum lactate in step 1 is polyaluminum chloride, and the rest of the implementation is the same as in Example 1;

[0219] Product testing:

[0220] Samples were prepared according to Examples 1-3 and Comparative Examples 1-10, respectively.

[0221] 1) Esterification conversion rate test: Take the unpurified mixture after the esterification reaction, measure it with a UV-Vis spectrometer to obtain the concentration of the precursor. The esterification conversion rate is the ratio of the precursor consumed to the original amount added (i.e., esterification conversion rate = 1 - residual amount of precursor / initial amount of precursor).

[0222] 2) Amination conversion rate test: The unpurified mixture after the amination reaction was completed was taken and measured by UV-Vis spectrometer to obtain the raw material concentration. The amination conversion rate is the ratio of the consumed 2,3-dimethyl-2-isopropylbutyrate to the original amount added (i.e., amination conversion rate = 1 - residual amount of 2,3-dimethyl-2-isopropylbutyrate / initial amount of 2,3-dimethyl-2-isopropylbutyrate).

[0223] 3) Catalytic conversion rate: Catalytic conversion rate = Amination conversion rate * Esterification conversion rate

[0224] 4) Product purity: Take 10g of the final obtained cooling agent product and obtain the specific purity information of N,2,3-trimethyl-2-isopropylbutyramide by infrared spectroscopy;

[0225] Table 1 Test Data Table Example 1 96.1% 96.2% 92.4% 99.3% Example 2 96.1% 96.6% 92.8% 99.1% Example 3 96.4% 95.7% 92.3% 99.1% Comparative Example 1 86.5% 95.1% 82.3% 93.7% Comparative Example 2 70.1% 95.2% 66.7% 96.3% Comparative Example 3 96.0% 95.0% 91.2% 99.1% Comparative Example 4 54.1% 94.8% 51.3% 96.4% Comparative Example 5 95.5% 85.1% 81.3% 92.1% Comparative Example 6 95.6% 79.2% 75.7% 96.2% Comparative Example 7 95.7% 96.1% 92.0% 98.7% Comparative Example 8 95.6% 68.1% 65.1% 96.2% Comparative Example 9 95.5% 95.1% 90.8% 81.1% Comparative Example 10 95.8% 94.8% 90.8% 78.1%

Claims

1. A method for preparing an N,2,3-trimethyl-2-isopropylbutyramide cooling agent, characterized in that: The steps are as follows: (1) Prepare 30 molar parts of sodium amino acid and 7.3 molar parts of liquid ammonia and place them in a container, then cool them to -60℃~40℃; (2) Add a mixture of 10 parts propionitrile and 30 parts 2-bromopropane to the container and react at a constant temperature for 30 h; (3) After the reaction is complete, allow it to heat up naturally until the liquid ammonia has completely evaporated. Add 10 parts of water to quench the reaction, then add 50 parts of water and mix thoroughly. Add 50 parts of ether to extract the aqueous phase and retain the organic phase. (4) The organic phase was washed once with water and once with saturated NaCl solution, then dried with anhydrous sodium sulfate and filtered. The filtrate was collected and dried using an evaporator to obtain a pale yellow liquid precursor. (5) Take 12-20 parts by molar weight of pale yellow liquid precursor, 60 parts of methanol, and 36-60 parts of esterification catalyst; (6) Add the pale yellow liquid precursor, methanol and esterification catalyst to a high-pressure reactor, heat under reflux for 6 hours with stirring, and distill to recover excess methanol to obtain reactant A; (7) After cooling reactant A, it was washed twice with sodium bicarbonate, extracted with saturated sodium chloride solution, and after standing, separation and drying, 2,3-dimethyl-2-isopropylbutyrate was obtained. (8) Take 12-40 parts of 2,3-dimethyl-2-isopropylbutyrate, 60 parts of monomethylamine, 60 parts of methanol, and 10-20 parts of amination catalyst in molar amounts; (9) Add 2,3-dimethyl-2-isopropylbutyrate, monomethylamine, methanol and amination catalyst to a high-pressure reactor and reflux for 8 hours under stirring. (10) Distillation was used to recover excess methylamine and methanol to obtain crude product; (12) Dissolve the crude product in diethyl ether, add 20-40 molar amounts of purification agent, stir well, filter, remove impurities and decolorize, and obtain a colorless, transparent, and clear solution; (13) Add sodium hydroxide to the solution to adjust the pH to neutral, then wash once with water and once with saturated NaCl solution, and separate the organic phase. (14) Provide a low temperature environment for the organic phase to recrystallize at 0°C. After crystallization, filter and dry to obtain white needle-like crystals, which is the cooling agent product. The chemical composition of the esterification catalyst is trimethylsinium tetrafluoroboric acid; The chemical composition of the amination catalyst is 1-butyl-3-methylimidazolium sulfate; The purification agent is prepared as follows: (1) Take 100 parts of potassium sodium titanate and 100 parts of aluminum lactate; (2) Crush the two solids into powder separately; (3) The powdered raw material was ball-milled using 150 parts of ethanol as a carrier; (4) Dry at room temperature to remove ethanol and sieve through an 80-mesh sieve to obtain purified powder.