A process for the preparation of 2,2-diisopropylpropionitrile

Abstract

The application discloses a preparation method of 2,2-diisopropylpropionitrile and belongs to the technical field of food additive intermediate synthesis. The method comprises the following steps: S1, adding sodium amide, a solvent and a catalyst into a reactor, stirring until being uniformly dispersed, and obtaining a reaction system; S2, uniformly mixing 2,3-dimethylbutyronitrile and 2-bromopropane to form a premix; dropping the premix into the reaction system, continuing to stir for 0.5-1 hours after dropping is completed; S3, adding deionized water into the reaction system to quench the reaction; after quenching the reaction, cooling and stirring the reaction system, layering after standing, and reserving an upper organic phase; S4, transferring the organic phase into a distillation device, performing normal pressure distillation, and separating the solvent; the normal pressure distillation temperature is 60-90 DEG C; performing vacuum distillation on the organic phase after the normal pressure distillation, collecting a distillate, and obtaining a product. The prepared 2,2-diisopropylpropionitrile has high yield and high purity.

Description

Technical Field

[0001] This invention discloses a method for preparing 2,2-diisopropylpropionitrile, which belongs to the field of fine chemical technology. Background Technology

[0002] 2,2-Diisopropylpropionitrile (DIPPN) is an important organic synthesis intermediate, primarily used as a key raw material in the novel cooling agent WS-23 (N,2,3-trimethyl-2-isopropylbutyramide). WS-23 is widely used in food, beverages, confectionery, cosmetics, tobacco products, and pharmaceuticals due to its low dosage, long-lasting cooling effect, and lack of pungent odor. In the traditional synthesis of WS-23, DIPPN is a crucial intermediate, and its purity and yield directly affect the quality and cost of the final product. With the increasing market demand for WS-23, the research and development of DIPPN synthesis and the optimization of its production processes have become important issues for the chemical and pharmaceutical industries.

[0003] Currently, existing technologies for synthesizing DIPPN mainly include the liquid ammonia method, solvent method, sulfonate ester method, pre-fraction solvent method, and by-product recovery method. The liquid ammonia method requires ultra-low temperature conditions (-35°C to -45°C), using liquid ammonia as the solvent and sodium amide (NaNH2) as the base. Propanonium reacts with 2-bromopropane in a nucleophilic substitution reaction to generate DIPPN. The liquid ammonia method requires the use of liquid ammonia, is hazardous to operation, has high equipment requirements (requiring low temperature and pressure resistance), and requires liquid ammonia recovery in post-processing. It also has high energy consumption costs, long reaction times (over 30 hours), and low production efficiency. The solvent method requires sodium amide to react with propionitrile in an organic solvent to generate carbanions, which then condense with 2-bromopropane. Existing solvent methods use solvents such as tetrahydrofuran, toluene, and methyl tert-butyl ether. Sodium amide has low solubility in organic solvents, requiring large amounts of organic solvent, resulting in high recovery costs and a high risk of side reactions. The sulfonate method requires the reaction of isopropanol with sulfonyl chloride (such as methanesulfonyl chloride) to generate isopropyl sulfonate, which is then condensed with propionitrile in the presence of sodium amide to generate DIPPN. The sulfonate method results in high costs for sulfonyl chloride. The pre-fraction solvent method utilizes the pre-fraction containing the intermediate 2-isopropylpropionitrile from the distillation of crude DIPPN as the reaction medium, reacting it with a sodium amide complex solution, followed by the dropwise addition of propionitrile and haloisopropane. The pre-fraction solvent method requires precise control of the pre-fraction composition. The byproduct recovery method involves the traditional synthesis of 2,3-dimethylbutyramide, which accounts for more than 10% of the DIPPN yield. This byproduct is deamidged under strong alkali (such as sodium amide) and then reacted with 2-bromopropane to generate DIPPN. The reaction conditions are harsh and require inert gas protection. Existing technologies for preparing 2,2-diisopropylpropionitrile generally suffer from high operational risks, high energy costs, and difficulty in controlling the reaction.

[0004] Developing a method for preparing 2,2-diisopropylpropionitrile with high yield, safe process, and mild reaction conditions has become an urgent technical problem to be solved. Summary of the Invention

[0005] The purpose of this invention is to solve the above-mentioned problems existing in the prior art and to provide a method for preparing 2,2-diisopropylpropionitrile with high yield, safe process and mild reaction conditions.

[0006] To achieve the above objectives, the following technical solution is adopted: This invention is based on the α-alkylation reaction mechanism of nitrile compounds, using sodium amide (NaNH2) as a strong base, whose amino anion (NH2) - It can selectively abstract the α-H from the α-carbon atom directly bonded to the cyano-CN in 2,3-dimethylbutyronitrile ((CH3)2CH-CH(CH3)-CN) to generate a carbanion intermediate [(CH3)2CH-CH(CH3)-C] with strong nucleophilic activity. - NNa + 2-Bromopropane ((CH3)2CHBr) is used as an alkylating agent. Its isopropyl carbon is electronegative due to the electron-withdrawing effect of bromine, and can undergo an SN2 nucleophilic substitution reaction with the aforementioned carbanion, producing the bromide ion Br. - As a favorable leaving group, it decomposes, ultimately forming 2,2-diisopropylpropionitrile ((CH3)2CH-C(CH(CH3)2)(CH3)-CN). The reaction mechanism is as follows:

[0007] This invention provides a method for preparing 2,2-diisopropylpropionitrile, the raw materials of which include: 2,3-dimethylbutyronitrile, 2-bromopropane, sodium amino, solvent, deionized water, and catalyst.

[0008] The solvent is one of ethylene glycol dimethyl ether, methyl tert-butyl ether, and ethyl tert-butyl ether; the catalyst is tetraethylammonium chloride.

[0009] The molar ratio of 2,3-dimethylbutyronitrile, 2-bromopropane, and sodium amino acid is 1:(0.92~0.98):(1.8~2.2).

[0010] The amount of solvent used is 3.3 to 6 times the mass of 2,3-dimethylbutyronitrile.

[0011] The mass ratio of deionized water to solvent is (0.8-1.5):1.

[0012] The amount of catalyst used is 0.5‰ to 1‰ of the mass of 2,3-dimethylbutyronitrile.

[0013] A method for preparing 2,2-diisopropylpropionitrile includes the following steps: S1. Preparation of the reaction system: Add sodium amino acid, solvent and catalyst to the reactor and stir until evenly dispersed to obtain the reaction system.

[0014] The stirring process involves controlling the temperature at 25~50℃ and the stirring time at 5~7h.

[0015] S2. Adding reaction raw materials: Mix 2,3-dimethylbutyronitrile and 2-bromopropane to form a premix. Add the premix dropwise to the reaction system, and continue stirring for 0.5~1h after the addition is complete; The premixed solution is added dropwise: the temperature of the reaction system is 25~50℃ during the dropwise addition process, and the dropwise addition rate is controlled so that the premixed solution is added completely in 6~7 hours.

[0016] S3. Reaction quenching: Add deionized water dropwise to the reaction system to quench the reaction; after quenching the reaction, cool the reaction system and stir it, let it stand to separate into layers, and retain the upper organic phase.

[0017] The addition of deionized water: control the dropping rate so that the deionized water is added completely in 3-4 hours; the cooling of the reaction system: reduce the temperature of the reaction system to below 20°C; the stirring: the stirring time is 0.5-1 hour.

[0018] S4, Product Separation The organic phase is transferred to a distillation apparatus for atmospheric distillation to separate the solvent; the atmospheric distillation temperature is 60~90℃. Then, the organic phase after atmospheric distillation is subjected to vacuum distillation, and the fraction is collected to obtain the product, 2,2-diisopropylpropionitrile. The vacuum distillation is carried out at a pressure < -0.09 MPa and a temperature of 103~107℃.

[0019] The beneficial effects of this invention are as follows: 1. This invention provides a method for preparing 2,2-diisopropylpropionitrile, which yields 2,2-diisopropylpropionitrile with high yield and high purity, with a yield of 91.74~94.22% and a chromatographic purity of 96.73~99.95%.

[0020] 2. This invention provides a safe and mild method for preparing 2,2-diisopropylpropionitrile, using ethylene glycol dimethyl ether as the reaction solvent. The reaction can be carried out at temperatures ranging from 25°C to 50°C, without the need for ultra-low temperature and high pressure equipment, thus avoiding the high costs and operational risks of traditional solvent methods.

[0021] 3. The preparation method of 2,2-diisopropylpropionitrile provided by the present invention does not require precise control of the front fraction or the use of inert gas protection. The operation method is simple and suitable for large-scale industrial production. Attached Figure Description

[0022] Figure 1The liquid chromatography detection report for 2,2-diisopropylpropionitrile prepared in Example 1; Figure 2 The liquid chromatography detection report for 2,2-diisopropylpropionitrile prepared in Example 2; Figure 3 The liquid chromatography detection report for 2,2-diisopropylpropionitrile prepared in Example 3; Figure 4 The liquid chromatography detection report for 2,2-diisopropylpropionitrile prepared in Example 4; Figure 5 This is a liquid chromatography detection report of 2,2-diisopropylpropionitrile prepared in Example 5. Detailed Implementation

[0023] To make the objectives, technical solutions, and advantages of the present invention clearer, the embodiments of the present invention will be described in further detail below. It should be understood that the specific embodiments described herein are for illustrative and explanatory purposes only and are not intended to limit the scope of the invention.

[0024] Example 1: A method for preparing 2,2-diisopropylpropionitrile Material preparation: 2,3-Dimethylbutyronitrile: 56 g (0.58 mol, denoted as 1.0 eq); 2-Bromopropane: 69.42 g (0.98 eq); Sodium amino acid: 49.47g (2.2eq); Ethylene glycol dimethyl ether: 252g (4.5 times the mass of 2,3-dimethylbutyronitrile); Deionized water: 252g (equal in mass to ethylene glycol dimethyl ether); Tetraethylammonium chloride: 0.056 g (1‰ of the mass of 2,3-dimethylbutyronitrile).

[0025] A method for preparing 2,2-diisopropylpropionitrile includes the following steps: S1. Preparation of the reaction system: Sodium amide, ethylene glycol dimethyl ether, and catalyst are added to the reactor. The temperature is controlled at 50℃, and the mixture is stirred continuously for 5 hours to ensure that the sodium amide is fully dispersed and forms a homogeneous reaction system. The catalyst is tetraethylammonium chloride.

[0026] S2. Adding the reaction raw materials: Weigh 2,3-dimethylbutyronitrile and 2-bromopropane, mix them thoroughly to form a premix. Control the reactor temperature at 50℃, and add the premix dropwise into the reactor using a constant pressure dropping funnel, controlling the dropping rate so that the premix is ​​completely added over 6 hours. After the premix is ​​completely added, continue stirring for 0.5 hours.

[0027] S3. Reaction Quenching: Weigh deionized water and add it dropwise into the reactor using a constant pressure dropping funnel to quench the reaction. Control the dropping rate so that the deionized water is added completely over 3 hours. After the deionized water has been added, lower the system temperature to below 20°C, stir for 1 hour, and allow the system to stand and separate into layers, retaining the upper organic phase.

[0028] S4, Product Separation The organic phase was transferred to a distillation apparatus for atmospheric distillation to separate the solvent; the atmospheric distillation temperature was 88℃. Then, the organic phase after atmospheric distillation was subjected to vacuum distillation, and the fraction was collected to obtain the product, 2,2-diisopropylpropionitrile. The vacuum distillation was carried out at a pressure < -0.09 MPa and a temperature of 107℃.

[0029] The yield of 2,2-diisopropylpropionitrile was calculated to be 94.22% (based on 2,3-dimethylbutyronitrile). The HPLC purity was 96.73%.

[0030] Example 2: A method for preparing 2,2-diisopropylpropionitrile Material preparation: 2,3-Dimethylbutyronitrile: 56 g (0.58 mol, denoted as 1.0 eq); 2-Bromopropane: 68g (0.96 eq); Sodium amino acid: 40.47g (1.8eq); Methyl tert-butyl ether: 336g (6 times the mass of 2,3-dimethylbutyronitrile); Deionized water: 336g (equal in mass to methyl tert-butyl ether); Tetraethylammonium chloride: 0.056 g (1‰ of the mass of 2,3-dimethylbutyronitrile).

[0031] A method for preparing 2,2-diisopropylpropionitrile includes the following steps: S1. Preparation of the reaction system: Sodium amino acid, methyl tert-butyl ether, and catalyst are added to the reactor. The temperature is controlled at 25°C, and the mixture is stirred continuously for 6 hours to ensure that the sodium amino acid is fully dispersed and forms a homogeneous reaction system. The catalyst is tetraethylammonium chloride.

[0032] S2. Adding the reaction raw materials: Weigh 2,3-dimethylbutyronitrile and 2-bromopropane, mix them thoroughly to form a premix. Control the reactor temperature at 25℃, and add the premix dropwise into the reactor using a constant pressure dropping funnel, controlling the dropping rate so that the premix is ​​completely added over 6 hours. After the premix is ​​completely added, continue stirring for 0.5 hours.

[0033] S3. Reaction Quenching: Weigh deionized water and add it dropwise into the reactor using a constant-pressure dropping funnel to quench the reaction. Control the dropping rate so that the deionized water is added completely over 4 hours. After the deionized water has been added, lower the system temperature to below 20°C, stir for 1 hour, and allow the system to stand and separate into layers, retaining the upper organic phase.

[0034] S4, Product Separation The organic phase was transferred to a distillation apparatus for atmospheric distillation to separate the solvent; the atmospheric distillation temperature was 60℃. Then, the organic phase after atmospheric distillation was subjected to vacuum distillation, and the fraction was collected to obtain the product, 2,2-diisopropylpropionitrile. The vacuum distillation was carried out at a pressure < -0.09 MPa and a temperature of 105℃.

[0035] The yield of 2,2-diisopropylpropionitrile was calculated to be 93.88% (based on 2,3-dimethylbutyronitrile). The HPLC purity was 97.69%.

[0036] Example 3: A method for preparing 2,2-diisopropylpropionitrile Material preparation: 2,3-Dimethylbutyronitrile: 56 g (0.58 mol, denoted as 1.0 eq); 2-Bromopropane: 66.59 g (0.94 eq); Sodium amino acid: 40.47g (1.8eq); Ethyl tert-butyl ether: 224g (4 times the mass of 2,3-dimethylbutyronitrile); Deionized water: 224g (equal in mass to ethyl tert-butyl ether); Tetraethylammonium chloride: 0.056 g (1‰ of the mass of 2,3-dimethylbutyronitrile).

[0037] A method for preparing 2,2-diisopropylpropionitrile includes the following steps: S1. Preparation of the reaction system: Sodium amino acid, ethyl tert-butyl ether, and catalyst are added to the reactor. The temperature is controlled at 50℃, and the mixture is stirred continuously for 7 hours to ensure that the sodium amino acid is fully dispersed and forms a homogeneous reaction system. The catalyst is tetraethylammonium chloride.

[0038] S2. Adding the reaction raw materials: Weigh 2,3-dimethylbutyronitrile and 2-bromopropane, mix them thoroughly to form a premix. Control the reactor temperature at 50℃, and add the premix dropwise into the reactor using a constant pressure dropping funnel, controlling the dropping rate so that the premix is ​​completely added over 7 hours. After the premix is ​​completely added, continue stirring for 0.5 hours.

[0039] S3. Reaction Quenching: Weigh deionized water and add it dropwise into the reactor using a constant pressure dropping funnel to quench the reaction. Control the dropping rate so that the deionized water is added completely over 4 hours. After the deionized water has been added, lower the system temperature to below 20°C and stir for 0.5 hours. After the system has settled and separated into layers, retain the upper organic phase.

[0040] S4, Product Separation The organic phase was transferred to a distillation apparatus for atmospheric distillation to separate the solvent; the atmospheric distillation temperature was 77℃. Then, the organic phase after atmospheric distillation was subjected to vacuum distillation, and the fraction was collected to obtain the product, 2,2-diisopropylpropionitrile. The vacuum distillation was carried out at a pressure < -0.09 MPa and a temperature of 105℃.

[0041] The yield of 2,2-diisopropylpropionitrile was calculated to be 93.3% (based on 2,3-dimethylbutyronitrile). The HPLC purity was 98.72%.

[0042] Example 4: A method for preparing 2,2-diisopropylpropionitrile Material preparation: 2,3-Dimethylbutyronitrile: 56 g (0.58 mol, denoted as 1.0 eq); 2-Bromopropane: 65.88 g (0.93 eq); Sodium amino acid: 44.97g (2.0eq); Ethylene glycol dimethyl ether: 224g (4 times the mass of 2,3-dimethylbutyronitrile); Deionized water: 224g (equal in mass to ethylene glycol dimethyl ether); Tetraethylammonium chloride: 0.028 g (0.5‰ of the mass of 2,3-dimethylbutyronitrile).

[0043] A method for preparing 2,2-diisopropylpropionitrile includes the following steps: S1. Preparation of the reaction system: Sodium amide, ethylene glycol dimethyl ether, and catalyst are added to the reactor. The temperature is controlled at 25°C, and the mixture is stirred continuously for 7 hours to ensure that the sodium amide is fully dispersed and forms a homogeneous reaction system. The catalyst is tetraethylammonium chloride.

[0044] S2. Adding the reaction raw materials: Weigh 2,3-dimethylbutyronitrile and 2-bromopropane, mix them thoroughly to form a premix. Control the reactor temperature at 25℃, and add the premix dropwise into the reactor using a constant pressure dropping funnel, controlling the dropping rate so that the premix is ​​completely added over 6 hours. After the premix is ​​completely added, continue stirring for 0.5 hours.

[0045] S3. Reaction Quenching: Weigh deionized water and add it dropwise into the reactor using a constant pressure dropping funnel to quench the reaction. Control the dropping rate so that the deionized water is added completely over 4 hours. After the deionized water has been added, lower the system temperature to below 20°C and stir for 0.5 hours. After the system has settled and separated into layers, retain the upper organic phase.

[0046] S4, Product Separation The organic phase was transferred to a distillation apparatus for atmospheric distillation to separate the solvent; the atmospheric distillation temperature was 88℃. Then, the organic phase after atmospheric distillation was subjected to vacuum distillation, and the fraction was collected to obtain the product, 2,2-diisopropylpropionitrile. The vacuum distillation was carried out at a pressure < -0.09 MPa and a temperature of 105℃.

[0047] The yield of 2,2-diisopropylpropionitrile was calculated to be 92.41% (based on 2,3-dimethylbutyronitrile). The HPLC purity was 99.95%.

[0048] Example 5: A method for preparing 2,2-diisopropylpropionitrile Material preparation: 2,3-Dimethylbutyronitrile: 56 g (0.58 mol, denoted as 1.0 eq); 2-Bromopropane: 65.17 g (0.92 eq); Sodium amino acid: 44.97g (2.0eq); Ethylene glycol dimethyl ether: 184.8g (3.3 times the mass of 2,3-dimethylbutyronitrile); Deionized water: 184.8g (equivalent to the mass of ethylene glycol dimethyl ether).

[0049] Tetraethylammonium chloride: 0.028 g (0.5‰ of the mass of 2,3-dimethylbutyronitrile).

[0050] A method for preparing 2,2-diisopropylpropionitrile includes the following steps: S1. Preparation of the reaction system: Sodium amide, ethylene glycol dimethyl ether, and catalyst are added to the reactor. The temperature is controlled at 30℃, and the mixture is stirred continuously for 7 hours to ensure that the sodium amide is fully dispersed and forms a homogeneous reaction system. The catalyst is tetraethylammonium chloride.

[0051] S2. Adding the reaction raw materials: Weigh 2,3-dimethylbutyronitrile and 2-bromopropane, mix them thoroughly to form a premix. Control the reactor temperature at 30℃, and add the premix dropwise into the reactor using a constant pressure dropping funnel, controlling the dropping rate so that the premix is ​​completely added over 6 hours. After the premix is ​​completely added, continue stirring for 0.5 hours.

[0052] S3. Reaction Quenching: Weigh deionized water and add it dropwise into the reactor using a constant pressure dropping funnel to quench the reaction. Control the dropping rate so that the deionized water is added completely over 4 hours. After the deionized water has been added, lower the system temperature to below 20°C and stir for 0.5 hours. After the system has settled and separated into layers, retain the upper organic phase.

[0053] S4, Product Separation The organic phase was transferred to a distillation apparatus for atmospheric distillation to separate the solvent; the atmospheric distillation temperature was 90℃. Then, the organic phase after atmospheric distillation was subjected to vacuum distillation, and the fraction was collected to obtain the product, 2,2-diisopropylpropionitrile. The vacuum distillation was carried out at a pressure < -0.09 MPa and a vacuum distillation temperature of 103℃.

[0054] The yield of 2,2-diisopropylpropionitrile was calculated to be 91.74% (based on 2,3-dimethylbutyronitrile). The HPLC purity was 99.87%.

[0055] Obviously, there are many other possible implementation methods under the concept of this invention. It should be stated here that any changes made under the inventive concept of this invention will fall within the protection scope of this invention.

Claims

1. A method for preparing 2,2-diisopropylpropionitrile, characterized in that: Includes the following steps: S1. Preparation of the reaction system: Add sodium amino acid, solvent and catalyst to the reactor and stir until evenly dispersed to obtain the reaction system; S2. Adding reaction raw materials: Mix 2,3-dimethylbutyronitrile with 2-bromopropane to form a premix; add the premix dropwise to the reaction system, and continue stirring the reaction for 0.5~1h after the dropwise addition is complete; the reaction temperature is 25℃ during the dropwise addition of the premix. S3. Reaction quenching: Add deionized water dropwise to the reaction system to quench the reaction; after quenching the reaction, cool the reaction system and stir it, let it stand to separate into layers, and retain the upper organic phase. S4. Product separation: The organic phase is transferred to a distillation apparatus and distilled under atmospheric pressure to separate the solvent; the atmospheric distillation temperature is 60~90℃; the organic phase after atmospheric distillation is then distilled under reduced pressure, and the fraction is collected to obtain the product. The molar ratio of 2,3-dimethylbutyronitrile, 2-bromopropane, and sodium amino group is 1:0.94:1.

8. The solvent is ethyl tert-butyl ether; The catalyst is tetraethylammonium chloride.

2. The method for preparing 2,2-diisopropylpropionitrile according to claim 1, characterized in that: The amount of solvent used is 3.3 to 6 times the mass of 2,3-dimethylbutyronitrile.

3. The method for preparing 2,2-diisopropylpropionitrile according to claim 1, characterized in that: The amount of catalyst used is 0.5‰ to 1‰ of the mass of 2,3-dimethylbutyronitrile.

4. The method for preparing 2,2-diisopropylpropionitrile according to claim 1, characterized in that: In step S1, the stirring is carried out at a temperature of 25-50°C for 5-7 hours.

5. The method for preparing 2,2-diisopropylpropionitrile according to claim 1, characterized in that: In step S2, the dripping speed of the premixed liquid is controlled so that the premixed liquid is dripped completely in 6-7 hours.

6. The method for preparing 2,2-diisopropylpropionitrile according to claim 1, characterized in that: In step S3, the deionized water is added by controlling the dropping speed so that the deionized water is added completely in 3-4 hours.

7. The method for preparing 2,2-diisopropylpropionitrile according to claim 1, characterized in that: In step S3, the reaction system is cooled down: the temperature of the reaction system is reduced to below 20°C; the stirring is carried out for 0.5 to 1 hour.

8. The method for preparing 2,2-diisopropylpropionitrile according to claim 1, characterized in that: In step S4, the atmospheric distillation is carried out at a temperature of 60~90℃.

9. The method for preparing 2,2-diisopropylpropionitrile according to claim 1, characterized in that: In step S4, the vacuum distillation is carried out at a pressure of < -0.09 MPa and a temperature of 103~107℃.

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