Method for synthesizing 2, 3-dimethyl-2-isopropyl butyronitrile

Abstract

The invention belongs to the field of fine chemical engineering, and discloses a method for synthesizing 2, 3-dimethyl-2-isopropyl butyronitrile, which comprises the following steps of: adding an organic amine solvent into a high-pressure reaction kettle, adding sodium amide, sodium iodide and a phase transfer catalyst into the reaction kettle under the protection of nitrogen and in a stirring state, stirring for a certain period of time, and reacting for 2-3 hours to obtain 2, 3-dimethyl-2-isopropyl butyronitrile. Dropwise adding a mixed solution of propionitrile and 2-bromopropane into the reactor, controlling the dropwise adding speed and the reaction temperature, continuously reacting for a period of time after the dropwise adding is finished to obtain a reactant solution, cooling the reactant solution, adding water, standing for layering, collecting an organic phase, distilling the organic phase at normal pressure to recover a solvent, and rectifying at reduced pressure to obtain 2, 3, 5-trimethyl-1, 3, 5-trimethyl-1, 3, 5-trimethyl-1, 3-pentanediol. According to the method, the sodium iodide, the phase transfer catalyst and the organic amine have a synergistic effect, so that the reaction time is shortened, and the yield of the product is improved.

Description

Technical Field

[0001] The present invention belongs to the field of fine chemicals, and particularly relates to a method for synthesizing 2,3-dimethyl-2-isopropylbutyronitrile. Background Art

[0002] 2,3-Dimethyl-2-isopropylbutyronitrile is an important chemical intermediate and can be used for synthesizing WS-23 (2-isopropyl-N,2,3-trimethylbutanamide). WS-23 is a typical monosubstituted aliphatic amide. Monosubstituted aliphatic amides have a cooling taste similar to menthol. WS-23 is a white powdery crystal, characterized by having a strong cooling taste without side effects such as burning or stinging sensations. It has been used as a cooling agent in pharmaceutical preparations, oral care products, foods, beverages, tobacco products, cosmetics and other products. It is synthesized by the Ritter reaction of 2,2-diisopropylpropionitrile and methanol in the presence of an acid. With the continuous increase in the application and market demand of WS-23, a method for efficiently synthesizing 2,3-dimethyl-2-isopropylbutyronitrile is particularly crucial.

[0003] Currently, the methods for synthesizing 2,3-dimethyl-2-isopropylbutyronitrile mainly include the following:

[0004] CN101823983A discloses a preparation method of 2,3-dimethyl-2-isopropylbutyronitrile. In this method, liquid ammonia is used as a solvent, sodium amide is added, and stirring is started to make the materials in the kettle mix evenly, and the temperature in the low-temperature reaction kettle is adjusted; propionitrile and 2-bromopropane are added to the high-level stirring dropping tank and mixed evenly; after evaporating the liquid ammonia, through a series of operations such as adding water, liquid separation, and distillation, a 2,3-dimethyl-2-isopropylbutyronitrile product is obtained.

[0005] CN103242194A discloses a preparation method of 2,3-dimethyl-2-isopropylbutyronitrile. In the first step, an ether organic solvent is added to the reactor, and then a strong base is added, and stirring is started to make the materials mix evenly and the temperature is raised to a certain temperature; in the second step, propionitrile and isopropyl halide are mixed evenly; in the third step, the mixture obtained in the second step is slowly added dropwise to the reactor, and after the dropping is completed, the reaction is continued to be kept warm until the end, and after cooling, water is added to destroy the strong base; in the fourth step, the separated organic phase is washed with brine respectively, the organic phase is dried, the solvent is recycled, and 2,2-diisopropylpropionitrile is prepared by vacuum distillation; the organic solvent is toluene or benzene or a C1-C4 monoether or cyclic ether or polyether inert solvent, and the strong base is a metal hydride or metal amide or metal alkoxide, and the metal is lithium or sodium or potassium or calcium.

[0006] CN102093257A provides a method for preparing 2,2 - diisopropylpropionitrile. First, isopropyl sulfonate is prepared using isopropyl alcohol and sulfonyl chloride as raw materials. Then, 2,2 - diisopropylpropionitrile is prepared by reacting the isopropyl sulfonate with propionitrile under the action of a strong base. The R in the isopropyl sulfonate includes alkyl groups with 1 - 4 carbon atoms, alkyl derivatives with 1 - 4 carbon atoms, phenyl groups, and phenyl derivatives.

[0007] CN116987005A provides a green and efficient method for preparing 2,2 - diisopropylpropionitrile. The raw material components include propionitrile, 2 - bromopropane, an organic solvent, and a metal - organic ligand catalyst. The organic solvent is one of methyl tert - butyl ether (MTBE), ether solvents, or organic amine solvents. The metal - organic ligand catalyst is one of metal carbonyl compounds Ni(CO)4, Fe(CO)5, Ru(CO)5, Os(CO)5, preferably Ni(CO)4.

[0008] The above - mentioned methods either involve low - temperature reactions and use dangerous liquid ammonia as a solvent, or have disadvantages such as slow reaction rates and poor selectivity. Therefore, it is of great significance to develop an efficient production process for 2,3 - dimethyl - 2 - isopropylbutyronitrile. Summary of the Invention

[0009] The purpose of the present invention is to overcome the deficiencies of the prior art and provide a method for preparing 2,3 - dimethyl - 2 - isopropylbutyronitrile with a short reaction time, high yield, and safe process.

[0010] To solve the above problems, the present invention adopts the following technical solutions:

[0011] The present invention provides a method for synthesizing 2,3 - dimethyl - 2 - isopropylbutyronitrile, which includes the following steps:

[0012] a) Add an organic amine solvent to a high - pressure reaction kettle. Under nitrogen protection and stirring, add sodium amide, sodium iodide, and a phase - transfer catalyst to the reaction kettle. After stirring for a certain time, dropwise add a mixed solution of propionitrile and 2 - bromopropane into the reactor, control the dropping rate and reaction temperature. After the dropping is completed, continue to react for a period of time to obtain a reactant solution:

[0013] b) After cooling the above reactant solution, add water, let it stand for stratification, collect the organic phase. First, distill the organic phase under normal pressure to recover the solvent, and then perform vacuum rectification to obtain the 2,3 - dimethyl - 2 - isopropylbutyronitrile product.

[0014] The reaction formula is:

[0015]

[0016]

[0017]

[0018] The phase transfer catalyst is one or more of tetrabutylammonium bromide, tetrabutylammonium chloride, tetrabutylammonium fluoride, trioctylmethylammonium chloride, tetradecyltrimethylammonium chloride, cetyltrimethylammonium bromide, dodecyltrimethylammonium chloride, benzyltriethylammonium chloride, 18-crown-6, dibenzo-18-crown-6, and sodium dodecylsulfonate.

[0019] Furthermore, the organic amine solvent in step a) is one or more of diethylamine, triethylamine, propylamine, dipropylamine, tripropylamine, butylamine, dibutylamine, tributylamine, pentylamine, dipentylamine, tripentylamine, hexylamine, dihexylamine, trihexylamine, cyclohexylamine, dicyclohexylamine, tricyclohexylamine, and ethylenediamine.

[0020] Furthermore, the reaction temperature in step a) is -10 - 0 o °C, preferably -5 o °C, and the reaction time is 1.5 - 2.5 hours.

[0021] Furthermore, the particle size of the sodium amide in step a) is 60 - 2000 mesh.

[0022] Furthermore, the molar ratio of the sodium amide to propionitrile in step a) is (2.05 - 2.5)∶1.

[0023] Furthermore, the dosage of 2-bromopropane in step a) is 2.1 - 2.4 times the molar amount of propionitrile.

[0024] Furthermore, the dosage of sodium iodide in step a) is 0.01 - 0.03 times the mass of propionitrile.

[0025] Furthermore, the dosage of the organic amine solvent in step a) is 2.5 - 10 times the mass of propionitrile. Preferably 2.5 - 5 times.

[0026] Furthermore, the dosage of the phase transfer catalyst in step a) is 0.001 - 0.02 times the mass of propionitrile. Preferably 0.001 - 0.01 times.

[0027] Furthermore, the temperature reduction in step b) is to -10 - 0 °C.

[0028] Furthermore, the amount of water added in step b) is 3 - 5 times the mass of propionitrile.

[0029] The beneficial effects of the advantages of the present invention are:

[0030] Sodium iodide in the present invention can undergo a halogen exchange reaction with 2-bromopropane to generate 2-iodopropane. In nucleophilic substitution reactions, the activity of iodides is higher than that of bromides. The atomic radius of the iodine atom is relatively large, resulting in a longer bond length and relatively smaller bond energy of the C-I bond. Therefore, iodides are more likely to break in the reaction, showing higher reactivity. On the contrary, the radius of the bromine atom is smaller, the bond length of the C-Br bond is shorter, and the bond energy is larger, making the reactivity of bromides relatively lower.

[0031] The phase transfer catalyst further increases the solubility of reactants and intermediates, accelerating the reaction rate. Organic amines are used to increase the alkalinity of the reaction system, suppressing the occurrence of side reactions. Through the synergistic effect of sodium iodide, the phase transfer catalyst, and organic amines, the reaction time is shortened and the yield is increased. After reacting for 2 hours, the yield can reach 95%. At the same time, the use of dangerous liquid ammonia is avoided, improving safety. Description of the Drawings

[0032] Figure 1 is the 1H NMR spectrum of 2,3-dimethyl-2-isopropylbutyronitrile synthesized in Example 1 of the present invention 1 1H NMR spectrum. Detailed Description of the Invention

[0033] The present invention will be further described in detail below through specific examples. The following examples are only descriptive and not restrictive, and the protection scope of the present invention cannot be limited thereby.

[0034] Example 1:

[0035] At room temperature and under nitrogen protection, 16.4 g of sodium amide (NaNH2), 40 g of triethylamine, 0.1 g of sodium iodide, and 0.05 g of the phase transfer catalyst 18-crown-6 were successively added to a 250 mL high-pressure reactor. The stirring speed was 150 rpm, and the mixture was stirred for 30 minutes. Open the low-temperature circulating water and cool down to -10 o °C. 10.0 g of propionitrile and 47 g of 2-bromopropane were stirred in a 100 mL beaker for 30 min to mix evenly. The stirring speed of the reactor was set to 300 rpm. At -10 o °C, the flow rate of the metering pump was adjusted to 0.2 mL / min, and the mixed solution was started to be added dropwise. During the addition process, due to the exothermic reaction, the temperature of the reactor began to rise. At this time, the flow rate of the circulating water was adjusted to keep the reaction temperature not exceeding 0 o °C. After the addition was completed, the temperature was reduced to -5 o °C, and the reaction was continued for 2 hours to ensure the completion of the reaction. Sampling was taken, and gas chromatography (GC) was used to detect that there was basically no propionitrile remaining. At 0 o °C, 50 g of deionized water was slowly added dropwise. After adding, the temperature rose to 25 oC. Stir for an additional 1 hour. Transfer to a separatory funnel, let stand for 1 hour to allow phase separation. After removing the oil layer, add anhydrous sodium sulfate for drying, then filter. Wash the filter cake twice with the solvent triethylamine and combine the filtrates. Distill the filtrate under atmospheric pressure to recover the solvent, and then perform vacuum distillation to obtain 39.6 g of colorless liquid 2,3-dimethyl-2-isopropylbutyronitrile with a finished product content of ≥99.1% and a yield of 93.1% (calculated based on propionitrile).

[0036] Example 2:

[0037] The difference from Example 1 is that triethylamine is replaced with dibutylamine, obtaining 40.0 g of colorless liquid 2,3-dimethyl-2-isopropylbutyronitrile with a finished product content of ≥99.3% and a yield of 94.0% (calculated based on propionitrile).

[0038] Example 3:

[0039] The difference from Example 1 is that triethylamine is replaced with ethylenediamine, obtaining 39.3 g of colorless liquid 2,3-dimethyl-2-isopropylbutyronitrile with a finished product content of ≥99.5% and a yield of 92.2% (calculated based on propionitrile).

[0040] Example 4:

[0041] The difference from Example 1 is that triethylamine is replaced with cyclohexylamine, obtaining 38.8 g of colorless liquid 2,3-dimethyl-2-isopropylbutyronitrile with a finished product content of ≥99.4% and a yield of 91.2% (calculated based on propionitrile).

[0042] Example 5:

[0043] The difference from Example 1 is that triethylamine is replaced with hexylamine, obtaining 38.5 g of colorless liquid 2,3-dimethyl-2-isopropylbutyronitrile with a finished product content of ≥99.6% and a yield of 90.4% (calculated based on propionitrile).

[0044] Example 6:

[0045] The difference from Example 1 is that triethylamine is replaced with pentylamine, obtaining 39.0 g of colorless liquid 2,3-dimethyl-2-isopropylbutyronitrile with a finished product content of ≥99.2% and a yield of 91.6% (calculated based on propionitrile).

[0046] Example 7:

[0047] The difference from Example 1 is that the catalyst 18-crown-6 is replaced with cetyltrimethylammonium bromide, obtaining 40.1 g of colorless liquid 2,3-dimethyl-2-isopropylbutyronitrile with a finished product content of ≥98.6% and a yield of 94.1% (calculated based on propionitrile).

[0048] Example 8:

[0049] The difference from Example 1 is that the catalyst 18-crown-6 is replaced by dodecyltrimethylammonium chloride, obtaining 40.4 g of a colorless liquid of 2,3-dimethyl-2-isopropylbutyronitrile, with the finished product content ≥ 98.0% and the yield 94.8% (calculated based on propionitrile).

[0050] Example 9:

[0051] The difference from Example 1 is that the catalyst 18-crown-6 is replaced by tetrabutylammonium chloride, obtaining 39.8 g of a colorless liquid of 2,3-dimethyl-2-isopropylbutyronitrile, with the finished product content ≥ 98.1% and the yield 93.4% (calculated based on propionitrile).

[0052] Example 10:

[0053] The difference from Example 1 is that the catalyst 18-crown-6 is replaced by tetrabutylammonium fluoride, obtaining 39.2 g of a colorless liquid of 2,3-dimethyl-2-isopropylbutyronitrile, with the finished product content ≥ 99.3% and the yield 92.3% (calculated based on propionitrile).

[0054] Example 11:

[0055] The difference from Example 1 is that the catalyst 18-crown-6 is replaced by benzyltriethylammonium chloride, obtaining 39.4 g of a colorless liquid of 2,3-dimethyl-2-isopropylbutyronitrile, with the finished product content ≥ 99.1% and the yield 92.6% (calculated based on propionitrile).

[0056] Example 12:

[0057] The difference from Example 1 is that the catalyst 18-crown-6 is replaced by sodium dodecylsulfonate, obtaining 38.4 g of a colorless liquid of 2,3-dimethyl-2-isopropylbutyronitrile, with the finished product content ≥ 99.7% and the yield 90.2% (calculated based on propionitrile).

[0058] Example 13:

[0059] The difference from Example 1 is that the catalyst 18-crown-6 is replaced by dibenzo-18-crown-6, obtaining 39.0 g of a colorless liquid of 2,3-dimethyl-2-isopropylbutyronitrile, with the finished product content ≥ 99.4% and the yield 91.6% (calculated based on propionitrile).

[0060] Example 14:

[0061] The difference from Example 1 is that the amount of triethylamine is 60 g, the amount of 2-bromopropane is 50 g, and the amount of sodium iodide is 0.2 g, obtaining 39.7 g of a colorless liquid of 2,3-dimethyl-2-isopropylbutyronitrile, with the finished product content ≥ 99.4% and the yield 93.2% (calculated based on propionitrile).

[0062] Example 15:

[0063] The difference from Example 1 is that the amount of sodium iodide used is 0.3 g, and 40.5 g of colorless liquid of 2,3-dimethyl-2-isopropylbutyronitrile is obtained. The content of the finished product is ≥96.0%, and the yield is 95.2% (calculated based on propionitrile).

[0064] Comparative Example 1:

[0065] The difference from Example 1 is that sodium iodide is not used, and 34.5 g of colorless liquid of 2,3-dimethyl-2-isopropylbutyronitrile is obtained. The content of the finished product is ≥99.0%, and the yield is 81.2% (calculated based on propionitrile).

[0066] Comparative Example 2:

[0067] The difference from Example 1 is that the phase transfer catalyst 18-crown-6 is not used, and 27.5 g of colorless liquid of 2,3-dimethyl-2-isopropylbutyronitrile is obtained. The content of the finished product is ≥99.0%, and the yield is 64.6% (calculated based on propionitrile).

[0068] Comparative Example 3:

[0069] The difference from Example 1 is that triethylamine is replaced by tetrahydrofuran, and 25.6 g of colorless liquid of 2,3-dimethyl-2-isopropylbutyronitrile is obtained. The content of the finished product is ≥99.0%, and the yield is 60.2% (calculated based on propionitrile).

[0070] The above are only the preferred embodiments of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the inventive concept, several modifications and improvements can be made, and these all belong to the protection scope of the present invention.

Claims

1. A method for synthesizing 2,3-dimethyl-2-isopropylbutyronitrile, characterized in that, It includes the following steps: a) Add an organic amine solvent into a high-pressure reactor. Under nitrogen protection and stirring, add sodium amide, sodium iodide and a phase transfer catalyst into the reactor. After stirring for a certain time, dropwise add a mixed solution of propionitrile and 2-bromopropane into the reactor, controlling the dropping rate and the reaction temperature at -10 - 0 o °C. After the dropping is completed, continue the reaction for 1.5 - 2.5 hours to obtain a reactant solution: b) After cooling down the reactant solution and adding water, let it stand for layering, collect the organic phase. First, distill the organic phase under normal pressure to recover the solvent, and then perform vacuum rectification to obtain the 2,3-dimethyl-2-isopropylbutyronitrile product. The phase transfer catalyst is one or more of tetrabutylammonium bromide, tetrabutylammonium chloride, tetrabutylammonium fluoride, trioctylmethylammonium chloride, tetradecyltrimethylammonium chloride, cetyltrimethylammonium bromide, dodecyltrimethylammonium chloride, benzyltriethylammonium chloride, 18-crown-6, dibenzo-18-crown-6, and sodium dodecylsulfonate.

2. The method according to claim 1, wherein The organic amine solvent in step a) is one or more of diethylamine, triethylamine, propylamine, dipropylamine, tripropylamine, butylamine, dibutylamine, tributylamine, pentylamine, dipentylamine, tripentylamine, hexylamine, dihexylamine, trihexylamine, cyclohexylamine, dicyclohexylamine, tricyclohexylamine, and ethylenediamine.

3. The method according to claim 1, wherein In step a), the molar ratio of sodium amide to propionitrile is 2.05 - 2.5∶1.

4. The method according to claim 1, wherein In step a), the dosage of 2-bromopropane is 2.1 - 2.4 times the molar amount of propionitrile.

5. The method according to claim 1, characterized in that, In step a), the dosage of sodium iodide is 0.01 - 0.03 times the mass of propionitrile.

6. The method according to claim 1, wherein In step a), the dosage of the organic amine solvent is 2.5 - 10 times the mass of propionitrile.

7. The method according to claim 1, wherein In step a), the dosage of the phase transfer catalyst is 0.001 - 0.02 times the mass of propionitrile.

8. The method according to claim 1, wherein In step b), the cooling temperature is reduced to -10 - 0°C.

9. The method according to claim 1, wherein In step b), the amount of water added is 3 - 5 times the mass of propionitrile.

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