A method for synthesizing 2,3-dimethyl-2-isopropylbutyronitrile

Abstract

The invention belongs to the field of fine chemicals and discloses a method for synthesizing 2,3-dimethyl-2-isopropylbutyronitrile. The method comprises the following steps: adding an organic amine solvent into a high-pressure reactor, and adding sodium amide, sodium iodide and a phase transfer catalyst into the reactor under nitrogen protection and stirring. After stirring for a certain period of time, a mixed solution of propionitrile and 2-bromopropane is added dropwise into the reactor, the dropping speed and the reaction temperature are controlled, and the reaction is continued for a period of time after the dropwise addition is completed to obtain a reactant solution. The reactant solution is cooled and then water is added, the solution is allowed to stand for stratification, an organic phase is collected, the organic phase is first subjected to atmospheric distillation to recover the solvent, and then vacuum distillation is performed to obtain a 2,3-dimethyl-2-isopropylbutyronitrile product. The method shortens the reaction time and improves the product yield through the synergistic effect of the sodium iodide, the phase transfer catalyst and the organic amine.

Description

Technical Field

[0001] The 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 used in the synthesis of WS-23 (2-isopropyl-N,2,3-trimethylbutyramide). WS-23 is a typical monosubstituted aliphatic amide. Monosubstituted aliphatic amides have a cooling effect similar to menthol. WS-23 is a white powdery crystal characterized by a strong cooling effect without side effects such as burning or stinging. It has been used as a cooling agent in pharmaceutical formulations, oral care products, food, beverages, tobacco products, cosmetics, and other products. It is synthesized by the Ritter reaction of 2,2-diisopropylpropionitrile with methanol in the presence of acid. With the increasing application and market demand for WS-23, efficient methods for the synthesis of 2,3-dimethyl-2-isopropylbutyronitrile are becoming increasingly critical.

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

[0004] CN101823983A discloses a method for preparing 2,3-dimethyl-2-isopropylbutyronitrile. The method uses liquid ammonia as a solvent, adds sodium amide, starts stirring to mix the materials in the kettle evenly, and adjusts the temperature in the low-temperature reactor; adds propionitrile and 2-bromopropane to a high-position stirring drop tank and mixes them evenly; after evaporating the liquid ammonia, a series of operations such as adding water, separating the liquids, and distilling are performed to obtain the 2,3-dimethyl-2-isopropylbutyronitrile product.

[0005] CN103242194A discloses a method for preparing 2,3-dimethyl-2-isopropylbutyronitrile. The method comprises the following steps: first, adding an ether organic solvent into a reactor, then adding a strong base, stirring to mix the materials evenly, and heating to a certain temperature; second, mixing propionitrile and isopropyl halogenated hydrocarbon evenly; third, slowly dropping the mixed solution obtained in the second step into the reactor, continuing to keep the temperature and react until the end after the dropping is complete, and adding water after cooling to destroy the strong base; fourth, washing the organic phases obtained by separation with brine, drying the organic phases, recovering the solvent, and performing reduced pressure distillation to obtain 2,2-diisopropylpropionitrile; the organic solvent is toluene or benzene or a C1-C4 monoether or cyclic ether or a polyether inert solvent; the strong base is a metal hydride or a metal amide or a metal alkoxide; and the metal is lithium or sodium or potassium or calcium.

[0006] CN102093257A provides a method for preparing 2,2-diisopropylpropionitrile. The method comprises the following steps: first, isopropyl alcohol and sulfonyl chloride are used as raw materials to prepare isopropyl sulfonate; then, the isopropyl sulfonate and propionitrile are reacted with a strong base to prepare 2,2-diisopropylpropionitrile. R in the isopropyl sulfonate includes a C1-C4 alkyl group, a C1-C4 alkyl derivative, a phenyl group, and a phenyl derivative.

[0007] CN116987005A provides a green and efficient method for preparing 2,2-diisopropylpropionitrile. The raw materials include propionitrile, 2-bromopropane, an organic solvent, and a metal organic ligand catalyst. The organic solvent is methyl tert-butyl ether (MTBE), an ether solvent, or an organic amine solvent. The metal organic ligand catalyst is a metal carbonyl compound selected from the group consisting of Ni(CO)₄, Fe(CO)₅, Ru(CO)₅, and Os(CO)₅, with Ni(CO)₄ being preferred.

[0008] The above methods either have disadvantages such as low temperature reaction, use of dangerous liquid ammonia as solvent, or slow reaction rate 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 short reaction time, high yield and safe process.

[0010] In order 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, comprising the following steps:

[0012] a) adding an organic amine solvent to a high-pressure reactor, and under nitrogen protection and stirring, adding sodium amide, sodium iodide and a phase transfer catalyst to the reactor, stirring for a certain period of time, and then adding a mixture of propionitrile and 2-bromopropane dropwise to the reactor, controlling the dropping rate and reaction temperature, and continuing the reaction for a period of time after the dropwise addition is completed to obtain a reactant solution:

[0013] b) cooling the above-mentioned reactant solution, adding water, standing and stratifying, collecting the organic phase, distilling the organic phase under normal pressure to recover the solvent, and then rectifying under reduced pressure to obtain 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, hexadecyltrimethylammonium 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, 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, in step a), the molar ratio of sodium amide to propionitrile is (2.05-2.5):1.

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

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

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

[0026] Furthermore, the amount 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 cooling 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] The sodium iodide of the present invention can undergo a halogen exchange reaction with 2-bromopropane to produce 2-iodopropane. Iodide is more active than bromide in nucleophilic substitution reactions. The larger atomic radius of the iodine atom results in a longer C-I bond and a relatively lower bond energy. Therefore, iodide is more likely to break during the reaction, exhibiting higher reactivity. In contrast, the smaller atomic radius of the bromine atom results in a shorter C-Br bond and a higher bond energy, resulting in a relatively lower reactivity of the bromide.

[0031] The phase transfer catalyst further increases the solubility of reactants and intermediates, accelerating the reaction rate. The organic amine increases the alkalinity of the reaction system, suppressing side reactions. The synergistic effect of sodium iodide, the phase transfer catalyst, and the organic amine shortens the reaction time and improves the yield. After a reaction time of 2 hours, the yield can reach 95%. Furthermore, the use of dangerous liquid ammonia is avoided, improving safety. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 2,3-dimethyl-2-isopropylbutyronitrile synthesized in Example 1 of the present invention 1 H NMR spectrum. DETAILED DESCRIPTION

[0033] The present invention will be further described in detail below through specific embodiments. The following embodiments are merely illustrative and non-restrictive, and should not be used to limit the scope of protection of the present invention.

[0034] Example 1:

[0035] At room temperature, under nitrogen protection, 16.4 g sodium amide (NaNH2), 40 g triethylamine, 0.1 g sodium iodide, and 0.05 g phase transfer catalyst 18-crown-6 were added to a 250 mL autoclave in sequence, stirred at 150 rpm for 30 minutes. Low temperature circulating water was turned on and the temperature was lowered to -10 o C. Stir 10.0 g propionitrile and 47 g 2-bromopropane in a 100 mL beaker for 30 min to mix well. The stirring speed of the reactor was set to 300 rpm at -10 o At 0°C, adjust the metering pump flow rate to 0.2 mL / min and start adding the mixed solution dropwise. During the addition process, the temperature of the reactor begins to rise due to the exothermic reaction. At this time, adjust the flow rate of the circulating water so that the reaction temperature does not exceed 0 o C. After the addition is complete, lower the temperature to -5 o C, and continue the reaction for 2 hours to ensure the completion of the reaction. Sampling was performed and gas chromatography (GC) was used to detect that there was no propionitrile remaining. o C, slowly add 50 g of deionized water. After adding, the temperature rises to 25 oC, continue stirring for 1 hour. Transfer to a separatory funnel and let stand for 1 hour to allow the layers to separate. Remove the oil layer, dry it over anhydrous sodium sulfate, and filter. Wash the filter cake twice with triethylamine, and combine the filtrates. Distill the filtrate under atmospheric pressure to recover the solvent, then distill under reduced pressure to obtain 39.6 g of 2,3-dimethyl-2-isopropylbutyronitrile as a colorless liquid. The finished product content is ≥99.1%, and the yield is 93.1% (calculated as propionitrile).

[0036] Example 2:

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

[0038] Example 3:

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

[0040] Example 4:

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

[0042] Example 5:

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

[0044] Example 6:

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

[0046] Example 7:

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

[0048] Example 8:

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

[0050] Example 9:

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

[0052] Example 10:

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

[0054] Example 11:

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

[0056] Example 12:

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

[0058] Example 13:

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

[0060] Example 14:

[0061] The difference from Example 1 is that the amount of triethylamine used is 60 g, the amount of 2-bromopropane used is 50 g, and the amount of sodium iodide used is 0.2 g to obtain 39.7 g of 2,3-dimethyl-2-isopropylbutyronitrile as a colorless liquid, the finished product content is ≥99.4%, and the yield is 93.2% (calculated as 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 2,3-dimethyl-2-isopropylbutyronitrile is obtained as a colorless liquid, the finished product content is ≥96.0%, and the yield is 95.2% (calculated as propionitrile).

[0064] Comparative Example 1:

[0065] The difference from Example 1 is that sodium iodide is not used, and 34.5 g of 2,3-dimethyl-2-isopropylbutyronitrile is obtained as a colorless liquid, the finished product content is ≥99.0%, and the yield is 81.2% (calculated as 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 2,3-dimethyl-2-isopropylbutyronitrile is obtained as a colorless liquid, the finished product content is ≥99.0%, and the yield is 64.6% (calculated as propionitrile).

[0068] Comparative Example 3:

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

[0070] The above is only a preferred embodiment of the present invention. It should be pointed out that a person skilled in the art can make several modifications and improvements without departing from the inventive concept, and these all fall within the scope of protection of the present invention.

Claims

1. A method for synthesizing 2,3-dimethyl-2-isopropylbutyronitrile, characterized in that: The following steps are involved: a) adding an organic amine solvent into a high-pressure reactor, and under nitrogen protection and stirring, adding sodium amide, sodium iodide and a phase transfer catalyst into the reactor, stirring for a certain period of time, and then adding a mixture of propionitrile and 2-bromopropane dropwise into the reactor, controlling the dropping speed and the reaction temperature to -10-0 o C, after the addition is complete, continue the reaction for 1.5-2.5 hours to obtain a reactant solution: b) cooling the reactant solution, adding water, standing and stratifying, collecting the organic phase, distilling the organic phase under normal pressure to recover the solvent, and then rectifying under reduced pressure to obtain a 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, hexadecyltrimethylammonium bromide, dodecyltrimethylammonium chloride, benzyltriethylammonium chloride, 18-crown-6, dibenzo-18-crown-6 and sodium dodecylsulfonate; The organic amine solvent is one or more of diethylamine, triethylamine, propylamine, dipropylamine, tripropylamine, butylamine, dibutylamine, tributylamine, pentylamine, dipentylamine, tripentylamine, hexylamine, dihexylamine, trihexylamine, cyclohexylamine, dicyclohexylamine, tricyclohexylamine, and ethylenediamine; The molar ratio of sodium amide to propionitrile is 2.05-2.5:1; The amount of 2-bromopropane used is 2.1-2.4 times the molar amount of propionitrile; The amount of sodium iodide used is 0.01-0.03 times the mass of propionitrile; The amount of the organic amine solvent is 2.5-10 times the mass of propionitrile; The amount of the phase transfer catalyst is 0.001-0.02 times the mass of propionitrile; The reaction time is shortened and the yield is improved through the synergistic effect of sodium iodide, phase transfer catalyst and organic amine.

2. The method according to claim 1, characterized in that The cooling in step b) is to -10-0°C.

3. The method according to claim 1, characterized in that The amount of water added in step b) is 3-5 times the mass of propionitrile.

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