阅读说明：本技术 一种2,2-二甲基丁腈、其衍生物及合成方法 (2, 2-dimethyl butyronitrile, derivative and synthetic method thereof ) 是由 张辰亮 徐鑫光 李娟� 袁康 范李科 琚朋朋 刘晓明 胡志彪 李成果 于 2020-12-15 设计创作，主要内容包括：本发明涉及化学合成技术领域,具体公开一种2,2-二甲基丁腈、其衍生物及合成方法。所述2,2-二甲基丁腈的合成方法为：溶剂中,超声条件下,2-氯代-2-甲基丁烷和氰化物,在催化剂与助催化剂,或催化剂、助催化剂与缚酸剂的作用下进行取代反应,得2,2-二甲基丁腈；所述催化剂为硬脂酰肌氨酸盐、月桂酰肌氨酸盐或油酰肌氨酸盐中至少一种,所述助催化剂为冠醚化合物或聚乙二醇。本发明通过特定的合成工艺,制备得到了纯度可达99％以上,收率大于88％的2,2-二甲基丁腈。以2,2-二甲基丁腈为原料,经水解可制备得到2,2-二甲基丁酸,将2,2-二甲基丁酸经酰化反应、或酯化反应可制备得到2,2-二甲基丁腈的衍生物。(The invention relates to the technical field of chemical synthesis, and particularly discloses 2, 2-dimethylbutyronitrile, a derivative thereof and a synthesis method. The synthesis method of the 2, 2-dimethyl butyronitrile comprises the following steps: in a solvent, under the ultrasonic condition, 2-chloro-2-methylbutane and cyanide carry out substitution reaction under the action of a catalyst and a cocatalyst or the catalyst, the cocatalyst and an acid-binding agent to obtain 2, 2-dimethylbutyranitrile; the catalyst is at least one of stearoyl sarcosinate, lauroyl sarcosinate or oleoyl sarcosinate, and the cocatalyst is crown ether compound or polyethylene glycol. The invention prepares the 2, 2-dimethyl butyronitrile with the purity of more than 99 percent and the yield of more than 88 percent by a specific synthesis process. 2, 2-dimethylbutyrate can be prepared by hydrolyzing 2, 2-dimethylbutyrate as a raw material, and the 2, 2-dimethylbutyrate can be prepared into a derivative of the 2, 2-dimethylbutyrate by acylation reaction or esterification reaction.)

1.2, 2-dimethylbutyronitrile, having the structure shown in formula (II):

2. a process for the synthesis of 2, 2-dimethylbutyronitrile according to claim 1, characterized in that it comprises the following steps:

in a solvent, under the ultrasonic condition, carrying out substitution reaction on 2-chloro-2-methylbutane and cyanide shown in a formula (I) under the action of a catalyst and a cocatalyst or the catalyst, the cocatalyst and an acid-binding agent to obtain 2, 2-dimethylbutyramide shown in a formula (II);

wherein the catalyst is at least one of stearoyl sarcosinate, lauroyl sarcosinate or oleoyl sarcosinate, and the cocatalyst is crown ether compound or polyethylene glycol.

3. The method for synthesizing 2, 2-dimethylbutyronitrile of claim 2, wherein the crown ether compound is at least one of 12-crown-4, 15-crown-5 or 18-crown-6; and/or

The solvent is at least one of water, methanol, ethanol, toluene or xylene; and/or

The cyanide is sodium cyanide, potassium cyanide or hydrogen cyanide; and/or

The acid-binding agent is at least one of sodium hydroxide, potassium hydroxide, triethanolamine or ammonia water.

4. A process for the synthesis of 2, 2-dimethylbutyronitrile according to claim 2 or 3, characterized in that it has an ultrasonic frequency of 20KHZ to 200MHz and an ultrasonic power density of 0.1 to 10W/cm²(ii) a And/or

The temperature of the substitution reaction is 5-120 ℃, and the reaction time is 1-6 h.

5. A process for the synthesis of 2, 2-dimethylbutyronitrile as claimed in claim 2, wherein the molar ratio of 2-chloro-2-methylbutane to cyanide is in the range of 1: 0.9-1.5; and/or

The dosage of the catalyst is 0.2-10% of the mass of the 2-chloro-2-methylbutane; and/or

The using amount of the cocatalyst is 0.01-5% of the mass of the 2-chloro-2-methylbutane; and/or

The dosage of the acid-binding agent is 1-2 times of the mass of the 2-chloro-2-methylbutane; and/or

The dosage of the solvent is 1 to 5 times of the mass of the 2-chloro-2-methylbutane.

6. The process for the synthesis of 2, 2-dimethylbutyronitrile of claim 5, wherein the molar ratio of 2-chloro-2-methylbutane to cyanide is 1: 0.98-1.2; and/or

The dosage of the catalyst is 0.5-3% of the mass of the 2-chloro-2-methylbutane; and/or

The using amount of the cocatalyst is 0.05-1% of the mass of the 2-chloro-2-methylbutane; and/or

The dosage of the acid-binding agent is 1-1.5 times of the mass of the 2-chloro-2-methylbutane; and/or

The dosage of the solvent is 2-3 times of the mass of the 2-chloro-2-methylbutane.

7. A synthetic method of a 2, 2-dimethyl butyronitrile derivative is characterized by comprising the following steps:

step a, preparing 2, 2-dimethylbutyronitrile according to the method for synthesizing 2, 2-dimethylbutyronitrile of any one of claims 2-6;

and b, adding the prepared 2, 2-dimethylbutyramide into an acid solution for hydrolysis, or adding the obtained product into an alkali solution for hydrolysis and then acidifying to obtain the 2, 2-dimethylbutyrate.

8. The method for synthesizing 2, 2-dimethylbutyronitrile derivative according to claim 7, further comprising a step c of subjecting the obtained 2, 2-dimethylbutyric acid to an acylation reaction with an acylating agent, or an esterification reaction with an alcohol, to obtain a compound represented by formula (iii);

wherein R is Cl, C1-C6 alkoxy, C3-C6 alkenyloxy orR₁Is methyl or ethyl, R₂Is H, halogen or nitro.

9. A process for the synthesis of 2, 2-dimethylbutyronitrile derivatives according to claim 7, wherein in step b, the hydrolysis temperature is 40-120 ℃ and the hydrolysis time is 0.5-8 h; and/or

In step b, the acid solution is sulfuric acid solution or hydrochloric acid solution, H₂SO₄Or the molar ratio of HCl to 2, 2-dimethylbutyronitrile is 1.5-2.5: 1; and/or

In the step b, the alkali solution is sodium hydroxide solution, and the molar ratio of NaOH to 2, 2-dimethyl butyronitrile is 1.0-2.6: 1.

10. A process for the synthesis of 2, 2-dimethylbutyronitrile derivatives according to claim 8, wherein in step c, the acylation reaction is carried out at a temperature of-5-130 ℃ for a time of 0.5-8 h; and/or

In the step c, the molar ratio of the acylating reagent to the 2, 2-dimethylbutyric acid is 0.3-1.5: 1; and/or

In the step c, the molar ratio of the alcohol to the 2, 2-dimethylbutyric acid is 2.5-4.5: 1; and/or

In the step c, the temperature of the esterification reaction is 60-160 ℃, and the time of the esterification reaction is 2-8 h.

Technical Field

The invention relates to the technical field of chemical synthesis, in particular to 2, 2-dimethylbutyronitrile, a derivative thereof and a synthesis method.

Background

2, 2-dimethyl butyric acid is an important intermediate for producing medicines and pesticides, and can be used as an intermediate for producing substances such as rubber, dye and the like, thereby having wide application. At present, the main synthesis process for industrially producing 2, 2-dimethylbutyric acid on a large scale is to react dimethyl acetic acid and bromoethane at-78 ℃ to prepare the product; or dimethyl acetate and methyl bromide are reacted to prepare the methyl bromide, or dimethyl propanol and carbon monoxide are carbonylated to prepare the methyl bromide. However, the above processes have problems of severe reaction conditions, low yield and high cost.

The derivatives of 2, 2-disubstituted butyric acid mainly comprise 2, 2-disubstituted butyryl chloride and 2, 2-disubstituted butyrate, and are mainly used for preparing medical intermediates or pesticide intermediates and also can be used as intermediates for producing rubber and dyes. Can be prepared by acylation reaction or esterification reaction of 2, 2-dimethyl butyric acid, but also has the problems of high production cost, low yield and the like. Therefore, it is necessary to develop a method for synthesizing 2, 2-dimethylbutyric acid and its derivatives with mild reaction conditions and high yield and purity.

Disclosure of Invention

Aiming at the technical problems, the invention provides 2, 2-dimethylbutyronitrile, derivatives thereof and a synthetic method.

In order to solve the technical problems, the technical scheme provided by the invention is as follows:

2, 2-dimethyl butyronitrile, the structure is shown as formula (II):

compared with the prior art, the invention provides a novel intermediate substance 2, 2-dimethylbutyric acid and derivatives thereof, namely 2, 2-dimethylbutyric acid, which is used as a raw material to prepare the 2, 2-dimethylbutyric acid only through conventional hydrolysis, and a series of 2, 2-dimethylbutyric acid derivatives, such as 2, 2-disubstituted butyryl chloride or 2, 2-disubstituted butyrate, can be prepared by using the 2, 2-dimethylbutyric acid as the raw material through conventional acylation reaction or esterification reaction. The 2, 2-dimethylbutyrate and the derivatives thereof prepared from the 2, 2-dimethylbutyrate serving as a raw material have the content of over 99 percent, the yield of over 80 percent, mild reaction conditions, low preparation cost and wide application prospect.

The invention also provides a synthetic method of the 2, 2-dimethyl butyronitrile, which comprises the following steps:

in a solvent, under the ultrasonic condition, carrying out substitution reaction on 2-chloro-2-methylbutane and cyanide shown in a formula (I) under the action of a catalyst and a cocatalyst or the catalyst, the cocatalyst and an acid-binding agent to obtain 2, 2-dimethylbutyramide shown in a formula (II);

wherein the catalyst is at least one of stearoyl sarcosinate, lauroyl sarcosinate or oleoyl sarcosinate, and the cocatalyst is crown ether compound or polyethylene glycol.

In the prior art, the method for preparing organic nitrile compounds mainly includes addition of hydrogen cyanide and aldehyde ketone compounds, and substitution reaction of sodium cyanide and acyl chloride, benzyl chloride, alkyl iodide and the like to prepare organic nitrile compounds, and also reports about preparation of organic nitrile compounds through amide dehydration reaction. The other method for producing the organic nitrile compound on a large scale is to prepare the organic nitrile from an alcohol substance, oxygen and ammonia by an ammoxidation method under the conditions of high temperature and high pressure, but the method needs higher reaction temperature and pressure and a large amount of ammonia, has high requirements on equipment, and has the problems of large three-waste pollution and the like. Further, since saturated chloroalkanes have low activity and conversion rate of organonitriles by substitution reaction thereof is low, they are rarely used as raw materials for producing organonitrile compounds.

Aiming at the prior art, the invention provides a new synthesis method of a new substance 2, 2-dimethyl butyronitrile, which takes stearoyl-sarcosinate, lauroyl-sarcosinate or oleoyl-sarcosinate as a catalyst, takes crown ether compound or polyethylene glycol as a cocatalyst and is matched with ultrasonic conditions, so that the reaction activity and selectivity of 2-chloro-2-methylbutane are obviously improved, the occurrence of side reactions is effectively reduced, the conversion rate of a target product is improved, the aim of preparing the 2, 2-dimethyl butyronitrile by taking saturated chloroalkane as a raw material is fulfilled, the content of the prepared 2, 2-dimethyl butyronitrile can reach more than 99 percent, the molar yield can reach more than 87 percent, special reaction equipment is not needed in the reaction, the production cost is low, the method is suitable for industrial production, and a new cheap intermediate substance or reaction raw material is provided for related industries, has remarkable social and economic benefits.

Preferably, the crown ether compound is at least one of 12-crown-4, 15-crown-5 or 18-crown-6.

Preferably, the polyethylene glycol is polyethylene glycol 200, polyethylene glycol 600, polyethylene glycol 800, polyethylene glycol 2000 or polyethylene glycol 4000.

Optionally, the stearoyl, lauroyl sarcosinate or oleoyl sarcosinate of the present invention is a sodium, potassium or ammonium salt.

The optimized catalyst can not only improve the reaction activity of the 2-chloro-2-methylbutane, accelerate the reaction rate and shorten the reaction time, but also improve the reaction selectivity and reduce the occurrence of side reactions, thereby improving the purity and the yield of the target compound.

Preferably, the solvent is at least one of water, methanol, ethanol, toluene or xylene

Preferred organic solvents can increase the reaction rate and reduce the occurrence of side reactions.

Preferably, the cyanide is sodium cyanide, potassium cyanide or hydrogen cyanide.

Preferably, the acid-binding agent is at least one of a sodium hydroxide solution, a potassium hydroxide solution, a triethanolamine solution or ammonia water.

Preferably, the ultrasonic frequency is 20KHZ-200MHz, and the ultrasonic power density is 0.1-10W/cm²。

More preferably, the ultrasonic frequency is 40KHZ-100MHz, and the ultrasonic power density is 0.3-5W/cm²。

More preferably, the ultrasonic frequency is 80KHZ-50MHz, and the ultrasonic power density is 0.35-3W/cm²。

The preferable ultrasonic condition can promote the reaction, improve the reaction rate and shorten the reaction time.

Preferably, the temperature of the substitution reaction is 5-120 ℃, and the reaction time is 1-6 h.

Further preferably, the temperature of the substitution reaction is 5-120 ℃, and the reaction time is 2-6 h.

Preferably, the molar ratio of the 2-chloro-2-methylbutane to the cyanide is 1: 0.9-1.5.

Further preferably, the molar ratio of the 2-chloro-2-methylbutane to the cyanide is 1: 0.98-1.2.

The optimized reaction temperature and the molar ratio of the reaction raw materials can improve the conversion rate of the 2-chloro-2-methylbutane, and further improve the purity and the yield of the 2, 2-dimethylbutyramide.

Preferably, the amount of the catalyst is 0.2-10% of the mass of the 2-chloro-2-methylbutane.

More preferably, the amount of the catalyst is 0.5-3% by mass of the 2-chloro-2-methylbutane.

Preferably, the amount of the cocatalyst is 0.01-5% of the mass of the 2-chloro-2-methylbutane.

More preferably, the amount of the cocatalyst is 0.05-1% of the mass of the 2-chloro-2-methylbutane.

The optimized dosage of the catalyst and the cocatalyst can ensure that the purity of a target product is prevented from being influenced by excessive addition of the catalyst while the reaction activity and the reaction selectivity are improved to the maximum extent, and the production cost is saved.

Preferably, the dosage of the acid-binding agent is 1-2 times of the mass of the 2-chloro-2-methylbutane.

More preferably, the dosage of the acid-binding agent is 1-1.5 times of the mass of the 2-chloro-2-methylbutane.

Preferably, the amount of the solvent is 1 to 5 times of the mass of the 2-chloro-2-methylbutane.

More preferably, the amount of the solvent is 2 to 3 times of the mass of the 2-chloro-2-methylbutane.

The optimized addition amount of the solvent can not only fully dissolve the reaction raw material, the catalyst and the cocatalyst, fully contact the raw material with the catalyst and the cocatalyst and fully play the catalytic action of the catalyst and the cocatalyst, but also ensure that the reaction rate is fully improved and the yield of the target product is improved on the premise of minimizing side reactions.

Preferably, the method further comprises the steps of standing, liquid separating, water washing, distilling and rectifying the reaction solution after the reaction is finished.

After the reaction is finished, the distillation and the rectification can be carried out according to the conventional operation in the field, and the distillation and the rectification temperature can be selected according to the conventional setting.

The invention also provides a synthetic method of the 2, 2-dimethyl butyronitrile derivative, which comprises the following steps:

step a, preparing 2, 2-dimethylbutyronitrile according to the synthesis method of 2, 2-dimethylbutyronitrile described in any one of the above;

and b, adding the prepared 2, 2-dimethylbutyramide into an acid solution for hydrolysis, or adding the obtained product into an alkali solution for hydrolysis and then acidifying to obtain the 2, 2-dimethylbutyrate.

The invention provides a new process route for preparing 2, 2-dimethylbutyric acid by taking 2-chloro-2-methylbutane as a raw material, which not only obviously reduces the production cost, but also has mild reaction conditions and less three-waste pollution, is suitable for industrial production and has wide application prospect.

The invention also provides a synthetic method of the 2, 2-dimethyl butyronitrile derivative, which comprises the following steps:

step a, preparing 2, 2-dimethylbutyronitrile according to the synthesis method of 2, 2-dimethylbutyronitrile described in any one of the above;

b, adding the prepared 2, 2-dimethylbutyramide into an acid solution for hydrolysis, or adding the obtained mixture into an alkali solution for hydrolysis and then acidifying to obtain 2, 2-dimethylbutyrate;

c, carrying out acylation reaction on the obtained 2, 2-dimethylbutyric acid and an acylation reagent, or carrying out esterification reaction on the obtained 2, 2-dimethylbutyric acid and alcohol to obtain a compound shown in a formula (III);

wherein R is Cl, C1-C6 alkoxy, C3-C6 alkenyloxy orR₁Is methyl or ethyl, R₂Is H, halogen or nitro.

The synthesis method of the 2, 2-dimethyl butyronitrile derivative provided by the invention not only obviously reduces the production cost, but also has mild reaction conditions and less three-waste pollution, is suitable for industrial production and has wide application prospect.

The derivatives of 2, 2-dimethylbutyronitrile of the present invention include 2, 2-dimethylbutyric acid, 2, 2-dimethylbutyric chloride, and 2, 2-dimethylbutyric acid ester.

Preferably, in step b, the temperature of the hydrolysis reaction is 40-120 ℃, and the time of the hydrolysis reaction is 0.5-8 h.

Preferably, in step b, the acid solution is sulfuric acid solution or hydrochloric acid solution, H₂SO₄Or the molar ratio of HCl to 2, 2-dimethylbutyronitrile is 1.5-2.5: 1.

Preferably, in step b, the alkali solution is sodium hydroxide solution, and the molar ratio of NaOH to 2, 2-dimethylbutyronitrile is 1.0-2.6: 1.

Preferably, in step c, the temperature of the acylation reaction is-5-130 ℃, and the reaction time is 0.5-8 h.

Preferably, in step c, the molar ratio of the acylating agent to 2, 2-dimethylbutyric acid is 0.3-1.5: 1.

Preferably, in step c, the molar ratio of the alcohol to 2, 2-dimethylbutyric acid is 2.5-4.5: 1.

Preferably, in step c, the temperature of the esterification reaction is 60-160 ℃, and the time of the esterification reaction is 2-8 h.

Optionally, in step c, the solvent required for the acylation reaction is dichloromethane, dichloroethane, chlorobenzene, toluene, dichlorobenzene or xylene.

Optionally, in step c, the catalyst for the esterification reaction is concentrated sulfuric acid.

Preferably, the acylating agent is chlorine, sulfuryl chloride, phosgene, triphosgene, thionyl chloride or triphosgene.

Preferably, the alcohol is methanol, ethanol, propanol, isopropanol, propenyl, butenol, 2-pentenol, 2-hexenol, n-butanol, isobutanol, tert-butanol, benzyl alcohol, phenethyl alcohol, halogen-substituted benzyl alcohol, nitro-substituted benzyl alcohol, halogen-substituted phenethyl alcohol or nitro-substituted phenethyl alcohol.

The preferable reaction conditions can improve the reaction rate and the conversion rate of raw materials, further improve the yield and the purity of the target product and shorten the reaction time.

The 2, 2-dimethylbutyramide is prepared under the ultrasonic condition by taking 2-chloro-2-methylbutane as a raw material and selecting a specific catalyst and a cocatalyst, so that a novel cheap reaction raw material and an intermediate are provided for related industries, the content of the prepared 2, 2-dimethylbutyramide can reach more than 99%, and the yield can reach more than 87%. The 2, 2-dimethyl butyronitrile is used as a raw material, 2-dimethyl butyric acid can be prepared through hydrolysis reaction, then the 2, 2-dimethyl butyric acid is used as a raw material, and 2, 2-disubstituted butyryl chloride or 2, 2-disubstituted butyrate can be prepared through acylation reaction or esterification reaction, wherein the molar yield can reach more than 80 percent and the purity can reach more than 99 percent based on the 2, 2-dimethyl butyronitrile, the reaction condition is mild, the energy consumption is low, the three-waste pollution is less, and the method is a green and environment-friendly low-cost synthetic route of the 2, 2-dimethyl butyric acid and the derivative thereof, is suitable for industrial production and has wide application prospect.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

In order to better illustrate the invention, the following examples are given by way of further illustration.

The purity of the 2-chloro-2-methylbutane used in the following examples of the invention was 99%.

Example 1

A synthetic method of 2, 2-dimethyl butyronitrile comprises the following steps:

adding 250mL of methanol and 56.5g (0.525mol) of 2-chloro-2-methylbutane into a reaction vessel containing ultrasonic waves, uniformly mixing, adding 0.5g of potassium lauroyl sarcosinate and 0.1g of 12-crown-4, starting the ultrasonic waves, adjusting the ultrasonic frequency to be 6MHZ and the power density to be 0.5W/cm²Controlling the temperature to be 5-10 ℃, simultaneously dropwise adding 17.01g (0.63mol) of liquid hydrogen cyanide and 100.8g (0.756mol) of sodium hydroxide solution with the mass concentration of 30 wt%, wherein the dropwise adding time is 0.5-1h, continuing the ultrasonic heat preservation reaction for 1.5-2h after the dropwise adding is finished, and sampling and controlling the content of 2-chloro-2-methylbutane in the sample0.21 percent of the total amount of the components, standing and separating the components to obtain a methanol solution of 2, 2-dimethylbutyronitrile, washing an oil phase with water, distilling to remove a solvent, and rectifying to obtain 48.9g of 2, 2-dimethylbutyronitrile with an HPLC content of 99.51 percent, wherein the molar yield is 95.43 percent in terms of 2-chloro-2-methylbutane.

m/e：97.09(100％)，98.09(7.0％)。

Anal.: c, 74.17; h, 11.41; n,14.42, so the molecular formula is determined to be C₆H₁₁N。

Examples 2 to 10

Examples 2-10 provide a method of synthesizing 2, 2-dimethylbutyronitrile, which is the same as example 1, with the specific reaction conditions shown in Table 1.

TABLE 1

Comparative example 1

The comparative example provides a method for synthesizing 2, 2-dimethylbutyronitrile:

adding 250mL of methanol and 56.5g (0.525mol) of 2-chloro-2-methylbutane into a reaction vessel containing ultrasonic waves, uniformly mixing, adding 1.0g of tetrabutylammonium bromide, adding 1.0g of 12-crown-4, starting the ultrasonic waves, adjusting the ultrasonic frequency to be 6MHZ and the power density to be 0.5W/cm²Controlling the temperature to be 85-100 ℃, simultaneously dropwise adding 17.01g (0.63mol) of liquid hydrogen cyanide and 100.8g (0.756mol) of sodium hydroxide solution with the mass concentration of 30 wt%, keeping the ultrasonic heat preservation reaction for 4 hours after the dropwise adding is finished, controlling the content of 2-chloro-2-methylbutane to be 43.21% in sampling, standing and separating liquid to obtain a methanol solution of 2, 2-dimethylbutyramide, washing an oil phase with water, distilling to remove a solvent, and rectifying to obtain 29.87g of 2, 2-dimethylbutyramide, wherein the HPLC content is 94.51%, the molar yield is 55.34% and the conversion rate is 56.79% in terms of 2-chloro-2-methylbutane.

Comparative example 2

The comparative example provides a method for synthesizing 2, 2-dimethylbutyronitrile:

adding 250mL of methanol and 56.5g (0.525mol) of 2-chloro-2-methylbutane into a reaction vessel containing ultrasonic waves, uniformly mixing, adding 1.0g of 12-crown-4, starting the ultrasonic waves, adjusting the ultrasonic frequency to be 6MHZ and the power density to be 0.5W/cm²Controlling the temperature to be 85-100 ℃, simultaneously dropwise adding 17.01g (0.63mol) of liquid hydrogen cyanide and 100.8g (0.756mol) of sodium hydroxide solution with the mass concentration of 30 wt%, keeping the ultrasonic heat preservation reaction for 4 hours after the dropwise adding is finished, controlling the content of 2-chloro-2-methylbutane to be 35.43% in sampling, standing and separating liquid to obtain a methanol solution of 2, 2-dimethylbutyramide, washing an oil phase with water, distilling to remove a solvent, and rectifying to obtain 29.87g of 2, 2-dimethylbutyramide, the HPLC content of 93.48%, the molar yield is 59.65% based on 2-chloro-2-methylbutane, and the conversion rate is 64.57%.

Comparative example 3

The comparative example provides a method for synthesizing 2, 2-dimethylbutyronitrile:

adding 250mL of methanol and 56.5g (0.525mol) of 2-chloro-2-methylbutane into a reaction vessel containing ultrasonic waves, uniformly mixing, adding 0.5g of potassium lauroyl sarcosinate and 1.0g of tetrahydrofuran, starting the ultrasonic waves, adjusting the ultrasonic frequency to be 6MHZ and the power density to be 0.5W/cm²Controlling the temperature to be 85-100 ℃, simultaneously dropwise adding 17.01g (0.63mol) of liquid hydrogen cyanide and 100.8g (0.756mol) of sodium hydroxide solution with the mass concentration of 30 wt%, keeping on the ultrasonic heat preservation reaction for 4 hours after dropwise adding is finished, controlling the content of 2-chloro-2-methylbutane to be 18.3% in sampling, standing and separating liquid to obtain a methanol solution of 2, 2-dimethylbutyramide, washing an oil phase with water, distilling to remove a solvent, and rectifying to obtain 39.30g of 2, 2-dimethylbutyramide, the HPLC content of which is 95.47%, wherein the molar yield is 78.48% and the conversion rate is 81.7% in terms of 2-chloro-2-methylbutane.

Example 11

A synthetic method of 2, 2-dimethylbutyric acid comprises the following steps:

adding 70g of 70% sulfuric acid solution into a 100mL four-neck bottle with a mechanical stirrer, a thermometer and a condenser, heating to 70-80 ℃, then dropwise adding 19.5g (0.2mol) of 2, 2-dimethylbutyronitrile for hydrolysis, wherein the dropwise adding time is 0.5-1.0h, the hydrolysis temperature is 70-110 ℃, carrying out reflux insulation reaction for 4-6h, monitoring the completion of the 2, 2-dimethylbutyronitrile reaction by thin-layer chromatography, cooling, standing for liquid separation, neutralizing and washing with water to obtain 22.44g of 2, 2-dimethylbutyronic acid, the HPLC content is 99.83%, and the molar yield is 96.53% based on 2, 2-dimethylbutyronitrile.

Example 12

A synthetic method of 2, 2-dimethylbutyric acid comprises the following steps:

adding 300g of 20% sodium hydroxide aqueous solution into a 500mL four-mouth bottle provided with a mechanical stirrer, a thermometer and a condenser, heating to 90-100 ℃, then dropwise adding 97.5g (1.0mol) of 2, 2-dimethylbutyramide for hydrolysis, wherein the dropwise adding time is 1.0-2.0h, the hydrolysis temperature is 90-110 ℃, carrying out reflux insulation reaction for 0.5-1.5h, monitoring the completion of the 2, 2-dimethylbutyramide reaction by thin-layer chromatography, cooling, standing for liquid separation, neutralizing and washing with water to obtain 114.41g of 2, 2-dimethylbutyrate, the HPLC content is 99.67%, and the molar yield is 98.24% in terms of 2, 2-dimethylbutyramide.

Examples 13 to 22

Examples 13 to 22 provide a method for synthesizing 2, 2-dimethylbutyric acid, which is the same as in examples 11 and 12, and the specific reaction conditions are shown in Table 2.

TABLE 2

Example 23

This example provides a method for synthesizing 2, 2-diethylbutyryl chloride:

adding 100mL of dichloromethane into a 250mL four-neck bottle provided with a mechanical stirrer, a thermometer and a condenser, then adding 23.35g (0.2mol) of 2, 2-dimethylbutyric acid, cooling to-5-0 ℃, introducing chlorine gas for 6-8h, maintaining the reaction temperature at-5-0 ℃, monitoring the complete reaction of the 2, 2-dimethylbutyric acid by liquid chromatography, stopping introducing the chlorine gas, blowing nitrogen gas to purge residual chlorine gas, removing a solvent to obtain 98.57% of crude 2, 2-dimethylbutyric chloride, and performing rectification under reduced pressure to obtain 25.65g of 2, 2-dimethylbutyric chloride product, 99.53% of HPLC (high performance liquid chromatography) content and 95.26% of molar yield based on the 2, 2-dimethylbutyric acid.

Examples 24 to 33

Examples 24 to 33 provide a method for synthesizing 2, 2-diethylbutyrylchloride, which is the same as in example 23, and the specific reaction conditions are shown in table 3.

TABLE 3

Example 34

The embodiment provides a synthesis method of methyl 2, 2-dimethylbutyrate:

adding 50g of anhydrous methanol into a 500mL four-mouth bottle provided with a mechanical stirrer, a thermometer and a condenser, then adding 116.5g (1.0mol) of 2, 2-dimethylbutyrate, heating to 70-90 ℃, adding a catalytic amount of concentrated sulfuric acid, carrying out reflux reaction for 1-2h, dropwise adding 90g of anhydrous methanol for 1-2h, simultaneously collecting fractions, keeping the balance of adding and collecting, carrying out reflux insulation reaction for 1-2h after the methanol is added, monitoring the complete reaction of the 2, 2-dimethylbutyrate by gas chromatography, cooling, standing, carrying out liquid separation, neutralizing an oil phase, washing with water and rectifying to obtain 122.56g of methyl 2, 2-dimethylbutyrate product, wherein the HPLC content is 99.09%, and the molar yield is 93.35% based on the 2, 2-dimethylbutyrate.

Examples 35 to 44

Examples 35 to 44 provide a method for synthesizing 2, 2-diethylbutyronitrile derivatives, which is the same as in example 34, and the specific reaction conditions are shown in Table 4.

TABLE 4

The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents or improvements made within the spirit and principle of the present invention should be included in the scope of the present invention.