阅读说明：本技术 戊二酸单叔丁酯的制备方法 (Preparation method of mono-tert-butyl glutarate ) 是由 不公告发明人 于 2021-09-14 设计创作，主要内容包括：本发明涉及一种戊二酸单叔丁酯的制备方法,属于化合物合成技术领域。戊二酸单叔丁酯的制备方法,包括以下步骤：取叔丁醇和路易斯酸催化剂加入反应器中,搅拌均匀,之后加入第一批戊二酸酐,在40～55℃条件下进行第一步反应,反应结束后将反应温度降至20～30℃,之后加入第二批戊二酸酐,在55～80℃条件下进行第二步反应,反应结束后提纯即得。该戊二酸单叔丁酯的制备方法,以路易斯酸作为催化剂,该方法不再使用正丁基锂拔除叔丁醇的活泼氢,无需低温反应,反应过程可控性好。在空气中反应替代传统的无水无氧的苛刻反应条件,方法简单、操作简便、产品收率高等优点,具有更好的批量化制备能力,具备很好的工业化应用前景。(The invention relates to a preparation method of mono-tert-butyl glutarate, belonging to the technical field of compound synthesis. The preparation method of the mono-tert-butyl glutarate comprises the following steps: adding tert-butyl alcohol and a Lewis acid catalyst into a reactor, uniformly stirring, then adding a first batch of glutaric anhydride, carrying out a first-step reaction at 40-55 ℃, reducing the reaction temperature to 20-30 ℃ after the reaction is finished, then adding a second batch of glutaric anhydride, carrying out a second-step reaction at 55-80 ℃, and purifying after the reaction is finished. According to the preparation method of the mono-tert-butyl glutarate, the Lewis acid is used as the catalyst, n-butyllithium is not used for removing active hydrogen of tert-butyl alcohol, low-temperature reaction is not needed, and the controllability of the reaction process is good. The reaction in the air replaces the traditional anhydrous and anaerobic harsh reaction conditions, and the method has the advantages of simplicity, simple and convenient operation, high product yield and the like, has better batch preparation capacity, and has good industrial application prospect.)

1. The preparation method of the mono-tert-butyl glutarate is characterized by comprising the following steps: adding tert-butyl alcohol and a Lewis acid catalyst into a reactor, uniformly stirring, then adding a first batch of glutaric anhydride, carrying out a first-step reaction at 40-55 ℃, reducing the reaction temperature to 20-30 ℃ after the reaction is finished, then adding a second batch of glutaric anhydride, carrying out a second-step reaction at 55-80 ℃, and purifying after the reaction is finished.

2. The method of claim 1, wherein the Lewis acid catalyst is zinc chloride or aluminum chloride.

3. The method of claim 1, wherein the mass ratio of the first glutaric anhydride to the second glutaric anhydride is 3: 7.

4. The method for preparing mono-tert-butyl glutarate according to claim 1, wherein the molar ratio of tert-butyl alcohol to glutaric anhydride is 1.2:1 to 1.8:1, and the molar amount of glutaric anhydride is the sum of the first and second glutaric anhydrides.

5. The method for preparing mono-tert-butyl glutarate according to claim 1, wherein the molar ratio of glutaric anhydride to catalyst is 1: 0.01-1: 0.03, and the molar amount of glutaric anhydride is the sum of the first and second glutaric anhydrides.

6. The method for preparing mono-tert-butyl glutarate according to claim 1, wherein the reaction time of the first reaction step is 12-20 hours.

7. The method for preparing mono-tert-butyl glutarate according to claim 1, wherein the reaction time of the second reaction step is 23 to 49 hours.

8. The method for preparing mono-tert-butyl glutarate according to claim 1, wherein the purification method comprises: naturally cooling the reactor to 20-30 ℃, then cooling to-20-30 ℃, preserving heat for 12-18 h, filtering while cold to obtain filtrate, washing filter residues with iced petroleum ether, combining the filtrate and concentrating to obtain the catalyst.

Technical Field

The invention belongs to the technical field of compound synthesis, and particularly relates to a preparation method of mono-tert-butyl glutarate.

Background

Glutarates are valuable industrial materials commonly used as solvents, plasticizers, and intermediates for certain pharmaceuticals and pesticides. Among them, glutaric acid mono-tert-butyl ester is focused on by many reagent manufacturers due to its simple synthesis and easily available raw materials. However, most of the existing synthesis methods for the mono-tert-butyl glutarate require harsh conditions, low temperature of-30 ℃ or dangerous chemicals such as lithium aluminum hydride and the like, most of the yield is below 30%, the comprehensive yield is low, and the industrial scale production, popularization and application of the mono-tert-butyl glutarate are limited.

Glutaric acid mono-tert-butyl ester has high application value, and in the prior art, various methods for synthesizing glutaric acid mono-tert-butyl ester exist. The first method is as shown in formula 1, under the anhydrous and oxygen-free conditions, n-butyl lithium is used for removing active hydrogen of tertiary butanol, then the low temperature is maintained, and tetrahydrofuran solution of glutaric anhydride is added, so that the target product can be synthesized with high yield. But the reaction condition is harsh, the temperature needs to be low at minus 78 ℃, the solvent needs to be subjected to anhydrous and oxygen-free treatment, and the n-butyl lithium is a flammable and explosive hazardous chemical and is not suitable for being purchased and stored in large quantities.

The second method is shown in formula 2, and the target product can be synthesized by adopting a Radical Alternative Reaction (radial Alternative Reaction), AIBN (aluminum-boron nitride) as an initiator, sodium borohydride to provide an alkaline environment, iodoacetic acid and tert-butyl acrylate as initial raw materials and ethanol as a Reaction solvent. However, the reaction yield is 22%, the yield is low, and sodium borohydride is an easily explosive controlled drug.

And a third method is shown as formula 3, and the reaction conditions of the scheme are harsh, raw materials need to be subjected to anhydrous and anaerobic treatment, the product separation is difficult, and the post-treatment process is complicated.

The prior synthesis method has the problem of limiting the industrial scale production, popularization and application of the mono-tert-butyl glutarate.

Disclosure of Invention

The invention aims to provide a preparation method of mono-tert-butyl glutarate, which is simple and convenient to operate and high in product yield, solves the problems of harsh reaction conditions and low product yield, and has an industrial application prospect.

In order to achieve the above purpose, the invention adopts the technical scheme that:

the preparation method of the mono-tert-butyl glutarate comprises the following steps: adding tert-butyl alcohol and a Lewis acid catalyst into a reactor, uniformly stirring, then adding a first batch of glutaric anhydride, carrying out a first-step reaction at 40-45 ℃, reducing the reaction temperature to 20-30 ℃ after the reaction is finished, then adding a second batch of glutaric anhydride, carrying out a second-step reaction at 55-80 ℃, and purifying after the reaction is finished.

Further, the lewis acid catalyst is zinc chloride or aluminum chloride.

Further, the mass ratio of the first glutaric anhydride to the second glutaric anhydride is 3: 7.

Further, the molar ratio of the tert-butyl alcohol to the glutaric anhydride is 1.2: 1-1.8: 1, and the molar amount of the glutaric anhydride is the sum of the first glutaric anhydride and the second glutaric anhydride.

Further, the mole ratio of the glutaric anhydride to the catalyst is 1: 0.01-1: 0.03, and the mole amount of the glutaric anhydride is the sum of the first glutaric anhydride and the second glutaric anhydride.

Further, the reaction time of the first step reaction is 12-20 h.

Further, the reaction time of the second step reaction is 23-49 h.

Further, the purification method comprises the following steps: naturally cooling the reactor to 20-30 ℃, then cooling to-20-30 ℃, preserving heat for 12-18 h, filtering while cold to obtain filtrate, washing filter residues with iced petroleum ether, combining the filtrate and concentrating to obtain the catalyst.

The invention has the beneficial effects that:

according to the preparation method of the mono-tert-butyl glutarate, Lewis acid is used as a catalyst, n-butyllithium is not used for removing active hydrogen of tert-butyl alcohol, the reaction at the low temperature of-78 ℃ is not needed, the preparation method is simple and easy to operate, the potential safety hazard of operation in the using process of the reagent is reduced, and the controllability of the reaction process is good.

The reaction in the air replaces the traditional anhydrous and anaerobic harsh reaction conditions, and the method has the advantages of simplicity, simple and convenient operation, high product yield and the like, has better batch preparation capacity, and has good industrial application prospect.

Drawings

FIG. 1 is a nuclear magnetic hydrogen spectrum of mono-tert-butyl glutarate prepared in example 1.

Detailed Description

The present invention will be further described with reference to the following examples and accompanying drawings.

Example 1

The preparation method of mono-tert-butyl glutarate of the embodiment comprises the following steps:

under the condition of air, 1.71g of anhydrous zinc chloride and 143mL of tert-butyl alcohol are added into a reactor provided with a thermometer, a stirrer and a condenser, the mixture is stirred to be in a white emulsion state at 25 ℃, 28.8g of glutaric anhydride is added into the reactor after the mixture is stirred for 1h, the temperature is increased to 50 ℃ for carrying out the first-step reaction, the temperature is reduced to 25 ℃ after the first-step reaction is carried out for 20h, 67.2g of glutaric anhydride is added into the reactor, the temperature is increased to 70 ℃ for carrying out the second-step reaction, the second-step reaction is carried out for 28h, the reaction end point is confirmed by TLC detection, the reactor is naturally cooled to 25 ℃, the temperature is programmed to-20 ℃, the temperature is kept for 15h, the filtrate is obtained by filtering while the reactor is cold, filter residues are washed by iced petroleum ether, the combined filtrate is concentrated to obtain 124g of glutaric acid mono-tert-butyl ester product, and the yield is 79%.

The glutaric acid mono-tert-butyl ester product obtained in the example is characterized, and the obtained nuclear magnetic resonance hydrogen spectrum is shown in figure 1, and figure 1¹H NMR δ 1.37(s,9H),1.83(m,2H),2.20(t,2H),2.38(t, 2H). As can be seen from FIG. 1, the product of mono-tert-butyl glutarate obtained in this example is mono-tert-butyl glutarate.

Example 2

The preparation method of mono-tert-butyl glutarate of the embodiment comprises the following steps:

under the condition of air, 1.15g of anhydrous zinc chloride and 96mL of tert-butyl alcohol are added into a reactor provided with a thermometer, a stirrer and a condenser, the mixture is stirred to be in a white emulsion state at 30 ℃, 28.8g of glutaric anhydride is added into the reactor after the mixture is stirred for 3 hours, the temperature is increased to 40 ℃ for carrying out the first-step reaction, the temperature is reduced to 20 ℃ after the first-step reaction is carried out for 20 hours, 67.2g of glutaric anhydride is added into the reactor, the temperature is increased to 55 ℃ for carrying out the second-step reaction, the second-step reaction is carried out for 49 hours, the reaction end point is confirmed by TLC detection, the reactor is naturally cooled to 25 ℃, the temperature is reduced to-30 ℃ after the temperature is kept for 18 hours, the filtrate is obtained by filtering while the reactor is cold, filter residues are washed by iced petroleum ether, the combined filtrate is concentrated to obtain 118g of glutaric acid mono-tert-butyl ester product, and the yield is 75%.

Example 3

The preparation method of mono-tert-butyl glutarate of the embodiment comprises the following steps:

under the condition of air, 3.45g of anhydrous zinc chloride and 240.6mL of tertiary butyl alcohol are added into a reactor provided with a thermometer, a stirrer and a condenser, the mixture is stirred to be white emulsion at 20 ℃, 28.8g of glutaric anhydride is added into the reactor after stirring for 2 hours, the temperature is increased to 55 ℃ for carrying out the first-step reaction, the temperature is reduced to 30 ℃ after the first-step reaction is carried out for 12 hours, 67.2g of glutaric anhydride is added into the reactor, the temperature is increased to 80 ℃ for carrying out the second-step reaction, the second-step reaction is carried out for 23 hours, the reaction end point is confirmed by TLC detection, the reactor is naturally cooled to 25 ℃, the temperature is reduced to 0 ℃ by program, the temperature is kept for 12 hours, the filtrate is obtained by filtering while the reactor is cold, the filter residue is washed by iced petroleum ether, the combined filtrate is concentrated to obtain 133.8g of glutaric acid mono-tertiary butyl ester product, and the yield is 85%.

Comparative example 1

The crude chemical pure tert-butanol (source: Annage, packaged in a common reagent bottle) was added to the reaction flask in the proportion of example 1 without using standard Schlenk technique, and the mixture was stirred at 60 ℃ for 48 hours without using nitrogen gas to protect water and oxygen, and the final yield was 52.1% after the product was treated by the post-treatment method of example 1. As can be seen, the yield of mono-tert-butyl glutarate prepared by adding glutaric anhydride in two batches in example 1 is high.

Comparative example 2

Using standard Schlenk technology operation, adding 1.71g of anhydrous zinc chloride and 143mL of tert-butyl alcohol (ultra-dry) into a reactor provided with a thermometer, a stirrer and a condenser, stirring at 25 ℃ until the mixture is in a white emulsion state, stirring for 1h, adding 28.8g of glutaric anhydride into the reactor, heating to 50 ℃ for first-step reaction, cooling to 25 ℃ after 20h of first-step reaction, adding 67.2g of glutaric anhydride into the reactor, heating to 70 ℃ for first-step reaction, reacting for 28h in the first step, detecting by TLC to confirm the reaction end point, naturally cooling the reactor to 25 ℃, then cooling to-20 ℃ by program, preserving heat for 12h, filtering while cold to obtain filtrate, washing filter residues with iced petroleum ether, merging the filtrate, concentrating to obtain 130g of glutaric acid mono-tert-butyl ester product, wherein the yield is 83%. It can be seen that whether or not water oxygen is excluded has little effect on the yield of the reaction of the present invention.

Comparative example 3

The ratio of glutaric anhydride added in the first and second reactions was adjusted under the same conditions as in example 1, and the yields are shown in Table 1.

TABLE 1 yield at different feed ratios

Group of	Proportion of the feed	Yield/%
			1	1:9	63.2
2	2:8	66.3
			3	4:6	69.5
4	5:5	69.0
			5	6:4	68.2
6	7:3	68.6
			7	8:2	69.8
8	9:1	69.0

The feeding proportion is the adding proportion of glutaric anhydride in the first step reaction and the second step reaction. Example 1 the addition ratio of glutaric anhydride for the first reaction and the second reaction was 3:7, and the yield was 79%, and it can be seen from table 1 that when the addition ratio of glutaric anhydride for the first reaction and the second reaction was adjusted to other ratios, the yield was significantly reduced.