Refining method of mono-tert-butyl glutarate
阅读说明：本技术 戊二酸单叔丁酯的精制方法 (Refining 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精制方法,属于化合物提纯技术领域。该戊二酸单叔丁酯的精制方法,包括以下步骤：取戊二酸单叔丁酯粗品,降温至-5～0℃,趁冷过滤,得一级滤液；将一级滤液降温至-15～-5℃,分层后趁冷过滤,得二级滤液,收集二级滤液,浓缩即得。该戊二酸单叔丁酯的精制方法采用冷冻精制的方法,解决了现有方法中多种无机盐水洗涤产生的三废多的问题,同时只使用少量石油醚提取,有机溶剂种类少,使用量少仅为粗品质量的0.2～0.4倍,简化了操作避免了柱层析的使用,环境友好,具有工业化应用前景。(The invention relates to a refining method of mono-tert-butyl glutarate, belonging to the technical field of compound purification. The refining method of the mono-tert-butyl glutarate comprises the following steps: taking a crude product of the mono-tert-butyl glutarate, cooling to-5-0 ℃, and filtering while the crude product is cold to obtain a first-stage filtrate; cooling the primary filtrate to-15 to-5 ℃, layering, filtering while the primary filtrate is cold to obtain secondary filtrate, collecting the secondary filtrate, and concentrating to obtain the product. The refining method of the mono-tert-butyl glutarate adopts a freezing refining method, solves the problem of more three wastes generated by washing various inorganic salt water in the prior art, simultaneously only uses a small amount of petroleum ether for extraction, has few organic solvents and small usage amount which is only 0.2-0.4 times of the mass of a crude product, simplifies the operation, avoids the use of column chromatography, is environment-friendly and has industrial application prospect.)
1. A method for purifying mono-tert-butyl glutarate, which is characterized by comprising the following steps:
1) taking a crude product of the mono-tert-butyl glutarate, cooling to-5-0 ℃, and filtering while the crude product is cold to obtain a first-stage filtrate;
2) cooling the primary filtrate obtained in the step 1) to-15 to-5 ℃, layering, filtering while the primary filtrate is cold to obtain secondary filtrate, collecting the secondary filtrate, and concentrating to obtain the product.
2. The method for purifying mono-tert-butyl glutarate according to claim 1, wherein the temperature in step 1) is reduced to-5 to 0 ℃ and then the temperature is maintained for 3 to 8 hours, followed by filtration.
3. The method for refining mono-tert-butyl glutarate according to claim 1, wherein the temperature in step 2) is reduced to-15 to-5 ℃, and then the temperature is maintained for 2 to 5 hours, followed by filtration.
4. The method of purifying mono-tert-butyl glutarate according to claim 1, wherein the filter paper and the filter are rinsed with tetrahydrofuran during the filtration in the steps 1) and 2) to attach the filter paper to the filter.
5. The method for purifying mono-tert-butyl glutarate according to claim 4, wherein the secondary filtrate is reduced in pressure and distilled at 50 to 60 ℃ for 6 to 8 hours, and then cooled.
6. The refining method of mono-tert-butyl glutarate according to claim 5, wherein the temperature of the secondary filtrate is reduced to-30 to-15 ℃, the secondary filtrate is filtered while being cold after layering, the filter paper and the filter are rinsed with tetrahydrofuran during filtering so that the filter paper is attached to the filter, the filter cake is washed with a solvent to obtain a tertiary filtrate, and the tertiary filtrate is collected and concentrated to obtain the final product.
7. The method for refining mono-tert-butyl glutarate according to claim 6, wherein the temperature is reduced to-30 to-15 ℃ and then kept for 4 to 6 hours, followed by filtration.
8. The method of purifying mono-tert-butyl glutarate according to claim 6, wherein the solvent is petroleum ether or n-hexane.
9. The method for purifying mono-tert-butyl glutarate according to claim 6, wherein the mass ratio of the solvent to the crude mono-tert-butyl glutarate is 0.1:1 to 0.4: 1.
Technical Field
The invention belongs to the technical field of synthetic substance purification, and particularly relates to a refining method of mono-tert-butyl glutarate.
Background
Glutarates are valuable industrial materials which are frequently used as solvents, plasticizers and intermediates for certain pharmaceuticals and pesticides. Among them, glutaric acid mono-tert-butyl ester has wide application due to its simple synthesis and easily available raw materials, and the purification of glutaric acid mono-tert-butyl ester is especially important.
The common synthetic methods of the glutaric acid mono-tert-butyl ester include the following methods:
the first method, as shown in formula 1, is to remove the active hydrogen of tert-butyl alcohol by n-butyl lithium under anhydrous and oxygen-free conditions, then to maintain low temperature, and to add tetrahydrofuran solution of glutaric anhydride, to synthesize the target product with high yield. However, the reaction conditions are harsh, the temperature needs to be low at-78 ℃, a solvent needs to be subjected to anhydrous and anaerobic treatment, n-butyllithium is a flammable and explosive hazardous chemical, a large amount of completely reacted n-butyllithium and excessive tert-butyl alcohol are not suitable to be purchased and stored, and the products prepared by the method mainly contain the completely reacted n-butyllithium and the excessive tert-butyl alcohol, so that the incompletely reacted n-butyllithium can bring potential safety hazards in the post-treatment process, and therefore, the purification method cannot be adopted for purification.
The second method, as shown in formula 2, adopts a Radical Alternative Reaction (radial alternating Reaction), uses AIBN as an initiator, sodium borohydride provides an alkaline environment, iodoacetic acid and tert-butyl acrylate as starting materials, and ethanol as a Reaction solvent, and can synthesize a target product. However, the reaction yields were low (22%) and sodium borohydride was an explosive controlled drug. Therefore, the experimental method is also difficult to apply to industrial production.
In the third method, as shown in formula 3, the tertiary butyl alcohol is used for synthesizing the mono-tertiary-butyl glutarate, and the byproducts of the reaction mainly comprise the tertiary butyl alcohol which does not participate in the reaction, zinc chloride and a small amount of organic solvent.
Currently, when the product of the third synthesis method is purified, there are two methods:
the first method is to pour the crude glutaric acid mono-tert-butyl ester into saturated NaHCO3In the aqueous solution and washed with chloroform,the aqueous phase was acidified with concentrated sulfuric acid and extracted with chloroform, and the combined organic phases were washed with brine, over Na2SO4Drying and concentrating. Various inorganic salts, chloroform and concentrated sulfuric acid are used, three wastes are more, the environmental pollution is larger, the purification loss is larger due to the complicated steps, and the product yield is lower.
In the second method, the crude glutaric acid mono-tert-butyl ester is diluted with ethyl acetate and then sequentially diluted with 5% NaHSO4The aqueous solution and brine were washed, and the organic layer was MgSO4Drying, filtering and concentrating, then carrying out column chromatography purification on the obtained mixture, and eluting with hexane/ethyl acetate. Uses various inorganic salts and organic solvents, and needs column chromatography purification, thus being not beneficial to large-scale production and having larger environmental pollution of three wastes.
Disclosure of Invention
The invention aims to provide a refining method of mono-tert-butyl glutarate, which adopts a freezing and purifying method, solves the problem of more three wastes caused by various inorganic salts, and obtains the mono-tert-butyl glutarate with higher purity.
In order to achieve the above purpose, the invention adopts the technical scheme that:
the refining method of the mono-tert-butyl glutarate comprises the following steps:
1) taking a crude product of the mono-tert-butyl glutarate, cooling to-5-0 ℃, and filtering while the crude product is cold to obtain a first-stage filtrate;
2) cooling the primary filtrate obtained in the step 1) to-15 to-5 ℃, layering, filtering while the primary filtrate is cold to obtain secondary filtrate, collecting the secondary filtrate, and concentrating to obtain the product.
Further, in the step 1), the temperature is reduced to-5-0 ℃, then the temperature is preserved for 3-8 hours, and then the filtration is carried out.
Further, the temperature in the step 2) is reduced to-15 to-5 ℃, then the temperature is preserved for 2 to 5 hours, and then the filtration is carried out.
Further, in the filtration in step 1) and step 2), the filter paper and the filter were rinsed with tetrahydrofuran to attach the filter paper to the filter.
Further, the secondary filtrate is subjected to reduced pressure distillation at 50-60 ℃ for 6-8 hours and then cooled.
Further, cooling the secondary filtrate to-30 to-15 ℃, filtering while the secondary filtrate is cold after layering, rinsing the filter paper and the filter by using tetrahydrofuran during filtering so that the filter paper is attached to the filter, washing a filter cake by using a solvent to obtain a tertiary filtrate, collecting the tertiary filtrate, distilling the tertiary filtrate at 50-60 ℃ under reduced pressure for 6-8 hours, and concentrating to obtain the product.
Further, the temperature is reduced to minus 30 to minus 15 ℃, then the temperature is preserved for 4 to 6 hours, and then the filtration is carried out.
Further, the solvent is petroleum ether or n-hexane.
Further, the mass ratio of the solvent to the crude product of the mono-tert-butyl glutarate is 0.1: 1-0.4: 1.
The invention has the beneficial effects that:
according to the refining method of the mono-tert-butyl glutarate, the mother liquor after reaction mainly contains tert-butyl alcohol which does not participate in the reaction, a small amount of zinc chloride and the target product of mono-tert-butyl glutarate, and the tert-butyl alcohol and the zinc chloride can be effectively removed through two times of low-temperature freezing and filtering. But a small amount of tetrahydrofuran for rinsing is introduced in the filtering process, because tetrahydrofuran is a good solvent of tert-butyl alcohol, when the filter paper is wetted by tetrahydrofuran, once the crude product is poured into a filter, the crude product is contacted with the filter paper, tert-butyl alcohol which is originally changed into solid is dissolved into tetrahydrofuran, the mixture is pumped into a filter flask along with the filtrate under reduced pressure, the secondary filtrate is heated and distilled under reduced pressure, the tert-butyl alcohol and the tetrahydrofuran are sufficiently removed, and then the secondary filtrate is frozen again, so that the excessive tert-butyl alcohol introduced by removing the tetrahydrofuran is reduced, and finally a pure product is obtained.
The refining method of the mono-tert-butyl glutarate adopts a freezing refining method, solves the problem of more three wastes generated by washing various inorganic salt water in the prior art, simultaneously uses a small amount of petroleum ether for washing, has less organic solvent types and less usage amount which is only 0.2-0.4 times of the mass of a crude product, simplifies the operation, avoids the use of column chromatography, is environment-friendly and has industrial application prospect.
Drawings
FIG. 1 is a gas chromatogram of purified mono-tert-butyl glutarate obtained in example 1;
FIG. 2 shows an embodiment1 purification of mono-tert-butyl glutarate1H NMR spectrum;
FIG. 3 shows the preparation of mono-tert-butyl glutarate obtained in comparative example 11H NMR spectrum.
Detailed Description
The present invention will be further described with reference to the following examples and accompanying drawings.
Example 1
The refining method of the mono-tert-butyl glutarate comprises the following steps:
1) 500g of a crude product of the mono-tert-butyl glutarate with the mass content of 66% of the mono-tert-butyl glutarate in the crude product of the mono-tert-butyl glutarate is taken, the crude product of the mono-tert-butyl glutarate is placed in a refrigerator, the temperature is reduced to-5 ℃, the temperature is kept for 3 hours, the filtration is carried out while the product is cold, the filter paper and a Buchner funnel are rinsed by tetrahydrofuran so that the filter paper is attached to the Buchner funnel, and the filtrate is collected to obtain 400g of a primary filtrate.
2) Putting the primary filtrate obtained in the step 1) into a refrigerator again, cooling to-5 ℃, preserving heat for 5 hours, filtering while the primary filtrate is cold after layering, rinsing the filter paper and the Buchner funnel by using tetrahydrofuran so as to enable the filter paper to be attached to the Buchner funnel, and collecting the filtrate to obtain 335g of secondary filtrate.
3) Distilling the secondary filtrate obtained in the step 2) under reduced pressure at 60 ℃ for 8h, putting the secondary filtrate into a refrigerator again, cooling to-30 ℃, preserving heat for 4h, filtering while the secondary filtrate is cold after layering, rinsing the filter paper and a Buchner funnel by using tetrahydrofuran to enable the filter paper to be attached to the Buchner funnel, washing a filter cake by using 100g of petroleum ether, collecting the filtrate to obtain a tertiary filtrate, distilling the tertiary filtrate under reduced pressure at 60 ℃ for 8h, and concentrating to obtain 280g of mono-tert-butyl glutarate, wherein the yield is 85% and the purity is 95.2%.
The gas chromatogram of purified mono-tert-butyl glutarate is shown in FIG. 1.
The gas chromatography data are shown in table 1.
TABLE 1 gas chromatography data for mono-tert-butyl glutarate in example 1
Peak number
Retention time
Area of
Height
Area%
1
1.940
73477
26585
0.591
2
2.575
22722
6679
0.183
3
2.978
57706
16817
0.464
4
3.398
27145
6545
0.218
5
3.617
13670
4403
0.110
6
4.561
11830461
1004131
95.208
7
5.704
400731
93407
3.225
Total of
12425912
1158568
100
By passing1H NMR determination of structure and purity of the reaction product of example 1, glutaric acid mono-tert-butyl ester, the test solvent is deuterated chloroform, the result is shown in figure 2, the peak 1 corresponds to tert-butyl, 9 alpha-H of tert-butyl have the same nuclear magnetic environment and the same chemical shift, tert-butyl is terminal group and appears in high field, the main chain of the product has three methylene groups, two methylene groups are subjected to electron withdrawing action of carbon-oxygen double bond, and appear in low field, meanwhile, the electron withdrawing ability of hydroxyl group is stronger than that of tert-butyloxycarbonyl group, the electron withdrawing ability of hydroxyl group appears in low field and corresponds to methylene group 4, which corresponds to tert-butyloxycarbonyl group1Peak 4 and methylene three on the H NMR spectrum1And the third peak and the 2 peak on the H NMR spectrum correspond to methylene on the main chain, and the chemical shift of the 2 peak is smaller due to the shielding effect of the methylene. Glutaric acid mono-tert-butyl ester Using MestReNova softwareIs/are as follows1H NMR spectrum is analyzed, and chemical shifts of peaks are delta1＝1.45、δ2＝1.91、δ3＝2.32、δ4＝2.47、δ511.69, the integrated area ratio is 9: 2: 2: 2: 1, corresponds to the target product1H can be determined as the target product.
Example 2
The method for purifying mono-tert-butyl glutarate of the embodiment comprises the following steps:
1) taking 500g of a crude product of the mono-tert-butyl glutarate, wherein the mass content of the mono-tert-butyl glutarate in the crude product of the mono-tert-butyl glutarate is 70%, placing the crude product of the mono-tert-butyl glutarate in a refrigerator, cooling to-2 ℃, preserving heat for 5 hours, filtering while the product is cold, rinsing the filter paper and a Buchner funnel by using tetrahydrofuran so as to enable the filter paper to be attached to the Buchner funnel, and collecting the filtrate to obtain 450g of a primary filtrate;
2) putting the primary filtrate obtained in the step 1) into a refrigerator again, cooling to-10 ℃, preserving heat for 3h, filtering while the filter paper and the Buchner funnel are cold after layering, rinsing the filter paper and the Buchner funnel by using tetrahydrofuran to attach the filter paper to the Buchner funnel, and collecting the filtrate to obtain 359g of secondary filtrate;
3) distilling the secondary filtrate obtained in the step 2) at 50 ℃ under reduced pressure for 8h, putting the secondary filtrate into a refrigerator again, cooling to-30 ℃, preserving heat for 4h, filtering while the secondary filtrate is cold after layering, washing a filter cake with 100g of petroleum ether, collecting the filtrate to obtain a tertiary filtrate, distilling the tertiary filtrate at 50 ℃ under reduced pressure for 8h, and concentrating to obtain 305g of mono-tert-butyl glutarate with the yield of 87% and the purity of 95.5%.
Example 3
The method for purifying mono-tert-butyl glutarate of the embodiment comprises the following steps:
1) 500g of a crude product of the mono-tert-butyl glutarate with the mass content of 60% of the mono-tert-butyl glutarate in the crude product of the mono-tert-butyl glutarate is taken, the crude product of the mono-tert-butyl glutarate is placed in a refrigerator, the temperature is reduced to 0 ℃, the temperature is kept for 8 hours, the filtration is carried out while the product is cold, the filter paper and a Buchner funnel are rinsed by using tetrahydrofuran so that the filter paper is attached to the Buchner funnel, and the filtrate is collected to obtain 410g of a primary filtrate.
2) Putting the primary filtrate obtained in the step 1) into a refrigerator again, cooling to-15 ℃, preserving heat for 2 hours, layering, filtering while cold, rinsing the filter paper and the Buchner funnel by using tetrahydrofuran so as to enable the filter paper to be attached to the Buchner funnel, and collecting the filtrate to obtain 361g of secondary filtrate.
3) Distilling the secondary filtrate obtained in the step 2) at 60 ℃ under reduced pressure for 6h, putting the secondary filtrate into a refrigerator again, cooling to-15 ℃, preserving heat for 6h, layering, filtering while the secondary filtrate is cold, washing a filter cake with 180g of petroleum ether, collecting the filtrate to obtain a tertiary filtrate, distilling the tertiary filtrate at 60 ℃ under reduced pressure for 6h, and concentrating to obtain 243g of mono-tert-butyl glutarate with the yield of 81% and the purity of 94.3%.
Comparative example 1
The method for refining the mono-tert-butyl glutarate of the comparative example comprises the following steps:
1) 500g of a crude product of the mono-tert-butyl glutarate with the mass content of 66% of the mono-tert-butyl glutarate in the crude product of the mono-tert-butyl glutarate is taken, the crude product of the mono-tert-butyl glutarate is placed in a refrigerator, the temperature is reduced to-5 ℃, the temperature is kept for 3h, the filtration is carried out while the product is cold, the filter paper and a Buchner funnel are rinsed by using tetrahydrofuran during the filtration so that the filter paper is attached to the Buchner funnel, and the filtrate is collected to obtain 400g of a primary filtrate.
2) Putting the primary filtrate obtained in the step 1) into a refrigerator again, cooling to-5 ℃, preserving heat for 5 hours, filtering while the primary filtrate is cold after layering, rinsing the filter paper and a Buchner funnel by using tetrahydrofuran during filtering so as to enable the filter paper to be attached to the Buchner funnel, collecting the filtrate to obtain 335g of secondary filtrate, and concentrating to obtain 264g of mono-tert-butyl glutarate with the yield of 80% and the purity of 92.5%.
The NMR of the mono-tert-butyl glutarate obtained in comparative example 1 is shown in FIG. 3. As can be seen from FIG. 3, peaks 1 to 4 are substantially identical to the NMR shown in FIG. 2, and correspond to 9. alpha. -H atoms (peak 1,. delta.) of tert-butyl11.45) and three methylene groups (. delta.) in the main chain of the product2＝1.88、δ3＝2.29、δ42.40), hydrogen No. 5 is an active hydrogen, appearing as a broad peak (broad), δ510.25. In addition, the peak at δ of 3.68ppm is tetrahydrofuranCharacteristic peak in deuterated chloroform. It can be seen that after the second refrigeration and filtration, tetrahydrofuran remained.
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