Preparation method of pivalate
By using isobutanol, formic acid and concentrated sulfuric acid as raw materials, combined with fatty alcohol alcoholization and extraction separation methods, the equipment corrosion and high cost problems in the synthesis of existing valerate ester is solved, and low-cost and efficient valerate ester production is achieved, which is suitable for industrial applications.
Patent Information
- Application Number
- CN202510425677.8
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-04-07
- Publication Date
- 2025-07-08
AI Technical Summary
In the existing pivalate esters synthesis methods, strong acid catalysts are prone to corrosion of the equipment, and the azeotropic valerate raw materials and the generated ester lead to high separation and purification costs, and the pivaloyl chloride is high, which is not suitable for commercialization and is difficult to meet industrial needs.
Isobutanol and formic acid are used as raw materials to synthesize valerate by a one-pot method, concentrated sulfuric acid is used as catalyst, combined with fatty alcohol for alcoholization, and purification is reduced through extraction, layering and distillation.
It realizes low-cost, high yield and high purity valerate production, suitable for industrial production, mild reaction conditions, simple operation, and few wastes.
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Abstract
Description
Technical Field
[0001] The present invention belongs to the technical field of pivalate synthesis, and particularly relates to a method for preparing pivalate. Background Art
[0002] Pivalate is an excellent ester solvent, insoluble in water and highly soluble in ethanol and ether. It is mainly used as a solvent and diluent. Compared with common carbonate and carboxylate solvents, pivalate has good stability to acids and bases, a low freezing point, a wider liquid range, and excellent surface properties, and is widely used in industries such as spices, paints, coatings, varnishes, glues, and adhesives. In addition to traditional applications, it is gradually applied to fields such as lithium battery electrolytes, electronic chemicals, and biopharmaceuticals. And with the progress of technology and the change of market demand, its development prospect is very broad.
[0003] There are mainly two existing methods for synthesizing pivalate: one is to prepare it by dehydrating pivalic acid and fatty alcohol under the action of a strong acid catalyst. In this preparation method, the strong acid catalyst is easy to corrode the equipment, and the pivalic acid raw material and the generated ester are azeotropic, and the separation and purification cost is very high; the other is to prepare pivalate by reacting a derivative of pivalic acid such as acyl chloride with fatty alcohol. In this preparation method, the cost of pivaloyl chloride is high, it is not economical enough, and it is difficult to commercialize. Summary of the Invention
[0004] In view of this, to solve the above technical problems, the present invention proposes a method for preparing pivalate, which uses inexpensive isobutanol and formic acid as raw materials to synthesize pivalate by a one-pot method, with low production cost, high product yield, and at the same time having the advantages of low reaction temperature, mild conditions, simple process, and simple operation, and can meet the requirements of industrial production.
[0005] To achieve the above object, the technical solution of the present invention is realized as follows:
[0006] A method for preparing pivalate, which performs a condensation reaction using isobutanol, formic acid, and concentrated sulfuric acid as raw materials, and then performs alcoholysis with a fatty alcohol. After the reaction is completed, extraction and layering are carried out, and the organic phase is desolvated to obtain a crude pivalate product. The reaction formula is as follows:
[0007]
[0008] In some preferred embodiments of the method for preparing pivalate of the present invention, the specific steps are as follows:
[0009] S1. After mixing and formulating isobutanol and formic acid into a solution, slowly add it to concentrated sulfuric acid to perform a condensation reaction;
[0010] S2. Slowly add the solution after the reaction in S1 to a fatty alcohol to perform alcoholysis;
[0011] S3. Add an extractant to the solution after alcoholysis in S2, perform extraction and layering, and remove the solvent from the organic phase to obtain a crude pivalate product;
[0012] S4. Rectify and purify the crude pivalate product obtained in S3 to obtain a pure pivalate product.
[0013] In some preferred embodiments of the method for preparing pivalate of the present invention, in S1, the molar ratio of isobutanol, formic acid, and concentrated sulfuric acid is 1:1-2:5-9.
[0014] In some preferred embodiments of the method for preparing pivalate of the present invention, in S1, the molar ratio of isobutanol, formic acid, and concentrated sulfuric acid is 1:1.2-1.4:5.5-6.5.
[0015] In some preferred embodiments of the method for preparing pivalate of the present invention, in S1, the concentrated sulfuric acid is heated to 35-40 °C, and the mixed solution of isobutanol and formic acid is added dropwise to the concentrated sulfuric acid, and the reaction is carried out while maintaining the temperature at 45-50 °C.
[0016] In some preferred embodiments of the method for preparing pivalate of the present invention, in S2, the amount of fatty alcohol is calculated based on the molar ratio with isobutanol in S1, and fatty alcohol:isobutanol is 4-6:1.
[0017] In some preferred embodiments of the method for preparing pivalate of the present invention, in S2, the molar ratio of fatty alcohol to isobutanol is 5.6:1.
[0018] In some preferred embodiments of the method for preparing pivalate of the present invention, in S2, the temperature of the fatty alcohol is controlled at 5-10 °C, and the solution after the reaction in S1 cooled to below 20 °C is added dropwise to the fatty alcohol, and after the addition is completed, the mixture is stirred while maintaining the temperature for half an hour.
[0019] In some preferred embodiments of the method for preparing pivalate of the present invention, after the solution after the reaction in S1 is cooled to 8-10 °C, it is added dropwise to the fatty alcohol.
[0020] In some preferred embodiments of the method for preparing pivalate of the present invention, in S3, the extractant is one or a mixture of several of halogenated alkanes with a carbon chain of 1-4, carboxylic acid esters with a carbon chain of 1-4, and alkanes with a carbon chain of 5-10.
[0021] Compared with the prior art, the method for preparing pivalate of the present invention has the following advantages:
[0022] (1) The method for preparing pivalate of the present invention uses inexpensive isobutanol and formic acid as raw materials and synthesizes pivalate by a one-pot method, which has the advantages of low production cost, high product quality, simple operation, and less three wastes;
[0023] (2) In the method for preparing pivalate according to the present invention, isobutanol first undergoes a condensation reaction with formic acid and concentrated sulfuric acid to obtain an intermediate, and then alcoholysis is carried out with fatty alcohol. Compared with other processes, the reaction temperature is low, the reaction conditions are milder, and the process is more simplified, which can meet the requirements of industrial production. Description of the Drawings
[0024] Figure 1 1H NMR spectrum of the pivalate prepared in Example 1 of the present invention;
[0025] Figure 2 HPLC chromatogram of the pivalate product prepared in Example 1 of the present invention;
[0026] Figure 3 HPLC chromatogram of the pivalate product prepared in Example 2 of the present invention;
[0027] Figure 4 HPLC chromatogram of the pivalate product prepared in Example 3 of the present invention;
[0028] Figure 5 HPLC chromatogram of the pivalate product prepared in Example 4 of the present invention;
[0029] Figure 6 HPLC chromatogram of the pivalate product prepared in Example 5 of the present invention;
[0030] Figure 7 HPLC chromatogram of the pivalate product prepared in Example 6 of the present invention;
[0031] Figure 8 HPLC chromatogram of the pivalate product prepared in Example 7 of the present invention. Detailed Description of the Invention
[0032] Unless otherwise defined, the technical terms used in the following examples have the same meanings as commonly understood by those skilled in the art to which the present invention belongs. The test reagents used in the following examples are all conventional biochemical reagents unless otherwise specified; the experimental methods are all conventional methods unless otherwise specified.
[0033] The present invention will be described in detail below with reference to the examples and the drawings.
[0034] Example 1
[0035] The preparation of pivalate is carried out as follows:
[0036] S1. In a 500 ml reactor equipped with a thermometer, a constant-pressure dropping funnel, and a stirrer, add 642 g of concentrated sulfuric acid and heat up to 40 °C. After preparing a mixed solution of 74.12 g of isobutanol and 72.34 g of formic acid and adding it to the constant-pressure dropping funnel, slowly drip the isobutanol and formic acid mixed solution into the reactor. After 1 h, the dropping is completed, and keep the temperature at 50 °C for 2 h.
[0037] S2. Add 150 g of methanol to a 1000 ml reactor, control the temperature at 5 - 10 °C, cool the reaction solution after the completion of reaction S1 to 8 °C, and slowly drip it into the fatty alcohol. After 1 h, the dripping is completed, and keep stirring while maintaining the temperature for 30 min.
[0038] S3. Add 150 g of cyclohexane to the solution after alcoholysis in S2, stir for 10 min, perform liquid - liquid extraction and separation twice. The organic phase is distilled under normal pressure to recover the solvent for reuse in the next batch. Distill and recover at an oil bath temperature of 110 °C to obtain 84.36 g of crude methyl pivalate, and the crude product yield is 72.62%.
[0039] S4. Rectify the crude methyl pivalate twice to obtain 79.3 g of the finished product of methyl pivalate, and the finished product yield is 68.27%.
[0040] As Figure 1 shown, it is the NMR spectrum of the prepared finished product of methyl pivalate.
[0041] As Figure 2 shown, it is the HPLC chromatogram of the prepared finished product of methyl pivalate.
[0042] Example 2
[0043] The preparation of pivalate ester is as follows:
[0044] S1. In a 500 ml reactor equipped with a thermometer, a constant-pressure dropping funnel, and a stirrer, add 642 g of concentrated sulfuric acid and heat up to 45 °C. After preparing a mixed solution of 74.12 g of isobutanol and 64.94 g of formic acid and adding it to the constant-pressure dropping funnel, slowly drip the isobutanol and formic acid mixed solution into the reactor. After 1 h, the dropping is completed, and keep the temperature at 50 °C for 2 h.
[0045] S2. Add 150 g of methanol to a 1000 ml reactor, control the temperature at 5 - 10 °C, cool the reaction solution after the completion of reaction S1 to 8 °C, and slowly drip it into the fatty alcohol. After 1 h, the dripping is completed, and keep stirring while maintaining the temperature for 30 min.
[0046] S3. Add 150 g of chloroform to the solution after alcoholysis in S2, stir for 10 min, perform liquid - liquid extraction and separation twice. The organic phase is distilled under normal pressure to recover the solvent for reuse in the next batch. Distill and recover at an oil bath temperature of 110 °C to obtain 83.22 g of crude methyl pivalate, and the crude product yield is 71.64%.
[0047] S4 distills the crude methyl pivalate twice to obtain 78.23 g of the finished product of methyl pivalate, and the yield of the finished product is 67.35%.
[0048] As Figure 3 shown, it is the HPLC spectrum of the prepared finished product of methyl pivalate
[0049] Example 3
[0050] To prepare pivalic esters, the steps are as follows:
[0051] S1. In a 500 ml reactor equipped with a thermometer, a constant pressure dropping funnel and a stirrer, add 620 g of concentrated sulfuric acid and heat it up to 40 °C; after mixing 74.12 g of isobutanol and 81.22 g of formic acid to form a mixed solution, add it to the constant pressure dropping funnel, and slowly drop the mixed solution of isobutanol and formic acid into the reactor. After 1 h, the dropping is completed, and keep the temperature at 50 °C for 2 h;
[0052] S2. Add 150 g of methanol to a 1000 ml reactor, control the temperature at 5 - 10 °C, cool the reaction solution after the completion of reaction S1 to 8 °C, and slowly drop it into the fatty alcohol. After 1 h, the dropping is completed, and keep stirring for 30 min;
[0053] S3. Add 150 g of dichloromethane to the solution after alcoholysis in S2, stir for 10 min, extract and separate it twice. The organic phase is distilled under normal pressure to recover the solvent for reuse in the next batch; distill and recover it in an oil bath at 110 °C to obtain 84.5 g of crude methyl pivalate, and the yield of the crude product is 72.74%;
[0054] S4 distills the crude methyl pivalate twice to obtain 79.46 g of the finished product of methyl pivalate, and the yield of the finished product is 68.4%.
[0055] As Figure 4 shown, it is the HPLC spectrum of the prepared finished product of methyl pivalate
[0056] Example 4
[0057] To prepare pivalic esters, the steps are as follows:
[0058] S1. In a 500 ml reactor equipped with a thermometer, a constant pressure dropping funnel and a stirrer, add 500 g of concentrated sulfuric acid and heat it up to 40 °C; after mixing 74.12 g of isobutanol and 72.34 g of formic acid to form a mixed solution, add it to the constant pressure dropping funnel, and slowly drop the mixed solution of isobutanol and formic acid into the reactor. After 1 h, the dropping is completed, and keep the temperature at 50 °C for 2 h;
[0059] S2. Add 150 g of methanol to a 1000 ml reactor, control the temperature at 5 - 10 °C, cool the reaction solution after the completion of reaction S1 to 8 °C, and slowly drop it into the fatty alcohol. After 1 h, the dropping is completed, and keep stirring for 30 min;
[0060] S3. Add 150 g of dichloromethane to the solution after S2 alcoholysis, stir for 10 min, extract and separate layers twice. Recover the solvent by atmospheric distillation of the organic phase for use in the next batch. Distill and recover using an oil bath at 110 °C to obtain 79.8 g of crude methyl pivalate, with a crude product yield of 68.7%.
[0061] S4. Rectify the crude methyl pivalate twice to obtain 75.02 g of the finished product of methyl pivalate, with a finished product yield of 64.58%.
[0062] As Figure 5 shown, it is the HPLC chromatogram of the prepared finished product of methyl pivalate.
[0063] Example 5
[0064] To prepare pivalic esters, the steps are as follows:
[0065] S1. In a 500 ml reactor equipped with a thermometer, a constant pressure dropping funnel and a stirrer, add 750 g of concentrated sulfuric acid and heat up to 40 °C. After preparing a mixed solution of 74.12 g of isobutanol and 72.34 g of formic acid, add it to the constant pressure dropping funnel and slowly drop the isobutanol and formic acid mixture into the reactor. The dropping is completed after 1 h, and keep the temperature at 50 °C for 2 h.
[0066] S2. Add 150 g of methanol to a 1000 ml reactor, control the temperature at 5 - 10 °C, cool the reaction solution after S1 reaction to 8 °C, and slowly drop it into the fatty alcohol. The dropping is completed after 1 h, and keep stirring for 30 min.
[0067] S3. Add 150 g of dichloromethane to the solution after S2 alcoholysis, stir for 10 min, extract and separate layers twice. Recover the solvent by atmospheric distillation of the organic phase for use in the next batch. Distill and recover using an oil bath at 110 °C to obtain 84.06 g of crude methyl pivalate, with a crude product yield of 72.37%.
[0068] S4. Rectify the crude methyl pivalate twice to obtain 79.86 g of the finished product of methyl pivalate, with a finished product yield of 68.75%.
[0069] As Figure 6 shown, it is the HPLC chromatogram of the prepared finished product of methyl pivalate.
[0070] Example 6
[0071] To prepare pivalic esters, the steps are as follows:
[0072] S1. In a 500 ml reactor equipped with a thermometer, a constant pressure dropping funnel and a stirrer, add 588 g of concentrated sulfuric acid and heat up to 40 °C. After preparing a mixed solution of 74.12 g of isobutanol and 70.4 g of formic acid, add it to the constant pressure dropping funnel and slowly drip the mixed solution of isobutanol and formic acid into the reactor. After 1 h, the dropping is completed, and keep the temperature at 50 °C for 2 h.
[0073] S2. Add 180 g of ethanol to a 1000 ml reactor, control the temperature at 5 - 10 °C, cool the reaction solution after the completion of reaction S1 to 8 °C, and slowly drip it into the fatty alcohol. After 1 h, the dropping is completed, and keep stirring at a constant temperature for 30 min.
[0074] S3. Add 150 g of dichloromethane to the solution after alcoholysis in S2, stir for 10 min, extract and separate layers twice. The organic phase is distilled under normal pressure to recover the solvent for reuse in the next batch. Distill and recover at an oil bath temperature of 110 °C to obtain 115.46 g of crude methyl pivalate, and the crude product yield is 76.06%.
[0075] S4. Rectify the crude methyl pivalate twice to obtain 93.18 g of the finished product of methyl pivalate, and the finished product yield is 71.52%.
[0076] As Figure 7 shown, it is the HPLC spectrum of the prepared finished product of methyl pivalate.
[0077] Example 7
[0078] To prepare pivalate, the steps are as follows:
[0079] S1. In a 500 ml reactor equipped with a thermometer, a constant pressure dropping funnel and a stirrer, add 588 g of concentrated sulfuric acid and heat up to 40 °C. After preparing a mixed solution of 74.12 g of isobutanol and 70.4 g of formic acid, add it to the constant pressure dropping funnel and slowly drip the mixed solution of isobutanol and formic acid into the reactor. After 1 h, the dropping is completed, and keep the temperature at 50 °C for 2 h.
[0080] S2. Add 200 g of isopropanol to a 1000 ml reactor, control the temperature at 5 - 10 °C, cool the reaction solution after the completion of reaction S1 to 8 °C, and slowly drip it into the fatty alcohol. After 1 h, the dropping is completed, and keep stirring at a constant temperature for 30 min.
[0081] S3. Add 150 g of dichloromethane to the solution after alcoholysis in S2, stir for 10 min, extract and separate layers twice. The organic phase is distilled under normal pressure to recover the solvent for reuse in the next batch. Distill and recover at an oil bath temperature of 110 °C to obtain 112.65 g of crude methyl pivalate, and the crude product yield is 75.98%.
[0082] S4. Rectify the crude methyl pivalate twice to obtain 102.74 g of the finished product of methyl pivalate, and the finished product yield is 71.07%.
[0083] As Figure 8 shown, it is the HPLC spectrum of the prepared methyl pivalate finished product.
[0084] The yields and purities of the methyl pivalate synthesized in Examples 1 to 7 are shown in Table 1.
[0085] Table 1
[0086]
[0087]
[0088] It can be seen from Table 1 that when synthesizing pivalate using the synthesis method of the present invention, the crude product yield is between 68.7% and 76.06%, the finished product yield is between 64.58% and 71.52%, and the product purity is above 99.93%.
[0089] In summary, the present invention uses inexpensive isobutanol and formic acid as raw materials. While reducing the production cost, it can maintain a high yield and purity. Moreover, the alcoholysis reaction temperature is low, the conditions are mild, the process is simple, and there are few side reactions, making it suitable for industrial production.
[0090] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.
Claims
1. A method for preparing pivalate, characterized in that: Using isobutanol, formic acid, and concentrated sulfuric acid as raw materials, a condensation reaction is carried out, followed by alcoholysis with a fatty alcohol. After the reaction is completed, extraction and layering are performed, and the organic phase is desolvated to obtain a crude product of pivalic acid ester.
2. The method for preparing pivalate according to claim 1, wherein: The specific steps are as follows: S1. After mixing isobutanol and formic acid to prepare a solution, it is slowly added to concentrated sulfuric acid for a condensation reaction. S2. The solution after the reaction in S1 is slowly added to a fatty alcohol for alcoholysis. S3. An extractant is added to the solution after alcoholysis in S2, extraction and layering are performed, and the organic phase is desolvated to obtain a crude product of pivalic acid ester. S4. The crude product of pivalic acid ester obtained in S3 is rectified and purified to obtain a pure product of pivalic acid ester.
3. The method for preparing pivalate according to claim 2, characterized in that: In S1, the molar ratio of isobutanol, formic acid, and concentrated sulfuric acid is 1:1 - 2:5 - 9.
4. The method for preparing pivalate according to claim 3, characterized in that: In S1, the molar ratio of isobutanol, formic acid, and concentrated sulfuric acid is 1:1.2 - 1.4:5.5 - 6.
5.
5. The method for preparing pivalate according to claim 2, characterized in that: In S1, the concentrated sulfuric acid is heated to 35 - 40 °C, and the mixed solution of isobutanol and formic acid is added dropwise to the concentrated sulfuric acid, and the reaction is carried out under heat preservation at 45 - 50 °C.
6. The method for preparing pivalate according to claim 2, characterized in that: In S2, based on the molar ratio of the fatty alcohol to isobutanol in S1, the molar ratio of fatty alcohol:isobutanol is 4 - 6:
1.
7. The method for preparing pivalate according to claim 6, characterized in that: In S2, the molar ratio of fatty alcohol to isobutanol is 5.6:
1.
8. The method for preparing pivalate according to claim 2, wherein: In S2, the temperature of the fatty alcohol is controlled at 5 - 10 °C, and the solution after the reaction in S1 cooled to below 20 °C is added dropwise to the fatty alcohol. After the addition is completed, it is stirred under heat preservation for half an hour.
9. The method for preparing pivalate according to claim 8, characterized in that: After the solution after the reaction in S1 is cooled to 8 - 10 °C, it is added dropwise to the fatty alcohol.
10. The preparation method of pivalate according to claim 2, characterized in that: In S3, the extractant is one or a mixture of several of halogenated alkanes with a carbon chain of 1 - 4, carboxylic acid esters with a carbon chain of 1 - 4, and alkanes with a carbon chain of 5 - 10.