A process for the preparation of hexanediol bis[3-3,5-di-tert-butyl-4-hydroxyphenyl]propionate

Abstract

The application provides a preparation method of hexanediol bis[3-3,5-di-tert-butyl-4-hydroxyphenyl]propionate, comprising the following steps: step one, adding 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propyl methyl ester, 1,6-hexanediol and immobilized lipase Novozym435 into a reaction kettle, filling CO2, and performing enzyme catalysis transesterification reaction in a supercritical CO2 state; step two, filtering the reaction liquid in step one, recycling and repeatedly using the filter cake which is the catalyst immobilized lipase Novozym435, and performing column chromatography treatment on the filtrate; step three, according to the separation conditions of each component in the reaction liquid sample in step one in thin layer chromatography or liquid chromatography, combining the target collection liquid in the column chromatography process and removing the solvent again; combining and removing the solvent of other collection liquids, and repeatedly participating in the reaction of the remaining substances; and step four, drying the remaining substances of the target collection liquid in step three to obtain a target product.

Description

Technical Field

[0001] This invention relates to the field of chemical synthesis technology, specifically to a method for preparing hexanediol bis[3-3,5-di-tert-butyl-4-hydroxyphenyl]propionate. Background Technology

[0002] During use, lubricating oil is exposed to oxygen and heat, generating free radicals and peroxides. These reactive intermediates undergo a series of reactions, ultimately forming deposits such as sludge and varnish in the engine, resulting in increased lubricating oil viscosity and increased engine wear. To effectively delay lubricating oil oxidation and extend oil change intervals, various shielding phenols have been added as antioxidants. However, with the rapid development of the automotive industry, higher demands are being placed on the antioxidant properties of oils, and traditional shielding phenol-based antioxidants can no longer meet the requirements for high-temperature operation.

[0003] Hexanediol bis[3,3,5-di-tert-butyl-4-hydroxyphenyl]propionate is a phenolic ester-type high-temperature ashless antioxidant. This antioxidant is obtained by transesterification of methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate with 1,6-hexanediol. By adding ester groups at the para-position of the hydroxyl group, it overcomes the defects of poor thermal stability and easy volatility of traditional shielding phenolic antioxidants. It can effectively control oxidation and high-temperature deposition in petroleum products.

[0004] Regarding the synthesis of hexanediol bis[3,3,5-di-tert-butyl-4-hydroxyphenyl]propionate, domestic and international literature reports all use methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate and 1,6-hexanediol as raw materials. The catalysts used are mostly conventional transesterification catalysts, including acidic catalysts (such as sulfuric acid), basic catalysts (alkali metal compounds, alkali metal alkoxides, etc.), and organotin compounds (dibutyltin oxide, dibutyltin maleate, etc.). Patent document US 3644482A uses LiH as a catalyst, but this catalyst has low catalytic activity. Patent document US 4228297A uses a mixture of potassium tert-butoxide and LiOH as a catalyst, and also faces the same problems mentioned above. Chinese literature reports the use of dibutyltin oxide as a catalyst, with an optimal reaction temperature of 120–140℃ to prepare hexanediol bis[3,3,5-di-tert-butyl-4-hydroxyphenyl]propionate, resulting in a significant improvement in reaction conversion.

[0005] The patents and literature currently found mainly utilize acids, bases, and organotin compounds as catalysts to directly transesterify methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate with 1,6-hexanediol under normal or low pressure to obtain a reaction mixture. Subsequent crystallization and purification processes yield the target product. However, this approach has the following three main drawbacks:

[0006] First, the production process involves high temperatures. In the synthesis process described in the aforementioned patents and literature, the transesterification reaction needs to be completed at high temperatures. This increases energy consumption and wastes energy; furthermore, the reaction solution is prone to oxidation and deterioration at higher temperatures, affecting the number of mother liquor cycles and product quality.

[0007] Secondly, the separation of products from the reaction mixture is difficult. The synthesized reaction mixture contains raw materials and intermediate products, including substituted monoester thiols, requiring multiple steps such as crystallization, filtration, washing, and drying to obtain a qualified product, making the production process cumbersome. Furthermore, during crystallization, the mother liquor easily forms paste-like agglomerates, which encapsulate impurities and the mother liquor, directly affecting the purity of the finished product.

[0008] Third, catalysts cause environmental pollution. The acids, bases, and organotin catalysts used in the transesterification process cannot be recovered and reused, and their direct discharge causes environmental pollution.

[0009] The aforementioned defects have greatly limited the industrialization of hexanediol bis[3-3,5-di-tert-butyl-4-hydroxyphenyl]propionate. Summary of the Invention

[0010] To address the shortcomings mentioned above, this invention provides a method for preparing hexanediol bis[3,3,5-di-tert-butyl-4-hydroxyphenyl]propionate, comprising the following steps:

[0011] Step 1: Add methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate, 1,6-hexanediol and immobilized lipase Novozym435 into the reaction vessel, purge with CO2, and carry out the enzyme-catalyzed transesterification reaction under supercritical CO2 conditions.

[0012] Step 2: Filter the reaction solution from Step 1. The filter cake, which is the catalyst-immobilized lipase Novozym435, is recovered and reused. The filtrate is then subjected to column chromatography.

[0013] Step 3: Based on the separation of each component in the reaction solution sample from Step 1 in thin-layer chromatography or liquid chromatography, combine the target collected liquids from the column chromatography process and then remove the solvent; combine the other collected liquids and also remove the solvent, and the residues are reused in the reaction.

[0014] Step 4: Dry the residue of the target collected liquid from Step 3 to obtain the target product.

[0015] As a further improvement of the present invention, the molar ratio of methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate to 1,6-hexanediol in step one is 2.0:1 to 2.2:1; specifically, the molar ratio of methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate to 1,6-hexanediol in step one is selected from: 2.0:1, 2.1:1 or 2.2:1.

[0016] As a further improvement of the present invention, the mass of the immobilized lipase Novozym435 added in step one is 5% to 15% of the mass of methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate; specifically, the ratio of the mass of the immobilized lipase Novozym435 to the mass of methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate added in step one is selected from: 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, and 15%.

[0017] As a further improvement of the present invention, the reactor in step one is a high-pressure reactor, the pressure of CO2 being introduced is 10 MPa to 20 MPa, and the temperature inside the reactor is 60 to 100°C; specifically, the pressure of CO2 being introduced is selected from: 10 MPa, 12 MPa, 14 MPa, 16 MPa, 18 MPa or 20 MPa, and the temperature inside the reactor is selected from: 60, 70, 80, 90 or 100°C.

[0018] As a further improvement of the present invention, the reaction time in step one is 10 to 20 hours; specifically, the reaction time in step one is selected from 10, 12, 14, 16, 18 or 20 hours.

[0019] As a further improvement of the present invention, the column chromatography process in step two is as follows:

[0020] Place defatted cotton at the bottom of the chromatography column and press it down to remove air bubbles. Weigh the packing material and put it in a container. Add solvent to disperse the packing material, stir and remove air bubbles. Close the stopcock of the chromatography column. Homogenize the packing mixture in the container and pack it into the column using the wet packing method. Allow the packing material to settle naturally. Once the packing material has been tapped to compact the column, open the stopcock of the chromatography column to release excess organic solvent. Maintain the liquid level at the top of the chromatography column at 0.5–1.0 cm. Fill the column with packing material to 3 / 4 of its height. Place defatted cotton at the top of the chromatography column.

[0021] Add solvent to the reaction solution obtained in step one, slowly feed the reaction solution onto the top of the chromatography column, immediately rinse the adhering material on the inner wall of the chromatography column with solvent, and then elute with eluent.

[0022] As a further improvement of the present invention, both the solvent and the eluent are methanol.

[0023] As a further improvement of the present invention, the filler is C18 silicone.

[0024] As a further improvement of the present invention, the flow rate of the eluent is controlled at 0.5-2.0 mL / min; specifically, the flow rate of the eluent is selected from: 0.5, 0.7, 0.9, 1.0, 1.2, 1.4, 1.6, 1.8 or 2.0 mL / min.

[0025] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0026] 1. Using immobilized lipase as a catalyst, the reaction is easy to recover after completion, and it can be reused multiple times after washing, which has the advantage of being environmentally friendly.

[0027] 2. The reaction is carried out in supercritical CO2 fluid, which allows the immobilized lipase to come into full contact with the reactants, improving the reaction conversion rate and maintaining the reaction at a lower temperature to avoid high-temperature oxidation and discoloration of the reaction solution. Unreacted raw materials can be continuously recycled for feeding. In addition, supercritical CO2 has the advantages of being non-toxic, odorless, chemically stable, and widely available.

[0028] 3. The purification stage changes the traditional crystallization purification method and uses column chromatography to purify the reaction solution. The traditional crystallization process requires multiple steps such as crystallization, filtration, washing, and drying, which is cumbersome and results in a low product yield, generally around 80%. Column chromatography is simple to operate, and the product can be effectively separated from the reaction solution, which can significantly improve the product yield to over 95% and the purity of the separated product can reach over 99%, making it easy to obtain high-quality products.

[0029] 4. In traditional crystallization processes, the drying temperature of solid materials must be below the product's melting point, resulting in a long drying time. Products purified by column chromatography can be directly descaled to remove solvents and granulated, greatly shortening the drying time and improving production efficiency. Attached Figure Description

[0030] Figure 1 This is a process flow diagram of a method for preparing hexanediol bis[3-3,5-di-tert-butyl-4-hydroxyphenyl]propionate according to an embodiment of the present invention. Detailed Implementation

[0031] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0032] It should be noted that: "3,5-methyl ester" in the text is the abbreviation of "methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate", "diester" is "hexanediol bis[3,3,5-di-tert-butyl-4-hydroxyphenyl]propionate", and "monoester" is "hexanediol [3,3,5-di-tert-butyl-4-hydroxyphenyl]propionate" obtained by insufficient reaction of raw materials.

[0033] Preparation process of hexanediol bis[3,3,5-di-tert-butyl-4-hydroxyphenyl]propionate

[0034] like Figure 1 As shown, a method for preparing hexanediol bis[3,3,5-di-tert-butyl-4-hydroxyphenyl]propionate includes:

[0035] Step 1: Methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate, 1,6-hexanediol, and immobilized lipase Novozym435 are added to the reaction vessel, CO2 is introduced, and the enzyme-catalyzed transesterification reaction is carried out under supercritical CO2 conditions; the reaction vessel is a high-pressure reaction vessel.

[0036] Step 2: Filter the reaction solution from Step 1. The filter cake is the catalyst-immobilized lipase Novozym435, which can be recovered and reused. Perform column chromatography on the filtrate.

[0037] Step 3: Based on the separation of each component in the reaction solution sample from Step 1 in thin-layer chromatography or liquid chromatography, combine the target collected liquids from the column chromatography process and then remove the solvent under reduced pressure; combine the other collected liquids and remove the solvent under reduced pressure as well, and the residues are reused in the reaction.

[0038] Step 4: Dry the residue of the target collected liquid from Step 3 to obtain the target product.

[0039] Example 1: Preparation of hexanediol bis[3,3,5-di-tert-butyl-4-hydroxyphenyl]propionate

[0040] According to the process flow, 100.00g of weighed methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate, 20.21g of 1,6-hexanediol, and 10g of immobilized lipase Novozym435 were added to the high-pressure reactor. After the feeding was completed, 10 MPa of CO2 was introduced into the reactor, the reactor temperature was adjusted to 80℃, and the reaction was maintained for 10 hours. After the reaction was completed, the pressure was reduced and the materials were discharged to obtain "reaction solution 1". Reaction solution 1 was purified by column chromatography to obtain "solid 1".

[0041] Example 2: Preparation of hexanediol bis[3,3,5-di-tert-butyl-4-hydroxyphenyl]propionate

[0042] The amount of immobilized lipase Novozym435 added in Example 1 was changed from 10g to 5g, while the rest remained the same as in Example 1, to obtain "reaction solution 2". Reaction solution 2 was purified by column chromatography to obtain "solid 2".

[0043] Example 3: Preparation of hexanediol bis[3,3,5-di-tert-butyl-4-hydroxyphenyl]propionate

[0044] The amount of 1,6-ethylene glycol in Example 1 was changed from 20.21g to 19.25g, while the rest remained the same as in Example 1, to obtain "reaction solution 3". Reaction solution 3 was purified by column chromatography to obtain "solid 3".

[0045] Example 4: Preparation of hexanediol bis[3,3,5-di-tert-butyl-4-hydroxyphenyl]propionate

[0046] The reaction temperature in Example 1 was changed from 80℃ to 100℃, while the rest remained the same as in Example 1, resulting in "reaction solution 4". Reaction solution 4 was purified by column chromatography to obtain "solid 4".

[0047] Example 5: Preparation of hexanediol bis[3,3,5-di-tert-butyl-4-hydroxyphenyl]propionate

[0048] The reaction time in Example 1 was changed from 10h to 20h, while the rest remained the same as in Example 1, to obtain "reaction solution 5". Reaction solution 5 was purified by column chromatography to obtain "solid 5".

[0049] Example 6: Preparation of hexanediol bis[3,3,5-di-tert-butyl-4-hydroxyphenyl]propionate

[0050] The CO2 pressure in Example 1 was changed from 10 MPa to 15 MPa, while the rest remained the same as in Example 1, to obtain "reaction solution 6". Reaction solution 6 was purified by column chromatography to obtain "solid 6".

[0051] Comparative Example 1: Preparation of hexanediol bis[3,3,5-di-tert-butyl-4-hydroxyphenyl]propionate

[0052] 100.00 g of methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate, 20.21 g of 1,6-hexanediol, and 1 g of dibutyltin oxide were added to a four-necked flask equipped with a stirrer, condenser, thermometer, and nitrogen inlet. The air in the reactor was replaced with nitrogen, and the temperature was raised to 140°C. The reaction was maintained at this temperature for 6 hours. The vacuum pump was turned on, and the mixture was vacuum distilled to obtain "reaction solution 7". Reaction solution 7 was purified by ethanol crystallization, filtered, washed, and dried to obtain "solid 7".

[0053] Comparative Example 2: Preparation of hexanediol bis[3,3,5-di-tert-butyl-4-hydroxyphenyl]propionate

[0054] In Comparative Example 1, dibutyltin oxide was replaced with zinc acetate, while the rest remained the same as in Comparative Example 1, resulting in "reaction solution 8". Reaction solution 8 was purified by ethanol crystallization, filtered, washed, and dried to obtain "solid 8".

[0055] Comparative Experiment of Liquid Chromatography Detection and Analysis

[0056] The components of reaction solutions 1-8 and products 1-8 were analyzed using liquid chromatography, and the results are shown in the table below:

[0057] Table 1. Component analysis of reaction solutions 1-8

[0058]

[0059] Table 2. Component Analysis of Products 1-8

[0060]

[0061] in conclusion:

[0062] The method for preparing hexanediol bis[3,3,5-di-tert-butyl-4-hydroxyphenyl]propionate provided by this invention has the following advantages:

[0063] 1. Using immobilized lipase as a catalyst, the reaction is easy to recover after completion, and it can be reused multiple times after washing, which has the advantage of being environmentally friendly.

[0064] 2. The reaction is carried out in supercritical CO2 fluid, which allows the immobilized lipase to come into full contact with the reactants, improving the reaction conversion rate and maintaining the reaction at a lower temperature to avoid high-temperature oxidation and discoloration of the reaction solution. Unreacted raw materials can be continuously recycled for feeding. In addition, supercritical CO2 has the advantages of being non-toxic, odorless, chemically stable, and widely available.

[0065] 3. The purification stage changes the traditional crystallization purification method and uses column chromatography to purify the reaction solution. The traditional crystallization process requires multiple steps such as crystallization, filtration, washing, and drying, which is cumbersome and results in a low product yield, generally around 80%. Column chromatography is simple to operate, and the product can be effectively separated from the reaction solution, which can significantly improve the product yield to over 95%, and the purity of the separated product can reach over 99%, making it easy to obtain high-quality products.

[0066] 4. In traditional crystallization processes, the drying temperature of solid materials must be below the product's melting point, resulting in a long drying time. Products purified by column chromatography can be directly descaled to remove solvents and granulated, greatly shortening the drying time and improving production efficiency.

[0067] The above are merely preferred embodiments of the present invention and are not intended to limit the present invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A process for the preparation of hexanediol bis[3-3,5-di-tert-butyl-4- hydroxyphenyl]propionate, characterized in that, Includes the following steps: Step 1: Methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate, 1,6-hexanediol, and immobilized lipase Novozym435 are added to a reaction vessel, CO2 is introduced, and the enzyme-catalyzed transesterification reaction is carried out under supercritical CO2 conditions; wherein, the molar ratio of methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate to 1,6-hexanediol is 2.0:1~2.2:1, and the mass of immobilized lipase Novozym435 is 5%~15% of the mass of methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate; the reaction vessel is a high-pressure reaction vessel, the CO2 pressure is 10 MPa~20 MPa, the temperature inside the reaction vessel is 60~100℃, and the reaction time is 10~20 h; Step 2: Filter the reaction solution from Step 1. The filter cake, which is the catalyst-immobilized lipase Novozym435, is recovered and reused. The filtrate is then subjected to column chromatography. The column chromatography process is as follows: Place defatted cotton at the bottom of the chromatography column and press it down to remove air bubbles. Weigh the packing material and place it in a container. Add solvent to disperse the packing material, stir to remove air bubbles, close the stopcock of the chromatography column, and wet pack the mixture of packing material in the container into the column. Allow the packing material to settle naturally. The packing material is compacted by tapping, and the piston of the chromatography column is opened to release excess organic solvent. The liquid level at the top of the column is maintained at 0.5~1.0 cm. The packing material is filled to 3 / 4 of the column height, and defatted cotton is placed at the top of the column. The filtrate obtained in step one is filtered, and solvent is added. The material is slowly fed onto the top of the column, and the adhering material on the inner wall of the column is immediately rinsed with solvent. Then, elution is performed using eluent. The solvent and eluent are both methanol, and the packing material is C18 silica gel. Step 3: Based on the separation of each component in the reaction solution sample from Step 1 in thin-layer chromatography or liquid chromatography, combine the target collected liquids from the column chromatography process and then remove the solvent; combine the other collected liquids and also remove the solvent, and the residues are reused in the reaction. Step 4: Dry the residue of the target collected liquid from Step 3 to obtain the target product.

2. The production method according to claim 1, characterized by, The flow rate of the eluent is controlled at 0.5-2.0 mL / min.

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