Preparation method of sorbitan trioleate

Abstract

The invention discloses a preparation method of sorbitan trioleate, which comprises the following steps: preparing a complexing adsorbent by using SiO2 as an adsorbent carrier and AgNO3 and CuCl2 as active components, purifying oleic acid by using the complexing adsorbent and methanol to realize refining of the oleic acid, and finally preparing the sorbitan trioleate by using the refined oleic acid. The refined oleic acid is obtained by purifying and refining the common oleic acid, and the product prepared by replacing the common oleic acid with the high-purity refined oleic acid not only reduces the reaction temperature and shortens the reaction time, but also is light in color and good in flowability.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceutical excipient preparation, in particular to a method for preparing sorbitan trioleate. Background Art

[0002] Sorbitan trioleate is a mixture of sorbitol and oleic acid esterified in a certain ratio. From the chemical structure, this type of surfactant is a partial fatty acid ester of polyols, a non-ionic surfactant, and an excellent water-in-oil or oil-in-water type surfactant. This type of surfactant is widely used as an emulsifier, lubricant, wetting agent, dispersant, thickener, etc.

[0003] There are generally two production processes for sorbitan trioleate in traditional technology: one is a two-step method: sorbitol is cycloetherified under the action of an acidic catalyst, and then oleic acid and an alkaline catalyst are added for esterification. The preparation steps of this process are complicated, a large amount of colloid is generated in the product, and the colloid needs to be removed, resulting in a large loss of product; the second method is a one-step method: using an alkaline catalyst, sorbitol and oleic acid are directly fed, and then the temperature is raised, and the etherification and esterification reactions are carried out simultaneously, but there is still sorbitol that has not undergone etherification reaction, and the appearance of the prepared product is poor in fluidity, turbidity, and more by-products. With the continuous improvement of application demand, the purity and color requirements of sorbitan trioleate are getting higher and higher. In order to better meet market demand, it is particularly urgent to develop a process for preparing sorbitan trioleate with high-purity oleic acid.

[0004] Patent CN1431185A discloses the use of oleic acid and acetone to mix to obtain unsaturated fatty acids, and then urea and methanol are used to purify unsaturated fatty acids to obtain high-purity oleic acid. This method has a strong effect on the separation and purification of saturated fatty acids, but it requires the use of a large amount of organic solvents, which is not only costly but also harmful to the environment. Patent CN113149936A discloses stirring and heating sorbitol, oleic acid, sodium hydroxide, phosphoric acid / phosphorous acid in a reactor, and heat-insulating the reaction to obtain trioleic acid sorbitan. This method has stable quality, is easy to control, and has low product loss. Since the esterification reaction is carried out at a high temperature of about 200°C, and oleic acid has a large number of unsaturated double bonds, oxidation reactions are very likely to occur during the esterification process, resulting in a darker product color. Directly using the method of patent CN113149936A for esterification, the product color has a darker color, which often cannot meet customer requirements or has an adverse effect on its subsequent application, so it is very necessary to control the color of the product. Summary of the invention

[0005] In view of the shortcomings of the prior art, the present invention provides a method for preparing sorbitan trioleate, aiming to solve the problems of high reaction temperature, long reaction time, dark color and poor fluidity of sorbitan trioleate.

[0006] To achieve the above object, the technical solution adopted by the present invention is: A method for preparing sorbitan trioleate comprises the following steps: (1) Preparation of complex adsorbent: the active salt and the carrier are mixed and impregnated in a solvent, and then calcined to obtain a complex adsorbent; the active salt is one or a mixture of AgNO3 or CuCl2; the carrier is SiO2; (2) Oleic acid purification: the complexing adsorbent and oleic acid are mixed and reacted at 40-60°C, followed by solid-liquid separation; (3) Elution: eluting the solid product obtained in step (2) with methanol to obtain an eluate, and removing the solvent from the eluate to obtain high-purity oleic acid; (4) Refining of oleic acid: the high-purity oleic acid obtained in step (3) is mixed with urea and an antioxidant in methanol at 40-60° C., then cooled, and then solid-liquid separated to obtain crystals. The crystals are added with hot water, stirred evenly, and then allowed to stand for stratification. The oil layer is dehydrated to obtain refined oleic acid. (5) Preparation of sorbitan trioleate: The refined oleic acid, sorbitol, esterification catalyst and etherification catalyst are mixed and heated to 180-220°C for reaction. After the reaction is completed, a water absorbent is added to remove water. After the water removal reaches the standard, the mixture is filtered to obtain sorbitan trioleate.

[0007] Preferably, in step (1), the mass ratio of the carrier to the active salt is 1:0.4-0.8.

[0008] Preferably, the solvent in step (1) is water.

[0009] Preferably, the calcination temperature in step (1) is 600-1000°C.

[0010] Preferably, the solid-liquid separation method in step (2) is centrifugation.

[0011] Preferably, the mass ratio of the methanol used in step (3) to the oleic acid used in step (2) is 5-15:1.

[0012] Preferably, step (3) further comprises the step of recovering the complex adsorbent after elution.

[0013] Preferably, the method for removing the solvent in step (3) is rotary evaporation.

[0014] Preferably, step (3) also includes a step of recovering the removed solvent.

[0015] Preferably, in step (4), the mass ratio of the high-purity oleic acid, the urea and the methanol is 1:3:6-10.

[0016] Preferably, the antioxidant in step (4) is antioxidant 168. More preferably, the antioxidant is MIANOX168.

[0017] Preferably, the amount of the antioxidant added in step (4) is 0.01% to 1.5%.

[0018] Preferably, the cooling temperature in step (4) is below -5°C.

[0019] Preferably, the mass ratio of the sorbitol to the refined oleic acid in step (5) is 1:2.5-4.5.

[0020] Preferably, in step (5), the esterification catalyst is sodium hydroxide, and the etherification catalyst is phosphorous acid.

[0021] Preferably, in step (5), the added amounts of the esterification catalyst and the etherification catalyst are 0.05-1.0% of the total mass of the sorbitol and the refined oleic acid, respectively.

[0022] Preferably, the reaction time in step (5) is 4 to 8 hours.

[0023] Preferably, step (5) further comprises the step of bubbling nitrogen onto the surface of the reaction mixture before the reaction.

[0024] Preferably, the dehydrating agent in step (5) is diatomaceous earth and magnesium polysilicate.

[0025] Preferably, the amount of diatomaceous earth and magnesium polysilicate used in step (5) is 1% of the total mass of sorbitol and refined oleic acid, respectively.

[0026] Compared with the prior art, the present invention has the following beneficial effects: (1) By purifying and refining ordinary oleic acid, the refined oleic acid obtained replaces ordinary oleic acid as the raw material to produce products, which not only reduces the reaction temperature but also shortens the reaction time.

[0027] (2) Oleic acid is adsorbed and separated by the prepared complex adsorbent, thereby reducing the amount of solvent used, greatly reducing the amount of organic solvent used, and enhancing the separation efficiency and oleic acid purity.

[0028] (3) The addition of refined oleic acid further optimizes the color of the product and enhances its fluidity. Refined oleic acid also has the characteristics of good stability and high safety.

[0029] (4) The addition of auxiliary antioxidants further lightened the color of the sorbitan trioleate solution.

[0030] (5) The process of the present invention is simple and economical. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 This is a process flow chart of Example 4 of the present invention.

[0032] Figure 2 This is a process flow chart of step (5) of Example 1. DETAILED DESCRIPTION

[0033] The present invention is not limited to the following specific embodiments. A person skilled in the art can implement the present invention in various other specific embodiments according to the content disclosed in the present invention, or any simple changes or modifications made to the design structure and ideas of the present invention fall within the protection scope of the present invention. It should be noted that the embodiments of the present invention and the features in the embodiments can be combined with each other without conflict. The present invention is further described in detail below in conjunction with the embodiments: Example 1

[0034] (1) Take 12g of AgNO3 and prepare a 10% aqueous solution. Then completely immerse 20g of SiO2 in the solution and calcine it at 800℃ for 3h to obtain a complex adsorbent.

[0035] (2) Take 12g of complex adsorbent and 60g of oleic acid and put them into a flask and stir evenly. The reaction temperature is 40℃. After stirring for 5h, centrifuge and take the filter cake after separation.

[0036] (3) Add 300 g of methanol to the filter cake for washing and desorption. After filtration, the adsorbent and filtrate are obtained. The filtrate is concentrated by rotary evaporation to obtain recovered methanol and high-purity oleic acid.

[0037] (4) Dissolve 141 g of urea in 470 g of methanol, add 0.1 g of antioxidant 168 and 47 g of high-purity oleic acid, heat to 50°C and stir, then cool to -5°C and filter under reduced pressure. Add hot water to the resulting crystals, stir evenly, let stand to separate, and vacuum dehydrate to obtain 43 g of refined oleic acid.

[0038] (5) A sorbitol solution with an effective sorbitol content of 10 g, 25 g of refined oleic acid, 0.035 g of phosphorous acid and 0.035 g of sodium hydroxide are added into a reaction container, stirred and heated; nitrogen is bubbled on the surface at 0.8 L / min, and then the reaction temperature is gradually and slowly raised to 180°C for esterification reaction. After the reaction is completed for 4 hours, 0.35 g of diatomaceous earth and 0.35 g of magnesium polysilicate are added for heat preservation and adsorption for 1 hour. After the moisture index is qualified, sorbitan trioleate is obtained after filtering through a filter. Example 2

[0039] (1) 12 g of the recovered adsorbent in Example 1 and 60 g of oleic acid were placed in a flask and stirred evenly. The reaction temperature was 40°C. After stirring for 5 h, the mixture was centrifuged and the filter cake was collected after separation.

[0040] (2) Add 300 g of methanol to the filter cake for washing and desorption. After filtration, the adsorbent and filtrate are obtained. The filtrate is concentrated by rotary evaporation to obtain recovered methanol and high-purity oleic acid.

[0041] (3) Dissolve 141 g of urea in 470 g of methanol, add 0.1 g of antioxidant 168 and 47 g of high-purity oleic acid, heat to 60°C and stir, then cool to -5°C and filter under reduced pressure. Add hot water to the resulting crystals, stir evenly, let stand to separate, and vacuum dehydrate to obtain 42 g of refined oleic acid.

[0042] (4) A sorbitol solution with an effective sorbitol content of 10 g, 25 g of refined oleic acid, 0.035 g of phosphorous acid and 0.035 g of sodium hydroxide are added into a reaction container, stirred and heated; nitrogen is bubbled on the surface at 0.8 L / min, and then the reaction temperature is gradually and slowly raised to 180°C for esterification reaction. After the reaction is completed for 4 hours, 0.35 g of diatomaceous earth and 0.35 g of magnesium polysilicate are added for heat preservation and adsorption for 1 hour. After the moisture index is qualified, sorbitan trioleate is obtained after filtering through a filter. Example 3

[0043] (1) Take 16g of CuCl2 and prepare a 10% aqueous solution. Completely immerse 20g of SiO2 in the solution and calcine at 600℃ for 3h to obtain a complex adsorbent.

[0044] (2) Take 12g of complex adsorbent and 60g of oleic acid and put them into a flask and stir evenly. The reaction temperature is 50℃. After stirring for 5h, centrifuge and take the filter cake after separation.

[0045] (3) Add 600 g of methanol to the filter cake for washing and desorption. After filtration, the adsorbent and filtrate are obtained. The filtrate is concentrated by rotary evaporation to obtain recovered methanol and high-purity oleic acid.

[0046] (4) Dissolve 150 g of urea in 423 g of methanol, add 0.1 g of antioxidant 168 and 50 g of high-purity oleic acid, heat to 40°C and stir, then cool to -5°C and filter under reduced pressure. Add hot water to the resulting crystals, stir evenly, let stand to separate, and vacuum dehydrate to obtain 46 g of refined oleic acid.

[0047] (5) A sorbitol solution with an effective sorbitol content of 10 g, 25 g of refined oleic acid, 0.35 g of phosphorous acid and 0.35 g of sodium hydroxide are added into a reaction container, stirred and heated; nitrogen is bubbled on the surface at 0.8 L / min, and then the reaction temperature is gradually and slowly raised to 200°C for esterification reaction. After the reaction is completed for 6 hours, 0.35 g of diatomaceous earth and 0.35 g of magnesium polysilicate are added for heat preservation and adsorption for 1 hour. After the moisture index is qualified, sorbitan trioleate is obtained after filtering through a filter. Example 4

[0048] (1) Take 4g of AgNO3 and 4g of CuCl2 to prepare a 10% aqueous solution, and completely immerse 20g of SiO2 in the solution. Calcine at 1000℃ for 3h to obtain a complex adsorbent.

[0049] (2) Take 12g of complex adsorbent and 60g of oleic acid and put them into a flask and stir evenly. The reaction temperature is 60℃. After stirring for 5h, centrifuge and take the filter cake after separation.

[0050] (3) Add 900 g of methanol to the filter cake for washing and desorption. After filtration, the adsorbent and filtrate are obtained. The filtrate is concentrated by rotary evaporation to obtain recovered methanol and high-purity oleic acid.

[0051] (4) Dissolve 156 g of urea in 416 g of methanol, add 0.1 g of antioxidant 168 and 52 g of high-purity oleic acid, heat to 55°C and stir, then cool to -5°C and filter under reduced pressure. Add hot water to the resulting crystals, stir evenly, let stand to separate, and vacuum dehydrate to obtain 48 g of refined oleic acid.

[0052] (5) A sorbitol solution with an effective sorbitol content of 10 g, 45 g of refined oleic acid, 0.275 g of phosphorous acid and 0.275 g of sodium hydroxide are added into a reaction container, stirred and heated; nitrogen is bubbled on the surface at 0.8 L / min, and then the reaction temperature is gradually and slowly raised to 220° C. for esterification reaction. After the reaction is performed for 8 hours, 0.35 g of diatomaceous earth and 0.35 g of magnesium polysilicate are added for heat preservation and adsorption for 1 hour. After the moisture index is qualified, sorbitan trioleate is obtained after filtering through a filter. Comparative Example 1

[0053] 10g of sorbitol, 25g of oleic acid, 0.035g of phosphorous acid and 0.035g of sodium hydroxide were added into a reaction container, stirred and heated; then the reaction temperature was gradually and slowly raised to 180°C for esterification reaction. After the reaction for 4h, 0.35g of diatomaceous earth and 0.35g of magnesium polysilicate were added for heat preservation and adsorption for 1h after the indicators were qualified. After the moisture index was qualified, sorbitan trioleate was obtained after filtering through a filter. Comparative Example 2

[0054] 10g of sorbitol, 25g of high-purity oleic acid, 0.035g of phosphorous acid and 0.035g of sodium hydroxide were added into a reaction container, stirred and heated; nitrogen was blown on the surface at 0.8L / min, and then the reaction temperature was gradually and slowly raised to 200°C for esterification reaction. After the reaction for 6h, 0.35g of diatomaceous earth and 0.35g of magnesium polysilicate were added for heat preservation and adsorption for 1h after the indicators were qualified. After the moisture index was qualified, sorbitan trioleate was obtained after filtering through a filter. Comparative Example 3

[0055] 10g of sorbitol, 25g of high-purity oleic acid, 0.035g of phosphoric acid and 0.035g of sodium hydroxide were added into a reaction container, stirred and heated; nitrogen was blown on the surface at 0.8L / min, and then the reaction temperature was gradually and slowly raised to 220°C for esterification reaction. After the reaction for 8h, 0.35g of diatomaceous earth and 0.35g of magnesium polysilicate were added for heat preservation and adsorption for 1h after the indicators were qualified. After the moisture index was qualified, sorbitan trioleate was obtained after filtering through a filter. Example 5

[0056] The results of the determination of the refined oleic acid obtained in each example are shown in Table 1.

[0057] Table 1 Comparison of refined oleic acid

[0058] project purity(%) High purity oleic acid: urea: methanol Chroma (G·D) Example 1 96.2 1:3:10 3 Example 2 95.9 1:3:10 3 Example 3 97.8 1:3:9 2 Example 4 99.2 1:3:8 1 The determination results of sorbitan trioleate obtained from each example and comparative example are shown in Table 2.

[0059] Table 2 Comparison of sorbitan trioleate synthesized from ordinary oleic acid and refined oleic acid of the present invention project Example 1 Example 2 Example 3 Example 4 Comparative Example 1 Comparative Example 2 Comparative Example 3 Hydroxyl value mgkoh / g 62 62 66 69 70 68 73 Saponification value mgkoh / g 174 174 176 178 171 170 171 Acid value mgkoh / g 9 9 11 7 14 16 16 Peroxide value meq / kg 0.1 0.1 0.3 0.6 0.8 1.2 1.6 Chroma (G·D) 3 3 2 2 7 7 8

Claims

1. A method for preparing sorbitan trioleate, characterized in that: The steps include: (1) Preparation of complex adsorbent: the active salt and the carrier are mixed and impregnated in a solvent, and then calcined to obtain a complex adsorbent; the active salt is one or a mixture of AgNO3 or CuCl2; the carrier is SiO2; (2) Oleic acid purification: the complexing adsorbent and oleic acid are mixed and reacted at 40-60°C, followed by solid-liquid separation; (3) Elution: eluting the solid product obtained in step (2) with methanol to obtain an eluate, and removing the solvent from the eluate to obtain high-purity oleic acid; (4) Refining of oleic acid: the high-purity oleic acid obtained in step (3) is mixed with urea and an antioxidant in methanol at 40-60° C., then cooled, and then solid-liquid separated to obtain crystals. The crystals are added with hot water, stirred evenly, and then allowed to stand for stratification. The oil layer is dehydrated to obtain refined oleic acid. (5) Preparation of sorbitan trioleate: The refined oleic acid, sorbitol, esterification catalyst and etherification catalyst are mixed and heated to 180-220°C for reaction. After the reaction is completed, a water absorbent is added to remove water. After the water removal reaches the standard, the mixture is filtered to obtain sorbitan trioleate.

2. The preparation method according to claim 1, characterized in that: The mass ratio of the carrier to the active salt in step (1) is 1:0.4-0.

8.

3. The preparation method according to claim 1, characterized in that: The calcination temperature in step (1) is 600-1000°C.

4. The preparation method according to claim 1, characterized in that: The mass ratio of the methanol used in step (3) to the oleic acid used in step (2) is 5-15:

1.

5. The preparation method according to claim 1, characterized in that: The mass ratio of the high-purity oleic acid, the urea and the methanol in step (4) is 1:3:6-10.

6. The preparation method according to claim 1, characterized in that The antioxidant in step (4) is antioxidant 168; more preferably, the antioxidant is MIANOX 168.

7. The preparation method according to claim 1, characterized in that: The amount of the antioxidant added in step (4) is 0.01% to 1.5%.

8. The preparation method according to claim 1, characterized in that: The mass ratio of sorbitol to refined oleic acid in step (5) is 1:2.5-4.

5.

9. The preparation method according to claim 1, characterized in that: In step (5), the esterification catalyst is sodium hydroxide, and the etherification catalyst is phosphorous acid.

10. The preparation method according to claim 1, characterized in that: In step (5), the added amounts of the esterification catalyst and the etherification catalyst are 0.05-1.0% of the total mass of the sorbitol and the refined oleic acid, respectively.

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