Separation and purification process of oleoyl monoethanolamine

Abstract

The invention discloses a separation and purification process of oleoyl monoethanolamine, which comprises the following steps: (1) dispersing an oleoyl monoethanolamine crude product a obtained by reacting ethanolamine with a methyl oleate crude product in low-carbon alcohol, heating, stirring and dissolving, and filtering to remove insoluble substances to obtain filtrate; (2) adding deionized water into the obtained filtrate, cooling, standing for crystallization, filtering, and removing a filter cake to obtain filtrate; (3) supplementing ethanolamine into the filtrate, freezing, standing for crystallization, filtering and drying to obtain an oleoyl monoethanolamine solid crystal crude product b; (4) dissolving the crude product b in a low-carbon alcohol aqueous solution, adding organic acid to adjust the pH value of the system, standing at low temperature for crystallization, filtering and drying to obtain a flaky oleoyl monoethanolamine crystal product with squamous gloss; the whole process is easy to industrialize, the content of the prepared oleoyl monoethanolamine is 90% or above, the purity is high, and the method has important significance in the oil industry, health food industry and medicine industry in China.

Description

Technical Field

[0001] This invention belongs to the field of oil and fat technology, specifically relating to a process for separating and purifying oleoyl monoethanolamine. Background Technology

[0002] Oleamide MEA, also known as N-(2-hydroxyethyl)-9-octadecenamide, is a monoethanolamide of oleic acid. Its English name is N-(2-Hydroxyethyl)-9-octadecenamide, CAS number 111-58-0, and its molecular formula is C2. 20 H 39 NO2, molecular weight 325.53. Oleyl monoethanolamine is an important nonionic surfactant widely used in lubricants, surfactants, and detergents. In recent years, fatty acid monoethanolamines have also attracted much attention as a novel endogenous signaling molecule and a lipid mediator in animal and plant tissues. For example, oleyl monoethanolamine can be used to control appetite and improve lipid metabolism. Its mechanism is that oleyl monoethanolamine can not only inhibit the absorption of fat in the intestine, but also accelerate the β-oxidation of fatty acids by promoting the hydrolysis of triglycerides in peripheral tissues (liver and fat), ultimately reducing fat accumulation and achieving weight control.

[0003] Generally, oleic acid monoethanolamide can be synthesized by reacting oleyl chloride (Koutek et al., Journal of Biological Chemistry, 1994, 269, 22937-22940), free oleic acid (Wang et al., Journal of Agricultural and Food Chemistry, 2012, 60, 451-457), or methyl oleate (or ethyl oleate) (Wang et al., Journal of Oleo Science, 2013, 62, 427-433) with ethanolamine. The reaction of methyl oleate or ethyl oleate with ethanolamine can be catalyzed by enzymes or chemical catalysts. However, compared to vegetable oils, high-purity methyl oleate is more expensive, resulting in higher synthesis costs.

[0004] Currently, commercially available methyl oleate products all use methyl oleate (molecular formula C) as the main impurity. 19 H 36 O2), methyl linoleate (molecular formula C) 19 H 34 O2), methyl linoleate (molecular formula C) 19 H 32 O2), methyl stearate (molecular formula C) 19 H 38A mixture of O2 is sold, in which the actual content of methyl oleate is 20%-60%. However, the refining process of methyl oleate with a purity of over 90% is complex and the cost is extremely high. Currently, it needs to be imported from Japan, and the market price remains high. If this complex, low-content methyl oleate is used as a raw material to synthesize oleyl monoethanolamine, the chemical and physical properties of fatty acid monoethanolamines with the same number of carbon atoms but different degrees of saturation are not significantly different. This makes the subsequent separation and purification to prepare high-purity oleyl monoethanolamine extremely difficult, and there are currently no relevant reports.

[0005] Due to the high price and reliance on imports of high-purity methyl oleate, the price of high-purity oleoyl monoethanolamine (95% or higher) is currently exorbitant. Therefore, developing a process for preparing oleoyl monoethanolamine, especially a process using a mixture of fatty acid methyl esters with low methyl oleate content (20-60%) as raw materials, is extremely urgent. Furthermore, a production method that achieves good process continuity, low raw material regeneration costs, high reaction conversion rate, high purification quality and yield, low overall production cost, and ease of industrialization has become a pressing issue for those skilled in the art. Summary of the Invention

[0006] The purpose of this invention is to provide a process for the separation and purification of oleoyl monoethanolamine.

[0007] The process of this invention uses low-content methyl oleate as a raw material to react and obtain crude oleoyl monoethanolamine. The crude oleoyl monoethanolamine is then separated and purified. The process is simple, low in cost and energy consumption, produces high-purity products, and is easy to implement for industrial production.

[0008] The above-mentioned objective of this invention can be achieved by the following technical solution: a process for separating and purifying oleoyl monoethanolamine, comprising the following steps:

[0009] (1) The crude oleoyl monoethanolamine product a obtained by reacting crude ethanolamine and crude methyl oleate is dispersed in a low carbon alcohol, heated, stirred and dissolved, and filtered to remove insoluble matter to obtain filtrate.

[0010] (2) Add deionized water to the filtrate obtained in step (1), then cool, let it stand to crystallize, filter, discard the filter cake, and obtain the filtrate;

[0011] (3) Add ethanolamine to the filtrate obtained in step (2), then freeze, let it stand to crystallize, filter, take the filter cake and dry it to obtain crude oleoyl monoethanolamine solid crystal product b;

[0012] (4) Dissolve crude oleoyl ethanolamine solid crystals b in a low-carbon alcohol aqueous solution, add organic acid to adjust the pH value of the system, let it stand at low temperature to crystallize, filter, take the filter cake and dry to obtain flaky oleoyl monoethanolamine crystals with a scaly luster.

[0013] In the above separation and purification process of oleoyl monoethanolamine:

[0014] Preferably, the crude methyl oleate in step (1) has a mass percentage of 25-60% and the main impurities in the crude methyl oleate are methyl stearate, methyl linoleate, methyl linolenic acid and other fatty acid methyl esters.

[0015] Other fatty acid methyl esters can be fatty acid methyl esters with more than 19 or fewer than 19 carbon atoms.

[0016] Crude methyl oleate can be obtained by reacting fatty acid glycerides from olive oil, tea seed oil or rapeseed oil with methanol under alkaline conditions via transesterification and then undergoing preliminary purification.

[0017] Preferably, the lower alcohol in step (1) is methanol or ethanol, and the ratio of its amount to the crude oleoyl monoethanolamine product a is 5-10 mL: 1 g.

[0018] Preferably, in step (1), the temperature is heated to 40°C-45°C.

[0019] The filtration to remove insoluble matter in step (1) includes filtration to remove ethanolamines, which are fatty acids with a carbon number of 16 or less and are insoluble in low alcohols.

[0020] Preferably, the amount of deionized water used in step (2) is 10-15% of the total volume of the lower alcohols used in step (1).

[0021] Preferably, in step (2), the temperature is cooled to 10-15°C and allowed to stand for 8-10 hours to crystallize.

[0022] In step (2), the filter cake is removed, including fatty acid ethanolamines with 17 or 18 carbon atoms and stearic acid ethanolamines with 19 carbon atoms and no double bonds.

[0023] Preferably, in step (3), ethanolamine is added until the concentration of ethanolamine is 0.15-0.2 g / mL.

[0024] In step (3), the addition of ethanolamine can solubilize fatty acid ethanolamines with 19 carbon atoms and 2 or 3 double bonds, making them less likely to precipitate during recrystallization.

[0025] Preferably, in step (3), the temperature is frozen to 0-5°C and allowed to stand for 5-8 hours to crystallize.

[0026] In step (3), filtration is performed to remove ethanolamines, which are fatty acids with 19 carbon atoms and contain 2 or 3 double bonds.

[0027] Preferably, in step (4), crude oleoylethanolamine solid crystals b are dissolved in a low-carbon alcohol aqueous solution at 30-35°C. The ratio of the amount of the low-carbon alcohol aqueous solution to the amount of crude oleoylethanolamine solid crystals b is 5-8 mL: 1 g. The volume percentage of the low-carbon alcohol in the low-carbon alcohol aqueous solution is 75%-80%, and the low-carbon alcohol is methanol or ethanol.

[0028] Recrystallization can be achieved by dissolving crude oleoylethanolamine solid crystals (b) in an aqueous solution of a low-carbon alcohol, thereby removing trace amounts of 19-carbon fatty acid ethanolamines with two or three double bonds and ethanolamines.

[0029] Preferably, in step (4), an organic acid is added to adjust the pH of the system to 6.9-7.1, wherein the organic acid is formic acid or acetic acid, and the system is allowed to stand at 0-5°C for 5-8 hours to crystallize.

[0030] Adding organic acids to adjust the pH of the system to 6.9-7.1 can neutralize alkaline substances in the system, ensuring that the product is slightly neutral, reducing its solubility in the solvent, and improving the yield of recrystallization.

[0031] Compared with the prior art, the present invention has the following advantages:

[0032] (1) The raw material used in this invention is crude oleyl monoethanolamine obtained by reacting low content methyl oleate (wherein the content of methyl oleate is 25%-60% by mass percentage), which is therefore inexpensive.

[0033] (2) The separation and purification method of oleoyl monoethanolamine of the present invention has a simple overall process and strong continuity, mild conditions, low overall cost, and is easy to industrialize. The oleoyl monoethanolamine obtained has a content of more than 90% and high purity, and at the same time, it obtains crystal particles with ideal crystal form.

[0034] (3) The preparation method of oleoyl monoethanolamine of the present invention will be of great significance to my country's oil and fat industry, health food and pharmaceutical industry. Attached Figure Description

[0035] Figure 1 It is the flaky, scaly luster of oleoyl monoethanolamine crystals prepared in Examples 1-5. Detailed Implementation

[0036] The following embodiments are for illustrative purposes only and do not limit the scope of protection of the present invention. Those skilled in the art can achieve the objectives of the present invention based on the above-disclosed scope.

[0037] Unless otherwise specified in the following implementation plan, standard test conditions or the test conditions recommended by the instrument company are generally followed. Unless otherwise specified, all materials and reagents used are commercially available.

[0038] Example 1

[0039] The separation and purification process for oleoyl monoethanolamine provided in this embodiment includes the following steps:

[0040] (1) 100g of crude oleoyl monoethanolamine a (the mass percentage of oleoyl monoethanolamine is 50%, and the mass percentage of oleoyl monoethanolamine is determined by HPLC after reaction) obtained by reacting ethanolamine and crude methyl oleate (from olive oil, with a mass percentage of methyl oleate of 60%) was dispersed in 500mL of methanol, heated to 40℃, stirred to dissolve, and filtered to remove insoluble matter to obtain filtrate;

[0041] (2) Slowly add 50 mL of deionized water to the filtrate, cool to 10°C, let it stand for 8 hours to crystallize, filter, discard the filter cake, and obtain the filtrate;

[0042] (3) Add ethanolamine to the filtrate from step (2) until the concentration of ethanolamine is 0.15 g / mL. Freeze the filtrate to 0°C, let it stand for 5 hours to crystallize, filter, and dry the filter cake to obtain 60 g of crude oleoylethanolamine solid crystals b. The oleoyl monoethanolamine content was found to be 80% by HPLC.

[0043] (4) Dissolve crude oleoylethanolamine solid crystals b in 300 mL of 80% methanol / water mixed solution under stirring at 30 °C, adjust the pH of the system to 6.9 with formic acid, let it stand at 5 °C for 5 hours to crystallize, filter, and dry the filter cake to obtain flaky oleoyl monoethanolamine crystals with a scaly luster. Figure 1 The total weight was 47g, and the content of oleoyl monoethanolamine was 95% as determined by HPLC.

[0044] The method for determining oleoyl monoethanolamine by HPLC in this embodiment is as follows: Column: Accucore™ C18 reversed-phase HPLC column, 2.6 μm, 2.1 mm x 100 mm; Mobile phase: methanol-water: 90:10 (volume ratio); Flow rate: 0.8 mL / min; Column temperature: 30℃; Detector: UV detector; Detection wavelength: 210 nm; Elution method: isocratic elution, the same below.

[0045] Example 2

[0046] The separation and purification process for oleoyl monoethanolamine provided in this embodiment includes the following steps:

[0047] (1) 100g of crude oleoyl monoethanolamine a (20% by mass) obtained by reacting ethanolamine and crude methyl oleate (from rapeseed oil, with methyl oleate content of 25%) was dispersed in 500mL of methanol, heated to 45℃, stirred to dissolve, and filtered to remove insoluble matter to obtain filtrate.

[0048] (2) Slowly add 60 mL of deionized water to the filtrate from step (1), cool to 10°C, let it stand for 8 hours to crystallize, filter, discard the filter cake, and obtain the filtrate.

[0049] (3) Add ethanolamine to the filtrate from step (2) until the concentration of ethanolamine is 0.17 g / mL. Freeze the filtrate to 3°C, let it stand for 5 hours to crystallize, filter, and dry the filter cake to obtain 25 g of crude oleoyl monoethanolamine solid crystals b. The oleoyl monoethanolamine content was determined to be 75% by HPLC.

[0050] (4) Dissolve crude oleoyl monoethanolamine solid crystals b in 200 mL of 75% methanol / water mixed solution under stirring at 30 °C, adjust the pH of the system to 6.9 with formic acid, let it stand at 0 °C for 5 hours to crystallize, filter, and dry the filter cake to obtain flaky oleoyl monoethanolamine crystals with a scaly luster. Figure 1 The total amount was 18g, and the content of oleoyl monoethanolamine was 90% as determined by HPLC.

[0051] Example 3

[0052] The separation and purification process for oleoyl monoethanolamine provided in this embodiment includes the following steps:

[0053] (1) 100g of crude oleyl monoethanolamine a (35% by mass) obtained by reacting crude ethanolamine and crude methyl oleate (from tea seed oil, with methyl oleate content of 40%) was dispersed in 500mL of ethanol, heated to 43℃, stirred to dissolve, and filtered to remove insoluble matter to obtain filtrate.

[0054] (2) Slowly add 50 mL of deionized water to the filtrate from step (1), cool to 12°C, let stand for 9 hours to crystallize, filter, discard the filter cake, and obtain the filtrate.

[0055] (3) Add ethanolamine to the filtrate from step (2) until the concentration of ethanolamine is 0.2 g / mL. Freeze the filtrate to 2°C, let it stand for 5 hours to crystallize, filter, and dry the filter cake to obtain 42 g of crude oleoyl monoethanolamine solid crystals b. The oleoyl monoethanolamine content was determined to be 77% by HPLC.

[0056] (4) Dissolve crude oleoyl monoethanolamine solid crystals b in 210 mL of 80% ethanol / water mixed solution under stirring at 30 °C, adjust the pH of the system to 7.0 with acetic acid, let it stand at 3 °C for 7 hours to crystallize, filter, and dry the filter cake to obtain flaky oleoyl monoethanolamine crystals with a scaly luster. Figure 1 The total amount was 32g, and the content of oleoyl monoethanolamine was 92% as determined by HPLC.

[0057] Example 4

[0058] The separation and purification process for oleoyl monoethanolamine provided in this embodiment includes the following steps:

[0059] (1) 100g of crude oleoyl monoethanolamine a (containing 26% oleoyl monoethanolamine) obtained by reacting ethanolamine and crude methyl oleate (from rapeseed oil, with a mass percentage of methyl oleate of 30%) was dispersed in 1000mL of ethanol, heated to 40℃, stirred to dissolve, and filtered to remove insoluble matter to obtain filtrate.

[0060] (2) Slowly add 120 mL of deionized water to the filtrate from step (1), cool to 15°C, let it stand for 10 hours to crystallize, filter, discard the filter cake, and obtain the filtrate.

[0061] (3) Add ethanolamine to the filtrate from step (2) until the concentration of ethanolamine is 0.2 g / mL. Freeze the filtrate to 5°C, let it stand for 8 hours to crystallize, filter, and dry the filter cake to obtain 31 g of crude oleoyl monoethanolamine solid crystals b. The oleoyl monoethanolamine content was determined to be 78% by HPLC.

[0062] (4) Dissolve crude oleoyl monoethanolamine solid crystals b in 186 mL of 75% ethanol / water mixed solution under stirring at 30 °C, adjust the pH of the system to 7.1 with acetic acid, let it stand at 5 °C for 6 hours to crystallize, filter, and dry the filter cake to obtain flaky oleoyl monoethanolamine crystals with a scaly luster. Figure 1 The total amount was 24g, and the content of oleoyl monoethanolamine was 93% as determined by HPLC.

[0063] Example 5

[0064] The separation and purification process for oleoyl monoethanolamine provided in this embodiment includes the following steps:

[0065] (1) 100g of crude oleyl monoethanolamine a (45% by mass) obtained by reacting crude ethanolamine and crude methyl oleate (from rapeseed oil, with methyl oleate content of 50%) was dispersed in 800mL of methanol, heated to 45℃, stirred to dissolve, and filtered to remove insoluble matter to obtain filtrate.

[0066] (2) Slowly add 120 mL of deionized water to the filtrate from step (1), cool to 12°C, let it stand for 9 hours to crystallize, filter, discard the filter cake, and obtain the filtrate.

[0067] (3) Add ethanolamine to the filtrate from step (2) until the concentration of ethanolamine is 0.18 g / mL. Freeze the filtrate to 5°C, let it stand for 7 hours to crystallize, filter, and dry the filter cake to obtain 54 g of crude oleoyl monoethanolamine solid crystals b. The oleoyl monoethanolamine content was determined to be 77% by HPLC.

[0068] (4) Dissolve crude oleoyl monoethanolamine solid crystals in 378 mL of 77% methanol / water mixed solution under stirring at 30 °C, adjust the pH of the system to 7.0 with acetic acid, let it stand at 0 °C for 8 hours to crystallize, filter, and dry the filter cake to obtain flaky oleoyl monoethanolamine crystals with a scaly luster. Figure 1 The total weight was 41g, and the content of oleoyl monoethanolamine was 94% as determined by HPLC.

[0069] The above embodiments are merely examples illustrating the technical solutions of the present invention and are not intended to limit the invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions claimed by the present invention.

Claims

1. A process for separating and purifying oleoyl monoethanolamine, characterized in that, Includes the following steps: (1) The crude oleoyl monoethanolamine product a obtained by reacting crude ethanolamine and crude methyl oleate is dispersed in a low carbon alcohol, heated, stirred and dissolved, and filtered to remove insoluble matter to obtain filtrate. (2) Add deionized water to the filtrate obtained in step (1), then cool, let stand to crystallize, filter, discard the filter cake, and obtain the filtrate; (3) Add ethanolamine to the filtrate obtained in step (2), then freeze, let it stand to crystallize, filter, take the filter cake and dry it to obtain crude oleoyl monoethanolamine solid crystal product b; (4) Dissolve crude oleoyl ethanolamine solid crystals b in a low-carbon alcohol aqueous solution, add organic acid to adjust the pH value of the system, let it stand at low temperature to crystallize, filter, take the filter cake and dry to obtain flaky oleoyl monoethanolamine crystals with a scaly luster.

2. The separation and purification process for oleoyl monoethanolamine according to claim 1, characterized in that, The crude methyl oleate in step (1) has a mass percentage of 25-60% and the main impurities in the crude methyl oleate are methyl stearate, methyl linoleate and methyl linoleate.

3. The separation and purification process for oleoyl monoethanolamine according to claim 1, characterized in that, The lower alcohol mentioned in step (1) is methanol or ethanol, and its dosage relationship with the crude oleoyl monoethanolamine product a is 5-10 mL: 1 g.

4. The separation and purification process for oleoyl monoethanolamine according to claim 1, characterized in that, In step (1), heat to 40℃-45℃.

5. The separation and purification process for oleoyl monoethanolamine according to claim 1, characterized in that, The amount of deionized water used in step (2) is 10-15% of the total volume of the lower alcohols used in step (1).

6. The separation and purification process for oleoyl monoethanolamine according to claim 1, characterized in that, In step (2), cool to 10-15℃ and let stand for 8-10 hours to allow crystals to settle.

7. The separation and purification process for oleoyl monoethanolamine according to claim 1, characterized in that, In step (3), ethanolamine is added until the concentration of ethanolamine is 0.15-0.2 g / mL.

8. The separation and purification process for oleoyl monoethanolamine according to claim 1, characterized in that, In step (3), freeze to 0-5℃ and let stand for 5-8 hours to crystallize.

9. The separation and purification process for oleoyl monoethanolamine according to claim 1, characterized in that, In step (4), crude oleoylethanolamine solid crystals b are dissolved in a low-carbon alcohol aqueous solution at 30-35°C. The ratio of the amount of the low-carbon alcohol aqueous solution to the amount of crude oleoylethanolamine solid crystals b is 5-8 mL: 1 g. The volume percentage of the low-carbon alcohol in the low-carbon alcohol aqueous solution is 75%-80%, and the low-carbon alcohol is methanol or ethanol.

10. The separation and purification process for oleoyl monoethanolamine according to claim 1, characterized in that, In step (4), an organic acid is added to adjust the pH of the system to 6.9-7.

1. The organic acid is formic acid or acetic acid. The system is allowed to stand at 0-5°C for 5-8 hours to crystallize.

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