A method for producing low-pollution conjugated linoleic acid

Abstract

This invention belongs to the field of chemical synthesis, specifically relating to a low-pollution method for producing conjugated linoleic acid. The reaction steps include: under inert gas protection, linoleic acid undergoes an isomerization reaction in the presence of a cobalt catalyst and a phosphorus ligand to generate conjugated linoleic acid. The catalytic system composed of cobalt salt and phosphorus ligand obtained by this invention can efficiently convert linoleic acid into conjugated linoleic acid, avoiding the use of highly polluting raw materials such as strong alkalis. The reaction temperature is low, the reaction time is short, and it still maintains high yield and purity even at large-scale production, making it suitable for industrial production.

Description

Technical Field

[0001] This invention belongs to the field of chemical synthesis, specifically relating to a method for producing low-pollution conjugated linoleic acid. Background Technology

[0002] Conjugated linoleic acid (CLAs) is a collective term for a class of octadecanedienoic acids containing conjugated double bonds. These double bonds can be arranged in four positions: C8, C10, C9, C11, C10, C12, and C11, C13. Each position has four stereogenomic isomers: cis-cis (cc), trans-trans (tt), cis-trans (ct), and trans-cis (tc). Therefore, theoretically, CLAs have as many as 28 isomers. Due to the structural characteristics of the conjugated double bonds in its molecular structure, conjugated linoleic acid exhibits high reactivity in polymerization reactions, making it a raw material for various industrial applications. Compared to non-conjugated systems, drying oils containing conjugated double bonds dry faster, and the resulting paint films exhibit superior water and alkali resistance, as well as better toughness. Furthermore, CLAs have been shown to possess activities including anti-cancer, anti-obesity, immune-enhancing, and growth-promoting effects, thus being considered a promising nutritional additive. Different CLA structures exhibit significant differences in physiological activity, with c9,t11-CLA and t10,c12-CLA being the configurations proven to have significant physiological activity.

[0003] CLA has strong health benefits for humans and animals; however, its abundance in nature is low, and the human body cannot synthesize it, so it must be obtained from food. Therefore, the preparation of high-purity, high-activity CLA and its application in the food and pharmaceutical industries have become a research hotspot in various sectors. Currently, the main methods for synthesizing CLA are biosynthesis and chemical synthesis.

[0004] Biosynthesis involves using specific enzymes or microorganisms to catalyze the production of CLA from corresponding substrates. Microbial synthesis is a commonly used method, as many microorganisms can produce enzymes for CLA synthesis through fermentation. Currently, lactic acid bacteria, butyric acid vibrio, rumen bacteria, propionibacterium, bifidobacteria, and Penicillium are commonly used to produce CLA. However, most CLA-producing strains are strict anaerobes, which are difficult to cultivate in industrial or laboratory settings and result in low yields, hindering their widespread application in food and pharmaceuticals. Furthermore, excessive free linoleic acid and the generation of byproducts can inhibit the growth of CLA-producing bacteria, thus affecting their conversion rate and making them unsuitable for industrial production.

[0005] There are three main types of chemical synthesis methods for CLA: base isomerization, dehydration of oleic acid-allyl alcohol, and synthesis of CLA from ricinoleic acid. Among these, base isomerization is relatively simple and practical. The essence of base isomerization is a carbanion process. Its reaction mechanism is as follows: a catalyst (base) abstracts a hydrogen atom from the allylic position of linoleic acid or linolenic acid, which have a pentanediene structure, to generate a carbanion; the carbanion rearranges to form a more stable conjugated structure, thus achieving conjugation. The raw materials or substrates for this type of reaction are usually linoleic acid, linoleic acid esters, or oils rich in linoleic acid, such as walnut oil, safflower oil, soybean oil, sunflower seed oil, corn germ oil, and melon seed oil. For example, CN101565367A discloses a method of using vegetable oil containing linoleic acid glycerides or mixed fatty acids containing linoleic acid or linoleic acid products obtained through extraction and separation as raw materials, low-boiling-point alcohol solvents and alkaline catalysts in a reaction vessel, and carrying out an isomerization reaction at a certain temperature. However, the above-mentioned alkaline isomerization method for converting CLA is mostly carried out under high temperature conditions, and the reaction time is relatively long. It is easy to generate certain by-products and consume energy. At the same time, it also uses a large amount of corrosive strong alkali, which causes certain pollution to the environment.

[0006] Given the problems of environmental pollution, high reaction temperature, long reaction time, low yield and purity of existing technologies, there is an urgent need to develop a low-pollution method for producing conjugated linoleic acid. Summary of the Invention

[0007] In view of the problems existing in the prior art, the purpose of this invention is to provide a low-pollution method for producing conjugated linoleic acid, so as to solve the problems of environmental pollution, high reaction temperature, long reaction time, low yield and purity existing in the prior art. This invention is achieved through the following technical solution:

[0008] A method for producing low-pollution conjugated linoleic acid includes the following steps:

[0009] Under inert gas protection, linoleic acid undergoes an isomerization reaction in the presence of a cobalt catalyst and phosphorus ligands to generate conjugated linoleic acid;

[0010] The cobalt catalyst is Co(OAc)2·4H2O, CoBr2, CoCl2 or Co(acac)2;

[0011] The phosphorus ligand is

[0012] In some embodiments, the reaction solvent is selected from one or more of methanol, ethanol, n-propanol, acetone, THF, n-hexane, DMSO, DMF, and toluene.

[0013] In some embodiments, the reaction solvent is selected from one or more of methanol, ethanol, n-propanol, acetone, and THF.

[0014] In some embodiments, the inert gas is selected from nitrogen or argon.

[0015] In some implementation schemes, the reaction temperature is 50–60°C and the reaction time is 30–60 min.

[0016] In some embodiments, the molar ratio of linoleic acid to cobalt catalyst is 1:(0.05-0.1), and the molar ratio of linoleic acid to phosphorus ligand is 1:(0.05-0.15).

[0017] In some implementation schemes, after the reaction is completed, the mixture is cooled to room temperature, filtered, and the filtrate is evaporated and concentrated to recover the reaction solvent. Deionized water is added to the concentrate, and dilute hydrochloric acid is slowly added to adjust the pH of the solution to 2.0-4.0. The solution is then extracted with n-hexane, and the extract is washed with saline and deionized water, respectively. Finally, the extract is evaporated, concentrated, and vacuum dried to obtain conjugated linoleic acid.

[0018] Some implementation schemes include the following specific steps:

[0019] At room temperature, linoleic acid, ethanol, CoCl2, and phosphorus ligands are added. Add the solution to a reaction vessel, seal it, and replace the gas in the reaction vessel with nitrogen three times. Stir the mixture at 600 rpm, then heat it to 60°C and stir for 45 min. After the reaction is complete, cool it to room temperature, filter it, evaporate and concentrate the filtrate, and recover the reaction solvent ethanol. Add deionized water to the concentrate, slowly add dilute hydrochloric acid to adjust the pH of the solution to 3.0, then extract it with n-hexane. Combine the n-hexane layers, wash them with 5% saline and deionized water respectively, and finally evaporate and concentrate the solvent n-hexane to remove it. Dry the solution under vacuum to obtain conjugated linoleic acid.

[0020] The present invention has achieved the following beneficial effects:

[0021] 1) The catalytic system composed of cobalt salt and phosphorus ligand obtained in this invention can efficiently convert linoleic acid into conjugated linoleic acid, and the main components are C9,T11-CLA and T10,C12-CLA. The yield of conjugated linoleic acid in this invention is as high as 98.5%, and the purity is as high as 99.7%.

[0022] 2) This invention avoids the use of highly polluting raw materials such as strong alkalis, has a low reaction temperature and short reaction time, and still has a high yield under large-scale production, making it suitable for industrial production. Detailed Implementation

[0023] The following non-limiting embodiments are intended to enable those skilled in the art to gain a more comprehensive understanding of the present invention, but do not limit the invention in any way. The following content is merely an exemplary description of the scope of protection of the present invention, and those skilled in the art can make various changes and modifications to the present invention based on the disclosed content, which should also fall within the scope of protection of the present invention.

[0024] When numerical ranges are given in the embodiments, it should be understood that, unless otherwise stated in the invention, both endpoints of each numerical range and any value between the two endpoints may be selected. Unless otherwise defined, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0025] The present invention will be further described below by way of specific embodiments. Unless otherwise specified, all chemical reagents used in the embodiments of the present invention are obtained through conventional commercial means.

[0026] Example 1

[0027] At room temperature, linoleic acid (10 kg, 35.71 mol), ethanol (3.0 L), CoCl2 (0.23 kg, 1.77 mol), and ligands were added. (1.92 kg, 3.57 mol) was added to a reaction vessel, sealed, and the gas in the reaction vessel was purged with nitrogen three times. The mixture was stirred at 600 rpm, and then heated to 60 °C and stirred for 45 min. After the reaction was complete, the mixture was cooled to room temperature, filtered, and the filtrate was evaporated and concentrated to recover the reaction solvent ethanol. Deionized water (5.0 L) was added to the concentrate, and dilute hydrochloric acid (1 M) was slowly added to adjust the pH of the solution to 3.0. The solution was then extracted with n-hexane (20 L * 3), and the n-hexane layers were combined. The layers were washed with 5% saline (50 L * 3) and deionized water (50 L * 3), respectively. Finally, the solvent n-hexane was removed by evaporation and concentration, and the product was dried under vacuum to obtain 9.85 kg of conjugated linoleic acid (mainly composed of C9, T11-CLA and T10, C12-CLA), with a yield of 98.5% and an HPLC purity of 99.7%.

[0028] Example 2

[0029] At room temperature, linoleic acid (10 kg, 35.71 mol), methanol (3.0 L), CoCl2 (0.23 kg, 1.77 mol), and ligands were added. (1.50 kg, 2.79 mol) was added to a reaction vessel, sealed, and the gas in the reaction vessel was purged with nitrogen three times. The mixture was stirred at 600 rpm, and then heated to 55 °C and stirred for 60 min. After the reaction was complete, the mixture was cooled to room temperature, filtered, and the filtrate was evaporated and concentrated to recover the reaction solvent methanol. Deionized water (5.0 L) was added to the concentrate, and dilute hydrochloric acid (1 M) was slowly added to adjust the pH of the solution to 3.0. The solution was then extracted with n-hexane (20 L * 3), and the n-hexane layers were combined. The layers were washed with 5% saline (50 L * 3) and deionized water (50 L * 3), respectively. Finally, the solvent n-hexane was removed by evaporation and concentration, and the product was dried under vacuum to obtain 9.51 kg of conjugated linoleic acid (mainly composed of C9, T11-CLA and T10, C12-CLA), with a yield of 95.1% and an HPLC purity of 99.4%.

[0030] Example 3

[0031] At room temperature, linoleic acid (10 kg, 35.71 mol), acetone (3.0 L), Co(acac)2 (0.50 kg, 1.95 mol), and ligands were added. (1.92 kg, 3.57 mol) was added to a reaction vessel, sealed, and the gas in the reaction vessel was purged with nitrogen three times. The mixture was stirred at 600 rpm, and then heated to 55 °C and stirred for 60 min. After the reaction was complete, the mixture was cooled to room temperature, filtered, and the filtrate was evaporated and concentrated to recover the reaction solvent acetone. Deionized water (5.0 L) was added to the concentrate, and dilute hydrochloric acid (1 M) was slowly added to adjust the pH of the solution to 3.0. The solution was then extracted with n-hexane (20 L * 3), and the n-hexane layers were combined. The layers were washed with 5% saline (50 L * 3) and deionized water (50 L * 3), respectively. Finally, the solvent n-hexane was removed by evaporation and concentration, and the product was dried under vacuum to obtain 9.64 kg of conjugated linoleic acid (mainly C9, T11-CLA and T10, C12-CLA), with a yield of 96.4% and an HPLC purity of 99.6%.

[0032] Example 4

[0033] At room temperature, linoleic acid (10 kg, 35.71 mol), THF (3.0 L), CoBr2 (0.40 kg, 1.83 mol), and ligands were added. (1.50 kg, 2.79 mol) was added to a reaction vessel, sealed, and the gas in the reaction vessel was purged with nitrogen three times. The mixture was stirred at 600 rpm, and then heated to 60 °C and stirred for 60 min. After the reaction was complete, the mixture was cooled to room temperature, filtered, and the filtrate was evaporated and concentrated to recover the reaction solvent THF. Deionized water (5.0 L) was added to the concentrate, and dilute hydrochloric acid (1 M) was slowly added to adjust the pH of the solution to 3.0. The solution was then extracted with n-hexane (20 L * 3), and the n-hexane layers were combined. The layers were washed with 5% saline (50 L * 3) and deionized water (50 L * 3), respectively. Finally, the solvent n-hexane was removed by evaporation and concentration, and the product was dried under vacuum to obtain 9.35 kg of conjugated linoleic acid (mainly composed of C9, T11-CLA and T10, C12-CLA), with a yield of 93.5% and an HPLC purity of 99.3%.

[0034] Comparative Example 1

[0035] Based on Example 1 Replace with PPh3.

[0036] At room temperature, linoleic acid (10 kg, 35.71 mol), ethanol (3.0 L), CoCl2 (0.23 kg, 1.77 mol), and ligand PPh3 (0.94 kg, 3.57 mol) were added to a reaction vessel. After sealing, the gas in the reaction vessel was purged with nitrogen three times. The mixture was stirred at 600 rpm, and then heated to 60 °C and stirred for 45 min. After the reaction was complete, the mixture was cooled to room temperature, filtered, and the filtrate was evaporated and concentrated to recover the reaction solvent ethanol. Deionized water (5.0 L) was added to the concentrate, and dilute hydrochloric acid (1 M) was slowly added to adjust the pH of the solution to 3.0. The solution was then extracted with n-hexane (20 L * 3), and the n-hexane layers were combined. The solutions were washed with 5% saline (50 L * 3) and deionized water (50 L * 3), respectively. Finally, the solvent n-hexane was removed by evaporation and concentration, and the solution was dried under vacuum to obtain 8.06 kg of conjugated linoleic acid, with a yield of 80.6% and an HPLC purity of 72.4%.

[0037] Comparative Example 2

[0038] Based on Example 1, CoCl2 was replaced with RhCl3.

[0039] At room temperature, linoleic acid (10 kg, 35.71 mol), ethanol (3.0 L), RhCl3 (0.37 kg, 1.77 mol), and ligands were added. (1.92 kg, 3.57 mol) was added to a reaction vessel, sealed, and the gas in the reaction vessel was purged with nitrogen three times. The mixture was stirred at 600 rpm, and then heated to 60 °C and stirred for 45 min. After the reaction was complete, the mixture was cooled to room temperature, filtered, and the filtrate was evaporated and concentrated to recover the reaction solvent ethanol. Deionized water (5.0 L) was added to the concentrate, and dilute hydrochloric acid (1 M) was slowly added to adjust the pH of the solution to 3.0. The solution was then extracted with n-hexane (20 L * 3), and the n-hexane layers were combined. The layers were washed with 5% saline (50 L * 3) and deionized water (50 L * 3), respectively. Finally, the solvent n-hexane was removed by evaporation and concentration, and the product was dried under vacuum to obtain 8.95 kg of conjugated linoleic acid, with a yield of 89.5% and an HPLC purity of 96.7%.

[0040] The above embodiments are merely illustrative examples and are not intended to limit the implementation. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.

Claims

1. A method for producing low-pollution conjugated linoleic acid, characterized in that, Under inert gas protection, linoleic acid undergoes an isomerization reaction in the presence of a cobalt catalyst and phosphorus ligands to generate conjugated linoleic acid; The cobalt catalyst is Co(OAc)2·4H2O, CoBr2, CoCl2 or Co(acac)2; The phosphorus ligand is 2. The production method according to claim 1, characterized in that, The reaction solvent is selected from one or more of methanol, ethanol, n-propanol, acetone, THF, n-hexane, DMSO, DMF and toluene.

3. The production method according to claim 2, characterized in that, The reaction solvent is selected from one or more of methanol, ethanol, n-propanol, acetone and THF.

4. The production method according to claim 1, characterized in that, The inert gas is selected from nitrogen or argon.

5. The production method according to claim 1, characterized in that, The reaction temperature is 50–60℃ and the reaction time is 30–60 min.

6. The production method according to claim 1, characterized in that, The molar ratio of linoleic acid to cobalt catalyst is 1:(0.05-0.1), and the molar ratio of linoleic acid to phosphorus ligand is 1:(0.05-0.15).

7. The production method according to claim 1, characterized in that, After the reaction was completed, the solution was cooled to room temperature, filtered, and the filtrate was evaporated and concentrated to recover the reaction solvent. Deionized water was added to the concentrate, and dilute hydrochloric acid was slowly added to adjust the pH of the solution to 2.0-4.

0. The solution was extracted with n-hexane, and the extract was washed with saline and deionized water, respectively. Then, the solution was evaporated, concentrated, and dried under vacuum to obtain conjugated linoleic acid.

8. The production method according to claim 1, characterized in that, The specific steps include the following: At room temperature, linoleic acid, ethanol, CoCl2, and phosphorus ligands are added. Add the solution to a reaction vessel, seal it, and replace the gas in the reaction vessel with nitrogen three times. Stir the mixture at 600 rpm, then heat it to 60°C and stir for 45 min. After the reaction is complete, cool it to room temperature, filter it, evaporate and concentrate the filtrate, and recover the reaction solvent ethanol. Add deionized water to the concentrate, slowly add dilute hydrochloric acid to adjust the pH of the solution to 3.0, then extract it with n-hexane. Combine the n-hexane layers, wash them with 5% saline and deionized water respectively, and finally evaporate and concentrate the solvent n-hexane to remove it. Dry the solution under vacuum to obtain conjugated linoleic acid.

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