Antibacterial feed additive and preparation method thereof

Abstract

The invention belongs to the field of organic synthesis, and particularly relates to an antibacterial feed additive and a preparation method thereof.The additive is glycerol monolaurate, and reaction steps include: taking glycerol and lauric acid as raw materials, and performing esterification reaction in the presence of an MgO / HMCM-22 molecular sieve catalyst to generate the glycerol monolaurate. The method has the advantages of high yield, high purity, mild reaction conditions and no need of very high reaction temperature. In addition, the method still has high yield and purity under large-scale production, and is suitable for industrial production.

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis, and specifically relates to an antibacterial feed additive and a preparation method thereof. Background Art

[0002] Lauric acid monoglyceride, also known as monolauric acid glyceride or dodecyl glyceride, has a CAS number of 142-18-7 and a structural formula of: Since monolaurin has a hydrophilic group and a hydrophobic group that is easily soluble in biological membranes, monolaurin can combine with cell walls and cell membranes to change the permeability and fluidity of cell membranes and cause cell autolysis. It also inhibits enzyme activity and oxygen intake, thereby inhibiting cell respiration, the entry of amino acids into cells, and the synthesis of biomacromolecules, and can effectively inhibit general bacteria, yeasts, and molds. Therefore, monolaurin is a safe, efficient, and broad-spectrum antibacterial agent with dual functions of emulsification and antibacterial and antiviral. Studies have shown that adding 0.4% monolaurin to feed has a certain emulsifying effect on soybean oil, which can effectively improve the growth performance of weaned piglets, improve intestinal morphology, function, and flora, and reduce the occurrence of diseases such as diarrhea.

[0003] At present, the main methods for synthesizing monolaurin include direct esterification, transesterification, group protection, enzyme method

[14] , microwave-assisted synthesis and solid acid catalysis. Among them, the industrial production of fatty acid monoglycerides is mainly synthesized by inorganic acid and base catalysis under high temperature conditions, which has problems such as high energy consumption, poor reaction selectivity, poor product quality and difficulty in separation and purification. However, the direct esterification method is mainly prepared by direct esterification reaction of lauric acid and glycerol (glycerol), which has the advantages of simple operation, low instrumentation requirements, diverse catalyst selection and high success rate. However, since the direct esterification reaction is a reversible reaction, its synthesis temperature requirements are high, it takes a long time, and it is accompanied by a large number of by-products (diglycerides and triglycerides), which need to be further separated and purified. From the perspective of green concept, the introduction of ultrasound can essentially accelerate the reaction rate of the preparation process of multiphase high viscosity system, thereby significantly increasing the product yield and reducing the use of expensive reagents. Transesterification is mainly a base-catalyzed reaction. Although lauric acid monoglyceride is prepared by transesterification of ethyl laurate (methyl laurate) with glycerol, the formation of by-products is reduced compared with the direct esterification method, a higher temperature is required to reduce the viscosity of the system and promote the miscibility of the multiphase reaction.

[0004] CN110699392A relates to a method for efficiently preparing monolaurin by enzyme catalysis in a microreactor, wherein lauric acid is dissolved in a solvent to obtain solution A, glycerol is dissolved in a solvent to obtain solution B, solution A and solution B are simultaneously pumped into a mixer of a microreactor to mix, and then enter a microreactor equipped with an immobilized enzyme device to obtain monolaurin by heating reaction. However, this method requires the use of a more complicated reaction unit, and the cost of using biological enzymes is relatively high. In addition, the prepared monolaurin purity is relatively low.

[0005] CN113214082A relates to a method for preparing lauric acid monoglyceride, which uses lauric acid and glycerol as raw materials, catalyzes the glycerol esterification reaction of long-chain fatty acid lauric acid by an acidic catalyst, and uses a low eutectic solvent as a solvent to reduce the activation energy of the esterification reaction, so that the esterification reaction can be carried out at a lower temperature. However, this method has a high reaction temperature, and the yield and purity are low.

[0006] Based on this, it is urgent to develop a method for preparing lauric acid monoglyceride antibacterial feed additive suitable for industrial production. Summary of the invention

[0007] In view of the problems existing in the prior art, the purpose of the present invention is to provide a method for preparing a monolaurin antibacterial feed additive to solve the problems existing in the prior art, such as harsh reaction conditions, low purity, low yield, poor selectivity, and unsuitability for industrial production. The present invention is achieved by the following technical solutions:

[0008] A method for preparing an antibacterial feed additive, characterized in that the additive is lauric acid monoglyceride, and the preparation method comprises the following steps:

[0009] Using glycerol and lauric acid as raw materials, an esterification reaction occurs in the presence of MgO / HMCM-22 molecular sieve catalyst to produce lauric acid monoglyceride antibacterial feed additive. The reaction formula is:

[0010]

[0011] In some embodiments, the method for preparing the MgO / HMCM-22 molecular sieve catalyst comprises the following steps:

[0012] 1) Mix NaMCM-22 molecular sieve with a silicon-aluminum ratio of 25 to 30 and NH 4 NO 3 The solution is reacted at 60-100° C. to obtain HMCM-22 molecular sieve;

[0013] 2) Weigh an appropriate amount of MgO powder, add deionized water and stir thoroughly to prepare a milky white MgO suspension, add the above HMCM-22 molecular sieve to the suspension and stir evenly, let it stand and then dry, and calcine after sieving to obtain a MgO / HMCM-22 molecular sieve catalyst.

[0014] In some embodiments, the reaction solvent is selected from one or more of DMSO, DMF, benzene and toluene.

[0015] In some embodiments, the molar ratio of glycerol to lauric acid is 1:(1.0-1.1); the mass ratio of MgO / HMCM-22 molecular sieve catalyst to lauric acid is 1:(8-12).

[0016] In some embodiments, the reaction temperature is 80-110° C. and the reaction time is 4-6 h.

[0017] In some embodiments, after the reaction is completed, the MgO / HMCM-22 molecular sieve catalyst is filtered out, deionized water is added to the filtrate to precipitate solids, the filtrate is filtered, and the solids are washed with deionized water for multiple times to obtain a crude product; isopropanol is then added to dissolve the crude product, and deionized water is added to recrystallize and precipitate solids, which are filtered and vacuum dried to obtain monolaurin.

[0018] In some embodiments, the volume ratio of isopropanol to deionized water is 1:(3-5).

[0019] In some embodiments, the loading amount of MgO in the MgO / HMCM-22 molecular sieve catalyst is 5% to 10%; the NaMCM-22 molecular sieve and NH 4 NO 3 The mass ratio of the solution is (20-30):1.

[0020] On the other hand, the present invention also protects the antibacterial feed additive prepared by the above preparation method.

[0021] The present invention has achieved the following beneficial effects:

[0022] 1) The MgO / HMCM-22 molecular sieve catalyst used in the present invention can improve the activity of the esterification reaction on the one hand, and on the other hand, due to the special structure of the catalyst, it has a high selectivity for generating monoester compounds. Therefore, the present invention has high yield, high purity, mild reaction conditions, and does not require a very high reaction temperature.

[0023] 2) The present invention still has a high yield and purity under large-scale production and is suitable for industrial production. Specific implementation method:

[0024] The technical solution of the present invention will be clearly and completely described below in conjunction with the embodiments. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0025] The endpoints and any values ​​of the scope described in the present invention are not limited to the precise scope or value, and these scopes or values ​​should be understood to include values ​​close to these scopes or values. For numerical ranges, the endpoint values ​​of each range, the endpoint values ​​of each range and the individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, and these numerical ranges should be considered as specifically disclosed in this article.

[0026] Preparation Example 1: Preparation of MgO / HMCM-22 molecular sieve catalyst

[0027] The NaMCM-22 molecular sieve with a silicon-aluminum ratio of 30 was mixed with 2 mol / L NH 4 NO 3 The solution was ion exchanged at 80°C for 3 hours, with a liquid-to-solid mass ratio of 20:1. It was then filtered, washed, dried, and calcined at 550°C for 5 hours to obtain HMCM-22 molecular sieve.

[0028] Weigh 5.0 g of MgO powder, add 200 mL of deionized water and stir thoroughly to prepare a milky white MgO suspension, add 100.0 g of HMCM-22 molecular sieve to the above suspension and stir thoroughly until it becomes homogeneous, let it stand for 12 hours, dry it at 120° C. for 12 hours, sieve it through a 20-mesh sieve, and calcine it at 550° C. for 5 hours to obtain a MgO / HMCM-22 molecular sieve catalyst, and the loading amount of MgO in the MgO / HMCM-22 catalyst is 5%.

[0029] Preparation Example 2: Preparation of MgO / HMCM-22 molecular sieve catalyst

[0030] The NaMCM-22 molecular sieve with a silicon-aluminum ratio of 30 was mixed with 2 mol / L NH 4 NO 3 The solution was ion exchanged at 80°C for 3 hours, with a liquid-to-solid ratio of 20:1. It was then filtered, washed, dried, and calcined at 550°C for 5 hours to obtain HMCM-22 molecular sieve.

[0031] Weigh 10.0 g of MgO powder, add 200 mL of deionized water and stir thoroughly to prepare a milky white MgO suspension, add 100.0 g of HMCM-22 molecular sieve to the above suspension and stir thoroughly until it is homogeneous, let it stand for 12 hours, then dry it at 120° C. for 12 hours, sieve it through a 20-mesh sieve, and calcine it at 550° C. for 5 hours to obtain a MgO / HMCM-22 molecular sieve catalyst, and the loading amount of MgO in the MgO / HMCM-22 catalyst is 10%.

[0032] Example 1 Preparation of lauric acid monoglyceride

[0033]

[0034] Glycerol (92.0 g, 1.0 mol), lauric acid (200.0 g, 1.0 mol), DMSO (100 mL) were added to the reactor, followed by the addition of MgO / HMCM-22 (20.0 g) with a loading of 5% obtained in Preparation Example 1, and the mixture was heated to 100 ° C and stirred for 6 h. After the reaction, the molecular sieve catalyst was removed by filtration, and the filtrate was added with deionized water (300 mL) to precipitate solids, filtered, and washed with deionized water for several times to obtain a crude product. Then, isopropanol (100 mL) was added to dissolve the crude product, and deionized water (300 mL) was added to recrystallize the precipitated solids, filtered, and vacuum dried to obtain 256.2 g of lauric acid monoglyceride as a white solid, with a yield of 93.5% and an HPLC purity of 99.3%.

[0035] LC-MS(ESI):[M+H] + =275.3. And by comparison, the HPLC retention time of the product of this example is consistent with that of monolaurin.

[0036] Example 2 Preparation of lauric acid monoglyceride

[0037]

[0038] Glycerol (92.0 g, 1.0 mol), lauric acid (200.0 g, 1.0 mol), and DMF (100 mL) were added to a reactor, followed by the addition of MgO / HMCM-22 (20.0 g) with a loading of 10% obtained in Preparation Example 2, and the mixture was heated to 110° C. and stirred for 5 h. After the reaction, the molecular sieve catalyst was removed by filtration, and the filtrate was added with deionized water (300 mL) to precipitate a white solid, which was filtered and washed with deionized water for several times to obtain a crude product. Isopropanol (100 mL) was then added to dissolve the crude product, and deionized water (300 mL) was added to recrystallize the precipitated solid, which was filtered and dried in vacuo to obtain 258.5 g of lauric acid monoglyceride as a white solid, with a yield of 94.3% and an HPLC purity of 99.5%.

[0039] LC-MS(ESI):[M+H] + =275.3. And by comparison, the HPLC retention time of the product of this example is consistent with that of monolaurin.

[0040] Example 3 Preparation of lauric acid monoglyceride

[0041]

[0042] Glycerol (9.2kg, 100.0mol), lauric acid (20.0kg, 100.0mol), DMSO (10.0L) were added to the reactor, followed by the addition of MgO / HMCM-22 (2.0kg) with a loading of 5% obtained in Preparation Example 1, and the temperature was raised to 100°C for stirring and reaction for 6h. After the reaction, the molecular sieve catalyst was removed by filtration, and the filtrate was added with deionized water (30.0L) to precipitate solids, filtered, and washed with deionized water for several times to obtain a crude product. Then, isopropanol (10.0L) was added to dissolve the crude product, and deionized water (30.0L) was added to recrystallize the precipitated solids, filtered, and vacuum dried to obtain 24.8kg of lauric acid monoglyceride as a white solid, with a yield of 90.5% and an HPLC purity of 99.1%.

[0043] LC-MS(ESI):[M+H] + =275.3. And by comparison, the HPLC retention time of the product of this example is consistent with that of monolaurin.

[0044] The above embodiments are merely examples for clear explanation, and are not intended to limit the implementation methods. For those skilled in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the implementation methods here. The obvious changes or modifications derived from these are still within the protection scope of the invention.

Claims

1. A method for preparing an antibacterial feed additive, characterized in that: The additive is lauric acid monoglyceride, and its preparation method comprises the following steps: Using glycerol and lauric acid as raw materials, an esterification reaction occurs in the presence of MgO / HMCM-22 molecular sieve catalyst to produce lauric acid monoglyceride antibacterial feed additive. The reaction formula is:

2. The preparation method according to claim 1, characterized in that: The preparation method of MgO / HMCM-22 molecular sieve catalyst comprises the following steps: 1) reacting NaMCM-22 molecular sieve having a silicon-aluminum ratio of 25 to 30 with NH4NO3 solution at 60 to 100°C to obtain HMCM-22 molecular sieve; 2) Weigh an appropriate amount of MgO powder, add deionized water and stir thoroughly to prepare a milky white MgO suspension, add the above HMCM-22 molecular sieve to the suspension and stir evenly, let it stand and then dry, and calcine after sieving to obtain a MgO / HMCM-22 molecular sieve catalyst.

3. The preparation method according to claim 1, characterized in that: The reaction solvent is selected from one or more of DMSO, DMF, benzene and toluene.

4. The preparation method according to claim 1, characterized in that: The molar ratio of the glycerol to the lauric acid is 1:(1.0-1.1); the mass ratio of the MgO / HMCM-22 molecular sieve catalyst to the lauric acid is 1:(8-12).

5. The preparation method according to claim 1, characterized in that: The reaction temperature is 80-110°C and the reaction time is 4-6h.

6. The preparation method according to claim 1, characterized in that: After the reaction is completed, the MgO / HMCM-22 molecular sieve catalyst is removed by filtration, and deionized water is added to the filtrate to precipitate a solid, which is then filtered and washed with deionized water for multiple times to obtain a crude product; isopropanol is then added to dissolve the crude product, and deionized water is then added to recrystallize and precipitate a solid, which is then filtered and vacuum dried to obtain lauric acid monoglyceride.

7. The preparation method according to claim 6, characterized in that: The volume ratio of the isopropanol to the deionized water is 1:(3-5).

8. The preparation method according to claim 2, characterized in that: The loading amount of MgO in the MgO / HMCM-22 molecular sieve catalyst is 5% to 10%; the mass ratio of the NaMCM-22 molecular sieve to the NH4NO3 solution is (20 to 30):

1.

9. The antibacterial feed additive prepared according to the preparation method according to any one of claims 1 to 8.

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