Preparation method of feed additive DL-methionine copper complex

Abstract

The present invention belongs to the field of organic synthesis, and specifically relates to a preparation method of a feed additive DL-methionine complex copper. The reaction steps include: using DL-methionine and a copper source as raw materials, and carrying out a chelation reaction in the presence of an ionic liquid catalyst to generate DL-methionine complex copper. The metal ionic liquid catalyst adopted by the present invention can improve the reaction activity of the copper source, enabling the reaction to proceed efficiently and rapidly. Moreover, there is no need to additionally add an alkali catalyst, the reaction temperature is low, the reaction time is short, and the post-treatment operation is simple, greatly reducing the production cost, conforming to the trend of green chemistry, and being suitable for industrial production.

Description

Technical Field

[0001] The present invention belongs to the field of organic synthesis, and particularly relates to a preparation method of a feed additive DL-methionine complex copper. Background Art

[0002] Since the chemical community discovered and prepared chelates in the early 17th century, the research and application of chelates have been greatly developed in many industries. In the 1970s of the 20th century, metal element amino acid chelates began to be applied in animal nutrition, and currently their application fields are becoming more and more extensive. The American Official Feed Control Officials Association defines the concept of amino acid chelates as follows: Amino acid metal element chelates refer to products formed by the reaction of metal ions in 1 mol of soluble metal salts with 1-3 mol (preferably 2 mol) of amino acids, which are combined by coordination covalent bonds. The molecular weight of the formed chelates generally does not exceed 800, which is not only conducive to the complete transport and absorption of trace elements in the form of chelates, but also can effectively release metal ions when needed.

[0003] Amino acid metal chelates have the characteristics of stable chemical structure, high biological potency, ability to enhance immunity, improve disease resistance, and being green and environmentally friendly. DL-methionine complex copper is absorbed by pinocytosis, which can alleviate the competitive antagonism between trace elements. It not only greatly improves the absorption utilization rate of copper ions and the absorption of other trace elements, but also methionine, as a carrier, has the characteristics of being safe and harmless. Therefore, adding it to feed will not damage various types of vitamins, nor will it catalyze the oxidation reaction of oils and fats in the feed, and at the same time, it can improve the quality of the feed.

[0004] CN111051317A discloses a preparation method of methionine-metal chelate. First, methionine (i.e., methionine) is mixed with calcium hydroxide, and then a metal chloride such as copper chloride is added to the mixture to form methionine copper chelate. This method utilizes the solubility difference between methionine copper chelate and methionine calcium chelate to displace the more insoluble methionine copper chelate. However, this method produces a by-product calcium chloride, that is, it will also generate unnecessary inorganic salts, and there are also problems that the mother liquor cannot be recycled and the subsequent environmental protection treatment cost is too high.

[0005] CN111978221A discloses a preparation method of feed additive DL-methionine copper complex. In this method, an aqueous solution of methionine is heated to 60-80 °C and kept at a constant temperature. Then copper salt is added. After stirring, an aqueous solution of methionine metal salt and corresponding carbonate is added to adjust the pH. Then it is heated to 60-110 °C and reacted for 0.5-1.0 hour. Then it is filtered and washed with normal temperature water to obtain the methionine copper product. This method is the most common method, but it has problems such as a large amount of wastewater discharge caused by many by-products, difficult treatment, and high treatment cost. Considering the current national environmental protection policy, it is urgent to find a new synthesis method to reduce the wastewater discharged during the production of methionine copper chelate and solve the pollution problem from the source. The existing preparation methods of methionine copper chelate that are green, environmentally friendly and economical have little improvement or the reactions are cumbersome and harsh, making it difficult to be promoted industrially.

[0006] CN115724778B discloses a preparation method of methionine copper chelate. Using methionine and copper hydroxide as raw materials, in the presence of water and a catalyst, methionine copper chelate is generated through a reaction. The catalyst is selected from water-soluble divalent copper salts. Preferably, the water-soluble divalent copper salt is selected from one or a combination of copper sulfate, copper chloride, copper nitrate, copper acetate and copper formate. However, this method has a high reaction temperature, a long reaction time, and a low chelation rate of the product, and is not suitable for industrial production.

[0007] Based on this, it is urgent to develop a method for preparing DL-methionine copper complex with mild reaction conditions, green environmental protection and suitable for industrial production. Summary of the Invention

[0008] In view of the problems existing in the prior art, the purpose of the present invention is to provide a preparation method of feed additive DL-methionine copper complex to solve the problems of non-environmental protection, non-mild reaction conditions, low chelation rate and unsuitability for industrial production in the prior art. The present invention is achieved through the following technical solutions:

[0009] A preparation method of feed additive DL-methionine copper complex includes the following steps:

[0010] Using DL-methionine and copper source as raw materials, a chelation reaction occurs in the presence of an ionic liquid catalyst to generate DL-methionine copper complex;

[0011] Among them, the copper source is selected from one or more of copper hydroxide, copper oxide and copper carbonate;

[0012] The structural formula of the ionic liquid catalyst is:

[0013] In some embodiments, the reaction solvent is selected from one or more of water, methanol, ethanol and isopropanol.

[0014] In some embodiments, the reaction solvent is water.

[0015] In some embodiments, the copper source is copper hydroxide or copper oxide.

[0016] In some embodiments, the molar ratio of DL-methionine to the copper source is (2.0 - 2.5):1; the molar ratio of DL-methionine to the ionic liquid catalyst is 1:(0.005 - 0.015).

[0017] In some embodiments, after the reaction is completed, the reaction solution is cooled to 10 - 15 °C and then filtered by suction, and the filter cake is washed with hot water, and then the obtained solid is dried in vacuo to obtain copper complex of DL-methionine.

[0018] In some embodiments, the residual solvent is removed by distillation under reduced pressure from the filtrate after filtration, and the residue is dried in vacuo to obtain the ionic liquid catalyst, which can be recycled.

[0019] In some embodiments, the reaction temperature is 25 - 45 °C and the reaction time is 20 - 40 min.

[0020] In some embodiments, the method preferably comprises the following steps:

[0021] Add DL-methionine, copper hydroxide and water into a reactor, then slowly add the ionic liquid catalyst, heat up to 40 °C and stir for reaction for 20 min; after the reaction is completed, cool the reaction solution to 15 °C and then filter by suction, and wash the filter cake with hot water at 90 °C, and then dry the obtained solid in vacuo at 100 °C for 5 h to obtain copper chelate of DL-methionine.

[0022] The present invention has achieved the following beneficial effects:

[0023] 1) The metal ionic liquid catalyst adopted by the present invention can improve the reaction activity of the copper source, and then can react with methionine efficiently to generate copper chelate of methionine, with high yield and chelation rate. In addition, compared with the prior art, the present invention does not produce inorganic salt wastewater, is green and environment-friendly, and is suitable for industrial production.

[0024] 2) The reaction conditions of the present invention are mild, with low reaction temperature and short reaction time.

[0025] 2) For the filtrate after filtration in the present invention, the residual solvent is removed by distillation under reduced pressure, and the residue is dried in vacuo to obtain the ionic liquid catalyst, which can be recycled. Detailed implementation manners

[0026] 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. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0027] The endpoints and any values of the ranges described in the present invention are not limited to the exact ranges or values. These ranges or values should be understood to include values close to these ranges or values. For numerical ranges, between the endpoint values of each range, between the endpoint values of each range and individual point values, and between individual point values, they can be combined with each other to obtain one or more new numerical ranges, and these numerical ranges should be regarded as specifically disclosed herein.

[0028] Preparation Example 1: Preparation of Metal Ionic Liquid Catalyst

[0029] Step 1: Preparation of Ionic Liquid Intermediate

[0030]

[0031] Under nitrogen protection, N,N'-carbonyldiimidazole (0.1 mol) and 1-chlorobutane (0.2 mol) were added to the reactor, and then acetonitrile (200 mL) and ethanol (30 mL) were added in sequence. The temperature was raised to 70 °C and refluxed with stirring for 12 h. After the reaction was completed, it was cooled to room temperature. Petroleum ether (200 mL) and ethyl acetate (100 mL) were added to the solution, and a brown viscous liquid precipitated. The mixture was extracted with a separatory funnel, and the residual solvent was removed by rotary evaporation. Finally, the collected viscous liquid was placed in a vacuum drying oven for 10 hours to obtain the ionic liquid intermediate, and the yield was 36.2%.

[0032] Step 2: Preparation of Metal Ionic Liquid Catalyst

[0033]

[0034] Under nitrogen protection, the ionic liquid intermediate (0.1 mol) prepared in Step 1 was added to the reactor, and then CuCl2·2H2O (0.2 mol) was added. The temperature was raised to 90 °C and stirred for 6 h. After the reaction was completed, the solvent was removed by rotary evaporation and vacuum dried at 100 °C for 12 h to obtain the metal ionic liquid catalyst, and the yield was 93.1%.

[0035] 11H NMR (400 MHz, DMSO-d6) δ 7.62 (s, 2H), 7.17 (s, 2H), 6.88 (s, 2H), 3.96 - 3.91 (s, 4H), 1.66 - 1.58 (s, 4H), 1.23 - 1.17 (s, 4H), 0.92 - 0.84 (s, 6H).

[0036] Example 1

[0037] DL-Methionine (30.0 g, 0.2 mol), copper hydroxide (9.8 g, 0.1 mol) and water (300 mL) were added to a reactor, and then the ionic liquid catalyst obtained in Preparation Example 1 (0.01 mol) was slowly added, and the temperature was raised to 40 °C and stirred for 20 min. After the reaction was completed, the reaction solution was cooled to 15 °C and then filtered by suction, and the filter cake was washed with hot water at 90 °C. Then the obtained solid was vacuum dried at 100 °C for 5 h to obtain DL-methionine complex copper chelate, with a yield of 98.7% and a chelation rate of 99.6%.

[0038] The filtrate after filtration was distilled under reduced pressure to remove the residual solvent, and the residue was vacuum dried to obtain the ionic liquid catalyst, which could be recycled.

[0039] By comparison, the HPLC retention time of the product in this example was consistent with that of the DL-methionine complex copper standard.

[0040] Example 2

[0041] DL-Methionine (30.0 g, 0.2 mol), CuO (8.0 g, 0.1 mol) and water (200 mL) were added to a reactor, and then the ionic liquid catalyst obtained in Preparation Example 1 (0.005 mol) was slowly added, and the temperature was raised to 35 °C and stirred for 30 min. After the reaction was completed, the reaction solution was cooled to 10 °C and then filtered by suction, and the filter cake was washed with hot water at 90 °C. Then the obtained solid was vacuum dried at 100 °C for 5 h to obtain DL-methionine complex copper chelate, with a yield of 96.9% and a chelation rate of 99.4%.

[0042] The filtrate after filtration was distilled under reduced pressure to remove the residual solvent, and the residue was vacuum dried to obtain the ionic liquid catalyst, which could be recycled.

[0043] By comparison, the HPLC retention time of the product in this example was consistent with that of the DL-methionine complex copper standard.

[0044] Example 3 (Scaled-up production)

[0045] DL-methionine (3.0 kg, 20.1 mol), copper hydroxide (0.98 kg, 10.0 mol) and water (30 L) were added to a reactor, and then the ionic liquid catalyst obtained in Preparation Example 1 (1.0 mol) was slowly added, and the temperature was raised to 40 °C and stirred for 30 min. After the reaction was completed, the reaction solution was cooled to 15 °C and then filtered by suction, and the filter cake was washed with hot water at 90 °C. Then the obtained solid was vacuum dried at 100 °C for 5 h to obtain DL-methionine complex copper chelate, with a yield of 97.0% and a chelation rate of 99.3%.

[0046] The filtrate after filtration was distilled under reduced pressure to remove the residual solvent, and the residue was vacuum dried to obtain the ionic liquid catalyst, which could be recycled.

[0047] By comparison, the HPLC retention time of the product in this example was consistent with that of the DL-methionine complex copper standard.

[0048] The above examples are only for clearly illustrating the examples and not for limiting the implementation mode. For those of ordinary skill in the art, other different forms of changes or variations can be made based on the above description. It is not necessary and impossible to list all implementation modes here. And the obvious changes or variations thus derived are still within the protection scope of the present invention.

Claims

1. A preparation method of feed additive DL-methionine copper complex, comprising the following steps: Using DL-methionine and copper source as raw materials, chelation reaction occurs in the presence of ionic liquid catalyst to generate DL-methionine copper complex; Among them, The structural formula of the ionic liquid catalyst is as follows: The reaction solvent is water; The copper source is copper hydroxide or copper oxide.

2. The preparation method according to claim 1, characterized in that, The molar ratio of DL-methionine to copper source is (2.0 - 2.5):1; the molar ratio of DL-methionine to ionic liquid catalyst is 1:(0.005 - 0.015).

3. The preparation method according to claim 1, wherein After the reaction is completed, the reaction solution is cooled to 10 - 15 °C and then filtered by suction, and the filter cake is washed with hot water, and then the obtained solid is dried in vacuum to obtain DL-methionine copper complex.

4. The preparation method according to claim 3, characterized in that, The filtrate after filtration is distilled under reduced pressure to remove the residual solvent, and the residue is dried in vacuum to obtain the ionic liquid catalyst, which can be recycled.

5. The preparation method according to claim 1, characterized in that, The reaction temperature is 25 - 45 °C and the reaction time is 20 - 40 min.

6. The preparation method according to claim 1, wherein, Comprising the following steps: Adding DL-methionine, copper hydroxide and water into the reactor, then slowly adding the ionic liquid catalyst, heating to 40 °C and stirring for reaction for 20 min; after the reaction is completed, the reaction solution is cooled to 15 °C and then filtered by suction, and the filter cake is washed with hot water at 90 °C, and then the obtained solid is dried in vacuum at 100 °C for 5 h to obtain DL-methionine copper complex chelate.

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