Dipeptide mother liquor treatment method and application thereof in dipeptide production process
阅读说明：本技术 一种二肽母液的处理方法及其在二肽的生产工艺中的应用 (Dipeptide mother liquor treatment method and application thereof in dipeptide production process ) 是由 陈进 王念 陈赟 于 2021-08-30 设计创作，主要内容包括：本申请提供一种二肽母液的处理方法及其在二肽的生产工艺中的应用,所述处理方法包括：将包括二肽母液和第一碱性物质在内的组分混合进行水解,得到二肽母液水解液；将所述二肽母液水解液进行酸化结晶,得到二肽回收粗品；将包括所述二肽回收粗品与第二碱性物质在内的组分混合进行溶清,得到二肽回收粗品溶清液；将所述二肽回收粗品溶清液与拆分剂混合进行拆分,然后固液分离；将所述固液分离后的固体进行酸化。本申请的二肽母液的处理方法处理过程简单、处理成本低、能够回收高价值的二肽以及异构体且回收效益高且绿色环保。(The application provides a treatment method of dipeptide mother liquor and application thereof in a dipeptide production process, wherein the treatment method comprises the following steps: mixing components including dipeptide mother liquor and a first alkaline substance, and hydrolyzing to obtain dipeptide mother liquor hydrolysate; acidifying and crystallizing the dipeptide mother liquor hydrolysate to obtain a dipeptide recovered crude product; mixing the components including the dipeptide crude product and a second alkaline substance for dissolving and clearing to obtain a dipeptide crude product dissolved and clear solution; mixing the dipeptide recovered crude product solution clear solution with a resolving agent for resolution, and then carrying out solid-liquid separation; and acidifying the solid after the solid-liquid separation. The treatment method of the dipeptide mother liquor has the advantages of simple treatment process, low treatment cost, high value dipeptide and isomer recovery, high recovery benefit and environmental protection.)
1. A method for treating a dipeptide mother liquor, comprising:
mixing components including dipeptide mother liquor and a first alkaline substance, and hydrolyzing to obtain dipeptide mother liquor hydrolysate;
acidifying and crystallizing the dipeptide mother liquor hydrolysate to obtain a dipeptide recovered crude product;
mixing the components including the dipeptide crude product and a second alkaline substance for dissolving and clearing to obtain a dipeptide crude product dissolved and clear solution;
mixing the dipeptide recovered crude product solution clear solution with a resolving agent for resolution, and then carrying out solid-liquid separation;
and acidifying the solid after the solid-liquid separation.
2. The method for treating dipeptide mother liquor according to claim 1, wherein the first alkaline substance comprises one or more of sodium hydroxide, potassium hydroxide, calcium hydroxide, lithium hydroxide, sodium carbonate and potassium carbonate; more preferably, the first basic substance is lithium hydroxide;
preferably, the dosage of the first alkaline substance is 0.1-2 times of the total mass of the dipeptide mother liquor;
preferably, the hydrolysis temperature is 20-60 ℃, and the hydrolysis time is 2-8 h; more preferably, the temperature of the hydrolysis is 35 ℃ and the time is 4 h.
3. The method for treating dipeptide mother liquor according to claim 1, wherein the acidification crystallization process comprises: mixing the components including the dipeptide mother liquor hydrolysate and the acidic substance, adjusting the pH value to 1-6, and then stirring and crystallizing at-10-25 ℃ for 2-12 h;
preferably, the acidic substance comprises one or more of hydrochloric acid, sulfuric acid, nitric acid, acetic acid, formic acid and oxalic acid; more preferably, the acidic substance is hydrochloric acid;
preferably, the mixing is performed to adjust the pH to 2-3, and then the stirring is performed at 0 ℃ for crystallization for 8 h;
preferably, the acidic substance is an acid solution with the concentration of 1-12mol/L, and more preferably, the acidic substance is an acid solution with the concentration of 1 mol/L.
4. The method for treating dipeptide mother liquor according to claim 1, further comprising concentrating before the acidifying crystallization;
preferably, the acidification and crystallization is followed by solid-liquid separation to obtain a solid, namely the dipeptide crude product.
5. The method for treating dipeptide mother liquor according to claim 1, wherein the second alkaline substance comprises one or more of ammonia, sodium hydroxide, potassium hydroxide, calcium hydroxide, lithium hydroxide, sodium carbonate and potassium carbonate; more preferably, the second basic substance is ammonia;
preferably, the temperature of the solvent is 25-100 ℃, and more preferably, the temperature of the solvent is 40 ℃;
preferably, the second alkaline substance is an alkaline solution with the mass fraction of 10-25%.
6. The method for treating dipeptide mother liquor according to claim 1, wherein the resolving agent comprises one or more of acetone, methyl ethyl ketone, methyl isobutyl ketone and isopropanol; preferably, the resolving agent is acetone.
7. The method of treating a dipeptide mother liquor according to claim 1, wherein the acidification of the solid after the solid-liquid separation comprises: adding an acidic substance into the solid after the solid-liquid separation to adjust the pH value to 1-6.
8. The method of treating a dipeptide mother liquor according to any of claims 1 to 7, characterised in that the acidification of the solid after the solid-liquid separation further comprises concentration;
preferably, the concentration also comprises dispersing by using a dispersing agent, then carrying out solid-liquid separation, and drying the solid.
9. The method for treating dipeptide mother liquor according to claim 8, wherein the dispersant comprises one or more of ethanol, methanol, isopropanol, ethyl acetate and acetone;
preferably, the dispersing agent is a mixture of ethanol and ethyl acetate in a mass ratio of (1-4) to (1-4).
10. An application of a dipeptide mother liquor treatment method in a dipeptide production process.
Technical Field
The application relates to the field of drug synthesis, in particular to a dipeptide mother liquor treatment method and application thereof in a dipeptide production process.
Background
The dipeptide is named L-alanine-p-acetyl-L-phenylalanine hydrochloride in chemical name, has chirality, is an important medical intermediate, is used as an unnatural amino acid, and is widely applied to synthesis of medicines based on the unnatural amino acid ADC.
At present, the domestic dipeptide production process mainly uses p-acetyl-L-phenylalanine hydrochloride as a raw material to perform ester exchange reaction with Boc-L-alanine active ester to obtain Boc-dipeptide, and then the Boc-dipeptide is hydrolyzed to remove Boc and acidified to obtain the dipeptide.
And carrying out ester exchange on the p-acetyl-L-phenylalanine hydrochloride and Boc-L-alanine active ester to generate Boc-dipeptide, then removing the Boc group to form a dipeptide crude product, refining the dipeptide crude product by using an ethanol/ethyl acetate mixed solvent, crystallizing, and centrifuging the residual mixed solution to obtain the dipeptide mother solution. Through detection and analysis, the dipeptide mother liquor mainly contains L-alanine-p-acetyl-phenylalanine methyl ester hydrochloride (racemic dipeptide methyl ester), ethyl acetate, ethanol, small amount of dipeptide (L-alanine-p-acetyl-L-phenylalanine hydrochloride), dipeptide isomer (L-alanine-p-acetyl-D-phenylalanine hydrochloride), and H+、Cl-And the like.
The dipeptide mother liquor is dark brown, is viscous liquid and contains certain suspended particles; through chemical detection, the COD of the dipeptide mother liquor is as high as 9.8 multiplied by 104Above ppm. The dipeptide mother liquor contains racemic dipeptide methyl ester, dipeptide and isomers thereof, and several substances have chirality and are difficult to separate. In the traditional dipeptide production process, a dipeptide mother solution is neutralized to be neutral by using an alkali solution, the dipeptide mother solution is kept stand for layering, and after ethanol and ethyl acetate are recovered from separated organic phases, the residual organic matters (various dipeptide derivatives) are barreled and treated outside; the separated water layer is distilled and centrifuged to obtain solid waste (mainly containing sodium salt), which is bagged and then disposed of. The method for treating the dipeptide mother liquor has the problems of high energy consumption, high cost and serious pollution to the environment, and simultaneously, the waste contains high-value dipeptide and derivatives thereof which are not recycled, so that the waste is extremely large.
Disclosure of Invention
The purpose of the application is to provide a method for treating dipeptide mother liquor, which has the advantages of simple treatment process, low treatment cost, high recovery benefit and environmental protection, and can recover high-value dipeptide and isomer, and the application of the method in the dipeptide production process.
In order to achieve the purpose, the following technical scheme is adopted in the application:
a method for treating dipeptide mother liquor comprises the following steps:
mixing components including dipeptide mother liquor and a first alkaline substance, and hydrolyzing to obtain dipeptide mother liquor hydrolysate;
acidifying and crystallizing the dipeptide mother liquor hydrolysate to obtain a dipeptide recovered crude product;
mixing the components including the dipeptide crude product and a second alkaline substance for dissolving and clearing to obtain a dipeptide crude product dissolved and clear solution;
mixing the dipeptide recovered crude product solution clear solution with a resolving agent for resolution, and then carrying out solid-liquid separation;
and acidifying the solid after the solid-liquid separation.
In some embodiments, the first alkaline substance comprises one or more of sodium hydroxide, potassium hydroxide, calcium hydroxide, lithium hydroxide, sodium carbonate, and potassium carbonate; more preferably, the first basic substance is lithium hydroxide.
In some embodiments, the first basic substance is used in an amount of 0.1 to 2 times the total mass of the dipeptide mother liquor.
In some embodiments, the hydrolysis is at a temperature of 20-60 ℃ for 2-8 hours; preferably, the hydrolysis temperature is 35 ℃ and the time is 4 h.
In some embodiments, the process of acidifying crystallization comprises: mixing the components including the dipeptide mother liquor hydrolysate and the acidic substance, adjusting the pH value to 1-6, and then stirring and crystallizing at-10-25 ℃ for 2-12 h;
preferably, the acidic substance comprises one or more of hydrochloric acid, sulfuric acid, nitric acid, acetic acid, formic acid and oxalic acid; more preferably, the acidic substance is hydrochloric acid;
preferably, the mixing is performed to adjust the pH to 2-3, and then the crystallization is performed for 8 hours under stirring at-0 ℃;
preferably, the acidic substance is an acid solution with the concentration of 1-12mol/L, and more preferably, the acidic substance is an acid solution with the concentration of 1 mol/L.
In some embodiments, the acidifying crystallization further comprises concentrating;
preferably, the acidification and crystallization is followed by solid-liquid separation to obtain a solid, namely the dipeptide crude product.
In some embodiments, the second basic substance comprises one or more of ammonia, sodium hydroxide, potassium hydroxide, calcium hydroxide, lithium hydroxide, sodium carbonate, and potassium carbonate; more preferably, the second basic substance is ammonia;
preferably, the temperature of the solvent is 25-100 ℃, and more preferably, the temperature of the solvent is 40 ℃;
preferably, the second alkaline substance is an alkaline solution with the mass fraction of 10-25%.
In some embodiments, the resolving agent comprises one or more of acetone, methyl ethyl ketone, methyl isobutyl ketone, and isopropanol; preferably, the resolving agent is acetone.
In some embodiments, the process of acidifying the solids after the solid-liquid separation comprises: adding an acidic substance into the solid after the solid-liquid separation to adjust the pH value to 1-6.
In some embodiments, acidifying the solids after the solid-liquid separation further comprises concentrating;
preferably, the concentration also comprises dispersing by using a dispersing agent, then carrying out solid-liquid separation, and drying the solid.
In some embodiments, the dispersant comprises one or more of ethanol, methanol, isopropanol, ethyl acetate, and acetone;
preferably, the dispersing agent is a mixture of ethanol and ethyl acetate in a mass ratio of (1-4) to (1-4).
The application also provides application of the dipeptide mother liquor treatment method in the dipeptide production process.
The beneficial effect of this application:
the method has the advantages that after the dipeptide mother liquor is subjected to hydrolysis, acidification crystallization, dissolution, resolution and secondary acidification, most substances in the dipeptide target liquor can be recycled, the treatment process is simple, the treatment cost is low, the recycling benefit is high, the method is green, safe and environment-friendly, the recycling of high-value and medium-value products of the dipeptide mother liquor is realized, and the problems of high energy consumption, high cost, high pollution and serious waste of the high-value and medium-value products caused by the traditional treatment of neutralizing with alkali in a sewage station are solved; the method for treating the dipeptide mother liquor changes waste into valuable and creates additional economic benefit.
Drawings
To more clearly illustrate the technical solutions of the embodiments of the present application, the drawings that are required to be used in the embodiments are briefly described below, and it should be understood that the following drawings only illustrate some embodiments of the present application and therefore should not be considered as limiting the scope of the present application.
FIG. 1 is an HPLC chromatogram of the dipeptide product recovered in example 1;
FIG. 2 is an infrared spectrum of a standard dipeptide reference;
FIG. 3 is an IR spectrum of the dipeptide product recovered in example 1.
Detailed Description
The terms as used herein:
"prepared from … …" is synonymous with "comprising". The terms "comprises," "comprising," "includes," "including," "has," "having," "contains," "containing," or any other variation thereof, as used herein, are intended to cover a non-exclusive inclusion. For example, a composition, process, method, article, or apparatus that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, process, method, article, or apparatus.
The conjunction "consisting of … …" excludes any unspecified elements, steps or components. If used in a claim, the phrase is intended to claim as closed, meaning that it does not contain materials other than those described, except for the conventional impurities associated therewith. When the phrase "consisting of … …" appears in a clause of the subject matter of the claims rather than immediately after the subject matter, it defines only the elements described in the clause; other elements are not excluded from the claims as a whole.
When an amount, concentration, or other value or parameter is expressed as a range, preferred range, or as a range of upper preferable values and lower preferable values, this is to be understood as specifically disclosing all ranges formed from any pair of any upper range limit or preferred value and any lower range limit or preferred value, regardless of whether ranges are separately disclosed. For example, when the range "1 ~ 5" is disclosed, the described range should be interpreted to include the ranges "1-4", "1-3", "1-2 and 4-5", "1-3 and 5", and the like. When a range of values is described herein, unless otherwise stated, the range is intended to include the endpoints thereof and all integers and fractions within the range.
In these examples, the parts and percentages are by mass unless otherwise indicated.
"part by mass" means a basic unit of measure indicating a mass ratio of a plurality of components, and 1 part may represent any unit mass, for example, 1g or 2.689 g. If we say that the part by mass of the component A is a part by mass and the part by mass of the component B is B part by mass, the ratio of the part by mass of the component A to the part by mass of the component B is a: b. alternatively, the mass of the A component is aK and the mass of the B component is bK (K is an arbitrary number, and represents a multiple factor). It is unmistakable that, unlike the parts by mass, the sum of the parts by mass of all the components is not limited to 100 parts.
"and/or" is used to indicate that one or both of the illustrated conditions may occur, e.g., a and/or B includes (a and B) and (a or B).
The application provides a dipeptide mother liquor treatment method, which comprises the following steps:
s100, mixing components including the dipeptide mother liquor and the first alkaline substance, and hydrolyzing to obtain the dipeptide mother liquor hydrolysate.
In some embodiments, the first alkaline substance comprises one or more of sodium hydroxide, potassium hydroxide, calcium hydroxide, lithium hydroxide, sodium carbonate, and potassium carbonate; more preferably, when the first alkaline substance is lithium hydroxide, the hydrolysis reaction is faster and more sufficient.
In some embodiments, the first basic substance is used in an amount of 0.1 to 2 times the total mass of the dipeptide mother liquor.
In some embodiments, the hydrolysis is at a temperature of 20-60 ℃ for 2-8 hours; preferably, the hydrolysis reaction is more complete when the hydrolysis temperature is 35 ℃ and the hydrolysis time is 4 hours.
It is noted that, because the main component of the dipeptide mother liquor is dipeptide ethanol ester, lithium hydroxide or other alkaline substances are hydrolyzed to form lithium salt (mixed spinning) of dipeptide, which is dissolved in water; the specific hydrolysis reaction equation is as follows:
s200, acidifying and crystallizing the dipeptide mother liquor hydrolysate to obtain a dipeptide recovered crude product.
In some embodiments, the process of acidifying crystallization comprises: mixing the components including the dipeptide mother liquor hydrolysate and the acidic substance, adjusting the pH value to 1-6, and then stirring and crystallizing at-10-25 ℃ for 2-12 h; preferably, the acidic substance comprises one or more of hydrochloric acid, sulfuric acid, nitric acid, acetic acid, formic acid and oxalic acid; more preferably, the acidic substance is hydrochloric acid.
In the step, after the pH is adjusted by adding dilute hydrochloric acid or other acidic substances, lithium salt (mixed spinning) of dipeptide is converted into dipeptide (mixed spinning), the solubility of dipeptide (mixed spinning) in water is reduced, and then the temperature is reduced for crystallization to obtain crude dipeptide (mixed spinning); the specific acidification equation is as follows:
preferably, the pH is adjusted to 2-3 by mixing, and then the mixture is stirred and crystallized for 8 hours at-0 ℃, under the condition, the acidification and crystallization are faster and more sufficient, so that the yield of the dipeptide lithium salt converted into the dipeptide recovery crude product is higher.
Preferably, the acidic substance is an acid solution with the concentration of 1-12mol/L, and more preferably, the acidic substance is an acid solution with the concentration of 1 mol/L.
In some embodiments, the acidification crystallization is preceded by concentration to accelerate subsequent acidification crystallization; and carrying out solid-liquid separation after the acidification and crystallization to obtain solid, namely the dipeptide recovered crude product.
The solid-liquid separation is preferably performed by vacuum filtration, but may be performed by centrifugation.
S300, mixing the components including the dipeptide crude product and a second alkaline substance for clearing, and obtaining a dipeptide crude product clear solution.
The pH value of the above components including the crude dipeptide product and the second basic substance is 7-8 before the components are mixed and dissolved.
In some embodiments, the second basic substance comprises one or more of ammonia, sodium hydroxide, potassium hydroxide, calcium hydroxide, lithium hydroxide, sodium carbonate, and potassium carbonate; more preferably, the second basic substance is ammonia.
It should be noted that, after adding ammonia water or the above-mentioned other alkaline substances into the dipeptide recovered crude product, the crude product is dissolved clearly to form amine salt (racemic) of dipeptide, which is easily dissolved in water; the specific chemical reaction equation of the step is as follows:
preferably, the temperature of the solvent is 25-100 ℃, more preferably, the temperature of the solvent is 40 ℃.
Preferably, the second alkaline substance is an alkaline solution with the mass fraction of 10-25%.
S400, mixing the dipeptide recovered crude product soluble clear liquid with a resolving agent for resolution, and then carrying out solid-liquid separation.
In some embodiments, the resolving agent comprises one or more of acetone, methyl ethyl ketone, methyl isobutyl ketone, and isopropanol; preferably, the resolving agent is acetone.
It is noted that, after acetone or other resolving agents are added into the amine salt of the dipeptide, the L-type dipeptide amine salt is separated out, and the D-type dipeptide amine salt is dissolved in the solution, so that the separation of mixed helices is realized; the specific chemical reaction equation of the step is as follows:
s500, acidifying the solid after solid-liquid separation.
In some embodiments, the process of acidifying the solids after the solid-liquid separation comprises: adding an acidic substance into the solid after the solid-liquid separation to adjust the pH value to 1-6; the acidic substance is the same as the above-mentioned acidic substance.
In some embodiments, acidifying the solids after the solid-liquid separation further comprises concentrating; preferably, the concentration also comprises dispersing by using a dispersing agent, then carrying out solid-liquid separation, and drying the solid.
In some embodiments, the dispersant comprises one or more of ethanol, methanol, isopropanol, ethyl acetate, and acetone; preferably, the dispersing agent is a mixture of ethanol and ethyl acetate in a mass ratio of (1-4) to (1-4).
It is to be noted that after separating the amine salt of dipeptide, acidifying with dilute hydrochloric acid or other acidic substances to convert into dipeptide product (L-type or D-type), concentrating and drying, dispersing with ethanol or other dispersing agents, filtering, drying to obtain the final qualified dipeptide and dipeptide isomer product; the acidification reaction equation of the step is as follows:
the application also provides application of the dipeptide mother liquor treatment method in the dipeptide production process.
The dipeptide mother liquor generated in the dipeptide production process is treated by adopting the treatment method of the dipeptide mother liquor, so that after the main material dipeptide derivative (mainly dipeptide methyl ester) in the dipeptide mother liquor is hydrolyzed and split, the dipeptide and the dipeptide isomer can be almost completely recycled, and the recycling rate reaches more than 99 percent; the organic solvent can be recovered by distillation or rectification, and the recovered solvent can be repeatedly applied in related working procedures; a small amount of organic matters, inorganic salt wastewater and other impurities can be collected and then enter a sewage treatment station to be treated and discharged after reaching the standard.
Specifically, taking a production workshop which produces 100kg of dipeptide every year as an example, the amount of dipeptide mother liquor produced is up to 5 tons every year, and the treatment cost consumed every year is up to 2.5 ten thousand yuan by adopting a traditional alkali neutralization post-treatment method for sewage disposal; moreover, the dipeptide mother liquor to be treated can be biochemically treated after being diluted by a large amount of water after entering a sewage station, and a large amount of water resources are consumed.
By adopting the dipeptide mother liquor treatment method, 5 tons of dipeptide mother liquor are treated at one time, the sewage treatment cost can be saved by 2 ten thousand yuan, about 20kg of dipeptide and about 20kg of dipeptide isomer can be recovered, the total value is about 200 ten thousand yuan, and about 200 ten thousand yuan of economic benefit is created for enterprises.
Embodiments of the present application will be described in detail below with reference to specific examples, but those skilled in the art will appreciate that the following examples are only illustrative of the present application and should not be construed as limiting the scope of the present application. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.
Example 1
(1) Adding 500ml dipeptide mother liquor into a 1000ml beaker for later use; adding 100g of LiOH into the beaker, keeping the temperature at 35 ℃, stirring and hydrolyzing, wherein the hydrolysis time is 4 h; after the hydrolysis is finished, decompressing and concentrating the dipeptide mother liquor hydrolysate to 1/3; after the concentration is finished, dropwise adding a hydrochloric acid solution with the concentration of 1mol/L into the concentrated solution, adjusting the pH of the concentrated solution to 2-3, then transferring the concentrated solution into a low-temperature cold well, cooling to 0 ℃ for crystallization, wherein the crystallization time is 8 h; after the crystallization is finished, vacuum filtration is carried out, and a filter cake is collected to obtain about 5g of dipeptide recovered crude product;
(2) adding the dipeptide recovered crude product into a glass reaction bottle filled with 25 mass percent of ammonia water to ensure that the pH is 7-8 and 20g of 25 mass percent of ammonia water is consumed, and then heating to 40 ℃, stirring and dissolving; adding 20g of acetone into the obtained dipeptide recovery crude product solution clear solution, stirring and dispersing, cooling to room temperature to obtain a large amount of crystals, and performing vacuum filtration to collect a filter cake to obtain about 2.4g of dipeptide amine salt; and simultaneously distilling the filtrate until obvious particles appear, cooling to room temperature, stirring and crystallizing to obtain about 2.3g of dipeptide isomer amine salt.
(3) The dipeptide amine salt and dipeptide isomer amine salt were acidified to pH 2-3 with 1mol/L diluted hydrochloric acid in 10ml of water, respectively, then concentrated to dryness, 10ml of a dispersant (ethyl acetate: ethanol ═ 1:1) was added thereto, dispersed at room temperature with stirring for 2 hours, finally vacuum-filtered, and the solid was dried to obtain 2.1g of dipeptide with a purity of 99.3% and 2.0g of dipeptide isomer with a purity of 99.5%.
FIG. 1 is an HPLC chromatogram of the dipeptide product recovered above; in this figure, the peak at RT ═ 10.217 is the absorption peak of the dipeptide, and the peak at RT ═ 12.923 is the absorption peak of the dipeptide isomer.
FIGS. 2 and 3 are graphs showing the IR spectra of the standard dipeptide reference and the recovered dipeptide product, respectively, and it can be seen that the IR spectrum of the recovered dipeptide is completely identical to that of the standard dipeptide reference.
Before the dipeptide mother liquor is treated, the contents of COD, dipeptide methyl ester, ethanol, acetone, ethyl acetate and other organic impurities in the dipeptide mother liquor are detected; after the dipeptide mother liquor was treated, the organic solvent was recovered from the waste liquors produced in the respective steps, and about 195ml of all the waste liquors were combined, and the contents of COD, dipeptide methyl ester, ethanol, acetone, ethyl acetate and other organic impurities were measured again, and the results are shown in Table 1 below.
TABLE 1 comparison table before and after dipeptide mother liquor treatment
Item
Before treatment
After treatment
Total mother liquor amount
500ml
195ml
COD
9.5×104ppm
4500ppm
Dipeptide methyl ester
0.8％
0.01％
Ethanol
25％
0.05％
Acetone (II)
-
0.02％
Ethyl acetate
25％
0.03％
Other organic impurities
＜0.5％
＜0.5％
As is apparent from the comparison of the data in Table 1, after the dipeptide mother liquor is treated, the amount of wastewater, COD and other organic impurities are greatly reduced, and the cost and the difficulty of wastewater treatment are reduced; while high-value dipeptide methyl ester and most of the organic solvent are recovered.
Example 2
(1) Adding 500ml dipeptide mother liquor into a 1000ml beaker for later use; adding 50g of KOH into the beaker, keeping the temperature at 25 ℃, stirring and hydrolyzing for 4 h; after the hydrolysis is finished, decompressing and concentrating the dipeptide mother liquor hydrolysate to 1/2; after the concentration is finished, dropwise adding a hydrochloric acid solution with the concentration of 6mol/L into the concentrated solution, adjusting the pH of the concentrated solution to 2-3, then transferring the concentrated solution into a low-temperature cold well, cooling to 0 ℃ for crystallization, wherein the crystallization time is 8 h; after the crystallization is finished, vacuum filtration is carried out, and a filter cake is collected to obtain about 4.6g of dipeptide recovered crude product;
(2) adding the dipeptide recovered crude product into a glass reaction bottle filled with 10% KOH solution by mass fraction, keeping the pH at 7-8, consuming 25g of 10% KOH solution, heating to 40 ℃, and stirring to dissolve; adding 25g of acetone into the obtained dipeptide recovery crude product solution clear solution, stirring and dispersing, cooling to room temperature to obtain a large amount of crystals, and performing vacuum filtration to collect a filter cake to obtain about 2.2g of dipeptide amine salt; and simultaneously distilling the filtrate until obvious particles appear, cooling to room temperature, stirring and crystallizing to obtain about 2.1g of dipeptide isomer amine salt.
(3) The dipeptide amine salt and dipeptide isomer amine salt are respectively acidified in 10ml of water with dilute hydrochloric acid with the concentration of 6mol/L until the pH value is 2-3, then concentrated to be dry, 10ml of dispersing agent (ethyl acetate: ethanol ═ 1:1) is added, the mixture is stirred and dispersed for 2 hours at room temperature, and finally the mixture is filtered in vacuum, and the solid is dried to obtain 1.9g of dipeptide with the purity of 99.8% and 1.9g of dipeptide isomer with the purity of 99.7%.
In this example 2, the dipeptide mother liquor before treatment was the same as that in example 1, and after the dipeptide mother liquor was treated, the organic solvent in the waste liquid produced in each step was recovered, and about 280ml of all the waste liquids were combined, and the contents of COD, dipeptide methyl ester, ethanol, acetone, ethyl acetate and other organic impurities were measured again, and the results are shown in Table 2 below.
TABLE 2 comparison table before and after dipeptide mother liquor treatment
Example 3
(1) Adding 500ml dipeptide mother liquor into a 1000ml beaker for later use; adding 50g K2CO3 into the beaker, keeping the temperature at 60 ℃, stirring and hydrolyzing for 4 h; after the hydrolysis is finished, decompressing and concentrating the dipeptide mother liquor hydrolysate to 1/4; after the concentration is finished, dropwise adding a hydrochloric acid solution with the concentration of 6mol/L into the concentrated solution, adjusting the pH of the concentrated solution to 2-3, then transferring the concentrated solution into a low-temperature cold well, cooling to 0 ℃ for crystallization, wherein the crystallization time is 8 h; after the crystallization is finished, vacuum filtration is carried out, and a filter cake is collected to obtain about 2.4g of dipeptide recovered crude product;
(2) adding the dipeptide recovered crude product into a glass reaction bottle filled with 25 mass percent of ammonia water to ensure that the pH is 7-8 and 10g of 25 mass percent of ammonia water is consumed, and then heating to 40 ℃, stirring and dissolving; adding 20g of acetone into the obtained dipeptide recovery crude product solution clear solution, stirring and dispersing, cooling to room temperature to obtain a large amount of crystals, and performing vacuum filtration to collect a filter cake to obtain about 1.1g of dipeptide amine salt; and simultaneously distilling the filtrate until obvious particles appear, cooling to room temperature, stirring and crystallizing to obtain about 1.1g of dipeptide isomer amine salt.
(3) The dipeptide amine salt and dipeptide isomer amine salt were acidified to pH 2-3 with 1mol/L diluted hydrochloric acid in 25ml water, respectively, then concentrated to dryness, 5ml of a dispersant (ethyl acetate: ethanol ═ 1:1) was added thereto, dispersed at room temperature with stirring for 2 hours, finally vacuum-filtered, and the solid was dried to obtain 1.1g of dipeptide with a purity of 99.6% and 1.2g of dipeptide isomer with a purity of 99.7%.
In this example 3, the dipeptide mother liquor before treatment was the same as that in example 1, and after the dipeptide mother liquor was treated, the organic solvent in the waste liquor produced in each step was recovered, and about 155ml of all the waste liquors were combined, and the contents of COD, dipeptide methyl ester, ethanol, acetone, ethyl acetate and other organic impurities were measured again, and the results are shown in Table 3 below.
TABLE 3 comparison table of dipeptide mother liquor before and after treatment
Example 4
(1) Adding 50L dipeptide mother liquor into a 100L glass reaction kettle for later use; adding 10kg of LiOH into the reaction kettle, keeping the temperature at 35 ℃, stirring and hydrolyzing for 4 h; after the hydrolysis is finished, decompressing and concentrating the dipeptide mother liquor hydrolysate to 1/3; after the concentration is finished, dropwise adding a hydrochloric acid solution with the concentration of 1mol/L into the concentrated solution, adjusting the pH of the concentrated solution to 2-3, then transferring the concentrated solution into a low-temperature cold well, cooling to 0 ℃ for crystallization, wherein the crystallization time is 8 h; after the crystallization is finished, vacuum filtration is carried out, and a filter cake is collected to obtain about 0.5kg of dipeptide recovered crude product;
(2) adding the dipeptide recovered crude product into a glass reaction bottle filled with 25 mass percent of ammonia water to ensure that the pH is 7-8 and 2kg of 25 mass percent of ammonia water is consumed, and then heating to 40 ℃, stirring and dissolving; adding 2kg of acetone into the obtained dipeptide recovered crude product solution, stirring and dispersing, cooling to room temperature to obtain a large amount of crystals, and performing vacuum filtration to collect a filter cake to obtain about 0.24g of dipeptide amine salt; and simultaneously distilling the filtrate until obvious particles appear, cooling to room temperature, stirring and crystallizing to obtain about 0.23kg of dipeptide isomer amine salt.
(3) The dipeptide amine salt and dipeptide isomer amine salt are respectively acidified in 1L of water by using diluted hydrochloric acid with the concentration of 1mol/L until the pH value is 2-3, then the mixture is concentrated to be dry, 1L of dispersing agent (ethyl acetate: ethanol is 1:1) is added, the mixture is stirred and dispersed for 2 hours at room temperature, finally, the mixture is filtered in vacuum, and the solid is dried to obtain 0.22kg of dipeptide with the purity of 99.7 percent and 0.21kg of dipeptide isomer with the purity of 99.6 percent.
In this example 4, the dipeptide mother liquor before treatment was the same as that before treatment in example 1, and after the dipeptide mother liquor was treated, the organic solvent in the waste liquor produced in each step was recovered, and about 20L of all the waste liquors were combined, and the contents of COD, dipeptide methyl ester, ethanol, acetone, ethyl acetate and other organic impurities were measured again, and the results are shown in Table 4 below.
TABLE 4 comparison table before and after dipeptide mother liquor treatment
Item
Before treatment
After treatment
Total mother liquor amount
50L
20L
COD
9.5×104ppm
4500ppm
Dipeptide methyl ester
0.8％
0.01％
Ethanol
25％
0.05％
Acetone (II)
-
0.02％
Ethyl acetate
25％
0.03％
Other organic impurities
＜0.5％
＜0.5％
Example 5
(1) Adding 500L dipeptide mother liquor into a 1000L glass lining reaction kettle for later use; adding 100kg of LiOH into the reaction kettle, keeping the temperature at 35 ℃, stirring and hydrolyzing for 4 h; after the hydrolysis is finished, decompressing and concentrating the dipeptide mother liquor hydrolysate to 1/3; after the concentration is finished, dropwise adding a hydrochloric acid solution with the concentration of 1mol/L into the concentrated solution, adjusting the pH of the concentrated solution to 2-3, then transferring the concentrated solution into a low-temperature cold well, cooling to 0 ℃ for crystallization, wherein the crystallization time is 8 h; after the crystallization is finished, vacuum filtration is carried out, and a filter cake is collected to obtain about 5kg of dipeptide recovery crude product;
(2) adding the dipeptide recovered crude product into a glass reaction bottle filled with 25 mass percent of ammonia water to ensure that the pH is 7-8 and 20kg of 25 mass percent of ammonia water is consumed, and then heating to 40 ℃, stirring and dissolving; adding 20kg of acetone into the obtained dipeptide recovery crude product solution, stirring and dispersing, cooling to room temperature to obtain a large amount of crystals, and performing vacuum filtration to collect a filter cake to obtain about 2.4kg of dipeptide amine salt; and simultaneously distilling the filtrate until obvious particles appear, cooling to room temperature, stirring and crystallizing to obtain about 2.3kg of dipeptide isomer amine salt.
(3) The dipeptide amine salt and dipeptide isomer amine salt are respectively acidified in 10L of water by using 1mol/L dilute hydrochloric acid until the pH value is 2-3, then the mixture is concentrated to be dry, 10L dispersing agent (ethyl acetate: ethanol ═ 1:1) is added, the mixture is stirred and dispersed for 2 hours at room temperature, finally the vacuum filtration and the solid drying are carried out, and 2.3kg of dipeptide with the purity of 99.6 percent and 2.3kg of dipeptide isomer with the purity of 99.6 percent are obtained.
In this example 4, the dipeptide mother liquor before treatment was the same as that before treatment in example 1, and after the dipeptide mother liquor was treated, the organic solvent in the waste liquid produced in each step was recovered, and about 200L of all the waste liquids were combined, and the contents of COD, dipeptide methyl ester, ethanol, acetone, ethyl acetate and other organic impurities were measured again, and the results are shown in Table 5 below.
TABLE 5 comparison table before and after dipeptide mother liquor treatment
Item
Before treatment
After treatment
Total mother liquor amount
500L
200L
COD
9.5×104ppm
4500ppm
Dipeptide methyl ester
0.8％
0.01％
Ethanol
25％
0.04％
Acetone (II)
-
0.02％
Ethyl acetate
25％
0.03％
Other organic impurities
＜0.5％
＜0.5％
Comparative example 1
(1) Adding 500L dipeptide mother liquor into a 1000L glass lining reaction kettle for later use; and adding sodium hydroxide into the reaction kettle for multiple times, and keeping the temperature in the kettle below 35 ℃ for neutralization reaction until the pH value of the feed liquid in the kettle is 6.5-7.5 and the sodium hydroxide consumption is about 50 kg. Standing for 2h for layering, and separating an organic layer and an aqueous layer.
(2) And pumping the organic layer into a rectifying still for rectification, respectively recovering ethyl acetate and ethanol, and after the recovery, filling 150L of still residue with sound, and temporarily storing in a barrel.
(3) Pumping the water layer into a concentration kettle, concentrating at about 65 deg.C under vacuum of-0.09 Mpa or less until a large amount of crystals are separated out, centrifuging, and drying to obtain solid waste containing 85% sodium chloride (50 kg).
Comparative example 1 the dipeptide mother liquor before treatment was the same as that in example 1, and after the dipeptide mother liquor was treated, the organic solvent in the waste liquid produced in each step was recovered, and about 150L of all the waste liquids were combined, and the contents of COD, dipeptide methyl ester, ethanol, acetone, ethyl acetate and other organic impurities were measured again, and the results are shown in Table 6 below.
TABLE 6 comparison table before and after dipeptide mother liquor treatment
Item
Before treatment
After treatment
Total mother liquor amount
500L
150L
COD
9.5×104ppm
1×106ppm
Dipeptide methyl ester
0.8％
2.5％
Ethanol
25％
10％
Acetone (II)
-
-
Ethyl acetate
25％
8％
Other organic impurities
＜0.5％
-
It should be noted that the contents of the COD, dipeptide methyl ester, ethanol, acetone, ethyl acetate and other organic impurities are detected by a conventional general detection method.
And (4) conclusion:
from the data of examples 1-5, comparative example 1 and the corresponding FIGS. 1-3, tables 1-6 above, it can be seen that: by adopting the method for treating the dipeptide mother liquor, most substances in the dipeptide target liquor can be recycled, the treatment process is simple, the treatment cost is low, the recovery benefit is high, the method is green, safe and environment-friendly, the recycling of medium and high-value products in the dipeptide mother liquor is realized, and the problems of high energy consumption, high cost, high pollution and serious waste of the medium and high-value products caused by the traditional treatment of neutralizing with alkali and delivering to a sewage station are solved.
The dipeptide mother liquor is treated according to the conventional method in the comparative example 1, which not only consumes a large amount of alkali and energy, but also only can recover partial solvent, and simultaneously, the treatment of a large amount of organic kettle residues with high COD is difficult, high in cost and wastes a large amount of water, and the solid waste containing sodium chloride needs to be treated by an outsourcing treatment qualified unit.
Finally, it should be noted that: the above embodiments are only used for illustrating the technical solutions of the present application, and not for limiting the same; although the present application has been described in detail with reference to the foregoing embodiments, it should be understood by those of ordinary skill in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some or all of the technical features may be equivalently replaced; and the modifications or the substitutions do not make the essence of the corresponding technical solutions depart from the scope of the technical solutions of the embodiments of the present application.
Moreover, those skilled in the art will appreciate that while some embodiments herein include some features included in other embodiments, rather than other features, combinations of features of different embodiments are meant to be within the scope of the application and form different embodiments. For example, in the claims above, any of the claimed embodiments may be used in any combination. The information disclosed in this background section is only for enhancement of understanding of the general background of the application and should not be taken as an acknowledgement or any form of suggestion that this information forms the prior art already known to a person skilled in the art.
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