阅读说明：本技术 一种l-草铵膦的生产方法 (Production method of L-glufosinate-ammonium ) 是由 李君占 于 2021-03-16 设计创作，主要内容包括：一种L-草铵膦的生产方法,特别是提供一种L-草铵膦酶转化反应液的纯化精制方法,采用双级超滤工艺,首先对L-草铵膦酶转化反应液进行合理的预处理,用第一超滤膜将反应液中的大分子蛋白等物质进行拦截。第一超滤滤液再经过蒸发浓缩,除去反应液中的丙酮等可挥发副产物。蒸发母液再进入第二超滤膜进行浓缩过滤,得到精制L-草铵膦料液。该精制L-草铵膦料液可直接用于配制制剂或通过甲醇结晶及干燥得到L-草铵膦固体产品。该方法工艺流程短,投资省,运行费用低,节能节水,操作简单,便于实现自动化控制,同时,还具有产品回收率高,产品质量稳定可靠等优点。(A method for producing L-glufosinate-ammonium, especially providing a method for purifying and refining L-glufosinate-ammonium conversion reaction liquid, adopting double-stage ultrafiltration process, firstly reasonably preprocessing the L-glufosinate-ammonium conversion reaction liquid, intercepting macromolecular protein and other substances in the reaction liquid by a first ultrafiltration membrane. Evaporating and concentrating the first ultrafiltration filtrate to remove volatile byproducts such as acetone and the like in the reaction solution. And (4) the evaporated mother liquor enters a second ultrafiltration membrane for concentration and filtration to obtain the refined L-glufosinate-ammonium feed liquid. The refined L-glufosinate-ammonium feed liquid can be directly used for preparing a preparation or used for obtaining an L-glufosinate-ammonium solid product through methanol crystallization and drying. The method has the advantages of short process flow, low investment, low operating cost, energy and water conservation, simple operation, convenient realization of automatic control, high product recovery rate, stable and reliable product quality and the like.)

1. A production method of L-glufosinate-ammonium comprises the following steps:

(1) pretreatment: adding a pH regulator, a coagulant and a flocculant into the L-glufosinate-ammonium conversion reaction solution for pretreatment to obtain a pretreatment solution;

(2) first ultrafiltration: the pretreatment solution enters a first ultrafiltration for concentration and washing treatment to obtain a first ultrafiltration filtrate;

(3) and (3) evaporation and concentration: evaporating and concentrating the first ultrafiltration filtrate to obtain an evaporation mother liquor;

(4) and (3) second ultrafiltration: the evaporation mother liquor enters a second ultrafiltration for concentration and washing treatment to obtain refined L-glufosinate-ammonium feed liquid;

(5) and (3) crystallization: refining the L-glufosinate-ammonium feed liquid to perform methanol crystallization to obtain wet L-glufosinate-ammonium solid;

(6) and (3) drying: drying the wet L-glufosinate-ammonium solid to obtain an L-glufosinate-ammonium solid product;

in the above steps, the second ultrafiltration can be omitted according to the process requirements.

2. The method for producing L-glufosinate-ammonium according to claim 1, wherein the pH regulator used in the pretreatment is hydrochloric acid or sulfuric acid, and the pH of the reaction solution of the conversion of the L-glufosinate-ammonium is adjusted to 2.0-4.0 by adding acid; the used coagulant is one or the combination of more than two of aluminum sulfate, polyaluminium chloride, ferric trichloride or polyferric sulfate, and the using amount of the coagulant is 0.01-1% (w/v); the flocculant is sodium polyacrylate or polyacrylamide, and the usage amount of the flocculant is 0-0.005% (w/v).

3. The method for producing L-glufosinate according to claim 1, wherein the pH regulator used in the pretreatment is hydrochloric acid, and the pH of the reaction solution of the conversion of the L-glufosinate-ammonium is adjusted to 3.0-4.0 by adding acid; the used coagulant is polyaluminium chloride, and the using amount of the coagulant is 0.05-0.5% (w/v); the flocculant is anionic or nonionic polyacrylamide, and the usage amount of the flocculant is 0-0.005% (w/v).

4. The method for producing L-glufosinate according to claim 1, wherein the pH regulator used in the pretreatment is hydrochloric acid, and the pH of the reaction solution of the conversion of the L-glufosinate-ammonium is adjusted to 3.0-3.6 by adding acid; the used coagulant is polyaluminium chloride, and the using amount of the coagulant is 0.08-0.2% (w/v); the flocculant is anionic or non-ionic polyacrylamide, and the usage amount of the flocculant is 0.0005-0.001% (w/v).

5. The method for producing L-glufosinate-ammonium according to claim 1, wherein the ultrafiltration membrane used in the first ultrafiltration and the second ultrafiltration is one or two of a tubular membrane, a flat membrane, a spiral membrane or a hollow fiber membrane, the material of the membrane used comprises a metal membrane, a ceramic membrane, an organic membrane or other inorganic membranes, and the separation precision of the membrane used is 1.0-50.0 nanometers or the cut molecular weight of the membrane used is 1.0-500 kD.

6. The method for producing L-glufosinate-ammonium according to claim 1, wherein the ultrafiltration membrane used in the first ultrafiltration and the second ultrafiltration is one or two of an organic tubular membrane, an inorganic tubular membrane, an organic flat membrane and an inorganic flat membrane, and the separation precision of the membrane is 2-20 nm or the cut molecular weight of the membrane is 2.0-200 kD.

7. The method for producing L-glufosinate-ammonium according to claim 1, wherein the ultrafiltration membranes used in the first ultrafiltration and the second ultrafiltration are one or both of tubular metal sintered membranes, tubular ceramic membranes and tubular organic sintered membranes, and the separation precision of the membranes used is between 5 and 20 nanometers or the cut molecular weight of the membranes is between 2.0 and 20 kD.

8. The process for producing L-glufosinate-ammonium according to claim 1, wherein the first ultrafiltration and the second ultrafiltration are carried out by adding diatomaceous earth as a filter aid to the treated liquid, the amount of the filter aid added being between 0.1 and 1% (w/v).

Technical Field

The invention relates to the technical field of pesticide production, and particularly provides a production method of L-glufosinate-ammonium.

Background

Glufosinate belongs to hypophosphorous acid type high-efficiency, low-toxicity and environment-friendly non-conductive biocidal herbicide. Because the herbicide is easy to degrade in soil, safe to crops, difficult to drift, wide in weeding spectrum, high in activity, low in dosage and low in environmental stress, the herbicide is a top-grade pesticide variety for replacing glyphosate and paraquat. Glufosinate was first developed successfully in the last 80 th century by hester (later on to bayer).

The glufosinate-ammonium has two different optical isomers, and all the glufosinate-ammonium sold in the market at present are racemes which are mixtures of L-glufosinate-ammonium and D-glufosinate-ammonium in equal proportion. After plants receive the medicine, only L-glufosinate-ammonium can inhibit the biological activity of L-glutamine synthetase, so that ammonium ion accumulation poisoning is caused, photosynthesis is inhibited, and finally plants die, but D-glufosinate-ammonium does not have the performance. Therefore, only L-glufosinate-ammonium has herbicidal activity, which is twice as high as that of common glufosinate-ammonium.

The development and commercialization of L-glufosinate-ammonium are firstly completed by Nippon Mingming company, and because the product is a single effective isomer, the L-glufosinate-ammonium has the advantages of less environmental chemical substance input amount, more environment-friendly production process and the like, and has good market prospect and environmental compatibility.

The synthesis method of L-glufosinate-ammonium can be mainly divided into three types: (1) performing stereochemical synthesis; (2) firstly synthesizing DL type, and then carrying out chemical chiral resolution; (3) and (3) carrying out biological enzyme catalytic synthesis. The stereochemical synthesis process has the disadvantages of multiple steps, low yield, expensive chiral raw materials, high production cost and no contribution to large-scale preparation. The chemical chiral resolution needs to use expensive chiral resolution reagent, the theoretical yield can only reach 50 percent, the single resolution efficiency is low, and the process is complex. The biological enzyme catalysis has the advantages of mild reaction conditions, high yield, strong specificity and the like, and is an advantageous method for producing the L-glufosinate-ammonium.

The preparation of L-glufosinate-ammonium by bio-enzyme catalysis is classified into 3 categories according to different starting materials and synthetic routes: (1) taking a derivative of L-glufosinate-ammonium as a substrate, and directly hydrolyzing by an enzyme method to obtain the L-glufosinate-ammonium salt; (2) using a precursor of racemic glufosinate-ammonium as a substrate, and obtaining the glufosinate-ammonium by selective resolution of enzyme; (3) d-glufosinate-ammonium is firstly converted into 2-carbonyl-4- (hydroxymethyl phosphonyl) butyric acid by taking a precursor of racemic glufosinate-ammonium as a substrate through a multi-enzyme reaction, and then the 2-carbonyl-4- (hydroxymethyl phosphonyl) butyric acid is converted into L-glufosinate-ammonium. The method (1) requires expensive chiral raw materials as precursors, and the raw materials are not easy to obtain. The theoretical yield of the method (2) can only reach 50 percent, which causes the waste of raw materials. The method (3) has the advantages of easily obtained raw materials, low production cost and wide market prospect.

The method for obtaining L-glufosinate-ammonium by enzyme selective conversion with racemic glufosinate-ammonium precursor as substrate is a multi-step enzyme catalytic reaction. Patents CN111321193A and CN111363775A disclose a method for asymmetric preparation of L-glufosinate by biological multi-enzyme coupling redox, respectively, using racemic glufosinate as a raw material, and obtaining L-glufosinate by catalysis of an enzyme catalysis system, where the enzyme catalysis system includes a D-amino acid oxidase mutant for catalyzing D-glufosinate in racemic glufosinate to 2-carbonyl-4- [ hydroxy (methyl) phosphono ] butanoic acid, and a transaminase for catalyzing 2-carbonyl-4- [ hydroxy (methyl) phosphono ] butanoic acid to L-glufosinate, and genetic engineering strains of the D-amino acid oxidase mutant and the glufosinate dehydrogenase mutant are obtained.

The enzymatic hydrolysate for preparing L-glufosinate by the two-enzyme method using racemic glufosinate as a substrate has complicated components, and contains not only enzymes used as catalysts and other hetero-proteins, but also by-products such as acetone and the like produced by the enzymatic conversion reaction. Therefore, the development of the post-treatment process of the L-glufosinate-ammonium enzyme conversion reaction liquid, which has the advantages of simple steps, easily obtained raw materials and controllable cost, has very important significance.

Disclosure of Invention

The invention aims to provide a method for producing L-glufosinate-ammonium, in particular to a method for purifying and refining L-glufosinate-ammonium enzyme conversion reaction liquid. Evaporating and concentrating the first ultrafiltration filtrate to remove volatile byproducts such as acetone and the like in the reaction solution. And (4) the evaporated mother liquor enters a second ultrafiltration membrane for concentration and filtration to obtain the refined L-glufosinate-ammonium feed liquid. The refined L-glufosinate-ammonium feed liquid can be directly used for preparing a preparation or used for obtaining an L-glufosinate-ammonium solid product through methanol crystallization and drying.

The invention adopts the following technical scheme:

a production method of L-glufosinate-ammonium comprises the following steps:

(1) pretreatment: adding a pH regulator, a coagulant and a flocculant into the L-glufosinate-ammonium conversion reaction solution for pretreatment to obtain a pretreatment solution;

(2) first ultrafiltration: the pretreatment solution enters a first ultrafiltration for concentration and washing treatment to obtain a first ultrafiltration filtrate;

(3) and (3) evaporation and concentration: evaporating and concentrating the first ultrafiltration filtrate to obtain an evaporation mother liquor;

(4) and (3) second ultrafiltration: the evaporation mother liquor enters a second ultrafiltration for concentration and washing treatment to obtain refined L-glufosinate-ammonium feed liquid;

(5) and (3) crystallization: refining the L-glufosinate-ammonium feed liquid to perform methanol crystallization to obtain wet L-glufosinate-ammonium solid;

(6) and (3) drying: drying the wet L-glufosinate-ammonium solid to obtain an L-glufosinate-ammonium solid product;

in the above steps, the second ultrafiltration can be omitted according to the process requirements.

In the method for producing L-glufosinate-ammonium, the pH regulator used for pretreatment is hydrochloric acid or sulfuric acid, and the pH range of the L-glufosinate-ammonium enzyme conversion reaction solution is regulated to 2.0-4.0 by adding acid; the used coagulant is one or the combination of more than two of aluminum sulfate, polyaluminium chloride, ferric trichloride or polyferric sulfate, and the using amount of the coagulant is 0.01-1% (w/v); the flocculant is sodium polyacrylate or polyacrylamide, and the usage amount of the flocculant is 0-0.005% (w/v).

In the method for producing L-glufosinate-ammonium, hydrochloric acid is used as a pH regulator for pretreatment, and acid is added to regulate the pH range of the L-glufosinate-ammonium enzyme conversion reaction liquid to 3.0-4.0; the used coagulant is polyaluminium chloride, and the using amount of the coagulant is 0.05-0.5% (w/v); the flocculant is anionic or nonionic polyacrylamide, and the usage amount of the flocculant is 0-0.005% (w/v).

As a further optimization, in the production method of the L-glufosinate-ammonium, the pH regulator used for pretreatment is hydrochloric acid, and acid is added to regulate the pH range of the L-glufosinate-ammonium enzyme conversion reaction liquid to be 3.0-3.6; the used coagulant is polyaluminium chloride, and the using amount of the coagulant is 0.08-0.2% (w/v); the flocculant is anionic or non-ionic polyacrylamide, and the usage amount of the flocculant is 0.0005-0.001% (w/v).

The production method of L-glufosinate-ammonium comprises the following steps that the ultrafiltration membranes used in the first ultrafiltration and the second ultrafiltration are one or two of tubular membranes, flat membranes, roll-type membranes and hollow fiber membranes, the materials of the membranes comprise metal membranes, ceramic membranes, organic membranes or other inorganic membranes, and the separation precision of the membranes is 1.0-50.0 nanometers or the cut molecular weight of the membranes is 1.0-500 kD.

Preferably, the method for producing L-glufosinate-ammonium comprises the step of subjecting the first ultrafiltration membrane and the second ultrafiltration membrane to one or two of organic tubular membranes, inorganic tubular membranes, organic flat membranes and inorganic flat membranes, wherein the separation precision of the membranes is 2-20 nanometers or the cut molecular weight of the membranes is 2.0-200 kD.

As a further optimization, the method for producing the L-glufosinate-ammonium is characterized in that the ultrafiltration membranes used in the first ultrafiltration and the second ultrafiltration are one or two of tubular metal sintered membranes, tubular ceramic membranes or tubular organic sintered membranes, and the separation precision of the membranes is 5-20 nanometers or the cut molecular weight of the membranes is 2.0-20 kD.

In the method for producing L-glufosinate-ammonium, the diatomite is added into the treated feed liquid as a filter aid during the first ultrafiltration and the second ultrafiltration, and the addition amount of the filter aid is 0.1-1% (w/v).

The production method of the L-glufosinate-ammonium is suitable for purification and refining of various L-glufosinate-ammonium enzyme conversion reaction liquids. The method has the advantages of short process flow, low investment, low operating cost, energy and water conservation, simple operation, convenient realization of automatic control, high product recovery rate, stable and reliable product quality and the like.

Detailed Description

The following examples further illustrate embodiments of the present invention.

Example 1

The L-glufosinate-ammonium enzyme conversion reaction liquid material contains 14.3wt% of L-glufosinate-ammonium, is at 24.5 ℃, has a pH value of 6.7 and a density of 1.05g/ml, and contains impurities such as protein, acetone and the like. The feed liquid is pretreated as follows:

taking 50ml of the feed liquid, adding a flocculating agent and/or a coagulant under electromagnetic stirring, adjusting the pH of the feed liquid by using acid, stirring for 5 minutes, filtering by using filter paper, and inspecting the filtering speed and effect. The results are as follows.

Example 2

100kg of the L-glufosinate-ammonium conversion reaction liquid feed in example 1 was adjusted to pH3.2 with hydrochloric acid, and 500ppm of PAC, 500ppm of ferric trichloride, and 5ppm of polyacrylamide (HPAM) were added and stirred for 5 to 10 minutes to obtain a pretreatment liquid.

And (3) performing circulating concentration treatment by using a ceramic membrane with the filtration precision of 5nm (the cut-off molecular weight is 10 kD), and collecting penetrating fluid.

The operating conditions are as follows: the material temperature is 24-50 ℃, the membrane inlet pressure is 0.39MPa, the membrane outlet pressure is 0.27MPa, the osmotic back pressure is 0.18MPa, and the average operating pressure (TMP) is 0.15 MPa.

When the volume of the collected penetrating fluid reaches 85kg, water is added into the concentrated solution for washing and filtering, the total water addition amount is 15kg, the water is added into the concentrated solution in three times, 5kg of water is produced in each penetration, and 5kg of water is added. After the last addition of water, the concentrate was further concentrated to 15kg (by titration).

The total mean permeate flow through the membrane during the test was 46.3 LMH.

Finally, 100kg of total permeate and 15kg of total concentrated solution are obtained (decrement method). Through analysis and test, the content of L-glufosinate in the total concentrated solution is 4.6wt%, the content of L-glufosinate in the total penetrating fluid is 11.9wt%, and the total yield is 83.2%.

The obtained total permeate was a clear amber liquid and the total concentrate was a yellow turbid liquid.

Example 3

100kg of the L-glufosinate-ammonium conversion reaction liquid feed in example 1 was adjusted to pH3.2 with hydrochloric acid, and 500ppm of PAC, 500ppm of ferric trichloride, and 5ppm of polyacrylamide (HPAM) were added and stirred for 5 to 10 minutes to obtain a pretreatment liquid.

And (3) performing circulating concentration treatment by using a ceramic membrane with the filtration precision of 5.5nm (the cut-off molecular weight is 15 kD), and collecting penetrating fluid.

The operating conditions and methods were the same as in example 2.

The total average permeate flow through the membrane during the test was 54.2 LMH.

Through analysis and test, the content of L-glufosinate in the total concentrated solution is 3.2wt%, the content of L-glufosinate in the total penetrating fluid is 13.6wt%, and the total yield is 95.1%.

The obtained total permeate was a clear amber liquid and the total concentrate was a yellow turbid liquid.

Example 4

The feed liquid of the L-glufosinate-ammonium conversion reaction liquid contains 14.7wt% of L-glufosinate-ammonium, the temperature is 24 ℃, the pH value is 6.7, and the density is 1.05 g/ml.

100kg of the above L-glufosinate-ammonium conversion reaction solution was taken, pH3.5 was adjusted with hydrochloric acid, and 1000ppm of PAC and 5ppm of polyacrylamide (HPAM) were added thereto and stirred for 5 to 10 minutes to obtain a pretreatment solution.

And (3) performing circulating concentration treatment by using a ceramic membrane with the filtration precision of 5nm (the cut-off molecular weight is 10 kD), and collecting penetrating fluid.

The operating conditions are as follows: the same as in example 2.

When the volume of the collected penetrating fluid reaches 85kg, water is added into the concentrated solution for washing and filtering, the total water addition amount is 30kg, the water is added into the concentrated solution for six times, 5kg of water is produced by each time of penetration, and 5kg of water is added. After the last addition of water, the concentrate was further concentrated to 15kg (by titration).

The total average permeate flow through the membrane during the test was 52.6 LMH.

Finally, 115kg of total permeate and 15kg of total concentrated solution are obtained (reduction method). Through analysis and test, the content of L-glufosinate in the total concentrated solution is 2.1wt%, the content of L-glufosinate in the total penetrating fluid is 12.2wt%, and the total yield is 95.4%.

The obtained total permeate was a clear amber liquid and the total concentrate was a yellow turbid liquid.

Example 5

The pretreatment method was the same as in example 4 except that 100kg of L-glufosinate-ammonium conversion reaction solution was used in example 4.

And (3) performing circulating concentration treatment by using a ceramic membrane with the filtration precision of 5.5nm (the cut-off molecular weight is 15 kD), and collecting penetrating fluid.

The operating conditions are as follows: the same as in example 1.

When the volume of the collected penetrating fluid reaches 85kg, water is added into the concentrated solution for washing and filtering, the total water addition amount is 30kg, the water is added into the concentrated solution for six times, 5kg of water is produced by each time of penetration, and 5kg of water is added. After the last addition of water, the concentrate was further concentrated to 15kg (by titration).

The total average permeate flow through the membrane during the test was 58.6 LMH.

Finally, 115kg of total permeate and 15kg of total concentrated solution are obtained (reduction method). Through analysis and assay, the content of L-glufosinate in the total concentrated solution is 1.2wt%, the content of L-glufosinate in the total penetrating fluid is 12.3wt%, and the total yield is 96.2%.

The obtained total permeate was a clear amber liquid and the total concentrate was a yellow turbid liquid.

Example 6

100kg of the L-glufosinate-ammonium conversion reaction solution feed liquid obtained in example 4 was taken, pH2.8 was adjusted with hydrochloric acid, 1000ppm of PAC was added thereto, and the mixture was stirred for 5 to 10 minutes to obtain a pretreatment solution.

And (3) performing circulating concentration treatment by using a ceramic membrane with the filtration precision of 5nm (the cut-off molecular weight is 10 kD), and collecting penetrating fluid.

The operating conditions are as follows: the same as in example 2.

When the volume of the collected penetrating fluid reaches 85kg, water is added into the concentrated solution for washing and filtering, the total water addition amount is 45kg, the water is added in nine times, 5kg of water is produced by each time of penetration, and 5kg of water is added. After the last addition of water, the concentrate was further concentrated to 15kg (by titration).

The total average permeate flow through the membrane during the test was 55.8 LMH.

130kg of total permeate and 15kg of total concentrated solution are finally obtained (decrement method). Through analysis and test, the content of L-glufosinate in the total concentrated solution is 1.09wt%, the content of L-glufosinate in the total penetrating fluid is 10.8wt%, and the total yield is 95.5%.

The obtained total permeate was a clear amber liquid and the total concentrate was a yellow turbid liquid.

Example 7

The pretreatment method was the same as in example 4 except that 100kg of L-glufosinate-ammonium conversion reaction solution was used in example 4.

And (3) performing circulating concentration treatment by using a ceramic membrane with the filtration precision of 5.5nm (the cut-off molecular weight is 15 kD), and collecting penetrating fluid.

The operating conditions are as follows: the same as in example 1.

When the volume of the collected penetrating fluid reaches 85kg, water is added into the concentrated solution for washing and filtering, the total water addition amount is 45kg, the water is added in nine times, 5kg of water is produced by each time of penetration, and 5kg of water is added. After the last addition of water, the concentrate was further concentrated to 15kg (by titration).

The total average permeate flow through the membrane during the test was 62.2 LMH.

130kg of total permeate and 15kg of total concentrated solution are finally obtained (decrement method). Through analysis and assay, the content of L-glufosinate in the total concentrated solution is 0.59wt%, the content of L-glufosinate in the total penetrating fluid is 10.9wt%, and the total yield is 96.4%.

The obtained total permeate was a clear amber liquid and the total concentrate was a yellow turbid liquid.

Example 8

The ceramic membrane permeates obtained in examples 2, 4 and 6 were combined to obtain 345kg of total feed liquid, in which the content of L-glufosinate-ammonium was 11.5 wt%.

And (3) carrying out evaporation concentration treatment on the feed liquid to obtain 102kg of clear amber concentrated solution, and detecting the content of the L-glufosinate-ammonium in the clear amber concentrated solution to be 37.7 wt%.

Example 9

The ceramic membrane permeates obtained in examples 3, 5 and 7 were combined to obtain 345kg of total feed liquid, in which the content of L-glufosinate-ammonium was 12.1 wt%.

The feed liquid is evaporated and concentrated to obtain 105kg of concentrated solution which is turbid and opaque and has obvious white flocculent substances. The content of L-glufosinate-ammonium is detected to be 38.6 wt%.

Example 10

The L-glufosinate concentrate obtained in example 9 was treated again with a ceramic membrane.

And (3) performing circulating concentration treatment by using a ceramic membrane with the filtration precision of 5.5nm (the cut-off molecular weight is 15 kD), and collecting penetrating fluid.

The operating conditions and methods were the same as in example 7.

The total average permeate flow through the membrane during the test was 45.6 LMH.

Finally, 135kg of total permeate and 15kg of total concentrated solution are obtained (decrement method). Through analysis and test, the content of L-glufosinate in the total concentrated solution is 1.89wt%, the content of L-glufosinate in the total penetrating fluid is 28.6wt%, and the total yield is 95.3%.

The obtained permeate was a clear amber liquid and the total concentrate was a yellow turbid liquid.