CN110330401B - Method for synthesizing phenylserine derivative based on fixed bed reactor - Google Patents
Method for synthesizing phenylserine derivative based on fixed bed reactor Download PDFInfo
- Publication number
- CN110330401B CN110330401B CN201910721382.XA CN201910721382A CN110330401B CN 110330401 B CN110330401 B CN 110330401B CN 201910721382 A CN201910721382 A CN 201910721382A CN 110330401 B CN110330401 B CN 110330401B
- Authority
- CN
- China
- Prior art keywords
- separator
- storage tank
- product
- fixed bed
- reaction
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J8/00—Chemical or physical processes in general, conducted in the presence of fluids and solid particles; Apparatus for such processes
- B01J8/02—Chemical or physical processes in general, conducted in the presence of fluids and solid particles; Apparatus for such processes with stationary particles, e.g. in fixed beds
- B01J8/0242—Chemical or physical processes in general, conducted in the presence of fluids and solid particles; Apparatus for such processes with stationary particles, e.g. in fixed beds the fluid flow within the bed being predominantly vertical
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J8/00—Chemical or physical processes in general, conducted in the presence of fluids and solid particles; Apparatus for such processes
- B01J8/02—Chemical or physical processes in general, conducted in the presence of fluids and solid particles; Apparatus for such processes with stationary particles, e.g. in fixed beds
- B01J8/04—Chemical or physical processes in general, conducted in the presence of fluids and solid particles; Apparatus for such processes with stationary particles, e.g. in fixed beds the fluid passing successively through two or more beds
- B01J8/0446—Chemical or physical processes in general, conducted in the presence of fluids and solid particles; Apparatus for such processes with stationary particles, e.g. in fixed beds the fluid passing successively through two or more beds the flow within the beds being predominantly vertical
- B01J8/0449—Chemical or physical processes in general, conducted in the presence of fluids and solid particles; Apparatus for such processes with stationary particles, e.g. in fixed beds the fluid passing successively through two or more beds the flow within the beds being predominantly vertical in two or more cylindrical beds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B37/00—Reactions without formation or introduction of functional groups containing hetero atoms, involving either the formation of a carbon-to-carbon bond between two carbon atoms not directly linked already or the disconnection of two directly linked carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B63/00—Purification; Separation; Stabilisation; Use of additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/16—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions not involving the amino or carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/38—Separation; Purification; Stabilisation; Use of additives
- C07C227/40—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
- C07C315/04—Preparation of sulfones; Preparation of sulfoxides by reactions not involving the formation of sulfone or sulfoxide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
- C07C315/06—Separation; Purification; Stabilisation; Use of additives
Abstract
The invention provides a process for synthesizing a phenylserine derivative based on a fixed bed reactor, which comprises the steps of uniformly mixing raw materials in a premixer, keeping the mixture at a certain temperature, allowing the raw materials to enter the upper part of a fixed bed to be in contact with a catalyst for Adol reaction, allowing the generated product to enter a first separator through an outlet, removing a small amount of metal ions, allowing the product to flow through a second separator, and separating the product from byproducts to obtain a high-purity phenylserine derivative product. The solvent materials used and related in the reaction can be recycled after separation and concentration. The invention has the beneficial effects that: (1) the reaction process is simple to operate, the whole process is in a flow type reaction, the efficiency is high, and the time consumption is low; (2) the solvent and excessive raw materials are used together, so that the emission of three wastes is little, and the environment is protected; (3) low energy consumption, high unit yield and suitability for mass production.
Description
[ technical field ] A method for producing a semiconductor device
The invention relates to the field of chemical industry, in particular to a method for synthesizing a phenylserine derivative based on a fixed bed reactor.
[ background ] A method for producing a semiconductor device
The phenylserine derivative is an important drug intermediate and a chemical intermediate, particularly 4-methylsulfonylphenylserine, 4-nitrophenylserine and the like, is widely used for preparing human antibiotics, poultry and livestock antibiotics and the like, and represents drugs such as chloramphenicol, thiamphenicol, florfenicol and the like.
The industrial production method of the phenylserine derivative is mainly a traditional chemical synthesis method, which takes mono-or multi-substituted benzaldehyde, glycine, copper sulfate and ammonia water as raw materials, and comprises the steps of heating and stirring for 30 hours at 45-50 ℃ to obtain mono-or multi-substituted phenylserine copper salt, adding water to dissolve the copper salt, introducing hydrogen sulfide gas to remove copper ions, filtering by activated carbon, concentrating and crystallizing to obtain the mono-or multi-substituted phenylserine. The synthesis method needs to use copper sulfate, uses highly toxic hydrogen sulfide with heavy odor to precipitate copper ions in post-treatment, generates a large amount of copper sulfide solid waste, belongs to a backward process with high pollution and low economy, does not meet the current requirement of environmental protection policy, and needs to be improved urgently.
[ summary of the invention ]
The invention provides a method for synthesizing a phenylserine derivative based on a fixed bed reactor, which can greatly reduce heavy metal pollution and the generation amount of wastewater.
The technical solution of the invention is as follows:
the method for synthesizing the phenylserine derivative based on the fixed bed reactor is characterized in that a top inlet of the fixed bed is connected with a premixer, a lower outlet of the fixed bed is connected with an upper inlet of a first separator, a lower outlet of the first separator is connected with an upper inlet of a second separator, and a lower outlet of the second separator is respectively connected with a first storage tank, a second storage tank and a third storage tank;
the synthesis method comprises the following steps:
(1) mixing raw materials: mixing mono/multi-substituted benzaldehyde, glycine, a buffer salt solution and a solvent in a premixer to form a raw material mixed solution with the pH of 7.5-9.0, wherein the raw material mixed solution enters the fixed bed from an inlet at the top of the fixed bed;
(2) and (3) catalytic reaction: contacting the raw material mixed liquor from the step (1) with a catalyst fixed on a fixed bed at 20-60 ℃ to perform Adol reaction, and allowing a product mixed liquor generated by the reaction to flow into an upper inlet of a first separator through a lower outlet of the fixed bed;
(3) primary separation: the product mixed liquor from the step (2) enters a first separator, contacts with a metal ion adsorption carrier for metal ion adsorption, removes residual trace metal ions in the reaction liquid, and enters an upper inlet of a second separator through a lower outlet of the first separator after the metal ions are removed;
(4) and (3) secondary separation: the product mixed liquor from the step (3) after removing the metal ions enters a second separator, is contacted with an adsorption separation carrier for separating the mixture, and then an eluent enters from another inlet arranged at the upper part of the second separator to elute and separate the product, the by-product and part of the excessive raw materials;
wherein the byproduct is preferentially eluted and enters the first storage tank from the lower outlet of the second separator; eluting partial excessive raw materials, and feeding the excessive raw materials into a second storage tank from a lower end outlet of a second separator; finally, eluting the product, and feeding the product into a third storage tank from an outlet at the lower end of the second separator;
(5) collecting: and respectively collecting the by-product of the first storage tank, the excessive raw material of the second storage tank and the product of the third storage tank.
Further, the step (5) collects: directly recovering the by-product from the step (4) in the first storage tank; concentrating part of the excessive raw material separation liquid from the step (4) in the second storage tank by using a concentrating device, adding a proper amount of raw materials for supplement, and then returning to the step (1); and (4) concentrating the product separation liquid from the step (4) in the third storage tank, and cooling and crystallizing to obtain a phenylserine derivative product with the purity of not less than 95%.
And (3) further, the raw material mixed liquor in the step (2) flows downwards through a catalyst bed layer, and the catalyst is modified and functionalized metal ions capable of being complexed with the immobilized carrier.
Further, the metal ions are one or more of iron, cobalt, nickel, copper and zinc.
Further, the carrier is one or more of amino carboxylic acids or amino modified silica gel, zeolite, cellulose, resin, carbon fiber, chitin and porous ceramsite which can form complexation with heavy metal ions.
Further, the metal ion adsorption carrier is one or more of aminocarboxylic acids or amino group-modified silica gel, zeolite, cellulose, resin, carbon fiber, chitin, and porous ceramsite capable of forming a complex with heavy metal ions, for example, CR11 and CR20 resins from Mitsubishi chemical corporation, CLR-08 and CLR-20 resins from Korea Mitsubishi corporation, and chelating resins such as LSC-100 and LSC-910 from Xian blue advanced technology materials Ltd.
Further, the adsorption separation carrier is an adsorption type resin having styrene or acrylic acid as a skeleton, such as LX-16, LX-18, LX-621, LX-1180 and LX-1600 of New science and technology Co., Ltd, D-101 and D-101-I, AB-8 of Tianjin Haoyu resin science and technology Co., Ltd, and C115E, C106 and A103S of British Brand. .
Further, the reaction solvent is water, an aqueous ethanol solution, an aqueous methanol solution or an aqueous dimethyl sulfoxide solution.
Further preferably, the reaction solvent is water.
Further, the eluent is water, an aqueous ethanol solution, an aqueous methanol solution, an aqueous dimethyl sulfoxide solution, an acid solution or an alkali solution.
More preferably, the eluent is water.
Further, the acid is one of hydrochloric acid, sulfuric acid, phosphoric acid and acetic acid, the base is one of sodium hydroxide, calcium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate and ammonia water, and the base is one of sodium chloride, calcium chloride, sodium hydrogen phosphate, sodium dihydrogen phosphate and potassium chloride.
The invention is a new generation synthesis process which meets the national green and environmental protection requirements, and has the following beneficial effects:
1) the process of the invention uses a fixed bed, the catalyst is loaded on the fixed carrier, the heavy metal ions participating in the reaction can be completely bound, a large amount of heavy metal ions can not enter the reaction solution, and the environmental pollution of the heavy metal is greatly reduced; after the reaction is finished, the heavy metal ions are adsorbed by the fixed heavy metal ion adsorption carrier in the separator to remove trace heavy metal ions, so that only a small amount of wastewater is generated in production, and trace (<10ppm) heavy metal ions are not contained or only contained, and the national emission standard is met;
2) the reaction and separation processes of the invention use a flow type process, which greatly reduces the manpower and time of the traditional material transfer post-treatment and improves the unit time efficiency;
3) the reaction and separation process of the invention can only use water or aqueous solution without using organic solvent with safety risk, thus greatly reducing the safety risk in the production process;
4) most of the water used by the invention can be recycled, thereby greatly reducing the discharge of waste water, and being beneficial to saving energy and protecting environment.
[ description of the drawings ]
FIG. 1 is a schematic view of the reaction apparatus of example 1.
Description of the labeling: 1, a premixer; 2, a fixed bed; 3, a first separator; 4, a second separator; 5, a first storage tank; 6, a second storage tank; 7, a third storage tank; 8, a concentration device; 9, a flow controller; 10, a water storage tank; 11, a liquid pump; 12, a control valve; and 13, a flow meter.
[ detailed description ] embodiments
The present invention will be described in further detail with reference to the following examples, but the present invention is not limited to the following examples.
The following examples are not provided to limit the scope of the present invention, nor are the steps described to limit the order of execution, and the directions described are limited to the drawings. All of the method or process steps disclosed in this specification (including any accompanying claims, abstract and drawings) may be combined in any combination, except methods and/or steps that are mutually exclusive and incompatible. Any feature disclosed in this specification (including any accompanying claims, abstract and drawings) may be replaced by alternative features serving equivalent or similar functions/acts, unless expressly stated otherwise. Modifications of the invention which are obvious to those skilled in the art in view of the prior art are also within the scope of the invention as claimed.
Example 1
As shown in FIG. 1, a fixed bed reaction apparatus for synthesizing phenylserine derivatives comprises a premixer 1, the premixer 1 is connected with a fixed bed 2, and the connecting pipes are provided with a liquid pump 11 and a control valve 12; the lower outlet (or called as a discharge outlet) of the fixed bed 1 is connected with the inlet of the first separator 3, and the connecting pipeline is provided with a liquid pump 11 and a control valve 12; the discharge port of the first separator 3 is connected with the inlet of the second separator 4, the connecting pipeline is provided with a liquid pump 11 and a control valve 12, the water storage tank 10 is connected with the inlet of the second separator 4, and the connecting pipeline is provided with a liquid pump 11, a control valve 12 and a flow meter 13 (or called as a flow controller); the second separator 4 is respectively connected with the first storage tank 5, the second storage tank 6 and the third storage tank 7, and a control valve 12 is arranged at each connecting pipeline; the second storage tank 6 is connected with a concentration device 8, and the concentration device 8 is connected with the premixer 1; the third storage tank 7 is connected to a concentration device (not shown in the figure) which is connected to a cooling crystallizer (not shown in the figure).
Example 2
The synthetic method of p-methylsulfonylphenylserine using the fixed bed reaction apparatus of example 1 comprises the following steps:
filling each reactor with a catalyst and a filler in advance, wherein the fixed bed catalyst is formed by fixing copper ions on chelate resin through complexation, the resin is selected from Landawn LSC-910 chelate resin, and the copper ion load is 1.5%; the metal ion adsorption resin is selected from a tri-nutrient CLR-08 chelate resin; selecting bleaching C115E resin as adsorption separation resin, passing purified water through equipment, thoroughly cleaning the equipment and filler, detecting with HPLC (230nm absorption wavelength, equal gradient elution) with washing water until no obvious impurity is detected (dissolving standard product with 50 times volume of washing water, wherein the maximum impurity introduced in the washing water is less than 0.1%);
starting a premixer, adding raw materials (namely 4-methylsulfonylbenzaldehyde, glycine, phosphate buffer salt and water) into the premixer, adjusting the pH value to be between 8.5 and 9.0, simultaneously heating the system to 45 to 50 ℃, sending the adjusted and preheated solution into a connected fixed bed through a liquid pump, and enabling the solution to flow through a catalyst bed layer from top to bottom, wherein the flow rate and the volume of the solution are 1 time of the volume of catalyst filler per hour;
the reaction mixed liquid flows out from an outlet at the lower part of the fixed bed, flows into an inlet at the upper part of the first separator, and flows through the metal ion adsorption carrier from top to bottom, and the flow rate of the reaction mixed liquid is 1 time of the volume of the adsorption carrier filler per hour;
the reaction mixed liquid flows out from an outlet at the lower part of the first separator, flows in from an inlet at the upper part of the second separator, and flows through the separation adsorption carrier from top to bottom, and the flow rate of the reaction mixed liquid is 0.5 times of the volume of the adsorption carrier filler per hour; the reaction mixed liquid enters a second separator for about one hour, a control valve between the first separator and the second separator is closed, a control valve connected with a water storage tank is opened, water is pumped from the water storage tank through a liquid pump, the flow rate of the water is 2 times of the volume of the adsorption carrier filler per hour, and different elution materials respectively flow into a first storage tank, a second storage tank and a third storage tank according to on-line monitoring equipment and valve control; the separated liquid in the second storage tank flows into a concentration device and is concentrated to 0.6 time of the original volume, and a proper amount of raw materials are added and then enter a premixer; and (3) enabling the separated liquid in the third storage tank to flow into a concentration device, concentrating to 0.2 time of the original volume, then enabling the separated liquid to flow into a cooling crystallization kettle, cooling and crystallizing at 0 ℃, concentrating the crystallization mother liquid by 2 times, crystallizing again at 0 ℃, and combining the crystallized solids for two times to obtain a p-methylsulfonylphenylserine product with the purity of 96.3%, wherein the yield is 77%.
Example 3
The synthetic method of p-methylsulfonylphenylserine using the fixed bed reaction apparatus of example 1 comprises the following steps:
filling each reactor with a catalyst and a filler in advance, wherein the fixed bed catalyst is copper ions fixed on chelating resin through complexation, the resin is LSC-910 chelating resin with blue dawn, the copper ion loading is 1.5%, the metal ion adsorption resin is LSC-910 chelating resin with blue dawn, the adsorption separation resin is blanc C115E resin, and purified water passes through the equipment, the equipment and the filler are thoroughly cleaned, and washing water is used for detecting (230nm absorption wavelength, equal gradient elution) by HPLC (high performance liquid chromatography) until no obvious impurity is generated (50 times of volume of washing water is used for dissolving a standard product, wherein the maximum impurity introduced in the washing water is less than 0.1%);
starting a premixer, adding materials of p-methylsulfonylbenzaldehyde, glycine, phosphate buffer salt and purified water, adjusting the pH value to 8.5-8.0, simultaneously heating the system to 45-55 ℃, feeding the adjusted and preheated solution into a connected fixed bed through a liquid pump, and enabling the solution to flow through a catalyst bed layer from top to bottom, wherein the flow rate and the volume of the solution are 1 time of the volume of catalyst filler per hour;
the reaction mixed liquid flows out from an outlet at the lower part of the fixed bed, flows in from an inlet at the upper part of the first separator, and flows through the ion adsorption carrier from top to bottom, and the flow rate of the reaction mixed liquid is 1 time of the volume of the adsorption carrier filler per hour;
the reaction mixed liquid flows out from an outlet at the lower part of the first separator, flows in from an inlet at the upper part of the second separator, flows through the separation adsorption carrier from top to bottom, has the flow rate of 0.3 times of the volume of the adsorption carrier filler per hour, enters the second separator for about one hour, closes a control valve between the first separator and the second separator, opens a control valve connected with a water storage tank, pumps purified water from the water storage tank into the second separator through a liquid pump, has the flow rate of 2 times of the volume of the adsorption carrier filler per hour, and simultaneously flows different elution materials into the first storage tank, the second storage tank and the third storage tank respectively according to the control of an online monitoring device and a valve; the separated liquid in the second storage tank flows into a concentration device and is concentrated to 0.8 time of the original volume, and then enters the premixer; and (3) enabling the separated liquid in the third storage tank to flow into a concentration device, concentrating to 0.2 time of the original volume, then enabling the separated liquid to flow into a cooling crystallization kettle, cooling and crystallizing at 0 ℃, concentrating the crystallization mother liquid by 2 times, crystallizing again at 0 ℃, and combining the crystallized solids for two times to obtain the p-methylsulfonylphenylserine product with the purity of 99.1%, wherein the yield is 83%.
Example 4
The synthetic method of p-methylsulfonylphenylserine using the fixed bed reaction apparatus of example 1 comprises the following steps:
filling each reactor with a catalyst and a filler in advance, wherein a fixed bed catalyst is nickel ions fixed on amino carboxylic acid group modified porous chitosan through complexation, the loading amount of nickel is 0.9%, a metal ion adsorption resin is a blue-dawn LSC-100 chelate resin, an adsorption separation resin is a blanc C115E resin, purified water passes through equipment, the equipment and the filler are thoroughly cleaned, and washing water is used for detecting (230nm absorption wavelength, equal gradient elution) by HPLC (HPLC) until no obvious impurity is generated (a standard product is dissolved by 50 times of volume of washing water, wherein the maximum impurity introduced in the washing water is less than 0.1%);
starting a premixer, adding the material substituted benzaldehyde, glycine, phosphate buffer salt and purified water into the premixer, adjusting the pH value to 8.5-9.0, simultaneously heating the system to 55-60 ℃, sending the adjusted and preheated solution into a connected fixed bed through a liquid pump, and enabling the solution to flow through a catalyst bed layer from top to bottom, wherein the flow rate and the volume of the solution are 1 time of the volume of catalyst filler per hour;
the reaction mixed liquid flows out from an outlet at the lower part of the fixed bed, flows in from an inlet at the upper part of the first separator, and flows through the ion adsorption carrier from top to bottom, and the flow rate of the reaction mixed liquid is 1 time of the volume of the adsorption carrier filler per hour; the reaction mixed liquid flows out from an outlet at the lower part of the first separator, flows in from an inlet at the upper part of the second separator, flows through the separation adsorption carrier from top to bottom, the flow rate of the reaction mixed liquid is 0.5 times of the volume of the adsorption carrier filler per hour, the reaction mixed liquid enters the second separator for about one hour, the control valve of the first separator is switched to a second set of second separator, the control valve connected with the first set of second separator is closed, the control valve connected with the first set of second separator and a water storage tank is opened, purified water is pumped into the first set of second separator from the water storage tank through a liquid pump, the flow rate of the purified water is 2 times of the volume of the adsorption carrier filler per hour, and different elution materials respectively flow into the first storage tank, the second storage tank and the third storage tank according to the control of an online monitoring device and the valves; the separated liquid in the second storage tank flows into a concentration device and is concentrated to 0.6 time of the original volume, and then enters a premixer; and (3) enabling the separated liquid in the third storage tank to flow into a concentration device, concentrating to 0.2 time of the original volume, then enabling the separated liquid to enter a cooling crystallization kettle for cooling crystallization at 0 ℃, concentrating the crystallization mother liquid by 2 times, performing crystallization again at 0 ℃, and combining the crystallization solids obtained in two times to obtain the p-methylsulfonylphenylserine product with the purity of 98.6%, wherein the yield is 80%.
Claims (3)
1. The method for synthesizing the phenylserine derivative based on the fixed bed reactor is characterized in that a top inlet of the fixed bed is connected with a premixer, a lower outlet of the fixed bed is connected with an upper inlet of a first separator, a lower outlet of the first separator is connected with an upper inlet of a second separator, and a lower outlet of the second separator is respectively connected with a first storage tank, a second storage tank and a third storage tank;
the synthesis method comprises the following steps:
(1) mixing raw materials: mixing mono/multi-substituted benzaldehyde, glycine, a buffer salt solution and a solvent in a premixer to form a raw material mixed solution with the pH of 7.5-9.0, wherein the raw material mixed solution enters the fixed bed from an inlet at the top of the fixed bed; wherein the solvent is water;
(2) and (3) catalytic reaction: contacting the raw material mixed liquor from the step (1) with a catalyst fixed on a fixed bed at 20-60 ℃ to perform Adol reaction, and allowing a product mixed liquor generated by the reaction to flow into an upper inlet of a first separator through a lower outlet of the fixed bed; the raw material mixed liquor flows downwards through a catalyst bed layer, the catalyst is modified functional metal ions capable of complexing with an immobilized carrier, the metal ions are one or two of nickel and copper, and the carrier is one or more of amino carboxylic acids capable of forming a complexing effect with heavy metal ions or amino modified silica gel, zeolite, cellulose, resin, carbon fibers, chitin and porous ceramsite;
(3) primary separation: the product mixed liquor from the step (2) enters a first separator, contacts with a metal ion adsorption carrier for metal ion adsorption, removes residual trace metal ions in the reaction liquid, and enters an upper inlet of a second separator through a lower outlet of the first separator after the metal ions are removed;
(4) and (3) secondary separation: the product mixed liquor from the step (3) after removing the metal ions enters a second separator, is contacted with an adsorption separation carrier for separating the mixture, and then an eluent enters from another inlet arranged at the upper part of the second separator to elute and separate the product, the by-product and part of the excessive raw materials; wherein the eluent is water;
wherein the byproduct is preferentially eluted and enters the first storage tank from the lower outlet of the second separator; part of the excessive raw materials are eluted and then enter a second storage tank from a lower outlet of a second separator; finally, eluting the product, and feeding the product into a third storage tank from an outlet at the lower end of the second separator;
(5) collecting: respectively collecting the by-product of the first storage tank, the excessive raw material of the second storage tank and the product of the third storage tank; wherein the by-product from step (4) in the first storage tank is directly recovered; concentrating part of the excessive raw material separation liquid from the step (4) in the second storage tank by using a concentrating device, adding a proper amount of raw materials for supplement, and then returning to the step (1); and (4) concentrating the product separation liquid from the step (4) in the third storage tank, and cooling and crystallizing to obtain a phenylserine derivative product with the purity of not less than 95%.
2. The method for synthesizing phenylserine derivatives based on a fixed bed reactor according to claim 1, wherein the metal ion adsorption carrier is one or more of amino carboxylic acids or amino modified silica gel, zeolite, cellulose, resin, carbon fiber, chitin, and porous ceramsite capable of forming a complexing effect with heavy metal ions.
3. The method of synthesizing phenylserine derivatives in fixed-bed reactor according to claim 1, wherein the adsorptive separation carrier is an adsorptive resin having styrene or acrylic acid as a skeleton.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910721382.XA CN110330401B (en) | 2019-08-06 | 2019-08-06 | Method for synthesizing phenylserine derivative based on fixed bed reactor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910721382.XA CN110330401B (en) | 2019-08-06 | 2019-08-06 | Method for synthesizing phenylserine derivative based on fixed bed reactor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110330401A CN110330401A (en) | 2019-10-15 |
| CN110330401B true CN110330401B (en) | 2022-06-21 |
Family
ID=68148573
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910721382.XA Active CN110330401B (en) | 2019-08-06 | 2019-08-06 | Method for synthesizing phenylserine derivative based on fixed bed reactor |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110330401B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115385504B (en) * | 2022-08-20 | 2024-03-29 | 杭州豪腾科技有限公司 | Comprehensive utilization process and system for acid-base etching solution |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2680135A (en) * | 1952-07-02 | 1954-06-01 | Du Pont | Sulfonamidophenylamido-1, 3-propanediol compositions and process |
| US2761873A (en) * | 1953-11-04 | 1956-09-04 | Du Pont | Preparation of 4-substituted mercaptophenyl aldehydes and ketones |
| US2816915A (en) * | 1953-11-20 | 1957-12-17 | Du Pont | Separation of phenyl-serines |
| CN102442930A (en) * | 2011-11-02 | 2012-05-09 | 江苏宇翔化工有限公司 | Preparation method of DL-p-methylsulfonylphenyl serine ethyl ester |
| CN108033903A (en) * | 2017-12-28 | 2018-05-15 | 山东汉兴医药科技有限公司 | Synthesis process for D L-p-methylsulfonylphenylserine ethyl ester with water esterification |
| CN109402098A (en) * | 2018-11-06 | 2019-03-01 | 王喆明 | Threonine aldolase, mutant and its preparing the application in substituted benzene serine derivative |
| CN109678766A (en) * | 2019-01-25 | 2019-04-26 | 湖北中牧安达药业有限公司 | A kind of synthetic method of pmethylsulfonyl phenyleneserine copper |
-
2019
- 2019-08-06 CN CN201910721382.XA patent/CN110330401B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2680135A (en) * | 1952-07-02 | 1954-06-01 | Du Pont | Sulfonamidophenylamido-1, 3-propanediol compositions and process |
| US2761873A (en) * | 1953-11-04 | 1956-09-04 | Du Pont | Preparation of 4-substituted mercaptophenyl aldehydes and ketones |
| US2816915A (en) * | 1953-11-20 | 1957-12-17 | Du Pont | Separation of phenyl-serines |
| CN102442930A (en) * | 2011-11-02 | 2012-05-09 | 江苏宇翔化工有限公司 | Preparation method of DL-p-methylsulfonylphenyl serine ethyl ester |
| CN108033903A (en) * | 2017-12-28 | 2018-05-15 | 山东汉兴医药科技有限公司 | Synthesis process for D L-p-methylsulfonylphenylserine ethyl ester with water esterification |
| CN109402098A (en) * | 2018-11-06 | 2019-03-01 | 王喆明 | Threonine aldolase, mutant and its preparing the application in substituted benzene serine derivative |
| CN109678766A (en) * | 2019-01-25 | 2019-04-26 | 湖北中牧安达药业有限公司 | A kind of synthetic method of pmethylsulfonyl phenyleneserine copper |
Non-Patent Citations (3)
| Title |
|---|
| Application of Threonine Aldolases for the Asymmetric Synthesis of α-Quaternary α-Amino Acids;Blesl,Julia等;《ChemCatChem(2018)》;20181231;第10卷(第16期);全文 * |
| Asymmetric Synthesis of Florfenicol by Dynamic Reductive Kinetic Resolution with Ketoreductases;Zou,Jie等;《European Journal of Organic Chemistry(2018)》;20181231;第36卷;全文 * |
| Threonine aldolases-an emerging tool for organic synthesis;Steinreiber,Johannes等;《Tetrahedron (2007)》;20061208;第63卷(第4期);全文 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110330401A (en) | 2019-10-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR100813368B1 (en) | Method of purifying amino acid | |
| US4855494A (en) | Process for producing citric acid | |
| EP2754652A1 (en) | Taurine preparation method | |
| WO2015025896A1 (en) | Method for producing 1,5-pentadiamine | |
| JP2008194043A (en) | Process for purifying l-cysteine | |
| CN101519348A (en) | Process for reclaiming o-chlorobenzoic acid from mother liquor or waste water | |
| MY145905A (en) | Process for production of terephthalic acid | |
| CN110330401B (en) | Method for synthesizing phenylserine derivative based on fixed bed reactor | |
| CN111004162B (en) | Method and device for preparing L-selenocysteine by using sodium triacetoxyborohydride as reducing agent | |
| CN115160108B (en) | Process for preparing inositol and phosphoric acid | |
| CN1990460B (en) | Comprehensive treatment of glycine crystallization mother liquid | |
| MY157728A (en) | Process for production of isophthalic acid | |
| CN114031058A (en) | Method for producing inositol and co-producing potassium dihydrogen phosphate by adopting corn steep liquor and inositol and potassium dihydrogen phosphate produced by method | |
| CN100364962C (en) | Method of recovering o-aminobenzoic acid from mother liquid or waste water | |
| CN1125037C (en) | Process for producing glutamic acid | |
| CN101519360B (en) | Method for preparing iminodiacetic acid | |
| CN103539285B (en) | The treatment process that a kind of wastewater of N-methylaniline production recycles | |
| CN104974054B (en) | The method and device of iminodiacetic acid is prepared using iminodiacetonitrile production mother liquor | |
| CN115403019A (en) | Preparation method of iron phosphate | |
| CN210683645U (en) | Taurine last mother liquor decoloration edulcoration device | |
| US4927541A (en) | Process for refining amino acids | |
| JP2005298369A (en) | Method for separating and producing organic acid | |
| CN101181983A (en) | Method for producing hypophosphorous acid | |
| CN210993108U (en) | Liquid acrylamide refining instrument | |
| CN105017047B (en) | The production method and device of a kind of iminodiacetic acid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |