CN110330401A - The synthetic method of benzene serine derivative based on fixed bed reactors - Google Patents
The synthetic method of benzene serine derivative based on fixed bed reactors Download PDFInfo
- Publication number
- CN110330401A CN110330401A CN201910721382.XA CN201910721382A CN110330401A CN 110330401 A CN110330401 A CN 110330401A CN 201910721382 A CN201910721382 A CN 201910721382A CN 110330401 A CN110330401 A CN 110330401A
- Authority
- CN
- China
- Prior art keywords
- fixed bed
- separator
- product
- storage tank
- synthetic method
- 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.)
- Granted
Links
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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Physics & Mathematics (AREA)
- Fluid Mechanics (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention provides a kind of benzene serine derivative synthesis technology based on fixed bed reactors, it is that raw material is uniformly mixed in premixed device and enters from the top of fixed bed in catalyst contact progress Adol reaction after remaining to certain temperature, the product of generation enters the first separator by outlet, remove a small amount of metal ion, then the second separator is passed through, product and by-product are separated, high pure benzene serine derivative product is obtained.It can be with recycled after separation concentration with the solvent material being related to used in reaction.The beneficial effects of the present invention are: (1) reaction process easy to operate, the reaction of whole process whole process flow-type, high efficiency, when low consumption；(2) solvent and excess raw material are applied, and three waste discharge is few, green economy environmental protection；(3) low energy consumption, specific yield is high, is suitable for amplification production.
Description
[technical field]
The present invention relates to chemical field more particularly to a kind of synthesis of the benzene serine derivative based on fixed bed reactors
Method.
[background technique]
Benzene serine derivative is a kind of important pharmaceutical intermediate and chemical intermediate, especially 4- methylsulfonyl benzene silk ammonia
Acid, 4- nitrobenzene serine etc. are widely used in mankind's antibiotic, the preparation of domestic birds and animals class antibiotic etc., represent drug such as chlorine
Mycin, Thiamphenicol, Florfenicol etc..
The industrial process of benzene serine derivative is mainly traditional chemical synthesis, with mono-/multi- substituted benzaldehyde,
Glycine, copper sulphate, ammonium hydroxide are raw material, obtain within heating stirring 30 hours mono-/multi- substituted benzene serine mantoquita at 45-50 DEG C, so
Mantoquita is dissolved in water afterwards, then is passed through hydrogen sulfide gas and removes copper ion, and after active carbon filters, concentration crystallization obtains mono-/multi- and takes
For benzene serine.The synthetic method must use copper sulphate, and carry out cement copper using the hydrogen sulfide of severe toxicity, smell weight in post-processing
Ion generates a large amount of copper sulfide solid waste, is the backwardness technique for belonging to high pollution, low economy, does not meet current environment and protects
Protect policy requirements, it would be highly desirable to improve.
[summary of the invention]
The present invention provides a kind of synthetic method of benzene serine derivative based on fixed bed reactors, can substantially reduce
The yield of heavy metal pollution and waste water.
Technical solution of the invention is as follows:
The synthetic method of benzene serine derivative based on fixed bed reactors, which is characterized in that the top of the fixed bed
Portion's entrance is connected with premixed device, and lower part outlet is connected with the upper entrance of the first separator, the lower part outlet of the first separator with
The upper entrance of second separator is connected, the lower part outlet of the second separator respectively with the first storage tank, the second storage tank, third storage tank
It is connected；
The synthetic method includes the following steps:
(1) raw material mixes: mono-/multi- substituted benzaldehyde, glycine, buffer salt solution and solvent are mixed shape in premixed device
The raw material mixed liquor for being 7.5-9.0 at pH, raw material mixed liquor enter fixed bed from the top entry of fixed bed；
(2) catalysis reaction: the raw material mixed liquor from step (1) connects at 20-60 DEG C with the catalyst for being fixed on fixed bed
Touching carries out Adol reaction, and the product mixture for reacting generation is entered by the top that the lower part outlet of fixed bed flows into the first separator
Mouthful；
(3) first separation: the product mixture from step (2) enters the first separator, and inhales for metal ion
Attached adsorption of metal ions carrier contact, removes remaining trace metal ion in reaction solution, the product after removing metal ion
Mixed liquor enters the upper entrance of the second separator through the first separator lower part outlet；
(4) secondary separation: the product mixture after the removal metal ion from step (3) enters the second separator,
The adsorbing separation carrier contact separated with for mixture, then eluent is from another entrance for being set to the second separator top
Into by the elution separation of product, by-product and part excess raw material；
Wherein, by-product preferentially elutes, and from the lower end of the second separator, outlet enters the first storage tank；Part excess raw material
Then it elutes, from the lower end of the second separator, outlet enters the second storage tank；Product finally elutes, from the lower end of the second separator
Outlet enters third storage tank；
(5) it collects: the product of the by-product of the first storage tank, the excess raw material of the second storage tank, third storage tank is collected respectively.
Further, step (5) is collected: the by-product from step (4) in the first storage tank directly recycles；Second storage tank
In the part excess raw material separating liquid from step (4) after concentrator is concentrated and appropriate raw material supplement is added, then
Return step (1)；The product separating liquid from step (4) in third storage tank is after concentration, cooling crystallization, obtain purity >=
95% benzene serine derivative product.
Further, the raw material mixed liquor of step (2) flows down through catalyst bed, and the catalyst is rhetorical function
, can with fixation support be complexed metal ion.
Further, above-mentioned metal ion is one or more of iron, cobalt, nickel, copper, zinc.
Further, above-mentioned carrier is the aminocarboxylic acids or amino that complexing can be formed with heavy metal ion
One or more of the silica gel of modification, zeolite, cellulose, resin, carbon fiber, chitin, porous ceramic grain.
Further, above-mentioned adsorption of metal ions carrier is the amino carboxylic acid that complexing can be formed with heavy metal ion
One of class or the silica gel of amino modification, zeolite, cellulose, resin, carbon fiber, chitin, porous ceramic grain are several
Kind, for example, CR11, CR20 resin of Mitsubishi chemical Co., Ltd, CLR-08, CLR-20 resin of company, Xi'an are supported by South Korea three
Indigo plant knows the chelating resins such as LSC-100, LSC-910 of scientific and technological new material limited liability company.
Further, above-mentioned adsorbing separation carrier be using styrene or acrylic acid as the absorbent-type resin of skeleton, such as west
Blue LX-16, LX-18, LX-621, LX-1180, the LX-1600 for knowing scientific and technological new material limited liability company of peace, the great poly resin in Tianjin
D-101, D-101-I, AB-8 of Science and Technology Ltd., C115E, C106, A103S of Piao Laite group, Britain.
Further, above-mentioned reaction dissolvent is water, ethanol water, methanol aqueous solution or dimethyl sulphoxide aqueous solution.
It is further preferred that above-mentioned reaction dissolvent is water.
Further, above-mentioned eluent is water, ethanol water, methanol aqueous solution, dimethyl sulphoxide aqueous solution, acid solution
Or aqueous slkali.
It is further preferred that above-mentioned eluent is water.
Further, above-mentioned acid is one of hydrochloric acid, sulfuric acid, phosphoric acid, acetic acid, and above-mentioned alkali is sodium hydroxide, hydroxide
One of calcium, potassium hydroxide, sodium carbonate, sodium bicarbonate, ammonium hydroxide, above-mentioned is sodium chloride, calcium chloride, dibastic sodium phosphate, di(2-ethylhexyl)phosphate
One of hydrogen sodium, potassium chloride.
The present invention is the synthesis technology of new generation for meeting national green environmental requirement, and its advantages are as follows:
1) technique of the invention uses fixed bed, and catalyst is supported on fixed carrier, " constraint " can live to join completely
With the heavy metal ion reacted, plurality of heavy metal ion not being had and enters reaction solution, the environment for greatly reducing heavy metal is dirty
Dye；Pass through the first separator after reaction, the heavy metal ion adsorption carrier fixed in separator can remove a micro huge sum of money
Belong to ion, ensure that in production and only generate a small amount of waste water, and be free of or contain only the heavy metal ion of trace (< 10ppm), reach state
The discharge standard that family requires；
2) flow-type technique is used in reaction of the invention and separation process, greatly reduces traditional material transfer post-processing
Manpower and the time, improve unit time efficiency；
3) water or aqueous solution can be used only without the use of there is the organic of security risk in reaction of the invention and separation process
Solvent greatly reduces the security risk in production process；
4) water used in the present invention largely can greatly reduce the discharge of waste water with recycled, be conducive to save
The energy, protection environment.
[Detailed description of the invention]
Fig. 1 is the reaction unit structural schematic diagram of embodiment 1.
Mark explanation: 1, premixed device；2, fixed bed；3, the first separator；4, the second separator；5, the first storage tank；6, the
Two storage tanks；7, third storage tank；8, concentrator；9, flow controller；10, water tank；11, liquid pump；12, control valve；13, stream
Meter.
[specific embodiment]
The present invention is described in further details with specific embodiment below, but the present invention is not only limited in detail below in fact
Apply example.
Embodiment provided below is not intended to limit the invention covered range, and described step is also not use
Sequence is executed to limit its, described direction is only limitted to attached drawing.It (include any accessory claim, abstract in this specification
And attached drawing) disclosed in all methods or in the process the step of, other than mutually exclusive and incompatible method/or step,
It can combine in any way.Any feature disclosed in (including any accessory claim, abstract and attached drawing) in this specification,
Unless special note, can be equivalent by other or be replaced with similar functions/effect alternative features.Those skilled in the art
Member does conspicuous improvement to the present invention in conjunction with existing common knowledge, also fall into the present invention claims protection scope within.
Embodiment 1
It is as shown in Figure 1 a kind of fixed-bed reactor for synthesizing benzene serine derivative, including premixed device 1, premixed device 1
It is connected with fixed bed 2, the pipeline that is connected is equipped with liquid pump 11 and control valve 12；The lower part outlet (or being discharge port) of fixed bed 1
It is connected with the entrance of the first separator 3, the pipeline that is connected is equipped with liquid pump 11 and control valve 12；The discharge port of first separator 3 and
The entrance of second separator 4 is connected, and the pipeline that is connected is equipped with liquid pump 11 and control valve 12, water tank 10 and the second separator 4
Entrance is connected, and the pipeline that is connected is equipped with liquid pump 11, control valve 12 and flowmeter 13 (or being flow controller)；Second separator
4 are connected with the first storage tank 5, the second storage tank 6, third storage tank 7 respectively, and control valve 12 is equipped at each connecting pipe；Second storage tank 6
It is connected with concentrator 8, concentrator 8 is connected with premixed device 1；Third storage tank 7 is connected (not shown) with concentrator,
Concentrator is connected (not shown) with cooling crystallization kettle.
Embodiment 2
Using the synthetic method of the pmethylsulfonyl phenyleneserine of the fixed-bed reactor of embodiment 1, process is as follows:
Each reactor is packed full with catalyst and filler in advance, wherein fixed bed catalyst is that copper ion passes through complexing
It is fixed on chelating resin, what resin was selected is the LSC-910 chelating resin of blue dawn, and copper ion load capacity is 1.5%；Metal from
What son absorption resin was selected is three feeding CLR-08 chelating resins；What adsorbing separation resin was selected is drift Lay spy C115E resin,
And thoroughly cleaned up equipment and filler with purified water by equipment, detected with washing water HPLC (230nm absorbing wavelength,
Gradient elution) it arrives and (dissolves standard items, the maximum contaminant wherein introduced in washing water with 50 times of volume washes water without obvious impurity
< 0.1%)；
Start premixed device, raw material (that is: 4- methyl sulfone benzaldehyde, glycine, phosphate-buffered salt, water) is added thereto, adjusts
PH value is saved between 8.5-9.0, while system is heated to 45-50 degree, adjusts and preheated solution is sent by liquid pump
Connected fixed bed, and flow through catalyst bed from top to bottom, flow rate volume are 1 times of catalyst filling volume/per hour；
Reaction mixture is flowed out from fixed bed lower part outlet, flows into the first separator upper entrance, and flow through from top to bottom
Adsorption of metal ions carrier, flow velocity are 1 times of absorption carrier packing volume/per hour；
Reaction mixture is flowed out from the first separator lower part outlet, from the second separator upper entrance flow into, and from up to
Under flow through separation absorption carrier, flow velocity is 0.5 times of absorption carrier packing volume/per hour；Reaction mixture enters second point
From device one hour or so, the control valve between the first separator and the second separator is closed, and open the control being connected with water tank
Water is pumped into from water tank by liquid pump by valve processed, and flow velocity is 2 times of absorption carrier packing volumes/per hour, at the same according to
Line monitoring device and valve, which are controlled, separately flows into the first storage tank, the second storage tank and third storage tank for different elution materials；Second
The separating liquid of storage tank flows into concentrator and is concentrated into 0.6 times of original volume, adds appropriate raw material, then enters back into premixed device；
The separating liquid of third storage tank flows into concentrator and is concentrated into 0.2 times of original volume, cooling crystallization kettle is then entered back into, at 0 degree
Cooling crystallization, crystallization mother liquor concentrations 2 are again again in 0 degree of crystallization, and crystallization solid merges twice, obtain purity 96.3% to methyl sulfone
Base benzene serine product, yield 77%.
Embodiment 3
Using the synthetic method of the pmethylsulfonyl phenyleneserine of the fixed-bed reactor of embodiment 1, process is as follows:
Each reactor is packed full with catalyst and filler in advance, wherein fixed bed catalyst is that copper ion passes through complexing
Be fixed on chelating resin, what resin was selected is the LSC-910 chelating resin of blue dawn, and copper ion load capacity is 1.5%, metal from
What son absorption resin was selected is the LSC-910 chelating resin of blue dawn, and what adsorbing separation resin was selected is drift Lay spy C115E resin,
And thoroughly cleaned up equipment and filler with purified water by equipment, detected with washing water HPLC (230nm absorbing wavelength,
Gradient elution) it arrives and (dissolves standard items, the maximum contaminant wherein introduced in washing water with 50 times of volume washes water without obvious impurity
< 0.1%)；
Start premixed device, material is added thereto methyl sulfone benzaldehyde, glycine, phosphate-buffered salt, purified water, adjusts
PH value is heated to 45-55 degree between 8.5-8.0, while by system, adjusts and preheated solution is sent into phase by liquid pump
Fixed bed even, and flows through catalyst bed from top to bottom, and flow rate volume is 1 times of catalyst filling volume/per hour；
Reaction mixture is flowed out from fixed bed lower part outlet, is flowed into from the first separator upper entrance, and flow from top to bottom
Through ion adsorption carrier, flow velocity is 1 times of absorption carrier packing volume/per hour；
Reaction mixture is flowed out from the first separator lower part outlet, from the second separator upper entrance flow into, and from up to
Under flow through separation absorption carrier, flow velocity is 0.3 times of absorption carrier packing volume/per hour, and reaction mixture enters second point
From device one hour or so, the control valve between the first separator and the second separator is closed, and open the control being connected with water tank
Purified water is pumped into the second separator by liquid pump from water tank by valve processed, and flow velocity is 2 times of absorption carrier packing volumes/every
Hour, while different elution materials is separately flowed by the first storage tank, the second storage tank according to on-line monitoring equipment and valve control
With third storage tank；The separating liquid of second storage tank flows into concentrator and is concentrated into 0.8 times of original volume, then enters back into premix
Device；The separating liquid of third storage tank flows into concentrator and is concentrated into 0.2 times of original volume, cooling crystallization kettle is then entered back into, 0
Spend cooling crystallization, crystallization mother liquor concentrations 2 are again again in 0 degree crystallization, crystallization solid merging twice, obtain purity 99.1% to first
Sulfuryl benzene serine product, yield 83%.
Embodiment 4
Using the synthetic method of the pmethylsulfonyl phenyleneserine of the fixed-bed reactor of embodiment 1, process is as follows:
Each reactor is packed full with catalyst and filler in advance, wherein fixed bed catalyst is that nickel ion passes through complexing
It is fixed on the porous chitosan modified by aminocarboxylic acidic group, the load capacity of nickel is 0.9%, what adsorption of metal ions resin was selected
It is the LSC-100 chelating resin of blue dawn, what adsorbing separation resin was selected is drift Lay spy C115E resin, and with purified water by setting
It is standby, equipment and filler are thoroughly cleaned up, (230nm absorbing wavelength, Gradient elution) is detected with HPLC with washing water and arrives nothing
Obvious impurity (dissolving standard items, maximum contaminant < 0.1% wherein introduced in washing water with 50 times of volume washes water)；
Start premixed device, material substituted benzaldehyde, glycine, phosphate-buffered salt, purified water are added thereto, adjusts pH
Value is heated to 55-60 degree between 8.5-9.0, while by system, adjusts and preheated solution is sent by liquid pump and is connected
Fixed bed, and flow through catalyst bed from top to bottom, flow rate volume is 1 times of catalyst filling volume/per hour；
Reaction mixture is flowed out from fixed bed lower part outlet, is flowed into from the first separator upper entrance, and flow from top to bottom
Through ion adsorption carrier, flow velocity is 1 times of absorption carrier packing volume/per hour；Reaction mixture is from the first separator lower part
Outlet outflow, flows into, and flow through separation absorption carrier from top to bottom from the second separator upper entrance, and flow velocity is 0.5 times of suction
Appendix body packing volume/per hour, reaction mixture enters the second separator one hour or so, by the control valve of the first separator
It is switched to second set of second separator, closes the control valve connected with the second separator of first set, opens and first set second divides
From the control valve that device is connected with water tank, purified water is pumped into the second separator of first set by liquid pump from water tank, is flowed
Speed is 2 times of absorption carrier packing volumes/per hour, while according to on-line monitoring equipment and valve control by different elution materials
Separately flow into the first storage tank, the second storage tank and third storage tank；The separating liquid of second storage tank flows into concentrator and is concentrated into substance
Long-pending 0.6 times, then enters back into premixed device；The separating liquid of third storage tank flows into concentrator and is concentrated into 0.2 times of original volume,
Then cooling crystallization kettle is entered back into 0 degree of cooling crystallization, and crystallization mother liquor concentrations 2 are again again in 0 degree of crystallization, and crystallization solid closes twice
And obtain the pmethylsulfonyl phenyleneserine product of purity 98.6%, yield 80%.
Claims (12)
1. the synthetic method of the benzene serine derivative based on fixed bed reactors, which is characterized in that the top of the fixed bed
Entrance is connected with premixed device, and lower part outlet is connected with the upper entrance of the first separator, the lower part outlet of the first separator and
The upper entrances of two separators is connected, the lower part outlet of the second separator respectively with the first storage tank, the second storage tank, third storage tank phase
Even；
The synthetic method includes the following steps:
(1) raw material mixes: mono-/multi- substituted benzaldehyde, glycine, buffer salt solution and solvent are mixed to form in premixed device
PH is the raw material mixed liquor of 7.5-9.0, and raw material mixed liquor enters fixed bed from the top entry of fixed bed；
(2) catalysis reaction: the raw material mixed liquor from step (1) contact at 20-60 DEG C with the catalyst for being fixed on fixed bed into
Row Adol reaction, the product mixture for reacting generation flow into the upper entrance of the first separator by the lower part outlet of fixed bed；
(3) first separation: the product mixture from step (2) enters the first separator, and for adsorption of metal ions
The contact of adsorption of metal ions carrier, removes remaining trace metal ion in reaction solution, the product mixing after removing metal ion
Liquid enters the upper entrance of the second separator through the first separator lower part outlet；
(4) secondary separation: the product mixture after the removal metal ion from step (3) enters the second separator, and uses
In the adsorbing separation carrier contact of mixture separation, then eluent from be set to another entrance on the second separator top into
Enter, product, by-product and part excess raw material are eluted and separated；
Wherein, by-product preferentially elutes, and from the lower end of the second separator, outlet enters the first storage tank；Part excess raw material is then
Elution, from the lower end of the second separator, outlet enters the second storage tank；Product finally elutes, and exports from the lower end of the second separator
Enter third storage tank；
(5) it collects: the product of the by-product of the first storage tank, the excess raw material of the second storage tank, third storage tank is collected respectively.
2. the synthetic method of the benzene serine derivative according to claim 1 based on fixed bed reactors, feature exist
In the collection of the step (5) includes:
The by-product from step (4) in first storage tank directly recycles；The part from step (4) in second storage tank is excessive
Raw material separating liquid is after concentrator is concentrated and appropriate raw material supplement is added, then return step (1)；Come in third storage tank
From the product separating liquid of step (4) after concentration, cooling crystallization obtains the benzene serine derivative product of purity >=95%.
3. the synthetic method of the benzene serine derivative according to claim 1 based on fixed bed reactors, feature exist
In the raw material mixed liquor of the step (2) flows down through catalyst bed, and the catalyst is rhetorical function, Neng Gouyu
The metal ion of fixation support complexing.
4. the synthetic method of the benzene serine derivative according to claim 3 based on fixed bed reactors, feature exist
In the metal ion is one or more of iron, cobalt, nickel, copper, zinc.
5. the synthetic method of the benzene serine derivative according to claim 3 based on fixed bed reactors, feature exist
In the carrier is the aminocarboxylic acids that can form complexing with heavy metal ion or silica gel, the boiling of amino modification
One or more of stone, cellulose, resin, carbon fiber, chitin, porous ceramic grain.
6. the synthetic method of the benzene serine derivative according to claim 1 based on fixed bed reactors, feature exist
In the adsorption of metal ions carrier is that can repair with the aminocarboxylic acids or amino of heavy metal ion formation complexing
One or more of the silica gel of decorations, zeolite, cellulose, resin, carbon fiber, chitin, porous ceramic grain.
7. the synthetic method of the benzene serine derivative according to claim 1 based on fixed bed reactors, feature exist
In the adsorbing separation carrier is using styrene or acrylic acid as the absorbent-type resin of skeleton.
8. the synthetic method of the benzene serine derivative according to claim 1 based on fixed bed reactors, feature exist
In the reaction dissolvent is water, ethanol water, methanol aqueous solution or dimethyl sulphoxide aqueous solution.
9. the synthetic method of the benzene serine derivative according to claim 8 based on fixed bed reactors, feature exist
In the reaction dissolvent is water.
10. the synthetic method of the benzene serine derivative according to claim 1 based on fixed bed reactors, feature exist
In the eluent is water, ethanol water, methanol aqueous solution, dimethyl sulphoxide aqueous solution, acid solution or aqueous slkali.
11. the synthetic method of the benzene serine derivative according to claim 10 based on fixed bed reactors, feature
It is, the eluent is water.
12. the synthetic method of the benzene serine derivative according to claim 10 based on fixed bed reactors, feature
Be, the acid is one of hydrochloric acid, sulfuric acid, phosphoric acid, acetic acid, the alkali be sodium hydroxide, calcium hydroxide, potassium hydroxide,
One of sodium carbonate, sodium bicarbonate, ammonium hydroxide, the salt are sodium chloride, calcium chloride, dibastic sodium phosphate, sodium dihydrogen phosphate, potassium chloride
One of.
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 true CN110330401A (en) | 2019-10-15 |
| CN110330401B 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) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115385504A (en) * | 2022-08-20 | 2022-11-25 | 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 |
|---|
| BLESL,JULIA等: "Application of Threonine Aldolases for the Asymmetric Synthesis of α-Quaternary α-Amino Acids", 《CHEMCATCHEM(2018)》 * |
| STEINREIBER,JOHANNES等: "Threonine aldolases-an emerging tool for organic synthesis", 《TETRAHEDRON (2007)》 * |
| ZOU,JIE等: "Asymmetric Synthesis of Florfenicol by Dynamic Reductive Kinetic Resolution with Ketoreductases", 《EUROPEAN JOURNAL OF ORGANIC CHEMISTRY(2018)》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115385504A (en) * | 2022-08-20 | 2022-11-25 | 杭州豪腾科技有限公司 | Comprehensive utilization process and system for acid-base etching solution |
| 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 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110330401B (en) | 2022-06-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101735372B (en) | Chelate resin and production method and application thereof | |
| CN102432478B (en) | Preparation process of glycine | |
| JP2019513688A (en) | Method for producing tauric acid | |
| JP2019513688A5 (en) | ||
| CN101830946B (en) | Method for synthesizing clindamycin phosphate | |
| CN103833593B (en) | A kind of preparation method of N-(the 9-fluorenylmethyloxycarbonyl)-O-tert-butyl group-TYR | |
| CN102321028A (en) | Method for synthesizing 2-methyl-5-nitroimidazole-1-ethanol | |
| CN101781346A (en) | Method for separating uridylic acid from biocatalytic conversion solution | |
| CN110330401A (en) | The synthetic method of benzene serine derivative based on fixed bed reactors | |
| CN101805371A (en) | Method for recycling glyphosate raw powder from glyphosate mother liquid | |
| CN102875332B (en) | Process for synthesizing 3-hexyne-2,5-diol through slurry bed based on low pressure method | |
| CN207376099U (en) | A kind of dead catalyst utilization system | |
| CN106478438A (en) | A kind of preparation method of magnesium glycinate chelate | |
| CN103288685B (en) | Preparation method of 3-guanidino propanoic acid | |
| CN113105379A (en) | Method and device for preparing selenocysteine by using sodium formaldehyde sulfoxylate as reducing agent | |
| CN106748932B (en) | A kind of post-processing approach and device preparing methionine | |
| CN101914005B (en) | Method for preparing palladium acetate compound | |
| CN108409554A (en) | A kind of synthetic method of acetic acid iridium | |
| CN109179458A (en) | It is a kind of industry level lithium carbonate to battery-level lithium carbonate method of purification | |
| CN108033914A (en) | A kind of preparation method of Ai Qu pools pa | |
| CN108178178A (en) | A kind of method for preparing small particle basic carbonate cerium | |
| CN104310504B (en) | The treatment process of organic pollutant in a kind of dyeing waste water | |
| CN103506138B (en) | Preparation method of copper powder carrier catalyst for bromamine acid Ullman condensation reaction | |
| CN108003049B (en) | A method of separating valine from valine fermentation liquid | |
| CN107129472B (en) | A kind of technique preparing acetazolamide intermediate |
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 |