CN101955438A - Method for preparing L-(+)-alpha-phenylglycine - Google Patents
Method for preparing L-(+)-alpha-phenylglycine Download PDFInfo
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- CN101955438A CN101955438A CN201010258696XA CN201010258696A CN101955438A CN 101955438 A CN101955438 A CN 101955438A CN 201010258696X A CN201010258696X A CN 201010258696XA CN 201010258696 A CN201010258696 A CN 201010258696A CN 101955438 A CN101955438 A CN 101955438A
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- phenylglycine
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- aqueous solution
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Abstract
The invention discloses a method for preparing L-(+)-alpha-phenylglycine, which belongs to a carbocyclic compound of which the carbon skeleton has a hexatomic aromatic ring and an amino and a carboxyl which are bonded with the same non-ring carbon atom of the carbon skeleton. The invention particularly relates to a method for preparing L-(+)-alpha-phenylglycine by splitting D(-)-alpha-aminophenylacetic acid. The method is characterized by comprising the following process steps: 1, splitting and salifying; 2, performing centrifugal separation; 3, racemizing and desalting; 4, separating in alkali and dehydrating; 5, crystallizing and performing centrifugal separation; and 6, recycling filtrate. The method for preparing L-(+)-alpha-phenylglycine has the advantages of short production period, high product yield, high equipment utilization rate and low production cost. The single-batch production period of the method is 7 to 10 hours; and the final levorotatory form yield of the method is up to 95 percent which is 10 to 15 percent higher than that of the prior art. The equipment utilization rate is high, the production capacity is improved to two times that of the prior art, and thus, the production cost is reduced greatly.
Description
Technical field
The present invention is a kind of preparation method of L-Phenylglycine.Belonging to carbon skeleton contains hexa-atomic aromatic ring and has the amino that is connected on the non-ring carbon atom of same carbon skeleton and the isocyclic compound of carboxyl.Be particularly related to a kind of passing through the dextrorotation phenylglycine is split, prepare the method for L-Phenylglycine.
Background technology
Levo form D-(-) phenylglycine of phenylglycine is that L-Phenylglycine is important medicine intermediate, is the important source material of synthetic ammonia penicillin G, Cefalexin Ampicillin and left-handed pair of medicine such as hydrogen phenylglycine.
Preparation method of the prior art mainly adopts resolving agent D-(+) camphorsulfonic acid that the DL-phenylglycine is split.There is following deficiency:
Production cycle long, single batch of production cycle reaches 24 hours, wherein the racemization time accounts for more than 75% of whole production cycle.
2. product yield is lower, below 85%.
3. plant factor is low, the production cost height.
Summary of the invention
The objective of the invention is to avoid above-mentioned weak point of the prior art, and a kind of preparation method of with short production cycle, product yield is high, plant factor is high, production cost is low left-handed glycine is provided.
Purpose of the present invention can reach by following measure:
The preparation method of L-Phenylglycine of the present invention is characterized in that comprising following processing step:
1.. fractionation, salify
With DL-phenylglycine 1 weight part and D-(+) camphorsulfonic acid 0.35～0.55 weight part, drop into to split in the still 1, in acidic aqueous solution, split, salt-forming reaction 90～105 ℃ of temperature of reaction, 0.5～1.5 hour reaction times;
2.. centrifugation
Step fractionation, salt-forming reaction product 1., through 4 centrifugations of double salt whizzer, filter cake is transferred in the hydrolysis kettle 2, treats that alkali is analysed, hydrolysis;
3.. racemization, desalination
From step centrifugation mother liquor 2., send back in the fractionation still 1 through double salt mother liquor tank 6, double salt mother liquor pump 8, add alkaline aqueous solution, regulating the pH scope is 6.5～11,85～105 ℃ of temperature, under the condition, carry out racemization 1.5～3.5 hours, and then, be cooled to 25～45 ℃, again through 4 centrifugations of double salt whizzer, desalination; Filtrate is sent into and is split still 1 utilization to be recycled;
4.. alkali is analysed, hydrolysis
In hydrolysis kettle 3, add alkaline aqueous solution, 75～90 ℃ of controlled temperature carry out that alkali is analysed, hydrolysis reaction, and control pH value 5.0～7.0 is for alkali is analysed, the hydrolysis terminal point;
5.. crystallization, centrifugation
From step alkali 4. analyse, hydrolysate, enter crystallization kettle 3, under 40～60 ℃ of temperature, crystallization 0.5～1.5 hour, through 5 centrifugations of finished product whizzer, filter cake is the L-Phenylglycine crude product, will be after its recrystallization, the drying the L-Phenylglycine finished product; Filtrate is sent into through crude product mother liquor tank 7, crude product mother liquor pump 9 and is split still 1, utilization to be recycled;
6.. the filtrate cycle utilization
From 2. centrifugation mother liquor and the mixing in splitting still 1 of step Crystallization Separation mother liquor 5. of step, 1. draft proportioning set by step, replenish input DL-phenylglycine and D-(+) camphorsulfonic acid and proceed salt-forming reaction.
Purpose of the present invention can also reach by following measure:
The preparation method of L-Phenylglycine of the present invention, step 1. described in acidic aqueous solution be dilute sulfuric acid aqueous solution.
The preparation method of L-Phenylglycine of the present invention, step 3. described in alkaline aqueous solution be aqueous sodium hydroxide solution.
The preparation method of L-Phenylglycine of the present invention, step 4. described in alkaline aqueous solution be ammonia soln.
The preparation method of L-Phenylglycine of the present invention has following positively effect compared to existing technology:
1. a kind of preparation method of with short production cycle, product yield is high, plant factor is high, production cost is low L-Phenylglycine is provided.
2. fast racemization, has been shortened the production cycle, single batch of 7～10 hours production cycle at the reaction conditions gentleness.
3. resolution reaction condition milder, the fractionation cycle is shorter, and the yield of final levo form can reach 95%, is higher than former process recovery ratio 10%～15%.
4. plant factor improves, and throughput is brought up to original twice, thereby production cost reduces greatly.
Description of drawings
Fig. 1 is the preparation method's of the L-Phenylglycine of the present invention schematic flow sheet of technology
Among the figure
1-splits still
The 2-hydrolysis kettle
The 3-crystallization kettle
4-double salt whizzer
5-crude product whizzer
6-double salt mother liquor tank
7-crude product mother liquor tank
8-double salt mother liquor pump
9-crude product mother liquor pump
10-L-Phenylglycine crude product goes the recrystallization operation.
Embodiment
The present invention is further described below in conjunction with embodiment:
Embodiment 1
Prepare left-handed benzene glycosides propylhomoserin according to preparation method of the present invention, step is as follows:
1.. fractionation, salify
With DL-phenylglycine 1 weight part and D-(+) camphorsulfonic acid 0.35～0.55 weight part, drop into to split in the still 1, in the dilute sulphuric acid acidic aqueous solution, split, salt-forming reaction 90～105 ℃ of temperature of reaction, 0.5～1.5 hour reaction times;
2.. centrifugation
Step fractionation, salt-forming reaction product 1., through 4 centrifugations of double salt whizzer, filter cake is transferred in the hydrolysis kettle 2, treats that alkali is analysed, hydrolysis;
3.. racemization, desalination
From step centrifugation mother liquor 2., send back in the fractionation still 1 through double salt mother liquor tank 6, double salt mother liquor pump 8, add aqueous sodium hydroxide solution, regulating the pH scope is 6.5～11,85～105 ℃ of temperature, under the condition, carry out racemization 1.5～3.5 hours, and then, be cooled to 25～45, again through 4 centrifugations of double salt whizzer, desalination; Filtrate is sent into and is split still 1 utilization to be recycled;
4.. alkali is analysed, hydrolysis
In hydrolysis kettle 3, add ammonia soln, 70～90 ℃ of controlled temperature carry out that alkali is analysed, hydrolysis reaction, and control pH value 5.0～7.0 is for alkali is analysed, the hydrolysis terminal point;
5.. crystallization, centrifugation
From step alkali 4. analyse, hydrolysate, enter crystallization kettle 3, under 40～60 ℃ of temperature, crystallization 0.5～1.5 hour, through 5 centrifugations of finished product whizzer, filter cake is the L-Phenylglycine crude product, will be after its recrystallization, the drying the L-Phenylglycine finished product; Filtrate is sent into through crude product mother liquor tank 7, crude product mother liquor pump 9 and is split still 1, utilization to be recycled;
6.. the filtrate cycle utilization
From 2. centrifugation mother liquor and the mixing in splitting still 1 of step Crystallization Separation mother liquor 5. of step, 1. draft proportioning set by step, replenish input DL-phenylglycine and D-(+) camphorsulfonic acid and proceed salt-forming reaction.
Reach following technical indicator:
1. 8 hours production cycles
2. the yield of levo form can reach 95%.
Claims (4)
1. the preparation method of a L-Phenylglycine is characterized in that comprising following processing step:
1.. fractionation, salify
With DL-phenylglycine 1 weight part and D-(+) camphorsulfonic acid 0.35～0.55 weight part, drop into to split in the still (1), in acidic aqueous solution, split, salt-forming reaction 90～105 ℃ of temperature of reaction, 0.5～1.5 hour reaction times;
2.. centrifugation
Step fractionation, salt-forming reaction product 1., through double salt whizzer (4) centrifugation, filter cake is transferred in the hydrolysis kettle (2), treats that alkali is analysed, hydrolysis;
3.. racemization, desalination
From step centrifugation mother liquor 2., send back in the fractionation still (1) through double salt mother liquor tank (6), double salt mother liquor pump (8), add alkaline aqueous solution, regulating the pH scope is 6.5～11,85～105 ℃ of temperature, under the condition, carry out racemization 1.5～3.5 hours, and then, be cooled to 25～45 ℃, again through double salt whizzer (4) centrifugation, desalination; Filtrate is sent into and is split still (1) utilization to be recycled;
4.. alkali is analysed, hydrolysis
In hydrolysis kettle (3), add alkaline aqueous solution, 75～90 ℃ of controlled temperature carry out that alkali is analysed, hydrolysis reaction, and control pH value 5.0～7.0 is for alkali is analysed, the hydrolysis terminal point;
5.. crystallization, centrifugation
From step alkali 4. analyse, hydrolysate, enter crystallization kettle (3), under 40～60 ℃ of temperature, crystallization 0.5～1.5 hour, through finished product whizzer (5) centrifugation, filter cake is the L-Phenylglycine crude product, will get the L-Phenylglycine finished product after its recrystallization, the drying; Filtrate is sent into through crude product mother liquor tank (7), crude product mother liquor pump (9) and is split still (1), utilization to be recycled;
6.. the filtrate cycle utilization
From 2. centrifugation mother liquor and the mixing in splitting still (1) of step Crystallization Separation mother liquor 5. of step, 1. draft proportioning set by step, replenish input DL-phenylglycine and D-(+) camphorsulfonic acid and proceed salt-forming reaction.
2. according to the preparation method of the L-Phenylglycine of claim 1, it is characterized in that acidic aqueous solution is a dilute sulfuric acid aqueous solution described in step 1..
3. according to the preparation method of the L-Phenylglycine of claim 1, it is characterized in that alkaline aqueous solution is an aqueous sodium hydroxide solution described in step 3..
4. according to the preparation method of the L-Phenylglycine of claim 1, it is characterized in that alkaline aqueous solution is an ammonia soln described in step 4..
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010258696.XA CN101955438B (en) | 2010-08-20 | 2010-08-20 | Method for preparing L-(+)-alpha-phenylglycine |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201010258696.XA CN101955438B (en) | 2010-08-20 | 2010-08-20 | Method for preparing L-(+)-alpha-phenylglycine |
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| CN101955438A true CN101955438A (en) | 2011-01-26 |
| CN101955438B CN101955438B (en) | 2014-06-25 |
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| CN201010258696.XA Expired - Fee Related CN101955438B (en) | 2010-08-20 | 2010-08-20 | Method for preparing L-(+)-alpha-phenylglycine |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106565550A (en) * | 2016-11-02 | 2017-04-19 | 河北美邦工程科技股份有限公司 | Method for concentrating and dewatering camphor sulfonic acid solution in production process of L-phenylglycine |
| CN114516811A (en) * | 2022-03-07 | 2022-05-20 | 浙江云涛生物技术股份有限公司 | Method for racemization reaction of phenylglycine in alkaline environment |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1030573A (en) * | 1988-03-02 | 1989-01-25 | 浙江医科大学 | The preparation method of L-Phenylglycine |
| US20040176637A1 (en) * | 2003-03-03 | 2004-09-09 | Robert C. C. Wu | Process for preparation of 2-chlorophenylglycine derivatives and enantiomerically separation |
| CN101045693A (en) * | 2006-03-29 | 2007-10-03 | 宝山钢铁股份有限公司 | Preparation method of para-hydroxybenzol gylcine |
-
2010
- 2010-08-20 CN CN201010258696.XA patent/CN101955438B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1030573A (en) * | 1988-03-02 | 1989-01-25 | 浙江医科大学 | The preparation method of L-Phenylglycine |
| US20040176637A1 (en) * | 2003-03-03 | 2004-09-09 | Robert C. C. Wu | Process for preparation of 2-chlorophenylglycine derivatives and enantiomerically separation |
| CN101045693A (en) * | 2006-03-29 | 2007-10-03 | 宝山钢铁股份有限公司 | Preparation method of para-hydroxybenzol gylcine |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106565550A (en) * | 2016-11-02 | 2017-04-19 | 河北美邦工程科技股份有限公司 | Method for concentrating and dewatering camphor sulfonic acid solution in production process of L-phenylglycine |
| CN106565550B (en) * | 2016-11-02 | 2018-04-13 | 河北美邦工程科技股份有限公司 | A kind of thickening method of camphorsulfonic acid solution in L-Phenylglycine production process |
| CN114516811A (en) * | 2022-03-07 | 2022-05-20 | 浙江云涛生物技术股份有限公司 | Method for racemization reaction of phenylglycine in alkaline environment |
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| CN101955438B (en) | 2014-06-25 |
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