CN109912439A - A kind of method that cyanalcohol method continuously quickly prepares DL- phenylglycine and the like - Google Patents
A kind of method that cyanalcohol method continuously quickly prepares DL- phenylglycine and the like Download PDFInfo
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Abstract
The present invention provides a kind of cyanalcohol method and continuously quickly prepares DL- phenylglycine and its similar method, include: (1) aminating reaction: micro passage reaction is added with ammonium hydroxide in 2- hydroxy-benzyl cyanide and the like (abbreviation cyanalcohol) and is reacted, controlling reaction temperature is 50~200 DEG C, pressure is 0.5~2.5MPa, reactant residence time in microchannel is 0.5~8min, obtains 2- amino-benzene acetonitrile and the like (abbreviation cyanamide) aqueous solution；(2) Basic fluxing raction: micro passage reaction is added with alkali in the cyanamide that step (1) obtains and is reacted, controlling reaction temperature is 90~200 DEG C, pressure is 1.0~3.0MPa, and residence time of the reactant in microchannel is 10~60min, obtains DL- phenylglycine and the like.The present invention uses micro passage reaction, accelerates ammonification and Basic fluxing raction rate, reduces cyanalcohol and cyanamide pyrolysis polymerization, is not necessarily to catalyst, improves product yield, reduce production cost.
Description
Technical field
The present invention relates to chemical field, in particular to a kind of cyanalcohol method continuously quickly prepares DL- phenylglycine and its similar
The method of object.
Background technique
DL- phenylglycine and its derivative are a kind of important medical synthetic intermediates, mainly for the preparation of beta-lactam
Class antibiotic, polypeptide hormone and pesticide.Begin to batch production DL- phenylglycine the external sixties, China is in ability at the beginning of the eighties
It realizes the industrialized production of DL- phenylglycine, and mainly uses sodium cyanide method.The method is using benzaldehyde as primary raw material, with cyaniding
Reaction synthesis DL- phenylglycine, the DL- phenylglycine that the method obtains under phase transfer catalyst effect such as sodium and solid ammonium salt
Poor product quality, color are compared with the disadvantages of deep, yield is low, by-product inorganic salts are more.
DL- phenylglycine and its derivative another synthetic method are using phase transfer catalyst, based on benzaldehyde
Raw material is wanted, is reacted with chloroform, sodium hydroxide, ammonium hydrogen carbonate, one-step synthesis DL- phenylglycine.The production technology yield is low, only
46%, and generate the inorganic salts of a large amount of brine wastes and low value.
And the synthesis technology of DL-p-hydroxyphenylglycine is used with phenol and glyoxalic acid, water, 4- nitro neighbour benzene two mostly
For carboximide under the action of Phase-transfer catalyst quaternary ammonium salt, one pot reaction preparation, synthesis procedure is complex, and DL- is to hydroxyl
Base phenylglycine yield is lower.DL-p-hydroxyphenylglycine obtains D-pHPG by splitting.D- para hydroxybenzene
Glycine is mainly used as semisynthetic penicillin and semi-synthetic head embraces the side chain compound of bacteriums drug.The main medicine produced with it
Product have through ammonia section penicillin (Amoxicillin), through ammonia section penicillin Clavulanate, light ammonia section header armful, light ammonia choker bar head armful, head
Croak ketone, head armful bent throat etc. is embraced, these medicinal usages are extensive, to gram-positive bacteria, Gram-negative bacteria, toxoplasm, conveyor screw
Deng there is killing effect;It is also applied to photosensitive field and the analytical reagent as iron, phosphorus, silicon etc. etc..The external seventies, that is, large quantities of
Amount production D-pHPG, produces for Amoxicillin.In recent years, developed countries' annual requirement such as America and Europe ten thousand tons with
On.Larger side chain compound D-pHPG supplier is Dutch DSM N. V., Spain in the world
Also there are kiloton scale production unit in DeriVados company etc., Singapore.
The production technology of DL- phenylglycine and its current mainstream of derivative be with benzaldehyde and the like, Cymag (or
Person's potassium cyanide) and ammonium chloride be that " one kettle way " Strecker of raw material reacts, i.e. formaldehyde and the like, Cymag (or cyanogen
Change potassium) and ammonium chloride hybrid reaction obtain 2- amino-benzene acetonitrile analog (abbreviation cyanamide), then acidolysis or alkaline hydrolysis again, obtain
To DL- phenylglycine and its derivative.However, at present using Cymag, ammonium chloride and benzaldehyde and its one kettle way of derivative
Aniline cyanogen analog is prepared, not only yield is low, and generates a large amount of reluctant cyanide wastewater.In addition to this, also
Following two glycolylurea method technique.
One is " two components " cyanalcohol glycolylurea methods, i.e., with hydrogen cyanide and benzaldehyde and the like for Material synthesis 2- hydroxyl
Base-benzene acetonitrile or 2- hydroxy-benzyl cyanide analog (abbreviation cyanalcohol), cyanalcohol synthesize glycolylurea aqueous solution again, glycolylurea alkaline hydrolysis, acid again
Change obtains product.If patent CN106380415A discloses a kind of D, the preparation method of L- phenylglycine and the like be with
Benzaldehyde and the like, hydrogen cyanide are raw material, generate 2- hydroxy-benzyl cyanide or 2- hydroxy-benzyl cyanide by cyanogenation
Analog (abbreviation cyanalcohol), the cyanalcohol reactant aqueous solution with carbon dioxide and ammonia again generate 5- phenyl-hydantoins and its similar
Object (abbreviation glycolylurea)；Glycolylurea is stripped, then is made through alkaline hydrolysis, stripping, decoloration, neutralization, crystallization, washing, centrifugation, drying and other steps
D, L- phenylglycine and the like.Although using cyanalcohol in the patent, the receipts of phenylglycine and the like are substantially increased
Rate, but be finally unavoidably to generate a large amount of sodium chloride or sodium sulphate, and a large amount of reluctant brine waste is
A kind of production technology of unclean environmental protection.
Another be using benzaldehyde and the like, Cymag, carbon ammonium aqueous solution as raw material " three components " glycolylurea method,
The glycolylurea aqueous solution of containing sodium carbonate, the sea are prepared using benzaldehyde and the like, Cymag, carbon ammonium aqueous solution as raw material
Because aqueous solution obtains product by alkaline hydrolysis, acidification.As patent CN106083628B is disclosed and a kind of system of p-chlorophenylglycine
Preparation Method is reacted completely in micro passage reaction with p-chlorobenzaldehyde, ammonium hydrogen carbonate and Cymag, then uses tubular reactor
Prepare p-chlorophenylglycine.Its main feature is that raw material is intermediate by carrying out cyclization preparation in micro passage reaction through flow gauge
Body is to chlorobenzene glycolylurea, then intermediate is carried out alkaline hydrolysis by tubular reactor through flow gauge and prepares p-chlorophenylglycine sodium,
Reaction can be completed within 8-18 minutes in total, finally imports in reaction flask and carry out acidification crystallization processing.Product purity is in 98 .0%
More than, yield is 95% or more.There are also described in CN103086905B for the patent of similar approach.Although in such methods, using cyanogen
Change sodium as cyanogen source, but be finally unavoidably generate a large amount of sodium chloride or sodium sulphate, and largely it is reluctant
Brine waste, and a kind of production technology of unclean environmental protection.
In conclusion preparation method either " one kettle way " Strecker of DL- phenylglycine and its derivative is anti-at present
Should or cyanalcohol glycolylurea method, either " three components " glycolylurea method, all have that preparation method is complicated, the production cycle is long, the reaction time
Long, side reaction is more, and product yield is low, of poor quality, color is compared with deep, by-product inorganic salts are more, not environmentally protective, a large amount of brine wastes rows
It puts, the problems such as poor product quality.
Summary of the invention
In view of the foregoing deficiencies of prior art, the purpose of the present invention is to provide a kind of cyanalcohol methods continuously quickly to prepare
The method of DL- phenylglycine and the like, reaction when for solving to prepare DL- phenylglycine and the like in the prior art
Time is long, reaction rate is slow, and yield is low, and raw material cyanide, which is easy to happen thermal polymerization, causes foreign pigment to generate, and generates a large amount of
The problems such as cyanide wastewater or a large amount of low value inorganic salts of by-product and a large amount of reluctant waste water.
In order to achieve the above objects and other related objects, first aspect present invention provides a kind of cyanalcohol method and continuously quickly prepares
DL- phenylglycine and its similar method, comprising: (1) aminating reaction: by 2- hydroxy-benzyl cyanide and the like (abbreviation cyanogen
Alcohol) it is reacted with ammonium hydroxide addition micro passage reaction, control reaction temperature is 50~200 DEG C, and pressure is 0.5~2.5MPa,
Reactant residence time in microchannel is 0.5~8min, and it is water-soluble to obtain 2- amino-benzene acetonitrile and the like (abbreviation cyanamide)
Liquid；(2) Basic fluxing raction: being added micro passage reaction with alkali for the cyanamide that step (1) obtains and react, and control reaction temperature is
90~200 DEG C, pressure is 1.0~3.0MPa, and residence time of the reactant in microchannel is 10~60min, and it is sweet to obtain DL- benzene
Propylhomoserin and the like.
In some embodiments of the invention, the temperature for controlling aminating reaction in step (1) is 90~170 DEG C, control
The pressure of aminating reaction is 0.8~2.0MPa, and residence time of the aminating reaction object in microchannel is 2~8min.
In some embodiments of the invention, in step (1) the mass percentage of the ammonia be 20wt%~
99.9wt%, remaining is water, and the mass percentage of 2- hydroxy-benzyl cyanide and the like is 70wt%~99.0wt%, ammonia and 2-
The molar ratio of hydroxy-benzyl cyanide and the like is 2.0~10:1, preferably 3.0~5.0:1.
In some embodiments of the invention, the temperature of control hydrolysis is 120~200 DEG C in step (2), control
The pressure of hydrolysis is 1.0~2.5MPa, and residence time of the hydrolysis reactant in microchannel is 10~40min.
In some embodiments of the invention, the alkali described in step (2) is selected from sodium hydroxide, potassium hydroxide, carbonic acid
At least one of sodium, potassium carbonate, calcium hydroxide, baryta water, particularly preferred sodium hydroxide, potassium hydroxide or carbon
Sour potassium, the mass percentage of the lye are 30wt%~50wt%.
In some embodiments of the invention, sodium ion or potassium ion and 2- hydroxyl-benzene in the alkali described in step (2)
The molar ratio of acetonitrile and the like is 1.0~2.0:1.0.
In some embodiments of the invention, for the hydrolyzate after stripping deamination, acidification obtains DL- phenylglycine
And the like, the acidizing reagent is selected from least one of sulfuric acid, phosphoric acid, hydrochloric acid, nitric acid, carbonic acid, carbon dioxide, special
Other preferably sulfuric acid, hydrochloric acid or carbon dioxide.
In some embodiments of the invention, the crystalline mother solution after the acidizing reagent carbon dioxide acidification is de- by heating
It is the wet chemical containing DL- phenylglycine salt and the like after carbon, is back to 2- amino-benzene acetonitrile and the like
Hydrolysis.
In some embodiments of the invention, the potassium ion and (2- hydroxy-benzyl cyanide and the like+phenylglycine
And the like) molar ratio be 1.2~2.0:1.0, control reaction temperature be 120~200 DEG C, pressure be 1.0~
2.5MPa, residence time of the reactant in microchannel are 10~40min.
Second aspect of the present invention provides above method preparation DL- phenylglycine and the like, the DL- phenylglycine
And the like selected from DL- phenylglycine, DL- o-chlorobenzene glycine, chlorophenyl glycine, DL- p-chlorophenylglycine, DL- between DL-
Between at least one of fluorophenyl glycine etc. fluorophenyl glycine, DL- o fluorobenzaldehyde, DL-.
As described above, a kind of cyanalcohol method of the invention continuously quickly prepares DL- phenylglycine and its similar method, have
Below the utility model has the advantages that the present invention uses micro passage reaction, reaches being sufficiently mixed for reaction mass, greatly increase intermolecular touch
It hits, substantially reduces the reaction time of 2- hydroxy-benzyl cyanide and the like with ammonia, avoid 2- hydroxy-benzyl cyanide and its class
Thermal polymerization, decomposition are easy like object ammonification and lead to the problem of by-product phenylglycine dintrile；It solves and hydrolyzes in the prior art not
It thoroughly can need to generate more by-product using a large amount of acetone, reaction rate is relatively slow, foreign pigment is caused to generate, react not
Sufficiently, do not have economical, result in waste of resources, it is not environmentally protective the problems such as.
Present invention solution prepares that DL- phenylglycine and the like the reaction time is long, reaction rate is slow in the prior art,
Yield is low, and raw material cyanide is easy to happen thermal polymerization, easily leads to foreign pigment generation, generates a large amount of cyanide wastewater or by-product
The problems such as a large amount of low value inorganic salts and a large amount of reluctant waste water.This method has Atom economy, is led to using micro-
Road reactor technology is easy thermal polymerization, decomposition and production for solving 2- hydroxy-benzyl cyanide and the like ammonification in the prior art
The problem of raw by-product phenylglycine dintrile, there are also solve existing skill using micro passage reaction alkaline hydrolysis 2- amino-benzene acetonitrile
Hydrolysis cannot be thorough in art, needs to generate more by-product using a large amount of acetone, reaction rate is relatively slow, leads to foreign pigment
Generate, react insufficient, do not have economical, result in waste of resources, it is not environmentally protective the problems such as.
In conclusion the present invention uses micro passage reaction, accelerates ammonification and Basic fluxing raction rate, reduce cyanalcohol and cyanogen
Amine pyrolysis polymerization, is not necessarily to catalyst, improves product yield, reduce production cost.
Specific embodiment
Illustrate embodiments of the present invention below by way of specific specific example, those skilled in the art can be by this specification
Other advantages and efficacy of the present invention can be easily understood for disclosed content.The present invention can also pass through in addition different specific realities
The mode of applying is embodied or practiced, the various details in this specification can also based on different viewpoints and application, without departing from
Various modifications or alterations are carried out under spirit of the invention.
The manufacturer of the micro passage reaction used in following embodiment is Mainz, Germany microtechnology research institute IMM, type
Number SIMM-V2-SS, microchannel internal diameter are 50 μm.
The reactant form of following embodiment is liquid, it should be noted that reactant is not limited by form, can also be with
For other forms such as gaseous state, reaction mass and alkali can be made smoothly to react in micro passage reaction.
Embodiment 1
The preparation (carbon dioxide acidification) of DL- phenylglycine:
166.4338 grams of the 2- hydroxy-benzyl cyanide aqueous solution (cyanalcohol) (1.0 moles) and quality for being 80wt% by mass percentage
Percentage composition is that 113.3333 grams of 60.0wt% ammonia spirit (cyanalcohol: ammonia=1.0:4.0) is pumped into microchannel by metering pump simultaneously
In reactor, flow velocity of the cyanalcohol in microchannel is 10.0g/min, and flow velocity of the ammonia spirit in microchannel is 6.81g/min,
The temperature of control reaction is 120 DEG C, pressure 1.5MPa, and the residence time is that 3min(, that is, reaction solution flows through time of microchannel),
The liquid of outflow is transparent 2- amino-benzene acetonitrile ammonia spirit (abbreviation cyanamide) 279.7671g of clear, colorless, wherein 2- ammonia
Base-benzene acetonitrile content is 47.24wt%, and 2- amino-benzene acetonitrile yield is greater than 99.9%(in terms of cyanalcohol).
The potassium carbonate for being 50wt% by 2- amino obtained above-benzene acetonitrile ammonia spirit (cyanamide) and mass percentage
207 grams of aqueous solution (cyanalcohol: potassium ion=1.0:1.5) is pumped into micro passage reaction by metering pump simultaneously, 2- amino-benzene second
Flow velocity of the nitrile ammonia spirit in microchannel is 7.0g/min, and flow velocity of the wet chemical in microchannel is 5.18g/min,
The temperature of control reaction is 170 DEG C, pressure 2.5MPa, and the residence time is that 30min(, that is, reaction solution flows through time of microchannel),
The liquid of outflow is clear light yellow transparent liquid, which passes through deamination, obtain the phenylglycine aqueous solutions of potassium containing potassium carbonate
415.4543g, wherein the mass percentage of phenylglycine is 36.39wt%, and potassium ion mass percentage is 14.08wt%,
The yield of phenylglycine is 99.9% or more.It is 8.5wt%, the sweet ammonia of benzene by the content that obtained hydrolyzate is diluted with water to potassium ion
The content of acid is 21.97wt%, and 688.1878g hydrolyzate is obtained after dilution.
Hydrolyzate obtained above is passed through carbon dioxide gas, the pressure for being passed through carbon dioxide gas is 0.2MPa, in
It is 20 DEG C, mixing speed 120r/min with temperature, is passed through in carbon dioxide and terminal pH is 8.0, filter out solid, wash,
Drying obtains phenylglycine product 115.6860g, and main content is 98wt%, the product be it is powdered, by recrystallization operation, obtain
To the DL- phenylglycine product of lenticular, purity reaches 99.5wt% or more, and recrystallization mother liquor is recycled.Filtrate is to contain benzene
The potassium bicarbonate aqueous solution of glycine, the quality of filtrate are 632.5018g, and wherein potassium ion mass percentage is 9.25wt%,
The mass percentage of phenylglycine is 5.97wt%, which is by heating decarburization, being concentrated into potassium ion mass percentage
The wet chemical 195.0214g containing phenylglycine potassium is obtained after 30.0wt%, wherein the mass percentage of phenylglycine
For 19.36wt%, the water solution cycle to lower batch glycolylurea is hydrolyzed.
Embodiment 2
The preparation (potassium carbonate Recycling Mother Solution) of DL- phenylglycine:
166.4338 grams of the 2- hydroxy-benzyl cyanide aqueous solution (cyanalcohol) (1.0 moles) and quality for being 80wt% by mass percentage
Percentage composition is that 113.3333 grams of 60.0wt% ammonia spirit (cyanalcohol: ammonia=1.0:4.0) is pumped into microchannel by metering pump simultaneously
In reactor, flow velocity of the cyanalcohol in microchannel is 10.0g/min, and flow velocity of the ammonia spirit in microchannel is 6.81g/min,
The temperature of control reaction is 120 DEG C, pressure 1.5MPa, and the residence time is that 3min(, that is, reaction solution flows through time of microchannel),
The liquid of outflow is transparent 2- amino-benzene acetonitrile ammonia spirit (abbreviation cyanamide) 279.7671g of clear, colorless, wherein 2- ammonia
Base-benzene acetonitrile content is 47.24wt%, and 2- amino-benzene acetonitrile yield is greater than 99.9%(in terms of cyanalcohol).
Contain phenylglycine potassium for what 2- amino obtained above-benzene acetonitrile ammonia spirit (cyanamide) and embodiment 1 obtained
Potassium carbonate mother liquor 195.0214g(wherein potassium content is 30wt%, phenylglycine content is 19.36wt%) and add
34.5 grams of 50wt% wet chemical ((cyanalcohol+phenylglycine): potassium ion=1.0:1.5) is pumped by metering pump micro- logical simultaneously
In road reactor, 2- amino-flow velocity of the benzene acetonitrile ammonia spirit in microchannel is 7.0g/min, and wet chemical is micro- logical
Flow velocity in road is 5.74g/min, and the temperature for controlling reaction is 170 DEG C, pressure 2.5MPa, and the residence time is 30min(, that is, anti-
Answer liquid stream through the time of microchannel), the liquid of outflow is clear light yellow transparent liquid, which passes through deamination, obtain containing carbon
The phenylglycine aqueous solutions of potassium 441.2885g of sour potassium, wherein the mass percentage of phenylglycine is 42.82wt%, potassium ion matter
Amount percentage composition is 15.47wt%, and the yield of phenylglycine is 99.9% or more.Obtained hydrolyzate is diluted with water to potassium ion
Content be 8.5wt%, the content of phenylglycine is 23.53wt%, and 803.1451g hydrolyzate is obtained after dilution.
Hydrolyzate obtained above is passed through carbon dioxide gas, the pressure for being passed through carbon dioxide gas is 0.2MPa, in
It is 20 DEG C, mixing speed 120r/min with temperature, is passed through in carbon dioxide and terminal pH is 8.0, filter out solid, wash,
Drying obtains phenylglycine product 144.6075g, and main content is 98wt%, the product be it is powdered, by recrystallization operation, obtain
To the DL- phenylglycine product of lenticular, purity reaches 99.5wt% or more, and recrystallization mother liquor is recycled.Filtrate is to contain benzene
The potassium bicarbonate aqueous solution of glycine, the quality of filtrate are 708.5018g, and wherein potassium ion mass percentage is 9.63wt%,
The mass percentage of phenylglycine is 6.67wt%, which is by heating decarburization, being concentrated into potassium ion mass percentage
The wet chemical 227.4291g containing phenylglycine potassium is obtained after 30.0wt%, wherein the mass percentage of phenylglycine
For 20.78wt%, the water solution cycle to lower batch glycolylurea is hydrolyzed.
Embodiment 3
The preparation (sulfuric acid acidification) of DL- phenylglycine:
166.4338 grams of the 2- hydroxy-benzyl cyanide aqueous solution (cyanalcohol) (1.0 moles) and quality for being 80wt% by mass percentage
Percentage composition is that 113.3333 grams of 60.0wt% ammonia spirit (cyanalcohol: ammonia=1.0:4.0) is pumped into microchannel by metering pump simultaneously
In reactor, flow velocity of the cyanalcohol in microchannel is 10.0g/min, and flow velocity of the ammonia spirit in microchannel is 6.81g/min,
The temperature of control reaction is 120 DEG C, pressure 1.5MPa, and the residence time is that 3min(, that is, reaction solution flows through time of microchannel),
The liquid of outflow is transparent 2- amino-benzene acetonitrile ammonia spirit (abbreviation cyanamide) 279.7671g of clear, colorless, wherein 2- ammonia
Base-benzene acetonitrile content is 47.24wt%, and 2- amino-benzene acetonitrile yield is greater than 99.9%(in terms of cyanalcohol).
The hydroxide for being 50wt% by 2- amino obtained above-benzene acetonitrile ammonia spirit (cyanamide) and mass percentage
96.0 grams of sodium water solution (cyanalcohol: sodium ion=1.0:1.2) is pumped into micro passage reaction by metering pump simultaneously, 2- amino-benzene
Flow velocity of the acetonitrile ammonia spirit in microchannel is 7.0g/min, and flow velocity of the sodium hydrate aqueous solution in microchannel is 2.4g/
Min, the temperature for controlling reaction is 180 DEG C, pressure 2.5MPa, the residence time be 30min(, that is, reaction solution flow through microchannel when
Between), the liquid of outflow is clear light yellow transparent liquid, which passes through deamination, obtain the sweet ammonia of the benzene containing a small amount of sodium hydroxide
Acid sodium aqueous solution 307.7671g, wherein the mass percentage of phenylglycine is 49.12wt%, and sodium ion mass percentage is
8.97wt%, the yield of phenylglycine are 99.9% or more.
The sulfuric acid that 70wt% is added in hydrolyzate obtained above is acidified and is neutralized, it is reaction end that be acidified to pH, which be 5.5, so
After be cooled to 30 DEG C under the conditions of stirred crystallization, filter, washing, drying, obtain phenylglycine product 147.3649g, main content is
99.5wt%, yield are 97%(in terms of cyanalcohol).Sodium sulphate filtrate 330.150g is obtained, wherein sodium sulphate content is 25.81wt%,
The content of phenylglycine is 1.37wt%, which obtains solid sodium sulfate, centrifugate circulation by high temperature condensing crystallizing, centrifugation
To lower batch phenylglycine acidizing crystal step.Therefore, by repeatedly recycling, the yield of phenylglycine reaches 99% or more.
Embodiment 4
The preparation (hydrochloric acid acidification) of DL- phenylglycine:
166.4338 grams of the 2- hydroxy-benzyl cyanide aqueous solution (cyanalcohol) (1.0 moles) and quality for being 80wt% by mass percentage
Percentage composition is that 113.3333 grams of 60.0wt% ammonia spirit (cyanalcohol: ammonia=1.0:4.0) is pumped into microchannel by metering pump simultaneously
In reactor, flow velocity of the cyanalcohol in microchannel is 10.0g/min, and flow velocity of the ammonia spirit in microchannel is 6.81g/min,
The temperature of control reaction is 120 DEG C, pressure 1.5MPa, and the residence time is that 3min(, that is, reaction solution flows through time of microchannel),
The liquid of outflow is transparent 2- amino-benzene acetonitrile ammonia spirit (abbreviation cyanamide) 279.7671g of clear, colorless, wherein 2- ammonia
Base-benzene acetonitrile content is 47.24wt%, and 2- amino-benzene acetonitrile yield is greater than 99.9%(in terms of cyanalcohol).
The hydroxide for being 50wt% by 2- amino obtained above-benzene acetonitrile ammonia spirit (cyanamide) and mass percentage
96.0 grams of sodium water solution (cyanalcohol: sodium ion=1.0:1.2) is pumped into micro passage reaction by metering pump simultaneously, 2- amino-benzene
Flow velocity of the acetonitrile ammonia spirit in microchannel is 7.0g/min, and flow velocity of the sodium hydrate aqueous solution in microchannel is 2.4g/
Min, the temperature for controlling reaction is 180 DEG C, pressure 2.5MPa, the residence time be 30min(, that is, reaction solution flow through microchannel when
Between), the liquid of outflow is clear light yellow transparent liquid, which passes through deamination, obtain the sweet ammonia of the benzene containing a small amount of sodium hydroxide
Acid sodium aqueous solution 307.7671g, wherein the mass percentage of phenylglycine is 49.12wt%, and sodium ion mass percentage is
8.97wt%, the yield of phenylglycine are 99.9% or more.
Concentrated hydrochloric acid acidification is added in hydrolyzate obtained above to neutralize, it is reaction end that be acidified to pH, which be 5.6, is then cooled down
Stirred crystallization under the conditions of to 15 DEG C filters, washing, drying, obtains phenylglycine product 148.7347g, main content is
99.6wt%, yield are 98%(in terms of cyanalcohol).Sodium chloride filtrate 350.150g is obtained, wherein sodium chloride content is 20.0wt%, benzene
The content of glycine is 0.86wt%, which obtains solid sodium chloride by high temperature condensing crystallizing, centrifugation, and centrifugate is recycled to
Lower batch phenylglycine acidizing crystal step.Therefore, by repeatedly recycling, the yield of phenylglycine reaches 99% or more.
Embodiment 5
The preparation (carbon dioxide acidification) of DL- p-chlorophenylglycine:
Mass percentage is first for 2- hydroxyl-(1.0 moles) of 186.2133 grams of p-chlorobenzyl cyanide aqueous solution (cyanalcohol) of 90wt%
45 DEG C are preheated to, is again then that 99.1667 grams of 60.0wt% ammonia spirit (cyanalcohol: ammonia=1.0:3.5) is same with mass percentage
When be pumped into micro passage reaction by metering pump, flow velocity of the cyanalcohol in microchannel is 10.0g/min, and ammonia spirit is micro- logical
Flow velocity in road is 5.33g/min, and the temperature for controlling reaction is 130 DEG C, pressure 1.6MPa, and the residence time is 2min(, that is, anti-
Answer liquid stream through the time of microchannel), the liquid of outflow is the transparent 2- amino-p-chlorobenzyl cyanide ammonia spirit of clear, colorless
(abbreviation cyanamide) 285.380g, wherein 2- amino-p-chlorobenzyl cyanide content is 58.38wt%, 2- amino-p-chlorobenzyl cyanide yield
Greater than 99.9%(in terms of cyanalcohol).
It is 30wt%'s by the ammonia spirit (cyanamide) of 2- amino-p-chlorobenzyl cyanide obtained above and mass percentage
460.0 grams of wet chemical (cyanalcohol: potassium ion=1.0:2.0) is pumped into micro passage reaction by metering pump simultaneously, 2- ammonia
Base-flow velocity of the p-chlorobenzyl cyanide ammonia spirit in microchannel is 7.0g/min, flow velocity of the wet chemical in microchannel
For 11.28g/min, the temperature for controlling reaction is 180 DEG C, pressure 2.6MPa, and the residence time is that 15min(, that is, reaction solution flows through
The time of microchannel), the liquid of outflow is clear light yellow transparent liquid, which passes through deamination, obtain pair containing potassium carbonate
The water-soluble 690.380g of chlorophenyl glycine potassium, wherein the mass percentage of p-chlorophenylglycine is 26.88wt%, potassium ion quality
Percentage composition is 11.30wt%, and the yield of p-chlorophenylglycine is 99.9% or more.By obtained hydrolyzate be diluted with water to potassium from
The content of son is 8.5wt%, and the content of p-chlorophenylglycine is 20.22wt%, and 917.7993g hydrolyzate is obtained after dilution.
Hydrolyzate obtained above is passed through carbon dioxide gas, the pressure for being passed through carbon dioxide gas is 0.2MPa, in
It is 20 DEG C, mixing speed 120r/min with temperature, is passed through in carbon dioxide and terminal pH is 8.0, filter out solid, wash,
Drying obtains p-chlorophenylglycine product 140.6121g, and main content is 99wt%, the product be it is powdered, grasped by recrystallization
Make, obtain the DL- p-chlorophenylglycine product of lenticular, purity reaches 99.5wt% or more, and recrystallization mother liquor is recycled.Filter
Liquid is the potassium bicarbonate aqueous solution containing p-chlorophenylglycine, and the quality of filtrate is 600.2523g, wherein potassium ion quality percentage
Content is 12.99wt%, and the mass percentage to p-chlorophenylglycine is 7.73wt%, and the filtrate is by heating decarburization, concentration
The wet chemical 259.9092g containing p-chlorophenylglycine potassium is obtained after being 30.0wt% to potassium ion mass percentage,
Wherein the mass percentage of p-chlorophenylglycine is 17.85wt%, and the water solution cycle to lower batch glycolylurea hydrolyzes.
Embodiment 6
The preparation (carbon dioxide acidification) of DL- o-chlorobenzene glycine:
Mass percentage is first for 2- hydroxyl-(1.0 moles) of 186.2133 grams of neighbour's chlorobenzene acetonitrile aqueous solution (cyanalcohol) of 90wt%
45 DEG C are preheated to, is again then that 99.1667 grams of 60.0wt% ammonia spirit (cyanalcohol: ammonia=1.0:3.5) is same with mass percentage
When be pumped into micro passage reaction by metering pump, flow velocity of the cyanalcohol in microchannel is 10.0g/min, and ammonia spirit is micro- logical
Flow velocity in road is 5.33g/min, and the temperature for controlling reaction is 130 DEG C, pressure 1.6MPa, and the residence time is 2min(, that is, anti-
Answer liquid stream through the time of microchannel), the liquid of outflow is the transparent 2- amino-neighbour's chlorobenzene acetonitrile ammonia spirit of clear, colorless
(abbreviation cyanamide) 285.380g, wherein 2- amino-p-chlorobenzyl cyanide content is 58.38wt%, 2- amino-neighbour's chlorobenzene acetonitrile yield
Greater than 99.9%(in terms of cyanalcohol).
It is 30wt%'s by the ammonia spirit (cyanamide) of 2- amino-neighbour's chlorobenzene acetonitrile obtained above and mass percentage
460.0 grams of wet chemical (cyanalcohol: potassium ion=1.0:2.0) is pumped into micro passage reaction by metering pump simultaneously, 2- ammonia
Base-flow velocity of neighbour's chlorobenzene acetonitrile ammonia spirit in microchannel is 7.0g/min, flow velocity of the wet chemical in microchannel
For 11.28g/min, the temperature for controlling reaction is 180 DEG C, pressure 2.6MPa, and the residence time is that 15min(, that is, reaction solution flows through
The time of microchannel), the liquid of outflow is clear light yellow transparent liquid, which passes through deamination, obtain the neighbour containing potassium carbonate
The water-soluble 690.380g of chlorophenyl glycine potassium, wherein the mass percentage of o-chlorobenzene glycine is 26.88wt%, potassium ion quality
Percentage composition is 11.30wt%, and the yield of o-chlorobenzene glycine is 99.9% or more.By obtained hydrolyzate be diluted with water to potassium from
The content of son is 8.5wt%, and the content of o-chlorobenzene glycine is 20.22wt%, and 917.7993g hydrolyzate is obtained after dilution.
Hydrolyzate obtained above is passed through carbon dioxide gas, the pressure for being passed through carbon dioxide gas is 0.2MPa, in
It is 20 DEG C, mixing speed 120r/min with temperature, is passed through in carbon dioxide and terminal pH is 8.0, filter out solid, wash,
Drying obtains o-chlorobenzene glycine product 140.6121g, and main content is 99wt%, the product be it is powdered, grasped by recrystallization
Make, obtain the DL- o-chlorobenzene glycine product of lenticular, purity reaches 99.5wt% or more, and recrystallization mother liquor is recycled.Filter
Liquid is the potassium bicarbonate aqueous solution containing o-chlorobenzene glycine, and the quality of filtrate is 600.2523g, wherein potassium ion quality percentage
Content is 12.99wt%, and the mass percentage of o-chlorobenzene glycine is 7.73wt%, and the filtrate is by heating decarburization, being concentrated into
Potassium ion mass percentage obtains the wet chemical 259.9092g containing o-chlorobenzene glycine potassium after being 30.0wt%,
The mass percentage of middle o-chlorobenzene glycine is 17.85wt%, and the water solution cycle to lower batch glycolylurea hydrolyzes.
Embodiment 7
The preparation (carbon dioxide acidification) of chlorophenyl glycine between DL-:
By (1.0 moles) elder generations of 186.2133 grams of 2- hydroxyl-chlorobenzene acetonitrile aqueous solution (cyanalcohol) that mass percentage is 90wt%
45 DEG C are preheated to, is again then that 99.1667 grams of 60.0wt% ammonia spirit (cyanalcohol: ammonia=1.0:3.5) is same with mass percentage
When be pumped into micro passage reaction by metering pump, flow velocity of the cyanalcohol in microchannel is 10.0g/min, and ammonia spirit is micro- logical
Flow velocity in road is 5.33g/min, and the temperature for controlling reaction is 130 DEG C, pressure 1.6MPa, and the residence time is 2min(, that is, anti-
Answer liquid stream through the time of microchannel), the liquid of outflow is the ammonia spirit of the transparent 2- amino-chlorobenzene acetonitrile of clear, colorless
(abbreviation cyanamide) 285.380g, wherein 2- amino-p-chlorobenzyl cyanide content is 58.38wt%, 2- amino-chlorobenzene acetonitrile yield
Greater than 99.9%(in terms of cyanalcohol).
It is 30wt%'s by the ammonia spirit (cyanamide) of 2- amino-chlorobenzene acetonitrile obtained above and mass percentage
460.0 grams of wet chemical (cyanalcohol: potassium ion=1.0:2.0) is pumped into micro passage reaction by metering pump simultaneously, 2- ammonia
Flow velocity of the base-chlorobenzene acetonitrile ammonia spirit in microchannel is 7.0g/min, flow velocity of the wet chemical in microchannel
For 11.28g/min, the temperature for controlling reaction is 180 DEG C, pressure 2.6MPa, and the residence time is that 15min(, that is, reaction solution flows through
The time of microchannel), the liquid of outflow is clear light yellow transparent liquid, which passes through deamination, obtain containing between potassium carbonate
The water-soluble 690.380g of chlorophenyl glycine potassium, the mass percentage of in-between chlorophenyl glycine are 26.88wt%, potassium ion quality
Percentage composition is 11.30wt%, and the yield of chlorophenyl glycine is 99.9% or more.By obtained hydrolyzate be diluted with water to potassium from
The content of son is 8.5wt%, and the content of chlorophenyl glycine is 20.22wt%, and 917.7993g hydrolyzate is obtained after dilution.
Hydrolyzate obtained above is passed through carbon dioxide gas, the pressure for being passed through carbon dioxide gas is 0.2MPa, in
It is 20 DEG C, mixing speed 120r/min with temperature, is passed through in carbon dioxide and terminal pH is 8.0, filter out solid, wash,
Drying obtains a chlorophenyl glycine product 140.6121g, and main content is 99wt%, the product be it is powdered, grasped by recrystallization
Make, obtain chlorophenyl glycine product between the DL- of lenticular, purity reaches 99.5wt% or more, and recrystallization mother liquor is recycled.Filter
Liquid is the potassium bicarbonate aqueous solution containing chlorophenyl glycine, and the quality of filtrate is 600.2523g, wherein potassium ion quality percentage
Content is 12.99wt%, and the mass percentage of chlorophenyl glycine is 7.73wt%, and the filtrate is by heating decarburization, being concentrated into
The wet chemical 259.9092g of chlorophenyl glycine potassium between potassium ion mass percentage is contained after being 30.0wt%,
The mass percentage of intermediate chlorophenyl glycine is 17.85wt%, and the water solution cycle to lower batch glycolylurea hydrolyzes.
Embodiment 8
The preparation (sulfuric acid acidification) of DL- p-chlorophenylglycine:
Mass percentage is first for 2- hydroxyl-(1.0 moles) of 186.2133 grams of p-chlorobenzyl cyanide aqueous solution (cyanalcohol) of 90wt%
45 DEG C are preheated to, is again then that 99.1667 grams of 60.0wt% ammonia spirit (cyanalcohol: ammonia=1.0:3.5) is same with mass percentage
When be pumped into micro passage reaction by metering pump, flow velocity of the cyanalcohol in microchannel is 10.0g/min, and ammonia spirit is micro- logical
Flow velocity in road is 5.33g/min, and the temperature for controlling reaction is 130 DEG C, pressure 1.6MPa, and the residence time is 2min(, that is, anti-
Answer liquid stream through the time of microchannel), the liquid of outflow is the transparent 2- amino-p-chlorobenzyl cyanide ammonia spirit of clear, colorless
(abbreviation cyanamide) 285.380g, wherein 2- amino-p-chlorobenzyl cyanide content is 58.38wt%, 2- amino-p-chlorobenzyl cyanide yield
Greater than 99.9%(in terms of cyanalcohol).
The hydrogen for being 50wt% by 2- amino obtained above-p-chlorobenzyl cyanide ammonia spirit (cyanamide) and mass percentage
96.0 grams of aqueous solution of sodium oxide (cyanalcohol: sodium ion=1.0:1.2) is pumped into micro passage reaction by metering pump simultaneously, 2- ammonia
Base-flow velocity of the p-chlorobenzyl cyanide ammonia spirit in microchannel is 7.0g/min, stream of the sodium hydrate aqueous solution in microchannel
Speed is 2.4g/min, and the temperature for controlling reaction is 170 DEG C, pressure 2.5MPa, and the residence time is that 20min(, that is, reaction solution flows through
The time of microchannel), the liquid of outflow is clear light yellow transparent liquid, which passes through deamination, obtain containing a small amount of hydroxide
The p-chlorophenylglycine sodium water solution 330.380g of sodium, wherein the mass percentage of p-chlorophenylglycine is 56.18wt%, sodium
Mass of ion percentage composition is 8.35wt%, and the yield of p-chlorophenylglycine is 99.9% or more.
The sulfuric acid that 40wt% is added in hydrolyzate obtained above is acidified and is neutralized, it is reaction end that be acidified to pH, which be 5.5, so
After be cooled to 30 DEG C under the conditions of stirred crystallization, filter, washing, drying, obtain p-chlorophenylglycine product 182.6263g, master contains
Amount is 99.6wt%, and yield is 98%(in terms of cyanalcohol).Sodium sulphate filtrate 430.150g is obtained, wherein sodium sulphate content is
19.81wt%, the content of p-chlorophenylglycine are 0.86wt%, which obtains sodium sulphate by high temperature condensing crystallizing, centrifugation and consolidate
Body, centrifugate are recycled to lower batch p-chlorophenylglycine acidizing crystal step.Therefore, by repeatedly recycling, p-chlorophenylglycine
Yield reach 99% or more.
Embodiment 9
Preparation (carbon dioxide acidification) of the DL- to fluorophenyl glycine:
By mass percentage be 70wt% 2- hydroxyl-to 215.9114 grams of fluorophenyl acetonitrile aqueous solution (cyanalcohol) (1.0 moles) with
Mass percentage is 113.3333 grams of 60.0wt% ammonia spirit (cyanalcohol: ammonia=1.0:4.0) while being pumped by metering pump micro-
In channel reactor, flow velocity of the cyanalcohol in microchannel is 10.0g/min, and flow velocity of the ammonia spirit in microchannel is 5.25g/
Min, the temperature for controlling reaction is 100 DEG C, pressure 1.0MPa, the residence time be 6min(, that is, reaction solution flow through microchannel when
Between), the liquid of outflow is ammonia spirit (abbreviation cyanamide) 329.2447g of the transparent 2- amino-of clear, colorless to fluorophenyl acetonitrile,
Wherein 2- amino-is 45.6wt% to fluorophenyl acetonitrile content, and 2- amino-is greater than 99.9%(in terms of cyanalcohol to fluorophenyl acetonitrile yield).
The carbon for being 50wt% to fluorophenyl acetonitrile ammonia spirit (cyanamide) and mass percentage by 2- amino-obtained above
207 grams of sour aqueous solutions of potassium (cyanalcohol: potassium ion=1.0:1.5) is pumped into micro passage reaction by metering pump simultaneously, 2- amino-
It is 7.0g/min to flow velocity of the fluorophenyl acetonitrile ammonia spirit in microchannel, flow velocity of the wet chemical in microchannel is
4.4g/min, the temperature for controlling reaction is 180 DEG C, pressure 2.5MPa, and it is micro- logical that the residence time is that 40min(, that is, reaction solution flows through
The time in road), the liquid of outflow is clear light yellow transparent liquid, which passes through deamination, obtain containing potassium carbonate to fluorobenzene
Glycine aqueous solutions of potassium 468.2447g, wherein being 36.13wt%, potassium ion quality hundred to the mass percentage of fluorophenyl glycine
Dividing content is 12.50wt%, and the yield to fluorophenyl glycine is 99.9% or more.Obtained hydrolyzate is diluted with water to potassium ion
Content be 8.5wt%, be 24.57wt% to the content of fluorophenyl glycine, 688.5951g hydrolyzate obtained after dilution.
Hydrolyzate obtained above is passed through carbon dioxide gas, the pressure for being passed through carbon dioxide gas is 0.2MPa, in
It is 20 DEG C, mixing speed 120r/min with temperature, is passed through in carbon dioxide and terminal pH is 8.0, filter out solid, wash,
Drying is obtained to fluorophenyl glycine product 138.0841g, and main content is 98wt%, the product be it is powdered, grasped by recrystallization
Make, obtain the DL- of lenticular to fluorophenyl glycine product, purity reaches 99.5wt% or more, and recrystallization mother liquor is recycled.Filter
Liquid is containing the potassium bicarbonate aqueous solution to fluorophenyl glycine, and the quality of filtrate is 600.5018g, wherein potassium ion quality percentage
Content is 9.74wt%, and the mass percentage to fluorophenyl glycine is 5.63wt%, and the filtrate is by heating decarburization, being concentrated into potassium
Mass of ion percentage composition obtains after being 30.0wt% containing the wet chemical 194.9629g to fluorophenyl glycine potassium, wherein
Mass percentage to fluorophenyl glycine is 17.34wt%, and the water solution cycle to lower batch glycolylurea hydrolyzes.
Embodiment 10
The preparation (carbon dioxide acidification) of DL- neighbour's fluorophenyl glycine:
By mass percentage be 70wt% 2- hydroxyl -215.9114 grams of neighbour fluorophenyl acetonitrile aqueous solution (cyanalcohol) (1.0 moles) and
Mass percentage is 113.3333 grams of 60.0wt% ammonia spirit (cyanalcohol: ammonia=1.0:4.0) while being pumped by metering pump micro-
In channel reactor, flow velocity of the cyanalcohol in microchannel is 10.0g/min, and flow velocity of the ammonia spirit in microchannel is 5.25g/
Min, the temperature for controlling reaction is 100 DEG C, pressure 1.0MPa, the residence time be 6min(, that is, reaction solution flow through microchannel when
Between), the liquid of outflow is transparent 2- amino-neighbour's fluorophenyl acetonitrile ammonia spirit (abbreviation cyanamide) 329.2447g of clear, colorless,
Wherein 2- amino-neighbour's fluorophenyl acetonitrile content is 45.6wt%, and 2- amino-neighbour's fluorophenyl acetonitrile yield is greater than 99.9%(in terms of cyanalcohol).
The carbon for being 50wt% by 2- amino obtained above-neighbour's fluorophenyl acetonitrile ammonia spirit (cyanamide) and mass percentage
207 grams of sour aqueous solutions of potassium (cyanalcohol: potassium ion=1.0:1.5) is pumped into micro passage reaction by metering pump simultaneously, 2- amino-
Flow velocity of the adjacent fluorophenyl acetonitrile ammonia spirit in microchannel is 7.0g/min, and flow velocity of the wet chemical in microchannel is
4.4g/min, the temperature for controlling reaction is 180 DEG C, pressure 2.5MPa, and it is micro- logical that the residence time is that 40min(, that is, reaction solution flows through
The time in road), the liquid of outflow is clear light yellow transparent liquid, which passes through deamination, obtain the adjacent fluorobenzene containing potassium carbonate
Glycine aqueous solutions of potassium 468.2447g, wherein the mass percentage of adjacent fluorophenyl glycine is 36.13wt%, potassium ion quality hundred
Dividing content is 12.50wt%, and the yield of adjacent fluorophenyl glycine is 99.9% or more.Obtained hydrolyzate is diluted with water to potassium ion
Content be 8.5wt%, the content of adjacent fluorophenyl glycine is 24.57wt%, and 688.5951g hydrolyzate is obtained after dilution.
Hydrolyzate obtained above is passed through carbon dioxide gas, the pressure for being passed through carbon dioxide gas is 0.2MPa, in
It is 20 DEG C, mixing speed 120r/min with temperature, is passed through in carbon dioxide and terminal pH is 8.0, filter out solid, wash,
Drying obtains adjacent fluorophenyl glycine product 138.0841g, and main content is 98wt%, the product be it is powdered, grasped by recrystallization
Make, obtain DL- neighbour's fluorophenyl glycine product of lenticular, purity reaches 99.5wt% or more, and recrystallization mother liquor is recycled.Filter
Liquid is containing the potassium bicarbonate aqueous solution to fluorophenyl glycine, and the quality of filtrate is 600.5018g, wherein potassium ion quality percentage
Content is 9.74wt%, and the mass percentage of adjacent fluorophenyl glycine is 5.63wt%, and the filtrate is by heating decarburization, being concentrated into potassium
Mass of ion percentage composition obtains the wet chemical 194.9629g containing adjacent fluorophenyl glycine potassium after being 30.0wt%, wherein
The mass percentage of adjacent fluorophenyl glycine is 17.34wt%, and the water solution cycle to lower batch glycolylurea hydrolyzes.
In conclusion the present invention use micro passage reaction, greatly shorten glycolylurea preparation and the alkaline hydrolysis time, acceleration react into
Row reduces cyanalcohol pyrolysis polymerization, and no coupling product generates and reduces brine waste and generates, and product yield is high, clean and environmental protection, reduces
Production cost.Above-described embodiment with (50 μm -300 μm) of German IMM micro passage reaction be experiment porch, microreactor mass transfer
Heat transfer rate is fast, and therefore, the present invention uses micro passage reaction, reaches being sufficiently mixed for reaction mass, greatly increases intermolecular
Collision, substantially reduce the reaction time of 2- hydroxy-benzyl cyanide and the like with ammonia, avoid 2- hydroxy-benzyl cyanide and
Its analog ammonification is easy thermal polymerization, decomposition and leads to the problem of by-product phenylglycine dintrile；Solves water in the prior art
Solution cannot be thorough, needs to generate more by-product using a large amount of acetone, reaction rate is relatively slow, causes foreign pigment to generate, is anti-
Answer it is insufficient, do not have economical, result in waste of resources, it is not environmentally protective the problems such as.
The above-described embodiments merely illustrate the principles and effects of the present invention, and is not intended to limit the present invention.It is any ripe
The personage for knowing this technology all without departing from the spirit and scope of the present invention, carries out modifications and changes to above-described embodiment.Cause
This, institute is complete without departing from the spirit and technical ideas disclosed in the present invention by those of ordinary skill in the art such as
At all equivalent modifications or change, should be covered by the claims of the present invention.
Claims (10)
1. a kind of method that cyanalcohol method continuously quickly prepares DL- phenylglycine and the like characterized by comprising (1) ammonia
Change reaction: micro passage reaction is added with ammonium hydroxide in 2- hydroxy-benzyl cyanide and the like and is reacted, control reaction temperature is
50~200 DEG C, pressure is 0.5~2.5MPa, and reactant residence time in microchannel is 0.5~8min, obtains 2- amino-benzene
Acetonitrile and the like aqueous solution；(2) Basic fluxing raction: the cyanamide and alkali that step (1) is obtained are added micro passage reaction and carry out
Reaction, control reaction temperature are 90~200 DEG C, and pressure is 1.0~3.0MPa, and residence time of the reactant in microchannel is 10
~60min obtains DL- phenylglycine and the like；The 2- hydroxy-benzyl cyanide and the like abbreviation cyanalcohol, the 2-
Amino-benzene acetonitrile and the like abbreviation cyanamide.
2. according to the method described in claim 1, it is characterized by: in step (1) control aminating reaction temperature be 90~
170 DEG C, control aminating reaction pressure be 0.8~2.0MPa, residence time of the aminating reaction object in microchannel be 2~
8min。
3. according to the method described in claim 1, it is characterized by: the mass percentage of the ammonia is in step (1)
20wt%~99.9wt%, remaining is water, the mass percentage of 2- hydroxy-benzyl cyanide and the like be 70wt%~
The molar ratio of 99.0wt%, ammonia and 2- hydroxy-benzyl cyanide and the like is 2.0~10:1.
4. according to the method described in claim 1, it is characterized by: in the step (2) temperature of control hydrolysis be 120~
200 DEG C, control hydrolysis pressure be 1.0~2.5MPa, residence time of the hydrolysis reactant in microchannel be 10~
40min。
5. according to the method described in claim 1, it is characterized by: the alkali described in step (2) is selected from sodium hydroxide, hydrogen-oxygen
Change at least one of potassium, sodium carbonate, potassium carbonate, calcium hydroxide, baryta water, the mass percentage of the lye
For 30wt%~50wt%.
6. according to the method described in claim 5, it is characterized by: sodium ion or potassium ion in the alkali described in step (2)
Molar ratio with 2- hydroxy-benzyl cyanide and the like is 1.0~2.0:1.0.
7. according to the method described in claim 1, acidification obtains it is characterized by: the hydrolyzate is after stripping deamination
DL- phenylglycine and the like, the acidizing reagent is in sulfuric acid, phosphoric acid, hydrochloric acid, nitric acid, carbonic acid, carbon dioxide
It is at least one.
8. according to the method described in claim 7, it is characterized by: the acidizing reagent carbon dioxide acidification after crystalline mother solution
It is the wet chemical containing DL- phenylglycine salt and the like after heating decarburization, is back to 2- amino-benzene acetonitrile
And the like hydrolysis.
9. according to the method described in claim 8, it is characterized by: the potassium ion and (2- hydroxy-benzyl cyanide and the like
+ phenylglycine and the like) molar ratio be 1.2~2.0:1.0, control reaction temperature be 120~200 DEG C, pressure
For 1.0~2.5MPa, residence time of the reactant in microchannel is 10~40min.
10. DL- phenylglycine made from any one the method and the like according to claim 1~9, which is characterized in that
Described DL- phenylglycine and the like is selected from chlorophenyl glycine, DL- between DL- phenylglycine, DL- o-chlorobenzene glycine, DL-
P-chlorophenylglycine, DL- are between at least one of fluorophenyl glycine etc. fluorophenyl glycine, DL- o fluorobenzaldehyde, DL-.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4350641A (en) * | 1980-01-25 | 1982-09-21 | Basf Aktiengesellschaft | 4-Tert.-butoxyphenylglycinonitrile and the preparation of D-(-)- and L-(+)-4-hydroxyphenylglycine |
| CN106380415A (en) * | 2016-08-29 | 2017-02-08 | 宁夏紫光天化蛋氨酸有限责任公司 | Preparation method for D, L-phenylglycine and analogue thereof |
| CN108623489A (en) * | 2017-03-23 | 2018-10-09 | 重庆紫光川庆化工有限责任公司 | A method of continuous quickly alkaline hydrolysis aminoacetonitriles synthesizes glycine |
-
2019
- 2019-04-02 CN CN201910262951.9A patent/CN109912439B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4350641A (en) * | 1980-01-25 | 1982-09-21 | Basf Aktiengesellschaft | 4-Tert.-butoxyphenylglycinonitrile and the preparation of D-(-)- and L-(+)-4-hydroxyphenylglycine |
| CN106380415A (en) * | 2016-08-29 | 2017-02-08 | 宁夏紫光天化蛋氨酸有限责任公司 | Preparation method for D, L-phenylglycine and analogue thereof |
| CN108623489A (en) * | 2017-03-23 | 2018-10-09 | 重庆紫光川庆化工有限责任公司 | A method of continuous quickly alkaline hydrolysis aminoacetonitriles synthesizes glycine |
Non-Patent Citations (1)
| Title |
|---|
| 杨国忠等: "微通道反应器连续快速合成氨基乙腈工艺研究", 《山东化工》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112574049A (en) * | 2020-12-17 | 2021-03-30 | 华阳新材料科技集团有限公司 | Novel method for preparing phenylglycine by using hydrocyanic acid |
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