CN109912439B - Method for continuously and rapidly preparing DL-phenylglycine and analogue thereof by using cyanohydrin method - Google Patents
Method for continuously and rapidly preparing DL-phenylglycine and analogue thereof by using cyanohydrin method Download PDFInfo
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Abstract
The invention provides a method for continuously and rapidly preparing DL-phenylglycine and analogues thereof by a cyanohydrin method, which comprises the following steps: (1) ammoniation reaction: adding 2-hydroxy-benzyl cyanide and analogues (cyanamide for short) thereof and ammonia water into a microchannel reactor for reaction, controlling the reaction temperature to be 50-200 ℃, the pressure to be 0.5-2.5 MPa, and the residence time of reactants in the microchannel to be 0.5-8 min to obtain 2-amino-benzyl cyanide and analogues (cyanamide for short) aqueous solution; (2) alkaline hydrolysis reaction: adding the cyanamide obtained in the step (1) and alkali into a microchannel reactor for reaction, controlling the reaction temperature to be 90-200 ℃, the pressure to be 1.0-3.0 MPa, and the retention time of reactants in the microchannel to be 10-60 min to obtain DL-phenylglycine and analogues thereof. The invention adopts the microchannel reactor to accelerate the ammonification and alkaline hydrolysis reaction rate, reduces the thermal decomposition polymerization of the cyanohydrin and the cyanamide, does not need a catalyst, improves the product yield and reduces the production cost.
Description
Technical Field
The invention relates to the field of chemical industry, in particular to a method for continuously and rapidly preparing DL-phenylglycine and analogues thereof by a cyanohydrin method.
Background
DL-phenylglycine and its derivatives are important intermediates for pharmaceutical synthesis, and are mainly used for preparing beta-lactam antibiotics, polypeptide hormones and pesticides. The foreign 60 s begin to produce DL-phenylglycine in batches, and the industrial production of DL-phenylglycine is realized in the early 80 s in China and mainly adopts a sodium cyanide method. The method takes benzaldehyde as a main raw material, and the benzaldehyde reacts with sodium cyanide, solid ammonium salt and the like under the action of a phase transfer catalyst to synthesize the DL-phenylglycine.
Another synthetic method of DL-phenylglycine and derivatives thereof is to adopt a phase transfer catalyst, take benzaldehyde as a main raw material, react with chloroform, sodium hydroxide and ammonium bicarbonate, and synthesize DL-phenylglycine in one step. The production process has a low yield of only 46%, and produces a large amount of salt-containing wastewater and low-value inorganic salts.
Most of the DL-p-hydroxyphenylglycine synthesis processes are prepared by reacting phenol, glyoxylic acid, water and 4-nitrophthalimide in a one-pot method under the action of a phase transfer catalyst quaternary ammonium salt, the synthesis process is complex, and the yield of DL-p-hydroxyphenylglycine is low. And splitting the DL-p-hydroxyphenylglycine to obtain the D-p-hydroxyphenylglycine. D-p-hydroxyphenylglycine is mainly used as a side chain compound of semi-synthetic penicillins and semi-synthetic cephalosporins. The main medicines produced by using the compound are penicillin (amoxicillin), penicillin clavulanate, light ammonia knot, dougutone, head loop and the like, the medicines have wide application, have killing effect on gram-positive bacteria, gram-negative bacteria, toxoplasma, spirochete and the like, and are also applied to the photosensitive field and used as analytical reagents of iron, phosphorus, silicon and the like. The mass production of D-p-hydroxyphenylglycine is carried out in the foreign 70 s, and the D-p-hydroxyphenylglycine is used for producing amoxicillin. In recent years, the annual demand in developed countries such as europe and the united states is over ten thousand tons. The suppliers of D-p-hydroxyphenylglycine, a large-scale side-chain compound, are from DSM in the Netherlands, Derivados in Spain, etc., and Singapore also has a kiloton-scale production apparatus.
The currently mainstream production process of DL-phenylglycine and derivatives thereof is a one-pot Strecker reaction taking benzaldehyde and analogs thereof, sodium cyanide (or potassium cyanide) and ammonium chloride as raw materials, namely a mixed reaction of the formaldehyde and the analogs thereof, the sodium cyanide (or potassium cyanide) and the ammonium chloride to obtain 2-amino-phenylacetonitrile analogs (cyanamide for short), and then acidolysis or alkaline hydrolysis is carried out to obtain the DL-phenylglycine and derivatives thereof. However, the current one-pot method of preparing aniline cyanide analogs using sodium cyanide, ammonium chloride and benzaldehyde and its derivatives is not only low in yield, but also produces a large amount of cyanide-containing wastewater that is difficult to handle. In addition, there are the following two hydantoin process.
One is "two-component" cyanhydrin hydantoin method, that is, taking hydrocyanic acid and benzaldehyde and its analogues as raw materials to synthesize 2-hydroxy-benzyl cyanide or 2-hydroxy-benzyl cyanide analogues (cyanhydrin for short), then the cyanhydrin synthesizes hydantoin aqueous solution, then the hydantoin is alkaline hydrolyzed and acidified to obtain the product. For example, patent CN106380415A discloses a method for preparing D, L-phenylglycine and its analogues, which comprises subjecting benzaldehyde and its analogues, hydrocyanic acid as raw materials to cyanidation reaction to generate 2-hydroxy-phenylacetonitrile or 2-hydroxy-phenylacetonitrile analogue (cyanohydrin for short), and reacting cyanohydrin with aqueous solution of carbon dioxide and ammonia to generate 5-phenyl-hydantoin and its analogues (hydantoin for short); the hydantoin is subjected to steam stripping, alkaline hydrolysis, steam stripping, decoloration, neutralization, crystallization, water washing, centrifugation, drying and other steps to prepare the D, L-phenylglycine and the analogues thereof. Although the use of cyanohydrin in this patent greatly improves the yield of phenylglycine and its analogues, the final process inevitably produces a large amount of sodium chloride or sodium sulfate and a large amount of saline wastewater which is difficult to treat, and is a non-clean and environment-friendly production process.
The other method is a 'three-component' hydantoin method which takes benzaldehyde and its analogues, sodium cyanide and ammonium bicarbonate aqueous solution as raw materials, namely, the hydantoin aqueous solution containing sodium carbonate is prepared by taking benzaldehyde and its analogues, sodium cyanide and ammonium bicarbonate aqueous solution as raw materials, and the hydantoin aqueous solution is subjected to alkaline hydrolysis and acidification to obtain a product. For example, patent CN106083628B discloses a method for preparing p-chlorophenylglycine, which comprises completely reacting p-chlorobenzaldehyde, ammonium bicarbonate and sodium cyanide in a microchannel reactor, and then preparing p-chlorophenylglycine by using a tubular reactor. The method is characterized in that raw materials are subjected to cyclization in a microchannel reactor through a flowmeter to prepare an intermediate p-chlorophenylhydantoin, the intermediate is subjected to alkaline hydrolysis in a tubular reactor through the flowmeter to prepare p-chlorophenylglycine sodium, the reaction can be completed in 8-18 minutes in total, and finally the reaction is conducted in a reaction bottle for acidification and crystallization. The product purity is over 98.0 percent, and the yield is over 95 percent. A patent for a similar process is also described in CN 103086905B. Although sodium cyanide is used as a cyanogen source in the method, a large amount of sodium chloride or sodium sulfate and a large amount of salt-containing wastewater which is difficult to treat are inevitably generated finally, and the method is a production process which is not clean and environment-friendly.
In conclusion, the existing preparation methods of DL-phenylglycine and derivatives thereof, namely the Strecker reaction by the one-pot method, the cyanohydrin hydantoin method or the three-component hydantoin method, have the problems of complex preparation method, long production period, long reaction time, more side reactions, low product yield, poor quality, deep color, more byproduct inorganic salts, no environmental protection, discharge of a large amount of salt-containing wastewater, poor product quality and the like.
Disclosure of Invention
In view of the above-mentioned disadvantages of the prior art, the present invention aims to provide a method for continuously and rapidly preparing DL-phenylglycine and its analogues by using a cyanohydrin method, which is used for solving the problems of the prior art, such as long reaction time, slow reaction rate, low yield, easy thermal polymerization of raw material cyanide, colored impurity generation, generation of a large amount of cyanide-containing wastewater or by-production of a large amount of low-value inorganic salts, and a large amount of wastewater which is difficult to treat.
In order to achieve the above objects and other related objects, there is provided in a first aspect of the present invention a method for continuously and rapidly preparing DL-phenylglycine and the like by a cyanohydrin process, comprising: (1) ammoniation reaction: adding 2-hydroxy-benzyl cyanide and analogues (cyanohydrin for short) thereof and ammonia water into a microchannel reactor for reaction, controlling the reaction temperature to be 50-200 ℃, the pressure to be 0.5-2.5 MPa, and the residence time of reactants in the microchannel to be 0.5-8 min to obtain 2-amino-benzyl cyanide and analogues (cyanamide for short) aqueous solution; (2) alkaline hydrolysis reaction: adding the cyanamide obtained in the step (1) and alkali into a microchannel reactor for reaction, controlling the reaction temperature to be 90-200 ℃, the pressure to be 1.0-3.0 MPa, and the retention time of reactants in the microchannel to be 10-60 min to obtain DL-phenylglycine and analogues thereof.
In some embodiments of the present invention, the temperature of the ammonification reaction in step (1) is controlled to be 90-170 ℃, the pressure of the ammonification reaction is controlled to be 0.8-2.0 MPa, and the residence time of the ammonification reactant in the microchannel is 2-8 min.
In some embodiments of the present invention, in step (1), the mass percentage of ammonia is 20wt% to 99.9wt%, the balance is water, the mass percentage of 2-hydroxy-phenylacetonitrile and the like is 70wt% to 99.0wt%, and the feeding molar ratio of ammonia to 2-hydroxy-phenylacetonitrile and the like is 2.0 to 10:1, preferably 3.0 to 5.0: 1.
In some embodiments of the present invention, in the step (2), the temperature of the hydrolysis reaction is controlled to be 120-200 ℃, the pressure of the hydrolysis reaction is controlled to be 1.0-2.5 MPa, and the residence time of the hydrolysis reactant in the microchannel is 10-40 min.
In some embodiments of the present invention, the alkali in step (2) is at least one selected from sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, calcium hydroxide, and barium hydroxide aqueous solution, and sodium hydroxide, potassium hydroxide, or potassium carbonate is particularly preferred, and the alkali solution is 30wt% to 50 wt%.
In some embodiments of the invention, the ratio of the sodium ions or potassium ions to the 2-hydroxy-phenylacetonitrile and the like in the alkali in the step (2) is 1.0-2.0: 1.0.
In some embodiments of the present invention, the hydrolysate is stripped to remove ammonia, and then acidified to obtain DL-phenylglycine and its analogues, wherein the acidifying agent is at least one selected from sulfuric acid, phosphoric acid, hydrochloric acid, nitric acid, carbonic acid, and carbon dioxide, and particularly preferably sulfuric acid, hydrochloric acid, or carbon dioxide.
In some embodiments of the invention, the crystallization mother liquor after acidification by carbon dioxide of the acidification reagent is heated and decarbonized to obtain potassium carbonate aqueous solution containing DL-phenylglycinate and analogues thereof, and the potassium carbonate aqueous solution is returned to hydrolysis of 2-amino-phenylacetonitrile and analogues thereof.
In some embodiments of the present invention, the feeding molar ratio of the potassium ions to the (2-hydroxy-phenylacetonitrile and the like + phenylglycine and the like) is 1.2-2.0: 1.0, the reaction temperature is controlled to be 120-200 ℃, the pressure is controlled to be 1.0-2.5 MPa, and the residence time of the reactants in the microchannel is 10-40 min.
In a second aspect, the present invention provides the above method for preparing DL-phenylglycine and its analogs, wherein the DL-phenylglycine and its analogs are selected from at least one of DL-phenylglycine, DL-o-chlorophenylglycine, DL-m-chlorophenylglycine, DL-p-fluorophenylglycine, DL-o-fluorobenzaldehyde, DL-m-fluorophenylglycine, etc.
As described above, the continuous and rapid preparation of DL-phenylglycine and its analogous method by using cyanohydrin method of the present invention has the following beneficial effects: the invention adopts the microchannel reactor to achieve the purpose of fully mixing reaction materials, greatly increases the collision among molecules, greatly shortens the reaction time of the 2-hydroxy-phenylacetonitrile and the analogues thereof with ammonia, and avoids the problems that the ammoniation of the 2-hydroxy-phenylacetonitrile and the analogues thereof is easy to thermally polymerize and decompose and generates byproduct phenylglycine dinitrile; the problems that in the prior art, hydrolysis cannot be thorough, a large amount of acetone is needed, more byproducts are generated, the reaction rate is low, colored impurities are generated, the reaction is insufficient, economic and economic properties are not achieved, resource waste is caused, and the like are solved.
The invention solves the problems that in the prior art, when DL-phenylglycine and analogues thereof are prepared, the reaction time is long, the reaction rate is slow, the yield is low, raw material cyanide is easy to generate thermal polymerization, colored impurities are easy to generate, a large amount of cyanide-containing waste water is generated, or a large amount of low-value inorganic salt and a large amount of waste water which is difficult to treat are generated as byproducts. The method has atom economy, and the microchannel reactor technology is used for solving the problems that in the prior art, 2-hydroxy-phenylacetonitrile and analogues thereof are easy to thermally polymerize and decompose and generate a byproduct phenylglycine dinitrile due to ammoniation, and the microchannel reactor technology is used for alkaline hydrolysis of 2-amino-phenylacetonitrile, so that the problems that in the prior art, hydrolysis cannot be thorough, a large amount of acetone is needed, a large number of byproducts are generated, the reaction rate is slow, colored impurities are generated, the reaction is insufficient, the economy and economy are unavailable, resources are wasted, the environment is not protected and the like are solved.
In conclusion, the invention adopts the microchannel reactor, accelerates the ammonification and alkaline hydrolysis reaction rate, reduces the thermal depolymerization of the cyanohydrin and the cyanamide, does not need a catalyst, improves the product yield and reduces the production cost.
Detailed Description
The embodiments of the present invention are described below with specific examples, and other advantages and effects of the present invention will be easily understood by those skilled in the art from the disclosure of the present specification. The invention is capable of other and different embodiments and its several details are capable of modifications and variations in various obvious respects, all without departing from the spirit of the invention.
The manufacturer of the microchannel reactor used in the following examples is the American Uniz micro technology institute, Germany, model SIMM-V2-SS, with a microchannel internal diameter of 50 μm.
The reactant in the following examples is in liquid form, and it should be noted that the reactant is not limited to the form, and may be in other forms such as gas form, and the reactant and the alkali can be smoothly reacted in the microchannel reactor.
Example 1
Preparation of DL-phenylglycine (carbon dioxide acidification):
166.4338 g (1.0 mol) of a 2-hydroxy-benzyl cyanide aqueous solution (cyanohydrin) with the mass percent of 80wt% and 113.3333 g (cyanohydrin: ammonia =1.0: 4.0) of an ammonia water solution with the mass percent of 60.0wt% are simultaneously pumped into a microchannel reactor through a metering pump, the flow rate of the cyanohydrin in a microchannel is 10.0g/min, the flow rate of the ammonia water solution in the microchannel is 6.81g/min, the reaction temperature is controlled to be 120 ℃, the pressure is controlled to be 1.5MPa, the retention time is 3min (namely the time for the reaction liquid to flow through the microchannel), and the effluent liquid is 279.7671g of a clear, colorless and transparent 2-amino-benzyl cyanide aqueous solution (cyanamide for short), wherein the content of the 2-amino-benzyl cyanide is 47.24wt%, and the yield of the 2-amino-benzyl cyanide is more than 99.9% (calculated by the cyanohydrin).
The obtained 2-amino-phenylacetonitrile ammonia water solution (cyanamide) and 207 g of potassium carbonate water solution with the mass percentage content of 50wt% (cyanalcohol: potassium ion =1.0: 1.5) are simultaneously pumped into a microchannel reactor through a metering pump, the flow rate of the 2-amino-phenylacetonitrile ammonia water solution in a microchannel is 7.0g/min, the flow rate of the potassium carbonate water solution in the microchannel is 5.18g/min, the reaction temperature is controlled to be 170 ℃, the pressure is 2.5MPa, the retention time is 30min (namely the time of a reaction liquid flowing through the microchannel), the flowing liquid is a clear transparent light yellow liquid, and the liquid is deaminated to obtain 415.4543g of potassium phenylglycinate water solution containing potassium carbonate, wherein the mass percentage content of phenylglycine is 36.39wt%, the mass percentage content of potassium ion is 14.08wt%, and the yield of phenylglycine is more than 99.9%. The obtained hydrolysate was diluted with water until the potassium ion content was 8.5wt% and the phenylglycine content was 21.97wt%, and 688.1878g of hydrolysate was obtained after dilution.
And (2) introducing carbon dioxide gas into the obtained hydrolysate, wherein the pressure of the introduced carbon dioxide gas is 0.2MPa, the neutralization temperature is 20 ℃, the stirring speed is 120r/min, the end point pH of the carbon dioxide gas is 8.0, filtering out solids, washing with water, and drying to obtain 115.6860g of phenylglycine product, wherein the main content of the phenylglycine product is 98wt%, the product is powdery, a crystalline DL-phenylglycine product is obtained through recrystallization, the purity of the DL-phenylglycine product reaches more than 99.5wt%, and the recrystallization mother liquor is recycled. The filtrate is potassium bicarbonate aqueous solution containing phenylglycine, the mass of the filtrate is 632.5018g, wherein the mass percentage of potassium ions is 9.25wt%, the mass percentage of phenylglycine is 5.97wt%, the filtrate is heated, decarburized and concentrated until the mass percentage of potassium ions is 30.0wt% to obtain 195.0214g of potassium carbonate aqueous solution containing potassium phenylglycine, wherein the mass percentage of phenylglycine is 19.36wt%, and the aqueous solution is circulated to the next hydantoin hydrolysis.
Example 2
Preparation of DL-phenylglycine (recycling of potassium carbonate mother liquor):
166.4338 g (1.0 mol) of a 2-hydroxy-phenylacetonitrile aqueous solution (cyanhydrin) with the mass percentage of 80wt% and 113.3333 g (cyanhydrin: ammonia =1.0: 4.0) of an ammonia water solution with the mass percentage of 60.0wt% are simultaneously pumped into a microchannel reactor through a metering pump, the flow rate of the cyanhydrin in a microchannel is 10.0g/min, the flow rate of the ammonia water solution in the microchannel is 6.81g/min, the reaction temperature is controlled to be 120 ℃, the pressure is controlled to be 1.5MPa, the retention time is 3min (namely the time of a reaction liquid flowing through the microchannel), the effluent liquid is 279.7671g of a clear, colorless and transparent 2-amino-phenylacetonitrile aqueous solution (cyanamide for short), wherein the content of the 2-amino-phenylacetonitrile is 47.24wt%, and the yield of the 2-amino-phenylacetonitrile is more than 99.9% (calculated by the cyanhydrin).
The 2-amino-phenylacetonitrile ammonia water solution (cyanamide) obtained above and 195.0214g of potassium carbonate mother liquor containing potassium phenylglycinate obtained in example 1 (wherein the potassium ion content is 30wt%, and the phenylglycine content is 19.36 wt%) and 34.5 g of additional 50wt% potassium carbonate aqueous solution ((cyanohydrin + phenylglycine): potassium ion =1.0: 1.5) were simultaneously pumped into a microchannel reactor through a metering pump, the flow rate of the 2-amino-phenylacetonitrile ammonia water solution in the microchannel was 7.0g/min, the flow rate of the potassium carbonate aqueous solution in the microchannel was 5.74g/min, the reaction temperature was controlled at 170 ℃, the pressure was 2.5MPa, the residence time was 30min (i.e., the time during which the reaction solution flowed through the microchannel), the liquid was a clear pale yellow transparent liquid, which was deaminated to obtain 441.2885g of potassium phenylglycinate aqueous solution containing potassium carbonate, wherein the mass percent of phenylglycine is 42.82wt%, the mass percent of potassium ions is 15.47wt%, and the yield of phenylglycine is more than 99.9%. The obtained hydrolysate was diluted with water until the potassium ion content was 8.5wt% and the phenylglycine content was 23.53wt%, and 803.1451g of the hydrolysate was obtained after dilution.
And (2) introducing carbon dioxide gas into the obtained hydrolysate, wherein the pressure of the introduced carbon dioxide gas is 0.2MPa, the neutralization temperature is 20 ℃, the stirring speed is 120r/min, the end point pH of the carbon dioxide gas is 8.0, filtering out solids, washing with water, and drying to obtain 144.6075g of phenylglycine product, wherein the main content of the phenylglycine product is 98wt%, the product is powdery, a crystalline DL-phenylglycine product is obtained through recrystallization, the purity of the DL-phenylglycine product reaches more than 99.5wt%, and the recrystallization mother liquor is recycled. The filtrate is potassium bicarbonate aqueous solution containing phenylglycine, the mass of the filtrate is 708.5018g, wherein the mass percentage of potassium ions is 9.63wt%, the mass percentage of phenylglycine is 6.67wt%, the filtrate is heated, decarburized and concentrated to 30.0wt% of potassium ions, so that 227.4291g of potassium carbonate aqueous solution containing potassium phenylglycine is obtained, wherein the mass percentage of phenylglycine is 20.78wt%, and the aqueous solution is circulated to the next hydantoin hydrolysis.
Example 3
Preparation of DL-phenylglycine (acidification with sulfuric acid):
166.4338 g (1.0 mol) of a 2-hydroxy-benzyl cyanide aqueous solution (cyanohydrin) with the mass percent of 80wt% and 113.3333 g (cyanohydrin: ammonia =1.0: 4.0) of an ammonia water solution with the mass percent of 60.0wt% are simultaneously pumped into a microchannel reactor through a metering pump, the flow rate of the cyanohydrin in a microchannel is 10.0g/min, the flow rate of the ammonia water solution in the microchannel is 6.81g/min, the reaction temperature is controlled to be 120 ℃, the pressure is controlled to be 1.5MPa, the retention time is 3min (namely the time for the reaction liquid to flow through the microchannel), and the effluent liquid is 279.7671g of a clear, colorless and transparent 2-amino-benzyl cyanide aqueous solution (cyanamide for short), wherein the content of the 2-amino-benzyl cyanide is 47.24wt%, and the yield of the 2-amino-benzyl cyanide is more than 99.9% (calculated by the cyanohydrin).
The obtained 2-amino-phenylacetonitrile ammonia water solution (cyanamide) and 96.0 g of sodium hydroxide water solution with the mass percentage of 50wt% (cyanhydrin: sodium ion =1.0: 1.2) are pumped into a micro-channel reactor through a metering pump at the same time, the flow rate of the 2-amino-benzyl cyanide ammonia water solution in the micro-channel is 7.0g/min, the flow rate of the sodium hydroxide water solution in the micro-channel is 2.4g/min, the reaction temperature is controlled at 180 ℃, the pressure is 2.5MPa, the retention time is 30min (namely the time that the reaction liquid flows through the micro-channel), the effluent liquid is a clear light yellow transparent liquid, the liquid is deaminated to obtain 307.7671g of sodium phenylglycinate aqueous solution containing a small amount of sodium hydroxide, wherein the mass percent of phenylglycine is 49.12 percent, the mass percent of sodium ions is 8.97 percent, and the yield of phenylglycine is more than 99.9 percent.
And adding 70wt% of sulfuric acid into the obtained hydrolysate for acidification and neutralization, acidifying until the pH value is 5.5 to serve as a reaction end point, then cooling to 30 ℃, stirring for crystallization, performing suction filtration, water washing and drying to obtain 147.3649g of phenylglycine product, wherein the main content of the phenylglycine product is 99.5wt%, and the yield of the phenylglycine product is 97% (calculated on cyanohydrin). 330.150g of sodium sulfate filtrate is obtained, wherein the content of sodium sulfate is 25.81wt%, the content of phenylglycine is 1.37wt%, the mother liquor is subjected to high-temperature concentration crystallization and centrifugation to obtain sodium sulfate solid, and the centrifugate is circulated to the next step of phenylglycine acidification crystallization. Therefore, the yield of phenylglycine can reach more than 99 percent after multiple cycles.
Example 4
Preparation of DL-phenylglycine (acidification with hydrochloric acid):
166.4338 g (1.0 mol) of a 2-hydroxy-phenylacetonitrile aqueous solution (cyanhydrin) with the mass percentage of 80wt% and 113.3333 g (cyanhydrin: ammonia =1.0: 4.0) of an ammonia water solution with the mass percentage of 60.0wt% are simultaneously pumped into a microchannel reactor through a metering pump, the flow rate of the cyanhydrin in a microchannel is 10.0g/min, the flow rate of the ammonia water solution in the microchannel is 6.81g/min, the reaction temperature is controlled to be 120 ℃, the pressure is controlled to be 1.5MPa, the retention time is 3min (namely the time of a reaction liquid flowing through the microchannel), the effluent liquid is 279.7671g of a clear, colorless and transparent 2-amino-phenylacetonitrile aqueous solution (cyanamide for short), wherein the content of the 2-amino-phenylacetonitrile is 47.24wt%, and the yield of the 2-amino-phenylacetonitrile is more than 99.9% (calculated by the cyanhydrin).
The obtained 2-amino-phenylacetonitrile ammonia water solution (cyanamide) and 96.0 g of sodium hydroxide water solution with the mass percentage of 50wt% (cyanhydrin: sodium ion =1.0: 1.2) are pumped into a micro-channel reactor through a metering pump at the same time, the flow rate of the 2-amino-benzyl cyanide ammonia water solution in the micro-channel is 7.0g/min, the flow rate of the sodium hydroxide water solution in the micro-channel is 2.4g/min, the reaction temperature is controlled at 180 ℃, the pressure is 2.5MPa, the retention time is 30min (namely the time for the reaction liquid to flow through the micro-channel), the effluent liquid is a clear light yellow transparent liquid, the liquid is deaminated to obtain 307.7671g of sodium phenylglycinate aqueous solution containing a small amount of sodium hydroxide, wherein the mass percent of phenylglycine is 49.12 percent, the mass percent of sodium ions is 8.97 percent, and the yield of phenylglycine is more than 99.9 percent.
Adding concentrated hydrochloric acid into the obtained hydrolysate for acidification and neutralization, acidifying until the pH value is 5.6 as a reaction end point, then cooling to 15 ℃, stirring and crystallizing, performing suction filtration, washing with water, and drying to obtain 148.7347g of phenylglycine product, wherein the main content is 99.6wt%, and the yield is 98% (calculated on cyanohydrin). 350.150g of sodium chloride filtrate is obtained, wherein the content of sodium chloride is 20.0wt%, the content of phenylglycine is 0.86wt%, sodium chloride solid is obtained by high-temperature concentration, crystallization and centrifugation of the mother liquor, and the centrifugate is circulated to the next step of phenylglycine acidification and crystallization. Therefore, the yield of phenylglycine can reach more than 99 percent after multiple cycles.
Example 5
Preparation of DL-p-chlorophenylglycine (carbon dioxide acidification):
186.2133 g (1.0 mol) of 2-hydroxy-p-chlorobenzene acetonitrile water solution (cyanohydrin) with the mass percentage of 90wt% is preheated to 45 ℃, then 99.1667 g of ammonia water solution with the mass percentage of 60.0wt% (cyanhydrin: ammonia =1.0: 3.5) are pumped into the micro-channel reactor through a metering pump, the flow rate of the cyanhydrin in the micro-channel is 10.0g/min, the flow rate of the ammonia water solution in the micro-channel is 5.33g/min, the temperature of the reaction is controlled at 130 ℃, the pressure is 1.6MPa, the retention time is 2min (namely the time of the reaction liquid flowing through the micro-channel), the effluent liquid is 285.380g of clear, colorless and transparent ammonia water solution (cyanamide for short) of 2-amino-p-chlorobenzonitrile, wherein the content of the 2-amino-p-chlorobenzene acetonitrile is 58.38wt%, and the yield of the 2-amino-p-chlorobenzene acetonitrile is more than 99.9% (calculated by cyanohydrin).
The aqueous ammonia solution (cyanamide) of 2-amino-p-chlorophenylacetonitrile obtained above and 460.0 g of potassium carbonate aqueous solution with the mass percentage of 30wt% (cyanohydrin: potassium ion =1.0: 2.0) were simultaneously pumped into a microchannel reactor by a metering pump, the flow rate of the 2-amino-p-chlorobenzonitrile ammonia water solution in the micro-channel is 7.0g/min, the flow rate of the potassium carbonate water solution in the micro-channel is 11.28g/min, the reaction temperature is controlled at 180 ℃, the pressure is 2.6MPa, the retention time is 15min (namely the time that the reaction liquid flows through the micro-channel), the effluent liquid is clear light yellow transparent liquid, the liquid is deaminated to obtain 690.380g of potassium p-chlorophenyl glycinate water solution containing potassium carbonate, wherein the mass percent of the p-chlorobenzene glycine is 26.88 percent, the mass percent of the potassium ions is 11.30 percent, and the yield of the p-chlorobenzene glycine is more than 99.9 percent. The obtained hydrolysate was diluted with water until the potassium ion content was 8.5wt% and the p-chlorophenylglycine content was 20.22wt%, and 917.7993g of hydrolysate was obtained after dilution.
And (2) introducing carbon dioxide gas into the obtained hydrolysate, wherein the pressure of the introduced carbon dioxide gas is 0.2MPa, the neutralization temperature is 20 ℃, the stirring speed is 120r/min, the end point pH of the carbon dioxide gas introduction neutralization is 8.0, filtering out solids, washing with water, drying to obtain 140.6121g of p-chlorophenylglycine product, wherein the main content is 99wt%, the product is powdery, and the recrystallization operation is carried out to obtain a crystalline DL-p-chlorophenylglycine product, the purity of the product reaches more than 99.5wt%, and the recrystallization mother liquor is recycled. The filtrate is a potassium bicarbonate aqueous solution containing p-chlorophenylglycine, the mass of the filtrate is 600.2523g, wherein the mass percentage of potassium ions is 12.99wt%, the mass percentage of the p-chlorophenylglycine is 7.73wt%, the filtrate is heated, decarburized and concentrated to 30.0wt% of the mass percentage of potassium ions to obtain 259.9092g of potassium carbonate aqueous solution containing the potassium p-chlorophenylglycine, wherein the mass percentage of the p-chlorophenylglycine is 17.85wt%, and the aqueous solution is circulated to the next hydantoin hydrolysis.
Example 6
Preparation of DL-o-chlorophenylglycine (carbon dioxide acidification):
186.2133 g (1.0 mol) of 2-hydroxy-o-chlorobenzene acetonitrile water solution (cyanohydrin) with the mass percentage of 90wt% is preheated to 45 ℃, then 99.1667 g of ammonia water solution with the mass percentage of 60.0wt% (cyanhydrin: ammonia =1.0: 3.5) are pumped into the micro-channel reactor through a metering pump, the flow rate of the cyanhydrin in the micro-channel is 10.0g/min, the flow rate of the ammonia water solution in the micro-channel is 5.33g/min, the temperature of the reaction is controlled at 130 ℃, the pressure is 1.6MPa, the retention time is 2min (namely the time of the reaction liquid flowing through the micro-channel), the effluent liquid is 285.380g of clear, colorless and transparent ammonia water solution (cyanamide for short) of 2-amino-o-chlorobenzene acetonitrile, wherein the content of the 2-amino-p-chlorobenzene acetonitrile is 58.38wt%, and the yield of the 2-amino-o-chlorobenzene acetonitrile is more than 99.9% (calculated by cyanohydrin).
The obtained ammonia water solution (cyanamide) of 2-amino-o-chlorobenzonitrile and 460.0 g of potassium carbonate water solution with the mass percentage of 30wt% (cyanhydrin: potassium ion =1.0: 2.0) are simultaneously pumped into a micro-channel reactor through a metering pump, the flow rate of the 2-amino-o-chlorobenzonitrile ammonia water solution in the micro-channel is 7.0g/min, the flow rate of the potassium carbonate water solution in the micro-channel is 11.28g/min, the reaction temperature is controlled at 180 ℃, the pressure is 2.6MPa, the retention time is 15min (namely the time that the reaction liquid flows through the micro-channel), the effluent liquid is clear light yellow transparent liquid, the liquid is deaminated to obtain 690.380g of potassium carbonate-containing o-chlorobenzene glycine potassium water solution, wherein the mass percent of the o-chlorophenylglycine is 26.88 percent, the mass percent of the potassium ions is 11.30 percent, and the yield of the o-chlorophenylglycine is more than 99.9 percent. The obtained hydrolysate was diluted with water until the potassium ion content was 8.5wt% and the o-chlorophenylglycine content was 20.22wt%, and 917.7993g of hydrolysate was obtained after dilution.
And (2) introducing carbon dioxide gas into the obtained hydrolysate, wherein the pressure of the introduced carbon dioxide gas is 0.2MPa, the neutralization temperature is 20 ℃, the stirring speed is 120r/min, the end point pH of the carbon dioxide gas introduction neutralization is 8.0, filtering out solids, washing with water, drying to obtain 140.6121g of an o-chlorobenzene glycine product, wherein the main content is 99wt%, the product is powdery, a crystalline DL-o-chlorobenzene glycine product is obtained through recrystallization, the purity is more than 99.5wt%, and the recrystallization mother liquor is recycled. The filtrate is a potassium bicarbonate aqueous solution containing o-chlorophenylglycine, the mass of the filtrate is 600.2523g, wherein the mass percentage of potassium ions is 12.99wt%, the mass percentage of o-chlorophenylglycine is 7.73wt%, the filtrate is heated, decarburized and concentrated to 30.0wt% of potassium ions, so that 259.9092g of potassium carbonate aqueous solution containing o-chlorophenylglycine potassium is obtained, wherein the mass percentage of o-chlorophenylglycine is 17.85wt%, and the aqueous solution is circulated to the next hydantoin hydrolysis.
Example 7
Preparation of DL-m-chlorophenylglycine (acidification with carbon dioxide):
186.2133 g (1.0 mol) of 2-hydroxy-m-chlorobenzene acetonitrile water solution (cyanohydrin) with the mass percentage of 90wt% is preheated to 45 ℃, then 99.1667 g of ammonia water solution with the mass percentage of 60.0wt% (cyanhydrin: ammonia =1.0: 3.5) are pumped into the micro-channel reactor through a metering pump, the flow rate of the cyanhydrin in the micro-channel is 10.0g/min, the flow rate of the ammonia water solution in the micro-channel is 5.33g/min, the temperature of the reaction is controlled at 130 ℃, the pressure is 1.6MPa, the retention time is 2min (namely the time of the reaction liquid flowing through the micro-channel), the effluent liquid is 285.380g of clear, colorless and transparent ammonia water solution (cyanamide for short) of 2-amino-m-chlorobenzonitrile, wherein the content of the 2-amino-p-chlorobenzene acetonitrile is 58.38wt%, and the yield of the 2-amino-m-chlorobenzene acetonitrile is more than 99.9% (calculated by cyanohydrin).
The obtained ammonia water solution (cyanamide) of 2-amino-m-chlorobenzene acetonitrile and 460.0 g of potassium carbonate water solution with the mass percentage of 30wt% (cyanalcohol: potassium ion =1.0: 2.0) are simultaneously pumped into a micro-channel reactor through a metering pump, the flow rate of the 2-amino-m-chlorobenzene acetonitrile ammonia water solution in the micro-channel is 7.0g/min, the flow rate of the potassium carbonate water solution in the micro-channel is 11.28g/min, the reaction temperature is controlled to be 180 ℃, the pressure is 2.6MPa, the retention time is 15min (namely the time for the reaction liquid to flow through the micro-channel), the effluent liquid is clear light yellow transparent liquid, the liquid is deaminated to obtain 690.380g of potassium m-chlorobenzene glycinate water solution containing potassium carbonate, the mass percentage of the m-chlorobenzene glycine is 26.88wt%, the mass percentage of the potassium ions is 11.30wt%, and the yield of the m-chlorobenzene glycine is more than 99.9%. The obtained hydrolysate was diluted with water until the potassium ion content was 8.5wt% and the m-chlorophenyl glycine content was 20.22wt%, and 917.7993g of hydrolysate was obtained after dilution.
And (2) introducing carbon dioxide gas into the obtained hydrolysate, wherein the pressure of the introduced carbon dioxide gas is 0.2MPa, the neutralization temperature is 20 ℃, the stirring speed is 120r/min, the end point pH of the carbon dioxide gas is 8.0, filtering out solids, washing with water, and drying to obtain 140.6121g of m-chlorobenzene glycine product, wherein the main content is 99wt%, the product is powdery, and the crystalline DL-m-chlorobenzene glycine product is obtained through recrystallization, the purity is more than 99.5wt%, and the recrystallization mother liquor is recycled. The filtrate is potassium bicarbonate aqueous solution containing m-chlorobenzene glycine, the mass of the filtrate is 600.2523g, wherein the mass percentage of potassium ions is 12.99wt%, the mass percentage of m-chlorobenzene glycine is 7.73wt%, the filtrate is heated, decarburized and concentrated to the mass percentage of potassium ions of 30.0wt% to obtain 259.9092g of potassium carbonate aqueous solution containing m-chlorobenzene glycine, the mass percentage of m-chlorobenzene glycine is 17.85wt%, and the aqueous solution is circulated to the next hydantoin hydrolysis.
Example 8
Preparation of DL-p-chlorophenyl glycine (acidification with sulfuric acid):
186.2133 g (1.0 mol) of 2-hydroxy-p-chlorobenzene acetonitrile water solution (cyanohydrin) with the mass percentage of 90wt% is preheated to 45 ℃, then 99.1667 g of ammonia water solution with the mass percentage of 60.0wt% (cyanhydrin: ammonia =1.0: 3.5) are pumped into the micro-channel reactor through a metering pump, the flow rate of the cyanhydrin in the micro-channel is 10.0g/min, the flow rate of the ammonia water solution in the micro-channel is 5.33g/min, the temperature of the reaction is controlled at 130 ℃, the pressure is 1.6MPa, the retention time is 2min (namely the time of the reaction liquid flowing through the micro-channel), the effluent liquid is 285.380g of clear, colorless and transparent ammonia water solution (cyanamide for short) of 2-amino-p-chlorobenzonitrile, wherein the content of the 2-amino-p-chlorobenzene acetonitrile is 58.38wt%, and the yield of the 2-amino-p-chlorobenzene acetonitrile is more than 99.9% (calculated by cyanohydrin).
The obtained 2-amino-p-chlorobenzonitrile ammonia water solution (cyanamide) and 96.0 g of sodium hydroxide aqueous solution with the mass percentage of 50wt% (cyanhydrin: sodium ion =1.0: 1.2) are pumped into a micro-channel reactor through a metering pump at the same time, the flow rate of the 2-amino-p-chlorobenzonitrile ammonia water solution in the micro-channel is 7.0g/min, the flow rate of the sodium hydroxide water solution in the micro-channel is 2.4g/min, the reaction temperature is controlled at 170 ℃, the pressure is 2.5MPa, the retention time is 20min (namely the time of the reaction liquid flowing through the micro-channel), the effluent liquid is clear light yellow transparent liquid, the liquid is deaminated to obtain 330.380g of sodium p-chlorophenyl glycinate aqueous solution containing a small amount of sodium hydroxide, wherein the mass percent of the p-chlorobenzene glycine is 56.18 percent, the mass percent of the sodium ions is 8.35 percent, and the yield of the p-chlorobenzene glycine is more than 99.9 percent.
And adding 40wt% of sulfuric acid into the obtained hydrolysate for acidification and neutralization, acidifying until the pH value is 5.5 to serve as a reaction end point, then cooling to 30 ℃, stirring and crystallizing, performing suction filtration, water washing and drying to obtain 182.6263g of p-chlorophenylglycine product, wherein the main content is 99.6wt%, and the yield is 98% (calculated on cyanohydrin). 430.150g of sodium sulfate filtrate is obtained, wherein the content of sodium sulfate is 19.81wt%, the content of p-chlorophenyl glycine is 0.86wt%, sodium sulfate solid is obtained by high-temperature concentration, crystallization and centrifugation of the mother liquor, and the centrifugate is circulated to the next p-chlorophenyl glycine acidification and crystallization step. Therefore, after multiple cycles, the yield of the p-chlorophenylglycine reaches more than 99 percent.
Example 9
Preparation of DL-p-fluorophenylglycine (carbon dioxide acidification):
215.9114 g (1.0 mol) of a 2-hydroxy-p-fluorophenylacetonitrile aqueous solution (cyanohydrin) with the mass percentage of 70wt% and 113.3333 g (cyanohydrin: ammonia =1.0: 4.0) of an ammonia aqueous solution with the mass percentage of 60.0wt% are pumped into a microchannel reactor through a metering pump at the same time, the flow rate of the cyanohydrin in a microchannel is 10.0g/min, the flow rate of the ammonia aqueous solution in the microchannel is 5.25g/min, the reaction temperature is controlled to be 100 ℃, the pressure is controlled to be 1.0MPa, the retention time is 6min (namely the time for the reaction liquid to flow through the microchannel), and the effluent liquid is 329.2447g of a clear, colorless and transparent 2-amino-p-fluorophenylacetonitrile aqueous solution (cyanamide for short), wherein the content of the 2-amino-p-fluorophenylacetonitrile is 45.6wt%, and the yield of the 2-amino-p-fluorophenylacetonitrile is more than 99.9% (calculated by the cyanohydrin).
The 2-amino-p-fluorophenylacetonitrile ammonia solution (cyanamide) obtained above and 207 g of potassium carbonate aqueous solution (cyanhydrin: potassium ion =1.0: 1.5) with a mass percentage of 50wt% are simultaneously pumped into a microchannel reactor through a metering pump, the flow rate of the 2-amino-p-fluorophenylacetonitrile ammonia water solution in the micro-channel is 7.0g/min, the flow rate of the potassium carbonate water solution in the micro-channel is 4.4g/min, the reaction temperature is controlled at 180 ℃, the pressure is 2.5MPa, the retention time is 40min (namely the time for the reaction liquid to flow through the micro-channel), the effluent liquid is clear light yellow transparent liquid, the liquid is deaminated to obtain 468.2447g of potassium p-fluorophenyl glycine potassium water solution containing potassium carbonate, wherein the mass percent of the p-fluorophenyl glycine is 36.13wt%, the mass percent of the potassium ions is 12.50wt%, and the yield of the p-fluorophenyl glycine is more than 99.9%. The obtained hydrolysate was diluted with water until the potassium ion content was 8.5wt% and the p-fluorophenylglycine content was 24.57wt%, and 688.5951g of the hydrolysate was obtained after dilution.
And introducing carbon dioxide gas into the obtained hydrolysate, wherein the pressure of the introduced carbon dioxide gas is 0.2MPa, the neutralization temperature is 20 ℃, the stirring speed is 120r/min, the end point pH of the carbon dioxide gas is 8.0, performing suction filtration to obtain solid, washing with water, and drying to obtain 138.0841g of p-fluorophenylglycine product, wherein the main content is 98wt%, the product is powdery, and the crystalline DL-p-fluorophenylglycine product is obtained through recrystallization operation, wherein the purity is more than 99.5wt%, and the recrystallization mother liquor is recycled. The filtrate is a potassium bicarbonate aqueous solution containing p-fluorophenylglycine, the mass of the filtrate is 600.5018g, wherein the mass percentage of potassium ions is 9.74wt%, the mass percentage of p-fluorophenylglycine is 5.63wt%, the filtrate is heated, decarburized and concentrated to 30.0wt% of the mass percentage of potassium ions, so that 194.9629g of potassium carbonate aqueous solution containing the potassium p-fluorophenylglycine is obtained, wherein the mass percentage of p-fluorophenylglycine is 17.34wt%, and the aqueous solution is circulated to the next hydantoin hydrolysis.
Example 10
Preparation of DL-o-fluorophenylglycine (carbon dioxide acidification):
215.9114 g (1.0 mol) of a 2-hydroxy-o-fluorobenzonitrile aqueous solution (cyanohydrin) with the mass percentage of 70wt% and 113.3333 g (cyanohydrin: ammonia =1.0: 4.0) of an ammonia water solution with the mass percentage of 60.0wt% are simultaneously pumped into a microchannel reactor through a metering pump, the flow rate of the cyanohydrin in a microchannel is 10.0g/min, the flow rate of the ammonia water solution in the microchannel is 5.25g/min, the reaction temperature is controlled to be 100 ℃, the pressure is controlled to be 1.0MPa, the retention time is 6min (namely the time of a reaction liquid flowing through the microchannel), and the effluent liquid is 329.2447g of a clear, colorless and transparent 2-amino-o-fluorobenzonitrile aqueous solution (cyanamide for short), wherein the content of the 2-amino-o-fluorobenzonitrile is 45.6wt%, and the yield of the 2-amino-o-fluorobenzonitrile is more than 99.9% (calculated by the cyanohydrin).
The 2-amino-o-fluorophenylacetonitrile aqueous ammonia solution (cyanamide) obtained above and 207 g of a potassium carbonate aqueous solution (cyanhydrin: potassium ion =1.0: 1.5) with a mass percentage of 50wt% were simultaneously pumped into a microchannel reactor via a metering pump, the flow rate of the 2-amino-o-fluorobenzonitrile ammonia water solution in the micro-channel is 7.0g/min, the flow rate of the potassium carbonate water solution in the micro-channel is 4.4g/min, the reaction temperature is controlled to be 180 ℃, the pressure is controlled to be 2.5MPa, the retention time is 40min (namely the time that the reaction liquid flows through the micro-channel), the effluent liquid is clear light yellow transparent liquid, the liquid is deaminated to obtain 468.2447g of potassium o-fluorophenyl glycine potassium water solution containing potassium carbonate, wherein the mass percent of the o-fluorophenyl glycine is 36.13wt%, the mass percent of the potassium ions is 12.50wt%, and the yield of the o-fluorophenyl glycine is more than 99.9%. The obtained hydrolysate was diluted with water until the potassium ion content was 8.5wt% and the o-fluorophenylglycine content was 24.57wt%, and 688.5951g of the hydrolysate was obtained after dilution.
And introducing carbon dioxide gas into the obtained hydrolysate, wherein the pressure of the introduced carbon dioxide gas is 0.2MPa, the neutralization temperature is 20 ℃, the stirring speed is 120r/min, the end point pH of the carbon dioxide gas is 8.0, performing suction filtration to obtain solid, washing with water, and drying to obtain 138.0841g of o-fluorophenylglycine product, wherein the main content is 98wt%, the product is powdery, a crystalline DL-o-fluorophenylglycine product is obtained through recrystallization, the purity is more than 99.5wt%, and the recrystallization mother liquor is recycled. The filtrate is a potassium bicarbonate aqueous solution containing p-fluorophenyl glycine, the mass of the filtrate is 600.5018g, wherein the mass percentage of potassium ions is 9.74wt%, the mass percentage of o-fluorophenyl glycine is 5.63wt%, the filtrate is heated, decarburized and concentrated to 30.0wt% of the mass percentage of potassium ions, so that 194.9629g of potassium carbonate aqueous solution containing o-fluorophenyl glycine potassium is obtained, wherein the mass percentage of o-fluorophenyl glycine is 17.34wt%, and the aqueous solution is circulated to the next hydantoin hydrolysis.
In conclusion, the microchannel reactor is adopted, so that the preparation and alkaline hydrolysis time of hydantoin is greatly shortened, the reaction is accelerated, the thermal hydrolysis polymerization of cyanohydrin is reduced, no by-product is generated, the generation of salt-containing wastewater is reduced, the product yield is high, the microchannel reactor is clean and environment-friendly, and the production cost is reduced. In the embodiment, a Germany IMM microchannel reactor (50-300 mu m) is used as an experimental platform, and the mass and heat transfer speed of the microreactor is high, so that the microchannel reactor is adopted, the reaction materials are fully mixed, the collision among molecules is greatly increased, the reaction time of the 2-hydroxy-phenylacetonitrile and the analogues thereof with ammonia is greatly shortened, and the problems that the 2-hydroxy-phenylacetonitrile and the analogues thereof are easy to ammonify, thermally polymerize and decompose and generate a byproduct phenylglycine dinitrile are solved; the problems that in the prior art, hydrolysis cannot be thorough, a large amount of acetone is needed, more byproducts are generated, the reaction rate is low, colored impurities are generated, the reaction is insufficient, economic and economic properties are not achieved, resource waste is caused, and the like are solved.
The foregoing embodiments are merely illustrative of the principles and utilities of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or change the above-mentioned embodiments without departing from the spirit and scope of the present invention. Accordingly, it is intended that all equivalent modifications or changes which can be made by those skilled in the art without departing from the spirit and technical spirit of the present invention be covered by the claims of the present invention.
Claims (8)
1. A method for continuously and rapidly preparing DL-phenylglycine and analogues thereof by a cyanohydrin method is characterized by comprising the following steps: (1) ammoniation reaction: adding 2-hydroxy-phenylacetonitrile and analogues thereof and ammonia water into a microchannel reactor for reaction, controlling the reaction temperature to be 90-170 ℃, the pressure to be 0.8-2.0 MPa, the feeding molar ratio of ammonia to 2-hydroxy-phenylacetonitrile and analogues thereof to be 2.0-10: 1, and the residence time of reactants in the microchannel to be 2-8 min to obtain 2-amino-phenylacetonitrile and analogue water solution thereof; (2) alkaline hydrolysis reaction: adding cyanamide obtained in the step (1) and alkali into a microchannel reactor for reaction, controlling the reaction temperature to be 120-200 ℃, the pressure to be 1.0-3.0 MPa, and the retention time of reactants in the microchannel to be 10-60 min to obtain DL-phenylglycine and analogues thereof; the 2-hydroxy-benzyl cyanide and the analogues thereof are referred to as cyanohydrin for short, and the 2-amino-benzyl cyanide and the analogues thereof are referred to as cyanamide for short; the DL-phenylglycine and the analogues thereof are selected from at least one of DL-phenylglycine, DL-o-chlorophenylglycine, DL-m-chlorophenylglycine, DL-p-fluorophenylglycine, DL-o-fluorophenylglycine and DL-m-fluorophenylglycine.
2. The method for continuously and rapidly preparing DL-phenylglycine and its analogues according to claim 1, wherein: in the step (1), the mass percentage of ammonia is 20-99.9 wt%, the rest is water, the mass percentage of 2-hydroxy-phenylacetonitrile and analogues thereof is 70-99.0 wt%, and the feeding molar ratio of ammonia to 2-hydroxy-phenylacetonitrile and analogues thereof is 2.0-10: 1.
3. the method for continuously and rapidly preparing DL-phenylglycine and its analogues according to the cyanohydrin process of claim 1, wherein: in the step (2), the temperature of the hydrolysis reaction is controlled to be 120-200 ℃, the pressure of the hydrolysis reaction is controlled to be 1.0-2.5 MPa, and the residence time of the hydrolysis reactant in the microchannel is 10-40 min.
4. The method for continuously and rapidly preparing DL-phenylglycine and its analogues according to claim 1, wherein: the alkali in the step (2) is at least one selected from sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, calcium hydroxide and barium hydroxide aqueous solution, and the mass percentage of the alkali liquor is 30wt% -50 wt%.
5. The method for continuously and rapidly preparing DL-phenylglycine and its analogues according to claim 4, wherein: in the step (2), the charging molar ratio of sodium ions or potassium ions in the alkali to the 2-hydroxy-phenylacetonitrile and the analogues thereof is 1.0-2.0: 1.0.
6. The method for continuously and rapidly preparing DL-phenylglycine and its analogues according to claim 1, wherein: and (3) after stripping and deaminating the reaction solution obtained by the alkaline hydrolysis reaction, acidifying to obtain DL-phenylglycine and analogues thereof, wherein the acidifying reagent is at least one of sulfuric acid, phosphoric acid, hydrochloric acid, nitric acid, carbonic acid and carbon dioxide.
7. The method for continuously and rapidly preparing DL-phenylglycine and its analogues according to claim 6, wherein: the crystallization mother liquor after acidification by the acidifying reagent carbon dioxide is heated for decarburization to obtain a potassium carbonate aqueous solution containing DL-phenylglycinate and analogues thereof, and the potassium carbonate aqueous solution is returned to hydrolysis of 2-amino-phenylacetonitrile and analogues thereof.
8. The method for continuously and rapidly preparing DL-phenylglycine and its analogues according to claim 7, wherein: the feeding molar ratio of the potassium ions to the (2-hydroxy-benzyl cyanide and the analogues thereof plus the phenylglycine and the analogues thereof) is 1.2-2.0: 1.0, the reaction temperature is controlled to be 120-200 ℃, the pressure is controlled to be 1.0-2.5 MPa, and the residence time of the reactants in the microchannel is 10-40 min.
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| 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 |
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| 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 |
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