CN115745828A - Method for producing phenylamide - Google Patents
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- CN115745828A CN115745828A CN202211390903.6A CN202211390903A CN115745828A CN 115745828 A CN115745828 A CN 115745828A CN 202211390903 A CN202211390903 A CN 202211390903A CN 115745828 A CN115745828 A CN 115745828A
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- 238000004519 manufacturing process Methods 0.000 title claims abstract description 45
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 title claims abstract description 17
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 116
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 58
- 238000005406 washing Methods 0.000 claims abstract description 54
- 239000006227 byproduct Substances 0.000 claims abstract description 44
- 239000000243 solution Substances 0.000 claims abstract description 43
- UNFGQCCHVMMMRF-UHFFFAOYSA-N 2-phenylbutanamide Chemical compound CCC(C(N)=O)C1=CC=CC=C1 UNFGQCCHVMMMRF-UHFFFAOYSA-N 0.000 claims abstract description 41
- 239000007788 liquid Substances 0.000 claims abstract description 39
- 238000000034 method Methods 0.000 claims abstract description 33
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 claims abstract description 29
- 229960002695 phenobarbital Drugs 0.000 claims abstract description 28
- 239000012043 crude product Substances 0.000 claims abstract description 26
- 239000007864 aqueous solution Substances 0.000 claims abstract description 25
- 238000000926 separation method Methods 0.000 claims abstract description 23
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 claims abstract description 21
- 238000006243 chemical reaction Methods 0.000 claims abstract description 19
- 239000007787 solid Substances 0.000 claims abstract description 18
- LMFLGETWXFOVMQ-UHFFFAOYSA-N diethyl 2-(2-phenylethyl)propanedioate Chemical compound CCOC(=O)C(C(=O)OCC)CCC1=CC=CC=C1 LMFLGETWXFOVMQ-UHFFFAOYSA-N 0.000 claims abstract description 17
- 239000000047 product Substances 0.000 claims abstract description 17
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000004202 carbamide Substances 0.000 claims abstract description 12
- 238000006555 catalytic reaction Methods 0.000 claims abstract description 12
- 229910052708 sodium Inorganic materials 0.000 claims abstract description 12
- 239000011734 sodium Substances 0.000 claims abstract description 12
- -1 sodium alkoxide Chemical class 0.000 claims abstract description 12
- 238000001816 cooling Methods 0.000 claims abstract description 9
- 238000001035 drying Methods 0.000 claims abstract description 9
- 230000008569 process Effects 0.000 claims description 20
- 239000000126 substance Substances 0.000 claims description 18
- 238000002425 crystallisation Methods 0.000 claims description 9
- 230000008025 crystallization Effects 0.000 claims description 9
- 239000000706 filtrate Substances 0.000 claims description 9
- 238000001953 recrystallisation Methods 0.000 claims description 9
- 238000001914 filtration Methods 0.000 claims description 8
- 239000008213 purified water Substances 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 3
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical class NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims 9
- 238000002156 mixing Methods 0.000 abstract description 7
- 229940079593 drug Drugs 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 239000000932 sedative agent Substances 0.000 abstract description 2
- 230000001624 sedative effect Effects 0.000 abstract description 2
- 238000003756 stirring Methods 0.000 description 12
- 239000012535 impurity Substances 0.000 description 6
- 239000002699 waste material Substances 0.000 description 4
- FGYDHYCFHBSNPE-UHFFFAOYSA-N diethyl phenylmalonate Chemical compound CCOC(=O)C(C(=O)OCC)C1=CC=CC=C1 FGYDHYCFHBSNPE-UHFFFAOYSA-N 0.000 description 3
- 238000009776 industrial production Methods 0.000 description 3
- PLWALTDUYKDGRF-UHFFFAOYSA-N 2-phenylbutan-1-amine Chemical compound CCC(CN)C1=CC=CC=C1 PLWALTDUYKDGRF-UHFFFAOYSA-N 0.000 description 2
- IZPUPXNVRNBDSW-UHFFFAOYSA-N 2-phenylbutanenitrile Chemical compound CCC(C#N)C1=CC=CC=C1 IZPUPXNVRNBDSW-UHFFFAOYSA-N 0.000 description 2
- QGXMHCMPIAYMGT-UHFFFAOYSA-N 2-phenylbutanoyl chloride Chemical compound CCC(C(Cl)=O)C1=CC=CC=C1 QGXMHCMPIAYMGT-UHFFFAOYSA-N 0.000 description 2
- 206010010904 Convulsion Diseases 0.000 description 2
- 239000001961 anticonvulsive agent Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000000147 hypnotic effect Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000004064 recycling Methods 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 1
- 206010013954 Dysphoria Diseases 0.000 description 1
- 208000034308 Grand mal convulsion Diseases 0.000 description 1
- 206010020741 Hyperpyrexia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010020850 Hyperthyroidism Diseases 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- 208000032140 Sleepiness Diseases 0.000 description 1
- 206010041349 Somnolence Diseases 0.000 description 1
- 206010043376 Tetanus Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 230000003556 anti-epileptic effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 239000012724 barbiturate sedative Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 208000027119 bilirubin metabolic disease Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 229910052949 galena Inorganic materials 0.000 description 1
- 208000036796 hyperbilirubinemia Diseases 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 230000035987 intoxication Effects 0.000 description 1
- 231100000566 intoxication Toxicity 0.000 description 1
- XCAUINMIESBTBL-UHFFFAOYSA-N lead(ii) sulfide Chemical compound [Pb]=S XCAUINMIESBTBL-UHFFFAOYSA-N 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 206010037628 pylorospasm Diseases 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 208000005809 status epilepticus Diseases 0.000 description 1
- 230000003867 tiredness Effects 0.000 description 1
- 208000016255 tiredness Diseases 0.000 description 1
- 230000002618 waking effect Effects 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
A method for producing phenylamide, which belongs to the technical field of sedative drugs. The method is characterized in that: reacting diethyl phenylethylmalonate with urea under the catalysis of sodium alkoxide, adding activated carbon into a system after the reaction is finished, mixing, carrying out solid-liquid separation, concentrating and crystallizing the liquid to obtain a phenobarbital product, wherein the solid is the activated carbon containing a byproduct; fully washing the by-product-containing activated carbon obtained in the step 1) by using an ethanol aqueous solution with the mass concentration of 90-97% and collecting a washing solution, wherein the washing temperature is 45-60 ℃; cooling and crystallizing the washing liquid concentrated solution, carrying out solid-liquid separation, drying and separating the obtained solid to obtain a crude product of the 2-phenylbutyramide; recrystallizing the 2-phenylbutanamide crude product obtained in the step 2) in an ethanol water solution for multiple times to obtain a 2-phenylbutanamide byproduct. The invention realizes the comprehensive utilization of main products and byproducts.
Description
Technical Field
A method for producing phenylamide, which belongs to the technical field of sedative drugs.
Background
5-Ethyl-5-phenyl-2, 4,6- (1H, 3H, 5H) -pyrimidinetrione is phenobarbital, alias luminal, galena, and Flora, and has molecular formula C 8 H 12 N1O 3 Is a barbiturate sedative and hypnotic. Is clinically used for: (1) Sedation, such as anxiety, dysphoria, hyperthyroidism, hypertension, functional nausea, infantile pylorospasm, etc.; (2) Hypnosis, which is occasionally used for intractable insomnia, but has the sequela effects of tiredness, somnolence and the like after waking up; (3) Anticonvulsant is used to treat convulsion caused by central stimulant intoxication or hyperpyrexia, tetanus, encephalitis, cerebral hemorrhage, etc.; (4) Anti-epileptic, can be used for treating grand mal and partial seizure, with quick action, and can also be used for status epilepticus; (5) administration before anesthesia; (6) It can be combined with antipyretic and analgesic to enhance its effect; (7) treating hyperbilirubinemia of newborn.
Diethyl phenylethylmalonate reacts with urea under the catalysis of sodium alkoxide to obtain phenobarbital, and other impurities such as 2-phenylbutanamide and the like are generated due to side reaction. The traditional treatment method of the impurities is to filter and separate the phenobarbital crude product and decolored activated carbon together in the post-treatment process to obtain mixture waste residue. If the 2-phenylbutanamide is not effectively recycled, the environment is polluted, and certain resource waste is caused.
Disclosure of Invention
The technical problem to be solved by the invention is as follows: overcomes the defects of the prior art and provides a method for producing the phenylamide, which realizes the joint production.
The technical scheme adopted by the invention for solving the technical problem is as follows: the method for producing the phenylamide is used for producing the phenobarbital by a traditional process, and is characterized in that:
1) In the production reaction process of the phenobarbital, diethyl phenylmalonate reacts with urea under the catalysis of sodium alkoxide, activated carbon is added into a system after the reaction is completed, the mixture is fully stirred and mixed, solid-liquid separation is carried out, the separated liquid is concentrated and crystallized to prepare a phenobarbital product, and the separated solid is the activated carbon containing a byproduct;
2) Fully washing the by-product-containing activated carbon obtained in the step 1) by using an ethanol aqueous solution with the mass concentration of 90-97% and collecting a washing solution, wherein the washing temperature is 45-60 ℃; cooling and crystallizing the washing liquid concentrated solution, carrying out solid-liquid separation, and then drying and separating the obtained solid to obtain a crude product of 2-phenylbutyramide;
3) Recrystallizing the crude product of 2-phenylbutyramide obtained in the step 2) in an ethanol aqueous solution for multiple times to obtain a 2-phenylbutyramide byproduct.
The invention provides a method for separating and purifying 2-phenylbutanamide as a byproduct while preparing phenobarbital. The related synthetic route of the phenobarbital mainly comprises an alpha-phenylbutyronitrile method, 2-phenylbutyryl chloride and the like, wherein diethyl phenylethylmalonate reacts with urea under the catalysis of sodium alkoxide in the production reaction process of the phenobarbital to generate the 2-phenylbutylamide. The method separates and purifies the 2-phenylbutanamide, realizes the comprehensive utilization of main products and byproducts in production, meets the product quality research and production requirements, utilizes the activated carbon for adsorption and then directly uses the activated carbon for the working procedure, realizes circular economy, reduces the production cost, has stable process, and is suitable for the industrial production requirement.
Preferably, in the method for producing phenylamide, the activated carbon in the step 1) is 20-30% of the mass of the diethyl phenylethyl malonate. The preferable adding amount of the activated carbon can sufficiently adsorb and take out the byproduct 2-phenylbutyramide without causing excessive waste of the activated carbon.
Preferably, in the method for producing phenylamide, the solid-liquid separation in the step 1) is continuous separation by using a horizontal screw centrifuge. The horizontal screw centrifuge is used for continuously separating the adsorbed active carbon, so that the separation efficiency is higher.
Preferably, in the method for producing phenylamide, the mass ratio of the by-product-containing activated carbon in the step 2) to the ethanol aqueous solution with the mass concentration of 90-97% for washing is 1:6 to 8. The preferred mass ratio of the activated carbon to the aqueous ethanol solution for washing ensures that the 2-phenylbutyramide by-produced in the activated carbon can be sufficiently washed out.
In a preferable method for producing the phenylamide, the ethanol aqueous solution with the mass concentration of 90% -97% in the step 2) is divided into three parts according to the mass ratio of 2.8-1.2. The ethanol water solution for washing is proportionally washed for three times, so that the byproduct 2-phenylbutyramide in the activated carbon is more sufficiently washed.
Preferably, in the method for producing phenylamide, the mass concentration of the ethanol aqueous solution in the step 3) is 20-30%. Impurities can be better separated out under the optimal mass concentration, and the impurity removal efficiency of single recrystallization is higher.
In a preferred method for producing phenyl amide, the mass ratio of the crude 2-phenyl butyramide to the aqueous ethanol solution in each recrystallization in step 3) is 1. Impurities can be better separated out under the preferable mass ratio of the crude product to the ethanol water solution, and the impurity removal efficiency of single recrystallization is higher.
Preferably, in the method for producing a phenylamide, the crude 2-phenylbutanamide in step 3) is recrystallized in an aqueous ethanol solution by adding purified water to precipitate insoluble substances, filtering the insoluble substances at room temperature, concentrating the filtrate, and recrystallizing the filtrate. Purified water is added in the recrystallization process to separate out insoluble substances, so that the removal efficiency of the insoluble substances can be accelerated, and the recrystallization times can be reduced.
Preferably, in the above process for producing a phenylamide, the recrystallization temperature in step 3) is 4 to 7 ℃. The crystallization rate at the preferred crystallization temperature is more suitable for the process, and the purity of the obtained by-product is higher.
Preferably, in the above-mentioned method for producing a phenylamide, the washing temperature in the step 2) is 55 ℃ to 57 ℃.
Compared with the prior art, the method for producing the phenylamide has the beneficial effects that: the invention provides a method for separating and purifying 2-phenylbutanamide as a byproduct while preparing phenobarbital. The related synthetic route of the phenobarbital mainly comprises an alpha-phenylbutyronitrile method, 2-phenylbutyryl chloride and the like, wherein diethyl phenylethylmalonate reacts with urea under the catalysis of sodium alkoxide in the production reaction process of the phenobarbital to generate the 2-phenylbutylamide. The invention separates and purifies the 2-phenyl butyramide, realizes the comprehensive utilization of main products and byproducts in production, meets the requirements of product quality research and production, utilizes the activated carbon for adsorption and then directly uses the activated carbon for the working procedure of the invention, realizes circular economy, reduces the production cost, has stable process, and is suitable for the requirements of industrial production. The method has the advantages of simple operation, easy control, high purity of the obtained product, high yield, realization of comprehensive recycling of production waste residues and product quality research and production requirements, direct use of the working procedure for recycling the activated carbon, realization of circular economy, reduction of production cost, stable process and suitability for industrial production requirements.
Detailed Description
It is noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of example embodiments according to the present application. As used herein, the singular forms "a", "an", and "the" are intended to include the plural forms as well, and furthermore, the terms "comprises" and "having", and any variations thereof, are intended to cover a non-exclusive inclusion, such that a process, method, system, article, or apparatus that comprises a list of steps or elements is not necessarily limited to those steps or elements expressly listed, but may include other steps or elements not expressly listed or inherent to such process, method, article, or apparatus.
It should be noted that the embodiments and features of the embodiments in the present application may be combined with each other without conflict.
The invention is further illustrated by the following specific examples, of which example 1 is the best mode of practice.
Example 1
1) Reacting diethyl phenylethylmalonate with urea under the catalysis of sodium alkoxide in the production reaction process of the phenobarbital, and adding activated carbon into a system after the reaction is finished, wherein the activated carbon accounts for 25% of the mass of the diethyl phenylethylmalonate; after fully stirring and mixing, continuously carrying out solid-liquid separation by using a horizontal screw centrifuge, concentrating and crystallizing the separated liquid to obtain a phenobarbital product, wherein the separated solid is activated carbon containing a byproduct;
2) Fully washing the by-product-containing activated carbon obtained in the step 1) by using an ethanol aqueous solution with the mass concentration of 95%, and collecting a washing solution, wherein the mass ratio of the by-product-containing activated carbon to the ethanol aqueous solution for washing is 1:7, washing the activated carbon containing the byproduct in three times, wherein the washing temperature is 55 ℃, and the ethanol aqueous solution is divided into three parts according to the mass ratio of (2); cooling and crystallizing the washing liquid concentrated solution, carrying out solid-liquid separation, drying and separating the obtained solid to obtain a crude product of the 2-phenylbutyramide;
3) Uniformly stirring the crude product of the 2-phenylbutyramide obtained in the step 2) in an ethanol water solution with the mass concentration of 26%, adding purified water to precipitate insoluble substances, filtering at room temperature to remove the insoluble substances, concentrating the filtrate, and recrystallizing at the crystallization temperature of 5-5.5 ℃; wherein the mass ratio of the 2-phenylbutanamide crude product to the ethanol water solution is 1.
Example 2
1) Reacting diethyl phenylethylmalonate with urea under the catalysis of sodium alkoxide in the production reaction process of the phenobarbital, and adding activated carbon into a system after the reaction is finished, wherein the activated carbon accounts for 22% of the mass of the diethyl phenylethylmalonate; after fully stirring and mixing, continuously carrying out solid-liquid separation by using a horizontal screw centrifuge, concentrating and crystallizing the separated liquid to obtain a phenobarbital product, wherein the separated solid is activated carbon containing a byproduct;
2) Fully washing the by-product-containing activated carbon obtained in the step 1) by using an ethanol aqueous solution with the mass concentration of 93%, and collecting a washing solution, wherein the mass ratio of the by-product-containing activated carbon to the ethanol aqueous solution for washing is 1:6.5, washing the activated carbon containing the byproduct for three times, wherein the washing temperature is 56 ℃, and the ethanol aqueous solution is divided into three parts according to the mass ratio of 2.8; cooling and crystallizing the washing liquid concentrated solution, carrying out solid-liquid separation, drying and separating the obtained solid to obtain a crude product of the 2-phenylbutyramide;
3) Uniformly stirring the crude product of the 2-phenylbutyramide obtained in the step 2) in an ethanol water solution with the mass concentration of 22%, adding purified water to precipitate insoluble substances, filtering at room temperature to remove the insoluble substances, concentrating the filtrate, and recrystallizing at the crystallization temperature of 4.5-5 ℃; wherein the mass ratio of the 2-phenylbutanamide crude product to the ethanol aqueous solution is 1.
Example 3
1) Reacting diethyl phenylethylmalonate with urea under the catalysis of sodium alkoxide in the production reaction process of the phenobarbital, and adding activated carbon into a system after the reaction is finished, wherein the activated carbon accounts for 27% of the mass of the diethyl phenylethylmalonate; fully stirring and mixing, continuously performing solid-liquid separation by using a horizontal screw centrifuge, concentrating and crystallizing the separated liquid to obtain a phenobarbital product, wherein the separated solid is activated carbon containing a byproduct;
2) Fully washing the by-product-containing activated carbon obtained in the step 1) by using an ethanol aqueous solution with the mass concentration of 96%, and collecting a washing solution, wherein the mass ratio of the by-product-containing activated carbon to the ethanol aqueous solution for washing is 1:7.5, washing the activated carbon containing the byproduct in three times, wherein the washing temperature is 57 ℃, and the mass ratio of the ethanol aqueous solution is (2); cooling and crystallizing the washing liquid concentrated solution, carrying out solid-liquid separation, and then drying and separating the obtained solid to obtain a crude product of 2-phenylbutyramide;
3) Uniformly stirring the crude product of the 2-phenylbutanamide obtained in the step 2) in an ethanol water solution with the mass concentration of 26%, adding purified water to separate out insoluble substances, filtering at room temperature to remove the insoluble substances, concentrating the filtrate, and recrystallizing at the crystallization temperature of 5.5-6 ℃; wherein the mass ratio of the 2-phenylbutanamide crude product to the ethanol water solution is 1.
Example 4
1) In the production reaction process of the phenobarbital, diethyl phenylmalonate reacts with urea under the catalysis of sodium alkoxide, and activated carbon is added into a system after the reaction is finished, wherein the activated carbon accounts for 20% of the mass of the diethyl phenylmalonate; after fully stirring and mixing, continuously carrying out solid-liquid separation by using a horizontal screw centrifuge, concentrating and crystallizing the separated liquid to obtain a phenobarbital product, wherein the separated solid is activated carbon containing a byproduct;
2) Fully washing the by-product-containing activated carbon obtained in the step 1) by using an ethanol water solution with the mass concentration of 90%, and collecting a washing solution, wherein the mass ratio of the by-product-containing activated carbon to the ethanol water solution for washing is 1:6, washing the activated carbon containing the byproduct at the washing temperature of 45 ℃ in three parts by mass ratio of the ethanol aqueous solution to the ethanol aqueous solution of 1.2; cooling and crystallizing the washing liquid concentrated solution, carrying out solid-liquid separation, drying and separating the obtained solid to obtain a crude product of the 2-phenylbutyramide;
3) Uniformly stirring the crude product of the 2-phenylbutanamide obtained in the step 2) in an ethanol water solution with the mass concentration of 20%, adding purified water to separate out insoluble substances, filtering at room temperature to remove the insoluble substances, concentrating the filtrate, and recrystallizing at the crystallization temperature of 4-5 ℃; wherein the mass ratio of the 2-phenylbutanamide crude product to the ethanol water solution is 1.
Example 5
1) Reacting diethyl phenylethylmalonate with urea under the catalysis of sodium alkoxide in the production reaction process of the phenobarbital, and adding active carbon into a system after the reaction is finished, wherein the active carbon accounts for 30% of the mass of the diethyl phenylethylmalonate; fully stirring and mixing, continuously performing solid-liquid separation by using a horizontal screw centrifuge, concentrating and crystallizing the separated liquid to obtain a phenobarbital product, wherein the separated solid is activated carbon containing a byproduct;
2) Fully washing the by-product-containing activated carbon obtained in the step 1) by using an ethanol water solution with the mass concentration of 97%, and collecting a washing solution, wherein the mass ratio of the by-product-containing activated carbon to the ethanol water solution for washing is 1:8, washing the activated carbon containing the byproduct for three times, wherein the washing temperature is 60 ℃, and the ethanol aqueous solution is divided into three parts according to the mass ratio of 2; cooling and crystallizing the washing liquid concentrated solution, carrying out solid-liquid separation, and then drying and separating the obtained solid to obtain a crude product of 2-phenylbutyramide;
3) Uniformly stirring the crude product of the 2-phenylbutanamide obtained in the step 2) in an ethanol water solution with the mass concentration of 30%, adding purified water to separate out insoluble substances, filtering at room temperature to remove the insoluble substances, concentrating the filtrate, and recrystallizing at the crystallization temperature of 6-7 ℃; wherein the mass ratio of the 2-phenylbutanamide crude product to the ethanol water solution is 1.5, and the 2-phenylbutanamide by-product is obtained after 2-time recrystallization.
Example 6
1) Reacting diethyl phenylethylmalonate with urea under the catalysis of sodium alkoxide in the production reaction process of the phenobarbital, and adding active carbon into a system after the reaction is finished, wherein the active carbon accounts for 26% of the mass of the diethyl phenylethylmalonate; fully stirring and mixing, continuously performing solid-liquid separation by using a horizontal screw centrifuge, concentrating and crystallizing the separated liquid to obtain a phenobarbital product, wherein the separated solid is activated carbon containing a byproduct;
2) Fully washing the by-product-containing activated carbon obtained in the step 1) by using an ethanol aqueous solution with the mass concentration of 95%, and collecting a washing solution, wherein the mass ratio of the by-product-containing activated carbon to the ethanol aqueous solution for washing is 1:7, washing the activated carbon containing the byproduct for three times, wherein the washing temperature is 56 ℃, and the ethanol aqueous solution is divided into three parts according to the mass ratio of 2; cooling and crystallizing the washing liquid concentrated solution, carrying out solid-liquid separation, drying and separating the obtained solid to obtain a crude product of the 2-phenylbutyramide;
3) Uniformly stirring the crude product of 2-phenylbutyramide obtained in the step 2) in an ethanol water solution with the mass concentration of 25%, separating out insoluble substances, filtering at room temperature to remove the insoluble substances, concentrating the filtrate, and recrystallizing at the crystallization temperature of 4.5-5.5 ℃; wherein the mass ratio of the 2-phenylbutanamide crude product to the ethanol water solution is 1.
The foregoing is directed to preferred embodiments of the present invention, other and further embodiments of the invention may be devised without departing from the basic scope thereof, and the scope thereof is determined by the claims that follow. However, any simple modification, equivalent change and modification of the above embodiments according to the technical essence of the present invention will still fall within the protection scope of the technical solution of the present invention.
Claims (10)
1. A method for producing phenylamide, which is used for producing phenobarbital by a traditional process and is characterized in that:
1) In the production reaction process of the phenobarbital, diethyl phenylethylmalonate reacts with urea under the catalysis of sodium alkoxide, activated carbon is added into a system after the reaction is completed, the mixture is fully stirred and mixed, then solid-liquid separation is carried out, the separated liquid is concentrated and crystallized to prepare a phenobarbital product, and the separated solid is the activated carbon containing a byproduct;
2) Fully washing the by-product-containing activated carbon obtained in the step 1) by using an ethanol aqueous solution with the mass concentration of 90-97%, and collecting washing liquid, wherein the washing temperature is 45-60 ℃; cooling and crystallizing the washing liquid concentrated solution, carrying out solid-liquid separation, and then drying and separating the obtained solid to obtain a crude product of 2-phenylbutyramide;
3) Recrystallizing the 2-phenylbutanamide crude product obtained in the step 2) in an ethanol water solution for multiple times to obtain a 2-phenylbutanamide byproduct.
2. A process for the production of phenylamides according to claim 1, characterized in that:
the active carbon in the step 1) accounts for 20-30% of the mass of the diethyl phenylethyl malonate.
3. A process according to claim 1 for the production of phenylamides characterized in that:
the solid-liquid separation in the step 1) is continuous separation by using a horizontal screw centrifuge.
4. A process for the production of phenylamides according to claim 1, characterized in that:
the mass ratio of the by-product-containing activated carbon in the step 2) to the ethanol aqueous solution with the mass concentration of 90% -97% for washing is 1:6 to 8.
5. A process according to claim 1 for the production of phenylamides characterized in that:
the ethanol aqueous solution with the mass concentration of 90-97% in the step 2) is divided into three parts according to the mass ratio of 2.
6. A process for the production of phenylamides according to claim 1, characterized in that:
the mass concentration of the ethanol water solution in the step 3) is 20-30%.
7. A process according to claim 1 for the production of phenylamides characterized in that:
the mass ratio of the crude 2-phenyl butyramide product to the aqueous ethanol solution in each recrystallization in the step 3) is 1.
8. A process for the production of phenylamides according to claim 1, characterized in that:
adding purified water to separate out insoluble substances when the crude 2-phenylbutanamide in the step 3) is recrystallized in an ethanol water solution, filtering at room temperature to remove the insoluble substances, concentrating the filtrate, and recrystallizing.
9. A process for the production of phenylamides according to claim 1 or 8, wherein:
the crystallization temperature of the recrystallization in the step 3) is 4-7 ℃.
10. A process according to claim 1 for the production of phenylamides characterized in that:
the washing temperature in the step 2) is 55-57 ℃.
Priority Applications (1)
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| CN109851519A (en) * | 2019-01-18 | 2019-06-07 | 山东新华制药股份有限公司 | A method of 2- phenylbutanamides are isolated and purified from phenobarbital production waste residue |
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