CN113563214A - Synthetic method of aminoacetic acid - Google Patents
Synthetic method of aminoacetic acid Download PDFInfo
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- CN113563214A CN113563214A CN202110764036.7A CN202110764036A CN113563214A CN 113563214 A CN113563214 A CN 113563214A CN 202110764036 A CN202110764036 A CN 202110764036A CN 113563214 A CN113563214 A CN 113563214A
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- ammonia water
- chloroacetic acid
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- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 title claims abstract description 110
- 229960002449 glycine Drugs 0.000 title claims abstract description 55
- 235000013905 glycine and its sodium salt Nutrition 0.000 title claims abstract description 41
- 238000010189 synthetic method Methods 0.000 title claims description 6
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 claims abstract description 62
- 229940106681 chloroacetic acid Drugs 0.000 claims abstract description 62
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims abstract description 59
- 235000011114 ammonium hydroxide Nutrition 0.000 claims abstract description 58
- 238000006243 chemical reaction Methods 0.000 claims abstract description 56
- 239000003054 catalyst Substances 0.000 claims abstract description 38
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000012043 crude product Substances 0.000 claims abstract description 13
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 claims abstract description 9
- 238000001308 synthesis method Methods 0.000 claims abstract description 9
- 239000002994 raw material Substances 0.000 claims abstract description 6
- UTPOUAZEFGTYAY-UHFFFAOYSA-N azanium;2-chloroacetate Chemical compound [NH4+].[O-]C(=O)CCl UTPOUAZEFGTYAY-UHFFFAOYSA-N 0.000 claims abstract description 5
- 238000006555 catalytic reaction Methods 0.000 claims abstract description 4
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 3
- 239000000047 product Substances 0.000 claims description 29
- 239000000243 solution Substances 0.000 claims description 29
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 27
- 238000001914 filtration Methods 0.000 claims description 27
- 238000000034 method Methods 0.000 claims description 21
- 239000013078 crystal Substances 0.000 claims description 16
- KKQBZNHBNPSGOP-UHFFFAOYSA-N azanium 2-aminoacetic acid chloride Chemical compound [NH4+].[Cl-].NCC(O)=O KKQBZNHBNPSGOP-UHFFFAOYSA-N 0.000 claims description 12
- 238000001035 drying Methods 0.000 claims description 11
- 239000011259 mixed solution Substances 0.000 claims description 10
- 239000012295 chemical reaction liquid Substances 0.000 claims description 9
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 claims description 9
- 239000007864 aqueous solution Substances 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 6
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 claims description 5
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 claims description 4
- 238000004821 distillation Methods 0.000 claims description 4
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 4
- 238000005406 washing Methods 0.000 claims description 3
- WEHWNAOGRSTTBQ-UHFFFAOYSA-N dipropylamine Chemical compound CCCNCCC WEHWNAOGRSTTBQ-UHFFFAOYSA-N 0.000 claims description 2
- DAZXVJBJRMWXJP-UHFFFAOYSA-N n,n-dimethylethylamine Chemical compound CCN(C)C DAZXVJBJRMWXJP-UHFFFAOYSA-N 0.000 claims description 2
- GNVRJGIVDSQCOP-UHFFFAOYSA-N n-ethyl-n-methylethanamine Chemical compound CCN(C)CC GNVRJGIVDSQCOP-UHFFFAOYSA-N 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 238000005576 amination reaction Methods 0.000 claims 1
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 abstract description 17
- 239000006227 byproduct Substances 0.000 abstract description 15
- 239000004471 Glycine Substances 0.000 abstract description 14
- 238000003786 synthesis reaction Methods 0.000 abstract description 6
- 150000003335 secondary amines Chemical class 0.000 abstract description 2
- 150000003512 tertiary amines Chemical class 0.000 abstract description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 37
- 230000001276 controlling effect Effects 0.000 description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- 235000019270 ammonium chloride Nutrition 0.000 description 18
- 238000001816 cooling Methods 0.000 description 16
- 238000010438 heat treatment Methods 0.000 description 14
- 239000000706 filtrate Substances 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 238000004321 preservation Methods 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 238000004448 titration Methods 0.000 description 7
- 238000001291 vacuum drying Methods 0.000 description 7
- 238000005303 weighing Methods 0.000 description 7
- 229910021529 ammonia Inorganic materials 0.000 description 6
- 238000005915 ammonolysis reaction Methods 0.000 description 5
- 235000010299 hexamethylene tetramine Nutrition 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- JQVDAXLFBXTEQA-UHFFFAOYSA-N dibutylamine Chemical compound CCCCNCCCC JQVDAXLFBXTEQA-UHFFFAOYSA-N 0.000 description 4
- 230000002194 synthesizing effect Effects 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- -1 amino acid compound Chemical class 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- NBZBKCUXIYYUSX-UHFFFAOYSA-N iminodiacetic acid Chemical compound OC(=O)CNCC(O)=O NBZBKCUXIYYUSX-UHFFFAOYSA-N 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 238000004176 ammonification Methods 0.000 description 2
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 238000009776 industrial production Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 238000007344 nucleophilic reaction Methods 0.000 description 2
- 150000003222 pyridines Chemical class 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 239000009759 San-Chi Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 239000013064 chemical raw material Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000003337 fertilizer Substances 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 150000003941 n-butylamines Chemical group 0.000 description 1
- MGFYIUFZLHCRTH-UHFFFAOYSA-N nitrilotriacetic acid Chemical compound OC(=O)CN(CC(O)=O)CC(O)=O MGFYIUFZLHCRTH-UHFFFAOYSA-N 0.000 description 1
- 238000013021 overheating Methods 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000007065 protein hydrolysis Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/04—Formation of amino groups in compounds containing carboxyl groups
- C07C227/06—Formation of amino groups in compounds containing carboxyl groups by addition or substitution reactions, without increasing the number of carbon atoms in the carbon skeleton of the acid
- C07C227/08—Formation of amino groups in compounds containing carboxyl groups by addition or substitution reactions, without increasing the number of carbon atoms in the carbon skeleton of the acid by reaction of ammonia or amines with acids containing functional groups
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
- B01J31/0235—Nitrogen containing compounds
- B01J31/0237—Amines
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
- B01J31/0235—Nitrogen containing compounds
- B01J31/0237—Amines
- B01J31/0238—Amines with a primary amino group
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
- B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
- B01J2231/4277—C-X Cross-coupling, e.g. nucleophilic aromatic amination, alkoxylation or analogues
- B01J2231/4283—C-X Cross-coupling, e.g. nucleophilic aromatic amination, alkoxylation or analogues using N nucleophiles, e.g. Buchwald-Hartwig amination
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a synthesis method of aminoacetic acid, belonging to the technical field of organic synthesis. The invention takes chloroacetic acid or ammonium chloroacetate as raw material and ammonia gas or ammonia water as aminating agent, and synthesizes aminoacetic acid under the catalysis of aliphatic amine. Compared with urotropine, the catalyst used in the invention has good thermal stability, can not be decomposed when the reaction temperature is higher, and ensures higher effective amount of the catalyst; and the generation of secondary amine and tertiary amine byproducts can be effectively inhibited through the steric hindrance regulation of the catalyst, so that the aminoacetic acid is selectively generated. The invention can obtain excellent reaction yield in a wider temperature range, and the crude product has less by-products and high glycine content.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a synthetic method of aminoacetic acid.
Background
Aminoacetic acid, also known as glycine, is an amino acid compound with the simplest structure, is used as an important fine chemical intermediate and chemical raw material, and is widely applied to various fields of medicines, pesticides, foods, fertilizers, feeds and the like. With the continuous improvement of living standard of people, the demand of aminoacetic acid in food and medicine industries is continuously expanded.
At present, the synthesis method of the aminoacetic acid mainly comprises a chloroacetic acid ammonolysis method, a natural protein hydrolysis method and a Strecker method. The Strecker method which mainly uses sodium cyanide as a main raw material is mostly adopted to produce glycine abroad, and the method has the advantages that the product is easy to refine and the production cost is low; the disadvantages are that sodium cyanide is a violent poison, the conditions are harsh and the process route is long. Glycine is produced by adopting a chloroacetic acid ammonolysis method generally in China, for example, technical schemes for preparing aminoacetic acid by adopting a chloroacetic acid ammonolysis method are reported in patents CN1058957, CN1136035, CN1803763, CN1896049B and the like, and urotropine is used as a catalyst in the technical schemes. The aminoacetic acid-ammonium chloride mixed crystal obtained by the traditional chloroacetic acid ammonolysis method has low aminoacetic acid content, which is only about 30-50%. After the aminoacetic acid-ammonium chloride mixed crystal is refined by an alcohol precipitation method, the obtained aminoacetic acid has low yield of only about 80 percent. Although the yield of glycine can be increased by raising the reaction temperature and increasing the amount of urotropin, the contents of iminodiacetic acid and nitrilotriacetic acid as by-products increase with the rise in the reaction temperature. In addition, due to poor thermal stability of urotropin, as the reaction temperature increases, urotropin decomposes to generate formaldehyde and ammonia, resulting in catalyst loss and deepening of the color of the reaction solution and products.
In order to solve the technical problem of the traditional catalyst urotropine in the preparation of aminoacetic acid, the prior patent provides a corresponding technical scheme. Patent CN111196768A adopts a two-step method to synthesize aminoacetic acid. In the technical scheme, a pyridine base compound is used for replacing a urotropine catalyst, ammonium chloroacetate is synthesized at a low temperature, and the pyridine base is used for catalyzing the reaction of the ammonium chloroacetate and ammonia to produce the aminoacetic acid. The amino acetic acid generated by the technical scheme has high purity, and the recycling of the mixed solvent and the catalyst is realized, but the following problems still exist: the reaction steps are complicated, and the yield is low; methanol with high toxicity is used as a solvent; the pyridine base compound is expensive, increases the production cost and is not beneficial to industrial production.
In patent CN108558687A, chloroacetic acid and ammonia gas are used as raw materials, and chloroacetic acid is subjected to an ammoniation reaction in an alcohol phase in the presence of a substituted pyridine catalyst, and the obtained reaction solution is subjected to multiple operations such as filtering and washing to obtain glycine and ammonium chloride, respectively. The technical scheme also overcomes the defects of poor thermal stability, easy loss and the like of the traditional catalyst urotropine, the purity of the synthesized aminoacetic acid is higher, and the catalyst can be recycled. The following disadvantages still remain: the catalytic efficiency is still not ideal, and when the dosage of the catalyst is 3 mol%, the total reaction yield is only 78.5%; the reaction solvent is methanol, ethanol and the like, and the consumption is large, so that the cost of a recovery working section is increased; the substituted pyridine catalyst is expensive, increases the production cost and is not beneficial to industrial production.
The patent CN111187173A resolves the traditional chloroacetic acid ammonolysis method into three procedures of 'ammonia dissolution', 'salt forming reaction' and 'ammonification'. (1) Preparing ammonia water; (2) mixing chloroacetic acid solution with prepared ammonia water to perform salt forming reaction to obtain solution A; (3) adding the mixed solution containing urotropine and ammonia water into the solution A in multiple parts for ammoniation reaction, and then cooling, crystallizing and separating to obtain glycine-ammonium chloride mixed crystal and mother liquor. The mother liquor can be used for preparing ammonia water in the step (1) or chloroacetic acid solution in the step (2), and the continuous glycine synthesis can be realized by continuing the reaction. The technical scheme effectively avoids the defects of the traditional technical scheme and realizes the cyclic utilization of the urotropine. The experimental result shows that when the dosage of the catalyst is 10 mol%, the content of the glycine in the mixed crystal is 50%, and the yield of the glycine is 96%. The technical scheme has the problems of large catalyst consumption, more byproducts in mixed crystals, low content of aminoacetic acid, complex operation steps, high cost and the like.
No report is found on a method for synthesizing glycine by using a cheap, efficient and stable catalyst. Penchun snow and the like report a method for synthesizing glycine by using triethylamine as an acid-binding agent (Penchun snow, Zhanshiping, Liu Sanchi, and the like, an experimental study on synthesis of glycine by using triethylamine as an acid-binding agent [ J ]. Shandong chemical industry, 2017,46(7): 44-47.). The method takes triethylamine as an acid-binding agent, paraformaldehyde as a catalyst and methanol as a solvent, and amino acetic acid is synthesized through an ammoniation reaction of chloroacetic acid. The yield of the reaction can reach 92% at most, and the main content of glycine can reach 98.5%. However, the catalyst in the method is still urotropin, and triethylamine is only used as an acid-binding agent, and the dosage is up to 115 mol%.
Disclosure of Invention
Aiming at the problems that most of catalysts for chloroacetic acid and aminoacetic acid are urotropine in the prior art, and ammonium chloride in products has high residue, low yield and the like, the invention provides a synthetic method of aminoacetic acid to solve the technical problems. The invention takes chloroacetic acid as an initial raw material, adopts aliphatic amines as a catalyst, and prepares and generates aminoacetic acid under the action of ammonia gas or ammonia water. Compared with urotropine, the catalyst used in the invention has good thermal stability, can not be decomposed when the reaction temperature is higher, and ensures higher effective amount of the catalyst; and the generation of secondary amine and tertiary amine byproducts can be effectively inhibited through the steric hindrance regulation of the catalyst, so that the aminoacetic acid is selectively generated. The invention can obtain excellent reaction yield in a wider temperature range, and the crude product has less by-products and high glycine content.
The technical scheme of the invention is as follows:
a synthesis method of aminoacetic acid, using chloroacetic acid or ammonium chloroacetate as raw material, ammonia gas or ammonia water as aminating agent, under the catalysis of aliphatic amine, synthesizing aminoacetic acid; the reaction equation is as follows:
wherein R is1，R2，R3Each independently is H or C1～C4Alkyl group of (1).
Preferably, the aliphatic amine is selected from n-butylamine, di-n-propylamine, diethylmethylamine, diisopropylethylamine, trimethylamine, triethylamine, tri-n-butylamine, or dimethylethylamine; triethylamine, n-butylamine, di-n-butylamine, or tri-n-butylamine are preferred.
The specific synthesis steps are as follows:
(1) adding an aliphatic amine catalyst into a reaction container, and controlling the temperature to preheat;
(2) preparing chloroacetic acid into an aqueous solution with a certain concentration, and transferring the aqueous solution into a chloroacetic acid aqueous solution dripping device;
(3) taking a proper amount of ammonia water, and transferring the ammonia water to an ammonia water dripping device;
(4) controlling the dripping speed of chloroacetic acid solution and ammonia water, and controlling the dripping temperature to be 25-45 ℃;
(5) after the dropwise addition is finished, controlling the reaction temperature to be 40-85 ℃, and controlling the reaction time to be 1-4 hours;
(6) after the reaction is finished, carrying out reduced pressure distillation and filtration on the reaction liquid to obtain a wet glycine-ammonium chloride mixed crystal product, and drying the wet product in vacuum at 65 ℃ until the weight is constant to obtain a crude product; the filtrate can be directly used for the synthesis of the aminoacetic acid of the next batch after a certain amount of catalyst is supplemented;
(7) recrystallizing the crude product at 50 ℃ by using 98% ethanol-water mixed solution, and obtaining the aminoacetic acid after filtering, alcohol washing and drying. Cooling, crystallizing and filtering the filtrate to obtain ammonium chloride, and reusing the filtrate;
preferably, in the step (1), the feeding molar ratio of the chloroacetic acid to the catalyst is 1: 0.005-0.05, and preferably 1: 0.02-0.05.
Preferably, in the step (1), the preheating temperature is 20 ℃ to 40 ℃.
Preferably, in the step (2), the concentration of the chloroacetic acid aqueous solution is 60 to 65%, preferably 62 to 63%.
Preferably, in the step (3), the concentration of ammonia water is 25% to 28%.
Preferably, in the step (4), the dropping speed of the ammonia water is 8.0g/min to 15.0g/min, preferably 10.0g/min to 13.0g/min, and the dropping speed of the chloroacetic acid solution is 13g/min to 22.0g/min, preferably 15.0g/min to 20.0 g/min. The dropping speed of the chloroacetic acid and the ammonia water is controlled to aim at: firstly, the local pH of the reaction solution is too high due to the excessively fast dropping, and excessive side reaction products are generated; and secondly, the dripping process is a heat releasing process, the control of the dripping speed is favorable for controlling the temperature of a reaction system, and the increase of the impurity content caused by local overheating is avoided.
Preferably, in the step (4), the dropping time of the ammonia water and the chloroacetic acid solution is controlled to be 1-2 hours, preferably 1.5 hours.
Preferably, in the step (5), the reaction temperature is controlled to be 50-80 ℃.
Preferably, in the step (6), the reduced pressure distillation pressure is-0.1 Mpa, and the temperature is controlled to be 60-70 ℃.
Preferably, in the step (6), the pure water obtained by distillation under reduced pressure can be used for preparing chloroacetic acid or aqueous ammonia solution.
The invention has the beneficial effects that:
(1) the invention uses the aliphatic amine compound as the catalyst for synthesizing the aminoacetic acid for the first time, the total yield of the aminoacetic acid can reach 99.0 percent at most, and the content of the ammonium chloride in the mixed crystal is between 41.6 and 42.9 percent and is close to the theoretical value (the theoretical content is 41.6 percent).
(2) The aliphatic amine catalyst used in the invention has good thermal stability, can efficiently catalyze the ammonification reaction of chloroacetic acid at the temperature of 40-85 ℃, and the use temperature of the traditional catalyst urotropine is generally 60-75 ℃. In contrast, the catalyst used in the present invention has better reaction adaptability than urotropin.
(3) The aliphatic amine catalyst used in the invention has high catalytic efficiency, and the dosage of the catalyst is between 0.5 mol% and 5.0 mol%, so that the ammoniation reaction of chloroacetic acid can be efficiently catalyzed. The dosage of the traditional catalyst urotropine is generally between 3.0mol percent and 10.0mol percent, even higher.
(4) The invention can effectively inhibit the generation of by-products such as iminodiacetic acid and the like by regulating and controlling the steric hindrance of the catalyst, and improve the product quality.
(5) The catalyst of the invention can be recycled, the operation condition is milder and simpler and more convenient than the prior art, the total ammonia consumption of the reaction is close to the theoretical equivalent, and the ammonia consumption is not more than 5 percent of the theoretical equivalent.
Drawings
In order to more clearly illustrate the embodiments or technical solutions in the prior art of the present invention, the drawings used in the description of the embodiments or prior art will be briefly described below, and it is obvious for those skilled in the art that other drawings can be obtained based on these drawings without creative efforts.
FIG. 1 is a diagram showing a catalytic reaction mechanism in example 1 of the present invention.
Detailed Description
In order to make those skilled in the art better understand the technical solution of the present invention, the technical solution in the embodiment of the present invention will be clearly and completely described below with reference to the drawings in the embodiment of the present invention, and it is obvious that the described embodiment is only a part of the embodiment of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
(1) Adding 39.7g (0.39mol) of triethylamine into a reaction container provided with a thermometer, a stirring device, a heating device, a circulating water cooling device and a dropping device, and controlling the temperature to be preheated at 30 ℃;
(2) weighing 1000.0g (10.6mol) of chloroacetic acid, adding 600g of water for dissolving, and transferring to a chloroacetic acid dripping device;
(3) taking 1600mL of 25% ammonia water, and transferring the ammonia water to an ammonia water dripping device;
(4) controlling the dripping speeds of the chloroacetic acid solution and the ammonia water to be 16.0g/min and 12.0g/min respectively, controlling the temperature to be 30 ℃, finishing dripping the chloroacetic acid solution for about 1.5 hours, and finishing dripping the ammonia water for about 2 hours;
(5) after the dropwise adding, heating to 60 ℃, and carrying out heat preservation reaction for 2 hours;
(6) after the reaction is finished, distilling the reaction liquid under reduced pressure to remove water, and filtering to obtain a glycine-ammonium chloride mixed crystal wet product; vacuum drying the wet product at 65 ℃ to constant weight, wherein the mass of the wet product is 1326.5g, and the content of a by-product ammonium chloride is 41.8%;
(7) the crude product is recrystallized by using 98 percent ethanol-water mixed solution at 50 ℃, and 741.2g of aminoacetic acid is obtained after filtration and drying, the yield is 93.3 percent, and the content is 98.9 percent by a titration method. Slowly cooling the filtrate to 10 ℃, and filtering and separating to obtain the ammonium chloride.
The catalytic mechanism of the invention is illustrated by example 1: firstly, triethylamine and chloroacetic acid are subjected to addition reaction to generate a quaternary ammonium salt intermediate, and the intermediate has larger steric hindrance; then the ammonia and the intermediate of the quaternary ammonium salt are subjected to nucleophilic reaction to generate aminoacetic acid and triethylamine hydrochloride. The amino acetic acid has larger steric hindrance and is not easy to generate nucleophilic reaction with the quaternary ammonium salt intermediate, so that the generation of byproducts such as iminodiacetic acid and the like can be effectively inhibited.
Example 2
(1) Adding 72.7g (0.39mol) of tri-n-butylamine into a reaction container provided with a thermometer, a stirring device, a heating device, a circulating water cooling device and a dropping device, and controlling the temperature to be 40 ℃ for preheating;
(2) weighing 1000.0g (10.6mol) of chloroacetic acid, adding 600g of water for dissolving, and transferring to a chloroacetic acid dripping device;
(3) taking 1600mL of 25% ammonia water, and transferring the ammonia water to an ammonia water dripping device;
(4) controlling the dripping speeds of the chloroacetic acid solution and the ammonia water to be 16.0g/min and 12.0g/min respectively, controlling the temperature to be 40 ℃, finishing dripping the chloroacetic acid solution for about 1.5 hours, and finishing dripping the ammonia water for about 2 hours;
(5) after the dropwise adding, heating to 60 ℃, and carrying out heat preservation reaction for 2 hours;
(6) after the reaction is finished, distilling the reaction liquid under reduced pressure to remove water, and filtering to obtain a glycine-ammonium chloride mixed crystal wet product; vacuum drying the wet product at 65 ℃ to constant weight, wherein the mass of the wet product is 1345.6g, and the content of a by-product ammonium chloride is 41.7%;
(7) the crude product is recrystallized by using 98 percent ethanol-water mixed solution at 50 ℃, and 761.1g of aminoacetic acid is obtained after filtration and drying, the yield is 95.8 percent, and the content is 99.0 percent by a titration method. Slowly cooling the filtrate to 10 ℃, and filtering and separating to obtain the ammonium chloride.
Example 3
(1) Adding 68.5g (0.53mol) of di-n-butylamine into a reaction container provided with a thermometer, a stirring device, a heating device, a circulating water cooling device and a dropping device, and controlling the temperature to be 40 ℃ for preheating;
(2) weighing 1000.0g (10.6mol) of chloroacetic acid, adding 600g of water for dissolving, and transferring to a chloroacetic acid dripping device;
(3) taking 1600mL of 28% ammonia water, and transferring the ammonia water to an ammonia water dripping device;
(4) controlling the dripping speeds of the chloroacetic acid solution and the ammonia water to be 15.0g/min and 10.0g/min respectively, controlling the temperature to be 40 ℃, finishing dripping the chloroacetic acid solution for about 1.5 hours, and finishing dripping the ammonia water for about 2.5 hours;
(5) after the dropwise adding, heating to 50 ℃, and carrying out heat preservation reaction for 4 hours;
(6) after the reaction is finished, distilling the reaction liquid under reduced pressure to remove water, and filtering to obtain a glycine-ammonium chloride mixed crystal wet product; vacuum drying the wet product at 65 ℃ to constant weight, wherein the mass of the wet product is 1269.4g, and the content of the by-product ammonium chloride is 42.9%;
(7) the crude product is recrystallized by using 98 percent ethanol-water mixed solution at 50 ℃, and 737.3g of aminoacetic acid is obtained after filtration and drying, the yield is 92.8 percent, and the content is 98.1 percent by a titration method. Slowly cooling the filtrate to 10 ℃, and filtering and separating to obtain the ammonium chloride.
Example 4
(1) Adding 38.8g (0.53mol) of n-butylamine into a reaction container provided with a thermometer, a stirring device, a heating device, a circulating water cooling device and a dropping device, and controlling the temperature to be preheated at 35 ℃;
(2) weighing 1000.0g (10.6mol) of chloroacetic acid, adding 600g of water for dissolving, and transferring to a chloroacetic acid dripping device;
(3) taking 1600mL of 28% ammonia water, and transferring the ammonia water to an ammonia water dripping device;
(4) controlling the dripping speeds of the chloroacetic acid solution and the ammonia water to be 15.0g/min and 10.0g/min respectively, controlling the temperature to be 40 ℃, finishing dripping the chloroacetic acid solution for about 1.5 hours, and finishing dripping the ammonia water for about 2.5 hours;
(5) after the dropwise adding, heating to 50 ℃, and carrying out heat preservation reaction for 4 hours;
(6) after the reaction is finished, distilling the reaction liquid under reduced pressure to remove water, and filtering to obtain a glycine-ammonium chloride mixed crystal wet product; vacuum drying the wet product at 65 ℃ to constant weight, wherein the mass of the wet product is 1201.4g, and the content of a by-product ammonium chloride is 42.4%;
(7) the crude product is recrystallized by using 98 percent ethanol-water mixed solution at 50 ℃, and 684.0g of aminoacetic acid is obtained after filtration and drying, the yield is 86.1 percent, and the content is 97.8 percent by a titration method. Slowly cooling the filtrate to 10 ℃, and filtering and separating to obtain the ammonium chloride.
Example 5
(1) Adding 6.85g (0.053mol) of diisopropylethylamine into a reaction vessel provided with a thermometer, a stirring device, a heating device, a circulating water cooling device and a dropping device, and controlling the temperature to be preheated at 30 ℃;
(2) weighing 1000.0g (10.6mol) of chloroacetic acid, adding 600g of water for dissolving, and transferring to a chloroacetic acid dripping device;
(3) taking 1600mL of 28% ammonia water, and transferring the ammonia water to an ammonia water dripping device;
(4) controlling the dripping speeds of the chloroacetic acid solution and the ammonia water to be 15.0g/min and 10.0g/min respectively, controlling the temperature to be 30 ℃, finishing dripping the chloroacetic acid solution for about 1.5 hours, and finishing dripping the ammonia water for about 2.5 hours;
(5) after the dropwise adding, heating to 80 ℃, and carrying out heat preservation reaction for 2 hours;
(6) after the reaction is finished, distilling the reaction liquid under reduced pressure to remove water, and filtering to obtain a glycine-ammonium chloride mixed crystal wet product; vacuum drying the wet product at 65 ℃ to constant weight, wherein the mass of the wet product is 1023.1g, and the content of the by-product ammonium chloride is 42.6%;
(7) the crude product is recrystallized by using 98 percent ethanol-water mixed solution at 50 ℃, and 576.0g of aminoacetic acid is obtained after filtration and drying, the yield is 72.5 percent, and the content is 89.0 percent by a titration method. Slowly cooling the filtrate to 10 ℃, and filtering and separating to obtain the ammonium chloride.
Example 6
(1) Adding 39.3g (0.21mol) of tri-n-butylamine and 11.6g (0.16mol) of n-butylamine into a reaction vessel provided with a thermometer, a stirring device, a heating device, a circulating water cooling device and a dropping device, and controlling the temperature to preheat at 40 ℃;
(2) weighing 1000.0g (10.6mol) of chloroacetic acid, adding 600g of water for dissolving, and transferring to a chloroacetic acid dripping device;
(3) taking 1600mL of 28% ammonia water, and transferring the ammonia water to an ammonia water dripping device;
(4) controlling the dripping speeds of the chloroacetic acid solution and the ammonia water to be 16.0g/min and 12.0g/min respectively, controlling the temperature to be 40 ℃, finishing dripping the chloroacetic acid solution for about 1.5 hours, and finishing dripping the ammonia water for about 2 hours;
(5) after the dropwise adding, heating to 60 ℃, and carrying out heat preservation reaction for 4 hours;
(6) after the reaction is finished, distilling the reaction liquid under reduced pressure to remove water, and filtering to obtain a glycine-ammonium chloride mixed crystal wet product; vacuum drying the wet product at 65 ℃ to constant weight, wherein the mass of the wet product is 1236.7g, and the content of a by-product ammonium chloride is 42.0%;
(7) the crude product is recrystallized by using 98 percent ethanol-water mixed solution at 50 ℃, and 725.4g of aminoacetic acid is obtained after filtration and drying, the yield is 91.3 percent, and the content is 96.7 percent through a titration method. Slowly cooling the filtrate to 10 ℃, and filtering and separating to obtain the ammonium chloride.
Comparative example
(1) Adding 74.3g (0.53mol) of urotropine into a reaction vessel provided with a thermometer, a stirring device, a heating device, a circulating water cooling device and a dropping device, and controlling the preheating at 40 ℃;
(2) weighing 1000.0g (10.6mol) of chloroacetic acid, adding 600g of water for dissolving, and transferring to a chloroacetic acid dripping device;
(3) taking 1600mL of 25% ammonia water, and transferring the ammonia water to an ammonia water dripping device;
(4) controlling the dripping speeds of the chloroacetic acid solution and the ammonia water to be 16.0g/min and 12.0g/min respectively, controlling the temperature to be 40 ℃, finishing dripping the chloroacetic acid solution for about 1.5 hours, and finishing dripping the ammonia water for about 2 hours;
(5) after the dropwise adding, heating to 60 ℃, and carrying out heat preservation reaction for 2 hours;
(6) after the reaction is finished, distilling the reaction liquid under reduced pressure to remove water, and filtering to obtain a glycine-ammonium chloride mixed crystal wet product; vacuum drying the wet product at 65 ℃ to constant weight, wherein the mass of the wet product is 1073.5g, and the content of a by-product ammonium chloride is 46.7%;
(7) the crude product is recrystallized by using 98 percent ethanol-water mixed solution at 50 ℃, and 630.0g of aminoacetic acid is obtained after filtration and drying, the yield is 79.3 percent, and the content is 96.5 percent through a titration method. Slowly cooling the filtrate to 10 ℃, and filtering and separating to obtain the ammonium chloride.
Although the present invention has been described in detail by referring to the drawings in connection with the preferred embodiments, the present invention is not limited thereto. Various equivalent modifications or substitutions can be made on the embodiments of the present invention by those skilled in the art without departing from the spirit and scope of the present invention, and these modifications or substitutions are within the scope of the present invention/any person skilled in the art can easily conceive of the changes or substitutions within the technical scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.
Claims (10)
1. A synthetic method of aminoacetic acid is characterized in that chloroacetic acid or ammonium chloroacetate is used as a raw material, ammonia gas or ammonia water is used as an amination agent, and aminoacetic acid is synthesized under the catalysis of aliphatic amine; the reaction equation is as follows:
wherein R is1，R2，R3Each independently is H or C1～C4Alkyl group of (1).
2. The method of claim 1, wherein the aliphatic amine is at least one selected from the group consisting of n-butylamine, di-n-propylamine, diethylmethylamine, diisopropylethylamine, trimethylamine, triethylamine, tri-n-butylamine, and dimethylethylamine.
3. The synthetic method according to any one of claims 1-2, wherein the specific synthetic steps are as follows:
(1) adding an aliphatic amine catalyst into a reaction container, and controlling the temperature to preheat;
(2) preparing chloroacetic acid into an aqueous solution with a certain concentration, and transferring the aqueous solution into a chloroacetic acid aqueous solution dripping device;
(3) taking a proper amount of ammonia water, and transferring the ammonia water to an ammonia water dripping device;
(4) controlling the dripping speed of chloroacetic acid solution and ammonia water, and controlling the dripping temperature to be 25-45 ℃;
(5) after the dropwise addition is finished, controlling the reaction temperature to be 40-85 ℃, and controlling the reaction time to be 1-4 hours;
(6) after the reaction is finished, carrying out reduced pressure distillation and filtration on the reaction liquid to obtain a glycine-ammonium chloride mixed crystal wet product, and drying the mixed crystal wet product at 65 ℃ in vacuum to constant weight to obtain a crude product;
(7) recrystallizing the crude product at 50 ℃ by using 98% ethanol-water mixed solution, and obtaining the aminoacetic acid after filtering, alcohol washing and drying.
4. The synthesis method according to claim 3, wherein in the step (1), the feeding molar ratio of chloroacetic acid to the catalyst is 1: 0.005-0.05.
5. The synthesis method according to claim 3, wherein in the step (1), the feeding molar ratio of chloroacetic acid to the catalyst is 1: 0.02-0.05.
6. The method of claim 3, wherein in step (2), the concentration of the chloroacetic acid aqueous solution is 60% to 65%.
7. The synthesis method according to claim 3, wherein in the step (3), the concentration of ammonia water is 25% to 28%.
8. The synthesis method according to claim 3, wherein in the step (4), the dropping speed of the ammonia water is 8.0g/min to 15.0 g/min; the dropping speed of the chloroacetic acid solution is 13 g/min-22.0 g/min.
9. The synthesis method according to claim 3, wherein in the step (4), the dropping time is controlled to be 1 to 2 hours.
10. The synthesis method according to claim 3, wherein in the step (5), the reaction temperature is controlled to be 50-80 ℃.
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