CN118184528A - Preparation method of sarcosine - Google Patents
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- CN118184528A CN118184528A CN202410371983.3A CN202410371983A CN118184528A CN 118184528 A CN118184528 A CN 118184528A CN 202410371983 A CN202410371983 A CN 202410371983A CN 118184528 A CN118184528 A CN 118184528A
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- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 title claims abstract description 138
- 108010077895 Sarcosine Proteins 0.000 title claims abstract description 84
- 229940043230 sarcosine Drugs 0.000 title claims abstract description 69
- 238000002360 preparation method Methods 0.000 title claims abstract description 41
- 238000000034 method Methods 0.000 claims abstract description 29
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 78
- 238000006243 chemical reaction Methods 0.000 claims description 62
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 30
- 239000002904 solvent Substances 0.000 claims description 29
- 239000003054 catalyst Substances 0.000 claims description 25
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 24
- 238000007327 hydrogenolysis reaction Methods 0.000 claims description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 22
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 20
- 239000000047 product Substances 0.000 claims description 20
- 239000001257 hydrogen Substances 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 238000003756 stirring Methods 0.000 claims description 16
- 229940048098 sodium sarcosinate Drugs 0.000 claims description 15
- ZUFONQSOSYEWCN-UHFFFAOYSA-M sodium;2-(methylamino)acetate Chemical compound [Na+].CNCC([O-])=O ZUFONQSOSYEWCN-UHFFFAOYSA-M 0.000 claims description 15
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 claims description 14
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 12
- 238000001035 drying Methods 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- 238000002156 mixing Methods 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 239000006184 cosolvent Substances 0.000 claims description 9
- 230000020477 pH reduction Effects 0.000 claims description 8
- 239000003513 alkali Substances 0.000 claims description 7
- 239000006185 dispersion Substances 0.000 claims description 7
- 239000007788 liquid Substances 0.000 claims description 7
- 238000001816 cooling Methods 0.000 claims description 6
- 239000000706 filtrate Substances 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 6
- 239000007789 gas Substances 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims 3
- 238000007599 discharging Methods 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 239000012535 impurity Substances 0.000 abstract description 7
- 230000008901 benefit Effects 0.000 abstract description 6
- 238000005265 energy consumption Methods 0.000 abstract description 5
- 238000011031 large-scale manufacturing process Methods 0.000 abstract description 5
- 230000009286 beneficial effect Effects 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 238000001514 detection method Methods 0.000 description 10
- 238000000605 extraction Methods 0.000 description 10
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 8
- 230000000052 comparative effect Effects 0.000 description 8
- 150000002431 hydrogen Chemical class 0.000 description 7
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 150000001413 amino acids Chemical class 0.000 description 4
- 239000001569 carbon dioxide Substances 0.000 description 4
- 229910002092 carbon dioxide Inorganic materials 0.000 description 4
- 210000003298 dental enamel Anatomy 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 239000012467 final product Substances 0.000 description 3
- 239000013067 intermediate product Substances 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 239000003344 environmental pollutant Substances 0.000 description 2
- 231100000719 pollutant Toxicity 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- MEJYXFHCRXAUIL-UHFFFAOYSA-N 2-[carbamimidoyl(methyl)amino]acetic acid;hydrate Chemical compound O.NC(=N)N(C)CC(O)=O MEJYXFHCRXAUIL-UHFFFAOYSA-N 0.000 description 1
- CBWFTZNMONHKNZ-UHFFFAOYSA-N 2-[methyl(phenylmethoxycarbonyl)amino]acetic acid Chemical group OC(=O)CN(C)C(=O)OCC1=CC=CC=C1 CBWFTZNMONHKNZ-UHFFFAOYSA-N 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 239000003124 biologic agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960004826 creatine monohydrate Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 235000019605 sweet taste sensations Nutrition 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
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
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C269/04—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups from amines with formation of carbamate groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The application discloses a preparation method of sarcosine, and relates to the technical field of organic synthesis. The preparation method of the sarcosine comprises the steps of Z-SAR preparation and sarcosine preparation, and the process method can effectively separate impurities, so that the obtained product sarcosine has good quality and high yield; the method is simple and convenient, low in energy consumption, environment-friendly, beneficial to large-scale production and application and extremely high in economic benefit.
Description
Technical Field
The application relates to the technical field of organic synthesis, in particular to a preparation method of sarcosine.
Background
Sarcosine has molecular formula of C 3H7NO2, is white crystal or crystalline powder, has slightly sweet taste, has hygroscopicity, is water-soluble, slightly ethanol-soluble, and is insoluble in acetone and ethers.
Sarcosine is an amino acid that can be naturally produced by the human body, which can supply energy to muscle cells, and at the same time can improve the intelligence of the human body, prevent injury caused by brain injury, and act as a fatigue recovery agent. In addition, sarcosine can also be used as a raw material for synthesizing creatine monohydrate, biological agents, etc. in general, industrial dye stabilizers, amino acid type surfactants, and the like.
In the existing sarcosine synthesis process, more impurities are easily introduced, so that the quality of the product sarcosine is reduced, and the yield is influenced; and the process steps are complicated, the energy consumption and the pollution are high, and the large-scale production and the application are difficult.
Disclosure of Invention
The application aims to provide a preparation method of sarcosine, which can effectively separate impurities, and the obtained product of the sarcosine has good quality and high yield; the method is simple and convenient, low in energy consumption, environment-friendly, beneficial to large-scale production and application and extremely high in economic benefit.
The technical scheme of the application is as follows:
the embodiment of the application provides a preparation method of sarcosine, which comprises the following steps:
Z-SAR preparation: adding sodium sarcosinate solution and cosolvent into a reaction kettle, stirring and mixing, then dropwise adding Z-Cl for reaction, adding a first solvent into a reaction system after the reaction is finished, adding hydrochloric acid for acidification, and standing for layering to obtain a water layer and a first solvent layer; extracting the water layer by using a first solvent, combining the extract with the first solvent layer, and concentrating under reduced pressure to remove the first solvent to obtain Z-SAR;
Preparation of sarcosine: adding a second solvent and a catalyst into the prepared Z-SAR, stirring and mixing, then replacing air in a reaction kettle with nitrogen, introducing hydrogen for hydrogenolysis reaction, evacuating the hydrogen after the reaction is finished, replacing the gas environment in the reaction kettle with nitrogen, filtering to remove the catalyst, concentrating the filtrate to dryness under negative pressure, adding the first solvent for dispersion, cooling, and performing aftertreatment to obtain the finished product sarcosine.
Wherein in the preparation method, Z-Cl is benzyl chloroformate, also called benzyloxycarbonyl chloride,
The structural formula is as follows:
Z-SAR is benzyloxycarbonyl sarcosine, and has a structural formula:
Further, in some embodiments of the present application, in the above-mentioned preparation step of Z-SAR, Z-Cl is added dropwise at 15-20deg.C, and liquid alkali is added to control pH to 8-9, and reaction is performed while maintaining the reaction temperature at 15-20deg.C and the pH of the reaction system at 8-9.
Further, in some embodiments of the present application, in the above-mentioned Z-SAR preparation step, when Z-Cl is added dropwise to perform a reaction, ninhydrin color development is detected by TLC on the reaction system, and if no sodium sarcosinate is found in the reaction system, it is judged that the reaction is completed, and the subsequent steps are continued.
Further, in some embodiments of the present application, in the above-mentioned Z-SAR preparation step, hydrochloric acid is added to adjust the pH to 2 to 3, and acidification is performed.
Further, in some embodiments of the present application, in the above-mentioned Z-SAR preparation step, the cosolvent is any one or more of tetrahydrofuran, acetone, and dioxane.
Further, in some embodiments of the present application, in the above-described Z-SAR preparation step, the first solvent is ethyl acetate.
Further, in some embodiments of the present application, in the above-mentioned Z-SAR preparation step, after standing and layering, the aqueous layer is extracted with the first solvent, TLC detection is performed on the aqueous layer after extraction, and if no Z-SAR is found, the extraction is determined to be complete, and the subsequent steps are continued.
Further, in some embodiments of the present application, in the above-mentioned step of preparing sarcosine, hydrogen is introduced to carry out the hydrogenolysis reaction, the pressure of the reaction vessel is maintained at 1.5 to 1.8kgf/m 2, and the reaction vessel is intermittently vented.
Further, in some embodiments of the present application, in the above sarcosine preparation step, the second solvent is methanol.
Further, in some embodiments of the present application, in the above sarcosine preparation step, the catalyst is pd/c catalyst.
Further, in some embodiments of the present application, in the above-mentioned sarcosine preparation step, after the hydrogenolysis reaction, if no Z-SAR is found in the system by TLC detection, it is determined that the hydrogenolysis is completed, and then the subsequent steps are continued.
Further, in some embodiments of the present application, in the above-mentioned sarcosine preparation step, the first solvent is added for dispersion, and then cooled to room temperature, and then post-treatment is performed.
Further, in some embodiments of the present application, in the above-mentioned sarcosine preparation step, the post-treatment includes the following process steps: centrifuging, rinsing, spin-drying and drying.
Compared with the prior art, the embodiment of the application has at least the following advantages or beneficial effects:
in view of the above, the embodiment of the application provides a preparation method of sarcosine, which comprises the following process paths:
In the preparation method, commercial industrial sodium sarcosinate solution is used as a raw material, the amino group on sodium sarcosinate is protected by utilizing Z-Cl, and then hydrochloric acid is used for acidification to prepare the Z-SAR which is almost insoluble in water, so that the separation and impurity removal are facilitated, and a high-purity Z-SAR intermediate product is obtained, so that the intermediate product is further used for preparing the sarcosine, the introduction of impurities can be reduced, and the quality of the final product sarcosine is guaranteed.
Then hydrogen is introduced into a catalyst, preferably a pd/c catalyst, to carry out hydrogenolysis reaction on the prepared Z-SAR, so as to generate sarcosine, toluene and carbon dioxide; the byproducts toluene and carbon dioxide can be very easily separated from the amino acid of the product, so that the high-purity and high-quality product sarcosine can be obtained, and the yield of the product sarcosine can be effectively improved.
Meanwhile, the whole preparation method has the advantages of simple flow, less resource and energy consumption, less pollutant generated in the process, environmental friendliness, contribution to large-scale production and utilization and popularization and application values.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present application more clear, the technical solutions of the embodiments of the present application will be clearly and completely described below. The specific conditions are not noted in the examples and are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention.
It is noted that relational terms such as "first" and "second", and the like, are used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions. Moreover, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. Without further limitation, the element defined by the phrase "comprising … …" does not exclude the presence of additional identical elements in a process, method, article, or apparatus that comprises an element thereof.
It should be noted that, without conflict, the embodiments of the present application and features of the embodiments may be combined with each other.
The features and capabilities of the present application are described in further detail below in connection with examples.
Example 1
The embodiment provides sarcosine, which is prepared by the following method:
Z-SAR preparation: adding 300kg of 34.5% sodium sarcosinate solution and 30kg of tetrahydrofuran into a 1000L enamel reaction kettle, stirring and mixing uniformly, dropwise adding 172kg of 97% Z-Cl at 15-20 ℃, adding 30% liquid alkali to control the pH of the system to 8-9, maintaining the reaction temperature at 15-20 ℃ and the pH of the reaction system to 8-9, detecting ninhydrin color by TLC after reacting for about 5 hours, and judging that the reaction system is basically free of sodium sarcosinate; 165kg of ethyl acetate is added into the reaction system after the reaction is finished, and then 30% hydrochloric acid is added to enable the pH of the reaction system to be 2-3 for acidification; acidifying and stirring for 30min, keeping the pH in the system basically unchanged, and standing for layering to obtain a water layer and a first solvent (ethyl acetate) layer; extracting the water layer with ethyl acetate for 2 times (165 kg/time), performing TLC detection on the water layer after extraction, and judging that the extraction is complete after the detection is basically free of Z-SAR; combining the obtained extract with a first solvent (ethyl acetate) layer, and concentrating under reduced pressure to remove ethyl acetate to obtain Z-SAR;
Preparation of sarcosine: adding 300kg of methanol and 0.3kg of 10% pd/c catalyst into the prepared Z-SAR, stirring and mixing uniformly, then replacing air in a reaction kettle with nitrogen, repeatedly replacing for 3 times, then introducing hydrogen, maintaining the kettle pressure to be 1.5-1.8 kgf/m 2, intermittently emptying, and carrying out hydrogenolysis reaction; after the hydrogenolysis reaction is carried out for 6 hours, detecting by TLC, and judging that the system has no Z-SAR, and ending the hydrogenolysis reaction; then evacuating hydrogen, replacing the gas environment in the reaction kettle with nitrogen, adding a proper amount of pure water for dissolution, filtering to remove the pd/c catalyst, concentrating the filtrate to dryness under negative pressure, recovering methanol, adding 300kg of ethyl acetate for dispersion, cooling to room temperature, centrifuging, rinsing, spin-drying and drying to obtain 79.3kg of white crystal sarcosine, wherein the product content is 99.21%, and the molar yield of the product is 95.6% calculated by sodium sarcosine.
Example 2
The embodiment provides sarcosine, which is prepared by the following method:
Z-SAR preparation: adding 300kg of 34.5% sodium sarcosinate solution and 30kg of acetone into a 1000L enamel reaction kettle, uniformly stirring and mixing, dropwise adding 172kg of 97% Z-Cl at 15-20 ℃, adding 30% liquid alkali to control the pH value of a system to 8-9, maintaining the reaction temperature at 15-20 ℃ and the pH value of the reaction system to 8-9, reacting for about 5 hours, detecting ninhydrin color by TLC, and judging that the reaction system is basically free of sodium sarcosinate; 165kg of ethyl acetate is added into the reaction system after the reaction is finished, and then 30% hydrochloric acid is added to enable the pH of the reaction system to be 2-3 for acidification; acidifying and stirring for 30min, keeping the pH in the system basically unchanged, and standing for layering to obtain a water layer and a first solvent (ethyl acetate) layer; extracting the water layer with ethyl acetate for 2 times (165 kg/time), performing TLC detection on the water layer after extraction, and judging that the extraction is complete after the detection is basically free of Z-SAR; combining the obtained extract with a first solvent (ethyl acetate) layer, and concentrating under reduced pressure to remove ethyl acetate to obtain Z-SAR;
Preparation of sarcosine: adding 300kg of methanol and 0.3kg of 10% pd/c catalyst into the prepared Z-SAR, stirring and mixing uniformly, then replacing air in a reaction kettle with nitrogen, repeatedly replacing for 3 times, then introducing hydrogen, maintaining the kettle pressure to be 1.5-1.8 kgf/m 2, intermittently emptying, and carrying out hydrogenolysis reaction; after the hydrogenolysis reaction is carried out for 6 hours, detecting by TLC, and judging that the system has no Z-SAR, and ending the hydrogenolysis reaction; then evacuating hydrogen, replacing the gas environment in the reaction kettle with nitrogen, adding a proper amount of pure water for dissolution, filtering to remove the pd/c catalyst, concentrating the filtrate to dryness under negative pressure, recovering methanol, adding 300kg of ethyl acetate for dispersion, cooling to room temperature, centrifuging, rinsing, spin-drying and drying to obtain 80kg of white crystal sarcosine, wherein the product content is 99.44%, and the molar yield of the product is 96.7% based on sodium sarcosine.
Comparative example 1
The comparative example provides a sarcosine, which is prepared by the following method:
Z-SAR preparation: adding 300kg of 34.5% sodium sarcosinate solution into a 1000L enamel reaction kettle, dropwise adding 172kg of 97% Z-Cl under stirring at 15-20 ℃, adding 30% liquid alkali to control the pH of the system to 8-9, maintaining the reaction temperature at 15-20 ℃ and the pH of the reaction system to 8-9, reacting for about 5 hours, detecting ninhydrin color by TLC, and finding that the reaction system has little sodium sarcosinate and is not reacted; 165kg of ethyl acetate and 30% hydrochloric acid are added into the reaction system to enable the pH of the reaction system to be 2-3, and acidification is carried out; acidifying and stirring for 30min, keeping the pH in the system basically unchanged, and standing for layering to obtain a water layer and a first solvent (ethyl acetate) layer; extracting the water layer with ethyl acetate for 2 times (165 kg/time), performing TLC detection on the water layer after extraction, and judging that the extraction is complete after the detection is basically free of Z-SAR; combining the obtained extract with a first solvent (ethyl acetate) layer, and concentrating under reduced pressure to remove ethyl acetate to obtain Z-SAR;
Preparation of sarcosine: adding 300kg of methanol and 0.3kg of 10% pd/c catalyst into the prepared Z-SAR, stirring and mixing uniformly, then replacing air in a reaction kettle with nitrogen, repeatedly replacing for 3 times, then introducing hydrogen, maintaining the kettle pressure to be 1.5-1.8 kgf/m 2, intermittently emptying, and carrying out hydrogenolysis reaction; after the hydrogenolysis reaction is carried out for 6 hours, detecting by TLC, and judging that the system has no Z-SAR, and ending the hydrogenolysis reaction; then evacuating hydrogen, replacing the gas environment in the reaction kettle with nitrogen, adding a proper amount of pure water for dissolution, filtering to remove the pd/c catalyst, concentrating the filtrate to dryness under negative pressure, recovering methanol, adding 300kg of ethyl acetate for dispersion, cooling to room temperature, centrifuging, rinsing, spin-drying and drying to obtain 68.9kg of white crystal sarcosine, wherein the product content is 99.20%, and the molar yield of the product is 83.1% calculated by sodium sarcosine.
Comparative example 2
The comparative example of the present application provides a sarcosine, which is prepared by the following method:
Z-SAR preparation: adding 300kg of 34.5% sodium sarcosinate solution and 30kg of tetrahydrofuran into a 1000L enamel reaction kettle, stirring and mixing uniformly, dropwise adding 172kg of 97% Z-Cl at 15-20 ℃, adding 30% liquid alkali to control the pH of the system to 8-9, maintaining the reaction temperature at 15-20 ℃ and the pH of the reaction system to 8-9, detecting ninhydrin color by TLC after reacting for about 5 hours, and judging that the reaction system is basically free of sodium sarcosinate; 165kg of ethyl acetate is added into the reaction system after the reaction is finished, and then 30% hydrochloric acid is added to enable the pH of the reaction system to be 2-3 for acidification; acidifying and stirring for 30min, keeping the pH in the system basically unchanged, and standing for layering to obtain a water layer and a first solvent (ethyl acetate) layer; extracting the water layer with ethyl acetate for 2 times (165 kg/time), performing TLC detection on the water layer after extraction, and judging that the extraction is complete after the detection is basically free of Z-SAR; combining the obtained extract with a first solvent (ethyl acetate) layer, and concentrating under reduced pressure to remove ethyl acetate to obtain Z-SAR;
Preparation of sarcosine: adding 300kg of methanol and 0.6kg of 5% pd/c catalyst into the prepared Z-SAR, stirring and mixing uniformly, then replacing air in a reaction kettle with nitrogen, repeatedly replacing for 3 times, then introducing hydrogen, maintaining the kettle pressure to be 1.5-1.8 kgf/m 2, intermittently emptying, and carrying out hydrogenolysis reaction; after 12h of hydrogenolysis reaction, detecting by TLC, and stopping the hydrogenolysis reaction if Z-SAR is found in the system and the hydrogenolysis is not completed; then evacuating hydrogen and replacing the gas environment in the reaction kettle with nitrogen, adding a proper amount of pure water for dissolution, filtering to remove the pd/c catalyst, concentrating the filtrate to dryness under negative pressure, recovering methanol, adding 300kg of ethyl acetate for dispersion, cooling to room temperature, centrifuging, rinsing, spin-drying and drying to obtain 62.7kg of white crystal sarcosine, wherein the product content is 89.83%, and the molar yield of the product is 68.4% calculated by sodium sarcosine.
In the above examples and comparative examples, the cosolvent used in example 1 was tetrahydrofuran, and the cosolvent used in example 2 was acetone; no cosolvent was used in the comparative example 1 scheme, and the pd/c catalyst was used in the comparative example 2 scheme in an amount of 5% and in an amount of 0.6kg.
As can be seen from the comparison of examples 1-2 and comparative examples 1-2, in the preparation method of sarcosine provided by the application, in the process of preparing Z-SAR, a cosolvent (such as tetrahydrofuran, acetone, dioxane and the like) needs to be added, otherwise, sodium sarcosine in a system cannot be fully reacted, and the yield and content of the product sarcosine are reduced; the addition amount of the cosolvent is generally 5 to 15%, preferably 10%.
Meanwhile, in the above-mentioned sarcosine preparation step, when the hydrogenolysis reaction is carried out, the catalyst (pd/c catalyst) is used, preferably, the catalyst content is 10%, and the use of 5% pd/c catalyst results in a longer hydrogenolysis time (12 hours), and the final product sarcosine content is also reduced (less than 90%), and the molar yield is also reduced.
In summary, the embodiment of the application provides a preparation method of sarcosine, which takes commercial industrial grade sodium sarcosinate solution as a raw material, utilizes Z-Cl to protect amino groups on sodium sarcosinate, and then utilizes hydrochloric acid to acidify to prepare and obtain Z-SAR which is almost insoluble in water, thereby facilitating separation and impurity removal to obtain a high-purity Z-SAR intermediate product, further being used for preparing the sarcosine, being capable of reducing the introduction of impurities and being beneficial to guaranteeing the quality of the final product of the sarcosine. Then hydrogen is introduced into a catalyst, preferably a pd/c catalyst, to carry out hydrogenolysis reaction on the prepared Z-SAR, so as to generate sarcosine, toluene and carbon dioxide; the byproducts toluene and carbon dioxide can be very easily separated from the amino acid of the product, so that the high-purity and high-quality product sarcosine can be obtained, and the yield of the product sarcosine can be effectively improved. Meanwhile, the whole preparation method has the advantages of simple flow, less resource and energy consumption, less pollutant generated in the process, environmental friendliness, contribution to large-scale production and utilization and popularization and application values.
The embodiments described above are some, but not all embodiments of the application. The detailed description of the embodiments of the application is not intended to limit the scope of the application, as claimed, but is merely representative of selected embodiments of the application. All other embodiments, which can be made by those skilled in the art based on the embodiments of the application without making any inventive effort, are intended to be within the scope of the application.
Claims (10)
1. A method for preparing sarcosine, which is characterized by comprising the following steps:
Z-SAR preparation: adding sodium sarcosinate solution and cosolvent into a reaction kettle, stirring and mixing, then dropwise adding Z-Cl, adding liquid alkali for reaction, adding a first solvent into a reaction system after the reaction is finished, adding hydrochloric acid for acidification, and standing for layering to obtain a water layer and a first solvent layer; extracting the water layer by using a first solvent, combining the extract with the first solvent layer, and concentrating under reduced pressure to remove the first solvent to obtain Z-SAR;
Preparation of sarcosine: adding a second solvent and a catalyst into the prepared Z-SAR, stirring and mixing, then replacing air in a reaction kettle with nitrogen, introducing hydrogen for hydrogenolysis reaction, evacuating the hydrogen after the reaction is finished, replacing the gas environment in the reaction kettle with nitrogen, filtering to remove the catalyst, concentrating the filtrate to dryness under negative pressure, adding the first solvent for dispersion, cooling, and performing aftertreatment to obtain the finished product sarcosine.
2. The method according to claim 1, wherein in the step of preparing the Z-SAR, Z-Cl is added dropwise at 15 to 20 ℃, a liquid alkali is added to control pH to 8 to 9, a reaction temperature is maintained at 15 to 20 ℃ and a reaction system pH is maintained at 8 to 9, and the reaction is performed.
3. The method for producing sarcosine according to claim 1, wherein hydrochloric acid is added to acidify the Z-SAR to a pH of 2 to 3 in the Z-SAR production step.
4. The method for preparing sarcosine according to claim 1, wherein in the step of preparing Z-SAR, the cosolvent is one or more of tetrahydrofuran, acetone, and dioxane.
5. The method according to claim 1, wherein in the Z-SAR preparation step, the first solvent is ethyl acetate.
6. The method for producing sarcosine according to claim 1, wherein in the step of producing sarcosine, hydrogen is introduced to carry out the hydrogenolysis reaction while maintaining the pressure of the reaction vessel at 1.5 to 1.8kgf/m 2, and intermittently discharging the hydrogen.
7. The method according to claim 1, wherein in the step of preparing sarcosine, the second solvent is methanol.
8. The method for preparing sarcosine according to claim 1, wherein in the step of preparing sarcosine, the catalyst is pd/c catalyst.
9. The method according to claim 1, wherein in the step of preparing sarcosine, the first solvent is added to disperse the sarcosine, and the mixture is cooled to room temperature and then subjected to post-treatment.
10. The method for preparing sarcosine according to claim 1, wherein the post-treatment comprises the steps of: centrifuging, rinsing, spin-drying and drying.
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