CN113200877B - Preparation method of tris (hydroxymethyl) aminomethane - Google Patents
Preparation method of tris (hydroxymethyl) aminomethane Download PDFInfo
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- CN113200877B CN113200877B CN202110558343.XA CN202110558343A CN113200877B CN 113200877 B CN113200877 B CN 113200877B CN 202110558343 A CN202110558343 A CN 202110558343A CN 113200877 B CN113200877 B CN 113200877B
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- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 title claims abstract description 86
- 238000002360 preparation method Methods 0.000 title claims abstract description 34
- 229930040373 Paraformaldehyde Natural products 0.000 claims abstract description 34
- 229920002866 paraformaldehyde Polymers 0.000 claims abstract description 34
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 claims abstract description 33
- 238000007670 refining Methods 0.000 claims abstract description 19
- OLQJQHSAWMFDJE-UHFFFAOYSA-N 2-(hydroxymethyl)-2-nitropropane-1,3-diol Chemical compound OCC(CO)(CO)[N+]([O-])=O OLQJQHSAWMFDJE-UHFFFAOYSA-N 0.000 claims abstract description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 117
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 58
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 57
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 54
- 238000006243 chemical reaction Methods 0.000 claims description 44
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 37
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 30
- 238000001914 filtration Methods 0.000 claims description 27
- 238000003756 stirring Methods 0.000 claims description 27
- 239000012043 crude product Substances 0.000 claims description 24
- 238000005984 hydrogenation reaction Methods 0.000 claims description 23
- 238000006116 polymerization reaction Methods 0.000 claims description 23
- 238000001816 cooling Methods 0.000 claims description 19
- 239000012046 mixed solvent Substances 0.000 claims description 19
- 239000000243 solution Substances 0.000 claims description 19
- 239000013078 crystal Substances 0.000 claims description 18
- 235000006408 oxalic acid Nutrition 0.000 claims description 18
- 239000003513 alkali Substances 0.000 claims description 17
- 238000010438 heat treatment Methods 0.000 claims description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 13
- 230000001376 precipitating effect Effects 0.000 claims description 13
- 238000005086 pumping Methods 0.000 claims description 11
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical group [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims description 9
- 229910000564 Raney nickel Inorganic materials 0.000 claims description 9
- 239000003054 catalyst Substances 0.000 claims description 9
- 239000012295 chemical reaction liquid Substances 0.000 claims description 9
- 238000001035 drying Methods 0.000 claims description 9
- 239000007868 Raney catalyst Substances 0.000 claims description 2
- 230000000052 comparative effect Effects 0.000 description 28
- 239000000047 product Substances 0.000 description 27
- 230000001276 controlling effect Effects 0.000 description 24
- 230000000694 effects Effects 0.000 description 11
- 239000012467 final product Substances 0.000 description 9
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- 239000012535 impurity Substances 0.000 description 6
- 238000006482 condensation reaction Methods 0.000 description 5
- 239000002585 base Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000009833 condensation Methods 0.000 description 3
- 230000005494 condensation Effects 0.000 description 3
- 150000007530 organic bases Chemical class 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 208000010444 Acidosis Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010027417 Metabolic acidosis Diseases 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- -1 inorganic base potassium hydroxide Chemical class 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000010979 pH adjustment Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000013112 stability test Methods 0.000 description 2
- OHVLMTFVQDZYHP-UHFFFAOYSA-N 1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-2-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]ethanone Chemical compound N1N=NC=2CN(CCC=21)C(CN1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)=O OHVLMTFVQDZYHP-UHFFFAOYSA-N 0.000 description 1
- KZEVSDGEBAJOTK-UHFFFAOYSA-N 1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-2-[5-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]-1,3,4-oxadiazol-2-yl]ethanone Chemical compound N1N=NC=2CN(CCC=21)C(CC=1OC(=NN=1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)=O KZEVSDGEBAJOTK-UHFFFAOYSA-N 0.000 description 1
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- WZFUQSJFWNHZHM-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)N1CC2=C(CC1)NN=N2 WZFUQSJFWNHZHM-UHFFFAOYSA-N 0.000 description 1
- IHCCLXNEEPMSIO-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperidin-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1CCN(CC1)CC(=O)N1CC2=C(CC1)NN=N2 IHCCLXNEEPMSIO-UHFFFAOYSA-N 0.000 description 1
- YJLUBHOZZTYQIP-UHFFFAOYSA-N 2-[5-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,3,4-oxadiazol-2-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NN=C(O1)CC(=O)N1CC2=C(CC1)NN=N2 YJLUBHOZZTYQIP-UHFFFAOYSA-N 0.000 description 1
- YLZOPXRUQYQQID-UHFFFAOYSA-N 3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]propan-1-one Chemical compound N1N=NC=2CN(CCC=21)CCC(=O)N1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F YLZOPXRUQYQQID-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical group [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 1
- 208000003826 Respiratory Acidosis Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- FYFFGSSZFBZTAH-UHFFFAOYSA-N methylaminomethanetriol Chemical compound CNC(O)(O)O FYFFGSSZFBZTAH-UHFFFAOYSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- BAVYZALUXZFZLV-UHFFFAOYSA-N mono-methylamine Natural products NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/10—Separation; Purification; Stabilisation; Use of additives
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a preparation method of tris (hydroxymethyl) aminomethane, which comprises the following steps: step A: paraformaldehyde and nitromethane generate tris (hydroxymethyl) nitromethane under alkaline conditions; and B: hydrogenating and reducing the tris (hydroxymethyl) nitromethane to generate a crude tris (hydroxymethyl) aminomethane product; and C: the tris (hydroxymethyl) aminomethane is obtained by refining, the molar yield of the tris (hydroxymethyl) aminomethane obtained by the invention is more than 85%, and the product content reaches 99.95%.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and relates to a preparation method of tris (hydroxymethyl) aminomethane.
Background
Tris (hydroxymethyl) aminomethane is an important biochemical, chemical and pharmaceutical intermediate with the molecular formula of (CH)2OH)3CNH2The compound has a structural formula shown in formula 1, is widely applied to acute metabolic and respiratory acidosis, is an alkaline buffer, has good buffering effect on metabolic acidosis and enzyme activity reaction, and can be used as a reference substance in an acid titration method, and the two applications have high requirements on the content of the acid, generally 99.9-100.1%.
Formula 1
Generally, the preparation of tris (hydroxymethyl) aminomethane uses nitromethane and formaldehyde as raw materials, and the tris (hydroxymethyl) nitromethane is obtained through post-treatment such as condensation, cooling crystallization and the like, and then is reduced to prepare the tris (hydroxymethyl) aminomethane.
Chinese patent CN200610037713.0 discloses that nitromethane and excess paraformaldehyde are used as main raw materials, and condensation reaction is performed at a certain temperature to obtain tris (hydroxymethyl) nitromethane; after the condensation reaction is finished, directly carrying out hydrogenation reduction reaction at a certain temperature and pressure under a solvent and a catalyst, crystallizing and recrystallizing to prepare the trihydroxymethyl aminomethane, wherein the condensation temperature is 40-55 ℃, the reduction temperature is 40-55 ℃, the pressure is 2-3 MPa, the catalyst is a nickel catalyst, the solvent is methanol, the feeding molar ratio of the nitromethane to the paraformaldehyde is 1: 3-4, the product yield is low, the condensation reaction temperature is high, the pressure of the reduction hydrogenation reaction is high, and the method is not suitable for industrial production.
Disclosure of Invention
The invention aims to overcome the defects and provide a preparation method of tris (hydroxymethyl) aminomethane, which has high product yield, high content, low reaction temperature and small hydrogenation pressure.
A preparation method of tris (hydroxymethyl) aminomethane comprises the following steps:
step A: preparation of tris (hydroxymethyl) nitromethane: adding methanol into a reaction kettle, starting stirring, adding paraformaldehyde and alkali, dissolving and stirring for 20-40 minutes until the solution is colorless and transparent; slowly dripping nitromethane, controlling the temperature of dripping nitromethane to be 35 +/-5 ℃, controlling the dripping time to be 1-1.5 hours, controlling the reaction temperature to be 35 +/-5 ℃ after dripping, reacting for 4-6 hours, and adding oxalic acid to adjust the pH to be 8-9.
And B: preparation of crude tris (hydroxymethyl) aminomethane: pumping the reaction liquid in the step (1) into a hydrogenation kettle, adding methanol and a catalyst, controlling the temperature to be 35 +/-5 ℃ and the pressure to be 1.2-1.5Mpa, and hydrogenating for 2-3 hours; and after the hydrogenation is finished, pumping the reaction solution into a decoloring kettle, heating to 55 +/-5 ℃, adding activated carbon for decoloring, filtering to remove the activated carbon, cooling to 0 +/-2 ℃, separating out crystals, and filtering to obtain a crude product of the tris (hydroxymethyl) aminomethane.
And C: refining: adding the crude product of the tris (hydroxymethyl) aminomethane obtained in the step (2) and a mixed solvent into a refining kettle,
heating to 80 +/-2 ℃, stirring for 0.5-1 hour, cooling to 0 +/-2 ℃, separating out crystals, filtering and drying to obtain the tris (hydroxymethyl) aminomethane.
In the step A, the weight ratio of the paraformaldehyde to the nitromethane is (1.65-1.98) to 1, preferably (1.70-1.82) to 1.
In the step A, the weight ratio of the methanol to the nitromethane is (1-3) to 1, preferably (1.70-1.95) to 1.
In the step A, the weight ratio of the alkali to the nitromethane is (1-10) to 1000, preferably (4-8) to 1000.
In the step A, the paraformaldehyde is prepared by dehydrating and polycondensing formaldehyde aqueous solution, and the molecular formula is (CH)2O)nH, wherein n is the degree of polymerization, the paraformaldehyde in the invention is paraformaldehyde with the degree of polymerization of 5-10, and the paraformaldehyde with the degree of polymerization of 7-8 is more preferable.
In the step A, the alkali comprises a combination of inorganic alkali and organic alkali, and the inorganic alkali is selected from sodium hydroxide and potassium hydroxide, preferably potassium hydroxide; the organic base is selected from methylamine, diethylamine, triethylamine and the like, and triethylamine is preferred.
In the step A, the alkali is potassium hydroxide and triethylamine, and the weight ratio of the potassium hydroxide to the triethylamine is 4-5:1, preferably 4.5: 1.
In the step A, the pH is adjusted to 8-9, preferably 8.4-8.6; preferably 8.5.
In the step B, the weight ratio of the methanol to the nitromethane in the step A is 5-10:1, preferably 7-10:1
In the step B, the catalyst is Raney nickel, and the weight ratio of the catalyst to the nitromethane in the step A is (0.1-0.15): 1, preferably 0.12: 1.
In the step C, the weight ratio of the mixed solvent to the nitromethane in the step A is 7-9:1, and preferably 8: 1.
In the step C, the mixed solvent is a mixed solvent of acetone, methanol and water, preferably a mixed solvent of (2-3) to (1-2) to 5 by weight ratio, and more preferably a mixed solvent of acetone, methanol and water by weight ratio of 2.4:1.2: 5.
Compared with the prior art, the invention has the following beneficial effects:
(1) in the step A, paraformaldehyde with a specific polymerization degree and alkali with a specific composition are selected, so that the generation of byproducts is reduced, the condensation reaction is more complete, and the product yield is obviously improved.
(2) In the step A, after condensation is finished, the pH value of the solution is adjusted to 8-9 by oxalic acid, so that the subsequent hydrogenation reaction can be carried out at reduced temperature and pressure, the side reaction of the subsequent hydrogenation reaction can be further reduced, and the product yield is obviously improved.
(3) In the step C, the crude product is purified by adding a mixed solvent of acetone, methanol and water in a specific proportion, so that the use of active carbon is avoided, the content of various impurities is further reduced, and the content of the product reaches more than 99.95 percent.
Under the combined action of the three technical schemes, the molar yield of the obtained tris (hydroxymethyl) aminomethane is more than 85%, and the product content reaches 99.95%.
Detailed Description
The invention discloses a preparation method of tris (hydroxymethyl) aminomethane, which can be realized by combining the relevant principle of organic chemistry and properly improving the process parameters by the technical personnel in the field for reference. It is expressly intended that all such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the scope of the invention. While the invention has been described in terms of preferred embodiments, it will be apparent to those skilled in the art that variations may be applied, or changes and combinations may be made, in the methods and applications described herein to achieve and use the inventive techniques without departing from the spirit, scope, and content of the invention.
For a better understanding of the invention, and not as a limitation on the scope thereof, all numbers expressing quantities, percentages, and other numerical values used in this application are to be understood as being modified in all instances by the term "about". At the very least, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.
The present invention is further illustrated by the following examples, which are not intended to limit the invention in any way.
Example 1; preparation of tris (hydroxymethyl) aminomethane
Step A: preparation of tris (hydroxymethyl) nitromethane: adding 153g of methanol into a reaction kettle, starting stirring, adding 149.6g of paraformaldehyde (with the polymerization degree of 7-8), 0.51g of potassium hydroxide and 0.11g of triethylamine, and dissolving and stirring for 30 minutes until the solution is colorless and transparent; dripping 85g of nitromethane within 1.2 hours, controlling the temperature of dripping the nitromethane within 30-40 ℃, controlling the reaction temperature within 30-40 ℃ after finishing dripping, reacting for 5 hours, and adding oxalic acid to adjust the pH value to 8.5.
And B: preparation of crude tris (hydroxymethyl) aminomethane: putting the reaction liquid in the step (1) into a hydrogenation kettle, adding 750g of methanol and 10.2g of Raney nickel catalyst, controlling the temperature to be 30-40 ℃, the pressure to be 1.3Mpa, and hydrogenating for 2.5 hours; after the hydrogenation is finished, pumping the reaction solution into a decoloring kettle, heating to 50-60 ℃, adding activated carbon for decoloring, filtering to remove the activated carbon, cooling to 0-2 ℃, precipitating crystals, and filtering to obtain a crude product of the tris (hydroxymethyl) aminomethane.
And C: refining: adding the crude product of the tris (hydroxymethyl) aminomethane obtained in the step (2), 190g of acetone, 95g of methanol and 395g of water into a refining kettle, controlling the temperature to be 78-82 ℃, stirring for 0.8 hour, cooling to be 0-2 ℃, separating out crystals, filtering and drying to obtain 151.8g of tris (hydroxymethyl) aminomethane, wherein the molar yield is 90% and the content is 99.99%.
Example 2; preparation of tris (hydroxymethyl) aminomethane
Step A: preparation of tris (hydroxymethyl) nitromethane: adding 157g of methanol into a reaction kettle, starting stirring, adding 149.6g of paraformaldehyde (with the polymerization degree of 7-8), 0.46g of potassium hydroxide and 0.10g of triethylamine, and dissolving and stirring for 30 minutes until the solution is colorless and transparent; dripping 85g of nitromethane within 1.5 hours, controlling the temperature of dripping the nitromethane within 30-40 ℃, controlling the reaction temperature within 30-40 ℃ after finishing dripping, reacting for 5.5 hours, and adding oxalic acid to adjust the pH value to 8.5.
And B: preparation of crude tris (hydroxymethyl) aminomethane: putting the reaction liquid in the step (1) into a hydrogenation kettle, adding 750g of methanol and 11.05g of Raney nickel catalyst, controlling the temperature to be 30-40 ℃, the pressure to be 1.2Mpa, and hydrogenating for 2.7 hours; after the hydrogenation is finished, pumping the reaction solution into a decoloring kettle, heating to 50-60 ℃, adding activated carbon for decoloring, filtering to remove the activated carbon, cooling to 0-2 ℃, precipitating crystals, and filtering to obtain a crude product of the tris (hydroxymethyl) aminomethane.
And C: refining: adding the crude product of the tris (hydroxymethyl) aminomethane obtained in the step (2), 202g of acetone, 101g of methanol and 420g of water into a refining kettle, heating to 78-82 ℃, stirring for 0.7 h, cooling to 0-2 ℃, precipitating crystals, filtering, and drying to obtain 149.3g of tris (hydroxymethyl) aminomethane, wherein the molar yield is 88.5%, and the content is 99.96%.
Example 3; preparation of tris (hydroxymethyl) aminomethane
Step A: preparation of tris (hydroxymethyl) nitromethane: adding 153g of methanol into a reaction kettle, starting stirring, adding 149.6g of paraformaldehyde (with the polymerization degree of 7-8), 0.51g of potassium hydroxide and 0.11g of triethylamine, and dissolving and stirring for 30 minutes until the solution is colorless and transparent; dripping 85g of nitromethane within 1.2 hours, controlling the temperature of dripping the nitromethane within 30-40 ℃, controlling the reaction temperature within 30-40 ℃ after finishing dripping, reacting for 5 hours, and adding oxalic acid to adjust the pH value to 8.5.
And B: preparation of crude tris (hydroxymethyl) aminomethane: putting the reaction liquid in the step (1) into a hydrogenation kettle, adding 710g of methanol and 8.5g of Raney nickel catalyst, controlling the temperature to be 30-40 ℃, the pressure to be 1.2Mpa, and hydrogenating for 3 hours; after the hydrogenation is finished, pumping the reaction solution into a decoloring kettle, heating to 50-60 ℃, adding activated carbon for decoloring, filtering to remove the activated carbon, cooling to 0-2 ℃, precipitating crystals, and filtering to obtain a crude product of the tris (hydroxymethyl) aminomethane.
And C: refining: adding the crude product of the tris (hydroxymethyl) aminomethane obtained in the step (2), 166g of acetone, 83g of methanol and 346g of water into a refining kettle, heating to 78-82 ℃, stirring for 1 hour, cooling to 0-2 ℃, separating out crystals, filtering, and drying to obtain 149.3g of tris (hydroxymethyl) aminomethane, wherein the molar yield is 88.5%, and the content is 99.97%.
Example 4; preparation of tris (hydroxymethyl) aminomethane
Step A: preparation of tris (hydroxymethyl) nitromethane: adding 157g of methanol into a reaction kettle, starting stirring, adding 149.6g of paraformaldehyde (with the polymerization degree of 7-8), 0.46g of potassium hydroxide and 0.10g of triethylamine, and dissolving and stirring for 30 minutes until the solution is colorless and transparent; dripping 85g of nitromethane within 1.5 hours, controlling the temperature of dripping the nitromethane within 30-40 ℃, controlling the reaction temperature within 30-40 ℃ after finishing dripping, reacting for 5.5 hours, and adding oxalic acid to adjust the pH value to 8.5.
And B: preparation of crude tris (hydroxymethyl) aminomethane: putting the reaction liquid in the step (1) into a hydrogenation kettle, adding 800g of methanol and 12.75g of Raney nickel catalyst, controlling the temperature to be 30-40 ℃, the pressure to be 1.5Mpa, and hydrogenating for 2 hours; after the hydrogenation is finished, pumping the reaction solution into a decoloring kettle, heating to 50-60 ℃, adding activated carbon for decoloring, filtering to remove the activated carbon, cooling to 0-2 ℃, precipitating crystals, and filtering to obtain a crude product of the tris (hydroxymethyl) aminomethane.
And C: refining: adding the crude product of the tris (hydroxymethyl) aminomethane obtained in the step (2), 213g of acetone, 107g of methanol and 445g of water into a refining kettle, heating to 78-82 ℃, stirring for 0.5 hour, cooling to 0-2 ℃, precipitating crystals, filtering, and drying to obtain 148.4g of tris (hydroxymethyl) aminomethane, wherein the molar yield is 88%, and the content is 99.98%.
Example 5; preparation of tris (hydroxymethyl) aminomethane
Step A: preparation of tris (hydroxymethyl) nitromethane: adding 143g of methanol into a reaction kettle, starting stirring, adding 144.93g of paraformaldehyde (with the polymerization degree of 7-8), 0.425g of potassium hydroxide and 0.11g of triethylamine, and dissolving and stirring for 40 minutes until the solution is colorless and transparent; dripping 85g of nitromethane within 1.5 hours, controlling the temperature of dripping the nitromethane within 30-40 ℃, controlling the reaction temperature within 30-40 ℃ after finishing dripping, reacting for 4.5 hours, and adding oxalic acid to adjust the pH value to 8.4.
And B: preparation of crude tris (hydroxymethyl) aminomethane: putting the reaction liquid in the step (1) into a hydrogenation kettle, adding 750g of methanol and 10.2g of Raney nickel catalyst, controlling the temperature to be 30-40 ℃, the pressure to be 1.3Mpa, and hydrogenating for 2.5 hours; after the hydrogenation is finished, pumping the reaction solution into a decoloring kettle, heating to 50-60 ℃, adding activated carbon for decoloring, filtering to remove the activated carbon, cooling to 0-2 ℃, precipitating crystals, and filtering to obtain a crude product of the tris (hydroxymethyl) aminomethane.
And C: refining: adding the crude product of the tris (hydroxymethyl) aminomethane obtained in the step (2), 190g of acetone, 95g of methanol and 395g of water into a refining kettle, heating to 78-82 ℃, stirring for 0.8 hour, cooling to 0-2 ℃, precipitating crystals, filtering, and drying to obtain 147.6g of tris (hydroxymethyl) aminomethane, wherein the molar yield is 87.5%, and the content is 99.96%.
Example 6; preparation of tris (hydroxymethyl) aminomethane
Step A: preparation of tris (hydroxymethyl) nitromethane: adding 165g of methanol into a reaction kettle, starting stirring, adding 154.28g of paraformaldehyde (with the polymerization degree of 7-8), 0.595g of potassium hydroxide and 0.12g of triethylamine, dissolving and stirring for 20 minutes until the solution is colorless and transparent; dripping 85g of nitromethane for 1 hour, controlling the temperature of dripping the nitromethane to be 30-40 ℃, controlling the reaction temperature to be 30-40 ℃ after finishing dripping, reacting for 6 hours, and adding oxalic acid to adjust the pH to be 8.6.
And B: preparation of crude tris (hydroxymethyl) aminomethane: putting the reaction liquid in the step (1) into a hydrogenation kettle, adding 750g of methanol and 11.05g of Raney nickel catalyst, controlling the temperature to be 30-40 ℃, the pressure to be 1.2Mpa, and hydrogenating for 2.7 hours; after the hydrogenation is finished, pumping the reaction solution into a decoloring kettle, heating to 50-60 ℃, adding activated carbon for decoloring, filtering to remove the activated carbon, cooling to 0-2 ℃, precipitating crystals, and filtering to obtain a crude product of the tris (hydroxymethyl) aminomethane.
And C: refining: adding the crude product of the tris (hydroxymethyl) aminomethane obtained in the step (2), 202g of acetone, 101g of methanol and 420g of water into a refining kettle, heating to 78-82 ℃, stirring for 0.7 h, cooling to 0-2 ℃, precipitating crystals, filtering, and drying to obtain 146.8g of tris (hydroxymethyl) aminomethane, wherein the molar yield is 87%, and the content is 99.97%.
Example 7; preparation of tris (hydroxymethyl) aminomethane
Step A: preparation of tris (hydroxymethyl) nitromethane: adding 1.8Kg of methanol into a reaction kettle, starting stirring, adding 1.76Kg of paraformaldehyde (with the polymerization degree of 7-8), 60g of potassium hydroxide and 13.33g of triethylamine, dissolving and stirring for 30 minutes until the solution is colorless and transparent; dropping nitromethane 1.0Kg in 1.2 hr at 30-40 deg.c, reacting at 30-40 deg.c for 5 hr, and regulating pH to 8.5 with oxalic acid.
And B: preparation of crude tris (hydroxymethyl) aminomethane: putting the reaction liquid in the step (1) into a hydrogenation kettle, adding 9Kg of methanol and 1200g of Raney nickel catalyst, controlling the temperature to be 30-40 ℃, the pressure to be 1.3Mpa, and hydrogenating for 2.5 hours; after the hydrogenation is finished, pumping the reaction solution into a decoloring kettle, heating to 50-60 ℃, adding activated carbon for decoloring, filtering to remove the activated carbon, cooling to 0-2 ℃, precipitating crystals, and filtering to obtain a crude product of the tris (hydroxymethyl) aminomethane.
And C: refining: adding the crude product of the tris (hydroxymethyl) aminomethane obtained in the step (2), 2.2Kg of acetone, 1.1Kg of methanol and 4.7Kg of water into a refining kettle, heating to 78-82 ℃, stirring for 0.8 hour, cooling to 0-2 ℃, separating out crystals, filtering, and drying to obtain 1.79Kg of tris (hydroxymethyl) aminomethane with the yield of 90% and the content of 99.99%.
Comparative example 1: influence of polymerization degree of paraformaldehyde on product yield and content in step A
The polymerization degree of paraformaldehyde in step A is shown in Table 1, which is otherwise the same as in example 1.
Table 1: effect of polymerization degree of Paraformaldehyde in step A of comparative example 1 on reaction yield
From Table 1 in combination with examples 1 to 6: the polymerization degree of paraformaldehyde in the step A influences the yield and the content of the final product of the tris (hydroxymethyl) aminomethane, namely, when the polymerization degree of paraformaldehyde in the step A is lower than 5 (as in a comparative example 1-1), the yield of the prepared product of the tris (hydroxymethyl) aminomethane is lower than 85%, and the content of the prepared product of the tris (hydroxymethyl) aminomethane is lower than 99.95%; ② when the polymerization degree of the paraformaldehyde in the step A is 5-10 (such as comparative examples 1-2, comparative examples 1-3 and example 1), the yield of the prepared product of the tris (hydroxymethyl) aminomethane is not less than 85 percent, and the content is more than 99.95 percent; especially when the polymerization degree of the paraformaldehyde in the step A is 7-8 (example 1), the yield of the prepared product, namely the tris (hydroxymethyl) aminomethane, is 90 percent, and the content is 99.99 percent; ③ when the polymerization degree of the paraformaldehyde in the step A is higher than 12 (as in comparative examples 1 to 4), the yield of the prepared product of the tris (hydroxymethyl) aminomethane is lower than 80 percent and the yield is lower.
The paraformaldehyde is therefore a paraformaldehyde with a degree of polymerization of 5 to 10, more preferably a paraformaldehyde with a degree of polymerization of 7 to 8.
Comparative example 2: effect of step A use of base on product yield and content
The base and weight used in step A are shown in Table 2, the remainder being the same as in example 1.
Table 2: effect of Using base in step A of comparative example 2 on reaction yield
From Table 2 in combination with examples 1-6, it can be seen that: the yield and the content of the final product of the tris (hydroxymethyl) aminomethane are influenced by using the alkali in the step A, namely, when only the inorganic alkali or the organic alkali is used in the step A (such as only the inorganic alkali potassium hydroxide in a comparative example 2-1 and only the organic alkali triethylamine in a comparative example 2-2), the yield of the prepared product of the tris (hydroxymethyl) aminomethane is lower than 80 percent, and the content of the prepared product of the tris (hydroxymethyl) aminomethane is lower than 99.95 percent; secondly, when the inorganic base potassium hydroxide and the organic base triethylamine are used in the step A (such as comparative examples 2-3, comparative examples 2-4, examples 2-5 and example 1), the weight ratio of the two influences the yield and the content of the product; when the weight ratio of the potassium hydroxide to the triethylamine is lower than 4:1 or higher than 5:1, the yield of the prepared product, namely the tris (hydroxymethyl) aminomethane, is lower than 80 percent, and the content of the tris (hydroxymethyl) aminomethane is lower than 99.95 percent; ③ when the step A uses the inorganic base potassium hydroxide and the organic base diethylamine, the yield of the prepared product, namely the tris (hydroxymethyl) aminomethane, is lower than 85 percent and lower than the yield.
In the step A, the alkali is a composition of potassium hydroxide and triethylamine, and the weight ratio of the potassium hydroxide to the triethylamine is 4-5:1, preferably 4.5: 1.
Comparative example 3: effect of step A reaction temperature on product yield and content
The reaction temperature in step A is shown in Table 3, and the rest is the same as in example 1.
Table 3: effect of Using base in step A on reaction yield in comparative example 3
From Table 3 in combination with examples 1 to 6: the reaction temperature in the step A influences the yield and the content of the final product of the tris (hydroxymethyl) aminomethane, and when the reaction temperature in the step A is higher than 40 ℃ or lower than 30 ℃, the yield of the prepared product of the tris (hydroxymethyl) aminomethane is lower than 85 percent and the yield is lower. The reaction temperature is therefore preferably from 30 ℃ to 40 ℃.
Comparative example 4: effect of pH adjustment with oxalic acid on yield in step A
Step A the pH was adjusted with oxalic acid as shown in Table 4, the same as in example 1.
Table 4: effect of pH adjustment with oxalic acid on yield in step A of comparative example 4
From Table 4 in combination with examples 1 to 6, it can be seen that: regulating the pH value by using oxalic acid to influence the yield of the final product of the tris (hydroxymethyl) aminomethane, namely directly performing the step B after the condensation reaction in the step A is finished, and when the step of regulating the pH value by using oxalic acid is not used (such as a comparative example 4-1), the yield of the prepared product of the tris (hydroxymethyl) aminomethane is lower than 80 percent; ② when the pH value of the step A is adjusted to be lower than 8 or higher than 9 by oxalic acid (such as comparative example 4-2 and comparative example 4-3), the yield of the prepared product of the tris (hydroxymethyl) aminomethane is lower than 80 percent; ③ when the pH value is adjusted to 8.5 by hydrochloric acid in the step A, the yield of the prepared product, namely the tris (hydroxymethyl) aminomethane, is lower than 85 percent and lower; (iv) when the pH value is adjusted to 8-9 by oxalic acid in the step A (as in examples 1-6), the yield of the prepared product of the tris (hydroxymethyl) aminomethane is higher than 85 percent and the content is higher than 99.95 percent. Thus, step A is adjusted to a pH of 8-9, preferably 8.4-8.6, more preferably 8.5, using oxalic acid.
Comparative example 5: influence of reaction temperature and pressure on the yield in step B
The reaction temperature and pressure in step B are shown in Table 5, and the same procedure as in example 1 was repeated.
Table 5: effect of reaction temperature and pressure on yield in step B of comparative example 5
From Table 5 in combination with examples 1-6, it can be seen that: and B, the yield and the content of the final product of the tris (hydroxymethyl) aminomethane are influenced by the reaction temperature and the reaction pressure in the step B, the reaction temperature in the step B is increased or the reaction pressure in the step B is increased, and the yield of the prepared product of the tris (hydroxymethyl) aminomethane is lower than 85%. Therefore, the reaction temperature in the step B is preferably 30-40 ℃ and the pressure is 1.2-1.5 MPa.
Comparative example 6: effect of Mixed solvent on product content in step C
The kind and amount of the mixed solvent used in step C are shown in Table 6, and the procedure was otherwise the same as in example 1.
Table 6: effect of step C Mixed solvent on product content in comparative example 6
As can be seen from Table 6 in conjunction with examples 1-6, the crude products differ in their impurity removal capacity for different solvents: firstly, when solvents such as water, methanol and the like are used independently (such as a comparative example 6-1 and a comparative example 6-2), impurities in a crude product cannot be effectively removed, and the content of the tris (hydroxymethyl) aminomethane in a final product is lower than 99.7%; ② when the mixed solvent of acetone and water or the mixed solvent of methanol and water is used (such as comparative example 6-3 and comparative example 6-4), the impurities in the crude product can not be effectively removed, and the content of the final product of tris (hydroxymethyl) aminomethane is less than 99.8%; ③ when the mixed solvent of acetone, methanol and water with the weight ratio of 1.2:2.4:5 or 1:1:2 is used (such as comparative examples 6-5 and 6-6), the impurities in the crude product can not be effectively removed, and the content of the tris (hydroxymethyl) aminomethane in the final product is lower than 99.9 percent; (iv) when a mixed solvent of acetone, methanol and water in a weight ratio of 2.4:1.2:5 is used (as in examples 1 to 6), impurities in the crude product can be effectively removed, and the content of tris (hydroxymethyl) aminomethane in the final product is less than 99.95%.
Example 7: stability test
Example 1-tris (hydroxymethyl) aminomethane obtained in example 6 at a temperature of 40 ℃. + -. 2 ℃; the samples were taken at 75% + -5% (accelerated) relative humidity for 6 months and measured for the content at the end of 0 and 6 months, and the results are shown in Table 7.
Table 7: stability test results table
The tris (hydroxymethyl) aminomethane prepared in the examples 1-6 of the invention is stored for 6 months under an accelerated condition, the content of the tris (hydroxymethyl) aminomethane meets the standard, no obvious change exists, and the quality of the tris (hydroxymethyl) aminomethane prepared by the invention is stable.
Claims (7)
1. A preparation method of tris (hydroxymethyl) aminomethane is characterized by comprising the following steps:
step A: preparation of tris (hydroxymethyl) nitromethane: adding methanol into a reaction kettle, starting stirring, adding paraformaldehyde and alkali, dissolving and stirring for 20-40 minutes until the solution is colorless and transparent; slowly dripping nitromethane, controlling the temperature of dripping nitromethane to be 35 +/-5 ℃, controlling the dripping time to be 1-1.5 hours, controlling the reaction temperature to be 35 +/-5 ℃ after dripping, reacting for 4-6 hours, and adding oxalic acid to adjust the pH to be 8-9;
and B: preparation of crude tris (hydroxymethyl) aminomethane: pumping the reaction liquid in the step (1) into a hydrogenation kettle, adding methanol and a catalyst, controlling the temperature to be 35 +/-5 ℃ and the pressure to be 1.2-1.5Mpa, and hydrogenating for 2-3 hours; after the hydrogenation is finished, pumping the reaction solution into a decoloring kettle, heating to 55 +/-5 ℃, adding activated carbon for decoloring, filtering to remove the activated carbon, cooling to 0 +/-2 ℃, precipitating crystals, and filtering to obtain a crude product of the tris (hydroxymethyl) aminomethane;
and C: refining: adding the crude product of the tris (hydroxymethyl) aminomethane obtained in the step (2) and a mixed solvent into a refining kettle,
heating to 80 + -2 deg.C, stirring for 0.5-1 hr, cooling to 0 + -2 deg.C, precipitating crystal, filtering, and drying to obtain tris (hydroxymethyl) aminomethane;
in the step A, the weight ratio of paraformaldehyde to nitromethane is (1.70-1.82) to 1;
in the step A, the weight ratio of the methanol to the nitromethane is (1.70-1.95) to 1;
in the step A, the weight ratio of the alkali to the nitromethane is (4-8) 1000;
in the step A, the paraformaldehyde is paraformaldehyde with the polymerization degree of 5-10;
in the step A, the alkali is potassium hydroxide and triethylamine, and the weight ratio of the potassium hydroxide to the triethylamine is 4-5: 1;
in the step B, the weight ratio of the methanol added in the step B to the nitromethane in the step A is 7-10: 1;
in the step B, the catalyst is Raney nickel, and the weight ratio of the catalyst to the nitromethane in the step A is (0.1-0.15): 1;
in the step C, the mixed solvent is a mixed solvent of acetone, methanol and water in a volume ratio of (2-3) to (1-2) to 5.
2. The method according to claim 1, wherein in the step A, the paraformaldehyde is a paraformaldehyde having a polymerization degree of 7 to 8.
3. The method according to claim 1, wherein in step A, the weight ratio of potassium hydroxide to triethylamine is 4.5: 1.
4. The method according to claim 1, wherein the pH is adjusted to 8.4 to 8.6 in step A to 8 to 9.
5. The method according to claim 1, wherein the pH is adjusted to 8 to 9 in step A to 8.5.
6. The method according to claim 1, wherein the weight ratio of the catalyst to the nitromethane in step A in step B is 0.12: 1.
7. the method according to claim 1, wherein in the step C, the mixed solvent is a mixed solvent of acetone, methanol and water in a weight ratio of 2.4:1.2: 5.
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Denomination of invention: A Preparation Method of Trihydroxymethylaminomethane Granted publication date: 20220415 Pledgee: China Everbright Bank Handan branch Pledgor: SHEXIAN JINDONG ECONOMIC AND TRADE CO.,LTD. Registration number: Y2024980006363 |