CN117142965A - Method for preparing tris (hydroxymethyl) aminomethane by continuous flow method - Google Patents
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- 238000000034 method Methods 0.000 title claims abstract description 31
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 title claims abstract description 28
- 238000006243 chemical reaction Methods 0.000 claims abstract description 58
- 239000011259 mixed solution Substances 0.000 claims abstract description 36
- 239000000243 solution Substances 0.000 claims abstract description 36
- 239000003513 alkali Substances 0.000 claims abstract description 15
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000002156 mixing Methods 0.000 claims abstract description 9
- 229930040373 Paraformaldehyde Natural products 0.000 claims abstract description 6
- 229920002866 paraformaldehyde Polymers 0.000 claims abstract description 6
- 239000003054 catalyst Substances 0.000 claims description 40
- 230000035939 shock Effects 0.000 claims description 22
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 17
- 229910021118 PdCo Inorganic materials 0.000 claims description 16
- 239000002585 base Substances 0.000 claims description 15
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 12
- 239000007983 Tris buffer Substances 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 238000004108 freeze drying Methods 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 229910052751 metal Inorganic materials 0.000 claims description 7
- 239000002184 metal Substances 0.000 claims description 7
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- 239000002243 precursor Substances 0.000 claims description 6
- 239000012266 salt solution Substances 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- 239000004744 fabric Substances 0.000 claims description 4
- 238000007710 freezing Methods 0.000 claims description 4
- 230000008014 freezing Effects 0.000 claims description 4
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- 239000001632 sodium acetate Substances 0.000 claims description 3
- 235000017281 sodium acetate Nutrition 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- 239000012670 alkaline solution Substances 0.000 claims 1
- 238000005112 continuous flow technique Methods 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- 230000000052 comparative effect Effects 0.000 description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 239000000047 product Substances 0.000 description 12
- 239000007864 aqueous solution Substances 0.000 description 8
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- 150000001868 cobalt Chemical class 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 5
- 238000012546 transfer Methods 0.000 description 5
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical group [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 4
- 229910000564 Raney nickel Inorganic materials 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000000376 reactant Substances 0.000 description 4
- 239000007868 Raney catalyst Substances 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 229910019041 PtMn Inorganic materials 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
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- 238000011031 large-scale manufacturing process Methods 0.000 description 2
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- 229910000510 noble metal Inorganic materials 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
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- 239000002994 raw material Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- 208000013824 Acidemia Diseases 0.000 description 1
- 208000010444 Acidosis Diseases 0.000 description 1
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- 125000003172 aldehyde group Chemical group 0.000 description 1
- -1 aliphatic nitro compound Chemical class 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 238000007036 catalytic synthesis reaction Methods 0.000 description 1
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- 230000005494 condensation Effects 0.000 description 1
- 238000010924 continuous production Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
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- 229940079593 drug Drugs 0.000 description 1
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Classifications
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- 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
-
- 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
- B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
- B01J23/70—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of the iron group metals or copper
- B01J23/89—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of the iron group metals or copper combined with noble metals
- B01J23/8913—Cobalt and noble metals
-
- 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
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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)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention relates to a method for preparing tris (hydroxymethyl) aminomethane by a continuous flow method, which comprises the following steps: mixing paraformaldehyde with an alkali solution to obtain a first mixed solution; taking the first mixed solution and the nitromethane solution as reaction solutions, introducing the reaction solutions into a first continuous flow reactor at a flow rate of 0.1-1.5 mL/min, and obtaining a second mixed solution after the reaction is finished, wherein the reaction temperature in the first continuous flow reactor is 20-30 ℃; pressurizing the second continuous flow reactor to 2-6 MPa, introducing the second mixed solution into the second continuous flow reactor at the flow rate of 0.1-0.6 mL/min, and obtaining the tris (hydroxymethyl) aminomethane after the reaction is finished, wherein the reaction temperature in the second continuous flow reactor is 40-80 ℃, so that the invention has the advantages of simple operation, high synthesis efficiency and high safety.
Description
Technical Field
The invention relates to the technical field of chemical synthesis, in particular to a method for preparing tris (hydroxymethyl) aminomethane by a continuous flow method.
Background
Tris (hydroxymethyl) aminomethane (Tris) is an important biochemical, chemical and pharmaceutical intermediate, is widely applied to acute metabolic and respiratory acidemia, is an alkaline buffer, has good buffering effect on metabolic enzyme poisoning and enzyme activity reaction, and is commonly applied to detection products such as biochemical diagnosis kits, DNA/RNA extraction kits, PCR diagnosis kits and the like.
Because the traditional synthetic route of Tris series products generally adopts production routes such as large-scale autoclave hydrogenation catalytic synthesis, the autoclave needs a high-temperature high-pressure system, and meanwhile, a large amount of raw materials such as nitromethane, hydrogen and the like are needed, so that the risk of safety is high, the traditional hydrogenation catalytic reduction system uses a noble metal catalyst, and the catalyst is difficult to recycle; the intermittent kettle type reaction needs a large amount of hydrogen, and the utilization rate of raw materials is low; the kettle type production equipment under the high-pressure system has higher maintenance and use cost, thus resulting in low yield of the tris (hydroxymethyl) aminomethane.
Disclosure of Invention
Based on this, it is necessary to provide a method for preparing tris (hydroxymethyl) aminomethane by a continuous flow method, which improves the yield of tris (hydroxymethyl) aminomethane.
In order to achieve the above object, the present invention provides a technical solution:
a method for preparing tris (hydroxymethyl) aminomethane by a continuous flow method, comprising the steps of:
mixing paraformaldehyde with an alkali solution to obtain a first mixed solution;
taking the first mixed solution and the nitromethane solution as reaction solutions, introducing the reaction solutions into a first continuous flow reactor at a flow rate of 0.1-1.5 mL/min, and obtaining a second mixed solution after the reaction is finished, wherein the reaction temperature in the first continuous flow reactor is 20-30 ℃;
pressurizing the second continuous flow reactor to 2-6 MPa, introducing the second mixed solution into the second continuous flow reactor at a flow rate of 0.1-0.6 mL/min, and obtaining the tris (hydroxymethyl) aminomethane after the reaction is finished, wherein the reaction temperature in the second continuous flow reactor is 40-80 ℃.
Preferably, the catalyst comprises a PdCo/C catalyst.
Preferably, the preparation step of the catalyst comprises:
mixing the activated carbon solution and the precursor metal salt solution to obtain a third mixed solution;
freeze-drying the third mixed solution to obtain a sample to be subjected to thermal shock;
and carrying out thermal shock on the sample to be thermally shocked to obtain the PdCo/C catalyst.
Preferably, the specific step of freeze-drying the third mixed solution includes:
and (3) placing the third mixed solution in a freeze dryer, freezing for 3-20 h, and then drying in vacuum for 10-30 h to obtain the sample to be subjected to thermal shock.
The specific steps of carrying out thermal shock on the sample to be thermally shocked include:
and uniformly paving the sample to be subjected to thermal shock on carbon cloth, wherein the impact voltage is 30V, the impact current is 10+ (2 n-1) A, n is the impact times, the impact current is 6s each time, the intermittent time between two adjacent impacts is 10s, and the impact is stopped until the surface temperature of the sample to be subjected to thermal shock reaches 850 ℃, thereby obtaining the PdCo/C catalyst.
Preferably, the equivalent of the alkali in the alkali solution is 0.01 to 0.1.
Preferably, in the alkali solution, the alkali includes at least one of potassium hydroxide, sodium acetate and potassium carbonate.
Preferably, the mass concentration of the substance of the first mixed liquid is 0.1mol/L to 0.5mol/L.
Preferably, the flow rate ratio of the first mixed liquor to the nitromethane solution is 1:1.
Preferably, the flow rate of the hydrogen introduced in the reaction process of the second continuous flow reactor is 10sccm to 50sccm.
The invention has the beneficial effects that:
the invention synthesizes the tris (hydroxymethyl) aminomethane by using a continuous flow reactor, has the characteristics of novel mode, simple and practical operation and higher product quality and yield, thereby reducing the production cost and simultaneously being environment-friendly and less in pollution;
the product obtained by the method is convenient to separate and treat, the process flow is simple to operate, the reaction condition is relatively mild, and the pollution is relatively small. The self-synthesized catalyst greatly reduces the problems of difficult separation of products, low utilization rate of the catalyst and the like. The method can effectively avoid the defect that the existing reaction cannot be produced in a large scale, is more beneficial to realizing the industrial large-scale production requirement, and improves the quality and the yield of tris.
The invention adopts a continuous flow synthesis method, strengthens the mass transfer and heat transfer performance of the reaction, keeps the reaction temperature constant, avoids phenomena of temperature runaway, material flushing, reaction runaway and the like during the reaction, and greatly improves the operability and the safety.
Drawings
FIG. 1 is a nuclear magnetic resonance hydrogen spectrum of the product of the example.
Detailed Description
For a better description of the objects, technical solutions and advantages of the present invention, the present invention will be further described with reference to the following specific examples.
In the examples, the test methods used are conventional methods unless otherwise specified, and the materials, reagents, etc. used are commercially available.
A method for preparing tris (hydroxymethyl) aminomethane by a continuous flow method, comprising the steps of:
s100, mixing paraformaldehyde with an alkali solution to obtain a first mixed solution;
s200, taking the first mixed solution and the nitromethane solution as reaction solutions, introducing the reaction solutions into a first continuous flow reactor at a flow rate of 0.1-1.5 mL/min, and obtaining a second mixed solution after the reaction is finished, wherein the reaction temperature in the first continuous flow reactor is 20-30 ℃; specifically, the molar amounts of paraformaldehyde and nitromethane are (1 to 4): 1.
s300, pressurizing the second continuous flow reactor to 2-6 MPa, introducing the second mixed solution into the second continuous flow reactor at a flow rate of 0.1-0.6 mL/min, and obtaining the tris (hydroxymethyl) aminomethane after the reaction is finished, wherein the reaction temperature in the second continuous flow reactor is 40-80 ℃.
Specifically, the condensation reaction is carried out in a first continuous flow reactor, the catalytic hydrogenation reaction is carried out in a second continuous flow reactor, and the catalytic hydrogenation reaction requires higher temperature and specific pressure (2 MPa-6 MP) to break the N-O bond of the aliphatic nitro compound for further reaction.
The invention synthesizes the tris (hydroxymethyl) aminomethane by using a continuous flow reactor, has the characteristics of novel mode, simple and practical operation and higher product quality and yield, thereby reducing the production cost and simultaneously being environment-friendly and less in pollution;
the product obtained by the method is convenient to separate and treat, the process flow is simple to operate, the reaction condition is relatively mild, and the pollution is relatively small. The self-synthesized catalyst greatly reduces the problems of difficult separation of products, low utilization rate of the catalyst and the like. The method can effectively avoid the defect that the existing reaction cannot be produced in a large scale, is more beneficial to realizing the industrial large-scale production requirement, and improves the quality and the yield of tris.
The invention adopts a continuous flow synthesis method, strengthens the mass transfer and heat transfer performance of the reaction, keeps the reaction temperature constant, avoids phenomena of temperature runaway, material flushing, reaction runaway and the like during the reaction, and greatly improves the operability and the safety.
Compared with the traditional batch reaction process, the continuous flow chemistry has the advantages of higher heat and mass transfer efficiency, narrower residence time, distribution, better repeatability, rapid system response, convenient automatic control, reduced amplification effect, smaller liquid holdup, higher safety and the like, and is very suitable for dangerous chemical reactions with strong heat release, unstable reactants or products, high toxicity and the like. The synthesis of more and more medicines and natural compounds obtains higher yield and purity under the condition of using continuous flow technology, realizes continuous production, reduces production cost and danger coefficient, finally completes reaction amplification production, and realizes industrial application.
The polymerization degree of the polymeric methanol is 1 to 4, and specifically, when the polymerization degree of the polymeric methanol is 3, the procedure for preparing the tris (hydroxymethyl) aminomethane is as follows:
in one embodiment, the catalyst comprises a PdCo/C catalyst. The preparation steps of the catalyst comprise:
mixing the activated carbon solution and the precursor metal salt solution to obtain a third mixed solution;
freeze-drying the third mixed solution to obtain a sample to be subjected to thermal shock;
and carrying out thermal shock on the sample to be thermally shocked to obtain the PdCo/C catalyst.
Specifically, the specific step of freeze-drying the third mixed solution includes:
and (3) placing the third mixed solution in a freeze dryer, freezing for 3-20 h, and then drying in vacuum for 10-30 h to obtain the sample to be subjected to thermal shock.
More specifically, the specific step of thermally shocking the sample to be thermally shocked comprises the following steps:
and uniformly paving the sample to be subjected to thermal shock on carbon cloth, wherein the impact voltage is 30V, the impact current is 10+ (2 n-1) A, n is the impact times, the impact current is 6s each time, the intermittent time between two adjacent impacts is 10s, and the impact is stopped until the surface temperature of the sample to be subjected to thermal shock reaches 850 ℃, thereby obtaining the PdCo/C catalyst.
The precursor metal salt solution comprises a palladium chloride aqueous solution and a cobalt salt aqueous solution; wherein the concentrations of the palladium chloride aqueous solution and the cobalt salt aqueous solution are respectively 0.007-0.150mol/L, and the concentration of the active carbon solution is 1-20mg/mL. The atomic ratio of Pd atoms in the palladium chloride aqueous solution to Co atoms in the cobalt salt aqueous solution is (1-3): 1, a step of; the ratio of the total mass of the palladium chloride and the cobalt salt to the mass of the activated carbon is 1 (5-15).
Specifically, the mass of the catalyst is 0.5 g-0.8 g.
In one embodiment, the equivalent weight of the base in the base solution is 0.01 to 0.1, specifically, equivalent weight (eq) is relative to nitromethane, eq=n base/n nitromethane. The aldehyde group has strong reducibility in the alkali solution, and the alkali solution can provide alkaline conditions and can be used as a catalyst to accelerate the condensation reaction.
Preferably, in the alkali solution, the alkali includes at least one of potassium hydroxide, sodium acetate and potassium carbonate.
In one embodiment, the alkali solution comprises methanol as the solvent.
In one embodiment, the first mixed liquor has an amount concentration of material of 0.1-0.5mol/L.
In one embodiment, the ratio of flow rates of the first mixed liquor and the nitromethane solution is 1:1.
In one embodiment, hydrogen is introduced during the reaction of the second continuous flow reactor.
In one embodiment, the hydrogen flow is 10sccm to 50sccm.
Specifically, before the second continuous flow reactor is pressurized to 2-6 MPa, the air and other impurities in the second continuous flow reactor device need to be thoroughly exhausted, and the specific steps are that methanol washes the second continuous flow reactor for 20-30 min at 4-6mL/min under the condition that the nitrogen flow is 20-30 sccm.
More specifically, the first continuous flow reactor and the second continuous flow reactor are built in the same continuous flow equipment, and are named as the first continuous flow reactor and the second continuous flow reactor for distinguishing reaction stages. The invention is further illustrated by the following examples, which are not intended to limit the invention in any way.
The experimental methods in the following examples are conventional methods unless otherwise specified. In the following examples, three replicates were set up for each quantification assay, and the data were the mean or mean ± standard deviation of the triplicate.
Example 1:
uniformly mixing 36g of paraformaldehyde and 0.45g of KOH in 790g of methanol to obtain a first mixed solution;
reversely putting the first mixed solution and 24.4g nitromethane serving as reaction solutions into corresponding feed inlets of a first continuous flow reactor at a flow rate of 0.2mL/min, setting the temperature of the first continuous flow reactor to be 25 ℃, and waiting for stable reaction to obtain a second mixed solution;
setting the pressure of the second continuous flow reactor to 4MPa, setting the reaction temperature to 50 ℃, introducing the second mixed solution into the second continuous flow reactor at 0.2mL/min and a hydrogen flow rate of 30sccm, adding 0.6g PdCo/C catalyst, collecting a crude product after the reaction reaches a steady state, purifying the crude product to obtain tris (hydroxymethyl) aminomethane, and drying to obtain 42.49g of tris (hydroxymethyl) aminomethane, wherein the yield is 87.8%, and the content is 99.9%.
The preparation procedure for the PdCo/C catalyst in example 1 was as follows:
mixing the activated carbon solution and the precursor metal salt solution to obtain a third mixed solution; wherein the precursor metal salt solution comprises 0.150mol/L palladium chloride aqueous solution and 0.150mol/L cobalt salt aqueous solution
Freeze-drying the third mixed solution to obtain a sample to be subjected to thermal shock; the concentration of the activated carbon solution was 20mg/mL.
And carrying out thermal shock on the sample to be thermally shocked to obtain the PdCo/C catalyst.
Specifically, the specific step of freeze-drying the third mixed solution includes:
and (3) placing the third mixed solution in a freeze dryer, freezing for 15 hours, and then drying in vacuum for 20 hours to obtain the sample to be subjected to thermal shock.
More specifically, the specific step of thermally shocking the sample to be thermally shocked comprises:
and uniformly paving a sample to be subjected to thermal shock on the carbon cloth, wherein the impact voltage is 30V, the impact current is 10+ (2 n-1) A, n is the impact times, the impact current is 6s each time, the intermittent time between two adjacent impacts is 10s, and stopping impacting until the surface temperature of the sample to be subjected to thermal shock reaches 850 ℃, thereby obtaining the PdCo/C catalyst.
Examples 2-21 differ from example 1 in the condition parameters of the second continuous flow reactor. The condition parameters of the second continuous flow reactor in examples 1-21 are shown in Table 1.
TABLE 1 Condition parameters of the second continuous flow reactor of examples 1-21
Comparative example 1 differs from example 4 in that the catalyst was PtMn/C.
Comparative example 2 differs from example 4 in that the catalyst is raney nickel.
Comparative example 3 differs from example 4 in that the catalyst was Pd/C.
The yields of the resulting products of tris (hydroxymethyl) aminomethane of example 4, comparative example 1, comparative example 2, comparative example 3 are shown in table 2.
TABLE 2 Trimethylolaminomethane yield (%)
| Example 4 | 95.3％ |
| Comparative example 1 | 74.38％ |
| Comparative example 2 | 77.9％ |
| Comparative example 3 | 76.4％ |
As can be seen from Table 2, the PdCo/C catalyst can successfully produce tris with yields up to 95.3% higher than the Raney nickel catalyst of comparative example 2; meanwhile, raney nickel is easy to burn when exposed in air, and harmful gas is generated when the Raney nickel burns; prolonged exposure may lead to dangerous properties such as pneumonia and other marked sensitization to nickel-like rashes.
The productivity of the PdCo/C catalyst is higher than that of the Pd/C catalyst of comparative example 3, indicating that doping of non-noble metals can greatly improve the activity of the catalyst, thereby improving the catalytic efficiency; the PtMn/C catalyst higher than that of comparative example 1 shows that the doping metal has different effects on the modification of catalytic activity, and the doping effect of Co is better.
The PdCo/C catalyst has the advantages of stability, safety, easiness in storage and the like, is more suitable for industrial production, and has better catalytic effect than other catalysts.
Examples 22 to 26 differ from example 1 in that the condition parameters of the first continuous flow reactor are different, and the catalysts used in examples 22 to 26 were recovered by washing the catalysts after the reaction in examples 1 to 21. The continuous flow reaction parameters in examples 22-26 are shown in Table 3.
TABLE 3 continuous flow reaction parameters in examples 6-10
It was found that the reaction was sufficiently carried out by reducing the equivalent amount of the base, reducing the reaction flow rate, increasing the reaction temperature, and reducing the concentration of the reactant, and the final yield was improved.
Comparative example 4 differs from example 6 in that the equivalent of the base is 0.04.
Comparative example 5 differs from example 6 in that the equivalent of the base is 0.06.
Comparative example 6 differs from example 6 in that the equivalent of the base is 0.1.
Comparative example 7 differs from example 6 in that the equivalent of base is 0.007.
Comparative example 8 differs from example 6 in that the equivalent of the base is 0.005.
The yields of the resulting products of tris (hydroxymethyl) aminomethane of example 6, comparative example 4, comparative example 5, comparative example 6, comparative example 7 and comparative example 8 are shown in table 4.
TABLE 4 yield of tris (%)
| Example 6 | 92.8％ |
| Comparative example 4 | 88.4％％ |
| Comparative example 5 | 86.2％ |
| Comparative example 6 | 80.9％ |
| Comparative example 7 | 74.4％ |
| Comparative example 8 | 65.3％ |
Excessive amounts of base do not increase the yield of final tris, and the analytical reasons may be that the equivalent amount of base is too large, and formaldehyde is condensed to form byproducts such as hydroxyaldehyde, so that the purity of the reactant in the second step is lowered, and the yield of the final product is lowered. Too low an equivalent of base does not provide a strong alkaline environment, which slows down the condensation rate, and the same reaction time does not allow the reaction to be completed, which reduces the purity of the second step reactant, resulting in a reduced yield of the final product.
If the amount of the base is too large, formaldehyde itself is condensed to produce a byproduct such as hydroxyaldehyde, and if the amount of the base is too small, no reaction occurs.
It should be noted that the specific parameters or some reagents in the above embodiments are specific embodiments or preferred embodiments under the concept of the present invention, and are not limited thereto; and can be adaptively adjusted by those skilled in the art within the concept and the protection scope of the invention.
Claims (10)
1. A method for preparing tris (hydroxymethyl) aminomethane by a continuous flow process, comprising the steps of:
mixing paraformaldehyde with an alkali solution to obtain a first mixed solution;
taking the first mixed solution and the nitromethane solution as reaction solutions, introducing the reaction solutions into a first continuous flow reactor at a flow rate of 0.1-1.5 mL/min, and obtaining a second mixed solution after the reaction is finished, wherein the reaction temperature in the first continuous flow reactor is 20-30 ℃;
pressurizing the second continuous flow reactor to 2-6 MPa, introducing the second mixed solution into the second continuous flow reactor at a flow rate of 0.1-0.6 mL/min, adding a catalyst, and ending the reaction to obtain the tris (hydroxymethyl) aminomethane, wherein the reaction temperature in the second continuous flow reactor is 40-80 ℃.
2. The method of preparing tris according to claim 1, wherein the catalyst comprises PdCo/C catalyst.
3. The method for preparing tris (hydroxymethyl) aminomethane according to claim 2, wherein the step of preparing the catalyst comprises:
mixing the activated carbon solution and the precursor metal salt solution to obtain a third mixed solution;
freeze-drying the third mixed solution to obtain a sample to be subjected to thermal shock;
and carrying out thermal shock on the sample to be thermally shocked to obtain the PdCo/C catalyst.
4. A method for preparing tris according to claim 3, characterized in that the specific step of freeze-drying the third mixed liquor comprises:
and (3) placing the third mixed solution in a freeze dryer, freezing for 3-20 h, and then drying in vacuum for 10-30 h to obtain the sample to be subjected to thermal shock.
5. The method for preparing the tris (hydroxymethyl) aminomethane according to claim 3, wherein the specific step of subjecting the sample to be subjected to thermal shock comprises:
and uniformly paving the sample to be subjected to thermal shock on carbon cloth, wherein the impact voltage is 30V, the impact current is 10+ (2 n-1) A, n is the impact times, the impact current is 6s each time, the intermittent time between two adjacent impacts is 10s, and the impact is stopped until the surface temperature of the sample to be subjected to thermal shock reaches 850 ℃, thereby obtaining the PdCo/C catalyst.
6. The method for preparing tris according to claim 1, wherein the equivalent amount of the base in the alkaline solution is 0.01 to 0.1.
7. The method for preparing tris according to claim 1, wherein the alkali in the alkali solution comprises at least one of potassium hydroxide, sodium acetate and potassium carbonate.
8. The method for producing tris according to claim 1, wherein the mass concentration of the substance in the first mixed solution is 0.1mol/L to 0.5mol/L.
9. The method for preparing tris according to claim 1, wherein the ratio of flow rates of the first mixed liquor and the nitromethane solution is 1:1.
10. The method for preparing the tris (hydroxymethyl) aminomethane according to claim 1, wherein hydrogen is introduced in the reaction process of the second continuous flow reactor, and the flow rate of the hydrogen is 10sccm to 50sccm.
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