CN114029089A - Preparation method of catalyst for synthesizing folic acid by oxidizing 6-R-tetrahydrofolic acid - Google Patents
Preparation method of catalyst for synthesizing folic acid by oxidizing 6-R-tetrahydrofolic acid Download PDFInfo
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- CN114029089A CN114029089A CN202111559660.XA CN202111559660A CN114029089A CN 114029089 A CN114029089 A CN 114029089A CN 202111559660 A CN202111559660 A CN 202111559660A CN 114029089 A CN114029089 A CN 114029089A
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- folic acid
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- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 title claims abstract description 104
- 239000003054 catalyst Substances 0.000 title claims abstract description 64
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 title claims abstract description 52
- 229960000304 folic acid Drugs 0.000 title claims abstract description 52
- 235000019152 folic acid Nutrition 0.000 title claims abstract description 52
- 239000011724 folic acid Substances 0.000 title claims abstract description 52
- MSTNYGQPCMXVAQ-NEPJUHHUSA-N 6R-Tetrahydrofolic acid Chemical compound C([C@@H]1CNC=2N=C(NC(=O)C=2N1)N)NC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 MSTNYGQPCMXVAQ-NEPJUHHUSA-N 0.000 title claims abstract description 18
- 230000001590 oxidative effect Effects 0.000 title claims abstract description 17
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 52
- 239000002131 composite material Substances 0.000 claims abstract description 48
- 238000000034 method Methods 0.000 claims abstract description 31
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims abstract description 29
- 238000006243 chemical reaction Methods 0.000 claims abstract description 12
- YNHJECZULSZAQK-UHFFFAOYSA-N tetraphenylporphyrin Chemical compound C1=CC(C(=C2C=CC(N2)=C(C=2C=CC=CC=2)C=2C=CC(N=2)=C(C=2C=CC=CC=2)C2=CC=C3N2)C=2C=CC=CC=2)=NC1=C3C1=CC=CC=C1 YNHJECZULSZAQK-UHFFFAOYSA-N 0.000 claims abstract description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000002994 raw material Substances 0.000 claims abstract description 6
- 238000010992 reflux Methods 0.000 claims abstract description 6
- 238000001914 filtration Methods 0.000 claims abstract description 5
- 238000003756 stirring Methods 0.000 claims abstract description 5
- 239000012153 distilled water Substances 0.000 claims abstract description 3
- 238000001291 vacuum drying Methods 0.000 claims abstract description 3
- 238000005406 washing Methods 0.000 claims abstract description 3
- MQRWBMAEBQOWAF-UHFFFAOYSA-N acetic acid;nickel Chemical compound [Ni].CC(O)=O.CC(O)=O MQRWBMAEBQOWAF-UHFFFAOYSA-N 0.000 claims abstract 6
- 229940071125 manganese acetate Drugs 0.000 claims abstract 6
- UOGMEBQRZBEZQT-UHFFFAOYSA-L manganese(2+);diacetate Chemical compound [Mn+2].CC([O-])=O.CC([O-])=O UOGMEBQRZBEZQT-UHFFFAOYSA-L 0.000 claims abstract 6
- 229940078494 nickel acetate Drugs 0.000 claims abstract 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract 4
- 238000003786 synthesis reaction Methods 0.000 claims description 23
- 230000015572 biosynthetic process Effects 0.000 claims description 22
- 239000000047 product Substances 0.000 claims description 20
- 230000035484 reaction time Effects 0.000 claims description 16
- 238000007254 oxidation reaction Methods 0.000 claims description 15
- 239000000243 solution Substances 0.000 claims description 9
- 230000003647 oxidation Effects 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 3
- 239000011259 mixed solution Substances 0.000 claims description 2
- 239000011148 porous material Substances 0.000 claims description 2
- 239000013065 commercial product Substances 0.000 claims 1
- 150000004685 tetrahydrates Chemical class 0.000 claims 1
- 230000003197 catalytic effect Effects 0.000 abstract description 2
- 238000007670 refining Methods 0.000 abstract description 2
- 230000000694 effects Effects 0.000 description 15
- 229940082328 manganese acetate tetrahydrate Drugs 0.000 description 15
- CESXSDZNZGSWSP-UHFFFAOYSA-L manganese(2+);diacetate;tetrahydrate Chemical compound O.O.O.O.[Mn+2].CC([O-])=O.CC([O-])=O CESXSDZNZGSWSP-UHFFFAOYSA-L 0.000 description 15
- 229940078487 nickel acetate tetrahydrate Drugs 0.000 description 14
- OINIXPNQKAZCRL-UHFFFAOYSA-L nickel(2+);diacetate;tetrahydrate Chemical compound O.O.O.O.[Ni+2].CC([O-])=O.CC([O-])=O OINIXPNQKAZCRL-UHFFFAOYSA-L 0.000 description 14
- 229960002163 hydrogen peroxide Drugs 0.000 description 13
- 230000008569 process Effects 0.000 description 10
- MSTNYGQPCMXVAQ-KIYNQFGBSA-N 5,6,7,8-tetrahydrofolic acid Chemical compound N1C=2C(=O)NC(N)=NC=2NCC1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 MSTNYGQPCMXVAQ-KIYNQFGBSA-N 0.000 description 9
- 238000004519 manufacturing process Methods 0.000 description 7
- 239000007800 oxidant agent Substances 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 3
- 239000002808 molecular sieve Substances 0.000 description 3
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 3
- HNXQXTQTPAJEJL-UHFFFAOYSA-N 2-aminopteridin-4-ol Chemical compound C1=CN=C2NC(N)=NC(=O)C2=N1 HNXQXTQTPAJEJL-UHFFFAOYSA-N 0.000 description 2
- 229940105150 5-methyltetrahydrofolic acid Drugs 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 229910001437 manganese ion Inorganic materials 0.000 description 2
- KMUONIBRACKNSN-UHFFFAOYSA-N potassium dichromate Chemical compound [K+].[K+].[O-][Cr](=O)(=O)O[Cr]([O-])(=O)=O KMUONIBRACKNSN-UHFFFAOYSA-N 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- MSTNYGQPCMXVAQ-RYUDHWBXSA-N (6S)-5,6,7,8-tetrahydrofolic acid Chemical compound C([C@H]1CNC=2N=C(NC(=O)C=2N1)N)NC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 MSTNYGQPCMXVAQ-RYUDHWBXSA-N 0.000 description 1
- GADGMZDHLQLZRI-VIFPVBQESA-N N-(4-aminobenzoyl)-L-glutamic acid Chemical compound NC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 GADGMZDHLQLZRI-VIFPVBQESA-N 0.000 description 1
- VEQPNABPJHWNSG-UHFFFAOYSA-N Nickel(2+) Chemical compound [Ni+2] VEQPNABPJHWNSG-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000003889 chemical engineering Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- OZRNSSUDZOLUSN-LBPRGKRZSA-N dihydrofolic acid Chemical compound N=1C=2C(=O)NC(N)=NC=2NCC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OZRNSSUDZOLUSN-LBPRGKRZSA-N 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000009878 intermolecular interaction Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- IPFASKMZBDWRNG-UHFFFAOYSA-N manganese 5,10,15,20-tetraphenyl-21,23-dihydroporphyrin Chemical compound [Mn].c1cc2nc1c(-c1ccccc1)c1ccc([nH]1)c(-c1ccccc1)c1ccc(n1)c(-c1ccccc1)c1ccc([nH]1)c2-c1ccccc1 IPFASKMZBDWRNG-UHFFFAOYSA-N 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- HDVPIMZXLWNIIP-UHFFFAOYSA-N nickel 5,10,15,20-tetraphenyl-21,23-dihydroporphyrin Chemical compound [Ni].c1cc2nc1c(-c1ccccc1)c1ccc([nH]1)c(-c1ccccc1)c1ccc(n1)c(-c1ccccc1)c1ccc([nH]1)c2-c1ccccc1 HDVPIMZXLWNIIP-UHFFFAOYSA-N 0.000 description 1
- 229910001453 nickel ion Inorganic materials 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000004032 porphyrins Chemical group 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000036632 reaction speed Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D475/00—Heterocyclic compounds containing pteridine ring systems
- C07D475/02—Heterocyclic compounds containing pteridine ring systems with an oxygen atom directly attached in position 4
- C07D475/04—Heterocyclic compounds containing pteridine ring systems with an oxygen atom directly attached in position 4 with a nitrogen atom directly attached in position 2
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
- B01J31/1805—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms the ligands containing nitrogen
- B01J31/181—Cyclic ligands, including e.g. non-condensed polycyclic ligands, comprising at least one complexing nitrogen atom as ring member, e.g. pyridine
- B01J31/1825—Ligands comprising condensed ring systems, e.g. acridine, carbazole
- B01J31/183—Ligands comprising condensed ring systems, e.g. acridine, carbazole with more than one complexing nitrogen atom, e.g. phenanthroline
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/70—Oxidation reactions, e.g. epoxidation, (di)hydroxylation, dehydrogenation and analogues
-
- 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
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/70—Complexes comprising metals of Group VII (VIIB) as the central metal
- B01J2531/72—Manganese
-
- 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
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/80—Complexes comprising metals of Group VIII as the central metal
- B01J2531/84—Metals of the iron group
- B01J2531/847—Nickel
Abstract
The invention mainly relates to a preparation method of a supported composite catalyst for synthesizing folic acid by oxidizing 6-R-tetrahydrofolic acid. The preparation of the supported composite catalyst for synthesizing folic acid by oxidizing 6-R-tetrahydrofolic acid is realized according to the following method: suspending a certain amount of SBA-15 molecular sieve in 10 times volume of chloroform/ethanol (2:1) solution, adding a certain amount of tetraphenylporphyrin, dissolving under stirring, refluxing for 2 hours, adding a certain amount of ethanol/water (5:1) solution of nickel acetate and manganese acetate, and continuously refluxing for 4 hours. Filtering, washing with distilled water for 3 times, and vacuum drying to obtain the supported composite catalyst. The catalyst is used in the reaction of synthesizing folic acid by oxidizing 6-R-tetrahydrofolic acid hydrogen peroxide, and has good catalytic effect. The purity of the obtained folic acid product after refining can reach more than 98.5 percent and the yield is more than 90 percent by using the catalyst with 2 percent of the weight of the raw materials.
Description
Technical Field
The invention relates to a preparation method of a supported composite catalyst for synthesizing folic acid by oxidizing 6-R-tetrahydrofolic acid, belonging to the technical field of fine chemical engineering.
Background
In the process of synthesizing 6-S-5-methyltetrahydrofolic acid by taking folic acid as a raw material, when folic acid is reduced into 6-R, S-tetrahydrofolic acid and the 6-S-tetrahydrofolic acid is obtained by splitting, a large amount of 6-R-tetrahydrofolic acid without biological activity is produced as a byproduct. As other purposes are not found at present, the waste water can only be treated as production waste, and the treatment process not only increases the production cost, but also brings about a larger environmental problem.
In order to solve the problem, one effective method is to obtain folic acid from 6-R-5-tetrahydrofolic acid through catalytic oxidation, and the folic acid is used as a production raw material and returned to the production flow of 6-S-5-methyltetrahydrofolic acid, so that a byproduct treatment process is omitted, the production cost is reduced, and the environmental risk is eliminated.
The tetrahydrofolic acid is a compound which is extremely unstable to an oxidant and can be oxidized by air in the standing process, and the tetrahydrofolic acid can be oxidized by common oxidants such as potassium permanganate, potassium dichromate, nitric acid, hydrogen peroxide and the like. However, the selectivity of the oxidation products of tetrahydrofolic acid is very poor, and the oxidation products obtained by various oxidants under common conditions are complex mixtures, including folic acid, dihydrofolic acid, pterin, p-aminobenzoylglutamic acid and the like, and have no synthetic significance. Therefore, how to improve the selectivity of the tetrahydrofolic acid oxidation product is the technical key to be solved by the invention.
Disclosure of Invention
Exploratory research work shows that hydrogen peroxide is a mild oxidant under neutral conditions and at lower temperatures, and tetrahydrofolic acid can be slowly oxidized under the conditions. Under the condition of no catalyst, the oxydol oxidation product is also a complex mixture, but the folic acid content can reach about 50 percent. The oxidation reaction under such conditions has a problem that the reaction speed is too slow. Under the conditions of room temperature and pH 7, 1 percent hydrogen peroxide is oxidized for 24 hours, the conversion rate of the tetrahydrofolic acid is only about 20 percent, and the requirement of industrial synthesis reaction is far from being met.
In consideration of the need of simultaneously improving the selectivity and the reactivity of the reaction, the used catalyst should have the functions of directionally adsorbing reactant molecules, ensuring the position specialization of the oxidation reaction, and simultaneously having the capability of properly catalyzing the oxidation reaction activity of the hydrogen peroxide.
The supported catalyst developed by the invention takes commercial large-pore molecular sieve SBA-15 as a carrier, and nickel tetraphenylporphyrin and manganese tetraphenylporphyrin synthesized in situ are taken as active components of the catalyst. The catalysis principle is as follows: tetraphenylporphyrin rings loaded on the surface of the molecular sieve adsorb 6-R-tetrahydrofolic acid by virtue of weak intermolecular interaction to form a reaction substrate enrichment region, and the reaction substrate enrichment region is coordinated with porphyrin rings to complex divalent nickel ions and divalent manganese ions to play a synergistic role in catalyzing the oxidation of hydrogen peroxide on tetrahydrofolic acid molecules. The space limiting effect in the local micro-reaction area improves the hydrogen peroxide oxidation reaction efficiency and improves the selectivity of the oxidation reaction.
After the oxidation reaction is finished, the supported catalyst can be recycled by simple filtration, so that the production cost is reduced, and the refining process of the product is simplified.
Because manganese ions in the catalyst can catalyze the decomposition of hydrogen peroxide, redundant hydrogen peroxide can be quickly decomposed under the action of the supported catalyst, and a reaction termination reagent is not required to be additionally added, so that the catalyst has multiple functions.
The invention has the following beneficial effects:
1. the supported composite catalyst has the advantages of improving the oxidation reaction efficiency and the product selectivity, and the technology for producing folic acid by oxidizing tetrahydrofolic acid with hydrogen peroxide reaches the level of industrial production, so that the supported composite catalyst is a high-efficiency multifunctional catalyst.
2. The supported composite catalyst has the function of catalyzing the decomposition of hydrogen peroxide, simplifies the treatment process of reacting residual hydrogen peroxide, does not introduce other impurities in the treatment process, and is beneficial to the purification of products.
3. The used supported composite catalyst can be simply recycled, the production cost is reduced, and the problem of treatment of waste catalysts is solved.
4. The supported composite catalyst of the invention has the advantages of simple synthesis process for producing folic acid by oxidizing tetrahydrofolic acid, convenient operation and no byproduct generation, and is an environment-friendly green synthesis process.
DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION
The following examples describe the specific implementation processes of the present invention, but the present invention is not limited to the specific implementation modes listed below, and includes any combinations of the specific implementation modes.
Example 1.10g of SBA-15 molecular sieves were suspended in 100ml of chloroform/ethanol (2:1) solution, and 1g of tetraphenylporphyrin was added, dissolved with stirring, and refluxed for 2 hours. 0.6g of nickel acetate tetrahydrate and 0.7g of manganese acetate tetrahydrate are dissolved in 30ml of an ethanol/water (5:1) solution. The mixed solution was added to the reaction system, and the reaction was continued under reflux for 4 hours. Filtering, washing with distilled water for 3 times, and vacuum drying to obtain the supported composite catalyst.
The effect test of the supported composite catalyst is carried out according to the following steps: 4.6g of 6-R-tetrahydrofolic acid was dissolved in 50ml of water. Adjusting the pH value to 7, adding 92mg of the supported composite catalyst, stirring at 25 ℃, slowly dropwise adding 40ml of 5% hydrogen peroxide, reacting for 6 hours, monitoring the total consumption of raw materials by TLC (thin layer chromatography), continuously stirring for 60min, and filtering to recover the composite catalyst. The crude product of folic acid is separated, 4.13g of folic acid is refined after ethanol recrystallization, and the purity is 98.5 percent. The yield of purified folic acid was 90.6%.
Example 2. Synthesis of Supported composite catalyst the procedure of example 1 was followed except that the amount of tetraphenylporphyrin was changed to 0.5g, the amount of nickel acetate tetrahydrate was changed to 0.3g, the amount of manganese acetate tetrahydrate was changed to 0.36g, and the aqueous solution of ethanol was 20 ml.
The reaction time in the effect test result of the supported composite catalyst is 12 hours. The product is separated and recrystallized by ethanol, and then 4.0g of refined folic acid with the purity of 98.4 percent is obtained. The yield of purified folic acid was 87.7%.
EXAMPLE 3 Synthesis of Supported composite catalyst the procedure of example 1 was followed except that the amount of tetraphenylporphyrin was changed to 1.5g, the amount of nickel acetate tetrahydrate was changed to 0.9g, the amount of manganese acetate tetrahydrate was changed to 1.1g, and the amount of aqueous ethanol solution was 50 ml.
The reaction time in the effect test result of the supported composite catalyst is 6 hours. The product is separated and recrystallized by ethanol, and then 4.1g of refined folic acid with the purity of 98.5 percent is obtained. The yield of purified folic acid was 89.9%.
EXAMPLE 4 Synthesis of Supported composite catalyst the procedure of example 1 was followed except that the amount of tetraphenylporphyrin was changed to 2g, the amount of nickel acetate tetrahydrate was changed to 1.2g, the amount of manganese acetate tetrahydrate was changed to 1.4g, and the aqueous solution of ethanol was 60 ml.
The reaction time in the effect test result of the supported composite catalyst is 5 hours. The product is separated and recrystallized by ethanol, and then 4.05g of refined folic acid with the purity of 98.6 percent is obtained. The yield of purified folic acid was 88.8%.
Example 5 Synthesis of a Supported composite catalyst the procedure of example 1 was followed except that the amount of nickel acetate tetrahydrate was changed to 0.91g and the amount of manganese acetate tetrahydrate was changed to 0.39 g.
The reaction time in the effect test result of the supported composite catalyst is 8 hours. The product is separated and recrystallized by ethanol, and then 3.6g of refined folic acid with the purity of 98.2 percent is obtained. The yield of purified folic acid was 78.9%.
Example 6. Synthesis of a Supported composite catalyst the procedure of example 1 was followed except that the amount of nickel acetate tetrahydrate was changed to 0. 68g of manganese acetate tetrahydrate, and the using amount of the manganese acetate tetrahydrate is changed to be 0.59 g.
The reaction time in the effect test result of the supported composite catalyst is 6 hours. The product is separated and recrystallized by ethanol, and then 3.95g of refined folic acid with the purity of 98.4 percent is obtained. The yield of purified folic acid was 86.6%.
Example 7. Synthesis of a Supported composite catalyst the procedure of example 1 was followed except that the amount of nickel acetate tetrahydrate was changed to 0.45g and the amount of manganese acetate tetrahydrate was changed to 0.78 g.
The reaction time in the effect test result of the supported composite catalyst is 6 hours. The product is separated and recrystallized by ethanol, and then 4,15g of folic acid is refined, and the purity is 98.5 percent. The yield of purified folic acid was 91.0%.
Example 8. Synthesis of a Supported composite catalyst the procedure of example 1 was followed except that the amount of nickel acetate tetrahydrate was changed to 0.34g and the amount of manganese acetate tetrahydrate was changed to 0.88 g.
The reaction time in the effect test result of the supported composite catalyst is 6 hours. The product is separated and recrystallized by ethanol, and then 4,05g of folic acid is refined, and the purity is 98.5 percent. The yield of purified folic acid was 88.8%.
Example 9 Synthesis of a Supported composite catalyst the procedure of example 1 was followed except that the amount of nickel acetate tetrahydrate was changed to 0.18g and the amount of manganese acetate tetrahydrate was changed to 0.24 g.
In the effect test result of the supported composite catalyst, the reaction time is 24 hours, and the reaction is stopped when the raw materials still do not react.
Example 10 Synthesis of a Supported composite catalyst the procedure of example 1 was followed except that the amount of nickel acetate tetrahydrate was changed to 0.36g and the amount of manganese acetate tetrahydrate was changed to 0.47.
The reaction time in the effect test result of the supported composite catalyst is 12 hours. The product is separated and recrystallized by ethanol, and then 3.8g of refined folic acid with the purity of 98.4 percent is obtained. The yield of purified folic acid was 83.3%.
EXAMPLE 11 Synthesis of Supported composite catalyst the procedure of example 1 was followed except that the amount of nickel acetate tetrahydrate was changed to 0.73g, the amount of manganese acetate tetrahydrate was changed to 0.94 and the aqueous ethanol solution was changed to 50 ml.
The reaction time in the effect test result of the supported composite catalyst is 6 hours. The product is separated and recrystallized by ethanol, and then 4.15g of refined folic acid with the purity of 98.6 percent is obtained. The yield of purified folic acid was 91.0%.
EXAMPLE 12 Synthesis of Supported composite catalyst the procedure of example 1 was followed except that the amount of nickel acetate tetrahydrate was changed to 0.91g, the amount of manganese acetate tetrahydrate was changed to 1.18g, and the ethanol solution was changed to 50 ml.
The reaction time in the effect test result of the supported composite catalyst is 6 hours. The product is separated and recrystallized by ethanol, and then 4.10g of refined folic acid with the purity of 98.5 percent is obtained. The yield of purified folic acid was 89.9%.
EXAMPLE 13 Synthesis of Supported composite catalyst the procedure of example 1 was followed except that the reaction time after addition of the ethanol solution of nickel acetate tetrahydrate and manganese acetate tetrahydrate was changed to 2 hours.
The reaction time in the effect test result of the supported composite catalyst is 8 hours. The product is separated and recrystallized by ethanol, and then 3,9g of folic acid is refined, and the purity is 98.3 percent. The yield of purified folic acid was 85.5%.
EXAMPLE 14 Synthesis of Supported composite catalyst the procedure of example 1 was followed except that the reaction time after addition of the ethanol solution of nickel acetate tetrahydrate and manganese acetate tetrahydrate was changed to 6 hours.
The reaction time in the effect test result of the supported composite catalyst is 8 hours. The product is separated and recrystallized by ethanol, and then 4.15g of refined folic acid with the purity of 98.5 percent is obtained. The yield of purified folic acid was 91.0%.
Claims (7)
1. A preparation method of a supported composite catalyst for synthesizing folic acid by oxidizing 6-R-tetrahydrofolic acid. The preparation method is characterized in that the preparation of the supported composite catalyst for synthesizing folic acid by oxidizing 6-R-tetrahydrofolic acid is realized according to the following method: suspending a certain amount of SBA-15 molecular sieve in 10 times volume of chloroform/ethanol (2:1) solution, adding a certain amount of tetraphenylporphyrin, dissolving under stirring, refluxing for 2 hours, adding a certain amount of ethanol/water (5:1) solution of nickel acetate and manganese acetate, and continuing to reflux and react for a period of time. Filtering, washing with distilled water for 3 times, and vacuum drying to obtain the supported composite catalyst.
2. The method for preparing the supported composite catalyst for the oxidative synthesis of folic acid from 6-R-tetrahydrofolic acid according to claim 1, characterized in that the SBA-15 molecular sieve is a commercial product and has the following basic structural parameters: pore diameter of 6-11nm, BET specific surface area of 550-600m2Relative degree of crystallinity in g>90％。
3. The method for preparing the supported composite catalyst for the oxidative synthesis of folic acid from 6-R-tetrahydrofolic acid according to claim 1, characterized in that the dosage ratio of the SBA-15 molecular sieve to tetraphenylporphyrin is 1: 0.05-0.2.
4. The method for preparing the supported composite catalyst for the oxidative synthesis of folic acid from 6-R-tetrahydrofolic acid according to claim 1, characterized in that both the nickel acetate and the manganese acetate are tetrahydrate, and the dosage (mol) ratio of the nickel acetate and the manganese acetate is 1: 0.5-2.
5. The method for preparing the supported composite catalyst for the oxidative synthesis of folic acid from 6-R-tetrahydrofolic acid according to claim 1, characterized in that the ratio of the amount (mol) of the mixture of tetraphenylporphyrin and nickel acetate/manganese acetate is 1: 1-10.
6. The method for preparing the supported composite catalyst for the oxidative synthesis of folic acid from 6-R-tetrahydrofolic acid according to claim 1, which is characterized in that the reflux reaction time after adding the mixed solution of nickel acetate and manganese acetate is 2-6 hours.
7. The preparation method of the supported composite catalyst for folic acid synthesis by oxidation of 6-R-tetrahydrofolic acid according to claim 1, wherein the catalyst is used in the reaction of folic acid synthesis by oxidation of 6-R-tetrahydrofolic acid with hydrogen peroxide, under optimized reaction conditions, the amount of the catalyst is 2% of the weight of the raw materials, the refined folic acid product has a purity of 98.5% or more and a yield of 90% or more.
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