CN114163439A - Method for preparing tetrahydrofolic acid by catalytic hydrogenation - Google Patents
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Abstract
The invention relates to a method for preparing tetrahydrofolic acid by catalytic hydrogenation, which comprises the following steps: adding catalysts Raney nickel and folic acid solution into a reaction kettle, filling hydrogen into the reaction kettle, placing the reaction kettle in an environment of 40-90 ℃, carrying out oxidation-reduction reaction on folic acid and hydrogen, and obtaining tetrahydrofolic acid after the reaction is finished. The preparation method of tetrahydrofolic acid provided by the invention solves the problem of low yield of tetrahydrofolic acid preparation under the condition of meeting the requirement of reducing the catalyst consumption.
Description
Technical Field
The invention relates to the technical field of drug synthesis, in particular to a method for preparing tetrahydrofolic acid by catalytic hydrogenation.
Background
Tetrahydrofolic acid is a carbon group (including CH)3、CH2CHO, etc.) transferase, tetrahydrofolic acid, has the function of transferring one-carbon groups and participates in many important reactions and the synthesis of nucleic acids and amino acids.
At present, tetrahydrofolic acid is generally prepared from folic acid by a catalytic hydrogenation reduction method.
Catalysts commonly used in catalytic hydrogenation reduction processes are Pt/C (platinum carbon catalyst), Rh/C (rhodium carbon catalyst) and PtO2(platinum dioxide catalyst) and the like, the amount of the catalyst used is large, and the catalytic effect is not ideal, so that the production yield of the tetrahydrofolic acid is low.
Disclosure of Invention
Based on the method, the invention provides a method for preparing tetrahydrofolic acid by catalytic hydrogenation, which solves the problem of low yield of the tetrahydrofolic acid preparation under the condition of meeting the requirement of reducing the using amount of a catalyst.
The invention provides a method for preparing tetrahydrofolic acid by catalytic hydrogenation, which comprises the following steps:
adding catalysts Raney nickel and folic acid solution into a reaction kettle, filling hydrogen into the reaction kettle, placing the reaction kettle in an environment of 40-90 ℃, carrying out oxidation-reduction reaction on folic acid and the hydrogen, and obtaining tetrahydrofolic acid after the reaction is finished;
the reaction equation for the preparation of tetrahydrofolic acid is as follows:
preferably, the pH of the folic acid solution is 6-10.
Preferably, the mass ratio of the folic acid to the Raney nickel catalyst is 100 (25-200).
Preferably, in the step of subjecting the folic acid to a redox reaction with the hydrogen gas, the pressure of the reaction kettle ranges from 20 bar to 65 bar.
Preferably, the reaction time of the folic acid and the hydrogen gas in the oxidation-reduction reaction is 6-24 h.
Preferably, the step of obtaining tetrahydrofolic acid after the reaction is finished comprises:
after the reaction is finished, obtaining a solution containing tetrahydrofolic acid, adjusting the pH of the solution containing tetrahydrofolic acid to 3-3.5 by using an acid solution to obtain a solution containing tetrahydrofolic acid precipitate, filtering the solution containing tetrahydrofolic acid precipitate, collecting the tetrahydrofolic acid precipitate, and drying the precipitate to obtain the tetrahydrofolic acid.
Preferably, the preparation of the folic acid solution with the pH of 6-10 comprises the following steps:
adding solid folic acid into a flask at the temperature of 25-35 ℃, filling nitrogen or inert gas into the flask until an oxygen-free environment is formed in the flask, adding a buffer solution with the pH of 4-10 into the flask, stirring uniformly to obtain a mixed solution, and adjusting the pH of the mixed solution to 6-10 by using an alkali solution to obtain a folic acid solution.
Preferably, the buffer solution includes any one of a disodium hydrogen phosphate-citric acid buffer solution, a sodium dihydrogen phosphate-disodium hydrogen phosphate buffer solution, a disodium hydrogen phosphate-potassium dihydrogen phosphate buffer solution, a barbituric sodium-hydrochloric acid buffer solution, a Tris buffer solution, a boric acid-borax buffer solution, a glycine-sodium hydroxide buffer solution, a borax-sodium hydroxide buffer solution, a sodium carbonate-sodium bicarbonate buffer solution, a Britton-Robinson buffer solution, and a Tris buffer solution.
Preferably, the alkali solution includes any one of a NaOH solution and a KOH solution.
Preferably, the amount of the buffer solution is 10-15ml/1g solid folic acid.
Compared with the prior art, the invention has the following beneficial effects:
according to the invention, the tetrahydrofolic acid is prepared by reducing folic acid under the catalysis of Raney nickel catalyst, the Raney nickel catalyst has high catalytic efficiency and can be recycled, and the problems of large catalyst dosage and low yield in the prior art are solved.
Drawings
FIG. 1 is a graph showing the experimental results of the effect of pH of folic acid solution on the yield of tetrahydrofolic acid;
FIG. 2 is a graph showing the experimental results of the effect of reaction time on the yield of tetrahydrofolic acid;
FIG. 3 is a graph showing the experimental results of the effect of reaction temperature on the yield of tetrahydrofolic acid;
FIG. 4 is a graph showing the experimental results of the effect of the amount of Raney nickel catalyst on the yield of tetrahydrofolic acid;
FIG. 5 is a nuclear magnetic diagram of the product tetrahydrofolic acid.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The experimental procedures in the following examples are conventional unless otherwise specified. Test materials, reagents and the like used in the following examples are commercially available unless otherwise specified. In the quantitative tests in the following examples, three replicates were set, and the data are the mean or the mean ± standard deviation of the three replicates.
In addition, "and/or" in the whole text includes three schemes, taking a and/or B as an example, including a technical scheme, and a technical scheme that a and B meet simultaneously; in addition, technical solutions between various embodiments may be combined with each other, but must be realized by a person skilled in the art, and when the technical solutions are contradictory or cannot be realized, such a combination should not be considered to exist, and is not within the protection scope of the present invention.
The invention provides a method for preparing tetrahydrofolic acid by catalytic hydrogenation, which comprises the following steps:
adding catalysts Raney nickel and folic acid solution into a reaction kettle, filling hydrogen into the reaction kettle, placing the reaction kettle in an environment of 40-90 ℃, carrying out oxidation-reduction reaction on folic acid and hydrogen, and obtaining tetrahydrofolic acid after the reaction is finished;
the reaction equation for the preparation of tetrahydrofolic acid is as follows:
according to the invention, the tetrahydrofolic acid is prepared by reducing folic acid under the catalysis of Raney nickel catalyst, the Raney nickel catalyst has high catalytic efficiency and can be recycled, and the problems of large catalyst dosage and low yield in the prior art are solved.
The hydrogen reduces carbon-nitrogen double bonds in the folic acid, specifically, hydrogen is adsorbed on the surface of catalyst raney nickel, folic acid is coordinated with the catalyst, hydrogen molecules of the hydrogen are subjected to bond fracture under the catalysis of the catalyst raney nickel to form active hydrogen atoms, and the hydrogen atoms of the hydrogen are combined with the carbon-nitrogen double bonds of the folic acid to be reduced to form carbon-nitrogen single bonds to generate the tetrahydrofolic acid.
The Raney nickel catalyst is a solid heterogeneous catalyst composed of fine grains of nickel-aluminum alloy with a porous structure.
Specifically, hydrogen is filled into the reaction kettle until the reaction kettle does not contain gases except the hydrogen;
in the step of adding catalyst Raney nickel into a reaction kettle and adding folic acid solution into the reaction kettle, nitrogen or inert gas is filled into the reaction kettle to ensure that an oxygen-free environment is formed in the reaction kettle.
In some embodiments, the pH of the folic acid solution is 6-10.
In some embodiments, the mass ratio of folic acid to Raney nickel catalyst is 100 (25-200).
In some embodiments, the pressure in the reaction vessel during the step of redox reaction of folic acid with hydrogen is in the range of 20-65 bar.
In some embodiments, the folic acid undergoes a redox reaction with hydrogen gas for a reaction time of 6-24 hours.
In some embodiments, the step of obtaining tetrahydrofolic acid after the reaction is finished comprises:
after the reaction is finished, obtaining a solution containing tetrahydrofolic acid, adjusting the pH of the solution containing tetrahydrofolic acid to 3-3.5 by using an acid solution to obtain a solution containing tetrahydrofolic acid precipitate, filtering the solution containing tetrahydrofolic acid precipitate, collecting the tetrahydrofolic acid precipitate, and drying the precipitate to obtain the tetrahydrofolic acid.
Specifically, after the reaction is finished, the whole system is homogeneous, tetrahydrofolic acid can be separated out under an acidic condition, and the yield of the separated tetrahydrofolic acid is 3-3.5 when the yield is the highest;
tetrahydrofolic acid is sensitive to oxygen and is easily oxidized into dihydrofolic acid;
the drying mode comprises freeze drying, vacuum drying and the like, and the drying is carried out under the oxygen-free condition to prevent the tetrahydrofolic acid from being oxidized;
filtering under nitrogen or inert gas to avoid oxidation of tetrahydrofolic acid.
In some embodiments, the preparation of the folic acid solution with the pH of 6-10 comprises the following steps:
adding solid folic acid into a flask at the temperature of 25-35 ℃, filling nitrogen or inert gas into the flask until an oxygen-free environment is formed in the flask, adding a buffer solution with the pH of 4-10 into the flask, stirring uniformly to obtain a mixed solution, and adjusting the pH of the mixed solution to 6-10 by using an alkali solution to obtain a folic acid solution.
Specifically, the buffer solution is added to control the pH of the solution and avoid titration jump;
specifically, folic acid is dissolved in an alkali solution, and when the pH of the folic acid solution is adjusted to 7 with the alkali solution, the yield of folic acid produced by the reaction of folic acid reaches the maximum.
In some embodiments, the buffer solution includes any one of a disodium hydrogen phosphate-citric acid buffer solution, a sodium dihydrogen phosphate-disodium hydrogen phosphate buffer solution, a disodium hydrogen phosphate-potassium dihydrogen phosphate buffer solution, a barbituric sodium-hydrochloric acid buffer solution, a Tris buffer solution, a boric acid-borax buffer solution, a glycine-sodium hydroxide buffer solution, a borax-sodium hydroxide buffer solution, a sodium carbonate-sodium bicarbonate buffer solution, a Britton-Robinson buffer solution, and a Tris buffer solution.
In some embodiments, the alkali solution comprises any one of a NaOH solution and a KOH solution.
In some embodiments, the buffer solution is used in an amount of 10-15ml per 1g of solid folic acid.
In some embodiments, further comprising:
and (3) carrying out nuclear magnetic detection on the tetrahydrofolic acid by using sym-trimethoxybenzene as an internal standard.
Example 1
1g of solid folic acid was added to a 100mL three-necked flask at 25 ℃ and the flask was replaced with nitrogen gas 3 times, and then 10mL of NaH (0.2 mol/LpH: 7) was added to the flask2PO4-Na2HPO4Stirring the buffer solution to be uniform to obtain a mixed solution, and adjusting the pH of the mixed solution to 7 by using a 20% NaOH solution to obtain a folic acid solution;
adding 0.5g of raney nickel into a 50mL reaction kettle, replacing the reaction kettle with nitrogen for 3 times, adding a folic acid solution with pH of 7 into the reaction kettle, replacing the reaction kettle with hydrogen for 5 times, filling hydrogen into the reaction kettle, adjusting the pressure of the reaction kettle to 50bar, placing the reaction kettle in an environment at 60 ℃ for oxidation-reduction reaction for 24 hours, obtaining a solution containing tetrahydrofolic acid after the reaction is finished, adjusting the pH of the solution containing tetrahydrofolic acid to 3 with 1mol/L hydrochloric acid solution, separating out tetrahydrofolic acid precipitate, filtering the precipitate, and drying for 8 hours by using a vacuum drying oven to obtain the tetrahydrofolic acid.
The tetrahydrofolic acid is detected by using sym-trimethoxybenzene as an internal standard, and the yield of the tetrahydrofolic acid is 95 percent.
Example 2
1g of solid folic acid was added to a 100mL three-necked flask at 28 ℃ and the flask was replaced with nitrogen gas 3 times, and then 10mL of NaH (0.2 mol/LpH: 7) was added to the flask2PO4-Na2HPO4Stirring the buffer solution to be uniform to obtain a mixed solution, and adjusting the pH of the mixed solution to 7 by using a 20% NaOH solution to obtain a folic acid solution;
adding 1g of raney nickel into a 50mL reaction kettle, replacing the reaction kettle with nitrogen for 3 times, adding a folic acid solution with pH of 7 into the reaction kettle, replacing the reaction kettle with hydrogen for 5 times, filling hydrogen into the reaction kettle, adjusting the pressure of the reaction kettle to 30bar, placing the reaction kettle in an environment at 70 ℃ for oxidation-reduction reaction for 15 hours, obtaining a solution containing tetrahydrofolic acid after the reaction is finished, adjusting the pH of the solution containing tetrahydrofolic acid to 3 with 1mol/L hydrochloric acid solution, separating out tetrahydrofolic acid precipitate, filtering the precipitate, and drying for 8 hours by using a vacuum drying oven to obtain the tetrahydrofolic acid.
The tetrahydrofolic acid is detected by using sym-trimethoxybenzene as an internal standard, and the yield of the tetrahydrofolic acid is 88 percent.
Example 3
1g of solid folic acid was added to a 100mL three-necked flask at 30 ℃ and the flask was replaced with nitrogen gas 3 times, and then 10mL of NaH (0.2 mol/LpH: 7) was added to the flask2PO4-Na2HPO4Stirring the buffer solution to be uniform to obtain a mixed solution, and adjusting the pH of the mixed solution to 7 by using a 20% NaOH solution to obtain a folic acid solution;
adding 1g of raney nickel into a 50mL reaction kettle, replacing the reaction kettle with nitrogen for 3 times, adding a folic acid solution with pH of 7 into the reaction kettle, replacing the reaction kettle with hydrogen for 5 times, filling hydrogen into the reaction kettle, adjusting the pressure of the reaction kettle to 50bar, placing the reaction kettle in an environment at 80 ℃ for oxidation-reduction reaction for 15 hours, obtaining a solution containing tetrahydrofolic acid after the reaction is finished, adjusting the pH of the solution containing tetrahydrofolic acid to 3.5 with 1mol/L hydrochloric acid solution, separating out tetrahydrofolic acid precipitate, filtering the precipitate, and drying for 8 hours by using a vacuum drying oven to obtain the tetrahydrofolic acid.
The tetrahydrofolic acid is detected by using sym-trimethoxybenzene as an internal standard, and the yield of the tetrahydrofolic acid is 84 percent.
Example 4
Other steps are as in example 1, the reaction temperature is 80 ℃, and experiments are carried out by changing the pH of the folic acid solution to verify the influence of the reaction pH on the yield of tetrahydrofolic acid, and the experimental results are shown in figure 1.
As can be seen from FIG. 1, the yield of tetrahydrofolic acid was only 70% when pH was selected to be 10, 83% when pH was selected to be 7, and 81% when pH was selected to be 6, indicating that the reaction yield was the highest at pH 7.
Example 5
Other steps are as in example 1, and experiments were conducted while changing the reaction time of the reaction to verify the effect of the reaction time on the yield of tetrahydrofolic acid, and the experimental results are shown in FIG. 2.
As can be seen from fig. 2, when the reaction time was 6 hours, the yield of tetrahydrofolic acid was only 81%, when the reaction time was 12 hours, the yield of tetrahydrofolic acid was 88%, when the reaction time was 18 hours, the yield of tetrahydrofolic acid reached 93%, when the reaction time was 24, the yield of tetrahydrofolic acid was 95%, when the reaction time exceeded 24, the yield of tetrahydrofolic acid decreased, indicating that the reaction yield was the highest when the reaction time was 24 hours.
Example 6
Other steps are as in example 1, and experiments are carried out by changing the reaction temperature of the reaction to verify the effect of the reaction temperature on the yield of tetrahydrofolic acid, and the experimental results are shown in fig. 3.
As can be seen from fig. 3, the yield of tetrahydrofolic acid was only 10% when the reaction temperature was 30 ℃, 79% when the reaction temperature was 40 ℃, and 95% and peaked when the reaction temperature was 60 ℃, indicating that the reaction temperature was 60 ℃, and the yield was the highest.
Example 8
Other steps are as in example 1, and the amount of raney nickel as a catalyst for reaction is changed to perform experiments to verify the effect of the amount of raney nickel as a catalyst for reaction on the yield of tetrahydrofolic acid, and the experimental results are shown in fig. 4.
As can be seen from fig. 4, when the mass of raney nickel catalyst is 25% of the mass of folic acid, the yield of tetrahydrofolic acid is 88%, and the amount of catalyst is increased, when the mass of raney nickel catalyst is more than 50% of the mass of folic acid, the yield tends to be stable, and the reaction yield is more than 93%.
FIG. 5 is a nuclear magnetic map of the product tetrahydrofolic acid, the results of which are as follows:
1H NMR(400MHz,DMSO-d6)δ8.10(d,J=7.7Hz,1H),7.66(d,J=8.5Hz,2H),6.63(d,J=8.5Hz,2H),6.42(s,1H),6.18(s,1H),5.74(s,2H),4.35(ddd,J=9.7,7.6,4.9Hz,1H),3.36(d,J=11.3Hz,1H),3.13(s,3H),3.06–2.91(m,1H),2.33(t,J=7.5Hz,2H),2.05(ddd,J=12.9,9.4,5.3Hz,1H),1.93(ddd,J=13.8,9.6,6.9Hz,1H).
the above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.
Claims (10)
1. A method for preparing tetrahydrofolic acid by catalytic hydrogenation is characterized by comprising the following steps:
adding catalysts Raney nickel and folic acid solution into a reaction kettle, filling hydrogen into the reaction kettle, placing the reaction kettle in an environment of 40-90 ℃, carrying out oxidation-reduction reaction on folic acid and the hydrogen, and obtaining tetrahydrofolic acid after the reaction is finished;
the reaction equation for the preparation of tetrahydrofolic acid is as follows:
2. the method for preparing tetrahydrofolic acid through catalytic hydrogenation according to claim 1, characterized in that the pH of the folic acid solution is 6-10.
3. The method for preparing tetrahydrofolic acid by catalytic hydrogenation according to claim 1, characterized in that the mass ratio of folic acid to Raney nickel catalyst is 100 (25-200).
4. The method for producing tetrahydrofolic acid by catalytic hydrogenation according to claim 1, characterized in that the pressure of the reaction kettle in the step of carrying out the oxidation-reduction reaction of folic acid and hydrogen is in the range of 20-65 bar.
5. The method for preparing tetrahydrofolic acid by catalytic hydrogenation according to claim 1, characterized in that the reaction time of folic acid and hydrogen gas undergoing redox reaction is 6-24 h.
6. The method for preparing tetrahydrofolic acid by catalytic hydrogenation according to claim 1, wherein the step of obtaining tetrahydrofolic acid by catalytic hydrogenation after the reaction is finished comprises the following steps:
after the reaction is finished, obtaining a solution containing tetrahydrofolic acid, adjusting the pH of the solution containing tetrahydrofolic acid to 3-3.5 by using an acid solution to obtain a solution containing tetrahydrofolic acid precipitate, filtering the solution containing tetrahydrofolic acid precipitate, collecting the tetrahydrofolic acid precipitate, and drying the precipitate to obtain the tetrahydrofolic acid.
7. The method for preparing tetrahydrofolic acid through catalytic hydrogenation according to claim 2, characterized in that the preparation of the folic acid solution with the pH of 6-10 comprises the following steps:
adding solid folic acid into a flask at the temperature of 25-35 ℃, filling nitrogen or inert gas into the flask until an oxygen-free environment is formed in the flask, adding a buffer solution with the pH of 4-10 into the flask, stirring uniformly to obtain a mixed solution, and adjusting the pH of the mixed solution to 6-10 by using an alkali solution to obtain a folic acid solution.
8. The catalytic hydrogenation production process of tetrahydrofolic acid according to claim 7, characterized in that the buffer solution includes any one of disodium hydrogen phosphate-citric acid buffer solution, sodium dihydrogen phosphate-disodium hydrogen phosphate buffer solution, disodium hydrogen phosphate-potassium dihydrogen phosphate buffer solution, barbiturate sodium-hydrochloric acid buffer solution, Tris-hydroxymethyl aminomethane-hydrochloric acid buffer solution, boric acid-borax buffer solution, glycine-sodium hydroxide buffer solution, borax-sodium hydroxide buffer solution, sodium carbonate-sodium bicarbonate buffer solution, Britton-Robinson buffer solution, and Tris buffer solution.
9. The method for preparing tetrahydrofolic acid by catalytic hydrogenation according to claim 7, characterized in that the alkali solution comprises any one of NaOH solution and KOH solution.
10. The method for preparing tetrahydrofolic acid by catalytic hydrogenation according to claim 7, characterized in that the amount of the buffer solution is 10-15ml per 1g of solid folic acid.
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115672321A (en) * | 2022-09-30 | 2023-02-03 | 哈尔滨工业大学(深圳) | Pt 3 Preparation method of Mn/CNTs catalyst and application of catalyst |
CN115850283A (en) * | 2022-12-05 | 2023-03-28 | 哈尔滨工业大学(深圳) | Method for preparing tetrahydrofolic acid by continuous hydrogenation with Raney Ni as catalyst |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102329318A (en) * | 2011-10-20 | 2012-01-25 | 浙江圣达药业有限公司 | Preparation method of high-purity tetrahydrofolic acid |
CN105209459A (en) * | 2013-05-17 | 2015-12-30 | 奥古斯特沃尔夫博士有限两合公司-医药 | Perhydroquinoxaline derivatives useful as analgesics |
-
2021
- 2021-12-01 CN CN202111453970.3A patent/CN114163439A/en active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102329318A (en) * | 2011-10-20 | 2012-01-25 | 浙江圣达药业有限公司 | Preparation method of high-purity tetrahydrofolic acid |
CN105209459A (en) * | 2013-05-17 | 2015-12-30 | 奥古斯特沃尔夫博士有限两合公司-医药 | Perhydroquinoxaline derivatives useful as analgesics |
Non-Patent Citations (2)
Title |
---|
ALBERT, ADRIEN ET AL.: "Pteridine studies. XVIII. Reduction of hydroxypteridines", 《JOURNAL OF THE CHEMICAL SOCIETY》 * |
MOLENVELD, PETER ET AL.: "Conformationally restricted κ-opioid receptor agonists: Synthesis and pharmacological evaluation of diastereoisomeric and enantiomeric decahydroquinoxalines", 《BIOORGANIC & MEDICINAL CHEMISTRY LETTERS》 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115672321A (en) * | 2022-09-30 | 2023-02-03 | 哈尔滨工业大学(深圳) | Pt 3 Preparation method of Mn/CNTs catalyst and application of catalyst |
CN115672321B (en) * | 2022-09-30 | 2024-01-02 | 哈尔滨工业大学(深圳) | Pt 3 Preparation method of Mn/CNTs catalyst and application of catalyst |
CN115850283A (en) * | 2022-12-05 | 2023-03-28 | 哈尔滨工业大学(深圳) | Method for preparing tetrahydrofolic acid by continuous hydrogenation with Raney Ni as catalyst |
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