CN116986980A - Preparation method of vanillic acid - Google Patents
Preparation method of vanillic acid Download PDFInfo
- Publication number
- CN116986980A CN116986980A CN202111180224.1A CN202111180224A CN116986980A CN 116986980 A CN116986980 A CN 116986980A CN 202111180224 A CN202111180224 A CN 202111180224A CN 116986980 A CN116986980 A CN 116986980A
- Authority
- CN
- China
- Prior art keywords
- reaction
- vanillic acid
- solvent
- vanillin
- organic solvent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- WKOLLVMJNQIZCI-UHFFFAOYSA-N vanillic acid Chemical compound COC1=CC(C(O)=O)=CC=C1O WKOLLVMJNQIZCI-UHFFFAOYSA-N 0.000 title claims abstract description 41
- TUUBOHWZSQXCSW-UHFFFAOYSA-N vanillic acid Natural products COC1=CC(O)=CC(C(O)=O)=C1 TUUBOHWZSQXCSW-UHFFFAOYSA-N 0.000 title claims abstract description 41
- YQUVCSBJEUQKSH-UHFFFAOYSA-N protochatechuic acid Natural products OC(=O)C1=CC=C(O)C(O)=C1 YQUVCSBJEUQKSH-UHFFFAOYSA-N 0.000 title claims abstract description 40
- 238000002360 preparation method Methods 0.000 title abstract description 12
- 238000006243 chemical reaction Methods 0.000 claims abstract description 56
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 claims abstract description 30
- 235000012141 vanillin Nutrition 0.000 claims abstract description 30
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 claims abstract description 29
- 238000000034 method Methods 0.000 claims abstract description 25
- 239000003960 organic solvent Substances 0.000 claims abstract description 19
- 238000005406 washing Methods 0.000 claims abstract description 17
- 239000012295 chemical reaction liquid Substances 0.000 claims abstract description 13
- 229910001867 inorganic solvent Inorganic materials 0.000 claims abstract description 13
- 239000003049 inorganic solvent Substances 0.000 claims abstract description 13
- 239000003054 catalyst Substances 0.000 claims abstract description 12
- 239000007800 oxidant agent Substances 0.000 claims abstract description 11
- 239000002904 solvent Substances 0.000 claims abstract description 10
- 230000001590 oxidative effect Effects 0.000 claims abstract description 9
- 238000001816 cooling Methods 0.000 claims abstract description 8
- 239000012043 crude product Substances 0.000 claims abstract description 7
- 238000002156 mixing Methods 0.000 claims abstract description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 38
- 238000010438 heat treatment Methods 0.000 claims description 21
- 238000001914 filtration Methods 0.000 claims description 20
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 18
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- HDMGAZBPFLDBCX-UHFFFAOYSA-M potassium;sulfooxy sulfate Chemical group [K+].OS(=O)(=O)OOS([O-])(=O)=O HDMGAZBPFLDBCX-UHFFFAOYSA-M 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
- 239000000706 filtrate Substances 0.000 claims description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 150000001879 copper Chemical class 0.000 claims description 6
- 230000035484 reaction time Effects 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- 239000006227 byproduct Substances 0.000 abstract description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 239000012065 filter cake Substances 0.000 description 14
- 239000000243 solution Substances 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 239000005457 ice water Substances 0.000 description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 9
- 239000013078 crystal Substances 0.000 description 9
- 238000001514 detection method Methods 0.000 description 9
- 239000007788 liquid Substances 0.000 description 8
- ZENOXNGFMSCLLL-UHFFFAOYSA-N vanillyl alcohol Chemical compound COC1=CC(CO)=CC=C1O ZENOXNGFMSCLLL-UHFFFAOYSA-N 0.000 description 8
- 239000007791 liquid phase Substances 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 235000009499 Vanilla fragrans Nutrition 0.000 description 6
- 244000263375 Vanilla tahitensis Species 0.000 description 6
- 235000012036 Vanilla tahitensis Nutrition 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 230000006837 decompression Effects 0.000 description 5
- 239000012535 impurity Substances 0.000 description 5
- 230000000813 microbial effect Effects 0.000 description 5
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 4
- 238000005705 Cannizzaro reaction Methods 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- 238000000967 suction filtration Methods 0.000 description 4
- 239000002253 acid Substances 0.000 description 3
- 230000008034 disappearance Effects 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000003513 alkali Substances 0.000 description 2
- ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 229910000365 copper sulfate Inorganic materials 0.000 description 2
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 2
- XTVVROIMIGLXTD-UHFFFAOYSA-N copper(II) nitrate Chemical compound [Cu+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O XTVVROIMIGLXTD-UHFFFAOYSA-N 0.000 description 2
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 2
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000002386 leaching Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000006479 redox reaction Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 238000011426 transformation method Methods 0.000 description 2
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 230000007131 anti Alzheimer effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 229910001431 copper ion Inorganic materials 0.000 description 1
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000002363 herbicidal effect Effects 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 230000005311 nuclear magnetism Effects 0.000 description 1
- USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/16—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation
- C07C51/305—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation with sulfur or sulfur-containing compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/42—Separation; Purification; Stabilisation; Use of additives
- C07C51/43—Separation; Purification; Stabilisation; Use of additives by change of the physical state, e.g. crystallisation
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Crystallography & Structural Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a preparation method of vanillic acid, which comprises the following steps: mixing vanillin, a catalyst and an oxidant in a solvent to react to obtain a first reaction solution, wherein the solvent comprises an organic solvent and an inorganic solvent; removing the organic solvent in the first reaction liquid to obtain a second reaction liquid; washing the second reaction liquid, and cooling and crystallizing to obtain a crude product of the vanillic acid; the method can perform a faster reaction at normal temperature and has the advantages of less byproducts, safety and economy.
Description
Technical Field
The invention relates to the field of organic synthesis, in particular to a preparation method of vanillic acid.
Background
Vanillic acid (C) 8 H 8 O 4 ) The chemical name is 4-hydroxy-3-methoxybenzoic acid, and the structural formula is as follows:
the vanillic acid is a multipurpose chemical product, can be used in the aspects of medicines, foods, environmental protection, daily chemicals and the like, is mainly used as a new anti-Alzheimer disease drug and a related intermediate of the new anti-tumor drug in the medicine field, can be used for disinfection, cleaning, reducing the harm of herbicide and the like in the environmental protection aspect, and can be used as a care component of cosmetics in the daily chemicals aspect. The most commonly used preparation methods in the prior art mainly comprise two types: one is synthesized by a microbial transformation method; the other is a chemical method, most commonly prepared by self-oxidation-reduction reaction (Cannizzaro reaction) of vanillin under strong alkali conditions. The two methods also have the following problems: on the one hand, the microbial conversion method has long time, usually takes at least about 3 to 7 days (according to a conventional reaction temperature), so the time cost is high, byproducts of the microbial conversion method are more and more complicated, which is a common problem of the microbial conversion method, so the requirement for the later purification is very high, on the other hand, the Cannizzaro reaction is self redox reaction, namely that 2 moles of vanillin can produce 1 mole of vanillic acid and 1 mole of vanillyl alcohol, so the method is very wasteful in terms of atomic economy, vanillyl alcohol is similar to vanillic acid in terms of the post treatment, the removal of the vanillyl alcohol is difficult, the preparation cost is increased, the Cannizzaro reaction is a reaction under the condition of strong alkali, and the raw vanillin has phenol groups structurally, phenol is very easy to oxidize under the alkaline and high-temperature conditions, other byproducts are easy to produce, and the subsequent treatment difficulty is further increased.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provides a preparation method of vanillic acid.
To achieve the above and other objects, the present invention is achieved by comprising the following technical solutions: the invention provides a preparation method of vanillic acid, which comprises the following steps: mixing vanillin, a catalyst and an oxidant in a solvent to react to obtain a first reaction solution, wherein the solvent comprises an organic solvent and an inorganic solvent; removing the organic solvent in the first reaction liquid to obtain a second reaction liquid; washing the second reaction liquid, and cooling and crystallizing to obtain a crude product of the vanillic acid; mixing the crude product of the vanillic acid and the activated carbon in an inorganic solvent, heating, filtering, cooling and crystallizing the filtrate to obtain the vanillic acid.
In one embodiment, the catalyst is an inorganic copper salt.
In one embodiment, the oxidizing agent is potassium hydrogen persulfate.
In an embodiment, the organic solvent comprises any one or more of acetonitrile, methanol, ethanol, isopropanol, tetrahydrofuran.
In one embodiment, the reaction time of the reaction is from 5 to 6 hours.
In one embodiment, the reaction temperature of the reaction is 25 to 30 ℃.
In one embodiment, the heating temperature of the heating is 95-100 ℃.
In one embodiment, the inorganic solvent is water.
In one embodiment, the molar ratio of the catalyst to the vanillin is (0.01 to 0.05): 1.
in one embodiment, the molar ratio of the oxidizing agent to the vanillin is (1-1.2): 1.
in one embodiment, the yield of vanillic acid is 90-95%.
As described above, the present invention provides a method for preparing vanillic acid, which comprises the steps of using vanillin as a substrate, copper salt as a catalyst, potassium hydrogen persulfate as an oxidant, and organic solvent and inorganic solvent as a mixed solvent to perform an oxidation reaction. The core of the invention is to synthesize vanillic acid through an oxidation way, and has the following advantages: compared with the microbial transformation method, the method has the advantages that the reaction time is greatly shortened, the occurrence of side reactions is reduced, and the later separation and purification difficulty is increased. The invention adopts the chemical synthesis method completely, so the problems are avoided, and compared with the Cannizzaro reaction commonly used in chemical synthesis, the method solves the problems that the atom economy is poor, the main byproduct vanillyl alcohol is difficult to remove completely, the reaction temperature is high, the raw material vanillin phenolic hydroxyl is oxidized to generate other byproducts due to high-temperature reaction under the condition of long-time strong alkalinity, and the like.
In the invention, copper salt is used as a catalyst, and potassium hydrogen persulfate which is a weak oxidant is used for oxidizing vanillin. Firstly, the potassium hydrogen persulfate is acidic, so that the phenolic hydroxyl group on the vanillin is more stable and is not easy to oxidize, and only the aldehyde group on the vanillin is possibly oxidized on the premise of not oxidizing the phenolic hydroxyl group, in addition, the potassium hydrogen persulfate also has the advantages of safety and economy, is suitable for industrial production, and is proved by a large number of experiments to have stronger promotion effect on the reaction by copper ions. The improvement makes the reaction fast at room temperature, and has the most obvious advantages of low reaction temperature, short reaction time, reuse of the solvent and water for recrystallization, and the method reduces purification difficulty, improves reaction yield, reduces production cost, shortens production period, reduces three wastes, and is a green, environment-friendly, economic and safe synthesis scheme.
Drawings
FIG. 1 shows a flow chart of the preparation method of the invention.
FIG. 2 is a schematic diagram showing the reaction equation of the preparation method of the present invention and a comparative example of the preparation method in the prior art.
FIG. 3 shows a HPLC detection result pattern of the sample 1 of the present invention.
Detailed Description
Referring to fig. 1 to 3, the following specific embodiments are provided to illustrate the embodiments of the present invention, and those skilled in the art can easily understand the advantages and effects of the present invention from the disclosure herein. The invention may be practiced or carried out in other embodiments that depart from the specific details, and the details of the present description may be modified or varied from the spirit and scope of the present invention.
Note that "%" and "parts" shown herein refer to "% by mass" and "parts by mass", respectively, unless otherwise specified.
The invention provides a preparation method of vanillic acid, which comprises the steps of reaction synthesis and subsequent purification, and specifically comprises the steps of S1-S4:
-S1: mixing vanillin, a catalyst and an oxidant in a solvent to react to obtain a first reaction solution, wherein the solvent comprises an organic solvent and an inorganic solvent;
-S2: removing the organic solvent in the first reaction liquid to obtain a second reaction liquid;
-S3: washing the second reaction liquid, and cooling and crystallizing to obtain a crude product of the vanillic acid;
-S4: mixing the crude product of the vanillic acid and the activated carbon in an inorganic solvent, heating, filtering, cooling and crystallizing the filtrate to obtain the vanillic acid.
In step S1, the catalyst may be an inorganic copper salt, which may include copper chloride, copper bromide, copper iodide, copper sulfate, copper nitrate, copper acetate, etc., the organic solvent may include any one or more combinations of acetonitrile, methanol, ethanol, isopropanol, tetrahydrofuran, etc., the inorganic solvent may be water, and the reaction may be a reaction performed at room temperature, which may be 25 to 30 ℃, such as 26 ℃, 27 ℃, 28 ℃, 29 ℃, etc. The end point of the reaction may be that the raw material vanillin is not detected in the first reaction liquid, and the detection method may be TLC or liquid chromatography detection, and in an embodiment, the reaction time of the reaction may be 5-6 hours, which is worth noting that, in consideration of practical application, the reaction time of the present invention is not suitable to exceed 10 hours. The molar ratio of the catalyst to the vanillin may be (0.01-0.05): 1, for example 0.03: 1. 0.04:1, etc., the molar ratio of the oxidizing agent to the vanillin may be (1 to 1.2): 1, the volume ratio of the solvent to the vanillin is (5-8): 1, the volume ratio of the organic solvent to the inorganic solvent may be 1: (0.5-1).
In step S2, the removal of the organic solvent in the first reaction solution may be performed by concentrating under reduced pressure. The second reaction solution may include a small amount of impurities, which may include a small amount of inorganic impurities such as potassium hydrogen persulfate, copper salt, etc., and also include organic matters which are not removed and a small amount of quinone substances formed after oxidation of phenolic hydroxyl groups, and the impurities may be removed in a subsequent purification step.
In step S3, the washing may include alkaline washing and extraction washing, the alkaline washing may be performed with saturated aqueous sodium carbonate, the extraction washing may be performed with ethyl acetate, the alkaline washing may remove inorganic impurities such as excessive potassium hydrogen persulfate in the second reaction solution, and dissolve the product vanillic acid in the form of sodium salt in water, in an embodiment, the volume ratio of the saturated aqueous sodium carbonate to the second reaction solution may be (0.5-1): 1, the extraction washing may be performed to wash off organic impurities remaining in the second reaction solution, the washing may be performed for a plurality of times, for example, 2-3 times, the cooling may be performed to 5-10 ℃, the crystallization may be performed to adjust the pH of the second reaction solution, the crystallization may be performed under the condition that the ph=2-3 of the second reaction solution, a large amount of white solids may be precipitated, the second reaction solution may be rinsed, the filter cake may be filtered, the filter cake may be rinsed, the filter cake may be dried, and the filter cake may be dried at a temperature of 2-50 ℃.
In the step S4, the inorganic solvent can also be water, the heating can be performed until the temperature reaches 95-100 ℃, a small amount of purple quinone substances can be removed by adopting the step S4, the heating end point can be the time when the liquid in the heating system is completely clarified, the filtering can be performed when the liquid is hot, the activated carbon and the heating liquid system can be separated by the suction filtration, the filtrate after the suction filtration can be cooled to 5-10 ℃, the crystallization can be performed under the condition of stirring, the time of the crystallization can be 1-2 hours, and the finished vanilla acid product can be obtained by the processes of suction filtration, leaching, drying and crushing, wherein the processes of leaching and drying can be the same as the process in the step S3.
Hereinafter, the present invention will be more specifically explained by referring to examples, which should not be construed as limiting. Appropriate modifications may be made within the scope consistent with the gist of the invention, which fall within the technical scope of the invention. In the following examples, unless otherwise specified, all experimental methods used were conventional and all materials, reagents, etc. were purchased from chemical reagent company. The yield calculation formula of the invention is as follows: yield = amount of actual formation of vanillic acid/theoretical formation of vanillic acid 100%, the molecular weight of said vanillic acid calculated as 168.
Example 1
Under the condition of room temperature (25-30 ℃), 152g (1 mol) of vanillin, 6.73g (0.05 mol) of copper chloride, 307g (1 mol) of potassium hydrogen persulfate, 500ml of acetonitrile and 500ml of water are added into a reaction bottle, stirred and reacted for about 5-6 hours until TLC or liquid phase detects the disappearance of vanillin, the reaction is stopped, the organic solvent is removed by decompression concentration, 500ml of saturated sodium carbonate aqueous solution is added, 300ml of ethyl acetate is used for washing the water layer for 2 times, then the water layer is cooled to 5-10 ℃, the pH of the water layer is regulated to approximately 2-3 by hydrochloric acid, a large amount of white solid is separated out, the filtration is carried out, and a filter cake is leached with 100ml of ice water for 2 times, thus obtaining 191.6g of crude vanillic acid containing water.
Adding 1000ml of crude vanillic acid, 1000ml of water and 9.5g of activated carbon into a reaction bottle, and heating to 95-100 ℃ until the liquid in the reaction bottle is clear. Stopping heating, and filtering while the reflux is hot. The filtrate is cooled to below 10 ℃ to separate out a large amount of white crystals, the white crystals are stirred for 1 to 2 hours, the filtration is carried out, the filter cake is leached for 1 time by 100ml of ice water below 10 ℃, the filtration is dried and crushed, and the total of 155.9g of vanilla acid sample 1 is obtained, and the yield is 92.8 percent. Sample 1 was tested by liquid phase and nuclear magnetism to obtain higher purity vanillic acid, and the liquid phase test results are shown in fig. 3 and table 1.
TABLE 1 HPLC detection result table (254 nm)
| No. | RT | Area of | Concentration of |
| 1 | 1.987 | 105113 | 0.401 |
| 2 | 2.373 | 86161 | 0.328 |
| 3 | 3.813 | 11802 | 0.045 |
| 4 | 4.627 | 18031 | 0.069 |
| 5 | 5.367 | 2585 | 0.010 |
| 6 | 6.587 | 25945937 | 98.860 |
| 7 | 9.933 | 29340 | 0.112 |
| 8 | 15.927 | 22132 | 0.084 |
| 9 | 25.393 | 24066 | 0.092 |
| Totalizing | 26245167 | 100.000 |
Sample 1 1 The H-NMR detection result was: (400 MHz, CD) 3 OD)δ7.56(1H,dd,J＝1.8Hz),7.50(1H,dd,J＝8.2Hz and 1.8Hz),6.77(1H,d,J＝8.2Hz),3.88(3H,s,OCH 3 )。
Example 2
Under the condition of room temperature (25-30 ℃), 152g (1 mol) of vanillin, 11.75g (0.05 mol) of copper bromide, 307g (1 mol) of potassium hydrogen persulfate, 500ml of methanol and 500ml of water are added into a reaction bottle, stirred and reacted for about 5-6 hours until the vanillin is detected to disappear by TLC or liquid phase, the reaction is stopped, the organic solvent is removed by decompression concentration, 500ml of saturated sodium carbonate aqueous solution is added, 300ml of ethyl acetate is used for washing the water layer for 2 times, then the water layer is cooled to 5-10 ℃, the pH of the water layer is regulated to approximately 2-3 by hydrochloric acid, a large amount of white solid is separated out, the water is filtered, and a filter cake is leached by 100ml of ice water for 2 times, so that 185.9g of crude vanillic acid containing water is obtained.
Adding 1000ml of crude vanillic acid, 1000ml of water and 9.5g of activated carbon into a reaction bottle, and heating to 95-100 ℃ until the liquid in the reaction bottle is clear. Stopping heating, and filtering while the reflux is hot. The filtrate is cooled to below 10 ℃ and separated outA large amount of white crystals are stirred for 1-2 hours, suction filtration is carried out, the filter cake is leached for 1 time by 100ml of ice water with the temperature below 10 ℃, and is dried and crushed, thus obtaining the vanilla acid sample 2 which is 151.7g in total, and the yield is 90.3%. HPLC content detection of sample 2 1 The H-NMR nuclear magnetic hydrogen spectrum results were similar to those of sample 1.
Example 3
Under the condition of room temperature (25-30 ℃), 152g (1 mol) of vanillin, 14.78g (0.05 mol) of copper nitrate, 307g (1 mol) of potassium persulfate, 500ml of isopropanol and 500ml of water are added into a reaction bottle, stirred and reacted for about 5-6 hours until TLC or liquid phase detects the disappearance of vanillin, the reaction is stopped, the organic solvent is removed by decompression concentration, 500ml of saturated sodium carbonate aqueous solution is added, 300ml of ethyl acetate is used for washing the water layer for 2 times, then the water layer is cooled to 5-10 ℃, the pH value of the water layer is regulated to be approximately equal to 2-3 by hydrochloric acid, a large amount of white solid is separated out, the filtration is carried out, and a filter cake is leached with 100ml of ice water for 2 times, thus obtaining 201.5g of crude vanillic acid containing water.
Adding crude vanillic acid, 1000ml of water and 9.5g of activated carbon into a reaction bottle, and heating to 95-100 ℃ until the liquid in the reaction bottle is clear. Stopping heating, and filtering while the reflux is hot. The filtrate is cooled to below 10 ℃ to separate out a large amount of white crystals, the white crystals are stirred for 1 to 2 hours, the filtration is carried out, the filter cake is leached for 1 time by 100ml of ice water below 10 ℃, the filtration is dried and crushed, 158.7g of vanilla sample 3 is obtained, and the yield is 94.5 percent. HPLC content detection of sample 3 1 The H-NMR nuclear magnetic hydrogen spectrum results were similar to those of sample 1.
Example 4
Under the condition of room temperature (25-30 ℃), 152g (1 mol) of vanillin, 12.5g (0.05 mol) of copper sulfate, 307g (1 mol) of potassium hydrogen persulfate, 500ml of ethanol and 500ml of water are added into a reaction bottle, stirred and reacted for about 5-6 hours until the vanillin is detected to disappear by TLC or liquid phase, the reaction is stopped, the organic solvent is removed by decompression concentration, 500ml of saturated sodium carbonate aqueous solution is added, 300ml of ethyl acetate is used for washing the water layer for 2 times, then the water layer is cooled to 5-10 ℃, the pH of the water layer is regulated to approximately 2-3 by hydrochloric acid, a large amount of white solid is separated out, the water is filtered, and a filter cake is leached by 100ml of ice water for 2 times, so that 185.7g of crude vanillic acid containing water is obtained.
Adding crude vanillic acid, 1000ml of water and 9.5g of activated carbon into a reaction bottle, and heating to 95-100 ℃ until the liquid in the reaction bottle is clear. Stopping heating, and filtering while the reflux is hot. The filtrate is cooled to below 10 ℃ to separate out a large amount of white crystals, the white crystals are stirred for 1 to 2 hours, the filtration is carried out, the filter cake is leached for 1 time by 100ml of ice water below 10 ℃, the filtration is dried and crushed, and 152.4g of vanilla sample 4 is obtained, and the yield is 90.7 percent. HPLC content detection of sample 4 1 The H-NMR nuclear magnetic hydrogen spectrum results were similar to those of sample 1.
Example 5
Under the condition of room temperature (25-30 ℃), 152g (1 mol) of vanillin, 9.98g (0.05 mol) of copper acetate, 307g (1 mol) of potassium hydrogen persulfate, 500ml of tetrahydrofuran and 500ml of water are added into a reaction bottle, stirred and reacted for about 5-6 hours until TLC or liquid phase detects the disappearance of vanillin, the reaction is stopped, the organic solvent is removed by decompression concentration, 500ml of saturated sodium carbonate aqueous solution is added, 300ml of ethyl acetate is used for washing the water layer for 2 times, then the water layer is cooled to 5-10 ℃, the pH value of the water layer is regulated to be approximately equal to 2-3 by hydrochloric acid, a large amount of white solid is separated out, the filtration is carried out, and a filter cake is leached with 100ml of ice water for 2 times, thus obtaining 203.1g of crude vanillic acid containing water.
Adding 1000ml of crude vanillic acid, 1000ml of water and 9.5g of activated carbon into a reaction bottle, and heating to 95-100 ℃ until the liquid in the reaction bottle is clear. Stopping heating, and filtering while the reflux is hot. The filtrate is cooled to below 10 ℃ to separate out a large amount of white crystals, the white crystals are stirred for 1 to 2 hours, the filtration is carried out, the filter cake is leached for 1 time by 100ml of ice water below 10 ℃, the filtration is dried and crushed, 159.1g of vanilla sample 5 is obtained, and the yield is 94.7 percent. HPLC content detection of sample 5 1 The H-NMR nuclear magnetic hydrogen spectrum results were similar to those of sample 1.
Therefore, the invention effectively overcomes various defects in the prior art and has high industrial utilization value. The above embodiments are merely illustrative of the principles of the present invention and its effectiveness, and are not intended to limit the invention. Modifications and variations may be made to the above-described embodiments by those skilled in the art without departing from the spirit and scope of the invention. Accordingly, it is intended that all equivalent modifications and variations of the invention be covered by the claims, which are within the ordinary skill of the art, be within the spirit and scope of the present disclosure.
Claims (10)
1. A method for preparing vanillic acid, which is characterized by comprising the following steps:
mixing vanillin, a catalyst and an oxidant in a solvent to react to obtain a first reaction solution, wherein the solvent comprises an organic solvent and an inorganic solvent;
removing the organic solvent in the first reaction liquid to obtain a second reaction liquid;
washing the second reaction liquid, and cooling and crystallizing to obtain a crude product of the vanillic acid;
mixing the crude product of the vanillic acid and the activated carbon in an inorganic solvent, heating, filtering, cooling and crystallizing the filtrate to obtain the vanillic acid.
2. The method according to claim 1, characterized in that: the catalyst is inorganic copper salt.
3. The method according to claim 1, characterized in that: the oxidant is potassium hydrogen persulfate.
4. The method according to claim 1, characterized in that: the organic solvent comprises any one or more of acetonitrile, methanol, ethanol, isopropanol and tetrahydrofuran.
5. The method according to claim 1, characterized in that: the reaction time of the reaction is 5-6 hours.
6. The method according to claim 1, characterized in that: the reaction temperature of the reaction is 25-30 ℃.
7. The method according to claim 1, characterized in that: the heating temperature of the heating is 95-100 ℃.
8. The method according to claim 1, characterized in that: the inorganic solvent is water.
9. The method according to claim 1, characterized in that: the molar ratio of the catalyst to the vanillin is (0.01-0.05): 1.
10. the method according to claim 1, characterized in that: the molar ratio of the oxidizing agent to the vanillin is (1-1.2): 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111180224.1A CN116986980A (en) | 2021-10-11 | 2021-10-11 | Preparation method of vanillic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111180224.1A CN116986980A (en) | 2021-10-11 | 2021-10-11 | Preparation method of vanillic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116986980A true CN116986980A (en) | 2023-11-03 |
Family
ID=88528868
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111180224.1A Pending CN116986980A (en) | 2021-10-11 | 2021-10-11 | Preparation method of vanillic acid |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116986980A (en) |
-
2021
- 2021-10-11 CN CN202111180224.1A patent/CN116986980A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5395908B2 (en) | Process for producing 4- (1-hydroxy-1-methylethyl) -2-propylimidazole-5-carboxylic acid ester | |
| CN110437294A (en) | A method of preparing Trenbolone acetate | |
| CN115093386B (en) | Production method of colorless, tasteless and borate-free vitreous chromogen | |
| CN107011404A (en) | A kind of method using cholic acid as Material synthesis lithocholic acid | |
| CN102993181B (en) | Preparation method of esomeprazole and preparation method of esomeprazole salt | |
| CN109553550B (en) | Method for synthesizing dihydrooat alkaloid | |
| CN101830793B (en) | Method for preparing hydroxyl-substituted phenylacetic acid compound | |
| CN105175317B (en) | A kind of method for preparing picosulfate sodium | |
| JPS6222740A (en) | Isolation of p-hydroxybenzaldehyde | |
| CN116986980A (en) | Preparation method of vanillic acid | |
| CN105175316B (en) | A kind of method for preparing laxative picosulfate sodium | |
| CN112645799B (en) | Resorcinol post-treatment process | |
| CN111100042B (en) | Preparation method of 2-methoxy-5-sulfonamide benzoic acid | |
| CN103980134A (en) | Preparation method of succinic acid S-metoprolol | |
| CN101323590B (en) | Novel synthetic method of aripiprazole and intermediate thereof | |
| CN103508898A (en) | Novel preparation method of alverine citrate | |
| CN102690211B (en) | The preparation method of tolvaptan intermediate | |
| CN107129466B (en) | Synthesis method of 4-chloro-3-methoxy-2-methylpyridine-N-oxide | |
| CN102127093B (en) | Refining process for Cefotiam hexetil hydrochloride | |
| CN106957313B (en) | A kind of preparation method and purposes of heteropoly acid crystal | |
| CN113061084B (en) | Novel method for preparing ferulic acid | |
| CN111440079A (en) | Synthesis method of D L-threo-p-chlorophenylserine | |
| CN103833796A (en) | Method of preparing 6-deoxy-L-talose | |
| JP2003261535A (en) | Method for producing 2-hydroxy-5-methylpyridine | |
| CN114716449B (en) | Preparation method of 2-methoxy-6-ethylene glycol ketal-5, 7, 8-trihydroquinoline |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |