CN104926637B - A kind of preparation method of vanillic acid - Google Patents
A kind of preparation method of vanillic acid Download PDFInfo
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- CN104926637B CN104926637B CN201510313374.3A CN201510313374A CN104926637B CN 104926637 B CN104926637 B CN 104926637B CN 201510313374 A CN201510313374 A CN 201510313374A CN 104926637 B CN104926637 B CN 104926637B
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- guaiacol
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
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- 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
Abstract
Disclosure one 4-hydroxy-3-methoxy-benzoic preparation method, with guaiacol for initiation material, water is as solvent, in the basic conditions through carboxylating reagent effect, it is only necessary to synthesize 4-hydroxyl-3 methoxy-benzoic acid salt through single step reaction, through acidifying after reaction, extract, concentrating under reduced pressure obtains crude product, after reclaiming raw material guaiacol, obtains sterling with water recrystallization。This method raw material is cheap and easily-available, and reaction condition is gentle, and easy and simple to handle, production cost is relatively low, has stronger industrial applications prospect。
Description
Technical field
The invention belongs to chemical field, particularly relate to a kind of vanillic acid, the preparation method of a kind of vanillic acid specifically。
Background technology
Vanillic acid, also known as vanillic acid, or vanillic acid, it it is a kind of broad-spectrum organic compound, field of medicaments can be widely applied to, owing to its antioxidative characteristic is applied to field of food as food additive, in addition as antioxidant or tyrosinase inhibitor etc., also it is widely used research at agriculture field, therefore has a good application prospect。
Vanillic acid synthetically prepared has had to be studied widely。Traditional chemical method is to prepare by aoxidizing (silver oxide) or alkali fusion (potassium hydroxide, temperature is below 240 DEG C) with vanillin for raw material, and it is expensive that the method exists cost of material, and reaction condition requires harshness, the shortcoming that running cost is high；With glyoxalic acid for Material synthesis vanillic acid, but this reactions steps is many, and operation is complicated, and yield is low。In addition with 4-methyl guaiacol and 4 for substrate, protecting phenolic hydroxyl group with acetic anhydride, synthesize vanillic acid with potassium permanganate oxidation methyl, it is many to there is step in this reaction process, pollutes big, and safety is relatively low。
Acetaldehyde acid system synthesis vanillic acid
Potassium permanganate oxidation method synthesis vanillic acid
Summary of the invention
For the defect existed in above-mentioned prior art, the preparation method that the technical problem to be solved is to provide a kind of vanillic acid, the preparation method of described this vanillic acid to solve the technical problems such as severe reaction conditions of the prior art, production cost is high, step is many, pollution is big, safety is low。
The preparation method that the invention provides a kind of vanillic acid, comprises the steps of
1) guaiacol and carboxylating reagent are weighed, described guaiacol and the mol ratio of carboxylating reagent are 1:1.0～4.0, guaiacol and carboxylating reagent are added in a reaction vessel, adding aqueous slkali and regulate pH value 11～14, terminate down to reaction at stirring, heating condition, the response time is 2～8h, question response adds acid solution after terminating and regulates pH to 2～3, with organic solvent extraction 2～5 times, taking upper organic phase, concentrating under reduced pressure obtains crude product；
2) crude product obtains vanillic acid through recrystallization。
Further, described Carboxylation reagent is Biformyl。
Further, described aqueous slkali is sodium hydroxide or potassium hydroxide, and the mass percent concentration of described aqueous slkali is 1～15%。Preferred diluted alkaline is sodium hydroxide。
Further, described acid solution is hydrochloric acid or sulphuric acid, and the mass percent concentration of described acid solution is 5～35%。Preferred diluted acid is dilute hydrochloric acid。
Further, described organic solvent is ethyl acetate。
Further, the temperature of described reaction is between 20～50 DEG C, it is preferable that temperature is 30～45 DEG C。
The preparation method of a kind of vanillic acid of the present invention, comprises the steps:
The reaction equation of the present invention is；
The present invention is with guaiacol for initiation material, water is as solvent, in the basic conditions through carboxylating reagent effect, only need to synthesize 4-hydroxyl-3 methoxy-benzoic acid salt through single step reaction, through acidifying after reaction, extracting, concentrating under reduced pressure obtains crude product, after reclaiming raw material guaiacol, obtain sterling with water recrystallization。
The present invention compares with prior art, and its technological progress is significant。The present invention only need single step reaction to product。And the method for the present invention has that raw material is easy to get, reaction condition is gentle, safety high, a step catalyzes and synthesizes vanillic acid, simple to operate, production cost is low。Pollute simultaneously little, selectivity good, has stronger industrial applications prospect。
Detailed description of the invention
In order to make those skilled in the art be more fully understood that the present invention, the present invention will be further described by the following examples, but these embodiments do not limit the scope of the invention。
Embodiment l
500ml three-neck flask has magnetic stirring apparatus, thermometer, detachable reflux condensate device。Add 24.8g (0.2mol) guaiacol, add 23.2g50% Biformyl (0.2mol) (namely guaiacol is 1:1 with the mol ratio of Biformyl), the sodium hydroxide adjustment pH value adding 10% is 12.0～12.5, stirring, 35～40 DEG C of insulation reaction 6.0 hours。Reaction is finished, dilute hydrochloric acid regulates, regulating reacting liquid pH value to 2～3, after product is extracted with ethyl acetate 3 times, concentrating under reduced pressure obtains crude product, it is 25% that product vanillic acid HPLC analyzes content, the unreacted raw material guaiacol of crude product recovered under reduced pressure, residue water recrystallization, obtain white solid 6.3g, reaction selectivity 83%, yield is 75%。
M.p.206～207 DEG C (lit.m.p.208～210 DEG C)；1HNMR (500MHz, DMSO-d6) d12.73 (brs, 1H), 9.99-9.68 (m, 1H), 7.43 (s, 2H), 6.85 (s, 1H), 3.80 (s, 3H)；HRMS (EI) calcdforC8H8O4 [M]+168.0421, found168.0423。
Embodiment 2
500ml three-neck flask has magnetic stirring apparatus, thermometer, detachable reflux condensate device。Add 12.4g (0.1mol) guaiacol, add 23.2g50% Biformyl (namely guaiacol is 1:2 with the mol ratio of Biformyl), adding 10% potassium hydroxide solid, to regulate pH value be 11.5-12.0, stirring, 30～35 DEG C of insulation reaction 6.0 hours。Reaction is finished, dilute sulfuric acid regulates, by reactant liquor pH regulator to 2～3, after product is extracted with ethyl acetate 3 times, concentrating under reduced pressure obtains crude product, product vanillic acid HPLC content is 18%, the unreacted raw material guaiacol of crude product recovered under reduced pressure, residue water crystallization, obtain white powder crystal 2.3g, reaction selectivity is 81%, yield 70%。
Embodiment 3
500ml three-neck flask has magnetic stirring apparatus, thermometer, detachable reflux condensate device。Add 12.4g (0.1mol) guaiacol, add 46.4g50% Biformyl (namely guaiacol is 1:4 with the mol ratio of Biformyl), adding the sodium hydroxide of 30%, to regulate pH value be 13.0～13.5, stirring, 45～50 DEG C of insulation reaction 2～2.5 hours。Reaction is finished, dilute hydrochloric acid regulates, regulating reacting liquid pH value to 2～3, after product is extracted with ethyl acetate 3 times, concentrating under reduced pressure obtains crude product, product vanillic acid HPLC content is 16%, the unreacted raw material guaiacol of crude product recovered under reduced pressure, residue water recrystallization, obtain white solid 1.69g, reaction selectivity is 73%, yield 58%。
Embodiment 4
500ml three-neck flask has magnetic stirring apparatus, thermometer, detachable reflux condensate device。Add 12.4g (0.1mol) guaiacol, add 46.4g50% Biformyl (namely guaiacol is 1:4 with the mol ratio of Biformyl), adding the sodium hydroxide of 10%, to regulate pH value be 12.0～12.5, stirring, 20～25 DEG C of insulation reaction 8 hours。Reaction is finished, dilute hydrochloric acid regulates, reacting liquid pH value is regulated after being extracted with ethyl acetate 2～3 times to 2～3 products, concentrating under reduced pressure obtains crude product, and product vanillic acid HPLC content is 11%, the unreacted raw material guaiacol of crude product recovered under reduced pressure, residue water recrystallization, obtaining white solid 0.64g, reaction selectivity is 55%, yield 32%。
Claims (3)
1. the preparation method of a vanillic acid, it is characterised in that comprise the steps of
Weigh guaiacol and carboxylating reagent, described Carboxylation reagent is Biformyl, described guaiacol and the mol ratio of carboxylating reagent are 1:1.0 ~ 4.0, guaiacol and carboxylating reagent are added in a reaction vessel, add aqueous slkali and regulate pH value 11 ~ 14, in stirring, heating condition terminates down to reaction, the temperature of described reaction is between 20 ~ 50 DEG C, response time is 2 ~ 8h, question response adds acid solution after terminating and regulates pH to 2 ~ 3, with organic solvent extraction 2 ~ 5 times, described organic solvent is ethyl acetate, take upper organic phase, concentrating under reduced pressure obtains crude product；Crude product obtains vanillic acid through recrystallization。
2. the preparation method of a kind of vanillic acid as claimed in claim 1, it is characterised in that: described aqueous slkali is sodium hydroxide or potassium hydroxide, and the mass percent concentration of described aqueous slkali is 5 ~ 35%。
3. the preparation method of a kind of vanillic acid as claimed in claim 1, it is characterised in that: described acid solution is hydrochloric acid or sulphuric acid, and the mass percent concentration of described acid solution is 1 ~ 15%。
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JP3018704B2 (en) * | 1992-01-22 | 2000-03-13 | 三菱化学株式会社 | Method for producing parahydroxybenzoic acids |
| FR2754533B1 (en) * | 1996-10-14 | 1998-11-27 | Rhodia Chimie Sa | PROCESS FOR THE SELECTIVE PREPARATION OF A 2-HYDROXYBENZOIC ACID AND A 4-HYDROXYBENZALDEHYDE AND DERIVATIVES |
| US20120107886A1 (en) * | 2009-06-01 | 2012-05-03 | Strategic Enzyme Applications, Inc. | Lignin Oxidation and Products Thereof |
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Effective date of registration: 20181112 Address after: 236800 Boju Road, Bozhou City Economic Development Zone, Anhui Province, south side of Zhuangzhou Road, west side Patentee after: Anhui Huaxin Fragrance Co., Ltd. Address before: 200235 No. 120, Xuhui District, Shanghai, Caobao Road Patentee before: Shanghai Institute of Technology |
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Address after: 236800 Boju Road, Bozhou City Economic Development Zone, Anhui Province, south side of Zhuangzhou Road, west side Patentee after: Anhui Huaxin Biotechnology Co.,Ltd. Address before: 236800 Boju Road, Bozhou City Economic Development Zone, Anhui Province, south side of Zhuangzhou Road, west side Patentee before: Anhui Huaxin Fragrance Co.,Ltd. |
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