CN104926637A - Preparation method for 4-hydroxy-3-methoxy benzoic acid - Google Patents
Preparation method for 4-hydroxy-3-methoxy benzoic acid Download PDFInfo
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- CN104926637A CN104926637A CN201510313374.3A CN201510313374A CN104926637A CN 104926637 A CN104926637 A CN 104926637A CN 201510313374 A CN201510313374 A CN 201510313374A CN 104926637 A CN104926637 A CN 104926637A
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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
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Abstract
The invention discloses a preparation method for 4-hydroxy-3-methoxy benzoic acid. The preparation method comprises the following stesp: using guaiacol as a starting material and water as a solvent, and through the action of a carboxylation reagent under the alkaline condition, synthesizing 4-hydroxy-3-methoxy benzoate only by one-step reaction; acidifying after the reaction, extracting and concentrating under reduced pressure to obtain a crude product; after the raw material of guaiacol is recycled, recrystallizing with water to obtain a pure product, namely 4-hydroxy-3-methoxy benzoic acid. According to the preparation method, the raw material is cheap and easy to obtain, the reaction condition is mild, the operation is simple and convenient, the production cost is relatively low, and the preparation method has a relatively wide industrial application prospect.
Description
Technical field
The invention belongs to chemical field, particularly relate to a kind of vanillic acid, specifically a kind of preparation method of vanillic acid.
Background technology
Vanillic acid, also known as vanillinated, or vanillic acid, it is a kind of broad-spectrum organic compound, field of medicaments can be widely applied to, because its oxidation resistant characteristic is applied to field of food as foodstuff additive, in addition as antioxidant or tyrosinase inhibitor etc., also to be widely used research at agriculture field, therefore to have a good application prospect.
The synthesis preparation of vanillic acid has had to be studied widely.Traditional chemical process is that raw material is obtained by oxidation (silver suboxide) or alkali fusion (potassium hydroxide, temperature is below 240 DEG C) with vanillin food grade,1000.000000ine mesh, and it is expensive that the method exists cost of material, and reaction conditions requires harsh, the shortcoming that running cost is high; They take oxoethanoic acid as Material synthesis vanillinated, but this reactions steps is many, operation is complicated, and yield is low.In addition with 4-methyl guaiacol and 4 for substrate, protect phenolic hydroxyl group with diacetyl oxide, with potassium permanganate oxidation methyl synthesis vanillinated, it is many to there is step in this reaction process, and pollute large, security is relatively low.
Acetaldehyde acid system synthesis vanillinated
Potassium permanganate oxidation method synthesis vanillinated
Summary of the invention
For the defect existed in above-mentioned prior art, technical problem to be solved by this invention is to provide a kind of preparation method of vanillic acid, and the preparation method of described this vanillic acid will solve the technical problems such as severe reaction conditions of the prior art, production cost is high, step is many, pollution is large, security is low.
The invention provides a kind of preparation method of vanillic acid, comprise following steps:
1) methyl catechol and carboxylating reagent is taken, described methyl catechol and the mol ratio of carboxylating reagent are 1:1.0 ~ 4.0, methyl catechol and carboxylating reagent are added in a reaction vessel, add alkaline solution adjust ph 11 ~ 14, terminate down to reaction at stirring, heating condition, the reaction times is 2 ~ 8h, add acid solution after question response terminates and regulate pH to 2 ~ 3, with organic solvent extraction 2 ~ 5 times, get upper organic phase, concentrating under reduced pressure obtains crude product;
2) crude product obtains vanillic acid through recrystallization.
Further, described Carboxylation reagent is oxalic dialdehyde.
Further, described alkaline solution is sodium hydroxide or potassium hydroxide, and the mass percent concentration of described alkaline solution is 1 ~ 15%.Preferred diluted alkaline is sodium hydroxide.
Further, described acid solution is hydrochloric acid or sulfuric 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, and preferable temperature is 30 ~ 45 DEG C.
The preparation method of a kind of vanillic acid of the present invention, comprises the steps:
Reaction equation of the present invention is;
The present invention take methyl catechol as starting raw material, water is as solvent, in the basic conditions through carboxylating reagent effect, only need through single step reaction synthesis 4-hydroxyl-3 methoxy-benzoic acid salt, through acidifying after reaction, extraction, concentrating under reduced pressure obtains crude product, after reclaiming raw material methyl catechol, obtain sterling with water recrystallization.
The present invention compares with prior art, and its technical progress is significant.The present invention only need single step reaction to product.And method of the present invention has that raw material is easy to get, reaction conditions gentle, security is high, a step catalyzes and synthesizes vanillinated, simple to operate, production cost is low.Pollute simultaneously little, selectivity good, has stronger industrial applications prospect.
Embodiment
In order to make those skilled in the art understand the present invention better, the present invention will be further described by the following examples, but these embodiments do not limit the scope of the invention.
EXAMPLE l
500ml three-necked flask has magnetic stirring apparatus, thermometer, detachable reflux condensate device.Add 24.8g (0.2mol) methyl catechol, add 23.2g 50% oxalic dialdehyde (0.2mol) (i.e. methyl catechol and oxalic dialdehyde mol ratio be 1:1) again, the sodium hydroxide adjust ph adding 10% is 12.0 ~ 12.5, stir, 35 ~ 40 DEG C of insulation reaction 6.0 hours.Reaction is finished, dilute hydrochloric acid regulates, reacting liquid pH value is adjusted to 2 ~ 3, and after product is extracted with ethyl acetate 3 times, concentrating under reduced pressure obtains crude product, it is 25% that product vanillinated HPLC analyzes content, the unreacted raw material methyl catechol of crude product reclaim under reduced pressure, residuum water recrystallization, obtains white solid 6.3g, reaction preference 83%, yield is 75%.
m.p.206～207℃(lit.m.p.208～210℃)；1H NMR(500MHz,DMSO-d6)d 12.73(brs,1H),9.99-9.68(m,1H),7.43(s,2H),6.85(s,1H),3.80(s,3H)；HRMS(EI)calcd for C8H8O4[M]+168.0421,found 168.0423。
Embodiment 2
500ml three-necked flask has magnetic stirring apparatus, thermometer, detachable reflux condensate device.Add 12.4g (0.1mol) methyl catechol, add 23.2g 50% oxalic dialdehyde (i.e. methyl catechol and oxalic dialdehyde mol ratio be 1:2) again, adding 10% potassium hydroxide solid adjust ph is 11.5-12.0, stirs, 30 ~ 35 DEG C of insulation reaction 6.0 hours.Reaction is finished, dilute sulphuric acid regulates, by reaction solution pH regulator to 2 ~ 3, after product is extracted with ethyl acetate 3 times, concentrating under reduced pressure obtains crude product, product vanillinated HPLC content is 18%, the unreacted raw material methyl catechol of crude product reclaim under reduced pressure, residuum water crystallization, obtains white powder crystal 2.3g, reaction preference is 81%, yield 70%.
Embodiment 3
500ml three-necked flask has magnetic stirring apparatus, thermometer, detachable reflux condensate device.Add 12.4g (0.1mol) methyl catechol, add 46.4g 50% oxalic dialdehyde (i.e. methyl catechol and oxalic dialdehyde mol ratio be 1:4) again, the sodium hydroxide adjust ph adding 30% is 13.0 ~ 13.5, stirs, 45 ~ 50 DEG C of insulation reaction 2 ~ 2.5 hours.Reaction is finished, dilute hydrochloric acid regulates, reacting liquid pH value is adjusted to 2 ~ 3, and after product is extracted with ethyl acetate 3 times, concentrating under reduced pressure obtains crude product, product vanillinated HPLC content is 16%, the unreacted raw material methyl catechol of crude product reclaim under reduced pressure, residuum water recrystallization, obtains white solid 1.69g, reaction preference is 73%, yield 58%.
Embodiment 4
500ml three-necked flask has magnetic stirring apparatus, thermometer, detachable reflux condensate device.Add 12.4g (0.1mol) methyl catechol, add 46.4g 50% oxalic dialdehyde (i.e. methyl catechol and oxalic dialdehyde mol ratio be 1:4) again, the sodium hydroxide adjust ph adding 10% is 12.0 ~ 12.5, stirs, 20 ~ 25 DEG C of insulation reaction 8 hours.Reaction is finished, dilute hydrochloric acid regulates, reacting liquid pH value is adjusted to after 2 ~ 3 products are extracted with ethyl acetate 2 ~ 3 times, concentrating under reduced pressure obtains crude product, and product vanillinated HPLC content is 11%, the unreacted raw material methyl catechol of crude product reclaim under reduced pressure, residuum water recrystallization, obtain white solid 0.64g, reaction preference is 55%, yield 32%.
Claims (6)
1. a preparation method for vanillic acid, is characterized in that comprising following steps:
Take methyl catechol and carboxylating reagent, described methyl catechol and the mol ratio of carboxylating reagent are 1:1.0 ~ 4.0, methyl catechol and carboxylating reagent are added in a reaction vessel, add alkaline solution adjust ph 11 ~ 14, terminate down to reaction at stirring, heating condition, the reaction times is 2 ~ 8h, add acid solution after question response terminates and regulate pH to 2 ~ 3, with organic solvent extraction 2 ~ 5 times, get 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 4-hydroxyl-3 methoxybenzoic acid as claimed in claim 1, is characterized in that: described Carboxylation reagent is oxalic dialdehyde.
3. the preparation method of a kind of 4-hydroxyl-3 methoxybenzoic acid as claimed in claim 1, is characterized in that: described alkaline solution is sodium hydroxide or potassium hydroxide, and the mass percent concentration of described alkaline solution is 5 ~ 35%.
4. the preparation method of a kind of 4-hydroxyl-3 methoxybenzoic acid as claimed in claim 1, is characterized in that: described acid solution is hydrochloric acid or sulfuric acid, and the mass percent concentration of described acid solution is 1 ~ 15%.
5. the preparation method of a kind of 4-hydroxyl-3 methoxybenzoic acid as claimed in claim 1, is characterized in that: described organic solvent is ethyl acetate.
6. the preparation method of a kind of 4-hydroxyl-3 methoxybenzoic acid as claimed in claim 1, is characterized in that: the temperature of described reaction is between 20 ~ 50 DEG C.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH05194308A (en) * | 1992-01-22 | 1993-08-03 | Mitsubishi Kasei Corp | Production of p-hydroxybenzoic acids |
| CN1233235A (en) * | 1996-10-14 | 1999-10-27 | 罗狄亚化学公司 | Method for selective preparation of a 2-hydroxybenzoic acid and a 4-hydroxybenzaldehyde and derivatives |
| WO2010141499A2 (en) * | 2009-06-01 | 2010-12-09 | Strategic Enzyme Applications, Inc. | Lignin oxidation and products thereof |
-
2015
- 2015-06-09 CN CN201510313374.3A patent/CN104926637B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH05194308A (en) * | 1992-01-22 | 1993-08-03 | Mitsubishi Kasei Corp | Production of p-hydroxybenzoic acids |
| CN1233235A (en) * | 1996-10-14 | 1999-10-27 | 罗狄亚化学公司 | Method for selective preparation of a 2-hydroxybenzoic acid and a 4-hydroxybenzaldehyde and derivatives |
| WO2010141499A2 (en) * | 2009-06-01 | 2010-12-09 | Strategic Enzyme Applications, Inc. | Lignin oxidation and products thereof |
Non-Patent Citations (1)
| Title |
|---|
| 张小林 等: "2-羟基-3-甲氧基苯甲酸甲酯的合成", 《化学世界》 * |
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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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