CN101830793A - Method for preparing hydroxyl-substituted phenylacetic acid compound - Google Patents
Method for preparing hydroxyl-substituted phenylacetic acid compound Download PDFInfo
- Publication number
- CN101830793A CN101830793A CN201010177430A CN201010177430A CN101830793A CN 101830793 A CN101830793 A CN 101830793A CN 201010177430 A CN201010177430 A CN 201010177430A CN 201010177430 A CN201010177430 A CN 201010177430A CN 101830793 A CN101830793 A CN 101830793A
- Authority
- CN
- China
- Prior art keywords
- acid compound
- phenylacetic acid
- hydroxyl
- preparation
- substituted phenylacetic
- 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.)
- Granted
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for preparing a hydroxyl-substituted phenylacetic acid compound. In the method, under normal pressure, at 80 to 120 DEG C and in a nitrogen protective atmosphere, a halogenated phenylacetic acid compound undergoes a substitution reaction in the presence of 8-oxine-copper(II) and an alkali to form the hydroxyl-substituted phenylacetic acid compound. The method has the advantages of high atomic economy, simple operation, short reaction time, mold reaction conditions, high yield, low cost, less pollution and the like and makes scale preparation realized easily.
Description
Technical field
The present invention relates to chemical field, particularly a kind of preparation method of hydroxyl-substituted phenylacetic acid compound.
Background technology
The toluylic acid compounds that hydroxyl replaces is important organic synthesis intermediate, is widely used in industries such as medicine, agricultural chemicals and spices.For example: with 3-hydroxyl-4-methoxyphenylacetic acid is the synthetic alkaloid dihydro thebainone-A with analgesia and syngignoscism of raw material; 3, the 5-dihydroxyphenyl acetic acid is synthetic important source material with natural product resveratrol of anti-oxidant, antithrombotic, Green Tea Extract and effect such as anticancer.
At present, the preparation method of hydroxyl-substituted phenylacetic acid compound mainly contains following several: (1) method of substitution: with halogeno-benzene acetate is raw material, Salzburg vitriol or copper powder are catalyzer, under high pressure, high temperature, alkaline condition, carry out substitution reaction and generate the toluylic acid that hydroxyl replaces; But this method needs High Temperature High Pressure, to the requirement of equipment very high (Speciality Petrochemicals progress, 2002,3:53-56).(2) cyanide process: the phenyl aldehyde that replaces with hydroxyl is a raw material, obtain the derivative of sulfur-bearing with the rhodanine dehydrating condensation, this derivative generates hydroximic acid through being hydrolyzed into corresponding thiocarboxylic acid with azanol reaction, through acidylate, hydrolysis, obtain the toluylic acid compounds that hydroxyl replaces again; But this method step is various, and yield is low, environmental pollution big (Zhengzhou University's journal (medicine), 2004,39 (2): 261-263).
Summary of the invention
The objective of the invention is to overcome the shortcoming that exists in the prior art, provide a kind of simple to operate, reaction conditions is gentle, cost is low, the preparation method of eco-friendly hydroxyl-substituted phenylacetic acid compound.
Purpose of the present invention is achieved through the following technical solutions:
A kind of preparation method of hydroxyl-substituted phenylacetic acid compound comprises the steps: under nitrogen protection, is catalyzer with copper 8-quinolinolate (II) (structural formula is a formula 3), halogeno-benzene phenylacetic acid compound (structural formula is a formula 2) and alkali generation substitution reaction; Cooling then, suction filtration, extraction, decolouring, recrystallization obtain hydroxyl-substituted phenylacetic acid compound (structural formula is a formula 1).
Wherein, m=1 or 2; R=H, OMe, Cl or Me; X=Br or Cl, X can be in any one or two positions of phenyl ring 2,3,5,6.
Described catalyzer copper 8-quinolinolate (II) is to adopt oxine and Cu (II) salt to produce in water-ethanol or water-methanol system, and wherein Cu (II) salt is CuSO
4.5H
2O, CuCl
2.2H
2O or Cu (NO
3)
2.3H
2O.
The mol ratio of described halogeno-benzene phenylacetic acid compound and copper 8-quinolinolate (II) is 1: (0.05～1), preferred molar ratio are 1: 0.1.
Described alkali is that mass concentration is 10%～50% the KOH or the NaOH aqueous solution, and preferred mass concentration is 30%.
The mol ratio of described halogeno-benzene phenylacetic acid compound and alkali is 1: (6～20), preferred molar ratio are 1: 10.
The temperature of described substitution reaction is 80～120 ℃, is preferably 110 ℃; Because the complexity difference of replacement takes place different halogeno-benzene phenylacetic acid compounds, so the time of required substitution reaction is also different, the preferential reaction time is 4～20 hours.
Described extraction is that filtrate is acidified to PH=2～3, uses ethyl acetate extraction, merges organic layer, drying, and concentrating under reduced pressure obtains crude product.Described filtrate acidifying, the acid of employing are hydrochloric acid or sulfuric acid.
Described decolouring is that the crude product that extraction obtains is adopted 5% activated carbon decolorizing.The solvent that is used for activated carbon decolorizing is ethanol or ethyl acetate, preferred alcohol; Bleaching time is 10～30min, and preferred bleaching time is 20min.
Described recrystallization, the solvent of employing are the mixture of mixture, ethyl acetate and chloroform of water, ethyl acetate and sherwood oil or the mixture of ethanol and chloroform; The solvent of preferred recrystallization is the mixture of ethyl acetate and chloroform.
Synthetic route of the present invention is as follows:
The present invention compared with prior art has following advantage and effect:
(1) raw material that adopts of the present invention and reagent all are that the Chemicals that are easy to get, especially catalyst consumption are little and can reuse.
(2) reaction conditions gentleness of the present invention has realized carrying out efficiently under the normal pressure hydroxyl substitution reaction.
(3) operation of the present invention is simple, and the reaction times is short, the transformation efficiency height, pollute little, cost is low, less demanding to equipment is easy to realize scale preparation.
Embodiment
Below in conjunction with embodiment the present invention is done further detailed description, but embodiments of the present invention are not limited thereto.
Embodiment 1
With 3, and 5-dibromobenzene acetate (23.44g, 0.08mol), copper 8-quinolinolate (2.82g, 0.008mol) and 30% sodium hydroxide solution (175mL, 1.44mol) put in the stainless steel reaction bottle, oil bath temperature rises to 120 ℃, stirring heating back flow reaction 6 hours.Stopped reaction filters by (recovery catalyzer), uses hcl acidifying filtrate to PH=2～3, ethyl acetate extraction, merge organic layer, concentrate, get red viscous liquid, use suitable dissolve with ethanol, 5% decolorizing with activated carbon, ethanol-chloroform recrystallization gets white solid 3,5-dihydroxyphenyl acetic acid 12.77g, yield about 95%.M.p.123～124℃.
1HNMR(CD
3COCD
3，400MHz)δ8.208(s，2H，OH)，6.303～6.297(d，2H，J＝2.4Hz，2，5-ArH)，6.241～6.230(t，1H，J＝2.4Hz，4-ArH)，3.427(s，2H，CH
2).MS，m/z(％)：168(M
+).
Embodiment 2
With 3, and 5-dibromobenzene acetate (23.44g, 0.08mol), copper 8-quinolinolate (2.82g, 0.008mol) and 30% sodium hydroxide solution (75mL, 0.8mol) put in the stainless steel reaction bottle, oil bath temperature rises to 110 ℃, stirring heating back flow reaction 6 hours.Stopped reaction filters by (recovery catalyzer), uses hcl acidifying filtrate between PH=2～3, ethyl acetate extraction, merge organic layer, concentrate, get red viscous liquid, use suitable dissolve with ethanol, 5% decolorizing with activated carbon, ethanol-chloroform recrystallization gets white solid 3,5-dihydroxyphenyl acetic acid 13.03g, yield about 97%.
Embodiment 3
With 3, and 5-dibromobenzene acetate (23.44g, 0.08mol), copper 8-quinolinolate (2.82g, 0.008mol) and 30% sodium hydroxide solution (75mL, 0.8mol) put in the stainless steel reaction bottle, oil bath temperature rises to 80 ℃, stirring heating back flow reaction 12 hours.Stopped reaction filters by (recovery catalyzer), uses hcl acidifying filtrate between PH=2～3, ethyl acetate extraction, merge organic layer, concentrate, get red viscous liquid, use suitable acetic acid ethyl dissolution, 5% decolorizing with activated carbon, ethyl acetate-chloroform recrystallization gets white solid 3,5-dihydroxyphenyl acetic acid 11.15g, yield about 83.0%.
Embodiment 4
With 3, and 5-dibromobenzene acetate (23.44g, 0.08mol), copper 8-quinolinolate (1.41g, 0.004mol) and 30% sodium hydroxide solution (75mL, 0.8mol) put in the stainless steel reaction bottle, oil bath temperature rises to 110 ℃, stirring heating back flow reaction 7 hours.Stopped reaction filters by (recovery catalyzer), uses hcl acidifying filtrate between PH=2～3, ethyl acetate extraction, merge organic layer, concentrate, get red viscous liquid, use suitable acetic acid ethyl dissolution, 5% decolorizing with activated carbon, ethyl acetate-chloroform recrystallization gets white solid 3,5-dihydroxyphenyl acetic acid 10.94g, yield about 81.47%.
Embodiment 5
With 3, and 5-dibromobenzene acetate (23.44g, 0.08mol), copper 8-quinolinolate (2.82g, 0.008mol) and 10% sodium hydroxide solution (173mL, 0.48mol) put in the stainless steel reaction bottle, oil bath temperature rises to 120 ℃, stirring heating back flow reaction 20 hours.Stopped reaction filters by (recovery catalyzer), uses hcl acidifying filtrate between PH=2～3, ethyl acetate extraction, merge organic layer, concentrate, get red viscous liquid, use suitable acetic acid ethyl dissolution, 5% decolorizing with activated carbon, ethyl acetate-chloroform recrystallization gets white solid 3,5-dihydroxyphenyl acetic acid 10.08g, yield about 75.0%.
Embodiment 6
With 3-bromo-4-methoxyphenylacetic acid (24.5g, 0.1mol), copper 8-quinolinolate (3.52g, 0.01mol) and 30% sodium hydroxide solution (94mL 1.0mol) puts in the stainless steel reaction bottle, oil bath temperature rises between 110 ℃, stirring heating back flow reaction 10 hours.Stopped reaction, filter by (recovery catalyzer), use hcl acidifying filtrate between PH=2～3, ethyl acetate extraction, merge organic layer, concentrate, get red viscous liquid, use suitable acetic acid ethyl dissolution, 5% decolorizing with activated carbon, with ethyl acetate-sherwood oil recrystallization, obtain white powder crystal 3-hydroxyl-4-methoxyphenylacetic acid 17.93g, yield about 98%.M.p.127.5-129℃.
1H?NMR(CD
3COCD
3，400MHz)δ7.54(S，1H，OH)，6.85～6.87(d，1H，J＝8.0Hz，5-ArH)，6.81(d，1H，J＝2.0Hz，2-ArH)，6.70～6.73(dd，1H，J
1＝8.0Hz，J
2＝2.0Hz，6-ArH)，3.80(s，3H，4-OCH
3)，3.55(s，2H，CH
2).MS，m/z(％)：182(M
+)，183(M
++1)，137，122，94，77.
Embodiment 7
With 3-bromo-4-methoxyphenylacetic acid (24.5g, 0.1mol), copper 8-quinolinolate (3.52g, 0.01mol) and 30% sodium hydroxide solution (94mL 1.0mol) puts in the middle of the stainless steel reaction bottle, oil bath temperature rises between 110 ℃-120 ℃, stirring heating back flow reaction 10 hours.Stopped reaction filters by (recovery catalyzer), uses hcl acidifying filtrate between PH=2～3, crystallisation by cooling, suction filtration gets crude product, uses suitable dissolve with ethanol, 5% decolorizing with activated carbon, water recrystallization can get the solid 3-hydroxyl-4-methoxyphenylacetic acid 16.74g of white needles, yield about 92%.
Embodiment 8
With 2,4 dichloro benzene acetate (10.25g, 0.05mol), copper 8-quinolinolate (17.6g, 0.05mol) and 30% sodium hydroxide solution (94mL 1.0mol) puts in the stainless steel reaction bottle, oil bath temperature rises between 110 ℃-120 ℃, stirring heating back flow reaction 4 days.Stopped reaction filters by (recovery catalyzer), uses hcl acidifying filtrate between PH=2～3, crystallisation by cooling, and suction filtration gets crude product, and the decolorizing with activated carbon with 5% is through product 2-hydroxyl-4-chlorobenzene acetic acid 4.0g that recrystallization can be further purified, yield about 43%.
1H?NMR(CD
3COCD
3，400MHz)δ7.20～7.18(d，1H，J＝8.0Hz，6-ArH)，6.89(d，1H，J＝2.0Hz，3-ArH)，6.84～6.82(dd，1H，J
1＝8.0Hz，J
2＝2.0Hz，5-ArH)，3.60(s，2H，CH
2).MS，m/z(％)：186(M
+).
Embodiment 9
With 2,4 dichloro benzene acetate (10.25g, 0.05mol), copper 8-quinolinolate (17.6g, 0.05mol) and 40% sodium hydroxide solution (60mL 1.0mol) puts in the middle of the stainless steel reaction bottle, and oil bath temperature rises to 120 ℃, stirring heating back flow reaction 20h.Stopped reaction filters by (recovery catalyzer), uses hcl acidifying filtrate between PH=2～3, crystallisation by cooling, and suction filtration gets crude product, and the decolorizing with activated carbon with 5% is through the product 2-hydroxyl-4 chlorobenzene acetic acid 2.1g that recrystallization can be further purified, yield about 22.6%.
Claims (9)
1. the preparation method of a hydroxyl-substituted phenylacetic acid compound is characterized in that comprising the steps: under nitrogen protection, is catalyzer with copper 8-quinolinolate (II) (formula 3), halogeno-benzene phenylacetic acid compound (formula 2) and alkali generation substitution reaction; Cooling then, suction filtration, extraction, decolouring, recrystallization obtain hydroxyl-substituted phenylacetic acid compound (formula 1);
Wherein, m=1 or 2; R=H, OMe, Cl or Me; X=Br or Cl, X can be in any one or two positions of phenyl ring 2,3,5,6.
2. the preparation method of hydroxyl-substituted phenylacetic acid compound according to claim 1, it is characterized in that: described catalyzer copper 8-quinolinolate (II) is to adopt oxine and Cu (II) salt to produce in water-ethanol or water-methanol system, and wherein Cu (II) salt is CuSO
4.5H
2O, CuCl
2.2H
2O or Cu (NO
3)
2.3H
2O.
3. the preparation method of hydroxyl-substituted phenylacetic acid compound according to claim 1, it is characterized in that: the mol ratio of described halogeno-benzene phenylacetic acid compound and copper 8-quinolinolate (II) is 1: (0.05～1).
4. the preparation method of hydroxyl-substituted phenylacetic acid compound according to claim 1, it is characterized in that: described alkali is that mass concentration is 10%～50% the KOH or the NaOH aqueous solution.
5. the preparation method of hydroxyl-substituted phenylacetic acid compound according to claim 1, it is characterized in that: the mol ratio of described halogeno-benzene phenylacetic acid compound and alkali is 1: (6～20).
6. the preparation method of hydroxyl-substituted phenylacetic acid compound according to claim 1, it is characterized in that: the temperature of described substitution reaction is 80～120 ℃; Reaction times is 4～20 hours.
7. the preparation method of hydroxyl-substituted phenylacetic acid compound according to claim 1, it is characterized in that: described extraction is that filtrate is acidified to PH=2～3, uses ethyl acetate extraction, merges organic layer, drying, concentrating under reduced pressure obtains crude product.
8. the preparation method of hydroxyl-substituted phenylacetic acid compound according to claim 1 is characterized in that: described decolouring is that the crude product that extraction obtains is adopted 5% activated carbon decolorizing; The solvent that is used for activated carbon decolorizing is ethanol or ethyl acetate; Bleaching time is 10～30min.
9. the preparation method of hydroxyl-substituted phenylacetic acid compound according to claim 1, it is characterized in that: described recrystallization, the solvent of employing are mixture or the mixture of ethyl acetate and chloroform or the mixture of ethanol and chloroform of water or ethyl acetate and sherwood oil.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010177430.2A CN101830793B (en) | 2010-05-13 | 2010-05-13 | Method for preparing hydroxyl-substituted phenylacetic acid compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010177430.2A CN101830793B (en) | 2010-05-13 | 2010-05-13 | Method for preparing hydroxyl-substituted phenylacetic acid compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101830793A true CN101830793A (en) | 2010-09-15 |
| CN101830793B CN101830793B (en) | 2014-01-15 |
Family
ID=42715036
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201010177430.2A Expired - Fee Related CN101830793B (en) | 2010-05-13 | 2010-05-13 | Method for preparing hydroxyl-substituted phenylacetic acid compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101830793B (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104230800A (en) * | 2014-08-20 | 2014-12-24 | 邯郸惠达化工有限公司 | Preparation method of copper 8-hydroxyquinoline |
| CN104230713A (en) * | 2013-06-18 | 2014-12-24 | 凯米诺瓦有限公司 | Method for preparing 2-(2-hydroxylphenyl)alkyl acetate |
| CN105152918A (en) * | 2015-09-06 | 2015-12-16 | 联化科技(盐城)有限公司 | Preparation method of methoxyphenylacetic acid and intermediate and salt thereof |
| CN105541597A (en) * | 2015-12-29 | 2016-05-04 | 中山大学 | Preparation method of 2,4-dihydroxyphenyl acetic acid |
| CN107686440A (en) * | 2016-08-04 | 2018-02-13 | 辽宁天予化工有限公司 | A kind of preparation method of m-trifluoromethyl phenol |
| CN113372367A (en) * | 2021-05-28 | 2021-09-10 | 无锡颐景丰科技有限公司 | Synthesis method of high-purity 8-hydroxyquinoline copper |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1733674A (en) * | 2005-08-05 | 2006-02-15 | 上海康鹏化学有限公司 | Preparation method of double(2-hydroxyl hexafluopropyl) phenol |
-
2010
- 2010-05-13 CN CN201010177430.2A patent/CN101830793B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1733674A (en) * | 2005-08-05 | 2006-02-15 | 上海康鹏化学有限公司 | Preparation method of double(2-hydroxyl hexafluopropyl) phenol |
Non-Patent Citations (1)
| Title |
|---|
| 蒋培华 等: "对羟基苯乙酸的合成研究", 《精细石油化工进展》, vol. 3, no. 7, 31 July 2002 (2002-07-31), pages 53 - 56 * |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104230713A (en) * | 2013-06-18 | 2014-12-24 | 凯米诺瓦有限公司 | Method for preparing 2-(2-hydroxylphenyl)alkyl acetate |
| CN104230713B (en) * | 2013-06-18 | 2018-11-27 | 凯米诺瓦有限公司 | The method for being used to prepare 2- (2- hydroxy phenyl) alkyl acetate |
| CN104230800A (en) * | 2014-08-20 | 2014-12-24 | 邯郸惠达化工有限公司 | Preparation method of copper 8-hydroxyquinoline |
| CN104230800B (en) * | 2014-08-20 | 2016-08-24 | 邯郸惠达化工有限公司 | A kind of preparation method of copper 8-quinolinolate |
| CN105152918A (en) * | 2015-09-06 | 2015-12-16 | 联化科技(盐城)有限公司 | Preparation method of methoxyphenylacetic acid and intermediate and salt thereof |
| CN105541597A (en) * | 2015-12-29 | 2016-05-04 | 中山大学 | Preparation method of 2,4-dihydroxyphenyl acetic acid |
| CN107686440A (en) * | 2016-08-04 | 2018-02-13 | 辽宁天予化工有限公司 | A kind of preparation method of m-trifluoromethyl phenol |
| CN107686440B (en) * | 2016-08-04 | 2022-07-08 | 辽宁天予化工有限公司 | Preparation method of m-trifluoromethylphenol |
| CN113372367A (en) * | 2021-05-28 | 2021-09-10 | 无锡颐景丰科技有限公司 | Synthesis method of high-purity 8-hydroxyquinoline copper |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101830793B (en) | 2014-01-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101830793B (en) | Method for preparing hydroxyl-substituted phenylacetic acid compound | |
| CN101891606B (en) | New method for synthesizing rhodium caprylate (II) | |
| CN103467525B (en) | Hydrogen peroxide oxidation method prepares the method for six (4-carboxy-phenoxy)-ring three phosphonitrile | |
| CN102079737B (en) | Method for preparing apigenin | |
| CN108623486A (en) | A kind of preparation method of V hydrochloride of salbutamol intermediate | |
| CN101353296B (en) | Method for preparing (Z)-3'-hydroxy-3,4,4',5-tetramethoxy diphenyl ethylene from regenerative natural plant resource | |
| CN108358987B (en) | Preparation method of high-content troxerutin | |
| CN108440409B (en) | Green and efficient preparation method of rebamipide | |
| CN103539662A (en) | Preparation and recovery method of 2-methyl-5-iodobenzoic acid | |
| CN109020938A (en) | A kind of preparation method of myricetin | |
| CN103242190A (en) | Synthetic method of propyzamide | |
| CN110615859B (en) | Preparation method of sodium gluconate | |
| CN101575301B (en) | Preparation method of 2-amino-5-chlorobenzamide | |
| CN113336764A (en) | Bipyridine ligand with axial chirality and synthetic method thereof | |
| CN104529726B (en) | A kind of preparation method of o-hydroxyacetophenone | |
| CN107641103A (en) | A kind of Bendazac preparation method | |
| CN102391170B (en) | A kind of preparation method of N, N-diallyl-5-methoxytryptamine hydrochlorides | |
| CN103965197B (en) | Allopurinol crystal preparation | |
| CN103408418B (en) | Preparation and purification method of solid malonic acid | |
| CN113185419B (en) | Synthetic method of oxybuprocaine hydrochloride | |
| CN101348444B (en) | Preparation of 2-ethoxy-4-acetaminobenzoic acid methyl ester | |
| CN101844997B (en) | Method for synthesizing benorilate by catalytically esterifying 4-dimethylamino pyridine | |
| CN101676276B (en) | Method for preparing N-tert-butyloxycarbonylpiperazine acetic acid hydrochloride | |
| CN103087006B (en) | Preparation method of N-methylphenothiazine | |
| CN104496900A (en) | Method for preparing 2-methoxy-6-one-5,7,8-trihydro-quinoline |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20140115 Termination date: 20160513 |