CN102276454A - Method for preparing p-acetoxy-benzoic acid - Google Patents
Method for preparing p-acetoxy-benzoic acid Download PDFInfo
- Publication number
- CN102276454A CN102276454A CN2010102012490A CN201010201249A CN102276454A CN 102276454 A CN102276454 A CN 102276454A CN 2010102012490 A CN2010102012490 A CN 2010102012490A CN 201010201249 A CN201010201249 A CN 201010201249A CN 102276454 A CN102276454 A CN 102276454A
- Authority
- CN
- China
- Prior art keywords
- acetoxy
- benzoic acid
- pyridine
- hydroxybenzoic acid
- preparation
- 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 p-acetoxy-benzoic acid. The method comprises the following steps of: reacting p-hydroxybenzoic acid as a raw material, acetic anhydride as an acylating agent and pyridine as a catalyst in a condition of 1.2-1.5 times of the excessive acetic anhydride: firstly, adding a certain amount of the p-hydroxybenzoic acid and the acetic anhydride into a reactor; dropwise adding the pyridine while stirring and raising the temperature to 80-85 DEG C; controlling the dropwise adding speed, wherein preferentially the temperature raising speed of a reactant is not beyond 10 DEG C; keeping the reaction temperature and continuously stirring for 2-3 h after adding the p-hydroxybenzoic acid and the pyridine and completely converting the reactant into crystals; and finally, repetitively washing the cooled reactant till the pH value of filtrate is 3-4 so as to obtain a crude product of acetoxy-benzoic acid. Both purities of a liquid chromatogram analysis result and a nuclear magnetic resonance hydrogen analysis result of the p-acetoxy-benzoic acid are more than 99.5%. According to the method disclosed by the invention, the conversion rate of the p-acetoxy-benzoic acid is more than 96%; furthermore, the content of by-products is low; and the difficultly for further refining and purifying the product is greatly reduced.
Description
Technical field
The present invention relates to a kind of preparation method, relate in particular to a kind of preparation method who uses P-hydroxybenzoic acid as raw material acetoxy-benzoic acid to acetoxy-benzoic acid.
Background technology
P-hydroxybenzoic acid is one of high molecular important source material of synthetic aroma adoption ester liquid crystal; but itself easy distillation; and phenolic hydroxyl group is lower for the activity of esterification; so; usually earlier its acetylize is handled and be converted into active higher intermediate, to improve reactive behavior to acetoxy-benzoic acid.Therefore, successfully preparing highly purified acetoxy-benzoic acid is to carry out liquid crystal polyester synthetic prerequisite.
Existing many from the P-hydroxybenzoic acid preparation to the technology of acetoxy-benzoic acid be catalyzer with the vitriol oil, diacetyl oxide is an acylating agent, and under the condition of adding acetic acid, toluene, pyridine equal solvent, carry out usually, as excessive 3.5 times of " First Gallamine-Tacrine Hybrid:Design and Characterization at Cholinesterases and the M2 MuscarinicReceptor " among the Journal of Medicinal Chemistry (2007) last diacetyl oxide of putting down in writing, pyridine is as the method for solvent, and its productive rate is 72%; And Chemical ﹠amp; Excessive 6 times of the diacetyl oxide that " HIV-1 integraseinhibition by biscoumarin analogues " upward puts down in writing among the Pharmaceutical Bulletin (2006), pyridine is made the method for solvent.Solvent-free, catalyst-free is also arranged or adopt the technology report of other catalyzer, excessive 3 times of the diacetyl oxide of " 4-hydroxy-benzoic acid-2 '-monooctyl ester synthetic " record of delivering in " New Chemical Materials " 2005 the 1st phases as Chemical College, Qingdao Science and Technology Univ, the method of sulphuric acid catalysis, its productive rate are 90%; Tensio-active agent fine chemistry industry component state key lab of Dalian University of Technology is excessive 4 times of the diacetyl oxide of " Dalian University of Technology's journal " 2000 the 2nd interim " di-esters liquid crystal 4-(4 '-octyloxy biphenyl-4-methanoyl) benzoic ether synthetic " record of delivering; The method of sulphuric acid catalysis, its productive rate are 92%; " Design among the European Journalof Medicinal Chemistry (2009), synthesis and evaluation ofgalanthamine derivatives as acetylcholinesterase inhibitors " go up excessive 2 times of the diacetyl oxide of record, the method that catalyst-free refluxed 6 hours, its productive rate is 82%, excessive more than 7 times with the diacetyl oxide of record in the Chinese patent 101503484,6 hours method of reflux; Excessive 2 times of the diacetyl oxide that " Ac20-Py/basic alumina as a versatile reagent foracetylations in solvent-free conditions under microwave irradiation " upward puts down in writing among the TetrahedronLetters (2002), adopt the method for pyridine and aluminium sesquioxide compounding catalyst, its productive rate is 91%.
In the aforesaid method, the diacetyl oxide of adding is all excessive more, and conversion rate of products is then many below 92%.Needing simultaneously increases complicated solvent recovery unit, and by product is many in the product, the product purification purification difficult.
Summary of the invention
Goal of the invention: big in order to overcome in the prior art diacetyl oxide usage quantity; the deficiency that by product is many, product purification is difficult; the invention provides a kind of is raw material with the P-hydroxybenzoic acid; diacetyl oxide is an acylating agent; pyridine is the preparation method to acetoxy-benzoic acid of catalyzer; not only the diacetyl oxide usage quantity is few for this method, and by-products content is low, conversion rate of products is high.
Technical scheme: in order to realize the foregoing invention purpose, the technical solution adopted in the present invention is:
A kind of is raw material with the P-hydroxybenzoic acid, and diacetyl oxide is an acylating agent, and pyridine is the preparation method to acetoxy-benzoic acid of catalyzer, realizes that the concrete steps of this method are as follows:
1) in reactor, adds whole diacetyl oxides and reach P-hydroxybenzoic acid partly or completely, begin to drip pyridine when being heated with stirring to 80～85 ℃, control its rate of addition, be no more than 10 ℃ with the reactant temperature rise and be advisable;
2) keep temperature of reaction in 80～100 ℃, continue to stir, material dissolve fully and along with the reaction carrying out slowly become the colloidal sol shape until being converted into crystalloid fully by liquid state, remaining P-hydroxybenzoic acid and pyridine are added in gradation in this process, and have added all residual contentes in after reactant is converted into crystal 30 minutes;
3) keep step 2) temperature of reaction, continue to stir 2～3 hours, stop heating then and stir;
4) the question response product is cooled to room temperature or near after the room temperature, washing and filtering, obtain after the drying white crystals shape to the acetoxy-benzoic acid crude product.
Using distilled water or deionized water wash filtering reaction product in step 4), is 3～4 until the pH value of filtrate.
P-hydroxybenzoic acid is divided 1～5 time or more times joins in the reactor, and preferred 3～5 times, the P-hydroxybenzoic acid addition that adds in step 1) is 70～100%, preferred 70～75% of its total charging capacity; Other preferred joining days and add-on are: apart from beginning to drip pyridine in about 20 minutes timed interval, add 10～15% of total charging capacity; Begin to be converted into the interpolation of finishing all residual contentes in retrolental 20～30 minutes at material.
The mol ratio of diacetyl oxide and P-hydroxybenzoic acid total addition level is 1.2～1.5: 1, preferred 1.3～1.5: 1.The diacetyl oxide add-on is too high, not only makes raw material consumption big, and volumetric efficiency is low, also will increase the burden that reactant recovery is handled, thereby increases production cost.But the diacetyl oxide add-on is low excessively, will be unfavorable for mixing of material, influences the mass-and heat-transfer of reactant, and reaction can not be complete, reduces transformation efficiency.
Pyridine divides 1～4 input or evenly is added drop-wise in the reactor.Its total addition level is 0.05%～0.3% of a P-hydroxybenzoic acid total addition level, and is preferred more than 0.1%.The pyridine consumption is low excessively, can reduce speed of response; Consumption is too high, can cause the poor selectivity of reaction, and by product is increased.The adding mode of pyridine is slowly to drip, and reaction heat is in time discharged, thereby avoid temperature sharply to rise.
Temperature of reaction is controlled at 80～100 ℃, preferred 90～100 ℃.Temperature is low excessively, and the reactant solubility reduction is unfavorable for mixing of material, makes speed of response slow, transforms insufficient; Temperature is too high, and side reaction easily takes place, and reduces degree of purity of production.
Beneficial effect: the present invention is at solvent-free, low catalyst consumption, low acetate acid anhydride consumption, carry out under the lower temperature of reaction, the purpose product is a white crystal, transformation efficiency is higher than 96%, product liquid chromatography and proton nmr spectra analytical results purity are all greater than 99.5%, by product is few, has reduced the product purification difficulty.
Embodiment
The present invention is described in further detail below in conjunction with embodiment, should understand these embodiment and only be used to the present invention is described and be not used in and limit the scope of the invention.
Embodiment 1: adding 35 gram diacetyl oxides and 26 gram P-hydroxybenzoic acid in the 100ml there-necked flask of agitator, thermometer, reflux condensing tube are being housed, stirring also is heated to 85 ℃, suspend heating, drip 0.03 gram pyridine, temperature is increased to 94 ℃, material dissolves fully, and separates out solid formation suspension very soon, keeps temperature of reaction about 92 ℃; Add 4 gram P-hydroxybenzoic acid and 0.03 gram pyridine after 15 minutes in this suspension, temperature is increased to 96 ℃, stirs 10 minutes under this temperature, and material is converted into crystalline thing; Continue to stir 18 minutes, add 3 gram P-hydroxybenzoic acid and 0.03 gram pyridine again, controlled temperature is about 98 ℃; Stir and add 3 gram P-hydroxybenzoic acid, insulated and stirred 2 hours after 15 minutes; Stopping heating and stir, treat after material is cooled to room temperature it to be filtered with distilled water or deionized water repetitive scrubbing, is 4 until the pH value of filtrate, obtains 45.5 gram crude products.Conversion rate of products is 98%, and crude product is carried and reined in the melting range that the pipe method records is 185-191 ℃, and carrying out the product melting range behind the recrystallization with 1: 4 50% ethanol of bath raio is 188-191.5 ℃, and the product final yield is 87%.
Embodiment 2: adding 27.7 gram diacetyl oxides and 25 gram P-hydroxybenzoic acid in the 100ml there-necked flask of agitator, thermometer, reflux condensing tube are being housed, stirring also is heated to 85 ℃, suspend heating, slowly splash into 0.06 gram pyridine, temperature is increased to 95 ℃, material dissolves fully, and separates out solid formation suspension very soon; Control reaction temperature fully stirs material near 95 ℃, material is converted into crystalline thing by paste after 30 minutes; Keep this temperature-resistant, continue reaction 2 hours; Last under 95～98 ℃ temperature restir stopped heating in 1 hour and stir, treat that material is cooled to room temperature, it is filtered with distilled water or deionized water repetitive scrubbing, be 3～4 until the pH value of filtrate, obtain 32.6 gram crude products.Purpose conversion rate of products 100%, crude product are carried and reined in the melting range that the pipe method records is 183-190 ℃, and differential thermal analysis (DSC) test melting range is 186.5-197.3 ℃; Carrying out the product melting range behind the recrystallization with 1: 4 50% ethanol of bath raio is 185-191 ℃, and the DSC test result is 188-197 ℃; One time the recrystallization yield is 86%.
Embodiment 3: in that adding 175.6 gram diacetyl oxides and 132 gram P-hydroxybenzoic acid in the 500ml four-hole boiling flask of agitator, thermometer, reflux condensing tube are housed, stir and be heated to 80 ℃, material is near dissolving fully, and the time-out heating splashes into 0.12 gram pyridine.Treat that the still temperature promptly adds 7.9 gram P-hydroxybenzoic acid after settling out at 90 ℃, have solid to separate out and form suspension very soon, splash into 0.09 gram pyrido again and continue to add 9.7 gram P-hydroxybenzoic acid, have a large amount of crystal to generate immediately; Control reaction temperature is near 95 ℃, continue to stir and add remaining 30.4 gram P-hydroxybenzoic acid after 15 minutes, and in 10 minutes, add, in 95～98 ℃ temperature range, continue to stir 3 hours, stop heating and stirring, treating material is cooled to after the room temperature, it is filtered with distilled water or deionized water repetitive scrubbing, is 3～4 until the pH value of filtrate, obtains 221 gram crude products.The purpose conversion rate of products is 96%, and to rein in the melting range that the pipe method records be 184-190 ℃ to crude product with carrying.
Embodiment 4: embodiment 4 is basic identical with embodiment 1, and the addition of different is pyridine is 0.03 gram.Purpose conversion rate of products 96%.
Comparative Examples 1: adding 16.6 gram diacetyl oxides and 3 gram P-hydroxybenzoic acid in the 100ml there-necked flask of agitator, thermometer, reflux condensing tube are being housed, add 0.05 gram pyridine simultaneously, heating is also stirred, material dissolves fully when being warming up to 65 ℃, add 6 gram P-hydroxybenzoic acid again, temperature of reaction sharply rises to more than 90 ℃, and material dissolves fully, and separates out solid formation suspension very soon; Be controlled at about 85 ℃ of temperature, continue in this suspension, to add 6 gram P-hydroxybenzoic acid after 25 minutes, begin to have crystal formation; Material all is converted into crystal after 3 hours, and temperature maintenance between 85～90 ℃, is continued reaction and stops heating and stirring after 2 hours.Treating that material is cooled to room temperature, it is filtered with distilled water repetitive scrubbing, is 3～4 until the pH value of filtrate, finally obtains 18.7 gram crude products, purpose conversion rate of products 95.8%.
Comparative Examples 2: adding 26.6 gram diacetyl oxides and 20 gram P-hydroxybenzoic acid in the 100ml there-necked flask of agitator, thermometer, reflux condensing tube are being housed, heating is also stirred, when treating that material is warming up to 86.5 ℃, suspend heating, drip 0.06 gram pyridine, temperature is increased to 107 ℃ immediately, and material dissolves fully, temperature of charge is reduced to 101 ℃ and separate out solid after 18 minutes, is formed with mobile jello; Add 5 gram P-hydroxybenzoic acid after stirring 50 minutes near 100 ℃ again, all the other P-hydroxybenzoic acid added (it is 30 grams that P-hydroxybenzoic acid adds total amount, with the mol ratio of diacetyl oxide be 1: 1.2) in 15 minutes, and material is converted into crystalline thing; Controlled temperature continues reaction 1 hour between 103～106 ℃, stop heating then and stir, and treats that material is cooled to room temperature, it is filtered with the distilled water repetitive scrubbing, and be 4 until the pH value of filtrate.This product is carried out recrystallization one time with 50% ethanol, can't obtain the crystalloid product.Use 95% ethyl alcohol recrystallization, the product melting range that obtains is 184-190 ℃, recrystallization yield only 54%.
Claims (7)
1. preparation method to acetoxy-benzoic acid, it is characterized in that: this method is raw material with the P-hydroxybenzoic acid, and diacetyl oxide is an acylating agent, and pyridine is a catalyzer.The concrete steps that realize this method are as follows:
1) in reactor, adds whole diacetyl oxides and reach P-hydroxybenzoic acid partly or completely, begin to drip pyridine when being heated with stirring to 80～85 ℃, control its rate of addition, make the reactant temperature rise be no more than 10 ℃;
2) keep temperature of reaction in 80～100 ℃, continue to stir, make reactant be converted into crystal fully.Remaining P-hydroxybenzoic acid and pyridine are added in gradation in the process of reaction, and have added in after reactant is converted into crystal 30 minutes;
3) keep step 2) temperature of reaction, continue to stir 2～3 hours, stop heating then and stir;
4) after the question response product is cooled to room temperature, washing and filtering, obtain after the drying white crystals shape to the acetoxy-benzoic acid crude product.
2. a kind of preparation method to acetoxy-benzoic acid according to claim 1 is characterized in that: described P-hydroxybenzoic acid is divided and is joined in the reactor for 1～5 time.
3. a kind of preparation method to acetoxy-benzoic acid according to claim 1 and 2 is characterized in that: the P-hydroxybenzoic acid addition that adds in step 1) is 70～100% of its total addition level.
4. a kind of preparation method to acetoxy-benzoic acid according to claim 1 is characterized in that: described pyridine gradation adds or evenly is added drop-wise in the reactor.
5. a kind of preparation method to acetoxy-benzoic acid according to claim 1 is characterized in that: the mol ratio of described diacetyl oxide and P-hydroxybenzoic acid total addition level is 1.2～1.5: 1.
6. a kind of preparation method to acetoxy-benzoic acid according to claim 1 is characterized in that: described pyridine total addition level is 0.05%～0.3% of a P-hydroxybenzoic acid total amount.
7. a kind of preparation method to acetoxy-benzoic acid according to claim 1 is characterized in that: using distilled water or deionized water wash filtering reaction product in step 4), is 3～4 until the pH value of filtrate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010201249 CN102276454B (en) | 2010-06-13 | 2010-06-13 | Method for preparing p-acetoxy-benzoic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010201249 CN102276454B (en) | 2010-06-13 | 2010-06-13 | Method for preparing p-acetoxy-benzoic acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102276454A true CN102276454A (en) | 2011-12-14 |
| CN102276454B CN102276454B (en) | 2013-12-25 |
Family
ID=45102246
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201010201249 Active CN102276454B (en) | 2010-06-13 | 2010-06-13 | Method for preparing p-acetoxy-benzoic acid |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102276454B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103626659A (en) * | 2012-08-27 | 2014-03-12 | 中国石油化工股份有限公司 | P-acetoxybenzoic acid preparation method |
| CN104448814A (en) * | 2014-11-27 | 2015-03-25 | 湖北洋田塑料制品有限公司 | High-strength and high-rigidity liquid crystal polymer reinforced nylon 66 composite and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1569839A (en) * | 2004-05-14 | 2005-01-26 | 复旦大学 | Meptazinol prodrug and its salts and its production method |
| WO2008157844A1 (en) * | 2007-06-21 | 2008-12-24 | Forest Laboratories Holdings Limited | Novel piperazine derivatives as inhibitors of stearoyl-coa desaturase |
-
2010
- 2010-06-13 CN CN 201010201249 patent/CN102276454B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1569839A (en) * | 2004-05-14 | 2005-01-26 | 复旦大学 | Meptazinol prodrug and its salts and its production method |
| WO2008157844A1 (en) * | 2007-06-21 | 2008-12-24 | Forest Laboratories Holdings Limited | Novel piperazine derivatives as inhibitors of stearoyl-coa desaturase |
Non-Patent Citations (5)
| Title |
|---|
| 《Angewandte Chemie International Edition in English》 20031222 Gerhard Hofle et al 4-Dialkylaminopyridines as Highly Active Acylation Catalysts 第569-583页 1-7 第17卷, * |
| 《Tetrahedron Letters》 20020603 Satya Paul et al Ac2O-Py/basic alumina as a versatile reagent for acetylations in solvent-free conditions under microwave irradiation 参见第4262页General procedure节，第4263页表2第16项,第4261页第4段，第4262页表1第9项,第4261页第1-6行 1-7 第43卷, * |
| GERHARD HOFLE ET AL: "4-Dialkylaminopyridines as Highly Active Acylation Catalysts", 《ANGEWANDTE CHEMIE INTERNATIONAL EDITION IN ENGLISH》 * |
| SATYA PAUL ET AL: "Ac2O–Py/basic alumina as a versatile reagent for acetylations in solvent-free conditions under microwave irradiation", 《TETRAHEDRON LETTERS》 * |
| 刘密等: "4-羟基苯甲酸-2＇-辛酯的合成", 《化工新型材料》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103626659A (en) * | 2012-08-27 | 2014-03-12 | 中国石油化工股份有限公司 | P-acetoxybenzoic acid preparation method |
| CN103626659B (en) * | 2012-08-27 | 2016-01-06 | 中国石油化工股份有限公司 | A kind of method prepared acetoxy-benzoic acid |
| CN104448814A (en) * | 2014-11-27 | 2015-03-25 | 湖北洋田塑料制品有限公司 | High-strength and high-rigidity liquid crystal polymer reinforced nylon 66 composite and preparation method thereof |
| CN104448814B (en) * | 2014-11-27 | 2016-05-11 | 湖北洋田塑料制品有限公司 | The high rigidity liquid crystal polymer of a kind of high strength reinforced nylon 66 compounds and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102276454B (en) | 2013-12-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TW499420B (en) | Catalytic processes for the preparation of acetic esters | |
| CN101538228B (en) | Method for synthesizing medical compound peramivir for resisting influenza viruses and avian influenza viruses | |
| CN105254603A (en) | Synthetic technology of furan ammonium salt | |
| CN102976917B (en) | Aqueous-phase refining method of long-chain dibasic acid | |
| CN101891649A (en) | Novel 3-cyano methyl benzoate preparing method | |
| CN102060902A (en) | Chenodeoxycholic acid synthesis method | |
| CN101225045A (en) | Micro-wave synthetic method for preparing methyl salicylate | |
| CN101486753A (en) | Novel method for synthesizing finasteroid | |
| CN102151583A (en) | Method for preparing vanadium phosphate catalyst used in reaction of acrylic acid synthesized by acetic acid and formaldehyde | |
| CN102652922A (en) | Supported phosphorus-vanadium-cesium-lanthanum catalyst and application thereof | |
| CN102276454B (en) | Method for preparing p-acetoxy-benzoic acid | |
| CN102276463A (en) | Process for producing ethyl trifluoroacetate | |
| CN102060701A (en) | Method for synthesizing beta-(3,5-di-tert-butyl-4-hydroxyphenyl)methyl propionate | |
| CN103864878A (en) | Preparation method for abiraterone acetate | |
| RU2404173C2 (en) | Method for synthesis of methyl ether of 5-acetylfuran-2-carboxylic acid | |
| CN113045412A (en) | Preparation process and equipment of adipic acid dibasic ester | |
| CN109879778A (en) | A kind of synthetic method of p-HBN | |
| JP4049534B2 (en) | Process for producing O-alkyl-N-cyanoacetimidate | |
| CN102146113A (en) | Method for synthesizing 16 alpha-hydroxy prednisolone | |
| CN103641876B (en) | The preparation method of cortisone acetic ester | |
| CN103102271B (en) | Industrialized preparation method of guacetisal and medical application of dry suspension | |
| CN102531896A (en) | Production method of ethyl trifluoroacetate | |
| CN103102379B (en) | A kind of production method by pregnenolone acetate synthetic table androsterone | |
| CN101508645A (en) | Method of preparing diacetyl rhein | |
| CN102952013B (en) | Preparation method of high-purity p-acetoxybenzoic acid |
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 |