CN102952013B - Preparation method of high-purity p-acetoxybenzoic acid - Google Patents
Preparation method of high-purity p-acetoxybenzoic acid Download PDFInfo
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- CN102952013B CN102952013B CN201110236677.1A CN201110236677A CN102952013B CN 102952013 B CN102952013 B CN 102952013B CN 201110236677 A CN201110236677 A CN 201110236677A CN 102952013 B CN102952013 B CN 102952013B
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Abstract
The invention provides a preparation method of high-purity p-acetoxybenzoic acid. According to the invention, p-acetoxybenzoic acid is synthesized under conditions of a proper amount of a solvent and non-excess or slightly excess acetic anhydride. The method comprises the steps that: an acylating agent acetic anhydride, a solvent glacial acetic acid, a catalyst pyridine, and a part of a hydroxybenzoic acid raw material are mixed under a temperature below 60 DEG C, and a reaction is started; during the reaction process, material heating rate is controlled below 15 DEG C/h; when the temperature is stable, hydroxybenzoic acid is added, and a subsequent reaction is carried out under a temperature below 80 DEG C; after the reaction is finished, part of acetic acid in the reaction system is removed; the reaction system is cooled; and crystals obtained by the reactions are repeatedly washed by using distilled water and are filtered, until a pH value of a filtrate is no lower than 4. The obtained product does not need further refining and purification, and an actual yield can reach a maximum of 98%.
Description
Technical field
The invention belongs to the preparation field to acetoxy-benzoic acid, being specifically related to a kind of P-hydroxybenzoic acid that adopts is that raw material is by the method for acetylization reaction preparation to acetoxy-benzoic acid.
Background technology
Existing employing P-hydroxybenzoic acid (PHB) and diacetyl oxide be raw material by acetylization reaction prepare to the technology of acetoxy-benzoic acid (PABA) usually add a large amount of solvent or make solvent with excessive diacetyl oxide condition under implement.Relative to the PHB of 1mol, diacetyl oxide add-on is many between 1.2 ~ 10mol.Reaction process is carried out mostly at higher temperature (65 ~ 110 DEG C).Also the report adopting cold condition is had, but because catalyst selectivity used is poor, or consumption is excessive, often cause the generation of side reaction, make the purity drop of product (being difficult to directly reach the high purity of more than 99%), therefore to the recrystallizing technology often comprising product in the technology of preparing of acetoxy-benzoic acid.As " Tianjin chemical industry " 01 phase in 2010, Chemical & Pharmaceutical Bulletin (2006) 54 (5), Journal of Medicinal Chemistry (2007) 50 (23), Journal of Chemical Research, Synopses (2003) (7), Tetrahedron Letters (2002), 43 (23), the method that the periodicals such as Tetrahedron Letters (2006) 47 (38) are recorded and application number are the Japan Kokai of flat 3-219433, application number is the world patent of WO2006117552A1, application number is the method proposed in the patents such as the Chinese patent of 200810060915.
Existing by the technique of acetylization reaction preparation to acetoxy-benzoic acid, because of the impact of the factors such as catalyzer improper use or temperature, side reaction very easily occurs in reaction process, and products therefrom needs further recrystallization purification processes.This not only needs to use a large amount of recrystallization solvents, also directly has influence on the yield of the finished product.If add a large amount of solvent and excessive acetic acid acid anhydride that add in reactant, raw material and solvent recuperation load can be very large.
Summary of the invention
The object of the invention is the weak point existed for prior art, low temperature synthesis process under appropriate solvent and the diacetyl oxide condition without the excessive or amount of skipping over is proposed, improve from product yield, equipment, technical process, production cost all respects, in the hope of obtaining maximum economic benefit.
Object of the present invention can be reached by following measures:
A preparation method for high-purity p-acetoxybenzoic acid, comprises the steps:
(1) acylating agent diacetyl oxide, solvent Glacial acetic acid, catalyst pyridine and the P-hydroxybenzoic acid raw material that accounts for total charging capacity 50 ~ 100% (preferably 70 ~ 75%) are mixed below 60 DEG C, start the acetylization reaction between P-hydroxybenzoic acid and diacetyl oxide;
(2) temperature rise rate controlling material in reaction process, at 15 DEG C/below h, continues to add remaining P-hydroxybenzoic acid until temperature-stable, and carry out subsequent reactions below 80 DEG C after 60 ~ 80 DEG C;
(3) react the part acetic acid that terminates in rear removing reaction system, cooling, the xln distilled water repetitive scrubbing of reaction gained is filtered, until pH value >=4 of filtrate.
The present invention is with P-hydroxybenzoic acid (PHB) for raw material, and diacetyl oxide is acylating agent, and pyridine is catalyzer, and Glacial acetic acid is solvent.Reaction point two stages carry out, and the first stage is the low-temp reaction stage, and subordinate phase is the temperature reaction stage.PHB is incorporated as suitable with gradation, the mol ratio of the whole charging capacity of final PHB and diacetyl oxide is 1: 1 ~ 1: 1.05.Excessive diacetyl oxide is conducive to the carrying out reacted, but excessive raw material consumption is more at most larger, and volumetric efficiency is lower, also will increase the burden of recycling, thus increases production cost.Pyridine add-on is 0.2 ~ 0.3% (W) of the total charging capacity of PHB.The add-on of Glacial acetic acid is 55 ~ 60% (W) of the total charging capacity of P-hydroxybenzoic acid.Lower than this scope, the mass-and heat-transfer of material can be affected, and add-on is too high then to be reduced volumetric efficiency and increases the burden recycled.The temperature of whole reaction process must control below 80 DEG C.Easily there is side reaction in temperature height, causes product purity not high, thus have to through recrystallization purification processes.
In step (1), each component such as diacetyl oxide, Glacial acetic acid, at 60 DEG C, preferably mixes at 40 ~ 50 DEG C and starts reaction.Can add each component while stirring in reaction unit in step (1), in order to fast reaction speed, can suitably heat, but temperature of charge is advisable to be no more than 60 DEG C.
In step (2), along with the carrying out of thermopositive reaction, temperature of charge can rise voluntarily, in this section of process, therefore need the temperature rise rate carrying out inhibited reaction material by controlling bath temperature.Start to add PHB after temperature-stable, remaining PHB slowly adds reaction system, within about 20 ~ 60 minutes, adds.At this moment and subsequently the temperature of reaction of system will control within 80 DEG C, is preferably 60 ~ 70 DEG C.The reaction of this step can be carried out under stirring or other hybrid modes.
In step (3), after reaction terminates, removed the acetic acid in reaction system by the mode of underpressure distillation.Quantity of distillate can be 1 ~ 100% of the contained all acetic acid of system, preferably 40 ~ 60%, and the temperature of distillation is advisable with 60 ~ 90 DEG C.
The processing condition such as the present invention is reinforced by Discrete control, temperature, effectively reduce the generation to side reaction in acetoxy-benzoic acid building-up process, products therefrom purity high (referring to dsc analysis test result), without the need to carrying out recrystallization purification processes, the actual recovery of object product can reach 98%.In addition owing to adopting inhomogeneous reaction technique, reduce the usage quantity of raw material and solvent, thus improve the volumetric efficiency of equipment, decrease solvent recuperation load and raw material consumption, simplify technical process, be conducive to the raising of production efficiency.
Accompanying drawing explanation
Fig. 1 is dsc and the dsc analysis test result figure of embodiment 4 product.
Embodiment
Below in conjunction with embodiment, the present invention is described in further detail, should understand these embodiments and only be not used in for illustration of the present invention and limit the scope of the invention.
Embodiment 1
In the 250ml there-necked flask that agitator, thermometer are housed, add 39.6 grams of Glacial acetic acid, 53.5 grams of diacetyl oxides and 53 grams of PHB, stir and heat.0.18 gram of pyridine is dripped when material is warming up to 32 DEG C.Continue heating, and maintain temperature of charge at about 59 DEG C.Start have PABA xln to separate out after 17 minutes.Control temperature of charge to make it in 65 minutes, rise to about 75 DEG C and start to add PHB.17 grams of PHB are added in 30 minutes.After this about 70 DEG C insulated and stirred 2 hours, then from reaction system, 41 grams of acetic acid are distillated by underpressure distillation.Finally stop heating and stir, material is cooled.Then this crystal material distilled water repetitive scrubbing is filtered, until the pH value of filtrate is 4.Namely PABA the finished product are obtained by after filtration cakes torrefaction.It is 192 DEG C that this product b type pipe records fusing point, dsc analysis test result: melting peak starting temperature is 188.3 DEG C; Peak temperature is 197.2 DEG C, product net yield 97.2%.
Embodiment 2
Except raw material mol adopts except 1/1 than PHB/ diacetyl oxide, other are all identical with embodiment 1.Net yield 97.8%.
Embodiment 3
In the 2000ml there-necked flask that agitator, thermometer are housed, add 283 grams of Glacial acetic acid, 378 grams of diacetyl oxides and 360 grams of PHB, stir and heat.1.05 grams of pyridines are dripped when material is warming up to 35 DEG C.Continue heating, and maintain temperature of charge at about 60 DEG C.Start have PABA xln to separate out after 22 minutes.Continue reaction after 20 minutes temperature of charge rise to about 71 DEG C and start to add PHB.140 grams of PHB are added in 27 minutes.Continuation reaction is warming up to 76 DEG C and carries out underpressure distillation after 55 minutes, distillate 265 grams of acetic acid from reaction system.Other processes are with embodiment 1.This product dsc analysis test result: melting peak starting temperature is 187.5 DEG C; Peak temperature is 196.7 DEG C, product net yield 97.2%.
Embodiment 4
In the 5000ml there-necked flask that agitator, thermometer are housed, add 860 grams of PHB, 678 grams of Glacial acetic acid, 897 grams of diacetyl oxides and 2.4 grams of pyridines, heat and stir.When material is warming up to 45 DEG C, control heating, holding temperature is below 50 DEG C.Start have PABA xln to separate out after 100 minutes.After 80 minutes, temperature of charge rises near 65 DEG C.Namely start subsequently to add PHB.340 grams of PHB are added in 26 minutes.Keep this temperature 20 minutes, be then warming up to 75 DEG C, underpressure distillation with 80 minutes, from reaction system, distillate about 630 grams of acetic acid.Stop heating and stir, and material is cooled.Then just this crystal material distilled water repetitive scrubbing filters, until the pH value of filtrate is 4.1538.3 grams of high-purity p-acetoxybenzoic acid will be obtained after filtration cakes torrefaction.Dsc (DSC) analytical test is carried out to this product, the results are shown in Figure 1.Product net yield 98.2%.
Fig. 1 is embodiment 4 product DSC graphic representation: melting peak starting temperature is 189.0 DEG C; Peak temperature is 197.3 DEG C.
Claims (6)
1. a preparation method for high-purity p-acetoxybenzoic acid, is characterized in that: comprise the steps:
(1) acylating agent diacetyl oxide, solvent Glacial acetic acid, catalyst pyridine and part P-hydroxybenzoic acid raw material are mixed below 60 DEG C, start the acetylization reaction between P-hydroxybenzoic acid and diacetyl oxide;
(2) temperature rise rate controlling material in reaction process, at 15 DEG C/below h, continues to add P-hydroxybenzoic acid until temperature-stable, and carry out subsequent reactions at 60 ~ 80 DEG C after 60 ~ 80 DEG C;
(3) react the part acetic acid that terminates in rear removing reaction system, cooling, the xln distilled water repetitive scrubbing of reaction gained is filtered, until pH value >=4 of filtrate;
The mol ratio of wherein said diacetyl oxide and the total charging capacity of P-hydroxybenzoic acid is 1:1 ~ 1.05:1, and the add-on of described Glacial acetic acid is 55 ~ 60%(W of the total charging capacity of P-hydroxybenzoic acid).
2. the preparation method of high-purity p-acetoxybenzoic acid according to claim 1, is characterized in that: in step (1), and each component mixes at 40 ~ 50 DEG C.
3. the preparation method of high-purity p-acetoxybenzoic acid according to claim 1, is characterized in that: in step (1), and the add-on of P-hydroxybenzoic acid raw material accounts for 70 ~ 75% of total charging capacity.
4. the preparation method of high-purity p-acetoxybenzoic acid according to claim 1, is characterized in that: the consumption of described pyridine is 0.2 ~ 0.3%(W of the total charging capacity of P-hydroxybenzoic acid).
5. the preparation method of high-purity p-acetoxybenzoic acid according to claim 1, is characterized in that: in step (2), and P-hydroxybenzoic acid slowly adds and enters reaction system.
6. the preparation method of high-purity p-acetoxybenzoic acid according to claim 1, it is characterized in that: in step (3), removed the acetic acid in reaction system after reaction terminates by the mode of underpressure distillation, its quantity of distillate is 40 ~ 60%(W of the contained all acetic acid of system).
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101845005A (en) * | 2010-06-18 | 2010-09-29 | 中科院广州化学有限公司 | Side substitution aromatic ester diphenol, preparation method and preparation method of mesomorphic epoxy monomer |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101845005A (en) * | 2010-06-18 | 2010-09-29 | 中科院广州化学有限公司 | Side substitution aromatic ester diphenol, preparation method and preparation method of mesomorphic epoxy monomer |
Non-Patent Citations (2)
| Title |
|---|
| CHAOBIN HE et al..Synthesis and Structure of Wholly Aromatic Liquid–Crystalline Polyesters Containing Meta- and Ortholinkages.《Journal of Polymer Science, Part A:Polymer Chemistry》.2001,第39卷(第8期),1242-1248. * |
| 李启然,田华.对甲基苯磺酸催化合成4-乙酰氧基苯甲酸的研究.《天津化工》.2010,第24卷(第1期),20-22. * |
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