CN102826946B - Green synthesis process of aryl methyl low-carbonate - Google Patents
Green synthesis process of aryl methyl low-carbonate Download PDFInfo
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Abstract
The invention belongs to the field of organic synthesis technique, and particularly relates to a green synthesis process of aryl methyl low-carbonate. The process is suitable for aryl low-carbonate, particularly for the synthesis of methyl esters of various non-steroidal anti-inflammatory drugs such as ibuprofen. The invention provides a universally applicable clean production process of aryl methyl carbonate. Through applying water absorption and polarity of glycerol and combining adoption of separation technique of simulated moving bed chromatography, the process simplifies treatment of reaction mixture, ensures complete separation of reaction product and the rest impurities such as surplus reaction raw materials, solves the problems of recycling of the surplus reaction raw materials, catalyst and water absorbent glycerol, can acquire product with high purity under the premises of water washing-free, no rectification and no three wastes, increases conversion rate of the raw material and yield of the product to be close to 100%, largely reduces production cost, achieves zero release of waste water and waste residue during the product production process, and has a broad application prospect in the fields of medicine, fine chemical industry and the like.
Description
Technical field
The invention belongs to technical field of organic synthesis, is specifically the green synthesis process belonging to a kind of aryl low carbon acid methyl esters.
Background technology
Aryl low carbon acid methyl esters is applied widely in fine chemistry industry, is the very common essence and flavoring agent of a class, wherein some, as wintergreen oil, the main attached pastil being used as medicine; Some as methyl phenylacetate, methyl cinnamate etc., is then food flavour and daily chemical essence.
Meanwhile, aryl low carbon acid methyl esters is also the important medicine intermediate of a class, wherein some, as wintergreen oil, diclofenac methyl esters [1], inherently can be used as bulk drug and use, some, as Ibuprofen BP/EP methyl esters [2], then it is the important intermediate of chiral separation.Therefore, the synthetic method of research and improvement aryl second (third) sour methyl esters, realizes the greenization of these medicine intermediates, environmental friendliness, has very important significance.
About the synthesis of aryl low carbon acid methyl esters, traditional chemical synthesis process has chloride method, sulphuric acid catalysis method, base catalysis method etc., this several technique all needs, with saturated aqueous common salt, product is washed till neutrality when reclaiming product, therefore a large amount of high COD high slat-containing wastewaters can be produced, not only can cause corrosion to equipment, and extremely serious pollution is caused to environment.
The pollution that traditional chemical industry brings to environment is very serious, works the mischief, and threaten the existence of the mankind to environment.The nineties in 20th century, knowledgeable people proposes the call of Green Chemistry, and obtains global active response immediately.The core of Green Chemistry will utilize the principles of chemistry from source decontamination exactly.Namely utilize the techniques and methods of chemistry, reduce the application of environmentally harmful supplementary material, and realize zero release as far as possible.The invention provides so a kind of green synthesis process.
[1] 2-(2-(2,6-dichlorophenyl amino) phenyl) ritalin and synthetic method thereof and application ZL 200710160504.X thereof
[2] the asymmetric alcoholysis reaction " Anhui medicine " 2011, No.7 of Novozym435 catalysis Ibuprofen BP/EP methyl esters
Summary of the invention
This patent relates to a kind of eco-friendly, absorbs that the mode that is separated in conjunction with simulated moving bed chromatography of dewatering carries out with glycerine, relatively inexpensive, high yield, the green synthesis process new synthetic process of blanket a kind of aryl low carbon acid methyl esters.More unique is, it relates to a kind of improved technique, " catalysis+dewater " system that this technique is formed with lipase or an acidic catalyst+glycerine substitutes the vitriol oil, the formation reaction of methyl esters is made to be tending towards complete, then be separated with simulation moving-bed continuous chromatography by stratification, the continuous print such as reaction product and catalyzer, glycerine and excessive reaction raw materials are separated, for solving water removal in methyl esters synthesis and product separation issues of purification provides simple and easy to do solution.Operate according to this patent, compared with traditional method before this, can dewater with economically viable method, be continuously separated purifying, waste water in thorough elimination aryl low carbon acid methyl esters synthesis technique produces, realize the environmental friendliness that aryl low carbon acid methyl esters is produced, and significantly improve the purity of productive rate and product.Above these improve aryl low carbon acid methyl esters is produced green, sustainable with environmental friendliness for be vital.
Specifically, first, we find, the moisture absorption that appropriate glycerine can will produce in esterification reaction of organic acid, thus ensure that reaction can reach satisfied transformation efficiency, and under a large amount of methyl alcohol existent condition, aryl low carbon acid can not generate aryl low carbon acid glyceryl ester with glycerine reaction, that is, " lipase or an acidic catalyst+glycerine " can reach with equivalent " catalysis+dewater " effect of the vitriol oil.
Secondly, we find, the aryl low carbon acid methyl esters that reaction generates is highly stable, remove in the process of residue methyl alcohol significant decomposition can not occur in distillation; Reaction mixture after methanol stripper is at 0 ~ 100 DEG C, preferably 10 ~ 60 DEG C, meeting AUTOMATIC ZONING after leaving standstill, its upper strata is aryl low carbon acid methyl esters mainly, separately has a small amount of remaining aryl low carbon acid and catalyzer, the large portion of lower floor mainly in aqueous glycerol and catalyzer, and lower floor can without any process, direct circulation reuse, and remarkably influenced can not be had, reuse capable of circulation 1 ~ 30 time to the transformation efficiency of reaction.Establish the basis of the green synthesis process of a kind of aryl low carbon acid methyl esters of the water generated with glycerine absorbing and removing thus.
Again, we find, coordinate with suitable sorbent material the separation system of simulated moving bed chromatography formed by suitable eluent, effectively the aryl low carbon acid methyl ester product in upper strata thoroughly can be separated with acid and a small amount of catalyzer, obtain the reaction product of very high purity, simultaneously can by isolated residue reaction raw materials and catalyzer, after removing eluent, cyclically utilizing.Establish glycerine water suction thus and engage the basis that simulated moving bed chromatography is separated aryl low carbon acid methyl esters synthesis and production process.
We find, this technique has general applicability for the synthesis of aryl low carbon acid first Ester, be applicable to all compounds had such as formula female ring constitutional features (I) Suo Shi, its enantiomorph, racemic mixture and diastereomer, the synthesis of methyl esters:
The catalyzer be suitable for can be lipase, also can be tosic acid, methylsulfonic acid, Phenylsulfonic acid, picric acid, Jiao's property picric acid, dinitrobenzoic acid, trichoroacetic acid(TCA), solid super-strong acid, acidic ion exchange resin or other any can an acidic catalyst that carries out of catalytic esterification.Esterification should be 30 ~ 200 DEG C in temperature, pressure is carry out under the condition of 0.0001 ~ 3.5MPa, being suitable for of esterification system consists of acid: alcohol: glycerine=1: 1.05 ~ 50: 0.5 ~ 50 (mol ratios), and the broiler diets of catalyzer is 0.1 ~ 5% (w/w) of the charging capacity of acid.The Distillation recovery of residue methyl alcohol should be 30 ~ 80 DEG C in temperature, and pressure is carry out under the condition of 0.0001MPa ~ normal pressure.The stratification of reaction mixture should at 0 ~ 100 DEG C, preferably 10 ~ 60 DEG C, temperature under carry out.To the processed that lower floor carries out, can carry out with the distillation technique of routine, also can be undertaken by the technology such as molecular sieve adsorption, membrane sepn.The eluent that separation system of simulated moving bed chromatography uses can be supercritical co, methylene dichloride, trichloromethane, isopropyl ether, methyl tertiary butyl ether, methyl alcohol, toluene and by formed the in any proportion mixed solvent of two or more in them, the sorbent material that separation system of simulated moving bed chromatography uses can be gac, silica gel, sex change silica gel, activated alumina, polyacrylamide, ion exchange resin or other anyly can coordinate with particular eluent the sorbing material be separated with non-ester components such as remaining acid by the ester in upper strata.It should be 0 ~ 100 DEG C in temperature that simulated moving bed chromatography is separated, and preferably 30 ~ 60 DEG C, pressure is carry out under the condition of 0.1 ~ 35MPa.
After the whole optimization of all important parameters mentioned in the present invention, the transformation efficiency of raw material and the yield of product all can be increased to 100%.The purity of product can be increased to more than 99% (chromatographic purity).
The esters product recovery technology used in the present invention continues to use traditional method substantially.
Embodiment
Example below will illustrate working method of the present invention, but can not as limitation of the invention.
Embodiment 1, the preparation of Ibuprofen BP/EP methyl esters
Get 100mL tri-mouthfuls of round-bottomed flasks, add 20.6g (0.1mol) Ibuprofen BP/EP, 0.2g tosic acid, 40.35mL (1mol) methyl alcohol, 20mL (0.274mol) glycerine, stir, heating mantle heats 70 DEG C backflow 4hr.After reaction terminates, 75 DEG C of air distillation removing unreacteds methyl alcohol completely.Be placed in separating funnel stratification, upper strata is methyl esters layer, and lower floor is glycerin layer.Glycerin layer is got back in reaction flask, recycles in next round reaction.Methyl esters stratification is sorbent material with silica gel, is to be separated in the separation system of simulated moving bed chromatography of eluent formation with methylene dichloride, obtains Ibuprofen BP/EP, tosic acid component and Ibuprofen BP/EP methyl esters component.Methylene dichloride is reclaimed in air distillation, and obtain Ibuprofen BP/EP methyl esters 21.35g, transformation efficiency reaches 97%.
Ibuprofen BP/EP methyl esters is through liquid phase-mass spectrometry inspection, and product purity reaches spectroscopically pure.
Ibuprofen BP/EP and tosic acid reclaim, and recycle in next round reaction.
Embodiment 2, the preparation of Ketoprofen methyl esters
Get 100mL tri-mouthfuls of round-bottomed flasks, add 25.4g (0.1mol) Ketoprofen, 0.5g methylsulfonic acid, 100mL (2.48mol) methyl alcohol, 50mL (0.69mol) glycerine, stir, heating mantle heats 75 DEG C backflow 6hr.30 DEG C of underpressure distillation removing unreacteds methyl alcohol completely.Be placed in separating funnel stratification, upper strata is methyl esters layer, and lower floor is glycerin layer.Glycerin layer is got back in reaction flask, recycles in next round reaction.Methyl esters stratification is sorbent material with polymeric amide, is to be separated in the separation system of simulated moving bed chromatography of eluent formation with methyl tertiary butyl ether, obtains Ketoprofen, methylsulfonic acid component and Ketoprofen methyl esters component.Methyl tertiary butyl ether is reclaimed in air distillation, and obtain Ketoprofen methyl esters 26.01g, transformation efficiency is greater than 97%.
Ketoprofen methyl esters is through liquid phase-mass spectrometry inspection, and product purity reaches spectroscopically pure.
Ketoprofen reclaims, and recycles in next round reaction.
The preparation of embodiment 3,2-phenylpropionic acid methyl ester
Get 100mL tri-mouthfuls of round-bottomed flasks, add 30.40g (0.2mol) 2-phenylpropionic acid, 0.03g Novozym435,30mL (0.74mol) methyl alcohol, 10mL (0.14mol) glycerine, stir, heat 55 DEG C of reaction 8hr.30 DEG C of underpressure distillation removing unreacteds methyl alcohol completely.Cross and filter lipase, be placed in separating funnel stratification, upper strata is methyl esters layer, and lower floor is glycerin layer.Glycerin layer is got back in reaction flask, recycles in next round reaction.Methyl esters stratification is sorbent material with silica gel, is to be separated in the separation system of simulated moving bed chromatography of eluent formation with methylene dichloride, obtains 2-phenylpropionic acid component and 2-phenylpropionic acid methyl ester component.Trichloromethane is reclaimed in air distillation, and obtain 2-phenylpropionic acid methyl ester 29.90g, transformation efficiency is greater than 90%.
2-phenylpropionic acid methyl ester is through liquid phase-mass spectrometry inspection, and product purity reaches spectroscopically pure.
2-phenylpropionic acid reclaims, and recycles in next round reaction.
Embodiment 4, the preparation of methyl phenylacetate
Get 100mL tri-mouthfuls of round-bottomed flasks, add 27.23g (0.2mol) toluylic acid, 1g Phenylsulfonic acid, 20mL (0.50mol) methyl alcohol, 20mL (0.27mol) glycerine, stir, heating mantle heats 70 DEG C backflow 2hr.75 DEG C of air distillation removing unreacteds methyl alcohol completely.Be placed in separating funnel stratification, upper strata is methyl esters layer, and lower floor is glycerin layer.Glycerin layer is got back in reaction flask, recycles in next round reaction.Methyl esters stratification is sorbent material with polymeric amide, with isopropyl ether: methyl alcohol=98: the mixed solvent of 2 is be separated in the separation system of simulated moving bed chromatography that formed of eluent, obtains toluylic acid, Phenylsulfonic acid component and methyl phenylacetate component.Air distillation recycling design, obtain methyl phenylacetate 28.55g, transformation efficiency is greater than 95%.
Methyl phenylacetate is through liquid phase-mass spectrometry inspection, and product purity reaches spectroscopically pure.
Toluylic acid and Phenylsulfonic acid reclaim, and recycle in next round reaction.
Embodiment 5, the preparation of methyl cinnamate
Get 1000mL tri-mouthfuls of round-bottomed flasks, add 29.63g (0.2mol) styracin, 1.0g dinitrobenzoic acid, 200mL (4.96mol) methyl alcohol, 200mL (2.74mol) glycerine, stir, heating mantle heats 75 DEG C backflow 2hr.75 DEG C of air distillation removing unreacteds methyl alcohol completely.Be placed in separating funnel stratification, upper strata is methyl esters layer, and lower floor is glycerin layer.Glycerin layer is got back in reaction flask, recycles in next round reaction.Methyl esters stratification with sex change silica gel for sorbent material, with toluene: methyl alcohol=9: the mixed solvent of 1 is be separated in the separation system of simulated moving bed chromatography that formed of eluent, obtains styracin, dinitrobenzoic acid component and methyl cinnamate component.Air distillation recycling design, obtain methyl cinnamate 30.82g, transformation efficiency is greater than 95%.
Methyl cinnamate is through liquid phase-mass spectrometry inspection, and product purity reaches spectroscopically pure.
Styracin and dinitrobenzoic acid reclaim, and recycle in next round reaction.
Embodiment 6, the preparation of wintergreen oil
Get 500mL tri-mouthfuls of round-bottomed flasks, add 27.62g (0.2mol) Whitfield's ointment, 1.4g acidic ion exchange resin, 200mL (4.96mol) methyl alcohol, 100mL (1.37mol) glycerine, stir, heating mantle heats 70 DEG C backflow 2hr.75 DEG C of air distillation removing unreacteds methyl alcohol completely.Be placed in separating funnel stratification, upper strata is methyl esters layer, and lower floor is glycerin layer.Glycerin layer is got back in reaction flask, recycles in next round reaction.Methyl esters stratification is sorbent material with silica gel, with methylene dichloride: methyl alcohol=95: the mixed solvent of 5 is be separated in the separation system of simulated moving bed chromatography that formed of eluent, obtains Whitfield's ointment component and wintergreen oil component.Air distillation recycling design, obtain wintergreen oil 29.52g, transformation efficiency is greater than 97%.Wintergreen oil is through liquid phase-mass spectrometry inspection, and product purity reaches spectroscopically pure.
Whitfield's ointment reclaims, and recycles in next round reaction.
Embodiment 7, the preparation of methyl benzoate
Get 250mL tri-mouthfuls of round-bottomed flasks, add 24.42g (0.2mol) phenylformic acid, 0.03g trichoroacetic acid(TCA), 50mL (1.24mol) methyl alcohol, 25mL (0.34mol) glycerine, stir, heating mantle heats 70 DEG C backflow 4hr.75 DEG C of air distillation removing unreacteds methyl alcohol completely.Be placed in separating funnel stratification, upper strata is methyl esters layer, and lower floor is glycerin layer.Glycerin layer is got back in reaction flask, recycles in next round reaction.Methyl esters stratification is sorbent material with silica gel, is to be separated in the separation system of simulated moving bed chromatography of eluent formation with methyl tertiary butyl ether, obtains phenylformic acid, trichoroacetic acid(TCA) component and methyl benzoate component.Air distillation recycling design, obtain methyl benzoate 25.86g, transformation efficiency is greater than 95%.
Methyl benzoate is through liquid phase-mass spectrometry inspection, and product purity reaches spectroscopically pure.
Phenylformic acid and trichoroacetic acid(TCA) reclaim, and recycle in next round reaction.
Embodiment 8, the preparation of methyl phenylpropionate
Get 250mL tri-mouthfuls of round-bottomed flasks, add 30.04g (0.2mol) phenylpropionic acid, 0.5g tosic acid, 10mL (0.25mol) methyl alcohol, 100mL (1.37mol) glycerine, stir, heating mantle heats 70 DEG C backflow 2hr.36 DEG C of underpressure distillation removing unreacteds methyl alcohol completely.Be placed in separating funnel stratification, upper strata is methyl esters layer, and lower floor is glycerin layer.Glycerin layer is got back in reaction flask, recycles in next round reaction.Methyl esters stratification is sorbent material with polymeric amide, is to be separated in the separation system of simulated moving bed chromatography of eluent formation with methyl tertiary butyl ether, obtains phenylpropionic acid, tosic acid component and methyl phenylpropionate component.Air distillation recycling design, obtain methyl phenylpropionate 29.57g, transformation efficiency is greater than 90%.
Methyl phenylpropionate is through liquid phase-mass spectrometry inspection, and product purity reaches spectroscopically pure.
Phenylpropionic acid reclaims, and recycles in next round reaction.
The preparation of embodiment 9,2-naphthalene methyl acetate
Get 100mL tri-mouthfuls of round-bottomed flasks, add 18.662g (0.1mol) 2-naphthylacetic acid, Jiao's 0.2g property picric acid, 20mL (0.50mol) methyl alcohol, 50mL (0.69mol) glycerine, stir, heating mantle heats 75 DEG C backflow 2hr.40 DEG C of underpressure distillation removing unreacteds methyl alcohol completely.Be placed in separating funnel stratification, upper strata is methyl esters layer, and lower floor is glycerin layer.Glycerin layer is got back in reaction flask, recycles in next round reaction.Methyl esters stratification is sorbent material with polymeric amide, is to be separated in the separation system of simulated moving bed chromatography of eluent formation with methylene dichloride, obtains 2-naphthylacetic acid, Jiao's property picric acid component and 2-naphthalene methyl acetate component.Air distillation recycling design, obtain 2-naphthalene methyl acetate 31.21g, transformation efficiency is greater than 95%.
2-naphthalene methyl acetate is through liquid phase-mass spectrometry inspection, and product purity reaches spectroscopically pure.
2-naphthylacetic acid and Jiao's property picric acid reclaim, and recycle in next round reaction.
Embodiment 10, the preparation of Naproxen methyl ester
Get 1000mL tri-mouthfuls of round-bottomed flasks, add 23.06g (0.1mol) Naproxen Base, 0.5g Phenylsulfonic acid, 200mL (4.96mol) methyl alcohol, 300mL (4.11mol) glycerine, stirs, vacuum tightness is 0.08MPa, heating mantle heats 45 DEG C backflow 2hr.45 DEG C of underpressure distillation removing unreacteds methyl alcohol completely.Be placed in separating funnel stratification, upper strata is methyl esters layer, and lower floor is glycerin layer.Glycerin layer is got back in reaction flask, recycles in next round reaction.Methyl esters stratification is sorbent material with silica gel, is to be separated in the separation system of simulated moving bed chromatography of eluent formation with methyl tertiary butyl ether, obtains Naproxen Base, Phenylsulfonic acid component and Naproxen methyl ester component.Air distillation recycling design, obtain Naproxen methyl ester 23.21g, transformation efficiency is greater than 95%.
Naproxen methyl ester is through liquid phase-mass spectrometry inspection, and product purity reaches spectroscopically pure.
Naproxen Base and Phenylsulfonic acid reclaim, and recycle in next round reaction.
Embodiment 11, the preparation of indomethacin methyl esters
Get 500mL tri-mouthfuls of round-bottomed flasks, add 35.78g (0.1mol) indomethacin, 1.0g methylsulfonic acid, 200mL (4.96mol) methyl alcohol, 50mL (0.69mol) glycerine, stir, heating mantle heats 75 DEG C backflow 6hr.80 DEG C of air distillation removing unreacteds methyl alcohol completely.Be placed in separating funnel stratification, upper strata is methyl esters layer, and lower floor is glycerin layer.Glycerin layer is got back in reaction flask, recycles in next round reaction.Methyl esters stratification is sorbent material with silica gel, is to be separated in the separation system of simulated moving bed chromatography of eluent formation with ether, obtains indomethacin, methylsulfonic acid component and indomethacin methyl esters component.Obtain indomethacin methyl esters 35.32g, transformation efficiency is greater than 95%.
Indomethacin methyl esters is through liquid phase-mass spectrometry inspection, and product purity reaches spectroscopically pure.
Indomethacin and methylsulfonic acid reclaim, and recycle in next round reaction.
Embodiment 12, the preparation of etodolac methyl ester
Get 100mL tri-mouthfuls of round-bottomed flasks, add 28.74g (0.1mol) R-ETODOLAC, 0.6g Phenylsulfonic acid, 30mL (0.74mol) methyl alcohol, 15mL (0.21mol) glycerine, stir, heating mantle heats 75 DEG C backflow 8hr.40 DEG C of underpressure distillation removing unreacteds methyl alcohol completely.Be placed in separating funnel stratification, upper strata is methyl esters layer, and lower floor is glycerin layer.Glycerin layer is got back in reaction flask, recycles in next round reaction.Methyl esters stratification is sorbent material with silica gel, with methylene dichloride: methyl tertiary butyl ether=1: the mixed solvent of 1 is be separated in the separation system of simulated moving bed chromatography that formed of eluent, obtains R-ETODOLAC, Phenylsulfonic acid component and etodolac methyl ester component.Air distillation recycling design, obtain etodolac methyl ester 28.63g, transformation efficiency is greater than 95%.Etodolac methyl ester is through liquid phase-mass spectrometry inspection, and product purity reaches spectroscopically pure.
R-ETODOLAC and Phenylsulfonic acid reclaim, and recycle in next round reaction.
Claims (5)
1. a green synthesis process for aryl low carbon acid methyl esters, this technique is made up of the following step:
1) prepare a mixture, this mixture by (i) aryl low-carbon (LC) acids, (ii) methyl alcohol, (iii) catalyzer and (iv) glycerine composition; Described catalyzer is selected from lipase, tosic acid, methylsulfonic acid, Phenylsulfonic acid, picric acid, Jiao's property picric acid, dinitrobenzoic acid, trichoroacetic acid(TCA), solid super-strong acid, acidic ion exchange resin; Wherein, acid: alcohol: mol ratio=1:1.05 ~ 50:0.5 ~ 50 of glycerine, the addition of catalyzer is 0.1 ~ 5% of the charging capacity of acid;
2) the aryl low-carbon (LC) acids in mixture and methyl alcohol generation esterification is allowed to generate corresponding ester and water; Esterification is 30 ~ 200 DEG C in temperature, and pressure is carry out under the condition of 0.0001 ~ 3.5MPa;
3), after reaction terminating, the remaining methyl alcohol of Distillation recovery, obtains a reaction mixture be made up of ester, remaining acid, catalyzer and aqueous glycerol;
4) allow reaction mixture sat layering, obtain based on ester, the upper strata simultaneously containing remaining acid and a small amount of catalyzer and based on aqueous glycerol, the lower floor simultaneously containing catalyzer, lower floor uses through processed Posterior circle;
5) chromatographic separation and purification is carried out with simulation moving-bed in upper strata, obtains only containing the elutriant of ester and the scrub raffinate containing all the other all the components in upper strata except ester; Scrub raffinate removes eluent Posterior circle and uses, and eluent reclaims, and recycles; The eluent that described separation system of simulated moving bed chromatography uses is selected from supercritical co, methylene dichloride, trichloromethane, isopropyl ether, ether, methyl tertiary butyl ether, methyl alcohol, toluene or by formed the in any proportion mixed solvent of two or more in them, the sorbent material used is selected from gac, silica gel, sex change silica gel, activated alumina, polyacrylamide, ion exchange resin;
6) after elutriant removes eluent, obtain ester, eluent reclaims, and recycles; Wherein, described aryl low-carbon (LC) acids has the compound such as formula female ring constitutional features (I) Suo Shi, its enantiomorph, racemic mixture and diastereomer:
2. the green synthesis process of aryl low carbon acid methyl esters as claimed in claim 1, it is characterized in that the Distillation recovery of described residue methyl alcohol is 30 ~ 80 DEG C in temperature, pressure is carry out under the condition of 0.0001MPa ~ normal pressure.
3. the green synthesis process of aryl low carbon acid methyl esters as claimed in claim 1, is characterized in that the stratification of described reaction mixture carries out at the temperature of 10 ~ 60 DEG C.
4. the green synthesis process of aryl low carbon acid methyl esters as claimed in claim 1, is characterized in that the described processed of carrying out lower floor, carries out with the distillation technique of routine, or undertaken by molecular sieve adsorption, membrane separation technique.
5. the green synthesis process of aryl low carbon acid methyl esters as claimed in claim 1, it is characterized in that simulated moving bed chromatography is separated in temperature is 30 ~ 60 DEG C, and pressure is carry out under the condition of 0.1 ~ 3.5MPa.
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| CN101429529A (en) * | 2008-12-11 | 2009-05-13 | 江南大学 | Ester zymoid method production process of azeotropy water elimination coupling simulated moving bed |
| CN101450898A (en) * | 2008-12-30 | 2009-06-10 | 张丽丽 | UV photo-curing monomer clean production process through coupling reactor and simulated moving bed |
| CN101531611A (en) * | 2009-03-06 | 2009-09-16 | 浙江工业大学 | Method for preparing aminoprofen with high purity |
| CN102267911A (en) * | 2011-08-08 | 2011-12-07 | 天津市化学试剂研究所 | Synthesis method of methyl salicylate |
| CN102408338A (en) * | 2011-10-27 | 2012-04-11 | 杭州友邦香料香精有限公司 | Method for synthesizing salicylate |
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