CN102010326B - Industrial method for synthesizing 2-(4-methoxyphenoxy)-propionic acid through phase transfer - Google Patents
Industrial method for synthesizing 2-(4-methoxyphenoxy)-propionic acid through phase transfer Download PDFInfo
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Abstract
The invention discloses an industrial method for synthesizing 2-(4-methoxyphenoxy)-propionic acid through phase transfer, which comprises the following steps of: stirring and mixing 4-Methoxyphenol, sodium hydroxide, a phase transfer catalyst and water, and reacting at normal temperature and normal pressure for 10 to 20 minutes to obtain mixed feed liquid; adding 2-chloro-propanoic acid and an organic phase into the mixed feed liquid, and reacting for 0.5 to 1.5 hours to obtain a product of 2-(4-methoxyphenoxy)-propionic acid; regulating the reaction liquid subjected to reaction to be acid by using HCl or sulfuric acid solution, and standing to separate a water phase and the organic phase; and evaporating organic phase separation liquid to remove a solvent, and performing acid-base recrystallization to obtain the 2-(4-methoxyphenoxy)-propionic acid. When the reaction is finished, the yield of the 2-(4-methoxyphenoxy)-propionic acid is over 90 percent, the reaction temperature is reduced to 40-60 DEG C, the reaction time is only 0.5 to 1.5 hours, and the content of 2-(4-methoxyphenoxy)-propionic acid in the final product is 99.5 percent.
Description
Technical field
The invention belongs to the Food science field, be specifically related to a kind of novel method of utilizing phase transfer method preparation of industrialization 2-(4-methoxyl group phenoxy group)-propionic acid.
Background technology
Sweetness inhibitor is the acceptor by the obstruction sugariness and the sense of taste, thereby control or reduction contain a class new additive agent of the sugariness of confectionery.Domestic a lot of traditional food, as preserved fruit, moon cake, chocolate etc., all with sucrose as sanitas, reaching rot-resistant simultaneously, in various degree existed sweet problem.And after having used sweetness inhibitor, can bring into play sucrose anticorrosion, improve functions such as matter structure, can not make food cross sweet again and influence mouthfeel.Therefore the application prospect of sweetness inhibitor is very extensive.
Chinese invention patent ZL200510101321.1 had reported a kind of industrialized preparing process of natural sweet taste inhibitor triterpene glucoside.It is to be present in the leaf of Rhamnaceae plant Hoveniadulcis Thumb. from gymnemic acid (Glymnemic acid), Hodulcin() and some jujube (as date, wild jujube) leaf, seed, fruit in separate.
In addition, 2-(4-methoxyl group phenoxy group)-propionic acid also is a kind of sweetness inhibitor commonly used, natural being present in the coffee berry.But the 2-in the natural coffee beans (4-methoxyl group phenoxy group)-propionic acid content is 0.55～1.2mg/kg only, utilizes plant extract 2-(4-methoxyl group phenoxy group)-propionic acid to be subjected to condition effect such as seasonal climate, yields poorly, and the cost height does not possess economic worth.
2-(4-methoxyl group phenoxy group)-propionic acid is a kind of crystalline solid of colourless or evaporated milk oil colours, in the organic solvents such as water soluble and ether, propylene glycol, to sucrose and all pleasantly sweet restraining effect of other artificial sweetening agent.It is a kind of safe, use additive that can add in foodstuffs industry is produced that international food perfume industry tissue (IOFI) is evaluated it.At present, produce 2-(4-methoxyl group phenoxy group)-main chemical synthesis of propionic acid method.U.S.'s patent of invention 4760172 has been reported the method for a kind of 2-of utilization chloropropionic acid and 4-hydroxyanisol chemosynthesis 2-(4-methoxyl group phenoxy group)-propionic acid, and product purity reaches more than 75%.The molar concentration rate of 2-chloropropionic acid and MEHQ is 1 in the reaction system: (3～10), adding NaOH makes to be reflected under the alkaline condition and carries out, during the reaction termination, by presenting different pH values, reclaim excessive 4-hydroxyanisol and product 2-(4-methoxyl group phenoxy group respectively with concentrated hydrochloric acid or vitriol oil conditioned reaction system)-propionic acid.Entire reaction is to carry out at aqueous phase, and temperature of reaction is 80～150 ℃, and the reaction times needs 4～10h.But this method temperature of reaction height, the time is long, yield is low, and product purity is low, so the production cost height.
Summary of the invention
The object of the invention is to overcome the shortcoming of prior art, provide a kind of total recovery more than 90%, purity can reach more than 99.5%, mild condition, technology is simple, cost is low, is fit to the industrial method of phase transfer method Synthetic 2-(4-methoxyl group the phenoxy group)-propionic acid of large-scale industrial production.
A kind of 2-(4-methoxyl group of the present invention phenoxy group)-compound structure such as the formula I of propionic acid
Be by raw material MEHQ such as formula II and 2-chloropropionic acid such as formula III under the phase-transfer catalyst effect, utilize water---the organic phase phase transfer method is synthetic.
Reaction formula is as follows:
In recent years, phase-transfer catalysis is used in chemosynthesis more and more widely, Chinese invention patent CN1296157A has reported a kind of phase-transfer catalysis production 2 that utilizes, 6-two [(4,6-dimethoxypyridin-2-yl) oxygen] synthetic method of Sodium Benzoate, have easy and simple to handle, the reaction yield advantages of higher.Utilizing the reaction of MEHQ and 2-chloropropionic acid Synthetic 2-(4-methoxyl group phenoxy group)-propionic acid is a reversible reaction, side reaction production by product easily takes place in the 2-chloropropionic acid in reaction process, so add-on is very high usually, to promote the conversion fully of MEHQ, product yield is low.2-(4-methoxyl group phenoxy group)-solubleness of propionic acid in organic solvents such as ether is far above water.The present invention utilizes this characteristic, in reaction process, add organic phase and phase-transfer catalyst, in time with reaction product 2-(4-methoxyl group phenoxy group)-propionic acid changes organic phase over to, to guarantee that the aqueous phase building-up reactions is to 2-(4-methoxyl group phenoxy group)-the propionic acid direction carries out fast.This method improves product yield when simplifying the operation of product separation and Extraction, reduced production cost.Also do not utilize phase-transfer catalysis chemosynthesis 2-(4-methoxyl group phenoxy group at present)-method of propionic acid report.
Purpose of the present invention is achieved through the following technical solutions:
The industrial method of a kind of phase transfer method Synthetic 2-(4-methoxyl group phenoxy group)-propionic acid comprises the steps:
(1) be 1 with MEHQ, sodium hydroxide, phase-transfer catalyst, water in mass ratio: (1～3): (0.2～0.4): the ratio of (15～20) mixes, mixing speed 100～200r/min, normal temperature and pressure reaction 10～20min, MEHQ is converted into p methoxy phenol sodium, obtains mixed liquor A; Described phase-transfer catalyst is Tetrabutyl amonium bromide, 4-butyl ammonium hydrogen sulfate; Chain polyoxyethylene glycol dialkyl ether, pyridine, Tributylamine or cyclodextrin;
(2) add 2-chloropropionic acid and organic phase in mixed liquor A, 2-chloropropionic acid adding quality is 1～3 times of MEHQ quality, and the volume ratio of water and organic phase is 1: (0.8～1.2); Temperature of reaction is increased to 40～60 ℃, and reaction pressure 2～3MPa, mixing speed are 60～120r/min, and reaction 0.5～1.5h obtains product 2-(4-methoxyl group phenoxy group)-propionic acid; Described organic phase is ether, sherwood oil, acetone, tetracol phenixin, benzene, 2-monochloroethane or Virahol; Described organic phase is a kind of in ether, sherwood oil, acetone, tetracol phenixin, benzene, 2-monochloroethane or the Virahol;
(3) reacted reaction solution is with HCl solution or sulphuric acid soln furnishing acidity, leaves standstill water is separated with organic phase the 2-(4-methoxyl group phenoxy group of aqueous phase)-Sodium Propionate is converted into carboxylic acid form, enters organic phase, the separated and collected organic phase;
(4) organic phase parting liquid evaporative removal solvent after the cooling, through the soda acid recrystallization, obtains 2-(4-methoxyl group phenoxy group)-the propionic acid product.
For further realizing the object of the invention, described organic phase is preferably ether, acetone, tetracol phenixin, benzene or Virahol.
Described phase-transfer catalyst is preferably Tetrabutyl amonium bromide, 4-butyl ammonium hydrogen sulfate, pyridine, Tributylamine or cyclodextrin.
Described HCl solution quality concentration is preferably 10～30%.
Described soda acid recrystallization is 1～3 time, and the processing condition of soda acid recrystallization are: the solid that obtains behind the organic phase parting liquid evaporative removal solvent adds the NaOH aqueous solution, and regulator solution pH to 8～10 are dissolved it fully; And then add HCl, regulate its pH to 1～3, leave standstill, the adularescent plate crystal is separated out, this process be the soda acid recrystallization once; Number of times according to recrystallization repeats aforesaid operations, final fractional crystallization, and drying obtains finished product.
Compared with prior art, the present invention has following advantage:
1. raising transformation efficiency.The reaction of MEHQ and 2-chloropropionic acid Synthetic 2-(4-methoxyl group phenoxy group)-propionic acid is a reversible reaction, will be in the reaction process by strengthening the volumetric molar concentration of certain reaction substrate, could guarantee transformation efficiency, after adding organic phase, product in time can be shifted from reaction system, not only improve the transformation efficiency of chemosynthesis, saved the step that reclaims the excessive response substrate in the production technique simultaneously;
2. reduction temperature of reaction.Temperature of reaction is 80～150 ℃ in the existing production technique, and by this kind production technique, temperature of reaction can be reduced to 40～60 ℃;
3. shorten the reaction times.The reaction times is 4～10h in the conventional production process, utilizes this production technique, improves transformation efficiency, and the reaction times can foreshorten to 0.5～2h.
Specific implementation method
The present invention is further illustrated below in conjunction with embodiment, but embodiment does not constitute the restriction to the claimed scope of the present invention.Organic phase is ether, sherwood oil, acetone, tetracol phenixin, benzene, 2-monochloroethane or Virahol;
Embodiment 1
(1) in reactor, adds MEHQ 10kg, sodium hydroxide 11kg, phase-transfer catalyst Tetrabutyl amonium bromide 0.4kg, water 150L respectively, mix at normal temperatures and pressures, mixing speed 150r/min, reaction 15min, MEHQ is transformed p methoxy phenol sodium, obtain mixed liquor A;
(2) in mixed liquor A, add the 2-chloropropionic acid of 15kg, the ether of 150L, 40 ℃ of temperature of reaction, reaction pressure are 3MPa, mixing speed is 150r/min, reaction 1.5h obtains product 2-(4-methoxyl group phenoxy group)-propionic acid;
(3) reacted reaction solution is with 20% HCl solution furnishing acidity, leave standstill water is separated with the organic phase ether, the 2-(4-methoxyl group phenoxy group of aqueous phase)-Sodium Propionate is converted into 2-(4-methoxyl group phenoxy group)-propionic acid enters the organic phase ether, the separated and collected organic phase.
(4) organic phase parting liquid evaporative removal solvent, the solid adding mass concentration that obtains after the cooling is 30% the NaOH aqueous solution, regulator solution pH to 8～10, it is dissolved fully, and then to add mass concentration be 30% HCl solution, regulates its pH to 1～2, leaves standstill, the adularescent plate crystal is separated out, add NaOH again, regulator solution pH to 8～9 are dissolved it fully, and then adding HCl, regulate its pH to 1～3, leave standstill, the adularescent plate crystal is separated out, the fractional crystallization drying obtains 2-(4-methoxyl group phenoxy group)-propionic acid finished product 14.38kg.The theoretical yield of product is 15.8g, and actual recovery is 91% of a theoretical yield, and product purity can reach 99.5%.
Embodiment 2
(1) in reactor, adds MEHQ 10kg, sodium hydroxide 20kg, phase-transfer catalyst cyclodextrin 0.6kg, water 200L respectively, mix at normal temperatures and pressures, mixing speed 200r/min, reaction 10min, MEHQ is transformed p methoxy phenol sodium, obtain mixed liquor A;
(2) in mixed liquor A, add 2-chloropropionic acid 15kg, normal hexane 200L is increased to 45 ℃ with temperature of reaction, and pressure 2MPa, mixing speed are 200r/min, reaction 1h obtains product 2-(4-methoxyl group phenoxy group)-propionic acid;
(3) reacted reaction solution is with 15% H
2SO
4Solution furnishing acidity leaves standstill water is separated with the organic phase normal hexane, the 2-(4-methoxyl group phenoxy group of aqueous phase)-Sodium Propionate is converted into 2-(4-methoxyl group phenoxy group)-propionic acid enters organic phase, the separated and collected organic phase;
(4) organic phase parting liquid evaporative removal solvent, the solid adding mass concentration that obtains after the cooling is 20% the NaOH aqueous solution, regulator solution pH to 9～10, it is dissolved fully, and then the adding mass concentration is 10% HCl solution, regulate its pH to 1, leave standstill, the adularescent plate crystal is separated out, this be the soda acid recrystallization once, repeat aforesaid operations, behind the soda acid recrystallization 3 times, collect crystallizing and drying, obtain 2-(4-methoxyl group phenoxy group)-propionic acid finished product 14.78kg, product yield is 93.5% of a theoretical yield, and product purity can reach 99.7%.
Embodiment 3
(1) in reactor, adds MEHQ 10kg, sodium hydroxide 25kg, phase-transfer catalyst cyclodextrin 0.8kg, water 150L respectively, mix at normal temperatures and pressures, mixing speed 200r/min, reaction 10min, MEHQ is transformed p methoxy phenol sodium, obtain mixed liquor A;
(2) in mixed liquor A, add 2-chloropropionic acid 20kg, sherwood oil 160L is increased to 40 ℃ with temperature of reaction, and pressure 2MPa, mixing speed are 200r/min, reaction 1h obtains product 2-(4-methoxyl group phenoxy group)-propionic acid;
(3) reacted reaction solution is with 10% H
2SO
4Solution furnishing acidity leaves standstill water is separated with the organic phase sherwood oil, the 2-(4-methoxyl group phenoxy group of aqueous phase)-Sodium Propionate is converted into 2-(4-methoxyl group phenoxy group)-propionic acid enters organic phase, the separated and collected organic phase;
(4) organic phase parting liquid evaporative removal solvent, after the cooling, the solid adding mass concentration that obtains is 25% NaOH solution, regulator solution pH to 9, it is dissolved fully, and then to add mass concentration be 10% HCl solution, regulate its pH to 2, leave standstill, the adularescent plate crystal is separated out, and collects crystallizing and drying, obtains 2-(4-methoxyl group phenoxy group)-propionic acid finished product 14.30kg, product yield is 90.4% of a theoretical yield, and product purity can reach 99.5%.
Embodiment 4
(1) in reactor, adds MEHQ 10kg, sodium hydroxide 20kg, phase-transfer catalyst Tributylamine 0.6kg, water 150L respectively, mix at normal temperatures and pressures, mixing speed 200r/min, reaction 20min, MEHQ is transformed p methoxy phenol sodium, obtain mixed liquor A;
(2) in mixed liquor A, add 2-chloropropionic acid 15kg, normal hexane 180L is increased to 50 ℃ with temperature of reaction, and pressure 2MPa is increased to 50 ℃ with temperature of reaction, and mixing speed is 150r/min, reaction 1.5h obtains product 2-(4-methoxyl group phenoxy group)-propionic acid;
(3) reacted reaction solution is with 30% HCl solution furnishing acidity, leaves standstill water is separated with organic phase the 2-(4-methoxyl group phenoxy group of aqueous phase)-Sodium Propionate is converted into 2-(4-methoxyl group phenoxy group)-propionic acid enters organic phase, the separated and collected organic phase;
(4) organic phase parting liquid evaporative removal solvent, the solid adding mass concentration that obtains after the cooling is 25% NaOH solution, regulator solution pH to 10 dissolves it fully, and then the adding mass concentration is a 15%HCl solution, regulate its pH to 3, leave standstill, the adularescent plate crystal is separated out, and adds mass concentration again and be 25% NaOH solution, regulator solution pH to 10, it is dissolved fully, and then add HCl, regulate its pH to 1～3, leave standstill, the adularescent plate crystal is separated out, and the fractional crystallization drying obtains 2-(4-methoxyl group phenoxy group)-propionic acid finished product 15kg, product yield is 94.9% of a theoretical yield, and product purity can reach 99.5%.
Claims (3)
1. the industrial method of phase transfer method Synthetic 2-(4-methoxyl group phenoxy group)-propionic acid is characterized in that comprising the steps:
(1) be 1 with MEHQ, sodium hydroxide, phase-transfer catalyst, water in mass ratio: (1～3): (0.2～0.4): the ratio of (15～20) mixes, mixing speed 100～200r/min, normal temperature and pressure reaction 10～20min, MEHQ is converted into p methoxy phenol sodium, obtains mixed liquor A; Described phase-transfer catalyst is Tetrabutyl amonium bromide, 4-butyl ammonium hydrogen sulfate; Chain polyoxyethylene glycol dialkyl ether, pyridine, Tributylamine or cyclodextrin;
(2) add 2-chloropropionic acid and organic phase in mixed liquor A, 2-chloropropionic acid add-on is 1～3 times of MEHQ quality, and the volume ratio of water and organic phase is 1: (0.8～1.2); Temperature of reaction is increased to 40～60 ℃, and reaction pressure 2～3MPa, mixing speed are 60～120r/min, and reaction 0.5～1.5h obtains product 2-(4-methoxyl group phenoxy group)-propionic acid; Described organic phase is ether, sherwood oil, acetone, tetracol phenixin, benzene, 2-monochloroethane or Virahol;
(3) reacted reaction solution is with HCl solution or sulphuric acid soln furnishing acidity, leaves standstill water is separated with organic phase the 2-(4-methoxyl group phenoxy group of aqueous phase)-Sodium Propionate is converted into carboxylic acid form, enters organic phase, the separated and collected organic phase;
(4) organic phase parting liquid evaporative removal solvent after the cooling, through the soda acid recrystallization, obtains 2-(4-methoxyl group phenoxy group)-the propionic acid product.
2. the industrial method of phase transfer method Synthetic 2 according to claim 1-(4-methoxyl group phenoxy group)-propionic acid is characterized in that: described HCl solution quality concentration is 10～30%.
3. the industrial method of phase transfer method Synthetic 2 according to claim 1-(4-methoxyl group phenoxy group)-propionic acid, it is characterized in that: described soda acid recrystallization is 1～3 time, the processing condition of soda acid recrystallization are: the solid that obtains behind the organic phase parting liquid evaporative removal solvent adds the NaOH aqueous solution, regulator solution pH to 8～10 are dissolved it fully; And then add HCl, regulate its pH to 1～3, leave standstill, the adularescent plate crystal is separated out, for the soda acid recrystallization once; Number of times according to recrystallization repeats aforesaid operations, final fractional crystallization, and drying obtains finished product.
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| CN1396157A (en) * | 2002-03-22 | 2003-02-12 | 浙江工业大学 | Process for chemically synthesizing 2,6-bis [(4,6-dimethoxypyrimidine-2-yl) oxy] sodium bezoate |
| CN101302149A (en) * | 2008-05-16 | 2008-11-12 | 梁小文 | Synthetic method of 4-methoxyl phenoxyl alkylphenate |
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| CN1396157A (en) * | 2002-03-22 | 2003-02-12 | 浙江工业大学 | Process for chemically synthesizing 2,6-bis [(4,6-dimethoxypyrimidine-2-yl) oxy] sodium bezoate |
| CN101302149A (en) * | 2008-05-16 | 2008-11-12 | 梁小文 | Synthetic method of 4-methoxyl phenoxyl alkylphenate |
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