CN1077877C - Process for preparing 4-hydroxy phenylpropionic acid compound - Google Patents
Process for preparing 4-hydroxy phenylpropionic acid compound Download PDFInfo
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- CN1077877C CN1077877C CN97109894A CN97109894A CN1077877C CN 1077877 C CN1077877 C CN 1077877C CN 97109894 A CN97109894 A CN 97109894A CN 97109894 A CN97109894 A CN 97109894A CN 1077877 C CN1077877 C CN 1077877C
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- CN
- China
- Prior art keywords
- acid compound
- phenylpropionic acid
- phenol
- preparation
- hydroxy phenylpropionic
- 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.)
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- -1 4-hydroxy phenylpropionic acid compound Chemical class 0.000 title claims abstract description 16
- 238000004519 manufacturing process Methods 0.000 title description 3
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims abstract description 16
- 238000002360 preparation method Methods 0.000 claims abstract description 13
- 239000002994 raw material Substances 0.000 claims abstract description 7
- 238000006555 catalytic reaction Methods 0.000 claims abstract description 5
- 239000011968 lewis acid catalyst Substances 0.000 claims abstract description 5
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 17
- 229960003742 phenol Drugs 0.000 claims description 15
- 238000006243 chemical reaction Methods 0.000 claims description 12
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 claims description 9
- 238000006460 hydrolysis reaction Methods 0.000 claims description 7
- 230000007062 hydrolysis Effects 0.000 claims description 6
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 6
- XORZQPOBDBXCGR-UHFFFAOYSA-N C1(=CC=CC=C1)O.C(CC)#N Chemical compound C1(=CC=CC=C1)O.C(CC)#N XORZQPOBDBXCGR-UHFFFAOYSA-N 0.000 claims description 5
- 239000003513 alkali Substances 0.000 claims description 5
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 239000011592 zinc chloride Substances 0.000 claims description 3
- 235000005074 zinc chloride Nutrition 0.000 claims description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 229920002521 macromolecule Polymers 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 230000035484 reaction time Effects 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 10
- 239000004215 Carbon black (E152) Substances 0.000 abstract 1
- 229930195733 hydrocarbon Natural products 0.000 abstract 1
- 150000002430 hydrocarbons Chemical class 0.000 abstract 1
- 230000003301 hydrolyzing effect Effects 0.000 abstract 1
- 238000002329 infrared spectrum Methods 0.000 abstract 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 abstract 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 abstract 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000005804 alkylation reaction Methods 0.000 description 5
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 5
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229940017219 methyl propionate Drugs 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- HCPOCMMGKBZWSJ-UHFFFAOYSA-N ethyl 3-hydrazinyl-3-oxopropanoate Chemical compound CCOC(=O)CC(=O)NN HCPOCMMGKBZWSJ-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
A preparation method of 4-hydroxy phenylpropionic acid compound belongs to hydrocarbon preparation, comprising using phenol and propylene wax as raw materials, characterized by preparing 4-hydroxy phenylpropyl nitrile intermediate by Lewis acid catalyst catalysis; hydrolyzing with alkaline water solution to obtain 4-hydroxy phenylpropionic acid compound. The NMR and IR spectrums of the target product prepared by the method are completely consistent with those of a standard product. The purity of the target product is high and reaches more than 99.5 percent. Compared with the traditional method, the method saves a plurality of operation units, saves a large amount of raw materials, equipment and working hours, and has the advantages of no pollution, economy, easy obtainment and convenient operation.
Description
The present invention relates to a kind of preparation method of 4-hydroxy phenylpropionic acid compound.
The 4-hydroxy phenylpropionic acid has purposes widely as the intermediate of Industrial products such as medicine, antioxidant, liquid crystalline cpd.
In the past, the synthetic of 4-hydroxy phenylpropionic acid can be implemented by following method: CA94:174782n puts down in writing as U.S. chemical abstract, will prepare this purpose product by hydro-reduction by 4-hydroxy benzaldehyde and propanedioic acid condenses; But this method is not only used the high 4-hydroxy benzaldehyde of cost of material, also will adopt complicated hydro-reduction technology and use the high palladium-Pd/carbon catalyst of price, and the purpose degree of purity of production is poor, and its fusing point only is 121-123 ℃.In addition, the clear 63-227542 of day disclosure special permission communique JP is put down in writing is 3-(3,5-di-tert-butyl-4-hydroxy phenyl) methyl propionate to be adopted take off the method that alkyl, hydrolysis remove alcohol and prepare the purpose product.Also there is the shortcoming of cost of material height and aftertreatment trouble in this method, not only uses 3-(3, the 5-di-tert-butyl-4-hydroxy phenyl) methyl propionate that is difficult for producing, and also will use multiple organic solvent to come purifying.Therefore, aforesaid method all is not easy to suitability for industrialized production.In the relevant method for preparing 4-hydroxy phenylpropionic acid intermediate 4-hydroxybenzene propionitrile, U.S. Pat 2789995 and US4051166 show, continue to use identical technology in decades always,, carry out the C-alkylation reaction with aluminum chloride catalysis promptly from phenol, vinyl cyanide, hydrogenchloride; And after frozen water decomposes aluminium complex, adopted the operating process of using potassium chloride solution washing, toluene extraction and fractionation by distillation.
The purpose of this invention is to provide that a kind of economy is easy to get, the preparation method of easy to operate 4-hydroxy phenylpropionic acid compound.
The preparation method of this 4-hydroxy phenylpropionic acid compound comprises that with phenol, vinyl cyanide be raw material, it is characterized in that through comprising the lewis acid catalyst catalysis of aluminum trichloride (anhydrous), iron trichloride or zinc chloride, preparation 4-hydroxybenzene propionitrile intermediate; Through the alkaline aqueous solution hydrolysis, prepare the 4-hydroxy phenylpropionic acid compound.
Distinctive feature of the present invention is only to use phenol, vinyl cyanide to be raw material, with aluminum chloride catalysis, has prescinded the hydrogenchloride raw material, has both saved the device that hydrogen chloride gas takes place, and has avoided the pollution of spent acid (sulfuric acid/hydrochloric acid) again; No longer adopt Klorvess Liquid washing, toluene to extract this operating unit in addition, both saved working hour, saved raw material again.The method for preparing the 4-hydroxy phenylpropionic acid compound by alkylate of the present invention can obtain and the identical effect of above-mentioned technology.
4-hydroxy phenylpropionic acid compound preparation method of the present invention is: adopt phenol and vinyl cyanide to carry out the C-alkylation reaction in lewis acid catalyst, then with alkylation reaction product hydrolysis in alkaline solution.
Employed lewis acid catalyst can be aluminum trichloride (anhydrous), iron trichloride, zinc chloride etc., and its consumption adds the 0.4-0.8 mole to be advisable in a moles of phenol; The C-alkylation reaction can also can be carried out in organic solvent, as tetracol phenixin, chlorobenzene, oil of mirbane etc., preferably without organic solvent in solvent-free.Vinyl cyanide add-on among the present invention (in a moles of phenol) is the 0.8-1.3 mole; Hydrolysis reaction can also can carry out in alkali in acid; The acid of using can be hydrochloric acid, sulfuric acid, and alkali can be potassium hydroxide or sodium hydroxide etc., is example with alkali, and its addition amount of sodium hydroxide (in a moles of phenol) is the 1-3 mole; Its concentration of lye is in the 10%-40% scope.Use in the sodium hydroxide hydrolysis process, the used acid of acidifying partial crystallization can be hydrochloric acid or sulfuric acid, and concentration is not limit.The C-alkylation temperature of reaction is carried out between-5 ℃-120 ℃, and in the process that adds aluminum trichloride (anhydrous), temperature of charge should be controlled at below 20 ℃, keeps this reaction 1-6 hour between 80 ℃-120 ℃; Hydrolysising reacting temperature is between 80 ℃-120 ℃, and the time is 2-8 hour.Reaction is undertaken by following formula:
Embodiment 1 adds phenol 400 grams (4.2 moles) in 1000 milliliters of four-hole round-bottomed flasks that water cooler, thermometer, electric mixer are housed, vinyl cyanide 225 grams (4.2 moles), open and stir, remain temperature of charge in the condition that is lower than below 20 ℃, add aluminum trichloride (anhydrous) 230 grams, slowly heat up then, between 80 ℃-120 ℃, keep reaction 1-6 hour.Reaction finishes, cooling.Reactant is added to ice in another 5000 ml flasks that frozen water is housed separates.Discard water layer, oil reservoir is 4-hydroxybenzene propionitrile, phenol and by product.
Alkylate is added in 3000 milliliters of there-necked flasks, adds sodium hydroxide 400 grams and water 1400 grams again, stir and heat the reaction that is hydrolyzed down, cooling after reaction finishes, behind the vacuum suction filter, under ice-cold condition, dripping hydrochloric acid to product is all separated out (strongly-acid) with filtrate.Vacuum suction filter is abandoned waste liquid, and the washing filter cake to constant weight, gets white crystals thing 4-hydroxy phenylpropionic acid 250 grams (yield 35%) with filtration cakes torrefaction, and fusing point is 129-131 ℃.Detect through HPLC, purity is 99.5%.
In full accord with the purpose product of the inventive method preparation and standard substance NMR, IR spectrogram.
Embodiment 2 adds phenol 400 grams (4.2 moles) in 1000 milliliters of four-hole round-bottomed flasks that water cooler, thermometer, electric mixer are housed, vinyl cyanide 203 grams (3.8 moles), open and stir, remain temperature of charge in the condition that is lower than below 20 ℃, add aluminum trichloride (anhydrous) 250 grams, slowly heat up then, between 80 ℃-120 ℃, keep reaction, reaction finishes, cooling.Reactant is added to ice in another 5000 ml flasks that frozen water is housed separates.Discard water layer, oil reservoir is 4-hydroxybenzene propionitrile, phenol and by product.
Alkylate is added in 3000 milliliters of there-necked flasks, adds potassium hydroxide 420 grams and water 1800 grams again, stir 80-120 ℃ of heating down, the reaction that is hydrolyzed, the reaction back cooling that finishes is behind the vacuum suction filter, under ice-cold condition, dripping hydrochloric acid to product is all separated out (strongly-acid) with filtrate.Vacuum suction filter is abandoned waste liquid, and the washing filter cake to constant weight, gets white crystals thing 4-hydroxy phenylpropionic acid 230 grams (yield 38%) with filtration cakes torrefaction, and fusing point is 129-131 ℃.Detect through HPLC, purity is 99.5%.
Embodiment 3 changes aluminum chloride into iron trichloride, and other is operated with embodiment 1, the result with
Embodiment 1.
Claims (3)
1, a kind of preparation method of 4-hydroxy phenylpropionic acid compound comprises that with phenol, vinyl cyanide be raw material, it is characterized in that through being selected from the lewis acid catalyst catalysis of aluminum trichloride (anhydrous), iron trichloride or zinc chloride, preparation 4-hydroxybenzene propionitrile intermediate; Through the alkaline aqueous solution hydrolysis, prepare the 4-hydroxy phenylpropionic acid compound.
2, the preparation method of 4-hydroxy phenylpropionic acid compound according to claim 1 is characterized in that buck concentration is 10%-40%; Relevant composition proportion is by mole:
The ratio 0.8-1.3 of vinyl cyanide and phenol
The ratio 0.4-0.8 of aluminum chloride and phenol
The ratio 1-3 of alkali and phenol
3, the preparation method of 4-hydroxy phenylpropionic acid compound according to claim 1, it is characterized in that aluminum chloride catalyzed carbon alkylated reaction temperature is between-5 ℃-120 ℃, temperature of charge should be controlled at below 20 ℃ when wherein adding aluminum trichloride (anhydrous), keeps reaction times 1-6 hour in 80 ℃-120 ℃; The macromolecule alkali for hydrolysis temperature is 80 ℃-120 ℃, time 2-8 hour.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN97109894A CN1077877C (en) | 1997-05-27 | 1997-05-27 | Process for preparing 4-hydroxy phenylpropionic acid compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN97109894A CN1077877C (en) | 1997-05-27 | 1997-05-27 | Process for preparing 4-hydroxy phenylpropionic acid compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1200367A CN1200367A (en) | 1998-12-02 |
| CN1077877C true CN1077877C (en) | 2002-01-16 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN97109894A Expired - Fee Related CN1077877C (en) | 1997-05-27 | 1997-05-27 | Process for preparing 4-hydroxy phenylpropionic acid compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1077877C (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103131747A (en) * | 2013-03-15 | 2013-06-05 | 康化（上海）新药研发有限公司 | Method for synthesizing (S)-3-(4-hydroxyl phenyl)-3-methylamino propionic acid by using biological enzymes through chiral resolution |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2789995A (en) * | 1954-04-29 | 1957-04-23 | Union Carbide & Carbon Corp | Alkylation of phenol with acrylonitrile |
| US4051166A (en) * | 1976-06-08 | 1977-09-27 | The Upjohn Company | Araliphatic diisocyanates |
-
1997
- 1997-05-27 CN CN97109894A patent/CN1077877C/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2789995A (en) * | 1954-04-29 | 1957-04-23 | Union Carbide & Carbon Corp | Alkylation of phenol with acrylonitrile |
| US4051166A (en) * | 1976-06-08 | 1977-09-27 | The Upjohn Company | Araliphatic diisocyanates |
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| Publication number | Publication date |
|---|---|
| CN1200367A (en) | 1998-12-02 |
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