CN105037139A - Preparation method for 2-phenylpropionic acid - Google Patents
Preparation method for 2-phenylpropionic acid Download PDFInfo
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- CN105037139A CN105037139A CN201510394670.0A CN201510394670A CN105037139A CN 105037139 A CN105037139 A CN 105037139A CN 201510394670 A CN201510394670 A CN 201510394670A CN 105037139 A CN105037139 A CN 105037139A
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- phenylpropionic acid
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- phenylpropanenitrile
- cyano group
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- YPGCWEMNNLXISK-UHFFFAOYSA-N hydratropic acid Chemical compound OC(=O)C(C)C1=CC=CC=C1 YPGCWEMNNLXISK-UHFFFAOYSA-N 0.000 title claims abstract description 49
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims abstract description 65
- 238000006243 chemical reaction Methods 0.000 claims abstract description 64
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 39
- NVAOLENBKNECGF-UHFFFAOYSA-N 2-phenylpropanenitrile Chemical compound N#CC(C)C1=CC=CC=C1 NVAOLENBKNECGF-UHFFFAOYSA-N 0.000 claims abstract description 32
- 229940017219 methyl propionate Drugs 0.000 claims abstract description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 31
- 238000003756 stirring Methods 0.000 claims abstract description 26
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims abstract description 18
- 238000009413 insulation Methods 0.000 claims abstract description 14
- 239000000047 product Substances 0.000 claims abstract description 14
- 238000010025 steaming Methods 0.000 claims abstract description 13
- 230000020477 pH reduction Effects 0.000 claims abstract description 10
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000006227 byproduct Substances 0.000 claims abstract description 7
- 238000002156 mixing Methods 0.000 claims abstract description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 48
- RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 claims description 29
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 29
- 238000010792 warming Methods 0.000 claims description 18
- 239000007788 liquid Substances 0.000 claims description 16
- 235000011121 sodium hydroxide Nutrition 0.000 claims description 16
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 14
- CXHHBNMLPJOKQD-UHFFFAOYSA-M methyl carbonate Chemical compound COC([O-])=O CXHHBNMLPJOKQD-UHFFFAOYSA-M 0.000 claims description 8
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 claims description 8
- IZGYIFFQBZWOLJ-CKAACLRMSA-N phaseic acid Chemical compound C1C(=O)C[C@@]2(C)OC[C@]1(C)[C@@]2(O)C=CC(/C)=C\C(O)=O IZGYIFFQBZWOLJ-CKAACLRMSA-N 0.000 claims description 5
- 239000012043 crude product Substances 0.000 claims description 4
- 238000004821 distillation Methods 0.000 claims description 4
- 230000003301 hydrolyzing effect Effects 0.000 claims description 4
- 238000001556 precipitation Methods 0.000 claims description 2
- 239000001117 sulphuric acid Substances 0.000 claims description 2
- 235000011149 sulphuric acid Nutrition 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 8
- 238000006460 hydrolysis reaction Methods 0.000 abstract description 3
- 239000000203 mixture Substances 0.000 abstract 3
- 238000001816 cooling Methods 0.000 abstract 2
- -1 compound ester Chemical class 0.000 abstract 1
- IEJIGPNLZYLLBP-UHFFFAOYSA-N dimethyl carbonate Chemical compound COC(=O)OC IEJIGPNLZYLLBP-UHFFFAOYSA-N 0.000 abstract 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 abstract 1
- 238000010438 heat treatment Methods 0.000 abstract 1
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- MNNZINNZIQVULG-UHFFFAOYSA-N 2-chloroethylbenzene Chemical compound ClCCC1=CC=CC=C1 MNNZINNZIQVULG-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 229960002373 loxoprofen Drugs 0.000 description 2
- YMBXTVYHTMGZDW-UHFFFAOYSA-N loxoprofen Chemical compound C1=CC(C(C(O)=O)C)=CC=C1CC1C(=O)CCC1 YMBXTVYHTMGZDW-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000003356 anti-rheumatic effect Effects 0.000 description 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/08—Preparation of carboxylic acids or their salts, halides or anhydrides from nitriles
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method for 2-phenylpropionic acid. The preparation method is characterized by comprising a 2-phenyl-2-cyano methyl propionate preparation stage, a 2-phenyl propionitrile preparation stage and a 2-phenylpropionic acid preparation stage, wherein the 2-phenyl-2-cyano methyl propionate preparation stage comprises: mixing benzyl cyanide, dimethyl carbonate, methylbenzene and sodium methoxide to obtain a mixture, heating the mixture to 20-100 DEG C, controlling the pressure to 0.5-6MPa and carrying out thermal-insulation reaction for 1-10 hours; after the reaction is ended, steaming out a byproduct methanol under the normal pressure, cooling the mixture to 35 DEG C, dropwise adding dimethyl sulfate DMS at constant speed by controlling the temperature to 35-85 DEG C, and carrying out the thermal-insulation reaction for 1-10 hours at 45-105 DEG C after the dropwise-adding is ended; cooling to 35 DEG C, adding water, stirring, dissolving, and layering; desolventizing to recycle toluene, thereby obtaining compound ester; and carrying out basic hydrolysis reaction and acidification reaction to finally prepare a finished product, wherein the purity of the finished product is high, and the yield of the finished product is higher than 92%. Besides, the production process disclosed by the invention adopts simple equipment and is low in production cost.
Description
Technical field
The present invention relates to a kind of 2-phenylpropionic acid preparation method.
Background technology
At present, 2-phenylpropionic acid is one of key intermediate of synthesis loxoprofen sodium, loxoprofen sodium belongs to the novel non-steroid antiinflammatory drug of arylprop acids, clinically show that it is that analgesia in current known arylprop acids medicine, anti-inflammatory, antirheumatic effect are best, thus dark in domestic and international expert and the favor of scholar and the high praise of the world of medicine and patient.Pharmaceutical Co., Ltd was in development listing in 1986 altogether by Japan three for these product, and at present in the listing of many countries such as Japan, Korea S, America and Europe, and growth is powerful.
The synthesis of 2-phenylpropionic acid disclosed in Chinese patent 201110288939.9 divides three steps to carry out, first reaction is that the hydrochloric acid soln of 20 ~ 25% is for raw material with vinylbenzene and mass concentration, at 30 ~ 40 DEG C, stirring reaction is after 8 ~ 14 hours, static layering, oil reservoir obtains 2-chloroethyl benzene after washing, and 2-chloroethyl benzene prepares 2-phenylpropionic acid more successively after sodium cyanide cyaniding and hydrolysis.
The synthesis of 2-phenylpropionic acid disclosed in Chinese patent 201410527921.3 is carried out in two steps, vinylbenzene, NaCN are dissolved in aprotic polar solvent by reaction, under certain temperature and pressure, react under saleratus and stopper effect, preparation 2-phenylpropanenitrile; 2-phenylpropanenitrile alkaline hydrolysis, acidifying, preparation 2-phenylpropionic acid.
Above production process equipment is complicated, production cost is high.
Summary of the invention
The object of the invention is to overcome the deficiencies in the prior art, and the 2-phenylpropionic acid preparation method that a kind of production technique is simple, product purity is high, yield is high is provided, thus reduce production cost.
The present invention's adopted technical scheme that solves the problem is:
A kind of 2-phenylpropionic acid preparation method, is characterized in that: comprise 2-(phenyl cyano group) methyl propionate preparatory phase, 2-phenylpropanenitrile preparatory phase and 2-phenylpropionic acid preparatory phase, concrete steps are as follows:
1) 2-(phenyl cyano group) methyl propionate preparatory phase
After the mixing of benzyl cyanide, methylcarbonate, toluene, sodium methylate, be warming up to 20 ~ 100 DEG C, insulation reaction 1 ~ 10 hour; After reaction terminates, normal pressure steams by-product methyl alcohol, to steaming without methyl alcohol, be cooled to 35 DEG C, temperature control 35 ~ 85 DEG C at the uniform velocity drips methyl-sulfate DMS, drips and finishes 45 ~ 105 DEG C of insulation reaction 1 ~ 10 hour, be cooled to 35 DEG C, add water, stir, dissolve, layering, precipitation reclaims toluene, to steaming without toluene, obtains 2-(phenyl cyano group) methyl propionate;
2) 2-phenylpropanenitrile preparatory phase
After the mixing of liquid caustic soda, water, 2-(phenyl cyano group) methyl propionate, be warming up to 50 ~ 110 DEG C of reactions 1 ~ 10 hour; Reaction is finished, and add water and stir, dissolve, layering, high vacuum rectification obtains 2-phenylpropanenitrile;
3) 2-phenylpropionic acid preparatory phase
After the mixing of liquid caustic soda, water, 2-phenylpropanenitrile, be warming up to 80 ~ 130 DEG C, back flow reaction 5 ~ 20 hours; After reaction terminates, be cooled to 20 ~ 60 DEG C and pass through to drip sulfuric acid, until PH < 5, layering, high vacuum rectification obtains 2-phenylpropionic acid.
Be further used as preferably, 2-(phenyl cyano group) methyl propionate preparatory phase, the mol ratio of benzyl cyanide, methylcarbonate, toluene, sodium methylate, methyl-sulfate and water is: 1 ~ 10: 1 ~ 20: 1 ~ 40: 0.05 ~ 3: 1 ~ 20: 1 ~ 30.
Be further used as preferably, in 2-phenylpropanenitrile preparatory phase, the weight part of liquid caustic soda, water and 2-(phenyl cyano group) methyl propionate is respectively: 1 ~ 10 part, 1 ~ 25 part, 1 ~ 20 part.
Be further used as preferably, in 2-phenylpropionic acid preparatory phase, the weight part of liquid caustic soda, water, dilute sulphuric acid and 2-phenylpropanenitrile is respectively: 1 ~ 25 part, 1 ~ 5 part, 1 ~ 20 part, 1 ~ 5 part.
The present invention compared with prior art, has the following advantages and effect: the present invention take benzyl cyanide as main raw material, finally makes finished product through methylation reaction, macromolecule alkali for hydrolysis and acidification reaction, and its finished product purity is high, and yield is up to more than 90%.In addition, production process equipment of the present invention is simple, production cost is low.
Embodiment
Principal reaction equation of the present invention is:
1) 2-(phenyl cyano group) methyl propionate preparatory phase:
2) 2-phenylpropanenitrile preparatory phase:
3) 2-phenylpropionic acid preparatory phase:
Below in conjunction with specific embodiment, the invention will be further described:
Embodiment one:
The preparation method of the present embodiment 2-phenylpropionic acid, comprise 2-(phenyl cyano group) methyl propionate preparatory phase, 2-phenylpropanenitrile preparatory phase and 2-phenylpropionic acid stage, concrete steps are as follows:
1) 2-(phenyl cyano group) methyl propionate preparatory phase
By benzyl cyanide: methylcarbonate: toluene: sodium methylate be 1: 1.5: 10: 1.05 mol ratio add in dry reaction still, in stirring under, be warming up to 75 DEG C, insulation reaction 5 hours; After reaction terminates, normal pressure steams by-product methyl alcohol, and to steaming without methyl alcohol, be cooled to 35 DEG C, temperature control 50 DEG C at the uniform velocity drips the methyl-sulfate DMS that mol ratio is 1.0, drips and finishes 50 DEG C of insulation reaction 5 hours.Be cooled to 35 DEG C, add the water that weight part is 1.0, stir, dissolve, layering.Toluene is reclaimed in underpressure distillation, to steaming without toluene, obtains 2-(phenyl cyano group) methyl propionate;
2) 2-phenylpropanenitrile preparatory phase
By liquid caustic soda: water: 2-(phenyl cyano group) methyl propionate is that 2: 1: 3 weight parts add in clean reactor, under stirring, be warming up to 80 DEG C of reactions 5 hours; Reaction is finished, and adds the water that weight part is 1.5, stirs, and dissolve, layering, high vacuum rectification obtains 2-phenylpropanenitrile;
3) 2-phenylpropionic acid preparatory phase
In hydrolytic reaction pot, add liquid caustic soda: water: 2-phenylpropanenitrile is that then 2: 1: 1 weight parts are warming up to 95 DEG C, stir, back flow reaction 15 hours, is cooled to 60 DEG C and proceeds to acidification reaction still; Slowly sulfuric acid is dripped, until PH < 5 in acidification reaction still; Layering obtains 2-phenylpropionic acid crude product, and high vacuum rectification obtains 2-phenylpropionic acid finished product.After testing, the high purity 98% of 2-phenylpropionic acid finished product, yield is up to 95%.
Embodiment two:
The preparation method of the present embodiment 2-phenylpropionic acid, comprise 2-(phenyl cyano group) methyl propionate preparatory phase, 2-phenylpropanenitrile preparatory phase and 2-phenylpropionic acid stage, concrete steps are as follows:
1) 2-(phenyl cyano group) methyl propionate preparatory phase
By benzyl cyanide: methylcarbonate: toluene: sodium methylate be 1: 3: 15: 1.2 mol ratio add in dry reaction still, in stirring under, be warming up to 90 DEG C, insulation reaction 2 hours; After reaction terminates, normal pressure steams by-product methyl alcohol, and to steaming without methyl alcohol, be cooled to 35 DEG C, temperature control 75 DEG C at the uniform velocity drips the methyl-sulfate DMS that mol ratio is 1.0, drips and finishes 70 DEG C of insulation reaction 2 hours.Be cooled to 35 DEG C, add the water that weight part is 2.0, stir, dissolve, layering.Toluene is reclaimed in underpressure distillation, to steaming without toluene, obtains 2-(phenyl cyano group) methyl propionate;
2) 2-phenylpropanenitrile preparatory phase
By liquid caustic soda: water: 2-(phenyl cyano group) methyl propionate is that 4: 2: 5 weight parts add in clean reactor, under stirring, be warming up to 60 DEG C of reactions 10 hours; Reaction is finished, and adds the water that weight part is 3.0, stirs, and dissolve, layering, high vacuum rectification obtains 2-phenylpropanenitrile;
3) 2-phenylpropionic acid preparatory phase
In hydrolytic reaction pot, add liquid caustic soda: water: 2-phenylpropanenitrile is that then 3: 1.5: 1 weight parts are warming up to 105 DEG C, stir, back flow reaction 10 hours, is cooled to 40 DEG C and proceeds to acidification reaction still; Slowly sulfuric acid is dripped, until PH < 5 in acidification reaction still; Layering obtains 2-phenylpropionic acid crude product, and high vacuum rectification obtains 2-phenylpropionic acid finished product.After testing, the high purity 98% of 2-phenylpropionic acid finished product, yield is up to 96%.
Embodiment three:
The preparation method of the present embodiment 2-phenylpropionic acid, comprise 2-(phenyl cyano group) methyl propionate preparatory phase, 2-phenylpropanenitrile preparatory phase and 2-phenylpropionic acid stage, concrete steps are as follows:
1) 2-(phenyl cyano group) methyl propionate preparatory phase
By benzyl cyanide: methylcarbonate: toluene: sodium methylate be 1: 5: 30: 2 mol ratio add in dry reaction still, in stirring under, be warming up to 60 DEG C, insulation reaction 10 hours; After reaction terminates, normal pressure steams by-product methyl alcohol, and to steaming without methyl alcohol, be cooled to 35 DEG C, temperature control 90 DEG C at the uniform velocity drips the methyl-sulfate (DMS) that mol ratio is 1.5, drips and finishes 80 DEG C of insulation reaction 1 hour.Be cooled to 35 DEG C, add the water that weight part is 2.0, stir, dissolve, layering.Toluene is reclaimed in underpressure distillation, to steaming without toluene, obtains 2-(phenyl cyano group) methyl propionate;
2) 2-phenylpropanenitrile preparatory phase
By liquid caustic soda: water: 2-(phenyl cyano group) methyl propionate is that 4: 2: 5 weight parts add in clean reactor, under stirring, be warming up to 90 DEG C of reactions 1 hour; Reaction is finished, and adds the water that weight part is 1.5, stirs, and dissolve, layering, high vacuum rectification obtains 2-phenylpropanenitrile;
3) 2-phenylpropionic acid preparatory phase
In hydrolytic reaction pot, add liquid caustic soda: water: 2-phenylpropanenitrile is that then 4: 2: 2 weight parts are warming up to 120 DEG C, stir, back flow reaction 6 hours, is cooled to 25 DEG C and proceeds to acidification reaction still; Slowly sulfuric acid is dripped, until PH < 5 in acidification reaction still; Layering obtains 2-phenylpropionic acid crude product, and high vacuum rectification obtains 2-phenylpropionic acid finished product.After testing, the high purity 98% of 2-phenylpropionic acid finished product, yield is up to 97%.
Above content described in this specification sheets is only made for the present invention illustrating.Those skilled in the art can make various amendment or supplement or adopt similar mode to substitute to described specific embodiment; only otherwise depart from the content of specification sheets of the present invention or surmount this scope as defined in the claims, protection scope of the present invention all should be belonged to.
Claims (6)
1. a 2-phenylpropionic acid preparation method, is characterized in that: comprise 2-(phenyl cyano group) methyl propionate preparatory phase, 2-phenylpropanenitrile preparatory phase and 2-phenylpropionic acid preparatory phase, concrete steps are as follows:
1) 2-(phenyl cyano group) methyl propionate preparatory phase
After the mixing of benzyl cyanide, methylcarbonate, toluene, sodium methylate, be warming up to 20 ~ 100 DEG C, insulation reaction 1 ~ 10 hour; After reaction terminates, normal pressure steams by-product methyl alcohol, to steaming without methyl alcohol, be cooled to 35 DEG C, temperature control 35 ~ 85 DEG C at the uniform velocity drips methyl-sulfate DMS, drips and finishes 45 ~ 105 DEG C of insulation reaction 1 ~ 10 hour, be cooled to 35 DEG C, add water, stir, dissolve, layering, precipitation reclaims toluene, to steaming without toluene, obtains 2-(phenyl cyano group) methyl propionate;
2) 2-phenylpropanenitrile preparatory phase
After the mixing of liquid caustic soda, water, 2-(phenyl cyano group) methyl propionate, be warming up to 50 ~ 110 DEG C of reactions 1 ~ 10 hour; Reaction is finished, and add water and stir, dissolve, layering, high vacuum rectification obtains 2-phenylpropanenitrile;
3) 2-phenylpropionic acid preparatory phase
After the mixing of liquid caustic soda, water, 2-phenylpropanenitrile, be warming up to 80 ~ 130 DEG C, back flow reaction 5 ~ 20 hours; After reaction terminates, be cooled to 20 ~ 60 DEG C and pass through to drip sulfuric acid, until PH < 5, layering, high vacuum rectification obtains 2-phenylpropionic acid.
2. a kind of 2-phenylpropionic acid preparation method according to claim 1, is characterized in that: its reaction equation is:
1) 2-(phenyl cyano group) methyl propionate preparatory phase:
2) 2-phenylpropanenitrile preparatory phase:
3) 2-phenylpropionic acid preparatory phase:
3. a kind of 2-phenylpropionic acid preparation method according to claim 1, it is characterized in that: described 2-(phenyl cyano group) methyl propionate preparatory phase, the mol ratio of benzyl cyanide, methylcarbonate, toluene, sodium methylate, methyl-sulfate and water is: 1 ~ 10:1 ~ 20:1 ~ 40:0.05 ~ 3:1 ~ 20:1 ~ 30.
4. a kind of 2-phenylpropionic acid preparation method according to claim 1, it is characterized in that: in described 2-phenylpropanenitrile preparatory phase, the weight part of liquid caustic soda, water and 2-(phenyl cyano group) methyl propionate is respectively: 1 ~ 10 part, 1 ~ 25 part, 1 ~ 20 part.
5. a kind of 2-phenylpropionic acid preparation method according to claim 1, it is characterized in that: in 2-phenylpropionic acid preparatory phase, the weight part of liquid caustic soda, water, dilute sulphuric acid and 2-phenylpropanenitrile is respectively: 1 ~ 25 part, 1 ~ 5 part, 1 ~ 20 part, 1 ~ 5 part.
6. a kind of 2-phenylpropionic acid preparation method according to claim 1, is characterized in that: comprise the steps:
1) 2-(phenyl cyano group) methyl propionate preparatory phase
By benzyl cyanide: methylcarbonate: toluene: sodium methylate is that the mol ratio of 1:5:30:2 adds in dry reaction still, under stirring, is warming up to 60 DEG C, insulation reaction 10 hours; After reaction terminates, normal pressure steams by-product methyl alcohol, to steaming without methyl alcohol, is cooled to 35 DEG C, temperature control 90 DEG C at the uniform velocity drips the methyl-sulfate DMS that mol ratio is 1.5, drips and finishes 80 DEG C of insulation reaction 1 hour, be cooled to 35 DEG C, add the water that weight part is 2.0, stir, dissolve, layering.Toluene is reclaimed in underpressure distillation, to steaming without toluene, obtains 2-(phenyl cyano group) methyl propionate;
2) 2-phenylpropanenitrile preparatory phase
By liquid caustic soda: water: 2-(phenyl cyano group) methyl propionate is that 4:2:5 weight part adds in clean reactor, under stirring, be warming up to 90 DEG C of reactions 1 hour; Reaction is finished, and adds the water that weight part is 1.5, stirs, and dissolve, layering, high vacuum rectification obtains 2-phenylpropanenitrile;
3) 2-phenylpropionic acid preparatory phase
In hydrolytic reaction pot, add liquid caustic soda: water: 2-phenylpropanenitrile is that then 4:2:2 weight part is warming up to 120 DEG C, stir, back flow reaction 3 hours, is cooled to 40 DEG C and proceeds to acidification reaction still; Slowly sulfuric acid is dripped, until PH < 5 in acidification reaction still; Layering obtains 2-phenylpropionic acid crude product, and high vacuum rectification obtains 2-phenylpropionic acid finished product.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105753685A (en) * | 2016-03-30 | 2016-07-13 | 浙江丽水有邦新材料有限公司 | Method for preparing loxoprofen intermediate |
| CN109485556A (en) * | 2018-10-19 | 2019-03-19 | 浙江大学 | The method of one pot process 2- phenylpropionic acid |
| CN109912399A (en) * | 2019-03-01 | 2019-06-21 | 浙江大学 | The method for high pressure synthesis of 2-phenylpropionic acid |
| CN110551027A (en) * | 2018-05-31 | 2019-12-10 | 南京理工大学 | Synthetic method of 3-hydroxy-2-phenylpropionic acid |
| CN110872237A (en) * | 2018-08-30 | 2020-03-10 | 江苏瑞科医药科技有限公司 | Application of novel methyl carbonate methylation catalyst in preparation of α -methylphenylacetic acid |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1434826A (en) * | 1973-11-14 | 1976-05-05 | Gallardo Antonio Sa | Esters and carbamates of aminoalkanols |
| RU2059612C1 (en) * | 1993-02-25 | 1996-05-10 | Центр по химии лекарственных средств (ЦХЛС-ВНИХФИ) | Method of synthesis of 1-phenyl-1-para-nitrobenzoylamino-5-n,n- diethylaminopentane hydrochloride and 1-phenyl-1-amino-5-n,n- diethylaminopentane |
| CN104744237B (en) * | 2015-02-16 | 2016-08-24 | 浙江博聚新材料有限公司 | A kind of 2-(4-2-bromomethylphenyl) propanoic acid preparation method |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105753685A (en) * | 2016-03-30 | 2016-07-13 | 浙江丽水有邦新材料有限公司 | Method for preparing loxoprofen intermediate |
| CN110551027A (en) * | 2018-05-31 | 2019-12-10 | 南京理工大学 | Synthetic method of 3-hydroxy-2-phenylpropionic acid |
| CN110551027B (en) * | 2018-05-31 | 2022-03-22 | 南京理工大学 | The synthetic method of 3-hydroxy-2-phenylpropionic acid |
| CN110872237A (en) * | 2018-08-30 | 2020-03-10 | 江苏瑞科医药科技有限公司 | Application of novel methyl carbonate methylation catalyst in preparation of α -methylphenylacetic acid |
| CN109485556A (en) * | 2018-10-19 | 2019-03-19 | 浙江大学 | The method of one pot process 2- phenylpropionic acid |
| CN109912399A (en) * | 2019-03-01 | 2019-06-21 | 浙江大学 | The method for high pressure synthesis of 2-phenylpropionic acid |
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