CN103508908A - Preparation method for 4-amino-3-methylphenol - Google Patents
Preparation method for 4-amino-3-methylphenol Download PDFInfo
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- CN103508908A CN103508908A CN201310505541.5A CN201310505541A CN103508908A CN 103508908 A CN103508908 A CN 103508908A CN 201310505541 A CN201310505541 A CN 201310505541A CN 103508908 A CN103508908 A CN 103508908A
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- methylphenol
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- QGNGOGOOPUYKMC-UHFFFAOYSA-N 4-hydroxy-6-methylaniline Chemical compound CC1=CC(O)=CC=C1N QGNGOGOOPUYKMC-UHFFFAOYSA-N 0.000 title claims abstract description 62
- 238000002360 preparation method Methods 0.000 title claims abstract description 26
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 claims abstract description 30
- 238000006722 reduction reaction Methods 0.000 claims abstract description 19
- 238000007034 nitrosation reaction Methods 0.000 claims abstract description 11
- 239000002994 raw material Substances 0.000 claims abstract description 8
- 238000000746 purification Methods 0.000 claims abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 75
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 38
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 36
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 32
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims description 28
- 239000000243 solution Substances 0.000 claims description 28
- 239000000047 product Substances 0.000 claims description 27
- 239000002904 solvent Substances 0.000 claims description 19
- 239000012043 crude product Substances 0.000 claims description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical group N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 14
- 235000010288 sodium nitrite Nutrition 0.000 claims description 14
- 230000001476 alcoholic effect Effects 0.000 claims description 13
- 238000001914 filtration Methods 0.000 claims description 10
- 230000009467 reduction Effects 0.000 claims description 10
- 238000010792 warming Methods 0.000 claims description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 8
- 238000009835 boiling Methods 0.000 claims description 8
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 claims description 8
- 229910021529 ammonia Inorganic materials 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 238000002425 crystallisation Methods 0.000 claims description 7
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 6
- 230000000694 effects Effects 0.000 claims description 6
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 5
- 230000035484 reaction time Effects 0.000 claims description 5
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- 238000001816 cooling Methods 0.000 claims description 4
- 230000008025 crystallization Effects 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- 229910052763 palladium Inorganic materials 0.000 claims description 4
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 3
- 229910000564 Raney nickel Inorganic materials 0.000 claims description 3
- 239000004411 aluminium Substances 0.000 claims description 3
- 229910052782 aluminium Inorganic materials 0.000 claims description 3
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 3
- 238000000034 method Methods 0.000 abstract description 21
- 239000011347 resin Substances 0.000 abstract description 4
- 229920005989 resin Polymers 0.000 abstract description 4
- 238000003912 environmental pollution Methods 0.000 abstract description 3
- 230000008569 process Effects 0.000 abstract description 2
- 238000005984 hydrogenation reaction Methods 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 32
- 229910052739 hydrogen Inorganic materials 0.000 description 15
- 239000001257 hydrogen Substances 0.000 description 15
- 239000007787 solid Substances 0.000 description 11
- 235000011121 sodium hydroxide Nutrition 0.000 description 10
- 238000000967 suction filtration Methods 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 238000001291 vacuum drying Methods 0.000 description 7
- 239000007788 liquid Substances 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 229910001220 stainless steel Inorganic materials 0.000 description 5
- 239000010935 stainless steel Substances 0.000 description 5
- 235000001018 Hibiscus sabdariffa Nutrition 0.000 description 4
- 235000005291 Rumex acetosa Nutrition 0.000 description 4
- 240000007001 Rumex acetosella Species 0.000 description 4
- 150000002431 hydrogen Chemical class 0.000 description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 235000003513 sheep sorrel Nutrition 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 238000010025 steaming Methods 0.000 description 3
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 230000006837 decompression Effects 0.000 description 2
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 231100000614 poison Toxicity 0.000 description 2
- 230000007096 poisonous effect Effects 0.000 description 2
- 239000012266 salt solution Substances 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- QTWJRLJHJPIABL-UHFFFAOYSA-N 2-methylphenol;3-methylphenol;4-methylphenol Chemical compound CC1=CC=C(O)C=C1.CC1=CC=CC(O)=C1.CC1=CC=CC=C1O QTWJRLJHJPIABL-UHFFFAOYSA-N 0.000 description 1
- PLAZTCDQAHEYBI-UHFFFAOYSA-N 2-nitrotoluene Chemical compound CC1=CC=CC=C1[N+]([O-])=O PLAZTCDQAHEYBI-UHFFFAOYSA-N 0.000 description 1
- PIIZYNQECPTVEO-UHFFFAOYSA-N 4-nitro-m-cresol Chemical compound CC1=CC(O)=CC=C1[N+]([O-])=O PIIZYNQECPTVEO-UHFFFAOYSA-N 0.000 description 1
- 229920000049 Carbon (fiber) Polymers 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000004917 carbon fiber Substances 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000002848 electrochemical method Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- FWQHNLCNFPYBCA-UHFFFAOYSA-N fluoran Chemical compound C12=CC=CC=C2OC2=CC=CC=C2C11OC(=O)C2=CC=CC=C21 FWQHNLCNFPYBCA-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N iron oxide Inorganic materials [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 1
- VBMVTYDPPZVILR-UHFFFAOYSA-N iron(2+);oxygen(2-) Chemical group [O-2].[Fe+2] VBMVTYDPPZVILR-UHFFFAOYSA-N 0.000 description 1
- 150000002730 mercury Chemical class 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- NDLPOXTZKUMGOV-UHFFFAOYSA-N oxo(oxoferriooxy)iron hydrate Chemical compound O.O=[Fe]O[Fe]=O NDLPOXTZKUMGOV-UHFFFAOYSA-N 0.000 description 1
- 239000004476 plant protection product Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000010970 precious metal Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000012209 synthetic fiber Substances 0.000 description 1
- 229920002994 synthetic fiber Polymers 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a preparation method for 4-amino-3-methylphenol. M-cresol is used as a raw material and subjected to nitrosation reaction, hydrogenation reduction reaction and purification to prepare high-quality 4-amino-3-methylphenol. The preparation method is simple in process, simple and convenient in product after-treatment and low in environmental pollution, and can obtain 4-amino-3-methylphenol which is higher in product quality and better in stability than 4-amino-3-methylphenol prepared by other methods; the obtained product can be used for preparation of high-end resin, beside common purposes; the preparation method provided by the invention is an industrially practicable better preparation method.
Description
Technical field
The present invention relates to a kind of preparation method of chemical intermediate, especially relate to a kind of preparation method of high-quality 4-amino-3-methylphenol.
Technical background
4-amino-3-methylphenol is Material of Fluoran dyestuff, plant protection product and the synthetic necessary intermediate of medicine, is industrial important raw and processed materials; Now high-quality 4-amino-3-methylphenol is also for the preparation of the synthetic and carbon fiber of high-end resin.
Preparation method about 4-amino-3-methylphenol roughly can be summarized as three classes.The first kind is to be raw material with Ortho Nitro Toluene, by reducing and having reset reaction, has following the whole bag of tricks: (a) electrochemical method, and this method negative electrode adopts poisonous mercury salt, and productive rate is low; (b) aluminium-aqueous solutions of organic acids, this method products obtained therefrom purity is low, and cost is high; (c) in dilute sulphuric acid, with hydrogen, carry out the method for catalytic reduction, this method catalyzer adopts the precious metals such as platinum, rhodium, palladium; Long reaction time, productive rate is low.Equations of The Second Kind preparation method is azo-compound reduction method and 4-nitro-3-methylphenol reduction method, and the main drawback of this reduction method is that raw material is rare, and synthetic route is long.The 3rd class methods are to be dissolved in ammoniacal liquor with 4-nitroso-group-3-methylphenol, and reduce under hydrogen sulfide effect, and this preparation method is simple, and productive rate is high, but hydrogen sulfide is poisonous, and expensive safety prevention measure declines its economic worth.European patent EP 43520(1982) a kind of method that 4-nitroso-group-3-methylphenol reduces under iron effect in acetic aid medium is disclosed, this method reductive agent is cheap, and transformation efficiency is high, but the filtering formality of iron oxide residue trouble in preparation process, and ferric oxide cannot process, pollute environment.Chinese patent CN1031526 has reported the method that adopts SODIUM HYDROSULPHITE sodium reduction 4-nitroso-group-3-methylphenol.Adopt 4-amino-3-methylphenol that above method obtains all to have following problems: the reductive agent method 1, adopting exists the problems large, that the three wastes are many of polluting; 2, because the technique adopting or reductive agent inevitably can exist certain residually in product, thereby affected the interior quality of product, causing producing the 4-nitroso-group-3-methylphenol obtaining cannot be for high-end resin purposes.
In order to improve the inherent quality of 4-amino-3-methylphenol, the present invention is through repeatedly attempting providing a kind of method of preparing high-quality 4-amino-3-methylphenol.
Summary of the invention
The preparation method who the invention provides a kind of new high-quality 4-amino-3-methylphenol reduces environmental pollution in the quality of improving the quality of products, and makes that products production cleans, environmental protection, makes product production in enormous quantities preferably.
A preparation method for 4-amino-3-methylphenol, comprises the steps:
(1) nitrosation reaction: the m-cresol of take prepares 4-nitroso-group-3-methylphenol through nitrosification as raw material;
(2) reduction reaction: 4-nitroso-group-3-methylphenol, in alcoholic solvent, obtains 4-amino-3-methylphenol crude product by hydrogenating reduction under catalyzer and promotor effect;
(3) purifying: 4-amino-3-methylphenol crude product carries out purification process through alcoholic solvent and obtains 4-amino-3-methylphenol highly finished product.
Synthetic route of the present invention is as follows:
Preferably, in step (1), take aqueous sodium hydroxide solution as solvent, Sodium Nitrite and hydrochloric acid are nitrosification agent, and nitrosation reaction temperature is controlled at-5～15 ℃; The weight ratio of described m-methyl phenol, sodium hydroxide, Sodium Nitrite is 1:0.35～0.45:0.6～0.8, and the concentration of described hydrochloric acid is 15～36%, and hydrochloric acid folding hundred weight ratio rear and m-methyl phenol is 0.8～1.2:1.
Step (1) be take m-cresol and through nitrosification, is prepared 4-nitroso-group-3-methylphenol as raw material: m-methyl phenol and Sodium Nitrite are dissolved in and in certain density alkaline aqueous solution, obtain reaction solution a, reaction solution a obtains reaction solution b in 0～15 ℃ is added drop-wise to the certain density hydrochloric acid preparing in advance, be added dropwise to complete reaction solution b continuation reaction certain hour to stock yard methylphenol and reacted, reaction generates 4-nitroso-group-3-methylphenol.After having reacted, through suction filtration, washing obtains damp product 4-nitroso-group-3-methylphenol, can be directly used in next step reaction.
Preferably, in step (2), reduction reaction temperature is controlled at 20～40 ℃, reaction times 2～8h, and described alcoholic solvent is a kind of in methyl alcohol, ethanol, Virahol, the weight ratio of itself and 4-nitroso-group-3-methylphenol is 2～10:1; Described catalyzer is a kind of in palladium carbon, palladium aluminium, Raney's nickel, and it is 0.005～0.05:1 with the ratio of the weight of 4-nitroso-group-3-methylphenol; Described promotor is ammonia or organic amine, and it is 0.01～0.1:1 with the ratio of the weight of 4-nitroso-group-3-methylphenol.
In step (2), 4-nitroso-group-3-methylphenol obtains 4-amino-3-methylphenol by hydrogenating reduction, in autoclave, drop into a certain amount of 4-nitroso-group-3-methylphenol and alcohol, then add a certain amount of catalyzer and promotor to obtain reaction solution a1, then be warming up to 20～40 ℃, pass into hydrogen reaction 2～8h and no longer inhale hydrogen to reacting, stopped reaction, reaction solution is removed, remove by filter catalyzer, the alcoholic solvent in reaction solution a1 is removed in decompression, obtains crude product 4-amino-3-methylphenol of solid.
Preferably, described organic amine is a kind of in Monomethylamine, dimethylamine, Trimethylamine 99.
Preferably, in step (3), through alcoholic solvent dissolving, crystallization, filtration, dry 4-amino-3-methylphenol that to obtain; Solvent temperature is 40～70 ℃, and described alcoholic solvent is low-boiling point alcohol or alcohol solution, and the weight ratio of alcoholic solvent and 4-amino-3-methylphenol is 1～4:1; In alcohol solution, the ratio of water and 4-amino-3-methylphenol is 0.5～1.5:1; Drying temperature is 30～60 ℃.
Preferably, described low-boiling point alcohol is methyl alcohol or ethanol, and described alcohol solution is methanol aqueous solution or aqueous ethanolic solution; The weight ratio of low-boiling point alcohol and 4-amino-3-methylphenol is 2～4:1, and the weight ratio of alcohol solution and 4-amino-3-methylphenol is 1～4:1.
Step (3) is put in a certain amount of alcoholic solvent for 4-amino-3-methylphenol that step (2) is obtained, and is warming up to backflow, and then cooling down crystallization, filtration, vacuum drying obtain high-quality 4-amino-3-methylphenol; The mixture that the alcohol that described method is used is the more lower boiling organic solvents such as methyl alcohol, ethanol or these alcohol and water, when using single alcohol, the weight ratio of its consumption and 4-amino-3-methylphenol is 2～4:1; If what use is alcohol-water mixture, the ratio of alcohol water is 1～4:1.
Preferably, the preparation method of 4-amino-3-methylphenol, comprises the steps:
(1) nitrosation reaction: take m-cresol as raw material, take aqueous sodium hydroxide solution as solvent, Sodium Nitrite and hydrochloric acid are nitrosification agent, prepares 4-nitroso-group-3-methylphenol through nitrosation reaction; Nitrosation reaction temperature is controlled at 3～10 ℃; The weight ratio of described m-methyl phenol, sodium hydroxide, Sodium Nitrite is 1:0.39:0.68, and the concentration of described hydrochloric acid is 36%, and hydrochloric acid folding hundred weight ratio rear and m-methyl phenol is 1.03:1;
(2) reduction reaction: 4-nitroso-group-3-methylphenol, in methyl alcohol, obtains 4-amino-3-methylphenol crude product by hydrogenating reduction under palladium carbon and ammonia effect; Reduction reaction temperature is controlled at 20～25 ℃, reaction times 2～8h, and the weight ratio of methyl alcohol and 4-nitroso-group-3-methylphenol is 7.5:1; Palladium carbon is 0.03:1 with the ratio of the weight of 4-nitroso-group-3-methylphenol; Described ammonia is 0.1:1 with the ratio of the weight of 4-nitroso-group-3-methylphenol;
(3) purifying: 4-amino-3-methylphenol crude product adds and is warming up to backflow in methyl alcohol, then through crystallisation by cooling, filtration, dry 4-amino-3-methylphenol highly finished product that to obtain; The weight ratio of methyl alcohol and 4-amino-3-methylphenol is 2:1; Drying temperature is 40 ℃.
Technique of the present invention is simple, and product aftertreatment is easy, and environmental pollution is little, 4-amino-3-methylphenol quality product the quality preparing is high, good stability, and the product making is except can be for general applications, can also, for the preparation of high-end resin, be a kind of method of applicable preparation of industrialization.
Embodiment
Below in conjunction with specific embodiment, the present invention is described further, but protection scope of the present invention is not limited in this.
Embodiment 1
Get 11.2g sodium hydrate solid, 120ml water and 28.5g m-cresol and stir at 10 ℃ of temperature, be cooled to 3～10 ℃ after adding 19.4g Sodium Nitrite to dissolve completely, standby.Get 81.4g 36% HCl (AR) and 58.1g water in four-hole bottle, slowly drip above-mentioned mixing solutions, controlling temperature is 3～10 ℃, finish and be incubated half an hour, reacting liquid filtering obtains sorrel solid, obtains 33.6g 4-nitroso-group-3-methylphenol after oven dry, and productive rate is 93.0%.
In 500ml stainless steel cauldron, add successively 75g methyl alcohol, 4g 25% ammoniacal liquor, 4-nitroso-group-3-methylphenol 10g and 5% palladium carbon 0.3g, envelope still, nitrogen replacement 3 times, after hydrogen exchange 3 times, be filled with hydrogen to 0.5Mpa, control 20～25 ℃ of stirring reactions of temperature of reaction kettle, reaction 2h, question response liquid is no longer eaten stopped reaction after hydrogen, drive still, reaction solution suction filtration is reclaimed to catalyzer, filtrate normal pressure reclaims methyl alcohol to there being a large amount of solids to separate out, stop steaming, be cooled to 10～15 ℃, suction filtration product with water rinse then vacuum drying obtain 4-amino-3-methylphenol crude product 9g, crude product adds in 20g methyl alcohol and is warming up to backflow, then be cooled to 10 ℃ of suction filtrations, 40 ℃ of vacuum-dryings of methanol wash obtain 4-amino-3-methylphenol highly finished product 7.65g, yield is 85%, product HPLC >=99.5%.
Embodiment 2
In 2000L stainless steel cauldron R1, suck water 900kg, drop into 96% sodium hydroxide 90kg, exothermic heat of reaction while dropping into sodium hydroxide, the logical icy salt solution of R1 chuck is cooled to 20～25 ℃, then drop into 214kg m-cresol at 10 ℃ of temperature stirring reaction 30min to the abundant salify of m-cresol, then after adding 146kg Sodium Nitrite to dissolve completely, be cooled to 3～10 ℃, standby.In 3000L glassed steel reaction vessels R2, suck 735kg 30% HCl and 440kg water and be uniformly mixed, the logical icy salt solution of chuck is cooled to 3～10 ℃ simultaneously; Ready, the alkali lye that contains Sodium Nitrite preparing in R1 is added drop-wise in the hydrochloric acid preparing in R2, the about 4h of time for adding adds, finish and be incubated half an hour, sampling HPLC detects to stock yard cresylol and reacts completely, and blowing, filters and obtains sorrel solid, with water rinse 2 times, remove the salt in product, obtain 4-nitroso-group-3-methylphenol.Product is not dried and is directly used in next step hydrogenating reduction.
In 2000L stainless steel autoclave, suck methyl alcohol 1000kg, pass into liquefied ammonia 5kg, 4-nitroso-group-3-methylphenol 240kg, drop into 5% palladium carbon 2kg, envelope still, nitrogen replacement 3 times, hydrogen exchange 3 times, reactor hydrogen pressure keeps 0.1～0.2Mpa, then be warming up to 20～25 ℃, start reaction, no longer change to hydrogen pressure, reaction 8h, sampling detects to 4-nitroso-group-3-monomethylaniline and reacts completely.Pressure release, reaction solution is removed to catalyzer by strainer, decompression steams methyl alcohol, steam about 600kg to methyl alcohol, be cooled to 10 ℃, be discharged in filtering jar, then centrifugal 4-amino-3-methylphenol crude product that obtains, 4-amino-3-methylphenol the crude product obtaining is put in the methanol aqueous solution 600kg of 50% concentration again, be warming up to 45 ℃, insulated and stirred 20min, then be cooled to 5～10 ℃, centrifugal, 45 ℃ of fast boilings are dried and obtain 4-amino-3-methylphenol highly finished product 99.4kg, and yield is 80.5%, product HPLC >=99.7%.
Embodiment 3
Get 13.5g sodium hydrate solid, 120ml water and 30g m-cresol and stir at 10 ℃ of temperature, be cooled to 5 ℃ after adding 24g Sodium Nitrite to dissolve completely, standby.Get 96g 25% HCl (AR) and 60g water in four-hole bottle, slowly drip above-mentioned mixing solutions, controlling temperature is 5 ℃, finish and be incubated half an hour, reacting liquid filtering obtains sorrel solid, obtains 36.6g 4-nitroso-group-3-methylphenol after oven dry, and productive rate is 96.2%.
In 500ml stainless steel cauldron, add successively 90g ethanol, 0.5g Trimethylamine 99, 4-nitroso-group-3-methylphenol 10g and Raney's nickel 0.1g, envelope still, nitrogen replacement 3 times, after hydrogen exchange 3 times, be filled with hydrogen to 0.5Mpa, control 30～35 ℃ of stirring reactions of temperature of reaction kettle, question response liquid is no longer eaten stopped reaction after hydrogen, drive still, reaction solution suction filtration is reclaimed to catalyzer, filtrate normal pressure reclaims ethanol to there being a large amount of solids to separate out, stop steaming, be cooled to 10～15 ℃, suction filtration product with water rinse then vacuum drying obtain 4-amino-3-methylphenol crude product 9.5g, crude product adds in 50g ethanol and is warming up to backflow, then be cooled to 10 ℃ of crystallizations, suction filtration, washing with alcohol, 50 ℃ of vacuum-dryings obtain 4-amino-3-methylphenol highly finished product 7.91g, yield is 88.1%, product HPLC >=99.3%.
Embodiment 4
Get 7.2g sodium hydrate solid, 100ml water and 20g m-cresol and stir at 10 ℃ of temperature, be cooled to 8 ℃ after adding 12g Sodium Nitrite to dissolve completely, standby.Get in the four-hole bottle of 150g 15% HCl (AR), slowly drip above-mentioned mixing solutions, controlling temperature is 8 ℃, finishes and is incubated half an hour, and reacting liquid filtering obtains sorrel solid, obtains 23.2g 4-nitroso-group-3-methylphenol after oven dry, and productive rate is 91.3%.
In 500ml stainless steel cauldron, add successively 45g Virahol, 0.2g Monomethylamine, 4-nitroso-group-3-methylphenol 10g and palladium aluminium 0.1g, envelope still, nitrogen replacement 3 times, after hydrogen exchange 3 times, be filled with hydrogen to 0.5Mpa, control 20～25 ℃ of stirring reactions of temperature of reaction kettle, question response liquid is no longer eaten stopped reaction after hydrogen, drive still, reaction solution suction filtration is reclaimed to catalyzer, filtrate normal pressure reclaims Virahol to there being a large amount of solids to separate out, stop steaming, be cooled to 10～15 ℃, suction filtration product with water rinse then vacuum drying obtain 4-amino-3-methylphenol crude product 8.7g, crude product adds in 30g methyl alcohol and is warming up to backflow, then be cooled to 10 ℃ of crystallisation by cooling, suction filtration, methanol wash, 60 ℃ of vacuum-dryings obtain 4-amino-3-methylphenol highly finished product 7.65g, yield is 82%, product HPLC >=99.7%.
Claims (7)
1. a preparation method for 4-amino-3-methylphenol, is characterized in that comprising the steps:
(1) nitrosation reaction: the m-cresol of take prepares 4-nitroso-group-3-methylphenol through nitrosification as raw material;
(2) reduction reaction: 4-nitroso-group-3-methylphenol, in alcoholic solvent, obtains 4-amino-3-methylphenol crude product by hydrogenating reduction under catalyzer and promotor effect;
(3) purifying: 4-amino-3-methylphenol crude product carries out purification process through alcoholic solvent and obtains 4-amino-3-methylphenol highly finished product.
2. the preparation method of 4-amino-3-methylphenol according to claim 1, is characterized in that: in step (1), take aqueous sodium hydroxide solution as solvent, Sodium Nitrite and hydrochloric acid are nitrosification agent, and nitrosation reaction temperature is controlled at-5～15 ℃; The weight ratio of described m-methyl phenol, sodium hydroxide, Sodium Nitrite is 1:0.35～0.45:0.6～0.8, and the concentration of described hydrochloric acid is 15～36%, and hydrochloric acid folding hundred weight ratio rear and m-methyl phenol is 0.8～1.2:1.
3. the preparation method of 4-amino-3-methylphenol according to claim 1, it is characterized in that: in step (2), reduction reaction temperature is controlled at 20～40 ℃, reaction times 2～8h, described alcoholic solvent is a kind of in methyl alcohol, ethanol, Virahol, and the weight ratio of itself and 4-nitroso-group-3-methylphenol is 2～10:1; Described catalyzer is a kind of in palladium carbon, palladium aluminium, Raney's nickel, and it is 0.005～0.05:1 with the ratio of the weight of 4-nitroso-group-3-methylphenol; Described promotor is ammonia or organic amine, and it is 0.01～0.1:1 with the ratio of the weight of 4-nitroso-group-3-methylphenol.
4. the preparation method of 4-amino-3-methylphenol according to claim 3, is characterized in that: described organic amine is a kind of in Monomethylamine, dimethylamine, Trimethylamine 99.
5. the preparation method of 4-amino-3-methylphenol according to claim 1, is characterized in that: in step (3), through alcoholic solvent dissolving, crystallization, filtration, dry 4-amino-3-methylphenol that to obtain; Solvent temperature is 40～70 ℃, and described alcoholic solvent is low-boiling point alcohol or alcohol solution, and the weight ratio of itself and 4-amino-3-methylphenol is 1～4:1; In alcohol solution, the weight ratio of water and 4-amino-3-methylphenol is 0.5～1.5:1; Drying temperature is 30～60 ℃.
6. the preparation method of 4-amino-3-methylphenol according to claim 5, is characterized in that: described low-boiling point alcohol is methyl alcohol or ethanol, and described alcohol solution is methanol aqueous solution or aqueous ethanolic solution; The weight ratio of low-boiling point alcohol and 4-amino-3-methylphenol is 2～4:1, and the weight ratio of alcohol solution and 4-amino-3-methylphenol is 1～4:1.
7. the preparation method of 4-amino-3-methylphenol according to claim 1, is characterized in that comprising the steps:
(1) nitrosation reaction: take m-cresol as raw material, take aqueous sodium hydroxide solution as solvent, Sodium Nitrite and hydrochloric acid are nitrosification agent, prepares 4-nitroso-group-3-methylphenol through nitrosation reaction; Nitrosation reaction temperature is controlled at 3～10 ℃; The weight ratio of described m-methyl phenol, sodium hydroxide, Sodium Nitrite is 1:0.39:0.68, and the concentration of described hydrochloric acid is 36%, and hydrochloric acid folding hundred weight ratio rear and m-methyl phenol is 1.03:1;
(2) reduction reaction: 4-nitroso-group-3-methylphenol, in methyl alcohol, obtains 4-amino-3-methylphenol crude product by hydrogenating reduction under palladium carbon and ammonia effect; Reduction reaction temperature is controlled at 20～25 ℃, reaction times 2～8h, and the weight ratio of methyl alcohol and 4-nitroso-group-3-methylphenol is 7.5:1; Palladium carbon is 0.03:1 with the ratio of the weight of 4-nitroso-group-3-methylphenol; Described ammonia is 0.1:1 with the ratio of the weight of 4-nitroso-group-3-methylphenol;
(3) purifying: 4-amino-3-methylphenol crude product adds and is warming up to backflow in methyl alcohol, then through crystallisation by cooling, filtration, dry 4-amino-3-methylphenol highly finished product that to obtain; The weight ratio of methyl alcohol and 4-amino-3-methylphenol is 2:1; Drying temperature is 40 ℃.
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| CN111072501A (en) * | 2019-12-16 | 2020-04-28 | 岳阳中展科技有限公司 | Production method of 2,4, 6-tri (dimethylamine methyl) phenol |
| CN113735721A (en) * | 2021-10-09 | 2021-12-03 | 上海昕凯医药科技有限公司 | Method for synthesizing 3-ethylamino-4-methylphenol |
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| CN111072501A (en) * | 2019-12-16 | 2020-04-28 | 岳阳中展科技有限公司 | Production method of 2,4, 6-tri (dimethylamine methyl) phenol |
| CN113735721A (en) * | 2021-10-09 | 2021-12-03 | 上海昕凯医药科技有限公司 | Method for synthesizing 3-ethylamino-4-methylphenol |
| CN113735721B (en) * | 2021-10-09 | 2023-09-29 | 上海昕凯医药科技有限公司 | Method for synthesizing 3-ethylamino-4-methylphenol |
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