CN117886700A - Preparation method of 2-methyl-3-trifluoromethyl aniline - Google Patents
Preparation method of 2-methyl-3-trifluoromethyl aniline Download PDFInfo
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- CN117886700A CN117886700A CN202311816657.0A CN202311816657A CN117886700A CN 117886700 A CN117886700 A CN 117886700A CN 202311816657 A CN202311816657 A CN 202311816657A CN 117886700 A CN117886700 A CN 117886700A
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- dichloro
- trifluoromethyl
- methyl
- toluene
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- TWLDBACVSHADLI-UHFFFAOYSA-N 2-methyl-3-(trifluoromethyl)aniline Chemical compound CC1=C(N)C=CC=C1C(F)(F)F TWLDBACVSHADLI-UHFFFAOYSA-N 0.000 title claims abstract description 31
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 60
- 238000006243 chemical reaction Methods 0.000 claims abstract description 47
- IBRWCYHTODRXJR-UHFFFAOYSA-N 1,2-dichloro-4-methyl-3-nitro-5-(trifluoromethyl)benzene Chemical compound CC1=C(C(F)(F)F)C=C(Cl)C(Cl)=C1[N+]([O-])=O IBRWCYHTODRXJR-UHFFFAOYSA-N 0.000 claims abstract description 34
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 34
- 239000001257 hydrogen Substances 0.000 claims abstract description 34
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims abstract description 33
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 25
- 238000005984 hydrogenation reaction Methods 0.000 claims abstract description 23
- 239000002253 acid Substances 0.000 claims abstract description 16
- 239000011230 binding agent Substances 0.000 claims abstract description 15
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 claims abstract description 15
- 239000000920 calcium hydroxide Substances 0.000 claims abstract description 15
- 229910001861 calcium hydroxide Inorganic materials 0.000 claims abstract description 15
- 238000000034 method Methods 0.000 claims abstract description 15
- 239000000395 magnesium oxide Substances 0.000 claims abstract description 12
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims abstract description 12
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000003444 phase transfer catalyst Substances 0.000 claims abstract description 11
- 238000000926 separation method Methods 0.000 claims abstract description 10
- 239000007810 chemical reaction solvent Substances 0.000 claims abstract description 9
- 238000000746 purification Methods 0.000 claims abstract description 8
- 239000003054 catalyst Substances 0.000 claims abstract description 7
- 239000012071 phase Substances 0.000 claims description 45
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 42
- 239000000203 mixture Substances 0.000 claims description 29
- 239000012074 organic phase Substances 0.000 claims description 28
- 239000000047 product Substances 0.000 claims description 28
- 239000012141 concentrate Substances 0.000 claims description 26
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 25
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 24
- 239000012065 filter cake Substances 0.000 claims description 24
- 238000001914 filtration Methods 0.000 claims description 23
- 239000008346 aqueous phase Substances 0.000 claims description 14
- 238000003682 fluorination reaction Methods 0.000 claims description 7
- 238000006396 nitration reaction Methods 0.000 claims description 7
- WYUIWKFIFOJVKW-UHFFFAOYSA-N 1,2-dichloro-4-methylbenzene Chemical compound CC1=CC=C(Cl)C(Cl)=C1 WYUIWKFIFOJVKW-UHFFFAOYSA-N 0.000 claims description 6
- JZWZPWDFZGTMIF-UHFFFAOYSA-N 1,2-dichloro-4-methyl-5-(trichloromethyl)benzene Chemical compound CC1=CC(Cl)=C(Cl)C=C1C(Cl)(Cl)Cl JZWZPWDFZGTMIF-UHFFFAOYSA-N 0.000 claims description 4
- OARYHYOOIUIKFZ-UHFFFAOYSA-N 1,2-dichloro-4-methyl-5-(trifluoromethyl)benzene Chemical compound CC1=CC(Cl)=C(Cl)C=C1C(F)(F)F OARYHYOOIUIKFZ-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- -1 crown ether compounds Chemical class 0.000 claims description 3
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims description 3
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 claims description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 229910000040 hydrogen fluoride Inorganic materials 0.000 claims description 2
- 229910017604 nitric acid Inorganic materials 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 abstract description 9
- 238000004519 manufacturing process Methods 0.000 abstract description 7
- 150000003839 salts Chemical class 0.000 abstract description 6
- 230000036632 reaction speed Effects 0.000 abstract description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 33
- 238000006467 substitution reaction Methods 0.000 description 26
- 238000003756 stirring Methods 0.000 description 22
- 238000001816 cooling Methods 0.000 description 21
- 229910052757 nitrogen Inorganic materials 0.000 description 21
- 229910052799 carbon Inorganic materials 0.000 description 19
- 239000002994 raw material Substances 0.000 description 16
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 10
- 239000001110 calcium chloride Substances 0.000 description 10
- 229910001628 calcium chloride Inorganic materials 0.000 description 10
- 238000007599 discharging Methods 0.000 description 10
- 238000010438 heat treatment Methods 0.000 description 10
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 10
- 238000005070 sampling Methods 0.000 description 10
- 238000001291 vacuum drying Methods 0.000 description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- SRTKIHVQZYXHHJ-UHFFFAOYSA-N n-methyl-3-(trifluoromethyl)aniline Chemical compound CNC1=CC=CC(C(F)(F)F)=C1 SRTKIHVQZYXHHJ-UHFFFAOYSA-N 0.000 description 9
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 9
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 239000002699 waste material Substances 0.000 description 6
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 5
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- 239000007868 Raney catalyst Substances 0.000 description 4
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 4
- 229910000564 Raney nickel Inorganic materials 0.000 description 4
- 230000008901 benefit Effects 0.000 description 3
- 238000006073 displacement reaction Methods 0.000 description 3
- 230000014509 gene expression Effects 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- DSVGQVZAZSZEEX-UHFFFAOYSA-N [C].[Pt] Chemical compound [C].[Pt] DSVGQVZAZSZEEX-UHFFFAOYSA-N 0.000 description 2
- 229940035676 analgesics Drugs 0.000 description 2
- 239000000730 antalgic agent Substances 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- NOOCSNJCXJYGPE-UHFFFAOYSA-N flunixin Chemical compound C1=CC=C(C(F)(F)F)C(C)=C1NC1=NC=CC=C1C(O)=O NOOCSNJCXJYGPE-UHFFFAOYSA-N 0.000 description 2
- 229960000588 flunixin Drugs 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- OHVLMTFVQDZYHP-UHFFFAOYSA-N 1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-2-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]ethanone Chemical compound N1N=NC=2CN(CCC=21)C(CN1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)=O OHVLMTFVQDZYHP-UHFFFAOYSA-N 0.000 description 1
- KZEVSDGEBAJOTK-UHFFFAOYSA-N 1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-2-[5-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]-1,3,4-oxadiazol-2-yl]ethanone Chemical compound N1N=NC=2CN(CCC=21)C(CC=1OC(=NN=1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)=O KZEVSDGEBAJOTK-UHFFFAOYSA-N 0.000 description 1
- LDXJRKWFNNFDSA-UHFFFAOYSA-N 2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]ethanone Chemical compound C1CN(CC2=NNN=C21)CC(=O)N3CCN(CC3)C4=CN=C(N=C4)NCC5=CC(=CC=C5)OC(F)(F)F LDXJRKWFNNFDSA-UHFFFAOYSA-N 0.000 description 1
- YRBRYHACQBMPLO-UHFFFAOYSA-N 2-[2-methyl-3-(trifluoromethyl)anilino]benzoic acid Chemical compound C1=CC=C(C(F)(F)F)C(C)=C1NC1=CC=CC=C1C(O)=O YRBRYHACQBMPLO-UHFFFAOYSA-N 0.000 description 1
- JQMFQLVAJGZSQS-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-N-(2-oxo-3H-1,3-benzoxazol-6-yl)acetamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)NC1=CC2=C(NC(O2)=O)C=C1 JQMFQLVAJGZSQS-UHFFFAOYSA-N 0.000 description 1
- JVKRKMWZYMKVTQ-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]pyrazol-1-yl]-N-(2-oxo-3H-1,3-benzoxazol-6-yl)acetamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C=NN(C=1)CC(=O)NC1=CC2=C(NC(O2)=O)C=C1 JVKRKMWZYMKVTQ-UHFFFAOYSA-N 0.000 description 1
- YLZOPXRUQYQQID-UHFFFAOYSA-N 3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]propan-1-one Chemical compound N1N=NC=2CN(CCC=21)CCC(=O)N1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F YLZOPXRUQYQQID-UHFFFAOYSA-N 0.000 description 1
- HYNSPMOGQKLMOO-UHFFFAOYSA-N CC1=C(N)C=CC=C1C(F)(F)F.CC1=C(C=CC=C1C(F)(F)F)N Chemical compound CC1=C(N)C=CC=C1C(F)(F)F.CC1=C(C=CC=C1C(F)(F)F)N HYNSPMOGQKLMOO-UHFFFAOYSA-N 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000001760 anti-analgesic effect Effects 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- DTYCRHCCLVCUDT-UHFFFAOYSA-J calcium;magnesium;tetrachloride Chemical group [Mg+2].[Cl-].[Cl-].[Cl-].[Cl-].[Ca+2] DTYCRHCCLVCUDT-UHFFFAOYSA-J 0.000 description 1
- 150000003983 crown ethers Chemical class 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a preparation method of 2-methyl-3-trifluoromethyl aniline, which comprises the following steps of: 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene, an acid binding agent, a phase transfer catalyst, a hydrogenation catalyst and water are put into a reaction kettle, and hydrogen atmosphere is introduced to carry out high-pressure hydrogenation reaction, so that 2-methyl-3-trifluoromethyl aniline is obtained. According to the technical scheme, water is used as a reaction solvent in the hydrogenation reaction, calcium hydroxide or magnesium oxide or triethylamine is used as an acid-binding agent, and a phase transfer catalyst is also added, so that the hydrogenation reaction speed can be increased, the reaction time can be shortened, the production efficiency can be improved, meanwhile, the separation and purification steps of the 2-methyl-3-trifluoromethyl aniline are simple, and the salt generated in the reaction is a related product, so that the method has economic value.
Description
Technical Field
The application relates to the field of fluoride engineering, in particular to a preparation method of 2-methyl-3-trifluoromethyl aniline.
Background
2-methyl-3-trifluoromethylaniline (2-methyl-3-trifluoromethyl-aniline) is abbreviated as MTA, CAS [54396-44-0 ]]Molecular formula C 8 H 8 F 3 N, molecular weight 175, melting point 40 ℃, boiling point 198 ℃. MTA is an important intermediate of medicines and pesticides, is mainly used for synthesizing tranquilizers, anti-inflammatory and analgesic drugs and herbicides, such as- (2-methyl-3-trifluoromethyl) anilino nicotinic acid and N- (2-methyl-3-trifluoromethyl phenyl) anthranilic acid, and has good anti-inflammatory and analgesic effects. MTA is a key intermediate for preparing flunixin, and the chemical name of flunixin is 2- [ [ 2-methyl-3- (trifluoromethyl) phenyl 1 amino group]-3-acids, which are potent analgesics, are particularly suitable for parenteral administration.
In the 2004 5-phase of China chemical abstracts of China, 3, 4-dichlorotoluene is used as a raw material, and a target product 2-methyl-3-trifluoromethyl aniline is obtained through trichloromethylation, displacement fluorination, nitration and reduction. The last hydrogenation reduction reaction in the literature adopts 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene as a starting material, sodium acetate as an acid binding agent, ethanol as a solvent and palladium carbon as a catalyst, the hydrogenation reaction time is 30-36 hours, the time is long, the obtained mixed salt of sodium chloride and sodium acetate after the reaction is finished, the separation is inconvenient, and the three-waste treatment pressure is high. Meanwhile, the ethanol is inflammable liquid, so that hidden danger of safety and environmental protection exists in the reaction process, distillation recovery treatment is needed to be carried out on the ethanol after the reaction is finished, the post-treatment procedure is complex, and the production efficiency is low.
Disclosure of Invention
In view of the problems, the preparation method of 2-methyl-3-trifluoromethyl aniline, which is simple in process raw materials, simple to operate, short in reaction time, simple and feasible in post-treatment, less in three wastes, high in economic benefit and suitable for industrial popularization, takes 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene as a starting raw material.
The preparation method provided by the application comprises the following steps:
hydrogenation reaction: 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene, an acid binding agent, a phase transfer catalyst, a hydrogenation catalyst and a reaction solvent are put into a reaction kettle, and hydrogen atmosphere is introduced to carry out high-pressure hydrogenation reaction to obtain 2-methyl-3-trifluoromethyl aniline; the reaction solvent is water, and the phase transfer catalyst is one or more of quaternary ammonium salt, polyethylene glycol and crown ether compounds; the acid binding agent is calcium hydroxide or magnesium oxide or triethylamine.
Compared with the prior art, the technical scheme adopts water as a reaction solvent in the hydrogenation reaction, calcium hydroxide or magnesium oxide or triethylamine as an acid-binding agent, and a phase transfer catalyst is also added, so that the hydrogenation reaction speed can be increased, the reaction time can be shortened, the production efficiency can be improved, meanwhile, the separation and purification steps of the 2-methyl-3-trifluoromethyl aniline are simple, the salt generated in the reaction is a single salt (calcium chloride, magnesium chloride or triethylamine hydrochloride), and the product can be prepared into a joint product, thereby having economic value. The technical proposal has the advantages of easily obtained raw materials, low price, simple steps of separation and purification, small impurity content in the product, high yield, less three wastes, reduction of the cost of three wastes treatment and contribution to the industrialized production of the product.
Further, the mass ratio of the 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene to the reaction solvent is 1:2-10.
Further, the mass ratio of the 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene to the phase transfer catalyst is 1000:5-250.
Further, the molar ratio of the 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene to the calcium hydroxide is 10:10 to 18.
Further, the molar ratio of the 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene to the magnesium oxide is 10:10 to 18.
Further, the molar ratio of the 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene to the triethylamine is 10:20 to 35.
Further, the hydrogenation catalyst comprises palladium carbon, platinum carbon, raney nickel or a mixture thereof.
Further, the hydrogenation reaction temperature is 40-150 ℃, the pressure is 0.3-2.0 MPa, and the time is 5-16 hours; after the hydrogenation reaction is completed, removing hydrogen in the reaction kettle to obtain a first mixture; and separating and purifying the first mixture to obtain the 2-methyl-3-trifluoromethyl aniline.
Further, the separation and purification comprises the following steps:
1) Standing and layering the first mixture, and collecting a first organic phase;
2) And distilling the first organic phase to obtain 2-methyl-3-trifluoromethyl aniline.
Further, the separation and purification comprises the following steps:
1) Standing and layering the first mixture, and collecting a first organic phase and a first aqueous phase;
2) Distilling the first organic phase to obtain 2-methyl-3-trifluoromethyl aniline;
3) Dropwise adding hydrochloric acid into the first water phase until the pH value is 6.5-7.5, and decoloring by using active carbon to obtain a second water phase;
4) Concentrating the second aqueous phase under reduced pressure to obtain a first concentrate;
5) Adding methanol into the first concentrate, and filtering to obtain a filter cake;
6) And (5) drying the filter cake in vacuum to obtain a related product.
The type of the associated product is related to the acid binding agent. Calcium hydroxide is used as an acid binding agent, and the associated product is calcium chloride; magnesium oxide is used as an acid binding agent, and the associated product is magnesium calcium chloride; triethylamine is used as an acid binding agent, and the related product is triethylamine hydrochloride. The above are all soluble salts, and the separation and purification process is simple and the cost is low.
Further, in the step 5), after methanol is added, stirring is started, the temperature is raised to 50-55 ℃ to stir and break up the first concentrate, so that organic impurities in the first concentrate can be fully dissolved in the methanol; and the content of related products can be increased by cooling to 20-25 ℃ and filtering.
Further, the method also comprises the steps of trichloromethylation, fluorination and nitration, wherein the trichloromethylation reaction comprises the following steps: 3, 4-dichloro toluene reacts with carbon tetrachloride and aluminum trichloride to obtain 3, 4-dichloro-6-trichloromethyl toluene;
fluorination reaction: carrying out fluorination reaction on the 3, 4-dichloro-6-trichloromethyl toluene and anhydrous hydrogen fluoride to obtain 3, 4-dichloro-6-trifluoromethyl toluene;
nitration reaction: and (3) performing nitration reaction on the 3, 4-dichloro-6-trifluoromethyl toluene and nitric acid and sulfuric acid to obtain the 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene.
The whole technical route is as follows:
the foregoing summary is merely an overview of the present application, and is provided to enable one of ordinary skill in the art to make and use the present application and to enable one of ordinary skill in the art to make and use the present application.
Detailed Description
In order to describe the technical content, constructional features, achieved objects and effects of the technical solution in detail, the following description is made in detail with reference to specific embodiments.
In order to describe the possible application scenarios, technical principles, practical embodiments, and the like of the present application in detail, the following description is made with reference to the specific embodiments listed below. The embodiments described herein are only used to more clearly illustrate the technical solutions of the present application, and are therefore only used as examples and are not intended to limit the scope of protection of the present application.
Reference herein to "an embodiment" means that a particular feature, structure, or characteristic described in connection with the embodiment may be included in at least one embodiment of the present application. The appearances of the phrase "in various places in the specification are not necessarily all referring to the same embodiment, nor are they particularly limited to independence or relevance from other embodiments. In principle, in the present application, as long as there is no technical contradiction or conflict, the technical features mentioned in the embodiments may be combined in any manner to form a corresponding implementable technical solution.
Unless defined otherwise, technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present application pertains; the use of related terms herein is for the description of specific embodiments only and is not intended to limit the present application.
In the description of the present application, the term "and/or" is a representation for describing a logical relationship between objects, which means that there may be three relationships, e.g., a and/or B, representing: there are three cases, a, B, and both a and B. In addition, the character "/" herein generally indicates that the front-to-back associated object is an "or" logical relationship.
In this application, terms such as "first" and "second" are used merely to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any actual number, order, or sequence of such entities or operations.
Without further limitation, the use of the terms "comprising," "including," "having," or other like terms in this application is intended to cover a non-exclusive inclusion, such that a process, method, or article of manufacture that comprises a list of elements does not include additional elements but may include other elements not expressly listed or inherent to such process, method, or article of manufacture.
As in the understanding of the "examination guideline," the expressions "greater than", "less than", "exceeding", and the like are understood to exclude the present number in this application; the expressions "above", "below", "within" and the like are understood to include this number. Furthermore, in the description of the embodiments of the present application, the meaning of "a plurality of" is two or more (including two), and similarly, the expression "a plurality of" is also to be understood as such, for example, "a plurality of groups", "a plurality of" and the like, unless specifically defined otherwise.
In the embodiment, 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene is taken as a hydrogenation raw material, a reaction solvent is water, an acid binding agent is calcium hydroxide, magnesium oxide or triethylamine, and a phase transfer catalyst is quaternary ammonium salt TBAB, polyethylene glycol PEG400 or crown ether compound 18 crown 6 (C1) 2 H 24 O 6 ) The acid-binding agent is calcium hydroxide or magnesium oxide or triethylamine, and the hydrogenation catalyst is palladium carbon or platinum carbon or Raney nickel.
Sequentially adding 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene, an acid binding agent (calcium hydroxide or magnesium oxide with the molar quantity of 1.1-1.8 times of 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene) and water (with the molar quantity of 2.0-3.5 times of 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene), a hydrogenation catalyst (with the molar quantity of 0.002-0.15 times of 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene), a phase transfer catalyst (with the mass of 0.005-0.25 times of 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene) into a high-pressure reaction kettle, stirring uniformly after the addition, covering a kettle cover, vacuumizing the system to the vacuum degree of < -0.096MPa, performing three nitrogen displacement, introducing hydrogen into the kettle for a slow reaction time ranging from 0.005-0.25 MPa to the temperature of between 0.5 and 150 ℃ after the three nitrogen displacement, and the reaction kettle is completed, and the reaction time is adjusted to the reaction time of between the temperature and between 0.0 and 150 ℃ and the pressure of the reaction kettle; sampling and controlling until the raw materials and the intermediate state are completely reacted, cooling to 20-30 ℃ after the reaction is finished, slowly opening an autoclave emptying valve, discharging unreacted hydrogen in the reaction kettle to a safe place, then performing nitrogen replacement for three times, and opening a kettle cover to obtain a first mixture; standing the first mixture for 30min for layering, and collecting a first organic phase and a first aqueous phase; distilling the first organic phase at 100-130 deg.c and vacuum degree below-0.95 MPa to obtain 2-methyl-3-trifluoro methylaniline product.
The purity of the 2-methyl-3-trifluoromethyl aniline obtained in the embodiment is 93.2% -99.6%, and the reaction yield is 96.0% -98.7%.
Dropwise adding hydrochloric acid into the first water phase until the pH value is 6.5-7.5, adding activated carbon (0.01 times of the mass of 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene) for 60min for decoloring, and filtering the activated carbon to obtain a second water phase; concentrating the second water phase under reduced pressure at 60-100 ℃ and vacuum degree of < -0.9MPa, and concentrating until the second water phase is dried to obtain a first concentrate; adding methanol (1.0-10.0 times of 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene) into the first concentrate, heating to 50-55 ℃, stirring for 60min, cooling to 20-25 ℃, and filtering to obtain a filter cake; and (3) vacuum drying the filter cake at 80-120 ℃ to obtain a related product (calcium chloride or magnesium chloride or triethylamine hydrochloride).
Example 12 preparation of methyl-3-trifluoromethylaniline (purity 99.6%, yield 97.1%)
Sequentially adding 27.4g (0.1 mol) of 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene, 7.4g (0.1 mol) of calcium hydroxide, 0.0548g (0.002 times mass) of palladium carbon, 0.137g (0.005 times mass) of TBAB and 274g (10 times mass) of water into a high-pressure reaction kettle, uniformly stirring after the material addition is finished, covering a kettle cover, vacuumizing the system to a vacuum degree of < -0.096MPa, performing three times of nitrogen substitution and three times of hydrogen substitution, slowly introducing hydrogen into the high-pressure kettle after the substitution is finished, and reacting at a temperature of 40-50 ℃ and a pressure of 0.3-0.5 MPa for 16 hours; sampling and controlling until the raw materials and the intermediate state are completely reacted, cooling to 20-30 ℃ after the reaction is finished, slowly opening an autoclave emptying valve, discharging unreacted hydrogen in the reaction kettle to a safe place, then performing nitrogen replacement for three times, and opening a kettle cover to obtain a first mixture; standing the first mixture for 30min for layering, and collecting a first organic phase and a first aqueous phase; the first organic phase is distilled at 100-130 ℃ and the vacuum degree is less than-0.95 MPa, 17.1g of 2-methyl-3-trifluoromethyl aniline is obtained, the purity is 99.6%, and the yield is 97.1%.
Dropwise adding hydrochloric acid into the first water phase until the pH value is 6.5-7.5, adding 0.274g (0.01 times of the mass) of active carbon for 60min for decoloration, and filtering the active carbon to obtain a second water phase; concentrating the second water phase under reduced pressure at 60-100 ℃ and vacuum degree of < -0.9MPa, and concentrating until the second water phase is dried to obtain a first concentrate; adding 137g (5 times mass) of methanol into the first concentrate, heating to 50-55 ℃, stirring for 60min, cooling to 20-25 ℃, and filtering to obtain a filter cake; and (3) vacuum drying the filter cake at 80-120 ℃ to obtain 10.5g of calcium chloride as a related product.
Example 2 2 preparation of methyl-3-trifluoromethylaniline (purity 98.6%, yield 98.7%)
Sequentially adding 27.4g (0.1 mol) of 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene, 13.3g (0.18 mol) of calcium hydroxide, 4.11g (0.15 times mass) of palladium-carbon, 6.85g (0.25 times mass) of TBAB and 137g (5 times mass) of water into a high-pressure reaction kettle, uniformly stirring after the material addition is finished, covering a kettle cover, vacuumizing the system to a vacuum degree of < -0.096MPa, performing three times of nitrogen substitution and three times of hydrogen substitution, slowly introducing hydrogen into the high-pressure kettle after the substitution is finished, and reacting at a temperature of 140-150 ℃ and a pressure of 1.8-2.0 MPa for 5 hours; sampling and controlling until the raw materials and the intermediate state are completely reacted, cooling to 20-30 ℃ after the reaction is finished, slowly opening an autoclave emptying valve, discharging unreacted hydrogen in the reaction kettle to a safe place, then performing nitrogen replacement for three times, and opening a kettle cover to obtain a first mixture; standing the first mixture for 30min for layering, and collecting a first organic phase and a first aqueous phase; the first organic phase is distilled at 100-130 ℃ and the vacuum degree is less than-0.95 MPa, 17.5g of 2-methyl-3-trifluoromethyl aniline is obtained, the purity is 98.6%, and the yield is 98.7%.
Dropwise adding hydrochloric acid into the first water phase until the pH value is 6.5-7.5, adding 0.274g (0.01 times of the mass) of active carbon for 60min for decoloration, and filtering the active carbon to obtain a second water phase; concentrating the second water phase under reduced pressure at 60-100 ℃ and vacuum degree of < -0.9MPa, and concentrating until the second water phase is dried to obtain a first concentrate; adding 137g (5 times mass) of methanol into the first concentrate, heating to 50-55 ℃, stirring for 60min, cooling to 20-25 ℃, and filtering to obtain a filter cake; and (3) vacuum drying the filter cake at 80-120 ℃ to obtain 10.8g of calcium chloride as a related product.
Example 3 2 preparation of methyl-3-trifluoromethylaniline (purity 98.4%, yield 97.1%)
Sequentially adding 27.4g (0.1 mol) of 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene, 4.0g (0.1 mol) of magnesium oxide, 0.137g (0.005 times mass) of palladium-carbon, 0.274g (0.01 times mass) of TBAB and 54.8g (2 times mass) of water into a high-pressure reaction kettle, stirring uniformly after the material addition is finished, covering a kettle cover, vacuumizing the system to a vacuum degree of < -0.096MPa, performing three times of nitrogen substitution and three times of hydrogen substitution, slowly introducing hydrogen into the high-pressure kettle after the substitution is finished, reacting at a temperature of 40-50 ℃ and a pressure of 0.3-0.5 MPa, and reacting for 13 hours; sampling and controlling until the raw materials and the intermediate state are completely reacted, cooling to 20-30 ℃ after the reaction is finished, slowly opening an autoclave emptying valve, discharging unreacted hydrogen in the reaction kettle to a safe place, then performing nitrogen replacement for three times, and opening a kettle cover to obtain a first mixture; standing the first mixture for 30min for layering, and collecting a first organic phase and a first aqueous phase; the first organic phase is distilled at 100-130 ℃ and the vacuum degree is less than-0.95 MPa, 17g of 2-methyl-3-trifluoromethyl aniline is obtained, the purity is 98.4%, and the yield is 97.1%.
Dropwise adding hydrochloric acid into the first water phase until the pH value is 6.5-7.5, adding 0.274g (0.01 times of the mass) of active carbon for 60min for decoloration, and filtering the active carbon to obtain a second water phase; concentrating the second water phase under reduced pressure at 60-100 ℃ and vacuum degree of < -0.9MPa, and concentrating until the second water phase is dried to obtain a first concentrate; adding 137g (5 times mass) of methanol into the first concentrate, heating to 50-55 ℃, stirring for 60min, cooling to 20-25 ℃, and filtering to obtain a filter cake; and (3) vacuum drying the filter cake at 80-120 ℃ to obtain 8.8g of calcium chloride as a related product.
Example 4 2 preparation of methyl-3-trifluoromethylaniline (purity 98.2%, yield 97.7%)
Sequentially adding 27.4g (0.1 mol) of 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene, 7.2g (0.18 mol) of magnesium oxide, 0.137g (0.005 times mass) of palladium-carbon, 0.274g (0.01 times mass) of TBAB and 54.8g (2 times mass) of water into a high-pressure reaction kettle, stirring uniformly after the material addition is finished, covering a kettle cover, vacuumizing the system to a vacuum degree of < -0.096MPa, performing three times of nitrogen substitution and three times of hydrogen substitution, slowly introducing hydrogen into the high-pressure kettle after the substitution is finished, reacting at a temperature of 80-90 ℃ and a pressure of 0.6-0.8 MPa, and reacting for 8 hours; sampling and controlling until the raw materials and the intermediate state are completely reacted, cooling to 20-30 ℃ after the reaction is finished, slowly opening an autoclave emptying valve, discharging unreacted hydrogen in the reaction kettle to a safe place, then performing nitrogen replacement for three times, and opening a kettle cover to obtain a first mixture; standing the first mixture for 30min for layering, and collecting a first organic phase and a first aqueous phase; the first organic phase is distilled at 100-130 ℃ and the vacuum degree is less than-0.95 MPa, 17.1g of 2-methyl-3-trifluoromethyl aniline is obtained, the purity is 98.2%, and the yield is 97.7%.
Dropwise adding hydrochloric acid into the first water phase until the pH value is 6.5-7.5, adding 0.274g (0.01 times of the mass) of active carbon for 60min for decoloration, and filtering the active carbon to obtain a second water phase; concentrating the second water phase under reduced pressure at 60-100 ℃ and vacuum degree of < -0.9MPa, and concentrating until the second water phase is dried to obtain a first concentrate; adding 137g (5 times mass) of methanol into the first concentrate, heating to 50-55 ℃, stirring for 60min, cooling to 20-25 ℃, and filtering to obtain a filter cake; and (3) vacuum drying the filter cake at 80-120 ℃ to obtain 9.1g of calcium chloride as a related product.
Example 5 2 preparation of methyl-3-trifluoromethylaniline (purity 98.4%, yield 96.0%)
Sequentially adding 27.4g (0.1 mol) of 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene, 20.2g (0.2 mol) of triethylamine, 0.137g (0.005 times mass) of palladium-carbon, 0.274g (0.01 times mass) of TBAB and 137g (5 times mass) of water into a high-pressure reaction kettle, uniformly stirring after the material addition is finished, covering a kettle cover, vacuumizing the system to a vacuum degree of < -0.096MPa, performing three times of nitrogen substitution and three times of hydrogen substitution, slowly introducing hydrogen into the high-pressure kettle after the substitution is finished, and reacting at a temperature of 60-80 ℃ and a pressure of 0.3-0.5 MPa for 10 hours; sampling and controlling until the raw materials and the intermediate state are completely reacted, cooling to 20-30 ℃ after the reaction is finished, slowly opening an autoclave emptying valve, discharging unreacted hydrogen in the reaction kettle to a safe place, then performing nitrogen replacement for three times, and opening a kettle cover to obtain a first mixture; standing the first mixture for 30min for layering, and collecting a first organic phase and a first aqueous phase; the first organic phase is distilled at 100-130 ℃ and the vacuum degree is less than-0.95 MPa, 16.8g of 2-methyl-3-trifluoromethyl aniline is obtained, the purity is 98.4%, and the yield is 96.0%.
Dropwise adding hydrochloric acid into the first water phase until the pH value is 6.5-7.5, adding 0.274g (0.01 times of the mass) of active carbon for 60min for decoloration, and filtering the active carbon to obtain a second water phase; concentrating the second water phase under reduced pressure at 60-100 ℃ and vacuum degree of < -0.9MPa, and concentrating until the second water phase is dried to obtain a first concentrate; adding 137g (5 times mass) of methanol into the first concentrate, heating to 50-55 ℃, stirring for 60min, cooling to 20-25 ℃, and filtering to obtain a filter cake; and (3) vacuum drying the filter cake at 80-120 ℃ to obtain 23.6g of triethylamine hydrochloride which is a related product. Example 6 2 preparation of methyl-3-trifluoromethylaniline (purity 98.8%, yield 97.7%)
Sequentially adding 27.4g (0.1 mol) of 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene, 35.35g (0.35 mol) of triethylamine, 0.137g (0.005 times mass) of palladium-carbon, 0.274g (0.01 times mass) of TBAB and 137g (5 times mass) of water into a high-pressure reaction kettle, uniformly stirring after the material addition is finished, covering a kettle cover, vacuumizing the system to a vacuum degree of < -0.096MPa, performing three times of nitrogen substitution and three times of hydrogen substitution, slowly introducing hydrogen into the high-pressure kettle after the substitution is finished, and reacting at a temperature of 60-80 ℃ and a pressure of 0.3-0.5 MPa for 10 hours; sampling and controlling until the raw materials and the intermediate state are completely reacted, cooling to 20-30 ℃ after the reaction is finished, slowly opening an autoclave emptying valve, discharging unreacted hydrogen in the reaction kettle to a safe place, then performing nitrogen replacement for three times, and opening a kettle cover to obtain a first mixture; standing the first mixture for 30min for layering, and collecting a first organic phase and a first aqueous phase; the first organic phase is distilled at 100-130 ℃ and the vacuum degree is less than-0.95 MPa, 17.1g of 2-methyl-3-trifluoromethyl aniline is obtained, the purity is 98.8%, and the yield is 97.7%.
Dropwise adding hydrochloric acid into the first water phase until the pH value is 6.5-7.5, adding 0.274g (0.01 times of the mass) of active carbon for 60min for decoloration, and filtering the active carbon to obtain a second water phase; concentrating the second water phase under reduced pressure at 60-100 ℃ and vacuum degree of < -0.9MPa, and concentrating until the second water phase is dried to obtain a first concentrate; adding 137g (5 times mass) of methanol into the first concentrate, heating to 50-55 ℃, stirring for 60min, cooling to 20-25 ℃, and filtering to obtain a filter cake; and (3) vacuum drying the filter cake at 80-120 ℃ to obtain 25.8g of triethylamine hydrochloride which is a related product. Example 7 2 preparation of methyl-3-trifluoromethylaniline (purity 98.5%, yield 96.6%)
Sequentially adding 27.4g (0.1 mol) of 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene, 9.6g (0.13 mol) of calcium hydroxide, 0.137g (0.005 times mass) of palladium-carbon, 4000.137g (0.005 times mass) of PEG and 137g (5 times mass) of water into a high-pressure reaction kettle, uniformly stirring after the material addition is finished, covering a kettle cover, vacuumizing the system to a vacuum degree of < -0.096MPa, performing three times of nitrogen substitution and three times of hydrogen substitution, slowly introducing hydrogen into the high-pressure kettle after the substitution is finished, and reacting at a temperature of 70-90 ℃ under a pressure of 0.7-0.9 MPa for 8 hours; sampling and controlling until the raw materials and the intermediate state are completely reacted, cooling to 20-30 ℃ after the reaction is finished, slowly opening an autoclave emptying valve, discharging unreacted hydrogen in the reaction kettle to a safe place, then performing nitrogen replacement for three times, and opening a kettle cover to obtain a first mixture; standing the first mixture for 30min for layering, and collecting a first organic phase and a first aqueous phase; the first organic phase is distilled at 100-130 ℃ and the vacuum degree is less than-0.95 MPa, thus obtaining 16.9g of 2-methyl-3-trifluoromethyl aniline with the purity of 98.5 percent and the yield of 96.6 percent.
Dropwise adding hydrochloric acid into the first water phase until the pH value is 6.5-7.5, adding 0.274g (0.01 times of the mass) of active carbon for 60min for decoloration, and filtering the active carbon to obtain a second water phase; concentrating the second water phase under reduced pressure at 60-100 ℃ and vacuum degree of < -0.9MPa, and concentrating until the second water phase is dried to obtain a first concentrate; adding 137g (5 times mass) of methanol into the first concentrate, heating to 50-55 ℃, stirring for 60min, cooling to 20-25 ℃, and filtering to obtain a filter cake; and (3) vacuum drying the filter cake at 80-120 ℃ to obtain 13.6g of calcium chloride as a related product.
Example 8 2 preparation of methyl-3-trifluoromethylaniline (purity 98.7%, yield 97.1%)
Sequentially adding 27.4g (0.1 mol) of 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene, 7.4g (0.1 mol) of calcium hydroxide, 0.274g (0.01 times mass) of Raney nickel, 6.85g (0.25 times mass) of PEG4006.85g (5 times mass) of water into a high-pressure reaction kettle, stirring uniformly after the material addition is finished, covering a kettle cover, vacuumizing the system to a vacuum degree of < -0.096MPa, performing three times of nitrogen substitution and three times of hydrogen substitution, slowly introducing hydrogen into the high-pressure kettle after the substitution is finished, and reacting at a temperature of 70-90 ℃ under a pressure of 0.7-0.9 MPa for 8 hours; sampling and controlling until the raw materials and the intermediate state are completely reacted, cooling to 20-30 ℃ after the reaction is finished, slowly opening an autoclave emptying valve, discharging unreacted hydrogen in the reaction kettle to a safe place, then performing nitrogen replacement for three times, and opening a kettle cover to obtain a first mixture; standing the first mixture for 30min for layering, and collecting a first organic phase and a first aqueous phase; the first organic phase is distilled at 100-130 ℃ and the vacuum degree is less than-0.95 MPa, 17g of 2-methyl-3-trifluoromethyl aniline is obtained, the purity is 98.7%, and the yield is 97.1%.
Dropwise adding hydrochloric acid into the first water phase until the pH value is 6.5-7.5, adding 0.274g (0.01 times of the mass) of active carbon for 60min for decoloration, and filtering the active carbon to obtain a second water phase; concentrating the second water phase under reduced pressure at 60-100 ℃ and vacuum degree of < -0.9MPa, and concentrating until the second water phase is dried to obtain a first concentrate; adding 137g (5 times mass) of methanol into the first concentrate, heating to 50-55 ℃, stirring for 60min, cooling to 20-25 ℃, and filtering to obtain a filter cake; and (3) vacuum drying the filter cake at 80-120 ℃ to obtain 10.9g of calcium chloride as a related product.
Example 9 2 preparation of methyl-3-trifluoromethylaniline (purity 98.2%, yield 98.3%)
Sequentially adding 27.4g (0.1 mol) of 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene, 7.4g (0.1 mol) of calcium hydroxide, 4.11g (0.15 times mass) of Raney nickel, 0.274g (0.01 times mass) of 18 crown and 164.4g (6 times mass) of water into a high-pressure reaction kettle, stirring uniformly after the material addition is finished, covering a kettle cover, vacuumizing the system, vacuumizing to a vacuum degree of < -0.096MPa, performing three times of nitrogen substitution and three times of hydrogen substitution, slowly introducing hydrogen into the high-pressure kettle, and reacting at a temperature of 80-100 ℃ and a pressure of 0.6-0.8 MPa for 9 hours; sampling and controlling until the raw materials and the intermediate state are completely reacted, cooling to 20-30 ℃ after the reaction is finished, slowly opening an autoclave emptying valve, discharging unreacted hydrogen in the reaction kettle to a safe place, then performing nitrogen replacement for three times, and opening a kettle cover to obtain a first mixture; standing the first mixture for 30min for layering, and collecting a first organic phase and a first aqueous phase; the first organic phase is distilled at 100-130 ℃ and the vacuum degree is less than-0.95 MPa, 17.2g of 2-methyl-3-trifluoromethyl aniline is obtained, the purity is 98.2%, and the yield is 98.3%.
Dropwise adding hydrochloric acid into the first water phase until the pH value is 6.5-7.5, adding 0.274g (0.01 times of the mass) of active carbon for 60min for decoloration, and filtering the active carbon to obtain a second water phase; concentrating the second water phase under reduced pressure at 60-100 ℃ and vacuum degree of < -0.9MPa, and concentrating until the second water phase is dried to obtain a first concentrate; adding 137g (5 times mass) of methanol into the first concentrate, heating to 50-55 ℃, stirring for 60min, cooling to 20-25 ℃, and filtering to obtain a filter cake; and (3) vacuum drying the filter cake at 80-120 ℃ to obtain 10.3g of calcium chloride as a related product.
The technical scheme adopted by the embodiment has the advantages of easily obtained raw materials, low price, high product selectivity and easy separation of products, and the obtained 2-methyl-3-trifluoromethyl aniline has small impurity, high yield, purity up to 99.6 percent and reaction yield up to 98.7 percent. Meanwhile, the hydrogenation reaction time can be shortened from 30-36 hours to 5-16 hours, the reaction time is shortened, the reaction efficiency is greatly improved, the production efficiency of the product is improved, single salt related products can be obtained, the generated three wastes are less, the three-waste treatment cost is reduced, and the industrial production of the product is facilitated.
Finally, it should be noted that, although the foregoing embodiments have been described in the text of the present application, the scope of the patent protection of the present application is not limited thereby. All technical schemes generated by replacing or modifying equivalent structures or equivalent processes based on the essential idea of the application and by directly or indirectly implementing the technical schemes of the embodiments in other related technical fields and the like are included in the patent protection scope of the application.
Claims (10)
1. The preparation method of the 2-methyl-3-trifluoromethyl aniline is characterized by comprising the following steps of: hydrogenation reaction: 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene, an acid binding agent, a phase transfer catalyst, a hydrogenation catalyst and a reaction solvent are put into a reaction kettle, and hydrogen atmosphere is introduced to carry out high-pressure hydrogenation reaction to obtain 2-methyl-3-trifluoromethyl aniline; the reaction solvent is water, and the phase transfer catalyst is one or more of quaternary ammonium salt, polyethylene glycol and crown ether compounds; the acid binding agent is calcium hydroxide or magnesium oxide or triethylamine.
2. The preparation method according to claim 1, wherein the mass ratio of the 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene to the reaction solvent is 1:2-10.
3. The preparation method according to claim 1, wherein the mass ratio of the 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene to the phase transfer catalyst is 1000:5-250.
4. The method according to claim 1, wherein the molar ratio of 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene to calcium hydroxide is 10:10 to 18.
5. The method according to claim 1, wherein the molar ratio of 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene to magnesium oxide is 10:10 to 18.
6. The method according to claim 1, wherein the molar ratio of 2-nitro-3, 4-dichloro-6-trifluoromethyltoluene to triethylamine is 10:20 to 35.
7. The preparation method according to claim 1, wherein the hydrogenation reaction temperature is 40-150 ℃, the pressure is 0.3-2.0 MPa, and the time is 5-16 hours; after the hydrogenation reaction is completed, removing hydrogen in the reaction kettle to obtain a first mixture; and separating and purifying the first mixture to obtain the 2-methyl-3-trifluoromethyl aniline.
8. The method of claim 7, wherein the separation and purification comprises the steps of:
1) Standing and layering the first mixture, and collecting a first organic phase;
2) And distilling the first organic phase to obtain 2-methyl-3-trifluoromethyl aniline.
9. The method of claim 8, wherein the separation and purification comprises the steps of:
1) Standing and layering the first mixture, and collecting a first organic phase and a first aqueous phase;
2) Distilling the first organic phase to obtain 2-methyl-3-trifluoromethyl aniline;
3) Dropwise adding hydrochloric acid into the first water phase until the pH value is 6.5-7.5, and decoloring by using activated carbon to obtain a second water phase;
4) Concentrating the second aqueous phase under reduced pressure to obtain a first concentrate;
5) Adding methanol into the first concentrate, and filtering to obtain a filter cake;
6) And (5) drying the filter cake in vacuum to obtain a related product.
10. The method of claim 1, further comprising the steps of trichloromethylation, fluorination, and nitration:
trichloromethylation reaction: 3, 4-dichloro toluene reacts with carbon tetrachloride and aluminum trichloride to obtain 3, 4-dichloro-6-trichloromethyl toluene;
fluorination reaction: carrying out fluorination reaction on the 3, 4-dichloro-6-trichloromethyl toluene and anhydrous hydrogen fluoride to obtain 3, 4-dichloro-6-trifluoromethyl toluene;
nitration reaction: and (3) performing nitration reaction on the 3, 4-dichloro-6-trifluoromethyl toluene and nitric acid and sulfuric acid to obtain the 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene.
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