CN102603531A - Method for preparing 2,3,4,5-tetrafluoro methyl benzoate in series reaction - Google Patents
Method for preparing 2,3,4,5-tetrafluoro methyl benzoate in series reaction Download PDFInfo
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- 238000006243 chemical reaction Methods 0.000 title claims abstract description 78
- 238000000034 method Methods 0.000 title claims abstract description 56
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 title abstract 8
- 229940095102 methyl benzoate Drugs 0.000 title abstract 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 39
- 239000007787 solid Substances 0.000 claims abstract description 28
- 239000003054 catalyst Substances 0.000 claims abstract description 26
- 239000002608 ionic liquid Substances 0.000 claims abstract description 14
- 238000002360 preparation method Methods 0.000 claims abstract description 14
- 230000032050 esterification Effects 0.000 claims abstract description 7
- 238000005886 esterification reaction Methods 0.000 claims abstract description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 30
- MAEQYZYOSFAUAF-UHFFFAOYSA-N methyl 2,3,4,5-tetrafluorobenzoate Chemical class COC(=O)C1=CC(F)=C(F)C(F)=C1F MAEQYZYOSFAUAF-UHFFFAOYSA-N 0.000 claims description 24
- -1 2,3,4,5-tetrachloro-phthalic acid acid anhydride Chemical class 0.000 claims description 18
- MMZYCBHLNZVROM-UHFFFAOYSA-N 1-fluoro-2-methylbenzene Chemical compound CC1=CC=CC=C1F MMZYCBHLNZVROM-UHFFFAOYSA-N 0.000 claims description 11
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 claims description 10
- 229910001512 metal fluoride Inorganic materials 0.000 claims description 9
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 claims description 9
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 239000011775 sodium fluoride Substances 0.000 claims description 4
- 235000013024 sodium fluoride Nutrition 0.000 claims description 4
- IQQRAVYLUAZUGX-UHFFFAOYSA-N 1-butyl-3-methylimidazolium Chemical compound CCCCN1C=C[N+](C)=C1 IQQRAVYLUAZUGX-UHFFFAOYSA-N 0.000 claims description 3
- 238000004334 fluoridation Methods 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 150000007522 mineralic acids Chemical class 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- 238000006114 decarboxylation reaction Methods 0.000 abstract description 3
- 238000003912 environmental pollution Methods 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 238000001816 cooling Methods 0.000 abstract description 2
- 239000012847 fine chemical Substances 0.000 abstract description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- NCXZQUNDWVKMGX-UHFFFAOYSA-N 5,6,7,7a-tetrachloro-3ah-2-benzofuran-1,3-dione Chemical compound ClC1=C(Cl)C(Cl)=CC2C(=O)OC(=O)C21Cl NCXZQUNDWVKMGX-UHFFFAOYSA-N 0.000 abstract 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 abstract 1
- 238000003682 fluorination reaction Methods 0.000 abstract 1
- 239000002585 base Substances 0.000 description 20
- 238000010523 cascade reaction Methods 0.000 description 8
- 238000009835 boiling Methods 0.000 description 7
- 238000004821 distillation Methods 0.000 description 7
- 239000003513 alkali Substances 0.000 description 5
- 229960001545 hydrotalcite Drugs 0.000 description 5
- 229910001701 hydrotalcite Inorganic materials 0.000 description 5
- WRWPPGUCZBJXKX-UHFFFAOYSA-N 1-fluoro-4-methylbenzene Chemical compound CC1=CC=C(F)C=C1 WRWPPGUCZBJXKX-UHFFFAOYSA-N 0.000 description 4
- GDVKFRBCXAPAQJ-UHFFFAOYSA-A dialuminum;hexamagnesium;carbonate;hexadecahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Al+3].[Al+3].[O-]C([O-])=O GDVKFRBCXAPAQJ-UHFFFAOYSA-A 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- GSDSWSVVBLHKDQ-UHFFFAOYSA-N 9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=C2)=O)=C3N2C(C)COC3=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- GSDSWSVVBLHKDQ-JTQLQIEISA-N Levofloxacin Chemical compound C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-JTQLQIEISA-N 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000007210 heterogeneous catalysis Methods 0.000 description 2
- 229960002422 lomefloxacin Drugs 0.000 description 2
- ZEKZLJVOYLTDKK-UHFFFAOYSA-N lomefloxacin Chemical compound FC1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNC(C)C1 ZEKZLJVOYLTDKK-UHFFFAOYSA-N 0.000 description 2
- YIXJRHPUWRPCBB-UHFFFAOYSA-N magnesium nitrate Chemical compound [Mg+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O YIXJRHPUWRPCBB-UHFFFAOYSA-N 0.000 description 2
- 229960001699 ofloxacin Drugs 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 229960004954 sparfloxacin Drugs 0.000 description 2
- DZZWHBIBMUVIIW-DTORHVGOSA-N sparfloxacin Chemical compound C1[C@@H](C)N[C@@H](C)CN1C1=C(F)C(N)=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1F DZZWHBIBMUVIIW-DTORHVGOSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- BNGXYYYYKUGPPF-UHFFFAOYSA-M (3-methylphenyl)methyl-triphenylphosphanium;chloride Chemical compound [Cl-].CC1=CC=CC(C[P+](C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 BNGXYYYYKUGPPF-UHFFFAOYSA-M 0.000 description 1
- DBAYTBHFIAGLLO-UHFFFAOYSA-N 1-methyl-3-nonyl-2h-imidazole Chemical compound CCCCCCCCCN1CN(C)C=C1 DBAYTBHFIAGLLO-UHFFFAOYSA-N 0.000 description 1
- WZHHYIOUKQNLQM-UHFFFAOYSA-N 3,4,5,6-tetrachlorophthalic acid Chemical compound OC(=O)C1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1C(O)=O WZHHYIOUKQNLQM-UHFFFAOYSA-N 0.000 description 1
- FRFSUUWVTVDAJG-UHFFFAOYSA-N 3-fluoro-1h-quinolin-2-one Chemical class C1=CC=C2NC(=O)C(F)=CC2=C1 FRFSUUWVTVDAJG-UHFFFAOYSA-N 0.000 description 1
- 229910001051 Magnalium Inorganic materials 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000000975 co-precipitation Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000004020 conductor Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229960003376 levofloxacin Drugs 0.000 description 1
- 239000004973 liquid crystal related substance Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 239000011973 solid acid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229920003002 synthetic resin Polymers 0.000 description 1
- 239000000057 synthetic resin Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000003245 working effect Effects 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention discloses a method for preparing 2,3,4,5-tetrafluoro methyl benzoate in series reaction, belonging to the technical field of fine chemical synthesis. The method comprises the following steps: carrying out fluorination reaction at 20-150 DEG C for 1-15 hours using ionic liquid, fluoride, a solid base catalyst and 2,3,4,5-tetrachlorophthalic anhydride, cooling the reaction solution to room temperature after the reaction is complete, adding methanol to perform esterification and decarboxylation reaction, and carrying out post treatment to obtain 2,3,4,5-tetrafluoro methyl benzoate. The preparation method provided by the invention uses ionic liquid and magnetic solid base catalyst, and performs series reaction between various components; the method is simple in operation, convenient in post treatment, good in technical performance, and low in environmental pollution; the yield of the obtained 2,3,4,5-tetrafluoro methyl benzoate is above 92%, and the content is >= 99.2%. The method is a green chemical synthesis technology and is suitable for industrialized production.
Description
Technical field
The invention belongs to technical field of fine chemical synthesis, be specifically related to a kind of method that heterogeneous catalysis cascade reaction technology prepares methyl 4-fluorobenzene of in ion liquid medium, using.
Background technology
2; 3; 4; The 5-methyl 4-fluorobenzene is a kind of important pharmaceutical intermediate, be mainly used in synthetic third generation QNS (lomefloxacin (lomefloxacin), Ofloxacine USP 23 (ofloxacin), the 4th generation QNS (RWJ 25213-097 (levofloxacin), sparfloxacin (sparfloxacin).Also be widely used in synthetic resins, electro-conductive material and liquid crystal material etc.The synthetic the earliest of methyl 4-fluorobenzene can be traced back to the twenties in last century, mainly is that raw material is respectively through imide route (comprise imidization, fluoridize, hydrolysis, decarboxylation and esterification five steps reaction) and through synthetic the making of chloride route (comprise hydrolysis, chloride, fluoridize, hydrolysis, decarboxylation and esterification) with the tetrachlorophthalic acid.But above-mentioned operational path is long, and cost is high, and environmental pollution is bigger.Along with the growth of fluoro-carbostyril class pharmaceutical requirements amount, at present State Planning Commission and national medical general bureau in " " eight or five " national levelization doctor series products tackle key problems guide ", clearly to adopt tetrafluorobenzoic aid and ester compound be that the new technology route of main raw material is the developing trend of national new drug.Therefore it is simple and direct to develop a reaction process, and flow process is short, pollutes little, with low cost methyl 4-fluorobenzene synthetic route, and making it as early as possible, large-scale industrial production has important social meaning and economic worth.
Summary of the invention
To the problems referred to above that exist in the prior art, the object of the present invention is to provide a kind of method that heterogeneous catalysis cascade reaction technology prepares methyl 4-fluorobenzene of in ion liquid medium, using.
Described a kind of series process prepares the method for 2,3,4,5 tetra fluoro benzoic acid methyl esters, it is characterized in that comprising the steps:
1) described 2,3,4,5 tetra fluoro benzoic acid methyl esters, 2,3,4,5-tetrachloro-phthalic acid acid anhydride and ionic liquid are respectively shown in formula I, formula II and formula III:
（Ⅰ） （Ⅱ） （Ⅲ）
2) in reaction flask, add successively ionic liquid shown in formula III, fluorizating agent, solid base catalyst and shown in formula II 2,3,4,5-tetrachloro-phthalic acid acid anhydride is 20 ℃-150 ℃ in temperature
Carried out fluoridation 1-15 hour, reaction is cooled to room temperature with reaction solution after finishing; Add methyl alcohol again and carry out esterification and decarboxylic reaction, after reaction finishes, through aftertreatment obtain title product shown in formula I 2; 3,4, the 5-methyl 4-fluorobenzene; Described fluorizating agent is an alkaline metal fluoride cpd, and described esterification and decarboxylic reaction temperature are 30 ℃-100 ℃; Reaction times is 1-15 hour.
Described a kind of series process preparation 2,3,4; The method of 5-methyl 4-fluorobenzene; It is characterized in that step 2) described alkaline metal fluoride cpd is any one in Potassium monofluoride, Sodium Fluoride or the cesium fluoride, 2,3; 4, the molar ratio of 5-tetrachloro-phthalic acid acid anhydride and alkaline metal fluoride cpd is 1:4-15.
Described a kind of series process prepares the method for 2,3,4,5 tetra fluoro benzoic acid methyl esters, it is characterized in that step 2) described ionic liquid is 3-Methylimidazole inorganic acid salt or 1-alkyl-3-Methylimidazole inorganic acid salt [Bmim] shown in formula III
+L
-, R is that H or carbon atom quantity are the alkyl of 1-18 in the formula, L is BF
4, PF
6, OA
COr a kind of among the OH, its consumption is 2,3,4, the 1-20 of 5-tetrachloro-phthalic acid acid anhydride quality is doubly.
Described a kind of series process prepares the method for 2,3,4,5 tetra fluoro benzoic acid methyl esters, it is characterized in that step 2) described solid base catalyst is magnetic solid base catalyst, its consumption is 2,3,4, the 1-20% of 5-tetrachloro-phthalic acid acid anhydride mass percent.
Described a kind of series process prepares the method for 2,3,4,5 tetra fluoro benzoic acid methyl esters, it is characterized in that step 2) described post-treating method is for to use extracted in toluene with reaction solution, again through distill the 2,3,4,5 tetra fluoro benzoic acid methyl esters.
Described a kind of series process prepares the method for 2,3,4,5 tetra fluoro benzoic acid methyl esters, it is characterized in that step 2) described methyl alcohol and 2,3,4, the molar ratio 1-5:1 of 5-tetrachloro-phthalic acid acid anhydride.
Described a kind of series process prepares the method for 2,3,4,5 tetra fluoro benzoic acid methyl esters, it is characterized in that step 2) described alkaline metal fluoride cpd is Potassium monofluoride.
Described a kind of series process preparation 2; 3; 4, the method for 5-methyl 4-fluorobenzene is characterized in that step 2) described in ionic liquid be 1-alkyl-3-methyl imidazolium tetrafluoroborate; Wherein alkyl is that carbon atom quantity is the alkyl of 1-18, is preferably 1-butyl-3-methyl imidazolium tetrafluoroborate or 1-ethyl-3-methyl imidazolium tetrafluoroborate.
Described a kind of series process prepares the method for 2,3,4,5 tetra fluoro benzoic acid methyl esters, it is characterized in that step 2) consumption of described solid base catalyst is 2,3,4, the 5-15% of 5-tetrachloro-phthalic acid acid anhydride mass percent.
Described a kind of series process preparation 2; 3,4, the method for 5-methyl 4-fluorobenzene; The preparation method who it is characterized in that described magnetic solid base catalyst is following: the magnetic solid base that magnetic mg_al hydrotalcite makes; Be magnesium aluminum-hydrotalcite to be carried out magnetic modify, make it have magnetic and catalysis dual-use function, reach the purpose that improves catalytic activity.Particularly, the preparation method of described magnetic solid base catalyst is following: get a certain amount of magnetic colloidal sol and join in the reaction flask, add zero(ppm) water again; Stirring at room, magnesium nitrate and the aluminum nitrate getting the magnalium ratio and be 1: 2 are mixed with solution, and other joins the sodium hydroxide solution of pH=10-13; Two kinds of solution are added in the reaction flask; 110 ℃ of stirrings, washing and drying makes magnetic mg_al hydrotalcite, forms magnetic solid base 450～500 ℃ of high-temperature roastings then.Magnetic colloidal sol is to adopt chemical coprecipitation, with Fe
3+And Fe
2+Vitriol or muriate in excessive alkali, mix to stir in the ratio of 1:1 and make.Specifically can be with reference to the 29th volume the 3rd phase (in March, 2002) " preparation of magnetic mg_al hydrotalcite solid alkali and sign " of applicating technology.
Reaction equation of the present invention is following:
Compound method of the present invention is preparation according to the following steps specifically: with 1 mole 2,3,4, and 5-tetrachloro-benzoic acid acid anhydride, 4-15 mole metal fluorochemical; Quality is 2,3,4; 5-tetrachloro-phthalic acid acid anhydride 1-20 ionic liquid doubly, quality is 2,3 of 1-20%; 4, the magnetic solid base catalyst of 5-tetrachloro-phthalic acid acid anhydride quality adds in the reaction flask successively, carries out fluoridation 1-15 hour at 20 ℃-150 ℃ earlier; Then,, add the methyl alcohol of 1-5 mole again with reaction solution cooling, 30 ℃-100 ℃ reactions 1-15 hour, after reaction finishes, with reaction solution with extracted in toluene after, distill the 2,3,4,5 tetra fluoro benzoic acid methyl esters.
Through adopting above-mentioned technology, compared with prior art, beneficial effect of the present invention is following:
1) the present invention is through replacing the liquid alkali catalyst catalyse organic reaction not only can reduce pollution with solid base catalyst; Can also increase activity of such catalysts and selectivity; Simultaneously through reclaiming (regeneration) and reusing the work-ing life of improving catalyzer; Be to realize an eco-friendly important channel, solid acid alkali catalytic has become one of main contents of Green Chemistry research;
2) the present invention is through adopting many group cascade reactions; Cascade reaction is claimed the domino reaction again, is meant the process that under identical conditions, forms two keys or multikey, and next step reaction of this process is after last single step reaction; Therefore cascade reaction is the process of differentiating in a reaction times; The polycomponent cascade reaction has very big meliority with synthetic the comparing of changes traditional step, and it can reduce reactions step greatly, saves the loaded down with trivial details sepn process of a lot of complicacies;
3) the present invention as solvent, is the fluid cpds of being made up of ion fully with ionic liquid, compare with organic solvent have non-volatile; Nonflammable explosive, organism and inorganics there are good solubility, reaction can be carried out at homogeneous phase; Stable to water and air; Be convenient to operation and processing, be prone to reclaim, but also catalysis is quickened the process of chemical reaction and improved the selectivity of reaction;
4) the present invention has used ionic liquid and magnetic solid base catalyst in reaction process, and various ingredients is carried out cascade reaction, and is simple to operate; Convenient post-treatment, technological performance, environmental pollution is little, obtain 2; 3,4,5-methyl 4-fluorobenzene yield is up to more than 92%; Content >=99.2% is a kind of Green Chemistry synthetic technology, is suitable for suitability for industrialized production.
Embodiment
Below in conjunction with specific embodiment the present invention is described further, but protection scope of the present invention is not limited to this.
Embodiment 1: with 2,3,4, and 5-tetrachloro-benzoic acid acid anhydride 286 grams (1 mole), Potassium monofluoride 232 grams (4 moles); 1-butyl-3-methyl imidazolium tetrafluoroborate 858 grams, magnetic solid base catalyst 14.3 grams that embodiment 1 makes add in the reaction flask,, after 5 hours reaction solution are cooled off 80 ℃ of reactions; Add methyl alcohol 96 grams (2 moles), 60 ℃ of reactions 10 hours, after reaction finishes, with reaction solution with extracted in toluene after; After the distillation, get 2,3,4; 5-methyl 4-fluorobenzene 199 grams, yield 96%, boiling point 220-249 ℃, fusing point 126-128 ℃.Content >=99.5%.
The solid base catalyst that uses among the present invention is magnetic solid base catalyst, and its preparation method is with reference to the 29th volume the 3rd phase (in March, 2002) " preparation of magnetic mg_al hydrotalcite solid alkali and sign " of applicating technology.
In the present embodiment, it is 2,3 that metal fluoride uses mole number; 4; 5-tetrachloro-phthalic acid acid anhydride 4-15 Sodium Fluoride or cesium fluoride doubly replaces Potassium monofluoride, and it is 2,3 that ionic liquid uses consumption; 4, the 1-20 of 5-tetrachloro-phthalic acid acid anhydride quality 3-Methylimidazole inorganic acid salt or 1-alkyl-3-Methylimidazole inorganic acid salt [Bmim] doubly
+L
-, R is that H or carbon atom quantity are the alkyl of 1-18 in the formula, L is BF
4, PF
6, OA
COr a kind of replacement 1-butyl-3-methyl imidazolium tetrafluoroborate among the OH, all can obtain same effect.
Embodiment 2: with 2,3,4, and 5-tetrachloro-benzoic acid acid anhydride 286 grams (1 mole), Sodium Fluoride 630 grams; 1-amyl group-3-Methylimidazole hexafluorophosphate 5720 grams, magnetic solid base catalyst 42.9 grams add in the reaction flask, after 15 hours, reaction solution are cooled to room temperature 20 ℃ of reactions; Add methyl alcohol 160 grams (5 moles), 30 ℃ of reactions 15 hours, after reaction finishes, with reaction solution with extracted in toluene after, after the distillation; Get 2,3,4,5 tetra fluoro benzoic acid methyl esters 194.8 grams; Yield 94%, boiling point 220-249 ℃, fusing point 126-128 ℃, content 99.3%.
Embodiment 3: with 2,3,4, and 5-tetrachloro-benzoic acid acid anhydride 286 grams (1 mole), cesium fluoride 608 grams (4 moles); 1-nonyl-3-N-Methylimidazoleacetic salt 5000 grams, magnetic solid base catalyst 2.86 grams add in the reaction flask,, after 2 hours reaction solution are cooled off 150 ℃ of reactions; Add methyl alcohol 32 grams (1 mole), 100 ℃ of reactions 1 hour, after reaction finishes, with reaction solution with extracted in toluene after, after the distillation; Get 2,3,4,5 tetra fluoro benzoic acid methyl esters 190.7 grams; Yield 92%, boiling point 220-249 ℃, fusing point 126-128 ℃, content 99.2%.
Embodiment 4: with 2,3,4, and 5-tetrachloro-benzoic acid acid anhydride 286 grams (1 mole), Potassium monofluoride 580 grams (10 moles); 1-nonyl-3-Methylimidazole subsalt 2860 grams, magnetic solid base catalyst 30 grams add in the reaction flask,, after 10 hours reaction solution are cooled off 90 ℃ of reactions; Add methyl alcohol 960 grams (3 moles), 70 ℃ of reactions 8 hours, after reaction finishes, with reaction solution with extracted in toluene after, after the distillation; Get 2,3,4,5 tetra fluoro benzoic acid methyl esters 203 grams; Yield 98%, boiling point 220-249 ℃, fusing point 126-128 ℃, content 99.7%.
Embodiment 5: with 2,3,4, and 5-tetrachloro-benzoic acid acid anhydride 286 grams (1 mole), cesium fluoride 630 grams (15 moles); 1-ethyl-3-methyl imidazolium tetrafluoroborate 45 grams, magnetic solid base catalyst 57.6 grams add in the reaction flask,, after 15 hours reaction solution are cooled off 60 ℃ of reactions; Add methyl alcohol 160 grams (5 moles), 60 ℃ of reactions 15 hours, after reaction finishes, with reaction solution with extracted in toluene after, after the distillation; Get 2,3,4,5 tetra fluoro benzoic acid methyl esters 197 grams; Yield 95%, boiling point 220-249 ℃, fusing point 126-128 ℃, content 99.6%.
Embodiment 6: with 2,3,4, and 5-tetrachloro-benzoic acid acid anhydride 286 grams (1 mole), Potassium monofluoride 378 grams (9 moles); 1-tridecyl-3-methyl imidazolium tetrafluoroborate 3432 grams, magnetic solid base catalyst 34.3 grams add in the reaction flask,, after 8 hours reaction solution are cooled off 90 ℃ of reactions; Add methyl alcohol 128 grams (4 moles), 70 ℃ of reactions 9 hours, after reaction finishes, with reaction solution with extracted in toluene after, after the distillation; Get 2,3,4,5 tetra fluoro benzoic acid methyl esters 201 grams; Yield 97%, boiling point 220-249 ℃, fusing point 126-128 ℃, content 99.7%.
Embodiment 7: with 2,3,4, and 5-tetrachloro-benzoic acid acid anhydride 286 grams (1 mole), Potassium monofluoride 378 grams (9 moles); 1-butyl-3-methyl imidazolium tetrafluoroborate 2860 grams, magnetic solid base catalyst 28.6 grams add in the reaction flask,, after 8 hours reaction solution are cooled off 90 ℃ of reactions; Add methyl alcohol 128 grams (4 moles), 70 ℃ of reactions 10 hours, after reaction finishes, with reaction solution with extracted in toluene after, after the distillation; Get 2,3,4,5 tetra fluoro benzoic acid methyl esters 201 grams; Yield 97%, boiling point 220-249 ℃, fusing point 126-128 ℃, content 99.6%.
Claims (9)
1. a series process prepares the method for 2,3,4,5 tetra fluoro benzoic acid methyl esters, it is characterized in that comprising the steps:
1) described 2,3,4,5 tetra fluoro benzoic acid methyl esters, 2,3,4,5-tetrachloro-phthalic acid acid anhydride and ionic liquid are respectively shown in formula I, formula II and formula III:
（Ⅰ） （Ⅱ） （Ⅲ）
2) in reaction flask, add successively ionic liquid shown in formula III, fluorizating agent, solid base catalyst and shown in formula II 2,3,4,5-tetrachloro-phthalic acid acid anhydride is 20 ℃-150 ℃ in temperature
Carried out fluoridation 1-15 hour, reaction is cooled to room temperature with reaction solution after finishing; Add methyl alcohol again and carry out esterification and decarboxylic reaction, after reaction finishes, through aftertreatment obtain title product shown in formula I 2; 3,4, the 5-methyl 4-fluorobenzene; Described fluorizating agent is an alkaline metal fluoride cpd, and described esterification and decarboxylic reaction temperature are 30 ℃-100 ℃; Reaction times is 1-15 hour.
2. a kind of series process preparation 2,3,4 according to claim 1; The method of 5-methyl 4-fluorobenzene; It is characterized in that step 2) described alkaline metal fluoride cpd is any one in Potassium monofluoride, Sodium Fluoride or the cesium fluoride, 2,3; 4, the molar ratio of 5-tetrachloro-phthalic acid acid anhydride and alkaline metal fluoride cpd is 1:4-15.
3. a kind of series process preparation 2 according to claim 1; 3; 4, the method for 5-methyl 4-fluorobenzene is characterized in that step 2) described ionic liquid is 3-Methylimidazole inorganic acid salt or 1-alkyl-3-Methylimidazole inorganic acid salt [Bmim] shown in formula III
+L
-, R is that H or carbon atom quantity are the alkyl of 1-18 in the formula, L is BF
4, PF
6, OA
COr a kind of among the OH, its consumption is 2,3,4, the 1-20 of 5-tetrachloro-phthalic acid acid anhydride quality is doubly.
4. a kind of series process preparation 2,3,4 according to claim 1; The method of 5-methyl 4-fluorobenzene is characterized in that step 2) described solid base catalyst is magnetic solid base catalyst, its consumption is 2; 3,4, the 1-20% of 5-tetrachloro-phthalic acid acid anhydride mass percent.
5. a kind of series process according to claim 1 prepares the method for 2,3,4,5 tetra fluoro benzoic acid methyl esters, it is characterized in that step 2) described post-treating method is for to use extracted in toluene with reaction solution, again through distill the 2,3,4,5 tetra fluoro benzoic acid methyl esters.
6. a kind of series process according to claim 1 prepares the method for 2,3,4,5 tetra fluoro benzoic acid methyl esters, it is characterized in that step 2) described methyl alcohol and 2,3,4, the molar ratio 1-5:1 of 5-tetrachloro-phthalic acid acid anhydride.
7. a kind of series process according to claim 2 prepares the method for 2,3,4,5 tetra fluoro benzoic acid methyl esters, it is characterized in that step 2) described alkaline metal fluoride cpd is Potassium monofluoride.
8. a kind of series process preparation 2 according to claim 3; 3; 4, the method for 5-methyl 4-fluorobenzene is characterized in that step 2) described in ionic liquid be 1-alkyl-3-methyl imidazolium tetrafluoroborate; Wherein alkyl is that carbon atom quantity is the alkyl of 1-18, is preferably 1-butyl-3-methyl imidazolium tetrafluoroborate or 1-ethyl-3-methyl imidazolium tetrafluoroborate.
9. a kind of series process according to claim 4 prepares the method for 2,3,4,5 tetra fluoro benzoic acid methyl esters, it is characterized in that step 2) consumption of described solid base catalyst is 2,3,4, the 5-15% of 5-tetrachloro-phthalic acid acid anhydride mass percent.
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| CN106565421A (en) * | 2016-11-08 | 2017-04-19 | 岳阳中科华昂精细化工科技有限公司 | Preparation method of 2,3,5,6-tetrafluorohydrazine-1,4-benzene dimethanol |
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| CN1112105A (en) * | 1993-09-18 | 1995-11-22 | 赫彻斯特股份公司 | Method for preparation 3-hydroxy-2,4,5-trifluorbenzoealkyl formate and/or 3-alkoxy-2,4,5-trifluorbenzoealkyformate |
| CN1265644A (en) * | 1997-08-01 | 2000-09-06 | 拜尔公司 | Method for preparing 3-cyano-2,4-dihalogen-5-flour-benzoic acid |
| CN1335301A (en) * | 1996-02-23 | 2002-02-13 | 拜尔公司 | 3-cyano-2, 4, 5-trifluorobenzoic acid and derivatives thereof and application thereof |
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| CN1112105A (en) * | 1993-09-18 | 1995-11-22 | 赫彻斯特股份公司 | Method for preparation 3-hydroxy-2,4,5-trifluorbenzoealkyl formate and/or 3-alkoxy-2,4,5-trifluorbenzoealkyformate |
| CN1335301A (en) * | 1996-02-23 | 2002-02-13 | 拜尔公司 | 3-cyano-2, 4, 5-trifluorobenzoic acid and derivatives thereof and application thereof |
| CN1265644A (en) * | 1997-08-01 | 2000-09-06 | 拜尔公司 | Method for preparing 3-cyano-2,4-dihalogen-5-flour-benzoic acid |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN106565421A (en) * | 2016-11-08 | 2017-04-19 | 岳阳中科华昂精细化工科技有限公司 | Preparation method of 2,3,5,6-tetrafluorohydrazine-1,4-benzene dimethanol |
| CN106565421B (en) * | 2016-11-08 | 2019-04-26 | 岳阳中科华昂精细化工科技有限公司 | A kind of preparation method of 2,3,5,6-tetrafluoro-1,4-benzenedimethanol |
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