CN104610035B - A kind of method preparing high-purity 4,4 '-difluoro benzophenone - Google Patents
A kind of method preparing high-purity 4,4 '-difluoro benzophenone Download PDFInfo
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- CN104610035B CN104610035B CN201410856102.3A CN201410856102A CN104610035B CN 104610035 B CN104610035 B CN 104610035B CN 201410856102 A CN201410856102 A CN 201410856102A CN 104610035 B CN104610035 B CN 104610035B
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- difluoro benzophenone
- fluorotoluene
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- 238000000034 method Methods 0.000 title claims abstract description 32
- LSQARZALBDFYQZ-UHFFFAOYSA-N 4,4'-difluorobenzophenone Chemical compound C1=CC(F)=CC=C1C(=O)C1=CC=C(F)C=C1 LSQARZALBDFYQZ-UHFFFAOYSA-N 0.000 title claims abstract description 15
- 238000006243 chemical reaction Methods 0.000 claims abstract description 37
- WRWPPGUCZBJXKX-UHFFFAOYSA-N 1-fluoro-4-methylbenzene Chemical compound CC1=CC=C(F)C=C1 WRWPPGUCZBJXKX-UHFFFAOYSA-N 0.000 claims abstract description 14
- 238000002360 preparation method Methods 0.000 claims abstract description 14
- 238000006482 condensation reaction Methods 0.000 claims abstract description 12
- 239000000463 material Substances 0.000 claims abstract description 12
- 150000001263 acyl chlorides Chemical class 0.000 claims abstract description 7
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 7
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 7
- 230000000977 initiatory effect Effects 0.000 claims abstract description 5
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 23
- RAAGZOYMEQDCTD-UHFFFAOYSA-N 2-fluorobenzoyl chloride Chemical compound FC1=CC=CC=C1C(Cl)=O RAAGZOYMEQDCTD-UHFFFAOYSA-N 0.000 claims description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- 239000000047 product Substances 0.000 claims description 17
- BBYDXOIZLAWGSL-UHFFFAOYSA-N 4-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C=C1 BBYDXOIZLAWGSL-UHFFFAOYSA-N 0.000 claims description 16
- 239000007787 solid Substances 0.000 claims description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 15
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 12
- 239000003054 catalyst Substances 0.000 claims description 12
- PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical compound FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 claims description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
- 238000004821 distillation Methods 0.000 claims description 9
- 239000012043 crude product Substances 0.000 claims description 8
- 230000006837 decompression Effects 0.000 claims description 7
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 5
- 150000002460 imidazoles Chemical class 0.000 claims description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
- 238000007254 oxidation reaction Methods 0.000 claims description 4
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims description 3
- 238000001953 recrystallisation Methods 0.000 claims description 3
- -1 triphosgene acyl chloride Chemical class 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 2
- 230000003197 catalytic effect Effects 0.000 claims description 2
- 230000003647 oxidation Effects 0.000 claims description 2
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 claims description 2
- 239000002994 raw material Substances 0.000 abstract description 10
- 239000004696 Poly ether ether ketone Substances 0.000 abstract description 7
- 229920002530 polyetherether ketone Polymers 0.000 abstract description 7
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 3
- 230000007613 environmental effect Effects 0.000 abstract description 3
- BWQOPMJTQPWHOZ-UHFFFAOYSA-N (2,3-difluorophenyl)-phenylmethanone Chemical class FC1=CC=CC(C(=O)C=2C=CC=CC=2)=C1F BWQOPMJTQPWHOZ-UHFFFAOYSA-N 0.000 abstract 1
- 238000001914 filtration Methods 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 8
- 238000001514 detection method Methods 0.000 description 8
- 239000002904 solvent Substances 0.000 description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
- 239000000376 reactant Substances 0.000 description 6
- JUPQTSLXMOCDHR-UHFFFAOYSA-N benzene-1,4-diol;bis(4-fluorophenyl)methanone Chemical compound OC1=CC=C(O)C=C1.C1=CC(F)=CC=C1C(=O)C1=CC=C(F)C=C1 JUPQTSLXMOCDHR-UHFFFAOYSA-N 0.000 description 4
- 238000006555 catalytic reaction Methods 0.000 description 4
- KZTYYGOKRVBIMI-UHFFFAOYSA-N diphenyl sulfone Chemical compound C=1C=CC=CC=1S(=O)(=O)C1=CC=CC=C1 KZTYYGOKRVBIMI-UHFFFAOYSA-N 0.000 description 4
- 230000000630 rising effect Effects 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 238000009795 derivation Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 150000004702 methyl esters Chemical class 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 2
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000007797 corrosion Effects 0.000 description 2
- 238000005260 corrosion Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- VTVKDANZRKHNCP-UHFFFAOYSA-N fluorobenzene formyl chloride Chemical compound C(=O)Cl.FC1=CC=CC=C1 VTVKDANZRKHNCP-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- JQSAYKKFZOSZGJ-UHFFFAOYSA-N 1-[bis(4-fluorophenyl)methyl]-4-[(2,3,4-trimethoxyphenyl)methyl]piperazine Chemical compound COC1=C(OC)C(OC)=CC=C1CN1CCN(C(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 JQSAYKKFZOSZGJ-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 229920000049 Carbon (fiber) Polymers 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 229910002666 PdCl2 Inorganic materials 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 238000000297 Sandmeyer reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- OBDOVFRMEYHSQB-UHFFFAOYSA-N almitrine Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)N1CCN(C=2N=C(NCC=C)N=C(NCC=C)N=2)CC1 OBDOVFRMEYHSQB-UHFFFAOYSA-N 0.000 description 1
- 229960005039 almitrine Drugs 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
- 239000012965 benzophenone Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000004917 carbon fiber Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 229910001882 dioxygen Inorganic materials 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000012777 electrically insulating material Substances 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 229960003750 ethyl chloride Drugs 0.000 description 1
- SMANXXCATUTDDT-QPJJXVBHSA-N flunarizine Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)N1CCN(C\C=C\C=2C=CC=CC=2)CC1 SMANXXCATUTDDT-QPJJXVBHSA-N 0.000 description 1
- 229960000326 flunarizine Drugs 0.000 description 1
- 238000003682 fluorination reaction Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 238000009413 insulation Methods 0.000 description 1
- 229950007692 lomerizine Drugs 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229920000090 poly(aryl ether) Polymers 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 239000012779 reinforcing material Substances 0.000 description 1
- 231100000004 severe toxicity Toxicity 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Substances [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
- C07C45/46—Friedel-Crafts reactions
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/58—Preparation of carboxylic acid halides
- C07C51/60—Preparation of carboxylic acid halides by conversion of carboxylic acids or their anhydrides or esters, lactones, salts into halides with the same carboxylic acid part
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention discloses one and prepare high-purity 4, the method of 4 ' difluoro benzophenones, with p-fluorotoluene as initiation material, oxidized reaction, acyl chloride reaction, condensation reaction finally give target product 4,4 ' difluoro benzophenones, the fusing point of this product is 107 DEG C 109 DEG C, and purity >=99.9% meets the purity requirement of synthesis of polyether-ether-ketone (PEEK).And in the preparation technology of the present invention, raw materials used cheap and easy to get, synthetic technological condition is gentle, and reagent used in building-up process, relative to environmental protection, has broad application prospects and industrial value.
Description
Technical field
The present invention relates to the preparation field of fluoro-containing intermediate, be specifically related to one and prepare high-purity 4, the method for 4 '-difluoro benzophenone.
Background technology
4,4 '-difluoro benzophenone is a kind of important fluoro-containing intermediate, be synthesis Drugs Containing Fluorine flunarizine, lomerizine, almitrine important
Intermediate, particularly application are that it is the monomer of special high-performance PEEK (PEEK), in chemistry and military industry field, and polyethers
Ether ketone (PEEK) belongs to speciality polymer material.There is the physical and chemical performances such as high temperature resistant, chemical resistance corrosion, be that a class can be used as high temperature resistant knot
Structure material and electrically insulating material, compound with glass fibre or carbon fiber can prepare reinforcing material.General use with the condensation of aromatic dicarboxylic phenol obtained by one
Class polyarylether class high polymer.By 4,4'-difluoro benzophenone, hydroquinone and sodium carbonate are raw material, prepare with diphenyl sulphone (DPS) for solvent synthesis.
At present the route about the open report of 4,4 '-difluoro benzophenone is a lot, mainly has following several: (1) patent EP 178184 report with
Fluorobenzene and be raw material to fluorobenzoyl chloride, prepares product under the catalysis of aluminum chloride, and the method yield is higher, and the purity of product is the most of a relatively high,
But the high expensive that the raw material of reaction is to fluorobenzoyl chloride, is unfavorable for industrialized production；(2) Chinese Journal of Pharmaceuticals, 40 (10), 737-738；2009
With fluorobenzene as raw material, under the directly catalysis of phosgene and aluminum chloride, obtain product, but isomer 2 in product, and the content of 4 '-difluoro benzophenone is relatively
Height, in addition phosgene severe toxicity, this route yield is the most on the low side；(3) Hebei University of Science and Technology's journal, 29 (1), 20-22；2008 report with fluorobenzene as raw material,
Carbon tetrachloride generates 4 under the catalysis of aluminum chloride, 4 '-difluorodiphenyl dichloromethane, then obtains product, the method operation letter through hydrolyzed under acidic conditions
Single, but by-product isomer 2, and 4 '-difluoro benzophenone is more, is unfavorable for purifying, and yield is the most on the low side；(4) patent JP 61221146 is with fluorobenzene
For raw material, in the presence of CO with air, with PdCl2And FeCl3Carrying out reacting prepared product for catalyst, temperature and pressure is required relatively by this reaction
Height, and the catalysis of reaction is the most relatively expensive, is difficult to realize industrialized cost control；(5) patent US 4453009 reports with 4,4 '-dichloro two
Benzophenone is initiation material, prepares 4 through KF fluorination, and 4 '-difluoro benzophenone, the method raw material is difficult to preparation, and converts not exclusively, is not easy to obtain
To the satisfactory product of purity；(6) patent EP 0004710 reports with 4,4 '-MDA as initiation material, with NaNO2And HF
4 are prepared through sandmeyer reaction, 4 '-difluoro-diphenylmethane, then aoxidize under nitric acid low temperature, this route industrialized production, but the response time is long,
Equipment corrosion is serious, there is the limitation such as dangerous hidden danger of blast in addition.
Summary of the invention
The present invention is in order to overcome defect and the deficiency of prior art, it is provided that a kind of cheaper starting materials is easy to get, and synthetic technological condition is gentle, institute in building-up process
Reagent relative to environmental protection, the one that reaction yield is high prepares high-purity 4, the method for 4 '-difluoro benzophenone.
Technical scheme provides one and prepares high-purity 4, and the method for 4 '-difluoro benzophenone is with p-fluorotoluene as initiation material, oxidized
Reaction, acyl chloride reaction, condensation reaction finally give target product 4,4 '-difluoro benzophenone, including following synthesis step:
1) oxidation reaction, with hydrobromic acid as catalyst, generates parafluorobenzoic acid by p-fluorotoluene photochemical catalytic oxidation in the presence of hydrogen peroxide；
2) acyl chloride reaction, adds 1 by above-mentioned parafluorobenzoic acid, in 2-dichloroethanes, prepares fluorobenzoyl chloride through Solid triphosgene acyl chloride reaction；
3) condensation reaction, with aluminum chloride as catalyst, by above-mentioned to fluorobenzoyl chloride and fluorobenzene condensation reaction, obtains 4,4 '-difluoro benzophenone
Crude product；
4) purifying products, by above-mentioned 4,4 '-difluoro benzophenone crude product, through decompression distillation, obtains white plates brilliant in methanol after recrystallization.
The method provided according to technique scheme, light-catalysed light source is selected from electric filament lamp, uviol lamp or natural light.
According to technique scheme provide method, step 1) described in reaction temperature be 50 DEG C-100 DEG C, the response time is 4h-7h.
The method provided according to technique scheme, step 1) described in reaction p-fluorotoluene, hydrogen peroxide, the ratio of amount of hydrobromic material be
1:2.5-5:0.1。
The method provided according to technique scheme, step 2) described in catalyst selected from imidazoles, triethylamine and ethamine or pyridine.
The method provided according to technique scheme, the reaction temperature of described acyl chloride reaction is 40 DEG C-80 DEG C, and the response time is 3h-8h.
The method provided according to technique scheme, step 2) in Solid triphosgene, the ratio of amount of material of parafluorobenzoic acid be 1:1.5-2.5.
The method provided according to technique scheme, the reaction temperature of condensation reaction is 25 DEG C-80 DEG C, and the response time is 2h-6h.
The method provided according to technique scheme, is 1:1.05-2:1 to fluorobenzoyl chloride, fluorobenzene, the ratio of amount of material of aluminum chloride in condensation reaction.
In some embodiments of the invention, decompression distillation is to obtain white solid after insulation in 110 DEG C of deep fat condensing tubes.
The water used in embodiments of the present invention is deionized water.
Terminology used in the present invention "or" represents alternative, if appropriate, can they be combined, say, that term "or" includes often
Individual listed independent alternative and combinations thereof.Such as, " described catalyst is selected from imidazoles, triethylamine and ethamine or pyridine " represents and urges
Agent can be the one among imidazoles, triethylamine, diethylamine or pyridine, it is also possible to be its more than one combination.
The most in contrast, otherwise, all scopes that the present invention quotes include end value.Such as, " the reaction temperature of described condensation reaction
Degree is 25 DEG C-80 DEG C ", represent that temperature T is in the range of 25 DEG C≤T≤80 DEG C.
The beneficial effects of the present invention is:
Present invention optimizes existing synthetic route, have selected the route synthesis 4 of an environmental protection, 4 '-difluoro benzophenone, is former with p-fluorotoluene
Expect oxidized, chloride, to be condensed to yield fusing point be 107 DEG C-109 DEG C, the 4 of purity >=99.9%, 4 '-difluoro benzophenone product, the purity of this product
Meet the purity requirement of synthesis of polyether-ether-ketone (PEEK).
In the preparation technology of the present invention, raw materials used cheap and easy to get, synthetic technological condition is gentle, the relatively green ring of reagent used in building-up process
Protect, have broad application prospects and industrial value.
Detailed description of the invention
The following stated is the preferred embodiment of the present invention, and what the present invention was protected is not limited to following preferred embodiment.It should be pointed out that, for this
For the technical staff in field on the basis of these innovation and creation are conceived, the some deformation made and improvement, broadly fall into protection scope of the present invention.Real
Executing raw material used in example all can be by being either commercially available.
Embodiment 1
The preparation of parafluorobenzoic acid:
Equipped with stirring, thermometer, reflux condenser round-bottomed flask in, be sequentially added into p-fluorotoluene 220g (2.0mol), hydrobromic acid 34g
(0.2mol), slowly rise high-temperature to after 75 DEG C, open electric filament lamp and give light source and irradiate.Start to drip 30% hydrogen peroxide 680g (6.0mol),
Drip complete in 3 hours, keep thermotonus 6 hours.Bromine color in question response system is taken off substantially, and vapor detection p-fluorotoluene converts completely,
It is cooled to room temperature, the product of reaction is poured in frozen water, have a large amount of white solid to separate out, i.e. obtain parafluorobenzoic acid about 266g through sucking filtration.Yield
95.1%.
Preparation to fluorobenzoyl chloride:
Weigh solid phosgene (BTC) 89.1g (0.3mol) and parafluorobenzoic acid 63g (0.45mol) in there-necked flask, add solvent 1.2-bis-
Ethyl chloride 500mL, adds catalyst of triethylamine 0.3g (0.003mol), and slowly the temperature of rising reaction is to 60 DEG C, and reaction 4 is little at this temperature
Time, reactant liquor, through filtering, removes solvent, after obtain fluorobenzoyl chloride about 60g, yield 95.1% through decompression distillation.
The preparation of 4,4 '-difluoro benzophenone:
Equipped with stirring, condenser, drying tube, thermometer round-bottomed flask in, be sequentially added into fluorobenzene 40.3g (0.42mol) under room temperature and to fluorobenzene
Formyl chloride 62.8g (0.4mol), opens stirring, is at room temperature dividedly in some parts aluminum trichloride (anhydrous) 53.2g (0.4mol), adds (every in four batches
Secondary addition about 1/4th), add after aluminum chloride completes and at room temperature react, maintain thermotonus 3 hours, vapor detection is to fluorobenzoyl chloride
(add and change into the detection of parafluorobenzoic acid derivation of methyl ester method in methanol) converts completely, terminates reaction.Reactant liquor is poured slowly in frozen water, has big
Amount solid separates out, and sucking filtration obtains crude product 83.2g, yield 94.5%.
Embodiment 2
The preparation of parafluorobenzoic acid:
Equipped with stirring, thermometer, reflux condenser round-bottomed flask in, be sequentially added into p-fluorotoluene 220g (2.0mol), hydrobromic acid 34g
(0.2mol), slowly rising high-temperature to after 100 DEG C, reaction is transferred under sunlight, gives to irradiate under sun nature light.Start to drip 30% dioxygen
Water 567g (5.0mol), drips complete in 3 hours, keep thermotonus 6 hours.Bromine color in question response system is taken off substantially, and gas phase is examined
Survey p-fluorotoluene to convert completely, be cooled to room temperature, the product of reaction is poured in frozen water, have a large amount of white solid to separate out, i.e. obtain fluorine through sucking filtration
Benzoic acid about 261g.Yield 93.2%.
Preparation to fluorobenzoyl chloride:
Weigh solid phosgene (BTC) 89.1g (0.3mol) and parafluorobenzoic acid 84g (0.6mol) in there-necked flask, add solvent 1.2-dichloro
Ethane 500mL, adds catalyst pyridine 0.24g (0.003mol), and slowly the temperature of rising reaction is to 60 DEG C, at this temperature reaction 4 hours,
Reactant liquor, through filtering, removes solvent, after obtain fluorobenzoyl chloride about 75.8g, yield 80.1% through decompression distillation.
The preparation of 4,4 '-difluoro benzophenone:
Equipped with stirring, condenser, drying tube, thermometer round-bottomed flask in, be sequentially added into fluorobenzene 57.6g (0.6mol) under room temperature and to fluorobenzene
Formyl chloride 62.8g (0.4mol), opens stirring, is at room temperature dividedly in some parts aluminum trichloride (anhydrous) 53.2g (0.4mol), adds in four batches (every time
Add about 1/4th), add liter high-temperature after aluminum chloride completes and, to 35 DEG C, maintain thermotonus 3 hours, vapor detection is to fluorobenzoyl chloride
(add and change into the detection of parafluorobenzoic acid derivation of methyl ester method in methanol) converts completely, terminates reaction.Reactant liquor is poured slowly in frozen water, has big
Amount solid separates out, and sucking filtration obtains crude product 85g, yield 96.5%.
Embodiment 3
Preparation to fluorobenzoyl chloride:
Equipped with stirring, thermometer, reflux condenser round-bottomed flask in, be sequentially added into p-fluorotoluene 220g (2.0mol), hydrobromic acid 34g (0.2
Mol), slowly rise high-temperature to after 50 DEG C, open uviol lamp, give and light source irradiates.Start to drip 30% hydrogen peroxide 1134g (10.0mol),
Drip complete in 3 hours, keep thermotonus 6 hours.Bromine color in question response system is taken off substantially, and vapor detection p-fluorotoluene converts completely,
It is cooled to room temperature, the product of reaction is poured in frozen water, have a large amount of white solid to separate out, i.e. obtain parafluorobenzoic acid about 269g through sucking filtration.Yield
96.8%.
Preparation to fluorobenzoyl chloride:
Weigh solid phosgene (BTC) 89.1g (0.3mol) and parafluorobenzoic acid 105g (0.75mol) in there-necked flask, add solvent 1.2-
Dichloroethanes 500mL, adds catalyst imidazoles 0.2g (0.003mol), and slowly the temperature of rising reaction is to 60 DEG C, and reaction 4 is little at this temperature
Time, reactant liquor, through filtering, removes solvent, after obtain fluorobenzoyl chloride about 100.6g, yield 85.0% through decompression distillation.
The preparation of 4,4 '-difluoro benzophenone:
Equipped with stirring, condenser, drying tube, thermometer round-bottomed flask in, be sequentially added into fluorobenzene 77g (0.8mol) under room temperature and to fluorobenzene first
Acyl chlorides 62.8g (0.4mol), opens stirring, is at room temperature dividedly in some parts aluminum trichloride (anhydrous) 53.2g (0.4mol), adds in four batches (every time
Add about 1/4th), add liter high-temperature after aluminum chloride completes and, to 80 DEG C, maintain thermotonus 3 hours, vapor detection is to fluorobenzoyl chloride
(add and change into the detection of parafluorobenzoic acid derivation of methyl ester method in methanol) converts completely, terminates reaction.Reactant liquor is poured slowly in frozen water, has big
Amount solid separates out, and sucking filtration obtains crude product 81g, yield 91%.
Embodiment 4
Purifying products
Equipped with condensing tube, above-mentioned crude product is added by the round-bottomed flask of still head, carries out decompression distillation, condensing tube is passed through 110 DEG C of flowing deep fats,
Prevent blocking.Distillation obtains white solid, and white solid distillation obtained adds recrystallization in methanol, obtains the 4 of white, 4 '-difluoro benzophenone
Flat crystal, purity more than 99.9%, fusing point 107 DEG C-109 DEG C.
Claims (2)
1. prepare 4 for one kind, the method for 4 '-difluoro benzophenone, it is characterised in that with p-fluorotoluene as initiation material, oxidized reaction, chloride
React, condensation reaction finally gives target product 4,4 '-difluoro benzophenone, including following synthesis step:
1) oxidation reaction, with hydrobromic acid as catalyst, generates parafluorobenzoic acid by p-fluorotoluene photochemical catalytic oxidation in the presence of hydrogen peroxide；
2) acyl chloride reaction, adds 1 by above-mentioned parafluorobenzoic acid, in 2-dichloroethanes, in the presence of a catalyst with Solid triphosgene acyl chloride reaction system
Must be to fluorobenzoyl chloride；
3) condensation reaction, with aluminum chloride as catalyst, by above-mentioned to fluorobenzoyl chloride and fluorobenzene condensation reaction, obtains 4,4 '-difluoro benzophenone
Crude product；
4) purifying products, by above-mentioned 4,4 '-difluoro benzophenone crude product, through decompression distillation, obtains white plates brilliant in methanol after recrystallization；
Described in wherein: step 1), in reaction, the ratio of the amount of p-fluorotoluene, hydrogen peroxide, hydrobromic material is 1:2.5-5:0.1；
Described light-catalysed light source is selected from electric filament lamp, uviol lamp or natural light；
Step 1) described in reaction temperature be 50 DEG C-100 DEG C, the response time is 4h-7h；
Step 2) in Solid triphosgene, the ratio of amount of parafluorobenzoic acid material be 1:1.5-2.5；
The reaction temperature of described acyl chloride reaction is 40 DEG C-80 DEG C, and the response time is 3h-8h；
The reaction temperature of described condensation reaction is 25 DEG C-80 DEG C, and the response time is 2h-6h；
Described condensation reaction is 1:1.05-2:1 to fluorobenzoyl chloride, fluorobenzene, the ratio of amount of material of aluminum chloride.
Preparation method the most according to claim 1, it is characterised in that step 2) described in catalyst selected from imidazoles, triethylamine, two
At least one in ethamine, pyridine.
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| CN105669462A (en) * | 2016-03-23 | 2016-06-15 | 叶芳 | 3-Hydroxyl-4-nitrobenzoic acid and preparation method thereof |
| CN107793313A (en) * | 2016-08-31 | 2018-03-13 | 江苏万隆科技有限公司 | The synthetic method of tetrachloro chlorobenzoyl chloride |
| CN107793312A (en) * | 2016-08-31 | 2018-03-13 | 江苏万隆科技有限公司 | The preparation method of 2,3,4,5 tetrachloro chlorobenzoyl chlorides |
| CN108610245A (en) * | 2018-05-22 | 2018-10-02 | 江苏万隆化学有限公司 | A kind of preparation method of high-purity difluoro benzophenone |
| CN111440058A (en) * | 2020-03-29 | 2020-07-24 | 吉林省中研高分子材料股份有限公司 | Preparation method of high-purity 4, 4' -difluorobenzophenone |
| CN112479839A (en) * | 2020-12-01 | 2021-03-12 | 维讯化工（南京）有限公司 | Method for reducing fluorobenzophenone isomer |
| CN113666818B (en) * | 2021-08-13 | 2024-03-08 | 吉林省中研高分子材料股份有限公司 | 4,4' -difluorobenzophenone, preparation method and application |
| CN113956141A (en) * | 2021-11-09 | 2022-01-21 | 济源市恒顺新材料有限公司 | Method for producing difluorobenzophenone |
| CN114292169A (en) * | 2022-01-04 | 2022-04-08 | 浙江三美化工股份有限公司 | Method for synthesizing 4,4' -difluorobenzophenone by fluorobenzene |
| CN115231992A (en) * | 2022-06-30 | 2022-10-25 | 济南鼎皓医药科技有限公司 | Preparation method of (2-chloro-5-iodophenyl) (4-fluorophenyl) ketone |
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