CN112409169A - Method for preparing polyfluorinated aromatic hydrocarbon - Google Patents
Method for preparing polyfluorinated aromatic hydrocarbon Download PDFInfo
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- CN112409169A CN112409169A CN202011381964.7A CN202011381964A CN112409169A CN 112409169 A CN112409169 A CN 112409169A CN 202011381964 A CN202011381964 A CN 202011381964A CN 112409169 A CN112409169 A CN 112409169A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/363—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by introduction of halogen; by substitution of halogen atoms by other halogen atoms
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
- B01J31/0235—Nitrogen containing compounds
- B01J31/0239—Quaternary ammonium compounds
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
- C07C17/20—Preparation of halogenated hydrocarbons by replacement by halogens of halogen atoms by other halogen atoms
- C07C17/202—Preparation of halogenated hydrocarbons by replacement by halogens of halogen atoms by other halogen atoms two or more compounds being involved in the reaction
- C07C17/208—Preparation of halogenated hydrocarbons by replacement by halogens of halogen atoms by other halogen atoms two or more compounds being involved in the reaction the other compound being MX
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
- B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
- B01J2231/4277—C-X Cross-coupling, e.g. nucleophilic aromatic amination, alkoxylation or analogues
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
Abstract
The invention discloses a method for preparing polyfluorinated aromatic hydrocarbon, which has a reaction formula as follows:
in the reactant, R1、R2、R3Are all groups on an aromatic ring, and are hydrogen or chlorine; r4Also a group on an aromatic ring, such as hydrogen, carboxyl, nitro, cyano, acyl and the like; in the product, R in the reactant1、R2、R3If it is chlorine, R is present in the product1、R2、R3Accordingly is fluorine, R4And is not changed. The catalyst is a chloride quaternary ammonium salt containing bispyrazoline. The method provides an efficient method for preparing the polyfluorinated aromatic compound with wide application and various structures.
Description
Technical Field
The invention belongs to the technical field of chemical production, and particularly relates to a preparation method of polyfluorinated aromatic hydrocarbon.
Background
Fluorine-containing compounds often exhibit unique physical and chemical properties, primarily due to the following properties of the fluorine atom: for example, fluorine is a small atom next to hydrogen in volume, has strong electronegativity, has a stronger bonding force with carbon than hydrogen and halogen atoms other than fluorine, and is bound by an electron cloud of fluorine, the bond distance of carbon-fluorine bonds is inflexible, the polarizability is low, the dispersion force of the interaction with other substance molecules is small, the hydrophobicity is large, and the lipophilicity is high. Therefore, the fluorine-containing compounds generally have better physiological activity. The introduction of fluorine atoms, especially a plurality of fluorine atoms, into aromatic compounds can obviously improve the stability and fat solubility of the compounds, change the electronic effect of compound molecules and improve the biological activity of the compounds, so that polyfluorinated aromatics have become important raw materials and intermediates of pesticide, medicine and dye industries and liquid crystal materials, such as trifluorobenzene used as medicine and liquid crystal material intermediates, tetrafluorobenzonitrile and tetrafluorotoluene used as intermediates of synthetic pyrethroid insecticides such as transfluthrin and tefluthrin, tetrafluorobenzoic acid used as an intermediate of fluoroquinolone medicines gatifloxacin, and 2, 4-difluoronitrobenzene used as an intermediate of diflunisal used for treating rheumatoid arthritis and osteoarthritis.
There are various methods for introducing fluorine atoms into aromatic compounds, among which the Balz-Schiemann method, the HF-diazotization method and the halogen exchange method are relatively well-established and sophisticated. However, the former two methods require a preparation process of diazotization and fluorination, and the preparation process needs the use of toxic reagents, so that diazonium salts are easy to explode, the process is unsafe, the route is long, the yield is low, the cost is high, and the industrial use is less. The halogen exchange fluorination method has the advantages of easily available raw materials, simple process and safety, and is a main industrial method for synthesizing fluorine-containing aromatic compounds in recent years.
Domestic and foreign documents report preparation methods of polyfluorinated aromatic hydrocarbon, generally adopt a halogen exchange method, namely monochlorinated aromatic hydrocarbon is taken as a substrate, KF is taken as a fluoro reagent, and monofluoro reaction is carried out under the action of a phase transfer catalyst, for example, trifluorobenzene adopts expensive 3, 5-difluorochlorobenzene as a raw material, so that the raw material is expensive and not easy to obtain, and industrialization is difficult to implement at low cost; the method for realizing the fluorination of a plurality of chlorine atoms in one step by using polychlorinated aromatic hydrocarbon as a substrate is also reported, the raw materials of the method are low in price and easy to obtain, but because the catalytic performance of the catalyst is not high enough, the plurality of chlorine atoms are difficult to replace by the fluorine atoms at the same time, so that byproducts such as monofluoroarene, difluoroaromatic hydrocarbon and the like can be generated, the byproducts and the product polyfluorinated aromatic hydrocarbon are difficult to separate, complicated post-treatment such as rectification is required, the process is complicated, the product purity is not high, and the method is not suitable for industrial production.
Disclosure of Invention
The invention aims to solve the technical problem of overcoming the defects that the prior art for preparing the polyfluorinated aromatic hydrocarbon shown in the formula (I) is not beneficial to industrial production, such as difficult acquisition of raw materials, high cost, easy generation of impurities, low yield, complex operation, poor process safety and the like, and provides an effective method for synthesizing the polyfluorinated aromatic hydrocarbon shown in the formula (I).
The technical scheme of the invention is summarized as follows:
adding the 1, 3-dichloroarene compound shown in the formula (II), potassium fluoride and a solvent into a reaction kettle, adding toluene, installing a water separation device, heating, refluxing and separating a small amount of water in a system, then adding PEG 6000 and a catalyst, reacting for a certain time at a certain temperature, and performing post-treatment to obtain the polyfluorinated arene shown in the formula (I).
The synthetic route is as follows:
in the reactant, R1、R2、R3Hydrogen and chlorine; r4Hydrogen, carboxyl, nitro, cyano, formyl, acetyl and the like; in the product, R in the reactant1、R2、R3If it is chlorine, R is present in the product1、R2、R3Accordingly is fluorine, R4And is not changed.
The catalyst is a bis-pyrazoline-containing quaternary ammonium chloride salt, and the structure of the catalyst is as follows:
wherein R is5And R6Is C1～C4Alkyl group of (1).
The catalyst is relatively simple to prepare, 1, 3-dimethyl-2-imidazolidinone reacts with triphosgene to obtain N, N-dimethyl imidazolidine chloride, then the dimethyl biguanide reacts with halohydrocarbon to obtain alkylated dimethyl biguanide, the two obtained compounds are mixed to carry out condensation reaction, and the condensation product reacts with sodium methoxide to obtain the bis-pyrazoline-containing quaternary ammonium salt.
The catalyst has high catalytic efficiency, and the using amount of the catalyst is only 2-8% of that of the compound shown in the formula (II), so that a plurality of chlorine atoms can be fluorinated simultaneously.
The catalyst is not required to be recycled, is directly recycled, is high in utilization rate and can be recycled for 4 times, and the yield is only reduced by 3-5%.
The heating temperature is 140-250 ℃.
The solvent is aprotic polar solvent such as sulfolane, 1, 3-dimethyl-2-imidazolidinone, DMF, DMSO, DMAC, N-methylpyrrolidone and the like, and most of the used solvents can be used repeatedly.
The method can convert the cheap and easily obtained polychlorinated aromatic hydrocarbon substrate into the polyfluorinated aromatic hydrocarbon in one step, and provides an efficient method for preparing the polyfluorinated aromatic hydrocarbon compound with wide application and various structures.
Detailed Description
The present invention will be further described with reference to the following examples; it should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention.
The starting materials or reagents used in the examples are, unless otherwise specified, commercially available.
Example 1
Preparation of 2,3,5, 6-tetrafluorobenzoic acid
The reaction formula is as follows:
6mol of potassium fluoride, 1mol of 2,3,5, 6-tetrachlorobenzoic acid, 500mL of sulfolane and 60mL of toluene are sequentially added into a reaction bottle provided with a water separator. Heating, stirring, refluxing and water dividing, opening a water divider switch after water dividing is finished, raising the temperature to completely evaporate toluene, wherein the evaporated toluene can be recycled. Slightly cooling, transferring the reaction mixture into a 1.5L reaction kettle, adding 5g of PEG 6000 and 0.06mol of catalyst, heating to 230 ℃ for reacting for 18h, starting a rectification column to receive a crude product of the 2,3,5, 6-tetrafluorobenzoic acid after reacting for 5h, and performing secondary rectification on the obtained crude product to obtain a product with the purity of 99%, wherein the yield is as follows: 86 percent.
After the reaction is finished, cooling and filtering, leaching a filter cake by sulfolane, and collecting filtrate containing the catalyst to be directly applied to the next batch of feed; the filter cake can be treated to recover white potassium chloride product.
Example 2
Preparation of 2,3,5, 6-tetrafluorobenzoic acid
0.9mol of 2,3,5, 6-tetrachlorobenzoic acid, 450mL of sulfolane recovered in example 1, 0.01mol of a catalyst, 4g of PEG 6000 and 5.5mol of potassium fluoride were sequentially added to a 1.5L reaction vessel, and the temperature was raised to 230 ℃ to react for 18 hours. Meanwhile, the rectification column receives a 2,3,5, 6-tetrafluorobenzoic acid crude product, and the obtained crude product is rectified for the second time to obtain a product with the purity of 99 percent, wherein the yield is as follows: 85 percent.
After the reaction is finished, cooling and filtering, leaching a filter cake by sulfolane, collecting filtrate containing the catalyst, and directly mechanically using the next batch of feed; the filter cake can be treated to recover white potassium chloride product.
Example 3
Preparation of sym-trifluorobenzene
The reaction formula is as follows:
4.5mol of potassium fluoride, 1mol of trichlorobenzene, 500mL of 1, 3-dimethyl-2-imidazolidinone and 60mL of toluene are sequentially added into a reaction bottle provided with a water separator. Heating, stirring, refluxing and water dividing, opening a water divider switch after water dividing is finished, raising the temperature to completely evaporate toluene, slightly cooling, transferring a reaction mixture into a 1.5L reaction kettle, adding 5g of PEG 6000 and 0.06mol of catalyst, and heating to 220 ℃ for reaction for 24 hours. After the reaction is finished, distilling at normal pressure, collecting fractions at 50-120 ℃ to obtain a crude product of trifluorobenzene, and performing secondary normal-pressure rectification on the obtained crude product to obtain a product with the purity of 99%, wherein the yield is as follows: 79 percent.
Combining the residue after rectification and the residue after the first distillation, filtering, leaching a filter cake by using 1, 3-dimethyl-2-imidazolidinone, and collecting the filtrate containing the catalyst to be directly applied to the next batch of feed; the filter cake can be treated to recover white potassium chloride product.
Example 4
Preparation of sym-trifluorobenzene
The filtrate containing the catalyst recovered in example 3 was directly used in the preparation of trifluorobenzene according to the experimental procedures of example 2 and example 3 to obtain the product with a purity of 99%, yield: 78.2 percent.
The residues after rectification and distillation are combined, and the filtrate containing the catalyst obtained after filtration can be reused for the next batch of feeding; the filter cake can be treated to recover white potassium chloride product.
Example 5
Preparation of 2, 4-difluoronitrobenzene
The reaction formula is as follows:
2.8mol of potassium fluoride, 1mol of 2, 4-dichloronitrobenzene, 400mL of 1, 3-dimethyl-2-imidazolidinone and 60mL of toluene are sequentially added into a reaction bottle provided with a water separator. Heating, stirring, refluxing and water dividing, opening a water divider switch after water dividing is finished, raising the temperature to completely evaporate toluene, slightly cooling, transferring a reaction mixture into a 1.5L reaction kettle, then adding 4.8g of PEG 6000 and 0.02mol of catalyst, heating to 140 ℃ for reaction for 3 hours, starting a rectifying column to receive a 2, 4-difluoronitrobenzene crude product after the reaction for 1.5 hours, and performing secondary rectification on the obtained crude product to obtain a product with the purity of 99%, wherein the yield is as follows: 93 percent.
After the reaction is finished, cooling and filtering, leaching a filter cake by using 1, 3-dimethyl-2-imidazolidinone, and collecting filtrate containing the catalyst to be directly applied to the next batch of feed; the filter cake can be treated to recover white potassium chloride product.
Claims (4)
1. A method for preparing polyfluorinated aromatic hydrocarbon is characterized in that the reaction formula of the preparation method is as follows:
in the reactant, R1、R2、R3Hydrogen and chlorine; r4Hydrogen, carboxyl, nitro, cyano, formyl and acetyl; in the product, R in the reactant1、R2、R3If it is chlorine, R is present in the product1、R2、R3Accordingly is fluorine, R4Hydrogen, carboxyl, nitro, cyano, formyl and acetyl;
the preparation steps are as follows: adding potassium fluoride, a polychlorinated aromatic hydrocarbon compound shown as a formula (II) and a solvent into a reaction kettle, adding toluene, installing a water separation device, heating, refluxing, removing a small amount of water in a system, evaporating the toluene, transferring the toluene into the reaction kettle, adding PEG 6000 and a catalyst, reacting for a certain time at a certain temperature, and performing post-treatment to obtain the polyfluorinated aromatic hydrocarbon shown as the formula (I);
the catalyst in the step is a chloride quaternary ammonium salt containing bispyrazoline, and the structure of the catalyst is as follows:
wherein R is5And R6Is C1～C4Alkyl group of (1).
2. The method for preparing polyfluoroaromatic hydrocarbon according to claim 1, wherein: the catalyst in the step has high catalytic efficiency, and the dosage of the catalyst is 2-8% of that of the compound substance in the formula (II).
3. The method for preparing polyfluoroaromatic hydrocarbon according to claim 1, wherein: the reaction temperature in the step is 140-250 ℃.
4. The method for preparing polyfluoroaromatic hydrocarbon according to claim 1, wherein: the solvent in the step is aprotic polar solvent sulfolane, 1, 3-dimethyl-2-imidazolidinone, DMF, DMSO, DMAC and N-methylpyrrolidone.
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| CN202011381964.7A CN112409169B (en) | 2020-12-01 | 2020-12-01 | Method for preparing polyfluoroaromatic hydrocarbon |
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| CN202011381964.7A CN112409169B (en) | 2020-12-01 | 2020-12-01 | Method for preparing polyfluoroaromatic hydrocarbon |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001058965A (en) * | 1999-08-20 | 2001-03-06 | Nippon Shokubai Co Ltd | Production of fluorinated aromatic compound |
| US6265627B1 (en) * | 1999-11-23 | 2001-07-24 | Sergei Mikhailovich Igumnov | Process for preparing polyfluoroaromatic compounds |
| CN105315142A (en) * | 2015-11-20 | 2016-02-10 | 扬州天辰精细化工有限公司 | Industrial production method for 2, 6-difluorobenzaldehyde |
| CN107141192A (en) * | 2017-05-09 | 2017-09-08 | 大连奇凯医药科技有限公司 | A kind of preparation method of equal trifluoro-benzene |
| CN111153779A (en) * | 2019-12-31 | 2020-05-15 | 浙江解氏新材料股份有限公司 | Efficient synthesis method of m-fluoroanisole |
-
2020
- 2020-12-01 CN CN202011381964.7A patent/CN112409169B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001058965A (en) * | 1999-08-20 | 2001-03-06 | Nippon Shokubai Co Ltd | Production of fluorinated aromatic compound |
| US6265627B1 (en) * | 1999-11-23 | 2001-07-24 | Sergei Mikhailovich Igumnov | Process for preparing polyfluoroaromatic compounds |
| CN105315142A (en) * | 2015-11-20 | 2016-02-10 | 扬州天辰精细化工有限公司 | Industrial production method for 2, 6-difluorobenzaldehyde |
| CN107141192A (en) * | 2017-05-09 | 2017-09-08 | 大连奇凯医药科技有限公司 | A kind of preparation method of equal trifluoro-benzene |
| CN111153779A (en) * | 2019-12-31 | 2020-05-15 | 浙江解氏新材料股份有限公司 | Efficient synthesis method of m-fluoroanisole |
Non-Patent Citations (1)
| Title |
|---|
| 梁飞: "药物中间体2，4-二氟苯甲酸的合成研究", 《中国优秀硕士学位论文全文数据库》 * |
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