CN108911944A - The preparation method of 2,4 dichloro fluorobenzene - Google Patents
The preparation method of 2,4 dichloro fluorobenzene Download PDFInfo
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- CN108911944A CN108911944A CN201810741733.9A CN201810741733A CN108911944A CN 108911944 A CN108911944 A CN 108911944A CN 201810741733 A CN201810741733 A CN 201810741733A CN 108911944 A CN108911944 A CN 108911944A
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- dichlorofluorobenzene
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/361—Preparation of halogenated hydrocarbons by reactions involving a decrease in the number of carbon atoms
- C07C17/363—Preparation of halogenated hydrocarbons by reactions involving a decrease in the number of carbon atoms by elimination of carboxyl groups
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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
- C07C51/16—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation
- C07C51/21—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation with molecular oxygen
- C07C51/23—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation with molecular oxygen of oxygen-containing groups to carboxyl groups
- C07C51/245—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation with molecular oxygen of oxygen-containing groups to carboxyl groups of keto groups or secondary alcohol groups
Abstract
The invention discloses a kind of preparation methods of 2,4-Dichlorofluorobenzene, include the following steps：（1）It is raw material using the chloro- 3- fluoro acetophenone of 2,6- bis-, above-mentioned raw materials is put into solvent, solvent one kind selected from the following：Sulfolane, formic acid and acetic acid, the dosage 1g of solvent:1~5mL；Dioxygen oxidation reacts to obtain the chloro- 3- fluobenzoic acid of 2,6- bis- under the catalysis of mantoquita；（2）By step（1）The obtained chloro- 3- fluoro acetophenone of 2,6- bis- obtains 2,4-Dichlorofluorobenzene through decarboxylation in the presence of catalyst DBU and mantoquita.The present invention can solve the method for how recycling 2,4 dichloro fluorobenzene.
Description
Technical field
The invention discloses a kind of preparation methods of 2,4-Dichlorofluorobenzene, belong to chemical intermediate preparation method technology
Field, using industrial production 2, the by-product 2 of the chloro- 5- fluoro acetophenone by-product of 4- bis-, the chloro- 3- fluoro acetophenone of 6- bis- is raw material,
Dioxygen oxidation obtains the chloro- 3- fluobenzoic acid of 2,6- bis- under the catalysis of mantoquita；Then the chloro- 3- fluobenzoic acid of 2,6- bis- that will be obtained
Mild decarboxylation obtains 2,4 dichloro fluorobenzene in the presence of DBU catalyst.The method of the present invention, oxidation step is using in air
Oxygen makees oxidant, environmentally protective, at low cost；For decarboxylic reaction step DBU as catalyst, reaction condition is relatively mild,
Simple process, it is easy to operate；The present invention is suitable for industrialized production, and can improve the city of product with recycled for multiple times
Field competitiveness.
Background technique
2,4 dichloro fluorobenzene（No. CAS：1435-48-9）, structure such as formula（Ⅰ）It is shown, it is in the important chemicals of one kind
Mesosome can be used for producing in the drugs such as methods for quinolones antibacterial agents fleraxacin, pefloxacin, Ciprofloxacin and Norfloxacin key
Mesosome, it can also be used to liquid crystal product raw material.
The disclosed preparation method in relation to 2,4-Dichlorofluorobenzene both at home and abroad, is mainly the following：（1）Using fluorobenzene as raw material, warp
2,4-Dichlorofluorobenzene is made in nitrification, two step of chlorination, and the route technique is more stable, high income, but fluorobenzene raw material valence is high.（2）With right
Nitro-chlorobenzene is raw material, and through chlorination, fluorination, 2,4-Dichlorofluorobenzene, process stabilizing is made in three step of chlorination again, but total recovery is not high.
（3）Using 2,4-dinitrochlorobenzene as raw material, perfluorinated, 2 step of chlorination is made 2,4-Dichlorofluorobenzene, raw material dinitrofluorobenzene valence compared with
Low, total recovery is higher, but technique is dangerous, the report to explode when once having high-temperature fluorination.（4）Using o-dichlorohenzene as raw material,
2,4-Dichlorofluorobenzene is prepared through nitrification, fluorination, three step of chlorination, which is used by many enterprises.
Summary of the invention
The object of the present invention is to provide a kind of preparation methods of 2,4-Dichlorofluorobenzene, solve how to recycle 2,4-Dichlorofluorobenzene
Method.
The preparation method of 2,4-Dichlorofluorobenzene, includes the following steps：
（1）It is raw material using the chloro- 3- fluoro acetophenone of 2,6- bis-, above-mentioned raw materials is put into solvent, solvent one kind selected from the following：
Sulfolane, formic acid and acetic acid, the dosage 1g of solvent:1~5mL；Dioxygen oxidation reacts to obtain 2,6- bis- under the catalysis of mantoquita
Chloro- 3- fluobenzoic acid；
（2）By step（1）The obtained chloro- 3- fluoro acetophenone of 2,6- bis- obtains 2 through decarboxylation in the presence of catalyst DBU and mantoquita,
4- dichlor fluorbenzene, reaction route are as follows：
。
The step（1）In, the reaction temperature is 50~80 DEG C, and the reaction time is 1~3h.
The step（1）In, the copper salt catalyst is selected from lower one or several kinds：Copper sulphate, copper chloride, protochloride
Copper, copper acetate, trifluoroacetic acid copper and copper trifluoromethanesulfcomposite, the dosage of catalyst are the quality of the chloro- 3- fluoro acetophenone of 2,6- bis-
1%~20%.
The step（1）In, after the oxidation reaction, filter out solid product 2, the chloro- 3- fluobenzoic acid of 6- bis-,
The mixed system recycled of catalysts and solvents.
The step（2）In, solvent one kind selected from the following：Sulfolane, imidazole quinoline, quinoline, isoquinolin and
Tri-n-butylamine, the dosage 1g of solvent:1~5mL.
The step（2）In, the reaction temperature is 60~100 DEG C, and the reaction time is 3~6h.
The step（2）In, the catalyst is selected from lower one or several kinds：DBU, that is, 1,8- diazabicyclo
[5.4.0] 11 carbon -7- alkene, copper oxide, cuprous oxide, copper acetate, trifluoroacetic acid copper and copper trifluoromethanesulfcomposite.Catalyst DBU
Dosage be 1eqv, the dosage of catalyst mantoquita is the 1%~20% of the quality of the chloro- 3- fluobenzoic acid of 2,6- bis-.
The step（2）In, after the decarboxylic reaction, it is evaporated under reduced pressure out 2,4-Dichlorofluorobenzene, catalyst and molten
The mixed system recycled of agent.
Compared with the existing technology, its advantages are embodied in the present invention：
（1）The chloro- 3- fluoro acetophenone of 2,6- bis- is the by-product for producing the chloro- 5- fluoro acetophenone of 2,4- bis-；To produce 2,4-
The by-product of two chloro- 5- fluoro acetophenones is raw material, and the recycling of by-product reduces the discharge of waste, cheap and easy to get, is even more become
Waste be changed into values, improves the competitiveness of product in market, is conducive to industrialization large-scale production；
（2）Two-step reaction condition involved in synthetic route is milder, easy to operate, high income；
（3）Organic solvent boiling point used in two-step reaction involved in synthetic route is all higher, and evaporation loss is few, and can be with
Recycled is effectively reduced the discharge of pollutant, has saved cost, protects environment；
（4）It is the recycling of by-product using the present invention compared to traditional 2,4-Dichlorofluorobenzene synthetic method, raw material is easy to get, and produces
The advantages of product high income.
Specific embodiment
The present embodiment first preparation to the chloro- 3- fluobenzoic acid of 2,6- bis-, then prepared by 2,4-Dichlorofluorobenzene.
Embodiment 1
In tetra- mouthfuls of reaction flasks of 1000mL, solvent glacial acetic acid 200mL, 10.0g copper acetate, the chloro- 3- fluorobenzene of 207g 2,6- bis- is added
Ethyl ketone is passed through the oxygen of 2 atm, and stirring is warming up to 70 DEG C, reacts 2h, and reaction terminates cooling, filters to obtain trifluoroacetophenone
201g, yield 96.2%.
In tetra- mouthfuls of reaction flasks of 1000mL, addition solvent quinoline 200mL, 10.0g copper acetate, 152.2g DBU, 209g 2,
The chloro- 3- fluobenzoic acid of 6- bis-, is vigorously stirred, and is warming up to 80 DEG C, reacts 2h, depressurizes whole 2,4-Dichlorofluorobenzene out after reaction,
Obtain 151.8g, yield 92.0%.
Embodiment 2
In tetra- mouthfuls of reaction flasks of 1000mL, solvent glacial acetic acid 200mL, 10.0g copper acetate, the chloro- 3- fluorobenzene of 207g 2,6- bis- is added
Ethyl ketone is passed through the oxygen of 2 atm, and stirring is warming up to 70 DEG C, reacts 2h, and reaction terminates cooling, filters to obtain trifluoroacetophenone
201g, yield 96.2%.
In tetra- mouthfuls of reaction flasks of 1000mL, addition solvent quinoline 200mL, 10.0g copper acetate, 152.2g DBU, 209g 2,
The chloro- 3- fluobenzoic acid of 6- bis-, is vigorously stirred, and is warming up to 90 DEG C, reacts 2h, depressurizes whole 2,4-Dichlorofluorobenzene out after reaction,
Obtain 157.7g, yield 95.6%.
Embodiment 3
In tetra- mouthfuls of reaction flasks of 1000mL, solvent glacial acetic acid 200mL, 10.0g copper acetate, the chloro- 3- fluorobenzene of 207g 2,6- bis- is added
Ethyl ketone is passed through the air of 2 atm, and stirring is warming up to 70 DEG C, reacts 2h, and reaction terminates cooling, filters to obtain trifluoroacetophenone
156g, yield 74.6%.
In tetra- mouthfuls of reaction flasks of 1000mL, addition solvent quinoline 200mL, 10.0g copper acetate, 152.2g DBU, 209g 2,
The chloro- 3- fluobenzoic acid of 6- bis-, is vigorously stirred, and is warming up to 80 DEG C, reacts 2h, depressurizes whole 2,4-Dichlorofluorobenzene out after reaction,
Obtain 151.8g, yield 92.0%.
Embodiment 4
In tetra- mouthfuls of reaction flasks of 1000mL, solvent glacial acetic acid 200mL, 10.0g copper acetate, the chloro- 3- fluorobenzene of 207g 2,6- bis- is added
Ethyl ketone is passed through the air of 2 atm, and stirring is warming up to 70 DEG C, reacts 2h, and reaction terminates cooling, filters to obtain trifluoroacetophenone
156g, yield 74.6%.
In tetra- mouthfuls of reaction flasks of 1000mL, addition solvent quinoline 200mL, 10.0g copper acetate, 152.2g DBU, 209g 2,
The chloro- 3- fluobenzoic acid of 6- bis-, is vigorously stirred, and is warming up to 90 DEG C, reacts 2h, depressurizes whole 2,4-Dichlorofluorobenzene out after reaction,
Obtain 157.7g, yield 95.6%.
Embodiment 5
In tetra- mouthfuls of reaction flasks of 1000mL, solvent glacial acetic acid 200mL, 10.0g copper acetate, the chloro- 3- fluorobenzene of 207g 2,6- bis- is added
Ethyl ketone is passed through the air of 10 atm, and stirring is warming up to 70 DEG C, reacts 2h, and reaction terminates cooling, filters to obtain trifluoroacetophenone
201g, yield 96.2%.
In tetra- mouthfuls of reaction flasks of 1000mL, addition solvent quinoline 200mL, 10.0g copper acetate, 152.2g DBU, 209g 2,
The chloro- 3- fluobenzoic acid of 6- bis-, is vigorously stirred, and is warming up to 80 DEG C, reacts 2h, depressurizes whole 2,4-Dichlorofluorobenzene out after reaction,
Obtain 151.8g, yield 92.0%.
Embodiment 6
In tetra- mouthfuls of reaction flasks of 1000mL, solvent glacial acetic acid 200mL, 10.0g copper acetate, the chloro- 3- fluorobenzene of 207g 2,6- bis- is added
Ethyl ketone is passed through the air of 10 atm, and stirring is warming up to 70 DEG C, reacts 2h, and reaction terminates cooling, filters to obtain trifluoroacetophenone
201g, yield 96.2%.
In tetra- mouthfuls of reaction flasks of 1000mL, addition solvent quinoline 200mL, 10.0g copper acetate, 152.2g DBU, 209g 2,
The chloro- 3- fluobenzoic acid of 6- bis-, is vigorously stirred, and is warming up to 90 DEG C, reacts 2h, depressurizes whole 2,4-Dichlorofluorobenzene out after reaction,
Obtain 157.7g, yield 95.6%.
Claims (8)
- The preparation method of 1.2,4- dichlor fluorbenzenes, includes the following steps：It is characterized in that：（1）Utilize the chloro- 3- fluorophenethyl of 2,6- bis- Ketone is raw material, and above-mentioned raw materials are put into solvent, solvent one kind selected from the following：Sulfolane, formic acid and acetic acid, the dosage of solvent 1g :1~5mL；Dioxygen oxidation reacts to obtain the chloro- 3- fluobenzoic acid of 2,6- bis- under the catalysis of mantoquita；（2）By step（1）The obtained chloro- 3- fluoro acetophenone of 2,6- bis- obtains 2 through decarboxylation in the presence of catalyst DBU and mantoquita, 4- dichlor fluorbenzene, reaction route are as follows：。
- 2. the preparation method of 2,4-Dichlorofluorobenzene according to claim 1, it is characterised in that：The step（1）In, institute The reaction temperature stated is 50~80 DEG C, and the reaction time is 1~3h.
- 3. the preparation method of 2,4-Dichlorofluorobenzene according to claim 1, it is characterised in that：The step（1）In, institute The copper salt catalyst stated is selected from lower one or several kinds：Copper sulphate, copper chloride, stannous chloride, copper acetate, trifluoroacetic acid copper and three Fluorine copper methane sulfonate, the dosage of catalyst are the 1%~20% of the quality of the chloro- 3- fluoro acetophenone of 2,6- bis-.
- 4. the preparation method of 2,4-Dichlorofluorobenzene according to claim 1, it is characterised in that：The step（1）In, institute After the oxidation reaction stated, solid product 2, the chloro- 3- fluobenzoic acid of 6- bis- are filtered out, the mixed system of catalysts and solvents follows Ring set is used.
- 5. the preparation method of 2,4-Dichlorofluorobenzene according to claim 1, it is characterised in that：The step（2）In, institute The solvent stated one kind selected from the following：Sulfolane, imidazole quinoline, quinoline, isoquinolin and tri-n-butylamine, the dosage 1g of solvent:1~ 5mL。
- 6. the preparation method of 2,4-Dichlorofluorobenzene according to claim 1, it is characterised in that：The step（2）In, institute The reaction temperature stated is 60~100 DEG C, and the reaction time is 3~6h.
- 7. the preparation method of 2,4-Dichlorofluorobenzene according to claim 1, it is characterised in that：The step（2）In, institute The catalyst stated is selected from lower one or several kinds：11 carbon -7- alkene of DBU, that is, 1,8- diazabicyclo [5.4.0], copper oxide, oxygen Change cuprous, copper acetate, trifluoroacetic acid copper and copper trifluoromethanesulfcomposite, the dosage of catalyst DBU is 1eqv, the dosage of catalyst mantoquita It is the 1%~20% of the quality of the chloro- 3- fluobenzoic acid of 2,6- bis-.
- 8. the preparation method of 2,4-Dichlorofluorobenzene according to claim 1, it is characterised in that：The step（2）In, institute After the decarboxylic reaction stated, it is evaporated under reduced pressure out 2,4-Dichlorofluorobenzene, the mixed system recycled of catalysts and solvents.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2020248278A1 (en) * | 2019-06-14 | 2020-12-17 | 吉林凯莱英医药化学有限公司 | Method for continuous synthesis of substituted benzoic-acid organic substance |
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| CN101851237A (en) * | 2010-06-18 | 2010-10-06 | 南方医科大学 | spiro compounds, method for preparing same and application thereof |
| CN108002968A (en) * | 2016-10-31 | 2018-05-08 | 中国科学院大连化学物理研究所 | A kind of method that ketone compounds oxidation scission carbon-carbon bond prepares carboxylic acid compound |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2020248278A1 (en) * | 2019-06-14 | 2020-12-17 | 吉林凯莱英医药化学有限公司 | Method for continuous synthesis of substituted benzoic-acid organic substance |
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