CN107141212B - Preparation method of 2-chloro-4' -fluoroacetophenone - Google Patents
Preparation method of 2-chloro-4' -fluoroacetophenone Download PDFInfo
- Publication number
- CN107141212B CN107141212B CN201610125763.8A CN201610125763A CN107141212B CN 107141212 B CN107141212 B CN 107141212B CN 201610125763 A CN201610125763 A CN 201610125763A CN 107141212 B CN107141212 B CN 107141212B
- Authority
- CN
- China
- Prior art keywords
- chloro
- fluoroacetophenone
- preparation
- reaction
- ionic liquid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the field of organic synthesis, and particularly relates to a preparation method of 2-chloro-4' -fluoroacetophenone. The invention aims to solve the technical problems that the prior method has high energy consumption, can generate a large amount of waste water and organic waste liquid containing aluminum trichloride, and has strong irritation on raw materials. The scheme for solving the technical problem is to provide a preparation method of 2-chloro-4' -fluoro acetophenone, which comprises the following steps: a. under the condition of room temperature, dropwise adding chloroacetyl chloride into fluorobenzene and ionic liquid; b. after the dropwise addition is finished, the reaction is carried out for 20-50 minutes at normal temperature, and the 2-chloro-4' -fluoro acetophenone is obtained by distillation. The method provided by the invention has simple process operation process and is easy to realize industrialization.
Description
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a preparation method of 2-chloro-4' -fluoroacetophenone.
Background
The 2-chloro-4' -fluoro acetophenone is an important fine chemical intermediate, and can be used for synthesizing fluvastatin, epoxiconazole pesticide and the like.
The traditional method for synthesizing 2-chloro-4' -fluoro acetophenone is to prepare fluorobenzene and chloroacetyl chloride through Friedel-crafts reaction under the catalytic action of anhydrous aluminum trichloride. The reaction is generally carried out in a large excess of organic solvents such as fluorobenzene or dichloroethane, the reaction is generally carried out at a low temperature for 1-2 hours, and after the reaction is finished, concentrated hydrochloric acid is added for acidolysis to obtain a final target product. The method has the disadvantages of high energy consumption and capability of generating a large amount of waste water and organic waste liquid containing aluminum trichloride; in addition, the 2-chloro-4' -fluoroacetophenone also has strong irritation, particularly lacrimation, and the traditional process inevitably needs to undergo multiple material transfers in the process of obtaining a final product, so that the field labor condition is poor and the safety control difficulty is high.
Disclosure of Invention
The invention aims to solve the technical problems that the prior method has high energy consumption, can generate a large amount of waste water and organic waste liquid containing aluminum trichloride, and has high safety and environmental protection risks caused by strong irritation of products.
The scheme for solving the technical problem is to provide a preparation method of 2-chloro-4' -fluoro acetophenone, which comprises the following steps:
a. reacting fluorobenzene and chloroacetyl chloride in ionic liquid to obtain 2-chloro-4' -fluoroacetophenone;
b. after the reaction is completed, directly separating the reaction solution by a distillation mode to obtain the 2-chloro-4' -fluoroacetophenone.
In the preparation method of the 2-chloro-4' -fluoroacetophenone, the ionic liquid in the step a is an aluminum chloride type ionic liquid. The aluminum chloride type ionic liquid is [ emim]Cl-0.5AlCl3、[emim]Cl-0.67AlCl3、[emim]Cl-0.75AlCl3、[emim]Cl-0.8AlCl3、[bmim]Cl-0.5AlCl3、[bmim]Cl-0.67AlCl3、[bmim]Cl-0.75AlCl3、[bmim]Cl-0.8AlCl3、[mmim]Cl-0.67AlCl3、[pmim]Cl-0.67AlCl3、[beim]Cl-0.67AlCl3、[veim]Cl-0.67AlCl3、[eim]Cl-0.67AlCl3、[amim]Cl-0.67AlCl3、[emmim]Cl-0.67AlCl3、[mim]Cl-0.67AlCl3Or [ eeim]Cl-0.67AlCl3Any one of them.
In the preparation method of the 2-chloro-4' -fluoroacetophenone, the reaction temperature in the step a is 0-30 ℃.
In the preparation method of 2-chloro-4' -fluoroacetophenone, the molar ratio of fluorobenzene to chloroacetyl chloride in the step a is 1.01-1.03: 1.
In the preparation method of the 2-chloro-4' -fluoroacetophenone, the molar ratio of the ionic liquid to chloroacetyl chloride in the step a is 0.5: 1.
in the preparation method of the 2-chloro-4' -fluoro acetophenone, the reaction in the step b is completely that the conversion rate of the fluoro benzene is more than 95%. The reaction time is generally 30 minutes at room temperature of about 25 ℃ and if the temperature is lowered, the reaction time may be appropriately prolonged.
In the preparation method of the 2-chloro-4' -fluoroacetophenone, the distillation in the step b is reduced pressure distillation. The reduced pressure distillation temperature is 130 deg.C, and the pressure is 10 mmHg.
As a preferable technical scheme of the invention, the residual ionic liquid after distillation can be recycled.
The preparation method of the 2-chloro-4' -fluoroacetophenone provided by the invention improves the selectivity and yield of the reaction, does not need to use anhydrous aluminum trichloride, reduces the cost and the generation of solid waste, and has milder reaction conditions. Meanwhile, the mode of directly distilling out the product under reduced pressure is adopted in the post-reaction treatment, the use of an organic solvent and the material transfer of an irritant product are avoided, the ionic liquid can be repeatedly used, the cost is saved, and the reaction is more green and environment-friendly. The process provided by the invention is simple in operation process and easy to realize industrialization.
Detailed Description
The preparation method of the 2-chloro-4' -fluoro acetophenone comprises the following steps:
a. dropwise adding chloroacetyl chloride into fluorobenzene and the ionic liquid at 0-30 ℃, and continuing to react at 0-30 ℃ after dropwise adding;
b. after the reaction is completed, distilling to obtain the 2-chloro-4' -fluoro acetophenone.
In the preparation method of the 2-chloro-4' -fluoroacetophenone, the ionic liquid in the step a is an aluminum chloride type ionic liquid. The aluminum chloride type ionic liquid is [ emim]Cl-0.5AlCl3、[emim]Cl-0.67AlCl3、[emim]Cl-0.75AlCl3、[emim]Cl-0.8AlCl3、[bmim]Cl-0.5AlCl3、[bmim]Cl-0.67AlCl3、[bmim]Cl-0.75AlCl3、[bmim]Cl-0.8AlCl3、[mmim]Cl-0.67AlCl3、[pmim]Cl-0.67AlCl3、[beim]Cl-0.67AlCl3、[veim]Cl-0.67AlCl3、[eim]Cl-0.67AlCl3、[amim]Cl-0.67AlCl3、[emmim]Cl-0.67AlCl3、[mim]Cl-0.67AlCl3Or [ eeim]Cl-0.67AlCl3Any one of them.
In the preparation method of 2-chloro-4' -fluoroacetophenone, the molar ratio of fluorobenzene to chloroacetyl chloride in the step a is 1.01-1.03: 1.
In the preparation method of the 2-chloro-4' -fluoroacetophenone, the molar ratio of the ionic liquid to chloroacetyl chloride in the step a is 0.5: 1.
in the preparation method of the 2-chloro-4' -fluoroacetophenone, the whole reaction process in the step a is insensitive to temperature, an ideal result can be obtained at the temperature of 0-30 ℃, a constant temperature device particularly used for heating/cooling is not needed, and the energy consumption and equipment investment are low.
In the preparation method of the 2-chloro-4' -fluoro acetophenone, the reaction in the step b is completely that the conversion rate of the fluoro benzene is more than 95%.
In the preparation method of the 2-chloro-4' -fluoroacetophenone, the distillation in the step b is reduced pressure distillation. The reduced pressure distillation temperature is 130 deg.C, and the pressure is 10 mmHg.
As a preferable technical scheme of the invention, the residual ionic liquid after distillation can be recycled.
Compared with experimental data, the invention discovers that the selectivity of the reaction and the yield of the product of the aluminum chloride type ionic liquid are obviously higher than those of other types of ionic liquids, and the aluminum chloride is low in price, low in cost and easy to recover.
Example 1
A500 mL reaction flask was charged with 97g (1.01mol, 1.01eq) of fluorobenzene and 206.6g (0.5mol, 0.5eq) of ionic liquid [ emim [ ]]Cl-0.67AlCl3113g (1mol, 1eq) of chloroacetyl chloride was added dropwise at room temperature, and after completion of the addition, the reaction was continued with stirring for 30 minutes. The intermediate control fluorobenzene basically disappears, then the reaction liquid is subjected to reduced pressure distillation under the pressure of 10mmHg, and the fraction at the temperature of 128-132 ℃ is collected to obtain 169.3g of 2-chloro-4 ' -fluoroacetophenone, wherein the selectivity of the reaction is 99.5%, the content of the 2-chloro-4 ' -fluoroacetophenone is 99.5%, and the yield of the 2-chloro-4 ' -fluoroacetophenone is 98.1%.
Example 2
Into a 500mL reaction flask was charged 98g (1.02mol, 1.02eq) of fluorobenzeneAnd 220.7g (0.5mol, 0.5eq) of an ionic liquid [ bmim [ ]]Cl-0.67AlCl3113g (1mol, 1eq) of chloroacetyl chloride was added dropwise at 0 ℃ and the reaction was continued for 1.5 hours with stirring after completion of the addition. The intermediate fluorobenzene basically disappears, the temperature is raised to 130 ℃, and the reduced pressure distillation is carried out under the condition of 10mmHg to obtain 167.2g of 2-chloro-4' -fluoroacetophenone with the content of 99.2 percent and the yield of 96.87 percent.
Example 3
A500 mL reaction flask was charged with 98g (1.02mol, 1.02eq) of fluorobenzene and 199.6g (0.5mol, 0.5eq) of ionic liquid [ mmim [ ]]Cl-0.67AlCl3113g (1mol, 1eq) of chloroacetyl chloride was added dropwise at 30 ℃ and the reaction was continued for 30 minutes with stirring after completion of the addition. The intermediate fluorobenzene basically disappears, the temperature is raised to 130 ℃, and the reduced pressure distillation is carried out under the condition of 10mmHg to obtain 166.8g of 2-chloro-4' -fluoroacetophenone, the content is 99.3 percent, and the yield is 96.65 percent.
Example 4
A500 mL reaction flask was charged with 98g (1.02mol, 1.02eq) of fluorobenzene and 273.3g (0.5mol, 0.5eq) of ionic liquid [ emim [ ]]Cl-0.75AlCl3113g (1mol, 1eq) of chloroacetyl chloride was added dropwise at room temperature (. about.25 ℃ C.), and the reaction was continued for 30 minutes with stirring after the addition was completed. The intermediate control fluorobenzene basically disappears, the temperature is raised to 130 ℃, and the reduced pressure distillation is carried out under the condition of 10mmHg to obtain 168.8g of 2-chloro-4' -fluoroacetophenone, wherein the content is 99.3 percent, and the yield is 97.8 percent.
Example 5
A500 mL reaction flask was charged with 98g (1.02mol, 1.02eq) of fluorobenzene and 140g (0.5mol, 0.5eq) of ionic liquid [ emim [ ]]Cl-0.5AlCl3113g (1mol, 1eq) of chloroacetyl chloride was added dropwise at room temperature (. about.25 ℃ C.), and the reaction was continued for 30 minutes with stirring after the addition was completed. The conversion rate of the intermediate fluorine benzene is controlled to be over 95 percent, the temperature is raised to 130 ℃, and the 2-chloro-4' -fluoro acetophenone is obtained by reduced pressure distillation under the condition of 10mmHg, the content is 98.8 percent, and the yield is 93.2 percent.
Example 6
A500 mL reaction flask was charged with 99g (1.03mol, 1.03eq) of fluorobenzene and 235.5g (0.5mol, 0.5eq) of ionic liquid [ emim [ ]]Cl-0.67FeCl3Dripping 113g (1mol, 1eq) of chloroacetyl chloride at room temperature (25 ℃), continuing stirring and reacting for 30 minutes after finishing dripping, heating to 130 ℃, and reacting at the temperature ofVacuum distilling under 10mmHg to obtain 145.3g of 2-chloro-4' -fluoro acetophenone with 96.6% content and 84.2% yield.
Example 7
Into a 500mL reaction flask were charged 99g (1.03mol, 1.03eq) of fluorobenzene and 209.6g (0.5mol, 0.5eq) of an ionic liquid [ emim ]]Cl-0.67ZnCl2113g (1mol, 1eq) of chloroacetyl chloride is dripped at room temperature (about 25 ℃), the mixture is continuously stirred and reacts for 30 minutes after the dripping is finished, the temperature is raised to 130 ℃, and the reduced pressure distillation is carried out under the condition of 10mmHg to obtain 129.1g of 2-chloro-4' -fluoroacetophenone with the content of 92.3 percent and the yield of 74.8 percent.
Example 8
A500 mL reaction flask was charged with 98g (1.02mol, 1.02eq) of fluorobenzene and 220.7g (0.5mol, 0.5eq) of ionic liquid [ i-bmim ]]Cl-0.67AlCl3113g (1mol, 1eq) of chloroacetyl chloride was added dropwise at room temperature (. about.25 ℃ C.), and the reaction was continued for 30 minutes with stirring after the addition was completed. The conversion rate of the intermediate fluorine benzene is controlled to be over 95 percent, the temperature is raised to 130 ℃, and the 2-chloro-4' -fluoro acetophenone is obtained by reduced pressure distillation under the condition of 10mmHg, the content is 97.3 percent, and the yield is 88.6 percent.
Example 9
The catalytic effect of other types of ionic liquids using the same reaction conditions as in example 1 is shown in table 1:
TABLE 1
Comparative example
Adding fluorobenzene (1.05eq), dichloroethane (3 times of the mass of fluorobenzene) and anhydrous aluminum trichloride (1.1eq) into a reaction kettle, dropwise adding chloroacetyl chloride (1eq) at-3 to-1 ℃, keeping the temperature for reaction for 1h after dropwise adding, adding concentrated hydrochloric acid for acidolysis, then carrying out phase splitting, washing an organic phase to be neutral (about 3 to 4 times), and concentrating. The reaction selectivity is 98%, the yield is 95%, and the product content is 98.5%.
Comparison of the comparative example with the process of the invention is shown in table 2:
TABLE 2
The process provided by the invention is simple in operation process and easy to realize industrialization.
Claims (8)
- A preparation method of 2-chloro-4' -fluoro acetophenone comprises the following steps:a. reacting fluorobenzene and chloroacetyl chloride in ionic liquid to obtain 2-chloro-4' -fluoroacetophenone;b. after the reaction is completed, directly separating the reaction solution by a distillation mode to obtain 2-chloro-4' -fluoroacetophenone;the ionic liquid in the step a is [ emim]Cl-0.5AlCl3、[emim]Cl-0.67AlCl3、[emim]Cl-0.75AlCl3、[emim]Cl-0.8AlCl3、[bmim]Cl-0.5AlCl3、[bmim]Cl-0.67AlCl3、[bmim]Cl-0.75AlCl3、[bmim]Cl-0.8AlCl3、[mmim]Cl-0.67AlCl3、[pmim]Cl-0.67AlCl3、[beim]Cl-0.67AlCl3、[veim]Cl-0.67AlCl3、[eim]Cl-0.67AlCl3、[amim]Cl-0.67AlCl3、[emmim]Cl-0.67AlCl3、[mim]Cl-0.67AlCl3Or [ eeim]Cl-0.67AlCl3Any one of them.
- 2. The process for the preparation of 2-chloro-4' -fluoroacetophenone according to claim 1, wherein: the reaction temperature in the step a is 0-30 ℃.
- 3. The process for the preparation of 2-chloro-4' -fluoroacetophenone according to claim 1, wherein: the molar ratio of fluorobenzene to chloroacetyl chloride in the step a is 1.01-1.03: 1.
- 4. The process for the preparation of 2-chloro-4' -fluoroacetophenone according to claim 1, wherein: the mol ratio of the ionic liquid to the chloroacetyl chloride in the step a is 0.5: 1.
- 5. The process for the preparation of 2-chloro-4' -fluoroacetophenone according to claim 1, wherein: the reaction in step b is completed to a fluorobenzene conversion rate of more than 95%.
- 6. The process for the preparation of 2-chloro-4' -fluoroacetophenone according to claim 1, wherein: and the distillation in the step b is reduced pressure distillation.
- 7. The process for preparing 2-chloro-4' -fluoroacetophenone according to claim 6, wherein: the reduced pressure distillation temperature is 130 deg.C, and the pressure is 10 mmHg.
- 8. The process for the preparation of 2-chloro-4' -fluoroacetophenone according to claim 1, wherein: the ionic liquid remaining after distillation can be recycled.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610125763.8A CN107141212B (en) | 2016-03-07 | 2016-03-07 | Preparation method of 2-chloro-4' -fluoroacetophenone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610125763.8A CN107141212B (en) | 2016-03-07 | 2016-03-07 | Preparation method of 2-chloro-4' -fluoroacetophenone |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107141212A CN107141212A (en) | 2017-09-08 |
| CN107141212B true CN107141212B (en) | 2020-12-22 |
Family
ID=59783921
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610125763.8A Active CN107141212B (en) | 2016-03-07 | 2016-03-07 | Preparation method of 2-chloro-4' -fluoroacetophenone |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107141212B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115073274A (en) * | 2022-07-05 | 2022-09-20 | 浙江工业大学 | Preparation method for catalytically synthesizing 2-chloro-4' -fluoro acetophenone by using ionic liquid |
| CN116217364A (en) * | 2022-12-29 | 2023-06-06 | 浙江工业大学 | Method for synthesizing fluorenol intermediate 4-chloroacetyl-2, 7-dichlorofluorene based on ionic liquid catalysis |
-
2016
- 2016-03-07 CN CN201610125763.8A patent/CN107141212B/en active Active
Non-Patent Citations (4)
| Title |
|---|
| "Design and synthesis of novel miconazole-based ciprofloxacin hybrids as potential antimicrobial agents"，H.-B. Liu et al.，Monatsh Chem，第146卷，第713-720页;H.-B. Liu et al.;《Monatsh Chem》;20151231;第713-720页 * |
| "三氯化铝系列催化剂在 Friedel-Crafts 酰基化反应中的应用进展"，张天旭等，第23卷第1期，第57-62页;张天旭等;《精细石油化工》;20060131;第23卷(第1期);第57-62页 * |
| Design, synthesis and evaluation of clinafloxacin triazole hybrids as a new type of antibacterial and antifungal agents;Cheng-He Zhou et al.;《Bioorganic & Medicinal Chemistry Letters》;20120723;第22卷;第5363-5366页 * |
| 离子液体[bmim_]Cl/AlCl3催化5-氰基吲哚酰化反应;蒋云霞;《化学研究与应用》;20150531;第27卷(第5期);第737-740页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107141212A (en) | 2017-09-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP3215481B1 (en) | Method for producing biphenylamines from azobenzoles by ruthenium catalysis | |
| CN107141212B (en) | Preparation method of 2-chloro-4' -fluoroacetophenone | |
| CN109942393B (en) | Preparation method of 1,1, 1-trifluoroacetone | |
| CN112142694A (en) | Polysubstituted tetrahydrofuran and tetrahydropyrane diene compound and preparation method thereof | |
| CN107473948B (en) | Synthetic method for preparing 3, 5-dichloro-2-pentanone from ethyl acetoacetate | |
| CN110272366B (en) | Method for synthesizing diaryl selenide | |
| Youn et al. | Asymmetric borane reduction of ketones catalyzed by oxazaborolidine | |
| DE69206423T2 (en) | Process for the preparation of 5- (2,4-difluorophenyl) salicylic acid. | |
| CN108164423B (en) | Preparation method of naftifine hydrochloride | |
| CN108752218A (en) | A kind of variation route prepared by Du Lutewei key intermediates 2,4- difluorobenzylamines | |
| CN112028906B (en) | Method for preparing pinoxaden by one-pot boiling method | |
| CN104447262B (en) | Method for synthesizing 1-chloro-1-chloroacetyl-cyclopropane by one-pot method | |
| CN111548257B (en) | Preparation method of (4-isopropoxy-2-methyl) phenyl isopropyl ketone | |
| KR20150118157A (en) | Process for producing pyridazinone compound and production intermediates thereof | |
| CN109265385B (en) | Synthesis process of chiral catalyst | |
| CN108675925B (en) | Production process of cyclopentanecarboxylic acid | |
| EP3275855B1 (en) | Methods for producing 2,6-dimethyl-1,5-heptadien-3-ol and 2,6-dimethyl-1,5-heptadien-3-yl acetate | |
| CN111440058A (en) | Preparation method of high-purity 4, 4' -difluorobenzophenone | |
| CN109748892B (en) | Preparation method of 3-halogenated tetrahydrofuran | |
| DE4225763A1 (en) | Process for the production of halogen aromatics | |
| CN117756625B (en) | Preparation method of o-ethoxybenzoyl chloride | |
| CN106810430A (en) | A kind of preparation method of the naphthoquinone derivatives of 2 trifluoromethyl 1,4 | |
| CN114276229B (en) | Method for recycling musk T-shaped kettle residues | |
| CN105859548A (en) | Method for catalyzed synthesis of 1,4-cyclohexanedicarboxylic acid | |
| CN109232261B (en) | Preparation method of benzyl bromide compound |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |