CN112110806B - Preparation method and intermediate of 1- (3, 5-dichloro-4-fluoro-phenyl) -2, 2-trifluoroacetone - Google Patents
Preparation method and intermediate of 1- (3, 5-dichloro-4-fluoro-phenyl) -2, 2-trifluoroacetone Download PDFInfo
- Publication number
- CN112110806B CN112110806B CN202010945533.2A CN202010945533A CN112110806B CN 112110806 B CN112110806 B CN 112110806B CN 202010945533 A CN202010945533 A CN 202010945533A CN 112110806 B CN112110806 B CN 112110806B
- Authority
- CN
- China
- Prior art keywords
- acid
- fluoro
- compound
- dichloro
- trifluoroacetone
- 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
Images
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
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/63—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of halogen; by substitution of halogen atoms by other halogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C221/00—Preparation of compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C225/00—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones
- C07C225/22—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
Abstract
The invention discloses a preparation method and an intermediate of 1- (3, 5-dichloro-4-fluoro-phenyl) -2, 2-trifluoroacetone, and relates to the technical field of synthetic chemical application. The method comprises the following steps as shown in the following formula: (1) Taking a compound I as a raw material, and carrying out hydrogenation reduction under the action of a solvent and a catalyst to obtain a compound II; (2) The compound II and a diazo reagent generate diazo reaction under the action of acid, and then generate chlorination reaction under the action of hydrochloric acid and a catalyst to obtain a compound III, so that the compound 1- (3, 5-dichloro-4-fluoro-phenyl) -2, 2-trifluoroacetone can be simply and effectively prepared, and the purity is high and the yield is good.
Description
Technical Field
The invention relates to the technical field of synthetic chemistry application, in particular to a preparation method and an intermediate of 1- (3, 5-dichloro-4-fluoro-phenyl) -2, 2-trifluoroacetone.
Background
1- (3, 5-dichloro-4-fluoro-phenyl) -2, 2-trifluoroacetone is an important intermediate for the preparation of isoxazoline substituted benzamides, which have the formula:
isoxazoline benzamides are disclosed in EP1932836Al to have pesticidal activity; chinese patent application 201910507840.X discloses application of isoxazoline benzamide compounds in prevention and treatment of bacterial infection, preparation of medicines for prevention and treatment of bacterial infection, preparation of bactericides or bacteriostats and preparation of FtsZ inhibitor medicines, and 1- (3, 5-dichloro-4-fluoro-phenyl) -2, 2-trifluoroacetone serving as an important intermediate for preparation of isoxazoline substituted benzamide has good market demand.
WO2017201134 discloses that 3, 5-dichloro-4-fluorobromobenzene is subjected to grignard reaction, and then is coupled with trifluoroacetic acid derivative to obtain 1- (3, 5-dichloro-4-fluoro-phenyl) -2, 2-trifluoroacetone, because the reaction relates to grignard reaction, grignard reaction liquid is easy to couple with itself to cause low yield, more impurities, poor effect and unfavorable industrial production, and the grignard reaction has high requirement on industrial equipment to cause high production cost; in addition, related researches have shown that 1- (3, 5-dichloro-4-fluoro-phenyl) -2, 2-trifluoroacetone is obtained by taking fluorobenzene as a raw material through Friedel-crafts reaction, then nitration, chlorination and free radical chlorination, the reaction cost is low, but the free radical chlorination needs to react at a temperature higher than 180 ℃, and under an acidic condition, the equipment is very corrosive, so that the industrialization is difficult.
Therefore, the present application provides a method for preparing 1- (3, 5-dichloro-4-fluoro-phenyl) -2, 2-trifluoroacetone, which is simple in process, low in equipment requirement, low in cost, beneficial to industrial production, high in purity and good in yield, and meets the production requirement of the field for 1- (3, 5-dichloro-4-fluoro-phenyl) -2, 2-trifluoroacetone.
Disclosure of Invention
The invention aims to provide a preparation method of 1- (3, 5-dichloro-4-fluoro-phenyl) -2, 2-trifluoroacetone and an intermediate thereof, which can simply and effectively prepare the compound 1- (3, 5-dichloro-4-fluoro-phenyl) -2, 2-trifluoroacetone with high purity and good yield.
In order to achieve the purpose, the technical scheme of the invention is as follows:
first, the present invention provides a method for preparing 1- (3, 5-dichloro-4-fluoro-phenyl) -2, 2-trifluoroacetone, comprising the steps of:
(1) Hydrogenating and reducing the compound I (2-fluoro-3-chloro-5-trifluoroacetyl nitrobenzene) to obtain a compound II (2-fluoro-3-chloro-5-trifluoroacetyl aniline);
(2) The compound II (2-fluoro-3-chloro-5-trifluoroacetylaniline) has diazo reaction with a diazo reagent under the action of acid, and then has chloro reaction under the action of hydrochloric acid and a catalyst to obtain a compound III (1- (3, 5-dichloro-4-fluoro-phenyl) -2, 2-trifluoroacetone),
preferably, the reaction of step (1) is carried out in the presence of a solvent selected from one or more of methanol, ethyl acetate, ethanol, toluene.
Preferably, the mass ratio of the compound I to the solvent is 1:2-6, more preferably 1:3-5.
Preferably, the reaction in step (1) is carried out in the presence of a catalyst selected from platinum carbon, palladium carbon, nickel, more preferably platinum carbon.
Preferably, in the step (1), the mass ratio of the compound I to the catalyst is 1:0.009-0.05, more preferably 1:0.009-0.02.
Preferably, in the step (1), the reaction temperature of the hydrogenation reduction is 30-80 ℃, and further preferably 50-60 ℃.
Preferably, in the step (1), the pressure of the hydrogenation is 1 to 5MPa, and more preferably 1 to 2MPa.
Preferably, in step (2), the acid is selected from sulfuric acid, hydrochloric acid, phosphoric acid, hydrobromic acid, hydroiodic acid, acetic anhydride, and more preferably sulfuric acid.
Preferably, in step (2), the diazonium reagent is sodium nitrite or nitrososulfuric acid.
Preferably, in the step (2), the temperature of the diazotization reaction is 20-80 ℃, and more preferably 40-60 ℃.
Preferably, in the step (2), the molar ratio of the compound II, the acid and the diazo reagent is 1:3-8, and further preferably 1.
Preferably, in the step (2), the catalyst is a copper salt, and the copper salt includes copper sulfate, cuprous chloride, cuprous oxide, cupric carbonate, cupric nitrate, and further preferably cuprous chloride.
Preferably, in the step (2), the reaction temperature of the chlorination reaction is 20 to 80 ℃, and more preferably 40 to 50 ℃.
In another aspect, the present invention also provides an intermediate compound, represented by the following formula:
preferably, the above compounds are used in the preparation of 1- (3, 5-dichloro-4-fluoro-phenyl) -2, 2-trifluoroacetone.
Compared with the prior art, the invention has the following beneficial effects:
(1) A new compound 2-fluoro-3-chloro-5-trifluoroacetylaniline is obtained for the first time;
(2) The preparation method of the 1- (3, 5-dichloro-4-fluoro-phenyl) -2, 2-trifluoroacetone is simple in preparation process, low in requirement on equipment, low in cost, good in purity and yield and beneficial to industrial production.
Drawings
FIG. 1 is a F spectrum of 2-fluoro-3-chloro-5-trifluoroacetylaniline prepared according to the invention;
FIG. 2 is a H spectrum of 2-fluoro-3-chloro-5-trifluoroacetylaniline prepared according to the present invention.
Detailed Description
The present invention will be further explained with reference to specific embodiments in order to make the technical means, the original characteristics, the achieved objects and the effects of the present invention easy to understand, but the following embodiments are only preferred embodiments of the present invention, and not all embodiments are possible. Based on the embodiments in the implementation, other embodiments obtained by those skilled in the art without any creative efforts belong to the protection scope of the present invention.
The experimental methods in the following examples are conventional methods unless otherwise specified, and materials, reagents and the like used in the following examples are commercially available unless otherwise specified.
In the following examples, 2-fluoro-3-chloro-5-trifluoroacetyl nitrobenzene was prepared according to the method described in patent CN106795080A with a purity of not less than 99%.
Example 1: preparation of 2-fluoro-3-chloro-5-trifluoroacetylaniline
1.1
271.5g (1 mol) of 2-fluoro-3-chloro-5-trifluoroacetyl nitrobenzene, 900g of methanol and 5g of platinum carbon are put into a 2L high-pressure kettle, the high-pressure kettle is closed, the temperature is raised to 50 ℃, the pressure of introduced hydrogen is 1-2MPa, the temperature is kept for 8h, sampling and central control are carried out, after the reaction is finished, the temperature is lowered to room temperature, filtration and concentration are carried out, and 225g of 2-fluoro-3-chloro-5-trifluoroacetyl aniline is obtained, the purity is 95.5 percent, and the yield is 93.2 percent.
1.2
Unlike example 1.1, this example uses ethyl acetate instead of methanol, the same procedure is followed:
271.5g (1 mol) of 2-fluoro-3-chloro-5-trifluoroacetyl nitrobenzene, 900g of ethyl acetate and 5g of platinum carbon are put into a 2L high-pressure kettle, the high-pressure kettle is closed, the temperature is raised to 50 ℃, the pressure of introduced hydrogen is 1-2MPa, the temperature is kept for 8h, sampling and central control are carried out, after the reaction is finished, the temperature is lowered to room temperature, filtration and concentration are carried out, 215g of 2-fluoro-3-chloro-5-trifluoroacetyl aniline is obtained, the purity is 95 percent, and the yield is 89 percent.
1.3
The difference from the embodiment 1.1 is that the pressure of the hydrogen gas introduced in the embodiment is 4-5MPa, and the steps are as follows:
271.5g (1 mol) of 2-fluoro-3-chloro-5-trifluoroacetyl nitrobenzene, 900g of methanol and 5g of platinum carbon are put into a 2L high-pressure kettle, the high-pressure kettle is closed, the temperature is raised to 50 ℃, the pressure of introduced hydrogen is 4-5MPa, the temperature is kept for 8h, sampling and control are carried out, after the reaction is finished, the temperature is lowered to room temperature, filtration and concentration are carried out, and 210g of 2-fluoro-3-chloro-5-trifluoroacetyl aniline with the purity of 93 percent and the yield of 87 percent is obtained.
1.4
The difference from example 1.1 is that the amount of platinum carbon used in this example is 2.5g, and the procedure is as follows:
271.5g (1 mol) of 2-fluoro-3-chloro-5-trifluoroacetyl nitrobenzene, 900g of methanol and 2.5g of platinum carbon are put into a 2L high-pressure kettle, the high-pressure kettle is closed, the temperature is raised to 50 ℃, the pressure of introduced hydrogen is 1-2MPa, the temperature is kept for 8h, sampling and central control are carried out, after the reaction is finished, the temperature is lowered to room temperature, filtering and concentrating are carried out, and 200g of 2-fluoro-3-chloro-5-trifluoroacetyl aniline is obtained, the purity is 88 percent, and the yield is 82.8 percent.
1.5
Unlike example 1.1, the temperature of the hydrogenation reduction reaction in this example was 30 ℃, and the procedure was the same as follows:
271.5g (1 mol) of 2-fluoro-3-chloro-5-trifluoroacetyl nitrobenzene, 900g of methanol and 5g of platinum carbon are put into a 2L high-pressure kettle, the high-pressure kettle is closed, the temperature is raised to 30 ℃, the pressure of introduced hydrogen is 1-2MPa, the temperature is kept for 8h, sampling and control are carried out, the temperature is lowered to room temperature after the reaction is finished, filtration and concentration are carried out, and 205g of 2-fluoro-3-chloro-5-trifluoroacetyl aniline is obtained, the purity is 92.5 percent, and the yield is 84.9 percent.
1.6
The difference from example 1.1 is that the temperature of the hydrogenation reduction reaction in this example is 80 ℃, and the steps are as follows:
271.5g (1 mol) of 2-fluoro-3-chloro-5-trifluoroacetyl nitrobenzene, 900g of methanol and 5g of platinum carbon are put into a 2L high-pressure kettle, the high-pressure kettle is closed, the temperature is raised to 80 ℃, the pressure of introduced hydrogen is 1-2MPa, the temperature is kept for 8h, sampling and controlling are carried out, after the reaction is finished, the temperature is lowered to room temperature, filtration and concentration are carried out, and 220g of 2-fluoro-3-chloro-5-trifluoroacetyl aniline is obtained, the purity is 90.5 percent, and the yield is 91.1 percent.
The nuclear magnetic spectrum of the 2-fluoro-3-chloro-5-trifluoroacetylaniline prepared by the invention is shown in figure 1 and figure 2.
Example 2: preparation of 1- (3, 5-dichloro-4-fluoro-phenyl) -2, 2-trifluoroacetone
2.1
327g (2.5 mol) of 75% sulfuric acid is put into a 1L four-mouth bottle, 121g (0.5 mol) of 2-fluoro-3-chloro-5-trifluoroacetylaniline prepared according to the method of example 1.1 is added at 45 ℃, then 190.5g (0.6 mol) of 40% nitrososulfuric acid is added dropwise, the mixture is kept warm for 1 hour after dropwise adding to obtain diazo liquid, 182.5g (1.5 mol) of hydrochloric acid and 30g of cuprous chloride are put into another 1L four-mouth bottle, the temperature is raised to 40-50 ℃, diazo liquid is added dropwise, the mixture is kept warm for 2 hours after dropwise adding, the mixture is kept still and layered, an acid layer is extracted, an oil layer is combined, and the oil layer is washed with water, alkali, layered, concentrated and rectified to obtain 107g, 99% purity and 82% of 1- (3, 5-dichloro-4-fluoro-phenyl) -2, 2-trifluoroacetone.
2.2
In contrast to example 2.1, the nitroso-sulfuric acid used in this example was 0.75mol, and the procedure was as follows:
327g (2.5 mol) of 75% sulfuric acid is added into a 1L four-mouth bottle, 121g (0.5 mol) of 2-fluoro-3-chloro-5-trifluoroacetylaniline is added at 45 ℃, then 238g (0.75 mol) of 40% nitrososulfuric acid is added dropwise, heat preservation is carried out for 1 hour after dripping to obtain diazo liquid, 182.5g (1.5 mol) of hydrochloric acid and 30g of cuprous chloride are added into the other 1L four-mouth bottle, the temperature is increased to 40-50 ℃, diazo liquid is added dropwise, heat preservation is carried out for 2 hours after dripping to obtain the diazo liquid, standing and layering are carried out, acid layer extraction is carried out, oil layers are combined, water washing, alkali washing, layering, concentration and rectification are carried out to obtain 105g of 1- (3, 5-dichloro-4-fluoro-phenyl) -2, 2-trifluoroacetone, the purity is 99%, and the yield is 80.5%.
2.3
The difference from example 2.1 is that the diazotization reaction temperature is 60 ℃, and the steps are as follows:
327g (2.5 mol) of 75% sulfuric acid is put into a 1L four-mouth bottle, 121g (0.5 mol) of 2-fluoro-3-chloro-5-trifluoroacetylaniline is added at 60 ℃, then 190.5g (0.6 mol) of 40% nitrososulfuric acid is added dropwise, the temperature is kept for 1 hour after dripping to obtain diazo liquid, 182.5g (1.5 mol) of hydrochloric acid and 30g of cuprous chloride are put into the other 1L four-mouth bottle, the temperature is raised to 40-50 ℃, diazo liquid is added dropwise, the temperature is kept for 2 hours after dripping to obtain a mixture, the mixture is kept stand for layering, an acid layer is extracted, an oil layer is combined, washed by water, washed by alkali, layered and concentrated, and rectified to obtain 100g of 1- (3, 5-dichloro-4-fluoro-phenyl) -2, 2-trifluoroacetone, the purity is 98.5%, and the yield is 76.6%.
2.4
The difference from the example 2.1 is that the amount of cuprous chloride used in this example is 50g, and the steps are the same as follows:
327g (2.5 mol) of 75% sulfuric acid is put into a 1L four-mouth bottle, 121g (0.5 mol) of 2-fluoro-3-chloro-5-trifluoroacetylaniline is added at 45 ℃, then 190.5g (0.6 mol) of 40% nitroso-sulfuric acid is added dropwise, heat preservation is carried out for 1 hour after dripping is finished to obtain diazo liquid, 182.5g (1.5 mol) of hydrochloric acid and 50g of cuprous chloride are put into the other 1L four-mouth bottle, the temperature is increased to 40-50 ℃, diazo liquid is added dropwise, heat preservation is carried out for 2 hours after dripping is finished, standing and layering are carried out, acid layer extraction is carried out, oil layers are combined, water washing, alkali washing, layering, concentration and rectification are carried out to obtain 106g of 1- (3, 5-dichloro-4-fluoro-phenyl) -2, 2-trifluoroacetone, the purity is 99%, and the yield is 81.2%.
2.5
The difference from example 2.1 is that the temperature of the chlorination reaction is 70-80 ℃, and the steps are as follows:
327g (2.5 mol) of 75% sulfuric acid is added into a 1L four-mouth bottle, 121g (0.5 mol) of 2-fluoro-3-chloro-5-trifluoroacetylaniline is added at 45 ℃, then 190.5g (0.6 mol) of 40% nitroso sulfuric acid is added dropwise, heat preservation is carried out for 1 hour after dripping is finished to obtain diazo liquid, 182.5g (1.5 mol) of hydrochloric acid and 30g of cuprous chloride are added into the other 1L four-mouth bottle, the temperature is increased to 70-80 ℃, the diazo liquid is added dropwise, heat preservation is carried out for 2 hours after dripping is finished, standing and layering are carried out, acid layer extraction is carried out, oil layers are combined, water washing, alkali washing, layering, concentration and rectification are carried out to obtain 101g, the purity is 99%, and the yield is 77.4%.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.
Claims (6)
1. A method for preparing 1- (3, 5-dichloro-4-fluoro-phenyl) -2, 2-trifluoroacetone, comprising the steps of:
(1) Hydrogenating and reducing the compound I to obtain a compound II, wherein the mass ratio of the compound I to the catalyst is 1.018-0.05;
(2) Performing diazo reaction on the compound II and a diazo reagent under the action of acid at the reaction temperature of 20-80 ℃, performing chlorination reaction under the action of hydrochloric acid and a catalyst at the reaction temperature of 20-80 ℃, wherein the catalyst is copper salt, obtaining a compound III,
2. the production method according to claim 1, wherein the step (1) is carried out in the presence of a catalyst; the catalyst is selected from platinum carbon, palladium carbon or nickel.
3. The method according to claim 1, wherein in the step (1), the reaction temperature of the hydrogenation reduction is 30-80 ℃ and the hydrogenation pressure is 1-5MPa.
4. The method according to claim 1, wherein in the step (2), the acid is one or more selected from the group consisting of sulfuric acid, hydrochloric acid, phosphoric acid, hydrobromic acid, hydroiodic acid, and acetic acid.
5. The production method according to claim 1, wherein in the step (2), the diazonium reagent is sodium nitrite or nitrososulfuric acid.
6. The method according to claim 1, wherein in the step (2), the molar ratio of the compound II, the acid and the diazonium reagent is 1:3-8:1-2.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010945533.2A CN112110806B (en) | 2020-09-10 | 2020-09-10 | Preparation method and intermediate of 1- (3, 5-dichloro-4-fluoro-phenyl) -2, 2-trifluoroacetone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010945533.2A CN112110806B (en) | 2020-09-10 | 2020-09-10 | Preparation method and intermediate of 1- (3, 5-dichloro-4-fluoro-phenyl) -2, 2-trifluoroacetone |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112110806A CN112110806A (en) | 2020-12-22 |
| CN112110806B true CN112110806B (en) | 2022-11-15 |
Family
ID=73802066
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010945533.2A Active CN112110806B (en) | 2020-09-10 | 2020-09-10 | Preparation method and intermediate of 1- (3, 5-dichloro-4-fluoro-phenyl) -2, 2-trifluoroacetone |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112110806B (en) |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4966975A (en) * | 1989-04-21 | 1990-10-30 | American Home Product | Processes for the preparation of novel naphthalenylmethyl-3H-1,2,3,5-oxathiadiazole 2-oxides useful as antihyperglycemic agents |
| CN104496951A (en) * | 2015-01-11 | 2015-04-08 | 景炜杰 | Preparation method of chlorophthalic anhydride |
| CN105348038A (en) * | 2015-11-06 | 2016-02-24 | 烟台九目化学制品有限公司 | Synthetic method for 4,4'-dihalogenated-3,3'-dialkyl(alkoxyl) biphenyl compounds |
| CN106795093A (en) * | 2014-10-14 | 2017-05-31 | 先正达参股股份有限公司 | Method for preparing 1 (3,5 dichlorophenyl) 2,2,2 trifluoroethanones and its derivative |
| CN106795080A (en) * | 2014-10-14 | 2017-05-31 | 先正达参股股份有限公司 | Method for preparing halo trifluoroacetophenone |
| CN107032979A (en) * | 2017-06-12 | 2017-08-11 | 青岛瀚生生物科技股份有限公司 | The preparation method of 3 (trifluoromethyl of 2 chlorine 4) phenoxy benzoic acids |
| CN110498730A (en) * | 2019-08-13 | 2019-11-26 | 浙江林江化工股份有限公司 | A kind of synthetic method of 1,2,4- trifluoro-benzene |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10556909B2 (en) * | 2016-05-20 | 2020-02-11 | Avista Pharma Solutions, Inc. | Synthetic process and intermediates |
-
2020
- 2020-09-10 CN CN202010945533.2A patent/CN112110806B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4966975A (en) * | 1989-04-21 | 1990-10-30 | American Home Product | Processes for the preparation of novel naphthalenylmethyl-3H-1,2,3,5-oxathiadiazole 2-oxides useful as antihyperglycemic agents |
| CN106795093A (en) * | 2014-10-14 | 2017-05-31 | 先正达参股股份有限公司 | Method for preparing 1 (3,5 dichlorophenyl) 2,2,2 trifluoroethanones and its derivative |
| CN106795080A (en) * | 2014-10-14 | 2017-05-31 | 先正达参股股份有限公司 | Method for preparing halo trifluoroacetophenone |
| CN104496951A (en) * | 2015-01-11 | 2015-04-08 | 景炜杰 | Preparation method of chlorophthalic anhydride |
| CN105348038A (en) * | 2015-11-06 | 2016-02-24 | 烟台九目化学制品有限公司 | Synthetic method for 4,4'-dihalogenated-3,3'-dialkyl(alkoxyl) biphenyl compounds |
| CN107032979A (en) * | 2017-06-12 | 2017-08-11 | 青岛瀚生生物科技股份有限公司 | The preparation method of 3 (trifluoromethyl of 2 chlorine 4) phenoxy benzoic acids |
| CN110498730A (en) * | 2019-08-13 | 2019-11-26 | 浙江林江化工股份有限公司 | A kind of synthetic method of 1,2,4- trifluoro-benzene |
Non-Patent Citations (3)
| Title |
|---|
| Benzylated 1,2,3-triazoles as anticoccidiostats;Bochis, Richard J. et al;《Journal of Medicinal Chemistry》;19910901;第34卷(第9期);第2843-2852页 * |
| Electrophilic aromatic substitution with N-methoxy-N-acylnitrenium ions generated from N-chloro-N-methoxy amides: syntheses of nitrogen heterocyclic compounds bearing a N-methoxy amide group;Kawase, Masami et al;《Journal of Organic Chemistry》;19890701;第54卷(第14期);第3394–3403页 * |
| Studies on antibacterial agents. I. Synthesis of substituted 6,7-dihydro-1-oxo-1H,5H-benzo[i,j]-quinolizine-2-carboxylic acids;Ishikawa, Hiroshi et al;《Chemical & Pharmaceutical Bulletin》;19890831;第37卷(第8期);第2103-2108页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112110806A (en) | 2020-12-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110961110B (en) | Catalyst and application thereof in 2,3,6-trichloropyridine hydrodechlorination | |
| CN108250041B (en) | Preparation method of fully deuterated methanol | |
| CN105080575A (en) | Molybdenum vanadium tellurium niobium oxygen catalyst for preparing ethene from ethane and preparation method and application | |
| CN112110806B (en) | Preparation method and intermediate of 1- (3, 5-dichloro-4-fluoro-phenyl) -2, 2-trifluoroacetone | |
| CN109336769A (en) | A kind of preparation method of p-phenylenediamine | |
| CN105601588A (en) | Method for synthesizing N-hydroxyethylpiperazine and piperazine by means of co-production | |
| CN103172480B (en) | Method for preparing iodo aromatic hydrocarbon | |
| CN101597223B (en) | Method for synthesizing filbertone | |
| CN112047804B (en) | Preparation method of 3, 5-dichloro-4-fluorobromobenzene compound | |
| CN110950778A (en) | Process and catalyst system for preparing aromatic malononitrile | |
| CN112010732B (en) | Preparation method of 3, 5-dichloro-4-fluorobromobenzene compound | |
| CN107353245B (en) | A kind of synthetic method of quinolines | |
| EP1819660A1 (en) | Process for the production of anilines | |
| CN106866425B (en) | A kind of green synthesis method of bromo aromatic amine and alpha-brominated aromatic ketone | |
| CN112142567B (en) | Preparation method of 2-fluoro-3-chlorophenol | |
| CN108794320B (en) | Preparation method of 2,4, 5-trifluorophenylacetic acid | |
| CN107497426B (en) | Preparation method and application of palladium/silver alloy nano catalyst | |
| CN110801842A (en) | Catalyst for preparing chlorine gas by catalytic oxidation of hydrogen chloride and preparation method and application thereof | |
| WO2003055844A1 (en) | Process for preparing terbinafine and hci salt thereof | |
| CN112341357B (en) | Preparation method of 4-methoxy phenylhydrazine hydrochloride | |
| CN107353179A (en) | A kind of preparation technology of difluoroethanol | |
| CN116217522A (en) | Chiral purification method of key intermediate of GLP-1 receptor agonist | |
| CN107880013A (en) | A kind of synthetic method of five-membered ring list sulfocarbonate | |
| CN107188855A (en) | A kind of preparation method of the methoxyl group pyridazine of 3 amino 6 | |
| CN107011123A (en) | A kind of method of catalytic hydrogen reduction 2-methyl-3-biphenylmethanol |
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 |