CN111517945A - Method for long-term stable preparation of 4-chlorobutyryl chloride - Google Patents
Method for long-term stable preparation of 4-chlorobutyryl chloride Download PDFInfo
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- CN111517945A CN111517945A CN202010480988.1A CN202010480988A CN111517945A CN 111517945 A CN111517945 A CN 111517945A CN 202010480988 A CN202010480988 A CN 202010480988A CN 111517945 A CN111517945 A CN 111517945A
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- reaction
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- chlorobutyryl chloride
- butyrolactone
- trichloromethyl
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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
- C07C51/58—Preparation of carboxylic acid halides
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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
- B01J27/00—Catalysts comprising the elements or compounds of halogens, sulfur, selenium, tellurium, phosphorus or nitrogen; Catalysts comprising carbon compounds
- B01J27/14—Phosphorus; Compounds thereof
- B01J27/16—Phosphorus; Compounds thereof containing oxygen, i.e. acids, anhydrides and their derivates with N, S, B or halogens without carriers or on carriers based on C, Si, Al or Zr; also salts of Si, Al and Zr
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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
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
- B01J31/1805—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms the ligands containing nitrogen
Abstract
The invention relates to a synthesis method of 4-chlorobutyryl chloride, which is characterized in that gamma-butyrolactone and di (trichloromethyl) carbonate are used as reaction raw materials, and a specific amine catalyst is used for chlorination reaction to obtain the 4-chlorobutyryl chloride. Wherein, the amine catalyst is an intercalation product obtained after the reaction of aluminium dihydrogen tripolyphosphate and a complex compound of organic amine and copper, and the structure of the intercalation product is as follows:
Description
Technical Field
The invention relates to a method for stably preparing 4-chlorobutyryl chloride for a long time.
Background
4-chlorobutyryl chloride is an important intermediate for organic synthesis and medicines and pesticides.
In the pharmaceutical industry, 4-chlorobutyryl chloride is used for producing antipsychotic drugs of trifluperidol, trichloropiperidinebenzene, levetiracetam, quinolone antibacterial drugs of ciprofloxacin, and the like. Can be used for preparing isoxachlorotole, isoxaflutole and the like in the pesticide industry.
At present, the existing industrial production method of 4-chlorobutyryl chloride is mainly obtained by chlorination of gamma-butyrolactone through thionyl chloride under the catalysis of zinc chloride, and the yield is about 82 percent.
In addition, U.S. Pat. No. 5,78852, GB743557, EP0413264 and the like, it has been proposed to synthesize 4-chlorobutyryl chloride from gamma-butyrolactone by using phosgene as a raw material instead of thionyl chloride as a chlorinating agent, with a yield of 95%. Such as. The method has high yield, the raw material phosgene is cheaper than thionyl chloride, the process is simple, and no SO is generated2The waste gas, three wastes are less, but the chloridizing reagent phosgene is a highly toxic chemical, and is inconvenient to transport and store and has high operation requirement.
In CN104592001A, the reaction of gamma-butyrolactone and thionyl chloride in the presence of a mixed catalyst is proposed, and the obtained product has high purity, but the problems of high raw material cost, high toxicity and more three wastes still exist.
CN104086402A proposes that the yield can be improved by using a phase transfer catalyst in the reaction of γ -butyrolactone and bis (trichloromethyl) carbonate to prepare 4-chlorobutyryl chloride, but there is a problem that the yield is significantly reduced after industrial amplification.
Since the market demand for 4-chlorobutyryl chloride is increasing, a method capable of producing 4-chlorobutyryl chloride on an industrial scale is required.
Disclosure of Invention
The invention aims to provide a preparation method of 4-chlorobutyryl chloride, which has high yield, can stably run for a long time and is suitable for industrial production.
In the reaction for preparing 4-chlorobutyryl chloride from gamma-butyrolactone and bis (trichloromethyl) carbonate, an organic amine catalyst is usually required, but the yield is not high, and although the solution is available, the industrial scale-up production is still difficult. CN108722494A filed by the applicant discloses a novel organic amine catalyst which can effectively improve the yield of chlorobutyryl chloride in industrial large-scale production when being used for preparing chlorobutyryl chloride. However, in subsequent studies by the applicant, it was found that the catalyst has a drawback of insufficient stability although it improves the yield in industrial production, and the catalyst activity cannot be maintained at all times in long-term continuous production, which is disadvantageous for industrial mass production. The reason for this is probably that the intercalation product decomposes after a long period of use, resulting in the deactivation of the catalyst. Therefore, how to solve the stability of the intercalation product is a key factor for improving the performance of the catalyst.
The applicant has made an intensive study in view of the above problems, and as a result, has found that the above problems can be solved by further introducing a Cu atom into an intercalation product obtained by reacting the aluminum dihydrogen tripolyphosphate with an organic amine to form a complex structure.
Aluminium dihydrogen tripolyphosphate is a compound with a layered structure and inorganic ion exchange properties known in the prior art. Its intercalation with amines is known in the art (see the intercalation characteristics of aluminium dihydrogen tripolyphosphate with organic amines, applied chemistry, 2014, 31 (7)).
In the preparation process of the intercalation product, a Cu salt is further added, a Cu complex is formed through heating reaction, and then the intercalation compound with a Cu complex structure is obtained according to the intercalation reaction process.
Specifically, the preparation method of the catalyst of the application is as follows:
adding amine compounds and a solvent into a reactor, stirring uniformly, then dripping a solution of copper salt into the reactor, stirring uniformly at room temperature, adding aluminium dihydrogen tripolyphosphate into the reactor, stirring for reaction at room temperature, separating, and treating to obtain the catalyst.
Wherein, the amine compound is methylamine, ethylamine and aniline, and the copper salt is cupric chloride or cupric sulfate, preferably cupric sulfate. The solvent is ethanol or ethyl acetate, preferably ethanol, and more preferably absolute ethanol. The separation is suction filtration separation, and the post-treatment is washing with ethanol and drying.
The structure of the resulting catalyst is as follows:
wherein R1 is alkyl, aryl, preferably C1-3Alkyl of (C)6-12More preferably methyl, ethyl, phenyl.
The technical scheme for synthesizing the 4-chlorobutyryl chloride comprises the following steps:
a method for synthesizing 4-chlorobutyryl chloride is characterized in that gamma-butyrolactone and bis (trichloromethyl) carbonate are used as reaction raw materials, and a specific amine catalyst is used for chlorination reaction to obtain the 4-chlorobutyryl chloride.
Wherein the amine catalyst is an amine intercalation compound with a copper complex structure prepared according to the method.
The applicant has found that in the reaction of gamma-butyrolactone with bis (trichloromethyl) carbonate, the use of this specific catalyst not only maintains a high reaction yield on an industrial scale, but also maintains the yield well even if it is operated for a long time without significant reduction, and the stable operation time can be up to 500 hours or more, which is significantly superior to the prior art.
The technical scheme of the invention comprises the following specific reaction steps:
at room temperature, gamma-butyrolactone and amine catalyst are mixed, bis (trichloromethyl) carbonate is added into the mixture under stirring, and chlorination is carried out by heating. After the reaction is finished, separating the product to obtain the 4-chlorobutyryl chloride.
In the reaction, the mass ratio of gamma-butyrolactone and bis (trichloromethyl) carbonate is 1: (0.5-2), preferably 1: (1-2). The mass ratio of gamma-butyrolactone to amine catalyst is 1: (0.1-3), preferably 1: (0.1-1). The heating temperature is 60-120 deg.C, preferably 80-100 deg.C. The heating reaction time is 0.5-4 h.
The organic solvent used in the chlorination reaction is selected from: toluene, 1, 2-dichloroethane, methyl 4-chlorobutyrate, xylene, chlorobenzene, o-chlorotoluene, o-dichlorobenzene and m-dichlorobenzene. The amount of the organic solvent is not limited as long as the reactant can be dissolved.
After the reaction is finished, post-treatment is needed, and the treatment process comprises the following steps: and distilling the reaction liquid to remove the solvent, and drying to obtain the 4-chlorobutyryl chloride. The following are preferred: distilling the reaction liquid to remove the solvent, rectifying to obtain a 105-112 ℃ fraction, and drying to obtain the 4-chlorobutyryl chloride.
The chlorination reaction according to the present invention may be carried out as follows: adding an organic solvent into a reaction container, then adding gamma-butyrolactone and an amine catalyst, then adding a solution dissolved with bis (trichloromethyl) carbonate, carrying out chlorination reaction for 0.5-4h at 60-120 ℃, after the reaction is finished, distilling the reaction solution to remove the solvent, then carrying out reduced pressure rectification to obtain a distillate at 105-112 ℃, and drying to obtain 4-chlorobutyryl chloride; the catalyst is as follows: the amine catalyst is an intercalation product containing a copper complex obtained after complexation reaction of aluminium dihydrogen tripolyphosphate, organic amine and copper, and has the following structure:
wherein R1 is alkyl, aryl, preferably C1-3Alkyl of (C)6-12More preferably methyl, ethyl and phenyl, and the addition amount of the catalyst is 0.1-10 mol% of gamma-butyrolactone; the mass ratio of the bis (trichloromethyl) carbonate to the gamma-butyrolactone is 1: 1-5, the organic solvent is o-chlorotoluene, m-dichlorobenzene or o-dichlorobenzene, and the dosage of the organic solvent is 2-10ml/g calculated by the mass of the gamma-butyrolactone.
According to the synthesis method of 4-chlorobutyryl chloride provided by the invention, after the synthesis method is amplified to an industrial grade, the reaction yield can be maintained above 90%, the stable operation can be carried out for more than 500 hours, and the method can be effectively used for industrial production.
Detailed Description
The invention is further illustrated by the following examples. It should be understood that the preparation method of the embodiment of the present invention is only for illustrating the present invention and not for limiting the present invention, and the simple modification of the preparation method of the present invention based on the concept of the present invention is within the scope of the claimed invention.
Catalyst preparation example 1:
adding 9g of methylamine and 50ml of absolute ethyl alcohol into a flask, uniformly stirring, then dripping an ethanol solution containing 16g of anhydrous copper sulfate into the flask, stirring the mixture at room temperature for reaction, adding an ethanol solution containing 100g of aluminium dihydrogen tripolyphosphate into the mixture after reactants disappear, stirring the mixture at room temperature for reaction, separating the mixture, and treating the mixture to obtain 79.8g of catalyst A.
Catalyst preparation example 2:
82.7 of catalyst B was obtained in the same manner as in preparation example 1, except that 14g of ethylamine was added in place of methylamine, and ethyl acetate was used as a solvent.
Catalyst preparation example 3:
the same procedures as in catalyst preparation example 1 were repeated except that 28g of aniline was added in place of methylamine, and 14g of anhydrous copper chloride was added in place of copper sulfate, to thereby obtain 96.6g of catalyst C.
Catalyst preparation example 4:
according to the method described in preparation example 1 of the CN108722494A catalyst, methylamine and water are added into a reactor, dissolved, put into aluminium dihydrogen tripolyphosphate, stirred at normal temperature for reaction, and separated to obtain the catalyst D.
Example 1: preparation of 4-chlorobutyryl chloride:
adding toluene into a flask, then adding 1.5mol of gamma-butyrolactone and 0.05mol of catalyst A, stirring, heating to 60 ℃ through a water bath, simultaneously slowly adding 1mol of toluene solution of bis (trichloromethyl) carbonate, keeping the reaction temperature after the addition is finished, reacting for 2h under stirring, introducing nitrogen for sweeping to obtain a crude reaction solution, carrying out reduced pressure distillation, and collecting fractions in sections, wherein the fraction (50mmHg) at 105-112 ℃ is 4-chlorobutyryl chloride, and drying the fractions to obtain 129g of 4-chlorobutyryl chloride, and the yield is 91.5%.
Example 2: preparation of 4-chlorobutyryl chloride:
adding toluene into a flask, then adding 1.5mol of gamma-butyrolactone and 0.1mol of catalyst B, stirring, heating to 80 ℃ through a water bath, simultaneously slowly adding 1mol of toluene solution of bis (trichloromethyl) carbonate, keeping the reaction temperature after the addition is finished, reacting for 2h under stirring, introducing nitrogen for sweeping to obtain a crude reaction solution, carrying out reduced pressure distillation, and collecting fractions in sections, wherein the fraction (50mmHg) at 105-112 ℃ is 4-chlorobutyryl chloride, and drying the fractions to obtain 133g of 4-chlorobutyryl chloride, wherein the yield is 94.3%.
Example 3: preparation of 4-chlorobutyryl chloride:
adding toluene into a flask, then adding 1.5mol of gamma-butyrolactone and 0.1mol of catalyst C, stirring, heating to 80 ℃ through a water bath, simultaneously slowly adding 1mol of toluene solution of bis (trichloromethyl) carbonate, keeping the reaction temperature after the addition is finished, reacting for 4h under stirring, introducing nitrogen for sweeping to obtain a crude reaction solution, carrying out reduced pressure distillation, and collecting fractions in sections, wherein the fraction (50mmHg) at 105-112 ℃ is 4-chlorobutyryl chloride, and drying the fractions to obtain 127g of 4-chlorobutyryl chloride, wherein the yield is 90.1%.
Example 4: preparation of 4-chlorobutyryl chloride:
adding toluene into a reaction kettle, then adding 35mol of gamma-butyrolactone and 2mol of catalyst A, stirring, heating to 80 ℃ in a jacket of the reaction kettle through a water bath, simultaneously slowly adding 30mol of toluene solution of bis (trichloromethyl) carbonate, keeping the reaction temperature after the addition is finished, reacting for 8h under stirring, introducing nitrogen for sweeping to obtain a crude reaction solution, carrying out reduced pressure distillation, and collecting fractions in sections, wherein a fraction (50mmHg) at 105-112 ℃ is 4-chlorobutyryl chloride, and drying the fractions to obtain 3.85kg of 4-chlorobutyryl chloride with a yield of 91.1%.
And (3) after the tower bottoms are evaporated and separated, recovering the catalyst A, reusing the catalyst A for 5 times according to the process, wherein the yields of the 2 nd to 6 th times are respectively as follows:
| yield (%) | |
| 2 | 90.8 |
| 3 | 90.4 |
| 4 | 91.0 |
| 5 | 90.6 |
| 6 | 89.8 |
Example 5: preparation of 4-chlorobutyryl chloride:
adding toluene into a reaction kettle, then adding 42mol of gamma-butyrolactone and 2mol of catalyst B, stirring, heating to 80 ℃ in a jacket of the reaction kettle through a water bath, simultaneously slowly adding 40mol of toluene solution of bis (trichloromethyl) carbonate, keeping the reaction temperature after the addition is finished, reacting for 6h under stirring, introducing nitrogen for sweeping to obtain a crude reaction solution, carrying out reduced pressure distillation, and collecting fractions in sections, wherein a fraction (50mmHg) at 105-112 ℃ is 4-chlorobutyryl chloride, and drying the fractions to obtain 5.10kg of 4-chlorobutyryl chloride with the yield of 90.4%.
And (3) after the tower bottoms are evaporated and separated, recovering the catalyst B, reusing the catalyst B for 6 times according to the process, wherein the yields of the 2 nd to 7 th times are respectively as follows:
| yield (%) | |
| 2 | 91.1 |
| 3 | 90.2 |
| 4 | 90.3 |
| 5 | 90.6 |
| 6 | 90.3 |
| 7 | 88.5 |
Example 6: preparation of 4-chlorobutyryl chloride:
adding toluene into a reaction kettle, adding 32mol of gamma-butyrolactone and 2mol of catalyst C, stirring, heating to 80 ℃ in a jacket of the reaction kettle through a water bath, slowly adding 30mol of toluene solution of bis (trichloromethyl) carbonate, keeping the reaction temperature after the addition is finished, reacting for 8 hours under stirring, introducing nitrogen for sweeping to obtain a crude reaction solution, carrying out reduced pressure distillation, and collecting fractions in sections, wherein a fraction (50mmHg) at 105-112 ℃ is 4-chlorobutyryl chloride, and drying the fractions to obtain 3.78kg of 4-chlorobutyryl chloride with the yield of 89.3%.
And (3) after the tower bottoms are evaporated and separated, recovering the catalyst C, reusing the catalyst C for 4 times according to the process, wherein the yields of the 2 nd to 5 th times are respectively as follows:
| yield (%) | |
| 2 | 89.8 |
| 3 | 89.5 |
| 4 | 90.0 |
| 5 | 84.1 |
Comparative example 1: preparation of 4-chlorobutyryl chloride (example 1 of CN 108722494A)
Adding toluene into a reaction kettle, then adding 20mol of gamma-butyrolactone and 2mol of catalyst D, stirring, heating to 80 ℃ in a jacket of the reaction kettle through a water bath, simultaneously slowly adding 20mol of toluene solution of bis (trichloromethyl) carbonate, keeping the reaction temperature after the addition is finished, reacting for 2.5h under stirring, introducing nitrogen for sweeping to obtain a crude reaction solution, carrying out reduced pressure distillation, and collecting fractions in sections, wherein a fraction (50mmHg) at 105-112 ℃ is 4-chlorobutyryl chloride, and drying the fractions to obtain 2.61kg of 4-chlorobutyryl chloride with a yield of 92.5%.
And (3) after the tower bottoms are evaporated and separated, recovering the catalyst D, reusing the catalyst D for 4 times according to the process, wherein the yields of the 2 nd to 5 th times are respectively as follows:
| yield (%) | |
| 2 | 92.1 |
| 3 | 89.4 |
| 4 | 86.2 |
| 5 | 79.0 |
As can be seen from the above comparative examples, the catalyst of comparative example 1 was reduced in product yield to 80% or less after being used repeatedly 4 times, and was significantly inferior in stability to the examples of the present application.
Example 7: preparation of 4-chlorobutyryl chloride:
introducing gamma-butyrolactone, di (trichloromethyl) carbonate, catalyst A and toluene into a tubular reactor at a certain flow rate from a batching tank, a pump and an adjusting valve, wherein the temperature of the tubular reactor is 80 ℃, the material ratio of the gamma-butyrolactone, the di (trichloromethyl) carbonate and the catalyst A is 1:1:0.06, and the reaction space velocity is 8h—1The reaction liquid obtained at the tail part of the reactor is separated by reduced pressure distillation, fractions are collected by sections, the liquid at the top of the tower is a product, and the unreacted raw materials and the catalyst are recycled to the reactor at the bottom of the tower.
The conversion rate of raw materials and the selectivity of products are monitored in the reaction process, and the monitoring method is to adopt the reaction liquid at the tail part of the reactor and analyze the reaction liquid by adopting liquid chromatography. After the reaction was stably operated, samples were taken at 50, 100, 300 and 500 hours from the reaction, and the results were as follows:
| reaction time | Conversion ratio of raw Material (%) | Product selectivity (%) |
| 50 | 85.4 | 92.6 |
| 100 | 94.2 | 98.3 |
| 300 | 95.0 | 97.5 |
| 500 | 80.4 | 89.5 |
From the above results, it can be seen that, in the initial stage of the reaction, since the reaction system is not stable yet, the reaction result is not ideal in 50h, but after 100h, the reaction is very stable, the conversion rate and the product selectivity are both very good, and when 500h, the conversion rate and the selectivity are reduced, but the yield is still about 80%, which is acceptable in industry. It can be seen that the catalyst of the present application did not show a significant activity decrease after 500 hours of operation.
Claims (8)
1. A method for preparing 4-chlorobutyryl chloride stably for a long time is characterized in that gamma-butyrolactone and di (trichloromethyl) carbonate are used as reaction raw materials, and a specific amine catalyst is used for chlorination reaction to obtain 4-chlorobutyryl chloride;
wherein, the amine catalyst is an intercalation product obtained after the reaction of aluminium dihydrogen tripolyphosphate and a complex compound of organic amine and copper, and the structure of the intercalation product is as follows:
wherein, R is alkyl and aryl, preferably C1-3 alkyl, and C6-12 aryl, more preferably methyl, ethyl, phenyl.
2. The method of claim 1, wherein the organic amine is methylamine, ethylamine, or aniline.
3. The method of claim 1, wherein the amount of material of γ -butyrolactone to amine catalyst is in a ratio of 1: (0.1-3), preferably 1: (0.1-1).
4. The method of claim 1, wherein the γ -butyrolactone and amine catalyst are mixed at room temperature, bis (trichloromethyl) carbonate is added thereto under stirring, and the chlorination reaction is carried out by heating, and after the reaction is completed, the product is separated to obtain 4-chlorobutyryl chloride.
5. The method of claim 4, wherein the mass ratio of γ -butyrolactone and bis (trichloromethyl) carbonate is 1: (0.5-2), preferably 1: (1-2).
6. The method according to claim 4, wherein the heating temperature is 60-120 ℃, preferably 60-80 ℃.
7. The process of claim 4, wherein the chlorination reaction is carried out using an organic solvent selected from the group consisting of toluene, 1, 2-dichloroethane, methyl 4-chlorobutyrate, xylene, chlorobenzene, o-chlorotoluene, o-dichlorobenzene, and m-dichlorobenzene.
8. The process of claim 1, wherein the catalyst is prepared by the following steps: adding amine compounds and a solvent into a reactor, stirring uniformly, then dripping a solution of copper salt into the reactor, stirring uniformly at room temperature, adding aluminium dihydrogen tripolyphosphate into the reactor, stirring for reaction at room temperature, separating, and treating to obtain the catalyst.
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| CN202010480988.1A CN111517945A (en) | 2020-05-30 | 2020-05-30 | Method for long-term stable preparation of 4-chlorobutyryl chloride |
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| CN202010480988.1A CN111517945A (en) | 2020-05-30 | 2020-05-30 | Method for long-term stable preparation of 4-chlorobutyryl chloride |
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