CN116553997A

CN116553997A - Synthesis method of intermediate 1,2, 3-trifluoro-benzene for synthesizing 3,4, 5-trifluoro-bromobenzene

Info

Publication number: CN116553997A
Application number: CN202310833487.0A
Authority: CN
Inventors: 申泽农; 张小垒; 王召平
Original assignee: Guobang Pharmaceutical Group Co Ltd; Shandong Guobang Pharmaceutical Co Ltd
Current assignee: Guobang Pharmaceutical Group Co Ltd; Shandong Guobang Pharmaceutical Co Ltd
Priority date: 2023-07-10
Filing date: 2023-07-10
Publication date: 2023-08-08
Anticipated expiration: 2043-07-10
Also published as: CN116553997B

Abstract

The invention discloses a synthesis method of an intermediate 1,2, 3-trifluoro-benzene for synthesizing 3,4, 5-trifluoro-bromobenzene, belonging to the technical field of organic chemical industry, which comprises the following steps: denitration, chlorination, dechlorination and hydrogenation; adding dry 2,3, 4-trifluoro nitrobenzene and azodiisobutyronitrile into a reaction vessel, mechanically heating to perform denitration chlorination reaction, introducing dry chlorine, continuously introducing chlorine after the product starts to flow out, continuously reacting, washing the collected crude product with sodium hydroxide aqueous solution, washing with water to be neutral, drying, and rectifying to obtain 2,3, 4-trifluoro chlorobenzene; the method can avoid the use of bromine and diazotization reaction, has mild and safe reaction, does not produce salt-containing waste acid, has low pollution, can recycle raw materials, has simple separation operation of products, fewer byproducts and high yield.

Description

Synthesis method of intermediate 1,2, 3-trifluoro-benzene for synthesizing 3,4, 5-trifluoro-bromobenzene

Technical Field

The invention relates to the technical field of organic chemical industry, in particular to a method for synthesizing an intermediate 1,2, 3-trifluorobenzene of 3,4, 5-trifluorobromobenzene.

Background

3,4, 5-trifluoro bromobenzene is an important pesticide intermediate, and is mainly used for synthesizing succinic acid dehydrogenase inhibitor (SDHI) bactericide fluxapyroxad. The fluxapyroxad is a high-selectivity pyrazole amide bactericide developed by Basiff company, has novel structure, broad spectrum and high efficiency, has a mode of action different from the existing bactericide, becomes a new hot spot for the research of bactericides, and meanwhile, 3,4, 5-trifluoro-bromobenzene is also an important liquid crystal intermediate, and can be used for producing a 4 th-generation TFT color liquid crystal material.

The common route for synthesizing 3,4, 5-trifluoro-bromobenzene is to take 2,3, 4-trifluoro-nitrobenzene as a raw material, and obtain 3,4, 5-trifluoro-bromobenzene through reduction, bromination and diazo deamination, as follows:

chinese patent CN112010733B discloses a method for synthesizing 3,4, 5-trifluorobromobenzene, which comprises the steps of dissolving 2,3, 4-trifluoronitrobenzene in methanol, adding a skeletal nickel catalyst, reducing under hydrogen, rectifying to obtain 2,3, 4-trifluoroaniline, then using bromine and hydrogen peroxide for bromination to prepare a 2,3, 4-trifluoro-6-bromoaniline crude product, then using nitrososulfuric acid for diazotization reaction, using a water-sulfuric acid-sodium hypophosphite-cuprous oxide system for reducing diazonium salt, and carrying out post treatment to obtain 3,4, 5-trifluorobromobenzene.

Chinese patent CN103601613A discloses a method for synthesizing 3,4, 5-trifluoro-bromobenzene, which comprises dispersing 2,3, 4-trifluoro-aniline in a solvent, dropwise adding bromine for bromination reaction, and after the reaction is completed, obtaining 2,3, 4-trifluoro-6-bromoaniline through post-treatment; sodium nitrite is dissolved in sulfuric acid, and 2,3, 4-trifluoro-6-bromoaniline obtained is dropwise added under the stirring condition to carry out diazotization reaction to obtain diazonium salt intermediate; under the action of hypophosphorous acid and copper catalyst, the obtained diazonium salt intermediate is subjected to deamination reaction, and after the reaction is completed, 3,4, 5-trifluoro bromobenzene is obtained through post-treatment.

The above route usually uses bromine for bromination, and has high cost and certain danger; the diazo process has severe heat release, is difficult to control and is easy to generate danger; the diazotization process often requires a large amount of acid and often uses sodium nitrite as a diazotizing agent, resulting in a large amount of salty waste acid which is difficult to treat; the deamination reduction step often uses sodium hypophosphite or hypophosphorous acid, and the resulting phosphorus-containing wastewater is difficult to treat.

In recent years, reports of preparing 3,4, 5-trifluorobromobenzene by using 1,2, 3-trifluorobenzene appear successively, bromine is not needed in the process, and the raw material cost is low; the diazonium reaction is not needed, the exothermic safety problem and the treatment problem of a large amount of salt-containing waste acid are avoided, the reaction cost is low, the reaction is mild, the environment is protected, the safety is realized, and meanwhile, the yield is high, so that the method is one of green ideal routes for synthesizing 3,4, 5-trifluoro-bromobenzene. The method comprises the following steps:

chinese patent CN108947763a discloses a method for preparing 3,4, 5-trifluorobromobenzene by using 1,2, 3-trifluorobenzene, which comprises dissolving 1,2, 3-trifluorobenzene in an organic solvent, adding aqueous sodium bromide solution containing buffer solution, dropwise adding sodium hypochlorite to react for bromination, desolventizing to obtain crude 3,4, 5-trifluorobromobenzene from the organic phase, and performing melt crystallization on the crude 3,4, 5-trifluorobromobenzene. The method is simple, high in yield, mild in preparation process, efficient, environment-friendly, safe and reliable.

Chinese patent CN114516780a discloses a process for preparing 3,4, 5-trifluorobromobenzene from 1,2, 3-trifluorobenzene by reacting 1,2, 3-trifluorobenzene with carbon tetrabromide under the catalysis of anhydrous aluminum trichloride to produce 1,2, 3-trifluoro-5-tribromomethylbenzene; 1,2, 3-trifluoro-5-tribromomethylbenzene and water undergo hydrolysis reaction to generate 1,2, 3-trifluoro-benzoic acid, and meanwhile, 1,2, 3-trifluoro-benzoic acid and 1,2, 3-trifluoro-5-tribromomethylbenzene undergo condensation reaction to generate 1,2, 3-trifluoro-benzoyl bromide; the 1,2, 3-trifluoro-benzoyl bromide is decarbonylated under the catalysis of rhodium chloride of tri (triphenylphosphine) to generate 3,4, 5-trifluoro-bromobenzene.

The literature 'new process for synthesizing 3,4, 5-trifluoro-bromobenzene [ J ]. World pesticide, yin Kai, 2020,42 (04): 54-56.' discloses a method for preparing 3,4, 5-trifluoro-bromobenzene by using 1,2, 3-trifluoro-benzene, wherein 1,2, 3-trifluoro-benzene is dissolved in a certain amount of dichloroethane, cooled to below 10 ℃, sodium bromide and sodium dihydrogen phosphate aqueous solution are added, the temperature is controlled below 15 ℃, a certain amount of sodium hypochlorite solution is slowly added dropwise for 1-2 hours, after reaction, liquid separation, organic phase water washing, desolventizing, melting crystallization are carried out, the purity of the product is 99.5%, and the yield is 94.5%.

Therefore, the demand of 1,2, 3-trifluorobenzene is increasing, in addition, besides being used for synthesizing 3,4, 5-trifluorobromobenzene, 1,2, 3-trifluorobenzene can also be used for synthesizing difluorobenzene alkyl ether and as an additive of nonaqueous electrolyte of a lithium ion battery, so that the compatibility of electrolyte and a pole piece can be effectively improved, the permeability of the electrolyte on the pole piece can be improved, and meanwhile, the 1,2, 3-trifluorobenzene has an anode film forming function, the anode can be protected, and the high-temperature storage performance and the cycle performance can be improved. However, the research reports on the synthesis of 1,2, 3-trifluoro benzene are less in China, the adopted raw materials are not fixed, the common cost is higher, and the yield is generally not high.

Chinese patent CN114516780a discloses a synthesis method of 1,2, 3-trifluorobenzene: performing fluorination reaction on hexachlorocyclohexane and anhydrous hydrogen fluoride to obtain hexafluorocyclohexane, and performing thermal decomposition on the obtained hexafluorocyclohexane to obtain 1,2, 3-trifluorobenzene and 1,2, 4-trifluorobenzene, and separating the 1,2, 3-trifluorobenzene and the 1,2, 4-trifluorobenzene by distillation; the literature "new process for synthesizing 3,4, 5-trifluorobromobenzene [ J ]. World pesticide, yin Kai, 2020,42 (04): 54-56." reports a synthetic method of 1,2, 3-trifluorobenzene: adding 181.5g of 1,2, 3-trichlorobenzene, 275 g sulfolane, 208 g potassium fluoride and 2g quaternary ammonium salt catalyst into a reactor, heating to 170-180 ℃ after nitrogen replacement, controlling the pressure at 2MPa, preserving heat and pressure for reaction, rectifying to obtain 1,2, 3-trifluorobenzene 105.6 g after sampling is qualified, wherein the characteristics are colorless transparent liquid, the purity is 99%, and the yield is 80%; however, the synthesis method of the 1,2, 3-trifluoro benzene is characterized by fluorination reaction, strong exothermic reaction, rapid reaction, great heat change and great danger, and the long-term contact of potassium fluoride has a certain degree of harm to human body; meanwhile, the synthesized 1,2, 3-trifluorobenzene is mainly used for further synthesizing 3,4, 5-trifluorobromobenzene, the main process for synthesizing 3,4, 5-trifluorobromobenzene in China is to prepare the 3,4, 5-trifluorobromobenzene from different raw materials through one-step or multi-step reaction, then the 3, 4-trifluorobromobenzene is reduced, brominated and deaminated, for enterprises of which the processes are mature and equipment starts to operate and produce, all process flows are not changed practically, and an intermediate product 2,3, 4-trifluoronitrobenzene in the whole synthesis process is taken as a starting point, and the 3,4, 5-trifluorobromobenzene is prepared through the research and development of a new process instead of the bromination with high original danger and high pollution and cost, so that the method not only accords with the ideas of safe, environment-friendly and safe production and green chemistry, but also can reduce the cost, inspires the improvement of the existing enterprise synthetic route, and has high feasibility and practical application value.

Therefore, in order to improve the original synthetic route of 3,4, 5-trifluorobromobenzene through a new process, and simultaneously to create a new synthetic route of 1,2, 3-trifluorobromobenzene, it is desirable to find a green, environment-friendly, safe and low-cost route for synthesizing 1,2, 3-trifluorobromobenzene by taking the raw material 2,3, 4-trifluoronitrobenzene of the traditional synthetic route of 3,4, 5-trifluorobromobenzene as a starting point, and further synthesize 3,4, 5-trifluorobromobenzene through a new process, so as to complete the improvement of the traditional synthetic route of 3,4, 5-trifluorobromobenzene.

Literature study of denitration halogenation Synthesis of aromatic halides [ D]2003 university of even-worker Han Yanli, "more specifically discloses the denitration chlorination reaction, and by selecting a catalyst containing F, cl, CF ₃ The study of the denitration chlorination reaction of aromatic compounds containing one or two nitro groups of the absorbing group is carried out, and the conclusion is drawn that: the presence of the electron withdrawing group is advantageous in reducing the electron cloud density of the carbon atoms attached to the nitro group and thus in facilitating the denitration chlorination reaction. Under the conditions, the yield of the denitration chlorination reaction of the o-fluoronitrobenzene is 79%.

The document "transition metal catalyzed dehalogenation hydrogenation of aromatic halides research [ D ].2022. Dung's university of China's teaching, dung's congratulation" discloses in more detail dehalogenation hydrogenation of aromatic halides which, under appropriate catalyst and reaction conditions, can successfully convert the Cl, br substituted substrates to the corresponding dehalogenated products in nearly equivalent amounts, but because of the higher C-F bond energy, it is difficult to conduct dehalogenation under ordinary conditions.

Inspired by the two documents, the invention develops a synthesis method of 1,2, 3-trifluorobenzene in order to improve the process by using the common raw materials for synthesizing 3,4, 5-trifluorobromobenzene at present and simultaneously to create a new thought for synthesizing 1,2, 3-trifluorobenzene.

Disclosure of Invention

Aiming at the defects existing in the prior art, the invention provides a synthesis method of the intermediate 1,2, 3-trifluorobromobenzene for synthesizing 3,4, 5-trifluorobromobenzene, which can avoid bromine use and diazotization reaction, has mild reaction, safety, no production of salt-containing waste acid, low pollution, repeated utilization of raw materials, simple separation operation of products, few byproducts and high yield.

In order to solve the technical problems, the technical scheme adopted by the invention is as follows:

a synthesis method of an intermediate 1,2, 3-trifluorobenzene for synthesizing 3,4, 5-trifluorobromobenzene comprises the following steps: denitration, chlorination, dechlorination and hydrogenation;

adding dry 2,3, 4-trifluoro nitrobenzene and azodiisobutyronitrile into a reaction vessel, stirring, heating to perform denitration chlorination reaction, introducing dry chlorine, continuously introducing chlorine after the product starts to flow out, continuously reacting, washing the collected crude product with sodium hydroxide aqueous solution, washing with water to be neutral, drying, and rectifying to obtain 2,3, 4-trifluoro chlorobenzene;

in the denitration chlorination, the mass ratio of the dried 2,3, 4-trifluoro nitrobenzene to the azodiisobutyronitrile is 1:0.005-0.02;

preferably, the mass ratio of the dried 2,3, 4-trifluoro-nitrobenzene to the azodiisobutyronitrile is 1:0.01;

the stirring speed is 300rpm;

the reaction temperature of the denitration chlorination reaction is 180-200 ℃;

preferably, the reaction temperature of the denitration chlorination reaction is 200 ℃;

the flow rate of the chlorine is 20-40g/h;

preferably, the flow rate of the chlorine is 25-30g/h;

the reaction continuing time is 6-12h;

preferably, the time for continuing the reaction is 8 hours;

adding 2,3, 4-trifluorochlorobenzene, sodium hydroxide and ethanol into a high-pressure reaction vessel, stirring until the solids are completely dissolved, stopping stirring, adding Raney Ni catalyst, sealing the high-pressure reaction vessel, introducing nitrogen to replace air in the vessel, using hydrogen to replace air in the vessel, continuing introducing hydrogen to the reaction pressure, heating, stirring, performing dechlorination hydrogenation reaction, supplementing hydrogen to the reaction pressure whenever the pressure in the sealed reaction vessel drops by 0.2MPa, and continuously maintaining the pressure for 10min when the pressure in the vessel does not drop any more, and rectifying to obtain 1,2, 3-trifluorobenzene;

in the dechlorination hydrogenation, the molar ratio of sodium hydroxide to 2,3, 4-trifluoro-chlorobenzene is 1-2:1;

preferably, the molar ratio of sodium hydroxide to 2,3, 4-trifluorochlorobenzene is 1.5:1;

the mass ratio of the 2,3, 4-trifluoro-chlorobenzene to the ethanol is 50.02:200;

the stirring speed is 300rpm;

the mass ratio of Raney Ni catalyst to 2,3, 4-trifluoro-chlorobenzene is 0.05-0.15:1;

preferably, the mass ratio of Raney Ni catalyst to 2,3, 4-trifluorochlorobenzene is 0.1:1;

the reaction temperature of the dechlorination hydrogenation reaction is 60-80 ℃;

preferably, the reaction temperature of the dechlorination hydrogenation reaction is 70 ℃;

the reaction pressure of the dechlorination hydrogenation reaction is 0.5-1.5MPa;

preferably, the reaction pressure of the dechlorination hydrogenation reaction is 1MPa.

The synthesis process of 1,2, 3-trifluoro benzene as intermediate for synthesizing 3,4, 5-trifluoro bromobenzene includes the first denitration and chlorination of 2,3, 4-trifluoro nitrobenzene to synthesize 2,3, 4-trifluoro chlorobenzene; then, under the catalysis of Raney nickel, the 2,3, 4-trifluoro-chlorobenzene reacts with hydrogen to produce 1,2, 3-trifluoro-benzene through dechlorination and hydrogenation, and the specific reaction route is as follows:

the mechanism of the denitration chlorination reaction is presumed to be as follows:

the dechlorination hydrogenation reaction mechanism is presumably summarized as follows:

the hydrogen is adsorbed and activated on the surface of the catalyst, and the main form of the hydrogen is hydrogen atoms which are finally generated by homolytic cleavage, and M-H adsorption bonds which form similar covalent bonds with metal atoms (M) are substituted with 2,3, 4-trifluorochlorobenzene through free radical process to generate hydrogen chloride of one molecule; the sodium hydroxide is used for neutralizing the generated hydrogen chloride and shifting the balance to the right, so that the existence of the sodium hydroxide is a necessary condition for hydrodechlorination, and the added sodium hydroxide must be larger than the removed hydrogen chloride, otherwise the reaction is incomplete; the pressure of the hydrogen gas together with the presence of the base promotes the reaction.

Compared with the prior art, the invention has the beneficial effects that:

(1) The invention relates to a method for synthesizing 3,4, 5-trifluoro-bromobenzene intermediate 1,2, 3-trifluoro-benzol, which takes 2,3, 4-trifluoro-nitrobenzene and chlorine as raw materials, azodiisobutyronitrile as initiator, prepares 2,3, 4-trifluoro-chlorobenzene at high temperature, and then prepares 1,2, 3-trifluoro-benzol by dehalogenation with hydrogen at high temperature under the condition of metal catalyst, and the prepared 1,2, 3-trifluoro-benzol can synthesize 3,4, 5-trifluoro-bromobenzene by a new process; compared with the traditional synthetic route of 3,4, 5-trifluoro bromobenzene through four steps of hydrogenation reduction, bromination, diazotization and deamination, the synthetic method only needs three steps of denitration chlorination, dechlorination hydrogenation and bromination, avoids the use of bromine, simultaneously avoids diazotization reaction, is mild and safe in reaction, does not generate salt-containing waste acid, and is characterized in that the two steps of the synthetic method are gas-liquid reactions, no solvent is used in the steps of denitration and chlorination, the pollution is low, raw material gas can be recycled after being treated, and the separation operation of products is simple;

(2) The synthesis method of the intermediate 1,2, 3-trifluorobenzene for synthesizing 3,4, 5-trifluorobromobenzene has less byproducts, and can obtain 1,2, 3-trifluorobenzene with high yield, wherein the purity of the prepared 1,2, 3-trifluorobenzene is 99.87-99.94%, and the yield is 74.45-98.43%.

Drawings

FIG. 1 is a gas chromatogram of 1,2, 3-trifluorobenzene prepared in example 13.

Detailed Description

Specific embodiments of the present invention will now be described in order to provide a clearer understanding of the technical features, objects and effects of the present invention.

Example 1

200.05g of dry 2,3, 4-trifluoronitrobenzene and 2.0186g of azodiisobutyronitrile are added into a four-port bottle provided with a thermometer, a vent pipe, a mechanical stirring device and a rectifying device, the stirring speed is controlled to 300rpm, the temperature is raised to 180 ℃ through an oil bath, dry chlorine with the flow rate of 30g/h is introduced, the product flows out after 7 minutes of reaction, the chlorine is continuously introduced after the product starts to flow out, the reaction is continued for 10 hours, the collected crude product is washed by 10wt% sodium hydroxide aqueous solution, then washed to be neutral, dried and rectified to obtain 169.82g of 2,3, 4-trifluorochlorobenzene, the yield is 90.19% (calculated by 2,3, 4-trifluoronitrobenzene, the same applies below), and the purity is detected to be 99.91% (the peak area ratio in a gas phase report, the same applies below).

Example 2

The reaction temperature in example 1 was changed to 190℃and the other operations were the same as in example 1 to obtain 175.95g of 2,3, 4-trifluorochlorobenzene, whose purity was 99.89% as measured in a gas phase, in 93.42% yield.

Example 3

The reaction temperature was changed to 200℃in example 1, and the other operations were the same as in example 1, to obtain 181.68g of 2,3, 4-trifluorochlorobenzene, yield 96.46% and purity of 99.88% as measured by gas phase.

In comparative examples 1 to 3, the reaction time, chlorine flow rate, ratio of raw materials to initiator were the same, the reaction temperature was 180 to 200℃and the yield of 2,3, 4-trifluorochlorobenzene was 90.19 to 96.46%, the yield increased with an increase in temperature, but the optimum reaction temperature was 200℃in view of the fact that the raw materials were easily distilled off to lower the conversion rate when the temperature was further increased.

Example 4

The procedure of example 3 was repeated except that the flow rate of chlorine gas was changed to 20g/h, and the same procedure was repeated except for using the catalyst in example 3, to obtain 174.69g of 2,3, 4-trifluorochlorobenzene, yield 92.76% and purity thereof as measured by gas phase was 99.90%.

Example 5

The flow rate of chlorine gas in example 3 was changed to 25g/h, and the same operation as in example 3 was repeated to obtain 182.05g of 2,3, 4-trifluorochlorobenzene, whose purity was 99.91% as measured by gas phase, in 96.68% yield.

Example 6

The flow rate of chlorine gas in example 3 was changed to 35g/h, and the same operation as in example 3 was repeated to obtain 180.65g of 2,3, 4-trifluorochlorobenzene, yield 95.94% and purity thereof as measured by gas phase was 99.91%.

Example 7

The flow rate of chlorine gas in example 3 was changed to 40g/h, and the same operation as in example 3 was repeated to obtain 181.03g of 2,3, 4-trifluorochlorobenzene, yield 96.12% and purity 99.89% by gas phase detection.

Comparative examples 3-7, where the reaction temperature, time, raw materials and initiator ratio were the same, the flow rate of chlorine was 20-40g/h, and the yield of 2,3, 4-trifluorochlorobenzene was 92.76-96.68%; the yield is basically the same when the flow rate of chlorine is 25-40g/h, the yield is the lowest when the flow rate of chlorine is 20g/h, deep chlorination is easy to occur to generate a small amount of polychlorinated benzene when the flow rate of chlorine exceeds 30g/h, and the utilization rate of chlorine is low at the flow rate, so that the optimal flow rate of chlorine is determined to be 25-30g/h.

Example 8

The same procedures as in example 5 were repeated except for changing the mass of azobisisobutyronitrile added in example 5 to 1.0079g to give 161.79g of 2,3, 4-trifluorochlorobenzene, yield 85.94% and purity 99.93% by gas phase detection.

Example 9

The same procedures as in example 5 were repeated except for changing the mass of azobisisobutyronitrile added in example 5 to 4.0003g to give 181.68g of 2,3, 4-trifluorochlorobenzene, yield 96.49% and purity 99.92% by gas phase detection.

In comparative examples 5,8-9, the reaction temperature, time and chlorine flow rate were the same, and when the mass of the initiator azobisisobutyronitrile was 0.5% of the mass of 2,3, 4-trifluoronitrobenzene, the initiation rate was slow, the reaction rate was decreased, and the yield of 2,3, 4-trifluorochlorobenzene was decreased. When the amount is increased to 2% by mass of 2,3, 4-trifluoronitrobenzene, the yield of 2,3, 4-trifluorochlorobenzene is not increased significantly, but the post-treatment is difficult, so that the optimum initiator amount is 1% by mass of 2,3, 4-trifluoronitrobenzene.

Example 10

The reaction time in example 5 was changed to 6 hours, and the other operations were the same as in example 5 to obtain 136.86g of 2,3, 4-trifluorochlorobenzene, yield 72.68% and purity thereof as measured in a gas phase was 99.91%.

Example 11

The reaction time was changed to 8 hours in example 5, and the same operation was conducted as in example 5 to obtain 181.86g of 2,3, 4-trifluorochlorobenzene, yield 96.52% and purity thereof as measured in a gas phase was 99.85%.

Example 12

The reaction time was changed to 12 hours in example 5, and the same operation as in example 5 was repeated to obtain 180.57g of 2,3, 4-trifluorochlorobenzene, the yield was 95.86%, and the purity thereof was 99.87% as measured in a gas phase.

In comparative examples 5, 10 and 12, the reaction temperature, the flow rate of chlorine and the ratio of raw materials to initiator are the same, the reaction time is between 6 and 12 hours, the yield of 2,3, 4-trifluorochlorobenzene is between 72.68 and 96.68 percent, the reaction is incomplete when the reaction time is short, the yield of the product is reduced, and the yield is basically unchanged when the reaction reaches 8 hours, so that the optimal reaction time is 8 hours.

Ten batches of 2,3, 4-trifluorochlorobenzene were prepared according to the procedure of example 11, and 1824.56g of the prepared 2,3, 4-trifluorochlorobenzene was mixed, and the purity thereof was 99.89% as measured in a gas phase, as a reaction raw material of examples 13-21.

Example 13

Adding octatooth type magneton into autoclave, adding 50.02g2,3, 4-trifluoro chlorobenzene, 18.07g sodium hydroxide and 200g ethanol, starting magnetic stirring, increasing the rotation speed to 300rpm, stopping stirring, adding 5.03g Raney Ni catalyst, sealing the autoclave, introducing nitrogen, replacing air in the autoclave with nitrogen for three times after confirming that the air tightness of the device is good, opening a hydrogen cylinder main valve, regulating to the required hydrogen pressure with a pressure reducing valve, opening an air inlet valve on the autoclave, making hydrogen enter the autoclave, replacing with hydrogen for three times, introducing hydrogen to 1MPa, heating the autoclave to 80 ℃, starting magnetic stirring, increasing the rotating speed to 300rpm, supplementing hydrogen to 1MPa whenever the pressure in the reaction kettle is reduced by 0.2MPa, keeping the pressure for 10min when the pressure in the kettle is not reduced any more, taking out the product from the kettle, rectifying and recovering ethanol to obtain 38.66g of 1,2, 3-trifluorobenzene, and carrying out gas chromatographic analysis on the prepared 1,2, 3-trifluorobenzene with the yield of 97.38% (calculated by 2,3, 4-trifluorochlorobenzene, the same applies hereinafter), wherein the obtained gas chromatographic chart is shown in figure 1, and the peak substance at 9.825min is the product 1,2, 3-trifluorobenzene, and the purity of the prepared 1,2, 3-trifluorobenzene is 99.94 as can be seen from figure 1;

the Raney Ni catalyst has nickel in 85 wt% and specific surface area of 100m ² /g。

Example 14

The mass of sodium hydroxide added in example 13 was changed to 12.05g, and the rest was the same as in example 13; 33.21g of 1,2, 3-trifluorobenzene was obtained in a yield of 83.60% and a purity of 99.87% as measured by gas phase.

Example 15

The mass of sodium hydroxide added in example 13 was changed to 24.08g, and the rest was the same as in example 13; 38.69g of 1,2, 3-trifluorobenzene was obtained in a yield of 97.45% and a purity of 99.93% as measured by gas phase.

Comparative examples 13 to 15, in which the reaction temperature, the catalyst equivalent and the reaction pressure were the same, the molar ratio of sodium hydroxide to 2,3, 4-trifluorochlorobenzene added in the reaction was 1 to 2:1, the yield increased from 83.60% to 97.38% when the molar ratio was increased from 1:1 to 1.5:1, and the yield did not vary much when the molar ratio was increased from 1.5:1 to 2:1, so that the optimum molar ratio of sodium hydroxide to 2,3, 4-trifluorochlorobenzene was 1.5:1.

Example 16

The same procedures as in example 13 were repeated except for changing the mass of Raney Ni catalyst added in example 13 to 2.48g to give 34.68g of 1,2, 3-trifluorobenzene in a yield of 87.03% and a purity of 99.90% by gas phase detection.

Example 17

The same procedures as in example 13 were repeated except for changing the mass of Raney Ni catalyst added in example 13 to 7.51g to give 38.82g of 1,2, 3-trifluorobenzene in 97.74% yield and 99.89% purity by gas phase detection.

In comparative examples 13, 16 to 17, the reaction temperature, the equivalent amount of sodium hydroxide and the reaction pressure were the same, and the mass of the catalyst added in the reaction was 5 to 15% of the mass of 2,3, 4-trifluorochlorobenzene, wherein when the mass of the catalyst was 5 to 10% of the mass of 2,3, 4-trifluorochlorobenzene, the yield was increased from 87.03% to 97.38%, and the yield was substantially unchanged when the catalyst amount was further increased, so that the optimum catalyst amount was 10% of the mass of 2,3, 4-trifluorochlorobenzene.

Example 18

The reaction temperature in example 13 was changed to 60℃and the other operations were the same as in example 13 to obtain 37.03g of 1,2, 3-trifluorobenzene in 93.24% yield and 99.90% purity as measured by gas phase.

Example 19

The reaction temperature in example 13 was changed to 70℃and the other operations were the same as in example 13, to obtain 39.03g of 1,2, 3-trifluorobenzene, yield 98.29% and purity 99.92% by gas phase detection.

In comparative examples 13, 18 to 19, the catalyst equivalent, sodium hydroxide equivalent and reaction pressure were the same, and the reaction temperature was in the range of 60 to 80℃where the reaction temperature was 70℃corresponding to the highest yield, the reaction rate was decreased when the temperature was decreased, the yield was decreased, and a small amount of excessive hydrogenation defluorination was likely to occur when the temperature was higher, so that the optimum reaction temperature was determined to be 70 ℃.

Example 20

The reaction pressure in example 19 was controlled to 0.5MPa, and the remaining operations were the same as in example 19, to obtain 29.56g of 1,2, 3-trifluorobenzene, yield 74.45% and purity 99.92% by gas phase detection.

Example 21

The reaction pressure in example 19 was controlled to 1.5MPa, and the remaining operations were the same as in example 19 to give 39.10g of 1,2, 3-trifluorobenzene in 98.43% yield and 99.88% purity by gas phase detection.

In comparative examples 19, 20 to 21, the catalyst equivalent, the sodium hydroxide equivalent and the reaction temperature were the same, the reaction pressure was in the range of 0.5 to 1.5MPa, and when the reaction pressure was increased from 0.5MPa to 1MPa, the yield was increased from 74.45% to 98.29%, and after the reaction pressure was further increased, the yield was not increased so much, so that the optimum reaction pressure was determined to be 1MPa.

The percentages used in the present invention are mass percentages unless otherwise indicated.

Finally, it should be noted that: the foregoing description is only a preferred embodiment of the present invention, and the present invention is not limited thereto, but it is to be understood that modifications and equivalents of some of the technical features described in the foregoing embodiments may be made by those skilled in the art, although the present invention has been described in detail with reference to the foregoing embodiments. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. The synthesis method of the intermediate 1,2, 3-trifluoro-benzene for synthesizing 3,4, 5-trifluoro-bromobenzene is characterized by comprising the following steps: denitration, chlorination, dechlorination and hydrogenation;

adding 2,3, 4-trifluorochlorobenzene, sodium hydroxide and ethanol into a high-pressure reaction vessel, stirring until the solids are completely dissolved, stopping stirring, adding Raney Ni catalyst, sealing the high-pressure reaction vessel, introducing nitrogen to replace air in the reaction vessel, using hydrogen to replace air in the reaction vessel, continuing introducing hydrogen to the reaction pressure, heating, stirring, performing dechlorination hydrogenation reaction, supplementing hydrogen to the reaction pressure whenever the pressure in the sealed reaction vessel drops by 0.2MPa, and continuing to keep the pressure for 10min when the pressure in the reaction vessel does not drop any more, and rectifying to obtain 1,2, 3-trifluorobenzene.

2. The method for synthesizing 3,4, 5-trifluorobromobenzene as claimed in claim 1,2, 3-trifluorobenzene as an intermediate, wherein the mass ratio of dry 2,3, 4-trifluoronitrobenzene to azodiisobutyronitrile in the denitration chlorination is 1:0.005-0.02.

3. The method for synthesizing 3,4, 5-trifluorobromobenzene intermediate 1,2, 3-trifluorobenzene as claimed in claim 1, wherein the reaction temperature of the denitration chlorination reaction is 180-200 ℃.

4. The method for synthesizing 3,4, 5-trifluorobromobenzene intermediate 1,2, 3-trifluorobenzene as claimed in claim 1, wherein the flow rate of chlorine gas is 20-40g/h.

5. The method for synthesizing 3,4, 5-trifluorobromobenzene intermediate 1,2, 3-trifluorobenzene as claimed in claim 1, wherein the continuous reaction time is 6-12h.

6. The method for synthesizing 3,4, 5-trifluorobromobenzene as claimed in claim 1, wherein the molar ratio of sodium hydroxide to 2,3, 4-trifluorochlorobenzene in the dechlorination hydrogenation is 1-2:1.

7. The method for synthesizing 3,4, 5-trifluorobromobenzene as claimed in claim 1,2, 3-trifluorobenzene, wherein the mass ratio of 2,3, 4-trifluorochlorobenzene to ethanol is 50.02:200.

8. The method for synthesizing 3,4, 5-trifluorobromobenzene intermediate 1,2, 3-trifluorobenzene as claimed in claim 1, wherein the mass ratio of Raney Ni catalyst to 2,3, 4-trifluorochlorobenzene is 0.05-0.15:1.

9. The method for synthesizing 3,4, 5-trifluorobromobenzene intermediate 1,2, 3-trifluorobenzene as claimed in claim 1, wherein the reaction temperature of the dechlorination hydrogenation reaction is 60-80 ℃.

10. The method for synthesizing 3,4, 5-trifluorobromobenzene intermediate 1,2, 3-trifluorobenzene as claimed in claim 1, wherein the reaction pressure of the dechlorination hydrogenation reaction is 0.5-1.5MPa.