CN101624348A - Preparation method of para-fluoroaniline - Google Patents

Abstract

The invention discloses a preparation method of p-fluoroaniline: 3,5-dichloro-4-fluoronitrobenzene is mixed with a solvent to form a reaction solution, and the reaction solution is hydrogenated in an autoclave under the action of a catalyst to carry out reduction dechlorination reaction , the reaction pressure is 1.0-4.0MPa, the reaction temperature is 60-120°C, and the reaction time is 2-5 hours; the mass ratio of the catalyst to 3,5-dichloro-4-fluoronitrobenzene is 1%-40%; After the reaction is finished, the liquid reaction product is collected, filtered, and the filtrate is added with an antioxidant to obtain p-fluoroaniline through rectification. The preparation of p-fluoroaniline by the method has the characteristics of simple process, high yield and low cost.

Description

A kind of preparation method of p-fluoroaniline

technical field

The invention relates to a method for synthesizing organic compounds, in particular to a method for synthesizing p-Fluoroaniline.

Background technique

The p-fluoroaniline with the structural formula shown as S-1 is an important fine chemical intermediate, which is mainly used in industries such as medicine, dyestuff and pesticide. The development of this product was earlier in foreign countries, while in China it began in the early 1990s.

According to comprehensive literature reports, the synthesis method of p-fluoroaniline can be divided into one-step method and two-step method.

The one-step method usually uses azidobenzene (US Patent US4145364) or N-phenylammonium hydroxide (US Patent US4291991) or p-chloronitrobenzene (US Patent US3900519) as raw materials to directly synthesize p-fluoroaniline through a one-step reaction. This type of method is difficult to industrialize due to the limitation of raw material sources or the need to use strong corrosive hydrofluoric acid.

The two-step method usually first synthesizes p-fluoronitrobenzene with fluorobenzene (Japanese Patent Laid-Open No. 63-225250) or p-chloronitrobenzene as a raw material, and then produces p-fluoroaniline through reduction. However, the selectivity of fluorobenzene nitration is poor, and a high-efficiency rectification tower is required to separate the nitrated products, and the price of fluorobenzene is relatively high, so the production cost of the fluorobenzene route is relatively high. It is relatively better to prepare p-fluoronitrobenzene with p-chloronitrobenzene as raw material and react with alkali metal fluoride. At present, most domestic manufacturers adopt this process. The reduction of p-fluoronitrobenzene has two processes: hydrogenation reduction method and iron powder reduction method. The former has a higher yield and less waste, but there are problems with catalyst use and regeneration; the latter is simple in equipment and easy to operate, but consumes iron powder. If the amount is large, waste water and waste residue will be generated.

2,3,4-Trifluoronitrobenzene is an important intermediate for the synthesis of ofloxacin. One route to synthesize this compound is to obtain the target product through nitration and fluorination of 2,6-dichlorofluorobenzene. One step will produce by-product 3,5-dichloro-4-fluoronitrobenzene. At present, the by-product 3,5-dichloro-4-fluoronitrobenzene often becomes waste because it has not been effectively utilized, and sometimes even produces pollution, it is of great significance to develop its valuable utilization.

Contents of the invention

The technical problem to be solved by the present invention is to provide a preparation method of p-fluoroaniline with simple process, high yield and low cost.

In order to solve the above technical problems, the present invention provides a preparation method of p-fluoroaniline: 3,5-dichloro-4-fluoronitrobenzene is mixed with a solvent to form a reaction solution, and the reaction solution is hydrogenated in an autoclave under the action of a catalyst Carry out reductive dechlorination reaction, the reaction pressure is 1.0-4.0MPa, the reaction temperature is 60-120°C, and the reaction time is 2-5 hours; the mass ratio of catalyst to 3,5-dichloro-4-fluoronitrobenzene is 1% ~40%; after the reaction, the liquid reaction product was collected and filtered, and the filtrate was added with an antioxidant to obtain p-fluoroaniline through rectification.

As an improvement of the preparation method of p-fluoroaniline in the present invention: the catalyst is a Pd/C catalyst, wherein the Pd loading is 5% or 10% (mass percentage).

As a further improvement of the preparation method of p-fluoroaniline of the present invention: the mass percentage of 3,5-dichloro-4-fluoronitrobenzene in the reaction liquid is 1%-20%.

As a further improvement of the preparation method of p-fluoroaniline of the present invention: the solvent is a lower aliphatic alcohol or an aqueous solution of a lower aliphatic alcohol, and the mass percentage of the lower aliphatic alcohol in the aqueous solution of a lower aliphatic alcohol is 70% to 99.9%; the lower aliphatic alcohol is, for example, Methanol, ethanol, or isopropanol.

As a further improvement of the preparation method of p-fluoroaniline of the present invention: the antioxidant is sodium thiosulfate or glycerin (glycerol); the amount of antioxidant is 2% of the quality of 3,5-dichloro-4-fluoronitrobenzene %~5%.

In the inventive preparation method of p-fluoroaniline: the mass ratio of the preferred catalyst to 3,5-dichloro-4-fluoronitrobenzene is 1% to 20%; the preferred solvent is ethanol aqueous solution, preferably The ethanol mass percentage content is 70%～98%, more preferably ethanol mass percentage content is 92%～97%; In the reaction liquid, the preferred mass percentage of 3,5-dichloro-4-fluoronitrobenzene is 2%-12%, and the optimum mass percentage is 5%-10%.

The present invention prepares the reaction equation of p-fluoroaniline as follows:

The main side effects are:

In the present invention, after the reaction is finished, the liquid reaction product is collected, filtered, and the solid catalyst (i.e. Pd/C catalyst) is recovered, and the filtrate is added with an antioxidant, and after rectification, the fraction at 184-186° C. is collected to obtain p-fluoroaniline. After GC-MS analysis, the obtained product was p-fluoroaniline.

The preparation method of p-fluoroaniline of the present invention has the following advantages:

1. The raw material 3,5-dichloro-4-fluoronitrobenzene used in the present invention is derived from the by-product in the production of 2,3,4-trifluoronitrobenzene, so the present invention can solve the problem of 2,3,4 -Comprehensive utilization of by-products in the production of trifluoronitrobenzene, on the other hand also provides a new process route for p-fluoroaniline.

Therefore, the present invention has the characteristics of wide sources, low cost, etc., fully embodies the characteristics of turning waste into wealth, and belongs to a green and environmentally friendly production route.

2. Compared with the raw material p-chloronitrobenzene of the conventional process of synthesizing p-fluoroaniline, the raw material 3,5-dichloro-4-fluoronitrobenzene used in the present invention has fluorine atoms substituted on the benzene ring, which can save To replace the reaction step of fluorination; at the same time, the fluorine resources in the by-products produced in the production of 2,3,4-trifluoronitrobenzene have been rationally utilized.

3. Pd/C is used as the catalyst, so it has the advantages of simple catalyst preparation, and the catalyst can be recycled for reuse, which can further reduce production costs.

4. The present invention completes the two-step reaction of nitro reduction and dechlorination under lower hydrogen pressure to prepare p-fluoroaniline, which has the characteristics of simple process and high yield.

Detailed ways

Embodiment 1, a kind of preparation method of p-fluoroaniline, take 3,5-dichloro-4-fluoronitrobenzene as starting raw material, carry out the following steps successively:

(1) Add 21g (0.1mol) of 3,5-dichloro-4-fluoronitrobenzene into 150mL of 95% ethanol aqueous solution, stir evenly, and make a compound containing 3,5-dichloro-4-fluoronitrobenzene the reaction solution.

(2) Transfer the reaction solution into a high-pressure reactor, and add a Pd/C catalyst (Pd loading 5%) in an amount of 5% by mass of 3,5-dichloro-4-fluoronitrobenzene.

(3) After the high-pressure reactor was checked for leaks with nitrogen, it was filled with hydrogen, the pressure was 1.0 MPa, the temperature was raised to 120° C., and the reaction was carried out for 5 hours.

(4) Collect the liquid reaction product, filter and reclaim the solid catalyst (i.e. Pd/C catalyst), add antioxidant sodium thiosulfate to the filtrate, the consumption of sodium thiosulfate is 3,5-dichloro-4-fluoronitrobenzene quality After rectification, the fraction at 184-186°C was collected to obtain p-fluoroaniline with a yield of 68%.

Embodiment 2, a kind of preparation method of p-fluoroaniline, take 3,5-dichloro-4-fluoronitrobenzene as starting raw material, carry out the following steps successively:

(1) Add 21g (0.1mol) 3,5-dichloro-4-fluoronitrobenzene into 150mL 95% ethanol aqueous solution, stir well, and prepare 3,5-dichloro-4-fluoronitrobenzene to react liquid.

(2) Transfer the reaction solution into a high-pressure reactor, and add a Pd/C catalyst (Pd loading 5%) in an amount of 1% by mass of 3,5-dichloro-4-fluoronitrobenzene.

(3) After the high-pressure reactor was checked for leaks with nitrogen, it was filled with hydrogen, the pressure was 1.0 MPa, the temperature was raised to 60° C., and the reaction was carried out for 5 hours.

(4) Collect the liquid reaction product, filter and reclaim the solid catalyst (i.e. Pd/C catalyst), add antioxidant sodium thiosulfate to the filtrate, the consumption of sodium thiosulfate is 3,5-dichloro-4-fluoronitrobenzene quality After rectification, the fraction at 184-186°C was collected to obtain p-fluoroaniline with a yield of 62%.

Embodiment 3, a kind of preparation method of p-fluoroaniline, take 3,5-dichloro-4-fluoronitrobenzene as starting raw material, carry out the following steps successively:

(1) Add 21g (0.1mol) 3,5-dichloro-4-fluoronitrobenzene into 150mL 95% aqueous methanol solution, stir well, and prepare 3,5-dichloro-4-fluoronitrobenzene to react liquid.

(2) Transfer the reaction solution into a high-pressure reactor, and add a Pd/C catalyst (Pd loading 5%) in an amount of 10% by mass of 3,5-dichloro-4-fluoronitrobenzene.

(3) After the high-pressure reactor was leak-checked with nitrogen, it was filled with hydrogen, the pressure was 4.0 MPa, the temperature was raised to 120° C., and the reaction was carried out for 2 hours.

(4) Collect the liquid reaction product, filter and reclaim the solid catalyst (i.e. Pd/C catalyst), add antioxidant sodium thiosulfate to the filtrate, the consumption of sodium thiosulfate is 3,5-dichloro-4-fluoronitrobenzene quality After rectification, the fraction at 184-186°C was collected to obtain p-fluoroaniline with a yield of 55%.

Embodiment 4, a kind of preparation method of p-fluoroaniline, take 3,5-dichloro-4-fluoronitrobenzene as starting raw material, carry out the following steps successively:

(1) Add 21g (0.1mol) 3,5-dichloro-4-fluoronitrobenzene into 150mL 95% aqueous methanol solution, stir well, and prepare 3,5-dichloro-4-fluoronitrobenzene to react liquid.

(2) Transfer the reaction solution into a high-pressure reactor, and add a Pd/C catalyst (Pd loading 5%) in an amount of 40% by mass of 3,5-dichloro-4-fluoronitrobenzene.

(3) After the high-pressure reactor was leak-checked with nitrogen, it was filled with hydrogen, the pressure was 3.0 MPa, the temperature was raised to 80° C., and the reaction was carried out for 3 hours.

(4) Collect the liquid reaction product, filter and reclaim the solid catalyst (i.e. Pd/C catalyst), add antioxidant sodium thiosulfate to the filtrate, the consumption of sodium thiosulfate is 3,5-dichloro-4-fluoronitrobenzene quality After rectification, the fraction at 184-186°C was collected to obtain p-fluoroaniline with a yield of 48%.

Embodiment 5, a kind of preparation method of p-fluoroaniline, take 3,5-dichloro-4-fluoronitrobenzene as starting material, carry out the following steps successively:

(1) Add 21g (0.1mol) 3,5-dichloro-4-fluoronitrobenzene into 150mL 95% ethanol aqueous solution, stir well, and prepare 3,5-dichloro-4-fluoronitrobenzene to react liquid.

(2) Transfer the reaction solution into a high-pressure reactor, and add a Pd/C catalyst (Pd loading 5%) in an amount of 10% by mass of 3,5-dichloro-4-fluoronitrobenzene.

(3) After the high-pressure reactor was leak-checked with nitrogen, it was filled with hydrogen, the pressure was 2.0 MPa, the temperature was raised to 100° C., and the reaction was carried out for 4 hours.

(4) Collect the liquid reaction product, filter and reclaim the solid catalyst (i.e. Pd/C catalyst), add antioxidant glycerol to the filtrate, and the consumption of glycerol is 2% of the quality of 3,5-dichloro-4-fluoronitrobenzene %, collecting fractions at 184-186°C to obtain p-fluoroaniline with a yield of 70%.

Embodiment 6, a preparation method of p-fluoroaniline, using 3,5-dichloro-4-fluoronitrobenzene as the starting material, the following steps are carried out in sequence:

(1) Add 21g (0.1mol) 3,5-dichloro-4-fluoronitrobenzene into 150mL 95% ethanol aqueous solution, stir well, and prepare 3,5-dichloro-4-fluoronitrobenzene to react liquid.

(2) Transfer the reaction solution into a high-pressure reactor, and add a Pd/C catalyst (Pd loading 5%) in an amount of 15% by mass of 3,5-dichloro-4-fluoronitrobenzene.

(3) After the high-pressure reactor was leak-checked with nitrogen, it was filled with hydrogen, the pressure was 2.0 MPa, the temperature was raised to 80° C., and the reaction was carried out for 4 hours.

(4) Collect the liquid reaction product, filter and reclaim the solid catalyst (i.e. Pd/C catalyst), add antioxidant glycerol to the filtrate, and the consumption of glycerol is 3,5-dichloro-4-fluoronitrobenzene quality %, collecting fractions at 184-186°C to obtain p-fluoroaniline with a yield of 65%.

Embodiment 7, a kind of preparation method of p-fluoroaniline, take 3,5-dichloro-4-fluoronitrobenzene as starting material, carry out the following steps successively:

(1) Add 21g (0.1mol) of 3,5-dichloro-4-fluoronitrobenzene into 150mL of 95% isopropanol aqueous solution, stir well, and make 3,5-dichloro-4-fluoronitrobenzene Benzene reaction solution.

(2) Transfer the reaction solution into a high-pressure reactor, and add a Pd/C catalyst (Pd loading 5%) in an amount of 5% by mass of 3,5-dichloro-4-fluoronitrobenzene.

(3) After checking the high-pressure reactor for leaks with nitrogen gas, fill it with hydrogen gas at a pressure of 2.0 MPa, raise the temperature to 70° C., and react for 3 hours.

(4) Collect the liquid reaction product, filter and reclaim the solid catalyst (i.e. Pd/C catalyst), the filtrate adds antioxidant glycerin, and the consumption of glycerin is raw material 3,5-dichloro-4-fluoronitrobenzene quality 5%, collecting fractions at 184-186°C to obtain p-fluoroaniline with a yield of 63%.

Embodiment 8, a preparation method of p-fluoroaniline, using 3,5-dichloro-4-fluoronitrobenzene as the starting material, the following steps are carried out in sequence:

(1) Add 21g (0.1mol) of 3,5-dichloro-4-fluoronitrobenzene into 150mL of 95% isopropanol aqueous solution, stir well, and make 3,5-dichloro-4-fluoronitrobenzene Benzene reaction solution.

(2) Transfer the reaction solution into a high-pressure reactor, and add a Pd/C catalyst (Pd loading 10%) in an amount of 10% by mass of 3,5-dichloro-4-fluoronitrobenzene.

(3) After the high-pressure reactor was leak-checked with nitrogen, it was filled with hydrogen, the pressure was 2.0 MPa, the temperature was raised to 100° C., and the reaction was carried out for 3 hours.

(4) Collect the liquid reaction product, filter and reclaim the solid catalyst (i.e. Pd/C catalyst), the filtrate adds antioxidant glycerin, and the consumption of glycerin is raw material 3,5-dichloro-4-fluoronitrobenzene quality 5%, collect the distillate at 184-186°C to obtain p-fluoroaniline with a yield of 69%.

Embodiment 9, a preparation method of p-fluoroaniline, using 3,5-dichloro-4-fluoronitrobenzene as the starting raw material, followed by the following steps:

(1) Add 21g (0.1mol) 3,5-dichloro-4-fluoronitrobenzene into 150mL 95% aqueous methanol solution, stir well, and prepare 3,5-dichloro-4-fluoronitrobenzene to react liquid.

(2) Transfer the reaction solution into a high-pressure reactor, and add a Pd/C catalyst (Pd loading 10%) in an amount of 1% by mass of 3,5-dichloro-4-fluoronitrobenzene.

(3) After the high-pressure reactor was leak-checked with nitrogen, it was filled with hydrogen, the pressure was 1.0 MPa, the temperature was raised to 50° C., and the reaction was carried out for 5 hours.

(4) Collect the liquid reaction product, filter and reclaim the solid catalyst (i.e. Pd/C catalyst), add antioxidant sodium thiosulfate to the filtrate, and the consumption of sodium thiosulfate is 3,5-dichloro-4-fluoronitrobenzene 3% of the mass, the fraction at 184-186°C was collected to obtain p-fluoroaniline with a yield of 67%.

Embodiment 10, a preparation method of p-fluoroaniline, using 3,5-dichloro-4-fluoronitrobenzene as the starting material, the following steps are carried out in sequence:

(1) Add 21g (0.1mol) 3,5-dichloro-4-fluoronitrobenzene into 150mL 95% aqueous methanol solution, stir well, and prepare 3,5-dichloro-4-fluoronitrobenzene to react liquid.

(2) Transfer the reaction solution into a high-pressure reactor, and add a Pd/C catalyst (Pd loading 10%) in an amount of 5% by mass of 3,5-dichloro-4-fluoronitrobenzene.

(3) After the high-pressure reactor was leak-checked with nitrogen, it was filled with hydrogen, the pressure was 2.0 MPa, the temperature was raised to 80° C., and the reaction was carried out for 4 hours.

(4) Collect the liquid reaction product, filter and reclaim the solid catalyst (i.e. Pd/C catalyst), the filtrate adds antioxidant glycerin, and the consumption of glycerin is raw material 3,5-dichloro-4-fluoronitrobenzene quality 3%, collecting fractions at 184-186°C to obtain p-fluoroaniline with a yield of 63%.

Finally, it should be noted that the above examples are only some specific embodiments of the present invention. Obviously, the present invention is not limited to the above embodiments, and many variations are possible. All deformations that can be directly derived or associated by those skilled in the art from the content disclosed in the present invention should be considered as the protection scope of the present invention.

Claims (6)

1. A preparation method for p-fluoroaniline, characterized in that: 3,5-dichloro-4-fluoronitrobenzene is mixed with a solvent to form a reaction solution, and the reaction solution is hydrogenated in an autoclave under the action of a catalyst Reductive dechlorination reaction, the reaction pressure is 1.0-4.0MPa, the reaction temperature is 60-120°C, the reaction time is 2-5 hours; the mass ratio of catalyst to 3,5-dichloro-4-fluoronitrobenzene is 1% ~40%; after the reaction, the liquid reaction product was collected and filtered, and the filtrate was added with an antioxidant to obtain p-fluoroaniline through rectification. 2. The preparation method of p-fluoroaniline according to claim 1, characterized in that: the catalyst is a Pd/C catalyst, wherein the loading of Pd is 5% or 10%. 3. The method for preparing p-fluoroaniline according to claim 2, characterized in that: the mass percentage of 3,5-dichloro-4-fluoronitrobenzene in the reaction solution is 1%-20%. 4. The preparation method of p-fluoroaniline according to claim 2 or 3, characterized in that: the solvent is a lower aliphatic alcohol or an aqueous solution of a lower aliphatic alcohol, and the mass percentage of the lower aliphatic alcohol in the aqueous solution of a lower aliphatic alcohol is 70% to 99.9%. 5. The preparation method of p-fluoroaniline according to claim 4, characterized in that: the lower aliphatic alcohol is methanol, ethanol or isopropanol. 6. The preparation method of p-fluoroaniline according to claim 5, characterized in that: the antioxidant is sodium thiosulfate or glycerol; the amount of antioxidant is 3,5-dichloro-4-fluoronitrate 2% to 5% of the mass of benzene.