阅读说明：本技术 一种间氟苯甲醛生产制造方法 (M-fluorobenzaldehyde production method ) 是由 马立强 张伟 任建军 于 2021-09-26 设计创作，主要内容包括：本发明属于有机合成工艺技术领域,特别涉及一种间氟苯甲醛生产制造方法。以苯为原料经一系列反应生成苯甲醛,苯甲醛与2-乙基己胺反应,经分层干燥后得到中间体I,中间体I在相转移催化剂作用下于氟化铵反应得到中间体II,中间体II经脱醛基保护后得到间氟苯甲醛,在该反应过程中,利用利用2-乙基己胺对苯环上的醛基进行保护,使其具有较大的空间位阻效应,减少了邻位副产物的生成,提高了产物的纯度,反应过程中合成路线简单,原料廉价易得,便于工业化大批量生产。(The invention belongs to the technical field of organic synthesis processes, and particularly relates to a m-fluorobenzaldehyde production and manufacturing method. Benzene is used as a raw material to generate benzaldehyde through a series of reactions, the benzaldehyde reacts with 2-ethylhexylamine, an intermediate I is obtained after layered drying, the intermediate I reacts with ammonium fluoride under the action of a phase transfer catalyst to obtain an intermediate II, the intermediate II is protected by removing aldehyde groups to obtain m-fluorobenzaldehyde, and in the reaction process, the aldehyde groups on the benzene ring are protected by using the 2-ethylhexylamine, so that the p-phenylaldehyde has a larger steric hindrance effect, the generation of ortho-position byproducts is reduced, the purity of the product is improved, the synthetic route in the reaction process is simple, the raw materials are cheap and easy to obtain, and the industrial mass production is facilitated.)

1. The m-fluorobenzaldehyde production and manufacturing method is characterized by comprising the following preparation steps:

s1, introducing methyl chloride into benzene, adding aluminum chloride, stirring uniformly, heating to raise the temperature, reacting for 4-6 hours, introducing chlorine under the condition of illumination, adding a sodium hydroxide aqueous solution, adding copper powder as a catalyst, heating, and filtering after the reaction is finished to obtain benzaldehyde;

s2, adding benzaldehyde into the reaction kettle, reducing the temperature to a certain value, slowly adding 2-ethylhexylamine into the reaction kettle, starting stirring, uniformly stirring, heating to raise the temperature for reaction, cooling to room temperature after the reaction is finished, and drying the organic layer by using a drying agent after layering to obtain an intermediate I;

s3, mixing the intermediate I with a solvent, adding ammonium fluoride and a phase transfer catalyst into the mixture, starting stirring, raising the temperature, reacting for 3-5 hours, and obtaining an intermediate II after the reaction is finished;

and S4, adding phosphoric acid into the intermediate II, starting stirring, raising the temperature, and after the reaction is finished, carrying out reduced pressure distillation to obtain the m-fluorobenzaldehyde.

2. The method for producing m-fluorobenzaldehyde according to claim 1, which comprises the following steps:

s1, introducing chloromethane into 30-50 parts by weight of benzene, adding 12-18 parts by weight of aluminum chloride, uniformly stirring, heating to raise the temperature to 50-65 ℃, reacting for 4-6 hours, introducing chlorine gas under the condition of illumination, then adding 35-55 parts by weight of sodium hydroxide aqueous solution, adding 6-10 parts by weight of copper powder as a catalyst, heating to 80-90 ℃, and filtering after the reaction is finished to obtain benzaldehyde;

s2, adding 25-30 parts by weight of benzaldehyde into a reaction kettle, reducing the temperature to 5 ℃, slowly adding 30-40 parts by weight of 2-ethylhexylamine into the reaction kettle, starting stirring, heating to raise the temperature to 30 ℃ after uniform stirring, reacting for 2-4 hours, cooling to room temperature after the reaction is finished, and drying an organic layer by using a drying agent after layering to obtain an intermediate I, wherein the reaction process is as follows:

s3, mixing 20-30 parts by weight of the intermediate I with 50-60 parts by weight of solvent, adding 25-35 parts by weight of ammonium fluoride and 15-20 parts by weight of phase transfer catalyst, starting stirring, raising the temperature to 85-95 ℃, reacting for 3-5h, and obtaining an intermediate II after the reaction is finished, wherein the reaction process is as follows:

s4, adding 12-15 parts by weight of phosphoric acid into 15-25 parts by weight of the intermediate II, starting stirring, raising the temperature to 45-55 ℃, and after the reaction is finished, carrying out reduced pressure distillation to obtain m-fluorobenzaldehyde, wherein the reaction process is as follows:

3. the method for producing m-fluorobenzaldehyde according to claim 2, which comprises the following steps:

s1, introducing methyl chloride into 45 parts by weight of benzene, adding 16 parts by weight of aluminum chloride, uniformly stirring, heating to raise the temperature to 55 ℃, reacting for 5 hours, introducing chlorine under the condition of illumination, then adding 45 parts by weight of sodium hydroxide aqueous solution, adding 8 parts by weight of copper powder as a catalyst, heating to 85 ℃, and filtering after the reaction is finished to obtain benzaldehyde;

s2, adding 28 parts by weight of benzaldehyde into a reaction kettle, reducing the temperature to 5 ℃, slowly adding 35 parts by weight of 2-ethylhexylamine into the reaction kettle, starting stirring, heating to raise the temperature to 30 ℃ after uniform stirring, reacting for 3 hours, cooling to room temperature after the reaction is finished, and drying an organic layer by using a drying agent after layering to obtain an intermediate I;

s3, mixing 25 parts by weight of the intermediate I with 55 parts by weight of a solvent, adding 30 parts by weight of ammonium fluoride and 16 parts by weight of a phase transfer catalyst, starting stirring, raising the temperature to 90 ℃, reacting for 4 hours, and obtaining an intermediate II after the reaction is finished;

s4, adding 13 parts by weight of phosphoric acid into 18 parts by weight of the intermediate II, starting stirring, raising the temperature to 50 ℃, and after the reaction is finished, carrying out reduced pressure distillation to obtain m-fluorobenzaldehyde.

4. The method as claimed in claim 1, wherein the drying agent in step S2 is anhydrous calcium chloride.

5. The method as claimed in claim 1, wherein the solvent used in step S3 is one or more selected from N, N-dimethylformamide, acetone, petroleum ether and carbon tetrachloride.

6. The method for producing m-fluorobenzaldehyde according to claim 1, wherein the phase transfer catalyst in step S3 is one or more of benzyltriethylammonium chloride, chain polyethylene glycol, and tributylamine.

Technical Field

The invention relates to the technical field of organic synthesis processes, in particular to a m-fluorobenzaldehyde production and manufacturing method.

Background

M-fluorobenzaldehyde is colorless or light yellow liquid, has pungent smell, is easily oxidized into m-fluorobenzoic acid by oxygen in the air, and needs to be stored in a sealed manner. M-fluorobenzaldehyde is an important organic synthesis intermediate, and can be widely applied to synthesis of fine chemicals such as medicines, pesticides, plastic additives and the like. The introduction of fluorine into the dye can enhance the luster and the brilliance of the dye and improve the properties of the dye such as sun resistance, water resistance, organic solvent resistance and the like. In addition, the reactivity of aldehyde group enables m-fluorobenzaldehyde to become an important intermediate for synthesizing fine chemical products such as medicines, pesticides, dyes and the like. The method for synthesizing aromatic aldehyde includes chemical oxidation, electrolytic oxidation, gas phase oxidation and the like. The chemical oxidation method uses heavy metal oxidant, so that a large amount of metal salt is produced as a byproduct while aromatic aldehyde is synthesized, the content of heavy metal exceeds the standard, the environmental pollution is serious, and the industrialization is limited; the electrolytic oxidation has the characteristics of good selectivity, high yield, easy separation of products, mild conditions and the like, but the electrochemical method has large equipment investment, the electrodes are generally expensive rare metals, the yield is low, the industrial mass production is difficult to realize, and the environment pollution is easily caused by high concentration of metal ions in the electrolyte; the gas-phase air oxidation method has the advantages of high speed, high efficiency, no need of solvent, no corrosion to equipment, high requirement on a solid catalyst, wide mixed explosion limit of materials and oxygen by taking gaseous oxygen as an oxidant, and potential safety hazard because the reaction is a strong exothermic reaction.

Chinese patent 201610972046.9 discloses a method for preparing m-fluorobenzaldehyde by continuously oxidizing m-fluorotoluene, which takes a m-fluorotoluene compound as a raw material, one or more metal ion complexes of cobalt, molybdenum and bromine as a catalyst, hydrogen peroxide as an oxidant and acetic acid as a solvent, can realize the continuous oxidation of m-fluorotoluene in a tubular reactor to prepare m-fluorobenzaldehyde, and has the advantages of mild conditions, short reaction time, high utilization rate of raw materials, effective control in the reaction process, safety, stability, continuous operation and high production efficiency.

Disclosure of Invention

Aiming at the problems of more byproducts, large equipment investment and difficult realization of industrial mass production in the production process, the invention provides a m-fluorobenzaldehyde production and manufacturing method, which has high product purity and less byproducts.

The technical scheme for solving the problems is as follows:

the m-fluorobenzaldehyde production and manufacturing method comprises the following preparation steps:

s1, introducing methyl chloride into benzene, adding aluminum chloride, stirring uniformly, heating to raise the temperature, reacting for 4-6 hours, introducing chlorine under the condition of illumination, adding a sodium hydroxide aqueous solution, adding copper powder as a catalyst, heating, and filtering after the reaction is finished to obtain benzaldehyde;

s2, adding benzaldehyde into the reaction kettle, reducing the temperature to a certain value, slowly adding 2-ethylhexylamine into the reaction kettle, starting stirring, uniformly stirring, heating to raise the temperature for reaction, cooling to room temperature after the reaction is finished, and drying the organic layer by using a drying agent after layering to obtain an intermediate I;

s3, mixing the intermediate I with a solvent, adding ammonium fluoride and a phase transfer catalyst into the mixture, starting stirring, raising the temperature, reacting for 3-5 hours, and obtaining an intermediate II after the reaction is finished;

and S4, adding phosphoric acid into the intermediate II, starting stirring, raising the temperature, and after the reaction is finished, carrying out reduced pressure distillation to obtain the m-fluorobenzaldehyde.

The invention has the following beneficial effects:

1. in the process of synthesizing m-fluorobenzaldehyde from benzaldehyde, benzaldehyde reacts with 2-ethylhexylamine, and a group with a larger steric hindrance effect is introduced on a benzene ring, so that the attack on the ortho position is effectively blocked, the generation of ortho position byproducts is reduced, and the purity of the product is greatly improved;

2. the synthetic route in the reaction process is simple, the operation is simple, and the operation is easy;

3. the raw materials used by the invention are cheap and easy to obtain, the equipment investment is less, and the industrial mass production is easy to realize.

Detailed Description

The technical solutions in the embodiments of the present application are clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present application, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present application.

Example 1

The m-fluorobenzaldehyde production and manufacturing method comprises the following preparation steps:

s1, synthesis of benzaldehyde: introducing chloromethane into 30 parts by weight of benzene, adding 12 parts by weight of aluminum chloride, uniformly stirring, heating to raise the temperature to 50 ℃, reacting for 4 hours, introducing chlorine under the condition of illumination, then adding 35 parts by weight of sodium hydroxide aqueous solution, adding 6 parts by weight of copper powder as a catalyst, heating to 80 ℃, and filtering after the reaction is finished to obtain benzaldehyde;

s2, protection of aldehyde group: adding 25 parts by weight of benzaldehyde into a reaction kettle, reducing the temperature to 5 ℃, slowly adding 30 parts by weight of 2-ethylhexylamine into the reaction kettle, starting stirring, uniformly stirring, heating to raise the temperature to 30 ℃ for reaction for 2 hours, cooling to room temperature after the reaction is finished, drying an organic layer by using a drying agent anhydrous calcium chloride after layering to obtain an intermediate I, wherein the reaction process is as follows:

s3, introducing fluorine: mixing 20 parts by weight of the intermediate I with 50 parts by weight of N, N-dimethylformamide, adding 25 parts by weight of ammonium fluoride and 15 parts by weight of benzyltriethylammonium chloride, starting stirring, raising the temperature to 85 ℃, reacting for 3 hours to obtain an intermediate II after the reaction is finished, wherein the reaction process is as follows:

s4, aldehyde group removal protection: adding 12 parts by weight of phosphoric acid into 15 parts by weight of the intermediate II, starting stirring, raising the temperature to 45 ℃, after the reaction is finished, carrying out reduced pressure distillation to obtain m-fluorobenzaldehyde, wherein the purity of the m-fluorobenzaldehyde is 98.2% by gas chromatography analysis, and the reaction process is as follows:

specifically, aldehyde group is a meta-position positioning group, has an electron-withdrawing effect, can reduce the electron cloud density on a benzene ring, has larger degree of ortho-position and para-position passivation than meta-position, and most of new substituent groups enter meta-position in a substitution reaction to form meta-position isomers. However, ortho-position and para-position isomers exist in the substitution process, the aldehyde group passivates the para position more than the ortho position, so the ortho position is a main byproduct, in order to reduce the content of the ortho-position and para-position byproducts, benzaldehyde reacts with 2-ethylhexylamine to generate an intermediate I, the aldehyde group is protected, the substituent group of the benzene ring on the intermediate I has a larger steric hindrance effect than the aldehyde group, and the generation of the ortho-position byproduct can be effectively reduced when fluorine element substitution is carried out.

Example 2

The m-fluorobenzaldehyde production and manufacturing method comprises the following preparation steps:

s1, synthesis of benzaldehyde: introducing chloromethane into 50 parts by weight of benzene, adding 18 parts by weight of aluminum chloride, uniformly stirring, heating to raise the temperature to 65 ℃, reacting for 6 hours, introducing chlorine under the condition of illumination, adding 55 parts by weight of sodium hydroxide aqueous solution, adding 10 parts by weight of copper powder as a catalyst, heating to 90 ℃, and filtering after the reaction is finished to obtain benzaldehyde;

s2, protection of aldehyde group: adding 30 parts by weight of benzaldehyde into a reaction kettle, reducing the temperature to 5 ℃, slowly adding 40 parts by weight of 2-ethylhexylamine into the reaction kettle, starting stirring, uniformly stirring, heating to raise the temperature to 30 ℃ for reaction for 4 hours, cooling to room temperature after the reaction is finished, drying an organic layer by using a drying agent anhydrous calcium chloride after layering to obtain an intermediate I, wherein the reaction process is as follows:

s3, introducing fluorine: mixing 30 parts by weight of the intermediate I with 60 parts by weight of N, N-dimethylformamide, adding 35 parts by weight of ammonium fluoride and 20 parts by weight of benzyltriethylammonium chloride, starting stirring, raising the temperature to 95 ℃, reacting for 5 hours, and obtaining an intermediate II after the reaction is finished, wherein the reaction process is as follows:

s4, aldehyde group removal protection: adding 15 parts by weight of phosphoric acid into 25 parts by weight of the intermediate II, starting stirring, raising the temperature to 55 ℃, after the reaction is finished, carrying out reduced pressure distillation to obtain m-fluorobenzaldehyde, wherein the purity of the m-fluorobenzaldehyde is 98.6% by gas chromatography analysis, and the reaction process is as follows:

example 3

The m-fluorobenzaldehyde production and manufacturing method comprises the following preparation steps:

s1, synthesis of benzaldehyde: introducing chloromethane into 45 parts by weight of benzene, adding 16 parts by weight of aluminum chloride, uniformly stirring, heating to raise the temperature to 55 ℃, reacting for 5 hours, introducing chlorine under the condition of illumination, then adding 45 parts by weight of sodium hydroxide aqueous solution, adding 8 parts by weight of copper powder as a catalyst, heating to 85 ℃, and filtering after the reaction is finished to obtain benzaldehyde;

s2, protection of aldehyde group: adding 28 parts by weight of benzaldehyde into a reaction kettle, reducing the temperature to 5 ℃, slowly adding 35 parts by weight of 2-ethylhexylamine into the reaction kettle, starting stirring, uniformly stirring, heating to raise the temperature to 30 ℃ for reaction for 3 hours, cooling to room temperature after the reaction is finished, drying an organic layer by using a drying agent anhydrous calcium chloride after layering to obtain an intermediate I, wherein the reaction process is as follows:

s3, introducing fluorine: mixing 25 parts by weight of the intermediate I with 55 parts by weight of N, N-dimethylformamide, adding 30 parts by weight of ammonium fluoride and 16 parts by weight of benzyltriethylammonium chloride, starting stirring, raising the temperature to 90 ℃, reacting for 4 hours, and obtaining an intermediate II after the reaction is finished, wherein the reaction process is as follows:

s4, aldehyde group removal protection: adding 13 parts by weight of phosphoric acid into 18 parts by weight of the intermediate II, starting stirring, raising the temperature to 50 ℃, after the reaction is finished, carrying out reduced pressure distillation to obtain m-fluorobenzaldehyde, wherein the purity of the m-fluorobenzaldehyde is 99.6% by gas chromatography analysis, and the reaction process is as follows:

example 4

The m-fluorobenzaldehyde production and manufacturing method comprises the following preparation steps:

s1, synthesis of benzaldehyde: introducing chloromethane into 42 parts by weight of benzene, adding 14 parts by weight of aluminum chloride, uniformly stirring, heating to raise the temperature to 55 ℃, reacting for 5 hours, introducing chlorine gas under the condition of illumination, then adding 42 parts by weight of sodium hydroxide aqueous solution, adding 7 parts by weight of copper powder as a catalyst, heating to 85 ℃, and filtering after the reaction is finished to obtain benzaldehyde;

s2, protection of aldehyde group: adding 26 parts by weight of benzaldehyde into a reaction kettle, reducing the temperature to 5 ℃, slowly adding 32 parts by weight of 2-ethylhexylamine into the reaction kettle, starting stirring, uniformly stirring, heating to raise the temperature to 30 ℃ for reaction for 2.5 hours, cooling to room temperature after the reaction is finished, drying an organic layer by using anhydrous calcium chloride serving as a drying agent after layering to obtain an intermediate I, wherein the reaction process is as follows:

s3, introducing fluorine: mixing 22 parts by weight of the intermediate I with 55 parts by weight of acetone, adding 28 parts by weight of ammonium fluoride and 16 parts by weight of tributylamine, starting stirring, raising the temperature to 88 ℃, reacting for 3.5 hours to obtain an intermediate II, wherein the reaction process is as follows:

s4, aldehyde group removal protection: adding 13 parts by weight of phosphoric acid into 16 parts by weight of the intermediate II, starting stirring, raising the temperature to 50 ℃, after the reaction is finished, carrying out reduced pressure distillation to obtain m-fluorobenzaldehyde, wherein the purity of the m-fluorobenzaldehyde is 99.1% by gas chromatography analysis, and the reaction process is as follows:

the above examples show that the m-fluorobenzaldehyde prepared by the method has high purity which can reach 99.6%. The invention firstly uses benzene as raw material to prepare benzaldehyde, and then uses benzaldehyde to react with 2-ethylhexylamine to protect aldehyde group, although aldehyde group is meta-position group, during reaction, ortho-position and para-position byproducts are inevitably generated, especially because aldehyde group passivates para-position rather than ortho-position, ortho-position byproduct becomes main byproduct. In the invention, as the substituent of the benzene ring on the intermediate I has larger steric hindrance effect compared with the aldehyde group, the attack of fluorine on the ortho position can be reduced, the generation of ortho position by-products is reduced, and the purity of the product is improved; the synthetic route in the reaction process is simple, the operation is easy, the raw materials are cheap and easy to obtain, and the industrial production is facilitated.

It is noted that, herein, relational terms such as first and second, and the like may be used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions. Also, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus.

Although embodiments of the present application have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the application, the scope of which is defined in the appended claims and their equivalents.