CN110372529B - N- [ (3,4, 5-trifluoro) phenyl ] acrylamide and preparation method thereof - Google Patents

Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to N- [ (3,4, 5-trifluoro) phenyl ] acrylamide and a preparation method thereof. The preparation method of the N- [ (3,4, 5-trifluoro) phenyl ] acrylamide comprises the following specific steps: (1) adding 3,4, 5-trifluoroaniline, a reaction solvent and a catalyst into a reaction container, uniformly stirring, adding acryloyl chloride, and reacting at-10-30 ℃ for 1-7 h; (2) and (2) adding water into the reaction liquid obtained in the step (1), uniformly stirring, filtering, separating out a precipitate, and drying the precipitate to obtain the N- [ (3,4, 5-trifluoro) phenyl ] acrylamide. The preparation method has the advantages of simple and easily obtained raw materials, low cost, simple operation, high yield and high purity of the N- [ (3,4, 5-trifluoro) phenyl ] acrylamide; the alkalescent catalyst, namely the sodium bicarbonate, ensures that the reaction amplification process is simple and feasible, the three wastes generated by the reaction are less, and the method is green and environment-friendly.

Description

N- [ (3,4, 5-trifluoro) phenyl ] acrylamide and preparation method thereof

Technical Field

The invention belongs to the technical field of organic synthesis, and particularly relates to N- [ (3,4, 5-trifluoro) phenyl ] acrylamide and a preparation method thereof.

Background

Fluorine is the element with the largest electronegativity, the covalent radius of atoms (0.064nm) is very small, the bond energy of C-F is very large (485KJ/mol), the arrangement of fluorine atoms on the outer layer of a carbon skeleton is very tight, a shielding effect can be formed on a main chain and an internal molecule, and the fluorinated acrylamide monomer has a unique function due to the existence of fluorine groups. Fluorinated acrylamide monomers are not only used as bactericides for preventing crop diseases and insect pests, but also used as tyrosine kinase inhibitors and widely applied to treating diseases such as cancer, atherosclerosis, restenosis, endometriosis, psoriasis and the like. In the field of macromolecules, polymers containing fluorinated acrylamide monomer structures have broad-spectrum bactericidal properties. They can be radically copolymerized with a methacrylate or N-substituted maleimide monomer to improve the properties of the copolymer, such as heat resistance, water resistance, transparency, hardness, etc., to various degrees. Particularly, the thermal stability of groups such as phenolic hydroxyl, sulfonamide, fluorine atoms and the like is better, and the glass transition temperature and the heat resistance of the polymer can be effectively improved by taking the N-aryl substituted (methyl) acrylamide containing the groups as a comonomer.

In the existing method for synthesizing fluorinated acrylamide monomers, triethylamine is mostly used as a catalyst, and the triethylamine has toxicity, strong irritation and corrosivity, is harmful to human bodies and environment, is flammable and explosive, and belongs to dangerous chemicals; in addition, when triethylamine is used as a catalyst, it is usually necessary to add a polymerization inhibitor (e.g., 2, 6-di-t-butyl-p-cresol) to the reaction system in order to prevent further polymerization of the fluorinated acrylamide-based monomer formed during the reaction. Therefore, the existing method for synthesizing fluorinated acrylamide monomers has the defects of high catalyst toxicity, great harm to human bodies and environment, no accordance with the current green and environment-friendly requirement, and high reaction cost because a polymerization inhibitor is additionally added in the reaction process.

Disclosure of Invention

In view of the problems and the defects existing in the prior art, the invention aims to provide a preparation method of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide and a N- [ (3,4, 5-trifluoro) phenyl ] acrylamide product prepared by the preparation method.

In order to realize the purpose of the invention, the technical scheme adopted by the invention is as follows:

n- [ (3,4, 5-trifluoro) phenyl ] acrylamide, characterized in that its structural formula is as follows:

the preparation method of the N- [ (3,4, 5-trifluoro) phenyl ] acrylamide comprises the following steps:

(1) adding 3,4, 5-trifluoroaniline, a reaction solvent and a catalyst into a reaction container, uniformly stirring, adding acryloyl chloride, and reacting at-10-30 ℃ for 1-7 h;

(2) and (2) adding water into the reaction liquid obtained in the step (1), uniformly stirring, filtering, separating out a precipitate, and drying the precipitate to obtain the N- [ (3,4, 5-trifluoro) phenyl ] acrylamide.

The reaction equation for this reaction is as follows:

according to the above preparation method, preferably, the catalyst is sodium bicarbonate.

According to the preparation method, the mass ratio of the sodium bicarbonate to the 3,4, 5-trifluoroaniline is (0.01-0.1): 1.

according to the preparation method, the molar ratio of the 3,4, 5-trifluoroaniline to the acryloyl chloride is preferably 1: (1-2.5).

According to the above production method, preferably, the reaction solvent is at least one of methanol, ethanol, acetone, and dimethylformamide.

According to the above preparation method, the acryloyl chloride is preferably added dropwise.

An N- [ (3,4, 5-trifluoro) phenyl ] acrylamide product prepared by the preparation method.

The N- [ (3,4, 5-trifluoro) phenyl ] acrylamide product is not only used as a bactericide for preventing crop diseases and insect pests, but also can be subjected to free radical copolymerization with monomers such as methacrylate or N-substituted maleimide and the like due to the existence of an amide group and a C-F bond, so that the properties of the copolymer, such as heat resistance, water resistance, transparency, hardness and the like, are improved to different degrees.

Compared with the prior art, the invention has the following positive beneficial effects:

(1) the method takes 3,4, 5-trifluoroaniline and acryloyl chloride as reaction raw materials, and takes sodium bicarbonate as a catalyst to catalyze and synthesize the N- [ (3,4, 5-trifluoro) phenyl ] acrylamide, compared with triethylamine, the sodium bicarbonate is safe and nontoxic, has no harm to human bodies and environment, is green and environment-friendly, has low raw material price, has weaker alkalinity, adopts the sodium bicarbonate as the reaction catalyst, has more stable reaction system, does not need to additionally add a polymerization inhibitor (2, 6-ditertbutyl-p-cresol) in the reaction process, and reduces the reaction cost.

(2) The method takes the sodium bicarbonate as the catalyst, the sodium bicarbonate can react with the hydrogen chloride which is a reaction byproduct to promote the forward progress of the reaction, the yield of the N- [ (3,4, 5-trifluoro) phenyl ] acrylamide is improved, and the sodium bicarbonate reacts with the hydrogen chloride to generate pollution-free sodium chloride, so that the treatment after the reaction is simple, the generated industrial three wastes are less, and the method is green and environment-friendly.

(3) The method adopts methanol, ethanol, acetone or dimethylformamide as a reaction solvent, the reaction solvent is easy to dissolve in water, the separation of the reaction solvent and a reaction product, namely N- [ (3,4, 5-trifluoro) phenyl ] acrylamide, can be realized by adding water into a reaction system and filtering after the reaction is finished, so that the reaction solvent is removed from the reaction system, the operation is simple, in addition, the reaction solvent is low in price, and the post-treatment has small influence on the environment.

(4) The preparation method has the advantages that the raw materials are simple and easy to obtain, the cost is low, the separation of the N- [ (3,4, 5-trifluoro) phenyl ] acrylamide from the catalyst, the reaction by-product and the reaction solvent can be realized through simple filtration treatment after the reaction is finished, the operation is simple, convenient and feasible, and the N- [ (3,4, 5-trifluoro) phenyl ] acrylamide has high yield and high purity; in addition, the alkalescent catalyst, namely the sodium bicarbonate, ensures that the reaction amplification process is simple and feasible, the three wastes generated by the reaction are less, and the method is green and environment-friendly. (5) Compared with N- [ (4-bromo-3, 5-difluoro) phenyl ] acrylamide in the prior art, fluorine atoms in the group are increased, fluorine is the element with the largest electronegativity, the covalent radius of atoms (0.064nm) is very small, the C-F bond energy is very large (485KJ/mol), and the arrangement of the fluorine atoms on the outer layer of the carbon skeleton is very tight, so that a shielding effect can be formed on a main chain and an internal molecule. When the N- [ (3,4, 5-trifluoro) phenyl ] acrylamide is applied to preparing polymers, the shielding effect of F atoms can enhance the surface tension of the polymers and improve the hydrophobic property of the polymers.

Drawings

FIG. 1 shows the NMR spectrum of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide prepared in example 1.

FIG. 2 is a high performance liquid chromatogram of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide prepared in example 1.

FIG. 3 is a high performance liquid chromatogram of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide prepared in example 7.

FIG. 4 is a high performance liquid chromatogram of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide prepared in example 13.

FIG. 5 is a high performance liquid chromatogram of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide prepared in example 19.

FIG. 6 is a high performance liquid chromatogram of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide prepared in example 9.

FIG. 7 is a high performance liquid chromatogram of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide prepared in comparative example 1.

Detailed Description

The present invention will be described in further detail with reference to the following examples, which are not intended to limit the scope of the present invention.

Discussion experiment of catalyst dosage

In order to examine the influence of the amount of the catalyst on the yield of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide (yield of the actual amount (mol) of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide/the theoretical amount (mol) of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide) and the purity, the inventors carried out the following experiments, i.e., examples 1 to 6, and the corresponding experimental results are shown in table 1.

Example 1:

a preparation method of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide comprises the following specific steps:

adding 14.7 g (0.1mol) of 3,4, 5-trifluoroaniline and 50 g of reaction solvent (the reaction solvent is dimethylformamide) into a 500ml four-neck flask, adding sodium bicarbonate, wherein the mass ratio of the sodium bicarbonate to the 3,4, 5-trifluoroaniline is 0.01:1, cooling to 5 ℃ under stirring, dropwise adding 22.6 g (0.25 mol) of acryloyl chloride, reacting for 5 hours at 5 ℃ after dropwise adding, cooling the reaction liquid to room temperature, then adding 300ml of deionized water into the reaction liquid, filtering, collecting precipitate, and drying the precipitate to obtain the N- [ (3,4, 5-trifluoro) phenyl ] acrylamide. The purity of the prepared N- [ (3,4, 5-trifluoro) phenyl ] acrylamide was measured by high performance liquid chromatography.

Example 2 to example 6:

examples 2 to 6 are basically the same as example 1 except that: the mass ratio of sodium bicarbonate to 3,4, 5-trifluoroaniline was varied, see in particular table 1.

TABLE 1 discussion of catalyst amounts

As can be seen from table 1, when the mass ratio of sodium bicarbonate to 3,4, 5-trifluoroaniline is 0.01:1, the yield of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide is low, only 35.3%, because the amount of catalyst used is small and the reaction activity is low, resulting in low product yield. The yield of the N- [ (3,4, 5-trifluoro) phenyl ] acrylamide is gradually improved along with the increase of the mass ratio of the sodium bicarbonate to the 3,4, 5-trifluoroaniline, when the mass ratio of the sodium bicarbonate to the 3,4, 5-trifluoroaniline is 0.05:1, the product yield reaches 74.2%, and the influence on the product yield is not great by further increasing the using amount of the sodium bicarbonate, so that the mass ratio of the sodium bicarbonate to the 3,4, 5-trifluoroaniline is preferably 0.05: 1.

Research experiment on dosage of (di) 3,4, 5-trifluoroaniline and acryloyl chloride

In order to examine the influence of the molar ratio of 3,4, 5-trifluoroaniline to acryloyl chloride on the yield (yield N- [ (3,4, 5-trifluoro) phenyl ] acrylamide (actual amount (mol) of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide produced)/theoretical amount (mol) of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide produced) and purity, the inventors carried out the following experiments, i.e., example 7 to example 11, and the corresponding experimental results are shown in table 2.

Example 7:

a preparation method of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide comprises the following specific steps:

adding 14.7 g (0.1mol) of 3,4, 5-trifluoroaniline and 50 g of reaction solvent (the reaction solvent is dimethylformamide) into a 500ml four-necked bottle, adding 0.735 g of sodium bicarbonate, wherein the mass ratio of the sodium bicarbonate to the 3,4, 5-trifluoroaniline is 0.05:1, cooling to 5 ℃ under stirring, dropwise adding acryloyl chloride, the molar ratio of the 3,4, 5-trifluoroaniline to the acryloyl chloride is 1:1, reacting for 5 hours at 5 ℃, cooling the reaction solution to room temperature, then adding 300ml of deionized water into the reaction solution, filtering, collecting precipitate, and drying the precipitate to obtain the N- [ (3,4, 5-trifluoro) phenyl ] acrylamide. The purity of the prepared N- [ (3,4, 5-trifluoro) phenyl ] acrylamide was measured by high performance liquid chromatography.

Example 8 to example 11:

examples 8 to 11 are substantially the same as example 7 except that: the molar ratio of 3,4, 5-trifluoroaniline to acryloyl chloride was varied, see in particular table 2.

TABLE 23 molar ratio of 4, 5-trifluoroaniline to acryloyl chloride Experiencial

As can be seen from table 2, when the molar ratio of 3,4, 5-trifluoroaniline to acryloyl chloride was 1:1, the yield of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide was low, and as the molar ratio of 3,4, 5-trifluoroaniline to acryloyl chloride was increased, the yield of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide gradually increased, and when the molar ratio of 3,4, 5-trifluoroaniline to acryloyl chloride was 1:1.2, the yield of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide was as high as 74.8%, and further, the amount of acryloyl chloride was increased, the yield of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide was not significantly increased, and the excess acryloyl chloride was not easily recovered, wasted raw materials, and contaminated the environment. Thus, the optimum molar ratio of 3,4, 5-trifluoroaniline to acryloyl chloride is 1: 1.2.

(III) investigation experiment of reaction temperature

In order to examine the influence of the reaction temperature on the yield of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide (yield of the actual amount (mol) of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide/the theoretical amount (mol) of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide) and the purity, the inventors carried out the following experiments, i.e., example 12 to example 17, and the corresponding experimental results are shown in table 3.

Example 12:

a preparation method of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide comprises the following specific steps:

adding 14.7 g (0.1mol) of 3,4, 5-trifluoroaniline and 50 g of reaction solvent (the reaction solvent is dimethylformamide) into a 500ml four-necked bottle, adding 0.735 g of sodium bicarbonate, wherein the mass ratio of the sodium bicarbonate to the 3,4, 5-trifluoroaniline is 0.05:1, cooling to-10 ℃ under stirring, dropwise adding acryloyl chloride, the molar ratio of the 3,4, 5-trifluoroaniline to the acryloyl chloride is 1:1.2, reacting for 5 hours at-10 ℃, cooling the reaction liquid to room temperature, then adding 300ml of deionized water into the reaction liquid, filtering, collecting precipitate, and drying the precipitate to obtain the N- [ (3,4, 5-trifluoro) phenyl ] acrylamide. The purity of the prepared N- [ (3,4, 5-trifluoro) phenyl ] acrylamide was measured by high performance liquid chromatography.

Example 13 to example 17:

examples 13 to 17 are substantially the same as example 12 except that: the reaction temperatures were varied, see in particular table 3.

TABLE 3 investigation of reaction temperature

As is clear from table 3, the yield of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide was high at a reaction temperature of 5 ℃ or lower, but the yield of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide decreased with an increase in the reaction temperature when the reaction temperature exceeded 5 ℃, because: when the reaction temperature exceeds 5 ℃, the activity of the acryloyl chloride is too high, the nucleophilic ability of the anilino and the generated amido to the carbonyl in the acyl chloride is very strong, and the side reaction is enhanced, so that the yield of the N- [ (3,4, 5-trifluoro) phenyl ] acrylamide is very low; when the reaction temperature is less than or equal to 5 ℃, the aniline group has strong activity and the amido group has weak activity, the reaction can be carried out towards the direction which is beneficial to the generation of a target product, good reaction selectivity is shown, and the yield of the N- [ (3,4, 5-trifluoro) phenyl ] acrylamide is high. When the reaction temperature is 5 ℃, the yield of the N- [ (3,4, 5-trifluoro) phenyl ] acrylamide reaches 76.3%, and when the reaction temperature is lower than 5 ℃, the yield of the N- [ (3,4, 5-trifluoro) phenyl ] acrylamide does not change greatly, so the reaction temperature is preferably 5 ℃ from the viewpoint of energy conservation and environmental protection.

(IV) investigation experiment of reaction time

In order to examine the influence of the reaction time on the yield of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide (yield of the actual amount (mol) of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide/the theoretical amount (mol) of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide) and the purity, the inventors carried out the following experiments, i.e., example 18 to example 23, and the corresponding experimental results are shown in table 4.

Example 18:

a preparation method of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide comprises the following specific steps:

adding 14.7 g (0.1mol) of 3,4, 5-trifluoroaniline and 50 g of reaction solvent (the reaction solvent is dimethylformamide) into a 500ml four-necked bottle, adding 0.735 g of sodium bicarbonate, wherein the mass ratio of the sodium bicarbonate to the 3,4, 5-trifluoroaniline is 0.05:1, cooling to 5 ℃ under stirring, dropwise adding acryloyl chloride, the molar ratio of the 3,4, 5-trifluoroaniline to the acryloyl chloride is 1:1.2, reacting for 1 hour at 5 ℃, cooling the reaction liquid to room temperature, then adding 300ml of deionized water into the reaction liquid, filtering, collecting precipitate, and drying the precipitate to obtain the N- [ (3,4, 5-trifluoro) phenyl ] acrylamide. The purity of the prepared N- [ (3,4, 5-trifluoro) phenyl ] acrylamide was measured by high performance liquid chromatography.

Example 19 to example 23:

examples 19 to 23 are basically the same as example 18 except that: the reaction times varied, see in particular table 4. TABLE 4 investigation of reaction time

As is clear from Table 4, the reaction time greatly affects the yield of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide. When the reaction time is less than 5 hours, the reaction of acryloyl chloride with 3,4, 5-trifluoroaniline is insufficient, resulting in a low yield of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide. When the reaction time reaches 5h, the yield of the N- [ (3,4, 5-trifluoro) phenyl ] acrylamide reaches 76.3 percent, the reaction time is continuously increased, and the yield of the N- [ (3,4, 5-trifluoro) phenyl ] acrylamide has no obvious change; therefore, the reaction time is preferably 5 hours.

Example 24:

example 24 is substantially the same as example 9 except that: the reaction solvent is methanol.

Example 25:

example 25 is substantially the same as example 9 except that: the reaction solvent is acetone.

Example 26:

example 26 is substantially the same as example 9 except that: the reaction solvent is ethanol.

Example 27:

example 27 is substantially the same as example 9 except that: the reaction solvent is a mixed solution of methanol and ethanol, and the methanol and the ethanol in the mixed solution are in any proportion.

Example 28:

example 28 is substantially the same as example 9 except that: the reaction solvent is a mixed solution of dimethylformamide and acetone, and the dimethylformamide and the acetone in the mixed solution are in any proportion.

Example 29:

example 29 is substantially the same as example 9 except that: the reaction solvent is a mixed solution of methanol, ethanol, dimethylformamide and acetone, and the methanol, the ethanol, the dimethylformamide and the acetone in the mixed solution are in any proportion.

(V) comparative experiment:

in order to compare the catalytic efficiencies of sodium bicarbonate and triethylamine, the inventors performed the following comparative experiments, comparative example 1 and comparative example 2, respectively.

Comparative example 1:

a preparation method of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide comprises the following specific steps:

adding 14.7 g (0.1mol) of 3,4, 5-trifluoroaniline and 50 g of dimethylformamide into a 500ml four-neck flask, adding triethylamine and a polymerization inhibitor 2, 6-di-tert-butyl-p-cresol, wherein the mass ratio of the triethylamine to the 3,4, 5-trifluoroaniline is 0.05:1, the addition amount of the 3,4, 5-trifluoroaniline is 1% of the mass of the 3,4, 5-trifluoroaniline, stirring, cooling to 5 ℃, dropwise adding acryloyl chloride, wherein the molar ratio of the 3,4, 5-trifluoroaniline to the acryloyl chloride is 1:1.2, reacting for 5h at 5 ℃, cooling the reaction liquid to room temperature, adding 300ml of deionized water into the reaction liquid, filtering, collecting precipitate, and drying the precipitate to obtain the N- [ (3,4, 5-trifluoro) phenyl ] acrylamide.

Comparative example 2:

comparative example 2 is substantially the same as comparative example 1 except that: the polymerization inhibitor 2, 6-di-tert-butyl-p-cresol is not added in the reaction system.

TABLE 5 comparative experiment of catalytic Properties of different catalysts

As can be seen from table 5, the yield of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide using sodium bicarbonate as the catalyst was improved by 28.9% as compared with triethylamine alone; compared with triethylamine as a catalyst and 2, 6-di-tert-butyl-p-cresol as a polymerization inhibitor, the yield of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide adopting sodium bicarbonate as a catalyst is improved by 22.1 percent. Therefore, the catalytic efficiency of the sodium bicarbonate as a catalyst is obviously higher than that of triethylamine, and 2, 6-di-tert-butyl-p-cresol as a polymerization inhibitor is not required to be added, so that the product yield is improved, and the reaction cost is reduced.

The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the present invention, but rather as the following description is intended to cover all modifications, equivalents and improvements falling within the spirit and scope of the present invention.

Claims (2)

1. A preparation method of N- [ (3,4, 5-trifluoro) phenyl ] acrylamide is characterized by comprising the following steps:

(1) adding 3,4, 5-trifluoroaniline, a reaction solvent and a catalyst into a reaction container, uniformly stirring, adding acryloyl chloride, and reacting at-10 ℃ for 4-7 h; the catalyst is sodium bicarbonate, and the mass ratio of the sodium bicarbonate to the 3,4, 5-trifluoroaniline is (0.03-0.1): 1; the reaction solvent is dimethylformamide; the molar ratio of the 3,4, 5-trifluoroaniline to the acryloyl chloride is 1: (1.1-2.5);

(2) and (2) adding water into the reaction liquid obtained in the step (1), uniformly stirring, filtering, separating out a precipitate, and drying the precipitate to obtain the N- [ (3,4, 5-trifluoro) phenyl ] acrylamide.

2. The method according to claim 1, wherein the acryloyl chloride is added dropwise.

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