CN111747841B

CN111747841B - Preparation method of 4-formylbenzoic acid and obtained 4-formylbenzoic acid

Info

Publication number: CN111747841B
Application number: CN201910248679.9A
Authority: CN
Inventors: 王旭东; 王丽颖
Original assignee: Ptg Advanced Catalyst Co ltd
Current assignee: Ptg Advanced Catalyst Co ltd
Priority date: 2019-03-29
Filing date: 2019-03-29
Publication date: 2022-09-06
Anticipated expiration: 2039-03-29
Also published as: CN111747841A

Abstract

The invention discloses a method for synthesizing 4-formyl benzoic acid suitable for industrial production, which comprises the steps of synthesizing p-carboxyl benzoyl chloride by utilizing terephthalic acid, and then carrying out reduction treatment to obtain p-formyl benzoic acid, wherein the yield can reach more than 70 percent and even more than 80 percent, and the preparation is simple and can be finished in one pot.

Description

Preparation method of 4-formyl benzoic acid and obtained 4-formyl benzoic acid

Technical Field

The invention relates to the field of organic synthesis, in particular to preparation of 4-formylbenzoic acid.

Background

4-formyl benzoic acid is a common chemical raw material and is widely applied to medicines, pesticides, fluorescent whitening agent intermediates and the like. Four million tons of 4-formylbenzoic acid are produced globally every year, and 4-formylbenzoic acid is therefore a huge industrial chemical.

In the prior art, 4-formyl benzoic acid is synthesized by oxidizing dimethylbenzene under an oxidant, and the method has the disadvantages of difficult operation, harsh conditions, low reaction yield and difficult separation. In addition, 4-formylbenzoic acid can also be obtained from aldehyde halohydrocarbon or terephthalaldehyde and other raw materials in the prior art, but the raw materials have higher cost and inhibit the industrial production thereof.

Therefore, a simple and efficient method for synthesizing 4-formylbenzoic acid is needed.

Disclosure of Invention

In order to overcome the above problems, the present inventors have conducted intensive studies to provide a method for synthesizing 4-formylbenzoic acid suitable for industrial production, which comprises synthesizing p-carboxybenzoyl chloride from terephthalic acid and then subjecting the p-carboxybenzoyl chloride to reduction treatment, wherein the preparation is simple and can be carried out in one pot.

The invention provides a preparation method of 4-formyl benzoic acid on one hand, which is embodied in the following aspects:

(1) a preparation method of 4-formyl benzoic acid is characterized in that 4-carboxylbenzoyl chloride is used as an intermediate, and the 4-formyl benzoic acid is prepared through catalytic hydrogenation reduction.

(2) The method according to the above (1), wherein the method comprises the steps of:

step 1, carrying out acyl chlorination reaction by using terephthalic acid and acyl chloride reagents as raw materials to obtain an intermediate 4-carboxybenzoyl chloride;

step 2, adding a catalyst, introducing hydrogen and optionally pressurizing, and carrying out catalytic hydrogenation reduction reaction on the intermediate 4-carboxybenzoyl chloride;

and 3, carrying out post-treatment after the reaction is finished to obtain the 4-formylbenzoic acid.

(3) The method according to the above (2), wherein the step 1 includes the sub-steps of:

step 1.1, mixing terephthalic acid with a first solvent to form a reaction system;

step 1.2, mixing an acyl chloride reagent with a solvent II to form an acyl chloride solution;

and step 1.3, slowly dropwise adding an acyl chloride solution into the reaction system, and heating and refluxing to perform acyl chlorination reaction to obtain an intermediate 4-carboxybenzoyl chloride.

(4) The method according to the above (3), wherein in step 1.3, one or more droppers for slowly dropping an acyl chloride reagent solution are uniformly distributed in the reaction system;

preferably, the plurality of drippers are spaced apart from each other when they are dripped.

(5) The method according to the above (3), wherein, in step 1.1,

the solvent one is selected from one or more of tetrahydrofuran, dioxane, toluene, xylene and dimethylformamide; and/or

The mass-to-volume ratio (m/v) of the terephthalic acid to the first solvent is 1 (5-30).

(6) The method according to the above (3), wherein, in step 1.2,

the acyl chloride reagent is a compound containing acyl chloride groups; preferably, the acid chloride reagent is selected from one or more of thionyl chloride, acetyl chloride and oxalyl chloride; and/or

The second solvent is an organic solvent; preferably, the solvent two is selected from one or more of tetrahydrofuran, dioxane, toluene, xylene and dichloromethane.

(7) The method according to the above (3), wherein,

in the step 1.2, the concentration of the acyl chloride solution is (0.5-2) mol/L; and/or in step 1.2, optionally subjecting the acid chloride reagent to a temperature reduction treatment; and/or

In the step 1.3, the dropping speed is 0.01-0.5 mL/s.

(8) The method according to one of the above (1) to (7), wherein,

in the step 1, the molar use ratio of terephthalic acid to acyl chloride reagent is (1-1.5): 1; and/or

In the step 2, the catalyst is a Rosenmend (Rosenmund) catalyst, and the dosage ratio of the catalyst to the terephthalic acid is (0.005-0.1): 1.

(9) The method according to the above (8), wherein in step 3, the post-processing is performed as follows:

step 3.1, filtering while hot after the reaction is finished, washing with toluene, and taking a filtrate I;

step 3.2, carrying out rotary evaporation on the filtrate I to obtain a crude product;

step 3.3, dissolving the crude product in ether, and filtering to obtain a filtrate II;

and 3.4, performing rotary evaporation on the filtrate II, and then optionally performing recrystallization treatment to obtain the 4-formylbenzoic acid, wherein the recrystallization is preferably performed in a polar solvent, preferably an alcohol solvent.

(10) The purity of the 4-formylbenzoic acid obtained by the production method according to any one of the above (1) to (9) is 99% or more.

Drawings

FIG. 1 shows the nuclear magnetic spectrum of the final product obtained in example 1;

FIG. 2 shows an HPLC plot of the product obtained in example 4;

figure 3 shows an HPLC profile of the product obtained in comparative example 3.

Detailed Description

The present invention will be described in further detail with reference to examples and experimental examples. The features and advantages of the present invention will become more apparent from the description.

The invention provides a preparation method of 4-formyl benzoic acid, which takes 4-carboxyl benzoyl chloride as an intermediate to prepare the 4-formyl benzoic acid through catalytic hydrogenation reduction.

According to a preferred embodiment of the invention, the method comprises the following steps:

Wherein the reaction process is shown as a formula (1).

In a further preferred embodiment, step 1 comprises the following sub-steps:

Since both carboxyl groups of the raw material terephthalic acid have reactivity and both the carboxyl groups have the possibility of acyl chlorination with an acyl chloride reagent to generate a side intermediate product terephthalic acid chloride, the acyl chloride reagent needs to be slowly dripped into the terephthalic acid during the reaction of the terephthalic acid and the acyl chloride reagent in the first step, so that a small amount of the acyl chloride reagent enters a large amount of the terephthalic acid and is rapidly diffused to reduce the local concentration of the acyl chloride reagent, and the intermediate 4-carboxyl benzoyl chloride is generated.

In a further preferred embodiment, in step 1.3, one or more droppers are uniformly distributed in the reaction system and used for slowly dripping the acyl chloride reagent solution.

Because the acyl chloride reagent needs to be slowly dripped, the reaction time is prolonged to a certain extent, and the reaction efficiency is reduced, therefore, the invention adopts the arrangement of a plurality of drippers at different places in the reaction system, and thus, the plurality of drippers are distributed at different positions of the reaction system, the local concentration of the acyl chloride reagent is hardly influenced, and the reaction efficiency is improved.

In a further preferred embodiment, the plurality of drip chambers are spaced apart from each other, preferably 0.1 to 0.5s apart, more preferably 0.2 to 0.4s apart, when they are dripping.

Therefore, not only the liquid dropping at different positions but also the liquid dropping at different positions are controlled, and the local low concentration of the acyl chloride reagent in the reaction system is further realized.

According to a preferred embodiment of the present invention, in step 1.1, the solvent one is selected from one or more of tetrahydrofuran, dioxane, toluene, xylene and dimethylformamide.

In a further preferred embodiment, in step 1.1, the solvent one is selected from one or more of toluene, xylene and dimethylformamide.

In a still further preferred embodiment, in step 1.1, the solvent is selected from xylene and/or dimethylformamide.

Among them, in the first reaction of the present invention, since terephthalic acid as a raw material is less soluble in an organic solvent, it is necessary to carry out the reaction at a high temperature, and thus a high boiling point solvent is preferable in the first reaction because it promotes the reaction, and thus xylene and/or dimethylformamide are preferable.

According to a preferred embodiment of the present invention, in step 1.1, the mass-to-volume ratio (m/v) of terephthalic acid to the first solvent is 1 (5-30).

In a further preferred embodiment, in step 1.1, the mass-to-volume ratio (m/v) of terephthalic acid to the first solvent is 1 (10 to 20).

Wherein the concentration of terephthalic acid in solvent one cannot be too great, which would otherwise result in the formation of terephthaloyl chloride in step 1.2.

According to a preferred embodiment of the invention, in step 1.2, the acid chloride reagent is a compound containing an acid chloride group.

In a further preferred embodiment, in step 1.2, the acid chloride reagent is selected from one or more of thionyl chloride, acetyl chloride and oxalyl chloride.

In a still further preferred embodiment, in step 1.2, the acid chloride reagent is thionyl chloride.

Among them, the inventors have found through a lot of experiments that the yield of the product is the highest when thionyl chloride is used as the acyl chlorination reagent.

According to a preferred embodiment of the present invention, in step 1.2, the second solvent is an organic solvent.

In a further preferred embodiment, in step 1.2, the solvent two is selected from one or more of tetrahydrofuran, dioxane, toluene, xylene and dichloromethane.

In still further step 1.2, the solvent two is selected from one or more of dioxane, toluene, xylene, and methylene chloride.

According to a preferred embodiment of the invention, in step 1.2, the concentration of the acid chloride solution is (0.5-2) mol/L.

In a further preferred embodiment, in step 1.2, the concentration of the acid chloride solution is (0.8-1.5) mol/L.

In a further preferred embodiment, in step 1.2, the concentration of the acid chloride solution is (1-1.2) mol/L.

In the invention, the acyl chloride reagent is dissolved in the solvent and then is dripped into the reaction system, rather than being directly dripped into the reaction system. Therefore, the concentration of the acyl chloride reagent can be diluted, the low-concentration acyl chloride reagent is further ensured to be dropped into the reaction system, the local concentration of the acyl chloride reagent in the reaction system is reduced, and the diacyl chlorination of the terephthalic acid is avoided.

According to a preferred embodiment of the present invention, in step 1.2, the acid chloride reagent is optionally subjected to a temperature reduction treatment.

In a further preferred embodiment, the temperature is lowered to-5 to 5 ℃, for example 0 to 5 ℃.

The acyl chloride reagent is cooled, so that the low-temperature acyl chloride reagent is not immediately reacted after being dripped into a reaction system, but is firstly diffused and then reacted, so that the local concentration of the acyl chloride reagent in the reaction system can be further prevented from being too high, and the generation of an intermediate byproduct, namely terephthaloyl chloride, can be further prevented. According to a preferred embodiment of the present invention, in step 1.3, the dropping rate is 0.01 to 0.5 mL/s.

In a more preferred embodiment, in step 1.3, the dropping rate is 0.05 to 0.2 mL/s.

Wherein, the lower the dripping speed is, the smaller the local concentration of the acyl chloride reagent in the reaction system is, and the more difficult the production of the intermediate paraphthaloyl chloride is. However, too slow of addition may result in too long a reaction time and thus in poor reaction efficiency. Therefore, the inventors have determined the optimum dropping rate after a large number of experiments.

According to a preferred embodiment of the invention, the molar ratio of the terephthalic acid to the acid chloride reagent is (1-1.5): 1, wherein the molar amount of the acid chloride reagent is calculated by the molar amount of the acid chloride groups in the acid chloride reagent, and the molar amount of the terephthalic acid is calculated by the molecular weight of the terephthalic acid.

In a further preferred embodiment, the molar ratio of terephthalic acid to acid chloride reagent is (1.05-1.3): 1, wherein the molar amount of acid chloride reagent is based on the molar amount of acid chloride groups therein and the molar amount of terephthalic acid is based on the molecules of terephthalic acid.

In a further preferred embodiment, the molar ratio of terephthalic acid to acid chloride reagent is (1.1-1.2): 1, wherein the molar amount of acid chloride reagent is based on the molar amount of acid chloride groups therein and the molar amount of terephthalic acid is based on the molecules of terephthalic acid.

In the present invention, a slight excess of terephthalic acid is employed for two reasons: (1) when the acyl chloride reagent is equivalent or excessive, terephthaloyl chloride may be generated, and then hydrogenation is carried out to form terephthalaldehyde by-product, wherein terephthalaldehyde is easily dissolved in an organic solvent and is not easily removed; (2) however, if a slight excess of terephthalic acid is used, it is more readily monoacylated, but a small amount of terephthalic acid remains, which is more readily removed (see details in the work-up section).

According to a preferred embodiment of the present invention, in step 1.3, the acyl chlorination reaction is carried out as follows: heating to 80-140 ℃ and carrying out reflux reaction for 10-30 h.

In a further preferred embodiment, in step 1.3, the acid chlorination reaction is carried out as follows: heating to 90-110 ℃ and carrying out reflux reaction for 20-25 h.

In the present invention, since terephthalic acid as a raw material is not easily soluble in an organic solvent, the reaction is promoted by controlling the acid chlorination reaction to proceed at a high temperature in order to increase the solubility thereof in the reaction system. Meanwhile, the reason why the reaction time is controlled to be long is that, even though there is terephthaloyl chloride in the system, if the reaction time is long enough, the terephthaloyl chloride reacts with terephthalic acid to some extent to form 4-carboxybenzoyl chloride.

According to a preferred embodiment of the present invention, in step 2, the catalyst is a rosenmond (Rosenmund) catalyst.

Wherein the Rosenmond catalyst is prepared by adding a toxic agent (2, 6-dimethylpyridine, quinoline-sulfur, etc.) into palladium powder on barium sulfate (BaSO 4). Under the action of the catalyst, the acyl chloride can be reduced into aldehyde by introducing hydrogen.

In a further preferred embodiment, the ratio of the amount of the catalyst to the amount of terephthalic acid is (0.005-0.1): 1.

In a further preferred embodiment, the catalyst and terephthalic acid are used in a ratio of (0.01-0.05): 1, for example (0.01-0.03): 1.

According to a preferred embodiment of the present invention, in step 2, the catalytic hydrogenation reduction reaction is performed at 80-140 ℃ for 8-30 h.

In a further preferred embodiment, in the step 2, the catalytic hydrogenation reduction reaction is carried out at 90-120 ℃ for 10-25 h.

According to a preferred embodiment of the invention, in step 3, the post-treatment is carried out as follows:

wherein, in step 3.1, the solid catalyst is filtered off and recovered. Wherein the solubility of the product is increased while hot, so that the product is not filtered out.

Step 3.2, rotatably steaming the filtrate I to obtain a crude product;

wherein the solvent is removed by rotary evaporation.

Step 3.3, dissolving the crude product in ether, and filtering to obtain a filtrate II; wherein, the crude product is mainly the product 4-formyl benzoic acid, and terephthalic acid residue is also existed, 4-formyl benzoic acid can be dissolved in diethyl ether, and terephthalic acid can not be dissolved in diethyl ether. Thus, the unreacted terephthalic acid can be very effectively removed by filtration after dissolution in diethyl ether.

And 3.4, carrying out rotary evaporation on the filtrate II, and then optionally carrying out recrystallization treatment to obtain the 4-formylbenzoic acid.

In a further preferred embodiment, in step 3.4, the recrystallization is carried out in a polar solvent.

In a still further preferred embodiment, in step 3.4, the recrystallization is carried out in an alcoholic solvent, such as ethanol.

Wherein, the inventor carries out chromatographic analysis on the product after the rotary evaporation in the step 3.4, wherein, almost no impurities remain, which indicates that the impurities are removed cleanly. However, when nuclear magnetic analysis is carried out, some fine burr peaks are found, so that the inventor finds that recrystallization can well remove the burr peaks on nuclear magnetic after multiple treatment measures, and obtains a very pure 4-formylbenzoic acid refined product.

By adopting the method, the yield reaches more than 70 percent, even reaches more than 80 percent.

According to another aspect of the present invention, there is provided 4-formylbenzoic acid obtained by the process according to the first aspect of the present invention, wherein the purity of the 4-formylbenzoic acid is more than 99%.

The invention has the advantages that:

(1) the method is simple and can be used for one-pot reaction;

(2) the method of the invention skillfully utilizes the acyl chlorination reagent to develop a novel method for preparing 4-formyl benzoic acid, thereby avoiding the reaction conditions of high temperature and high pressure;

(3) the final product of the method is easy to purify, and the final product with higher purity is obtained.

Examples

The invention is further described below by means of specific examples. However, these examples are only illustrative and do not limit the scope of the present invention.

In the examples and comparative examples, the Rosenmond catalyst was purchased from Annagi reagent.

Example 1

In a 500mL four-necked flask, 11g of terephthalic acid and 200mL of toluene were added. While the mixture was heated to 110 ℃ and stirred under reflux, 60mL of a methylene chloride solution of thionyl chloride (1M, 0 ℃) was added dropwise at a rate of 0.1mL/s, and the reaction was carried out for 24 hours to give p-carboxybenzoyl chloride. Wherein, the toluene solution of acetyl chloride is dripped into the openings at the two ends of the four-mouth bottle at the same speed, and the dripping at the two positions are staggered with the interval of 0.5 s.

Cooling to room temperature, adding 200mg of Rosenmond catalyst, introducing hydrogen into the reaction system, heating to 100 ℃, and reacting for 24 hours.

The heating was stopped and the solid was filtered while hot and washed with copious amounts of toluene. The solid catalyst is recovered and the filtrate is spin-dried to give the crude product. The crude product was dissolved in ether, then filtered, and the filtrate was rotary evaporated, followed by recrystallization from ethanol to give 7.4g of p-formylbenzoic acid.

The purity of the product after recrystallization is 99.07 percent by chromatographic detection.

Meanwhile, the product after recrystallization is subjected to nuclear magnetism characterization, as shown in figure 1, the structure is shown in ¹ H-NMR analysis confirmed that: a benzene ring resonance peak appears between 7.8 ppm and 8.3ppm, corresponding to hydrogen on the benzene ring; an aldehyde group formant appears near 10.2ppm, corresponding to hydrogen on the aldehyde group; a carboxyl resonance peak appears at 13.4ppm, corresponding to hydrogen on carboxyl; it was found that the synthesis of p-formylbenzoic acid was successful.

Example 2

In a 500mL four-necked flask was added 13.2g of terephthalic acid and 200mL of toluene. While the mixture was stirred under reflux at 120 ℃ and 55mL of a toluene solution of acetyl chloride (1.2M, 0 ℃) was added dropwise thereto at a rate of 0.05mL/s, the reaction was carried out for 20 hours to give p-carboxybenzoyl chloride. Wherein, the toluene solution of acetyl chloride is dripped into the openings at the two ends of the four-mouth bottle at the same speed, and the dripping at the two positions are staggered with the interval of 0.5 s.

Cooling to room temperature, adding 200mg of Rosenmond catalyst, introducing hydrogen into the reaction system, heating to 90 ℃, and reacting for 30 hours.

The heating was stopped and the solid was filtered while hot and washed with copious amounts of toluene. The solid catalyst is recovered and the filtrate is spin-dried to give the crude product. The crude product is dissolved in diethyl ether, filtered and the filtrate is evaporated off with rotation, and the crude product is recrystallized from ethanol to give 6.5g of p-formylbenzoic acid.

The purity of the product after recrystallization is 99.22 percent by chromatographic detection.

Meanwhile, the nuclear magnetic detection is carried out on the product, the nuclear magnetic spectrum is similar to that of the example 1, and the synthesis of the p-formylbenzoic acid is realized.

Example 3

In a 500mL four-necked flask was added 13g of terephthalic acid and 300mL of toluene. While the mixture was stirred under reflux at 110 ℃ and 76mL of a xylene solution of oxalyl chloride (0.8M, 0 ℃) was added dropwise at a rate of 0.2mL/s, the reaction was carried out for 24 hours to give p-carboxybenzoyl chloride. Wherein, the toluene solution of oxalyl chloride is dripped at the same speed at the three-end opening of the four-mouth bottle, and the dripping at the three positions are staggered with each other at the interval of 0.33 s.

Cooling to room temperature, adding 200mg of Rosenmend catalyst, introducing hydrogen into the reaction system, and heating to 120 ℃. The reaction was carried out for 20 hours.

The heating was stopped and the solid was filtered while hot and washed with copious amounts of toluene. The solid catalyst is recovered and the filtrate is spin-dried to give the crude product. The crude product is dissolved in diethyl ether, filtered and the filtrate is evaporated off with rotation, and the crude product is recrystallized from ethanol to give 6.1g of p-formylbenzoic acid.

And (4) carrying out chromatographic detection on the recrystallized product to obtain the purity of 99.12%.

Meanwhile, nuclear magnetic detection is carried out on the product, and the nuclear magnetic spectrogram is similar to that in example 1, so that the synthesis of the p-formylbenzoic acid is realized.

Comparing examples 1 to 3, it is known that when thionyl chloride is selected as the acid chloride reagent, the yield of the obtained product is the highest, indicating that thionyl chloride is more likely to promote the first step of the acid chlorination reaction.

Example 4

In a 500mL four-necked flask, 15g of terephthalic acid and 450mL of xylene were added. While the mixture was stirred under reflux while heating to 140 ℃ at the same time, 60mL of a thionyl chloride solution in methylene chloride (1M, 0 ℃) was added dropwise thereto at a rate of 0.01mL/s, and the reaction was carried out for 10 hours. To produce p-carboxybenzoyl chloride. Wherein, the toluene solution of acetyl chloride is dripped into the openings at the two ends of the four-mouth bottle at the same speed, and the dripping at the two positions are staggered with the interval of 0.5 s.

Cooling to room temperature, adding 200mg of Rosenmend catalyst, and introducing hydrogen into the reaction system. Heating to 100 deg.C. The reaction was carried out for 12 hours.

The heating was stopped and the solid was filtered while hot and washed with copious amounts of xylene. The solid catalyst is recovered and the filtrate is spin-dried to give the crude product. The crude product was dissolved in ether, then filtered and the filtrate was rotary evaporated and then recrystallized from ethanol to give 7.8g of p-formylbenzoic acid.

The product after recrystallization was chromatographed to 99.16% purity, the results are shown in table 1 and fig. 2.

Table 1:

peak #	Retention time	Area of	Area%	Height
					3.620	43626	0.3906	3615	3.620
4.176	11073637	99.1561	796993	4.176
					6.334	50625	0.4533	2237	6.334

Example 5

A500 mL four-necked flask was charged with 12g of terephthalic acid and 200mL of dioxane was added. While the mixture was stirred under reflux while heating to 110 ℃ at the same time, 60mL of a thionyl chloride solution in methylene chloride (1M, 0 ℃) was added dropwise thereto at a rate of 0.02mL/s, and the reaction was carried out for 12 hours. To produce p-carboxybenzoyl chloride. Wherein, the toluene solution of acetyl chloride is dripped into the openings at the two ends of the four-mouth bottle at the same speed, and the dripping at the two positions are staggered with the interval of 0.5 s.

The heating was stopped and the solid was filtered while hot and washed with copious amounts of xylene. Recovering the solid catalyst. And spin-drying the filtrate to obtain a crude product. The crude product is dissolved in diethyl ether, filtered off and the filtrate is evaporated off with rotation and then recrystallized from ethanol to give 6.5g of p-formylbenzoic acid.

The product after recrystallization is subjected to chromatographic detection, and the purity reaches 99.31 percent.

Example 6

13g of terephthalic acid and 200mL of DMF were added to a 500mL four-necked flask. While the mixture was stirred under reflux while heating to 120 ℃ and 0.05mL/s, 60mL of a thionyl chloride solution in methylene chloride (1M, 0 ℃) was added dropwise thereto, and the reaction was carried out for 24 hours. The solvent was distilled off under reduced pressure. To produce p-carboxybenzoyl chloride.

Cooling to room temperature, adding 200mg of Rosenmond catalyst, and introducing hydrogen into the reaction system. Heated to reflux. The reaction was carried out for 24 hours.

The heating was stopped and the solid was filtered while hot and washed with copious amounts of toluene. Recovering the solid catalyst. And spin-drying the filtrate to obtain a crude product. The crude product was dissolved in ether, then filtered and the filtrate was rotary evaporated and then recrystallized from ethanol to give 8.3g of p-formylbenzoic acid.

The purity of the product after recrystallization is 99.03 percent by chromatographic detection.

Comparing example 1 with example 6, the difference is in the choice of reaction solvent, it is seen that when Dimethylformamide (DMF) is used, the yield is 12% higher than when toluene is used.

Example 7

A500 mL four-necked flask was charged with 14g of terephthalic acid and 200mL of DMF. While the mixture was heated to 110 ℃ and stirred under reflux, 60mL of a thionyl chloride solution (1M, 0 ℃) was added dropwise thereto at a rate of 0.1mL/s, and the reaction was carried out for 24 hours. The solvent was distilled off under reduced pressure. To produce p-carboxybenzoyl chloride. Wherein, the toluene solution of acetyl chloride is dripped into the openings at the two ends of the four-mouth bottle at the same speed, and the dripping at the two positions are staggered with an interval of 0.5 s.

Cooled to room temperature, 200mg of rosemond catalyst was added and transferred to a high pressure autoclave. The pressure of hydrogen introduced into the reaction system is controlled at 5M Pa. Heating to 100 deg.C. The reaction was carried out for 12 hours.

The heating was stopped and the solid was filtered while hot and washed with copious amounts of toluene. The solid catalyst is recovered and the filtrate is spin-dried to give the crude product. The crude product was dissolved in ether, then filtered and the filtrate was rotary evaporated and then recrystallized from ethanol to give 8.7g of p-formylbenzoic acid.

And (4) carrying out chromatographic detection on the recrystallized product to ensure that the purity reaches 99.15%.

Comparative example

Comparative example 1

In a 500mL four-necked flask was placed 12g of terephthalic acid and 200mL of tetrahydrofuran. 60mL of thionyl chloride (1M, 0 ℃) was slowly added dropwise with stirring, the dropwise addition being completed in ten minutes. The temperature is increased to reflux and the reaction is carried out for 12 hours. To produce p-carboxybenzoyl chloride. Wherein, the toluene solution of acetyl chloride is dripped into the openings at the two ends of the four-mouth bottle at the same speed, and the dripping at the two positions are staggered with the interval of 0.5 s.

Cooling to room temperature, adding 200mg of Rosenmend catalyst, and introducing hydrogen into the reaction system. Heating to 60 deg.C. The reaction was carried out for 12 hours.

The heating was stopped and the solid was filtered while hot and washed with copious amounts of xylene. The solid catalyst is recovered and the filtrate is spin-dried to give the crude product. The crude product was dissolved in ether, then filtered and the filtrate was rotary evaporated and then recrystallized from ethanol to give 4.8g of p-formylbenzoic acid.

Among them, in comparative example 1, tetrahydrofuran was used as a solvent, and the reaction time was short, and only 4.8g of the product was finally obtained, and the yield was remarkably reduced.

Comparative example 2

The procedure of example 4 was repeated except that: directly adding thionyl chloride into the terephthalic acid solution, adding the thionyl chloride and the terephthalic acid solution with equivalent weight, and keeping the rest conditions unchanged.

The majority of the obtained product was terephthalaldehyde.

Performing nuclear magnetism characterization on the obtained product, and obtaining the product with a structure ¹ H-NMR analysis confirmed that: a benzene ring formant appears between 7.95 ppm and 8.01ppm, and an aldehyde group formant appears at 9.72 ppm; it is known that the obtained product is terephthalaldehyde.

Comparative example 3

The procedure of example 4 was repeated except that: without recrystallization, the HPLC profile of the final product was found to contain some impurities with a purity of only 95.66%, with the results shown in table 2 and fig. 3.

Table 2:

retention time	Area of	Area%	Height
				2.214	7765	0.1368	437
2.585	19218	0.3385	702
				3.620	104400	1.8386	8629
4.172	5431935	95.6608	405086
				6.323	51265	0.9028	2696
8.622	2371	0.0418	113
				10.357	61374	1.0808	2134

The invention has been described in detail with reference to the preferred embodiments and illustrative examples. It should be noted, however, that these specific embodiments are merely illustrative of the present invention and do not limit the scope of the present invention in any way. Various modifications, equivalent substitutions and alterations can be made to the technical content and embodiments of the present invention without departing from the spirit and scope of the present invention, and these are within the scope of the present invention. The scope of the invention is defined by the appended claims.

Claims

1. A preparation method of 4-formyl benzoic acid is characterized by comprising the following steps:

step 1, carrying out acyl chlorination reaction by using terephthalic acid and acyl chloride reagents as raw materials to obtain an intermediate 4-carboxyl benzoyl chloride; the molar use ratio of the terephthalic acid to the acyl chloride reagent is (1.1-1.2): 1;

step 2, adding a catalyst, introducing hydrogen and pressurizing, and carrying out catalytic hydrogenation reduction reaction on the intermediate 4-carboxybenzoyl chloride; the catalyst is a Rosenmend catalyst, and the dosage ratio of the catalyst to terephthalic acid is (0.01-0.03): 1;

the catalytic hydrogenation reduction reaction is carried out for 8-30 h at the temperature of 80-140 ℃;

step 3, carrying out post-treatment after the reaction is finished to obtain the 4-formylbenzoic acid;

step 1 comprises the following substeps:

in the step 1.2, cooling the acyl chloride reagent to-5 ℃;

step 1.3, slowly dripping acyl chloride solution into a reaction system, and heating and refluxing to perform acyl chlorination reaction to obtain an intermediate 4-carboxybenzoyl chloride;

in step 1.3, one or more droppers are uniformly distributed in the reaction system and used for slowly dropping acyl chloride reagent solution;

when the plurality of the drip droppers are used for dripping, the drip droppers are spaced from each other at intervals of 0.1-0.5 s.

2. A method according to claim 1, characterized in that, in step 1.1,

3. A method according to claim 1, characterized in that, in step 1.2,

the acyl chloride reagent is a compound containing acyl chloride groups; the acyl chloride reagent is selected from one or more of thionyl chloride, acetyl chloride and oxalyl chloride; and/or

The second solvent is an organic solvent; the solvent II is one or more selected from tetrahydrofuran, dioxane, toluene, xylene and dichloromethane.

4. The method of claim 1, wherein,

in the step 1.2, the concentration of the acyl chloride solution is (0.5-2) mol/L; and/or

In the step 1.3, the dropping speed is 0.01-0.5 mL/s.

5. The method according to claim 1, wherein in step 3 the post-processing is performed as follows:

and 3.4, carrying out rotary evaporation on the filtrate II, and then carrying out recrystallization treatment to obtain the 4-formylbenzoic acid, wherein the recrystallization is carried out in an alcohol solvent.