Method for synthesizing p-fluorobenzoyl chloride from p-fluorobenzoic acid in two steps

Abstract

The invention discloses a method for synthesizing p-fluorobenzoyl chloride by a two-step method of p-fluorobenzoic acid, wherein the method uses p-fluorobenzoic acid and p-fluorobenzoyl chloride as starting materials, and an acidolysis reaction of acyl chloride is carried out by a catalyst to obtain intermediate p-fluorobenzoic anhydride and hydrogen chloride; intermediate p-fluorobenzoic anhydride and p-fluorobenzyl chloride are subjected to anhydride acylation reaction under a catalyst to obtain p-fluorobenzoyl chloride. The method for synthesizing p-fluorobenzoyl chloride by a two-step method of p-fluorobenzoic acid of the present invention has the characteristics of ingenious and simple process design, high product yield and excellent quality, and can also significantly reduce the production cost of p-fluorobenzoyl chloride, with good economic and social benefits. Therefore, the present invention adds a synthetic route that reduces raw material costs and is more concise to the synthesis of p-fluorobenzoyl chloride. The p-fluorobenzoyl chloride obtained by the present invention can be used for the synthesis of 4,4′-difluorobenzophenone in a conventional manner.

Description

Technical Field

[0001] The invention belongs to the field of fine chemicals and relates to a synthesis and purification technology of fine chemical intermediates, in particular to a method for synthesizing p-fluorobenzoyl chloride from p-fluorobenzoic acid in two steps. Background Art

[0002] 4,4'-Difluorobenzophenone, CAS NO: 345-92-6, can be used as an imaging agent and charge control agent for optical and electrical recording materials, as well as an initiator for certain polymerization reactions, and is a monomer material for many copolymers. 4,4'-Difluorobenzophenone is a key monomer for the synthesis of PEEK resin. The consumption of PEEK resin in the international market has increased from less than 50 tons in the early 1980s to nearly 5,500 tons in 2014. In recent years, the consumption has been growing rapidly at an annual rate of about 30%. In the demand for PEEK resin, Western Europe accounts for 55%, the United States accounts for 35%, and Asia Pacific accounts for 10%.

[0003] As an important monomer of special engineering plastics, the development of 4,4′-difluorobenzophenone industry has always been the focus of attention and is a key area of ​​scientific and technological research; as a pharmaceutical intermediate, 4,4′-difluorobenzophenone can be used to synthesize the new powerful cerebral vasodilator "Flubencin" and the drug "Du Kexi" for the treatment of Alzheimer's disease, and both drugs are drugs with great market development potential. Therefore, from 2011 to 2016, the 4,4′-difluorobenzophenone industry has achieved good development, and the market size has shown a rapid growth trend.

[0004] According to literature reports, there are several routes for synthesizing 4,4′-difluorobenzophenone. However, from the perspective of economy, safety and product quality, the mainstream domestic production process is a synthetic route using p-fluorobenzoyl chloride and fluorobenzene as raw materials and a Friedel-Crafts reaction with aluminum chloride as a catalyst. The synthetic route is as follows:

[0005]

[0006] However, as for the source of the main raw material p-fluorobenzoyl chloride, the mainstream synthetic route is to obtain p-fluorobenzyl trichloride by photochlorination of p-fluorotoluene, and then catalytic hydrolysis to obtain p-fluorobenzoyl chloride, which is also the simplest production technology.

[0007] There are also literature reports that when p-fluorobenzoic acid and dichlorothionyl are used as raw materials for the reaction, p-fluorobenzoyl chloride is obtained and a mixed gas of sulfur dioxide and hydrogen chloride is also produced as a by-product, which is difficult to recycle and is not environmentally friendly.

[0008] The production process of p-fluorobenzaldehyde also produces p-fluorobenzoic acid as a byproduct. Even if the byproduct p-fluorobenzoic acid is purified by various means, it is difficult to meet the quality requirements of commodities. If it is disposed of as hazardous waste, it will not only consume a lot of costs, but also cause resource losses. Therefore, enterprises also need to come up with feasible resource utilization plans through technical research. Summary of the invention

[0009] The technical problem to be solved by the present invention is that p-fluorobenzoic acid is also produced as a byproduct during the production of p-fluorobenzaldehyde. Even if the byproduct p-fluorobenzoic acid is purified by various means, it is difficult to meet the quality requirements of commodities. If it is disposed of as hazardous waste, it will not only consume a lot of costs, but also cause resource losses.

[0010] In order to solve the above technical problems, the present invention adopts the following technical solutions:

[0011] The invention provides a method for synthesizing p-fluorobenzoyl chloride from p-fluorobenzoic acid in two steps. The method uses p-fluorobenzoic acid and p-fluorobenzoyl chloride as starting materials, performs an acid hydrolysis reaction of the acyl chloride by using a catalyst to obtain intermediate p-fluorobenzoic anhydride and hydrogen chloride; and performs an acid anhydride acylation reaction of the intermediate p-fluorobenzoic anhydride and p-fluorobenzyl trichloride under the catalyst to obtain p-fluorobenzoyl chloride.

[0012] As a preferred embodiment of the present invention, the synthetic route of the method is:

[0013] Step 1:

[0014]

[0015] Step 2:

[0016]

[0017] As a preferred embodiment of the present invention, the method comprises the following steps:

[0018] 1) Adding p-fluorobenzoic acid and p-fluorobenzoyl chloride as starting materials into a reactor, adding an appropriate amount of catalyst into the reactor, and then heating to 105±5° C. to perform an acid hydrolysis reaction of the acyl chloride, and monitoring the reaction progress by gas chromatography. When p-fluorobenzoic acid in the material in the reactor is ≤1.0%, the reaction is stopped to obtain a post-reaction material I; in step 1), the hydrogen chloride generated during the reaction enters a hydrogen chloride absorber, and finally forms hydrochloric acid as a by-product after meeting water.

[0019] 2) Add p-fluorobenzyl chloride to the reaction material I obtained in step 1) and carry out anhydride acylation reaction at 105±5°C, and monitor the reaction progress by gas chromatography. When p-fluorobenzoic anhydride in the material in the reactor is ≤0.5%, the reaction is stopped to obtain the reaction material II;

[0020] 3) transferring the reaction material II obtained in step 2) into a transfer tank for natural anhydride acylation reaction to obtain anhydride acylation reaction material III;

[0021] 4) After the acylation reaction of the acid anhydride obtained in step 3), the material III is subjected to reduced pressure distillation, and the top fraction is collected to obtain the finished product of p-fluorobenzoyl chloride.

[0022] As a preferred embodiment of the present invention, in step 1), the weight of the catalyst is 0.03-0.04% of the p-fluorobenzoic acid as the starting material, and the reaction time in step 1) is 2-3 hours.

[0023] Most preferably, the weight of the catalyst is 0.035% of the p-fluorobenzoic acid as the starting material.

[0024] As a preferred embodiment of the present invention, in step 1), the mass ratio of p-fluorobenzoyl chloride to p-fluorobenzoic acid is 1:0.25-0.35.

[0025] As a preferred embodiment of the present invention, the catalysts in step 1) and step 2) are both anhydrous ferric chloride.

[0026] As a preferred embodiment of the present invention, in step 2), the molar ratio of p-fluorobenzyl chloride:p-fluorobenzoic acid is 1:1.0-1.02, and the reaction time of step 2) is 3-5h.

[0027] As a preferred embodiment of the present invention, the raw material p-fluorobenzoic acid in step 1) is a by-product of producing p-fluorobenzaldehyde, and its quality indicators are as follows: p-fluorobenzoic acid 95.22%, p-fluorobenzaldehyde 0.12%, p-fluorobenzyl trichloride 0.23%, water 0.18%, and the rest are sodium sulfate, sodium chloride and tar.

[0028] As a preferred embodiment of the present invention, in step 3), the temperature of the natural anhydride acylation reaction is room temperature, and the reaction time is 24 hours.

[0029] As a preferred embodiment of the present invention, in step 4), the pressure of the reduced pressure distillation is -0.090 MPa to -0.01 MPa, and the conditions for collecting the top fraction are a kettle temperature of 95-100°C and a tower top temperature of 80-82°C.

[0030] Compared with the prior art, the present invention has the following beneficial effects:

[0031] The method for synthesizing p-fluorobenzoyl chloride from p-fluorobenzoic acid in two steps of the present invention has the characteristics of ingenious and simple process design, high product yield and excellent quality, and can also significantly reduce the production cost of p-fluorobenzoyl chloride, and has good economic and social benefits. Therefore, the present invention adds a synthetic route that reduces raw material costs and is more concise to the synthesis of p-fluorobenzoyl chloride. The p-fluorobenzoyl chloride obtained by the present invention can be subsequently used for the synthesis of 4,4′-difluorobenzophenone in a conventional manner.

[0032] The method for synthesizing p-fluorobenzoyl chloride from p-fluorobenzoic acid in two steps has low raw material cost, few reaction steps, high product yield, and can realize circular economy without additional three wastes. The method uses by-product p-fluorobenzoic acid as a starting raw material, can significantly reduce production costs, and does not require the use of highly toxic chlorination reagents. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] The specific implementation modes of the present invention are further described in detail below with reference to the accompanying drawings.

[0034] Figure 1 It is a process flow chart of the present invention.

[0035] Figure 2 Example 1 Fluorobenzoyl chloride finished product spectrum.

[0036] Figure 3 Example 2 Fluorobenzoyl chloride finished product spectrum. DETAILED DESCRIPTION

[0037] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0038] The raw materials described in the present invention are:

[0039] Parafluorobenzoic acid is a by-product of the production of parafluorobenzaldehyde, consisting of 95.22% parafluorobenzoic acid, 0.12% parafluorobenzaldehyde, 0.23% parafluorobenzyl chloride, 0.18% water, and the rest being sodium sulfate, sodium chloride and tar.

[0040] 4-Fluorobenzyltrichloride, industrial grade (content 99.3%), commercially available.

[0041] p-Fluorobenzoyl chloride, technical grade (content 99.86%), commercially available.

[0042] Anhydrous ferric chloride, technical grade, commercially available.

[0043] Room temperature generally refers to 15-25℃.

[0044] See also Figure 1 The present invention provides a two-step method for synthesizing p-fluorobenzoyl chloride from p-fluorobenzoic acid. The method uses p-fluorobenzoic acid and p-fluorobenzoyl chloride as starting materials, performs an acid hydrolysis reaction of the acyl chloride by a catalyst to obtain intermediates p-fluorobenzoic anhydride and hydrogen chloride; and performs an acid anhydride acylation reaction of the intermediates p-fluorobenzoic anhydride and p-fluorobenzyl trichloride under a catalyst to obtain p-fluorobenzoyl chloride.

[0045] The synthetic route of the method is:

[0046] Step 1:

[0047]

[0048] Step 2:

[0049]

[0050] Example 1

[0051] This embodiment provides a method for synthesizing p-fluorobenzoyl chloride from p-fluorobenzoic acid in two steps, comprising the following steps:

[0052] 1) Add p-fluorobenzoic acid (300 Kg, content 95.22%, pure 2038.83 mol) and p-fluorobenzoyl chloride (1000 Kg, content 99.86%, pure 6297.94 mol) as starting materials into a reactor, and add 105 g of catalyst (anhydrous ferric chloride, equivalent to 0.035% of p-fluorobenzoic acid) into the reactor, then heat to 105±5° C., carry out acid hydrolysis of the acyl chloride, and monitor the reaction progress by gas chromatography. When p-fluorobenzoic acid in the material in the reactor is ≤1.0%, the reaction is stopped to obtain the reacted material I;

[0053] After the reaction, the content of p-fluorobenzoic acid in material Ⅰ was 0.28%.

[0054] The above % are all weight %;

[0055] p-Fluorobenzoyl chloride: p-Fluorobenzoic acid = 1:0.3;

[0056] The reaction time of step 1) is 2.5h.

[0057] Note: Step 1) The hydrogen chloride produced during the reaction enters the hydrogen chloride absorber and eventually forms hydrochloric acid as a by-product after meeting water.

[0058] 2) Add 365.5 kg (content 99.3%, pure 2038.83 mol) of p-fluorobenzyl trichloride (added all at once) to the reaction material I obtained in step 1), and carry out anhydride acylation reaction at 105±5°C, and monitor the reaction progress by gas chromatography. Stop the reaction when p-fluorobenzoic anhydride in the material in the reactor is ≤0.5%, and obtain the reaction material II;

[0059] After the reaction, the content of p-fluorobenzoyl chloride in material II is 99.01%, p-fluorobenzoic acid is 0.032%, p-fluorobenzyl chloride is 0.42%, p-fluorobenzoic anhydride is 0.39%, and the rest are impurities.

[0060] The reaction time is 4.5h.

[0061] p-Fluorobenzyl trichloride: p-Fluorobenzoic acid = 1:1.0 (molar ratio)

[0062] 3) Transfer the reaction material II obtained in step 2) into a transfer tank for natural anhydride acylation reaction (reaction temperature is room temperature, reaction time is 24h), and obtain the anhydride acylation reaction material III (content of p-fluorobenzoyl chloride 99.74%, p-fluorobenzyl trichloride 0.06%, anhydride 0.12%, and the rest are impurities);

[0063] 4) After the acylation reaction of the acid anhydride obtained in step 3), the material III is distilled under reduced pressure (pressure of about -0.095 MPa), and the top fraction is collected (kettle temperature 95-100°C, tower top temperature 80-82°C) to obtain 1640 kg of p-fluorobenzoyl chloride product, wherein the content of p-fluorobenzoyl chloride is 99.92%, p-fluorobenzoic anhydride is 0.083%, and the rest is impurities.

[0064] See also Figure 2 The analysis results obtained in Example 1 are shown in Table 1.

[0065] Table 1. Analysis results

[0066]

[0067] Example 2

[0068] This embodiment provides a method for synthesizing p-fluorobenzoyl chloride from p-fluorobenzoic acid in two steps, comprising the following steps:

[0069] 1) Add p-fluorobenzoic acid (300 Kg, content 95.22%, pure 2038.83 mol) and p-fluorobenzoyl chloride (1000 Kg, content 99.86%, pure 6297.94 mol) as starting materials into a reactor, and add 105 g of catalyst (anhydrous ferric chloride, equivalent to 0.035% of p-fluorobenzoic acid) into the reactor, then heat to 105±5° C., carry out acid hydrolysis of the acyl chloride, and monitor the reaction progress by gas chromatography. When p-fluorobenzoic acid in the material in the reactor is ≤1.0%, the reaction is stopped to obtain the reacted material I;

[0070] After the reaction, the content of p-fluorobenzoic acid in material Ⅰ is 0.32%.

[0071] The above % are all weight %;

[0072] p-Fluorobenzoyl chloride: p-Fluorobenzoic acid = 1:0.3;

[0073] The reaction time of step 1) is 2.5h.

[0074] Note: Step 1) The hydrogen chloride produced during the reaction enters the hydrogen chloride absorber and eventually forms hydrochloric acid as a by-product after meeting water.

[0075] 2) Add 373 kg (content 99.3%, pure 2079.60 mol) of p-fluorobenzyl trichloride (added all at once) to the reaction material I obtained in step 1), and carry out anhydride acylation reaction at 105±5°C, and monitor the reaction progress by gas chromatography. Stop the reaction when p-fluorobenzoic anhydride in the material in the reactor is ≤0.5%, and obtain the reaction material II;

[0076] After the reaction, the content of p-fluorobenzoyl chloride in material II is 98.78%, p-fluorobenzoic acid is 0.030%, p-fluorobenzyl chloride is 0.86%, p-fluorobenzoic anhydride is 0.34%, and the rest are impurities.

[0077] The reaction time is 4.5h.

[0078] p-Fluorobenzyl trichloride: p-Fluorobenzoic acid = 1:1.02 (molar ratio)

[0079] 3) Transfer the reaction material II obtained in step 2) into a transfer tank for natural anhydride acylation reaction (reaction temperature is room temperature, reaction time is 24h), and obtain the anhydride acylation reaction material III (content of p-fluorobenzoyl chloride 99.36%, p-fluorobenzyl trichloride 0.51%, anhydride 0.09%, and the rest are impurities);

[0080] 4) After the acylation reaction of the acid anhydride obtained in step 3), the material III is distilled under reduced pressure (pressure of about -0.095 MPa), and the top fraction is collected (kettle temperature 95-100°C, tower top temperature 80-82°C) to obtain 1642 kg of p-fluorobenzoyl chloride product, wherein the content of p-fluorobenzoyl chloride is 99.86%, p-fluorobenzyl chloride is 0.079%, p-fluorobenzoic anhydride is 0.061%, and the rest is impurities.

[0081] See also Figure 3 The analysis results obtained in Example 2 are shown in Table 2.

[0082] Table 2. Analysis results

[0083]

[0084] Comparative Example 1

[0085] The catalyst in step 1) and step 2) of Example 1 is eliminated, and the other steps are the same as those of Example 1.

[0086] 1) Adding p-fluorobenzoic acid (300 Kg, content 95.22%, pure 2038.83 mol) and p-fluorobenzoyl chloride (1000 Kg, content 99.86%, pure 6297.94 mol) as starting materials into a reactor, then heating to 105±5° C. to perform acid hydrolysis of the acyl chloride, and monitoring the reaction progress by gas chromatography. When p-fluorobenzoic acid in the reactor is ≤1.0%, the reaction is stopped to obtain the reacted material I;

[0087] The above % are all weight %;

[0088] p-Fluorobenzoyl chloride: p-Fluorobenzoic acid = 1:0.3;

[0089] Step 1) When the reaction time is 2.5 h, 5.0 h, 7.5 h and 10 h, the amount of p-fluorobenzoic acid in the reactor does not decrease, indicating that no reaction occurs without a catalyst.

[0090] Comparative Example 2

[0091] The catalyst in step 1) and step 2) of Example 1 was changed from ferric chloride to zinc chloride, and the other steps were the same as Example 1.

[0092] 1) Add p-fluorobenzoic acid (300 Kg, content 95.22%, pure 2038.83 mol) and p-fluorobenzoyl chloride (1000 Kg, content 99.86%, pure 6297.94 mol) as starting materials into a reactor, and add 105 g of catalyst (anhydrous zinc chloride, equivalent to 0.035% of p-fluorobenzoic acid) into the reactor, then heat to 105±5° C., carry out acid hydrolysis of the acyl chloride, and monitor the reaction progress by gas chromatography. Stop the reaction when p-fluorobenzoic acid in the reactor is ≤1.0%, and obtain the reacted material I;

[0093] The above % are all weight %;

[0094] p-Fluorobenzoyl chloride: p-Fluorobenzoic acid = 1:0.3;

[0095] Step 1) When the reaction time is 2.5 h, 5.0 h, 7.5 h and 10 h, the content of p-fluorobenzoic acid in the reactor exceeds 5%, indicating that the activity of zinc chloride as a catalyst is insufficient and cannot meet the design requirements.

[0096] After 10 hours of reaction, the content of p-fluorobenzoic acid in the reaction material I was 5.47%.

[0097] Note: Step 1) The hydrogen chloride produced during the reaction enters the hydrogen chloride absorber and eventually forms hydrochloric acid as a by-product after meeting water.

[0098] 2) Add 365.5 kg (content 99.3%, pure 2038.83 mol) of p-fluorobenzyl trichloride (added all at once) to the reaction material I obtained in step 1), and carry out anhydride acylation reaction at 105±5°C, and monitor the reaction progress by gas chromatography. Stop the reaction when p-fluorobenzoic anhydride in the material in the reactor is ≤0.5%, and obtain the reaction material II;

[0099] After the reaction, the content of p-fluorobenzoyl chloride in material II is 82.49%, p-fluorobenzoic acid is 4.65%, p-fluorobenzyl trichloride is 5.62%, p-fluorobenzoic anhydride is 2.84%, and the rest are impurities.

[0100] The reaction time is 72h.

[0101] p-Fluorobenzyl trichloride: p-Fluorobenzoic acid = 1:1.0 (molar ratio)

[0102] 3) Transfer the reaction material II obtained in step 2) into a transfer tank for natural anhydride acylation reaction (reaction temperature is room temperature, reaction time is 24h), and obtain the anhydride acylation reaction material III (content of p-fluorobenzoyl chloride 83.76%, p-fluorobenzyl trichloride 5.12%, anhydride 0.89%, and the rest are impurities);

[0103] 4) After the acylation reaction of the acid anhydride obtained in step 3), the material III is distilled under reduced pressure (pressure of about -0.095 MPa), and the top fraction is collected (kettle temperature 95-100°C, tower top temperature 80-82°C) to obtain 1467 kg of p-fluorobenzoyl chloride product, wherein the content of p-fluorobenzoyl chloride is 96.42%, p-fluorobenzyl chloride is 0.38%, p-fluorobenzoic anhydride is 0.54%, p-fluorobenzoic acid is 0.87%, and the rest is impurities.

[0104] This indicates that zinc chloride as a catalyst does not meet the design requirements.

[0105] Comparative Example 3

[0106] The ratio of p-fluorobenzoyl chloride to p-fluorobenzoic acid in step 1) of Example 1 was increased from 1:0.3 to 1:0.5, and the other steps were the same as those of Example 1.

[0107] 1) Add p-fluorobenzoic acid (500 Kg, content 95.22%, pure 3398.04 mol) and p-fluorobenzoyl chloride (1000 Kg, content 99.86%, pure 6297.94 mol) as starting materials into a reactor, and add 175 g of catalyst (anhydrous ferric chloride, equivalent to 0.035% of p-fluorobenzoic acid) into the reactor, then heat to 105±5° C., carry out acid hydrolysis of the acyl chloride, and monitor the reaction progress by gas chromatography. When p-fluorobenzoic acid in the material in the reactor is ≤1.0%, the reaction is stopped to obtain the reacted material I;

[0108] The above % are all weight %;

[0109] p-Fluorobenzoyl chloride: p-Fluorobenzoic acid = 1:0.5;

[0110] Step 1) When the reaction time is 2.5h, 5.0h and 10h, the p-fluorobenzoic acid in the material I after the reaction is higher than 6%, and is 6.84% when the reaction time is 10h.

[0111] Note: Step 1) The hydrogen chloride produced during the reaction enters the hydrogen chloride absorber and eventually forms hydrochloric acid as a by-product after meeting water.

[0112] This indicates that the ratio of p-fluorobenzoyl chloride to p-fluorobenzoic acid is too high (1:0.5), and the acidolysis reaction of the acyl chloride cannot be completed in an equimolar manner (the conversion rate is low), which affects the subsequent process.

[0113] Comparative Example 4

[0114] Step 3) of Example 1 is cancelled, and the other steps are the same as those of Example 1.

[0115] 1) Add p-fluorobenzoic acid (300 Kg, content 95.22%, pure 2038.83 mol) and p-fluorobenzoyl chloride (1000 Kg, content 99.86%, pure 6297.94 mol) as starting materials into a reactor, and add 105 g of catalyst (anhydrous ferric chloride, equivalent to 0.035% of p-fluorobenzoic acid) into the reactor, then heat to 105±5° C., carry out acid hydrolysis of the acyl chloride, and monitor the reaction progress by gas chromatography. When p-fluorobenzoic acid in the material in the reactor is ≤1.0%, the reaction is stopped to obtain the reacted material I;

[0116] After the reaction, the content of p-fluorobenzoic acid in material Ⅰ was 0.28%.

[0117] The above % are all weight %;

[0118] p-Fluorobenzoyl chloride: p-Fluorobenzoic acid = 1:0.3;

[0119] The reaction time of step 1) is 2.5h.

[0120] Note: Step 1) The hydrogen chloride produced during the reaction enters the hydrogen chloride absorber and eventually forms hydrochloric acid as a by-product after meeting water.

[0121] 2) Add 365.5 kg (content 99.3%, pure 2038.83 mol) of p-fluorobenzyl trichloride (added all at once) to the reaction material I obtained in step 1), and carry out anhydride acylation reaction at 105±5°C, and monitor the reaction progress by gas chromatography. Stop the reaction when p-fluorobenzoic anhydride in the material in the reactor is ≤0.5%, and obtain the reaction material II;

[0122] After the reaction, the content of p-fluorobenzoyl chloride in material II is 99.01%, p-fluorobenzoic acid is 0.032%, p-fluorobenzyl chloride is 0.42%, p-fluorobenzoic anhydride is 0.39%, and the rest are impurities.

[0123] The reaction time is 4.5h.

[0124] p-Fluorobenzyl trichloride: p-Fluorobenzoic acid = 1:1.0 (molar ratio).

[0125] 3) The reaction material II obtained in step 2) was distilled under reduced pressure (pressure of about -0.095 MPa), and the top fraction was collected (kettle temperature 95-100°C, tower top temperature 80-82°C), and 1632 kg of p-fluorobenzoyl chloride was obtained, wherein the p-fluorobenzoyl chloride content was 99.14%, p-fluorobenzyl chloride 0.16%, p-fluorobenzoic anhydride 0.38%, p-fluorobenzoic acid 0.16%, and the rest were impurities. It is explained that the natural anhydride acylation reaction (reaction temperature is room temperature, reaction time is 24h) process of step 3) of Example 1 is eliminated, and the quality of p-fluorobenzoyl chloride obtained by direct distillation does not meet the specified requirements (p-fluorobenzoyl chloride content is greater than 99.5%, p-fluorobenzyl chloride is less than 0.1%, p-fluorobenzoic anhydride is less than 0.2%, and p-fluorobenzoic acid is 0.10%).

[0126] Comparative Example 5

[0127] The p-fluorobenzoyl chloride in step 1) of Example 1 was eliminated, and the process directly proceeded to step 2). The other steps were the same as those in Example 1.

[0128] 1) Add 300 kg of p-fluorobenzoic acid (95.22% content, 2038.83 mol pure) as starting materials, 1500 g of catalyst (anhydrous ferric chloride, equivalent to 0.5% of p-fluorobenzoic acid), and 365.5 kg (99.3% content, 2038.83 mol pure) p-fluorobenzyl chloride (all at once), and react at 105±5°C, and monitor the reaction progress by gas chromatography

[0129] When the content of p-fluorobenzoic acid in the reactor reaches 1.0%, the reaction is stopped to obtain the reacted material Ⅰ;

[0130] During the reaction, the material is in a paste-like state and is difficult to stir.

[0131] The reaction time is 10h.

[0132] p-Fluorobenzyl trichloride: p-Fluorobenzoic acid = 1:1.0 (molar ratio)

[0133] After the reaction, the content of p-fluorobenzoyl chloride in material I is 78.16%, p-fluorobenzoic acid is 9.16%, p-fluorobenzyl trichloride is 9.43%, p-fluorobenzoic anhydride is 3.56%, and the rest are impurities.

[0134] 2) After the reaction in step 1), the material I is distilled under reduced pressure (pressure of about -0.095 MPa), and the top fraction is collected (kettle temperature 95-100°C, tower top temperature 80-82°C) to obtain 423 kg of p-fluorobenzoyl chloride product, wherein the content of p-fluorobenzoyl chloride is 95.63%, p-fluorobenzyl chloride is 0.79%, p-fluorobenzoic anhydride is 2.87%, p-fluorobenzoic acid is 1.22%, and the rest are impurities.

[0135] From the data of Comparative Example 5, it can be seen that not only the product quality does not meet the requirements, but also the product yield is also on the low side.

[0136] 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 there are many variations. All variations that can be directly derived or associated with the content disclosed by a person skilled in the art should be considered as the protection scope of the present invention.

[0137] The above is only a preferred embodiment of the present invention, and is not any formal or substantial limitation of the present invention. It should be pointed out that ordinary technicians in this technical field can make several improvements and supplements without departing from the method of the present invention, and these improvements and supplements should also be regarded as the protection scope of the present invention. Any technician familiar with this profession, without departing from the spirit and scope of the present invention, can make some changes, modifications and evolutions of the technical content disclosed above, which are equivalent embodiments of the present invention; at the same time, any changes, modifications and evolutions of any equivalent changes made to the above embodiments based on the essential technology of the present invention are still within the scope of the technical solution of the present invention.

Claims

1. A two-step method for synthesizing p-fluorobenzoyl chloride from p-fluorobenzoic acid, characterized in that: The method comprises the following steps: 1) Adding p-fluorobenzoic acid and p-fluorobenzoyl chloride as starting materials into a reactor, and adding an appropriate amount of catalyst into the reactor, then heating to 105±5°C, performing an acid hydrolysis reaction of the acyl chloride, and monitoring the reaction progress by gas chromatography, and stopping the reaction when p-fluorobenzoic acid in the material in the reactor is ≤1.0%, to obtain a post-reaction material I; the weight of the catalyst is 0.03-0.04% of the p-fluorobenzoic acid as the starting material, and the reaction time is 2-3h; the mass ratio of p-fluorobenzoyl chloride: p-fluorobenzoic acid is 1:0.25-0.35; 2) Add p-fluorobenzyl chloride to the reaction material I obtained in step 1) and carry out anhydride acylation reaction at 105±5°C, and monitor the reaction progress by gas chromatography. When p-fluorobenzoic anhydride in the material in the reactor is ≤0.5%, the reaction is stopped to obtain the reaction material II; 3) Transfer the reaction material II obtained in step 2) into a transfer tank for natural anhydride acylation reaction to obtain anhydride acylation reaction material III; the temperature of the natural anhydride acylation reaction is room temperature, and the reaction time is 24h; 4) After the acylation reaction of the acid anhydride obtained in step 3), the material III is subjected to reduced pressure distillation, and the top fraction is collected to obtain the finished product of p-fluorobenzoyl chloride; Wherein, the catalysts described in step 1) and step 2) are both anhydrous ferric chloride.

2. The method for synthesizing p-fluorobenzoyl chloride from p-fluorobenzoic acid in two steps according to claim 1, characterized in that: The synthetic route of the method is: Step 1: Step 2:

3. The method for synthesizing p-fluorobenzoyl chloride from p-fluorobenzoic acid in two steps according to claim 1, characterized in that: In step 2), the molar ratio of p-fluorobenzyl chloride to p-fluorobenzoic acid is 1:1.0-1.02, and the reaction time of step 2) is 3-5h.

4. The method for synthesizing p-fluorobenzoyl chloride from p-fluorobenzoic acid in two steps according to claim 1, characterized in that: The raw material p-fluorobenzoic acid in step 1) is a byproduct of producing p-fluorobenzaldehyde, and its quality indexes are as follows: p-fluorobenzoic acid 95.22%, p-fluorobenzaldehyde 0.12%, p-fluorobenzyl chloride 0.23%, water 0.18%, and the rest are sodium sulfate, sodium chloride and tar.

5. The method for synthesizing p-fluorobenzoyl chloride from p-fluorobenzoic acid in two steps according to claim 1, characterized in that: In step 4), the pressure of the reduced pressure distillation is -0.090 MPa to -0.01 MPa, and the conditions for collecting the top fraction are a kettle temperature of 95-100°C and a tower top temperature of 80-82°C.

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