Method for preparing p-aminobenzoyl chloride hydrochloride

Abstract

The invention provides a method for preparing p-aminobenzoyl chloride hydrochloride, which comprises the following steps: (1) mixing p-aminobenzoic acid, thionyl chloride and a weak polar solvent to form a reaction mixture, and reacting at a reaction pressure greater than one standard atmospheric pressure to obtain a product mixture containing p-aminobenzoyl chloride hydrochloride; and (2) carrying out post-treatment on the product mixture to obtain a p-aminobenzoyl chloride hydrochloride product.

Description

Technical Field

[0001] The present application relates to the field of organic chemistry, and in particular to a method for preparing p-aminobenzoyl chloride hydrochloride. Background Art

[0002] Poly(p-aminobenzoyl)amide (PBA) is an aromatic polyamide with high strength, high modulus and low density. It is widely used in the reinforcement of thermoplastics and thermosetting plastics. It is an efficient reinforcing agent for cutting-edge composite materials. p-Aminobenzoyl chloride hydrochloride is the key monomer for the synthesis of PBA.

[0003] At present, the preparation technology of p-aminobenzoyl chloride hydrochloride mainly comes from the patent disclosed by Monsanto and Dow Dupont in the 1960s and 1970s, such as US3225011A, GB1242200A etc., these early methods mainly use sulfolane as solvent under normal pressure, pass into and introduce excessive hydrogen chloride gas to make p-aminobenzoic acid salify, avoid p-aminobenzoyl chloride self-polymerization, p-aminobenzoyl chloride hydrochloride reacts with thionyl chloride to obtain p-aminobenzoyl chloride hydrochloride. In addition, because sulfolane and thionyl chloride of strong polarity have good solubility to product, after reaction ends, a large amount of poor solvents must be added in reaction system to make product precipitate. Nevertheless, part of the product is still dissolved in the reaction system, resulting in a lower p-aminobenzoyl chloride hydrochloride yield, and the energy consumption of solvent separation and recovery is high, which increases the generation of "three wastes". In addition, the excessive use of hydrogen chloride and its escape have caused the generation of a large amount of acidic waste gas, which constitutes a potential threat to the environment.

[0004] In the face of the growing market demand for p-aminobenzoyl chloride hydrochloride, the limitations of existing processes are becoming more and more significant. Therefore, it is urgent to develop a more efficient, economical and environmentally friendly preparation method. In order to solve this problem, the present invention proposes a preparation method for preparing p-aminobenzoyl chloride hydrochloride using a weak polar solvent and pressurized reaction conditions. In the reaction system of the present invention, p-aminobenzoic acid does not need to be salified in advance, but directly undergoes chlorination reaction. Under pressurized conditions, the byproduct hydrogen chloride remains in the reaction system and salifies with the amino group to obtain a product, thereby reducing the consumption of hydrogen chloride. After the reaction is completed, thionyl chloride in the reaction system is distilled and removed. Since p-aminobenzoyl chloride hydrochloride has poor solubility in weak polar solvents, p-aminobenzoyl chloride hydrochloride is precipitated from the reaction system. The method eliminates the step of salifying p-aminobenzoic acid alone and simplifies the operating process. In addition, the product is precipitated by removing thionyl chloride, reducing or completely avoiding the use of a large number of poor solvents, thereby significantly reducing the consumption of solvents, simplifying the steps of subsequent separation and recovery, and greatly reducing the complexity of production costs and environmental protection treatment.

[0005] The invention provides a method for preparing p-aminobenzoyl chloride hydrochloride by using a weakly polar solvent and a pressurized reaction system, which simplifies the operation process, reduces material consumption and energy consumption, and has the advantages of low cost, simple process, high product quality and yield, and being green and environmentally friendly. Summary of the invention

[0006] The present application provides a method for preparing p-aminobenzoyl chloride hydrochloride, comprising the following steps:

[0007] (1) mixing p-aminobenzoic acid, thionyl chloride and a weakly polar solvent to form a reaction mixture, and reacting at a reaction pressure greater than one standard atmospheric pressure to obtain a product mixture containing p-aminobenzoyl chloride hydrochloride;

[0008] (2) post-treating the product mixture to obtain p-aminobenzoyl chloride hydrochloride product.

[0009] The method for preparing p-aminobenzoyl chloride hydrochloride provided by the present invention utilizes pressurized (i.e., greater than 1 standard atmospheric pressure) reaction conditions, and p-aminobenzoic acid can directly undergo chlorination reaction without prior salt formation, and has low oligomer content, thereby simplifying the operation process; at the same time, hydrogen chloride generated during the chlorination reaction forms a salt with the amino group in the p-aminobenzoic acid, thereby realizing the reuse of hydrogen chloride and reducing energy consumption.

[0010] The method for preparing p-aminobenzoyl chloride hydrochloride provided by the present invention utilizes a weakly polar solvent reaction system, does not need to add a large amount of poor solvent to precipitate the product from the reaction system, does not need a large amount of solvent separation and recovery in the subsequent process, and is stable, efficient, economical and environmentally friendly. DETAILED DESCRIPTION

[0011] "Scope" disclosed herein is defined in the form of lower limit and upper limit, and a given range is defined by selecting a lower limit and an upper limit, and the selected lower limit and upper limit define the boundary of a particular range. The scope defined in this way can be including end values ​​or not including end values, and can be arbitrarily combined, that is, any lower limit can be combined with any upper limit to form a scope. For example, if the scope of 60-120 and 80-110 is listed for a particular parameter, it is understood that the scope of 60-110 and 80-120 is also expected. In addition, if the minimum range values ​​1 and 2 are listed, and if the maximum range values ​​3, 4 and 5 are listed, the following scope can all be expected: 1-3, 1-4, 1-5, 2-3, 2-4 and 2-5. In this application, unless otherwise specified, the numerical range "ab" represents the abbreviation of any real number combination between a and b, wherein a and b are real numbers. For example, the numerical range "0-5" means that all real numbers between "0-5" are listed in this document, and "0-5" is just an abbreviation of these numerical combinations. In addition, when a parameter is expressed as an integer ≥ 2, it is equivalent to disclosing that the parameter is, for example, an integer of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, etc.

[0012] In this application, unless otherwise specified, all embodiments and preferred embodiments mentioned herein can be combined with each other to form a new technical solution.

[0013] In this application, unless otherwise specified, all technical features and preferred features mentioned herein can be combined with each other to form a new technical solution.

[0014] In the present application, unless otherwise specified, all steps mentioned herein may be performed sequentially or randomly, but are preferably performed sequentially. For example, the method includes steps (a) and (b), which means that the method may include steps (a) and (b) performed sequentially, or may include steps (b) and (a) performed sequentially. For example, the method may further include step (c), which means that step (c) may be added to the method in any order, for example, the method may include steps (a), (b) and (c), or may include steps (a), (c) and (b), or may include steps (c), (a) and (b), etc.

[0015] In this application, unless otherwise specified, the terms "include" and "comprising" mentioned herein may be open-ended or closed-ended. For example, the terms "include" and "comprising" may mean that other components not listed may also be included or only the listed components may be included or only the listed components may be included.

[0016] In the description of this article, it should be noted that, unless otherwise specified, "above" and "below" are inclusive of the number itself, and "several" in "one or several" means two or more.

[0017] In the description herein, unless otherwise specified, the term "or" is inclusive. For example, the phrase "A or B" means "A, B, or both A and B". More specifically, any of the following conditions satisfies the condition "A or B": A is true (or exists) and B is false (or does not exist); A is false (or does not exist) and B is true (or exists); or both A and B are true (or exist).

[0018] Herein, unless otherwise specified, percentage (%) or part refers to percentage by weight or part by weight relative to the composition.

[0019] Herein, if there is no contrary description, the sum of the contents of the various components in the composition is 100%.

[0020] Herein, if there is no contrary description, the sum of the parts of each component in the composition may be 100 parts by weight.

[0021] In this document, unless otherwise specified, "a combination thereof" means a multi-component mixture of the elements described, for example a mixture of two, three, four and up to the maximum possible multi-component mixture.

[0022] If not specifically stated, the terms "a" or "an" used in the present specification means "at least one".

[0023] The present application provides a method for preparing p-aminobenzoyl chloride hydrochloride, comprising the following steps:

[0024] (1) mixing p-aminobenzoic acid, thionyl chloride and a weakly polar solvent to form a reaction mixture, and reacting at a reaction pressure greater than one standard atmospheric pressure to obtain a product mixture containing p-aminobenzoyl chloride hydrochloride;

[0025] (2) post-treating the product mixture to obtain p-aminobenzoyl chloride hydrochloride product.

[0026] Solvents

[0027] In the traditional method, p-aminobenzoic acid is first dissolved in a solvent, hydrogen chloride gas is passed through, p-aminobenzoic acid and hydrogen chloride are reacted, and p-aminobenzoic acid hydrochloride is prepared. Then, chlorination reaction is carried out by an acyl chloride reagent to obtain p-aminobenzoyl chloride hydrochloride. From the perspective of faster reaction rate and / or higher yield, traditionally preferred solvents are polar solvents, such as cyclopentane, ethylene glycol dimethyl ether, tetraethylene glycol dimethyl ether, diethylene glycol dimethyl ether and hexamethylphosphoramide. Weakly polar solvents such as benzene are generally considered to be inapplicable because their solubility for p-aminobenzoic acid hydrochloride is too low. In the traditional method, after the chlorination reaction is completed, a large amount of poor solvents need to be added to the reaction system, so that p-aminobenzoyl chloride hydrochloride is precipitated therefrom. Here, poor solvents can refer to reagents that can dilute the reaction system, reduce the solubility of the target product in the reaction system, and thus precipitate the target product from the reaction system.

[0028] In the present invention, contrary to the previous technical teaching, a weak polar solvent is used. The method of the present invention avoids the use of undesirable reagents and reduces costs.

[0029] Preferably, the weakly polar solvent of the present invention is selected from aromatic solvents.

[0030] Preferably, the weak polar solvent of the present invention is selected from one or more of toluene, chlorobenzene, dichlorobenzene, trichlorobenzene, p-xylene, o-xylene, m-xylene, benzene and nitrobenzene.

[0031] Reactants

[0032] Acylation refers to the process of reacting an acyl-containing substance (such as a carboxyl group or anhydride) with an active chlorine-containing reagent to produce an acyl chloride substance. In other words, acylation is a chemical reaction in which an acyl substance reacts with an active chlorine reagent to produce an acyl chloride compound.

[0033] In the present invention, the acyl-containing substance is p-aminobenzoic acid, also known as 4-aminobenzoic acid, which is an organic compound with a chemical formula of C7H7NO2.

[0034] In the present invention, the reagent containing active chlorine is thionyl chloride, also known as dithionyl chloride or thionyl chloride, which is an inorganic compound with a chemical formula of SOCl2. Alternatively, the reagent containing active chlorine may also be phosphorus pentachloride or phosphorus oxychloride.

[0035] For example, the molar ratio of thionyl chloride to p-aminobenzoic acid in the reaction mixture is 2: 1 to 20: 1, or 3: 1 to 12: 1, or 3.5: 1 to 8: 1. For example, in step (1), the concentration of p-aminobenzoic acid in the reaction mixture is 5 to 30% by weight.

[0036] In the present invention, other compounds may be added optionally, i.e., the present invention does not exclude the addition of other chemical substances. Additional chemical reagents may be added before, during or after the reaction. Additional chemical reagents may be, for example, additives, catalysts, adjuvants, diluents, etc. suitable for the present invention, or additional hydrogen chloride. For example, additional hydrogen chloride may be added after the reaction is completed to further improve the yield of p-aminobenzoyl chloride hydrochloride.

[0037] Reaction conditions

[0038] The reaction process of carboxylic acid and thionyl chloride to form acyl chloride compounds can be expressed by the following equation:

[0039] RCOOH+SOCl2→RCOCl+HCl+SO2

[0040] In the present invention, the byproduct hydrogen chloride of the chlorination reaction reacts with p-aminobenzoyl chloride to generate p-aminobenzoyl chloride hydrochloride. Since hydrogen chloride is a gas, the reaction pressure is one of the important factors in the reaction conditions of the present invention.

[0041] The reaction of the present invention is carried out under a reaction pressure greater than a standard pressure, preferably, the reaction pressure is 0.11-1 MPa, or 0.12-0.8 MPa, or 0.13-0.6 MPa, or 0.14-0.4 MPa, or 0.15-0.2 MPa. For example, the reaction of the present invention is carried out in an autoclave.

[0042] Preferably, the reaction is carried out in an atmosphere of a non-reactive gas, preferably in an atmosphere selected from nitrogen, argon or helium. In this context, "non-reactive gas" refers to a gas that does not participate in the reaction of the present invention.

[0043] Preferably, the reaction temperature is 60 to 140° C., or 70 to 120° C., or 80 to 100° C.; and the reaction time is 6 to 30 hours.

[0044] Preferably, the method of the present invention comprises fully stirring the reaction mixture before the reaction so that p-aminobenzoic acid and thionyl chloride are fully dispersed in the solvent.

[0045] Preferably, the method of the present invention further comprises continuous stirring during the reaction process to make the reaction mixture uniformly distributed. For example, the reaction can be carried out in an autoclave with a top-entry stirrer.

[0046] Preferably, the method of the present invention further comprises cooling to room temperature and maintaining it for a period of time after the reaction is completed. Preferably, the room temperature maintenance time is 1 to 3 hours.

[0047] Post-processing of products

[0048] The product mixture obtained after the reaction is completed may include: target product p-aminobenzoyl chloride hydrochloride, weak polar solvent, unreacted p-aminobenzoic acid and thionyl chloride, dissolved hydrogen chloride and sulfur dioxide, etc. Among them, in most cases, thionyl chloride is excessive. Since p-aminobenzoyl chloride hydrochloride has a high solubility in thionyl chloride. Therefore, advantageously, thionyl chloride is removed from the product mixture by distillation after the reaction is completed, thereby facilitating the precipitation of p-aminobenzoyl chloride hydrochloride. The distillation can be a vacuum distillation, for example, the reaction solution is transferred to a glass four-necked bottle for vacuum distillation, the vacuum degree is -0.04 to -0.09Mpa, and the distillation temperature is controlled within the reaction temperature.

[0049] After distillation, the temperature is lowered and the mixture is allowed to stand to precipitate the p-aminobenzoyl chloride hydrochloride product. Preferably, the standing temperature is 0 to 10° C. Preferably, the standing time is 1 to 3 hours.

[0050] Preferably, the method of the present invention further comprises washing and drying the precipitated p-aminobenzoyl chloride hydrochloride product, for example, washing with a low boiling point solvent (for example, dichloromethane solvent), and the washing times may be once, twice, three times or more than three times.

[0051] Example

[0052] The present invention will be further described below in conjunction with specific embodiments.

[0053] In the examples, the sources and specifications of the raw materials are summarized in Table 1, and the experimental instruments used are summarized in Table 2.

[0054] Table 1 Experimental materials

[0055]

[0056] Table 2 Experimental instruments

[0057]

[0058] The determination and calculation methods of the reaction conversion rate and selectivity and the purity and yield of the solid in the embodiments and comparative examples are as follows:

[0059] After the reaction is completed, the reaction solution is sampled, and the combined total amount of p-aminobenzoyl chloride and p-aminobenzoyl chloride hydrochloride in the sample is expressed as the amount of methyl p-aminobenzoate by a methanol derivatization reagent. The p-aminobenzoic acid content and the methyl p-aminobenzoate content (which reflects the amount of p-aminobenzoyl chloride generated by the chlorination reaction) in the reaction solution are analyzed by high performance liquid chromatography. The conversion rate of p-aminobenzoic acid and the selectivity of p-aminobenzoyl chloride in the chlorination reaction are calculated accordingly.

[0060] The obtained white solid is sampled, and the content of p-aminobenzoyl chloride hydrochloride in the solid product is analyzed by high performance liquid chromatography, and then the purity and yield of p-aminobenzoyl chloride hydrochloride in the final product are calculated. The p-aminobenzoyl chloride hydrochloride yield is calculated based on the amount of p-aminobenzoyl chloride hydrochloride in the white solid relative to the initial charge amount of p-aminobenzoic acid.

[0061] Example 1

[0062] (1) 1.05 mol of p-aminobenzoic acid, 5.54 mol of toluene and 4.2 mol of thionyl chloride were mixed and added to an autoclave after nitrogen substitution, and p-aminobenzoic acid was fully dispersed in the solvent by stirring. The temperature was raised to 80° C. to react p-aminobenzoic acid with thionyl chloride. The reaction pressure was 0.15 MPa and the reaction time was 15 hours. After the reaction was completed, the temperature was lowered to room temperature and kept for 2 hours, and then nitrogen substitution was performed. Samples were taken to detect the composition content in the reaction solution, and the conversion rate of p-aminobenzoic acid and the selectivity of p-aminobenzoyl chloride were calculated;

[0063] (2) The reaction solution was transferred to a glass four-necked bottle and the thionyl chloride was separated by vacuum distillation, the vacuum degree was -0.07 MPa, the kettle temperature was 70°C, and the gas phase temperature was 60°C, until the thionyl chloride in the reaction solution was completely removed, and then the temperature was lowered to 10°C and allowed to stand for 3 hours. The product was precipitated in the reaction solution, filtered and the filter cake was washed three times with 90g of dichloromethane solvent each time, and then dried at 30°C for 2 hours under a pressure of 1 kPa until the product had a constant weight. A white solid was obtained, and the white solid was analyzed for product purity by liquid chromatography, and the yield of p-aminobenzoyl chloride hydrochloride was calculated.

[0064] Comparative Example 1

[0065] According to the results of the embodiment in patent US3681450A, 1.14 mol of p-aminobenzoic acid and 9.16 mol of cyclopentane are mixed, stirred continuously and heated to 70°C until the p-aminobenzoic acid is completely dissolved, then cooled to 50°C, 1.37 mol of HCl is introduced under stirring, solid precipitates, the reaction solution is cooled to 25°C, 7.98 mol of thionyl chloride is added, and the reaction is kept at 20°C to 25°C for 4h. After the reaction is completed, 25.88 mol of anhydrous dichloromethane (a small amount of thionyl chloride (0.1 to 2%) is added for dehydration) and cooled to 5°C, filtered under anhydrous conditions and washed with a large amount of anhydrous dichloromethane, and then the solid product is dried with a dry nitrogen gas stream at room temperature. The yield of the dried solid product is 0.97 mol, that is, the yield of p-aminobenzoyl chloride hydrochloride is 86%.

[0066] Solvents

[0067] Based on Example 1, further Examples 2-4 and Comparative Examples 2-3 were used to compare the results of using different solvents. Except for the different solvents, the other conditions of Examples 2-4 and Comparative Example 2 were the same as those of Example 1. Comparative Example 3 did not remove thionyl chloride by distillation, but directly cooled and filtered, and the other conditions were the same as those of Example 1.

[0068] The results are summarized in Table 3 below:

[0069] Table 3

[0070]

[0071]

[0072] As can be seen from the above table, if sulfolane (polar solvent) is used, the selectivity of generating p-aminobenzoyl chloride will be reduced. Without being limited to theory, it is believed that the weakly polar solvent of the present invention can suppress the self-polymerization of p-aminobenzoic acid to a certain extent. In addition, the use of sulfolane significantly reduces the product yield, because the solubility of the product in sulfolane is relatively large, and therefore it is difficult to separate out.

[0073] It can also be seen from the above table that if the unreacted thionyl chloride is not distilled to remove, a large amount of p-aminobenzoyl chloride hydrochloride will remain in the reaction solution, which will have a significant impact on the final yield of the product.

[0074] Reaction pressure

[0075] Based on Example 1, the results produced by using different reaction pressures were compared through further Examples 5-7 and Comparative Example 4. Except for the different reaction pressures, other conditions of Examples 5-7 and Comparative Example 4 were the same as those of Example 1.

[0076] The results are summarized in Table 4 below:

[0077] Table 4

[0078]

[0079] As can be seen from the table above, the pressure between 0.15 and 0.2 MPa can effectively improve the product yield. The pressure above 0.2 has no obvious effect on the product yield, but will increase the equipment cost. Under normal pressure, due to the escape of HCl, it is difficult to form a salt with p-aminobenzoyl chloride in the system, resulting in a low product yield.

[0080] Reaction temperature

[0081] Based on Example 1, further Examples 8-9 were conducted to compare the results of using different reaction temperatures. Except for the different reaction temperatures, other conditions of Examples 8-9 were the same as those of Example 1.

[0082] The results are summarized in Table 5 below:

[0083] Table 5

[0084]

[0085] Increasing the reaction temperature slightly decreases the reaction selectivity because p-aminobenzoyl chloride hydrochloride easily forms polymers under high temperature conditions. Therefore, it is better to control the reaction temperature between 80 and 100°C.

[0086] Mole ratio of reactants

[0087] Based on Example 1, further Examples 10-13 were used to compare the results produced by using different reactant molar ratios. Except for the different reactant molar ratios, the other conditions of Examples 10-13 were the same as those of Example 1. The reactant molar ratio refers to the molar ratio of thionyl chloride to p-aminobenzoic acid in the reaction mixture.

[0088] The results are summarized in Table 6 below:

[0089] Table 6

[0090]

[0091]

[0092] As can be seen from the table above, when the reaction molar ratio increases to 8:1, the reaction rate can be increased and the reaction time can be shortened. When the reaction molar ratio continues to increase to 12:1, the reaction rate does not change significantly. In addition, increasing the reaction molar ratio has no significant effect on product purity and yield.

[0093] The above description is only a specific implementation mode of the present invention, but the protection scope of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily thought of by those skilled in the art within the technical scope disclosed by the present invention are within the protection scope and disclosure scope of the present invention.

Claims

1. A method for preparing p-aminobenzoyl chloride hydrochloride, comprising the following steps: (1) mixing p-aminobenzoic acid, thionyl chloride and a weakly polar solvent to form a reaction mixture, and reacting at a reaction pressure greater than one standard atmospheric pressure to obtain a product mixture containing p-aminobenzoyl chloride hydrochloride; (2) post-treating the product mixture to obtain p-aminobenzoyl chloride hydrochloride product.

2. The method of claim 1, wherein the weakly polar solvent is selected from aromatic solvents; Preferably, the weak polar solvent is selected from one or more of toluene, chlorobenzene, dichlorobenzene, trichlorobenzene, p-xylene, o-xylene, m-xylene, benzene and nitrobenzene.

3. The method according to any one of the preceding claims, wherein the reaction pressure is 0.11 to 1 MPa, or 0.12 to 0.8 MPa, or 0.13 to 0.6 MPa, or 0.14 to 0.4 MPa, or 0.15 to 0.2 MPa; For example, the reaction in step (1) is carried out in an autoclave.

4. The method according to any one of the preceding claims, wherein in step (2): The post-treatment comprises distilling the product mixture to remove thionyl chloride, cooling and standing to precipitate the p-aminobenzoyl chloride hydrochloride product. Preferably, the distillation is a reduced pressure distillation, and preferably, the vacuum degree of the reduced pressure distillation is -0.04 to -0.09 Mpa; Preferably, the standing temperature is 0 to 10°C; Preferably, the standing time is 1 to 3 hours.

5. A method as claimed in any one of the preceding claims, wherein: In the reaction of step (1), The reaction temperature is 60-140°C, or 70-120°C, or 80-100°C; The reaction time is 6 to 30 hours.

6. The method according to any one of the preceding claims, comprising stirring the reaction mixture thoroughly before the reaction in step (1); Optionally, the method further comprises continuous stirring during the reaction process of step (1) to make the reaction mixture uniformly distributed; for example, the reaction in step (1) is carried out in an autoclave equipped with a stirrer.

7. A method as claimed in any one of the preceding claims, wherein: In step (1), the concentration of p-aminobenzoic acid in the reaction mixture is 5 to 30% by weight; In step (1), the molar ratio of thionyl chloride to p-aminobenzoic acid in the reaction mixture is 2:1 to 20:1, or 3:1 to 12:1, or 3.5:1 to 8:

1.

8. A method as claimed in any one of the preceding claims, wherein Step (1) further comprises cooling the mixture to room temperature and maintaining the temperature for a period of time after the reaction is completed; Preferably, the room temperature keeping time is 1 to 3 hours.

9. The method according to any one of the preceding claims, wherein the reaction of step (1) is carried out in an atmosphere of a non-reactive gas, preferably in an atmosphere selected from nitrogen, argon or helium.

10. The method according to any one of the preceding claims, further comprising washing and drying the precipitated p-aminobenzoyl chloride hydrochloride product; Preferably, the washing comprises washing three times with a low boiling point solvent.

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