A low-residual benzalkonium chloride aqueous solution, a preparation method and application thereof

Abstract

The application discloses a kind of low residual benzalkonium chloride aqueous solution and preparation method and application thereof, belong to disinfectant technical field.The application comprises the following steps: (1) the fatty alkyl tertiary amine is mixed with water in microchannel reactor mixing block;(2) the microchannel reactor is heated to 40-120 DEG C, mixed liquid and benzyl chloride are simultaneously introduced into reaction block to carry out reaction;(3) the reaction time in reaction block is 5-10 min, and benzalkonium chloride aqueous solution is obtained.The preparation of benzalkonium chloride aqueous solution of the application is obtained by one-step reaction of fatty alkyl tertiary amine and benzyl chloride, and the reaction time is shorter, and the production cycle can be reduced from 6~8h to 3~4h per ton.

Description

Technical Field

[0001] This invention relates to the field of disinfectant technology, specifically to a low-residue benzalkonium chloride aqueous solution, its preparation method, and its application. Background Technology

[0002] Benzalkonium chloride is a cationic surfactant, primarily used as a bactericide and disinfectant. It can also be added as a cationic surfactant to improve the dispersibility and penetration of corresponding products. Its main applications as a disinfectant and bactericide are water disinfection and sterilization, and medical disinfection.

[0003] Currently, benzalkonium chloride is generally a white waxy solid or a yellow gel, or it can be further dried to obtain benzalkonium chloride powder. The production process of benzalkonium chloride powder generally involves reacting a C12-C16 alkyl dimethyl tertiary amine with benzyl chloride. After the reaction, a solvent is added for purification and recrystallization, followed by centrifugation and drying. The overall production cycle is over 24 hours. However, most benzalkonium chloride is prepared as a solution for use. The synthesis method of benzalkonium chloride solution generally involves directly mixing and reacting aliphatic alkyl tertiary amine with benzyl chloride. However, the viscosity of the resulting benzalkonium chloride product increases with the reaction, causing the aliphatic alkyl tertiary amine and benzyl chloride to not mix evenly and fully contact in subsequent reactions. This leads to localized overheating of the reaction temperature, decomposition of benzyl chloride, and ultimately, excessive residual free amines, high levels of benzyl chloride, benzyl alcohol, and benzaldehyde in the final product. The stability of indicators such as pH value of the solution is poor, failing to meet medical-grade standards and affecting the subsequent compounding of disinfectants. If water is added during the reaction to reduce viscosity, the water and the aliphatic alkyl tertiary amines become immiscible, preventing the formation of a homogeneous solution. This results in insufficient contact and reaction between benzyl chloride and the aliphatic alkyl tertiary amines. Simultaneously, some benzyl chloride reacts with water and hydrolyzes into impurities such as benzyl alcohol and benzaldehyde, leading to excessively high levels of benzyl chloride, benzyl alcohol, and benzaldehyde residues in the product, failing to meet medical-grade standards. Therefore, existing benzalkonium chloride solutions are prepared and purified from solid benzalkonium chloride before being dissolved to obtain an aqueous solution.

[0004] The existing benzalkonium chloride solid is mainly benzalkonium chloride powder and benzalkonium chloride paste. The benzalkonium chloride paste is not only difficult to dissolve, but also has high viscosity and is difficult to weigh and use. The benzalkonium chloride powder needs to be heated or other solubilizers are added to dissolve into an aqueous solution. Heating dissolution increases energy consumption, and the benzalkonium chloride with other solubilizers is also easy to be dissolved in solid form, such as the household disinfectant containing benzalkonium chloride sterilizing agent and the preparation method thereof disclosed in Publication No. CN112400874A, which includes benzalkonium chloride, sodium bicarbonate, water for injection, penetration enhancer, tackifier, coolant and PH buffer solution. The benzalkonium chloride solution and the preparation method thereof disclosed in Publication No. CN115737706A include 0.05-0.1% benzalkonium chloride, 0.3-0.5% myrtle extract, 1-2% chrysanthemum extract, 1-3% film-forming agent, 3-5% purslane extract and the balance of water. Whether the benzalkonium chloride solution in the prior art is a single aqueous solution or has other functional components or solubilizers added, the benzalkonium chloride solid is used in the preparation process. The benzalkonium chloride needs to be prepared into a solid through many processes such as desolubilization, crystallization, distillation and drying, and the process is complicated. At the same time, the content of impurities such as benzaldehyde and benzyl alcohol in the benzalkonium chloride solid is still high.

[0005] Publication No. CN113861037A discloses a production process of low-residual medicinal benzalkonium chloride. The preparation method is to react mixed alkyl tertiary amine with benzyl chloride first, and then remove impurities by desolubilization. Since the reaction of alkyl tertiary amine with benzyl chloride is easy to form a colloid, the reaction is not complete, and there are many by-products. Therefore, this technical solution is to add benzyl chloride multiple times to achieve complete reaction. Although this technical solution is to add dropwise multiple times, which reduces the by-products to a certain extent, the dropwise addition is intermittent. At the moment when benzyl chloride is added to alkyl tertiary amine, it will react quickly and release a large amount of heat, causing the temperature of the whole reaction to be uneven, and thus the reaction is also uneven. Although multiple dropwise additions achieve the purpose of reducing by-products to a certain extent, the content of final impurities is still high, and therefore deionized water needs to be added to remove impurities by azeotropic action. Publication No. JP1994157432A discloses a production method of benzalkonium chloride. This technical solution also provides a low-residual benzalkonium chloride. The reaction of alkyl tertiary amine with benzyl chloride is carried out first, and then the reacted material is passed through a thin film evaporator, and the impurities are removed by inert gas or water vapor.

[0006] Publication No. CN106946717A discloses a benzalkonium chloride monomer synthesis process, the technical solution is mainly through mixing reaction of alkyl tertiary amine, thiourea and benzyl chloride, and then a series of impurity removal to obtain benzalkonium chloride solid. Publication No. CN106631817A discloses a production process of alkyl dimethyl benzyl ammonium chloride, first adding benzyl chloride in a proportion of 1:1 with water, a large amount of benzyl chloride is in contact with water instantaneously, benzyl chloride is hydrolyzed, causing waste of raw materials; in addition, a large amount of benzyl chloride reacts with alkyl tertiary amine to generate heat too fast, and there are too many side reactions and by-products.

[0007] In summary, the purification of benzalkonium chloride in the prior art is mostly through reaction of alkyl tertiary amine and benzyl chloride, and then a series of solvent impurity removal. The aqueous solution of benzalkonium chloride is obtained by dissolving the solid, and a cosolvent or heating is needed in the dissolving process, which increases the input of cosolvent and energy, so there is no low-residue benzalkonium chloride aqueous solution obtained by direct reaction of alkyl tertiary amine and benzyl chloride at present. SUMMARY

[0008] In order to solve the above problems, the present application provides a preparation method of low-residue benzalkonium chloride aqueous solution, which is simple, has low content of benzyl chloride and free amine, and does not contain a cosolvent, so it is more convenient and fast to use.

[0009] In order to achieve the above purpose, the present application is realized by the following technical scheme:

[0010] A preparation method of low-residue benzalkonium chloride aqueous solution, comprising the following steps:

[0011] The fatty alkyl tertiary amine is mixed with water in a microchannel reactor, then the microchannel reactor is heated to 40-120℃, and benzyl chloride is added for reaction; the microchannel reactor is formed by a reaction module with a heart-shaped structure to form a mixing plate and a reaction plate, the fatty alkyl tertiary amine is mixed with water in the mixing plate to obtain a mixed solution, the mixed solution and the benzyl chloride are simultaneously introduced into the reaction plate for reaction, the reaction time of the mixed solution and the benzyl chloride in the reaction plate is 5-10 min, and the benzalkonium chloride aqueous solution is obtained.

[0012] Further, in step (1), the fatty alkyl tertiary amine is mixed with water in the mixing plate, the mixing flow rate is 20-50 ml / min, and the inlet pressure is 0.2-5 MPa.

[0013] Further, the temperature of the mixing plate is 40-80℃.

[0014] Further, the temperature of the reaction plate is 80-120℃. More preferably, the temperature of the reaction plate is 100-120℃.

[0015] Further, the water added in step (1) is 20%-50% of the total weight of the raw materials, and the total weight of the raw materials is the total weight of the fatty alkyl tertiary amine, water, and benzyl chloride.

[0016] Further, the weight ratio of the fatty alkyl tertiary amine to the benzyl chloride is 1.5-2:1.

[0017] Further, the fatty alkyl tertiary amine in step (1) is any one or several of dodecyl dimethyl tertiary amine, tetradecyl dimethyl tertiary amine, and hexadecyl dimethyl tertiary amine.

[0018] The application also protects a benzalkonium chloride aqueous solution obtained by a preparation method of a low-residue benzalkonium chloride aqueous solution.

[0019] The application also protects the use of a low-residue benzalkonium chloride and a bactericidal solution formed by compounding the benzalkonium chloride aqueous solution with other chemically acceptable components.

[0020] Further, the other chemically acceptable components include any one or several of water, a cosolvent, a penetrant, a surfactant, a bactericide, a preservative, a pH buffer, a film former, a plant extract, and a fragrance.

[0021] The low-residue benzalkonium chloride aqueous solution, the preparation method thereof, and the use thereof have the following beneficial effects:

[0022] (1) In the preparation method of the benzalkonium chloride aqueous solution, the fatty alkyl tertiary amine is first dispersed in water in a liquid phase, and then the benzyl chloride is added. The fatty alkyl tertiary amine and the benzyl chloride react in the water environment, and the reaction does not require any other cosolvent or additive. The obtained benzalkonium chloride aqueous solution has high purity.

[0023] (2) In the preparation method, due to the specific ratio among the fatty alkyl tertiary amine, the benzyl chloride, and the water, and due to the continuous dropwise addition of the benzyl chloride into the fatty alkyl tertiary amine, the heat released during the reaction is uniform, and the non-uniform heat release caused by the large addition of the benzyl chloride is avoided. The addition in the liquid phase makes the contact between the two more uniform, and the reaction is more complete. The obtained benzalkonium chloride aqueous solution has high benzalkonium chloride purity, and the benzalkonium chloride aqueous solution product has benzaldehyde ≤0.03%, benzyl alcohol ≤0.1%, and benzyl chloride ≤0.001%.

[0024] (3) due to the micro-channel structure, the material back mixing effect is good, the fatty alkyl tertiary amine, water and benzyl chloride are mixed more fully, the reaction efficiency is faster, the conversion rate is higher; the heat exchange specific surface area of the reactor is larger than that of the conventional reactor, which can rapidly exchange heat, reduce the decomposition of benzyl chloride due to the violent heat release, make the reaction more sufficient, thereby improve the conversion rate and improve the purity of the final product benzalkonium chloride. Since the micro-channel reaction is a high-speed mixing reaction, the reaction period is further shortened.

[0025] (4) the preparation of the benzalkonium chloride aqueous solution of the present application, the benzalkonium chloride aqueous solution is obtained by one-step reaction of fatty alkyl tertiary amine and benzyl chloride, without going through the complex processes of purification, impurity removal, drying and dissolution after reaction in the prior art. The production cycle of the existing benzalkonium chloride solid powder is > 24h, the reaction time required by the benzalkonium chloride aqueous solution as a medical grade is shorter, and the production cycle can be reduced from 6~8h to 3~4h per ton. DETAILED DESCRIPTION

[0026] In order to enable the personnel in the technical field to better understand the present application, the technical solutions of the present application will be described clearly and completely in combination with the embodiments below. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by the personnel in the field without creative labor belong to the scope of protection of the present application.

[0027] A preparation method of a low-residual benzalkonium chloride aqueous solution, comprising the following steps:

[0028] The fatty alkyl tertiary amine and water are mixed in the micro-channel reactor, then the micro-channel reactor is heated to 40℃-120℃, and then benzyl chloride is added for reaction; the micro-channel reactor forms a mixing plate and a reaction plate through a heart-shaped structure reaction module, the fatty alkyl tertiary amine and water are mixed in the mixing plate to obtain a mixed solution, the mixed solution and the benzyl chloride enter the reaction plate at the same time for reaction, the reaction time of the mixed solution and the benzyl chloride in the reaction plate is 5min-10min, and the water solution is obtained by discharging.

[0029] It should be noted that the fatty alkyl tertiary amine and water are mixed in the mixing plate in step (1), and the mixing flow rate is 20ml / min-50ml / min.

[0030] It should be noted that the temperature of the mixing plate is 40℃-80℃.

[0031] It should be noted that the temperature of the reaction plate is 80℃-120℃. More preferably, the temperature of the reaction plate is 100℃-120℃. Most preferably, the temperature of the reaction plate is 110℃-115℃.

[0032] It should be noted that the water added in step (1) is 20%-50% of the total weight of the raw materials. As a preferred, the water added in step (1) is 30%-50% of the total weight of the raw materials. And the total weight of the raw materials is the total weight of the fatty alkyl tertiary amine, water and benzyl chloride.

[0033] It should be noted that the weight ratio of the fatty alkyl tertiary amine to the benzyl chloride is 1.5-2:1. As a preferred, the weight ratio of the fatty alkyl tertiary amine to the benzyl chloride is 1.7-1.9:1. The fatty alkyl tertiary amine is any one or several of dodecyl dimethyl tertiary amine, tetradecyl dimethyl tertiary amine, and hexadecyl dimethyl tertiary amine.

[0034] The micro-channel reactor used in the present application is a Corning Advanced-Flow G3 reactor.

[0035] Example 1

[0036] The formula of each component: dodecyl dimethyl tertiary amine 30%, benzyl chloride 20%, water 50%;

[0037] A preparation method of a low-residual benzalkonium chloride aqueous solution, comprising the following steps:

[0038] (1) The dodecyl dimethyl tertiary amine and water are mixed by a reciprocating pump and introduced into a micro-channel reactor. The micro-channel reactor forms a mixing plate and a reaction plate through a reaction module with a heart-shaped structure. The fatty alkyl tertiary amine and water are mixed in the mixing plate to obtain a mixed liquid. The temperature of the mixing plate is 80℃, the mixing flow rate is 20ml / min, and the inlet pressure is 0.2MPa.

[0039] (2) The mixed liquid and the benzyl chloride are simultaneously introduced into the reaction plate for reaction. The temperature of the reaction plate is set to 120℃. The reaction time of the mixed liquid and the benzyl chloride in the reaction plate is 5min. After the reaction is completed, the benzalkonium chloride aqueous solution is obtained.

[0040] Example 2

[0041] The formula of each component: dodecyl dimethyl tertiary amine 30%, benzyl chloride 20%, water 50%;

[0042] A preparation method of a low-residual benzalkonium chloride aqueous solution, comprising the following steps:

[0043] (1) The dodecyl dimethyl tertiary amine and water are mixed by a reciprocating pump and introduced into a micro-channel reactor. The micro-channel reactor forms a mixing plate and a reaction plate through a reaction module with a heart-shaped structure. The fatty alkyl tertiary amine and water are mixed in the mixing plate to obtain a mixed liquid. The temperature of the mixing plate is 60℃, the mixing flow rate is 50ml / min, and the inlet pressure is 0.2MPa.

[0044] (2) The mixed solution and benzyl chloride are simultaneously introduced into the reaction plate block for reaction, the temperature of the reaction plate block is set to 100℃, the reaction time of the mixed solution and benzyl chloride in the reaction plate block is 10 min, and the benzalkonium chloride aqueous solution is obtained after the reaction is completed.

[0045] Example 3

[0046] The component formula is: dodecyl dimethyl tertiary amine 33%, benzyl chloride 17%, and water 50%;

[0047] A preparation method of a low-residual benzalkonium chloride aqueous solution, comprising the following steps:

[0048] (1) The dodecyl dimethyl tertiary amine and water are mixed by a reciprocating pump and introduced into a micro-channel reactor, the micro-channel reactor forms a mixing plate block and a reaction plate block through a reaction module with a heart-shaped structure, the fatty alkyl tertiary amine and water are mixed in the mixing plate block to obtain a mixed solution, the temperature of the mixing plate block is 40℃, the mixing flow rate is 40 ml / min, and the inlet pressure is 0.5 MPa;

[0049] (2) The mixed solution and benzyl chloride are simultaneously introduced into the reaction plate block for reaction, the temperature of the reaction plate block is set to 90℃, the reaction time of the mixed solution and benzyl chloride in the reaction plate block is 8 min, and the benzalkonium chloride aqueous solution is obtained after the reaction is completed.

[0050] Example 4

[0051] The component formula is: dodecyl dimethyl tertiary amine 32%, benzyl chloride 18%, and water 50%;

[0052] A preparation method of a low-residual benzalkonium chloride aqueous solution, comprising the following steps:

[0053] (1) The dodecyl dimethyl tertiary amine and water are mixed by a reciprocating pump and introduced into a micro-channel reactor, the micro-channel reactor forms a mixing plate block and a reaction plate block through a reaction module with a heart-shaped structure, the fatty alkyl tertiary amine and water are mixed in the mixing plate block to obtain a mixed solution, the temperature of the mixing plate block is 60℃, the mixing flow rate is 30 ml / min, and the inlet pressure is 0.5 MPa;

[0054] (2) The mixed solution and benzyl chloride are simultaneously introduced into the reaction plate block for reaction, the temperature of the reaction plate block is set to 110℃, the reaction time of the mixed solution and benzyl chloride in the reaction plate block is 10 min, and the benzalkonium chloride aqueous solution is obtained after the reaction is completed.

[0055] Example 5

[0056] The component formula is: dodecyl dimethyl tertiary amine 42%, benzyl chloride 28%, and water 30%;

[0057] A preparation method of a low-residual benzalkonium chloride aqueous solution, comprising the following steps:

[0058] (1) A dodecyl dimethyl tertiary amine and water are mixed by a reciprocating pump and introduced into a micro-channel reactor, the micro-channel reactor is formed by a reaction module with a heart-shaped structure into a mixing plate and a reaction plate, the fatty alkyl tertiary amine and water are mixed in the mixing plate to obtain a mixed liquid, the temperature of the mixing plate is 60 DEG C, the mixing flow rate is 30 ml / min, and the inlet pressure is 0.5 MPa;

[0059] (2) The mixed liquid and benzyl chloride are simultaneously introduced into the reaction plate to react, the temperature of the reaction plate is set to 120 DEG C, the reaction time of the mixed liquid and benzyl chloride in the reaction plate is 6 min, and the benzalkonium chloride aqueous solution is obtained after the reaction is completed.

[0060] Example 6

[0061] The component formula is: dodecyl dimethyl tertiary amine 36%, benzyl chloride 24%, and water 40%;

[0062] A preparation method of a low-residual benzalkonium chloride aqueous solution, comprising the following steps:

[0063] (1) A dodecyl dimethyl tertiary amine and water are mixed by a reciprocating pump and introduced into a micro-channel reactor, the micro-channel reactor is formed by a reaction module with a heart-shaped structure into a mixing plate and a reaction plate, the fatty alkyl tertiary amine and water are mixed in the mixing plate to obtain a mixed liquid, the temperature of the mixing plate is 60 DEG C, the mixing flow rate is 35 ml / min, and the inlet pressure is 0.5 MPa;

[0064] (2) The mixed liquid and benzyl chloride are simultaneously introduced into the reaction plate to react, the temperature of the reaction plate is set to 120 DEG C, the reaction time of the mixed liquid and benzyl chloride in the reaction plate is 10 min, and the benzalkonium chloride aqueous solution is obtained after the reaction is completed.

[0065] Example 7

[0066] The component formula is: dodecyl dimethyl tertiary amine 50%, benzyl chloride 30%, and water 20%;

[0067] A preparation method of a low-residual benzalkonium chloride aqueous solution, comprising the following steps:

[0068] (1) A dodecyl dimethyl tertiary amine and water are mixed by a reciprocating pump and introduced into a micro-channel reactor, the micro-channel reactor is formed by a reaction module with a heart-shaped structure into a mixing plate and a reaction plate, the fatty alkyl tertiary amine and water are mixed in the mixing plate to obtain a mixed liquid, the temperature of the mixing plate is 60 DEG C, the mixing flow rate is 35 ml / min, and the inlet pressure is 0.5 MPa;

[0069] (2) the mixed solution and benzyl chloride enter the reaction plate at the same time to react, the temperature of the reaction plate is set to 110°C, the reaction time of the mixed solution and benzyl chloride in the reaction plate is 10 min, and the benzalkonium chloride aqueous solution is obtained after the reaction is completed.

[0070] Example 8

[0071] The component formula is: dodecyl dimethyl tertiary amine 46%, benzyl chloride 24%, and water 30%.

[0072] A preparation method of a low-residual benzalkonium chloride aqueous solution, comprising the following steps:

[0073] (1) dodecyl dimethyl tertiary amine and water are mixed and introduced into a micro-channel reactor through a reciprocating pump, the micro-channel reactor forms a mixing plate and a reaction plate through a reaction module with a heart-shaped structure, the fatty alkyl tertiary amine and water are mixed in the mixing plate to obtain a mixed solution, the temperature of the mixing plate is 60°C, the mixing flow rate is 35 ml / min, and the inlet pressure is 0.5 MPa;

[0074] (2) the mixed solution and benzyl chloride enter the reaction plate at the same time to react, the temperature of the reaction plate is set to 110°C, the reaction time of the mixed solution and benzyl chloride in the reaction plate is 10 min, and the benzalkonium chloride aqueous solution is obtained after the reaction is completed.

[0075] Example 9

[0076] The component formula is: dodecyl dimethyl tertiary amine 32%, benzyl chloride 18%, and water 50%.

[0077] A preparation method of a low-residual benzalkonium chloride aqueous solution, comprising the following steps:

[0078] (1) dodecyl dimethyl tertiary amine and water are mixed and introduced into a micro-channel reactor through a reciprocating pump, the micro-channel reactor forms a mixing plate and a reaction plate through a reaction module with a heart-shaped structure, the fatty alkyl tertiary amine and water are mixed in the mixing plate to obtain a mixed solution, the temperature of the mixing plate is 60°C, the mixing flow rate is 35 ml / min, and the inlet pressure is 0.5 MPa;

[0079] (2) the mixed solution and benzyl chloride enter the reaction plate at the same time to react, the temperature of the reaction plate is set to 110°C, the reaction time of the mixed solution and benzyl chloride in the reaction plate is 10 min, and the benzalkonium chloride aqueous solution is obtained after the reaction is completed.

[0080] Example 10

[0081] The component formula is: dodecyl dimethyl tertiary amine 32%, benzyl chloride 18%, and water 50%.

[0082] A preparation method of a low-residual benzalkonium chloride aqueous solution, comprising the following steps:

[0083] (1) A dodecyl dimethyl tertiary amine and water are mixed by a reciprocating pump and introduced into a micro-channel reactor, the micro-channel reactor is formed by a reaction module with a heart-shaped structure into a mixing plate and a reaction plate, the fatty alkyl tertiary amine and water are mixed in the mixing plate to obtain a mixed liquid, the temperature of the mixing plate is 60 DEG C, the mixing flow rate is 35 ml / min, and the inlet pressure is 0.5 MPa;

[0084] (2) The mixed liquid and benzyl chloride are simultaneously introduced into the reaction plate to react, the temperature of the reaction plate is set to 90 DEG C, the reaction time of the mixed liquid and benzyl chloride in the reaction plate is 10 min, and the benzalkonium chloride aqueous solution is obtained after the reaction is completed.

[0085] Example 11

[0086] The component formula: dodecyl dimethyl tertiary amine 32%, benzyl chloride 18%, water 50%;

[0087] A preparation method of a low-residual benzalkonium chloride aqueous solution, comprising the following steps:

[0088] (1) A dodecyl dimethyl tertiary amine and water are mixed by a reciprocating pump and introduced into a micro-channel reactor, the micro-channel reactor is formed by a reaction module with a heart-shaped structure into a mixing plate and a reaction plate, the fatty alkyl tertiary amine and water are mixed in the mixing plate to obtain a mixed liquid, the temperature of the mixing plate is 60 DEG C, the mixing flow rate is 35 ml / min, and the inlet pressure is 0.5 MPa;

[0089] (2) The mixed liquid and benzyl chloride are simultaneously introduced into the reaction plate to react, the temperature of the reaction plate is set to 80 DEG C, the reaction time of the mixed liquid and benzyl chloride in the reaction plate is 10 min, and the benzalkonium chloride aqueous solution is obtained after the reaction is completed.

[0090] Comparative Example 1

[0091] The component formula: dodecyl dimethyl tertiary amine 32%, benzyl chloride 18%, water 50%;

[0092] (1) A dodecyl dimethyl tertiary amine and water are mixed by a reciprocating pump and introduced into a micro-channel reactor, the micro-channel reactor is formed by a reaction module with a heart-shaped structure into a mixing plate and a reaction plate, the fatty alkyl tertiary amine and water are mixed in the mixing plate to obtain a mixed liquid, the temperature of the mixing plate is 60 DEG C, the mixing flow rate is 35 ml / min, and the inlet pressure is 0.5 MPa;

[0093] (2) The mixed solution and benzyl chloride are simultaneously introduced into the reaction plate block to react, the temperature of the reaction plate block is set to 110°C, the reaction time of the mixed solution and benzyl chloride in the reaction plate block is 10 min, and the benzalkonium chloride aqueous solution is obtained after the reaction is completed.

[0094] Comparative Example 2

[0095] The allocation formula of each component is: dodecyl dimethyl tertiary amine 32%, benzyl chloride 18%, and water 50%.

[0096] (1) The dodecyl dimethyl tertiary amine, water and benzyl chloride are simultaneously mixed and introduced into the reaction plate block in the micro-channel reactor through the reciprocating pump, the inlet pressure is 0.5 MPa, the reaction temperature is set to 110°C; the reaction time is 10 min, and the benzalkonium chloride aqueous solution is obtained after the reaction is completed.

[0097] Comparative Example 3

[0098] The allocation formula of each component is: dodecyl dimethyl tertiary amine 32%, benzyl chloride 18%, and water 50%.

[0099] (1) The dodecyl dimethyl tertiary amine and water are mixed and introduced into the micro-channel reactor through the reciprocating pump, the micro-channel reactor forms a mixing plate block and a reaction plate block through the reaction module of the heart-shaped structure, the fatty alkyl tertiary amine and water are mixed in the mixing plate block to obtain a mixed solution, the temperature of the mixing plate block is 60°C, the mixing flow rate is 30 ml / min, and the inlet pressure is 0.5 MPa.

[0100] (2) The mixed solution and benzyl chloride are simultaneously introduced into the reaction plate block to react, the temperature of the reaction plate block is set to 140°C, the reaction time of the mixed solution and benzyl chloride in the reaction plate block is 10 min, and the benzalkonium chloride aqueous solution is obtained after the reaction is completed.

[0101] Comparative Example 4

[0102] The allocation formula of each component is: dodecyl dimethyl tertiary amine 32%, benzyl chloride 18%, and water 50%.

[0103] (1) The dodecyl dimethyl tertiary amine is heated to 60°C, and then benzyl chloride is added dropwise, the benzyl chloride is controlled to be added at a uniform speed within 2 h; the reaction temperature is controlled at 110°C, the reaction time is 6 h, the recrystallization solvent is added after the reaction is completed, the powder is centrifuged and dried after being dissolved by heating and then cooled and crystallized.

[0104] (2) The benzalkonium chloride powder obtained by centrifugal drying is added to the reaction kettle, heated to 80°C to completely dissolve, and a solution is obtained after cooling.

[0105] Comparative Example 5

[0106] The allocation formula of each component is: dodecyl dimethyl tertiary amine 32%, benzyl chloride 18%, and water 50%.

[0107] The dodecyl dimethyl tertiary amine is warmed to 60°C, and then benzyl chloride is added. The benzyl chloride is added at a uniform speed within 2h. The reaction temperature is controlled at 110°C, and the reaction time is 6h. After the reaction is completed, water and propylene glycol are added, stirred and dissolved, and then a solution is obtained by cooling.

[0108] Comparative Example 6

[0109] The component formula is: dodecyl dimethyl tertiary amine 32%, benzyl chloride 18%, and water 50%.

[0110] The dodecyl dimethyl tertiary amine is warmed to 60°C, and then benzyl chloride is added. The benzyl chloride is added at a uniform speed within 2h. The reaction temperature is controlled at 110°C, and the reaction time is 6h. After the reaction is completed, water and propylene glycol are added, stirred and dissolved, and then a solution is obtained by cooling.

[0111] Test verification

[0112] The solutions obtained in Examples 1-11 and Comparative Examples 1-6 are used as benzalkonium chloride aqueous solution samples, and the results obtained by referring to the standard “Chinese Pharmacopoeia” 2020 edition Part II are shown in Table 1:

[0113] Table 1 Content in benzalkonium chloride solution

[0114]

[0115] As can be seen from Table 1, the impurity detection of benzalkonium chloride in the prior art generally only detects the residual benzyl chloride, and rarely detects the residual free amine, benzaldehyde and benzyl alcohol, etc. Therefore, most of the directly produced benzalkonium chloride aqueous solution in the prior art is difficult to apply in the medical industry. However, the free amine, benzyl chloride residue, benzaldehyde and benzyl alcohol impurities can be maintained at a low level after adjusting the process of the present application, and the medical grade is reached.

[0116] As can be seen from the data of Example 4 and Comparative Examples 1 and 3, the reaction of Comparative Example 1 is not complete at a lower temperature, so the residual benzyl chloride is larger. Although the residual benzyl chloride is not detected in Comparative Example 3, the residual benzyl alcohol and benzaldehyde are higher. It is shown that the fatty alkyl tertiary amine and benzyl chloride in the present application need to be reacted at a specific temperature range, so as to simultaneously reduce the residual free amine, benzyl alcohol, benzaldehyde and benzyl chloride, and improve the purity of the benzalkonium chloride aqueous solution.

[0117] From Example 4 and Comparative Example 2, it can be seen that Example 4 is that the fatty alkyl tertiary amine is mixed with water first and then reacted with benzyl chloride, while Comparative Example 2 is that the fatty alkyl tertiary amine is directly mixed with benzyl chloride and water for reaction, but the benzyl chloride impurity is still detected in Comparative Example 2, indicating that the process of mixing the fatty alkyl tertiary amine with water first and then reacting with benzyl chloride can effectively reduce the residual benzyl chloride in benzalkonium chloride. Since the reaction time of Comparative Example 3 is shorter, the residual benzaldehyde is higher.

[0118] Comparative Example 4 is a conventional solvent recrystallization reaction to obtain benzalkonium chloride powder, and then the benzalkonium chloride powder is dissolved. Since it is recrystallization, the benzalkonium chloride powder is a high-purity refined powder, so the residual amount of benzyl chloride is small or even no residual, but the whole process time is longer, and needs operations such as crystallization, centrifugation, and drying, which has high energy consumption and is complicated, and also produces a large amount of waste water and waste gas. The present application greatly improves the work efficiency, and is more environmentally friendly, energy-saving and efficient.

[0119] Comparative Examples 5 and 6 are that the fatty alkyl tertiary amine is reacted with benzyl chloride and then water is directly added. Comparative Example 5 also adds a commonly used solubilizer propylene glycol. Although this method is relatively convenient for the production of benzalkonium chloride aqueous solution, it can be seen from Table 1 that there are residual benzyl chloride and benzyl alcohol, and the purity is not high.

[0120] Comparison of process conditions

[0121] Taking the production capacity of 50% benzalkonium chloride aqueous solution per ton as a standard, the process of Example 4 and Comparative Examples 1-6 is compared in terms of time and energy saving, and the results are shown in Table 2.

[0122] Table 2 Comparison of processes of each group

[0123]

[0124] As can be seen from Table 2, the preparation process adopted by the present application greatly improves the production efficiency while improving the purity of the benzalkonium chloride aqueous solution.

[0125] Reference herein to "an embodiment" means that a particular feature, structure, or characteristic described in connection with the embodiment can be included in at least one embodiment of the application. The appearances of the phrase in various places in the specification are not necessarily all referring to the same embodiment, nor are they necessarily mutually exclusive of one another. As will be apparent to those of ordinary skill in the art, embodiments described herein can be combinable with other embodiments.

[0126] It should be pointed out finally that the embodiments disclosed by the present application are only the preferred embodiments of the present application, and are only used to illustrate the technical solutions of the present application, but not to limit them; although the present application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that the technical solutions recorded in the foregoing embodiments can be modified, or some technical features can be replaced equivalently; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the spirit and scope of the technical solutions of the embodiments of the present application.

Claims

1. A method for preparing a low-residue benzalkonium chloride aqueous solution, characterized in that: Includes the following steps: Aliphatic alkyl tertiary amines are mixed with water in a microchannel reactor. The microchannel reactor is then heated to 40℃-120℃, and benzyl chloride is added to react. The microchannel reactor is divided into a mixing plate and a reaction plate by a heart-shaped reaction module. The aliphatic alkyl tertiary amines and water are mixed in the mixing plate to obtain a mixed solution. The mixed solution and benzyl chloride are then simultaneously introduced into the reaction plate to react. The reaction time of the mixed solution and benzyl chloride in the reaction plate is 5min-10min. The product is then discharged as a benzalkonium chloride aqueous solution.

2. The method for preparing the low-residue benzalkonium chloride aqueous solution according to claim 1, characterized in that: In step (1), fatty alkyl tertiary amines and water are mixed in the mixing plate at a flow rate of 20 ml / min-50 ml / min.

3. The method for preparing the low-residue benzalkonium chloride aqueous solution according to claim 1, characterized in that: The temperature of the mixing plate is 40℃-80℃.

4. The method for preparing the low-residue benzalkonium chloride aqueous solution according to claim 1, characterized in that: The temperature of the reaction plate is 80℃-120℃.

5. The method for preparing the low-residue benzalkonium chloride aqueous solution according to claim 1, characterized in that: The water added in step (1) is 20%-50% of the total weight of the raw materials, and the total weight of the raw materials is the total weight of the fatty alkyl tertiary amine, water, and benzyl chloride.

6. The method for preparing the low-residue benzalkonium chloride aqueous solution according to claim 1, characterized in that: The weight ratio of the fatty alkyl tertiary amine to benzyl chloride is 1.5-2:

1.

7. The method for preparing a low-residue benzalkonium chloride aqueous solution according to claim 1, characterized in that: The fatty alkyl tertiary amine mentioned in step (1) is any one or more of dodecyl dimethyl tertiary amine, tetradecyl dimethyl tertiary amine, and hexadecyl dimethyl tertiary amine.

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