Preparation method and device of N-(8-[2-hydroxybenzoyl]-amino) sodium caprylate

Abstract

The invention belongs to the technical field of medicine preparation, and particularly relates to a preparation method and device of sodium N-(8-[2-hydroxybenzoyl]-amino) caprylate. The preparation method of the sodium N-(8-[2-hydroxybenzoyl]-amino) caprylate comprises the following steps: preparing sodium N-(8-[2-hydroxybenzoyl]-amino) caprylate; the preparation method comprises the following steps: firstly, mixing methyl salicylate with ethyl acetate and 8-amino caprylic acid for reaction, and then carrying out reduced pressure distillation to obtain an N-(8-[2-hydroxybenzoyl]-amino) caprylic acid crude product; and then, adding water to dissolve the crude product, reacting with a sodium hydroxide solution, adding isopropanol to crystallize, recrystallizing with absolute ethyl alcohol, filtering and drying to finally obtain the target product. According to the preparation method, ethyl acetate is selected as a solvent, so that the potential harm to operators is reduced, the environmental protection treatment pressure is relieved, and meanwhile, a good environment is provided for reaction; sodium hydroxide is used as alkali, so that the salt forming reaction can be accelerated, the production efficiency is improved, and the purity and yield of the product are guaranteed.

Description

Technical Field

[0001] The present invention belongs to the technical field of pharmaceutical preparation, and particularly relates to a preparation method and device for sodium N-(8-[2-hydroxybenzoyl]-amino) octanoate. Background Art

[0002] As an organic compound with a specific structure, sodium N-(8-[2-hydroxybenzoyl]-amino) octanoate shows potential application value in multiple fields; in the pharmaceutical field, it is found that it has a regulatory effect on inflammation-related signaling pathways and is expected to be used in the development of anti-inflammatory drugs; with the in-depth study of related research, the demand for high-purity and low-cost sodium N-(8-[2-hydroxybenzoyl]-amino) octanoate is increasing.

[0003] For example, Chinese Patent Application No. (2021112611379) discloses a synthesis method of sodium N-(8-[2-hydroxybenzoyl]-amino) octanoate, and the solvent used is any one of dichloromethane, chloroform, acetonitrile and dimethylformamide. These substances all have certain toxicity, and long-term exposure or use may cause harm to the health of operators, and there are also certain difficulties in environmental protection treatment. And it uses sodium bicarbonate as the base to participate in the reaction, and the alkalinity is relatively weak, which is likely to lead to a slow reaction rate and incomplete reaction. Summary of the Invention

[0004] The purpose of the present invention is to solve the above-mentioned existing technical problems, and provide a preparation method and device for sodium N-(8-[2-hydroxybenzoyl]-amino) octanoate, achieving the effects of improving the selectivity of the reaction, the purity of the product and effectively improving the preparation efficiency.

[0005] In view of this, the present invention provides a preparation method for sodium N-(8-[2-hydroxybenzoyl]-amino) octanoate, including the following steps:

[0006] S1: Add methyl o-hydroxybenzoate as a raw material into a reaction vessel, add ethyl acetate as a solvent, then add 8-aminooctanoic acid, control the temperature at 25-35 °C, and control the stirring speed at 200-300 r / min;

[0007] S2: Transfer the reaction solution in S1 to a vacuum distillation device, and carry out vacuum distillation for 2-3 h at 40-50 °C and a vacuum degree of -0.09 MPa to remove ethyl acetate, and naturally cool to room temperature to obtain a crude product of N-(8-[2-hydroxybenzoyl]-amino) octanoic acid;

[0008] S3: Add the crude N-(8-[2-hydroxybenzoyl]-amino)octanoic acid into the reaction vessel, and add deionized water with a mass 7 - 8 times that of methyl o-hydroxybenzoate for dissolution, and stir for 30 - 60 min for dissolution;

[0009] S4: After fully stirring and dissolving, slowly add a sodium hydroxide solution with a concentration of 1 mol / L, control the reaction temperature at 25 - 30 °C, and the reaction time is 2 - 3 h until the reaction is complete;

[0010] S5: Slowly add isopropanol with a mass 18 - 20 times that of methyl o-hydroxybenzoate to the reaction solution for crystallization; after stirring evenly, let the solution stand at 0 - 5 °C for 2 - 3 h to fully precipitate the crystals;

[0011] S6: Filter the reaction solution, collect the solid product, and recrystallize it with absolute ethanol;

[0012] S7: Filter and dry the reaction solution to obtain sodium N-(8-[2-hydroxybenzoyl]-amino)octanoate.

[0013] In the above technical solution, further:

[0014] In S1, the molar ratio of methyl o-hydroxybenzoate to 8-aminooctanoic acid is controlled at 1:1.05 - 1.2.

[0015] In the above technical solution, further:

[0016] In S4, the molar ratio of sodium hydroxide to N-(8-[2-hydroxybenzoyl]-amino)octanoic acid is 1:1.05 - 1.2.

[0017] In the above technical solution, further:

[0018] The specific recrystallization steps in S6 are: heat to 50 - 60 °C to completely dissolve the solid, then slowly cool to room temperature, and then stand at 0 - 5 °C for 1 - 2 h to precipitate the crystals again.

[0019] The present invention provides a device for a preparation method of sodium N-(8-[2-hydroxybenzoyl]-amino)octanoate, including:

[0020] A kettle body, internally provided with a device cavity and a reaction cavity, and the reaction cavity is provided with a feed inlet and a discharge outlet;

[0021] A stirring mechanism, including a main shaft, stirring blades installed on the surface of the main shaft, and a driving motor for driving the main shaft to rotate;

[0022] An adjusting mechanism, installed in the device cavity and used to increase or restore the inclination angle of the stirring blades;

[0023] The triggering mechanism is installed in the device cavity and is used to trigger the opening and closing of the adjustment mechanism.

[0024] In the above technical solution, further, the stirring blade includes:

[0025] A connecting end is arranged on the surface of the main shaft, and an installation cavity is opened inside;

[0026] A first connecting rod, one end of which extends into the installation cavity and is connected to the inner wall of the installation cavity by a bearing;

[0027] A blade end is connected to one end of the first connecting rod far from the connecting end and is inclined;

[0028] Among them, the stirring blades are arranged in pairs on both radial sides of the main shaft.

[0029] In the above technical solution, further, the adjustment mechanism includes:

[0030] A gear is located in the installation cavity and is sleeved on the surface of the first connecting rod;

[0031] A rack, a chute is axially opened in the main shaft, and the rack is installed in the chute and meshes with the gear;

[0032] A driving component is installed in the device cavity and is used to drive the rack to lift;

[0033] Among them, the two first connecting rods in the pair of stirring blades are respectively located on both sides of the rack.

[0034] In the above technical solution, further, the driving component includes:

[0035] A second connecting rod, one end of which extends into the chute and is connected to the rack, the other end forms a ball head, and a strip groove adapted to the second connecting rod is opened on the inner wall of the chute;

[0036] An iron ring is slidably installed in the device cavity, and an annular groove adapted to the ball head is opened on the surface close to the axis;

[0037] An electromagnet is installed in the device cavity and is used to adsorb the iron ring when energized and desorb the iron ring when powered off;

[0038] Among them, the ball head is slidably connected to the annular groove, and the electromagnet is powered on and off by the triggering mechanism.

[0039] In the above technical solution, further, the triggering mechanism includes:

[0040] A first electrode plate is installed on the inner wall of the device cavity and is provided with a first electrode piece;

[0041] A second electrode plate is installed on the inner wall of the device cavity and is provided with a second electrode piece, and a gap is formed between the second electrode piece and the first electrode piece;

[0042] A cam disk is sleeved on the main shaft, and a ratchet member is provided between the cam disk and the main shaft, and a trigger electrode piece corresponding to the gap is provided on the protruding part;

[0043] Among them, the first electrode piece and the second electrode piece are respectively electrically connected to both ends of the electrode of the electromagnet, and the static friction resistance between the cam disk and the first electrode plate and the second electrode plate is greater than the mechanical resistance generated when the ratchet member is not engaged.

[0044] In the above technical solution, further, the ratchet member includes:

[0045] A bracket is sleeved on the surface of the main shaft, and a plurality of pawls are provided on the circumference, and a torsion spring is provided at the connection;

[0046] Ratchet teeth are installed on the cam disk and are arranged corresponding to the pawls;

[0047] Among them, the cam disk and the main shaft are connected by a bearing.

[0048] The beneficial effects of the present invention are:

[0049] 1. Using ethyl acetate as a solvent, during the production process, it can reduce the potential harm to the operator's body, and at the same time reduce the environmental protection treatment pressure caused by the use of toxic solvents, reduce the difficulty and cost of three-waste treatment, and ethyl acetate has good solubility for methyl o-hydroxybenzoate and 8-aminocaprylic acid, which can make the reactants fully dispersed in the solvent, provide a good homogeneous environment for the reaction, and is conducive to the full contact and collision between reactant molecules, thereby promoting the progress of the reaction. Moreover, the chemical properties of ethyl acetate are relatively stable and it is not easy to have side reactions with reactants or products under the reaction conditions, ensuring the selectivity of the reaction and the purity of the product.

[0050] 2. By using sodium hydroxide as a base to participate in the reaction, it can quickly provide hydroxide ions in the reaction, and quickly carry out an acid-base neutralization reaction with N-(8-[2-hydroxybenzoyl]-amino)octanoic acid, accelerating the speed of the salt-forming reaction, shortening the reaction time, improving the production efficiency, and the high reaction activity of sodium hydroxide can make the reaction proceed more quickly in the direction of the target product, reducing the residence time of the reactants in the reaction system, thereby reducing the possibility of side reactions caused by the long-term existence of the reactants, and improving the purity and yield of the product.

[0051] 3. By adjusting the tilt angle of the stirring blades to increase or restore it, at the initial stage of the reaction, the stirrer can push more liquid to flow when rotating, forming a stronger liquid circulation, thereby accelerating the mixing speed of methyl salicylate, 8 - amino - octanoic acid, and ethyl acetate in step S1, as well as N-(8 - [2 - hydroxybenzoyl] - amino) octanoic acid and sodium hydroxide solution in step S4, enabling the reactants to be more quickly and evenly distributed in the reaction system, increasing the collision probability between molecules, and facilitating the rapid initiation of the reaction.

[0052] 4. In the later stage of the reaction, resetting the tilt angle of the stirring blades to the normal state can relatively weaken the stirring intensity and avoid damaging the formed product structure or reaction intermediates due to over - stirring; at this time, the reaction system is already relatively uniform, and strong stirring like in the early stage is not required to promote mixing and mass transfer. A more stable stirring helps to maintain the stability of the reaction. Brief Description of the Drawings

[0053] Figure 1 is the structural schematic diagram of the present invention;

[0054] Figure 2 is the top view of the present invention;

[0055] Figure 3 is the present invention Figure 2 the cross - sectional view taken along A - A in;

[0056] Figure 4 is the present invention Figure 3 the enlarged view at B in;

[0057] Figure 5 is the present invention Figure 3 the enlarged view at C in;

[0058] Figure 6 is the structural schematic diagram inside the present invention;

[0059] The markings in the figure are represented as: 1, kettle body; 2, equipment cavity; 3, reaction cavity; 4, feed inlet; 5, discharge outlet; 6, stirring mechanism; 60, main shaft; 61, stirring blades; 610, connection end; 611, installation cavity; 612, first connecting rod; 613, blade end; 62, drive motor; 7, adjustment mechanism; 70, gear; 71, rack; 72, chute; 73, drive assembly; 730, second connecting rod; 731, ball head; 732, strip groove; 733, iron ring; 734, annular groove; 735, electromagnet; 8, trigger mechanism; 80, first electrode plate; 81, first electrode piece; 82, second electrode plate; 83, second electrode piece; 84, gap; 85, cam disk; 86, ratchet member; 860, bracket; 861, pawl; 862, ratchet teeth; 87, trigger electrode piece. Detailed Embodiments

[0060] The technical solutions in the embodiments of the present application will be clearly described below with reference to the accompanying drawings in the embodiments of the present application. Obviously, the described embodiments are part of the embodiments of the present application, rather than all of the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments in the present application belong to the scope of protection of the present application.

[0061] Embodiment 1:

[0062] This embodiment provides a preparation method of sodium N-(8-[2-hydroxybenzoyl]-amino) octanoate, which includes the following steps:

[0063] S1: Add methyl o-hydroxybenzoate as a raw material into a reaction vessel, add ethyl acetate as a solvent, and then add 8-aminooctanoic acid. Control the temperature at 25-35 °C and the stirring speed at 200-300 r / min;

[0064] S2: Transfer the reaction solution in S1 to a vacuum distillation device, and carry out vacuum distillation for 2-3 h at 40-50 °C and a vacuum degree of -0.09 MPa to remove ethyl acetate, and naturally cool to room temperature to obtain a crude product of N-(8-[2-hydroxybenzoyl]-amino) octanoic acid;

[0065] S3: Add the crude product of N-(8-[2-hydroxybenzoyl]-amino) octanoic acid into a reaction vessel, and add deionized water with a mass 7-8 times that of methyl o-hydroxybenzoate for dissolution, and stir for 30-60 min for dissolution;

[0066] S4: After fully stirring and dissolving, slowly add a sodium hydroxide solution with a concentration of 1 mol / L, control the reaction temperature at 25-30 °C, and the reaction time at 2-3 h until the reaction is complete;

[0067] S5: Slowly add isopropanol with a mass 18-20 times that of methyl o-hydroxybenzoate to the reaction solution for crystallization; after stirring evenly, let the solution stand at 0-5 °C for 2-3 h to fully precipitate the crystals;

[0068] S6: Filter the reaction solution, collect the solid product and recrystallize it with absolute ethanol;

[0069] S7: Filter and dry the reaction solution to obtain sodium N-(8-[2-hydroxybenzoyl]-amino) octanoate;

[0070] Among them, the molar ratio of methyl o-hydroxybenzoate to 8-aminooctanoic acid in S1 is controlled at 1:1.05-1.2;

[0071] In S4, the molar ratio of sodium hydroxide to N-(8-[2-hydroxybenzoyl]-amino)octanoic acid is 1:1.05 - 1.2;

[0072] The specific recrystallization steps in S6 are as follows: Heat to 50 - 60 °C to completely dissolve the solid, then slowly cool to room temperature, and then stand at 0 - 5 °C for 1 - 2 h to precipitate the crystals again.

[0073] As can be seen from this example, using ethyl acetate as the solvent can reduce the potential harm to the operators' bodies during the production process. At the same time, it also reduces the environmental protection treatment pressure caused by the use of toxic solvents, alleviates the difficulty and cost of treating the three wastes, and ethyl acetate has good solubility for methyl o-hydroxybenzoate and 8-aminooctanoic acid, enabling the reactants to be fully dispersed in the solvent, providing a good homogeneous environment for the reaction, facilitating the full contact and collision between reactant molecules, and thus promoting the progress of the reaction. Moreover, the chemical properties of ethyl acetate are relatively stable and it is not likely to undergo side reactions with reactants or products under the reaction conditions, ensuring the selectivity of the reaction and the purity of the product;

[0074] By using sodium hydroxide as the base to participate in the reaction, it can quickly provide hydroxide ions in the reaction, undergo a rapid acid-base neutralization reaction with N-(8-[2-hydroxybenzoyl]-amino)octanoic acid, accelerate the speed of the salt formation reaction, shorten the reaction time, improve the production efficiency, and the high reaction activity of sodium hydroxide enables the reaction to proceed more quickly towards the direction of the target product, reducing the residence time of the reactants in the reaction system, thereby reducing the possibility of side reactions caused by the long-term presence of the reactants and improving the purity and yield of the product.

[0075] Example 2:

[0076] This example provides a preparation device for the preparation method of sodium N-(8-[2-hydroxybenzoyl]-amino)octanoate, including:

[0077] The kettle body 1 is internally provided with a device cavity 2 and a reaction cavity 3, and a feed inlet 4 and a discharge outlet 5 are provided on the reaction cavity 3;

[0078] The stirring mechanism 6 includes a main shaft 60, stirring blades 61 installed on the surface of the main shaft 60, and a driving motor 62 for driving the main shaft 60 to rotate;

[0079] The adjusting mechanism 7 is installed in the device cavity 2 and is used to increase or restore the inclination angle of the stirring blades 61;

[0080] The triggering mechanism 8 is installed in the device cavity 2 and is used to trigger the opening and closing of the adjusting mechanism 7;

[0081] Among them, the specific structure of the drive motor 62 is a prior art and can achieve the forward and reverse rotation of the main shaft 60 (i.e., clockwise or counterclockwise drive), which will not be elaborated here.

[0082] It can be seen from this embodiment that by adjusting the inclination angle of the stirring blade 61 to increase or restore it, more liquid can be pushed to flow when the stirrer rotates at the primary stage of the reaction, forming a stronger liquid circulation, thereby accelerating the mixing speed of methyl o-hydroxybenzoate, 8-aminooctanoic acid, and ethyl acetate in step S1, as well as N-(8-[2-hydroxybenzoyl]-amino)octanoic acid and sodium hydroxide solution in step S4, enabling the reactants to be more evenly distributed in the reaction system more quickly, increasing the collision probability between molecules, and facilitating the rapid initiation of the reaction.

[0083] In the later stage of the reaction, resetting the inclination angle of the stirring blade 61 to the normal state can relatively weaken the stirring intensity and avoid damaging the formed product structure or reaction intermediate due to excessive stirring; at this time, the reaction system is already relatively uniform, and strong stirring like in the early stage is not required to promote mixing and mass transfer. A more stable stirring helps to maintain the stability of the reaction.

[0084] Example 3:

[0085] This embodiment provides a preparation device for the preparation method of sodium N-(8-[2-hydroxybenzoyl]-amino)octanoate. In addition to including the technical solutions of the above embodiment, it also has the following technical features. The stirring blade 61 includes:

[0086] A connection end 610, arranged on the surface of the main shaft 60 and having an installation cavity 611 inside.

[0087] A first connecting rod 612, one end of which extends into the installation cavity 611 and is connected to the inner wall of the installation cavity 611 by a bearing.

[0088] A blade end 613, connected to the end of the first connecting rod 612 far from the connection end 610 and inclined.

[0089] Among them, the stirring blades 61 are arranged in pairs on both radial sides of the main shaft 60.

[0090] At the same time, the bearing connection between the first connecting rod 612 and the inner wall of the installation cavity 611 is installed and connected by two bearings to improve the connection strength and stability between the stirring blade 61 and the main shaft 60, and the initial inclination angle of the blade end 613 can be 10° - 15°.

[0091] As can be seen from this embodiment, by using the first connecting rod 612 for bearing connection, the smooth rotation of the blade end 613 by the adjusting mechanism 7 is ensured. At the same time, the connection end 610 and the installation cavity 611 are provided. On the one hand, it is convenient for the installation of the bearing. On the other hand, the connection end 610 can avoid the influence on the structural strength caused by the opening of the installation cavity 611 and ensure the structural strength.

[0092] Embodiment 4:

[0093] This embodiment provides a preparation device for a method for preparing sodium N-(8-[2-hydroxybenzoyl]-amino) octanoate. In addition to including the technical solutions of the above embodiments, it also has the following technical features. The adjusting mechanism 7 includes:

[0094] A gear 70, located in the installation cavity 611 and sleeved on the surface of the first connecting rod 612;

[0095] A rack 71. A chute 72 is axially opened in the main shaft 60, and the rack 71 is installed in the chute 72 and meshes with the gear 70;

[0096] A driving component 73, installed in the equipment cavity 2 and used to drive the rack 71 to move up and down;

[0097] Among them, the two first connecting rods 612 in each pair of stirring blades 61 are respectively located on both sides of the rack 71;

[0098] At the same time, the gear 70 and the first connecting rod 612 can adopt an integral structure, and the rack 71 is a double-sided tooth structure, and the gears 70 on the two first connecting rods 612 in each pair of stirring blades 61 are all meshed with the rack 71.

[0099] As can be seen from this embodiment, by using the driving component 73 to drive the rack 71 to move up and down, and then driving the gear 70 on the first connecting rod 612 to rotate, to adjust (specifically increase) the inclination angle of the stirring blade 61, which is convenient for forming a stronger liquid circulation at the initial stage of the reaction, accelerating the mixing speed, enabling the reactants to be evenly distributed in the reaction system faster, and facilitating the faster start of the reaction.

[0100] Embodiment 5:

[0101] This embodiment provides a preparation device for a method for preparing sodium N-(8-[2-hydroxybenzoyl]-amino) octanoate. In addition to including the technical solutions of the above embodiments, it also has the following technical features. The driving component 73 includes:

[0102] A second connecting rod 730, one end extends into the chute 72 and is connected to the rack 71, the other end forms a ball head 731, and a strip-shaped groove 732 adapted to the second connecting rod 730 is opened on the inner wall of the chute 72;

[0103] The iron ring 733 is slidably installed in the device cavity 2, and an annular groove 734 adapted to the ball head 731 is provided on the surface close to the axis;

[0104] The electromagnet 735 is installed in the device cavity 2 and is used to adsorb the iron ring 733 when powered on and desorb the iron ring 733 when powered off;

[0105] Among them, the ball head 731 is slidably connected to the annular groove 734, and the electromagnet 735 is powered on and off by the trigger mechanism 8;

[0106] At the same time, the specific structure of the electromagnet 735 is the prior art and will not be elaborated here. It is fixed on the inner wall of the device cavity 2 through a mounting bracket, and a mounting hole through which the main shaft 60 passes is provided in the mounting bracket, and a gap 84 is left between the mounting hole and the surface of the main shaft 60 to avoid affecting the rotation of the main shaft 60;

[0107] Moreover, in order to reduce the frictional resistance between the ball head 731 and the inner wall of the annular groove 734, a lubricating and wear-resistant layer can be provided on the inner wall of the annular groove 734, and polytetrafluoroethylene material can be specifically used.

[0108] It can be seen from this embodiment that by triggering the electromagnet 735 to be powered on and off by the trigger mechanism 8, the adsorption and desorption of the electromagnet 735 to the iron ring 733 are controlled, so as to adjust the lifting of the rack 71. At the same time, the lifting of the rack 71 drives the rotation of the stirring blade 61, realizing an increase in the inclination angle and a restoration of the inclination angle, so that different stirring methods are presented in the initial stage and the later stage of the reaction, which is more convenient for the rapid start of the reaction in the initial stage of the reaction and to ensure the reaction stability in the later stage of the reaction;

[0109] The second connecting rod 730 facilitates the connection between the rack 71 in the main shaft 60 and the iron ring 733, and the strip-shaped groove 732 facilitates controlling and limiting the lifting range of the rack 71. The ball head 731 at one end of the second connecting rod 730 and the annular groove 734 on the iron ring 733 facilitate that when the electromagnet 735 adsorbs the iron ring 733, the second connecting rod 730 will not hinder the rotation of the main shaft 60.

[0110] Embodiment 6:

[0111] This embodiment provides a preparation device for a method for preparing sodium N-(8-[2-hydroxybenzoyl]-amino) octanoate. In addition to including the technical solutions of the above embodiments, it also has the following technical features. The trigger mechanism 8 includes:

[0112] The first electrode plate 80 is installed on the inner wall of the device cavity 2 and is provided with a first electrode piece 81;

[0113] The second electrode plate 82 is installed on the inner wall of the device cavity 2 and is provided with a second electrode piece 83, and a gap 84 is formed between it and the first electrode piece 81;

[0114] The cam disk 85 is sleeved on the main shaft 60, and a ratchet member 86 is provided between the cam disk 85 and the main shaft 60, and a trigger electrode piece 87 corresponding to the gap 84 is provided on the surface of the protruding portion of the cam disk 85;

[0115] Wherein, the first electrode piece 81 and the second electrode piece 83 are respectively electrically connected to both ends of the electrode of the electromagnet 735, and the static friction resistance between the cam disk 85 and the first electrode plate 80 and the second electrode plate 82 is greater than the mechanical resistance generated when the ratchet member 86 is not engaged;

[0116] Meanwhile, a power source is also provided to supply electrical energy to the electromagnet 735, which is the prior art and will not be elaborated here.

[0117] It can be seen from this embodiment that the two poles of the switch are formed by the first electrode plate 80 and the second electrode plate 82, and driven by the main shaft 60, the trigger electrode piece 87 on the cam disk 85 forms a connecting conductor for connecting the two poles of the switch. Then, in cooperation with the ratchet member 86, when it is necessary to switch the on-off state of the electromagnet 735, the ratchet member 86 is engaged, thereby driving the cam disk 85 to rotate, so that the trigger electrode piece 87 enters or exits between the first electrode piece 81 and the second electrode piece 83, or the ratchet member 86 is not engaged, and the electromagnet 735 remains powered on or off, thereby driving the stirring blade 61 to stir the reactants to promote the progress of the reaction;

[0118] And making the static friction resistance between the cam disk 85 and the first electrode plate 80 and the second electrode plate 82 greater than the mechanical resistance generated when the ratchet member 86 is not engaged can prevent the cam disk 85 from entering the gap 84 when it is necessary for the ratchet member 86 not to be engaged (i.e., during the stirring stage), thereby preventing the trigger electrode piece 87 from contacting the first electrode piece 81 and the second electrode piece 83, causing the angle adjustment of the stirring blade 61 and improving the stability of the system.

[0119] Embodiment 7:

[0120] This embodiment provides a preparation device for a method of preparing sodium N-(8-[2-hydroxybenzoyl]-amino) octanoate. In addition to including the technical solutions of the above embodiments, it also has the following technical features. The ratchet member 86 includes:

[0121] A bracket 860 is sleeved on the surface of the main shaft 60, and a plurality of pawls 861 are provided on the circumference, and a torsion spring is provided at the connection;

[0122] A ratchet tooth 862 is installed on the cam disk 85 and is arranged corresponding to the pawl 861;

[0123] Wherein, the cam disk 85 and the main shaft 60 are connected by a bearing;

[0124] Meanwhile, the installation of the torsion spring is prior art and will not be elaborated here.

[0125] As can be seen from this embodiment, through the setting of the bracket 860, it is convenient to install the pawl 861 on the surface of the main shaft 60. The cam disc 85 and the main shaft 60 are connected by bearings. On the one hand, it is convenient to install the cam disc 85, and on the other hand, when the pawl 861 and the ratchet tooth 862 are not engaged, relative rotation can occur between the cam disc 85 and the main shaft 60.

[0126] The embodiments of the present application have been described above in conjunction with the accompanying drawings. Without conflict, the embodiments and the features in the embodiments in the present application can be combined with each other. The present application is not limited to the above specific embodiments. The above specific embodiments are merely illustrative rather than restrictive. Under the inspiration of the present application, those of ordinary skill in the art can also make many forms without departing from the purpose of the present application and the scope protected by the claims, and all of them fall within the protection scope of the present application.

Claims

1. A preparation method of sodium N-(8-[2-hydroxybenzoyl]-amino) octanoate, characterized in that, It includes the following steps: S1: Add methyl salicylate as the raw material into the reaction vessel, add ethyl acetate as the solvent, then add 8 - aminocaprylic acid, control the temperature at 25 - 35 °C, and control the stirring speed at 200 - 300 r / min; S2: Transfer the reaction solution in S1 to a vacuum distillation device, carry out vacuum distillation for 2 - 3 h at 40 - 50 °C and a vacuum degree of -0.09 MPa to remove ethyl acetate, and naturally cool to room temperature to obtain the crude product of N-(8-[2 - hydroxybenzoyl]-amino)octanoic acid; S3: Add the crude product of N-(8-[2 - hydroxybenzoyl]-amino)octanoic acid into the reaction vessel, and add deionized water with a mass 7 - 8 times that of methyl salicylate for dissolution, and stir for 30 - 60 min for dissolution; S4: After fully stirring and dissolving, slowly add a sodium hydroxide solution with a concentration of 1 mol / L, control the reaction temperature at 25 - 30 °C, and the reaction time at 2 - 3 h until the reaction is complete; S5: Slowly add isopropanol with a mass 18 - 20 times that of methyl salicylate to the reaction solution for crystallization; after stirring evenly, let the solution stand at 0 - 5 °C for 2 - 3 h to fully precipitate the crystals; S6: Filter the reaction solution, collect the solid product, and recrystallize it with absolute ethanol; S7: Filter and dry the reaction solution to obtain sodium N-(8-[2 - hydroxybenzoyl]-amino)octanoate.

2. The preparation method of sodium N-(8-[2 - hydroxybenzoyl]-amino)octanoate according to claim 1, characterized in that: In S1, the molar ratio of methyl salicylate to 8 - aminocaprylic acid is controlled at 1:1.05 - 1.

2.

3. The preparation method of sodium N-(8-[2 - hydroxybenzoyl]-amino)octanoate according to claim 1, characterized in that: In S4, the molar ratio of sodium hydroxide to N-(8-[2 - hydroxybenzoyl]-amino)octanoic acid is 1:1.05 - 1.

2.

4. The preparation method of sodium N-(8-[2 - hydroxybenzoyl]-amino)octanoate according to claim 1, characterized in that: The specific recrystallization step in S6 is: heat to 50 - 60 °C to completely dissolve the solid, then slowly cool to room temperature, and then stand at 0 - 5 °C for 1 - 2 h to precipitate the crystals again.

5. An apparatus for the preparation method of sodium N-(8-[2-hydroxybenzoyl]-amino) octanoate according to any one of claims 1-4, characterized in that, It includes: The kettle body (1) has a device cavity (2) and a reaction cavity (3) inside, and a feed inlet (4) and a discharge outlet (5) are provided on the reaction cavity (3); The stirring mechanism (6) includes a main shaft (60), stirring blades (61) installed on the surface of the main shaft (60), and a driving motor (62) for driving the main shaft (60) to rotate; The adjusting mechanism (7) is installed in the device cavity (2) and is used to increase or restore the inclination angle of the stirring blades (61); The triggering mechanism (8) is installed in the device cavity (2) and is used to trigger the opening and closing of the adjusting mechanism (7).

6. The apparatus for the preparation method of sodium N-(8-[2-hydroxybenzoyl]-amino) octanoate according to claim 5, characterized in that, The stirring blade (61) includes: A connection end (610) is provided on the surface of the main shaft (60), and an installation cavity (611) is opened inside; The first connecting rod (612), one end of which extends into the installation cavity (611) and is connected to the inner wall of the installation cavity (611) by a bearing; The blade end (613), which is connected to the end of the first connecting rod (612) far from the connecting end (610) and is inclined; Among them, the stirring blades (61) are arranged in pairs on both radial sides of the main shaft (60).

7. The apparatus for the preparation method of sodium N-(8-[2-hydroxybenzoyl]-amino) octanoate according to claim 6, characterized in that, The adjusting mechanism (7) includes: A gear (70), which is located in the installation cavity (611) and sleeved on the surface of the first connecting rod (612); A rack (71), a chute (72) is axially opened in the main shaft (60), and the rack (71) is installed in the chute (72) and meshes with the gear (70); A driving component (73), which is installed in the equipment cavity (2) and is used to drive the rack (71) to move up and down; Among them, the two first connecting rods (612) in the stirring blades (61) arranged in pairs are respectively located on both sides of the rack (71).

8. An apparatus for the preparation method of sodium N-(8-[2-hydroxybenzoyl]-amino) octanoate according to claim 7, characterized in that, The driving component (73) includes: A second connecting rod (730), one end of which extends into the chute (72) and is connected to the rack (71), and the other end forms a ball head (731), and a strip groove (732) adapted to the second connecting rod (730) is opened on the inner wall of the chute (72); An iron ring (733), which is slidably installed in the equipment cavity (2), and an annular groove (734) adapted to the ball head (731) is opened on the surface close to the axis; An electromagnet (735), which is installed in the equipment cavity (2) and is used to adsorb the iron ring (733) when energized and desorb the iron ring (733) when powered off; Among them, the ball head (731) is slidably connected to the annular groove (734), and the electromagnet (735) is powered on and off by the trigger mechanism (8).

9. The apparatus for the preparation method of sodium N-(8-[2-hydroxybenzoyl]-amino) octanoate according to claim 8, characterized in that, The trigger mechanism (8) includes: A first electrode plate (80), which is installed on the inner wall of the equipment cavity (2) and is provided with a first electrode piece (81); A second electrode plate (82), which is installed on the inner wall of the equipment cavity (2) and is provided with a second electrode piece (83), and a gap (84) is formed between the second electrode plate (82) and the first electrode piece (81); A cam disk (85), which is sleeved on the main shaft (60), and a ratchet member (86) is arranged between the cam disk (85) and the main shaft (60), and a trigger electrode piece (87) corresponding to the gap (84) is arranged on the protruding part surface of the cam disk (85); Among them, the first electrode piece (81) and the second electrode piece (83) are respectively electrically connected to both ends of the electrode of the electromagnet (735), and the static friction resistance between the cam disk (85) and the first electrode plate (80) and the second electrode plate (82) is greater than the mechanical resistance generated when the ratchet member (86) is not engaged.

10. The apparatus for the preparation method of sodium N-(8-[2-hydroxybenzoyl]-amino) octanoate according to claim 9, characterized in that, The ratchet member (86) includes: A bracket (860), which is sleeved on the surface of the main shaft (60), and a plurality of pawls (861) are arranged on the circumference, and a torsion spring is arranged at the connection; Ratchet teeth (862), which are installed on the cam disk (85) and are arranged corresponding to the pawls (861); Among them, the cam disk (85) and the main shaft (60) are connected by a bearing.

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