A method for preparing a thioester compound

Abstract

This invention provides a method for preparing thioester compounds, comprising: (1) mixing sulfur-containing reactants with a propylene solvent, dissolving them to obtain a mixed organic solution; and (2) conveying the mixed organic solution obtained in step (1) to a microchannel reactor for a continuous flow rearrangement reaction to obtain the thioester compounds. The production method provided by this invention is safe and controllable, enabling continuous production, reducing environmental pollution from byproducts, and requiring less space in the reaction equipment. Furthermore, by using a propylene solvent with a high flash point and high boiling point, this invention can reduce the pressure load on the reaction equipment during the high-temperature continuous flow rearrangement reaction, thereby lowering the pressure level of the chemical reaction and improving safety.

Description

Technical Field

[0001] This invention belongs to the field of chemical engineering technology and relates to a method for producing thioester compounds, specifically a continuous flow preparation method for thioester compounds. Background Technology

[0002] Thioesters are a vital class of skeletal molecules found in various natural products and pharmaceutical molecules, attracting significant attention due to their unique properties. They serve as important intermediates in many fields. Polythioesters (PTEs), formed by the ring-opening polymerization of cyclic thioesters, possess valuable properties distinct from their oxyester counterparts, demonstrating immense potential in materials science. The role of thioesters in biochemistry is equally significant, including in peptide bond and protein formation, and the acetyltransfer of acetyl-CoA. These highly efficient acyling agents are also commonly used in organic synthesis to construct esters, aldehydes, ketones, thioethers, and alkenyl thioethers.

[0003] Currently, the main method for synthesizing thioesters is the direct acylation reaction of thiols with carboxylic acids and their derivatives. However, transition metal-catalyzed carbonylation reactions have emerged as an alternative strategy for thioester synthesis in recent years, attracting widespread attention. These reactions mostly use thiols as the commonly used sulfur source, but their main limitation lies in their unpleasant odor and tendency to poison the catalyst. Therefore, the development and application of sulfur sources in carbonylation reactions for thioester synthesis has significant potential and warrants further in-depth research.

[0004] CN 112239384A discloses a method for preparing thioester compounds. The method includes the following steps: adding a nickel catalyst, a ligand, molybdenum carbonyl, a base, zinc iodide, water, arylboronic acid, and sulfonyl chloride to an organic solvent, reacting at 110–130°C for 15–20 hours, and after complete reaction, post-treatment to obtain the thioester compound. While this patented method can achieve efficient synthesis of thioester compounds, the synthesis method is relatively complex and requires a wide variety of raw materials.

[0005] Sulfur-containing organic compounds can be prepared through simple continuous flow reactions. However, existing continuous flow reactions typically use conventional reactors or other reaction equipment at atmospheric pressure and high temperature, which presents the following technical problems: 1. The reaction generates irritating gases, causing environmental pollution; 2. Conventional equipment occupies a large space; 3. The reaction liquid temperature, ambient temperature, and discharge liquid temperature are all high, leading to poor safety; 4. During rearrangement reactions, pressure has little effect on the reaction rate, while temperature is crucial; high temperatures result in more side reactions and even carbonization; low temperatures may lead to incomplete reactions or no rearrangement reaction. Furthermore, rearrangement often requires high reaction temperatures, and when using low-boiling-point solvents (Class A or Class B solvents), the continuous flow equipment experiences high back pressure and heavy pressure load. In the event of splashing, Class A or Class B solvents, due to their low boiling point, can cause fires or other accidents. Summary of the Invention

[0006] To address the shortcomings of existing technologies, the present invention aims to provide a method for preparing thioester compounds. The preparation method of the present invention utilizes a propionic acid solvent with high flash point and high boiling point, which reduces the pressure load on the reaction equipment during the preparation process (continuous flow rearrangement high-temperature reaction), lowers the pressure level of the chemical reaction, and improves safety. Furthermore, the preparation method enables continuous production and reduces environmental pollution from byproducts.

[0007] To achieve this objective, the present invention employs the following technical solution:

[0008] This invention provides a method for preparing thioester compounds, the method comprising the following steps:

[0009] (1) Mix sulfur-containing reactants with a type C solvent, and dissolve them to obtain a mixed organic solution;

[0010] (2) The mixed organic solution obtained in step (1) is subjected to a continuous flow rearrangement reaction to obtain the thioester compound;

[0011] The structural formula of the sulfur-containing reactant is: Wherein, R is selected from aryl groups with a number of substituted or unsubstituted C atoms not less than 6; the substituents include any one of halogens, straight-chain or branched alkyl or fluorinated alkyl groups of C1 to C6, and straight-chain or branched alkoxy or fluorinated alkoxy groups of C1 to C6.

[0012] R' is selected from -NR1R2, wherein R1 and R2 are each independently selected from H, and any one of straight-chain or branched alkyl groups from C1 to C6.

[0013] In this invention, by using acetic acid solvents with high flash points and high boiling points, the pressure load on the reaction equipment can be reduced during high-temperature rearrangement reactions, the pressure level of the chemical reaction can be reduced, safety can be improved, and the severity of accidents such as splashing can be mitigated. Furthermore, due to the high flash point of acetic acid solvents, serious accidents such as fires are less likely to occur.

[0014] Furthermore, this invention allows the raw materials to flow and react effectively in a high-temperature continuous flow device by mixing sulfur-containing reactants with a class C solvent.

[0015] Preferably, R is

[0016] X1, X2 and X3 are each independently selected from any one of -H, -F, -Cl, methyl, trifluoromethyl, methoxy or trifluoromethoxy;

[0017] R3 and R4 are each independently selected from any one of halogens, C1-C6 straight-chain or branched alkyl or fluorinated alkyl groups, C1-C6 straight-chain or branched alkoxy groups, fluorinated alkoxy groups, or phenyl groups; at least one -H in the phenyl group may be substituted with -CN, -F, -Cl, -CH3, or -OCH3.

[0018] More specifically, the preparation process of the thioester compounds described in this invention is as follows:

[0019]

[0020] As a preferred embodiment of the present invention, the class C solvent includes any one or a combination of at least two of trichlorobenzene, dichlorobenzene, γ-valerolactone, C12-C16 isoalkanes or dipropylene glycol dimethyl ether. Typical but non-limiting combinations include: a combination of trichlorobenzene and dichlorobenzene, trichlorobenzene and γ-valerolactone, dichlorobenzene and γ-valerolactone, or a combination of trichlorobenzene, dichlorobenzene, γ-valerolactone, C12-C16 isoalkanes or dipropylene glycol dimethyl ether; preferably trichlorobenzene and / or dichlorobenzene.

[0021] It is worth noting that the Class C solvent described in this invention has a high flash point and a high boiling point; wherein, the flash point of the Class C solvent is ≥60℃, for example, it can be 60℃, 65℃, 70℃, 75℃ or 80℃, etc., but is not limited to the listed values, and other unlisted values ​​within the range are also applicable.

[0022] Preferably, the boiling point of the C-type solvent is >150°C, for example, it can be 152°C, 155°C, 160°C, 165°C or 170°C, etc., but is not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0023] Preferably, the mass ratio of the sulfur-containing reactant to the C-type solvent is 1:1 to 20, for example, it can be 1:1, 1:4, 1:8, 1:12, 1:16 or 1:20, but is not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0024] Preferably, the dissolution temperature in step (1) is 0 to 100°C, for example, it can be 0°C, 20°C, 40°C, 60°C, 80°C or 100°C, but is not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0025] As a preferred embodiment of the present invention, the continuous flow rearrangement reaction in step (2) is carried out in a microchannel reaction device.

[0026] Preferably, the microchannel reaction device includes a feed pump, a reaction zone coil, a cooling zone coil, a back pressure valve, and a receiver arranged in sequence.

[0027] The microchannel reaction device described in this invention is a near-closed reaction device, which can reduce the emission of irritating gases and reduce environmental pollution; and it occupies less space.

[0028] In addition, both the reaction zone coil and the cooling zone coil are temperature-controlled via an oil bath;

[0029] Furthermore, by combining the microchannel reaction device and C-type dissolution, the present invention enables the mixed organic solution to achieve a conversion rate and yield superior to that in conventional reactors within a continuous flow reaction time, reducing the occurrence of related side reactions. At the same time, it avoids abnormal fluctuations in temperature and concentration during the reaction process, eliminating runaway and overheating phenomena. The reaction process is safe and controllable, and continuous production reaction is possible. In addition, the space occupied by the equipment is much smaller than that of traditional conventional equipment, improving the utilization rate of production space.

[0030] As a preferred embodiment of the present invention, the feed pump is selected from any one of a plunger pump, a diaphragm pump, or a peristaltic pump, preferably a plunger pump or a diaphragm pump.

[0031] Preferably, the materials of the reaction zone coil and the cooling zone coil are each independently selected from any one of stainless steel 316L, Monel alloy, Hastelloy alloy or silicon carbide, with Hastelloy alloy being preferred.

[0032] As a preferred embodiment of the present invention, the diameter of the tubing of the microchannel reaction device is 0.1 to 20 mm, for example, it can be 0.1 mm, 1 mm, 4 mm, 8 mm, 12 mm, 16 mm or 20 mm, but is not limited to the listed values. Other unlisted values ​​within the range are also applicable; preferably 6 mm.

[0033] As a preferred technical solution of the present invention, the specific operation of the continuous flow rearrangement reaction in step (2) includes: the mixed organic solution in step (1) is fed to the reaction zone coil by the feed pump for heating reaction, then kept warm and flowed to the cooling zone coil for cooling treatment, and then the sulfur ester compound is collected into the receiver after pressure control treatment by the back pressure valve.

[0034] It is worth noting that the present invention further includes pretreatment of the microchannel reaction device before the mixed organic solution in step (1) is transported to the microchannel reaction device.

[0035] Preferably, the pretreatment specifically includes the following operations: firstly, a class C solvent is pumped into the reaction device through a feed pump, and the back pressure valve is adjusted to control the pressure, and the temperatures of the reaction zone coil and the cooling zone coil are set; and during the heating process, the class C solvent is pumped in through a feed pump in a circulating manner.

[0036] In addition, after the continuous flow rearrangement reaction described in step (2) of the present invention, the following steps are also included: after the product is pumped out, an appropriate amount of C-type solvent is pumped in through the feed pump to displace the reaction liquid in the reaction zone of the microchannel reaction device.

[0037] As a preferred embodiment of the present invention, the temperature of the heating reaction is 200-300°C, for example, 200°C, 220°C, 240°C, 260°C, 280°C or 300°C, but is not limited to the listed values. Other unlisted values ​​within the range are also applicable; preferably 255-260°C.

[0038] In this invention, the heating reaction temperature is 200-300°C. If the reaction temperature is too high, it will lead to an increase in side reactions during the reaction process, or even carbonization of the product; if the reaction temperature is too low, it will lead to a slow reaction rate or no reaction, thereby reducing the reaction efficiency.

[0039] Preferably, the heat preservation flow time is 1 to 120 minutes, for example, it can be 1 minute, 10 minutes, 20 minutes, 40 minutes, 60 minutes, 80 minutes, 100 minutes or 120 minutes, but is not limited to the listed values. Other unlisted values ​​within the range are also applicable; preferably 40 minutes.

[0040] In this invention, the heat preservation flow time is 1 to 120 minutes. If the heat preservation flow time is too long, it will lead to an increase in side reactions during the reaction process, or even carbonization of the product; conversely, if the heat preservation flow time is too short, it will lead to incomplete reaction, thereby affecting the reaction efficiency.

[0041] Preferably, the temperature of the cooling treatment is 0 to 100°C, for example, it can be 0°C, 10°C, 20°C, 30°C, 40°C, 50°C, 60°C, 70°C, 80°C, 90°C or 100°C, but is not limited to the listed values. Other unlisted values ​​within the range are also applicable; preferably 40 to 50°C.

[0042] In this invention, the temperature of the cooling process is 0 to 100°C. If the temperature of the cooling process is too low, it will cause the product to precipitate and block the pipes; if the temperature is too high, it will cause the reaction liquid to be hot, which may cause safety risks such as burns.

[0043] Preferably, the flow rate of the mixed organic solution in the microchannel reaction device is 1 to 1000 ml / min, for example, it can be 1 ml / min, 10 ml / min, 100 ml / min, 200 ml / min, 400 ml / min, 600 ml / min, 800 ml / min or 1000 ml / min, but is not limited to the listed values, and other unlisted values ​​within the range are also applicable; preferably 200 ml / min.

[0044] Preferably, the final pressure of the pressure control treatment is 0.1 to 5 MPa, for example, it can be 0.1 MPa, 1 MPa, 2 MPa, 3 MPa, 4 MPa or 5 MPa, but is not limited to the listed values. Other unlisted values ​​within the range are also applicable; preferably 0.8 to 1.2 MPa.

[0045] Preferably, the preparation method further includes distilling the product in the receiver to remove the propyl solvent.

[0046] The numerical range described in this invention includes not only the point values ​​listed above, but also any point values ​​within the numerical ranges not listed above. Due to space limitations and for the sake of brevity, this invention will not exhaustively list all the specific point values ​​included in the range.

[0047] Compared with the prior art, the present invention has the following beneficial effects:

[0048] (1) The method for preparing thioester compounds provided by the present invention utilizes a class C solvent with high flash point and high boiling point, which can reduce the pressure load of the reaction equipment during the high-temperature rearrangement reaction, reduce the pressure level of the chemical reaction, improve safety, and mitigate the degree of accident in the event of splashing or other unexpected situations.

[0049] (2) The production method provided by the present invention can achieve a conversion rate and yield that are superior to those in conventional reactors, and reduce the occurrence of related side reactions;

[0050] (3) The microchannel reaction device used in the preparation method of thioester compounds provided by the present invention occupies less space and is almost a closed reaction device, which can reduce the emission of irritating gases and reduce environmental pollution.

[0051] (4) The post-processing temperature of the preparation method of the thioester compounds provided by the present invention is relatively low, which is beneficial to the improvement of safety performance. Attached Figure Description

[0052] Figure 1 This is a schematic diagram of the microchannel reaction device provided in a specific embodiment of the present invention;

[0053] Figure 2 This is a mass spectrum of the thioester compound provided in Example 1 of the present invention;

[0054] Figure 3 This is a mass spectrum of the thioester compounds provided in Example 2 of the present invention;

[0055] Among them, 1 is the feed pump, 2 is the reaction zone coil, 3 is the cooling zone coil, 4 is the back pressure valve, and 5 is the receiver. Detailed Implementation

[0056] The technical solution of the present invention will be further illustrated below through specific embodiments. Those skilled in the art should understand that the embodiments described are merely illustrative of the present invention and should not be construed as limiting the invention in any way.

[0057] In one specific embodiment, the present invention provides a method for preparing thioester compounds, the method comprising the following steps:

[0058] (1) Mix sulfur-containing reactants with a type C solvent, and dissolve them to obtain a mixed organic solution;

[0059] The mass ratio of the sulfur-containing reactant to the C-type solvent is 1:1 to 20; the dissolution temperature is 0 to 100°C.

[0060] The Class C solvents include any one or a combination of at least two of the following: trichlorobenzene, dichlorobenzene, γ-valerolactone, C12-C16 isoalkanes, or dipropylene glycol dimethyl ether.

[0061] (2) First, the C-type solvent is pumped into the reaction device by the feed pump 1, and the back pressure valve 4 is adjusted to control the pressure and set the temperature of the reaction zone coil 2 and the cooling zone coil 3; and the C-type solvent is pumped into the reaction device by the feed pump 1 during the heating process.

[0062] After the temperature of the reaction zone coil 2 and the cooling zone coil 3 reaches the set temperature and stabilizes, the mixed organic solution obtained in step (1) is transported to the microchannel reaction device for continuous flow rearrangement reaction to obtain the sulfur ester compound.

[0063] Finally, after the mixed organic solution obtained in step (1) has been pumped out, continue to pump in an appropriate amount of C-type solvent to displace the reaction solution in the reaction zone.

[0064] like Figure 1 As shown, the microchannel reaction device includes a feed pump 1, a reaction zone coil 2, a cooling zone coil 3, a back pressure valve 4, and a receiver 5 connected in sequence; the pipe diameter of the microchannel reaction device is 0.1-20 mm.

[0065] The specific operation of the continuous flow rearrangement reaction includes: in step (1), the mixed organic solution is fed to the reaction zone coil at a flow rate of 1 to 1000 ml / min by a feed pump for heating and reaction, and then kept at the temperature for 1 to 120 min to the cooling zone coil for cooling treatment. After that, the pressure is controlled to 0.1 to 5 MPa by a back pressure valve and the thioester compounds are collected into the receiver.

[0066] The heating reaction temperature is 200–300°C; the cooling treatment temperature is 0–100°C.

[0067] Example 1

[0068] This embodiment provides a method for preparing thioester compounds, the method comprising the following steps:

[0069] (1) Mix 3 kg of sulfur-containing reactant ((4-ethoxy-2',3,3'-trifluoro-[1,1'-biphenyl]-2-yl)dimethylaminothiocarbamate) with 15 kg of propyl solvent (o-dichlorobenzene) in a 20 L solvent tank, and obtain a mixed organic solution after dissolution;

[0070] (2) First, the peristaltic pump 1 is used to pump the material into the peristaltic pump. Figure 1 In the microchannel reaction apparatus shown, a propyl solvent (o-dichlorobenzene) is circulated in, the flow rate is set to 200 ml / min, and the back pressure valve 4 is adjusted to control the pressure to 1 MPa. The temperature of the reaction zone coil 2 is set to 257°C and the temperature of the cooling zone coil 3 is set to 50°C through an oil bath. During the heating process, the propyl solvent (o-dichlorobenzene) is circulated in through a peristaltic pump 1.

[0071] After the temperatures of the reaction zone coil 2 and the cooling zone coil 3 reach the set temperature and stabilize, the mixed organic solution obtained in step (1) is transported to the microchannel reaction device for continuous flow rearrangement reaction, and the thioester compound ((4-ethoxy-2',3,3'-trifluoro-[1,1'-biphenyl]-2-yl)dimethylaminothioester) is collected into the receiver 5; wherein, the holding time is 40 min;

[0072] Finally, after the mixed organic solution obtained in step (1) has been pumped out, continue to pump in an appropriate amount of C-type solvent to displace the reaction solution in the reaction zone.

[0073] In this embodiment, both the reaction zone coil 2 and the cooling zone coil 3 are Hastelloy alloy coils with an inner diameter of 6 mm; the synthesis process of the thioester compound is as follows:

[0074]

[0075] Example 2

[0076] This embodiment provides a method for preparing thioester compounds, the method comprising the following steps:

[0077] (1) Mix 50g of sulfur-containing reactant ((4-butoxy-2',3,3'-trifluoro-[1,1'-biphenyl]-2-yl)dimethylaminothiocarbamate) with 150g of propionic solvent (γ-valerol) in a 1L beaker and dissolve at room temperature to obtain a mixed organic solution.

[0078] (2) First, the piston pump 1 is used to pump the fluid into the piston. Figure 1 The microchannel reaction apparatus shown is circulated with a propionic solvent (γ-valerolactone), the flow rate is set to 1.5 ml / min, and the back pressure valve 4 is adjusted to control the pressure to 1 MPa. The temperature of the reaction zone coil 2 is set to 255°C and the temperature of the cooling zone coil 3 is set to 50°C through an oil bath. During the heating process, the propionic solvent (γ-valerolactone) is circulated through a plunger pump 1.

[0079] After the temperatures of the reaction zone coil 2 and the cooling zone coil 3 reach the set temperature and stabilize, the mixed organic solution obtained in step (1) is transported to a microchannel reaction device for continuous flow rearrangement reaction, and the thioester compound ((4-butoxy-2',3,3'-trifluoro-[1,1'-biphenyl]-2-yl)dimethylaminothiocarbamate) is collected into receiver 5; wherein, the holding time is 55 min.

[0080] Finally, after the mixed organic solution obtained in step (1) has been pumped out, an appropriate amount of propionic acid solvent (γ-valerol) is pumped in to displace the reaction solution in the reaction zone.

[0081] In this embodiment, both the reaction zone coil 2 and the cooling zone coil 3 are Hastelloy alloy coils with an inner diameter of 1.1 mm; the synthesis process of the thioester compound is as follows:

[0082]

[0083] Example 3

[0084] This embodiment provides a method for preparing thioester compounds, the only difference between this method and Example 1 is that:

[0085] In this embodiment, the propylene solvent mentioned in step (1) is adjusted to dipropylene glycol dimethyl ether.

[0086] Example 4

[0087] This embodiment provides a method for preparing thioester compounds, the only difference between this method and Example 1 is that:

[0088] In this embodiment, the C-type solvent mentioned in step (1) is changed to ethanol.

[0089] Example 5

[0090] This embodiment provides a method for preparing thioester compounds, the only difference between this method and Example 1 is that:

[0091] In this embodiment, the C-type solvent mentioned in step (1) is changed to acetone.

[0092] Example 6

[0093] This embodiment provides a method for preparing thioester compounds, the only difference between this method and Example 1 is that:

[0094] In this embodiment, the heat preservation flow time in step (2) is adjusted to 150 min.

[0095] Example 7

[0096] This embodiment provides a method for preparing thioester compounds, the only difference between this method and Example 1 is that:

[0097] This embodiment omits the back pressure valve in the microchannel reaction device described in step (2).

[0098] Example 8

[0099] This embodiment provides a method for preparing thioester compounds, the only difference between this method and Example 1 is that:

[0100] In this embodiment, the pressure controlled by the back pressure valve in step (2) is adjusted to 8MPa.

[0101] Example 9

[0102] This embodiment provides a method for preparing thioester compounds, the only difference between this method and Example 1 is that:

[0103] This embodiment omits the cooling zone coil in the microchannel reaction device described in step (2).

[0104] Example 10

[0105] This embodiment provides a method for preparing thioester compounds, the only difference between this method and Example 1 is that:

[0106] In this embodiment, the inner diameters of the reaction zone coil 2 and the cooling zone coil 3 in the microchannel reaction device described in step (2) are both adjusted to 25 mm.

[0107] Example 11

[0108] This embodiment provides a method for preparing thioester compounds, the only difference between this method and Example 1 is that:

[0109] In this embodiment, the microchannel reaction device used in the continuous flow rearrangement reaction described in step (2) is adjusted to a conventional reaction device;

[0110] The conventional reaction apparatus includes a heated reaction vessel, a condenser, and post-processing equipment.

[0111] Comparative Example 1

[0112] This comparative example provides a method for preparing a thioester compound, the only difference between this method and Example 1 is that:

[0113] This comparative example omits the mixing process of the C-type solvent described in step (1).

[0114] The thioester compounds provided in the above embodiments and comparative examples were distilled, and the purity of the products was detected by gas chromatography. The results are shown in Table 1.

[0115] In addition, the operating status of the microchannel reaction device during the preparation process provided in the above embodiments and comparative examples is shown in Table 1.

[0116] Table 1

[0117] purity / % Operating status of the reaction device Example 1 96 Stable operation Example 2 95 Stable operation Example 3 85 Stable operation Example 4 87 The device was under overpressure, resulting in a liquid output rate far lower than the set flow rate and an extended feed time. Example 5 80 The device was under overpressure, resulting in a liquid output rate far below the set flow rate; the feed time was extended. Example 6 84 Stable operation Example 7 10 Spraying device Example 8 78 The device was under overpressure, resulting in a liquid output rate far lower than the set flow rate and an extended feed time. Example 9 92 The liquid temperature is high, and a mist-like liquid is sprayed out. Example 10 65 The liquid flow is intermittent, the flow rate is unstable, and the back pressure valve experiences pressure loss. Example 11 94 Unable to achieve continuous production Comparative Example 1 84 The output product is dark in color and contains carbonized particles.

[0118] According to Table 1, the following points can be observed:

[0119] (1) Comprehensive analysis of Examples 1 and 2 shows that the method provided by the present invention can efficiently obtain high-purity thioester compounds with a purity of ≥95%, with a yield of up to 100%.

[0120] Additionally, regarding the mass spectrum of the product provided in Example 1 (e.g.) Figure 2 The mass spectrum of the main peak (355) shown in Example 2 is 17%; Figure 3 As shown in the figure, the abundance of the main peak (383) is 15%.

[0121] (2) A comprehensive analysis of Examples 1, 3-5 and Comparative Example 1 shows that the choice of Class C solvent has an impact;

[0122] Compared to C-type solvents, choosing ethanol or acetone as solvents will increase the pressure load on the reaction apparatus during the reaction process, reduce safety, and result in a liquid output that is far lower than the set flow rate.

[0123] If the mixing of the C-type solvent is omitted, the output product will be dark in color and contain carbonized particles, with more side reaction impurities, thereby reducing the purity of the product.

[0124] (3) A comprehensive analysis of Examples 1 and 6-10 shows that the selection of process conditions and the setting of the apparatus in the continuous flow rearrangement reaction described in step (2) will affect the process or result of the reaction.

[0125] When the heat preservation flow time is too long (as in Example 6), it will cause the product to react excessively, resulting in a larger amount of by-products and thus reducing the purity of the product.

[0126] When the microchannel reaction device is not equipped with a back pressure valve, the pressure in the reaction tube cannot be maintained, resulting in material spraying and a significant decrease in the purity of the obtained product.

[0127] When the back pressure valve pressure control pressure in the continuous flow rearrangement reaction is too high, it will lead to an increase in equipment pressure load, reduced safety, and a liquid output rate that is far lower than the set flow rate.

[0128] When the cooling zone coil is not set in the continuous flow rearrangement reaction, the reaction liquid obtained after the first reaction will have a mist sprayed out due to the high outlet temperature, which will affect the product yield.

[0129] When the inner diameter of the reaction zone coil 2 and the cooling zone coil 3 in the microchannel reaction device is too large, it will cause cavities to easily form in the pipeline during the operation of the equipment, resulting in unstable pressure in the pipeline, unstable liquid flow rate, and pressure loss of the back pressure valve, which will cause safety problems in the reaction device during the reaction process.

[0130] (4) Comprehensive analysis of Examples 1 and 11 shows that if the reaction equipment is adjusted to a conventional heating reactor and cooler, continuous reaction cannot be achieved (i.e., the reaction needs to be produced in batches). The ambient temperature is high during the reaction process, and there is an irritating odor. There are safety issues during the production process, which does not meet the green production process standards. In addition, the post-processing process is more complicated than that of continuous flow equipment.

[0131] In summary, the production method provided by this invention is safe and controllable, enables continuous production, reduces environmental pollution from byproducts, and requires less space in the reaction equipment. In addition, by using high flash point and high boiling point propylene solvents, this invention can reduce the pressure load on the reaction equipment during continuous flow rearrangement high-temperature reactions, thereby reducing the pressure level of the chemical reaction and improving safety.

[0132] The applicant declares that the above description is only a specific embodiment 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 conceived by those skilled in the art within the technical scope disclosed in the present invention fall within the protection and disclosure scope of the present invention.

Claims

1. A method for producing a thioester compound, characterized by, The preparation method includes the following steps: (1) Mix sulfur-containing reactants with a type C solvent, and dissolve them to obtain a mixed organic solution; (2) The mixed organic solution obtained in step (1) is subjected to a continuous flow rearrangement reaction to obtain the thioester compound; The structural formula of the sulfur-containing reactant is: Wherein, R is selected from aryl groups with a number of substituted or unsubstituted C atoms not less than 6; the substituents include any one of halogens, straight-chain or branched alkyl or fluorinated alkyl groups of C1 to C6, and straight-chain or branched alkoxy or fluorinated alkoxy groups of C1 to C6. R' is selected from -NR1R2, wherein R1 and R2 are each independently selected from H, and any one of straight-chain or branched alkyl groups from C1 to C6.

2. The preparation method according to claim 1, characterized in that, The R is wherein X1, X2and X3are each independently selected from any one of -H, -F, -Cl, methyl, trifluoromethyl, methoxy or trifluoromethoxy; R3 and R4 are each independently selected from any one of halogens, C1-C6 straight-chain or branched alkyl or fluorinated alkyl groups, C1-C6 straight-chain or branched alkoxy or fluorinated alkoxy groups, or phenyl groups; at least one -H in the phenyl group may be substituted with -CN, -F, -Cl, -CH3 or -OCH3.

3. The production method according to claim 1 or 2, characterized by, The class C solvent includes any one or a combination of at least two of the following: trichlorobenzene, dichlorobenzene, γ-valerolactone, C12-C16 isoalkanes or dipropylene glycol dimethyl ether, preferably trichlorobenzene and / or dichlorobenzene; Preferably, the mass ratio of the sulfur-containing reactant to the C-type solvent is 1:1 to 20; Preferably, the dissolution temperature in step (1) is 0 to 100°C.

4. The production method according to any one of claims 1 to 3, characterized by, The continuous flow rearrangement reaction described in step (2) is carried out in a microchannel reactor. Preferably, the microchannel reaction device includes a feed pump, a reaction zone coil, a cooling zone coil, a back pressure valve, and a receiver arranged in sequence.

5. The preparation method according to claim 4, characterized in that, The feed pump is selected from any one of a plunger pump, a diaphragm pump, or a peristaltic pump, preferably a plunger pump or a diaphragm pump. Preferably, the materials of the reaction zone coil and the cooling zone coil are each independently selected from any one of stainless steel 316L, Monel alloy, Hastelloy alloy or silicon carbide, with Hastelloy alloy being preferred.

6. The preparation method according to claim 4, characterized in that, The diameter of the tubing in the microchannel reaction device is 0.1–20 mm, preferably 6 mm.

7. The preparation method according to claim 4, characterized in that, The specific operation of the continuous flow rearrangement reaction in step (2) includes: the mixed organic solution in step (1) is fed to the reaction zone coil by the feed pump for heating and reaction, then kept warm and flowed to the cooling zone coil for cooling treatment, and then the sulfur ester compound is collected into the receiver after pressure control treatment by the back pressure valve.

8. The preparation method according to claim 7, characterized in that, The temperature of the heating reaction is 200–300°C, preferably 255–260°C; Preferably, the heat preservation flow time is 1 to 120 minutes, more preferably 40 minutes; Preferably, the temperature of the cooling treatment is 0–100°C, more preferably 40–50°C.

9. The preparation method according to claim 7, characterized in that, The flow rate of the mixed organic solution in the microchannel reaction device is 1 to 1000 ml / min, preferably 200 ml / min.

10. The method of claim 7, wherein, The final pressure of the pressure control process is 0.1 to 5 MPa, preferably 0.8 to 1.2 MPa.

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