Continuous process for the synthesis of 2-chloromethylthiophene

Abstract

The application discloses a continuous synthesis method of 2-chloromethyl thiophene and belongs to the technical field of chemical industry. The method comprises the following steps: adding a mixed solution of paraformaldehyde and concentrated hydrochloric acid into a decanter in initial reaction; adding formaldehyde into water phase output from the decanter and heating to 20-30 DEG C during reaction, and then sending to the top of a rectifying column; introducing HC1 gas into the bottom of the rectifying column and controlling the introduction speed to make the top of the rectifying column not discharge HC1 or discharge a small amount of HC1; adding a mixed solution of thiophene and a solvent into the upper part of the rectifying column; the reaction temperature in the rectifying column is 10-30 DEG C, and the reaction liquid at the bottom of the rectifying column is refluxed to the decanter; cooling to -5-0 DEG C in the decanter and carrying out three-phase separation, the organic phase is 2-chloromethyl thiophene mother liquor, and the water phase is continuously output to the rectifying column. The continuous production is realized by combining the principle of gas-liquid reactor design and reaction rectification, and the production efficiency is improved.

Description

Technical Field

[0001] This invention belongs to the field of chemical technology, and specifically relates to a continuous synthesis method for 2-chloromethylthiophene, and more particularly to an industrial synthesis method for 2-chloromethylthiophene. Background Technology

[0002] 2-Chloromethylthiophene is an important intermediate in the thiophene series of derivatives. Typically, 2-chloromethylthiophene is used as the first-step intermediate in the synthesis of thiophene ring intermediates. Typical downstream synthetic intermediates include 2-thiopheneacetonitrile, 2-thiopheneacetic acid, and 2-thiopheneacetyl chloride. The synthesis of 2-chloromethylthiophene utilizes the Blanc chloromethylation reaction, a process in which an aromatic or aromatic compound introduces a chloromethyl group via formaldehyde and hydrogen chloride. Typically, this reaction occurs at the α-position, generating 2-chloromethylthiophene.

[0003] Patents US2527680, US4501903, and US0161008 describe a process where hydrogen chloride gas is introduced into a mixture of thiophene, hydrochloric acid, and formaldehyde at -5°C to -10°C. After the reaction is complete, the mixture is diluted with water, and the separated organic phase is washed until neutral to obtain a 2-chloromethylthiophene compound with a yield of 61-75%. Byproducts include dithiophene methane, 3-chloromethylthiophene, and 2,5-dichloromethylthiophene.

[0004] Patent CN1511148A discloses a method for the chloromethylation of thiophene. Thiophene, methyl isobutyl ketone, hydrochloric acid, and paraformaldehyde are added to a reaction flask at a temperature of 0-5°C. HCl gas is introduced, and the reactants are added over 6 hours. After reacting for 1 hour, 2-chloromethylthiophene is obtained. This method requires the action of a ketone compound and employs a one-pot process. As the reaction continues, byproducts gradually increase, particularly the formation of high-boiling-point substances such as 2,5-dichlorothiophene and dithienyl-methane, which significantly increases the yield of thiophene and complicates subsequent separation.

[0005] All the methods described above for producing 2-chloromethylthiophene are carried out at low temperatures (around 0°C) in a reaction vessel. This method involves a vigorous reaction (especially at the hydrogen chloride inlet), which can easily lead to explosions. The low reaction temperature also results in a slow reaction rate.

[0006] Patent CN113072532 discloses a method for the continuous synthesis of 2-chloromethylthiophene using a microchannel reactor. This method utilizes two sets of premixing modules and two sets of reaction modules to obtain 2-chloromethylthiophene at room temperature. However, this method employs a relatively expensive and complex microchannel reactor, resulting in a cumbersome process and high investment. Summary of the Invention

[0007] To address the aforementioned problems, this invention provides a continuous synthesis method for 2-chloromethylthiophene. By combining a gas-liquid reactor design with the principle of reactive distillation, continuous production is achieved, thus improving production efficiency. The technical solution is as follows:

[0008] This invention provides a continuous synthesis method for 2-chloromethylthiophene, the method comprising:

[0009] Initially, a mixed solution of paraformaldehyde and concentrated hydrochloric acid is added to the decanter (depolymerization occurs simultaneously with mixing). During the reaction, formaldehyde (formaldehyde solution) is added to the aqueous phase output from the decanter and heated to 20-30°C before being sent to the top of the distillation column. HCl gas is introduced into the bottom of the distillation column, with the rate controlled to prevent or minimize HCl discharge from the top (ensuring no white smoke appears). A mixed solution of thiophene and solvent is added to the upper part of the distillation column. The reaction temperature inside the distillation column is maintained at 10-30°C, and the reaction liquid at the bottom is refluxed to the decanter. In the decanter, the temperature is lowered to -5 to 0°C, and three-phase separation is performed (paraformaldehyde is solid; some paraformaldehyde cannot depolymerize quickly and needs to be separated to avoid clogging). The organic phase is 2-chloromethylthiophene mother liquor (output intermittently or continuously, yielding the 2-chloromethylthiophene product after solvent removal and purification), while the aqueous phase is continuously output to the distillation column.

[0010] In this patent, paraformaldehyde and hydrochloric acid are mixed, depolymerized, and then fed into a decanter. The lower outlet of the decanter is connected to a circulating pump, which uses this pump to send an aqueous solution of formaldehyde and hydrochloric acid to the top of a reactive distillation column, flowing downwards. HCl gas enters from the bottom of the distillation column and flows upwards. It is absorbed countercurrently with the hydrochloric acid and formaldehyde solution from the previous step, resulting in a high HCl concentration at the top and low at the bottom of the column. Thiophene and a solvent are mixed and pumped to the top of the distillation column, flowing downwards. In the column, thiophene reacts with paraformaldehyde and hydrochloric acid to produce 2-chloromethylthiophene. The liquid phase flows by gravity from the bottom of the distillation column into the decanter, which contains cooling coils to cool the material. The cooled material separates into phases: the lower aqueous phase consists of hydrogen chloride and formaldehyde, while the upper organic phase consists of thiophene, 2-chloromethylthiophene, and the solvent. The lower aqueous phase is recycled back into the circulating pump, while the upper organic phase is collected as the product.

[0011] The concentration of added formaldehyde is 20-30 wt%, and the concentration of concentrated hydrochloric acid is ≥35 wt%.

[0012] In this patent, a specific process is used to prepare 2-chloromethylthiophene, and the raw material ratio is adjusted accordingly. The molar ratio of thiophene, paraformaldehyde, and concentrated hydrochloric acid is 1:1.1-1.5:2-3.

[0013] The mass ratio of added formaldehyde to water is 1:8-12.

[0014] In the mixed solution of thiophene and solvent, the volume ratio of thiophene to solvent is 1:0.5-1.0.

[0015] The solvent is selected from dichloromethane or trichloromethane, etc.

[0016] The distillation column is a packed column, and the packing material inside is selected from structured packing or random packing, etc.

[0017] Specifically, the packing material is selected from BX500 packing material.

[0018] Preferably, the reaction temperature inside the distillation column is 25-30℃.

[0019] Specifically, this invention provides a continuous synthesis method for 2-chloromethylthiophene, the method comprising:

[0020] During the initial reaction, a mixed solution of paraformaldehyde and concentrated hydrochloric acid with a concentration of ≥35wt% is added to the decanter, with a molar ratio of paraformaldehyde to concentrated hydrochloric acid of 1.1-1.5:2-3.

[0021] During the reaction, formaldehyde with a concentration of 20-30 wt% is added to the aqueous phase output from the decanter and heated to 20-30℃, then sent to the top of the distillation column. The mass ratio of formaldehyde to aqueous phase is 1:8-12. HCl gas is introduced into the bottom of the distillation column, and the introduction rate is controlled so that no HCl is discharged from the top of the column or only a small amount of HCl is discharged. A mixed solution of thiophene and solvent is added to the upper part of the distillation column. The volume ratio of thiophene to solvent is 1:0.5-1.0, and the molar ratio of thiophene to paraformaldehyde is 1:1.1-1.5. The reaction temperature in the distillation column is 25-30℃, and the reaction liquid at the bottom is refluxed to the decanter. In the decanter, the temperature is lowered to -5 to 0℃ and three-phase separation is performed. The organic phase is 2-chloromethylthiophene mother liquor, and the aqueous phase is continuously output to the distillation column.

[0022] The solvent is selected from dichloromethane or trichloromethane, and the packing of the distillation column is selected from BX500 packing.

[0023] The beneficial effects of the technical solution provided by the embodiments of the present invention are as follows:

[0024] (1) Compared with the method carried out in the reactor, the continuous reaction in the distillation column increases the reaction temperature and shortens the reaction time (which can reduce the production time by 20-50% (plus the preparation time)), and can efficiently synthesize 2-chloromethylthiophene.

[0025] (2) By utilizing the principle of reactive distillation, the reaction process is precisely controlled by the temperature and concentration distribution in the distillation column, which can achieve rapid main reaction (the reaction time of this patent is short. In this patent, the main reaction is fast and the side reaction is slow. In addition, due to the more uniform temperature and concentration distribution, the main reaction can also be guaranteed to proceed smoothly. In the reaction vessel, the hydrogen chloride introduced reacts rapidly with the reaction liquid, releasing a large amount of heat, which leads to local overheating and thus more side reactions. At the moment the hydrogen chloride is introduced, the hydrogen chloride is in excess relative to the reaction liquid, which will lead to the synthesis of more 2,5-dichloromethylthiophene, etc.), suppressing side reactions and chain reactions, and reducing by-products. The purity and impurity content of the product are similar to those of the microchannel reactor used in the prior art.

[0026] (3) By utilizing the principle of decanter separation, the reaction products are quickly separated, the raw materials are recycled, and the utilization rate of raw materials formaldehyde and hydrochloric acid is improved.

[0027] (4) Compared with the scheme carried out in multiple microchannel reactors, the traditional distillation column equipment and heat exchanger equipment are simple and have low investment.

[0028] (5) It realizes the continuous reaction and separation, which is easy to scale up production.

[0029] (6) The amount of organic solvent used is small, which can reduce costs and the amount of wastewater to be treated.

[0030] (7) Concentrated hydrochloric acid is recycled and HCl gas undergoes a gas-liquid countercurrent reaction, which can reduce the amount of HCl gas used (which is more difficult to store than concentrated hydrochloric acid), ensure that there is no HCl gas or only a trace amount of HCl gas at the top of the distillation column, and reduce the amount of tail gas to be treated.

[0031] (8) During production, aqueous phase separation and solid-liquid separation are achieved without the need for drying process, which reduces the difficulty of purification. Attached Figure Description

[0032] Figure 1 This is a schematic diagram of the continuous synthesis system of 2-chloromethylthiophene provided in the embodiments of the present invention.

[0033] In the diagram: 1. Aqueous phase, 2. HCl gas, 3. Mixed solution of thiophene and solvent, 4. Formaldehyde addition, 5. 2-chloromethylthiophene mother liquor, 6. Tail gas, 7. Decanter, 8. Circulating pump, 9. Heat exchanger, 10. Distillation column. Detailed Implementation

[0034] To make the objectives, technical solutions, and advantages of the present invention clearer, the present invention will be further described in detail below with reference to the accompanying drawings.

[0035] Example 1

[0036] Example 1 provides a continuous synthesis method for 2-chloromethylthiophene, the method comprising:

[0037] In the initial reaction, a mixed solution of paraformaldehyde and concentrated hydrochloric acid with a concentration of 35 wt% was added to the decanter, with a molar ratio of paraformaldehyde to concentrated hydrochloric acid of 1:1. The decanter then separated the mixed solution into solid and liquid components.

[0038] During the reaction, 24 wt% formaldehyde was added to the aqueous phase output from the decanter and heated to 25°C before being sent to the top of the distillation column. The mass ratio of formaldehyde to aqueous phase was 1:9. HCl gas was introduced into the bottom of the distillation column, with the introduction rate controlled to prevent HCl discharge from the top. A mixed solution of thiophene and dichloromethane was added to the upper part of the distillation column, with a volume ratio of thiophene to dichloromethane of 1:0.7 and a molar ratio of thiophene to paraformaldehyde of 1:1.2. The reaction temperature inside the distillation column was 27°C, and the reaction liquid at the bottom was refluxed to the decanter. In the decanter, the temperature was lowered to -5°C, and oil-water separation was performed. The organic phase was 2-chloromethylthiophene mother liquor, while the aqueous phase was continuously output to the distillation column. The 2-chloromethylthiophene mother liquor was purified to obtain 2-chloromethylthiophene.

[0039] Example 2

[0040] See Figure 1 Example 2 provides a continuous synthesis method for 2-chloromethylthiophene, the method comprising:

[0041] Aqueous phase 1 in decanter 7 is mixed with added formaldehyde 4 via circulating pump 8, then preheated to 20-30℃ in heat exchanger 9 before entering the top of distillation column 10. A mixed solution 3 of thiophene and solvent simultaneously enters from the top of distillation column 10, while HCl gas 2 enters from the bottom of distillation column 10. The gas and liquid phases react countercurrently in distillation column 10, with the reaction temperature controlled at 25-30℃. The tail gas 6 is discharged from the top of distillation column 10 (without white mist), while the liquid phase enters decanter 7 from the bottom of distillation column 9. Phase separation occurs due to the density difference between the organic and aqueous layers. 2-chloromethylthiophene mother liquor 5 (organic phase) is sent as product (subsequently purified and desolventized to obtain the final product), while aqueous phase 1 is recycled.

[0042] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A process for the continuous synthesis of 2-chloromethylthiophene, characterized in that, The method includes: In the initial reaction, a mixed solution of paraformaldehyde and concentrated hydrochloric acid with a concentration of 35 wt% was added to the decanter, with a molar ratio of paraformaldehyde to concentrated hydrochloric acid of 1:

1. The decanter was used to separate the solid and liquid components of the mixed solution. During the reaction, formaldehyde with a concentration of 24 wt% was added to the aqueous phase output from the decanter and heated to 25°C before being sent to the top of the distillation column. The mass ratio of formaldehyde to aqueous phase was 1:

9. HCl gas was introduced into the bottom of the distillation column, and the rate of introduction was controlled to prevent HCl from being discharged from the top. A mixed solution of thiophene and dichloromethane was added to the upper part of the distillation column, with a volume ratio of thiophene to dichloromethane of 1:0.7 and a molar ratio of thiophene to paraformaldehyde of 1:1.

2. The reaction temperature in the distillation column was 27°C, and the reaction liquid at the bottom was refluxed to the decanter. In the decanter, the temperature was lowered to -5°C and oil-water separation was performed. The organic phase was 2-chloromethylthiophene mother liquor, and the aqueous phase was continuously output to the distillation column. The distillation column is a packed column, and the packing material inside is selected from structured packing or random packing, and the packing material is selected from BX500 packing.

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