Preparation method of N, N-diethylaminoethanethiol

Abstract

The invention particularly relates to a preparation method of N, N-diethylaminoethanethiol in the technical field of medicines, and the preparation method comprises the following steps: ethylene carbonate and thiourea react to generate episulfide ethane, and the episulfide ethane in a gas state and diethylamine are mixed by a micro-nano bubble device and enter a tower reactor to react to prepare the N, N-diethylaminoethanethiol. The preparation method of the N, N-diethylaminoethanethiol is continuous in production, clean in process, free of emission of toxic and odorous ethane episulfide, free of self-polymerization, high in product yield, good in purity, low in cost and suitable for industrial production.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, and in particular to a method for preparing N,N-diethylaminoethanethiol. Background Technology

[0002] Currently, the industrial process commonly uses the reaction of thiocyanate with ethylene carbonate to first prepare cyclothioethane, and then the cyclothioethane reacts with diethylamine to prepare N,N-diethylaminoethanethiol. However, the process of preparing cyclothioethane by reacting thiocyanate with ethylene carbonate, for example, as described in CN200810080197.9, suffers from defects such as the reaction byproduct cyanate forming oily lumps with unreacted thiocyanate, leading to incomplete thiocyanate reaction. Furthermore, despite the use of deep cooling with condensers and sealed containers, the loss of cyclothioethane due to CO2 entrainment cannot be avoided, and the self-polymerization of cyclothioethane upon contact with moisture in the air cannot be prevented, resulting in low product yield and environmental pollution. The process for preparing N,N-diethylaminoethanethiol by reacting cyclothioethane with diethylamine, such as CN200810080197.9 and CN201110051948.6, both employ a production process in which cyclothioethane and diethylamine react in a closed batch reactor. This process suffers from drawbacks such as significant raw material volatilization losses, poor operating environment, high cost, and weak industrial competitiveness. Summary of the Invention

[0003] To address the problems existing in the prior art, this invention provides a novel method for preparing N,N-diethylaminoethanethiol. This method yields N,N-diethylaminoethanethiol with high yield, good purity, a short process flow, and no pollution.

[0004] The reaction route in the method of this invention is shown below:

[0005] Specifically, the method for preparing N,N-diethylaminoethanethiol according to the present invention includes the following steps: Under a nitrogen atmosphere, ethylene carbonate and thiourea are added to a reaction vessel and reacted at 90-130℃ to produce cyclothioethane, urea and CO2. Gaseous cyclothioethane, CO2 and diethylamine are mixed in a micro-nano bubbler and introduced into a packed tower reactor. The temperature of the tower reactor is maintained at 80~100℃ and the reaction is carried out for 3~6 hours. (3) After the reaction is complete, the reaction liquid is separated into gas and liquid by a gas-liquid separator. The gas phase is discharged and the liquid phase is distilled at atmospheric pressure to recover diethylamine. Then, it is distilled under reduced pressure to collect N,N-diethylaminoethanethiol.

[0006] Furthermore, the molar ratio of ethylene carbonate, thiourea and diethylamine is 1:1.05-1.2:1.05-1.5.

[0007] Furthermore, the height-to-diameter ratio of the tower reactor is 3-10.

[0008] Furthermore, the packing material is one or more of Raschig rings, Pall rings, and step rings.

[0009] The beneficial effects of this invention are as follows: This invention prepares cyclothioethane by reacting thiourea with ethylene carbonate. The byproducts of the reaction between thiourea and ethylene carbonate are urea and CO2. The reaction process is free of agglomeration, overcoming the shortcomings of existing technologies where the byproduct cyanate from the reaction of thiocyanate and ethylene carbonate forms oily lumps with unreacted thiocyanate, leading to incomplete thiocyanate reaction. The cyclothioethane of this invention is directly introduced into a tower reactor in a gaseous state, mixed with CO2 via a micro-nano bubbler, without the deep cooling and gas-liquid separation steps of existing technologies. This avoids losses caused by incomplete condensation of cyclothioethane due to CO2 entrainment and prevents self-polymerization of cyclothioethane upon contact with moisture in the air during condensation, thus preventing the harmful effects of cyclothioethane entering the atmosphere and being absorbed by the human body. This invention enables continuous production, eliminating the problem of raw material volatilization loss compared to existing preparation technologies. It features a short production cycle, simple processes, low energy consumption and production costs, no pollution, high product yield, and good purity, making it suitable for industrial production. Detailed Implementation

[0010] The present invention will be further described below with reference to specific embodiments, but the scope of protection of the present invention is not limited thereto. Example 1

[0011] Under a nitrogen atmosphere, 88 kg (1 kmol) of ethylene carbonate and 79.9 kg (1.05 kmol) of thiourea were added to a reactor and reacted at 90 °C to produce cyclothioethane, urea, and CO2. The gaseous cyclothioethane and CO2 discharged from the reaction were mixed with 109.6 kg (1.5 kmol) of diethylamine via a micro-nano bubbler and introduced into a tower reactor with a height-to-diameter ratio of 10 packed with Raschig rings. The temperature of the tower reactor was maintained at 100 °C, and the reaction was carried out for 3 hours. After the reaction was completed, the reaction liquid was separated by a gas-liquid separator. The gas phase was discharged, and the liquid phase was distilled at atmospheric pressure to recover diethylamine. Then, it was distilled under reduced pressure to obtain N,N-diethylaminoethanethiol with a yield of 96.0% and a purity of 99.0%. Example 2

[0012] Under a nitrogen atmosphere, 88 kg (1 kmol) of ethylene carbonate and 91.2 kg (1.2 kmol) of thiourea were added to a reactor and reacted at 130 °C to produce cyclothioethane, urea, and CO2. The gaseous cyclothioethane and CO2 discharged from the reaction were mixed with 76.7 kg (1.05 kmol) of diethylamine via a micro-nano bubbler and introduced into a tower reactor with a height-to-diameter ratio of 6 packed with Pall ring packing. The temperature of the tower reactor was maintained at 90 °C, and the reaction was carried out for 4 hours. After the reaction was completed, the reaction liquid was separated into gas and liquid phases by a gas-liquid separator. The gas phase was discharged, and the liquid phase was distilled at atmospheric pressure to recover diethylamine. Then, it was distilled under reduced pressure to obtain N,N-diethylaminoethanethiol with a yield of 96.3% and a purity of 99.2%. Example 3

[0013] Under a nitrogen atmosphere, 88 kg (1 kmol) of ethylene carbonate and 83.7 kg (1.1 kmol) of thiourea were added to a reactor and reacted at 110 °C to produce cyclothioethane, urea, and CO2. The gaseous cyclothioethane and CO2 discharged from the reaction were mixed with 87.7 kg (1.2 kmol) of diethylamine via a micro-nano bubbler and introduced into a tower reactor with a height-to-diameter ratio of 3 packed with stepped ring packing. The temperature of the tower reactor was maintained at 80 °C, and the reaction was carried out for 6 hours. After the reaction was completed, the reaction liquid was separated into gas and liquid phases by a gas-liquid separator. The gas phase was discharged, and the liquid phase was distilled at atmospheric pressure to recover diethylamine. Then, it was distilled under reduced pressure to obtain N,N-diethylaminoethanethiol with a yield of 95.3% and a purity of 99.1%. Example 4

[0014] Under a nitrogen atmosphere, 88 kg (1 kmol) of ethylene carbonate and 83.7 kg (1.1 kmol) of thiourea were added to a reactor and reacted at 120 °C to produce cyclothioethane, urea, and CO2. The gaseous cyclothioethane and CO2 discharged from the reaction were mixed with 95 kg (1.3 kmol) of diethylamine via a micro-nano bubble apparatus and fed into a tower reactor with a height-to-diameter ratio of 5 packed with Pall ring packing. The temperature of the tower reactor was maintained at 95 °C, and the reaction was carried out for 4 hours. After the reaction was completed, the reaction liquid was separated into gas and liquid phases by a gas-liquid separator. The gas phase was discharged, and the liquid phase was distilled at atmospheric pressure to recover diethylamine. Then, it was distilled under reduced pressure to obtain N,N-diethylaminoethanethiol with a yield of 97.0% and a purity of 99.2%.

Claims

1. A method for preparing N,N-diethylaminoethanethiol, characterized in that, The preparation method includes the following steps: (1) Under a nitrogen atmosphere, ethylene carbonate and thiourea are added to a reaction vessel and reacted at 90-130℃ to produce cyclothioethane, urea and CO2. (2) Gaseous cyclothioethane, CO2 and diethylamine are mixed in a micro-nano bubbler and introduced into a tower reactor filled with packing material. The temperature of the tower reactor is maintained at 80~100℃ and the reaction is carried out for 3~6 hours. (3) After the reaction is complete, the reaction liquid is separated by a gas-liquid separator. The gas phase is discharged and the liquid phase is distilled at atmospheric pressure to recover diethylamine. Then, it is distilled under reduced pressure to collect N,N-diethylaminoethanethiol.

2. The method for preparing N,N-diethylaminoethanethiol according to claim 1, characterized in that, The molar ratio of ethylene carbonate, thiourea and diethylamine is 1:1.05-1.2:1.05-1.

5.

3. The method for preparing N,N-diethylaminoethanethiol according to claim 1, characterized in that, The height-to-diameter ratio of the tower reactor is 3-10; the packing material is one or more of Raschig rings, Pall rings, and step rings.

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