A method for preparing difluoromethanesulfonyl chloride

Abstract

This invention relates to the field of fluorine-containing fine chemicals, specifically disclosing a method for preparing difluoromethanesulfonyl chloride. The specific steps include: adding an alkaline solution, a phase transfer catalyst, benzyl mercaptan, and R22 to a reaction vessel; closing the vessel and reacting under set conditions; taking the upper organic phase for alkaline washing and vacuum distillation to obtain the intermediate benzyl difluoromethyl sulfide; mixing water and benzyl difluoromethyl sulfide, controlling the reaction temperature, and introducing chlorine gas for reaction; subsequently purging with nitrogen gas at room temperature and stopping stirring to separate the phases; drying the organic phase with a dehydrating agent, filtering, and vacuum distillation to obtain difluoromethanesulfonyl chloride. This method effectively improves the selectivity and yield of difluoromethanesulfonyl chloride.

Description

Technical Field

[0001] This invention belongs to the field of fluorine-containing fine chemicals technology, specifically relating to a method for preparing difluoromethanesulfonyl chloride. Background Technology

[0002] Difluoromethanesulfonyl chloride molecular formula: CHCIFOS, density: 1.696 g / cm³ 3 Its vapor pressure at 25°C is 79.9 mmHg, flash point is 5°C, and boiling point is 84.7°C. Difluoromethanesulfonyl chloride exhibits excellent chemical reactivity and can undergo many useful chemical reactions. It is a very useful difluoromethylating reagent, characterized by mild reaction conditions, simple operation, good chemical selectivity, and easy scale-up. Furthermore, as a difluoromethyl radical source, difluoromethanesulfonyl chloride provides a relatively simple reaction system, eliminating the need for complex ligands to promote the reaction, and resulting in milder reaction conditions.

[0003] CN115594617B discloses a method for synthesizing difluoromethanesulfonyl chloride, comprising the following steps: adding benzyl mercaptan to a Freon-22 solution to obtain solution A; adding tetrabutylammonium bromide to an aqueous sodium hydroxide solution to obtain solution B; passing solutions A and B into a continuous flow microreactor, removing the lower aqueous phase from the mixture obtained by the reaction, and performing vacuum distillation on the upper organic phase to obtain an intermediate; dissolving the intermediate in a solvent to obtain an intermediate solution, passing the intermediate solution and chlorosulfonic acid solution into a continuous flow microreactor, and distilling the mixture obtained by the reaction to obtain the target product difluoromethanesulfonyl chloride.

[0004] CN116063208A discloses a method for synthesizing difluoromethanesulfonyl chloride. First, benzyl isothiourea salt is prepared using benzyl chloride and thiourea as raw materials. Then, in a bilayer system of water and organic components, benzyl isothiourea salt reacts with halodifluoromethane to obtain benzyl difluoromethyl sulfide in the presence of a phase transfer catalyst. The benzyl difluoromethyl sulfide reacts with chlorine gas in the aqueous phase to generate difluoromethanesulfonyl chloride.

[0005] The method for preparing difluoromethanesulfonyl chloride (IN1572DEL2010A) yields a product with good yield and high purity in the presence of chlorooxidation difluoromethylbenzyl sulfide in water and water-immiscible organic solvents.

[0006] Existing methods suffer from unavailable and expensive raw materials, making cost control difficult. They also have high requirements for equipment and facilities, hindering cost control. Furthermore, the reactants have poor solubility, resulting in low product yields, making them unsuitable for large-scale production. Summary of the Invention

[0007] To solve the above problems, the present invention adopts the following technical solution:

[0008] A method for preparing difluoromethanesulfonyl chloride, characterized by comprising the following steps:

[0009] Step 1: Add 30-50 parts by weight of alkaline solution, 3-10 parts by weight of phase transfer catalyst, 100-150 parts by weight of benzyl mercaptan, and 80-100 parts by weight of R22 to the reactor. After closing the reactor, react at 90-95℃ for 4-5 hours. Take the upper organic phase, wash it with alkali, and then distill it under reduced pressure to obtain the intermediate benzyl difluoromethyl sulfide.

[0010] Step 2: Mix 70-80 parts water and 20-30 parts benzyl difluoromethyl sulfide, control the reaction temperature at 10-15℃, and introduce 25-35 parts chlorine gas over 150-210 minutes. After the reaction is complete, purge with nitrogen at room temperature and stop stirring. After separation, dry the organic phase with a dehydrating agent, filter, and distill under reduced pressure to obtain difluoromethanesulfonyl chloride.

[0011] Furthermore, the alkaline solution mentioned in step one is potassium hydroxide, sodium hydroxide, or lithium hydroxide.

[0012] Furthermore, the mass concentration of the alkaline solution in step one is 30%-40%.

[0013] Furthermore, the synthesis scheme for the phase transfer catalyst described in step one is carried out according to the following steps:

[0014] Take 16 to 32 parts by weight of (2-mercaptoethyl)trimethylammonium chloride, 30 to 60 parts by weight of 1,4-disacryloylpiperazine, 0.05 to 0.6 parts by weight of (1-amino-2,2,2-trifluoroethyl)phosphonic acid / cerium complex, and 1 to 4 parts by weight of 8-diazacyclo[5,4,0]undecene-7; add the above raw materials to 200 to 300 parts by volume of toluene, and stir at 50 to 70 degrees Celsius for 30 to 100 minutes; remove the solvent by vacuum evaporation to obtain the desired phase transfer catalyst.

[0015] Further, the preparation method of the (1-amino-2,2,2-trifluoroethyl)phosphonic acid / cerium complex is as follows:

[0016] Take 18 to 36 parts by weight of (1-amino-2,2,2-trifluoroethyl)phosphonic acid, 24 to 48 parts by weight of cerium trichloride, and 300 to 500 parts by volume of anhydrous ethanol according to the mass fractions; stir at room temperature for 100 to 180 minutes to carry out the complexation reaction; after the reaction is completed, remove the solvent by vacuum evaporation to obtain the (1-amino-2,2,2-trifluoroethyl)phosphonic acid / cerium complex.

[0017] Furthermore, the alkaline washing solution mentioned in step one is one or more of sodium hydroxide, sodium carbonate, and sodium bicarbonate solutions.

[0018] Furthermore, the dehydrating agent mentioned in step two is one or more of anhydrous sodium sulfate, anhydrous magnesium sulfate, and anhydrous sodium carbonate.

[0019] Furthermore, in step two, the temperature of the vacuum distillation is below 60°C, and the absolute pressure is 0.001-0.01 MPa. After the vacuum distillation of difluoromethanesulfonyl chloride is completed, the temperature can be increased and vacuum distillation can continue to recover the raw material benzyl chloride.

[0020] The reaction equation for difluoromethanesulfonyl chloride is:

[0021]

[0022] The reaction mechanism of the phase transfer catalyst described in step one is as follows:

[0023] (2-Mercaptoethyl)trimethylammonium chloride undergoes a mercapto addition reaction with 1,4-disacryloylpiperazine; (1-amino-2,2,2-trifluoroethyl)phosphonic acid / cerium complex undergoes an amino addition reaction with 1,4-disacryloylpiperazine; thus, the desired phase transfer catalyst is obtained.

[0024] The thiol group (-SH) in (2-mercaptoethyl)trimethylammonium chloride undergoes a Michael addition reaction with the double bond in 1,4-disacryloylpiperazine. This reaction connects the two molecules by forming a thioether bond, thereby generating a new intermediate.

[0025] The amino group in the (1-amino-2,2,2-trifluoroethyl)phosphonic acid / cerium complex undergoes a Michael addition reaction with the double bond in 1,4-disacryloylpiperazine to form a carbon-nitrogen single bond.

[0026] Technical effect

[0027] 1. Improve reaction efficiency: The use of phase transfer catalysts can significantly accelerate the reaction rate and shorten the reaction time, thereby improving the overall synthesis efficiency.

[0028] 2. Enhanced product selectivity: Specific phase transfer catalysts can improve the selectivity of specific products, reduce the formation of by-products, and obtain purer target products.

[0029] 3. Simplified post-processing: Reactions using phase transfer catalysts can often reduce solvent usage and lessen the environmental burden. At the same time, due to the high efficiency of the reaction, the separation and purification of products in the post-processing is also simplified. Attached Figure Description

[0030] Figure 1 The infrared spectrum of difluoromethylsulfonyl chloride prepared in Example 2. Detailed Implementation

[0031] In view of the shortcomings of the prior art, the inventors of this case, through long-term research and extensive practice, have proposed the technical solution of this invention, which will be further explained below, including its implementation process and principles.

[0032] Example Evaluation Method:

[0033] Detection was performed using a gas chromatograph with the following conditions: injection volume: 1 μL; injection port temperature: 280℃; split ratio: 10:1; column flow rate: 9 mL / min (carrier gas: high-purity nitrogen); constant flow rate; column temperature: 35℃ for 3 min, increasing to 80℃ at 5℃ / min and holding for 5 min, increasing to 120℃ at 20℃ / min and holding for 1 min. Detection conditions using a flame ionization detector (FID): temperature: 260℃; air flow rate: 300 mL / min; hydrogen flow rate: 30 mL / min; make-up gas flow rate (high-purity nitrogen): 20 mL / min.

[0034] Example 1

[0035] A method for preparing difluoromethanesulfonyl chloride includes the following steps:

[0036] Step 1: Add 30g of 30% sodium hydroxide, 3g of phase transfer catalyst, 100g of benzyl mercaptan, and 80g of R22 (refrigerant) to the reaction vessel. After closing the vessel, react at 90℃ for 4 hours. Take the upper organic phase, wash it with sodium hydroxide alkali, and then distill it under reduced pressure to obtain the intermediate benzyl difluoromethyl sulfide.

[0037] Step 2: Mix 70g of water and 20g of benzyl difluoromethyl sulfide, control the reaction temperature at 10℃, and introduce 25g of chlorine gas over 150min. After the reaction is complete, the organic phase is dehydrated by anhydrous sodium sulfate, dried, filtered, and recovered by vacuum distillation to obtain difluoromethanesulfonyl chloride.

[0038] The synthesis scheme of the phase transfer catalyst described in step one is as follows:

[0039] 16 g of (2-mercaptoethyl)trimethylammonium chloride, 30 g of 1,4-disacryloylpiperazine, 0.05 g of (1-amino-2,2,2-trifluoroethyl)phosphonic acid / cerium complex, and 1 g of 8-diazacyclic [5,4,0]undecene-7 were added to 200 ml of toluene and stirred at 50 °C for 30 minutes. The solvent was removed by vacuum evaporation to obtain the desired phase transfer catalyst.

[0040] The preparation method of (1-amino-2,2,2-trifluoroethyl)phosphonic acid / cerium complex is as follows:

[0041] 18 g of (1-amino-2,2,2-trifluoroethyl)phosphonic acid, 24 g of cerium trichloride, and 300 ml of anhydrous ethanol were added. The mixture was stirred at room temperature for 100 minutes to carry out the complexation reaction. After the reaction was completed, the solvent was removed by vacuum evaporation to obtain the (1-amino-2,2,2-trifluoroethyl)phosphonic acid / cerium complex.

[0042] Example 2

[0043] A method for preparing difluoromethanesulfonyl chloride includes the following steps:

[0044] Step 1: Add 40g of 35% potassium hydroxide, 7g of phase transfer catalyst, 125g of benzyl mercaptan, and 90g of R22 (refrigerant) to the reaction vessel. After closing the vessel, react at 93℃ for 4.5h. Take the upper organic phase, wash it with sodium carbonate alkali, and then distill it under reduced pressure to obtain the intermediate benzyl difluoromethyl sulfide.

[0045] Step 2: Mix 75g of water and 25g of benzyl difluoromethyl sulfide, control the reaction temperature at 13℃, and pass chlorine gas through the mixture for 30h over 180min. After the reaction is complete, the organic phase is dried with anhydrous magnesium sulfate dehydrating agent, filtered, and recovered by vacuum distillation to obtain difluoromethanesulfonyl chloride.

[0046] The synthesis scheme of the phase transfer catalyst described in step one is as follows:

[0047] 19 g of (2-mercaptoethyl)trimethylammonium chloride, 45 g of 1,4-diacryloylpiperazine, 0.3 g of (1-amino-2,2,2-trifluoroethyl)phosphonic acid / cerium complex, and 2.5 g of 8-diazacyclic [5,4,0]undecene-7 were added to 250 ml of toluene and stirred at 60 °C for 65 minutes. The solvent was removed by vacuum evaporation to obtain the desired phase transfer catalyst.

[0048] The preparation method of (1-amino-2,2,2-trifluoroethyl)phosphonic acid / cerium complex is as follows:

[0049] 27 g of (1-amino-2,2,2-trifluoroethyl)phosphonic acid, 36 g of cerium trichloride, and 400 ml of anhydrous ethanol were used to carry out the complexation reaction by stirring at room temperature for 100 to 180 minutes. After the reaction was completed, the solvent was removed by vacuum evaporation to obtain the (1-amino-2,2,2-trifluoroethyl)phosphonic acid / cerium complex.

[0050] Example 3

[0051] A method for preparing difluoromethanesulfonyl chloride includes the following steps:

[0052] Step 1: Add 50g of 40% lithium hydroxide alkaline solution, 10g of phase transfer catalyst, 150g of benzyl mercaptan, and 100g of R22 (refrigerant) to the reaction vessel. After closing the vessel, react at 95℃ for 5h. Take the upper organic phase, wash it with sodium bicarbonate alkali, and then distill it under reduced pressure to obtain the intermediate benzyl difluoromethyl sulfide.

[0053] Step 2: Mix 80g of water and 30g of benzyl difluoromethyl sulfide, control the reaction temperature at 15℃, and introduce 35g of chlorine gas over 210 minutes. After the reaction is complete, the organic phase is dried with anhydrous sodium carbonate dehydrating agent, filtered, and recovered by vacuum distillation to obtain difluoromethanesulfonyl chloride.

[0054] The synthesis scheme of the phase transfer catalyst described in step one is as follows:

[0055] 32 g of (2-mercaptoethyl)trimethylammonium chloride, 60 g of 1,4-diacryloylpiperazine, 0.6 g of (1-amino-2,2,2-trifluoroethyl)phosphonic acid / cerium complex, and 4 g of 8-diazacyclic [5,4,0]undecene-7 were added to 300 ml of toluene and stirred at 70 °C for 100 minutes. The solvent was removed by vacuum evaporation to obtain the desired phase transfer catalyst.

[0056] The preparation method of (1-amino-2,2,2-trifluoroethyl)phosphonic acid / cerium complex is as follows:

[0057] 36 g of (1-amino-2,2,2-trifluoroethyl)phosphonic acid, 48 g of cerium trichloride, and 500 ml of anhydrous ethanol were used to carry out the complexation reaction by stirring at room temperature for 180 minutes. After the reaction was completed, the solvent was removed by vacuum evaporation to obtain the (1-amino-2,2,2-trifluoroethyl)phosphonic acid / cerium complex.

[0058] Comparative Example 1

[0059] In this example, no phase transfer catalyst is added in step one, and the remaining steps are the same as in Example 1.

[0060] Comparative Example 2

[0061] In this example, (2-mercaptoethyl)trimethylammonium chloride is not added to the phase transfer catalyst in step one, and the remaining steps are consistent with those in Example 1.

[0062] Comparative Example 3

[0063] In this example, the (1-amino-2,2,2-trifluoroethyl)phosphonic acid / cerium complex is not added to the phase transfer catalyst in step one, and the remaining steps are consistent with those in Example 1.

[0064] The test results are shown in Table 1.

[0065] Table 1

[0066] Example 1 80.1％ 80.5％ Example 2 81.4％ 81.8％ Example 3 82.6％ 83.1％ Comparative Example 1 71.3％ 72.3％ Comparative Example 2 75.7％ 75.3％ Comparative Example 3 76.2％ 76.4％

[0067] Through data analysis of the above examples and comparative examples, this method effectively improves the selectivity and yield of difluoromethanesulfonyl chloride.

[0068] It should be understood that the above embodiments are merely illustrative of the technical concept and features of the present invention, and are intended to enable those skilled in the art to understand the content of the present invention and implement it accordingly. They should not be construed as limiting the scope of protection of the present invention. All equivalent changes or modifications made in accordance with the spirit and essence of the present invention should be covered within the scope of protection of the present invention.

Claims

1. A method for preparing difluoromethanesulfonyl chloride, characterized in that, Includes the following steps: Step 1: Add 30-50 parts by weight of alkaline solution, 3-10 parts by weight of phase transfer catalyst, 100-150 parts by weight of benzyl mercaptan, and 80-100 parts by weight of R22 to the reactor. After closing the reactor, react at 90-95℃ for 4-5 hours. Take the upper organic phase, wash it with alkali, and then distill it under reduced pressure to obtain the intermediate benzyl difluoromethyl sulfide. Step 2: Mix 70-80 parts of water and 20-30 parts of benzyl difluoromethyl sulfide, control the reaction temperature at 10-15℃, and introduce 25-35 parts of chlorine gas over 150-210 minutes. After the reaction is complete, purge with nitrogen at room temperature and stop stirring. After separation, dry the organic phase with a dehydrating agent, filter, and distill under reduced pressure to obtain difluoromethanesulfonyl chloride. The synthesis scheme of the phase transfer catalyst described in step one is as follows: According to the mass fractions, take 16 to 32 parts by weight of (2-mercaptoethyl)trimethylammonium chloride, 30 to 60 parts by weight of 1,4-disacryloylpiperazine, 0.05 to 0.6 parts by weight of (1-amino-2,2,2-trifluoroethyl)phosphonic acid / cerium complex, and 1 to 4 parts by weight of 8-diazacyclic [5,4,0]undecene-7; add the above raw materials to 200 to 300 parts by volume of toluene, and stir at 50 to 70 degrees Celsius for 30 to 100 minutes; remove the solvent by vacuum evaporation to obtain the desired phase transfer catalyst; The preparation method of the (1-amino-2,2,2-trifluoroethyl)phosphonic acid / cerium complex is as follows: Take 18 to 36 parts by weight of (1-amino-2,2,2-trifluoroethyl)phosphonic acid, 24 to 48 parts by weight of cerium trichloride, and 300 to 500 parts by volume of anhydrous ethanol according to the mass fractions; stir at room temperature for 100 to 180 minutes to carry out the complexation reaction; after the reaction is completed, remove the solvent by vacuum evaporation to obtain the (1-amino-2,2,2-trifluoroethyl)phosphonic acid / cerium complex.

2. The method for preparing difluoromethanesulfonyl chloride according to claim 1, characterized in that, The alkaline solution mentioned in step one is potassium hydroxide, sodium hydroxide, or lithium hydroxide.

3. The method for preparing difluoromethanesulfonyl chloride according to claim 1, characterized in that, The mass concentration of the alkaline solution mentioned in step one is 30%-40%.

4. The method for preparing difluoromethanesulfonyl chloride according to claim 1, characterized in that, The alkaline washing solution mentioned in step one is one or more of sodium hydroxide, sodium carbonate, and sodium bicarbonate solutions.

5. The method for preparing difluoromethanesulfonyl chloride according to claim 1, characterized in that, The dehydrating agent mentioned in step two is one or more of anhydrous sodium sulfate, anhydrous magnesium sulfate, and anhydrous sodium carbonate.

6. The method for preparing difluoromethanesulfonyl chloride according to claim 1, characterized in that, In step two, the temperature of the vacuum distillation is below 60°C and the absolute pressure is 0.001-0.01 MPa. After the vacuum distillation of difluoromethanesulfonyl chloride is completed, the temperature can be increased and vacuum distillation can continue to recover the raw material benzyl chloride.

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