Preparation method of methyl trifluoromethanesulfonate

Abstract

The invention relates to the technical field of fine chemical engineering, in particular to a preparation method of methyl trifluoromethanesulfonate, which comprises the following steps: adding trifluoromethanesulfonic acid into a reaction kettle, adding a catalyst 4-dimethylaminopyridine under the conditions of cooling and stirring, and continuously stirring to obtain a pre-reaction system; raising the temperature, dropwise adding dimethyl carbonate, and after dropwise adding is completed, continuously reacting to obtain a mixed solution containing a product methyl trifluoromethanesulfonate; standing and layering to obtain an organic phase and a water phase; taking an organic phase, rectifying at normal pressure, and collecting fractions to obtain a product methyl trifluoromethanesulfonate; and taking a water phase, carrying out reduced pressure distillation, removing water, and recovering the catalyst. 4-dimethylaminopyridine is used as a catalyst to catalyze trifluoromethanesulfonic acid to react with dimethyl carbonate to prepare methyl trifluoromethanesulfonate. Compared with the prior art, the method has the advantages that steps and devices are simple, the used catalyst is low in toxicity and small in dosage, no organic solvent is used, and harm to human health is reduced.

Description

Technical Field

[0001] The invention relates to the technical field of fine chemicals, and in particular to a method for preparing methyl trifluoromethanesulfonate. Background Art

[0002] Methyl trifluoromethanesulfonate is an important monomethylating agent in organic synthesis, mainly used as an intermediate in organic synthesis and pharmaceutical synthesis. The trifluoromethanesulfonyl group of trifluoromethanesulfonate compounds has a strong electron-withdrawing ability, and its reaction activity is much higher than that of conventional alkylating agents, such as chloro compounds or alkyl sulfonates. Since these compounds are very active, only methyl trifluoromethanesulfonate is relatively stable, while other trifluoromethanesulfonates are prone to side reactions such as elimination and rearrangement, and need to be synthesized and post-processed under mild conditions.

[0003] In the prior art, methyl trifluoromethanesulfonate is prepared by the following common production processes: (1) trifluoromethanesulfonic acid and potassium carbonate are first salified, and the resulting salt is then reacted with dimethyl sulfate in an organic solvent dimethylformamide (DMF) to prepare methyl trifluoromethanesulfonate. The process steps are complicated and a large amount of organic solvent is used; (2) trimethyl orthoformate is reacted with trifluoromethanesulfonic anhydride and distilled to obtain methyl trifluoromethanesulfonate. The process steps are simple, but the raw material trifluoromethanesulfonic anhydride is expensive; (3) Patent application document CN202311564121.4 discloses the reaction of trifluoromethanesulfonic acid with dimethyl carbonate under the catalysis of thionyl chloride to prepare methyl trifluoromethanesulfonate. Trifluoromethanesulfonic acid is added to the reactor, thionyl chloride is added dropwise at room temperature, and then the temperature is raised to 60-80°C, dimethyl carbonate is added dropwise, the reaction is kept warm for 2-8h, and then distilled at normal pressure to remove the front fraction, collect the fraction at 94-99°C, and obtain methyl trifluoromethanesulfonate. The process only requires one step of reaction to obtain the product and does not use organic solvents. However, the process uses thionyl chloride as a toxic chemical, and its rat inhalation LC50 is 2435 mg / m 3 , which is equivalent to a weight ratio of 1.486 mg / kg. (4) In another process, trifluoromethanesulfonic acid and dimethyl carbonate react under the catalysis of benzoyl chloride to synthesize methyl trifluoromethanesulfonate, and then distill to obtain the product methyl trifluoromethanesulfonate. This method has simple steps, but the rat inhalation LC50 of its catalyst benzoyl chloride is 1870 mg / m 3 , which is not only highly toxic but also expensive.

[0004] Therefore, it is urgent to find a catalyst with lower toxicity and less usage for the reaction of preparing methyl trifluoromethanesulfonate using trifluoromethanesulfonic acid and dimethyl carbonate as reactants. Summary of the invention

[0005] In order to solve the technical problem that the catalyst used in the preparation of methyl trifluoromethanesulfonate in the prior art is too toxic, the present invention provides a method for preparing methyl trifluoromethanesulfonate, wherein the product is synthesized through a one-step reaction, the steps are simple, and 4-dimethylaminopyridine (DMAP) is used as a catalyst, which has low toxicity, small dosage and higher catalytic efficiency.

[0006] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0007] A method for preparing methyl trifluoromethanesulfonate comprises the following steps:

[0008] S1, preparation of a pre-reaction system: adding trifluoromethanesulfonic acid to a reaction kettle, cooling to 0°C to 20°C, adding a catalyst 4-dimethylaminopyridine under stirring conditions, and continuing stirring to obtain a pre-reaction system;

[0009] S2, reaction: heating the pre-reaction system, adding dimethyl carbonate dropwise, so that the molar ratio of trifluoromethanesulfonic acid: catalyst: dimethyl carbonate in the reaction system is (2-2.1): (0.03-0.08): 1, after the addition is complete, continuing the reaction for 4-8 hours to obtain a mixed solution containing the product methyl trifluoromethanesulfonate;

[0010] S3, standing and stratifying: standing and stratifying the mixed solution to obtain an organic phase and an aqueous phase;

[0011] S4, atmospheric distillation: take the organic phase, perform atmospheric distillation, collect the fractions, and obtain the product methyl trifluoromethanesulfonate.

[0012] Preferably, in S1, the stirring speed is 100 r / min to 200 r / min, and the stirring time is 0.5 h to 1 h.

[0013] Preferably, in S2, the pre-reaction system is heated to 60°C to 80°C, and the temperature is always maintained at 60°C to 80°C before the reaction is terminated.

[0014] Preferably, the entire process of S2 is carried out under stirring conditions, and the stirring speed is the same as the stirring speed of S1.

[0015] Preferably, in S2, the dropping speed of dimethyl carbonate is controlled to be 1d / 2s to 5d / s.

[0016] Preferably, in S3, the standing time of the mixed solution is 2 h to 3 h, and after the mixed solution is separated into layers, the upper layer is the organic phase and the lower layer is the aqueous phase.

[0017] Preferably, in S4, the atmospheric distillation temperature is 100°C to 120°C, and the fraction is collected when the outlet temperature reaches 92°C to 99°C.

[0018] Preferably, the aqueous phase in S3 is taken and distilled under reduced pressure to remove water, and then the catalyst is recovered. The recovered catalyst 4-dimethylaminopyridine is further used to prepare methyl trifluoromethanesulfonate.

[0019] Preferably, the operating conditions of the reduced pressure distillation are a pressure of -0.05Mpa to -0.09Mpa and a temperature of 70°C to 100°C.

[0020] Based on the above technical solutions, the present invention has the following beneficial effects:

[0021] 1. The present invention uses trifluoromethanesulfonic acid and dimethyl carbonate as reactants, and synthesizes the product methyl trifluoromethanesulfonate through a one-step reaction under the action of a catalyst. Not only is the step simple, the reaction conditions are mild, and the use of an organic solvent is avoided.

[0022] 2. The product mixture obtained by the reaction of the present invention is sequentially subjected to static stratification and atmospheric distillation to obtain a purified product, thereby improving the purity of the product methyl trifluoromethanesulfonate, and the product mixture can be purified by a simple distillation device.

[0023] 3. Compared with the catalysts benzoyl chloride and thionyl chloride used in the prior art, the present invention uses 4-dimethylaminopyridine (DMAP) as a catalyst, which has low toxicity, and its rat inhalation LC50 is only 530 mg / m 3 , reducing the harm to human health.

[0024] In summary, the reaction for preparing dimethyl carbonate in the present invention is simple, and the use of organic solvents is avoided. The catalyst 4-dimethylaminopyridine used has low toxicity and a small amount, and the prepared product has high purity. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] In order to more clearly illustrate the specific implementation of the present invention or the technical solution in the prior art, the drawings required for use in the specific implementation or the description of the prior art will be briefly introduced below.

[0026] Figure 1 It is a process flow chart of the preparation method of methyl trifluoromethanesulfonate of the present invention. DETAILED DESCRIPTION

[0027] In order to further explain the technical means and effects adopted by the present invention to achieve the predetermined application purpose, a clear and complete description is given below in conjunction with the accompanying drawings and preferred embodiments.

[0028] The reactor involved in the present invention is a jacketed reactor with stirring, the jacket contains water, and both the refrigerant and the heat medium are external circulation systems. The distillation kettle involved in the present invention is a jacketed distillation kettle with stirring, the jacket contains heat transfer oil, which is operated by the external circulation system of the hot oil machine, and the temperature control is linked to the automatic valve of the heat transfer oil inlet.

[0029] The raw materials involved in the present invention are trifluoromethanesulfonic acid, dimethyl carbonate and 4-dimethylaminopyridine (DMAP), and the raw material information is shown in Table 1. The detection items and indicators of the product methyl trifluoromethanesulfonate prepared by the present invention are shown in Table 2.

[0030] Table 1 Raw material information

[0031]

[0032] Table 2 Detection items and indicators of methyl trifluoromethanesulfonate

[0033]

[0034]

[0035] The specific embodiments are as follows:

[0036] Example 1

[0037] This embodiment provides a method for preparing methyl trifluoromethanesulfonate. The process flow of the preparation method is as follows: Figure 1 As shown, the specific steps include:

[0038] 304.5 g of trifluoromethanesulfonic acid was delivered to a jacketed reactor with a volume of 500 mL via a feed pump, and the temperature was lowered to 10° C. 6.1 g (0.05 mol) of catalyst 4-dimethylaminopyridine (DMAP) was added under stirring at a speed of 150 r / min, and stirring was continued for 45 min to obtain a pre-reaction system; the temperature was raised to 70° C., 90 g (84.1 mL) of dimethyl carbonate was pumped into a quantitative tank, and dimethyl carbonate was started to be added dropwise, and the dropping rate was controlled to 1 d / s. After the addition was completed, the temperature was controlled at 7 The mixture was reacted at 0°C for 6 hours to obtain a mixed solution containing the product methyl trifluoromethanesulfonate; the stirring was stopped and the mixed solution was allowed to stand for 2.5 hours to allow the liquid to separate into layers to obtain an upper organic phase and a lower aqueous phase; the organic phase was separated and then distilled at atmospheric pressure at a distillation temperature of 110°C, and the fractions were collected when the outlet temperature reached 96°C to obtain methyl trifluoromethanesulfonate; the aqueous phase remaining in the reactor was taken and distilled under reduced pressure at a pressure of -0.07Mpa and a temperature of 85°C to remove water, and the remaining aqueous phase DMAP was reused as a catalyst.

[0039] Under the action of catalyst DMAP, the principle equation for the reaction of trifluoromethanesulfonic acid and dimethyl carbonate is:

[0040] 2CF3SO3H+(CH3O)2CO→2CF3SO2OCH3+H2O+CO2

[0041] The prepared product methyl trifluoromethanesulfonate was tested by indicators, and the test results are shown in Table 3.

[0042] Table 3 Product testing data table of Example 1

[0043]

[0044] Example 2

[0045] This embodiment provides a method for preparing methyl trifluoromethanesulfonate. The process flow of the preparation method is as follows: Figure 1 As shown, the specific steps include:

[0046] 300 g of trifluoromethanesulfonic acid was delivered to a jacketed reactor with a volume of 500 mL via a feeding pump, and the temperature was lowered to 0° C. 3.66 g of catalyst 4-dimethylaminopyridine (DMAP) was added under stirring at a speed of 200 r / min, and stirring was continued for 0.5 h to obtain a pre-reaction system; the temperature was raised to 60° C., 90 g (84.1 mL) of dimethyl carbonate was pumped into a quantitative tank, the temperature was controlled at 60° C., dimethyl carbonate was started to be added dropwise, and the dropping rate was controlled to 1 d / 2 s. After the addition was completed, the temperature was controlled at 60° C. ℃ for 8h to obtain a mixed solution containing the product methyl trifluoromethanesulfonate; stop stirring, let the mixed solution stand for 2h to separate the liquid, and obtain an upper organic phase and a lower aqueous phase; separate the organic phase and perform atmospheric distillation at 100℃, collect the fraction when the outlet temperature reaches 92℃, and obtain methyl trifluoromethanesulfonate; take the aqueous phase remaining in the reactor, and perform vacuum distillation at a pressure of -0.09Mpa and a temperature of 70℃ to remove water, and the remaining aqueous phase DMAP is reused as a catalyst. The prepared product methyl trifluoromethanesulfonate is tested by indicators, and the test results are shown in Table 3.

[0047] Table 4 Example 2 Product Testing Data Table

[0048]

[0049] Example 3

[0050] This embodiment provides a method for preparing methyl trifluoromethanesulfonate. The process flow of the preparation method is as follows: Figure 1 As shown, the specific steps include:

[0051] 315 g of trifluoromethanesulfonic acid was delivered to a jacketed reactor with a volume of 500 mL via a feed pump, cooled to 20° C., 9.76 g of catalyst 4-dimethylaminopyridine (DMAP) was added under stirring at a speed of 100 r / min, and stirring was continued for 1 h to obtain a pre-reaction system; the temperature was raised to 80° C., 90 g (84.1 mL) of dimethyl carbonate was pumped into a quantitative tank, the temperature was controlled at 80° C., dimethyl carbonate was added dropwise, and the dropping rate was controlled to 5 d / s. After the addition was completed, the temperature was controlled at 80° C. The reaction was carried out for 4 hours to obtain a mixed solution containing the product methyl trifluoromethanesulfonate; the stirring was stopped, and the mixed solution was allowed to stand for 3 hours to allow the liquid to separate, to obtain an upper organic phase and a lower aqueous phase; the organic phase was separated and then distilled at normal pressure, the distillation temperature was 120°C, and the fraction was collected when the outlet temperature reached 99°C, to obtain methyl trifluoromethanesulfonate; the aqueous phase remaining in the reactor was taken, and the water was removed by vacuum distillation under the conditions of a pressure of -0.05Mpa and a temperature of 100°C, and the remaining aqueous phase DMAP was reused as a catalyst. The prepared product methyl trifluoromethanesulfonate was tested by indicators, and the test results are shown in Table 3.

[0052] Table 5 Example 3 Product Testing Data Table

[0053]

[0054]

[0055] Comparative Example 1

[0056] The difference between this comparative example and Example 1 is that the catalyst used is 10.71 g (0.09 mol) of thionyl chloride, and the other reaction conditions are the same, and finally the product methyl trifluoromethanesulfonate is obtained. After testing, the product methyl trifluoromethanesulfonate has a transparent liquid appearance, a purity of 95.1%, a water content of 0.3853%, and a Hazen color of 35.

[0057] Compared with Example 1, the purity of the product methyl trifluoromethanesulfonate in Comparative Example 1 is 95.1%, which is lower than the purity of 99.6% of the product prepared in Example 1. At the same time, the product of Comparative Example 1 has high water content, high chroma and high catalyst dosage, indicating that the preparation method of Example 1 is better and the obtained product quality is higher.

[0058] In addition, the rat inhalation LC50 of the catalyst DMAP in Example 1 is 530 mg / m 3 The rat inhalation LC50 of the catalyst thionyl chloride in this comparative example is 2435 mg / m 3 , which is equivalent to 1.486 mg / kg in weight ratio. Therefore, the toxicity of the catalyst used in Example 1 is greatly reduced.

[0059] Comparative Example 2

[0060] The difference between this comparative example and Example 1 is that the catalyst used is 7.05 g (0.05 mol) of benzoyl chloride, and the other reaction conditions are the same, and finally the product methyl trifluoromethanesulfonate is obtained. After testing, the product methyl trifluoromethanesulfonate has an appearance of a transparent liquid, a purity of 94.7%, a water content of 0.5953%, and a Hazen chromaticity of 68.

[0061] Comparative Example 1 and Example 1 use the same molar number of catalysts, but the product methyl trifluoromethanesulfonate in Comparative Example 1 has low purity, high water content and high chroma, indicating that the product obtained by the preparation method of Example 1 is of higher quality and the catalytic effect of the catalyst DMAP is better.

[0062] In addition, the rat inhalation LC50 of the catalyst DMAP in Example 1 is 530 mg / m 3 The rat inhalation LC50 of the catalyst benzoyl chloride in this comparative example is 1870 mg / m 3 Therefore, the toxicity of the catalyst used in Example 1 is greatly reduced.

[0063] In summary of the above technical scheme, the present invention uses 4-dimethylaminopyridine (DMAP) as a catalyst to catalyze the reaction of trifluoromethanesulfonic acid and dimethyl carbonate to prepare methyl trifluoromethanesulfonate. The steps are simple, and the desired product can be synthesized through only one-step reaction, and the reaction process does not involve the participation of organic solvents in the reaction and the harsh conditions reaction, which shortens the reaction time, reduces the process cost, and has a simple impurity removal process, which provides a reliable process guarantee for the industrial development of methyl trifluoromethanesulfonate. In addition, compared with the catalysts benzoyl chloride and thionyl chloride used in the prior art, the catalyst 4-dimethylaminopyridine used in the present invention has low toxicity and small consumption, which reduces the harm to human health.

[0064] The above description is only a preferred embodiment of the present invention and does not limit the present invention in any form. Although the present invention has been disclosed as a preferred embodiment as above, it is not used to limit the present invention. Any technical personnel in this field can make some changes or modify the technical contents disclosed above into equivalent embodiments without departing from the scope of the technical solution of the present invention. However, any brief modifications, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention are still within the scope of the technical solution of the present invention.

Claims

1. A method for preparing methyl trifluoromethanesulfonate, characterized in that: The steps include: S1, preparation of a pre-reaction system: adding trifluoromethanesulfonic acid to a reaction kettle, cooling to 0°C to 20°C, adding a catalyst 4-dimethylaminopyridine under stirring conditions, and continuing stirring to obtain a pre-reaction system; S2, reaction: heating the pre-reaction system, adding dimethyl carbonate dropwise, so that the molar ratio of trifluoromethanesulfonic acid: catalyst: dimethyl carbonate in the reaction system is (2-2.1): (0.03-0.08): 1, after the addition is complete, continuing the reaction for 4h-8h to obtain a mixed solution containing the product methyl trifluoromethanesulfonate; S3, standing and stratifying: standing and stratifying the mixed solution to obtain an organic phase and an aqueous phase; S4, atmospheric distillation: take the organic phase, perform atmospheric distillation, collect the fractions, and obtain the product methyl trifluoromethanesulfonate.

2. A method for preparing methyl trifluoromethanesulfonate according to claim 1, characterized in that, In S1, the stirring speed is 100 r / min to 200 r / min, and the stirring time is 0.5 h to 1 h.

3. The method for preparing trimethylsilane according to claim 1, characterized in that: In S2, the pre-reaction system is heated to 60°C to 80°C, and the temperature is always maintained at 60°C to 80°C before the reaction is terminated.

4. A method for preparing methyl trifluoromethanesulfonate according to claim 1, characterized in that, The entire process of S2 is carried out under stirring conditions, and the stirring speed is the same as that of S1.

5. A method for preparing methyl trifluoromethanesulfonate according to claim 1, characterized in that, In S2, the dropping speed of dimethyl carbonate is controlled to be 1d / 2s to 5d / s.

6. The method for preparing methyl trifluoromethanesulfonate according to claim 1, wherein: In S3, the standing time of the mixed solution is 2 h to 3 h, and after the mixed solution is separated into layers, the upper layer is the organic phase and the lower layer is the aqueous phase.

7. A method for preparing methyl trifluoromethanesulfonate according to claim 1, characterized in that, In S4, the atmospheric distillation temperature is 100°C to 120°C, and the fraction is collected when the outlet temperature reaches 92°C to 99°C.

8. A method for preparing methyl trifluoromethanesulfonate according to claim 1, characterized in that, The aqueous phase in S3 is taken and distilled under reduced pressure to remove water, and then the catalyst is recovered. The recovered catalyst 4-dimethylaminopyridine is further used to prepare methyl trifluoromethanesulfonate.

9. A method for preparing methyl trifluoromethanesulfonate according to claim 8, characterized in that, The operating conditions of the reduced pressure distillation are a pressure of -0.05Mpa to -0.09Mpa and a temperature of 70°C to 100°C.

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