A method for synthesizing sodium 2-(cyclohexylamine)ethanesulfonate

Abstract

The present invention relates to the technical field of organic synthesis and provides a method for synthesizing sodium 2-(cyclohexylamine)ethanesulfonate. The present invention uses cyclohexylamine and sodium vinylsulfonate to react to prepare sodium 2-(cyclohexylamine)ethanesulfonate. Among them, cyclohexylamine is used as a reaction raw material and also as a solvent at the same time. The operation is simple, no additional solvent needs to be added, the reaction raw materials are simple, the introduction of impurities is avoided, and no other by-products are generated, so the production efficiency is greatly improved. The results of the examples show that when the method of the present invention is used to synthesize sodium 2-(cyclohexylamine)ethanesulfonate, the yield of the product can reach 99.5%, and the HPLC purity can reach 99.6%.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and in particular to a method for synthesizing sodium 2-(cyclohexylamine)ethanesulfonate. Background Art

[0002] The molecular formula of sodium 2-(cyclohexylamine)ethanesulfonate is C8H 16 NNaO3S, and the structural formula is as follows:

[0003]

[0004] Sodium 2-(cyclohexylamine)ethanesulfonate has self-buffering property and biocompatibility, and is considered to be a good biological buffer.

[0005] Currently, sodium 2-(cyclohexylamine)ethanesulfonate is usually prepared using cyclohexylamine and sodium 2-chloroethylsulfonate as raw materials, and its synthesis route is shown in the following formula:

[0006]

[0007] This synthesis method uses sodium 2-chloroethylsulfonate as a raw material, which is prone to produce by-products, and the purity and yield of the product are relatively low.

[0008] Chinese Patent CN112479938A discloses a method for preparing N-cyclohexyl-2-aminoethanesulfonic acid, in which cyclohexylamine, 1,2-dichloroethane and sodium sulfite are used as raw materials, water and ethanol are used as solvents, and reflux reaction is carried out under catalyst conditions to obtain N-cyclohexyl-2-aminoethanesulfonate, and then acidification is carried out to obtain N-cyclohexyl-2-aminoethanesulfonic acid. The raw materials used in this patent are various, the operation is complex, impurities are easily introduced into the product, and the purity and yield of the product need to be further improved.

[0009] Yang Huirong et al. (Yang Huirong et al., Optimization of the synthesis process conditions of cyclohexylaminosulfonic acid sweetener [J]. Modern Chemical Industry, 1998(6): 30-31) provided a method for preparing cyclohexylaminosulfonic acid sodium, in which sulfamic acid was added to light oil, and then cyclohexylamine was slowly added for reaction. After the reaction was completed, sodium bicarbonate solution was added for stirring and dissolution; light oil was required as a solvent in this literature, and this solvent is irritating to the human body and flammable and explosive.

[0010] Chinese Patent CN110790687A published a production method of 3-(cyclohexylamine)-1-propanesulfonic acid, in which propyl propanesulfonate was dissolved in DMF, and then cyclohexylamine was introduced for reaction. DMF was used as a solvent in this method, and the highest product yield was only 86%, and there was no record of the product purity.

[0011] Chinese Patent CN110885299A provides a preparation method of 3-(cyclohexylamine)-1-propanesulfonic acid. In this method, 1,3-propane sultone is dissolved in ethyl acetate to obtain an organic solution of 1,3-propane sultone, and cyclohexylamine is dissolved in dichloromethane to obtain an organic solution of cyclohexylamine. Then, the two organic solutions are pumped into a microchannel reactor for reaction. This method requires the use of two organic solvents and a microchannel reactor, and the operation is relatively complex.

[0012] In summary, in the current preparation methods, additional organic solvents need to be introduced, and the operation is relatively complex. There is still no preparation method of sodium 2-(cyclohexylamine)ethanesulfonate with simple operation, high product yield and high purity. Summary of the Invention

[0013] In view of this, the present invention provides a synthesis method of sodium 2-(cyclohexylamine)ethanesulfonate. The synthesis method provided by the present invention does not require the addition of additional organic solvents, has simple steps, low cost, high product yield and high purity, and can be used in the biomedical field.

[0014] In order to achieve the above-mentioned invention purpose, the present invention provides the following technical solutions:

[0015] A synthesis method of sodium 2-(cyclohexylamine)ethanesulfonate, comprising the following steps: mixing cyclohexylamine and sodium vinyl sulfonate for reaction to obtain sodium 2-(cyclohexylamine)ethanesulfonate.

[0016] Preferably, the weight ratio of cyclohexylamine to sodium vinyl sulfonate is (5-10):1.

[0017] Preferably, the reaction temperature is 40-80 °C.

[0018] Preferably, the reaction time is 24-48 h.

[0019] Preferably, sodium vinyl sulfonate is added to cyclohexylamine for reaction.

[0020] Preferably, after the reaction, the obtained product liquid is further subjected to post-treatment; the post-treatment includes: centrifugally separating the obtained product liquid to obtain cyclohexylamine and wet sodium 2-(cyclohexylamine)ethanesulfonate; vacuum negative pressure drying the wet sodium 2-(cyclohexylamine)ethanesulfonate to obtain sodium 2-(cyclohexylamine)ethanesulfonate finished product and cyclohexylamine.

[0021] Preferably, the cyclohexylamine obtained by centrifugal separation and the cyclohexylamine obtained by vacuum negative pressure drying are recycled.

[0022] The present invention provides a method for synthesizing sodium 2-(cyclohexylamine)ethanesulfonate, which comprises the following steps: mixing cyclohexylamine and sodium vinylsulfonate for reaction to obtain sodium 2-(cyclohexylamine)ethanesulfonate. The present invention utilizes the reaction of cyclohexylamine and sodium vinylsulfonate to prepare sodium 2-(cyclohexylamine)ethanesulfonate, wherein cyclohexylamine serves as both a reaction raw material and a solvent, without the need to additionally add other solvents. The reaction raw materials are simple, avoiding the introduction of impurities and generating no other by-products, thus greatly improving the production efficiency. The results of the examples show that when the method of the present invention is used to synthesize sodium 2-(cyclohexylamine)ethanesulfonate, the yield of the product can reach 99.5%, and the HPLC purity can reach 99.6%. Detailed implementation mode

[0023] The present invention provides a method for synthesizing sodium 2-(cyclohexylamine)ethanesulfonate, which comprises the following steps: mixing cyclohexylamine and sodium vinylsulfonate for reaction to obtain sodium 2-(cyclohexylamine)ethanesulfonate.

[0024] In the present invention, the molar ratio weight ratio of cyclohexylamine to sodium vinylsulfonate is preferably (5-10):1, more preferably (6-8):1; the temperature of the reaction is preferably 40-80°C, more preferably 50-60°C; the time of the reaction is preferably 24-48 h, more preferably 30-40 h, and further preferably 36 h; in the specific embodiments of the present invention, it is preferred to add the sodium vinylsulfonate to the cyclohexylamine for reaction.

[0025] In the present invention, the reaction formula of the reaction is shown in Formula I:

[0026]

[0027] In the present invention, after the reaction, it is preferably further included to post-treat the obtained product liquid; the post-treatment preferably includes: centrifugally separating the obtained product liquid to obtain cyclohexylamine and wet sodium 2-(cyclohexylamine)ethanesulfonate (containing cyclohexylamine); vacuum negative pressure drying the wet sodium 2-(cyclohexylamine)ethanesulfonate to obtain the finished product of sodium 2-(cyclohexylamine)ethanesulfonate and cyclohexylamine; the purity and yield of the finished product of sodium 2-(cyclohexylamine)ethanesulfonate are both above 99%; the vacuum degree of the vacuum negative pressure drying is preferably -0.095 MPa to -0.098 MPa, and the drying temperature is preferably 40-60°C; in the present invention, the excess cyclohexylamine solvent is first separated by centrifugation, and the wet sodium 2-(cyclohexylamine)ethanesulfonate obtained contains about 5 wt% of cyclohexylamine, and then this part of cyclohexylamine is recovered by vacuum negative pressure drying.

[0028] In the present invention, it is preferred to recycle the cyclohexylamine obtained by the centrifugal separation and the cyclohexylamine obtained by the vacuum negative pressure drying.

[0029] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts belong to the scope of protection of the present invention.

[0030] Example 1

[0031] 26 g of sodium vinyl sulfonate was added to 200 g of cyclohexylamine, and the reaction was carried out at 70 °C for 24 h. After the reaction was completed, the obtained product liquid was centrifuged to separate the excess cyclohexylamine. The obtained wet material of sodium 2-(cyclohexylamino)ethanesulfonate was dried under vacuum negative pressure to obtain the finished product of sodium 2-(cyclohexylamino)ethanesulfonate and cyclohexylamine. The two parts of the recovered cyclohexylamine were recycled; the yield of the finished product of sodium 2-(cyclohexylamino)ethanesulfonate was 99.1%, and the HPLC purity was 99.2%.

[0032] Example 2

[0033] 13 g of sodium vinyl sulfonate was added to 100 g of cyclohexylamine, and the reaction was carried out at 55 °C for 36 h. After the reaction was completed, the obtained product liquid was centrifuged to separate the excess cyclohexylamine. The obtained wet material of sodium 2-(cyclohexylamino)ethanesulfonate was dried under vacuum negative pressure to obtain the finished product of sodium 2-(cyclohexylamino)ethanesulfonate and cyclohexylamine. The two parts of the recovered cyclohexylamine were recycled; the yield of the finished product of sodium 2-(cyclohexylamino)ethanesulfonate was 99.5%, and the HPLC purity was 99.6%.

[0034] Example 3

[0035] 130 g of sodium vinyl sulfonate was added to 1000 g of cyclohexylamine, and the reaction was carried out at 65 °C for 24 h. After the reaction was completed, the obtained product liquid was centrifuged to separate the excess cyclohexylamine. The obtained wet material of sodium 2-(cyclohexylamino)ethanesulfonate was dried under vacuum negative pressure to obtain the finished product of sodium 2-(cyclohexylamino)ethanesulfonate and cyclohexylamine. The two parts of the recovered cyclohexylamine were recycled; the yield of the finished product of sodium 2-(cyclohexylamino)ethanesulfonate was 99%, and the HPLC purity was 99.1%.

[0036] Comparative Example 1

[0037] 13 g of sodium vinyl sulfonate was added to 100 g of cyclohexylamine, and the reaction was carried out at 85 °C for 24 h. After the reaction was completed, the resulting product liquid was centrifuged to separate the excess cyclohexylamine. The obtained wet material of sodium 2-(cyclohexylamino)ethanesulfonate was dried under vacuum negative pressure to obtain the finished product of sodium 2-(cyclohexylamino)ethanesulfonate and cyclohexylamine. The two parts of the recovered cyclohexylamine were recycled; the yield of the finished product of sodium 2-(cyclohexylamino)ethanesulfonate was 92.1%, and the HPLC purity was 97.2%. In Comparative Example 1, the reaction temperature was relatively high, resulting in more impurities in the product, and the yield and purity of the product decreased.

[0038] Comparative Example 2

[0039] 13 g of sodium vinyl sulfonate was added to 100 g of cyclohexylamine, and the reaction was carried out at 45 °C for 20 h. After the reaction was completed, the resulting product liquid was centrifuged to separate the excess cyclohexylamine. The obtained wet material of sodium 2-(cyclohexylamino)ethanesulfonate was dried under vacuum negative pressure to obtain the finished product of sodium 2-(cyclohexylamino)ethanesulfonate and cyclohexylamine. The two parts of the recovered cyclohexylamine were recycled; the yield of the finished product of sodium 2-(cyclohexylamino)ethanesulfonate was 96.5%, and the HPLC purity was 97.2%; in Comparative Example 2, the reaction time was relatively short, resulting in a decrease in the product yield and purity.

[0040] The above are only the preferred embodiments of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and refinements can be made, and these improvements and refinements should also be regarded as the protection scope of the present invention.

Claims

1. A method for synthesizing sodium 2-(cyclohexylamine)ethanesulfonate, characterized in that, It includes the following steps: mixing cyclohexylamine and sodium vinyl sulfonate for reaction to obtain sodium 2-(cyclohexylamino)ethanesulfonate; wherein cyclohexylamine is used as both a reaction raw material and a solvent, and no other solvent needs to be added additionally. The weight ratio of the cyclohexylamine to the sodium vinyl sulfonate is (5~10):1; the temperature of the reaction is 40~80 °C; the time of the reaction is 24~48 h.

2. The synthesis method according to claim 1, characterized in that, Adding the sodium vinyl sulfonate to the cyclohexylamine for reaction.

3. The synthesis method according to claim 1, characterized in that, After the reaction, it further includes post-treating the obtained product liquid; the post-treatment includes: centrifugally separating the obtained product liquid to obtain cyclohexylamine and wet sodium 2-(cyclohexylamino)ethanesulfonate; subjecting the wet sodium 2-(cyclohexylamino)ethanesulfonate to vacuum negative pressure drying to obtain the finished product of sodium 2-(cyclohexylamino)ethanesulfonate and cyclohexylamine.

4. The synthesis method according to claim 3, wherein Recycling the cyclohexylamine obtained by the centrifugal separation and the cyclohexylamine obtained by the vacuum negative pressure drying.

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