A kind of preparation method of 18-crown ether-6

Abstract

The invention discloses a method for preparing 18-crown-6, which comprises the following steps: under stirring, tetrahydrofuran or 1,4-dioxane is added to a reaction bottle containing triethylene glycol and potassium hydroxide; p-toluenesulfonyl chloride is then added dropwise to the reaction bottle, the reaction temperature is controlled to be 30-80°C, and the reaction time is 2-6h; a separating agent is added to the reaction solution to separate the potassium p-toluenesulfonate by-product, the reaction temperature is controlled to be 70-100°C, and the reaction time is 3-6h; the obtained solution is filtered, concentrated, and vacuum distilled, and the distilled liquid is washed with distilled water and stratified, and the lower layer solution is centrifuged and precipitated, and the precipitate is dried to obtain 18-crown-6. The preparation method of the present invention is simple, and while ensuring a higher reaction rate and a reactant conversion rate, it also simplifies subsequent separation operations, reduces subsequent processing links, and ensures the purity of the final product.

Description

Technical Field

[0001] The invention relates to the field of chemical synthesis, and in particular to a method for preparing 18-crown ether-6. Background Art

[0002] The biggest feature of crown ethers is that they can complex with positive ions and form stable complexes with different metal ions depending on the size of the ring. This special property of crown ethers has aroused great interest and attention. It has now penetrated into many fields of chemistry and has been widely used in organic synthesis, coordination chemistry, analytical chemistry, extraction chemistry, molecular catalysis, enzyme simulation, biology, soil chemistry and medicine.

[0003] At present, the traditional preparation method of 18-crown ether-6 is the Williamson synthesis method. The essence of the reaction is a substitution reaction. Dichlorotriethylene ethyl diether removes chlorine atoms, and triethylene glycol hydroxyl removes hydrogen atoms to form a macrocyclic compound. The reaction solution is washed with dichloromethane and concentrated to evaporate the solvent, and vacuum distilled and complexed and recrystallized to obtain the final product. The yield of the final product of this synthesis method is low and the cost is high. Later studies found that the yield of the final product was significantly improved by using triethylene glycol and p-toluenesulfonyl chloride as raw materials for synthesis, which can reach 65%. However, the by-product separation steps of this preparation process are relatively cumbersome and complicated, and it is necessary to repeatedly reflux, distill and recrystallize to improve the purity of the final product. The purity of the product after separation is not very high, so it has not been applied in production. Summary of the invention

[0004] The technical problem to be solved by the present invention is to provide a method for preparing 18-crown ether-6, which can solve the defects in the prior art that the final product yield is low, the subsequent separation operation is cumbersome and complicated, and the purity of the separated product is not high.

[0005] In order to solve the above problems, the present invention adopts the following technical solutions:

[0006] A method for preparing 18-crown ether-6 comprises the following steps:

[0007] (1) Under stirring conditions, tetrahydrofuran or 1,4-dioxane is added to a reaction bottle containing triethylene glycol and potassium hydroxide;

[0008] (2) adding p-toluenesulfonyl chloride dropwise to the reaction flask, controlling the reaction temperature to 30-80°C and the reaction time to 2-6h;

[0009] (3) adding a separating agent to the reaction solution in step (2) to separate the potassium p-toluenesulfonate by-product, controlling the reaction temperature to 70-100° C. and the reaction time to 3-6 h;

[0010] (4) filtering, concentrating, and vacuum distilling the solution obtained in step (3);

[0011] (5) washing the distilled liquid in step (4) with distilled water, standing for stratification, centrifuging the lower layer of the solution for precipitation, and drying the precipitate to obtain 18-crown ether-6;

[0012] In the step (3), the separating agent is dimethyl sulfate, diethyl sulfate or a mixture of the two.

[0013] According to a further technical solution, in step (1), the molar ratio of triethylene glycol to potassium hydroxide is 1:1-1:3.

[0014] According to a further technical solution, the molar ratio of p-toluenesulfonyl chloride to triethylene glycol added in step (2) is 1:1.

[0015] According to a further technical solution, the molar ratio of the separating agent added in step (3) to triethylene glycol is 1.5:1-2:1.

[0016] According to a further technical solution, the reaction temperature in step (1) is 50-60°C.

[0017] The present invention has the following beneficial effects compared with the prior art:

[0018] (1) In the present invention, triethylene glycol, p-toluenesulfonyl chloride and potassium hydroxide are used as reactants, tetrahydrofuran or 1,4-dioxane is selected as the solvent, and the molar ratio of the reactants and the temperature and reaction time during the reaction process are controlled to make the entire reaction have a higher reaction rate and a higher conversion rate of the reactants;

[0019] (2) In the present invention, dimethyl sulfate, diethyl sulfate or a mixture of the two is added to the reaction solution after the reaction to separate the potassium p-toluenesulfonate by-product, and the temperature and time of the reaction are controlled. This operation not only improves the yield and purity of the final product, but also makes the subsequent separation operation of the product simple and easy. In addition, the reaction solvent in the separation process of the separating agent is the same as the reaction solvent in the synthesis process, thereby avoiding the introduction of new by-products and reducing the post-processing steps. DETAILED DESCRIPTION

[0020] The present invention is further described below in conjunction with examples, but the embodiments of the present invention are not limited thereto.

[0021] Example 1

[0022] A method for preparing 18-crown ether-6, the preparation steps are as follows:

[0023] (1) Weigh 15 g of triethylene glycol and 12 g of potassium hydroxide into a 500 mL reaction bottle, then add 300 mL of tetrahydrofuran into the reaction bottle and start stirring;

[0024] (2) Add 19 g of p-toluenesulfonyl chloride dropwise to the reaction flask, control the reaction temperature at 55-60°C, and react for 3 hours;

[0025] (3) adding 6.5 g of dimethyl sulfate to the reaction solution to separate potassium p-toluenesulfonate, controlling the reaction temperature at 80° C., reacting for 3 h, and generating methyl p-toluenesulfonate and potassium sulfate;

[0026] (4) filtering, concentrating, and vacuum distilling the final solution obtained after the reaction, and the distillate contains 18-crown ether-6, methyl p-toluenesulfonate, triethylene glycol, etc.;

[0027] (5) The distilled liquid is washed with 20 mL of distilled water and allowed to stand for stratification. The upper layer solution is methyl p-toluenesulfonate, and the lower layer solution is 18-crown-6, triethylene glycol, etc. The lower layer solution is centrifuged and precipitated. The precipitate is dried to obtain 18-crown-6.

[0028] The final mass of the prepared 18-crown ether-6 was 17.1 g, and the yield was 64.8%.

[0029] Example 2

[0030] A method for preparing 18-crown ether-6, the preparation steps are as follows:

[0031] (1) Weigh 15 g of triethylene glycol and 12 g of potassium hydroxide into a 500 mL reaction bottle, then add 300 mL of tetrahydrofuran into the reaction bottle and start stirring;

[0032] (2) Add 19 g of p-toluenesulfonyl chloride dropwise to the reaction flask, control the reaction temperature at 55-60°C, and react for 3 hours;

[0033] (3) adding 7.7 g of diethyl sulfate to the reaction solution to separate potassium p-toluenesulfonate, controlling the reaction temperature at 80° C. and reacting for 3 h to generate ethyl p-toluenesulfonate and potassium sulfate;

[0034] (4) filtering, concentrating, and vacuum distilling the final solution obtained after the reaction, and the distillate contains 18-crown ether-6, ethyl p-toluenesulfonate, triethylene glycol, etc.;

[0035] (5) The distilled liquid is washed with 20 mL of distilled water and allowed to stand for stratification. The upper layer solution is ethyl p-toluenesulfonate, and the lower layer solution is 18-crown-6, triethylene glycol, etc. The lower layer solution is centrifuged and precipitated. The precipitate is dried to obtain 18-crown-6.

[0036] The final mass of the prepared 18-crown ether-6 was 17.2 g, and the yield was 65.2%.

[0037] Example 3

[0038] A method for preparing 18-crown ether-6, the preparation steps are as follows:

[0039] (1) Weigh 15 g of triethylene glycol and 12 g of potassium hydroxide into a 500 mL reaction bottle, then add 300 mL of 1,4-dioxane into the reaction bottle, start stirring, and heat to 55-60° C.;

[0040] (2) Add 17.6 g of p-toluenesulfonyl chloride dropwise to the reaction flask, control the reaction temperature at 55-60°C, and react for 3 hours;

[0041] (3) adding 7.7 g of diethyl sulfate to the reaction solution to separate potassium p-toluenesulfonate, controlling the reaction temperature at 90° C. and reacting for 4 h to generate ethyl p-toluenesulfonate and potassium sulfate;

[0042] (4) filtering, concentrating, and vacuum distilling the final solution obtained after the reaction, and the distillate contains 18-crown ether-6, ethyl p-toluenesulfonate, triethylene glycol, etc.;

[0043] (5) The distilled liquid is washed with 20 mL of distilled water and allowed to stand for stratification. The upper layer solution is ethyl p-toluenesulfonate, and the lower layer solution is 18-crown-6, triethylene glycol, etc. The lower layer solution is centrifuged and precipitated. The precipitate is dried to obtain 18-crown-6.

[0044] The final mass of the prepared 18-crown ether-6 was 16.2 g, and the yield was 61.4%.

[0045] Example 4

[0046] A method for preparing 18-crown ether-6, wherein the raw materials and operation steps are the same as those in Example 1, except that dimethyl sulfate is not added from the beginning to the end. The mass of 18-crown ether-6 finally obtained by this preparation method is 5.2 g, and the yield is 19.7%.

[0047] It can be seen from the above experimental results that the quality of the final product obtained in Examples 1-3 is significantly higher than that obtained in Example 4, indicating that the addition of a separating agent (one of dimethyl sulfate and diethyl sulfate or a mixture of the two) can significantly improve the yield and purity of the final product, and the subsequent separation operation of the product is simple and easy, reducing the post-processing steps.

[0048] The above specific examples are used to illustrate the present invention, which is only used to help understand the present invention and is not intended to limit the present invention. For those skilled in the art, according to the concept of the present invention, some simple deductions, modifications or substitutions can be made.

Claims

1. A method for preparing 18-crown ether-6, characterized in that: The following steps are involved: (1) Add tetrahydrofuran or 1,4-dioxane into a reaction flask containing triethylene glycol and potassium hydroxide under stirring; (2) Add p-toluenesulfonyl chloride dropwise into the reaction flask, control the reaction temperature to 30-80°C, and the reaction time to 2-6h; (3) adding a separating agent to the reaction solution in step (2) to separate the potassium p-toluenesulfonate by-product, controlling the reaction temperature to 70-100° C. and the reaction time to 3-6 h; (4) filtering, concentrating and vacuum distilling the solution obtained in step (3); (5) washing the distilled liquid in step (4) with distilled water, standing for stratification, centrifuging the lower layer of the solution for precipitation, and drying the precipitate to obtain 18-crown ether-6; In step (3), the separating agent is dimethyl sulfate, diethyl sulfate or a mixture of the two.

2. The method for preparing 18-crown ether-6 according to claim 1, characterized in that: In the step (1), the molar ratio of triethylene glycol to potassium hydroxide is 1:1-1:

3.

3. The method for preparing 18-crown ether-6 according to claim 1 or 2, characterized in that: The molar ratio of p-toluenesulfonyl chloride to triethylene glycol added in step (2) is 1:

1.

4. The method for preparing 18-crown ether-6 according to claim 3, characterized in that: The molar ratio of the separating agent added in step (3) to triethylene glycol is 1.5:1-2:

1.

5. The method for preparing 18-crown ether-6 according to claim 1, characterized in that: The reaction temperature in step (1) is 50-60°C.