CN110938057B - A kind of preparation method of water-soluble sulfonated calixarene - Google Patents

Abstract

The present invention relates to a preparation method of a water-soluble sulfonated calixarene, which specifically comprises the following steps: (1) adding the calixarene to a calculated amount of concentrated sulfuric acid to carry out a sulfonation reaction, and monitoring the progress of the reaction to ensure that the reaction is completed; ( 2) After the reaction is completed, cool to room temperature, pour the reactant into crushed ice, separate out the flocculent precipitate, and collect the solid product to obtain a crude sulfonated calixarene; (3) use a solvent to dissolve, separate and purify the crude product to obtain pure calixarene. Water-soluble sulfonated calixarene products. The present invention adjusts the optimum sulfuric acid concentration by controlling the optimum ratio of reactants calixarene and concentrated sulfuric acid in combination with the different solubility of reaction products in sulfuric acid solution, without adding sodium chloride salt for salting out, and simultaneously dissolving and purifying the crude product to obtain High-purity, sulfuric-free, water-soluble sulfonated calixarene.

Description

A kind of preparation method of water-soluble sulfonated calixarene

technical field

The invention belongs to the field of functional compound preparation, in particular to a water-soluble sulfonated calixarene and a preparation method thereof.

Background technique

As we all know, biological-related systems are all in the environment of aqueous solution, and many biological processes occur in aqueous solution. Therefore, the research on molecular recognition in aqueous solution will become an inevitable trend in the development of fluorescent sensors, and various fluorescent sensors reported so far. Most of the molecular recognition research is limited to a pure organic solvent environment or a mixed system of organic solvent and water. This may be attributed to the natural properties of organic compounds—insoluble in water, and related organic compounds are difficult to derivatize into water-soluble compounds, thus limiting their application scope and practical value. Research investigations show that calixarene is a good molecular recognition platform, and it is easy to derivatize, and water-soluble calixarene derivatives can be obtained by introducing functional groups such as sulfonates at the lower edge. Designing, modifying, and synthesizing a water-soluble calixarene fluorescent sensor for molecular recognition research has very important scientific and practical significance—making our experimental simulation results closer to the real situation.

In 1986, Seiji Shinkai et al. first reported the first case of water-soluble calixarene sulfonate-hexasulfonate calixarene series derivatives, which opened the door for the study of water-soluble calixarene; Nobuhiko Iki et al. (1998) subsequently The method is applied to the preparation of water-soluble sulfonic thiacalixarenes. Briefly, the method is as follows: a mixture of 1.5 g of calixarene and 80 mL of concentrated sulfuric acid is heated to 80 °C and reacted for 4 hours. It was cooled to room temperature, 500 mL of ice water was added, and the insolubles were removed by filtration. 100g of sodium chloride was added, and the target product was obtained by salting out. The precipitated product is purified by ethanol/water multiple times of recrystallization to obtain the final product.

Although the method proposed by Shinkai et al. is indeed feasible, so far, there are very few studies on water-soluble calixarene. Through our own practical experimental repetition, we found that it is still related to the actual yield and purity of the method, which limits people's development in this area. Especially in the salting-out process, the target product actually contains a large amount of NaCl, and our nuclear magnetic data cannot know its content. The obtained 1g product may actually contain a large part of NaCl, which cannot be quantified, which will directly affect the subsequent experiments. Accuracy and Feasibility. Although several times of recrystallization with ethanol water have been tried in the literature, the actual effect is not obvious and the time is too long.

Aiming at the problems existing in the current preparation method of water-soluble sulfonated calixarene, the present invention optimizes and develops a preparation method for high-purity, salt-free, sulfuric-free water-soluble sulfonated calixarene through long-term experimental research.

SUMMARY OF THE INVENTION

The object of the present invention is to overcome the above-mentioned deficiencies of the prior art, and to provide a preparation method of sulfonated calixarene, aiming to solve the undesirable problems such as low product purity, inclusion of acid and salt obtained by the existing preparation method of sulfonated calixarene.

The present invention provides a kind of preparation method of sulfonated calixarene (TCAS), adopts such as formula (I) one-step method to react:

The specific steps are:

(1) calixarene (TCA) is added in the vitriol oil and carries out sulfonation reaction, simultaneously monitoring reaction progress, ensures that reaction is completed;

(2) after the reaction is completed, cool to room temperature, pour the reactant into crushed ice, adjust the sulfuric acid concentration by adding water, so that the flocculent precipitate is separated out, and the solid product is collected to obtain the sulfonated calixarene crude product;

(3) The crude product is dissolved, separated and purified in a solvent to obtain a water-soluble sulfonated calixarene product.

Further, the ratio of the calixarene to the concentrated sulfuric acid is less than or equal to 2g:100ml, preferably the ratio of the calixarene to the concentrated sulfuric acid is 2g:100ml.

Further, the reaction time is 20-40h, preferably 24h.

Further, the reaction temperature is 60-100°C, preferably 80°C.

Further, in step (1), the progress of the reaction is monitored, and if one drop of the reaction solution is completely dissolved in 10 ml of water, the reaction is complete.

Further, the amount of crushed ice in step (2) is 40-50 times, preferably 45 times, the weight of calixarene.

Further, the purification step in step (3) is specifically as follows: dissolving the crude sulfonated calixarene in N,N-dimethylformamide (DMF), filtering to remove insoluble matter, and evaporating and drying to obtain a solid, which is water-soluble sulfonic acid. Calix aromatics products.

Further, in step (2), the floc precipitation is collected by means of centrifugal separation or suction filtration.

Further, the step (2) also includes a step of removing sulfuric acid from the crude sulfonated calixarene, specifically dissolving the crude sulfonated calixarene with a small amount of water, then adding an appropriate amount of NaOH to neutralize to neutrality, and concentrating to remove water.

Beneficial effects of the present invention:

1. The inventor team of the present invention found in long-term research that the solubility of sulfonated calixarene in sulfuric acid solutions of different concentrations is different. Using this phenomenon, it is only necessary to add water to adjust the appropriate sulfuric acid concentration without adding sodium chloride salt. The product can be precipitated directly by means of a sudden temperature drop. The salting-out step is directly omitted, the addition of sodium chloride is avoided, and the step of removing sodium chloride from the product is not required in the later stage.

2. After the crude sulfonated calixarene is prepared, the sulfuric acid is removed by neutralization with acid and alkali. At the same time, the different solubility differences of Na ₂ SO ₄ and sulfonated calixarene in different solvents were studied. After a lot of experimental research, N,N-dimethylformamide (DMF) was found as the separation solvent, Na ₂ SO ₄ is insoluble in it, but the sulfonated calixarene is soluble in it, so that the crude product is dissolved, filtered and evaporated with N,N-dimethylformamide (DMF) to obtain high-purity sulfonated calixarene.

3. The preparation method of the sulfonated calixarene of the present invention is simple and feasible, and the purification step is also very simple, and the salting-out step of the traditional preparation method is omitted, and the purification method can also obtain a salt-free product of the sulfonated calixarene with higher purity, which is suitable for the sulfonated calixarene. Mass production process.

Description of drawings

Fig. 1 is the hydrogen nuclear magnetic spectrum of the water-soluble sulfonated calixarene obtained in Example 1-3 of the present invention.

Detailed ways

The present invention has been tested for many times, and now some test results are used as a reference to further describe the invention, and the following is a detailed description in conjunction with specific embodiments.

The instrument model and analysis conditions of nuclear magnetic resonance in the embodiment of the present invention: Bruker AVANCE III400 superconducting nuclear magnetic resonance spectrometer is used; resonance frequency: 400MHZ; D ₂ O is used as solvent.

Example 1

Add 100 mL of concentrated sulfuric acid with a concentration of 98% in a three-port reaction vessel with a temperature-controlled base, then accurately weigh 2 g of calixarene (TCA) and add it to the concentrated sulfuric acid, adjust the temperature of the temperature-controlled base to ensure that the reaction temperature is at 80 ° C, the reaction In the device, a PTFE stirring paddle is used for stirring. During the reaction, the reaction progress is monitored by monitoring the solubility of the reaction solution in water, and the reaction is complete when the reaction solution is completely water-soluble. After about 20 hours of reaction, drop a drop of the reaction into 10 mL of aqueous solution every 1 hour, and observe whether it can be completely dissolved in 10 mL of water. After the final reaction for 24 hours, all the reactants can be dissolved in water, and the solution is clear and transparent, indicating the reaction completely. Then cool the reaction solution to room temperature, prepare a wide-mouthed reactor filled with 90g of crushed ice, slowly pour the reaction solution into 90g of crushed ice, the solution gradually separates out flocculent precipitation, after slow stirring for 10 minutes, centrifuge to collect the solid product, That is the crude product of sulfonated calixarene.

The crude product is dissolved with as little water as possible, then neutralized to pH 7.0 by adding an appropriate amount of NaOH, then evaporated in vacuo and concentrated to remove water. The obtained solid product was dissolved in 10 mL of N,N-dimethylformamide (DMF), wherein the insoluble matter was Na ₂ SO ₄ , then the insoluble Na ₂ SO ₄ was separated by filtration, and then DMF was evaporated to obtain high-purity sulfonic acid. Calixaromatics (TCAS) products. The product has the characteristics of high purity, no salt and no sulfuric acid.

Figure 1 in the accompanying drawings is the hydrogen spectrum of the sulfonated calixarene in Example 1. The results of nuclear magnetic resonance data analysis are: ¹ H-NMR (D ₂ O, 400 Hz) δ: 8.02 (s, 8H, Ar-H)

Example 2

Add 180mL of concentrated sulfuric acid (concentration 98%) in a three-port reaction vessel with a temperature-controlled base, then accurately weigh 3g of calixarene (TCA) and add it to the concentrated sulfuric acid, adjust the temperature of the temperature-controlled base to ensure that the reaction temperature is at 85 ℃, The reactor was stirred with a Teflon stirring paddle. During the reaction, the reaction progress is monitored by monitoring the solubility of the reaction solution in water, and the reaction is complete when the reaction solution is completely water-soluble. After about 15 hours of reaction, drop a drop of the reaction into 10 mL of aqueous solution every 1 hour, and observe whether it can be completely dissolved in 10 mL of water. After the final reaction for 22 hours, all the reactants can be dissolved in water, and the solution is clear and transparent, indicating the reaction completely. Then cool the reaction solution to room temperature, prepare a wide-mouth reactor containing 160g of crushed ice, slowly pour the reaction solution into 160g of crushed ice, the solution gradually separates out a flocculent precipitate, and after slow stirring for 10 minutes, centrifuge to collect the solid product, That is the crude product of sulfonated calixarene.

The crude product is dissolved with as little water as possible, then neutralized to pH 7.0 by adding an appropriate amount of NaOH, then evaporated in vacuo and concentrated to remove water. The obtained solid product was dissolved in 20 mL of N,N-dimethylformamide (DMF), wherein the insoluble matter was Na ₂ SO ₄ , and then the insoluble Na ₂ SO ₄ was separated by filtration. Re-evaporation to remove DMF resulted in a high purity sulfonated calixarene (TCAS) product. The product has the characteristics of high purity, no salt and no sulfuric acid.

The hydrogen spectrum of the sulfonated calixarene in Example 2 is consistent with that in Example 1, as shown in FIG. 1 . Analysis of nuclear magnetic resonance data: ¹ H-NMR (D ₂ O, 400 Hz) δ: 8.02 (s, 8H, Ar-H).

Example 3

Add 60 mL of concentrated sulfuric acid (concentration 98%) to a three-port reaction vessel with a temperature-controlled base, then accurately weigh 1.0 g of calixarene (TCA) and add it to the concentrated sulfuric acid, adjust the temperature of the temperature-controlled base to ensure that the reaction temperature is at 75°C , the reactor is stirred with a PTFE stirring paddle. During the reaction, the reaction progress is monitored by monitoring the solubility of the reaction solution in water, and the reaction is complete when the reaction solution is completely water-soluble. After about 20 hours of reaction, drop a drop of the reaction into 10 mL of aqueous solution every 1 hour, and observe whether it can be completely dissolved in 10 mL of water. After the final reaction for 28 hours, all the reactants can be dissolved in water, and the solution is clear and transparent, indicating the reaction completely. Then cool the reaction solution to room temperature, prepare a wide-mouth reactor filled with 50g of crushed ice, slowly pour the reaction solution into 50g of crushed ice, the solution gradually separates out a flocculent precipitate, and after stirring slowly for 10 minutes, the solid product is collected by centrifugation. That is the crude product of sulfonated calixarene.

The crude product is dissolved with as little water as possible, then neutralized to pH 7.0 by adding an appropriate amount of NaOH, then evaporated in vacuo and concentrated to remove water. The obtained solid product was dissolved with 5 mL of N,N-dimethylformamide (DMF), wherein the insoluble matter was Na ₂ SO ₄ , and then the insoluble Na ₂ SO ₄ was separated by filtration. Re-evaporation to remove DMF resulted in a high purity sulfonated calixarene (TCAS) product. The product has the characteristics of high purity, no salt and no sulfuric acid.

The hydrogen spectrum of the sulfonated calixarene in Example 3 is consistent with that in Example 1, as shown in FIG. 1 . Results of nuclear magnetic resonance data analysis: ¹ H-NMR (D ₂ O, 400 Hz) δ: 8.02 (s, 8H, Ar-H).

The above descriptions are only preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements and improvements made within the spirit and principles of the present invention shall be included in the protection of the present invention. within the range.

Claims (8)

1. a preparation method of water-soluble sulfonated calixarene, is characterized in that, adopts the synthetic step of following formula (I):

The specific steps are: (1) calixarene is added in 98% vitriol oil to carry out sulfonation reaction, and the ratio of calixarene to the vitriol oil is less than or equal to 2g: 100mL, and the progress of the reaction is monitored simultaneously to ensure that the reaction is completed; (2) After the reaction is completed, cool to room temperature, pour the reactant into crushed ice, the consumption of crushed ice is 40-50 times of the weight of calix aromatic hydrocarbon, adjust the concentration of sulfuric acid by adding water, until the maximum precipitation flocculent precipitate , collecting the solid product to obtain the sulfonated calixarene crude product; removing the sulfuric acid from the sulfonated calixarene crude product, specifically using a small amount of water to dissolve the sulfonated calixarene crude product, then adding an appropriate amount of NaOH to neutralize to neutrality, and concentrating to remove water; (3) use N,N-dimethylformamide solvent to dissolve, separate and purify the crude product, and the purification steps are as follows: dissolving the crude product of sulfonated calixarene in N,N-dimethylformamide, filtering to remove insoluble matter, and then evaporating The solid obtained by drying is the water-soluble sulfonated calixarene product. 2. preparation method as claimed in claim 1 is characterized in that, described reaction duration is 20-40h. 3. preparation method as claimed in claim 2, is characterized in that, described reaction duration is 24h. 4. The preparation method of claim 1, wherein the reaction temperature is 60-100°C. 5. The preparation method of claim 4, wherein the reaction temperature is 80°C. 6. The preparation method according to any one of claims 1 to 5, wherein the step (1) monitors the progress of the reaction, so that taking 1 drop of the reaction solution can be completely dissolved in 10 ml of water to represent that the reaction is complete. 7. preparation method as claimed in claim 1 is characterized in that, the consumption of crushed ice in step (2) is 45 times of calixarene weight. 8. The preparation method according to any one of claims 1 to 5, characterized in that, in step (2), the floc precipitation is collected by means of centrifugal separation or suction filtration.

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