CN110452244B

CN110452244B - Synthetic method of cyclohexyl modified cucurbituril

Info

Publication number: CN110452244B
Application number: CN201910819716.7A
Authority: CN
Inventors: 马培华; 蒙叶; 周开志; 程思远; 赵威威; 蒋道法
Original assignee: Guizhou University
Current assignee: Guizhou University
Priority date: 2019-08-31
Filing date: 2019-08-31
Publication date: 2022-02-18
Anticipated expiration: 2039-08-31
Also published as: CN110452244A

Abstract

The invention discloses a method for modifying cucurbituril by cyclohexyl, which adopts 1, 2-cyclohexanedione hemihydrate and uses H in water₂SO₄、HNO₃And HCl and other inorganic acids or organic acids are acidified and reacted with urea to synthesize cyclohexyl modified glycoluril, and the cyclohexyl modified glycoluril diether and the fully substituted cyclohexyl cucurbituril are further reacted with paraformaldehyde to synthesize the cyclohexyl modified glycoluril diether and the fully substituted cyclohexyl cucurbituril. By X-ray single crystal diffraction,¹H MNR and the like. The method is simple and easy to operate, can overcome the defects of complicated reaction steps, low reaction yield, environmental pollution and high price of the original method, avoids the toxicity of selenium dioxide, reduces the pollution and improves the yield.

Description

Synthetic method of cyclohexyl modified cucurbituril

Technical Field

The invention discloses a synthetic method of cyclohexyl modified cucurbituril, and particularly relates to a novel synthetic way of cyclohexyl cucurbituril.

Background

Cucurbiturils (qn) are macrocyclic cage-like compounds bridged by n glycoside urea units and 2n methylene groups, are novel materials discovered in the last ten years, but limit the development of cucurbiturils under certain conditions due to the solubility problem and the harsh reaction conditions. The original route for synthesizing the cyclohexyl glycoluril is to oxidize cyclohexanone into 1, 2-cyclohexanedione by selenium dioxide, and then react the 1, 2-cyclohexanedione with urea under inorganic acid to obtain the cyclohexyl glycoluril, wherein the defects mainly comprise high toxicity of the selenium dioxide, poor water solubility of the 1, 2-cyclohexanedione, low reaction yield and high pollution. The modified cucurbiturils have the factors of complicated reaction steps, low reaction yield, environmental pollution and high price on a synthesis route.

Disclosure of Invention

The invention aims to disclose a cyclohexyl modified cucurbituril synthesis attack method, which is simple and easy to operate, can overcome the defects of complicated reaction steps, low reaction yield, environmental pollution and high price of the original method, avoids the toxicity of selenium dioxide, reduces the pollution and improves the yield. The invention aims to optimize the existing synthesis route of the cyclohexyl cucurbituril, hopes to push the synthesis method to a higher step, and provides better raw material guarantee for future research.

The technical scheme of the invention is that cyclohexanol and nitric acid are used as raw materials to synthesize 1, 2-cyclohexanedione hemihydrate, then the 1, 2-cyclohexanedione hemihydrate and urea are used as raw materials to synthesize cyclohexyl glycoluril, the cyclohexyl glycoluril hemihydrate reacts with paraformaldehyde to generate cyclohexyl glycoluril diether, and cyclohexyl glycoluril diether is used to further prepare cyclohexyl modified melon ring, and the steps are as follows:

step one, after adding a catalyst into concentrated nitric acid, putting the concentrated nitric acid solution into a salt bath for cooling, and controlling the temperature to be-5-20 ℃; slowly dripping cyclohexanol into concentrated nitric acid, controlling the temperature at 10-15 ℃, and finishing dripping within 2 h; after the temperature is reduced to below 0 ℃, air is blown to the liquid surface for 2 to 4 hours, and the liquid is washed for 3 times by hot water at the temperature of 75 to 80 ℃ to synthesize the 1, 2-cyclohexanedione hemihydrate:

2HNO₃→2NO+3O+H₂O；

step two, synthesizing cyclohexyl glycoluril by using 1, 2-cyclohexanedione hemihydrate and urea under an acidic condition:

step three, synthesizing cyclohexyl glycoluril diether by cyclohexyl glycoluril and paraformaldehyde under an acidic condition:

step four, heating and dissolving cyclohexyl glycoluril diether under an acidic condition, and refluxing to synthesize cyclohexyl modified cucurbituril:

the dosage ratio of the urea to the 1, 2-cyclohexanedione hemihydrate in the step 2 is more than 4: 1.

The condition for reacting the urea with the 1, 2-cyclohexanedione hemihydrate in the step 2 is acidification with an inorganic acid or an organic acid in water.

The reaction temperature in the second step is 0-100 ℃.

The reaction time of the step 2 is not less than 0.5 h.

The dosage ratio of the trioxymethylene to the cyclohexyl glycoluril in the step is more than 4: 1.

Compared with the prior art, the invention has the advantages that: the method comprises the steps of adopting 1, 2-cyclohexanedione hemihydrate to react with urea under certain conditions to synthesize cyclohexyl modified glycoluril, and further synthesizing cyclohexyl modified glycoluril diether and fully-substituted cyclohexyl cucurbituril by taking the cyclohexyl modified glycoluril diether and the fully-substituted cyclohexyl cucurbituril as raw materials. The method is simple and easy to operate, can overcome the defects of complicated reaction steps, low reaction yield, environmental pollution and high price of the original method, avoids the toxicity of selenium dioxide, reduces the pollution and improves the yield.

Drawings

FIG. 1 is a nuclear magnetic hydrogen spectrum of 1, 2-cyclohexanedione hemihydrate;

FIG. 2 is an X-ray single crystal diffractogram of 1, 2-cyclohexanedione hemihydrate;

FIG. 3 is a nuclear magnetic hydrogen spectrum of cyclohexyl glycoluril;

FIG. 4 is a nuclear magnetic hydrogen spectrum of cyclohexyl glycoluril diether;

FIG. 5 is the nuclear magnetic hydrogen spectrum of five-membered cyclohexyl cucurbituril.

Detailed Description

Example 1

The method comprises the following steps: synthesis of 1, 2-dicyclohexyl ketone hemihydrate

104.3ml of concentrated nitric acid is measured and added into a three-neck flask, and a proper amount of catalyst (V) is added₂O₅) When brown gas is discharged from the bottle, the bottle is put into a cold salt bath for cooling, the temperature is controlled to be minus 5 ℃ to 20 ℃, 52ml of cyclohexanol is put into a dropper, the cyclohexanol is slowly dripped into nitric acid, and the temperature is controlled in the dripping processThe temperature is controlled at 10-15 ℃ and the dripping is finished within 2 h. When the cyclohexanol is dripped off, air is blown to the liquid surface for 2-4h after the temperature is lower than 0 ℃. Washing with 75-80 deg.C hot water for 3 times to obtain white solid 1, 2-cyclohexanedione hemihydrate with yield of 42%;

step two: synthesis of cyclohexyl glycoluril

Taking 2.4g of 1, 2-cyclohexanedione hemihydrate and 4.8g of urea into a 200mL round-neck flask, adding 60mL of water and 30mL of ethanol to improve the solubility of the 1, 2-cyclohexanedione hemihydrate, stirring for 30min at room temperature, adding 1mL of concentrated hydrochloric acid, reacting for 12h at room temperature, and performing suction filtration by using a porous suction filtration funnel to obtain 1.06g of white solid cyclohexyl glycoluril, wherein the conversion rate is 41.40%;

step three: synthesis of cyclohexyl glycoluril diether

Adding 6g of paraformaldehyde into a 100mL round-neck flask, adding 40mL of 6mol of hydrochloric acid, heating for dissolving, cooling to room temperature after the solution is clear, adding 3.92g of cyclohexyl glycoluril for reacting for 1 hour, separating out a large amount of white solids, namely a cyclohexyl glycoluril diether crude product, and adding formic acid: heating the solution with the volume ratio of 1, 4-dioxane being 3:4 to 60 ℃ for recrystallization to obtain a pure product.

Step four: synthesis of cyclohexyl modified cucurbituril

Taking 2g of cyclohexyl glycoluril diether, adding 50mL of 8mol hydrochloric acid into a 100mL round-neck flask, heating to dissolve, and refluxing for 24h after the solution is clear to obtain the cyclohexyl modified cucurbituril.

Examples 2 to 20

Examples 2-20 differ from example 1 in that the reaction conditions in step two are different acids or different temperatures, as shown in the table:

synthesis of cyclohexyl glycoluril at different acids or at different temperatures of the same acid

The protonation is provided by acid to promote the dehydration of the hemihydrate, so that the 1, 2-cyclohexanedione hemihydrate and urea are synthesized into glycoluril. As shown in the table above, the yield of glycoluril increases from 41.40% to 96.60% with the temperature as a variable by a controlled variable method, and the yield increases from room temperature to 65 ℃ with the temperature as a variable, and becomes more stable at a temperature higher than 65 ℃, and the reaction is not easy to control due to the excessively high temperature, so the reaction is most suitable for being selected at 65 ℃. The same phenomenon appears when sulfuric acid is used as a protonic agent, the yield of glycoluril increases from 42.2% to 91.4% along with the temperature increase in the process of changing the temperature from room temperature to 65 ℃ by taking the temperature as a variable, and the yield is stable and has a trend of decreasing when the temperature is higher than 65 ℃, and the temperature of 65 ℃ is taken as the reaction condition for the convenience of the experiment. It is clear from the table that the same trend is shown when the same temperature is the hydrochloric acid and the sulfuric acid as the protonic agent, and the hydrochloric acid should be selected as the protonic agent in consideration of price and safety. The conclusion is that the glycoluril synthesis should be optimized with hydrochloric acid as the protonating agent and reaction at 65 ℃.

Although the present application has been described with reference to a few embodiments, it should be understood that various changes, substitutions and alterations can be made herein without departing from the spirit and scope of the application as defined by the appended claims.

Claims

1. A synthetic method of cyclohexyl modified cucurbituril is characterized by comprising the following steps: the method comprises the following steps:

the method comprises the following steps: when a catalyst is added into the concentrated nitric acid and brown gas is discharged, putting the concentrated nitric acid solution into a salt-ice bath for cooling, and controlling the temperature to be-5-20 ℃; slowly dripping cyclohexanol into concentrated nitric acid, controlling the temperature at 10-15 ℃, and finishing dripping within 2 h; after the temperature is reduced to below 0 ℃, blowing air to the liquid surface for 2-4h, washing for 3 times by hot water at the temperature of 75-80 ℃ to synthesize 1, 2-cyclohexanedione hemihydrate;

step two: reacting 1, 2-cyclohexanedione hemihydrate with urea under an acidic condition to synthesize cyclohexyl glycoluril, wherein the reaction temperature in the second step is 65 ℃;

step three: synthesizing cyclohexyl glycoluril and paraformaldehyde into cyclohexyl glycoluril diether under acidic conditions;

step four: heating, dissolving and refluxing cyclohexyl glycoluril diether in strong inorganic acid to obtain cyclohexyl modified cucurbituril, wherein the cyclohexyl modified cucurbituril is as follows:

2. the method for synthesizing cyclohexyl modified cucurbituril according to claim 1, wherein the method comprises the following steps: in the first step, the dosage of the concentrated nitric acid is 1-4 times of that of the cyclohexanol.

3. The method for synthesizing cyclohexyl modified cucurbituril according to claim 1, wherein the method comprises the following steps: and in the second step, the dosage ratio of the urea to the 1, 2-cyclohexanedione hemihydrate is more than 4: 1.

4. The method for synthesizing cyclohexyl modified cucurbituril according to claim 1, wherein the method comprises the following steps: the reaction condition of the second step is acidification with inorganic acid or organic acid in water.

5. The method for synthesizing cyclohexyl modified cucurbituril according to claim 1, wherein the method comprises the following steps: the reaction time in the second step is not less than 0.5 h.

6. The method for synthesizing cyclohexyl modified cucurbituril according to claim 1, wherein the method comprises the following steps: the dosage ratio of the trioxymethylene to the cyclohexyl glycoluril in the step is more than 4: 1.