Synthesis method of p-tert-butyl calix [4] arene bridged ketone derivative

Abstract

The invention discloses a synthetic method of a p-tert-butyl calix [4] arene bridged ketone derivative. The synthetic method comprises the following steps: (1) dissolving a p-tert-butyl calix [4] arene derivative in a solvent; (2) adding iodobenzene diacetic acid, and meanwhile, monitoring the reaction progress to ensure that the reaction is completed; and (3) carrying out column chromatography separation and purification on the crude product to obtain the high-purity p-tert-butyl calix [4] arene bridged ketone derivative. The p-tert-butyl calix [4] arene bridged ketone derivative is synthesized from the p-tert-butyl calix [4] arene derivative through long-term experimental research, continuous screening of conditions and adoption of safer and simpler experimental steps.

Description

Technical Field

[0001] The present invention relates to the technical field of intermediate compounds, and in particular to a method for synthesizing a p-tert-butylcalix[4]arene bridge ketone derivative. Background Art

[0002] Calixarenes are a class of macrocyclic compounds formed by connecting several phenol units with methylene as the intermediary. Calix[4]arene derivatives can be widely used in many fields, including molecular and ion recognition, ion transport, drug sustained release, supramolecular gel, extraction and separation, ion selective electrodes, chromatography, functional materials, catalysis and enzyme simulation. There are many derivatization methods for calix[4]arene. Among them, the most common derivatization reactions for the bridging methylene are substitution reaction and oxidation reaction. After the bridging methylene of calix[4]arene is oxidized, calix[4]arene bridging ketone can be obtained. The calix[4]arene bridging ketone is subjected to the next derivatization, such as addition reaction and reduction reaction, to obtain calix[4]arene derivatives of various structures. Therefore, the synthesis of calix[4]arene bridging ketone has very important scientific and practical significance.

[0003] In 1982, Ali A. Moshfegh et al. used resorcinol to condense with several aromatic aldehydes under acid catalysis to obtain cyclic macrocyclic compounds, and then used chromium trioxide in acetic anhydride to oxidize the cross-methylene to obtain calix[4]arene bridge ketone. Akira Ninagawa et al. synthesized p-tert-butylcalix[4]arene bridge ketone in 1985 as follows: 2.0 g of p-tert-butylcalix[4]arene, 70 mL of acetic anhydride and a drop of concentrated sulfuric acid were mixed together and refluxed for 1 hour. After cooling, a mixed solution of 2.0 g of chromium trioxide in 15 mL of acetic anhydride and 5 mL of acetic acid was added dropwise at 25°C within 2 hours under stirring. The mixture was stirred at 45°C for 4 hours, then poured into 200 mL of water and allowed to stand at room temperature overnight. The yellow precipitate was filtered out, washed with water, and dried at room temperature. The solvent was removed in vacuo and the product was dissolved in a mixture of 50 mL of ethanol and 150 mL of sodium hydroxide and stirred and refluxed for 1 hour. Then, the reaction mixture is neutralized with hydrochloric acid, the precipitate is filtered out, washed with a dilute hydrochloric acid solution and an aqueous solution in sequence, dried in vacuo, and then purified by column chromatography.

[0004] Although the oxidation synthesis method proposed by Akira Ninagawa et al. is indeed feasible, the reaction process must use strong oxidants such as chromium trioxide and acetic anhydride, which have serious safety risks, and the yield of brindone is less than 5%. Summary of the invention

[0005] The object of the present invention is to overcome the drawbacks of the existing synthesis of p-tert-butylcalix[4]arene bridged ketone, and to provide a new, simple and safe method for synthesizing p-tert-butylcalix[4]arene bridged ketone derivatives from p-tert-butylcalix[4]arene derivatives. This method lays a foundation for the subsequent synthesis of various p-tert-butylcalix[4]arene bridged derivatives.

[0006] Aiming at the problems existing in the synthesis of p-tert-butylcalix[4]arene bridged ketone derivatives at present, through long-term experimental research and continuous screening of conditions, the present invention adopts a safer and more concise experimental procedure to synthesize p-tert-butylcalix[4]arene bridged ketone derivatives from p-tert-butylcalix[4]arene derivatives.

[0007] A method for synthesizing p-tert-butylcalix[4]arene bridged ketone derivatives provided by the present invention comprises the following steps:

[0008] (1) Dissolve the p-tert-butylcalix[4]arene derivative in a solvent;

[0009] (2) Add iodobenzenediacetic acid, and simultaneously monitor the reaction progress to ensure the completion of the reaction;

[0010] (3) Subject the crude product to column chromatography for separation and purification to obtain a p-tert-butylcalix[4]arene bridged ketone derivative with high purity.

[0011] In some embodiments, the p-tert-butylcalix[4]arene derivative has the following structural formula:

[0012]

[0013] Wherein: R 1 、R 2 、R 3 、R 4 are selected from alkyl, acyl, sulfonyl or carbamoyl;

[0014] The alkyl is selected from -CH 3 、-CH 2 CH 3 、-CH 2 CH 2 CH 3 、-CH(CH 3 ) 2 、-CH 2 CH 2 CH 2 CH 3 、-CH 2 CH(CH 3 ) 2 、-CH 2 CH 2 OCH 3 、-CH 2COR, -CH 2 CN or -CH 2 (CH 2 OCH 2 ) n CH 2 -, R = alkyl, n = 2, 3, 4, 5;

[0015] The acyl group is selected from RC(O)-, where R = alkyl or aryl;

[0016] The sulfonyl group is selected from RSO 2 -, where R = alkyl or aryl;

[0017] The carbamoyl group is selected from RNC(O)-, where R = alkyl.

[0018] In certain embodiments, the reaction temperature in step (1) is 60 - 100 °C.

[0019] In certain embodiments, the reaction temperature in step (1) is 80 °C.

[0020] Wherein: In step (1), pay attention to observing the reaction temperature, and it should be slowly heated to a specific temperature to avoid sudden temperature rises and drops.

[0021] In certain embodiments, the solvent in step (1) is selected from methanol, ethanol, propanol, isopropanol, n-butanol, isobutanol, sec-butanol, tert-butanol, dichloromethane, chloroform, tetrahydrofuran, ethyl acetate, acetonitrile, N,N-dimethylformamide, toluene, 1,4-dioxane or 1,2-dichloroethane; the ratio of the p-tert-butylcalix[4]arene derivative to the solvent is 100 mg:3 mL; the molar ratio of the p-tert-butylcalix[4]arene derivative to iodobenzenediacetic acid is 1:5.

[0022] Wherein: Through multiple experiments, more solvents are selected, the use of chromium trioxide and acetic anhydride is avoided, and an attempt is made to simplify its purification steps.

[0023] In certain embodiments, the solvent in step (1) is selected from 1,4-dioxane.

[0024] In certain embodiments, the reaction temperature in step (2) is 60 - 100 °C, and the reaction time is 1 - 96 h.

[0025] In certain embodiments, the reaction temperature in step (2) is 80 °C, and the reaction time is 12 h.

[0026] Wherein: In step (2), monitor the reaction progress, and take the time when as much product as possible is generated with fewer impurities as the standard.

[0027] In certain embodiments, the purification step in step (3) is specifically as follows: The 1,4-dioxane solvent used is rotary evaporated to dryness, and separation is carried out using silica gel column chromatography.

[0028] In certain embodiments, the p-tert-butylcalix[4]arene bridge ketone derivative has the following structural formula:

[0029]

[0030] Wherein: R 1 , R 2 , R 3 , R 4 are selected from alkyl, acyl, sulfonyl or carbamoyl;

[0031] The alkyl is selected from -CH 3 , -CH 2 CH 3 , -CH 2 CH 2 CH 3 , -CH(CH 3 ) 2 , -CH 2 CH 2 CH 2 CH 3 , -CH 2 CH(CH 3 ) 2 , -CH 2 CH 2 OCH 3 , -CH 2 COR, -CH 2 CN or -CH 2 (CH 2 OCH 2 ) n CH 2 -, R = alkyl, n = 2, 3, 4, 5;

[0032] The acyl is selected from RC(O)-, R = alkyl or aryl;

[0033] The sulfonyl is selected from RSO 2 -, R = alkyl or aryl;

[0034] The carbamoyl is selected from RNC(O)-, R = alkyl.

[0035] In certain embodiments, it is prepared by using the reaction equation shown in formula (I):

[0036]

[0037] Wherein: 1a: R 1 , R2 , R 3 , R 4 is selected from -CH 2 CH 2 CH 3 ,

[0038] 2a: R 1 , R 2 , R 3 , R 4 is selected from -CH 2 CH 2 CH 3 ;

[0039] 1b: R 1 , R 3 is selected from -Pr, R 2 , R 4 is selected from -CH 2 COOCH 2 CH 3 ,

[0040] 2b: R 1 , R 3 is selected from -Pr, R 2 , R 4 is selected from -CH 2 COOCH 2 CH 3 ;

[0041] 1c: R 1 , R 2 , R 3 , R 4 is selected from -CH 2 CH 2 OCH 3 ,

[0042] 2c: R 1 , R 2 , R 3 , R 4 is selected from -CH 2 CH 2 OCH 3 ;

[0043] 1d: R 1 , R 2 is selected from -CH 2 (CH 2 OCH 2 ) 2 CH 2 -, R 3 , R 4 is selected from -CH 2 (CH 2 OCH2 ) 2 CH 2 -,

[0044] 2d: R 1 、R 2 selected from -CH 2 (CH 2 OCH 2 ) 2 CH 2 -、R 3 、R 4 selected from -CH 2 (CH 2 OCH 2 ) 2 CH 2 -;

[0045] 1e: R 1 、R 3 selected from -CH 2 (CH 2 OCH 2 ) 3 CH 2 -、R 2 、R 4 selected from -CH 2 (CH 2 OCH 2 ) 3 CH 2 -,

[0046] 2e: R 1 、R 2 selected from -CH 2 (CH 2 OCH 2 ) 3 CH 2 -、R 2 、R 4 selected from -CH 2 (CH 2 OCH 2 ) 3 CH 2 -。

[0047] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0048] 1. In the long-term research, the inventor team of the present invention tried a variety of different oxidants and found that only by adding an appropriate amount of iodobenzenedicarboxylic acid and without adding an additional catalyst, the product of p-tert-butylcalix[4]arene bridged ketone can be obtained; a variety of different solvents were tried and it was found that the synthesis efficiency of bridged ketone is the best in 1,4-dioxane;

[0049] 2. After the crude product of the tert-butylcalix[4]arene bridge ketone derivative is prepared, the solvent is removed by rotary evaporation; a high-purity product can be obtained by dry loading and column chromatography. The purification method is simple and easy to operate;

[0050] 3. The present invention synthesizes p-tert-butylcalix[4]arene bridge ketone derivatives by reacting p-tert-butylcalix[4]arene derivatives with iodophenyldiacetic acid. The method is simple and feasible, and avoids the disadvantages of using strong oxidants and acetic anhydride in the known synthesis of p-tert-butylcalix[4]arene bridge ketone.

[0051] 4. The reaction mechanism of the present invention: Iodophenyl diacetic acid decomposes under heating to generate acetoxy free radicals and iodophenyl monoacetic acid free radicals. Subsequently, the acetoxy free radical acts on calix[4]arene to capture its bridging hydrogen atom, and this process promotes the generation of acetic acid and calix[4]arene bridge free radicals. Next, the newly generated calix[4]arene bridge free radical combines with another molecule of acetoxy free radical, and at this time, the remaining bridging hydrogen atom is captured by another molecule of acetoxy free radical, thereby generating acetic acid and calix[4]arene acetoxy bridge free radical. Finally, one molecule of acetoxy free radical reacts with the acetyl group on the calix[4]arene acetoxy bridge free radical, and the two combine to generate acetic anhydride and calix[4]arene bridge ketone.

[0052] DETAILED DESCRIPTION

[0053] The present invention is further described in detail below through embodiments.

[0054] The instrument model and analysis conditions of the nuclear magnetic resonance of the embodiment of the present invention are: Bruker Avance III 400 superconducting nuclear magnetic resonance spectrometer; resonance frequency: 400 MHz; CDCl 3 As solvent.

[0055] Example 1

[0056] A round-bottom flask was placed on a magnetic stirrer with a temperature-controlled base, 15 mL of 1,4-dioxane was added, and then 500 mg of p-tert-butylcalix[4]arene derivative (R 1 =R 2 =R 3 =R 4 =-CH 2 CH 2 CH 3) It was added to 1,4-dioxane. 986 mg of iodobenzenediacetic acid was also added to the reaction solution. Subsequently, a spherical condenser was installed at the mouth of the reactor for reflux. The temperature was adjusted to ensure that the reaction temperature was 80 °C, and a PTFE magnetic stir bar was used for stirring inside the reactor. The reaction progress was continuously monitored during the reaction. After 12 h of reaction, the reaction was completed.

[0057] Then the reaction solution was cooled to room temperature, and the solvent was rotary evaporated to dryness. After column chromatography separation, a high-purity p-tert-butylcalix[4]arene bridge ketone product was obtained with a yield of 25%. This product has the characteristics of high purity, safety, and simple synthesis operation.

[0058] The nuclear magnetic resonance data analysis results of the product are as follows: 1 H NMR(400MHz,Chloroform-d)δ7.28(d,J=2.7Hz,2H,Ar-H),7.19(s,2H,Ar-H),6.97(d,J=2.5Hz,2H,Ar-H),6.87(d,J=2.5Hz,2H,Ar-H),3.87(d,J=16.8Hz,2H,Ar-CH 2 -Ar),3.81(s,2H,Ar-CH 2 -Ar),3.68(d,J=16.7Hz,2H,Ar-CH 2 -Ar),3.50-3.39(m,2H,O-CH 2 CH 2 CH 3 ),3.30(ddd,J=16.0,11.1,7.2Hz,4H,O-CH 2 CH 2 CH 3 ),3.15(ddd,J=13.8,9.6,5.4Hz,2H,O-CH 2 CH 2 CH 3 ),1.22(s,18H,t-Bu),1.19(s,18H,t-Bu),0.96(t,J=4.5Hz,4H,O-CH 2 CH 2 CH 3 ),0.85-0.74(m,4H,O-CH 2 CH 2 CH 3 ),0.59(t,J=7.5Hz,6H,O-CH 2 CH 2 CH 3 ),0.33(d,J=4.1Hz,6H,O-CH 2CH 2 CH 3 ) ppm.

[0059] Example 2

[0060] A round-bottom flask is placed on the magnetic stirrer with a temperature-controlled base, and 15 mL of 1,4-dioxane is added thereto. Then, 500 mg of p-tert-butylcalix[4]arene derivative (R 1 = R 3 = CH 2 CH 2 CH 3 , R 2 = R 4 = CH 2 COOCH 2 CH 3 ) is added to 1,4-dioxane, and 890 mg of iodobenzenediacetic acid is also added to the reaction solution. Subsequently, a spherical condenser is installed at the mouth of the reactor for reflux, and the temperature is adjusted to ensure that the reaction temperature is 80 °C. A PTFE magnetic stir bar is used for stirring inside the reactor. The reaction progress is continuously monitored during the reaction. After 24 h of reaction, the reaction is completed.

[0061] Then, the reaction solution is cooled to room temperature, and the solvent is rotary-evaporated to dryness. After column chromatography separation, a high-purity p-tert-butylcalix[4]arene bridged ketone product is obtained with a yield of 20%. This product has the characteristics of high purity, safety, and simple synthesis operation.

[0062] The nuclear magnetic resonance data analysis results of the product are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.52 (d, J = 2.6 Hz, 1H, Ar-H), 7.28 (d, J = 2.6 Hz, 1H, Ar-H), 7.25 (d, J = 2.6 Hz, 1H, Ar-H), 7.16 (d, J = 2.6 Hz, 1H, Ar-H), 7.14 (d, J = 2.6 Hz, Ar-H), 7.13 (d, J = 2.7 Hz, 1H, Ar-H), 7.02 (d, J = 2.6 Hz, 1H, Ar-H), 6.88 (d, J = 2.6 Hz, 1H, Ar-H), 4.20 (d, J = 10.2 Hz, 1H, Ar-CH 2 -Ar), 4.16 (d, J = 11.1 Hz, 1H, Ar-CH 2 -Ar), 3.99 (d, J = 6.3 Hz, 1H, Ar-CH 2 -Ar), 3.97 - 3.95 (m, 2HO-CH 2 COOCH 2 CH 3), 3.92 (td, J=7.0, 3.6 Hz, 2H O-CH 2 COOCH 2 CH 3 ), 3.88 (d, J=5.9 Hz, 1H, Ar-CH 2 -Ar), 3.84 (s, 1H, Ar-CH 2 -Ar), 3.78 (s, 1H, Ar-CH 2 -Ar), 3.74 (d, J=1.8 Hz, 2H O-CH 2 COOCH 2 CH 3 ), 3.72 - 3.66 (m, 2H, O-CH 2 COOCH 2 CH 3 ), 3.57 (td, J=8.9, 6.0 Hz, 1H, O-CH 2 CH 2 CH 3 ), 3.48 (dd, J=9.1, 6.1 Hz, 1H, O-CH 2 CH 2 CH 3 ), 2.97 (ddd, J=12.0, 7.8, 4.8 Hz, 1H, O-CH 2 CH 2 CH 3 ), 2.61 (ddd, J=12.0, 8.1, 4.5 Hz, 1H, O-CH 2 CH 2 CH 3 ), 1.37 - 1.29 (m, 2H, O-CH 2 CH 2 CH 3 ), 1.29 - 1.25 (m, 2H, O-CH 2 CH 2 CH 3 ), 1.23 (s, 9H, t-Bu), 1.21 (s, 9H, t-Bu), 1.18 (s, 9H, t-Bu), 1.17 (s, 9H, t-Bu), 1.07 (t, J=7.2 Hz, 3H, O-CH 2 COOCH 2 CH 3 ), 0.96 (t, J=7.1 Hz, 3H, O-CH 2 COOCH 2 CH 3 ), 0.74 (t, J=7.5 Hz, 3H, O-CH 2 CH 2CH 3 ), 0.30 (t, J = 7.3 Hz, 3H, O-CH 2 CH 2 CH 3 ) ppm。

[0063] Example 3

[0064] A round-bottom flask was placed on a magnetic stirrer with a temperature-controlled base, and 15 mL of 1,4-dioxane was added thereto. Then, 500 mg of p-tert-butylcalix[4]arene derivative (R 1 = R 2 = R 3 = R 4 = CH 2 CH 2 OCH 3 ) was added to 1,4-dioxane, and 914 mg of iodobenzenediacetic acid was also added to the reaction solution. Subsequently, a spherical condenser was installed at the mouth of the reactor for reflux, and the temperature was adjusted to ensure that the reaction temperature was 80 °C. A PTFE magnetic stir bar was used for stirring inside the reactor. The reaction progress was continuously monitored during the reaction, and after 12 h of reaction, the reaction was completed.

[0065] Then, the reaction solution was cooled to room temperature, and the solvent was evaporated to dryness using a rotary evaporator. After column chromatography separation, a high-purity p-tert-butylcalix[4]arene bridge ketone product was obtained with a yield of 27%. This product has the characteristics of high purity, safety, and simple synthesis operation.

[0066] The nuclear magnetic resonance data analysis results of the product are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.34 (d, J = 2.5 Hz, 2H, Ar-H), 7.26 (d, J = 2.6 Hz, 2H, Ar-H), 7.03 (d, J = 2.5 Hz, 2H, Ar-H), 6.95 (d, J = 2.4 Hz, 2H, Ar-H), 3.93 (d, J = 16.8 Hz, 2H, Ar-CH 2 -Ar), 3.84 (s, 2H, Ar-CH 2 -Ar), 3.72 (d, J = 16.9 Hz, 2H, Ar-CH 2 -Ar), 3.70 - 3.59 (m, 4H, O-CH 2 CH 2 OCH 3 ), 3.54 - 3.46 (m, 4H, O-CH 2 CH 2 OCH 3 ), 3.39 - 3.31 (m, 4H, O-CH 2 CH2 OCH 3 ), 3.14 (s, 6H, O-CH 2 CH 2 OCH 3 ), 3.09 (td, J=8.9, 5.5Hz, 2H, O-CH 2 CH 2 OCH 3 ), 3.00 (s, 6H, O-CH 2 CH 2 OCH 3 ), 2.98 - 2.92 (m, 2H, O-CH 2 CH 2 OCH 3 ), 1.28 (s, 18H, t-Bu), 1.26 (s, 18H, t-Bu) ppm。

[0067] Example 4

[0068] A round-bottom flask was placed on the magnetic stirrer with a temperature-controlled base, and 15 mL of 1,4-dioxane was added thereto. Then, 500 mg of p-tert-butylcalix[4]arene derivative (R 1 = R 2 = CH 2 (CH 2 OCH 2 ) 2 CH 2 , R 3 = R 4 = CH 2 (CH 2 OCH 2 ) 2 CH 2 ) was added to 1,4-dioxane, and 919 mg of iodobenzenediacetic acid was also added to the reaction solution. Subsequently, a spherical condenser was installed at the mouth of the reactor for reflux, and the temperature was adjusted to ensure that the reaction temperature was 80 °C. A PTFE magnetic stir bar was used for stirring inside the reactor. During the reaction, the reaction progress was continuously monitored. After 12 h of reaction, the reaction was completed.

[0069] Then, the reaction solution was cooled to room temperature, and the solvent was evaporated to dryness using a rotary evaporator. After column chromatography separation, a high-purity p-tert-butylcalix[4]arene bridged ketone product was obtained with a yield of 53%. This product has the characteristics of high purity, safety, and simple synthesis operation.

[0070] The nuclear magnetic resonance data analysis results of the product are as follows: 11H NMR (400 MHz, Chloroform-d) δ 7.56 (d, J = 2.6 Hz, 2H, Ar-H), 7.47 (d, J = 2.6 Hz, 2H, Ar-H), 7.11 (d, J = 2.5 Hz, 2H, Ar-H), 7.03 (d, J = 2.5 Hz, 2H, Ar-H), 4.33 (d, J = 12.4 Hz, 2H, Ar-CH 2 -Ar), 3.81 - 3.77 (m, 2H, Ar-CH 2 -Ar), 3.74 - 3.54 (m, 12H, O-CH 2 CH 2 -O), 3.47 - 3.42 (m, 2H, O-CH 2 CH 2 -O), 3.39 - 3.27 (m, 6H, O-CH 2 CH 2 -O), 3.12 (d, J = 12.5 Hz, 2H, Ar-CH 2 -Ar), 2.91 (ddd, J = 10.6, 8.8, 4.6 Hz, 2H, O-CH 2 CH 2 -O), 2.80 (td, J = 8.1, 5.8 Hz, 2H, O-CH 2 CH 2 -O), 1.31 (s, 18H, t-Bu), 1.26 (s, 18H, t-Bu) ppm。

[0071] Example 5

[0072] A round-bottom flask was placed on the magnetic stirrer with a temperature-controlled base, and 15 mL of 1,4-dioxane was added thereto. Then, 500 mg of p-tert-butylcalix[4]arene derivative (R 1 = R 3 = CH 2 (CH 2 OCH 2 ) 3 CH 2 , R 2 = R 4 = CH 2 (CH 2 OCH 2 ) 3 CH 2) It was added to 1,4-dioxane. 835 mg of iodobenzenediacetic acid was also added to the reaction solution. Subsequently, a spherical condenser was installed at the mouth of the reactor for reflux. The temperature was adjusted to ensure that the reaction temperature was 80 °C, and a PTFE magnetic stir bar was used for stirring inside the reactor. During the reaction process, the reaction progress was continuously monitored. After 12 h of reaction, the reaction was completed.

[0073] Then the reaction solution was cooled to room temperature, and the solvent was rotary evaporated to dryness. After column chromatography separation, a high-purity p-tert-butylcalix[4]arene bridged ketone product was obtained with a yield of 28%. This product has the characteristics of high purity, safety, and simple synthesis operation.

[0074] The nuclear magnetic resonance data analysis results of the product are as follows: 1 H NMR(400MHz,Chloroform-d)δ7.35(d,J=2.5Hz,2H,Ar-H),7.26(d,J=2.6Hz,2H,Ar-H),7.03(d,J=2.4Hz,2H,Ar-H),6.95(d,J=2.4Hz,2H,Ar-H),3.90(d,J=16.9Hz,2H,Ar-CH 2 -Ar),3.84(s,2H,Ar-CH 2 -Ar),3.73(d,J=17.0Hz,2H,Ar-CH 2 -Ar),3.59-3.48(m,8H,O-CH 2 CH 2 -O),3.42(ddd,J=13.0,5.8,3.9Hz,4H,O-CH 2 CH 2 -O),3.37-3.23(m,12H,O-CH 2 CH 2 -O),3.07(td,J=10.0,5.2Hz,4H,O-CH 2 CH 2 -O),3.01-2.92(m,4H,O-CH 2 CH 2 -O),1.33(s,18H,t-Bu),1.31(s,18H,t-Bu)ppm.

[0075] In summary, the synthesis method of the p-tert-butylcalix[4]arene bridged ketone derivative of the present invention has the following advantages:

[0076] 1. p-tert-Butylcalix[4]arene derivatives have good solubility in 1,4-dioxane and the best reaction effect. Only by adding an appropriate amount of iodobenzenediacetic acid and without adding an additional catalyst, the product of p-tert-butylcalix[4]arene bridged ketone with a high yield can be obtained; the safety hazard problems caused by other reagents are avoided;

[0077] 2. After obtaining the crude product of p-tert-butylcalix[4]arene bridged ketone derivative, the solvent is removed by rotary evaporation; dry loading is used, and the high-purity product can be obtained after column chromatography. This purification method is simple and easy to operate;

[0078] 3. p-tert-Butylcalix[4]arene bridged ketone derivative is synthesized from p-tert-butylcalix[4]arene derivative and iodobenzenediacetic acid. The method is simple and feasible, avoiding the disadvantages of using strong oxidants and acetic anhydride in the traditional synthesis of calix[4]arene bridged ketone, and significantly improving the yield at the same time.

[0079] The above description is only the preferred mode of the present invention. It should be pointed out that for those of ordinary skill in the art, without departing from the creative concept of the present invention, several modifications and improvements can still be made, and these should also be regarded as within the protection scope of the invention.

Claims

1. A method for synthesizing a tert-butylcalix[4]arene bridge ketone derivative, characterized in that: The following steps are involved: (1) dissolving a p-tert-butylcalix[4]arene derivative in a solvent; (2) adding iodophenyldiacetic acid while monitoring the reaction progress to ensure that the reaction is complete; (3) The crude product is separated and purified by column chromatography to obtain a high-purity tert-butylcalix[4]arene bridge ketone derivative.

2. The method for synthesizing a tert-butylcalix[4]arene bridge ketone derivative according to claim 1, characterized in that: The p-tert-butylcalix[4]arene derivative has the following structural formula: Where: R 1 , R 2 , R 3 , R 4 is selected from alkyl, acyl, sulfonyl or carbamoyl; Alkyl is selected from -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CH2CH2CH2CH3, -CH2CH(CH3)2, -CH2CH2OCH3, -CH2COR, -CH2CN or -CH2(CH2OCH2) n CH2-, R = alkyl, n = 2, 3, 4, 5; Acyl is selected from RC(O)-, R = alkyl or aryl; Sulfonyl is selected from RSO2-, R = alkyl or aryl; The carbamoyl group is selected from RNC(O)-, R = alkyl.

3. The method for synthesizing a tert-butylcalix[4]arene bridge ketone derivative according to claim 1, characterized in that: The reaction temperature in step (1) is 60-100°C.

4. The method for synthesizing a tert-butylcalix[4]arene bridge ketone derivative according to claim 1, characterized in that: The reaction temperature in step (1) is 80°C.

5. The method for synthesizing a tert-butylcalix[4]arene bridge ketone derivative according to claim 1, characterized in that: In step (1), the solvent is selected from methanol, ethanol, propanol, isopropanol, n-butanol, isobutanol, sec-butanol, tert-butanol, dichloromethane, chloroform, tetrahydrofuran, ethyl acetate, acetonitrile, N,N-dimethylformamide, toluene, 1,4-dioxane or 1,2-dichloroethane; the ratio of p-tert-butylcalix[4]arene derivative to solvent is 100 mg:3 mL; the molar ratio of p-tert-butylcalix[4]arene derivative to iodophenyldiacetic acid is 1:

5.

6. The method for synthesizing a p-tert-butylcalix[4]arene bridge ketone derivative according to claim 1, characterized in that: In step (1), the solvent is selected from 1,4-dioxane.

7. The method for synthesizing a p-tert-butylcalix[4]arene bridge ketone derivative according to claim 1, characterized in that: In step (2), the reaction temperature is 60-100° C. and the reaction time is 1-96 h.

8. The method for synthesizing a p-tert-butylcalix[4]arene bridge ketone derivative according to claim 1, characterized in that: In step (2), the reaction temperature is 80° C. and the reaction time is 12 h.

9. The method for synthesizing a tert-butylcalix[4]arene bridge ketone derivative according to claim 1, characterized in that: The p-tert-butylcalix[4]arene bridge ketone derivative has the following structural formula: Where: R 1 , R 2 , R 3 , R 4 is selected from alkyl, acyl, sulfonyl or carbamoyl; Alkyl is selected from -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CH2CH2CH2CH3, -CH2CH(CH3)2, -CH2CH2OCH3, -CH2COR, -CH2CN or -CH2(CH2OCH2) n CH2-, R = alkyl, n = 2, 3, 4, 5; Acyl is selected from RC(O)-, R = alkyl or aryl; Sulfonyl is selected from RSO2-, R = alkyl or aryl; The carbamoyl group is selected from RNC(O)-, R = alkyl.

10. The method for synthesizing a p-tert-butylcalix[4]arene bridge ketone derivative according to claim 1, characterized in that: The reaction equation shown in formula (I) is used to prepare: Among them: 1a: R 1 , R 2 , R 3 , R 4 Selected from -CH2CH2CH3, 2a: R 1 , R 2 , R 3 , R 4 Selected from -CH2CH2CH3; 1b: R 1 , R 3 Selected from -Pr, R 2 , R 4 Selected from -CH2COOCH2CH3, 2b: R 1 , R 3 Selected from -Pr, R 2 , R 4 Selected from -CH2COOCH2CH3; 1c: R 1 , R 2 , R 3 , R 4 Selected from -CH2CH2OCH3, 2c: R 1 , R 2 , R 3 , R 4 Selected from -CH2CH2OCH3; 1d: R 1 , R 2 Selected from -CH2(CH2OCH2)2CH2-, R 3 , R 4 Selected from -CH2(CH2OCH2)2CH2-, 2d: R 1 , R 2 Selected from -CH2(CH2OCH2)2CH2-, R 3 , R 4 Selected from -CH2(CH2OCH2)2CH2-; 1e: R 1 , R 3 Selected from -CH2(CH2OCH2)3CH2-, R 2 , R 4 Selected from -CH2(CH2OCH2)3CH2-, 2e: R 1 , R 2 Selected from -CH2(CH2OCH2)3CH2-, R 2 , R 4 Selected from -CH2(CH2OCH2)3CH2-.

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