阅读说明：本技术 一种冠醚类化合物及其制备方法与其在离子识别中的应用 (Crown ether compound, preparation method thereof and application thereof in ion recognition ) 是由 曲大辉 赵蔡鑫 茆敏 刘月 田禾 于 2019-10-25 设计创作，主要内容包括：本发明公开了一种冠醚类化合物,通式如式I所示化合物或其异构体：<Image he="511" wi="627" file="DDA0002247312910000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>式I中,n为2～5的整数。本发明经广泛且深入的研究,设计并合成了一种结构新颖的冠醚类化合物,该类冠醚类化合物不仅可与钾、钠、铵盐形成配合物,而且能够特异性地识别钠离子。因此,本发明不仅丰富了冠醚的种类,而且拓宽了冠醚的应用领域,本发明所述冠醚类化合物可用于离子识别和药物载体等技术领域。(The invention discloses a crown ether compound, which has a general formula as shown in formula I: in the formula I, n is an integer of 2-5. The invention designs and synthesizes a crown ether compound with a novel structure through extensive and intensive research, and the crown ether compound not only can form a complex with potassium, sodium and ammonium salt, but also can specifically identify sodium ions. Therefore, the invention not only enriches the variety of crown ethers, but also widens the application field of crown ethers, and the crown ether compound can be used for ion recognition, drug carriers and the likeThe technical field is as follows.)

1. A crown ether compound is characterized in that the general formula of the compound is shown as a formula I:

in the formula I, n is an integer of 2-5.

2. A method for preparing a crown ether compound according to claim 1, comprising the steps of:

dissolving 9, 10-phenanthrenequinone and aniline in a molar ratio of 1 (2-4) in a solvent, adding 4 equivalents of titanium tetrachloride under an ice bath condition, removing the solvent after complete reaction at room temperature, then adding a mixed solvent for dissolving, adding sodium borohydride in batches for reflux reaction, wherein the molar ratio of the sodium borohydride to the 9, 10-phenanthrenequinone is 1 (1.01-2), and performing aftertreatment to obtain a compound shown in a formula IV;

dissolving a compound shown as a formula IV with a molar ratio of 1 (1.1-2) to (1.5-2.5), iodobenzene, potassium carbonate and copper trifluoromethanesulfonate in a solvent, completely carrying out reflux reaction, and carrying out post-treatment to obtain a compound shown as a formula VI;

injecting phosphorus oxychloride into a solvent at 0 ℃ under the protection of nitrogen, violently stirring, slowly dropping the solvent in which the compound shown in the formula VI is dissolved, wherein the molar ratio of the compound shown in the formula VI to the phosphorus oxychloride is 1 (8-12), and completely reacting at 70-90 ℃ to obtain the compound shown in the formula VII;

dissolving a compound shown in a formula VII in a solvent, slowly adding sodium borohydride under ice bath, wherein the molar ratio of the compound shown in the formula VII to the sodium borohydride is 1 (8-12), and completely reacting at room temperature to obtain a compound shown in a formula VIII;

dissolving a compound shown in a formula VIII and a compound shown in a formula IX in a molar ratio of 1 (1.01-2) in a solvent, adding sodium hydride, wherein the molar ratio of the compound shown in the formula VIII to the sodium hydride is 1 (8-12), and completely carrying out reflux reaction to obtain the compound shown in the formula I.

3. The method for preparing a crown ether compound according to claim 2, wherein the method for preparing the compound represented by the formula IX comprises the following steps:

n is an integer of 2-5;

dissolving a compound shown as a formula X in a solvent, adding an organic base, wherein the molar ratio of the compound shown as the formula X to the organic base is 1 (2-4), dropwise adding p-toluenesulfonyl chloride in an ice bath, the molar ratio of the compound shown as the formula X to the p-toluenesulfonyl chloride is 1 (2-4), stirring in the ice bath after dropwise adding is finished, and stirring at normal temperature to react completely to obtain the compound shown as the formula IX.

4. The method for preparing crown ether compounds according to claim 2 or 3, wherein the solvent is toluene, 1,3, 5-trichlorobenzene, N-dimethylformamide, methanol, tetrahydrofuran.

5. The method for preparing a crown ether compound according to claim 2, wherein the mixed solvent is a mixture of tetrahydrofuran and ethanol.

6. The method for preparing a crown ether compound according to claim 2, wherein the organic base is triethylamine.

7. Use of the crown ether compound of claim 1 in ion recognition or drug carriers.

8. The use of crown ether compounds in ion recognition or drug carriers according to claim 7, wherein the ion recognition refers to recognition of sodium ions.

Technical Field

The invention belongs to the technical field of organic synthesis, and particularly relates to a crown ether compound containing a dihydrophenazine group, a preparation method thereof, and application thereof in ion recognition.

Background

A crown ether is a heterocyclic organic compound containing multiple ether groups that is capable of complexing alkali metal ions (c.j.pedersen, j.am.chem.soc., 1967, 89, 7017). The existing crown ether can complex alkali metal ions such as potassium, sodium and the like, and can also be used as a host molecule to form a complex with ammonium salt (guest molecule) through hydrogen bonds. However, it is difficult to intuitively show that a crown ether (e.g., benzo 24 crown 8) forms a complex with the above-mentioned ion to specifically recognize a certain ion. Thus, the application field of crown ethers is limited.

Disclosure of Invention

The first purpose of the invention is to provide a novel crown ether compound.

The second purpose of the invention is to provide a preparation method of the crown ether compound.

The third purpose of the invention is to provide the application of the crown ether compound in ion recognition.

In order to achieve the purpose, the technical scheme adopted by the invention is as follows:

the first aspect of the invention provides a crown ether compound, which has a general formula as shown in formula I or an isomer (including stereoisomerism or cis-trans-isomerism) thereof:

in the formula I, n is an integer of 2-5.

The second aspect of the invention provides a preparation method of the crown ether compound, which comprises the following steps:

dissolving 9, 10-phenanthrenequinone and aniline in a molar ratio of 1 (2-4) in a solvent, adding 4 equivalents of titanium tetrachloride under an ice bath condition, removing the solvent after complete reaction at room temperature, then adding a mixed solvent for dissolving, adding sodium borohydride in batches for reflux reaction, wherein the molar ratio of the sodium borohydride to the 9, 10-phenanthrenequinone is 1 (1.01-2), and performing aftertreatment to obtain a compound shown in a formula IV;

dissolving a compound shown as a formula IV with a molar ratio of 1 (1.1-2) to (1.5-2.5), iodobenzene, potassium carbonate and copper trifluoromethanesulfonate in a solvent, completely carrying out reflux reaction, and carrying out post-treatment to obtain a compound shown as a formula VI;

injecting phosphorus oxychloride into a solvent at 0 ℃ under the protection of nitrogen, violently stirring, slowly dropping the solvent in which the compound shown in the formula VI is dissolved, wherein the molar ratio of the compound shown in the formula VI to the phosphorus oxychloride is 1 (8-12), and completely reacting at 70-90 ℃ to obtain the compound shown in the formula VII;

dissolving a compound shown in a formula VII in a solvent, slowly adding sodium borohydride under ice bath, wherein the molar ratio of the compound shown in the formula VII to the sodium borohydride is 1 (8-12), and completely reacting at room temperature to obtain a compound shown in a formula VIII;

n is an integer of 2-5;

dissolving a compound shown as a formula X in a solvent, adding organic base (triethylamine), wherein the molar ratio of the compound shown as the formula X to the organic base (triethylamine) is 1 (2-4), dropwise adding p-toluenesulfonyl chloride in an ice bath, wherein the molar ratio of the compound shown as the formula X to the p-toluenesulfonyl chloride is 1 (2-4), stirring in the ice bath after dropwise adding, and stirring at normal temperature for complete reaction to obtain a compound shown as a formula IX;

dissolving a compound shown in a formula VIII and a compound shown in a formula IX in a molar ratio of 1 (1.01-2) in a solvent, adding sodium hydride, wherein the molar ratio of the compound shown in the formula VIII to the sodium hydride is 1 (8-12), and completely carrying out reflux reaction to obtain the compound shown in the formula I.

The solvent is toluene, 1,3, 5-trichlorobenzene, N-dimethylformamide, methanol and tetrahydrofuran.

The mixed solvent is a mixture of tetrahydrofuran and ethanol.

The preparation method of the formula X is referred to J.Med.chem.2016,59,17, 7840-.

The third aspect of the invention provides an application of the crown ether compound in ion recognition or drug carriers.

The ion recognition refers to recognition of sodium ions.

Due to the adoption of the technical scheme, the invention has the following advantages and beneficial effects:

the invention designs and synthesizes a crown ether compound with a novel structure through extensive and intensive research, and the crown ether compound not only can form a complex with potassium, sodium and ammonium salt, but also can specifically identify sodium ions. Therefore, the crown ether compound not only enriches the variety of crown ethers, but also widens the application field of crown ethers, and can be used in the technical fields of ion recognition, drug carriers and the like.

Drawings

FIG. 1 shows the NMR spectrum of VIE24C4, a compound represented by formula I-1.

FIG. 2 shows the NMR spectrum of VIE27C5, a compound represented by formula I-2.

FIG. 3 is a nuclear magnetic resonance hydrogen spectrum of a compound VIE30C6 shown in formula I-3.

FIG. 4 is a nuclear magnetic resonance hydrogen spectrum of a compound VIE33C7 shown in formula I-4.

FIG. 5 is a graph showing the change in fluorescence spectrum of sodium hexafluorophosphate added stepwise to the compound VIE24C4 represented by the formula I-1.

FIG. 6 is a graph showing the change in fluorescence spectrum of a stepwise addition of ammonium hexafluorophosphate to the compound VIE24C4 shown in formula I-1.

FIG. 7 is a graph showing the change in fluorescence spectrum of potassium hexafluorophosphate added stepwise to the compound VIE24C4 represented by the formula I-1.

FIG. 8 is a graph showing the change in fluorescence spectrum of sodium hexafluorophosphate added stepwise to the compound VIE27C5 represented by the formula I-2.

FIG. 9 is a graph showing the change in fluorescence spectrum of a stepwise addition of ammonium hexafluorophosphate to the compound VIE27C5 shown in formula I-2.

FIG. 10 is a graph showing the change in fluorescence spectrum of potassium hexafluorophosphate added stepwise to the compound VIE27C5 represented by the formula I-2.

FIG. 11 is a graph showing the change in fluorescence spectrum of sodium hexafluorophosphate added stepwise to the compound VIE30C6 represented by the formula I-3.

FIG. 12 is a graph showing the change in fluorescence spectrum of a stepwise addition of ammonium hexafluorophosphate to the compound VIE30C6 represented by the formula I-3.

FIG. 13 is a graph showing the change in fluorescence spectrum of potassium hexafluorophosphate added stepwise to the compound VIE30C6 represented by the formula I-3.

FIG. 14 is a graph showing the change in fluorescence spectrum of sodium hexafluorophosphate added stepwise to the compound VIE33C7 represented by the formula I-4.

FIG. 15 is a graph showing the change in fluorescence spectrum of a stepwise addition of ammonium hexafluorophosphate to a compound of formula I-4, VIE33C 7.

FIG. 16 is a graph showing the change in fluorescence spectrum of potassium hexafluorophosphate added stepwise to the compound VIE33C7 represented by the formula I-4.

FIG. 17 is a comparison graph of fluorescence colors of compounds represented by formulas I-1, I-2, I-3, and I-4 after adding sodium hexafluorophosphate, ammonium hexafluorophosphate, and potassium hexafluorophosphate, respectively.

Detailed Description

In order to more clearly illustrate the invention, the invention is further described below in connection with preferred embodiments. It is to be understood by persons skilled in the art that the following detailed description is illustrative and not restrictive, and is not to be taken as limiting the scope of the invention.