A chiral binaphthyl enantiomeric macrocyclic aromatic hydrocarbon, its synthesis method and application

Abstract

The present invention discloses a chiral binaphthyl enantiomeric macrocyclic aromatic hydrocarbon, its preparation method and application. The structural formulas of the chiral binaphthyl enantiomeric macrocyclic aromatic hydrocarbon are the RR-1 and SS-1 compounds as follows: #imgabs0# Its selective recognition of iodide anions is significantly better than that of AcO ‑ , NO 3‑ , ClO4 ‑ , HSO4 ‑ , Br ‑ , PF6 ‑ , H2PO4 ‑ , BF4 ‑ , CO3F3S ‑ and other anions, and the recognition process can cause a visible color change, which can be used for the detection of iodide anions.

Description

Technical Field

[0001] The present invention relates to a macrocyclic aromatic hydrocarbon, in particular to a chiral binaphthyl enantiomeric macrocyclic aromatic hydrocarbon, and also relates to a synthesis method thereof and its application as a molecular probe in the detection of iodide anions in a solution system, belonging to the technical field of organic small molecule materials. Background Art

[0002] Negative ions are ubiquitous and play an important role in the human body. For example, iodine is a raw material for synthesizing thyroid hormones, which can promote material metabolism, regulate the metabolism of proteins, fats and sugars, and contribute to the regulation of water and salt metabolism. However, iodine deficiency can lead to diseases such as goiter or hypothyroidism. However, the most common effects of high iodine on thyroid function are iodine-induced goiter (IH) and hyperthyroidism due to high iodine. In addition, 129 I - and 130 the radioactive isotopes of I- are considered harmful to the environment. Therefore, the development of iodide anion receptors and sensors for detecting iodide anions has great value and has attracted considerable interest.

[0003] The continuous synthesis of novel macrocyclic host molecules and their unique molecular recognition properties have promoted the development of supramolecular chemistry. In the past few decades, various macrocyclic hosts have been developed and have shown excellent recognition properties for anions (such as fluoride ions, nitrate ions, oxyacids and other anions). Prominent examples include Sessler's calixpyrrole, Farnham's fluorinated macrocyclic ether, Flood's triazane, Sindelar's bambusuril macrocycle, Beer's rotaxane and catenane, etc. Most strategies involve binding anions by utilizing hydrogen bonds provided by specific binding sites, thus having size and shape selectivity in various media. However, there are relatively few reports on the construction of iodide anion receptor macrocycles because iodide anions have a large diameter and low electron density, making it difficult to form hydrogen bonds and anion-π interactions. The literature (Angew. Chem., Int. Ed., 2008, 47, 788; Angew. Chem., Int. Ed., 2008, 47, 2649; Angew. Chem., Int. Ed.,

[0004] 2008, 47, 3740; J. Am. Chem. Soc., 2008, 130, 10895.) elucidated the neutral C–H… anion interaction, and this interaction has attracted great interest from chemists and has developed rapidly. The literature

[0005] (Science, 2019, 365, 159; Chem. Soc. Rev., 2010, 39, 1262; Chem. Commun.,

[0006] (Disclosed in 2012, 48, 5065.) A triazole macrocycle and cage were disclosed, and it was found that these triazole macrocycles and cages showed strong affinity for anions through neutral C–H…anion interactions. The literature (Org.

[0007] Lett., 2020, 22, 4878; J. Am. Chem. Soc., 2020, 142, 20182; Angew. Chem. Int.

[0008] Ed., 2022, e202209078.) reported the recognition of anions in water by molecular cages through neutral C–H…anion interactions. The literature (Org. Lett., 2016, 18, 5054.) demonstrated that the pre-organized rigid macrocycle [4]carbazole could act as an iodide anion receptor through neutral C–H…anion interactions. Despite these pioneering reports, macrocyclic host molecules with selective recognition of iodide anions have been rarely reported. Summary of the Invention

[0009] Aiming at the defects existing in the prior art, the first object of the present invention is to provide a chiral binaphthyl enantiomeric macrocyclic aromatic hydrocarbon, which has a large number of neutral aryl C-H bonds and a special cavity structure, has selective recognition and complexation effects on iodide anions, and has a visible color change after complexing with iodide anions, and is particularly suitable for detecting iodide anions in solution systems.

[0010] The second object of the present invention is to provide a synthesis method of the chiral binaphthyl enantiomeric macrocyclic aromatic hydrocarbon, which is simple, has mild conditions and a high yield, and is conducive to expanding production.

[0011] The third object of the present invention is to provide an application of the chiral binaphthyl enantiomeric macrocyclic aromatic hydrocarbon, which has selective recognition and complexation effects on iodide anions in solution systems containing anions such as AcO - , NO 3- , ClO4 - , HSO4 - , Br - , PF6 - , H2PO4 - , BF4 - , CO3F3S - etc., and has a visible color change after complexing with iodide anions, and can be used for detecting iodide anions in solution systems.

[0012] To achieve the above technical objectives, the present invention provides a chiral binaphthyl enantiomeric macrocyclic aromatic hydrocarbon, which includes RR-1 and / or SS-1 compounds;

[0013]

[0014] Both the chiral binaphthyl enantiomeric macrocyclic arenes RR-1 and SS-1 provided by the present invention have a box-like structure, with cavity sizes of approximately 10.100×9.000 and 9.000×9.000 respectively, and both RR-1 and SS-1 contain a large number of neutral aryl C-H bonds, and can be used as receptors for iodide anions to achieve the complexation of iodide anions. Particularly unexpectedly, the chiral binaphthyl enantiomeric macrocyclic arene compounds RR-1 and SS-1 have a selective recognition effect on complex anion solution systems, and obvious color changes visible to the naked eye occur after the compounds RR-1 and SS-1 complex with iodide anions, making it possible to use the compounds RR-1 and SS-1 for the detection of iodide anions.

[0015] The present invention also provides a method for synthesizing chiral binaphthyl enantiomeric macrocyclic arenes. This method involves subjecting 2,4-dimethoxybenzeneboronic acid and the R-3 or S-3 compound to a Suzuki coupling reaction to obtain the R-2 or S-2 compound; and subjecting the R-2 or S-2 compound and paraformaldehyde to a condensation reaction to obtain the RR-1 or SS-1 structural compound.

[0016] The structural formula of the R-3 compound is as follows:

[0017]

[0018] The structural formula of the S-3 compound is as follows:

[0019]

[0020] The structural formula of the R-2 compound is as follows:

[0021]

[0022] The structural formula of the S-2 compound is as follows:

[0023]

[0024] The synthesis method of the chiral binaphthyl enantiomeric macrocyclic arenes of the present invention can be achieved through two steps of Suzuki coupling and condensation reactions. The synthesis method is simple and the product yield is relatively high.

[0025] As a preferred embodiment, in a sodium carbonate ethanol solution system, 2,4-dimethoxybenzeneboronic acid and the R-3 or S-3 compound are reacted at a temperature of 85-95°C for 12-36 hours under the catalysis of Pd(PPh3)4 and CuI. Further preferably, the reaction is carried out at a temperature of 90°C for 24 hours.

[0026] As a more preferred embodiment, the molar ratio of sodium carbonate to the R-3 or S-3 compound is 1:(2-3).

[0027] As a more preferred embodiment, the molar ratio of 2,4-dimethoxyphenylboronic acid to the R-3 or S-3 compound is 1:(2-2.5).

[0028] As a more preferred embodiment, the addition amounts of Pd(PPh3)4 and CuI are catalytic amounts, such as 5-20 mol%.

[0029] As a preferred embodiment, in a dichloromethane solution system, the R-2 or S-2 compound and paraformaldehyde react at room temperature for 0.4-0.6 hours under the catalysis of boron trifluoride diethyl ether. The addition amount of boron trifluoride diethyl ether is 1-1.5 times the molar amount of the R-2 or S-2 compound.

[0030] As a more preferred embodiment, the molar ratio of the R-2 or S-2 compound to paraformaldehyde is 1:(2-4).

[0031] The specific synthesis route of the chiral binaphthyl enantiomeric macrocyclic aromatic hydrocarbon of the present invention is as follows:

[0032]

[0033] The present invention also provides an application of the chiral binaphthyl enantiomeric macrocyclic aromatic hydrocarbon, which is used as a molecular probe for detecting iodide ions in a solution system. The selective recognition of iodide ions by the chiral binaphthyl enantiomeric macrocyclic aromatic hydrocarbon is significantly better than that of other anions, such as AcO - , NO 3- , ClO4 - , HSO4 - , Br - , PF6 - , H2PO4 - , BF4 - , CO3F3S - , etc., and the recognition process can be observed with the naked eye, such as the solution color changing from colorless to light orange. Compared with the prior art, the beneficial technical effects brought by the technical solution of the present invention:

[0034] The chiral binaphthyl enantiomeric macrocyclic aromatic hydrocarbon provided by the present invention has a large number of neutral aryl C-H bonds and a special cavity structure, and it has a selective recognition and complexation effect on iodide ions. For example, in the presence of AcO - , NO 3- , ClO4 - , HSO4 - , Br - , PF6 - , H2PO4 - , BF4 - , CO3F3S -In a solution system of anions such as this, it can highly selectively recognize and complex iodide anions, accompanied by a visible color change, and can be used for the detection of iodide anions in a solution system.

[0035] The synthetic method of the chiral binaphthyl enantiomeric macrocyclic aromatic hydrocarbon of the present invention is simple, the conditions are mild, and the yield is relatively high, which is conducive to expanding production. Brief Description of the Drawings

[0036] Figure 1 In (a) and (b), they are the energy-minimized structures of RR-1 and SS-1 simulated by the Gaussian computer program; (c) is the CD spectrum of RR-1 (black line) and SS-1 (red line).

[0037] Figure 2 In (a), it is the UV-visible spectrum of RR-1 (1.00×10 -2 mM) in a chloroform mixed solution. RR-1 and TBAX (X = AcO - , NO 3- , ClO4 - , HSO4 - , Br - , I - , PF6 - , H2PO4 - , BF4 - , CO3F3S - )(5.0 equivalents); (b) is the UV-visible spectrum of SS-1 (1.00×10 -2 mM) in a chloroform mixed solution. SS-1 and TBAX (X = AcO - , NO 3- , ClO4 - , HSO4 - , Br - , I - , PF6 - , H2PO4 - , BF4 - , CO3F3S - )(5. equivalents). The inset shows a photograph of the color of these mixed solutions.

[0038] Figure 3 In (a), it is free RR-1, and in (b), it is the 1H NMR spectrum (400 MHz, CDCl3, 298 K) of a part of RR-1, 1.0 equivalent, and in (c), it is free TBAI, [RR-1]0 = 4.0 mmol / L. 1 H NMR spectrum (400 MHz, CDCl3, 298 K), 1.0 equivalent, (c) is free TBAI, [RR-1]0 = 4.0 mmol / L.

[0039] Figure 4 They are the energy-minimized structures of RR-1 / iodide and SS-1 / iodide simulated by the Gaussian computer program.

[0040] Figure 5 for the RR-1 and SS-1 compounds 1 H NMR and 13 C NMR. Detailed implementation mode

[0041] The following specific examples are intended to further illustrate the content of the present invention rather than limit the scope of protection of the claims.

[0042] In the following examples, all reactions were carried out in oven-dried glassware. Commercial reagents were used without further purification. Column chromatography separation was carried out using silica gel of 100 - 200 mesh.

[0043] In the following examples, R-3 and S-3 were prepared according to the literature (Org. Biomol. Chem., 2011, 9, 2938.).

[0044] Example 1

[0045] A mixture of R-3 (4.70 g, 10 mmol), Na2CO3 (2.96 g, 28 mmol), 2,4-dimethoxyphenylboronic acid (4.00 g, 22 mmol), a catalytic amount of CuI (21 mg) and tetrakis(triphenylphosphine)palladium (320 mg) was added to a flask containing 100 mL of CH3CH2OH and stirred. Under N2 protection, it was stirred at 90 °C for 24 h. After evaporation of the solvent, the mixture was extracted with dichloromethane (3 × 50 mL) and washed successively with water and brine. The organic layer was dried over anhydrous Na2SO4 and evaporated. Column chromatography separation on silica gel was carried out using dichloromethane / petroleum ether (4:1) as the eluent to obtain the compound R-2 (3.99 g, yield 68%) as a yellow solid.

[0046] 1 H NMR (400 MHz, Chloroform-d) δ 8.01 (d, J = 10.3 Hz, 4H), 7.46 (dd, J = 17.5, 8.9 Hz, 4H), 7.36 (d, J = 8.4 Hz, 2H), 7.19 (d, J = 8.8 Hz, 2H), 6.61 (d, J = 7.6 Hz, 4H), 3.88 (s, 6H), 3.82 (d, J = 2.2 Hz, 12H). 13 C NMR (101 MHz, CDCl3) δ 160.2, 157.6, 155.0, 133.6, 132.9, 131.5, 129.5, 129.3, 128.6, 127.8, 124.9, 123.7, 119.6, 114.3, 104.7, 99.0, 57.0, 55.6, 55.5. HRMS (APCI) m / z: [M+H] +Calcd for C 38 H 35 O 6,587.2434; found, 587.2428.

[0047] Example 2

[0048] Use S-3 to replace R-3 in Example 1, and other conditions and steps are the same.

[0049] Compound S-2 was obtained as a yellow solid (4.10 g, yield 70%).

[0050] 1 H NMR (400 MHz, Chloroform-d) δ 8.09–7.97 (m, 4H), 7.46 (dd, J = 17.1, 8.9 Hz, 4H), 7.36 (d, J = 8.2 Hz, 2H), 7.19 (d, J = 8.8 Hz, 2H), 6.61 (d, J = 7.5 Hz, 4H), 3.88 (s, 6H), 3.86–3.73 (m, 12H). 13 C NMR (101 MHz, CDCl3) δ 160.2, 157.6, 155.0, 133.6, 132.9, 131.5, 129.5, 129.3, 128.6, 127.8, 124.9, 123.7, 119.6, 114.3, 104.7, 99.0, 57.0, 55.56, 55.5. HRMS (APCI) m / z: [M+H] + Calcd for C 38 H 35 O 6,587.2434; found, 587.2431.

[0051] Example 3

[0052] Add boron trifluoride diethyl ether (0.3 mL, 2.4 mmol) to a mixture of R-2 (1.17 g, 2.0 mmol) and paraformaldehyde (180 mg, 6.0 mmol) in dichloromethane (150 mL). Stir at room temperature for 0.5 h, and add 150 ml of water to quench the reaction. Separate the organic layer and dry it with anhydrous MgSO4. Remove the solvent under vacuum, and separate the residue by silica gel column chromatography (eluent: 2:1 DCM / petroleum ether) to obtain RR-1 as a yellow solid product (538 mg, 45%).

[0053] 11H NMR (400 MHz, Chloroform-d) δ 7.90 (d, J = 9.0 Hz, 4H), 7.84 (s, 4H), 7.39 (d, J = 9.0 Hz, 4H), 7.26 (s, 4H), 7.01–6.93 (m, 8H), 6.60 (s, 4H), 3.97 (s, 4H), 3.93 (s, 12H), 3.81 (s, 12H), 3.76 (s, 12H). 13 13C NMR (101 MHz, CDCl3) δ 157.6, 155.8, 154.8, 133.7, 132.7, 132.1, 129.3, 129.2, 128.7, 127.5, 124.6, 122.7, 121.4, 119.6, 114.1, 96.0, 57.0, 56.0, 55.9, 27.8. HRMS (APCI) m / z: [M+H] + calcd for C 78 H 69 O 12 , 1197.4789; found, 1197.4785.

[0054] Example 4

[0055] Use S-2 to replace R-2 in Example 1, with other conditions and steps remaining the same.

[0056] Compound SS-1 was obtained as a yellow solid (491 mg, yield 41%).

[0057] 1 1H NMR (400 MHz, Chloroform-d) δ 7.90 (d, J = 9.0 Hz, 4H), 7.83 (s, 4H), 7.39 (d, J = 9.0 Hz, 4H), 7.26 (s, 4H), 7.01–6.93 (m, 8H), 6.60 (s, 4H), 3.97 (s, 4H), 3.93 (s, 12H), 3.81 (s, 12H), 3.76 (s, 12H). 13 13C NMR (101 MHz, CDCl3) δ 157.6, 155.8, 154.8, 133.7, 132.7, 132.1, 129.3, 129.2, 128.73, 127.5, 124.6, 122.7, 121.4, 119.6, 114.1, 96.0, 57.0, 55.9, 55.9, 27.8. HRMS (APCI) m / z: [M+H] + calcd for C 78 H 69 O 12, 1197.4789; found, 1197.4785.

[0058] The structural formulas of SS-1 and SS-2 synthesized in Example 3 and Example 4 are as follows:

[0059]

[0060] Through Figure 1 In c), it can be seen that the CD spectra of RR-1 and SS-1 show mirror images, which provides strong evidence for enantiopure macrocycles.

[0061] To understand the structures of RR-1 and SS-1 through Gaussian 09, 6-311G was selected as the basis set. As Figure 1 shown in a and b, both RR-1 and SS-1 have a box-like structure, and the cavity sizes are approximately 10.100×9.000 and 9.000×9.000, respectively.

[0062] Using commercially available tetrabutylammonium salts (TBAX) as the anion source, as Figure 2 shown in a, when 5.0 equivalents of tetrabutylammonium salts (TBAX, X = AcO - , NO 3- , ClO4 - , HSO4 - , Br - , I - , PF6 - , H2PO4 - , BF4 - , CO3F3S - ) were added to RR-1 in chloroform, the color of the solution containing RR-1 and TBAI changed from colorless to light orange, while the other solutions remained colorless. This obvious color change indicates that the interaction between RR-1 and TBAI may have occurred. The UV-visible spectroscopy experiment further revealed the interaction behavior between RR-1 and TBAX. After adding 5.0 equivalents of TBAI, the absorption at 300 nm and 350 nm increased significantly, and a new absorption band appeared at 375 nm, indicating the formation of the RR-1 / iodide complex in the solution. On the other hand, no change in the absorption spectrum was observed after adding the above other TBAX. All the above results show that RR-1 has the ability to selectively recognize iodide anions over other tested anions. Similar to RR-1, SS-1 also shows better selectivity for iodide anions than other tested anions, as Figure 2 shown in b.

[0063] After mixing RR-1 and TBAI with a molar ratio of 1:1 in CDCl3, in 1A new set of proton signals different from those of RR-1 and TBAI were observed on the ¹H NMR spectrum, indicating the formation of a new complex RR-1 / iodide, as Figure 3 shown. The protons b and e corresponding to RR-1 shifted upfield by 0.006 and 0.004 ppm, respectively, which may be attributed to the formation of neutral C–H…anion interactions between RR-1 and TBAI. Only the protons b and e corresponding to RR-1 showed a shift, probably because the recognition of iodide by RR-1 occurred outside the cavity. In addition, different from the recognition of iodide by cyclophane[4]carbazole (which is a slow process occurring inside the cavity), the complexation and decomplexation between RR-1 and TBAI are fast exchange processes on the NMR time scale at room temperature. This difference may be due to the fact that RR-1 recognizes iodide through neutral C–H…anion interactions outside the cavity. To further understand the complexation process between RR-1 and TBAI, then 1 ¹H NMR spectroscopic titration experiments were carried out. By monitoring the change of proton b corresponding to RR-1 after adding TBAI, a 1:1 complex was formed between RR-1 and TBAI through a molar ratio plot. The binding constant Ka of the complex RR-1 / iodide was measured to be 132.8 ± 33.8 M -1 . By the same method, it was also measured that SS-1 and TBAI formed a 1:1 complex of SS-1 / iodide, and the binding constant was calculated to be Ka =

[0064] 119.1 ± 32.6 M -1 .

[0065] The energy-minimized optimized structures of RR-1 / iodide and SS-1 / iodide further supported the formation of neutral C–H…anion interactions. As Figure 4 shown in a, the iodide anion is located outside the cavity of RR-1 through C–H…anion interactions, with distances of 3.307 and 3.123, respectively. Only the protons b and e corresponding to RR-1 participated in the formation of hydrogen bonds with the iodide anion, which is consistent with the result that only protons b and e showed a shift in the ¹H NMR experiment. In the structure of the complex SS-1 / iodide, the iodide anion is also located outside the cavity of SS-1 through C–H…anion interactions, with distances of 3.307 and 3.123, respectively, as Figure 4 shown in b.

[0066] In summary, the present invention successfully designed and synthesized chiral binaphthyl enantiopure macrocyclic arenes RR-1 and SS-1. The abilities of RR-1 and SS-1 as anion receptors were tested by means such as ultraviolet-visible spectroscopy and proton nuclear magnetic resonance spectroscopy. It was found that RR-1 and SS-1 can selectively bind iodide anions in a 1:1 manner. Among the 10 anions tested, neutral C–H. Anion interactions play an important role in the formation of RR-1 / iodide and SS-1 / iodide anion complexes. The complexation of iodide with RR-1 or SS-1 can be observed with the naked eye, and the color of the solution changes from colorless to light orange.

Claims

1. A chiral binaphthalene enantiomeric macrocyclic aromatic hydrocarbon, characterized in that: Comprising RR-1 and / or SS-1 compounds; 2. The synthesis method of a chiral binaphthyl enantiomeric macrocyclic aromatic hydrocarbon according to claim 1, characterized in that: React 2,4-dimethoxyphenylboronic acid with R-3 or S-3 compounds through Suzuki coupling reaction to obtain R-2 or S-2 compounds; Condense R-2 or S-2 with paraformaldehyde to obtain RR-1 or SS-1 structure compounds; The structural formula of R-3 compound is as follows: The structural formula of S-3 compound is as follows: The structural formula of R-2 compound is as follows: The structural formula of S-2 compound is as follows:

3. The synthesis method of a chiral binaphthyl enantiomeric macrocyclic aromatic hydrocarbon according to claim 2, wherein: The process of the Suzuki coupling reaction is as follows: In a sodium carbonate ethanol solution system, 2,4-dimethoxyphenylboronic acid and R-3 or S-3 compounds are reacted at 85-95 °C for 12-36 hours under the catalysis of Pd(PPh3)4 and CuI.

4. The synthesis method of a chiral binaphthyl enantiomeric macrocyclic aromatic hydrocarbon according to claim 3, characterized in that: The molar ratio of sodium carbonate to R-3 or S-3 compounds is 1:(2-3); The molar ratio of 2,4-dimethoxyphenylboronic acid to R-3 or S-3 compounds is 1:(2-2.5).

5. The synthesis method of a chiral binaphthyl enantiomeric macrocyclic aromatic hydrocarbon according to claim 2, characterized in that: The process of the condensation reaction is as follows: In a dichloromethane solution system, R-2 or S-2 compounds and paraformaldehyde are reacted at room temperature for 0.4-0.6 hours under the catalysis of boron trifluoride diethyl ether.

6. The synthesis method of a chiral binaphthyl enantiomeric macrocyclic aromatic hydrocarbon according to claim 5, characterized in that: The molar ratio of R-2 or S-2 compounds to paraformaldehyde is 1:(2-4).

7. Use of a chiral binaphthyl enantiomeric macrocyclic aromatic hydrocarbon according to claim 1, characterized in that: Applied as a molecular probe for the detection of iodide anions in a solution system.

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