CN116693373A - Chiral binaphthyl enantiomer macrocyclic arene, and synthetic method and application thereof - Google Patents

Abstract

The invention discloses a chiral binaphthyl enantiocyclic aromatic hydrocarbon, a preparation method and application thereof. The structural formula of chiral binaphthalene enantiomacroaromatic is as follows RR-1 and SS-1 compound: Its selective recognition of iodide anions is significantly better than AcO ^‑ , NO ^3‑ , ClO ₄ ^‑ , HSO ₄ ^‑ , Br ^‑ , PF ₆ ^‑ , H ₂ PO 4 ^‑ , BF _{4 ‑} ^, CO ₃ F ₃ S ^‑, etc. anion, and the recognition process can produce a color change visible to the naked eye, which can be used for the detection of iodide anion.

Description

A kind of chiral binaphthalene enantio-macrocyclic aromatic hydrocarbon and its synthesis method and application

technical field

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

Background technique

Negative ions are ubiquitous and play an important role in the human body. For example, iodine is a raw material for the synthesis of thyroid hormones, which can promote the metabolism of substances, regulate the metabolism of protein, fat and sugar, and help regulate the metabolism of water and salt. However, iodine deficiency can lead to conditions such as goiter or hypothyroidism. However, the most common effects of excessive iodine on thyroid function are iodine-induced goiter (IH) and hyperiodine hyperthyroidism. In addition, ^{129 I-} and ¹³⁰ I- radioisotopes are considered harmful to the environment. Therefore, the development of iodide anion receptors and sensors for the detection of iodide anions is of great value and has attracted considerable interest.

The continuous synthesis of novel macrocyclic host molecules and their unique molecular recognition properties have driven the development of supramolecular chemistry. Over the past decades, various macrocyclic hosts have been developed and exhibit excellent recognition properties for anions such as fluoride, nitrate, oxoacids, and others. Prominent examples are Sessler's calixyrrole, Farnham's fluorinated macrocyclic ether, Flood's triazolidine, Sindelar's bambusuril macrocycle, Beer's rotaxane and catenane, etc. Most strategies involve binding anions with size and shape selectivity in various media by exploiting hydrogen bonds provided by specific binding sites. However, there are relatively few reports on the construction of iodide anion acceptor macrocycles because of the large diameter and low electron density of iodide anions, which make it difficult to form hydrogen bonds and anion-π interactions. Literature (Angew.Chem., Int.Ed., 2008, 47,788; Angew.Chem., Int.Ed., 2008, 47, 2649; Angew.Chem., Int.Ed.,

2008,47,3740; J.Am.Chem.Soc.,2008,130,10895.) After elucidating the neutral C–H… anion interaction, this interaction has aroused great interest among chemists and developed rapidly . literature

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

2012, 48, 5065.) disclosed a triazole macrocycle and cage, and found that these triazole macrocycles and cages exhibit strong affinity for anions through neutral C–H… anion interactions. Literature (Org.

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

Ed., 2022, e202209078.) reported the recognition of anions in water by molecular cages through neutral C–H… anion interactions. Literature (Org. Lett., 2016, 18, 5054.) demonstrated that pre-organized rigid macrocyclic [4] carbazoles can act as iodide anion acceptors through neutral C–H…anion interactions. Despite these pioneering reports, macrocyclic host molecules with selective recognition of iodide anions have been rarely reported.

Contents of the invention

In view of the defects in the prior art, the first object of the present invention is to provide a chiral binaphthyl enantiomacrocyclic aromatic hydrocarbon, which has a large number of neutral aryl C-H bonds and a special cavity structure. It has selective recognition and complexation, and there is a color change visible to the naked eye after complexing iodide anions, and is especially suitable for the detection of iodide anions in a solution system.

The second object of the present invention is to provide a method for synthesizing chiral binaphthyl enantiocyclic aromatic hydrocarbons, which is simple, mild in conditions, high in yield, and conducive to expanding production.

The third object of the present invention is to provide the application of a chiral binaphthalene enantio-macrocyclic aromatic hydrocarbon, which contains AcO ^- , NO ^3- , ClO ₄ ^- , HSO ₄ ^- , Br ^- , PF ₆ ^- , H ₂ PO ₄ ^- , BF ₄ ^- , CO ₃ F ₃ S ^- and other anions in the solution system have selective recognition and complexation of iodide anions, and the color changes visible to the naked eye after complexing iodide anions, and can be used in solutions Detection of iodide anions in the system.

In order to achieve the above-mentioned technical purpose, the present invention provides a kind of chiral binaphthalene enantiocyclic aromatic hydrocarbon, which includes RR-1 and/or SS-1 compounds;

Both RR-1 and SS-1 of chiral binaphthalene enantiomacroaromatics provided by the present invention have a box-like structure, and the cavity sizes are about 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 can be used as iodide anion acceptors to realize the complexation of iodide anions. It is particularly unexpected that the chiral binaphthyl enantiomer macrocyclic aromatic hydrocarbons RR-1 and SS-1 compounds are It has selective recognition in complex anion solution systems, and RR-1 and SS-1 compounds have obvious color changes visible to the naked eye after complexing iodide anions, making it possible for RR-1 and SS-1 compounds to be used for the detection of iodide anions .

The present invention also provides a synthesis method of chiral binaphthalene enantiomacrocyclic aromatic hydrocarbons, the method is to react 2,4-dimethoxyphenylboronic acid with R-3 or S-3 compound through Suzuki coupling reaction to obtain R-2 or S-2 compound; R-2 or S-2 and paraformaldehyde undergo condensation reaction to obtain RR-1 or SS-1 structure compound;

R-3 compound structural formula is as follows:

S-3 compound structural formula is as follows:

R-2 compound structural formula is as follows:

S-2 compound structural formula is as follows:

The synthesis method of chiral binaphthalene enantiomacrocyclic aromatic hydrocarbon of the present invention can be realized through the two-step reaction of Suzuki coupling and condensation, the synthesis method is simple, and the product yield is high.

As a preferred scheme, in the sodium carbonate ethanol solution system, 2,4-dimethoxyphenylboronic acid and R-3 or S-3 compound are catalyzed by Pd(PPh ₃ ) ₄ and CuI, at 85-95 Under the temperature of ℃, react for 12-36 hours. More preferably, the reaction is carried out at a temperature of 90°C for 24 hours.

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

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

As a more preferred scheme, the addition amount of Pd(PPh ₃ ) ₄ and CuI is a catalytic amount, for example, 5-20 mol%.

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

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

The specific synthesis route of chiral binaphthalene enantio-macrocyclic arene of the present invention is as follows:

The invention also provides an application of chiral binaphthalene enantio-macrocyclic aromatic hydrocarbon, which is used as a molecular probe for the detection of iodide anions in a solution system. The selective recognition of chiral binaphthalene enantioaromatic macrocyclic aromatics to iodide anion is obviously better than other anions, such as AcO ^- , NO ^3- , ClO ₄ ^- , HSO ₄ ^- , Br ^- , PF ₆ ^- , H ₂ PO ₄ ^- , BF ₄ ^- , CO ₃ F ₃ S ^-, etc., and the identification process can be observed by naked eyes, such as the color of the solution changing from colorless to light orange. Compared with the prior art, the beneficial technical effect brought by the technical solution of the present invention:

The chiral binaphthalene enantiomacrocyclic aromatic hydrocarbons provided by the present invention have a large number of neutral aryl CH bonds and a special cavity structure, which can selectively recognize and complex iodide anions, such as in the presence of AcO ^- , NO ^{3 -} , ClO ₄ ^- , HSO ₄ ^- , Br ^- , PF ₆ ^- , H ₂ PO ₄ ^- , BF ₄ ^- , CO ₃ F ₃ S ^- and other anions in the solution system can recognize and complex iodide anions with high selectivity, And a color change visible to the naked eye occurs, and can be used for the detection of iodide negative ions in a solution system.

The synthesis method of the chiral binaphthyl enantiocyclic aromatic hydrocarbon is simple, the condition is mild, and the yield is high, which is beneficial to expanding production.

Description of drawings

In Fig. 1, a) and b) are the energy-minimized structures of RR-1 and SS-1 simulated by a Gaussian computer program; c) are the CD spectra of RR-1 (black line) and SS-1 (red line).

Figure 2 a) is the UV-Vis spectrum of RR-1 (1.00×10 ^-2 mM) in chloroform mixed solution, RR-1 and TBAX (X=AcO ^- , NO ^3- , ClO ₄ ^- , HSO ₄ ^- , Br ^- , I ^- , PF ₆ ^- , H ₂ PO ₄ ^- , BF ₄ ^- , CO ₃ F ₃ S ^- ) (5.0 equiv); b) is SS-1 (1.00×10 ^-2 mM) mixed in chloroform UV-Vis spectrum in solution, SS-1 and TBAX (X=AcO ^- , NO ^3- , ClO ₄ ^- , HSO ₄ ^- , Br ^- , I ^- , PF ₆ ^- , H ₂ PO ₄ ^- , BF ₄ ^- , CO ₃ F ₃ S ⁻ ) (5. equivalents), the inset shows photographs of the colors of these mixed solutions.

In Fig. 3, a) is free RR-1, b) is part of ¹ H NMR spectrum (400MHz, CDCl ₃ , 298K) of RR-1, 1.0 equivalent, c) is free TBAI, [RR-1] ₀ =4.0mmol /L.

Figure 4 shows the energy-minimized structures of RR-1/iodide and SS-1/iodide simulated by a Gaussian computer program.

Fig. 5 is ¹ H NMR and ¹³ C NMR of compounds RR-1 and SS-1.

Detailed ways

The following specific examples are intended to further illustrate the contents of the present invention, rather than limit the protection scope of the claims.

In the following examples, all reactions were performed in oven-dried glassware. Commercial reagents were used without further purification. The chromatographic column separation adopts 100-200 mesh silica gel.

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

Example 1

R-3 (4.70g, 10mmol), Na ₂ CO ₃ (2.96g, 28mmol), 2,4-dimethoxyphenylboronic acid (4.00g, 22mmol), catalytic amount CuI (21mg) and tetrakis (triphenyl A mixture of phosphine)palladium (320mg) was added into a flask filled with 100mL CH ₃ CH ₂ OH for stirring, and stirred at 90°C for 24h under the protection of N ₂ . After evaporation of the solvent, the mixture was extracted with dichloromethane (3 x 50 mL), washed successively with water and brine. The organic layer was dried over _{anhydrous Na2SO4} and evaporated. Separation by silica gel column chromatography with dichloromethane/petroleum ether (4:1) as the eluent gave compound R-2 (3.99 g, yield 68%) as a yellow solid.

¹ H NMR (400MHz, Chloroform-d) δ8.01 (d, J = 10.3Hz, 4H), 7.46 (dd, J = 17.5, 8.9Hz, 4H), 7.36 (d, J = 8.4Hz, 2H), 7.19(d, J=8.8Hz, 2H), 6.61(d, J=7.6Hz, 4H), 3.88(s, 6H), 3.82(d, J=2.2Hz, 12H). ¹³ C NMR (101MHz, CDCl ₃ ) δ160.2, 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.

Example 2

Adopt S-3 to replace R-3 in embodiment 1, other conditions and steps are the same.

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

¹ H NMR (400MHz, Chloroform-d) δ8.09–7.97(m, 4H), 7.46(dd, J=17.1, 8.9Hz, 4H), 7.36(d, J=8.2Hz, 2H), 7.19(d , J＝8.8Hz, 2H), 6.61(d, J＝7.5Hz, 4H), 3.88(s, 6H), 3.86–3.73(m, 12H). ¹³ C NMR (101MHz, CDCl ₃ ) δ160.2, 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.

Example 3

To a mixture of R-2 (1.17 g, 2.0 mmol) and paraformaldehyde (180 mg, 6.0 mmol) in dichloromethane (150 mL) was added boron trifluoride ether (0.3 mL, 2.4 mmol). Stir at room temperature for 0.5 h, add 150 ml of water to quench the reaction. The organic layer was separated and dried over anhydrous _MgSO4 . The solvent was removed in vacuo and the residue was separated by silica gel column chromatography (eluent: 2:1 DCM/petroleum ether) to give RR-1 as a yellow solid product (538 mg, 45%).

¹ H NMR (400MHz, Chloroform-d) δ7.90(d, J=9.0Hz, 4H), 7.84(s, 4H), 7.39(d, J=9.0Hz, 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 C NMR(101MHz, CDCl ₃ )δ157.6, 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.

Example 4

Adopt S-2 to replace R-2 in embodiment 1, other conditions and steps are the same.

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

¹ H NMR (400MHz, Chloroform-d) δ7.90(d, J=9.0Hz, 4H), 7.83(s, 4H), 7.39(d, J=9.0Hz, 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 C NMR(101MHz, CDCl ₃ )δ157.6, 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.

The SS-1 and SS-2 structural formulas of embodiment 3 and embodiment 4 synthesis are as follows:

It can be seen from c) in Figure 1 that the CD spectra of RR-1 and SS-1 show mirror images, which provides strong evidence for enantiopure macrocycles.

To understand the structure of RR-1 and SS-1 through Gaussian 09, choose 6-311G as the basis set, as shown in a and b in Figure 1, both RR-1 and SS-1 have a box-like structure, and the cavity sizes are respectively Approximately 10.100×9.000 and 9.000×9.000.

Commercially available tetrabutylammonium salt ⁽ TBAX) was used _as anion source, as shown in a in ^{Fig .} HSO ₄ ^- , Br ^- , I ^- , PF ₆ ^- , H ₂ PO ₄ ^- , BF ₄ ^- , CO ₃ F ₃ S ^- ) were added to RR-1 in chloroform, and the color of the solution containing RR-1 and TBAI changed from none to The color changed to light orange, while the other solutions remained colorless. This apparent color change suggests that an interaction between RR-1 and TBAI may have occurred. UV-Vis spectroscopy experiments further revealed the interaction between RR-1 and TBAX. After adding 5.0 equivalents of TBAI, the absorption at 300nm and 350nm was significantly enhanced, and a new absorption band appeared at 375nm, indicating the formation of RR-1/iodide complex in solution. On the other hand, no change in the absorption spectrum was observed after the addition of the above-mentioned other TBAXs. All of the above results indicate that RR-1 has the ability to recognize iodide anions selectively over the other tested anions. Similar to RR-1, SS-1 also showed selective recognition of iodide anion over other tested anions, as shown in Fig. 2b.

After mixing RR-1 and TBAI at a molar ratio of 1:1 in CDCl ₃ , a new set of proton signals different from RR-1 and TBAI was observed on the ¹ H NMR spectrum, indicating the formation of a new complex RR-1/Iodide, as shown in Figure 3. The protons b and e corresponding to RR-1 were shifted up 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 are shifted, which may be that the recognition of iodide by RR-1 occurs outside the cavity. Furthermore, unlike iodide recognition by cyclo[4]carbazole, which is a slow process and occurs inside the cavity, the recombination and decomplexation between RR-1 and TBAI are fast on the NMR timescale at room temperature exchange process. This difference may be due to the recognition of iodide by RR-1 through the neutral C–H… anion interaction outside the cavity. In order to further understand the complexation process between RR-1 and TBAI, ¹ H NMR spectroscopic titration experiments were then carried out. A 1:1 complex was formed between RR-1 and TBAI by molar ratio plots by monitoring the change in b corresponding to the proton of RR-1 upon addition of TBAI. The binding constant Ka of complex RR-1/iodide was determined by BindFit software to be 132.8±33.8M ^-1 . Measured by the same method, SS-1 and TBAI also formed a 1:1 complex of SS-1/iodide, and the binding constant was calculated as Ka=

119.1±32.6M ⁻¹ .

The energy-minimized optimized structures of RR-1/iodide and SS-1/iodide further support the formation of neutral C–H…anion interactions. As shown in a in Fig. 4, the iodide anion is located outside the cavity of RR-1 through the C–H…anion interaction with distances of 3.307 and 3.123, respectively. Only 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 were displaced 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 the C–H… anion interaction, with distances of 3.307 and 3.123, respectively, as shown in b in Fig. 4.

In summary, the present invention has successfully designed and synthesized enantiopure macrocyclic aromatic hydrocarbons RR-1 and SS-1 from chiral binaphthalene. The abilities of RR-1 and SS-1 as anion acceptors were tested by means of UV-Vis spectroscopy and H-NMR spectroscopy. It was found that RR-1 and SS-1 could selectively bind iodide anion in a 1:1 manner. Among the 10 tested anions, neutral C–H. Anionic interactions play an important role in the formation of RR-1/iodine and SS-1/iodide anion complexes. The complexation between iodide and 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 (7)

1. A chiral binaphthyl enantiocyclic aromatic hydrocarbon, characterized in that: comprising RR-1 and/or SS-1 compounds; 2. the synthetic method of a kind of chiral binaphthalene enantio-macrocyclic arene according to claim 1, is characterized in that: 2,4-dimethoxyphenylboronic acid and R-3 or S-3 compound are passed through bell Wood coupling reaction to obtain R-2 or S-2 compound; R-2 or S-2 and paraformaldehyde through condensation reaction to obtain RR-1 or SS-1 structure compound; R-3 compound structural formula is as follows: S-3 compound structural formula is as follows: R-2 compound structural formula is as follows: S-2 compound structural formula is as follows: 3. the synthetic method of a kind of chiral binaphthalene enantiomacrocyclic aromatic hydrocarbon according to claim 2, is characterized in that: in sodium carbonate ethanol solution system, 2,4-dimethoxyphenylboronic acid and R-3 Or the compound S-3 is reacted at 85-95° C. for 12-36 hours under the catalysis of Pd(PPh ₃ ) ₄ and CuI. 4. the synthetic method of a kind of chiral binaphthalene enantiocyclic aromatic hydrocarbon according to claim 3, is characterized in that: sodium carbonate and R-3 or S-3 compound mol ratio are 1:(2～3); The molar ratio of 2,4-dimethoxyphenylboronic acid to R-3 or S-3 compound is 1:(2～2.5). 5. the synthetic method of a kind of chiral binaphthalene enantiocyclic aromatic hydrocarbon according to claim 2, is characterized in that: in dichloromethane solution system, R-2 or S-2 compound and paraformaldehyde are in three Catalyzed by boron fluoride ether, react at room temperature for 0.4-0.6 hours. 6. the synthetic method of a kind of chiral binaphthyl enantiocyclic aromatic hydrocarbon according to claim 5, is characterized in that: the mol ratio of R-2 or S-2 compound and paraformaldehyde is 1:(2～4 ). 7. The application of a kind of chiral binaphthalene enantiomacrocyclic aromatic hydrocarbon as claimed in claim 1, characterized in that: it is used as a molecular probe for the detection of iodide anions in a solution system.