Synthesis method and application of trifluoromethanesulfonyl ester substituted macrocyclic aromatic hydrocarbon

Abstract

The invention discloses a one-pot synthesis method of trifluoromethanesulfonyl ester substituted macrocyclic aromatic hydrocarbon and application of the trifluoromethanesulfonyl ester substituted macrocyclic aromatic hydrocarbon. The core of the invention is to design the trifluoromethanesulfonyl ester substituted biphenyl aromatic hydrocarbon monomer, and the trifluoromethanesulfonyl ester substituted biphenyl aromatic hydrocarbon is prepared with high yield by a'one-pot method '. The trifluoromethanesulfonyl ester substituted biphenyl aromatic hydrocarbon can be used for synthesizing a carbon nanotube minimum fragment-ring p-phenylene skeleton conjugated nanoring and fluorescence sensing.

Description

Technical Field

[0001] The present invention belongs to the synthesis and application of supramolecular macrocycles, and particularly relates to a "one-pot" synthesis method of trifluoromethanesulfonyl ester group-substituted macrocyclic arenes. Background Art

[0002] Macrocyclic arenes are a class of typical supramolecular macrocyclic host molecules formed by bridging alkoxy-substituted aromatic rings with methylene groups. The discovery of macrocyclic arenes has provided continuous vitality for the development of supramolecular chemistry, mainly because macrocyclic arenes are easy to functionalize. In the past decade, the synthesis of novel macrocyclic arenes has become one of the main hotspots in the field of supramolecular chemistry. The synthesis of macrocyclic arenes is mainly achieved by Friedel-Crafts alkylation reaction, which requires macrocyclic arene synthesis monomers to have a high electron cloud density. Therefore, for trifluoromethanesulfonyl ester group-substituted macrocyclic arenes, generally three independent reaction and post-treatment processes are required to achieve, and for some synthesis monomers with poor solubility, it is difficult to achieve the efficient synthesis of macrocyclic arenes. In this patent, we disclose a "one-pot" synthesis method of trifluoromethanesulfonyl ester group-substituted macrocyclic arenes. Through a one-step reaction, two trifluoromethanesulfonyl ester group-substituted biphenyl arenes can be obtained with a yield of 93%. This synthesis strategy opens a new door for the synthesis methods in the field of supramolecular macrocyclic chemistry and has important academic significance; the obtained trifluoromethanesulfonyl ester group-substituted biphenyl arenes are used for the synthesis of the smallest fragment of carbon nanotubes - the conjugated nanoring of the cycloparaphenylene skeleton and fluorescence sensing, which has important practical significance. Summary of the Invention

[0003] The present invention aims at some practical problems faced in the synthesis of macrocyclic arenes: (1) Some synthesis monomers have poor solubility, and it is difficult to achieve the efficient synthesis of macrocyclic arenes; (2) For trifluoromethanesulfonyl ester group-substituted macrocyclic arenes, three independent reaction and post-treatment processes are required to achieve. In the present invention, a trifluoromethanesulfonyl ester group-substituted biphenyl monomer molecule is designed, and through a one-step reaction, two trifluoromethanesulfonyl ester group-substituted macrocyclic arenes can be obtained with a yield of 93%. These trifluoromethanesulfonyl ester group-substituted macrocyclic arenes are used for the synthesis of the smallest fragment of carbon nanotubes - the conjugated nanoring of the cycloparaphenylene skeleton and fluorescence sensing.

[0004] To achieve the above object, the present invention discloses the following technical content: A "one-pot" synthesis method and application of trifluoromethanesulfonyl ester group-substituted macrocyclic arenes, characterized by having the following synthesis method and structure: (1) A synthesis method of trifluoromethanesulfonyl ester group-substituted biphenyl monomers; (2) A "one-pot" synthesis method of trifluoromethanesulfonyl ester group-substituted biphenyl arene macrocycles; (3) The application of trifluoromethanesulfonyl ester group-substituted biphenyl arene macrocycles in the construction of conjugated nanorings of cycloparaphenylene skeletons and fluorescence sensing.

[0005] Specific synthesis methods and structures: Here, taking compound 1 as the raw material to react and generate compound 2 and compound 3 as an example.

[0006]

[0007] Note: OTf is trifluoromethanesulfonate group Among them, the structure of the trifluoromethanesulfonate-substituted biphenyl monomer compound 1 can be replaced by the following structure, and homologues of compound 2 and compound 3 can be obtained in the same way:

[0008] The present invention further discloses a synthesis method of trifluoromethanesulfonate-substituted biphenyl monomers and a "one-pot" synthesis method of trifluoromethanesulfonate-substituted biphenyl aromatic macrocycles, which are characterized in that: through Suzuki coupling reaction, a trifluoromethanesulfonate-substituted biphenyl monomer molecule is designed; further reacting with paraformaldehyde to obtain two trifluoromethanesulfonate-substituted biphenyl aromatics with a yield of 93%. Finally, these trifluoromethanesulfonate-substituted biphenyl aromatics are used for synthesizing the smallest fragment of carbon nanotubes - the cycloparaphenylene framework conjugated nanoring and fluorescence sensing.

[0009] Its characteristics include the following aspects: (1) Synthesis method of trifluoromethanesulfonate-substituted biphenyl monomers; (2) "One-pot" synthesis method of trifluoromethanesulfonate-substituted biphenyl aromatic macrocycles; (3) Application of trifluoromethanesulfonate-substituted biphenyl aromatic macrocycles in the construction of cycloparaphenylene framework conjugated nanorings and fluorescence sensing.

[0010] Among them: (1) The synthesis method of trifluoromethanesulfonate-substituted biphenyl monomer 1 is as follows: Add 2,7-diboron bis(pinacolato)-9-fluorenone (4.32 g), 2-bromo-5-q-hydroxyanisole (5.0 g), Pd(dppf)Cl2 (0.2 g), K2CO3 (5.25 g), 1,4-dioxane (140 mL), H2O (20 mL) into a 250 mL round-bottom flask, and reflux for 8 h under argon protection. Quench with hydrochloric acid, neutralize with an excessive amount of saturated sodium bicarbonate aqueous solution, extract with ethyl acetate, dry the organic phase with anhydrous sodium sulfate, and concentrate under reduced pressure. Subsequently, add dichloromethane (30 mL), pyridine (4 mL), and trifluoromethanesulfonic anhydride (1.6 mL) to the reaction system, react for 3 h, quench with water, extract with dichloromethane, dry the organic phase with anhydrous sodium sulfate, concentrate under reduced pressure, mix with silica gel, and purify by silica gel column chromatography to obtain the monomer as a yellow solid.

[0011] (2)The synthetic method for trifluoromethanesulfonyl ester-substituted biphenyl aromatic macrocycles by the "one-pot method" is as follows: Add monomer 1 (0.67 g), paraformaldehyde (0.3 g), and dichloroethane (100 mL) to a 250 mL round-bottom flask. Add the catalyst under stirring and react for 9 minutes. After quenching with saturated sodium chloride solution, extract with dichloromethane. Dry the organic phase with anhydrous sodium sulfate, concentrate under reduced pressure, and separate by silica gel column chromatography to obtain the bicyclic and tricyclic rings, both of which are yellow solids.

[0012] The "one-pot method" synthetic method for trifluoromethanesulfonyl ester-substituted macrocyclic aromatic hydrocarbons disclosed in the present invention and its application in the construction of conjugated nanorings mainly include: designing a trifluoromethanesulfonyl ester-substituted biphenyl monomer molecule through the Suzuki coupling reaction; further reacting with paraformaldehyde to obtain two trifluoromethanesulfonyl ester-substituted biphenyl aromatic hydrocarbons with a yield of 93%. Finally, these trifluoromethanesulfonyl ester-substituted biphenyl aromatic hydrocarbons are used for the synthesis of the smallest fragment of carbon nanotubes - the conjugated nanoring of the cycloparaphenylene skeleton and fluorescence sensing. The results show that when using the trifluoromethanesulfonyl ester-substituted biphenyl aromatic hydrocarbon monomer molecule as the starting material to construct the conjugated nanoring of the cycloparaphenylene skeleton, the total yield can reach 88%.

[0013] The positive effects of the "one-pot method" synthetic method for trifluoromethanesulfonyl ester-substituted biphenyl aromatic hydrocarbons disclosed in the present invention and its application are as follows: Designed and synthesized a trifluoromethanesulfonyl ester-substituted biphenyl monomer molecule, breaking the traditional method that the synthetic monomer of macrocyclic aromatic hydrocarbons needs to have a high electron cloud density; For the first time, invented the "one-pot method" synthesis of trifluoromethanesulfonyl ester-substituted biphenyl aromatic macrocycles. The method is simple, the yield is as high as 93%, and the post-treatment is convenient, providing a new idea for the synthesis of trifluoromethanesulfonyl ester-substituted macrocyclic aromatic hydrocarbons; The trifluoromethanesulfonyl ester-substituted macrocyclic aromatic hydrocarbon monomer has excellent solubility, solving the problem of low solubility in the synthesis of electron-deficient macrocyclic aromatic hydrocarbons; Simplified the three-step reaction in the traditional method to one step, saving labor costs and economic costs. Description of the Drawings

[0014] Figure 1 . Nuclear magnetic resonance spectrum of the trifluoromethanesulfonyl ester-substituted biphenyl monomer molecule; Figure 2 . Assembly structure of the smallest fragment of carbon nanotubes - the conjugated nanoring of the cycloparaphenylene skeleton synthesized from trifluoromethanesulfonyl ester-substituted biphenyl aromatic hydrocarbons; Figure 3 . Application of trifluoromethanesulfonyl ester-substituted biphenyl aromatic hydrocarbon 2 and the conjugated nanoring [8]CPP of the cycloparaphenylene skeleton in fluorescence sensing. Detailed Description of the Invention

[0015] Unless otherwise specified, the technical means used in the present invention are all methods well-known to those skilled in the art. In addition, the embodiments should be understood as illustrative rather than limiting the scope of the present invention. The essence and scope of the present invention are only defined by the claims. For those skilled in the art, various changes or modifications made to the material components and dosages in these embodiments without departing from the essence and scope of the present invention also fall within the protection scope of the present invention. The raw materials and reagents used in the present invention are all commercially available (purchased from Bidepharm).

[0016] Taking the Suzuki coupling reaction of 2,7-diboronpinacol ester-9-fluorenone and 4-bromo-3-methoxyphenol as an example. First, a trifluoromethanesulfonyl ester-substituted biphenyl monomer molecule (named monomer 1) is obtained. Subsequently, using monomer 1 and paraformaldehyde as raw materials, 1,2-dichloroethane as the solvent, and ferric chloride as the catalyst, a trifluoromethanesulfonyl ester-substituted biphenyl aromatic macrocycle (named 2 and 3) is obtained through reaction. The steps include: Step 1: Synthesis of trifluoromethanesulfonyl ester-substituted biphenyl monomer molecule; Step 2: "One-pot" synthesis of trifluoromethanesulfonyl ester-substituted biphenyl aromatic macrocycle; After the detailed description of the preferred embodiments, those skilled in the art can clearly understand that various changes and modifications can be made without departing from the above-mentioned scope and spirit of the patent application. Any simple modifications, equivalent changes, and modifications made to the above embodiments based on the technical essence of the present invention all fall within the scope of the technical solution of the present invention. Moreover, the present invention is not limited by the implementation manners of the examples given in the specification. Example

[0017] The synthesis method of the trifluoromethanesulfonyl ester-substituted biphenyl monomer molecule is as follows:

[0018] Synthesis method and steps of monomer 1: The first step: Add 2,7-dibromofluorene-9-one (6 mmol), bis(pinacolato)diboron (4.68 g, 18 mmol), Pd(dppf)Cl 2 (1% mmol), KOAc (1.81 g, 18 mmol), 1,4-dioxane (160 mL) into a 250 mL round-bottom flask, and reflux at 100 °C for 12 h. Remove the solvent under reduced pressure concentration, mix with silica gel, and separate by silica gel column chromatography to obtain the product aryl diboronic acid bis(pinacolato) as a white solid.

[0019] Step 2: Add diaryldiboronic acid bis(pinacol ester) (4 g), 2-bromo-5-methoxyphenol (5 g), Pd(dppf)Cl 2 (0.2 g), K 2 CO 3 (5 g), 1,4-dioxane (140 mL), H 2 O (20 mL) to a 250 mL round-bottom flask and reflux for 8 h.

[0020] Step 3: React the mixture from Step 2 with pyridine (4.0 mL) and trifluoromethanesulfonic anhydride (1.6 mL) for 2 h. After quenching with water, the organic phase is dried over anhydrous sodium sulfate. Silica gel column chromatography is carried out using PE / DCM (V:V = 1:1) as the eluent to obtain monomer 1 (see attachment Figure 1 ).

[0021] Experimental results: Characterization data of monomer 1: 1H NMR (400 MHz, CDCl 3 ) δ 7.82 (s,2H), 7.66 – 7.57 (m, 4H), 7.41 (d, J = 8.4 Hz, 2H), 6.98 (dd, J = 8.4, 2.1Hz, 2H), 6.89 (d, J = 2.0 Hz, 2H), 3.87 (s, 6H). 19F NMR (376 MHz,CDCl 3 ) δ -72.71. 13C NMR (101 MHz, CDCl 3 ) δ 193.54, 157.55, 149.73,143.32, 137.92, 135.80, 134.53, 131.29, 129.74, 125.58, 120.33, 117.19,113.33, 105.06, 56.12. Matrix-assisted time-of-flight mass spectrometry: m / z calcd for [1] •+ , C 29 H 18 F 6 O 9 S 2 •+ ,688.0291, found 688.0289. Example

[0022] The one-pot synthesis method of trifluoromethanesulfonyl ester-substituted biphenylarene macrocycles is as follows:

[0023] Synthetic methods and steps of trifluoromethanesulfonyl group-substituted biphenyl aromatic macrocycles 2 and 3: In a 250 mL round-bottom flask, add monomer 1 (0.67 g), paraformaldehyde (0.3 g), and dichloroethane (100 mL). Add the catalyst under stirring and react for 9 minutes. After quenching with saturated sodium chloride solution, extract with dichloromethane. The organic phase is dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by silica gel column chromatography to obtain 2 and 3, both of which are yellow solids.

[0024] Experimental results: Characterization data of macrocyclic aromatic hydrocarbons 2 and 3: For 2, nuclear magnetic resonance hydrogen spectrum (400 MHz, CDCl 3 ) δ 7.76 (dd, J = 7.7, 1.6 Hz, 4H), 7.60 (d, J = 7.7 Hz, 4H), 7.44 – 7.36 (m,4H), 6.93 (s, 4H), 4.13 (s, 4H), 3.87 (s, 12H). Nuclear magnetic resonance fluorine spectrum (376 MHz, CDCl 3 ) δ -73.40. Nuclear magnetic resonance carbon spectrum (101 MHz, CDCl 3 ) δ 156.3, 147.2, 143.6, 137.9, 135.5,135.3, 133.2, 130.1, 125.3, 122.8, 120.44, 120.35, 117.3, 56.3, 29.9. Matrix-assisted time-of-flight mass spectrometry: m / z calcd for [2] •+ , C 60 H 36 F 16 O 18 S 4 •+ , 1400.0587, found1400.0586. For 3, nuclear magnetic resonance hydrogen spectrum (400 MHz, CDCl 3 ) δ 7.76 (dd, J = 7.7, 1.3 Hz,6H), 7.60 (d, J = 7.7 Hz, 6H), 7.45 – 7.32 (m, 6H), 6.93 (s, 6H), 4.13 (s,6H), 3.87 (s, 18H). Nuclear magnetic resonance fluorine spectrum (376 MHz, CDCl 3 ) δ -73.39. Nuclear magnetic resonance carbon spectrum (101MHz, CDCl 3) δ 193.51, 156.30, 147.53, 143.31, 137.70, 135.81, 134.39, 132.44, 129.98, 125.58, 123.21, 120.41, 120.21, 117.02, 56.17, 28.27. Matrix-assisted time-of-flight mass spectrometry: m / z calcd for [3] •+ , C 90 H 54 F 18 O 27 S 6 •+ , 2100.0889, found 2100.0872. Example

[0025] Method for synthesizing the smallest fragment of carbon nanotubes - the conjugated nanoring of the cycloparaphenylene skeleton using trifluoromethanesulfonyl ester-substituted biphenylarene macrocycles is as follows:

[0026] Synthesis method and steps of the smallest fragment of carbon nanotubes - the conjugated nanorings of [8]CPP and

[12] CPP of the cycloparaphenylene skeleton: Add nickel catalyst (0.54 mmol), 2, 2'-bipyridine (0.54 mmol) and N-methyl-2-pyrrolidone (6.0 mL) to a dry reaction tube. In an oil bath at 85 °C, add 2 (0.02 mmol) and 3 (0.015 mmol) to the reaction tube and react for 12 hours. Pour the mixture into a mixed solution of dichloromethane (30 ml) and saturated ammonium chloride solution (30 ml). After extraction and separation, the organic layer is concentrated and subjected to silica gel column chromatography separation (dichloromethane:ethyl acetate = 40:1) to obtain orange-red products, namely [8]CPP and

[12] CPP.

[0027] Experimental results: The structures of [8]CPP and

[12] CPP were characterized by X-ray single crystal diffraction. The crystal shows that the assembled structure of [8]CPP has a super-regular carbon nanotube shape (see attachment Figure 2 ). Table 1. Crystals of [8]CPP and their structure refinement data Table 2. Crystals of

[12] CPP and their structure refinement data Example

[0028] Application of trifluoromethanesulfonyl ester-substituted biphenylarene 2 and the conjugated nanoring of the cycloparaphenylene skeleton [8]CPP in fluorescence sensing is as follows:

[0029] Specific implementation methods and steps for the application of trifluoromethanesulfonyl ester group-substituted biphenyl aromatic hydrocarbon 2 and cycloparaphenylene framework conjugated nanoring [8]CPP in fluorescence sensing: (1) Disperse 2 and [8]CPP separately in spectroscopically pure cyclohexane to prepare solutions with a concentration of 1×10 -5 mol / L, and use a fluorescence spectrometer for testing to record the initial fluorescence intensity I 0 ; (2) Add a small amount of methanol to the standard solution and use a fluorescence spectrometer for testing to record the measured fluorescence intensity I e ; Experimental results: It was found that trifluoromethanesulfonyl ester group-substituted biphenyl aromatic hydrocarbon 2 and cycloparaphenylene framework conjugated nanoring [8]CPP both exhibited excellent fluorescence sensing properties for methanol (see attachment Figure 3 ).

Claims

1. A one-pot synthesis method of trifluoromethanesulfonyl ester-substituted macrocyclic aromatic hydrocarbons, characterized in that The synthesis method and structure are as follows: (1) A method for synthesizing trifluoromethanesulfonyl ester-substituted biphenyl monomers; (2) A one-pot synthesis of trifluoromethanesulfonyl ester-substituted biphenyl aromatic macrocycles; Specific synthesis method and structure: Here, compound 1 is used as the raw material to generate compound 2 and compound 3. Note: OTf is trifluoromethanesulfonyl ester Among them, the structure of trifluoromethanesulfonyl ester substituted biphenyl compound 1 can be replaced by the following structure, and the same series of analogs of compound 2 and compound 3 can be obtained by the same method: 。 2. The method for synthesizing trifluoromethanesulfonyl ester-substituted macrocyclic aromatic hydrocarbons by a one-pot method according to claim 1, characterized in that: (1) The synthesis method of trifluoromethanesulfonyl ester substituted biphenyl monomer is as follows: In a 250 mL round-bottom flask, 4.32 g of 2,7-diboronic acid bis(pinacol ester)-9-fluorenone, 5.0 g of 2-bromo-5-q-hydroxyanisole, 0.2 g of Pd(dppf)Cl2, 5.25 g of K2CO3, 140 mL of 1, 4-dioxane, and 20 mL of H2O were added. The mixture was refluxed under argon protection for 8 h, quenched with hydrochloric acid, neutralized with excess saturated sodium bicarbonate aqueous solution, extracted with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Subsequently, 30 mL of dichloromethane, 4 mL of pyridine, and 1.6 mL of trifluoromethanesulfonic anhydride were added to the reaction system, and the reaction was allowed to react for 3 h. Finally, water was added to quench the mixture, and dichloromethane was extracted. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The sample was mixed with silica gel and purified by silica gel column chromatography to obtain a monomer as a yellow solid. (2) The one-pot synthesis of trifluoromethanesulfonyl ester-substituted biphenyl aromatic macrocycles is as follows: 0.67 g monomer, 0.3 g paraformaldehyde and 100 mL dichloroethane were added to a 250 mL round-bottom flask, and the catalyst was added under stirring for 9 minutes; after quenching with saturated sodium chloride solution, the product was extracted with dichloromethane, and the organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by silica gel column chromatography to obtain a binary ring and a ternary ring, all of which were yellow solids.

3. Application of the trifluoromethanesulfonyl ester-substituted macrocyclic aromatic hydrocarbons synthesized by the "one-pot method" as described in claim 1 in the synthesis of the smallest fragment of carbon nanotubes - cycloparaphenylene skeleton conjugated nanorings and fluorescence sensing.

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