A chiral azaspiro compound and its preparation method and application

Abstract

The present invention relates to the field of materials, and provides a chiral azaspiro compound and a preparation method and application thereof. The chemical structure of the chiral azaspiro compound is shown in Formula I: The chiral azaspiro compound provided by the present invention is a high-performance circularly polarized luminescent helicene compound with long-wave emission (red light or near infrared), which can be widely used in the fields of liquid crystal materials, biomedicine, and photodetectors.

Description

Technical Field

[0001] The present invention relates to the field of materials, and in particular to a chiral azaspiro compound and a preparation method and application thereof. Background Art

[0002] Pure organic luminescent free radicals are a class of organic compounds that combine light, electricity and magnetism. In recent years, chiral molecules with long-wave emission (red or near-infrared) have attracted extensive attention in the fields of liquid crystal materials, biomedicine and photodetectors.

[0003] Helicene is a class of condensed aromatic compounds with twisted conjugated structures. Due to its helical molecular conformation, it produces unique chiral optical properties, including optical rotation (OR), electronic circular dichroism (ECD), circularly polarized luminescence (CPL), etc. However, there are few high-performance circularly polarized luminescent helicene compounds with long-wave emission (red light or near-infrared). Therefore, the research and development of a high-performance circularly polarized luminescent helicene compound with long-wave emission (red light or near-infrared) is of great significance to further promote the application and development of liquid crystal materials, biomedicine, and photodetectors. Summary of the invention

[0004] In view of the above-mentioned deficiencies in the prior art, the object of the present invention is to provide a chiral azaspiro compound and a preparation method and application thereof, wherein the chiral azaspiro compound is a high-performance circularly polarized luminescent helicene compound with long-wave emission (red light or near-infrared).

[0005] In order to achieve the above-mentioned invention object, the technical solution adopted by the present invention is as follows:

[0006] In a first aspect, the present invention provides a chiral azaspiro compound, the chemical structure of the chiral azaspiro compound is shown in Formula I:

[0007]

[0008] The chiral azaspiro compound provided in the embodiment of the present invention has a chemical structure as shown in Formula I. It is modified by introducing a TTM free radical (tris(2,4,6-trichlorophenyl)methyl free radical) with a narrow luminescence band gap into the helical skeleton of aza[7]helicene. When the open-shell free radical (TTM free radical) encounters a chiral red light molecule, the circularly polarized luminescence performance of aza[7]helicene can be further improved, and preliminary application exploration can be made in the bioimaging research of free radicals.

[0009] In a second aspect, the present invention provides a method for preparing a chiral azaspiro compound, comprising the following steps:

[0010]

[0011]

[0012] S1. Synthesis of Compound IV:

[0013] Compound II having a structure of formula II reacts with compound III having a structure of formula III in a first solvent in the presence of a first catalyst and a first base to obtain compound IV having a structure of formula IV;

[0014] S2. Synthesis of Compound V:

[0015] Under a nitrogen atmosphere, a compound IV having a structure of formula IV reacts with n-butyl lithium and trimethyl borate in a second solvent in the presence of an acid to obtain a compound V having a structure of formula V;

[0016] S3. Synthesis of Compound VII:

[0017] Compound V having a structure of formula V reacts with compound VI having a structure of formula VI in the presence of a second catalyst and a second base in a third solvent to obtain compound VII having a structure of formula VII;

[0018] S4. Synthesis of Compound VIII:

[0019] Under a nitrogen atmosphere, a compound VII having a structure of formula VII reacts with a nitromethane solution containing ferric chloride in a fourth solvent to obtain a compound VIII having a structure of formula VIII;

[0020] S5. Synthesis of Compound X:

[0021] Compound VIII having a structure of formula VIII reacts with compound IX having a structure of formula IX in a fifth solvent in the presence of a third base to obtain compound X having a structure of formula X;

[0022] S6. Synthesis of Compound Ⅰ:

[0023] Compound X having the formula X is reacted in the presence of potassium tert-butoxide and chlorobenzoquinone in a sixth solvent to obtain compound I having the structure of formula I.

[0024] The preparation method of the chiral azaspiro compound provided in the embodiment of the present invention is simple, mild in conditions, convenient in operation, has low requirements on equipment conditions, is extremely easy to implement, and has simple post-processing, and is suitable for industrial large-scale production.

[0025] In a third aspect, the present invention provides the use of the chiral azaspiro compound as described in the first aspect in the preparation of liquid crystal materials, biomedicine and optoelectronic materials.

[0026] The chiral azaspiro compound provided in the embodiment of the present invention has red light emission performance and good circularly polarized luminescence performance, and can be used to prepare liquid crystal materials, biomedicine and optoelectronic materials, and can also be used in information storage, fluorescence sensing, light detectors and the like. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0028] Figure 1 is a single crystal diffraction pattern of compound X prepared in Example 1 of the present invention;

[0029] Figure 2 is a single crystal arrangement diagram of compound X obtained in Example 1 of the present invention;

[0030] Figure 3 It is the light absorption and emission spectra of compound I prepared in Example 1 of the present invention in different organic solvents. DETAILED DESCRIPTION

[0031] In order to make the technical problems, technical solutions and beneficial effects to be solved by the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention, but the embodiments of the present invention are not limited thereto.

[0032] Unless otherwise defined, the technical terms used in the following examples have the same meanings as those generally understood by those skilled in the art to which the present invention belongs. The experimental reagents used in the following examples, unless otherwise specified, are all conventional biochemical reagents; the amounts of the experimental reagents, unless otherwise specified, are all the amounts of reagents used in conventional experimental operations; the experimental methods, unless otherwise specified, are all conventional methods.

[0033] In the first aspect, this embodiment provides a chiral azaspiro compound, the chemical structure of the chiral azaspiro compound is shown in Formula I:

[0034]

[0035] According to research, tris(2,4,6-trichlorophenyl)methyl radical (TTM radical) not only exhibits special stability, but also has the characteristics of red light emission. The synthesis route of TTM radical is as follows:

[0036]

[0037] The TTM free radical can be synthesized according to the relevant method described in the literature J. Phys. Chem. 1977, 91, 5607-5616.

[0038] t-BuOK means potassium tert-butoxide; Chloranil means chloroaniline.

[0039] The chiral azaspiro compound provided in the embodiment of the present invention has a chemical structure as shown in Formula I. It is modified by introducing a TTM free radical (tris(2,4,6-trichlorophenyl)methyl free radical) with a narrow luminescence band gap into the helical skeleton of aza[7]helicene. When the open-shell free radical (TTM free radical) encounters a chiral red light molecule, the circularly polarized luminescence performance of aza[7]helicene can be further improved, and preliminary application exploration can be made in the bioimaging research of free radicals.

[0040] In a second aspect, the present invention provides a method for preparing a chiral azaspiro compound, comprising the following steps:

[0041]

[0042]

[0043] S1. Synthesis of Compound IV:

[0044] Compound II having a structure of formula II reacts with compound III having a structure of formula III in a first solvent in the presence of a first catalyst and a first base to obtain compound IV having a structure of formula IV;

[0045] S2. Synthesis of Compound V:

[0046] Under a nitrogen atmosphere, a compound IV having a structure of formula IV reacts with n-butyl lithium and trimethyl borate in a second solvent in the presence of an acid to obtain a compound V having a structure of formula V;

[0047] S3. Synthesis of Compound VII:

[0048] Compound V having a structure of formula V reacts with compound VI having a structure of formula VI in the presence of a second catalyst and a second base in a third solvent to obtain compound VII having a structure of formula VII;

[0049] S4. Synthesis of Compound VIII:

[0050] Under a nitrogen atmosphere, a compound VII having a structure of formula VII is reacted in a fourth solvent in the presence of ferric chloride and nitromethane to obtain a compound VIII having a structure of formula VIII;

[0051] S5. Synthesis of Compound X:

[0052] Compound VIII having a structure of formula VIII reacts with compound IX having a structure of formula IX in a fifth solvent in the presence of a third base to obtain compound X having a structure of formula X;

[0053] S6. Synthesis of Compound Ⅰ:

[0054] Compound X having the formula X is reacted in the presence of potassium tert-butoxide and chlorobenzoquinone in a sixth solvent to obtain compound I having the structure of formula I.

[0055] The preparation method of the chiral azaspiro compound provided in the embodiment of the present invention is simple, mild in conditions, convenient in operation, has low requirements on equipment conditions, is extremely easy to implement, and has simple post-processing, and is suitable for industrial large-scale production.

[0056] In the embodiments of the present invention, the operations need to be carried out strictly in accordance with the synthesis conditions of the above steps, otherwise the reaction yield will be reduced or even the target product cannot be synthesized.

[0057] Further, in step S1, the compound III is prepared by the following steps:

[0058]

[0059] Synthesis of compound b:

[0060] Compound a reacts with N-bromosuccinimide in a seventh solvent to obtain compound b;

[0061] Synthesis of compound III:

[0062] Compound b reacts with aqueous sulfuric acid, aqueous sodium nitrate, potassium iodide and aqueous sodium bisulfite to obtain compound III.

[0063] Wherein, the seventh solvent is N,N-dimethylformamide (DMF).

[0064] Furthermore, in step S1, the first catalyst is palladium; the first base is anhydrous potassium carbonate; and the first solvent is a mixture of ethylene glycol diethyl ether and water.

[0065] Furthermore, in step S2, the acid is dilute hydrochloric acid; the second solvent is tetrahydrofuran; and the reaction temperature is -77°C.

[0066] Furthermore, in step S3, the second catalyst is palladium; the second base is potassium carbonate; and the third solvent is a mixture of toluene, ethanol and water. In this reaction step, it is necessary to strictly control the reaction under anhydrous and oxygen-free conditions, otherwise the reaction effect is poor.

[0067] Furthermore, in step S4, the fourth solvent is anhydrous dichloromethane.

[0068] Furthermore, in step S5, the third base is cesium carbonate; and the fifth solvent is N,N-dimethylformamide.

[0069] Furthermore, in step S6, the sixth solvent is tetrahydrofuran.

[0070] In a third aspect, the present invention provides the use of the chiral azaspiro compound as described in the first aspect in the preparation of liquid crystal materials, biomedicine and optoelectronic materials.

[0071] The chiral azaspiro compound provided in the embodiment of the present invention has red light emission performance and good circularly polarized luminescence performance, and can be used to prepare liquid crystal materials, biomedicine and optoelectronic materials, and can also be used in information storage, fluorescence sensing, light detectors and the like.

[0072] The present invention has been tested for many times, and some test results are now cited as references to further describe the invention in detail, and the following is a detailed description in conjunction with specific embodiments.

[0073] Example 1 Preparation of Compound Ⅰ

[0074]

[0075] S1. Synthesis of compound b:

[0076] Compound a (4-tert-butylaniline) (5.0 g, 33.5 mmol) was added to a 250 mL three-necked round-bottom flask, N-bromosuccinimide (6.3 g, 35.2 mmol) was added, and 100 mL of N,N-dimethylformamide (DMF) was added. The mixture was stirred at room temperature overnight. After the reaction was completed, the mixture was extracted three times, each time with 10 mL of ethyl acetate and 30 mL of water to remove DMF. The product was purified by column chromatography to obtain 5.94 g of 2-bromo-4-tert-butylaniline (i.e., compound b) with a yield of 77%.

[0077] S2. Synthesis of Compound III:

[0078] Weigh 2-bromo-4-tert-butylaniline (compound b) (2.0 g, 7.71 mmol), add 100 mL of 10% H2SO4 aqueous solution, stir at 25°C for 10 min, then slowly drop an aqueous solution of NaNO3, stir at 10°C for 2 h, slowly drop an aqueous solution of KI (any concentration) into the reaction solution after 2 h, and a reddish brown color appears. After the addition is complete, stir at room temperature for 3 h and then heat to 50°C, continue stirring at 50°C for 20 min, then add a 5% sodium bisulfite aqueous solution, stir at room temperature, and then extract three times, each time using 10 mL of ethyl acetate and 30 mL of water for extraction. The product is purified by column chromatography to obtain 2.37 g of 3-bromo-4-iodo-tert-butylbenzene (i.e., compound III) with a yield of 70%.

[0079]

[0080] S3. Synthesis of Compound IV:

[0081] Weigh 3-bromo-4-iodotert-butylbenzene (Compound III) (1.22 g, 3.61 mmol), phenylboric acid (Compound II) (464 mg, 3.71 mmol), palladium (43 mg), and anhydrous potassium carbonate (1.27 g) into a 100 mL reaction bottle, add 30 mL of ethylene glycol diethyl ether and 6 mL of water, and freeze deoxygenate three times under nitrogen protection. After the deoxygenation, heat the reaction system to 60°C and stir overnight. After the reaction is completed the next day, extract three times, each time using 10 mL of dichloromethane and 30 mL of water for extraction, combine the organic phases, and purify the product by column chromatography to obtain 0.57 g of compound IV with a yield of 55%.

[0082] S4. Synthesis of Compound V:

[0083] Weigh compound IV (700 mg, 277.05 mmol) and put it into a 50 mL reaction bottle. Replace nitrogen 3 times to put the reaction bottle in a nitrogen atmosphere. Add 30 mL of tetrahydrofuran to the reaction bottle and place it in a low temperature instrument at -77 ° C for 10 min. After 10 min, measure 1.6 mL of 1.6 mol / L n-butyl lithium and slowly add it to the reaction bottle. Stir for 1 h at -77 ° C, and the solution becomes clear and light yellow. After 1 hour, trimethyl borate (1 mL, 7.29 mmol) is slowly added dropwise to the reaction bottle. After the addition is completed, turn off the refrigeration and slowly return it to room temperature. Then add 1 mL of dilute hydrochloric acid to the reaction bottle and extract three times, each time using 10 mL of dichloromethane and 30 mL of water for extraction. After drying, spin dry and recrystallize with petroleum ether to obtain 401 mg of compound V with a yield of 65%.

[0084]

[0085] S5. Synthesis of compound VII: Weigh compound V (197 mg, 0.774 mmol), compound VI (3,6-dicarbazole) (100 mg, 0.31 mmol), potassium carbonate (104 mg, 0.775 mmol), palladium (17 mg, 0.016 mmol), add 7 mL of toluene, 1 mL of ethanol, and 1 mL of water into a 25 mL reaction bottle, and freeze-deoxygenate three times under nitrogen protection. After deoxygenation is completed, heat and stir the reaction at 60°C overnight, extract three times the next day, each time using 10 mL of dichloromethane and 30 mL of water for extraction, combine the organic phases, spin-dry and separate by column chromatography to obtain 94 mg of compound VII with a yield of 52%.

[0086] S6. Synthesis of compound VIII: Weigh compound VII (100 mg, 0.171 mmol) in a 100 mL reaction bottle, fill the bottle with nitrogen, and add 20 mL of anhydrous dichloromethane. Take another vial, add ferric chloride (554 mg, 3.42 mmol), fill the bottle with nitrogen atmosphere, add 2 mL of nitromethane to the vial and bubble to deoxygenate, and obtain a nitromethane solution of ferric chloride; slowly drop the nitromethane solution of ferric chloride into the above 100 mL reaction bottle, add it in about 10 minutes, and stir at room temperature for 30 minutes. After the reaction is completed, extract three times, each time using 30 mL of saturated sodium bicarbonate aqueous solution and 10 mL of dichloromethane solution for extraction, combine the organic phases, spin dry and separate by column chromatography to obtain 37 mg of compound VIII, with a yield of 37%.

[0087]

[0088] S7. Synthesis of compound X: Weigh compound VIII (140 mg, 0.24 mmol), compound IX (172 mg, 0.32 mmol) and cesium carbonate (467 mg, 1.44 mmol) and add them into a reaction tube. After heating at 160°C for 2 h, add 15 mL of N,N-dimethylformamide into the reaction tube and heat to 160°C for 12 h in the dark. After the reaction is completed, cool to room temperature and add 5 mol / L dilute hydrochloric acid aqueous solution. Shake and filter and wash the residue. Then extract the residue three times, each time using 10 mL of dichloromethane and 30 mL of saturated brine. Combine the organic phases, spin dry, and separate by column chromatography to obtain 27 mg of compound X with a yield of 10%.

[0089] S7. Synthesis of compound Ⅰ: Add compound Ⅹ (150 mg, 0.137 mmol), potassium tert-butoxide (31 mg, 0.27 mmol), and tetrachlorobenzoquinone (67 mg, 0.27 mmol) into a reaction flask. Heat at 60°C for 2 h, then add 15 mL of tetrahydrofuran. Protect from light and react at room temperature for 3 h. After the reaction is completed, extract three times, each time using 30 mL of water and 10 mL of dichloromethane. Combine the organic phases and separate by column chromatography to obtain 15 mg of the final product (i.e., compound Ⅰ) with a yield of 10%.

[0090] The compound X obtained in Example 1 was subjected to single crystal diffraction test:

[0091] Test method:

[0092] The single crystal diffraction test was carried out using a Bruker D7 X-ray single crystal diffractometer, the crystal data were restored and corrected using SAINT5.0 and SADABS programs, and the crystal structure was analyzed and refined using SHELXTL-97 software.

[0093] The test results are as follows Figure 1 and Figure 2 shown.

[0094] Figure 1 It is the single crystal diffraction pattern of compound X prepared in the example of the present application.

[0095] Figure 2 It is a single crystal arrangement diagram of compound X prepared in the example of the present application.

[0096] Combination Figure 1 and Figure 2 , it can be seen from the crystal structure that compound Ⅹ has two configurations, P and M, without alternating arrangement.

[0097] The light emission and absorption tests were performed on the compound I obtained in Example 1:

[0098] Test method:

[0099] The UV-visible absorption spectra were recorded on a JASCO V770 UV-visible spectrophotometer, and the fluorescence spectra were recorded on a Cold Light Technology F97 Pro spectrophotometer.

[0100] Test sample: Compound I was dissolved in dichloromethane solution to a concentration of 1×10 -5 mol / L test solution 1; Compound I was dissolved in n-hexane solution to a concentration of 1×10 -5 mol / L test solution 2.

[0101] The test results are as follows Figure 3 shown.

[0102] from Figure 3 It can be seen that in test solution 1, compound I does not emit light in dichloromethane solution; in test solution 2, the maximum emission wavelength of compound I in n-hexane solution reaches 700nm, which has typical red light emission characteristics. It can be seen that compound I prepared in Example 1 of the present invention has the characteristics of long-wave emission (red light or near infrared) and can be applied to liquid crystal materials, biomedicine, photodetectors and other fields.

[0103] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that the technical solutions described in the aforementioned embodiments may still be modified, or some of the technical features may be replaced by equivalents. Such modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention, and should be included in the protection scope of the present invention.

Claims

1. A chiral azaspiro compound, characterized in that: The chemical structure of the chiral azaspiro compound is shown in Formula I:

2. The method for preparing a chiral azaspiro compound according to claim 1, wherein The steps include: S1. Synthesis of Compound IV: Compound II having a structure of formula II reacts with compound III having a structure of formula III in a first solvent in the presence of a first catalyst and a first base to obtain compound IV having a structure of formula IV; S2. Synthesis of Compound V: Under a nitrogen atmosphere, a compound IV having a structure of formula IV reacts with n-butyl lithium and trimethyl borate in a second solvent in the presence of an acid to obtain a compound V having a structure of formula V; S3. Synthesis of Compound VII: Compound V having a structure of formula V reacts with compound VI having a structure of formula VI in the presence of a second catalyst and a second base in a third solvent to obtain compound VII having a structure of formula VII; S4. Synthesis of Compound VIII: Under a nitrogen atmosphere, a compound VII having a structure of formula VII reacts with a nitromethane solution containing ferric chloride in a fourth solvent to obtain a compound VIII having a structure of formula VIII; S5. Synthesis of Compound X: Compound VIII having a structure of formula VIII reacts with compound IX having a structure of formula IX in a fifth solvent in the presence of a third base to obtain compound X having a structure of formula X; the third base is cesium carbonate; the fifth solvent is N,N-dimethylformamide; S6. Synthesis of Compound Ⅰ: Compound X having the formula X is reacted in the presence of potassium tert-butoxide and chlorobenzoquinone in a sixth solvent to obtain compound I having the structure of formula I.

3. The method for preparing a chiral azaspiro compound according to claim 2, wherein In step S1, the compound III is prepared by the following steps: Synthesis of compound b: Compound a reacts with N-bromosuccinimide in a seventh solvent to obtain compound b; Synthesis of compound III: Compound b reacts with aqueous sulfuric acid, aqueous sodium nitrate, potassium iodide and aqueous sodium bisulfite to obtain compound III.

4. The method for preparing a chiral azaspiro compound according to claim 2, wherein In step S1, the first catalyst is palladium; The first base is anhydrous potassium carbonate; The first solvent is a mixture of ethylene glycol diethyl ether and water.

5. The method for preparing a chiral azaspiro compound according to claim 2, wherein In step S2, the acid is dilute hydrochloric acid; The second solvent is tetrahydrofuran; The reaction temperature was -78°C.

6. The method for preparing a chiral azaspiro compound according to claim 2, characterized in that: In step S3, the second catalyst is palladium; The second base is potassium carbonate; The third solvent is a mixture of toluene, ethanol and water.

7. The method for preparing a chiral azaspiro compound according to claim 2, characterized in that: In step S4, the fourth solvent is anhydrous dichloromethane.

8. The method for preparing a chiral azaspiro compound according to claim 2, wherein: In step S6, the sixth solvent is tetrahydrofuran.

9. Use of the chiral azaspiro compound according to claim 1 in the preparation of liquid crystal materials, biomedicine and optoelectronic materials.

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