Preparation method and application of fully-substituted 5, 5 '-bisoxazole compound

Abstract

The invention relates to a full-substituted 5, 5 '-bisoxazole compound which is constructed by N-(1-aryl vinyl) amide catalyzed by transition metal through a repeated cross dehydrogenation coupling strategy. Specifically, under the condition of an inert solvent, under the common promotion of a transition metal catalyst and a silver salt oxidizing agent, multi-time dehydrogenation 1, 1-bifunctionalization of olefin is realized. The method has better regioselectivity and chemical selectivity, and is worthy of noting that the invention reports the first case of simple construction of a fully-substituted 5, 5 '-biazole compound skeleton based on a multi-dehydrocyclization strategy through transition metal catalysis, and the converted substrate is wide in application range and strong in functional group tolerance. The applicant also realizes modification of drug molecules such as probenecid. Furthermore, the obtained 5, 5 '-bisoxazole molecules are subjected to fluorescence test, and the fluorescence quantum yield reaches 83.14%, which indicates that the novel skeleton has great application potential in the aspect of luminescent materials.

Description

Technical Field

[0001] The present application relates to the technical field of organic compound synthesis, and more specifically, to a preparation method of a fully substituted 5,5'-bioxazole compound and its application. Background Art

[0002] It is highly desirable to develop efficient atomic and step-economic strategies to synthesize biaryl heterocyclic skeletons that are widely present in the field of bioactive molecules and optoelectronic materials. In recent years, people have developed transition metal-catalyzed methods to expand the synthetic molecular library of bioxazole compounds. Most of the classical synthetic methods are based on the coupling reaction of heteroaryl halides and organometallic reagents. This type of method can prepare a variety of heterodiaryls and exhibits high levels of activity for the coupling of heteroaryl chlorides and large sterically hindered aryls and heteroaryl halides (J.Am.Chem.Soc., 2007, 129, 3358-3366). However, the synthesis of bioxazole compounds catalyzed by transition metals has the following challenges:

[0003] 1) The substrates often need to be prepared in advance, and the reaction produces stoichiometric byproducts that are environmentally unfriendly, resulting in poor atom economy;

[0004] 2) When electron-poor aromatic rings are selected as substrates for aromatic coupling to obtain azole compounds, their substrate compatibility is poor and their chemical selectivity is poor and difficult to control;

[0005] 3) Using stoichiometric strong base as an additive pollutes the environment and does not conform to the concept of green chemistry.

[0006] In addition, people have also developed strategies to use existing heterocyclic skeletons to achieve oxidative coupling through CH bond activation to synthesize heterocyclic compounds, which has better step economy and atom economy. For example, in 2011, Ofial reported a method for selective CC coupling of benzoazoles and azoles by breaking two CH bonds at the C2 position, synthesizing a class of asymmetric 2,2'-bisheteroaryl compounds that have not been widely explored (Angew. Chem. Int. Ed. 2011, 50, 2178-2182); in 2012, You Jinsong's research group used two structurally similar non-benzo-fused cyclic azoles to selectively perform oxidative cross-coupling (Chem. Eur. J. 2012, 18, 6158-6162.), but there are still limitations, that is, the substrate starts with a heterocyclic compound, only one cross-dehydrogenation coupling reaction is achieved, the functional group compatibility is poor, and it is difficult to carry out later modification.

[0007] Although many natural products with important biological activities contain directly connected azole compounds, the 2,2'-connection of azole compounds is already a rare skeleton structure in nature. The 5,5'-connection of azole compounds is even less reported. The synthesis of the rare 5,5'-bioxazole compounds is obtained by direct carbon-carbon coupling of two molecules of oxazole compounds (Chin. Chem. Lett., 2021, 32, 425-428). In 2014, Zhao Yu's research group only reported one case of using oxalate and isocyanoacetate to synthesize 5,5'-bioxazole substituted with methyl formate at the 4th position under silver catalysis (Angew. Chem. Int. Ed., 2014, 53, 5435-5439). It should be pointed out that the one-step synthesis of fully substituted 5,5'-bioxazoles through a simple raw material direct multiple dehydrogenation strategy has not been reported.

[0008] On the other hand, enamines are versatile reaction intermediates for the synthesis of nitrogen-containing skeletons due to their intrinsic nucleophilicity. They can participate in a series of selective functionalization reactions. The directed CH functionalization of olefins by enamines has become an effective synthetic strategy for the preparation of various polysubstituted amines and olefin derivatives. In 2015, Wang Jian's research group reported a ruthenium-catalyzed [4+2] cycloaddition reaction of enamides and alkynes, and published a mild and economical scheme for the construction of polysubstituted pyridines (J.Am.Chem.Soc.2015,137,9489-9496), where enamines act as four-atom synthons.

[0009] In 2019, Teck-Peng Loh reported a practical method for synthesizing N-acyl enamine amides by iron-catalyzed oxidative coupling of enamides with formamide (ACS Catal. 2019, 9, 8128-8135). The products can be further converted into important biologically active molecules such as pyrimidine-4-ones and 4-hydroxypyridin-2-ones. Here, enamines serve as C1 synthons.

[0010] Application Contents

[0011] In order to overcome at least one problem existing in the above-mentioned prior art, the present application provides a method for preparing a fully substituted 5,5'-bioxazole compound: with the assistance of an easily available and traceless weakly coordinating directing group, 1,1-multiple dehydrogenation difunctionalization of olefins under metal catalysis is achieved to construct a polycyclic aromatic heterocyclic molecular skeleton.

[0012] In order to solve the above technical problems, the technical solution adopted in this application is:

[0013] A method for preparing a fully substituted 5,5'-bioxazole compound: In an inert solvent and under the action of a metal catalyst, the N-(1-aryl vinyl)amide compound represented by formula II is subjected to multiple dehydrogenation to obtain a fully substituted 5,5'-bioxazole compound represented by formula I. The reaction equation is as follows:

[0014]

[0015] Wherein Ar is an o-, m- or p-substituted aromatic compound, and R is an alkyl group or a phenyl group.

[0016] Preferably, the inert solvent is any one or more of toluene, tetrahydrofuran, 1,4-dioxane, ethylene glycol dimethyl ether, N,N'-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, acetonitrile, 1,2-dichloroethane, ethanol, and water.

[0017] Preferably, the metal catalyst is any one of pentamethylcyclopentadienylrhodium chloride dimer, pentamethylcyclopentadienyliridium chloride dimer, palladium acetate, and dichloro(p-methylisopropylphenyl)ruthenium dimer, or a combination thereof.

[0018] Preferably, the halide ion extractor is any one of silver hexafluoroantimonate and silver bistrifluoromethanesulfonyl imide or a combination thereof.

[0019] Preferably, the oxidant is any one or more of silver acetate, silver carbonate, silver oxide, copper acetate, and potassium persulfate.

[0020] Preferably, the additive is any one of lithium acetate and lithium carbonate or a combination thereof.

[0021] Preferably, the amount of the metal catalyst used is 2 mol% of the amount of the N-(1-aryl vinyl)amide compound represented by formula II.

[0022] Preferably, the reaction is carried out at 120-140° C.; the reaction is carried out for 6-24 hours.

[0023] The preparation method of the fully substituted 5,5'-bioxazole compound in some preferred embodiments of the present application comprises the following specific steps:

[0024] S1: In a reactor, 1.6 mg of pentamethylcyclopentadiene iridium dichloride dimer, 1.9 mg of silver trifluoromethanesulfonimide, 55.2 mg of silver carbonate, 26.4 mg of lithium acetate, 1.0 mL of solvent toluene, and 32.2 mg of N-(1-arylvinyl)acetamide were added in sequence in air;

[0025] S2: reacting the reaction solution at 140°C for 12 hours;

[0026] S3: After the reaction is completed, the mixture is separated by column chromatography to obtain the target compound.

[0027] The present application also provides the use of the fully substituted 5,5'-bioxazole compound prepared by the above preparation method in luminescent materials.

[0028] The present invention realizes multiple dehydrogenation 1,1 difunctionalization of olefins under the conditions of inert solvents by co-promoting metal catalysts and silver salt oxidants to synthesize fully substituted 5,5'-bioxazole compounds. Specifically, firstly, N-(1-aryl vinyl)amide) is used as an easily available and easily converted raw material, and amide is used as a weakly coordinated traceless directing group to realize the C( sp 2 )-H activation, and then the amide undergoes enol tautomerism and intramolecular oxidative cyclization, thereby constructing carbon-carbon bonds and carbon-hetero bonds to obtain fully substituted 5,5'-bioxazole compound products. This method has high atom economy (the product is obtained by cross-dehydrogenation coupling, and the transformation removes 4 CH bonds and 2 NH bonds) and step economy (no need to pre-halogenate or metallate the raw materials), and the substrate has a wide range of applicability. The easily available N-(1-aryl vinyl) amide is used as a reaction substrate and participates in the construction of nitrogen-containing fused heterocycles as a traceless directing group.

[0029] Compared with the prior art, the beneficial effects of this application are:

[0030] The preparation method of the fully substituted 5,5'-bioxazole compound provided in the present patent application has the characteristics of easy availability of raw materials, multiple dehydrogenation, high efficiency in atom economy and step economy. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 This is the hydrogen nuclear magnetic resonance spectrum of compound 1a prepared in Example 1 of the present application;

[0032] Figure 2 The carbon NMR spectrum of compound 1a prepared in Example 1 of the present application;

[0033] Figure 3 This is the hydrogen nuclear magnetic resonance spectrum of compound 1b prepared in Example 2 of the present application;

[0034] Figure 4 This is the carbon NMR spectrum of compound 1b prepared in Example 2 of the present application;

[0035] Figure 5 The NMR fluorine spectrum of compound 1b prepared in Example 2 of the present application;

[0036] Figure 6 This is the hydrogen nuclear magnetic resonance spectrum of compound 1c prepared in Example 3 of the present application;

[0037] Figure 7 This is the carbon NMR spectrum of compound 1c prepared in Example 3 of the present application;

[0038] Figure 8 This is the hydrogen nuclear magnetic resonance spectrum of compound 1d prepared in Example 4 of the present application;

[0039] Fig. 9 This is the carbon NMR spectrum of compound 1d prepared in Example 4 of the present application;

[0040] Fig.10 This is the hydrogen nuclear magnetic resonance spectrum of compound 1e prepared in Example 5 of the present application;

[0041] Fig.11 This is the carbon NMR spectrum of compound 1e prepared in Example 5 of the present application;

[0042] Fig.12 This is the hydrogen nuclear magnetic resonance spectrum of compound 1f prepared in Example 6 of the present application;

[0043] Fig.13 This is the carbon NMR spectrum of compound 1f prepared in Example 6 of the present application;

[0044] Fig.14 This is the hydrogen nuclear magnetic resonance spectrum of compound 1g prepared in Example 7 of the present application;

[0045] Fig.15 This is the carbon NMR spectrum of compound 1g prepared in Example 7 of the present application;

[0046] Fig.16 This is the hydrogen nuclear magnetic resonance spectrum of compound 1h prepared in Example 8 of the present application;

[0047] Fig.17 This is the carbon NMR spectrum of compound 1h prepared in Example 8 of the present application;

[0048] Fig.18 Compound 1h prepared in Application Example 1 of this application was dissolved in dichloromethane (1.0×10 -5 mol L -1 ) in ultraviolet / visible absorption spectra (UV) and photoluminescence (PL) emission spectra;

[0049] Fig.19 Compound 1h prepared in Application Example 1 of this application was dissolved in different solvents (1.0×10 -5 mol L -1 ) in photoluminescence (PL) emission spectra;

[0050] Fig. 20The compound 1h prepared in Application Example 1 of this application was dissolved in toluene solvent (1.0×10 -5 mol L -1 ) in fluorescence quantum yield (QY). DETAILED DESCRIPTION

[0051] The embodiments of the present application will be described in detail below in conjunction with the examples, but it will be appreciated by those skilled in the art that the following examples are only used to illustrate the present application and should not be considered as limiting the scope of the present application. In the examples, if specific conditions are not specified, they are carried out according to normal conditions or the conditions recommended by the manufacturer. If the manufacturer is not specified for the reagents or instruments used, they are all conventional products that can be purchased commercially.

[0052] It should be noted that:

[0053] In this application, unless otherwise specified, all the embodiments and preferred implementation methods mentioned herein can be combined with each other to form a new technical solution.

[0054] In the present application, unless otherwise specified, each reaction or operation step can be carried out sequentially or in a sequential manner. Preferably, the reaction method herein is carried out sequentially.

[0055] Unless otherwise specified, the professional and scientific terms used herein are the same as those familiar to those skilled in the art. In addition, any method or material similar or equivalent to the described content may also be applied to the present application.

[0056] The present application provides a method for preparing a fully substituted 5,5'-bioxazole compound: in an inert solvent and under the action of a metal catalyst, the N-(1-aryl vinyl)amide compound shown in Formula II is subjected to multiple dehydrogenation to obtain a fully substituted 5,5'-bioxazole compound shown in Formula I, and the reaction equation is as follows:

[0057]

[0058] Wherein Ar is an o-, m- or p-substituted aromatic compound, and R is an alkyl group or a phenyl group.

[0059] The preparation method in the present application achieves the simple construction of fully substituted 5,5'-bioxazole compounds through a weak coordination-guided olefin multiple dehydrogenation difunctionalization reaction strategy under the action of enamine in the presence of a metal catalyst, so as to enrich the molecular library in the field of functional materials.

[0060] Next, the preparation method of the fully substituted 5,5'-bioxazole compound of the present application is described in detail with specific examples.

[0061] 1. Preparation Example

[0062] Example 1 4,4'-bis(2,4-dichlorophenyl)-2,2'-dimethyl-5,5'-bioxazole (1a)

[0063]

[0064] Under an atmospheric pressure, 2,4-dichlorostyrylacetamide 2a (23.0 mg, 0.10 mmol), pentamethylcyclopentadienyl iridium dichloride dimer [Cp*IrCl2]2 (1.6 mg, 0.002 mmol), silver trifluoromethanesulfonimide (1.9 mg, 0.005 mmol), silver carbonate (55.2 mg, 0.20 mmol), lithium acetate (26.4 mg, 0.40 mmol), toluene (Tol, 1.0 mL) were added to a 15 mL Schlenk reaction tube in sequence, and the mixture was reacted at 140°C for 12 hours. The crude product was separated by chromatography on a prepared silica gel plate, and the selected developing solvent or eluent was a volume ratio of petroleum ether to ethyl acetate of 20:1, and the product 4,4'-bis(2,4-dichlorophenyl)-2,2'-dimethyl-5,5'-bioxazole (1a) was obtained with a yield of 69%.

[0065] The H-NMR spectrum of the compound prepared in Example 1: 1 H NMR (400MHz,CDCl3)δ7.16(d,J=8.4Hz,2H),7.12-7.08(m,4H),2.56(s,6H). The molecular hydrogen spectrum peaks can correspond to the target product one by one, and the quantity is reasonable. 13 C NMR (100MHz, CDCl3) δ161.9, 137.0, 135.0, 134.9, 133.6, 131.8, 129.3, 128.8, 126.7, 14.0. The molecular carbon spectrum peaks can correspond to the target product one by one, and the number is reasonable. Combining the results of the above nuclear magnetic hydrogen spectrum and carbon spectrum data, it can be seen that the product prepared in Example 1 is 4,4'-bis(2,4-dichlorophenyl)-2,2'-dimethyl-5,5'-bioxazole (1a).

[0066] The chemical transformation in this example can rapidly construct multi-substituted 5,5'-bioxazole molecules and easily convertible halogen functional groups, thereby providing a platform for the construction of more complex molecules.

[0067] Example 2 4,4'-Bis(4-fluorophenyl)-2,2'-dimethyl-5,5'-bioxazole (1b).

[0068]

[0069] Under an atmospheric pressure, 4-fluorostyrylacetamide 2b (17.9 mg, 0.10 mmol), dichloro(p-methylisopropylphenyl)ruthenium dimer [Ru(p-cymene)Cl2]2 (1.3 mg, 0.002 mmol), silver trifluoromethanesulfonimide (1.9 mg, 0.005 mmol), silver carbonate (55.2 mg, 0.20 mmol), lithium acetate (26.4 mg, 0.40 mmol), toluene (Tol, 1.0 mL) were added to a 15 mL Schlenk reaction tube in sequence, and the mixture was reacted at 140°C for 12 hours. The crude product was separated by chromatography on a prepared silica gel plate, and the selected developing solvent or eluent was a volume ratio of petroleum ether to ethyl acetate of 20:1, and the product 4,4'-bis(4-fluorophenyl)-2,2'-dimethyl-5,5'-bioxazole (1b) was obtained with a yield of 65%.

[0070] The H-NMR spectrum of the compound prepared in Example 2: 1 H NMR (CDCl3, 400MHz) δ7.51 (dd, J = 8.8Hz, 5.6Hz, 4H), 6.91 (t, J = 8.8Hz, 4H), 2.58 (s, 6H). The molecular hydrogen spectrum peaks can correspond to the target product one by one, and the quantity is reasonable. NMR carbon spectrum: 13 C NMR (100MHz,CDCl3)δ162.8(d,J=248Hz,1C),162.5,161.5,139.0,128.6,128.5,115.5,115.3,14.1. The molecular carbon spectrum peaks can correspond to the target product one by one, and the quantity is reasonable. NMR fluorine spectrum: 19 F NMR (376MHz, CDCl3) δ-112.5. The molecular carbon spectrum peaks can correspond to the target product one by one, and the number is reasonable. Combining the results of the above nuclear magnetic hydrogen spectrum, carbon spectrum, and fluorine spectrum data, it can be seen that the product prepared in Example 2 is 4,4'-bis(4-fluorophenyl)-2,2'-dimethyl-5,5'-bioxazole (1b).

[0071] The chemical transformation in this example can rapidly construct multi-substituted 5,5'-bioxazole molecules and easily convertible halogen functional groups, thereby providing a platform for the construction of more complex molecules.

[0072] Example 3 4,4'-bis(2-bromophenyl)-2,2'-dimethyl-5,5'-bioxazole (1c)

[0073]

[0074] Under an atmospheric pressure, 2-bromostyrylacetamide 2c (23.9 mg, 0.10 mmol), dichloro(p-methylisopropylphenyl)ruthenium dimer [Ru(p-cymene)Cl2]2 (1.3 mg, 0.002 mmol), silver trifluoromethanesulfonimide (1.9 mg, 0.005 mmol), silver carbonate (55.2 mg, 0.20 mmol), lithium carbonate (29.6 mg, 0.40 mmol), toluene (Tol, 1.0 mL) were added to a 15 mL Schlenk reaction tube in sequence, and the mixture was reacted at 140°C for 12 hours. The crude product was separated by chromatography on a prepared silica gel plate, and the selected developing solvent or eluent was a volume ratio of petroleum ether to ethyl acetate of 20:1, and the product 4,4'-bis(2-bromophenyl)-2,2'-dimethyl-5,5'-bioxazole (1c) was obtained with a yield of 53%.

[0075] The compound prepared in Example 3: 1 H NMR (CDCl3, 400MHz) δ7.34 (d, J = 7.6Hz, 2H), 7.17-7.15 (m, 2H), 7.12-7.08 (m, 2H), 7.03-6.98 (m, 2H), 2.54 (s, 6H). The molecular hydrogen spectrum peaks can correspond to the target product one by one, and the quantity is reasonable. NMR carbon spectrum: 13 C NMR (100MHz, CDCl3) δ161.5, 137.9, 137.4, 132.8, 132.2, 131.3, 129.6, 127.0, 122.9, 14.0. The molecular carbon spectrum peaks can correspond to the target product one by one, and the number is reasonable. Combining the results of the above nuclear magnetic hydrogen spectrum and carbon spectrum data, it can be seen that the product obtained in Example 3 is 4,4'-bis(2-bromophenyl)-2,2'-dimethyl-5,5'-bioxazole (1c).

[0076] The chemical transformation in this embodiment can rapidly construct multi-substituted 5,5'-bioxazole molecules and easily convert halogen functional group bromine atoms, thereby providing a platform for the construction of more complex molecules.

[0077] Example 4 2,2'-Dimethyl-4,4'-diphenyl-5,5'-bioxazole (1d)

[0078]

[0079] In an atmosphere of air at atmospheric pressure, N-(1-phenylvinyl)acetamide 2d (16.1 mg, 0.10 mmol), pentamethylcyclopentadienyl iridium dichloride dimer [Cp*IrCl2]2 (1.6 mg, 0.002 mmol), silver trifluoromethanesulfonimide (1.9 mg, 0.005 mmol), silver oxide (46.3 mg, 0.20 mmol), lithium acetate (26.4 mg, 0.40 mmol), toluene (Tol, 1.0 mL) were added to a 15 mL Schlenk reaction tube in sequence, and the mixture was reacted at 140°C for 12 hours. The crude product was separated by chromatography on a prepared silica gel plate, and the selected developing solvent or eluent was a volume ratio of petroleum ether to ethyl acetate of 20:1, and the product 2,2'-dimethyl-4,4'-diphenyl-5,5'-bioxazole (1d) was obtained with a yield of 68%.

[0080] The H-NMR spectrum of the compound prepared in Example 4: 1 H NMR (CDCl3, 400MHz) δ7.57-7.54 (m, 4H), 7.23-7.22 (m, 6H), 2.58 (s, 6H). The molecular hydrogen spectrum peaks can correspond to the target product one by one, and the quantity is reasonable. 13 C NMR (100MHz, CDCl3) δ162.4, 140.1, 133.9, 130.5, 129.1, 128.4, 126.6, 14.1. The molecular carbon spectrum peaks can correspond to the target product one by one, and the number is reasonable. Combining the results of the above nuclear magnetic hydrogen spectrum and carbon spectrum data, it can be seen that the product prepared in Example 4 is 2,2'-dimethyl-4,4'-diphenyl-5,5'-bioxazole (1d).

[0081] The chemical transformation in this example can rapidly construct multi-substituted 5,5'-bioxazole molecules, thereby providing a platform for the construction of more complex molecules.

[0082] Example 5 2,2'-Dimethyl-4,4'-di-p-tolyl-5,5'-bioxazole (1e)

[0083]

[0084] In an atmosphere of air at atmospheric pressure, N-(1-(4-methoxyphenyl)vinyl)acetamide 2e (19.1 mg, 0.10 mmol), pentamethylcyclopentadiene rhodium dichloride dimer [Cp*RhCl2]2 (1.4 mg, 0.002 mmol), silver trifluoromethanesulfonimide (1.9 mg, 0.005 mmol), silver carbonate (55.2 mg, 0.20 mmol), lithium acetate (26.4 mg, 0.40 mmol), toluene (Tol, 1.0 mL) were added to a 15 mL Schlenk reaction tube in sequence, and the mixture was reacted at 140°C for 12 hours. The crude product was separated by chromatography on a prepared silica gel plate, and the selected developing solvent or eluent was a volume ratio of petroleum ether to ethyl acetate of 20:1, and the product 2,2'-dimethyl-4,4'-di-p-tolyl-5,5'-bioxazole (1e) was obtained with a yield of 58%.

[0085] The H-NMR spectrum of the compound prepared in Example 5: 1 H NMR (CDCl3, 400MHz) δ7.49 (d, J = 8.8Hz, 4H), 6.76 (d, J = 8.8Hz, 4H), 3.76 (s, 6H), 2.56 (s, 6H). The molecular hydrogen spectrum peaks can correspond to the target product one by one, and the quantity is reasonable. NMR carbon spectrum: 13 C NMR (100MHz, CDCl3) δ162.2, 159.7, 139.7, 133.0, 128.0, 123.2, 113.8, 55.2, 14.1. The molecular carbon spectrum peaks can correspond to the target product one by one, and the number is reasonable. Combining the results of the above nuclear magnetic hydrogen spectrum and carbon spectrum data, it can be seen that the product obtained in Example 5 is 2,2'-dimethyl-4,4'-di-p-tolyl-5,5'-bioxazole (1e).

[0086] The chemical transformation in this embodiment can rapidly construct multi-substituted 5,5'-bioxazole molecules and is compatible with electron-donating groups, thereby providing a platform for the construction of complex molecules.

[0087] Example 6 2,2'-Dimethyl-4,4'-dinaphth-2-yl-5,5'-bioxazole (1f)

[0088]

[0089] In an atmospheric pressure air atmosphere, N-(1-naphthyl)vinyl acetamide 2f (21.1 mg, 0.10 mmol), pentamethylcyclopentadienyl iridium dichloride dimer [Cp*IrCl2]2 (1.6 mg, 0.002 mmol), silver trifluoromethanesulfonimide (1.9 mg, 0.005 mmol), silver acetate (33.4 mg, 0.20 mmol), lithium acetate (26.4 mg, 0.40 mmol), toluene (Tol, 1.0 mL) were added to a 15 mL Schlenk reaction tube in sequence, and the mixture was reacted at 140°C for 12 hours. The crude product was separated by chromatography on a prepared silica gel plate, and the selected developing solvent or eluent was a volume ratio of petroleum ether to ethyl acetate of 20:1, and the product 2,2'-dimethyl-4,4'-dinaphthyl-2-yl-5,5'-bioxazole (1f) was obtained with a yield of 58%.

[0090] H NMR spectrum of the compound prepared in Example 6 1 H NMR (CDCl3, 400MHz) δ8.20 (d, J = 2.4Hz, 1H), 7.57 (dd, J = 2.4Hz, 8.8Hz, 1H), 7.49 -7.45 (m, 2H), 7.36 -7.32 (m, 2H), 6.69 (d, J = 8.8Hz, 1H), 3.92 (s, 3H), 2.58 (s, 3H). The molecular hydrogen spectrum peaks can correspond to the target product one by one, and the quantity is reasonable. NMR carbon spectrum: 13 CNMR (100MHz,CDCl3)δ169.1,167.4,151.0,143.8,139.7,135.3,134.2,132.3,131.9,130.8,130.2,127.1,122.4,111.6,54.4,14.0. The molecular carbon spectrum peaks can correspond to the target product one by one, and the quantity is reasonable. Combined with the results of the above nuclear magnetic hydrogen spectrum and carbon spectrum data, it can be seen that the product obtained in Example 6 is 2,2'-dimethyl-4,4'-dinaphth-2-yl-5,5'-bioxazole (1f).

[0091] The chemical transformation in this example can rapidly construct multi-substituted 5,5'-bioxazole molecules and is compatible with fused rings, thereby providing a platform for the construction of complex molecules.

[0092] Example 7 2,2'-Dimethyl[5,5'-bioxazole]-4,4'-diphenylbis(4,1-phenylene)bis(N,N-dipropylsulfonamido)benzoate (1 g)

[0093]

[0094] Under an atmospheric pressure air atmosphere, 2 g (44.4 mg, 0.10 mmol) of 4-(1-acetylaminovinyl)phenyl 4-(N,N-dipropylaminosulfonyl)benzoate, palladium acetate Pd(OAc)2 (0.5 mg, 0.002 mmol), silver oxide (23.1 mg, 0.10 mmol), copper acetate (20.0 mg, 0.10 mmol), lithium acetate (26.4 mg, 0.40 mmol), and toluene (Tol, 1.0 mL) were added sequentially into a 15 mL Schlenk reaction tube and reacted at 140°C for 12 hours. The crude product was separated by chromatography using a prepared silica gel plate. The selected developing solvent or eluent was a volume ratio of petroleum ether to ethyl acetate of 20:1. The product 2,2'-dimethyl[5,5'-bioxazole]-4,4'-diphenylbis(4,1-phenylene)bis(N,N-dipropylsulfonamido)benzoate (1 g) was obtained with a yield of 51%.

[0095] The H-NMR spectrum of the compound prepared in Example 7: 1 H NMR (CDCl3, 400MHz) δ8.32 (d, J = 8.4Hz, 4H), 8.07 (d, J = 8.8Hz, 4H), 7.96 (d, J = 8.4Hz, 4H), 7.34 (d, J = 8.8Hz, 4H), 3.14 (t, J = 8.0Hz, 8H), 2.63 (s, 6H), 1.60-1.55 (m, 8H), 0.89 (t, J = 7.2Hz, 12H). The molecular hydrogen spectrum peaks can correspond to the target product one by one, and the quantity is reasonable. Nuclear magnetic carbon spectrum: 13 C NMR (100MHz, CDCl3) δ166.7, 163.3, 154.3, 146.5, 145.4, 140.0, 135.2, 132.3, 130.9, 130.1, 127.3, 121.8, 49.9, 21.9, 14.1, 11.1. The molecular carbon spectrum peaks can correspond to the target product one by one, and the quantity is reasonable. Combining the results of the above nuclear magnetic hydrogen spectrum and carbon spectrum data, it can be seen that the product obtained in Example 7 is 2,2'-dimethyl[5,5'-bioxazole]-4,4'-diphenylbis(4,1-phenylene)bis(N,N-dipropylsulfonamido)benzoate (1g).

[0096] The chemical transformation in this embodiment uses the drug star molecule probenecid as a raw material to quickly construct a multi-substituted 5,5'-bioxazole compound, which can achieve the transformation of drug molecules.

[0097] Example 8 4,4'-bis(4-(9,9-dimethylacridin-10(9H)-yl)phenyl)-2,2'-dimethyl-5,5'-bioxazole (1h)

[0098]

[0099] Under an atmospheric pressure air atmosphere, N-(1-(4-(9,9-dimethylacridin-10(9H)-yl)phenyl)vinyl)acetamide 2h (36.8 mg, 0.10 mmol), pentamethylcyclopentadiene iridium dichloride dimer [Cp*IrCl2]2 (1.6 mg, 0.002 mmol), silver trifluoromethanesulfonimide (1.9 mg, 0.005 mmol), silver acetate (33.4 mg, 0.20 mmol), lithium carbonate (29.6 mg, 0.40 mmol), and toluene (Tol, 1.0 mL) were added sequentially into a 15 mL Schlenk reaction tube and reacted at 140°C for 12 hours. The crude product was separated by chromatography on a prepared silica gel plate, and the selected developing solvent or eluent was a volume ratio of petroleum ether to ethyl acetate of 20:1, and the product 4,4'-bis(4-(9,9-dimethylacridin-10(9H)-yl)phenyl)-2,2'-dimethyl-5,5'-bioxazole (1h) was obtained with a yield of 66%.

[0100] The H-NMR spectrum, C-NMR spectrum and F-NMR spectrum of the compound prepared in Example 8 are as follows: Figure 1 , Figure 2 As shown. Figure 1 It can be seen that: 1 HNMR (400MHz,CDCl3)δ7.89(d,J=8.4Hz,4H),7.46-7.40(m,4H),7.32(d,J=8.4Hz,4H),6.91-6.85(m,8H),6.26-6.22(m,4H),2.65(s,6H),1.67(s,12H). The molecular hydrogen spectrum peaks can correspond to the target product one by one, and the quantity is reasonable. Figure 2 It can be seen that: 13 C NMR (100MHz, CDCl3) δ162.8, 141.5, 140.7, 140.0, 134.2, 131.6, 130.5, 130.0, 129.3, 126.3, 125.1, 120.6, 114.0, 35.9, 31.1, 14.2. The molecular carbon spectrum peaks can correspond to the target product one by one, and the quantity is reasonable. Combining the results of the above nuclear magnetic hydrogen spectrum and carbon spectrum data, it can be seen that the product obtained in Example 8 is 4,4'-bis(4-(9,9-dimethylacridine-10(9H)-yl)phenyl)-2,2'-dimethyl-5,5'-bioxazole (1h).

[0101] 2. Application Example 1

[0102] The molecules were dissolved in dichloromethane (1.0×10 -5 mol L -1) in the ultraviolet / visible absorption spectrum (UV) and photoluminescence (PL) emission spectrum ( Figure 3 ). Maximum absorption wavelength (λ max ) appears at 287nm, which is due to the π→π of the conjugated double bond. * Transition; photoluminescence spectrum was obtained by excitation at the maximum absorption wavelength. 1h showed blue PL emission at 509 nm in dichloromethane. Subsequently, the fluorescence emission of molecule 1j in different solvents was tested ( Figure 4 ), such as benzonitrile (ACN), dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), tetrahydrofuran (THF), toluene (Tol). There is a certain interaction between the molecule 1h and the solvent, which causes its fluorescence emission to have different degrees of red shift or blue shift in different solvents. Then, in toluene solvent (1.0×10 -5 mol L -1 ) was tested for 1h and the fluorescence quantum yield (QY) was 83.14% ( Figure 5 ). This indicates that 1h has good application prospects in luminescent materials.

[0103] The present invention realizes multiple dehydrogenation 1,1 difunctionalization of olefins under the conditions of inert solvents by co-promoting metal catalysts and silver salt oxidants to synthesize fully substituted 5,5'-bioxazole compounds. Specifically, firstly, N-(1-aryl vinyl)amide) is used as an easily available and easily converted raw material, and amide is used as a weakly coordinated traceless directing group to realize the C( sp 2 )-H activation, and then the amide undergoes enol tautomerism and intramolecular oxidative cyclization, thereby constructing carbon-carbon bonds and carbon-hetero bonds to obtain fully substituted 5,5'-bioxazole compound products. This method has high atom economy (the product is obtained by cross-dehydrogenation coupling, and the transformation removes 4 CH bonds and 2 NH bonds) and step economy (no need to pre-halogenate or metallate the raw materials), and the substrate has a wide range of applicability. The easily available N-(1-aryl vinyl) amide is used as a reaction substrate and participates in the construction of nitrogen-containing fused heterocycles as a traceless directing group.

[0104] In summary, this application reports the first transition metal-catalyzed simple construction of a fully substituted 5,5'-oxazole compound skeleton based on a multiple dehydrogenation cyclization strategy. The substrates for this transformation have a wide range of applications and strong functional group tolerance. The applicant also achieved the modification of drug molecules such as probenecid. Furthermore, we conducted a fluorescence test on the obtained 5,5'-oxazole molecule, and its fluorescence quantum yield reached 83.14%, indicating that this type of new skeleton has great application potential in luminescent materials.

[0105] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "illustrative embodiments", "examples", "specific examples", or "some examples" means that the specific features, structures, materials, or characteristics described in conjunction with the embodiments or examples are included in at least one embodiment or example of the present application. In this specification, the schematic representation of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials, or characteristics described may be combined in any one or more embodiments or examples in a suitable manner.

[0106] Although several embodiments of the present application have been shown and described, those skilled in the art will appreciate that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present application, and that the scope of the present application is defined by the claims and their equivalents.

Claims

1. A method for preparing a fully substituted 5,5'-bioxazole compound, characterized in that: In an inert solvent and under the action of a metal catalyst, the N-(1-aryl vinyl)amide compound represented by Formula II is subjected to multiple dehydrogenation to obtain a fully substituted 5,5'-bioxazole compound represented by Formula I. The reaction equation is as follows: Wherein Ar is an o-, m- or p-substituted aromatic compound, and R is an alkyl group or a phenyl group.

2. The method for preparing a fully substituted 5,5'-bioxazole compound according to claim 1, characterized in that: The inert solvent is any one or more of toluene, tetrahydrofuran, 1,4-dioxane, ethylene glycol dimethyl ether, N,N'-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, acetonitrile, 1,2-dichloroethane, ethanol and water.

3. The method for preparing a fully substituted 5,5'-bioxazole compound according to claim 1, characterized in that: The metal catalyst is any one of pentamethylcyclopentadienyl rhodium chloride dimer, pentamethylcyclopentadienyl iridium chloride dimer, palladium acetate, and dichloro (p-methylisopropylphenyl) ruthenium dimer or a combination thereof.

4. The method for preparing a fully substituted 5,5'-bioxazole compound according to claim 1, characterized in that: The halide ion extractor is any one of silver hexafluoroantimonate and silver bis(trifluoromethanesulfonyl)imide or a combination thereof.

5. The method for preparing a fully substituted 5,5'-bioxazole compound according to claim 1, characterized in that: The oxidant is any one or more of silver acetate, silver carbonate, silver oxide, copper acetate and potassium persulfate.

6. The method for preparing a fully substituted 5,5'-bioxazole compound according to claim 1, characterized in that: The additive is any one of lithium acetate and lithium carbonate or a combination thereof.

7. The method for preparing a fully substituted 5,5'-bioxazole compound according to claim 3, characterized in that: The amount of the metal catalyst used is 2 mol% of the amount of the N-(1-aryl vinyl)amide compound represented by formula II.

8. The method for preparing a fully substituted 5,5'-bioxazole compound according to claim 1, characterized in that: The reaction is carried out at 120-140° C. and for 6-24 hours.

9. The method for preparing a fully substituted 5,5'-bioxazole compound according to claim 1, characterized in that: The specific steps include: S1: In a reactor, 1.6 mg of pentamethylcyclopentadiene iridium dichloride dimer, 1.9 mg of silver trifluoromethanesulfonimide, 55.2 mg of silver carbonate, 26.4 mg of lithium acetate, 1.0 mL of solvent toluene, and 32.2 mg of N-(1-arylvinyl)acetamide were added in sequence in air; S2: reacting the reaction solution at 140°C for 12 hours; S3: After the reaction is completed, the mixture is separated by column chromatography to obtain the target compound.

10. Use of the fully substituted 5,5'-bioxazole compound prepared by the preparation method of claim 1 in luminescent materials.

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