Process for the preparation of a fully substituted 5,5'-bioxazole compound and use thereof

Abstract

The application relates to a transition metal-catalyzed N-(1-arylvinyl)amide for constructing a fully substituted 5,5'-oxazole compound through a multiple cross-dehydrogenative coupling strategy. Specifically, under the condition of an inert solvent, through the joint promotion of a transition metal catalyst and a silver salt oxidant, multiple dehydrogenation 1,1-bifunctionalization of olefins is realized. The method has good regioselectivity and chemical selectivity. Notably, the application reports the first case of a transition metal-catalyzed simple construction of a fully substituted 5,5'-oxazole compound skeleton based on a multiple dehydrogenation cyclization strategy. The substrate of the conversion has a wide application range and strong functional group tolerance. The applicant also realizes the modification of drug molecules such as propyl sulfone. Further, the obtained 5,5'-oxazole molecules are subjected to fluorescence testing, and the fluorescence quantum yield reaches 83.14%, indicating that the novel skeleton has great application potential in luminescent materials.

Description

TECHNICAL FIELD

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

[0002] It is very desirable to develop a strategy with high atom and step economy to simply synthesize the biaryl heterocyclic skeleton widely existing in the field of bioactive molecules and optoelectronic materials. In recent years, people have developed a transition metal-catalyzed method to expand the molecular library of bi-oxazole compounds. The classic synthesis method is mostly based on the coupling reaction of heteroaryl halide and organometallic reagent. This method can prepare various hetero-diaryl groups and shows high activity in the coupling of heteroaryl chloride and large steric aryl and heteroaryl halide (J. Am. Chem. Soc., 2007, 129, 3358-3366). However, there are still the following challenges in the synthesis of transition metal-catalyzed bi-oxazole compounds:

[0003] 1) The substrate often needs to be prepared in advance, and the reaction produces a stoichiometric amount of environmentally unfriendly by-products, which is poor in atom economy;

[0004] 2) When an electron-poor aromatic ring is used as a substrate for aryl coupling to obtain a bi-oxazole compound, the substrate compatibility is poor, and the chemical selectivity is poor and difficult to control;

[0005] 3) Stoichiometric strong base is used as an additive, which pollutes the environment and does not meet the concept of green chemistry.

[0006] Moreover, people have also developed a strategy for synthesizing bi-heterocyclic compounds by C-H bond activation of existing heterocyclic skeletons through oxidative coupling, which has better step economy and atom economy. For example, in 2011, Ofial reported a method for selective C-C coupling of the cleavage of two C-H bonds at the C2 position of benzoxazole and oxazole compounds, synthesizing a class of unsymmetric 2,2'-biheteroaryl compounds that have not been widely explored (Angew. Chem. Int. Ed. 2011, 50, 2178-2182); In 2012, the group of You Jinsong selectively carried out oxidative cross-coupling with two structurally similar non-benzofused oxazole compounds (Chem. Eur. J. 2012, 18, 6158-6162.). However, there are still limitations, i.e., the substrate starts from a heterocyclic compound, only one cross-dehydrogenative coupling reaction is realized, the functional group compatibility is poor, and it is difficult to modify later.

[0007] Although many natural products with important biological activities contain directly linked azole compounds, 2,2'-linked azoles are a rare backbone structure in nature. 5,5'-linked azoles are even less reported. The synthesis of few 5,5'-linked azoles is achieved by direct carbon-carbon coupling of two molecules of azole compounds (Chin. Chem. Lett., 2021, 32, 425-428). In 2014, Zhao's group reported a case of 5,5'-linked azoles with a methyl formate at the 4-position synthesized from oxalate and isocyanoacetate under silver catalysis (Angew. Chem. Int. Ed., 2014, 53, 5435-5439). It is worth noting that the one-step synthesis of fully substituted 5,5'-linked azoles by a simple starting material through multiple dehydrogenation strategies has not been reported.

[0008] On the other hand, enamines are versatile intermediates for the synthesis of nitrogen-containing skeletons due to their inherent nucleophilicity, and they can participate in a series of selective functionalization reactions. The directed olefin C-H functionalization of enamines has become an effective synthetic strategy for the preparation of various polysubstituted amines and olefin derivatives. In 2015, Wang's group reported a ruthenium-catalyzed [4+2] cycloaddition of enamides and alkynes, publishing a mild and economical solution for the construction of polysubstituted pyridines (J. Am. Chem. Soc. 2015, 137, 9489-9496), where the enamine acts as a four-atom synthon.

[0009] In 2019, Teck-Peng Loh reported a practical method for the oxidative coupling of enamides with formamides to form N-acyl enamine amides using iron catalysis (ACS Catal. 2019, 9, 8128-8135), and the products can be further converted into important bioactive molecules such as pyrimidine-4-ketones and 4-hydroxypyridine-2-ketones, where the enamine acts as a C1 synthon.

[0010] SUMMARY

[0011] To overcome at least one problem existing in the prior art, the present application provides a preparation method of fully substituted 5,5'-linked azole compounds: through the assistance of an easily available, traceless, weakly coordinating directing group, 1,1-multiple dehydrogenation of olefins and bifunctionalization under metal catalysis are achieved, and a multi-linked aromatic heterocyclic molecular skeleton is constructed.

[0012] To solve the above technical problems, the technical scheme adopted by the present application is:

[0013] A method for preparing a fully substituted 5,5'-bi-oxazole compound: in an inert solvent, and in the presence of a metal catalyst, a N-(1-arylvinyl)amide compound shown in formula II is dehydrogenated for multiple times to obtain a fully substituted 5,5'-bi-oxazole compound shown in formula I, and the reaction equation is as follows:

[0014]

[0015] wherein Ar is an ortho-, meta-, or para-substituted aryl compound, and R is an alkyl or 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, water.

[0017] Preferably, the metal catalyst is any one or a combination of the following: pentamethylcyclopentadienyl rhodium chloride dimer, pentamethylcyclopentadiene iridium chloride dimer, palladium acetate, dichloro(p-methylisopropylphenyl) ruthenium dimer.

[0018] Preferably, the halide scavenger is any one or a combination of the following: silver hexafluoroantimonate, silver bistrifluoromethanesulfonimide.

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

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

[0021] Preferably, the amount of the metal catalyst is 2 mol% of the amount of the N-(1-arylvinyl)amide compound shown in formula II.

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

[0023] The method for preparing a fully substituted 5,5'-bi-oxazole compound in some preferred embodiments of the present application comprises the following specific steps:

[0024] S1: in a reactor, in air, 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 are sequentially added;

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

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

[0027] The application also provides application of the fully substituted 5,5'-oxazolyl compound prepared by the preparation method to a light-emitting material.

[0028] The application realizes multiple dehydrogenation 1,1 bifunctionalization of olefins under inert solvent conditions through co-promotion of a metal catalyst and a silver salt oxidant to synthesize a fully substituted 5,5'-oxazolyl compound. Specifically, first, N-(1-arylvinyl) amide is used as an easily available and easily converted raw material to realize C( sp 2 )-H activation of the olefin, and then enol tautomerization and intramolecular oxidative cyclization of the amide occur to construct a carbon-carbon bond and a carbon heteroatom bond, thereby obtaining the fully substituted 5,5'-oxazolyl compound product. The method has high atom economy (the product is obtained through cross dehydrogenative coupling, which removes 4 C-H bonds and 2 N-H bonds) and step economy (halogenation or metallation of the raw material is not required), has a wide range of applicable substrates, and simple and easily available N-(1-arylvinyl) amide is used as the reaction substrate and participates in the construction of the nitrogen-containing fused heterocycle as a traceless directing group.

[0029] Compared with the prior art, the application has the beneficial effects that:

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

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

[0032] Figure 2 The nuclear magnetic resonance carbon spectrum of compound 1a prepared in Example 1 of the application is shown in the figure;

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

[0034] Figure 4 The nuclear magnetic resonance carbon spectrum of compound 1b prepared in Example 2 of the application is shown in the figure;

[0035] Figure 5 The nuclear magnetic resonance fluorine spectrum of compound 1b prepared in Example 2 of the application is shown in the figure;

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

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

[0038] Figure 8 NMR spectrum of the compound 1d prepared in Example 4 of the present application;

[0039] Figure 9 NMR spectrum of the compound 1d prepared in Example 4 of the present application;

[0040] Figure 10 NMR spectrum of the compound 1e prepared in Example 5 of the present application;

[0041] Figure 11 NMR spectrum of the compound 1e prepared in Example 5 of the present application;

[0042] Figure 12 NMR spectrum of the compound 1f prepared in Example 6 of the present application;

[0043] Figure 13 NMR spectrum of the compound 1f prepared in Example 6 of the present application;

[0044] Figure 14 NMR spectrum of the compound 1g prepared in Example 7 of the present application;

[0045] Figure 15 NMR spectrum of the compound 1g prepared in Example 7 of the present application;

[0046] Figure 16 NMR spectrum of the compound 1h prepared in Example 8 of the present application;

[0047] Figure 17 NMR spectrum of the compound 1h prepared in Example 8 of the present application;

[0048] Figure 18 UV / visible absorption spectrum (UV) and photoluminescence (PL) emission spectrum of the compound 1h prepared in Application Example 1 of the present application dissolved in dichloromethane (1.0 x 10 -5 mol L -1 );

[0049] Figure 19 Photoluminescence (PL) emission spectrum of the compound 1h prepared in Application Example 1 of the present application dissolved in different solvents (1.0 x 10 -5 mol L -1 );

[0050] Figure 20The fluorescence quantum yield (QY) of the compound 1h prepared in the application example 1 was dissolved in toluene solvent (1.0 x 10 -5 mol L -1 ). DETAILED DESCRIPTION

[0051] The embodiments of the present application will be described in detail below with examples, but those skilled in the art will understand that the following examples are only for illustration of the present application and should not be regarded as limiting the scope of the present application. If the specific conditions are not specified in the examples, the conventional conditions or the conditions recommended by the manufacturer are carried out. If the manufacturer of the reagent or instrument used is not specified, it is a conventional product that can be obtained by commercial purchase.

[0052] It should be noted that:

[0053] In the present application, all the embodiments and preferred embodiments mentioned in the present application can be combined to form new technical solutions if not specifically stated.

[0054] In the present application, unless otherwise specified, each reaction or operation step can be carried out in sequence or according to the sequence. Preferably, the reaction method herein is carried out in sequence.

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

[0056] The present application provides a preparation method of a fully substituted 5,5'-bisoxazole compound: in an inert solvent and under the action of a metal catalyst, a N-(1-arylvinyl) amide compound represented by formula II is subjected to multiple dehydrogenation to obtain a fully substituted 5,5'-bisoxazole compound represented by formula I, and the reaction equation is as follows:

[0057]

[0058] wherein Ar is an ortho, meta or para substituted aryl compound, and R is an alkyl or phenyl group.

[0059] The preparation method in the present application realizes simple construction of a fully substituted 5,5'-bisoxazole compound through a weak coordination directed olefin multiple dehydrogenation bifunctionalization reaction strategy under the action of a metal catalyst, enriches the molecular library in the field of functional materials.

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

[0061] 1. Preparation Example

[0062] Example 1 4,4'-Bis(2,4-dichlorophenyl)-2,2'-dimethyl-5,5'-bi-oxazole (1a)

[0063]

[0064] Into a 15 mL Schlenk tube, 2,4-dichlorostyrylacetamide 2a (23.0 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 carbonate (55.2 mg, 0.20 mmol), lithium acetate (26.4 mg, 0.40 mmol), toluene (Tol, 1.0 mL) were added successively under an atmosphere of air at 140 °C for 12 h. The crude product was isolated by chromatography on a preparative silica gel plate with the selected eluent or developing solvent of petroleum ether and ethyl acetate in a volume ratio of 20:1 to give the product 4,4'-bis(2,4-dichlorophenyl)-2,2'-dimethyl-5,5'-bi-oxazole (1a) in 69% yield.

[0065] NMR of the compound prepared in Example 1: 1 H NMR (400 MHz, CDC13) δ 7.16 (d, J = 8.4 Hz, 2H), 7.12-7.08 (m, 4H), 2.56 (s, 6H). The molecular hydrogen spectrum peaks can be one-to-one corresponding to the target product, and the number is reasonable. Carbon spectrum: 13 C NMR (100 MHz, CDC13) δ 161.9, 137.0, 135.0, 134.9, 133.6, 131.8, 129.3, 128.8, 126.7, 14.0. The molecular carbon spectrum peaks can be one-to-one corresponding to the target product, and the number is reasonable. The results of the above nuclear magnetic hydrogen spectrum, carbon spectrum data show that the product prepared in Example 1 is 4,4'-bis(2,4-dichlorophenyl)-2,2'-dimethyl-5,5'-bi-oxazole (1a).

[0066] The chemical transformation in this example can quickly build multisubstituted 5,5'-bi-oxazole molecules, and the halogen functional groups are easy to transform, thereby providing a platform for the construction of more complex molecules.

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

[0068]

[0069] Into a 15 mL Schlenk tube, 4-fluorostyrylacetamide 2b (17.9 mg, 0.10 mmol), dichloro(p-cymene)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 successively under an atmosphere of air at 140 °C for 12 h. The crude product was isolated by chromatography on a preparative silica gel plate with the selected eluent or developing solvent of petroleum ether and ethyl acetate in a volume ratio of 20:1 to give the product 4,4'-bis(4-fluorophenyl)-2,2'-dimethyl-5,5'-bi- oxazole (1b) in 65% yield.

[0070] NMR of the compound prepared in Example 2: 1 H NMR (CDC13, 400 MHz) δ 7.51 (dd, J = 8.8 Hz, 5.6 Hz, 4H), 6.91 (t, J = 8.8 Hz, 4H), 2.58 (s, 6H). The molecular hydrogen spectrum peaks can be one-to-one corresponding to the target product, and the number is reasonable. Carbon magnetic resonance spectrum: 13 C NMR (100 MHz, CDC13) δ 162.8 (d, J = 248 Hz, 1C), 162.5, 161.5, 139.0, 128.6, 128.5, 115.5, 115.3, 14.1. The molecular carbon spectrum peaks can be one-to-one corresponding to the target product, and the number is reasonable. Fluorine magnetic resonance spectrum: 19 F NMR (376 MHz, CDC13) δ -112.5. The molecular carbon spectrum peaks can be one-to-one corresponding to the target product, and the number is reasonable. The results of the above hydrogen spectrum, carbon spectrum, and fluorine spectrum data show that the product prepared in Example 2 is 4,4'-bis(4-fluorophenyl)-2,2'-dimethyl-5,5'-bi- oxazole (1b).

[0071] The chemical transformation in this example can quickly build a multi-substituted 5,5'-bi- oxazole molecule, and the halogen functional group is easy to transform, thereby providing a platform for the construction of more complex molecules.

[0072] Example 3 4,4'-Bis(2-bromophenyl)-2,2'-dimethyl-5,5'-bi-oxazole (1c)

[0073]

[0074] Into a 15 mL Schlenk tube, 2-bromostyrylacetamide 2c (23.9 mg, 0.10 mmol), dichloro(p-cymene)ruthenium(II) 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 successively under an atmosphere of air at 140 °C for 12 h. The crude product was isolated by chromatography on a preparative silica gel plate with the selected eluent or developing solvent of petroleum ether and ethyl acetate in a volume ratio of 20:1 to give product 4,4'-bis(2-bromophenyl)-2,2'-dimethyl-5,5'-oxazolyl (1c) in 53% yield.

[0075] Example 3: Preparation of compound: 1 H NMR (CDC13, 400 MHz) δ 7.34 (d, J = 7.6 Hz, 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 be one-to-one corresponding to the target product, and the number is reasonable. Carbon spectrum: 13 C NMR (100 MHz, CDC13) δ 161.5, 137.9, 137.4, 132.8, 132.2, 131.3, 129.6, 127.0, 122.9, 14.0. The molecular carbon spectrum peaks can be one-to-one corresponding to the target product, and the number is reasonable. According to the results of the above nuclear magnetic hydrogen spectrum and carbon spectrum data, it can be known that the product prepared in Example 3 is 4,4'-bis(2-bromophenyl)-2,2'-dimethyl-5,5'-oxazolyl (1c).

[0076] The chemical transformation in this example can quickly construct polysubstituted 5,5'-oxazolyl molecules, and the easily transformed halogen functional group bromine atom, thereby providing a platform for the construction of more complex molecules.

[0077] Example 4: 2,2'-dimethyl-4,4'-diphenyl-5,5'-oxazolyl (1d)

[0078]

[0079] Into a 15 mL Schlenk tube, N-(1-phenylvinyl)acetamide 2d (16.1 mg, 0.10 mmol), pentamethylcyclopentadiene diiridium 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 successively under an atmosphere of air at 140 °C for 12 h. The crude product was separated by chromatography on a preparative silica gel plate with the selected eluent or solvent system petroleum ether: ethyl acetate 20:1 to give product 2,2'-dimethyl-4,4'-diphenyl-5,5'-bi oxazole (1d) in 68% yield.

[0080] NMR of the compound prepared in example 4: 1 H NMR (CDC13, 400 MHz) δ 7.57-7.54 (m, 4H), 7.23-7.22 (m, 6H), 2.58 (s, 6H). The molecular hydrogen spectrum peaks can be one-to-one corresponding to the target product, and the number is reasonable. NMR of carbon: 13 C NMR (100 MHz, CDC13) δ 162.4, 140.1, 133.9, 130.5, 129.1, 128.4, 126.6, 14.1. The molecular carbon spectrum peaks can be one-to-one corresponding to the target product, and the number is reasonable. The results of the above NMR hydrogen spectrum, carbon spectrum data show that the product prepared in example 4 is 2,2'-dimethyl-4,4'-diphenyl-5,5'-bi oxazole (1d).

[0081] The chemical transformation in this example can quickly build multisubstituted 5,5'-bi oxazole 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'-bi oxazole (1e)

[0083]

[0084] Into a 15 mL Schlenk tube, 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 successively under an atmosphere of air at 140 °C for 12 h. The crude product was isolated by chromatography on a preparative silica gel plate with the selected eluent or developing solvent of petroleum ether and ethyl acetate in a volume ratio of 20:1 to give the product 2,2'-dimethyl-4,4'-di-p-tolyl-5,5'-bi-oxazole (1e) in 58% yield.

[0085] NMR of the compound prepared in Example 5: 1 H NMR (CDC13, 400 MHz) δ 7.49 (d, J = 8.8 Hz, 4H), 6.76 (d, J = 8.8 Hz, 4H), 3.76 (s, 6H), 2.56 (s, 6H). The molecular hydrogen spectrum peaks can be one-to-one corresponding to the target product, and the number is reasonable. NMR of carbon: 13 C NMR (100 MHz, CDC13) δ 162.2, 159.7, 139.7, 133.0, 128.0, 123.2, 113.8, 55.2, 14.1. The molecular carbon spectrum peaks can be one-to-one corresponding to the target product, and the number is reasonable. Based on the results of the above NMR hydrogen spectrum and carbon spectrum data, it can be known that the product prepared in Example 5 is 2,2'-dimethyl-4,4'-di-p-tolyl-5,5'-bi-oxazole (1e).

[0086] The chemical transformation in this example can quickly construct polysubstituted 5,5'-bi-oxazole 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'-dinaphthalen-2-yl-5,5'-bi-oxazole (1f)

[0088]

[0089] Into a 15 mL Schlenk tube, N-(1-naphthalen-2-yl)vinylacetamide 2f (21.1 mg, 0.10 mmol), pentamethylcyclopentadiene diiridium 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 successively under air atmosphere. The reaction was carried out at 140 °C for 12 h. The crude product was isolated by chromatography on a preparative silica gel plate with the selected eluent or solvent system petroleum ether: ethyl acetate 20: 1 to give product 2,2'-dimethyl-4,4'-dinaphthalen-2-yl-5,5'-oxazolylidene (1f) in 58% yield.

[0090] NMR of the compound prepared in example 6 1 H NMR (CDC13, 400 MHz) δ 8.20 (d, J = 2.4 Hz, 1H), 7.57 (dd, J = 2.4 Hz, 8.8 Hz, 1H), 7.49 - 7.45 (m, 2H), 7.36 - 7.32 (m, 2H), 6.69 (d, J = 8.8 Hz, 1H), 3.92 (s, 3H), 2.58 (s, 3H). The molecular hydrogen spectrum peaks can be one-to-one corresponding to the target product, and the number is reasonable. Carbon spectrum: 13 CNMR (100 MHz, CDC13) δ 169.1, 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 be one-to-one corresponding to the target product, and the number is reasonable. According to the results of the above nuclear magnetic hydrogen spectrum and carbon spectrum data, it can be known that the product prepared in example 6 is 2,2'-dimethyl-4,4'-dinaphthalen-2-yl-5,5'-oxazolylidene (1f).

[0091] The chemical transformation in this example can quickly construct polysubstituted 5,5'-oxazolyl 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'-oxazolyl]-4,4'-diphenyl bis(4,1-phenylene) bis(N,N- dipropylsulfonamidyl)benzoate (1g)

[0093]

[0094] Into a 15 mL Schlenk tube, 4-(1-acetylamino vinyl)phenyl 4-(N,N- dipropylsulfamoyl)benzoate 2g (44.4 mg, 0.10 mmol), 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), toluene (Tol, 1.0 mL) were added successively under air atmosphere, and reacted at 140 °C for 12 h. The crude product was separated by chromatography on a preparative silica gel plate with the selected eluent or solvent system petroleum ether: ethyl acetate 20:1 to give the product 2,2'-dimethyl[5,5'-bi oxazol]-4,4'-diphenyl bis(4,1-phenylene) bis(N,N-dipropylsulfonamidyl)benzoate (1g) in 51% yield.

[0095] NMR of the compound prepared in example 7: 1 H NMR (CDC13, 400 MHz) δ 8.32 (d, J = 8.4 Hz, 4H), 8.07 (d, J = 8.8 Hz, 4H), 7.96 (d, J = 8.4 Hz, 4H), 7.34 (d, J = 8.8 Hz, 4H), 3.14 (t, J = 8.0 Hz, 8H), 2.63 (s, 6H), 1.60-1.55 (m, 8H), 0.89 (t, J = 7.2 Hz, 12H). The molecular hydrogen spectrum peaks can be one-to-one corresponding to the target product, and the number is reasonable. NMR of carbon: 13 C NMR (100 MHz, CDC13) δ 166.7, 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 be one-to-one corresponding to the target product, and the number is reasonable. According to the results of the above nuclear magnetic hydrogen spectrum and carbon spectrum data, it can be known that the product prepared in example 7 is 2,2'-dimethyl[5,5'-bi oxazol]-4,4'-diphenyl bis(4,1-phenylene) bis(N,N-dipropylsulfonamidyl)benzoate (1g).

[0096] The chemical transformation in this example uses the drug star molecule probenecid as the raw material to quickly construct a polysubstituted 5,5'-bi oxazole compound, which can realize the transformation of the drug molecule.

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

[0098]

[0099] Into a 15 mL Schlenk tube, N-(1-(4-(9,9-dimethylacridin-10(9H)-yl)phenyl)vinyl)acetamide 2h (36.8 mg, 0.10 mmol), pentamethylcyclopentadiene diiridium 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), toluene (Tol, 1.0 mL) were added successively under air atmosphere. The reaction was carried out at 140 °C for 12 h. The crude product was isolated by chromatography on a preparative silica gel plate with the selected eluent or developing solvent of petroleum ether and ethyl acetate in the volume ratio of 20:1 to give product 4,4'-bis(4-(9,9-dimethylacridin-10(9H)-yl)phenyl)-2,2'-dimethyl-5,5'-bi- oxazole (1h) in 66% yield.

[0100] The nuclear magnetic hydrogen spectrum, carbon spectrum, fluorine profile of the compound prepared in Example 8 are shown in Figure 1 、 Figure 2 It can be seen from Figure 1 that: 1 HNMR (400 MHz, CDC13) δ 7.89 (d, J = 8.4 Hz, 4H), 7.46-7.40 (m, 4H), 7.32 (d, J = 8.4 Hz, 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 peak can correspond to the target product one by one, and the number is reasonable. It can be seen from Figure 2 that: 13 C NMR (100 MHz, CDC13) δ 162.8, 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 peak can correspond to the target product one by one, and the number is reasonable. In combination with the results of the above nuclear magnetic hydrogen spectrum and carbon spectrum data, it can be known that the product prepared in Example 8 is 4,4'-bis(4-(9,9-dimethylacridin-10(9H)-yl)phenyl)-2,2'-dimethyl-5,5'-bi-oxazole (1h).

[0101] 2, Application Example 1

[0102] The molecule 1h was tested to be dissolved in dichloromethane (1.0 x 10 -5 mol L -1The ultraviolet / visible absorption spectrum (UV) and photoluminescence (PL) emission spectrum ( ) Figure 3 Maximum absorption wavelength (λ) max The phenomenon appears at 287nm, which originates from the π→π transition of the conjugated double bond. * Transition; photoluminescence spectrum was obtained by excitation at the maximum absorption wavelength. Blue PL emission at 509 nm was observed in dichloromethane after 1 h. 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), and toluene (Tol). The molecule exhibits certain interactions with the solvent, causing varying degrees of red-shift or blue-shift in its fluorescence emission in different solvents. Subsequently, in toluene solvent (1.0 × 10⁻⁶), -5 mol L -1 The fluorescence quantum yield (QY) tested after 1 hour was 83.14%. Figure 5 This indicates that 1h has promising applications in luminescent materials.

[0103] This application describes a method for synthesizing fully substituted 5,5'-bioxazole compounds through multiple dehydrogenation and 1,1-bifunctionalization of olefins under inert solvent conditions, facilitated by a metal catalyst and a silver salt oxidant. Specifically, N-(1-arylvinyl)amide is used as an readily available and easily convertible starting material, with the amide serving as a weakly coordinating, traceless directing group to achieve the C( sp 2 The amide undergoes 5,5'-H activation, followed by enol tautomerism and intramolecular oxidative cyclization, thereby constructing carbon-carbon and carbon-heterocyclic bonds to obtain a fully substituted 5,5'-bioxazole compound. This method is highly atom-economical (the product is obtained through cross-dehydrogenation coupling, which removes 4 CH bonds and 2 NH bonds) and step-economical (no prior halogenation or metallization of the starting material is required). It has a wide range of substrates, and readily available N-(1-arylvinyl)amides can be used as reaction substrates while also acting as traceless directing groups in the construction of nitrogen-containing fused heterocycles.

[0104] In summary, this application reports the first simplified construction of a fully substituted 5,5'-bioxazole framework using a transition metal-catalyzed multiple dehydrogenation cyclization strategy. This transformation exhibits a wide substrate applicability and strong functional group tolerance. The applicant has also achieved modification of drug molecules such as probenecid. Furthermore, we conducted fluorescence tests on the obtained 5,5'-bioxazole molecule, achieving a fluorescence quantum yield of 83.14%, demonstrating the significant application potential of this novel framework in luminescent materials.

[0105] In the description of the specification, reference to "one embodiment", "some embodiments", "an exemplary embodiment", "an example", "a specific example", or "some examples" means that a particular feature, structure, material, or characteristic being described is included in at least one embodiment or example of the application. The appearances of the phrases "in one embodiment", "in some embodiments", "in an exemplary embodiment", "an example", "a specific example", or "some examples" in various places in the specification are not necessarily referring to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics can be combined in any suitable manner in one or more embodiments or examples.

[0106] Although several embodiments of the application have been shown and described, it is understood that changes, modifications, substitutions and alterations can be made to these embodiments without departing from the spirit and scope of the application, which 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, as shown in Formula II N The -(1-arylvinyl)amide compound is converted into the fully substituted 5,5'-bioxazole compound of Formula I via multiple dehydrogenation processes, as shown in the following reaction equation: ； Where Ar is an ortho, meta, or para monosubstituted aryl group, and R is an alkyl or phenyl group; The metal catalyst is selected from any one of: pentamethylcyclopentadienyl rhodium chloride dimer, pentamethylcyclopentadienyl iridium chloride dimer, palladium acetate, and dichloro(p-methylisopropylphenyl)ruthenium dimer; The halide ion grabber is selected from any one of: silver hexafluoroantimonate and silver bis(trifluoromethanesulfonyl)imide. The oxidizing agent is selected from any one of: silver acetate, silver carbonate, silver oxide, copper acetate, and potassium persulfate; The additive is selected from either lithium acetate or lithium carbonate.

2. The method for preparing the 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 the fully substituted 5,5'-bioxazole compound according to claim 1, characterized in that: The amount of the metal catalyst is as shown in Formula II. N -2 mol% of the (1-arylvinyl)amide compound.

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

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

6. The application of the fully substituted 5,5'-bioxazole compound prepared by the method of claim 1 in luminescent materials, wherein the structural formula of the fully substituted 5,5'-bioxazole compound is as follows: 。

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