Preparation method of 1, 2-benzisoxazole

Abstract

The invention provides a preparation method of a 1, 2-benzisoxazole derivative. According to the preparation method, a method for generating 1, 2-benzisoxazole by taking N-phenoxy amide as a substrate and alkyne halide as a coupling reagent under the catalysis of rhodium (III) by utilizing a C-H activation strategy is developed for the first time. The method comprises the following steps: under the condition of an inert solvent, under the combined action of a transition metal catalyst and an oxidizing agent, firstly carrying out ortho-position carbon-hydrogen bond alkynylation on alkyne halide under the guiding action of N-phenoxy amide, and then carrying out intramolecular amine metallization on alkyne carbon-carbon triple bonds by N-phenoxy amide; and finally, deacylating under the action of alkali, and eliminating beta-OH to generate the 1, 2-benzisoxazole derivative with multiple functional groups. At present, synthesis of 1, 2-benzisoxazole derivatives is still challenged (multi-step synthesis, poor functional group compatibility and the like) due to lack of synthesis means and limitation of specific substrates in synthesis of 1, 2-benzisoxazole derivatives, and the reaction is expected to provide a new thought for development and application of the 1, 2-benzisoxazole derivatives. It needs to be pointed out that the obtained product can also be applied to a perovskite solar cell hole transport material, that is, a triphenylamine group with excellent hole transport capacity and a benzoxazole group capable of being used as an electron acceptor form a donor-acceptor structure, and the power conversion efficiency of the molecule is 16.01%.

Description

Technical Field

[0001] The present application relates to the technical field of organic compound synthesis, and more specifically, to a method for preparing 1,2-benzisoxazole. Background Art

[0002] Benzisoxazole is a class of benzoheterocyclic compounds containing adjacent oxygen atoms and nitrogen atoms, which have high biological activity and pharmaceutical properties. Heterocycles containing benzisoxazole skeletons and their derivatives are widely present in drug molecules. The molecular skeleton formed by the benzisoxazole template has multifunctional binding properties with frequently occurring binding motifs, providing effective selective ligands for a series of different biological targets in medicinal chemistry. Benzisoxazole scaffolds and their analogs are important drug carriers, and biologically active compounds have been found in many different therapeutic areas, such as anti-HIV, antibacterial, antipsychotic, anti-inflammatory, analgesic, dopamine and 5-hydroxytryptamine receptors, anticonvulsant, acetylcholinesterase, anticancer, antioxidant, antidiabetic drugs, etc. (Med.Chem.Commun., 2017, 8, 2023-2039.).

[0003] However, most applications of benzisoxazole still use the 2,1-benzisoxazole skeleton, and its isomer 1,2-benzisoxazole is difficult to obtain multi-functional 1,2-benzisoxazole due to the lack of synthetic methods and limited reaction conditions. Therefore, research and development of low-cost and simple 1,2-benzisoxazole preparation methods have good application prospects.

[0004] Application Contents

[0005] In order to overcome at least one problem of the above-mentioned prior art, the present application provides a method for preparing 1,2-benzisoxazole. The method is simple and low-cost, has a high yield, and is environmentally friendly.

[0006] In order to solve the above technical problems, the technical solution adopted in this application is:

[0007] A method for preparing 1,2-benzisoxazole comprises the following steps: in an inert solvent, under the combined action of a transition metal catalyst and an oxidant, an acetylene halide represented by formula III reacts with an N-phenoxyamide represented by formula II; finally, under the action of a base, a 1,2-benzisoxazole derivative represented by formula I is generated, and the reaction equation is as follows:

[0008]

[0009] Where R is a variety of substituents, R 1 , R 2 is H or alkyl or aryl.

[0010] The present application also provides a solar cell, which is a perovskite solar cell, and the hole transport material in the perovskite solar cell adopts the 1,2-benzisoxazole compound prepared by the above preparation method.

[0011] Compared with the prior art, this application has the following beneficial effects:

[0012] The substrates used in this paper are derived from phenol / boron reagents and ketones, and these three functional groups are widely present in natural products. In the study of carbon-hydrogen bond activation by N-phenoxyamide, there are few reports on the nucleophilicity of the N center as a reaction mode. This paper enriches the method of using this directing group to construct a heterocyclic molecule library. The synthesis of the product of this reaction, 1,2-benzisoxazole, still faces the following challenges: the traditional synthesis method starts from salicylaldehyde oxime, and such a specific substrate will lead to product limitations, but the raw materials in this paper are derived from phenol, and the substrate range is wide. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 This is the hydrogen nuclear magnetic resonance spectrum of compound 1a prepared in Example 1 of the present application.

[0014] Figure 2 This is the carbon nuclear magnetic resonance spectrum of compound 1a prepared in Example 1 of the present application.

[0015] Figure 3 This is the hydrogen nuclear magnetic resonance spectrum of compound 1b prepared in Example 2 of the present application.

[0016] Figure 4 This is the carbon nuclear magnetic resonance spectrum of compound 1b prepared in Example 2 of the present application.

[0017] Figure 5 This is the hydrogen nuclear magnetic resonance spectrum of compound 1c prepared in Example 3 of the present application.

[0018] Figure 6 This is the carbon nuclear magnetic resonance spectrum of compound 1c prepared in Example 3 of the present application.

[0019] Figure 7 This is the hydrogen nuclear magnetic resonance spectrum of compound 1d prepared in Example 4 of the present application.

[0020] Figure 8 This is the carbon nuclear magnetic resonance spectrum of compound 1d prepared in Example 4 of the present application.

[0021] Fig. 9 This is the hydrogen nuclear magnetic resonance spectrum of compound 1e prepared in Example 5 of the present application.

[0022] Fig.10 This is the carbon nuclear magnetic resonance spectrum of compound 1e prepared in Example 5 of the present application.

[0023] Fig.11 This is the hydrogen nuclear magnetic resonance spectrum of compound 1f prepared in Example 6 of the present application.

[0024] Fig.12 This is the carbon nuclear magnetic resonance spectrum of compound 1f prepared in Example 6 of the present application.

[0025] Fig.13 This is the hydrogen nuclear magnetic resonance spectrum of compound 1g prepared in Example 7 of the present application.

[0026] Fig.14 This is the carbon nuclear magnetic resonance spectrum of compound 1g prepared in Example 7 of the present application.

[0027] Fig.15 This is the hydrogen nuclear magnetic resonance spectrum of compound 1h prepared in Example 8 of the present application.

[0028] Fig.16 This is the carbon nuclear magnetic resonance spectrum of compound 1h prepared in Example 8 of the present application.

[0029] Fig.17 This is the hydrogen nuclear magnetic resonance spectrum of compound 1i prepared in Example 9 of the present application.

[0030] Fig.18 This is the carbon NMR spectrum of compound 1i prepared in Example 9 of the present application.

[0031] Fig.19 This is the hydrogen nuclear magnetic resonance spectrum of compound 1j prepared in Example 10 of the present application.

[0032] Fig. 20 This is the carbon NMR spectrum of compound 1j prepared in Example 10 of the present application.

[0033] Fig.21 This is the CV chart of compound 1h prepared in Example 8 of the present application.

[0034] Fig. 22 This is the UV-PL image of compound 1h prepared in Example 8 of the present application.

[0035] Fig.23 This is the corresponding JV test curve diagram when the compound 1h prepared in Example 8 is used as a hole transport material for perovskite solar cells. DETAILED DESCRIPTION

[0036] 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.

[0037] It should be noted that:

[0038] 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.

[0039] The applicant has found in the research that 1,2-benzisoxazole derivatives in the prior art have been widely used in the medical field. The following are four drug molecules containing a 1,2-benzisoxazole skeleton: antipsychotic drugs risperidone and paliperidone, MAO-A inhibitor RS-1636, and anti-epileptic drug zonisamide.

[0040]

[0041] At the same time, the applicant has found that there are several synthesis methods for 1,2-benzisoxazole, which can be expressed as follows:

[0042]

[0043] The synthesis method of 1,2-benzisoxazole is specifically described as follows:

[0044] 1) Based on the intramolecular dehydration condensation reaction of salicylaldehyde oxime and o-hydroxyphenyl ketone oxime:

[0045] In 1977, Uttam et al. used salicylaldehyde oxime as a substrate and treated it with dry pyridine and thionyl chloride in anhydrous ether at 0°C to obtain the corresponding 1,2-benzisoxazole (Aust. J. Chem., 1977, 30, 1847-1848). Due to the limitation of the source of salicylaldehyde, the range of synthesized 1,2-benzisoxazole products was relatively narrow.

[0046] Merck et al. used trichloroacetyl isocyanate and salicylaldehyde oxime to synthesize 1,2-benzisoxazole in 1983. However, the reaction was limited by high cost (trichloroacetyl isocyanate was expensive) and specific substrates, which resulted in a limited range of synthesized 1,2-benzisoxazole products. (J. Org. Chem., 1983, 48, 2613-2615.);

[0047] In 1997, Guillaume used salicylaldehyde oxime as a raw material to synthesize 1,2-benzisoxazole through intramolecular Mitsunobu reaction. This reaction also faced the problem of limited range of 1,2-benzisoxazole products. (Synth. Commun. 1997, 27, 3839-3846.);

[0048] 2) Cyclization reaction involving transition metals:

[0049] In 2014, Zhao reported that palladium-catalyzed N-phenoxyacetamide reacted with aldehydes to form 1,2-benzisoxazole via an intermolecular [4+1] cyclization pathway (Chem. Sci., 2014, 5, 1574-1578). 1 The functional groups are only compatible with (-CH3, -F, -Cl, -Br, -OMe) and it is impossible to obtain multifunctionalized 1,2-benzisoxazole products with an unsaturated double bond at the third position.

[0050] In 2015, Phongprapan used aromatic aldehydes and aromatic ketones as substrates. Aldehydes or ketones were activated by Lewis acids and underwent nucleophilic addition and elimination pathways with azides to generate imine diazonium ion intermediates. Interestingly, in the case of substrates containing ortho-hydroxyl groups, ON bonds were formed through nucleophilic substitution to obtain 1,2-benzisoxazole as a byproduct. The problems faced by this reaction are: 1,2-benzisoxazole is a byproduct, and the reaction conditions are difficult to optimize, resulting in low yields and a very limited substrate range (J.Org.Chem.2015,80,8657-8667.).

[0051] In summary, the synthesis of 1,2-benzisoxazole faces the limitation of using high-cost isocyanates or specific substrates, which also leads to its limited practical application value. Therefore, research and development of low-cost and simple preparation methods of 1,2-benzisoxazole has good application prospects.

[0052] Based on the research interests in weakly coordinated carbon-hydrogen bond alkynylation, we have achieved Csp promoted by weakly coordinated and easily convertible functional groups such as esters, ketones, sulfonamides, amides, alcohols, and amine derivatives. 2 -H and Csp 3-H alkynylation reaction (Angew.Chem.Int.Ed.2014,53,14485-144895.Org.Chem.Front.,2021,8,6484-6490.(Front Cover);Chem.Commun.,2020,56,11255-11258.Chin.J.Chem.,2020,38,929-934.Org.Chem.Front.,2019,6,284-289.(Front Cover,Hot Paper);J.Org.Chem.,2017,82,13003-13011.) provides a new idea for the simple synthesis of multi-functionalized alkynes.

[0053] On the other hand, as a readily available multifunctional synthon, acetylene halides have provided a simple route for the highly selective synthesis of various functional molecules in transition metal catalysis in recent years. The applicant summarizes the various reaction modes of acetylene halides here: first, under alkaline conditions, acetylene halides break the CX bond to obtain acetylene anions through the exchange of metal-halogen atoms; second, acetylene halides react with nucleophiles as electrophilic acetylene reagents; third, acetylene halides dissociate halogen cations under the action of organic lithium reagents to react as electrophilic halogenating reagents. Fourth, acetylene halides react as both electrophilic halogenating reagents and nucleophilic acetylene reagents. In general, further development of more reactivity of acetylene halides is still highly anticipated.

[0054] Based on a new type of alkyne halide reagent developed by the research group (Org. Lett. 2024, 26, 2186-2191.), this paper broadens the types of alkyne halides. Alkyl halides are versatile synthetic compounds that concisely deliver complex skeletons in a selective manner. However, in order to achieve reactivity, in order to avoid the potential over-coordination of the CH alkylation product with the metal catalyst, sterically hindered silicon-substituted haloalkyl groups are usually required. In addition, side reactions including isomerization of aliphatic halides hinder further applications. It is worth noting that although their synthetic applications have not been fully explored, the α-alcohol aliphatic halide alkyls in this paper are potential bifunctional reagents that contain electrophilic halides, multifunctional alkyne functional groups, and alcohols also serve as traceless directing groups in the reaction.

[0055] Directing group-directed transition metal-catalyzed carbon-hydrogen bond activation has become one of the most direct and effective strategies for the direct functionalization of inert carbon-hydrogen bonds because it can construct carbon-carbon bonds or carbon-heteroatom bonds under mild reaction conditions. It is widely used in many fields such as material chemistry and drug synthesis. The role of directing groups is not only to guide and activate ortho-carbon-hydrogen bonds; it is also usually used for further condensation reactions in situ to produce compounds with diverse structures. In recent years, oxyamides have attracted widespread attention from researchers because of their uniqueness as directing groups for carbon-hydrogen bond activation. The uniqueness of N-phenoxyamide directing groups is reflected in their multiple reaction modes, which greatly promotes the construction of complex molecular libraries. The following reaction modes have been developed for the carbon-hydrogen bond activation of N-phenoxyamide: (1) Internal oxidation of NO bond cleavage: No external oxidant is required in the reaction because the ON bond in the substrate N-phenoloxyacetamide is broken, which acts as an internal oxidant. To date, various olefin and alkyne derivatives have been used as coupling partners (CPs) to generate functionalized phenol derivatives. (2) O in phenol derivatives acts as a nucleophile to generate benzofuran structures: This type of reaction provides an efficient and regioselective route for the synthesis of benzofuran derivatives with good functional group compatibility and high yield. (3) External oxidation, retaining the NO bond to generate nitrogen heterocycles: In 2014, Zhao's group (Chem. Commun. 2014, 50, 12135-12138.) reported the rhodium-catalyzed reaction of N-phenoxyacetamide with α,β-unsaturated aldehydes to synthesize 1,2-oxazacycloheptane compounds through carbon-hydrogen bond activation / [4+3] cyclization. Since the NO bond energy is small and easy to break, it is still a great challenge to use suitable coupling reagents and catalytic systems to achieve this reaction mode.

[0056] In summary, based on N-phenoxyamide substrates, carbon-hydrogen bond activation has been established based on rhodium, iridium, ruthenium, palladium, cobalt and non-metal catalytic systems, using olefins, alkynes, diazo and other compounds as reaction substrates to construct CC, CN and CS bonds through unique regio- and stereo-selectivity under mild reaction conditions. There are still many challenging problems to be solved:

[0057] 1) How to successfully use cheap metals to activate the carbon-hydrogen bonds of N-phenoxyamides remains a future development direction;

[0058] 2) How to achieve the construction of CX (F, Cl, Br, I, etc.) bonds using mild reaction conditions;

[0059] 3) How to utilize the rapidly developing electrochemical oxidation and photocatalytic oxidation to develop greener and safer oxidation conditions to replace silver oxidants.

[0060] The present application provides a method for generating 1,2-benzisoxazole using N-phenoxyacetamide as a guide and acetylene halide as a coupling reagent under the catalysis of rhodium:

[0061]

[0062] This reaction has the following advantages: (1) The substrates used in this paper are derived from phenol / boron reagents and ketones, and these three functional groups are widely present in natural products. (2) In the study of carbon-hydrogen bond activation by N-phenoxyamide, there are few reports on the nucleophilicity of the N center as a reaction mode. This paper enriches the method of using this directing group to construct a heterocyclic molecular library. (3) The synthesis of the product 1,2-benzisoxazole of this reaction still faces the following challenges: the traditional synthesis method starts from salicylaldehyde oxime, and such a specific substrate will lead to product limitation, but the raw material of this paper is derived from phenol, and the substrate range is wide. (4) This reaction obtains a multifunctional 1,2-benzisoxazole product, and the introduced olefins can be further transformed such as olefin metathesis reaction, olefin hydroboration reaction, Heck reaction, etc., providing a means for constructing a complex molecular library. (5) Through CV, PL, and UV testing, the real energy levels of the molecule were obtained, with HOMO of -4.89eV and LUMO of -1.21eV. It is suitable for application as a perovskite solar cell.

[0063] The present application provides a method for preparing 1,2-benzisoxazole, wherein under the conditions of an inert solvent, under the joint action of a transition metal catalyst and an oxidant, an acetylene halide shown in formula III reacts with an N-phenoxyamide shown in formula II; finally, under the action of a base, a 1,2-benzisoxazole derivative shown in formula I is generated, and the reaction equation is as follows:

[0064]

[0065] Where R is a variety of substituents, R 1 , R 2 is H or alkyl or aryl.

[0066] The preparation method of 1,2-benzisoxazole provided in the present application comprises the following steps: under the conditions of an inert solvent, under the joint action of a transition metal catalyst and an oxidant, the acetylene halide first undergoes acetylation of the ortho-carbon-hydrogen bond under the guidance of N-phenoxyamide, and then N-phenoxyamide performs intramolecular amine metalation on the alkyne carbon-carbon triple bond; finally, under the action of a base, deacylation and β-OH elimination are carried out to generate multifunctional 1,2-benzisoxazole derivatives. Nowadays, the synthesis of 1,2-benzisoxazole and its derivatives still face challenges due to the limitation of specific substrates. This reaction is expected to provide new ideas for the development and application of 1,2-benzisoxazole derivatives. In the preparation method of the present application, the possible reaction mechanism flow chart is as follows:

[0067]

[0068] Specific mechanism: Under the guidance of N-phenoxyamide, the acetylenic halide first undergoes ortho-carbon-hydrogen bond alkynylation, and then N-phenoxyamide undergoes intramolecular amine metallation of the alkyne carbon-carbon triple bond; finally, under the action of base, deacylation and β-OH elimination are carried out to generate multifunctional 1,2-benzisoxazole derivatives.

[0069] In some preferred embodiments, the amount of the transition metal catalyst used is 2 mol% of the amount of the N-phenoxyamide compound represented by Formula II.

[0070] In some preferred embodiments, the catalyst is any one of pentamethylcyclopentadienyl rhodium chloride dimer, pentamethylcyclopentadienyl iridium chloride dimer, palladium acetate, dichloro(p-methylisopropylphenyl)ruthenium dimer, cobalt acetylacetonate, pentacarbonyl manganese bromide or a combination thereof.

[0071] In some preferred embodiments, the oxidant is any one or more of silver acetate, silver carbonate, silver oxide, and potassium persulfate.

[0072] In some preferred embodiments, the additive is any one of silver hexafluoroantimonate, silver bis(trifluoromethanesulfonyl)imide, sodium bicarbonate, lithium acetate, lithium carbonate and dipotassium hydrogen phosphate, or a combination thereof.

[0073] In some more preferred embodiments, the inert solvent is any one or more of 1,2-dichloroethane, toluene, tetrahydrofuran, 1,4-dioxane, ethylene glycol dimethyl ether, N,N'-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, acetonitrile, and ethanol.

[0074] In some preferred embodiments, the reaction is carried out at 60-100° C.; the reaction is carried out for 0.5 hour.

[0075] In some preferred embodiments, the method for preparing 1,2-benzisoxazole is characterized by comprising the following specific steps:

[0076] S1. In a reactor, 16.5 mg of N-(o-tolyloxy)acetamide, 24.2 mg of 1-bromo-2-methylbut-2-yn-2-ol, 1.2 mg of pentamethylcyclopentadiene rhodium dichloride dimer, 1.9 mg of silver trifluoromethanesulfonimide, 14.8 mg of lithium carbonate, 33.4 mg of silver acetate, and 1.0 mL of 1,2-dichloroethane were added in sequence in air;

[0077] S2. The reaction solution is reacted at 100°C for 0.5-2 hours;

[0078] S3. After the reaction is completed, the above mixture is separated by column chromatography to obtain the target compound.

[0079] In some preferred embodiments, the developing solvent or eluent selected in the column chromatography separation technology is petroleum ether and ethyl acetate, and the usage ratio of petroleum ether:ethyl acetate is 40:1.

[0080] The present application also provides a solar cell, which is a perovskite solar cell, and the hole transport material in the perovskite solar cell adopts the 1,2-benzisoxazole compound prepared by the above preparation method.

[0081] Next, the preparation method of 1,2-benzisoxazole of the present application is described in detail with specific examples.

[0082] Preparation Example 1 Preparation of 3-(cyclohexylmethoxy)-7-methylbenzo[d]isoxazole (1a)

[0083] Under an atmospheric pressure air atmosphere, N-(o-tolyloxy)acetamide 2a (16.5 mg, 0.10 mmol), 1-(bromoethynyl)cyclohexane-1-ol 3a (30.1 mg, 0.15 mmol), pentamethylcyclopentadiene rhodium dichloride dimer [Cp*RhCl2]2 (1.2 mg, 0.002 mmol), silver trifluoromethanesulfonimide (1.9 mg, 0.005 mmol), lithium carbonate (14.8 mg, 0.20 mmol), silver oxide (46.2 mg, 0.20 mmol), 1,2-dichloroethane (DCE, 1.0 mL) were added to a 15 mL Schlenk tube in sequence and reacted at 100 ° C for 0.5 hours. The crude product was separated by chromatography on a prepared silica gel plate, and the selected developing solvent or eluent was petroleum ether (PE): ethyl acetate (EA) = 40:1, and the product 3-(cyclohexylmethene)-7-methylbenzo[d]isoxazole (1a) was obtained with a yield of 99%. The chemical reaction equation corresponding to this example is as follows:

[0084]

[0085] The H NMR spectrum and C NMR spectrum of the compound prepared in Example 1 are as follows: Figure 1 and Figure 2 As shown. Figure 1 It can be seen that: 1H NMR (400MHz,CDCl3)δ7.46(d,J=7.6Hz,1H),7.30(d,J=7.2Hz,1H),7.19(t,J=7.6Hz,1H),6.21(s,1H),2.79-2.68(m,2H),2.57(s,3H),2.41-2.38(m,2H),1.73-1.71(m,2H),1.65-1.62(m,4H). 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) δ162.0, 155.5, 153.9, 130.0, 123.5, 122.1, 120.6, 118.8, 107.2, 37.9, 31.6, 28.7, 27.9, 26.4, 15.3. 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, it can be seen that the product prepared in Example 1 is 3-(cyclohexyl methylene)-7-methylbenzo[d]isoxazole (1a).

[0086] The N-(o-tolyloxy)acetamide 2a in this embodiment contains an amide functional group that is ubiquitous in human production and life. Under the promotion of the amide functional group, the aromatic ring carbon-hydrogen bond is activated, intramolecular cyclization, deacylation, and finally the β-OH of the acetylene halide 1-(bromoethynyl)cyclohexane-1-ol 3a is eliminated to generate 3-(cyclohexylmethene)-7-methylbenzo[d]isoxazole. The reaction in this embodiment only needs to be carried out at 100° C. for half an hour under atmospheric pressure air atmosphere, and then a simple subsequent treatment is performed to obtain the final target product 3-(cyclohexylmethene)-7-methylbenzo[d]isoxazole (1a) with an excellent yield (99%).

[0087] The chemical transformation in this example can generate 1,2-benzisoxazole derivatives efficiently and quickly.

[0088] Example 2 Preparation of 3-(((1r, 3r, 5R, 7S)-adamantan-2-ylidene)-methyl)-5-bromobenzo[d]isoxazole (1b)

[0089] Under an atmospheric pressure air atmosphere, N-(4-bromophenoxy)acetamide 2b (23.0 mg, 0.10 mmol), (1R, 3R)-2-(bromoethynyl)polyoxazine-2-ol 3b (39.7 mg, 0.15 mmol), pentamethylcyclopentadiene rhodium dichloride dimer [Cp*RhCl2]2 (1.2 mg, 0.002 mmol), silver trifluoromethanesulfonimide (1.9 mg, 0.005 mmol), lithium carbonate (14.8 mg, 0.20 mmol), silver acetate (33.4 mg, 0.20 mmol), 1,2-dichloroethane (DCE, 1.0 mL) were added to a 15 mL Schlenk tube in sequence and reacted at 100 ° C for half an hour. The crude product was separated by chromatography using the prepared silica gel plate, and the selected developing solvent or eluent was petroleum ether (PE): ethyl acetate (EA) = 40:1, and the product 3-(((1r, 3r, 5R, 7S)-adamantan-2-ylidene)-methyl)-5-bromobenzo[d]isoxazole (1b) was obtained with a yield of 82%. The chemical reaction equation corresponding to this example is as follows:

[0090]

[0091] The H-NMR and C-NMR spectra of the compound prepared in Example 2 are as follows: Figure 3 and Figure 4 As shown. Figure 3 It can be seen that: 1 H NMR (400MHz,CDCl3)δ7.80(d,J=1.6Hz,1H),7.61(dd,J=8.8,1.6Hz,1H),7.44(d,J=8.8Hz,1H),6.10(s,1H),3.62(s,1H),2.68(s,1H),2.04-1.87(m,12H). The molecular hydrogen spectrum peaks can correspond to the target product one by one, and the quantity is reasonable. Figure 4 It can be seen that: 13 C NMR (100MHz, CDCl3) δ163.6, 161.5, 154.7, 132.6, 124.8, 124.1, 116.1, 111.3, 101.3, 41.5, 40.2, 39.3, 37.1, 34.8, 28.2. 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, it can be seen that the product prepared in Example 2 is 3-(((1r, 3r, 5R, 7S)-adamantan-2-ylidene)-methyl)-5-bromobenzo[d]isoxazole (1b).

[0092] The N-(4-bromophenoxy)acetamide 2b in this example contains an amide functional group that is ubiquitous in human production and life. Under the promotion of the amide functional group, the aromatic ring carbon-hydrogen bond is activated, intramolecular cyclization is carried out, and deacylation is carried out. Finally, the β-OH of the acetylene halide (1R, 3R)-2-(bromoethynyl)polyoxazol-2-ol 3b is eliminated to generate 3-(((1r, 3r, 5R, 7S)-adamantan-2-ylidene)-methyl)-5-bromobenzo[d]isoxazole. The reaction in this example only needs to be carried out at 100° C. for half an hour under atmospheric pressure air atmosphere, and then a simple subsequent treatment is carried out to obtain the final target product 3-(((1r, 3r, 5R, 7S)-adamantan-2-ylidene)-methyl)-5-bromobenzo[d]isoxazole (1b) with an excellent yield (82%).

[0093] This embodiment is compatible with halogen bromine functional groups to facilitate subsequent transformations such as metal-catalyzed coupling reactions, including Suzuki reaction, Sonogashira reaction, Buchwald-Hartwig coupling, etc., to construct complex molecules.

[0094] Example 3 Preparation of (1-methyl-2-methyl-1-propene-1-yl)benzo[d]isoxazole (1c)

[0095] Under an atmospheric pressure air atmosphere, N-(o-tolyloxy)acetamide 2c (16.5 mg, 0.10 mmol), 1-bromo-2-methylbut-2-yn-2-ol 3c (24.3 mg, 0.15 mmol), pentamethylcyclopentadiene rhodium dichloride dimer [Cp*RhCl2]2 (1.2 mg, 0.002 mmol), silver trifluoromethanesulfonimide (1.9 mg, 0.005 mmol), lithium carbonate (14.8 mg, 0.20 mmol), silver acetate (33.4 mg, 0.20 mmol), 1,2-dichloroethane (DCE, 1.0 mL) were added to a 15 mL Schlenk tube in sequence and reacted at 100 ° C for 0.5 hours. The crude product was separated by chromatography on a prepared silica gel plate, and the selected developing solvent or eluent was petroleum ether (PE): ethyl acetate (EA) = 40:1, and the product (1-methyl-2-methyl-1-propene-1-yl)benzo[d]isoxazole (1c) was obtained with a yield of 88%. The chemical reaction equation corresponding to this example is as follows:

[0096]

[0097] The H-NMR and C-NMR spectra of the compound prepared in Example 3 are as follows: Figure 5 and Figure 6 As shown. Figure 5 It can be seen that: 1H NMR (400MHz,CDCl3)δ7.46(d,J=8.0Hz,1H),7.30(d,J=7.2Hz,1H),7.20(t,J=7.6Hz,1H),6.29(s,1H),2.57(s,3H),2.16(s,3H),2.06(s,3H). The molecular hydrogen spectrum peaks can correspond to the target product one by one, and the quantity is reasonable. Figure 6 It can be seen that: 13 C NMR (100MHz, CDCl3) δ162.0, 155.6, 146.6, 130.1, 123.6, 121.9, 120.6, 118.7, 110.5, 27.2, 21.7, 15.3. 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, it can be seen that the product prepared in Example 3 is (1-methyl-2-methyl-1-propene-1-yl)benzo[d]isoxazole (1c).

[0098] The N-(o-tolyloxy)acetamide 2c in this embodiment contains an amide functional group that is ubiquitous in human production and life. Under the promotion of the amide functional group, the aromatic ring carbon-hydrogen bond is activated, intramolecular cyclization, deacylation, and finally the β-OH of the acetylene halide 1-bromo-2-methylbut-2-yn-2-ol 3c is eliminated to generate (1-methyl-2-methyl-1-propene-1-yl)benzo[d]isoxazole. The reaction in this embodiment only needs to be carried out at atmospheric pressure air atmosphere at 100° C. for half an hour, and then a simple subsequent treatment is performed to obtain the final target product (1-methyl-2-methyl-1-propene-1-yl)benzo[d]isoxazole (1c) with an excellent yield (88%).

[0099] The chemical transformation in this example can generate 1,2-benzisoxazole derivatives efficiently and quickly.

[0100] Example 4 Preparation of (E)-1-methyl-3-(prop-1-en-1-yl)benzo[d]isoxazole (1d)

[0101] Under an atmospheric pressure air atmosphere, N-(o-tolyloxy)acetamide 2d (16.5 mg, 0.10 mmol), 4-bromobut-3-yn-2-ol 3d (21.7 mg, 0.15 mmol), pentamethylcyclopentadiene rhodium dichloride dimer [Cp*RhCl2]2 (1.2 mg, 0.002 mmol), silver trifluoromethanesulfonimide (1.9 mg, 0.005 mmol), lithium carbonate (14.8 mg, 0.20 mmol), silver acetate (33.4 mg, 0.20 mmol), N,N'-dimethylformamide (DMF, 1.0 mL) were added to a 15 mL Schlenk tube in sequence and reacted at 100 ° C for 1 hour. The crude product was separated by chromatography on a prepared silica gel plate, and the selected developing solvent or eluent was petroleum ether (PE): ethyl acetate (EA) = 40:1, and the product (E)-1-methyl-3-(prop-1-en-1-yl)benzo[d]isoxazole (1d) was obtained with a yield of 65%. The chemical reaction equation corresponding to this example is as follows:

[0102]

[0103] The H-NMR and C-NMR spectra of the compound prepared in Example 4 are as follows: Figure 7 and Figure 8 As shown. Figure 7 It can be seen that: 1 H NMR (400MHz,CDCl3)δ7.65(d,J=7.6Hz,1H),7.31(d,J=7.2Hz,1H),7.22(t,J=7.6Hz,1H),6.89-6.80(m,1H),6.71(dd,J=16.0,1.6Hz,1H),2.57(s,3H),2.03(dd,J=6.4,1.6Hz,3H). The molecular hydrogen spectrum peaks can correspond to the target product one by one, and the quantity is reasonable. Figure 8 It can be seen that: 13 C NMR (100MHz, CDCl3) δ162.8, 155.8, 149.7, 135.4, 130.1, 123.9, 120.9, 119.9, 119.5, 119.4, 29.8, 19.3, 15.3. 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, it can be seen that the product prepared in Example 4 is (E)-1-methyl-3-(prop-1-en-1-yl)benzo[d]isoxazole (1d).

[0104] The N-(o-tolyloxy)acetamide 2d in this embodiment contains an amide functional group that is ubiquitous in human production and life. Under the promotion of the amide functional group, the aromatic ring carbon-hydrogen bond is activated, intramolecular cyclization, deacylation, and finally the β-OH of the acetylene halide 4-bromobut-3-yn-2-ol 3d is eliminated to generate (E)-1-methyl-3-(prop-1-en-1-yl)benzo[d]isoxazole. The reaction in this embodiment only needs to be carried out at 100° C. for half an hour under atmospheric pressure air atmosphere, and then a simple subsequent treatment is performed to obtain the final target product (E)-1-methyl-3-(prop-1-en-1-yl)benzo[d]isoxazole (1d) with an excellent yield (65%).

[0105] The chemical transformation in this example can generate 1,2-benzisoxazole derivatives efficiently and quickly.

[0106] Example 5 Preparation of 5-tert-butyl-3-(2,2-diphenylvinyl)benzo[d]isoxazole (1e)

[0107] Under an atmospheric pressure air atmosphere, N-(4-(tert-butyl)phenoxy)acetamide 2e (20.7 mg, 0.10 mmol), 3-bromo-1,1-diphenyl-2-propyn-1-ol 3e (43.0 mg, 0.15 mmol), pentamethylcyclopentadiene rhodium dichloride dimer [Cp*RhCl2]2 (1.2 mg, 0.002 mmol), silver trifluoromethanesulfonimide (1.9 mg, 0.005 mmol), lithium carbonate (14.8 mg, 0.20 mmol), silver acetate (33.4 mg, 0.20 mmol), 1,2-dichloroethane (DCE, 1.0 mL) were added to a 15 mL Schlenk tube in sequence and reacted at 100 ° C for half an hour. The crude product was separated by chromatography using the prepared silica gel plate, and the selected developing solvent or eluent was petroleum ether (PE): ethyl acetate (EA) = 40:1, and the product 5-tert-butyl-3-(2,2-diphenylvinyl)benzo[d]isoxazole (1e) was obtained with a yield of 92%. The chemical reaction equation corresponding to this example is as follows:

[0108]

[0109] The H-NMR and C-NMR spectra of the compound prepared in Example 5 are as follows: Fig. 9 and Fig.10 As shown. Fig. 9 It can be seen that: 1 HNMR (400MHz,CDCl3)δ7.46-7.37(m,7H),7.27-7.22(m,5H),7.13(s,1H),6.69(s,1H),1.12(s,9H). The molecular hydrogen spectrum peaks can correspond to the target product one by one, and the quantity is reasonable. Fig.10 It can be seen that: 13 C NMR (100MHz, CDCl3) δ161.9, 156.3, 150.3, 146.2, 142.4, 139.7, 130.8, 128.8, 128.7, 128.7, 128.6, 128.5, 127.8, 120.0, 118.6, 114.9, 109.0, 34.8, 31.5. 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, it can be seen that the product obtained in Example 5 is 5-tert-butyl-3-(2,2-diphenylvinyl)benzo[d]isoxazole (1e).

[0110] The N-(4-(tert-butyl)phenoxy)acetamide 2e in this embodiment contains an amide functional group that is ubiquitous in human production and life. Under the promotion of the amide functional group, the aromatic ring carbon-hydrogen bond is activated, intramolecular cyclization, deacylation, and finally the β-OH of the acetylene halide 3-bromo-1,1-diphenyl-2-propyn-1-ol 3e is eliminated to generate 5-tert-butyl-3-(2,2-diphenylvinyl)benzo[d]isoxazole. The reaction in this embodiment only needs to be carried out at 100° C. for half an hour under atmospheric pressure air atmosphere, and then a simple subsequent treatment is performed to obtain the final target product 5-tert-butyl-3-(2,2-diphenylvinyl)benzo[d]isoxazole (1e) with an excellent yield (92%).

[0111] The chemical transformation in this example uses a diaryl alkyne halide, which broadens the types of alkyne halides.

[0112] Example 6 Preparation of (E)-3-((2-methylcyclohexylidene)-methyl)-7-methylbenzo[d]isoxazole (1f)

[0113] Under an atmospheric pressure air atmosphere, N-(o-tolyloxy)acetamide 2f (16.5 mg, 0.10 mmol), 1-bromoethynyl-2-isopropyl-5-methylcyclohexane-1-ol 3f (39.0 mg, 0.15 mmol), pentamethylcyclopentadiene rhodium dichloride dimer [Cp*RhCl2]2 (3.0 mg, 0.005 mmol), silver trifluoromethanesulfonimide (3.8 mg, 0.010 mmol), lithium carbonate (14.8 mg, 0.20 mmol), silver acetate (33.4 mg, 0.25 mmol), 1,2-dichloroethane (DCE, 1.0 mL) were added to a 15 mL Schlenk tube in sequence and reacted at 100 ° C for 1 hour. The crude product was separated by chromatography on a prepared silica gel plate, and the selected developing solvent or eluent was petroleum ether (PE): ethyl acetate (EA) = 30:1, and the product (E)-3-((2-methylcyclohexylidene)-methyl)-7-methylbenzo[d]isoxazole (1f) was obtained with a yield of 66%. The chemical reaction equation corresponding to this example is as follows:

[0114]

[0115] The H-NMR and C-NMR spectra of the compound prepared in Example 6 are as follows: Fig.11 and Fig.12 As shown. Fig.11 It can be seen that: 1 HNMR (400MHz,CDCl3)δ7.44(d,J=8.0Hz,1H),7.30(d,J=7.2Hz,1H),7.20(t,J=7.6Hz,1H),6.22(s,1H),2.89(dd,J=13.2,4.4Hz,1H),2.58(s,3H),2.21-2.10(m,2H),1.96-1.81(m,4H),1.49-1.42(m,1H),1.23-1.19(m,1H),1.01(dd,J=6.4,3.6Hz,6H),0.93(d,J=6.4Hz,3H). The molecular hydrogen spectrum peaks can correspond to the target product one by one, and the quantity is reasonable. Fig.12 It can be seen that: 13C NMR (100MHz, CDCl3) δ162.0, 155.9, 155.0, 130.1, 123.5, 122.3, 120.6, 118.8, 107.4, 52.0, 38.2, 33.5, 32.0, 27.4, 27.1, 22.2, 20.8, 19.7, 15.3. 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, it can be seen that the product obtained in Example 6 is (E)-3-((2-methylcyclohexylidene)-methyl)-7-methylbenzo[d]isoxazole (1f).

[0116] The N-(o-tolyloxy)acetamide 2f in this embodiment contains an amide functional group that is ubiquitous in human production and life. Under the promotion of the amide functional group, the aromatic ring carbon-hydrogen bond is activated, intramolecular cyclization, and deacylation are carried out, and finally the β-OH of the acetylene halide 1-bromoethynyl-2-isopropyl-5-methylcyclohexane-1-ol 3f is eliminated to generate (E)-3-((2-methylcyclohexylidene)-methyl)-7-methylbenzo[d]isoxazole. The reaction in this embodiment only needs to be carried out at 100° C. for 1 hour under atmospheric pressure air atmosphere, and then a simple subsequent treatment is performed to obtain the final target product (E)-3-((2-methylcyclohexylidene)-methyl)-7-methylbenzo[d]isoxazole (1f) with an excellent yield (66%).

[0117] The chemical transformation in this example uses menthol-derived natural product alkyne halides to broaden the scope of substrates.

[0118] Example 7 Preparation of 7-methyl-3-(Z)-((1S,4S)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-ylidene)methyl)benzo[d]isoxazole (1 g)

[0119] Under an atmospheric pressure air atmosphere, 2 g (16.5 mg, 0.10 mmol) of N-(o-tolyloxy)acetamide, 3 g (38.4 mg, 0.15 mmol) of (1S, 4S)-2-(bromoethynyl)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-ol, pentamethylcyclopentadiene rhodium dichloride dimer [Cp*RhCl2]2 (3.0 mg, 0.005 mmol), silver trifluoromethanesulfonimide (3.8 mg, 0.01 mmol), lithium carbonate (14.8 mg, 0.20 mmol), silver oxide (58.7 mg, 0.25 mmol), and 1,2-dichloroethane (DCE, 1.0 mL) were added to a 15 mL Schlenk tube in sequence, and the mixture was reacted at 100 ° C for 2 hours. The crude product was separated by chromatography on a prepared silica gel plate, and the selected developing solvent or eluent was petroleum ether (PE): ethyl acetate (EA) = 30:1, and the product 7-methyl-3-(Z)-((1S, 4S)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-ylidene)methyl)benzo[d]isoxazole (1 g) was obtained with a yield of 60%. The chemical reaction equation corresponding to this example is as follows:

[0120]

[0121] The H-NMR and C-NMR spectra of the compound prepared in Example 7 are as follows: Fig.13 and Fig.14 As shown. Fig.13 It can be seen that: 1 HNMR (400MHz,CDCl3)δ7.53(d,J=7.6Hz,1H),7.29(d,J=7.2Hz,1H),7.21(d,J=7.2Hz,1H),6.25(s,1H),2.91-2.85(m,1H),2.57(s,3H),2.44(dd,J=18.8,2.4Hz,1H),1.95(t,J=4.4Hz,1H),1.87-1.77(m,2H),1.13(s,3H),0.97(s,3H),0.79(s,3H). The molecular hydrogen spectrum peaks can correspond to the target product one by one, and the quantity is reasonable. Fig.14 It can be seen that: 13C NMR (100MHz, CDCl3) δ176.8,165.2,155.7,130.0,123.4,121.8,120.5,118.5,101.8,53.5,48.54,45.0,39.8,34.7,32.1,29.8,27.7,19.8,19.2,15.3,12.9. 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, it can be seen that the product obtained in Example 7 is 7-methyl-3-(Z)-((1S, 4S)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-ylidene)methyl)benzo[d]isoxazole (1g).

[0122] The N-(o-tolyloxy)acetamide 2g in this example contains an amide functional group that is ubiquitous in human production and life. Under the promotion of the amide functional group, the aromatic ring carbon-hydrogen bond is activated, intramolecular cyclization, and deacylation is carried out, and finally the β-OH of the acetylene halide (1S, 4S)-2-(bromoethynyl)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-ol 3g is eliminated to generate (E)-3-((2-methylcyclohexylidene)-methyl)-7-methylbenzo[d]isoxazole. The reaction in this example only needs to be carried out at atmospheric pressure air atmosphere at 100°C for 2 hours, and then a simple subsequent treatment is performed to obtain the final target product 7-methyl-3-(Z)-((1S, 4S)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-ylidene)methyl)benzo[d]isoxazole (1g) with an excellent yield (60%).

[0123] The chemical transformation in this example uses a camphor-derived natural product alkyne halide, which broadens the scope of substrates.

[0124] Example 8 Preparation of 4-(1r, 3r, 5R, 7S)-benzo[d]isoxazol-5-yl)-N,N-diphenylaniline (1h)

[0125] Under an atmospheric pressure air atmosphere, N-(4'-(diphenylamino)-[1,1'-biphenyl]-4-yl)oxy)acetamide 2h (39.4 mg, 0.10 mmol), (1R, 3R)-2-(bromoethynyl)polyoxo-2-ol 3h (39.7 mg, 0.15 mmol), pentamethylcyclopentadiene rhodium dichloride dimer [Cp*RhCl2]2 (1.2 mg, 0.002 mmol), silver trifluoromethanesulfonimide (1.9 mg, 0.005 mmol), lithium carbonate (14.8 mg, 0.20 mmol), silver acetate (33.4 mg, 0.20 mmol), 1,2-dichloroethane (DCE, 1.0 mL) were added to a 15 mL Schlenk tube in sequence and reacted at 100 ° C for 1 hour. The crude product was separated by chromatography on a prepared silica gel plate, and the selected developing solvent or eluent was petroleum ether (PE): ethyl acetate (EA) = 40:1, and the product 4-(1r, 3r, 5R, 7S)-benzo[d]isoxazol-5-yl)-N,N-diphenylaniline (1h) was obtained with a yield of 78%. The chemical reaction equation corresponding to this embodiment is as follows:

[0126]

[0127] The H-NMR and C-NMR spectra of the compound prepared in Example 8 are as follows: Fig.15 and Fig.16 As shown. Fig.15 It can be seen that: 1 HNMR (400MHz,CDCl3)δ7.79(d,J=1.2Hz,1H),7.73(dd,J=8.8,1.6Hz,1H),7.57(d,J=8.4Hz,1H),7.48(d,J=8.8Hz,2H),7.27(t,J=8.4Hz,4H),7.15(t,J=8.4Hz,6H),7.04(t,J=7.2Hz,2H),6.21(s,1H),3.66(s,1H),2.70(s,1H),2.05-1.90(m,12H). The molecular hydrogen spectrum peaks can correspond to the target product one by one, and the quantity is reasonable. Fig.16 It can be seen that: 13C NMR (100MHz, CDCl3) δ162.7, 162.0, 155.4, 147.7, 147.4, 136.6, 134.6, 129.4, 129.1, 128.1, 124.6, 124.1, 123.5, 123.2, 119.0, 110.0, 102.0, 41.4, 40.2, 39.3, 37.1, 34.7, 28.2. 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, it can be seen that the product obtained in Example 8 is 4-(1r, 3r, 5R, 7S)-benzo[d]isoxazol-5-yl)-N, N-diphenylaniline (1h).

[0128] The N-(4'-(diphenylamino)-[1,1'-biphenyl]-4-yl)oxy)acetamide 2h in this embodiment contains an amide functional group that is ubiquitous in human production and life. Under the promotion of the amide functional group, the aromatic ring carbon-hydrogen bond is activated, intramolecular cyclization, and deacylation are carried out, and finally the β-OH of the acetylene halide (1R, 3R)-2-(bromoethynyl)polyoxazol-2-ol 3h is eliminated to generate 4-(1r, 3r, 5R, 7S)-benzo[d]isoxazol-5-yl)-N, N-diphenylaniline. The reaction in this embodiment only needs to be reacted at 100° C. for half an hour under atmospheric pressure air atmosphere, and then a simple subsequent treatment is performed to obtain the final target product 4-(1r, 3r, 5R, 7S)-benzo[d]isoxazol-5-yl)-N, N-diphenylaniline (1h) with an excellent yield (78%).

[0129] In this embodiment, the donor-acceptor structure is formed by the triphenylamine group having excellent hole transporting ability and the benzoxazole group which can be used as an electron acceptor, and it is expected to obtain a high-luminescent material with high charge transfer ability and low energy band gap.

[0130] Example 9 Preparation of 1-(3-(((1R, 3R, 5R, 7S)-adamantan-2-ylidene)methyl)benzo[d]isoxazol-5-yl)ethan-1-one (1i)

[0131] Under an atmospheric pressure air atmosphere, N-(4-acetylphenoxy)acetamide 2i (19.3 mg, 0.10 mmol), (1R, 3R)-2-(bromoethynyl)polyoxazine-2-ol 3i (39.7 mg, 0.15 mmol), pentamethylcyclopentadiene rhodium dichloride dimer [Cp*RhCl2]2 (1.2 mg, 0.002 mmol), silver trifluoromethanesulfonimide (1.9 mg, 0.005 mmol), sodium acetate (16.4 mg, 0.20 mmol), silver acetate (33.4 mg, 0.20 mmol), 1,2-dichloroethane (DCE, 1.0 mL) were added to a 15 mL Schlenk tube in sequence and reacted at 100 ° C for half an hour. The crude product was separated by chromatography on a prepared silica gel plate, and the selected developing solvent or eluent was petroleum ether (PE): ethyl acetate (EA) = 40:1, and the product 1-(3-(((1R, 3R, 5R, 7S)-adamantan-2-ylidene)methyl)benzo[d]isoxazol-5-yl)ethan-1-one (1i) was obtained with a yield of 64%. The chemical reaction equation corresponding to this example is as follows:

[0132]

[0133] The H-NMR and C-NMR spectra of the compound prepared in Example 9 are as follows: Fig.17 and Fig.18 As shown. Fig.17 It can be seen that: 1 HNMR (400MHz, CDCl3) δ8.32 (d, J = 0.8Hz, 1H), 8.18 (dd, J = 8.8, 1.6Hz, 1H), 7.60 (d, J = 8.8Hz, 1H), 6.21 (s, 1H), 3.96 (s, 1H), 2.72 (s, 1H), 2.69 (s, 3H), 2.05-1.91 (m, 12H). The molecular hydrogen spectrum peaks can correspond to the target product one by one, and the quantity is reasonable. Fig.18 It can be seen that: 13 C NMR (100MHz, CDCl3) δ196.8, 164.7, 164.2, 155.9, 133.2, 130.1, 123.2, 110.0, 101.2, 41.6, 40.2, 39.3, 37.0, 34.9, 29.8, 28.2, 26.9. 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, it can be seen that the product obtained in Example 9 is 1-(3-(((1R, 3R, 5R, 7S)-adamantan-2-ylidene)methyl)benzo[d]isoxazol-5-yl)ethan-1-one (1i).

[0134] The N-(4-acetylphenoxy)acetamide 2i in this embodiment contains an amide functional group that is ubiquitous in human production and life. Under the promotion of the amide functional group, the aromatic ring carbon-hydrogen bond is activated, intramolecular cyclization is carried out, and deacylation is carried out. Finally, the β-OH of the acetylene halide (1R, 3R)-2-(bromoethynyl)polyoxazol-2-ol 3i is eliminated to generate 1-(3-(((1R, 3R, 5R, 7S)-adamantan-2-ylidene)methyl)benzo[d]isoxazol-5-yl)ethan-1-one. The reaction in this embodiment only needs to be carried out at 100° C. for half an hour under atmospheric pressure air atmosphere, and then a simple subsequent treatment is carried out to obtain the final target product 1-(3-(((1R, 3R, 5R, 7S)-adamantan-2-ylidene)methyl)benzo[d]isoxazol-5-yl)ethan-1-one (1i) with an excellent yield (64%).

[0135] This embodiment is compatible with acetyl functional groups, and the functional group compatibility is good.

[0136] Example 10 Preparation of methyl 3-(cyclohexylmethoxy)benzo[D]isoxazole-5-carboxylate (1j)

[0137] Under an atmospheric pressure air atmosphere, methyl 4-(acetylaminooxy)benzoate 2j (20.9 mg, 0.10 mmol), 1-(bromoethynyl)cyclohexane-1-ol 3j (30.1 mg, 0.15 mmol), pentamethylcyclopentadiene rhodium dichloride dimer [Cp*RhCl2]2 (1.2 mg, 0.002 mmol), silver trifluoromethanesulfonimide (1.9 mg, 0.005 mmol), sodium carbonate (21.0 mg, 0.20 mmol), silver acetate (33.4 mg, 0.20 mmol), and 1,2-dichloroethane (DCE, 1.0 mL) were added to a 15 mL Schlenk tube in sequence and reacted at 100 ° C for half an hour. The crude product was separated by chromatography on a prepared silica gel plate, and the selected developing solvent or eluent was petroleum ether (PE): ethyl acetate (EA) = 40:1, and the product 3-(cyclohexylmethy1)benzo[D]isoxazole-5-carboxylic acid methyl ester (1j) was obtained with a yield of 78%. The chemical reaction equation corresponding to this example is as follows:

[0138]

[0139] The H-NMR and C-NMR spectra of the compound prepared in Example 10 are as follows: Fig.19 and Fig. 20 As shown. Fig.19 It can be seen that: 1HNMR (400MHz,CDCl3)δ8.42-8.39(m,1H),8.24(dd,J=8.8,1.6Hz,1H),7.58(d,J=8.8Hz,1H),6.24(s,1H),3.96(s,3H),2.71(d,J=5.6Hz,2H),2.42(dd,J=6.0,5.2Hz,2H),1.76-1.72(m,2H),1.67-1.64(m,4H). The molecular hydrogen spectrum peaks can correspond to the target product one by one, and the quantity is reasonable. Fig. 20 It can be seen that: 13 C NMR (100MHz, CDCl3) δ166.6, 164.8, 155.7, 155.6, 131.1, 125.9, 124.5, 123.2, 109.8, 106.2, 52.5, 38.0, 31.7, 29.8, 28.7, 27.9, 26.6, 1.2. 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, it can be seen that the product obtained in Example 10 is 3-(cyclohexylmethene)benzo[D]isoxazole-5-carboxylic acid methyl ester (1j).

[0140] The 4-(acetylaminooxy)benzoic acid methyl ester 2j in this embodiment contains an amide functional group that is ubiquitous in human production and life. Under the promotion of the amide functional group, the aromatic ring carbon-hydrogen bond is activated, intramolecular cyclization, deacylation, and finally the β-OH of the acetylene halide 1-(bromoethynyl)cyclohexane-1-ol 3j is eliminated to generate 3-(cyclohexylmethene)benzo[D]isoxazole-5-carboxylic acid methyl ester. The reaction in this embodiment only needs to be reacted at 100° C. for half an hour under atmospheric pressure air atmosphere, and then simple subsequent treatment is performed to obtain the final target product 3-(cyclohexylmethene)benzo[D]isoxazole-5-carboxylic acid methyl ester (1j) with an excellent yield (78%).

[0141] This embodiment is compatible with acetyl functional groups, and the functional group compatibility is good.

[0142] Application example: Preparation and material characterization of hole transport material molecules for perovskite solar cells: 4-(1r, 3r, 5R, 7S)-benzo[d]isoxazol-5-yl)-N,N-diphenylaniline (1h)

[0143] When characterizing the material of 1h molecule, we found that it exhibited good hole transport material performance. Specifically, Fig.21 , 22It can be calculated that the highest occupied molecular orbital (HOMO) of 1h is delocalized in the entire molecule, which is beneficial to charge transfer, and the lowest unoccupied molecular orbital (LUMO) is mainly located on the core skeleton. The overlap of the HOMO orbital and the LUMO orbital is beneficial to hole extraction, and the E of 1h calculated by DFT is HOMO or E LUMO The value is -4.89 / -1.21eV, which meets the requirements of hole transport materials for perovskite solar cells. Next, the application of this 1,2-benzisoxazole derivative to perovskite solar cells is explained in detail.

[0144] 3.5 mg of compound 1h was dissolved in 1 mL of chlorobenzene solvent, spin-coated on the cleaned conductive glass at 4000 rpm, and then annealed at 100 °C for 10 minutes. After cooling, the perovskite precursor solution was spin-coated on the substrate at 1000 rpm and 5000 rpm, respectively, and annealed at 100 °C for 30 minutes. After cooling to room temperature, the chlorobenzene solution of [6,6]-phenyl-C61-butyric acid isomethyl ester (PCBM) was spin-coated on the perovskite layer and annealed at 65 °C for 10 minutes. After cooling, bathocuproin (BCP) was spin-coated on the PCBM and annealed at 65 °C for 5 minutes. Finally, the metal electrode was evaporated under high vacuum conditions. Fig.23 As shown in the figure, the JV curve was measured under 1 sun, and the best device performance was: the short-circuit current density was 24.4849 mA cm -2 , the open circuit voltage is 1.0549V, the fill factor is 61.97%, and the power conversion efficiency is 16.01%. Previously, the transfer efficiency of triphenylamine in the study of hole transport materials in perovskite solar cells was about 15% (Chem. Soc. Rev. 2022, 51, 5974-6064.). Through the above corresponding photovoltaic parameters, it can be analyzed that the transfer of interface carriers can be achieved in 1h, which is consistent with expectations.

[0145] Table: Device performance of P1-W and PTAA inverted PSCs

[0146]

[0147] In summary, the present application provides a method for preparing 1,2-benzisoxazole, wherein under the conditions of an inert solvent, under the joint action of a transition metal catalyst and an oxidant, the acetylene halide shown in formula III reacts with the N-phenoxyamide shown in formula II; finally, under the action of a base, a 1,2-benzisoxazole derivative shown in formula I is generated, and the reaction equation is as follows:

[0148]

[0149] Where R is a variety of substituents, R 1 , R2 is H or alkyl or aryl.

[0150] This preparation method is the first to develop a method for generating 1,2-benzisoxazole using a CH activation strategy under the catalysis of rhodium (III) using N-phenoxyamide as a substrate and alkyne halide as a coupling reagent. Under inert solvent conditions, under the joint action of transition metal catalyst and oxidant, the alkyne halide first generates an ortho-alkynylated product under the guidance of N-phenoxyamide, and then undergoes intramolecular cyclization with alkyne due to the nucleophilicity of N, and deacylates under the action of base, and finally β-OH is eliminated to generate 1,2-benzisoxazole.

[0151] This reaction has the following advantages:

[0152] (1) The substrates used in this paper are derived from phenol / boron reagents and ketones, three functional groups that are widely present in natural products.

[0153] (2) In the study of carbon-hydrogen bond activation by N-phenoxyamide, there are few reports on the nucleophilicity of the N center as a reaction mode. This paper enriches the method of using this directing group to construct a heterocyclic molecule library.

[0154] (3) The synthesis of the product 1,2-benzisoxazole of this reaction still faces the following challenges: the traditional synthesis method starts from salicylaldehyde oxime, and such a specific substrate will lead to product limitation. However, the raw material in this article is derived from phenol, and the substrate range is wide.

[0155] (4) The reaction yields a multifunctionalized 1,2-benzisoxazole product, and the introduced olefins can be further transformed, such as olefin metathesis, olefin hydroboration, Heck reaction, etc., providing a means for constructing a complex molecular library. Through CV, PL, and UV testing, the real energy levels of the molecule were obtained, with HOMO being -4.89 and LUMO being -1.21. This is suitable for use as a perovskite solar cell.

[0156] The present application provides a method for preparing multifunctional 1,2-benzisoxazole derivatives. This preparation method develops for the first time a method for generating 1,2-benzisoxazole using a CH activation strategy under the catalysis of rhodium (III) using N-phenoxyamide as a substrate and acetylene halide as a coupling reagent. Under inert solvent conditions, under the joint action of a transition metal catalyst and an oxidant, the acetylene halide first undergoes ortho-carbon-hydrogen bond alkynylation under the guidance of N-phenoxyamide, and then N-phenoxyamide performs intramolecular amine metalation on the alkyne carbon-carbon triple bond; finally, under the action of a base, deacylation and β-OH elimination are performed to generate multifunctional 1,2-benzisoxazole derivatives. It should be pointed out that at present, the synthesis of 1,2-benzisoxazole derivatives still faces challenges (multi-step synthesis, poor functional group compatibility) due to the limitation of specific substrates. This reaction is expected to provide new ideas for the development and application of 1,2-benzisoxazole derivatives. The obtained 1h product exhibits good performance as a hole transport layer material in solar cells (the triphenylamine-benzisoxazole skeleton in this application can obtain a power conversion efficiency of 16.01%. Previously, the transfer efficiency of triphenylamine in the study of hole transport materials for perovskite solar cells was about 15% (Chem. Soc. Rev. 2022, 51, 5974-6064.)).

[0157] 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. Moreover, the specific features, structures, materials, or characteristics described may be combined in any one or more embodiments or examples in a suitable manner.

[0158] 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 1,2-benzisoxazole, characterized in that: Under the conditions of an inert solvent, under the joint action of a transition metal catalyst and an oxidant, the acetylene halide shown in Formula III reacts with the N-phenoxyamide shown in Formula II; finally, under the action of a base, a 1,2-benzisoxazole derivative shown in Formula I is generated, and the reaction equation is as follows: Where R is a variety of substituents, R 1 , R 2 is H or alkyl or aryl.

2. The method for preparing 1,2-benzisoxazole according to claim 1, characterized in that: The amount of the transition metal catalyst used is 2 mol% of the amount of the N-phenoxyamide compound represented by formula II.

3. The method for preparing 1,2-benzisoxazole according to claim 1, characterized in that: The catalyst is any one of pentamethylcyclopentadienyl rhodium chloride dimer, pentamethylcyclopentadienyl iridium chloride dimer, palladium acetate, dichloro (p-methylisopropylphenyl) ruthenium dimer, cobalt acetylacetonate, pentacarbonyl manganese bromide or a combination thereof.

4. The method for preparing 1,2-benzisoxazole according to claim 1, characterized in that: The oxidant is any one or more of silver acetate, silver carbonate, silver oxide and potassium persulfate.

5. The method for preparing 1,2-benzisoxazole according to claim 1, characterized in that: The additive is any one of silver hexafluoroantimonate, silver bis(trifluoromethanesulfonyl)imide, sodium bicarbonate, lithium acetate, lithium carbonate and dipotassium hydrogen phosphate, or a combination thereof.

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

7. The method for preparing 1,2-benzisoxazole according to claim 1, characterized in that: The reaction is carried out at 60-100° C. and for 0.5 hours.

8. The method for preparing 1,2-benzisoxazole according to claim 1, characterized in that: The specific steps include: S1. In a reactor, 16.5 mg of N-(o-tolyloxy)acetamide, 24.2 mg of 1-bromo-2-methylbut-2-yn-2-ol, 1.2 mg of pentamethylcyclopentadiene rhodium dichloride dimer, 1.9 mg of silver trifluoromethanesulfonimide, 14.8 mg of lithium carbonate, 33.4 mg of silver acetate, and 1.0 mL of 1,2-dichloroethane were added in sequence in air; S2. The reaction solution is reacted at 100°C for 0.5-2 hours; S3. After the reaction is completed, the above mixture is separated by column chromatography to obtain the target compound.

9. The method for preparing 1,2-benzisoxazole according to claim 8, characterized in that: The developing solvent or eluent selected in the column chromatography separation technology is petroleum ether and ethyl acetate, and the usage ratio of petroleum ether:ethyl acetate is 40:

1.

10. A solar cell, characterized in that: The solar cell is a perovskite solar cell, and the hole transport material in the perovskite solar cell is a 1,2-benzisoxazole compound prepared by the preparation method according to claim 1.

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