A process for the preparation of 1,2-benzisoxazole

Abstract

This application provides a method for preparing 1,2-benzisoxazole derivatives. This method is the first to develop a C-H activation strategy for generating 1,2-benzisoxazole using N-phenoxyamide as a substrate and acetic halide as a coupling agent under rhodium(III) catalysis. Under inert solvent conditions, and with the combined action of a transition metal catalyst and an oxidant, the acetic halide undergoes ortho-C-H bond alkynylation under the guidance of N-phenoxyamide, followed by intramolecular amine metallation of the carbon-carbon triple bond of the acetic acid. Finally, under the action of a base, deacylation and β-OH elimination occur, yielding a multifunctional 1,2-benzisoxazole derivative. Currently, the synthesis of 1,2-benzisoxazole remains challenging due to the scarcity of synthetic methods and limitations on specific substrates (multi-step synthesis, poor functional group compatibility, etc.). This reaction is expected to provide a new approach for the development and application of 1,2-benzisoxazole derivatives. It should be noted that the obtained product can also be applied to hole transport materials for perovskite solar cells. Specifically, a donor-acceptor structure is formed by combining a triphenylamine group with excellent hole transport capability and a benzoxazole group that can act as an electron acceptor. This molecule achieves a power conversion efficiency of 16.01%.

Description

Technical Field

[0001] This application relates to the field of organic compound synthesis technology, and more specifically, to a method for preparing 1,2-benzisoxazole. Background Technology

[0002] Benzisoxazoles are a class of benzo[a]heterocyclic compounds containing adjacent oxygen and nitrogen atoms, exhibiting high biological activity and pharmaceutical properties. Heterocyclic compounds containing the benzisoxazole skeleton and their derivatives are widely found in drug molecules. Molecular skeletons formed using benzisoxazole templates possess multifunctional binding properties with frequently occurring binding motifs, providing effective selective ligands for a range of diverse biological targets in medicinal chemistry. Benzisoxazole scaffolds and their analogues are important drug carriers, with compounds found to possess biological activity in many different therapeutic areas, such as anti-HIV, antibacterial, antipsychotic, anti-inflammatory, analgesic, dopamine and serotonin receptor, anticonvulsant, acetylcholinesterase, anticancer, antioxidant, and antidiabetic drugs (Med. Chem. Commun., 2017, 8, 2023-2039.).

[0003] However, most applications of benzisoxazole still use the 2,1-benzisoxazole skeleton, while its isomer 1,2-benzisoxazole is difficult to obtain due to the lack of synthetic methods and the limitation of reaction conditions. Therefore, researching and developing a low-cost and simple method for preparing 1,2-benzisoxazole has good application prospects.

[0004] Application content

[0005] To overcome at least one of the problems existing in the prior art, this application provides a method for preparing 1,2-benzisoxazole. This method is simple, yields high efficiency, and is environmentally friendly.

[0006] To solve the above-mentioned technical problems, the technical solution adopted in this application is:

[0007] A method for preparing 1,2-benzisoxazole involves reacting an acetylene halide of formula III with an N-phenoxyamide of formula II under inert solvent conditions and in the combined action of a transition metal catalyst and an oxidant. Finally, under the action of a base, a 1,2-benzisoxazole derivative of formula I is generated. The reaction equation is as follows:

[0008]

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

[0010] This application also provides a solar cell, which 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 described above.

[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, three functional groups widely present in natural products. In studies of C-H bond activation by N-phenoxyamides, there are few reports on the nucleophilicity of the N-center as a reaction mode; this paper enriches the methods for constructing heterocyclic molecular libraries using this directing group. The synthesis of the product 1,2-benzisoxazole still faces the following challenges: traditional synthetic methods start from salicylaldehyde oxime, such a specific substrate leads to product limitation; however, the starting material in this paper is derived from phenol, resulting in a broad substrate range. Attached Figure Description

[0013] Figure 1 The photon nuclear magnetic resonance (NMR) spectrum of compound 1a prepared in Example 1 of this application is shown.

[0014] Figure 2 The image shows the carbon NMR spectrum of compound 1a prepared in Example 1 of this application.

[0015] Figure 3 The photon nuclear magnetic resonance (NMR) spectrum of compound 1b prepared in Example 2 of this application is shown.

[0016] Figure 4 The image shows the carbon NMR spectrum of compound 1b prepared in Example 2 of this application.

[0017] Figure 5 The photon nuclear magnetic resonance (NMR) spectrum of compound 1c prepared in Example 3 of this application is shown.

[0018] Figure 6 The image shows the carbon NMR spectrum of compound 1c prepared in Example 3 of this application.

[0019] Figure 7 The photon nuclear magnetic resonance (NMR) spectrum of compound 1d prepared in Example 4 of this application is shown.

[0020] Figure 8 The image shows the carbon NMR spectrum of compound 1d prepared in Example 4 of this application.

[0021] Figure 9 The photon nuclear magnetic resonance (NMR) spectrum of compound 1e prepared in Example 5 of this application is shown.

[0022] Figure 10 The image shows the carbon NMR spectrum of compound 1e prepared in Example 5 of this application.

[0023] Figure 11 The photon nuclear magnetic resonance (NMR) spectrum of compound 1f prepared in Example 6 of this application is shown.

[0024] Figure 12 The image shows the carbon NMR spectrum of compound 1f prepared in Example 6 of this application.

[0025] Figure 13 The photon nuclear magnetic resonance (NMR) spectrum of 1 g of the compound prepared in Example 7 of this application is shown.

[0026] Figure 14 The image shows the carbon NMR spectrum of 1 g of the compound prepared in Example 7 of this application.

[0027] Figure 15 The 1H NMR spectrum of the compound prepared in Example 8 of this application is shown.

[0028] Figure 16 The image shows the carbon NMR spectrum of compound 1h prepared in Example 8 of this application.

[0029] Figure 17 The photon nuclear magnetic resonance (NMR) spectrum of compound 1i prepared in Example 9 of this application is shown.

[0030] Figure 18 The image shows the carbon NMR spectrum of compound 1i prepared in Example 9 of this application.

[0031] Figure 19 The photon nuclear magnetic resonance (NMR) spectrum of compound 1j prepared in Example 10 of this application is shown.

[0032] Figure 20 The image shows the carbon NMR spectrum of compound 1j prepared in Example 10 of this application.

[0033] Figure 21 The CV chromatogram is for compound 1h prepared in Example 8 of this application.

[0034] Figure 22 This is a UV-PL image of the compound prepared in Example 8 of this application for 1 hour.

[0035] Figure 23 The JV test curve of compound 1h prepared in Example 8 when used as a hole transport material in a perovskite solar cell. Detailed Implementation

[0036] The embodiments of this application will be described in detail below with reference to examples. However, those skilled in the art will understand that the following examples are for illustrative purposes only and should not be considered as limiting the scope of this application. Unless otherwise specified in the examples, conventional conditions or conditions recommended by the manufacturer shall apply. Reagents or instruments whose manufacturers are not specified are all commercially available conventional products.

[0037] It should be noted that:

[0038] Unless otherwise specified, all embodiments and preferred embodiments mentioned herein can be combined to form new technical solutions.

[0039] In its research, the applicant discovered that 1,2-benzisoxazole derivatives are widely used in the pharmaceutical field. The following are four drug molecules containing the 1,2-benzisoxazole skeleton: the antipsychotic drugs risperidone and paliperidone, the MAO-A inhibitor RS-1636, and the antiepileptic drug zonisamide.

[0040]

[0041] Meanwhile, the applicant has discovered that 1,2-benzisoxazole can be synthesized using the following methods:

[0042]

[0043] The specific method for synthesizing 1,2-benzisoxazole is as follows:

[0044] 1) Intramolecular dehydration condensation reaction based on salicylaldehyde oxime and o-hydroxyphenyl ketone oxime:

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

[0046] In 1983, Merck et al. synthesized 1,2-benzisoxazole using trichloroacetyl isocyanate and salicylaldehyde oxime. This reaction faced limitations due to high cost (trichloroacetyl isocyanate is expensive) and specific substrate requirements, resulting in a limited range of synthesized 1,2-benzisoxazole products. (J.Org.Chem., 1983, 48, 2613-2615.)

[0047] In 1997, Guillaume synthesized 1,2-benzisoxazole via an intramolecular Mitsunobu reaction using salicylaldehyde oxime as a starting material. This reaction also faced the problem of limited product range for 1,2-benzisoxazole. (Synth. Commun. 1997, 27, 3839-3846.)

[0048] 2) Cyclization reactions involving transition metals:

[0049] In 2014, Zhao reported the formation of 1,2-benzisoxazole from N-phenoxyacetamide and aldehydes via an intermolecular [4+1] cyclization pathway catalyzed by palladium (Chem. Sci., 2014, 5, 1574-1578), but R... 1 The functional groups are only compatible with (-CH3,-F,-Cl,-Br,-OMe) and the polyfunctionalized 1,2-benzisoxazole product with an unsaturated double bond at position 3 cannot be obtained.

[0050] In 2015, Phongprapan used aryl aldehydes and aryl ketones as substrates. The aldehydes or ketones were activated by Lewis acids and reacted with azides via nucleophilic addition and elimination pathways to generate imine diazo ion intermediates. Interestingly, in the case of substrates containing ortho-hydroxyl groups, an ON bond was formed through nucleophilic substitution to give 1,2-benzisoxazole as a byproduct. The problems faced by this reaction are: 1,2-benzisoxazole is a byproduct, 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 limitations due to the use of expensive isocyanates or specific substrates, which limits its practical application value. Therefore, researching and developing low-cost and simple methods for preparing 1,2-benzisoxazole has good application prospects.

[0052] Based on our research interest in C-H bond alkynylation promoted by weak coordination, we have achieved Csp-H bond alkynylation 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 alkyneation (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 approach for the simplified synthesis of polyfunctional alkynes.

[0053] On the other hand, as readily available and multifunctional synthons, acetylene halides have recently provided a simple route for the highly selective synthesis of various functional molecules in transition metal catalysis. The applicant summarizes several reaction modes of acetylene halides: First, under basic conditions, acetylene halides break the CX bond through metal-halogen atom exchange to obtain acetyl anions; second, acetylene halides react with nucleophiles as electrophilic acetyl reagents; third, acetylene halides dissociate into halide cations under the action of organolithium reagents, which then act as electrophilic halogenating reagents in the reaction; fourth, acetylene halides react simultaneously as both electrophilic halogenating reagents and nucleophilic acetyl reagents. In general, further development of more reactivity of acetylene halides remains highly anticipated.

[0054] Building upon a novel alkyne halide reagent developed by our research group (Org. Lett. 2024, 26, 2186-2191.), this paper expands the range of alkyne halides. Alkyl halides are versatile synthetic compounds that concisely and selectively deliver complex skeletons. However, to achieve reactivity, sterically hindered silicon substitution of the alkyl halide is typically required to avoid potential overcoordination of the CH alkylation product with the metal catalyst. Furthermore, side reactions, including the isomerization of aliphatic alkyl halides, impede further applications. Notably, although their synthetic applications are still not fully explored, the α-alcohol aliphatic alkyl halide presented in this paper is a potential bifunctional reagent, containing an electrophilic halide, a multifunctional alkyne functional group, and the alcohol acting as a traceless directing group in the reaction.

[0055] Directing group-guided transition metal-catalyzed C-H bond activation reactions, due to their ability to construct carbon-carbon or carbon-heteroatom bonds under mild reaction conditions, have become one of the direct and effective strategies for the direct functionalization of inert C-H bonds and are widely used in many fields such as materials chemistry and drug synthesis. The role of the directing group is not only to direct and activate the ortho-position C-H bond; it is also often used for further in-situ condensation reactions to produce compounds with diverse structures. In recent years, oxyamides have attracted widespread attention from researchers for their unique characteristics when used as directing groups for C-H bond activation. The uniqueness of N-phenoxyamide directing groups lies in their multiple reaction modes, which greatly promotes the construction of complex molecular libraries. The C-H bond activation research of N-phenoxyamide has developed the following reaction modes: (1) Internal oxidation of NO bond cleavage: no external oxidant is needed in the reaction because the ON bond in the substrate N-phenoxyacetamide 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 synthesizing 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 research group (Chem. Commun. 2014, 50, 12135-12138.) reported the rhodium-catalyzed reaction of N-phenoxyacetamide with α,β-unsaturated aldehydes to synthesize 1,2-oxazylidene compounds via C-H bond activation / [4+3] cyclization. Due to the low NO bond energy and easy breakage, there is still a significant challenge in realizing this reaction mode using suitable coupling reagents and catalytic systems.

[0056] In summary, carbon-hydrogen bond activation based on N-phenoxyamide substrates has been established using rhodium, iridium, ruthenium, palladium, cobalt, and non-metallic catalytic systems. Alkenes, alkynes, diazo compounds, and other compounds are used as substrates, and under mild reaction conditions, unique regio and stereoselectivity are employed to construct CC, CN, and CS bonds. However, many challenging problems remain to be solved.

[0057] 1) How to successfully activate the C-H bonds of N-phenoxyamides using inexpensive metals remains a future research direction;

[0058] 2) How to construct CX (F, Cl, Br, and I, etc.) bonds using mild reaction conditions;

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

[0060] This application provides a method for generating 1,2-benzisoxazole using N-phenoxyacetamide as a guide and alkyne halide as a coupling agent under rhodium catalysis:

[0061]

[0062] The 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 of N-phenoxyamides, there are few reports on the nucleophilicity of the N-center as a reaction mode. This paper enriches the method of constructing heterocyclic molecular libraries using this directing group. (3) The synthesis of the product 1,2-benzisoxazole still faces the following challenges: the traditional synthesis method starts from salicylaldehyde oxime, such a specific substrate will lead to product limitation, but the starting material in this paper is derived from phenol, and the substrate range is wide. (4) The reaction yields a multifunctionalized 1,2-benzisoxazole product, and the introduced olefin can be further transformed, such as: olefin metathesis reaction, olefin hydroboration reaction, Heck reaction, etc., providing a means to construct complex molecular libraries. (5) The true molecular energy levels were obtained by CV, PL, and UV tests, with HOMO being -4.89 eV and LUMO being -1.21 eV. This is consistent with its application as a perovskite solar cell.

[0063] This application provides a method for preparing 1,2-benzisoxazole. Under inert solvent conditions, and with the combined action of a transition metal catalyst and an oxidant, the acetylene halide of Formula III reacts with the N-phenoxyamide of Formula II. Finally, under the action of a base, the 1,2-benzisoxazole derivative of Formula I is generated. The reaction equation is as follows:

[0064]

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

[0066] The method for preparing 1,2-benzisoxazole provided in this application includes the following steps: Under inert solvent conditions, and with the combined action of a transition metal catalyst and an oxidant, the alkyne halide undergoes ortho-C-H bond alkynylation under the guidance of N-phenoxyamide, followed by intramolecular amine metallization of the carbon-carbon triple bond of the alkyne by N-phenoxyamide; finally, deacylation and β-OH elimination occur under the action of a base to generate a multifunctional 1,2-benzisoxazole derivative. Currently, the synthesis of 1,2-benzisoxazole remains challenging due to limitations in specific substrates, and this reaction is expected to provide a new approach for the development and application of 1,2-benzisoxazole derivatives. The possible reaction mechanism flow chart of the preparation method in this application is as follows:

[0067]

[0068] The specific mechanism is as follows: under the guidance of N-phenoxyamide, the alkyne halide first undergoes ortho-C-H bond alkynylation, and then N-phenoxyamide performs intramolecular amine metallization on the carbon-carbon triple bond of the alkyne. Finally, under the action of a base, the acylation group is removed and the β-OH is eliminated to generate a multifunctional 1,2-benzisoxazole derivative.

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

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

[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 or a combination of silver hexafluoroantimonate, silver bis(trifluoromethanesulfonyl)imide, sodium bicarbonate, lithium acetate, and dipotassium hydrogen phosphate.

[0073] In some 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 for 0.5 hours.

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

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

[0077] S2. React the reaction solution at 100℃ for 0.5-2 hours;

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

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

[0080] This application also provides a solar cell, which 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 described above.

[0081] The preparation method of 1,2-benzisoxazole of this application will be described in detail below with specific embodiments.

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

[0083] Under an atmospheric pressure 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 trifluoromethanesulfonylimide (1.9 mg, 0.005 mmol), lithium carbonate (14.8 mg, 0.20 mmol), silver oxide (46.2 mg, 0.20 mmol), and 1,2-dichloroethane (DCE, 1.0 mL) were added sequentially to a 15 mL Schlenk tube, and the reaction was carried out at 100 °C for 0.5 hours. The crude product was separated by silica gel chromatography using a petroleum ether (PE):ethyl acetate (EA) ratio of 40:1 as the developing or eluent, yielding 3-(cyclohexamethylene)-7-methylbenzo[d]isoxazole (1a) in 99% yield. The corresponding chemical reaction equation for this example is as follows:

[0084]

[0085] The 1H and 1C NMR spectra of the compound prepared in Example 1 are shown below. Figure 1 and Figure 2 As shown. From Figure 1 It can be seen that: 1¹H NMR (400MHz, CDCl₃) δ 7.46 (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 ¹H NMR peak energies correspond one-to-one with the target product, and the number is reasonable. Figure 2 It can be seen that: 13 C10 NMR (100MHz, CDCl3) δ 162.0, 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 correspond one-to-one with the target product, and the number is reasonable. Combining the above 1H and 1C NMR results, it can be seen that the product obtained in Example 1 is 3-(cyclohexylmethylene)-7-methylbenzo[d]isoxazole (1a).

[0086] In this embodiment, N-(o-tolyloxy)acetamide 2a contains an amide functional group that is ubiquitous in human production and daily life. Promoted by this amide functional group, it undergoes activation via aromatic ring C-H bonds, intramolecular cyclization, deacylation, and finally, β-OH elimination of the acetylene halide 1-(bromoethynyl)cyclohexane-1-ol 3a, to generate 3-(cyclohexylmethylene)-7-methylbenzo[d]isoxazole. The reaction in this embodiment only requires reacting in atmospheric air at 100°C for half an hour, followed by simple post-treatment, to obtain the final target product 3-(cyclohexylmethylene)-7-methylbenzo[d]isoxazole (1a) in excellent yield (99%).

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

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

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

[0090]

[0091] The 1H and 1C NMR spectra of the compounds prepared in Example 2 are shown below. Figure 3 and Figure 4 As shown. From Figure 3 It can be seen that: 1 ¹H NMR (400MHz, CDCl₃) δ 7.80 (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 ¹H NMR peak energies correspond one-to-one with the target product, and the number is reasonable. Figure 4 It can be seen that: 13 C10 NMR (100MHz, CDCl3) δ 163.6, 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 correspond one-to-one with the target product, and the number is reasonable. Combining the results of the above 1H and 1C NMR spectra, it can be seen that the product obtained in Example 2 is 3-(((1r, 3r, 5R, 7S)-adamantane-2-ylidene)-methyl)-5-bromobenzo[d]isoxazole (1b).

[0092] In this embodiment, N-(4-bromophenoxy)acetamide 2b contains an amide functional group that is ubiquitous in human production and daily life. Promoted by this amide functional group, it undergoes aromatic ring C-H bond activation, intramolecular cyclization, deacylation, and finally β-OH elimination of the acetylide halide (1R,3R)-2-(bromoethynyl)polytrim-2-ol 3b to generate 3-(((1r,3r,5R,7S)-adamantane-2-ylidene)-methyl)-5-bromobenzo[d]isoxazole. The reaction in this embodiment only requires reacting in atmospheric air at 100°C for half an hour, followed by simple post-treatment, to obtain the final target product 3-(((1r,3r,5R,7S)-adamantane-2-ylidene)-methyl)-5-bromobenzo[d]isoxazole (1b) in excellent yield (82%).

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

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

[0095] Under an atmospheric pressure 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 trifluoromethanesulfonylimide (1.9 mg, 0.005 mmol), lithium carbonate (14.8 mg, 0.20 mmol), silver acetate (33.4 mg, 0.20 mmol), and 1,2-dichloroethane (DCE, 1.0 mL) were added sequentially to a 15 mL Schlenk tube, and the reaction was carried out at 100 °C for 0.5 hours. The crude product was separated by silica gel chromatography using a petroleum ether (PE):ethyl acetate (EA) ratio of 40:1 as the developing or eluent, yielding the product (1-methyl-2-methyl-1-propen-1-yl)benzo[d]isoxazole (1c) in 88% yield. The corresponding chemical reaction equation for this example is as follows:

[0096]

[0097] The 1H and 1C NMR spectra of the compounds prepared in Example 3 are shown below. Figure 5 and Figure 6 As shown. From Figure 5 It can be seen that: 1¹H NMR (400MHz, CDCl₃) δ 7.46 (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 ¹H NMR peak energies correspond one-to-one with the target product, and the number is reasonable. From Figure 6 It can be seen that: 13 C10 NMR (100MHz, CDCl3) δ 162.0, 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 correspond one-to-one with the target product, and the number is reasonable. Combining the results of the above 1H and 1C NMR spectra, it can be seen that the product obtained in Example 3 is (1-methyl-2-methyl-1-propen-1-yl)benzo[d]isoxazole (1c).

[0098] In this embodiment, N-(o-tolyloxy)acetamide 2c contains an amide functional group that is ubiquitous in human production and daily life. Promoted by this amide functional group, it undergoes aromatic ring C-H bond activation, intramolecular cyclization, deacylation, and finally β-OH elimination at the acetic halide 1-bromo-2-methylbut-2-yn-2-ol 3c, generating (1-methyl-2-methyl-1-propen-1-yl)benzo[d]isoxazole. The reaction in this embodiment only requires reacting in atmospheric air at 100°C for half an hour, followed by simple post-treatment, to obtain the final target product (1-methyl-2-methyl-1-propen-1-yl)benzo[d]isoxazole (1c) in excellent yield (88%).

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

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

[0101] Under an atmospheric pressure, 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 trifluoromethanesulfonyl imide (1.9 mg, 0.005 mmol), lithium carbonate (14.8 mg, 0.20 mmol), silver acetate (33.4 mg, 0.20 mmol), and N,N'-dimethylformamide (DMF, 1.0 mL) were added sequentially to a 15 mL Schlenk tube, and the reaction was carried out at 100 °C for 1 hour. The crude product was separated by silica gel chromatography using a petroleum ether (PE):ethyl acetate (EA) ratio of 40:1, yielding product (E)-1-methyl-3-(prop-1-en-1-yl)benzo[d]isoxazole (1d) in 65% yield. The corresponding chemical reaction equation for this example is as follows:

[0102]

[0103] The 1H and 1C NMR spectra of the compound prepared in Example 4 are shown below. Figure 7 and Figure 8 As shown. From Figure 7 It can be seen that: 1 ¹H NMR (400MHz, CDCl₃) δ 7.65 (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 ¹H NMR peak energies correspond one-to-one with the target product, and the number is reasonable. From Figure 8 It can be seen that: 13 C10 NMR (100MHz, CDCl3) δ 162.8, 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 correspond one-to-one with the target product, and the number is reasonable. Combining the above 1H and 1C NMR results, it can be seen that the product obtained in Example 4 is (E)-1-methyl-3-(prop-1-en-1-yl)benzo[d]isoxazole (1d).

[0104] In this embodiment, N-(o-tolyloxy)acetamide 2d contains an amide functional group that is ubiquitous in human production and daily life. Promoted by this amide functional group, it undergoes activation via aromatic ring C-H bonds, intramolecular cyclization, deacylation, and finally β-OH elimination of the acetic halide 4-bromobut-3-yn-2-ol 3d, to generate (E)-1-methyl-3-(prop-1-en-1-yl)benzo[d]isoxazole. The reaction in this embodiment only requires reacting in atmospheric air at 100°C for half an hour, followed by simple post-treatment, to obtain the final target product (E)-1-methyl-3-(prop-1-en-1-yl)benzo[d]isoxazole (1d) in excellent yield (65%).

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

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

[0107] Under an atmospheric pressure, 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 trifluoromethanesulfonylimide (1.9 mg, 0.005 mmol), lithium carbonate (14.8 mg, 0.20 mmol), silver acetate (33.4 mg, 0.20 mmol), and 1,2-dichloroethane (DCE, 1.0 mL) were added sequentially to a 15 mL Schlenk tube, and the reaction was carried out at 100 °C for half an hour. The crude product was separated by silica gel chromatography using a petroleum ether (PE):ethyl acetate (EA) ratio of 40:1 as the developing or eluent, yielding 5-tert-butyl-3-(2,2-diphenylvinyl)benzo[d]isoxazole (1e) in 92% yield. The corresponding chemical reaction equation for this example is as follows:

[0108]

[0109] The 1H and 1C NMR spectra of the compounds prepared in Example 5 are shown below. Figure 9 and Figure 10 As shown. From Figure 9 It can be seen that: 1 ¹H NMR (400MHz, CDCl₃) δ 7.46–7.37 (m, 7H), 7.27–7.22 (m, 5H), 7.13 (s, 1H), 6.69 (s, 1H), 1.12 (s, 9H). The molecular proton NMR peak energies correspond one-to-one with the target product, and the number is reasonable. Figure 10 It can be seen that: 13 C10 NMR (100MHz, CDCl3) δ 161.9, 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 correspond one-to-one with the target product, and the number is reasonable. Combining the above 1H and 1C NMR results, it can be seen that the product obtained in Example 5 is 5-tert-butyl-3-(2,2-diphenylvinyl)benzo[d]isoxazole (1e).

[0110] In this embodiment, N-(4-(tert-butyl)phenoxy)acetamide 2e contains an amide functional group ubiquitous in human production and daily life. Promoted by this amide functional group, it undergoes aromatic ring C-H bond activation, intramolecular cyclization, deacylation, and finally β-OH elimination of the acetylide halide 3-bromo-1,1-diphenyl-2-propyn-1-ol 3e to generate 5-tert-butyl-3-(2,2-diphenylvinyl)benzo[d]isoxazole. The reaction in this embodiment only requires reacting in atmospheric air at 100°C for half an hour, followed by simple post-treatment, to obtain the final target product 5-tert-butyl-3-(2,2-diphenylvinyl)benzo[d]isoxazole (1e) in excellent yield (92%).

[0111] The chemical transformation in this embodiment uses diaryl acetylene halides, which broadens the range of acetylene halides.

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

[0113] Under an atmospheric pressure 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 trifluoromethanesulfonylimide (3.8 mg, 0.010 mmol), lithium carbonate (14.8 mg, 0.20 mmol), silver acetate (33.4 mg, 0.25 mmol), and 1,2-dichloroethane (DCE, 1.0 mL) were added sequentially to a 15 mL Schlenk tube, and the reaction was carried out at 100 °C for 1 hour. The crude product was separated by silica gel chromatography using a petroleum ether (PE):ethyl acetate (EA) ratio of 30:1, yielding product (E)-3-((2-methylcyclohexylene)-methyl)-7-methylbenzo[d]isoxazole (1f) in 66% yield. The corresponding chemical reaction equation for this example is as follows:

[0114]

[0115] The 1H and 1C NMR spectra of the compound prepared in Example 6 are shown below. Figure 11 and Figure 12 As shown. From Figure 11 It can be seen that: 1 ¹H NMR (400MHz, CDCl₃) δ 7.44 (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 ¹H peak energies correspond one-to-one with the target product, and the number is reasonable. Figure 12 It can be seen that: 13C10 NMR (100MHz, CDCl3) δ 162.0, 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 correspond one-to-one with the target product, and the number is reasonable. Combining the above 1H and 1C NMR results, it can be seen that the product obtained in Example 6 is (E)-3-((2-methylcyclohexylene)-methyl)-7-methylbenzo[d]isoxazole (1f).

[0116] In this embodiment, N-(o-tolyloxy)acetamide 2f contains an amide functional group ubiquitous in human production and daily life. Promoted by this amide functional group, it undergoes aromatic ring C-H bond activation, intramolecular cyclization, deacylation, and finally β-OH elimination at the alkyne halide 1-bromoethynyl-2-isopropyl-5-methylcyclohexane-1-ol 3f to generate (E)-3-((2-methylcyclohexylene)-methyl)-7-methylbenzo[d]isoxazole. The reaction in this embodiment only requires reacting in atmospheric air at 100°C for 1 hour, followed by simple post-treatment, to obtain the final target product (E)-3-((2-methylcyclohexylene)-methyl)-7-methylbenzo[d]isoxazole (1f) in excellent yield (66%).

[0117] The chemical transformation in this example uses menthol-derived natural product acetylsyl halides, broadening the substrate range.

[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 (1g)

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

[0120]

[0121] The 1H and 1C NMR spectra of the compounds prepared in Example 7 are shown below. Figure 13 and Figure 14 As shown. From Figure 13 It can be seen that: 1 ¹H NMR (400MHz, CDCl₃) δ 7.53 (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 ¹H NMR peak energies correspond one-to-one with the target product, and the number is reasonable. Figure 14 It can be seen that: 13C NMR (100MHz, CDCl3) δ 176.8, 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 correspond one-to-one with the target product, and the number is reasonable. Combining the above 1H NMR and 1C NMR results, 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] In this embodiment, 2g of N-(o-tolyloxy)acetamide contains amide functional groups that are ubiquitous in human production and daily life. Promoted by these amide functional groups, the product undergoes activation via aromatic ring C-H bonds, intramolecular cyclization, deacylation, and finally, β-OH elimination of 3g of acetylene halide (1S,4S)-2-(bromoethynyl)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-ol, generating (E)-3-((2-methylcyclohexylene)-methyl)-7-methylbenzo[d]isoxazole. The reaction in this embodiment only requires reacting at atmospheric pressure and air atmosphere at 100°C for 2 hours, followed by simple post-treatment, to obtain the final target product 7-methyl-3-(Z)-((1S,4S)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-ene)methyl)benzo[d]isoxazole (1g) in an excellent yield (60%).

[0123] The chemical transformation in this embodiment uses camphor-derived natural product acetylsalicylic halides, which broadens the substrate range.

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

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

[0126]

[0127] The 1H and 1C NMR spectra of the compound prepared in Example 8 are shown below. Figure 15 and Figure 16 As shown. From Figure 15 It can be seen that: 1 ¹H NMR (400MHz, CDCl₃) δ 7.79 (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 proton NMR peak energies correspond one-to-one with the target product, and the number is reasonable. Figure 16 It can be seen that: 13C10 NMR (100MHz, CDCl3) δ 162.7, 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 correspond one-to-one with the target product, and the number is reasonable. Combining the results of the above 1H and 1C NMR spectra, 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] In this embodiment, N-(4'-(diphenylamino)-[1,1'-biphenyl]-4-yl)oxy)acetamide 2h contains amide functional groups ubiquitous in human production and daily life. Promoted by these amide functional groups, it undergoes aromatic ring C-H bond activation, intramolecular cyclization, deacylation, and finally β-OH elimination of the acetylide halide (1R,3R)-2-(bromoethynyl)polytrimethylene-2-ol 3h, yielding 4-(1r,3r,5R,7S)-benzo[d]isoxazol-5-yl)-N,N-diphenylaniline. The reaction in this embodiment only requires reacting at atmospheric pressure and air atmosphere at 100°C for half an hour, followed by simple post-treatment, to obtain the final target product 4-(1r,3r,5R,7S)-benzo[d]isoxazol-5-yl)-N,N-diphenylaniline (1h) in excellent yield (78%).

[0129] In this embodiment, a donor-acceptor structure is formed by combining a triphenylamine group with excellent hole transport capability and a benzoxazole group that can act as an electron acceptor. This structure is expected to yield high-luminescent materials with high charge transfer capability and low band gap.

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

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

[0132]

[0133] The 1H and 1C NMR spectra of the compound prepared in Example 9 are shown below. Figure 17 and Figure 18 As shown. From Figure 17 It can be seen that: 1 ¹H NMR (400MHz, CDCl₃) δ 8.32 (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 proton NMR peak energies correspond one-to-one with the target product, and the number is reasonable. Figure 18 It can be seen that: 13 C10 NMR (100MHz, CDCl3) δ 196.8, 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 correspond one-to-one with the target product, and the number is reasonable. Combining the results of the above 1H and 1C NMR spectra, it can be seen that the product obtained in Example 9 is 1-(3-(((1R,3R,5R,7S)-adamantane-2-ylidene)methyl)benzo[d]isoxazol-5-yl)ethyl-1-one (1i).

[0134] In this embodiment, N-(4-acetylphenoxy)acetamide 2i contains amide functional groups that are ubiquitous in human production and daily life. Promoted by these amide functional groups, it undergoes aromatic ring C-H bond activation, intramolecular cyclization, deacylation, and finally β-OH elimination of the acetylide halide (1R,3R)-2-(bromoethynyl)polytrim-2-ol 3i to generate 1-(3-(((1R,3R,5R,7S)-adamantane-2-ylidene)methyl)benzo[d]isoxazol-5-yl)ethyl-1-one. The reaction in this embodiment only requires reacting in atmospheric air at 100°C for half an hour, followed by simple post-treatment, to obtain the final target product 1-(3-(((1R,3R,5R,7S)-adamantane-2-ylidene)methyl)benzo[d]isoxazol-5-yl)ethyl-1-one (1i) in 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-(cyclohexylmethylene)benzo[D]isoxazole-5-carboxylate (1j)

[0137] Under an atmospheric pressure, methyl 4-(acetaminophen)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 trifluoromethanesulfonylimide (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 sequentially to a 15 mL Schlenk tube, and the reaction was carried out at 100 °C for half an hour. The crude product was separated by silica gel chromatography using a petroleum ether (PE):ethyl acetate (EA) ratio of 40:1 as the developing solvent or eluent, yielding methyl 3-(cyclohexylmethyl)benzo[D]isoxazole-5-carboxylate (1j) in 78% yield. The corresponding chemical reaction equation for this example is as follows:

[0138]

[0139] The 1H and 1C NMR spectra of the compound prepared in Example 10 are shown below. Figure 19 and Figure 20 As shown. From Figure 19 It can be seen that: 1¹H NMR (400MHz, CDCl₃) δ 8.42–8.39 (m, 1H), 8.24 (dd, J = 8.8, 1.6 Hz, 1H), 7.58 (d, J = 8.8 Hz, 1H), 6.24 (s, 1H), 3.96 (s, 3H), 2.71 (d, J = 5.6 Hz, 2H), 2.42 (dd, J = 6.0, 5.2 Hz, 2H), 1.76–1.72 (m, 2H), 1.67–1.64 (m, 4H). The molecular proton NMR peak energies correspond one-to-one with the target product, and the number is reasonable. Figure 20 It can be seen that: 13 C10 NMR (100MHz, CDCl3) δ 166.6, 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 correspond one-to-one with the target product, and the number is reasonable. Combining the above 1H and 1C NMR results, it can be seen that the product obtained in Example 10 is methyl 3-(cyclohexylmethyl)benzo[D]isoxazole-5-carboxylic acid (1j).

[0140] In this embodiment, methyl 4-(acetaminooxy)benzoate 2j contains an amide functional group ubiquitous in human production and daily life. Promoted by this amide functional group, it undergoes aromatic ring C-H bond activation, intramolecular cyclization, deacylation, and finally β-OH elimination of the acetylide halide 1-(bromoethynyl)cyclohexane-1-ol 3j, yielding methyl 3-(cyclohexylmethylene)benzo[D]isoxazole-5-carboxylic acid. The reaction in this embodiment only requires reacting in atmospheric pressure at 100°C for half an hour, followed by simple post-treatment, to obtain the final target product, methyl 3-(cyclohexylmethylene)benzo[D]isoxazole-5-carboxylic acid (1j), in excellent yield (78%).

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

[0142] Application Example: Hole Transport Material Molecule for Perovskite Solar Cells: Preparation and Characterization of 4-(1r,3r,5R,7S)-Benzo[d]isoxazol-5-yl)-N,N-diphenylaniline (1h)

[0143] In the material characterization of the 1h molecule, we found that it exhibited good hole transport material properties, specifically, due to... Figure 21 , 22It can be calculated that the highest occupied molecular orbital (HOMO) of 1h is delocalized throughout the molecule, which is beneficial for charge transport, while the lowest unoccupied molecular orbital (LUMO) is mainly located on the core framework. The overlap of HOMO and LUMO orbitals is beneficial for hole extraction, and the E1h is calculated by DFT. HOMO or E LUMO The values ​​are -4.89 / -1.21 eV, which meet the requirements for hole transport materials in perovskite solar cells. The application of this 1,2-benzisoxazole derivative to perovskite solar cells will be described in detail below.

[0144] 3.5 mg of the compound was dissolved in 1 mL of chlorobenzene solvent and spin-coated onto a cleaned conductive glass substrate at 4000 rpm, followed by annealing at 100 °C for 10 min. After cooling, the perovskite precursor solution was spin-coated onto the substrate sequentially at 1000 rpm and 5000 rpm, and annealed at 100 °C for 30 min. After cooling to room temperature, a chlorobenzene solution of [6,6]-phenyl-C61-butyrate isomethyl ester (PCBM) was spin-coated onto the perovskite layer and annealed at 65 °C for 10 min. After cooling, copper bath (BCP) was spin-coated onto the PCBM and annealed at 65 °C for 5 min. Finally, a metal electrode was deposited under high vacuum. Figure 23 As shown, the JV curve was measured under one sun. The optimal device performance is: short-circuit current density of 24.4849 mA / cm². -2 The open-circuit voltage was 1.0549V, the fill factor was 61.97%, and the power conversion efficiency was 16.01%. Previously, in studies of triphenylamine's application as a hole transport material in perovskite solar cells, the transport efficiency was around 15% (Chem. Soc. Rev. 2022, 51, 5974-6064). Based on the above photovoltaic parameters, it can be analyzed that interfacial carrier transfer can be achieved in 1 hour, consistent with expectations.

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

[0146]

[0147] In summary, this application provides a method for preparing 1,2-benzisoxazole. Under inert solvent conditions, and with the combined action of a transition metal catalyst and an oxidant, the acetylene halide of Formula III reacts with the N-phenoxyamide of Formula II. Finally, under the action of a base, the 1,2-benzisoxazole derivative of Formula I is generated. The reaction equation is as follows:

[0148]

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

[0150] This preparation method is the first to develop a way to generate 1,2-benzisoxazole using N-phenoxyamide as a substrate and alkyne halide as a coupling agent under rhodium(III) catalysis via a CH activation strategy. Under inert solvent conditions, and with the combined action of a transition metal catalyst and an oxidant, the alkyne halide first forms an ortho-alkynylated product under the guidance of N-phenoxyamide. Subsequently, due to the nucleophilicity of N, it undergoes intramolecular cyclization with the alkyne, followed by deacylation under the action of a base, and finally β-OH elimination 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, and these three functional groups are widely present in natural products.

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

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

[0155] (4) This reaction yields a multifunctionalized 1,2-benzisoxazole product. The introduced olefin can undergo further transformations such as metathesis, hydroboration, and Heck reactions, providing a means to construct complex molecular libraries. The actual molecular energy levels were obtained through CV, PL, and UV measurements, with the HOMO at -4.89 and the LUMO at -1.21. This aligns with its application as a perovskite solar cell.

[0156] This application provides a method for preparing a multifunctional 1,2-benzisoxazole derivative. This method is the first to develop a way to generate 1,2-benzisoxazole using an CH activation strategy under rhodium(III) catalysis, with N-phenoxyamide as the substrate and alkyne halide as the coupling agent. Under inert solvent conditions, and with the combined action of a transition metal catalyst and an oxidant, the alkyne halide first undergoes ortho-C-H bond alkynylation under the guidance of N-phenoxyamide, followed by intramolecular amine metallation of the carbon-carbon triple bond of the alkyne by N-phenoxyamide; finally, deacylation and β-OH elimination occur under the action of a base to generate a multifunctional 1,2-benzisoxazole derivative. It should be noted that currently, the synthesis of 1,2-benzisoxazole still faces challenges due to limitations in specific substrates (multi-step synthesis, poor functional group compatibility). This reaction is expected to provide a new approach for the development and application of 1,2-benzisoxazole derivatives. The obtained 1h product exhibits performance as a hole transport layer material in solar cells (the triphenylamine-benzisoxazole framework in this application can achieve a power conversion efficiency of 16.01%. Previously, the transport efficiency of triphenylamine in the study of hole transport materials for perovskite solar cells was around 15% (Chem.Soc.Rev.2022,51,5974-6064.)).

[0157] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "illustrative embodiment," "example," "specific example," or "some examples," etc., refer to specific features, structures, materials, or characteristics described in connection with an embodiment or example that are included in at least one embodiment or example of this application. Moreover, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples.

[0158] Although several embodiments of this application have been shown and described, those skilled in the art will understand that various changes, modifications, substitutions and variations can be made to these embodiments without departing from the principles and spirit of this application, the scope of which is defined by the claims and their equivalents.

Claims

1. A method for preparing 1,2-benzisoxazole, characterized in that, Under inert solvent conditions, and with the combined action of a transition metal catalyst and an oxidant, the acetylene halide of Formula III reacts with the N-phenoxyamide of Formula II; finally, under the action of a base, the 1,2-benzisoxazole derivative of Formula I is generated, and the reaction equation is as follows: ； The amount of transition metal catalyst used is 2 mol% of the amount of N-phenoxyamide shown in Formula II. The catalyst is any one or a combination of pentamethylcyclopentadienyl rhodium chloride dimer, pentamethylcyclopentadienyl iridium chloride dimer, palladium acetate, dichloro(p-methylisopropylphenyl)ruthenium dimer, cobalt acetylacetonate, and manganese pentacarbonyl bromide. The oxidant is any one or more of silver acetate, silver carbonate, silver oxide, and potassium persulfate. The 1,2-benzisoxazole derivative shown in Formula I is selected from one of the following structural formulas: , , , , , , , and .

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

3. 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.

4. The method for preparing 1,2-benzisoxazole according to claim 1, characterized in that, The reaction was carried out at 60–100°C for 0.5 hours.

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

6. The method for preparing 1,2-benzisoxazole according to claim 5, characterized in that, The developing agent or eluent selected in the column chromatography separation technique is petroleum ether and ethyl acetate, and the ratio of petroleum ether to ethyl acetate is 40:

1.

7. 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 derivative prepared by the preparation method described in claim 1.

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