Mechanically driven synthesis method of hydroarylation product

Abstract

The invention relates to a mechanically driven synthesis method of a hydroarylation product in the technical field of mechanochemical synthesis, which comprises the following steps: taking aryl or alkyl acrylamide as shown in a formula 1a and aryl halide as shown in a formula 2a as substrates, and taking a piezoelectric material as a catalyst; a hydroarylation product as shown in a formula 3 is synthesized in a mechanical driving mode under the conditions of a liquid auxiliary grinding agent (LAG) and an alkaline substance, and the synthesis route is as shown in the specification. The synthesis method provided by the invention has the advantages of high efficiency and greenness.

Description

Technical Field

[0001] This invention relates to the field of mechanochemical synthesis technology, specifically to a mechanically driven synthesis method for hydrogen arylation products. Background Technology

[0002] β-arylamides are an important class of pharmaceutical intermediates with great potential for treating or preventing pain, especially neuropathic pain. Their synthesis can be relatively easily achieved through the hydroarylation of olefins; however, traditional olefin hydroarylation reactions face multiple challenges: noble metal catalysis systems not only rely on scarce metal resources such as palladium and rhodium, but their demanding reaction conditions (high temperature, high pressure) and complex ligand design also lead to increased synthesis costs. Furthermore, they present challenges to green chemistry, including heavy metal pollution, solvent abuse, and safety risks.

[0003] In recent years, mechanically driven processes have offered innovative pathways to address the aforementioned challenges due to their unique energy input methods and green chemistry characteristics. Compared to traditional liquid-phase catalytic systems, mechanochemical methods directly drive reactions using mechanical energy such as ball milling, eliminating the need for solvents and fundamentally removing the environmental burden of organic solvents. Simultaneously, this method avoids the use of precious metal catalysts, achieving efficient conversion at room temperature or lower temperatures, significantly reducing energy consumption and equipment requirements. Mechanical force also promotes close contact between reactants, accelerates reaction kinetics, reduces byproduct formation, and improves atom economy. Furthermore, mechanically driven processes are simple to operate, highly safe, and easily scaled up, opening up a sustainable new route for the green, low-cost, large-scale synthesis of β-arylamide drugs. Therefore, leveraging these advantages of mechanically driven processes to develop an efficient and green synthetic method provides a new strategy for the construction of hydroarylized products, possessing significant theoretical innovation and practical application value. Summary of the Invention

[0004] The present invention aims to provide an efficient and green mechanically driven synthesis method for hydrogenated aryl products.

[0005] To achieve the above objectives, the present invention adopts the following technical solution: a mechanically driven synthesis method for hydrogen aryl products, comprising the following steps: using aryl or alkyl acrylamides of formula 1a and aryl halides of formula 2a as substrates, and piezoelectric materials as catalysts, the hydrogen aryl products of formula 3 are synthesized mechanically under conditions of liquid assisted abrasive (LAG) and alkaline substances. The synthesis route is shown in the figure below: ; R1 is independently selected from methyl, phenyl, 2-methylphenyl, 2-isopropylphenyl, 2-chlorophenyl, 2-bromophenyl, 2-iodophenyl, 2-pyrrolephenyl, 3-methylphenyl, 4-methylphenyl, 4-methoxyphenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 2,6-dimethylphenyl, 2-naphthyl, 2-phenylprophiazolyl; R2 is independently selected from hydrogen, methyl, ethyl, and phenyl; R3 is independently selected from hydrogen and methyl; R4 is independently selected from hydrogen, 5-methyl, 5-methoxy, 5-fluoro, 5-trifluoromethyl, 3-methyl, 6-methyl, 4-trifluoromethyl, and 6-trifluoromethyl. n is the number of carbon atoms, either 0 or 1; X is a halogen (chlorine, bromine, iodine); A represents the type of atom (carbon or nitrogen). The beneficial effects of this scheme are as follows: This scheme employs mechanical driving combined with piezoelectric catalysis, conducting the reaction under solvent-free or minimally soluble liquid assisted abrasive (LAG) conditions, significantly reducing the use of organic solvents, lowering environmental pollution, and meeting the requirements of green chemistry. Simultaneously, replacing traditional precious metal catalysts with piezoelectric materials avoids the use of scarce metals such as palladium and rhodium, reducing costs and eliminating heavy metal residues. The reaction can proceed efficiently at room temperature and pressure, with mild conditions, safe operation, low energy consumption, and easy scale-up. The method has a wide substrate applicability, including various electron-donating and electron-withdrawing groups and heterocyclic structures, with good functional group compatibility. It can selectively construct β-arylamide products with well-defined structures, high yields, few side reactions, and simple post-processing. The synthesized products have important application value in the development of pharmaceutical intermediates, especially neuropathic pain treatment agents, providing a new route for green drug synthesis. Furthermore, this invention also provides a new strategy for the mechanochemical construction of C–C bonds, enriching the methodology of mechano-organic synthesis, and possesses strong theoretical innovation and practical application potential.

[0006] Furthermore, the piezoelectric material is one of barium titanate, zinc oxide, copper borate, and titanium dioxide.

[0007] Furthermore, the piezoelectric material is barium titanate, which is prepared by hydrothermal synthesis combined with heat treatment at a temperature of 0~1000°C. o C, heat treatment time is 1-6 hours. The preferred heat treatment temperature is 700°C. o C.

[0008] Furthermore, the amounts of the aryl or alkyl acrylamide 1a, aryl halide 2a, piezoelectric material, liquid auxiliary abrasive and alkaline substance added are 0.1~1.5 mmol (1 equiv), 2~5 equiv, 0~250 mg, 0~0.3 μL / mg, and 0~3 equiv, respectively.

[0009] Furthermore, the alkaline substance is at least one selected from cesium carbonate, potassium carbonate, potassium bicarbonate, sodium carbonate, sodium bicarbonate, sodium hydroxide, potassium hydroxide, potassium tert-butoxide, triethylamine, and diethylamine. Cesium carbonate is preferred.

[0010] Furthermore, the liquid auxiliary abrasive is at least one of DMSO (dimethyl sulfoxide), DMF (N,N-dimethylformamide), DCM (dichloromethane), THF (tetrahydrofuran), MeCN (acetonitrile), Acetone (acetone), 1,4-Dioxane (1,4-dioxane), H2O (water), MeOH (methanol), n-hexane (n-hexane), and Toluene (toluene), or solvent-free. DMSO is preferred.

[0011] Furthermore, the amount of the liquid-assisted grinding agent is 0~0.3 μL / mg; preferably 0.2 μL / mg. The amount of liquid-assisted grinding agent refers to the ratio of the liquid volume to the weight of all solid substances in the system, and is therefore relative to the solid substances in the reaction system.

[0012] Furthermore, the ball-to-material ratio of the mechanically driven device is 35:1 to 245:1; when the substrate concentration is 0.1 mmol, the preferred ball-to-material ratio is 130:1, and when the substrate concentration is 0.3 mmol, the preferred ball-to-material ratio is 100:1.

[0013] Furthermore, the ball milling speed is 400~600 rpm; preferably 500 rpm.

[0014] Furthermore, the reaction time of the mechanical drive is 3 to 36 hours; preferably 18 hours.

[0015] Furthermore, the reaction atmosphere is at least one of argon, vacuum, air, or oxygen; argon is preferred.

[0016] Furthermore, the mechanically driven milling media is at least one of stainless steel balls, tungsten carbide balls, alumina balls, and agate balls; stainless steel balls are preferred. Attached Figure Description

[0017] Figure 1The following is a comparison chart for screening conditions (I); where A1 is a screening bar chart for catalyst type; A2 is a screening bar chart for catalyst calcination temperature; A3 is a screening bar chart for substrate equivalence ratio; A4 is a screening bar chart for catalyst dosage; A5 is a screening bar chart for base type; and A6 is a screening bar chart for base dosage.

[0018] Figure 2 The following is a comparison chart for conditional screening (II); where A7 is a screening bar chart for LAG types; A8 is a screening bar chart for LAG dosage; A9 is a screening bar chart for ball-to-material ratio with a substrate concentration of 0.1 mmol; A10 is a screening bar chart for ball-to-material ratio with a substrate concentration of 0.3 mmol; A11 is a screening bar chart for ball milling speed; and A12 is a screening bar chart for reaction time.

[0019] Figure 3 The following is a comparison chart of screening conditions (III); where A13 is a screening bar chart of reaction atmosphere; A14 is a screening bar chart of ball milling media; A15 is a bar chart of barium titanate thermogravimetric curve monitoring; and A16 is the XRD obtained by calcining barium titanate at different temperatures in air atmosphere.

[0020] Figure 4 This is a comparison of the morphological changes of barium titanate before and after calcination.

[0021] Figure 5 This is a SEM image of the piezoelectric material after one cycle.

[0022] Figure 6 A bar chart comparing the effects of adding different trapping agents to the reaction system. Detailed Implementation

[0023] The following detailed description illustrates the specific implementation method: Example 1 Using N-methyl-N-phenylmethylacrylamide (1a, 0.1 mmol, 17.5 mg) and 2-bromo-5-(trifluoromethyl)pyridine (2a, 3 equiv., 0.3 mmol, 67.8 mg) as template substrates, DMSO (0.2 μL / mg) as liquid auxiliary abrasive (LAG), Cs₂CO₃ (2 equiv.) as base, and barium titanate (200 mg) as piezoelectric catalyst, 10 stainless steel balls with a diameter of 10 mm and 30 stainless steel balls with a diameter of 5 mm were added to a 100 mL vacuum stainless steel container. The rotation speed was set to 500 rpm, the reaction atmosphere was argon, and the reaction time was 12 h as the initial reaction conditions. Under the initial reaction conditions, different materials (no material, ZnO, CBO, PbTiO₃, g-C₃N₄, commercial BTO, BTO, TiO₂, BaCO₃) were investigated. Figure 1-A1), experimental results show that although ZnO and TiO2 possess catalytic activity, their yields (27.1% and 23.4%, respectively) are significantly lower than those of copper borate (CBO, 43.2%) and barium titanate (BTO, 51% and 66.7%, respectively). This difference may be related to the polarization electric field strength and carrier migration efficiency of piezoelectric materials. For example, barium titanate has a piezoelectric coefficient as high as 190 pm / V, which can generate a strong piezoelectric potential under mechanical stress, effectively separating electron-hole pairs and lowering the activation energy barrier of CC coupling. In addition, hydrothermally synthesized barium titanate (BTO, 66.7% yield) is significantly better than commercial barium titanate (BaTiO3, 51% yield), which may be attributed to the higher oxygen vacancy concentration and more uniform nanoscale grains of hydrothermally synthesized particles, thereby optimizing carrier dynamics. Notably, lead titanate (PbTiO3) and carbon nitride (g-C3N4) did not exhibit catalytic activity. The results of the blank experiment (conversion rate 4.4%) and the control results of barium carbonate (BaCO3, conversion rate 14.0%), a non-piezoelectric material, further verified the necessity of the piezoelectric effect in catalysis. Therefore, barium titanate (BTO) synthesized hydrothermally was selected as the optimal piezoelectric material.

[0024] Example 2 Based on the piezoelectric material BTO in Example 1, the heat treatment temperature of BTO was adjusted to (100-1000 °C). o C) Perform screening ( Figure 1 -A2), experimental results show that its yield exhibits a specific pattern with calcination temperature. At low-temperature calcination (100-500℃), the yield varies with calcination temperature. o In step C), production first increases and then decreases, reaching 300. o The highest yield of 83.7% was achieved at temperature C. This is likely because at lower temperatures, oxygen vacancies begin to become ordered, promoting electron transport. However, as the temperature increases further, the material structure begins to change, leading to a decrease in yield. High-temperature calcination (600-1000 °C) further contributes to this yield. o In case C), the yield also first increases and then decreases slightly, reaching 700. o The highest yield of 88.2% was achieved at calcination temperature C. It is worth noting that the yield was highest at calcination temperature 600°C. o At calcination temperature C, the yield decreased to 58.1%, likely due to a phase transition in BTO at this temperature, leading to a reduction in catalytically active sites and consequently decreased catalytic performance. The yield was higher at calcination at 700 °C than at 300 °C. This is probably because at 700 °C, oxygen vacancy migration and structural rearrangement in the material reach their optimal state, forming more efficient electron transport channels and thus improving catalytic performance. Therefore, 700 °C was chosen as the optimal calcination temperature.

[0025] Example 3 Based on Example 2, the equivalence ratio (2~5 equivalents) of substrate 2a was screened. Figure 1 Experimental results (-A3) show that the yield increases non-linearly with increasing 2a equivalents: when 2a is increased from 2 equiv. to 3 equiv., the yield increases from 74.2% to 88.2%, indicating that increasing the substrate concentration can effectively drive the reaction forward; further increasing to 4 equiv., the yield only increases by about 1% to 89.3%; and further increasing to 5 equiv., the yield tends to stabilize. Based on the principle of maximizing yield, 4 equiv. 2a was ultimately selected as the baseline condition for subsequent optimization. However, it is worth noting that, considering the balance between economics and reaction efficiency for industrial applications, 3 equiv. 2a may be a more practical compromise.

[0026] Example 4 Based on the substrate equivalent in Example 3, the catalyst dosages (50, 100, 150, 200, 250 mg) were further screened. Figure 1 (-A4) Experimental results showed that when the catalyst dosage increased from 50 mg to 200 mg, the yield jumped from 10.3% to 89.3%, indicating that the increased density of active sites effectively promoted the catalytic cycle. However, when the dosage was further increased to 250 mg, the yield slightly decreased to 83.2%. This phenomenon may be because excess catalyst particles increase the system viscosity, reduce the substrate diffusion rate, and cause mass transfer limitations. Therefore, 200 mg was selected as the optimal catalyst dosage.

[0027] Example 5 Based on the catalyst dosage in Example 4, the types of alkalis (Cs2CO3, K2CO3, KHCO3, Na2CO3, NaHCO3, NaOH, KOH, t-BuOK, Et3N, DEA) were further screened. Figure 1 Experimental results showed that Cs₂CO₃ exhibited the best catalytic effect (yield 89.3%). Furthermore, strong bases such as NaOH, KOH, and t-BuOK also showed high yields, at 83.3%, 86.3%, and 85.5%, respectively. In contrast, bases such as Na₂CO₃, Et₃N, and DEA had lower yields, at 37.5%, 26.3%, and 26.6%, respectively. Theoretical analysis of the experimental results indicates that the catalytic efficiency is positively correlated with the basicity. In cesium carbonate, Cs₂CO₃… + Its larger ionic radius results in a lower charge density, which weakens its resistance to CO3. 2-The polarization effect of cesium carbonate makes it easier for carbonate ions to release basic sites, thereby more effectively promoting the formation and stabilization of reaction intermediates. This mechanism also explains the decreasing trend in catalytic efficiency between K₂CO₃ and Na₂CO₃. Therefore, cesium carbonate was determined to be the optimal base.

[0028] Example 6 Based on the types of alkali used in Example 5, the dosage of alkali (0, 1, 2, 3 equiv.) was further screened. Figure 1 Experimental results (-A6) show that even without the addition of a base, the reaction still achieves a 24% yield. This phenomenon verifies that mechanically driven piezoelectric materials can directly induce the C-Br bond breakage of aryl halides, generating initial free radical species. However, the catalytic efficiency of the system without a base is low, possibly because the generated bromide ions quench the free radical reaction, while the base can stabilize the bromide ions and promote the forward reaction. When the amount of base is gradually increased to 2 equiv., the yield significantly increases to 89.3%, while further increasing the amount of base inhibits the reaction. Therefore, the amount of base is chosen to be 2 equiv.

[0029] Example 7 Based on the amount of alkali used in Example 6, further screening was conducted on the types of liquid-assisted grinding (LAG) (DMSO, DMF, DCM, THF, MeCN, Acetone, 1,4-Dioxane, H2O, MeOH, n-hexane, Toluene) and solvent-free systems. Figure 2 Experimental results show that DMSO, when used as an additive, significantly outperforms other systems in terms of product yield. This is likely because DMSO's high dielectric constant effectively stabilizes the charge formed on the surface of piezoelectric materials, prolonging carrier lifetime and enhancing catalytic activity. Furthermore, DMSO's moderate vapor pressure ensures solvent stability during grinding while avoiding excessive evaporation that could hinder mass transfer. Compared to solvents like DMF, DMSO has higher surface tension, which facilitates the formation of a uniform liquid film encapsulating solid particles during ball milling, ensuring effective mechanical force transfer and increasing reactant contact area. In contrast, low surface tension solvents like n-hexane tend to cause particle agglomeration, resulting in lower catalytic efficiency. Therefore, DMSO was chosen as the optimal additive (LAG).

[0030] Example 8 Based on the types of LAGs in Example 7, the dosage of LAGs (0-0.3 μL / mg, in intervals of 0.05 μL / mg) was further screened. Figure 2Experimental results (-A8) show that the solvent-free system still achieves a yield of 16.5%, while the reaction efficiency after introducing LAG exhibits an evolution trend of first increasing and then slowing down: when the addition amount reaches 0.2 μL / mg, a peak yield of 89.3% is obtained, which is 5.4 times higher than that of the solvent-free system; when the addition amount is further increased to 0.3 μL / mg, the yield decreases to 84.2%. It is speculated that the optimal point of 0.2 μL / mg achieves the best balance between solid-liquid dispersion and mechanical energy transfer efficiency, while excessive solvent may form an excessively thick liquid film, hindering the effective stress loading of the piezoelectric material by the ball milling media, and reducing the diffusion rate of reactants. Therefore, 0.2 μL / mg is determined to be the optimal LAG dosage.

[0031] Example 9 Based on the LAG dosage in Example 8, the ball-to-particle ratio (65:1 ~ 245:1) was further screened. Figure 2 -A9), experimental results show that when the ball-to-material ratio is too low (e.g., 65:1), insufficient ball milling media leads to a reduced probability of effective collisions, with only a portion of the material participating in the reaction (yield 20.2%). The optimal ball-to-material ratio (130:1) achieves the best balance between collision intensity and contact area (yield 89.3%). A high ball-to-material ratio (above 195:1) leads to an increase in ineffective collisions and a decrease in energy utilization (yield drops to 83%). Furthermore, an optimization strategy using a 3:1 ratio of large balls (10 mm) to small balls (5 mm) was employed. The large balls provide high-intensity impact crushing of particles and provide energy, while the small balls increase the contact area and improve grinding efficiency. Therefore, the optimal ball-to-material ratio is 130:1 when the substrate concentration is 0.1 mmol.

[0032] Example 10 Based on the pellet-to-substrate ratio in Example 9, the substrate concentration was further increased to 0.3 mmol, and screening was continued for pellet-to-substrate ratios (35:1 ~ 130:1). Figure 2 (-A10) Experimental results show that in a 0.3 mmol scale-up system, although a ball-to-material ratio of 130:1 can achieve a yield of 76.1% (a 4% improvement over 100:1), it requires an increase of 30% in grinding media, which does not meet the economic principles of industrial scale-up. Furthermore, a high ball-to-material ratio reduces the media collision space, leading to more material residue. Therefore, considering all factors, a ball-to-material ratio of 100:1 is selected as the optimal ratio when the substrate concentration is 0.3 mmol.

[0033] Example 11 Based on the ball-to-material ratio in Example 10, the ball milling speed (400~600 rpm) was further screened. Figure 2-A11), experimental results show that the maximum yield is 80.3% at 500 rpm, while the yields at 400 rpm and 600 rpm are 66.7% and 77.7%, respectively. The energy required for material deformation during ball milling comes from the impact and shearing action of the grinding balls. Piezoelectric materials have cubic and tetragonal phases. Under the combined action of frictional shearing and normal impact, the energy required for material deformation mainly comes from the impact during ball milling. When the ball milling speed is low (400 rpm), the mutual motion of the balls is mainly due to friction or shearing, and the proportion of impact is very small, which may not provide enough energy. As the ball milling speed increases (500 rpm), the proportion of impact increases, while friction and shearing decrease, and the ball milling mechanism becomes mainly impact-based. However, higher ball milling energy is not always better (600 rpm). Excessive impact may lead to nano-agglomeration of grains, increasing the specific surface area but decreasing the polarization intensity, resulting in a decrease in catalytic performance. Therefore, 500 rpm is the optimal ball milling speed.

[0034] Example 12 Based on the ball milling speed in Example 11, the reaction time (3~36 h) was further screened. Figure 2 The reaction results (-A12) show that the reaction yield increases non-linearly with grinding time: the yield increases rapidly in the first 9 hours; the rate of increase gradually slows down from 9 to 15 hours; and after 18 hours, the reaction enters the kinetic equilibrium period, and the yield tends to stabilize. Therefore, 18 hours was selected as the optimal reaction time.

[0035] Example 13 Based on the reaction time in Example 12, the reaction atmosphere (air, oxygen, argon, and vacuum) was further screened. Figure 3 (-A13) Experimental results show that the reaction was completely inhibited under air and oxygen conditions, with no target product formed. Under argon and vacuum conditions, the reactivity was similar, with yields of 80.3% and 76%, respectively. This indicates that the reaction requires a strictly inert atmosphere for protection. This may be because the free radical intermediate is easily quenched by O2, while argon and vacuum can effectively isolate oxygen and maintain the free radical chain reaction. Therefore, argon was chosen as the optimal reaction atmosphere.

[0036] Example 14 Based on the reaction atmosphere of Example 13, the types of milling media (stainless steel balls, tungsten carbide balls, alumina balls, and agate balls) were further screened. Figure 3(-A14) Experimental results show that the reaction performance of the four grinding media differs significantly: the reaction is almost completely suppressed when agate balls are used as grinding media; the yields of tungsten carbide balls (48%) and alumina balls (48.6%) are similar and at a moderate level; while stainless steel balls show an absolute advantage with a yield of 80.3%. Further analysis shows that the low efficiency of agate balls stems from insufficient kinetic energy due to their low density, which prevents the piezoelectric material from undergoing effective mechanical deformation to induce polarization charge separation; although tungsten carbide and alumina balls have higher densities, their high hardness causes energy to dissipate through elastic deformation, and their surface inertia inhibits electron transfer; in contrast, stainless steel balls, through the synergistic effect of density-hardness-conductivity, can both trigger effective polarization of the piezoelectric material during collision and conduct electron transfer through the metal surface, thereby significantly improving the reaction efficiency. Therefore, stainless steel balls are selected as the optimal grinding media.

[0037] Example 15 To evaluate the thermal stability, composition, and decomposition behavior of barium titanate, and thus provide a theoretical basis for optimizing its heat treatment modification process, this invention uses barium titanate prepared by a two-step hydrothermal method as the research object and conducts thermogravimetric characterization tests. The test conditions were set as follows: under air atmosphere, the temperature was increased from room temperature to 1000 °C at a rate of 5 °C / min, and the sample mass change was monitored by thermogravimetric curves. The test results are as follows. Figure 3 As shown in Figure A15, the thermogravimetric (TG) curves reveal a weight loss of 0.4 wt% in the range of 0–252 °C, increasing to 1.2 wt% in the range of 252–356 °C, 0.7 wt% in the range of 356–500 °C, 0.4 wt% in the range of 500–700 °C, 0.6 wt% in the range of 700–800 °C, and 0.3% in the range of 800–1000 °C, with a total weight loss of only 3.6 wt%, indicating good thermal stability of the material. The differential thermogravimetric (DTG) curves show three distinct weight loss peaks at temperatures of 310.4, 415.8, and 772.2 °C, corresponding to three phase transitions. Based on literature analysis, the weight loss peak at 310.4 °C corresponds to the dehydration reaction of residual hydroxyl groups on the barium titanate surface, and its removal temperature range is consistent with the thermal decomposition behavior of hydroxyl groups on the titanium oxide surface (250~450 °C). The weight loss at 415.8 °C may originate from the oxidative decomposition of residual organic impurities during synthesis. The weight loss peak at 772.2 °C is speculated to be related to the further reaction of trace inorganic impurities (such as unreacted TiO2) or grain boundary migration at high temperatures. This thermogravimetric curve fully reveals the entire process of hydrothermal BTO from the removal of physically adsorbed water, decomposition of hydroxyl / organic matter to the pyrolysis of impurities, confirming the literature conclusion that "surface adsorption and impurity control should be considered for hydrothermal products," and providing a basis for optimizing the material calcination process (such as removing impurities and stabilizing the crystal phase).

[0038] Example 16 To determine the crystal structure and phase transition of barium titanate, X-ray diffraction (XRD) was used for qualitative phase analysis of the sample. Figure 3 -A16 shows barium titanate (no calcined) obtained by hydrothermal synthesis and its reaction in air at 100~1000°C. o XRD patterns were obtained from a series of materials calcined at C for 2 hours. The results showed that all samples exhibited sharp diffraction peaks, with the main peak position consistent with the BaTiO3 standard card (PDF#04-007-6865, Pm3m), confirming the successful synthesis of pure-phase barium titanate. Notably, the diffraction peaks of the uncalcined samples were weaker and relatively wider, indicating lower crystallinity and smaller grain size. This may be due to lattice defects or residual stress during the hydrothermal synthesis process.

[0039] Example 17 To investigate the morphological changes of barium titanate before and after calcination and to reveal the influence of heat treatment processes on the microstructure of the material, scanning electron microscopy (SEM) was used to observe the morphological characteristics of uncalcined BTO and BTO calcined at 700 ℃ for 2 hours (BTO-700). Differences in particle distribution, agglomeration state, pore structure, and crystal morphology were compared at different magnifications (low, medium, and high). Figure 4As shown, (a-c) are SEM images of BTO, and (d-f) are SEM images of BTO-700. From the overall morphology, the uncalcined BTO particles are relatively randomly distributed and show obvious agglomeration, possibly because their internal atomic arrangement is disordered, lacking sufficient energy for atomic migration and the formation of a regular crystal structure. In contrast, the calcined BTO-700 nanorod-like structure is clearer and more prominent, with increased porosity and more distinct particle boundaries. This is because the high temperature at 700 ℃ provides sufficient activation energy for the atoms, prompting them to overcome the lattice energy barrier and migrate and rearrange, arranging themselves according to the regular crystal structure of barium titanate, gradually forming a nanorod-like crystal structure. At different magnifications, BTO exhibits a densely packed particle structure at low magnification, irregular particle shapes at medium magnification, and a relatively rough particle surface at high magnification. BTO-700 shows a distinct rod-like structure dispersed throughout the system at low magnification, with the rod-like structure becoming clearer and showing some orientation at medium magnification, and a relatively smooth surface at high magnification. The primary particles composing the rod-like structure are tightly packed. This is because during high-temperature calcination, smaller particles undergo Ostwald ripening through mechanisms such as surface atomic diffusion. This process involves the gradual dissolution of smaller particles and the deposition of solute on the surface of larger particles, leading to continuous growth of larger particles and thus a more pronounced nanorod-like structure after calcination. Simultaneously, the high temperature may cause some surface-adsorbed organic matter to volatilize, reducing agglomeration caused by organic bridging between particles, resulting in clearer particle boundaries and a smoother surface structure. The increased porosity after calcination increases the specific surface area of ​​the material, providing abundant active sites for reactants, which is beneficial for the adsorption of reactant molecules and thus improves catalytic efficiency. In addition, the crystallinity of the material is significantly improved after calcination, which helps to generate the piezoelectric effect more effectively.

[0040] Example 18 To test the cycling performance of the piezoelectric material, the material after the reaction was completed was washed with ethyl acetate to remove surface-adsorbed reactants and byproducts. The solid material was collected using a vacuum filtration funnel and dried in a vacuum drying oven at 70 °C for 12 h. This solid material was then used entirely in the next reaction, and this cycle was repeated until the yield significantly decreased. Experimental results showed that the material's cycling performance exhibited a significant degradation trend, with the yield plummeting to 23.3% after the third cycle. To investigate the performance degradation mechanism, the material after one cycle was characterized by SEM, as shown below. Figure 5 Compared to fresh material, the material undergoes significant deformation after one reaction, with the rod-like structure disappearing and dense aggregates forming. The formation of these aggregates reduces the effective reaction interface and destroys the defective structure, leading to impaired substrate mass transfer. This may be related to the decline in the material's cycling performance.

[0041] Example 19 To verify the presence and mechanism of action of free radicals in the reaction system, this study systematically conducted free radical scavenging experiments. The following scavenging agents were added under standard reaction conditions: 2,2,6,6-tetramethylpiperidine oxide (Tempo, for scavenging free radicals), 2,6-di-tert-butyl-p-cresol (BHT, for scavenging free radicals), isopropanol (IPA, for quenching hydroxyl radicals), and ethylenediaminetetraacetic acid (EDTA, for quenching holes). Figure 6 As shown, the reaction was completely inhibited upon the addition of Tempo, while 2 equiv. BHT only reduced the yield to 46%. When the amount of BHT increased to 3 equiv., the yield dropped sharply to 14.9%, exhibiting a typical concentration-dependent inhibition pattern. Notably, the addition of IPA and EDTA reduced the yield to 37.4% and 34.2%, respectively, indicating that hydroxyl radicals and holes also participated in the reaction. This series of experimental data confirms the synergistic effect of aryl radicals, hydroxyl radicals, and holes in the reaction system. Based on this mechanism, HRMS detection successfully captured the adducts of BHT with aryl radicals (Calc. 366.2045, Found 366.2049) and the adducts with aryl radical intermediates (Calc. 563.2861, Found 563.2863). In addition, Tempo was captured in aryl radical intermediates (Calc. 303.1684, Found 303.1691) and adducts of radical intermediates (Calc. 478.2681, Found 478.2679), providing direct evidence for the radical pathway.

[0042] Example 20 Add 15 stainless steel balls with a diameter of 10 mm and 45 stainless steel balls with a diameter of 5 mm to a 100 mL stainless steel ball mill jar, and weigh them sequentially. N -methyl- N 2-Phenylacetylacrylamide (1a, 0.3 mmol), 2-bromo-5-(trifluoromethyl)pyridine (2a, 4 equiv.), Cs₂CO₃ (2 equiv.), and BTO-700 (200 mg) were added to a stainless steel ball mill jar. Then, DMSO (0.2 μL / mg) was added to the jar using a pipette. After the addition was complete, the jar was sealed, evacuated, and purged with argon gas. This evacuation and purging process was repeated three times until the stainless steel jar was filled with argon gas. The jar was then placed in a planetary ball mill at 500 rpm and reacted at room temperature for 24 h. After the reaction, 20 mL of ethyl acetate was added to the stainless steel jar for extraction. The material was then filtered using a vacuum funnel and washed with ethyl acetate until the supernatant showed no fluorescence. The solvent was evaporated to dryness, and the sample was purified by silica gel column chromatography. The sample was eluted with a petroleum ether / dichloromethane / ethyl acetate system, yielding the desired product in 75% yield.N 2-Dimethyl- N -Phenylacetyl-3-(5-(trifluoromethyl)pyridin-2-yl)propionamide (3a).

[0043] The reaction process described above is shown in the following formula:

[0044] The characterization data of product 3a are as follows: Yellow solid (Yield 75%, 72.4 mg). 1 H-NMR (400MHz, CDCl3) δ 8.73 (s, 1H), 7.81 (d, J = 8.4 Hz, 1H), 7.37 – 7.31 (m, 3H), 7.26 (t, J = 3.6 Hz, 1H), 6.88 (d, J = 6.8 Hz, 2H), 3.28 (dd, J = 14.0, 10.4 Hz,1H), 3.16 (s, 3H), 3.08 – 2.99 (m, 1H), 2.76 (dd, J = 13.6, 4.8 Hz, 1H), 1.12(d, J = 6.8 Hz, 3H). 13 C-NMR (101 MHz, CDCl3) δ 175.5, 164.3, 146.0 (q, J C-F = 4.0Hz), 143.7, 133.2 (q, J C-F = 4.0 Hz), 129.7, 127.9, 127.2, 124.4 (q, J C-F = 33.3Hz), 123.8 (q, J C-F = 272.7 Hz), 123.4, 42.5, 37.4, 37.0, 18.5. 19 F-NMR (376 MHz, CDCl3) δ -62.2. Melting point = 71.5–73.5 o C. HRMS (ESI) m / z Calcd. forC 17 H 17 F3N2ONa [M+Na] +345.1191, Found 345.1192. Example 21 Add 15 stainless steel balls with a diameter of 10 mm and 45 stainless steel balls with a diameter of 5 mm to a 100 mL stainless steel ball mill jar, and weigh them sequentially. N -methyl- N 1,3-(o-toluyl)methacrylamide (1b, 0.3 mmol), 2-bromo-5-(trifluoromethyl)pyridine (2a, 4 equiv.), Cs₂CO₃ (2 equiv.), and BTO-700 (200 mg) were added to a stainless steel ball mill jar. Then, DMSO (0.2 μL / mg) was added to the jar using a pipette. After the addition was complete, the jar was sealed, evacuated, and purged with argon gas. This evacuation and purging process was repeated three times until the stainless steel jar was filled with argon gas. The jar was then placed in a planetary ball mill at 500 rpm and reacted at room temperature for 24 h. After the reaction, 20 mL of ethyl acetate was added to the stainless steel jar for extraction. The material was then filtered using a vacuum funnel and washed with ethyl acetate until the supernatant showed no fluorescence. The solvent was evaporated to dryness, and the sample was purified by silica gel column chromatography. The sample was eluted with a petroleum ether / dichloromethane / ethyl acetate system, yielding the product in 59% yield. N 2-Dimethyl- N -(o-tolyl)-3-(5-(trifluoromethyl)pyridin-2-yl)propionamide (3b).

[0045] The reaction process described above is shown in the following formula:

[0046] The characterization data for product 3b are as follows: Yellow liquid (Yield 59%, 59.4 mg). 1 H-NMR (400MHz, CDCl3) (rotamers): δ 8.70 (d, J = 13.6 Hz, 1H), 7.78 (t, J = 9.6 Hz, 1H), 7.32 (d, J = 8.0 Hz, 0.6H), 7.24 – 7.17 (m, 3H), 7.08 (d, J = 7.6 Hz, 0.5H), 7.02 (t, J = 7.6 Hz, 0.5H), 6.26 (d, J = 7.6 Hz, 0.4H), 3.32 – 3.20 (m, 1H), 3.06 (d, J= 8.0 Hz, 3H), 2.85 – 2.80 (m, 0.5H), 2.76 – 2.66 (m, 1.5H), 2.20(s, 1.4H), 1.62 (s, 1.6H), 1.09 (dd, J = 16.0, 6.4 Hz, 3H). 13 C-NMR (101 MHz,CDCl3) (rotamers): δ 175.6 (d, J = 22.2 Hz), 164.4 (d, J = 28.3 Hz), 146.2 (q, J C-F =3.0 Hz), 142.0 (d, J = 4.0 Hz), 135.4 (d, J = 19.2 Hz), 133.3 (d, J = 4.0Hz), 131.5 (d, J = 8.1 Hz), 128.4 (d, J = 15.2 Hz), 128.0 (d, J = 19.2 Hz),127.2 (d, J = 2.0 Hz), 124.5 (q, J C-F = 33.3 Hz), 123.8 (q, J C-F = 272.7 Hz),123.7 (d, J = 57.6 Hz), 42.6 (d, J = 41.4 Hz), 37.8 (d, J = 85.9 Hz), 36.2 (d, J = 7.1 Hz), 18.7 (d, J = 74.7 Hz), 16.9 (d, J = 106.1 Hz). 19 F-NMR (376 MHz,CDCl3) (rotamers): δ -62.2, -62.3. HRMS (ESI) m / z Calcd. for C 18 H 20 F3N2O [M+H] + 337.1528, Found 337.1533. Example 22 Add 15 stainless steel balls with a diameter of 10 mm and 45 stainless steel balls with a diameter of 5 mm to a 100 mL stainless steel ball mill jar, and weigh them sequentially. N -(2-Chlorophenyl)- N 1-Methylmethacrylamide (1c, 0.3 mmol), 2-bromo-5-(trifluoromethyl)pyridine (2a, 4 equiv.), Cs₂CO₃ (2 equiv.), and BTO-700 (200 mg) were added to a stainless steel ball mill jar. Then, DMSO (0.2 μL / mg) was added to the jar using a pipette. After the addition was complete, the jar was sealed, evacuated, and purged with argon gas. This evacuation and purging process was repeated three times until the stainless steel jar was filled with argon gas. The jar was then placed in a planetary ball mill at 500 rpm and reacted at room temperature for 24 h. After the reaction, 20 mL of ethyl acetate was added to the stainless steel jar for complete extraction. The material was then filtered using a vacuum funnel and washed with ethyl acetate until the supernatant showed no fluorescence. The solvent was evaporated to dryness, and the sample was purified by silica gel column chromatography. The sample was eluted with a petroleum ether / dichloromethane / ethyl acetate system, yielding the desired product in 79% yield. N -(2-Chlorophenyl)- N ,2-Dimethyl-3-(5-(trifluoromethyl)pyridin-2-yl)propionamide (3c).

[0047] The reaction process described above is shown in the following formula:

[0048] The characterization data of product 3c are as follows: Yellow liquid (Yield 79%, 85 mg). 1 H-NMR (400MHz, CDCl3) (rotamers): δ 8.66 (d, J = 18.8 Hz, 1H), 7.77 (d, J = 8.0 Hz, 0.5H), 7.71 (d, J = 8.0 Hz, 0.5H), 7.40 (dd, J = 8.0, 1.6 Hz, 0.5H), 7.37 –7.34 (m, 0.5H), 7.25 – 7.19 (m, 3H), 7.11 (td, J = 8.0, 1.6 Hz, 0.5H), 6.46(dd, J = 7.6, 1.6 Hz, 0.5H), 3.29 – 3.17 (m, 1H), 3.05 (d, J= 3.2 Hz, 3H),2.83 – 2.76 (m, 0.5H), 2.73 – 2.68 (m, 1H), 2.66 – 2.61 (m, 0.5H), 1.08 (dd, J = 8.8, 6.8 Hz, 3H). 13 C-NMR (101 MHz, CDCl3) (rotamers): δ 175.6 (d, J = 13.1Hz), 164.2 (d, J = 11.1 Hz), 146.2 (q, J C-F = 4.0 Hz) , 140.7 (d, J = 6.1 Hz),133.4 (q, J C-F = 3.0 Hz), 132.9 (d, J = 8.1 Hz), 130.8 (d, J = 12.1 Hz), 129.9(d, J = 23.2 Hz), 129.6, 128.1 (d, J = 14.1 Hz), 124.6 (q, J C-F = 33.3 Hz, majorrotamer), 124.4 (q, J C-F = 32.3 Hz, minor rotamer), 123.8 (q, J C-F = 272.7 Hz),123.8 (d, J = 43.4 Hz), 42.5 (d, J = 53.5 Hz), 38.0 (d, J = 86.9 Hz), 36.0 (d, J = 5.1 Hz), 18.6 (d, J = 53.5 Hz). 19 F-NMR (376 MHz, CDCl3) (rotamers): δ -62.2,-62.3. HRMS (ESI) m / z Calcd. for C 17 H 17 F3N2OCl [M+H] +357.0982, Found 357.0987. Example 23 Add 15 stainless steel balls with a diameter of 10 mm and 45 stainless steel balls with a diameter of 5 mm to a 100 mL stainless steel ball mill jar, and weigh them sequentially. N -methyl- N 1,3-(p-Tolyl)methacrylamide (1d, 0.3 mmol), 2-bromo-5-(trifluoromethyl)pyridine (2a, 4 equiv.), Cs₂CO₃ (2 equiv.), and BTO-700 (200 mg) were added to a stainless steel ball mill jar. Then, DMSO (0.2 μL / mg) was added to the jar using a pipette. After the addition was complete, the jar was sealed, evacuated, and purged with argon gas. This evacuation and purging process was repeated three times until the stainless steel jar was filled with argon gas. The jar was then placed in a planetary ball mill at 500 rpm and reacted at room temperature for 24 h. After the reaction, 20 mL of ethyl acetate was added to the stainless steel jar for extraction. The material was then filtered using a vacuum funnel and washed with ethyl acetate until the supernatant showed no fluorescence. The solvent was evaporated to dryness, and the sample was purified by silica gel column chromatography. The sample was eluted with a petroleum ether / dichloromethane / ethyl acetate system, yielding the product in 73% yield. N 2-Dimethyl- N -(p-Tolyl)-3-(5-(trifluoromethyl)pyridin-2-yl)propionamide (3d).

[0049] The reaction process described above is shown in the following formula:

[0050] The characterization data of the product on day 3 are as follows: Yellow brown solid (Yield 73%, 73.2 mg). 1 H-NMR (400 MHz, CDCl3): δ 8.72 (s, 1H), 7.79 (dd, J = 8.4, 2.4 Hz, 1H), 7.25 (d, J =8.8 Hz, 1H), 7.12 (d, J = 8.0 Hz, 2H), 6.72 (d, J = 7.6 Hz, 2H), 3.26 (dd, J =13.2, 9.6 Hz, 1H), 3.12 (s, 3H), 3.06-2.97 (m, 1H), 2.74 (dd, J = 13.6, 4.8Hz, 1H), 2.34 (s, 3H), 1.10 (d,J = 6.8 Hz, 3H). 13 C-NMR (101 MHz, CDCl3): δ175.7, 164.4, 146.1 (q, J C-F = 4.0 Hz), 141.1, 137.9, 133.3 (q, J C-F = 3.0 Hz),130.3, 127.0, 124.4 (q, J C-F = 32.3 Hz), 123.9 (q, J C-F = 273.7 Hz), 123.5, 42.5,37.5, 37.1, 21.2, 18.6. 19 F-NMR(376 MHz, CDCl3): δ -62.3. Melting point = 91.7–93.1 o C.HRMS (ESI) m / z Calcd. for C 18 H 20 F3N2O [M+H] + 337.1528, Found 337.1531. Example 24 Add 15 stainless steel balls with a diameter of 10 mm and 45 stainless steel balls with a diameter of 5 mm to a 100 mL stainless steel ball mill jar, and weigh them sequentially. N -(4-Methoxyphenyl)- N 1-Methylmethacrylamide (1e, 0.3 mmol), 2-bromo-5-(trifluoromethyl)pyridine (2a, 4 equiv.), Cs₂CO₃ (2 equiv.), and BTO-700 (200 mg) were added to a stainless steel ball mill jar. Then, DMSO (0.2 μL / mg) was added to the jar using a pipette. After the addition was complete, the jar was sealed, evacuated, and purged with argon gas. This evacuation and purging process was repeated three times until the stainless steel jar was filled with argon gas. The jar was then placed in a planetary ball mill at 500 rpm and reacted at room temperature for 24 h. After the reaction, 20 mL of ethyl acetate was added to the stainless steel jar for complete extraction. The material was then filtered using a vacuum funnel and washed with ethyl acetate until the supernatant showed no fluorescence. The solvent was evaporated to dryness, and the sample was purified by silica gel column chromatography. The sample was eluted with a petroleum ether / dichloromethane / ethyl acetate system, yielding the desired product in 69% yield. N -(4-Methoxyphenyl)- N ,2-Dimethyl-3-(5-(trifluoromethyl)pyridin-2-yl)propionamide (3e).

[0051] The reaction process described above is shown in the following formula:

[0052] The characterization data of product 3e are as follows: Yellow brown solid (Yield 69%, 73.7 mg). 1 H-NMR (400 MHz, CDCl3): δ 8.73 (d, J = 2.4 Hz, 1H), 7.79 (dd, J = 8.0, 2.4 Hz, 1H), 7.26 (d, J = 8.4 Hz, 1H), 6.85 – 6.77 (m, 4H), 3.80 (s, 3H), 3.26 (dd, J =13.6, 9.6 Hz, 1H), 3.11 (s, 3H), 3.06 – 2.98 (m, 1H), 2.74 (dd, J = 13.6, 4.8Hz, 1H), 1.10 (d, J = 7.2 Hz, 3H). 13 C-NMR (101 MHz, CDCl3): δ 175.9, 164.4,159.0, 146.1 (q, J C-F = 4.0 Hz), 136.5, 133.3 (q, J C-F = 4.0 Hz), 128.3, 124.4 (q, J C-F = 33.3 Hz), 123.9 (q, J C-F = 272.7 Hz), 123.5, 114.8, 55.6, 42.5, 37.6,36.9, 18.6. 19 F-NMR(376 MHz, CDCl3): δ -62.2. Melting point = 61.4–63.1 o C.HRMS(ESI) m / z Calcd. for C 18 H 19 F3N2O2Na[M+Na] + 375.1296, Found 375.1301. Example 25 Add 15 stainless steel balls with a diameter of 10 mm and 45 stainless steel balls with a diameter of 5 mm to a 100 mL stainless steel ball mill jar, and weigh them sequentially. N -(4-Chlorophenyl)- N 1-Methylmethacrylamide (1f, 0.3 mmol), 2-bromo-5-(trifluoromethyl)pyridine (2a, 4 equiv.), Cs₂CO₃ (2 equiv.), and BTO-700 (200 mg) were added to a stainless steel ball mill jar. Then, DMSO (0.2 μL / mg) was added to the jar using a pipette. After the addition was complete, the jar was sealed, evacuated, and purged with argon gas. This evacuation and purging process was repeated three times until the stainless steel jar was filled with argon gas. The jar was then placed in a planetary ball mill at 500 rpm and reacted at room temperature for 24 h. After the reaction, 20 mL of ethyl acetate was added to the stainless steel jar for extraction. The material was then filtered using a vacuum funnel and washed with ethyl acetate until the supernatant showed no fluorescence. The solvent was evaporated to dryness, and the sample was purified by silica gel column chromatography. The sample was eluted with a petroleum ether / dichloromethane / ethyl acetate system, yielding the desired product in 66% yield. N -(4-Chlorophenyl)- N ,2-Dimethyl-3-(5-(trifluoromethyl)pyridin-2-yl)propionamide (3f).

[0053] The reaction process described above is shown in the following formula:

[0054] The characterization data of the product at 3f are as follows: Yellow brown solid (Yield 66%, 70.2 mg). 1 H-NMR (400 MHz, CDCl3): δ 8.72 (s, 1H), 7.79 (dd, J = 8.0, 2.0 Hz, 1H), 7.31 (d, J =8.4 Hz, 2H), 7.25 (d, J = 8.0 Hz, 1H), 6.87 (d, J = 8.4 Hz, 2H), 3.27 (dd, J =14.4, 10.4 Hz, 1H), 3.12 (s, 3H), 3.06 – 3.00 (m, 1H), 2.75 (dd, J = 14.0, 4.4Hz, 1H), 1.10 (d, J =7.2 Hz, 3H). 13C-NMR (101 MHz, CDCl3): δ 175.5, 164.1,146.0 (q, J C-F = 4.0 Hz), 142.3, 133.7, 133.3 (q, J C-F = 3.0 Hz), 129.9, 128.7,124.5 (q, J C-F = 32.3 Hz), 123.8 (q, J C-F = 273.7 Hz), 123.5, 42.3, 37.4, 36.8,18.5. 19 F-NMR(376 MHz, CDCl3): δ -62.2. Melting point = 65.9–67.6 o C. HRMS (ESI) m / z Calcd. for C 17 H 17 F3N2OCl [M+H + 357.0982, Found 357.0986. Example 26 Add 15 stainless steel balls with a diameter of 10 mm and 45 stainless steel balls with a diameter of 5 mm to a 100 mL stainless steel ball mill jar, and weigh them sequentially. N -(4-bromophenyl)- N 1 g of methylmethacrylamide (0.3 mmol), 2-bromo-5-(trifluoromethyl)pyridine (2a, 4 equiv.), Cs₂CO₃ (2 equiv.), and BTO-700 (200 mg) were added to a stainless steel ball mill jar. Then, 0.2 μL / mg of DMSO was added to the jar using a pipette. After the addition was complete, the jar was sealed, evacuated, and purged with argon. This evacuation and purging process was repeated three times until the stainless steel jar was filled with argon. The jar was then placed in a planetary ball mill at 500 rpm and reacted at room temperature for 24 h. After the reaction, 20 mL of ethyl acetate was added to the stainless steel jar for extraction. The material was then filtered using a vacuum funnel and washed with ethyl acetate until the supernatant showed no fluorescence. The solvent was evaporated to dryness, and the sample was purified by silica gel column chromatography. The sample was eluted with a petroleum ether / dichloromethane / ethyl acetate system, yielding the desired product in 71% yield. N -(4-bromophenyl)- N 2-Dimethyl-3-(5-(trifluoromethyl)pyridin-2-yl)propionamide (3g).

[0055] The reaction process described above is shown in the following formula:

[0056] The characterization data for 3g of the product are as follows: Yellow brown solid (Yield 71%, 85.2 mg). 1 H-NMR (400 MHz, CDCl3): δ 8.71 (s, 1H), 7.77 (dd, J = 8.4, 2.4 Hz, 1H), 7.45 (d, J =8.4 Hz, 2H), 7.23 (d, J = 8.0 Hz, 1H), 6.80 (d, J = 8.4 Hz, 2H), 3.26 (dd, J =13.6, 9.6 Hz, 1H), 3.10 (s, 3H), 3.05 – 3.00 (m, 1H), 2.73 (dd, J = 14.0, 4.8Hz, 1H), 1.08 (d, J = 6.8 Hz, 3H). 13 C-NMR (101 MHz, CDCl3): δ 175.4, 164.1,146.0 (q, J C-F = 4.0 Hz), 142.8, 133.3 (q, J C-F = 3.0 Hz), 132.9, 129.0, 124.4(q, J C-F = 33.3 Hz), 123.8 (q, J C-F = 273.7 Hz), 123.4, 121.6, 42.3, 37.4, 36.7,18.5. 19 F-NMR(376 MHz, CDCl3): δ -62.2. Melting point = 84.7–86.5 o C.HRMS (ESI)m / z Calcd. for C 17 H 17 F3N2OBr [M+H] + 401.0476, Found 401.0477. Example 27 Add 15 stainless steel balls with a diameter of 10 mm and 45 stainless steel balls with a diameter of 5 mm to a 100 mL stainless steel ball mill jar, and weigh them sequentially. N -(4-Iodophenyl)- N 1-Methylmethacrylamide (1 h, 0.3 mmol), 2-bromo-5-(trifluoromethyl)pyridine (2a, 4 equiv.), Cs₂CO₃ (2 equiv.), and BTO-700 (200 mg) were added to a stainless steel ball mill jar. Then, DMSO (0.2 μL / mg) was added to the jar using a pipette. After the addition was complete, the jar was sealed, evacuated, and purged with argon gas. This evacuation and purging process was repeated three times until the stainless steel jar was filled with argon gas. The jar was then placed in a planetary ball mill at 500 rpm and reacted at room temperature for 24 h. After the reaction, 20 mL of ethyl acetate was added to the stainless steel jar for extraction. The material was then filtered using a vacuum funnel and washed with ethyl acetate until the supernatant showed no fluorescence. The solvent was evaporated to dryness, and the sample was purified by silica gel column chromatography. The sample was eluted with a petroleum ether / dichloromethane / ethyl acetate system, yielding the desired product in 51% yield. N -(4-Iodophenyl)- N ,2-Dimethyl-3-(5-(trifluoromethyl)pyridin-2-yl)propionamide (3h).

[0057] The reaction process described above is shown in the following formula:

[0058] The product characterization data at 3 hours are as follows: Yellow brown solid (Yield 51%, 68.2 mg). 1 H-NMR (400 MHz, CDCl3): δ 8.72 (s, 1H), 7.79 (dd, J = 8.0, 2.4 Hz, 1H), 7.67 (d, J =8.0 Hz, 2H), 7.25 (d, J = 8.0 Hz, 1H), 6.68 (d, J = 8.0 Hz, 2H), 3.27 (dd, J =14.0, 10.0 Hz, 1H), 3.11 (s, 3H), 3.08-3.00 (m, 1H), 2.75 (dd, J = 14.0, 4.8Hz, 1H), 1.10 (d, J = 6.8 Hz, 3H). 13C-NMR (101 MHz, CDCl3): δ 175.5, 164.1,146.1 (q, J C-F = 4.0 Hz), 143.5, 139.0, 133.4 (q, J C-F = 3.0 Hz), 129.8, 129.3,124.5 (q, J C-F = 32.3Hz), 123.8 (q). J C-F = 272.7 Hz), 123.5, 42.3, 37.4, 36.8,18.6. 19 F-NMR(376 MHz, CDCl3): δ -62.2. Melting point = 85.5–86.4 o C.HRMS (ESI)m / z Calcd. for C 17 H 17 F3N2OI [M+H] + 449.0338, Found 449.0341. Example 28 Add 15 stainless steel balls with a diameter of 10 mm and 45 stainless steel balls with a diameter of 5 mm to a 100 mL stainless steel ball mill jar, and weigh them sequentially. N -(2,6-dimethylphenyl)- N 1-Methylmethacrylamide (1 mmol, 0.3 mmol), 2-bromo-5-(trifluoromethyl)pyridine (2a, 4 equiv.), Cs₂CO₃ (2 equiv.), and BTO-700 (200 mg) were added to a stainless steel ball mill jar. Then, DMSO (0.2 μL / mg) was added to the jar using a pipette. After the addition was complete, the jar was sealed, evacuated, and purged with argon gas. This evacuation and purging process was repeated three times until the stainless steel jar was filled with argon gas. The jar was then placed in a planetary ball mill at 500 rpm and reacted at room temperature for 24 h. After the reaction, 20 mL of ethyl acetate was added to the stainless steel jar for extraction. The material was then filtered using a vacuum funnel and washed with ethyl acetate until the supernatant showed no fluorescence. The solvent was evaporated to dryness, and the sample was purified by silica gel column chromatography. The sample was eluted with a petroleum ether / dichloromethane / ethyl acetate system, yielding the desired product in 75% yield. N -(2,6-dimethylphenyl)- N ,2-Dimethyl-3-(5-(trifluoromethyl)pyridin-2-yl)propionamide (3i).

[0059] The reaction process described above is shown in the following formula:

[0060] The characterization data of product 3i are as follows: Yellow brown liquid (Yield 75%, 79 mg). 1 H-NMR (400 MHz, CDCl3): δ 8.68 (s, 1H), 7.75 (dd, J = 8.4, 2.4 Hz, 1H), 7.25 (d, J =8.4 Hz, 1H), 7.15-7.04 (m, 3H), 3.26-3.21 (m, 1H), 3.07 (s, 3H), 2.77 (dd, J =13.2, 6.8 Hz, 1H), 2.67 (q, J = 6.8 Hz, 1H), 2.21 (s, 3H), 1.80 (s, 3H), 0.98(d, J = 6.8 Hz, 3H). 13 C-NMR (101 MHz, CDCl3): δ 175.9, 164.3, 146.1 (q, J C-F =4.0 Hz), 140.7, 135.9, 135.7, 133.4 (q, J C-F = 4.0 Hz), 129.1, 129.0, 128.2,124.5 (q, J C-F = 33.3 Hz), 123.8 (q, J C-F = 273.7 Hz), 124.1, 42.5, 37.8, 35.0,18.0, 17.8, 17.2. 19 F-NMR(376 MHz, CDCl3): δ -62.3. HRMS (ESI) m / z Calcd. forC 19 H 22 F3N2O [M+H] + 351.1684, Found 351.1688. Example 29 Add 15 stainless steel balls with a diameter of 10 mm and 45 stainless steel balls with a diameter of 5 mm to a 100 mL stainless steel ball mill jar, and weigh them sequentially. N -Benzyl- N1-Methylmethacrylamide (1 mmol, 0.3 mmol), 2-bromo-5-(trifluoromethyl)pyridine (2a, 4 equiv.), Cs₂CO₃ (2 equiv.), and BTO-700 (200 mg) were added to a stainless steel ball mill jar. Then, DMSO (0.2 μL / mg) was added to the jar using a pipette. After the addition was complete, the jar was sealed, evacuated, and purged with argon gas. This evacuation and purging process was repeated three times until the stainless steel jar was filled with argon gas. The jar was then placed in a planetary ball mill at 500 rpm and reacted at room temperature for 24 h. After the reaction, 20 mL of ethyl acetate was added to the stainless steel jar for complete extraction. The material was then filtered using a vacuum funnel and washed with ethyl acetate until the supernatant showed no fluorescence. The solvent was evaporated to dryness, and the sample was purified by silica gel column chromatography. The sample was eluted with a petroleum ether / dichloromethane / ethyl acetate system, yielding the desired product in 70% yield. N -Benzyl- N ,2-Dimethyl-3-(5-(trifluoromethyl)pyridin-2-yl)propionamide (3j).

[0061] The reaction process described above is shown in the following formula:

[0062] The characterization data of product 3j are as follows: Yellow brown liquid (Yield 70%, 70.2 mg). 1 H-NMR (400 MHz, CDCl3): δ 8.73 (dd, J = 20.8, 2.8 Hz, 1H), 7.83-7.77 (m, 1H), 7.34(d, J = 8.4 Hz, 1H), 7.28-7.22 (m, 3H), 7.02 – 6.97 (m, 2H), 4.80 (d, J = 14.8Hz, 0.6H), 4.61 (d, J = 16.8 Hz, 0.4H), 4.48 (d, J = 16.4 Hz, 0.4H), 4.27 (d, J = 14.8 Hz, 0.6H), 3.57 – 3.50 (m, 0.6H), 3.47 – 3.36 (m, 1.4H), 2.99-2.86 (m,4H), 1.26 (dd, J = 13.6, 6.8 Hz, 3H). 13 C-NMR (101 MHz, CDCl3): δ 175.8 (d,J = 24.2 Hz), 164.3, 146.0 (q, J C-F = 4.0 Hz), 137.0 (d, J = 56.6 Hz), 133.3 (q, J C-F = 3.0 Hz), 128.6 (d, J = 30.3 Hz), 127.6 (d, J = 18.2 Hz), 126.8 (d, J = 98.0 Hz), 124.3 (q, J C-F = 32.3 Hz), 123.8 (q, J C-F = 272.7 Hz), 123.9 (d, J = 13.1 Hz), 52.0 (d, J = 222.2 Hz), 42.2 (d, J = 15.2 Hz), 35.9 (d, J = 56.6 Hz), 34.5 (d, J = 69.7 Hz), 18.2 (d, J = 80.8 Hz). 19 F-NMR(376 MHz, CDCl3): δ -62.2. HRMS(ESI) m / z Calcd. for C 18 H 20 F3N2O [M + H] + 359.1347, Found 359.1352. Example 30 Fifteen stainless steel balls with a diameter of 10 mm and forty-five stainless steel balls with a diameter of 5 mm were added to a 100 mL stainless steel ball mill jar. Then, 3-methyl-1-(aniline)-3-buten-2-one (1 kJ, 0.3 mmol), 2-bromo-5-(trifluoromethyl)pyridine (2a, 4 equiv.), Cs₂CO₃ (2 equiv.), and BTO-700 (200 mg) were weighed and added to the jar. Finally, DMSO (0.2 μL / mg) was added to the jar using a pipette. After the addition was complete, the jar was sealed, evacuated, and filled with argon gas. This evacuation and gas exchange was repeated three times until the stainless steel jar was filled with argon gas. The jar was then placed in a planetary ball mill, and the reaction was carried out at 500 rpm for 24 hours at room temperature. After the reaction was completed, 20 mL of ethyl acetate was added to the stainless steel container for extraction. The material was then filtered using a vacuum funnel and washed with ethyl acetate until the supernatant showed no fluorescence. The solvent was then evaporated to dryness. The sample was purified by silica gel column chromatography and eluted with a petroleum ether / dichloromethane / ethyl acetate system to obtain 3-methyl-1-(phenylamino)-4-[5-(trifluoromethyl)-2-pyridyl]-2-butanone (3k) in 59% yield.

[0063] The reaction process described above is shown in the following formula:

[0064] The characterization data of product 3k are as follows: Yellow solid (Yield 59%, 56.8 mg). 1 H-NMR (400MHz, CDCl3): δ 8.68 (s, 1H), 7.75 (dd, J = 8.4, 2.4 Hz, 1H), 7.24-7.22 (m,4H), 7.03-7.01 (m, 2H), 6.17 (t, J = 6.0 Hz, 1H), 4.42 (dd, J = 14.8, 6.4 Hz, 1H), 4.19 (dd, J = 14.4, 4.8 Hz, 1H), 3.21 (dd, J = 15.6, 10.4 Hz, 1H), 2.95-2.86 (m, 2H), 1.25 (d, J = 6.4 Hz, 3H). 13 C-NMR (101 MHz, CDCl3): δ 175.2,163.8, 146.0 (q, J C-F= 4.0 Hz), 138.3, 133.7 (q, J C-F = 4.0 Hz), 128.7, 127.7,127.5, 124.7 (q, J C-F = 33.3 Hz), 124.0, 123.7 (q, J C-F = 272.7 Hz), 43.4, 42.1, 41.1, 18.2. 19 F-NMR(376 MHz, CDCl3): δ -62.2. Melting point = 77.5–79.1 o C.HRMS(ESI) m / z Calcd. for C 17 H 18 F3N2O [M+H] + 323.1371, Found 323.1376. Example 31 Add 15 stainless steel balls with a diameter of 10 mm and 45 stainless steel balls with a diameter of 5 mm to a 100 mL stainless steel ball mill jar, and weigh them sequentially. N 2-Bromo-5-(trifluoromethyl)pyridine (2a, 4 equiv.), Cs₂CO₃ (2 equiv.), and BTO-700 (200 mg) were added to a stainless steel ball mill jar. Then, DMSO (0.2 μL / mg) was added to the jar using a pipette. After the addition was complete, the jar was sealed, evacuated, and purged with argon. This evacuation and purging process was repeated three times until the stainless steel jar was filled with argon. The jar was then placed in a planetary ball mill at 500 rpm and reacted at room temperature for 24 h. After the reaction, 20 mL of ethyl acetate was added to the stainless steel jar for extraction. The material was then filtered using a vacuum funnel and washed with ethyl acetate until the supernatant showed no fluorescence. The solvent was evaporated to dryness, and the sample was purified by silica gel column chromatography. Elution was performed using a petroleum ether / dichloromethane / ethyl acetate system to obtain 2-methyl- N -Phenylacetyl-3-(5-(trifluoromethyl)pyridin-2-yl)propionamide (3l).

[0065] The reaction process described above is shown in the following formula:

[0066] The characterization data of product 3l are as follows: Yellowish-white solid (Yield 68%, 62.9 mg). 1H-NMR (400 MHz, CDCl3): δ 8.80 (d, J = 2.4 Hz, 1H), 8.24 (s, 1H), 7.81 (dd, J =8.0, 2.4 Hz, 1H), 7.45 (d, J = 8.0 Hz, 2H), 7.32 – 7.24 (m, 3H), 7.06 (t, J =7.6 Hz, 1H), 3.31 (dd, J = 14.4, 8.4 Hz, 1H), 3.16 – 3.05 (m, 1H), 2.98 (dd, J = 14.8, 5.6 Hz, 1H), 1.30 (d, J = 6.8 Hz, 3H). 13 C-NMR (101 MHz, CDCl3): δ174.0, 163.7, 146.0 (q, J C-F = 4.0 Hz), 138.2, 133.9 (q, J C-F = 3.0 Hz), 129.0, 124.8 (q, J C-F = 33.3 Hz), 124.2, 124.0, 123.6 (q, J C-F = 272.7 Hz), 119.9, 41.9,41.3, 18.0. 19 F-NMR(376 MHz, CDCl3): δ -62.3. Melting point = 131.2–133.1 o C.HRMS (ESI) m / z Calcd. for C 16 H 16 F3N2O [M+H] + 309.1215, Found 309.1219. Example 32 Add 15 stainless steel balls with a diameter of 10 mm and 45 stainless steel balls with a diameter of 5 mm to a 100 mL stainless steel ball mill jar, and weigh them sequentially. N , NDiphenylmethylacrylamide (1 mL, 0.3 mmol), 2-bromo-5-(trifluoromethyl)pyridine (2a, 4 equiv.), Cs₂CO₃ (2 equiv.), and BTO-700 (200 mg) were added to a stainless steel ball mill jar. Then, DMSO (0.2 μL / mg) was added to the jar using a pipette. After the addition was complete, the jar was sealed, evacuated, and purged with argon. This evacuation and purging process was repeated three times until the stainless steel jar was filled with argon. The jar was then placed in a planetary ball mill at 500 rpm and reacted at room temperature for 24 h. After the reaction, 20 mL of ethyl acetate was added to the stainless steel jar for extraction. The material was then filtered using a vacuum funnel and washed with ethyl acetate until the supernatant showed no fluorescence. The solvent was evaporated to dryness, and the sample was purified by silica gel column chromatography. Elution was performed using a petroleum ether / dichloromethane / ethyl acetate system to obtain 2-methyl- N , N -Diphenyl-3-(5-(trifluoromethyl)pyridin-2-yl)propionamide (3m).

[0067] The reaction process described above is shown in the following formula:

[0068] The characterization data of product 3m are as follows: Yellow brown solid (Yield 71%, 82.3 mg). 1 H-NMR (400 MHz, CDCl3): δ 8.80 (s, 1H), 7.84 (dd, J = 8.0, 2.0 Hz, 1H), 7.38-7.32(m, 4H), 7.29-7.26 (m, 2H), 7.15-7.07 (m, 5H), 3.43 – 3.35 (m, 1H), 3.30-3.22(m, 1H), 2.85 (dd, J = 13.6, 4.4 Hz, 1H), 1.26 (d, J = 6.8 Hz, 3H). 13 C-NMR (101MHz, CDCl3): δ 175.9, 164.2, 146.1 (q, J C-F = 4.0 Hz), 142.8, 133.3 (q, J C-F =3.0 Hz), 129.7, 129.0, 128.7, 128.0, 126.5, 126.2, 124.5 (q, J C-F= 33.3 Hz), 123.8 (q, J C-F = 273.7 Hz), 123.7, 42.5, 37.7, 18.6. 19 F-NMR(376 MHz, CDCl3): δ -62.1. Melting point= 97.7–98.9 o C.HRMS (ESI) m / z Calcd. for C 22 H 20 F3N2O [M+H] + 385.1528, Found 385.1532. Example 33 Add 15 stainless steel balls with a diameter of 10 mm and 45 stainless steel balls with a diameter of 5 mm to a 100 mL stainless steel ball mill jar, and weigh them sequentially. N -Ethyl- N 2-Phenylacetylacrylamide (1n, 0.3 mmol), 2-bromo-5-(trifluoromethyl)pyridine (2a, 4 equiv.), Cs₂CO₃ (2 equiv.), and BTO-700 (200 mg) were added to a stainless steel ball mill jar. Then, DMSO (0.2 μL / mg) was added to the jar using a pipette. After the addition was complete, the jar was sealed, evacuated, and purged with argon gas. This evacuation and purging process was repeated three times until the stainless steel jar was filled with argon gas. The jar was then placed in a planetary ball mill at 500 rpm and reacted at room temperature for 24 h. After the reaction, 20 mL of ethyl acetate was added to the stainless steel jar for extraction. The material was then filtered using a vacuum funnel and washed with ethyl acetate until the supernatant showed no fluorescence. The solvent was evaporated to dryness, and the sample was purified by silica gel column chromatography. The sample was eluted with a petroleum ether / dichloromethane / ethyl acetate system, yielding the product in 71% yield. N -Ethyl-2-methyl- N -Phenyl-3-(5-(trifluoromethyl)pyridin-2-yl)propionamide (3n).

[0069] The reaction process described above is shown in the following formula:

[0070] The characterization data of product 3n are as follows: Yellow brown liquid (Yield 71%, 72.1 mg). 1 H-NMR (400 MHz, CDCl3): δ 8.67 (s, 1H), 7.74 (dd, J= 8.0, 2.0 Hz, 1H), 7.30 – 7.24(m, 3H), 7.20 (d, J = 8.4 Hz, 1H), 6.76 (s, 2H), 3.67-3.59 (m, 1H), 3.54-3.45(m, 1H), 3.21 (dd, J = 13.6, 10.0 Hz, 1H), 2.88- – 2.80 (m, 1H), 2.68 (dd, J =13.6, 4.8 Hz, 1H), 1.05 (d, J = 6.8 Hz, 3H), 0.93 (t, J = 7.2 Hz, 3H). 13 C-NMR (101 MHz, CDCl3): δ 174.9, 164.4, 146.0 (q, J C-F = 4.0 Hz), 142.1, 133.2 (q, J C-F = 4.0 Hz), 129.6, 128.3, 128.0, 124.4 (q, J C-F = 33.3 Hz), 123.8 (q, J C-F =272.7 Hz), 123.5, 44.1, 42.5, 37.4, 18.5, 13.0. 19 F-NMR(376 MHz, CDCl3): δ -62.2. HRMS (ESI) m / z Calcd. for C 18 H 20 F3N2O [M+H] + 337.1528, Found 337.1533. Example 34 Add 15 stainless steel balls with a diameter of 10 mm and 45 stainless steel balls with a diameter of 5 mm to a 100 mL stainless steel ball mill jar, and weigh them sequentially. N -methyl- N1,03 mmol of 2-(naphthyl-2-yl)methacrylamide, 2-bromo-5-(trifluoromethyl)pyridine (2a, 4 equiv.), Cs₂CO₃ (2 equiv.), and BTO-700 (200 mg) were added to a stainless steel ball mill jar. Then, 0.2 μL / mg of DMSO was added to the jar using a pipette. After the addition was complete, the jar was sealed, evacuated, and purged with argon gas. This evacuation and purging process was repeated three times until the stainless steel jar was filled with argon gas. The jar was then placed in a planetary ball mill at 500 rpm and reacted at room temperature for 24 h. After the reaction, 20 mL of ethyl acetate was added to the stainless steel jar for extraction. The material was then filtered using a vacuum funnel and washed with ethyl acetate until the supernatant showed no fluorescence. The solvent was evaporated to dryness, and the sample was purified by silica gel column chromatography. The sample was eluted with a petroleum ether / dichloromethane / ethyl acetate system, yielding a product with a yield of 37%. N 2-Dimethyl- N -(naphthyl-2-yl)-3-(5-(trifluoromethyl)pyridin-2-yl)propionamide (3o).

[0071] The reaction process described above is shown in the following formula:

[0072] The characterization data of product 3o are as follows: Yellow brown solid (Yield 37%, 40.9 mg). 1 H-NMR (400 MHz, CDCl3): δ 8.72 (s, 1H), 7.83 (t, J = 8.8 Hz, 3H), 7.73 – 7.71 (m,1H), 7.54 – 7.49 (m, 2H), 7.26 (t, J = 8.8 Hz, 2H), 7.00 (d, J = 8.8 Hz, 1H), 3.31 (dd, J = 13.2, 10.0 Hz, 1H), 3.23 (s, 3H), 3.12-3.03 (m, 1H), 2.74 (dd, J = 13.2, 4.4 Hz, 1H), 1.15 (d, J = 6.8 Hz, 3H). 13 C-NMR (101 MHz, CDCl3): δ175.8, 164.4, 146.1 (q, J C-F = 4.0 Hz), 141.1, 133.7, 133.4 (q,J C-F = 3.0 Hz),132.5, 129.9, 127.9, 127.9, 127.0, 126.8, 125.7, 125.3, 124.5 (q, J C-F =33.3Hz), 123.9 (q, J C-F = 272.7 Hz), 123.5, 42.6, 37.6, 37.3, 18.7. 19 F-NMR(376MHz, CDCl3): δ -62.1. Melting point = 107.8–109.5 o C.HRMS (ESI) m / z Calcd. forC 21 H 20 F3N2O [M+H] + 373.1528, Found 373.1532. Example 35 Add 15 stainless steel balls with a diameter of 10 mm and 45 stainless steel balls with a diameter of 5 mm to a 100 mL stainless steel ball mill jar, and weigh them sequentially. N -(benzo[d]thiazo-2-yl)- N 1,3-methylmethacrylamide (1 p 0.3 mmol), 2-bromo-5-(trifluoromethyl)pyridine (2a, 4 equiv.), Cs₂CO₃ (2 equiv.), and BTO-700 (200 mg) were added to a stainless steel ball mill jar. Then, DMSO (0.2 μL / mg) was added to the jar using a pipette. After the addition was complete, the jar was sealed, evacuated, and purged with argon gas. This evacuation and purging process was repeated three times until the stainless steel jar was filled with argon gas. The jar was then placed in a planetary ball mill at 500 rpm and reacted at room temperature for 24 h. After the reaction, 20 mL of ethyl acetate was added to the stainless steel jar for extraction. The material was then filtered using a vacuum funnel and washed with ethyl acetate until the supernatant showed no fluorescence. The solvent was evaporated to dryness, and the sample was purified by silica gel column chromatography. The sample was eluted with a petroleum ether / dichloromethane / ethyl acetate system, yielding a product with a yield of 38%. N -(benzo[d]thiazo-2-yl)- N ,2-Dimethyl-3-(5-(trifluoromethyl)pyridin-2-yl)propionamide (3p).

[0073] The reaction process described above is shown in the following formula:

[0074] The characterization data of product 3p are as follows: Yellow brown solid (Yield 38%, 42.6 mg). 1 H-NMR (400 MHz, CDCl3): δ 8.78 (d, J = 2.4 Hz, 1H), 7.77 (dd, J = 8.4, 2.4 Hz, 1H), 7.62 (d, J = 7.6 Hz, 1H), 7.43 (t, J = 7.6 Hz, 1H), 7.33 – 7.25 (m, 3H), 3.78(s, 3H), 3.47 (dd, J = 13.6, 7.6 Hz, 1H), 3.34- 3.25(m, 1H), 3.00 (dd, J =14.0, 6.8 Hz, 1H), 1.29 (d, J = 6.8 Hz, 3H). 13 C-NMR (101 MHz, CDCl3): δ 186.0,167.3, 165.1, 146.2 (q, J CF = 4.0 Hz), 137.2, 133.3 (q, J C-F = 4.0 Hz), 127.0,126.6, 124.2 (q, J C-F = 32.3 Hz), 123.9 (q, J C-F = 272.7 Hz), 123.9, 123.4,122.9, 111.3, 44.1, 42.4, 32.1, 17.9. 19 F-NMR(376 MHz, CDCl3): δ -62.2. Meltingpoint = 69.7–70.5 o C.HRMS (ESI) m / z Calcd. for C 18 H 16 F3N3OSNa [M+Na] + 402.0864, ​​Found 402.0869. Example 36 Add 15 stainless steel balls with a diameter of 10 mm and 45 stainless steel balls with a diameter of 5 mm to a 100 mL stainless steel ball mill jar, and weigh them sequentially. N, N Dimethylmethacrylamide (1q, 0.3 mmol), 2-bromo-5-(trifluoromethyl)pyridine (2a, 4 equiv.), Cs₂CO₃ (2 equiv.), and BTO-700 (200 mg) were added to a stainless steel ball mill jar. Then, DMSO (0.2 μL / mg) was added to the jar using a pipette. After the addition was complete, the jar was sealed, evacuated, and purged with argon gas. This evacuation and purging process was repeated three times until the stainless steel jar was filled with argon gas. The jar was then placed in a planetary ball mill at 500 rpm and reacted at room temperature for 24 h. After the reaction, 20 mL of ethyl acetate was added to the stainless steel jar for extraction. The material was then filtered using a vacuum funnel and washed with ethyl acetate until the supernatant showed no fluorescence. The solvent was evaporated to dryness, and the sample was purified by silica gel column chromatography. The sample was eluted with a petroleum ether / dichloromethane / ethyl acetate system, yielding the desired product in 56% yield. N , N ,2-Trimethyl-3-(5-(trifluoromethyl)pyridin-2-yl)propionamide (3q).

[0075] The reaction process described above is shown in the following formula:

[0076] The characterization data of product 3q are as follows: Yellow brown liquid (Yield 56%, 43.4 mg). 1 H-NMR (400 MHz, CDCl3): δ 8.72 (s, 1H), 7.76 (dd, J = 8.0, 2.4 Hz, 1H), 7.28 (d, J =8.4 Hz, 1H), 3.44 – 3.36 (m, 1H), 3.25 (dd, J = 14.0, 8.8 Hz, 1H), 2.97 (s,3H), 2.86-2.80 (m, 4H), 1.14 (d, J = 7.2 Hz, 3H). 13 C-NMR (101 MHz, CDCl3): δ175.5, 164.4, 146.1 (q, J C-F = 4.0 Hz), 133.3 (q, J C-F = 4.0 Hz), 124.4 (q, J C-F =33.3 Hz), 123.8 (q, JC-F = 273.7 Hz), 123.8, 42.1, 37.2, 35.7, 17.7. 19 F-NMR(376MHz, CDCl3): δ -62.3. HRMS (ESI) m / z Calcd. for C 12 H 16 F3N2O [M+H] + 261.1215, Found 261.1220. Example 37 Add 15 stainless steel balls with a diameter of 10 mm and 45 stainless steel balls with a diameter of 5 mm to a 100 mL stainless steel ball mill jar, and weigh them sequentially. N , N Dimethylacrylamide (1r, 0.3 mmol), 2-bromo-5-(trifluoromethyl)pyridine (2a, 4 equiv.), Cs₂CO₃ (2 equiv.), and BTO-700 (200 mg) were added to a stainless steel ball mill jar. Then, DMSO (0.2 μL / mg) was added to the jar using a pipette. After the addition was complete, the jar was sealed, evacuated, and purged with argon gas. This evacuation and purging process was repeated three times until the stainless steel jar was filled with argon gas. The jar was then placed in a planetary ball mill at 500 rpm and reacted at room temperature for 24 h. After the reaction, 20 mL of ethyl acetate was added to the stainless steel jar for extraction. The material was then filtered using a vacuum funnel and washed with ethyl acetate until the supernatant showed no fluorescence. The solvent was evaporated to dryness, and the sample was purified by silica gel column chromatography. The sample was eluted with a petroleum ether / dichloromethane / ethyl acetate system, yielding a product with a yield of 39%. N , N -Dimethyl-3-(5-(trifluoromethyl)pyridin-2-yl)propionamide (3r).

[0077] The reaction process described above is shown in the following formula:

[0078] The characterization data of product 3r are as follows: Yellow brown solid (Yield 39%, 28.6 mg). 1 H-NMR (400 MHz, CDCl3): δ 8.74 (s, 1H), 7.79 (dd, J = 8.0, 2.0 Hz, 1H), 7.39 (d, J =8.0 Hz, 1H), 3.18 (t, J= 7.2 Hz, 2H), 3.00 (s, 3H), 2.91 (s, 3H), 2.84 (t, J =7.2 Hz, 2H). 13 C-NMR (101 MHz, CDCl3): δ 171.8, 165.3, 146.1 (q, J C-F = 4.0 Hz), 133.5 (q, J C-F = 3.0 Hz), 124.3 (q, J C-F = 33.3 Hz), 123.8 (q, J C-F = 272.7 Hz),123.5, 37.2, 35.5, 33.1, 32.0. 19 F-NMR(376 MHz, CDCl3): δ -62.3. Melting point= 78.0–79.2 o C.HRMS (ESI) m / z Calcd. for C 11 H 14 F3N2O [M+H] + 247.1058, Found247.1063. Example 38 Add 15 stainless steel balls with a diameter of 10 mm and 45 stainless steel balls with a diameter of 5 mm to a 100 mL stainless steel ball mill jar, and weigh them sequentially. N -methyl- N 1-Phenylenemethylacrylamide (1a, 0.3 mmol), 2-bromo-5-methylpyridine (2b, 4 equiv.), Cs₂CO₃ (2 equiv.), and BTO-700 (200 mg) were added to a stainless steel ball mill jar. Then, DMSO (0.2 μL / mg) was added to the jar using a pipette. After the addition was complete, the jar was sealed, evacuated, and purged with argon gas. This evacuation and purging process was repeated three times until the stainless steel jar was filled with argon gas. The jar was then placed in a planetary ball mill at 500 rpm and reacted at room temperature for 24 h. After the reaction, 20 mL of ethyl acetate was added to the stainless steel jar for extraction. The material was then filtered using a vacuum funnel and washed with ethyl acetate until the supernatant showed no fluorescence. The solvent was evaporated to dryness, and the sample was purified by silica gel column chromatography. The sample was eluted with a petroleum ether / dichloromethane / ethyl acetate system, yielding the desired product in 77% yield. N 2-Dimethyl-3-(5-methylpyridin-2-yl)- N -Phenylacetamide (4b).

[0079] The reaction process described above is shown in the following formula:

[0080] The characterization data for product 4b are as follows: Yellow solid (Yield 77%, 61.6 mg). 1 H-NMR (400MHz, CDCl3): δ 8.30 (s, 1H), 7.38 (dd, J = 8.0, 2.4 Hz, 1H), 7.34 – 7.28 (m,3H), 7.01 (d, J = 8.0 Hz, 1H), 6.80 (d, J = 7.2 Hz, 2H), 3.19-3.11 (m, 4H), 2.99 – 2.91 (m, 1H), 2.65 (dd, J = 13.2, 4.8 Hz, 1H), 2.31 (s, 3H), 1.10 (d, J = 6.8 Hz, 3H). 13 C-NMR (101 MHz, CDCl3): δ 175.9, 157.0, 149.3, 143.8, 136.8,130.4, 129.5, 127.6, 127.2, 123.1, 42.2, 37.5, 37.3, 18.4, 18.1. Meltingpoint= 85.6–86.7 o C.HRMS (ESI) m / z Calcd. for C 17 H 21 N2O [M+H] + 269.1654, Found269.1655. Example 39 Add 15 stainless steel balls with a diameter of 10 mm and 45 stainless steel balls with a diameter of 5 mm to a 100 mL stainless steel ball mill jar, and weigh them sequentially. N -methyl- N3-(5-methoxypyridine-2-yl)-phenylmethylacrylamide (1a, 0.3 mmol), 2-bromo-5-methoxypyridine (2c, 4 equiv.), Cs₂CO₃ (2 equiv.), and BTO-700 (200 mg) were added to a stainless steel ball mill jar. Then, DMSO (0.2 μL / mg) was added to the jar using a pipette. After the addition was complete, the jar was sealed, evacuated, and purged with argon gas. This evacuation and purging process was repeated three times until the stainless steel jar was filled with argon gas. The jar was then placed in a planetary ball mill at 500 rpm and reacted at room temperature for 24 h. After the reaction, 20 mL of ethyl acetate was added to the stainless steel jar for extraction. The material was then filtered using a vacuum funnel and washed with ethyl acetate until the supernatant showed no fluorescence. The solvent was evaporated to dryness, and the sample was purified by silica gel column chromatography. Elution was performed using a petroleum ether / dichloromethane / ethyl acetate system to obtain 3-(5-methoxypyridine-2-yl)- N 2-Dimethyl- N -Phenylacetamide (4c).

[0081] The reaction process described above is shown in the following formula:

[0082] The characterization data of product 4c are as follows: Yellow brown liquid (Yield 65%, 55 mg). 1 H-NMR (400 MHz, CDCl3): δ 8.14 (d, J = 2.8 Hz, 1H), 7.33-7.27 (m, 3H), 7.11 – 7.07(m, 1H), 7.02 (d, J = 8.8 Hz, 1H), 6.79 (d, J = 7.2 Hz, 2H), 3.82 (s, 3H), 3.13(s, 3H), 3.09 – 3.06 (m, 1H), 2.94 – 2.87 (m, 1H), 2.61 (dd, J = 13.6, 5.2 Hz, 1H), 1.07 (d, J = 6.4 Hz, 3H). 13 C-NMR (101 MHz, CDCl3): δ 176.0, 154.1, 152.0,143.8, 136.4, 129.6, 127.7, 127.2, 123.7, 120.9, 55.6, 41.6, 37.6, 37.3,18.4. HRMS (ESI) m / z Calcd. for C17 H 21 N₂O₂[M+H] + 285.1603, Found 285.1608. Example 40 Add 15 stainless steel balls with a diameter of 10 mm and 45 stainless steel balls with a diameter of 5 mm to a 100 mL stainless steel ball mill jar, and weigh them sequentially. N -methyl- N 3-(5-fluoropyridine-2-yl)-phenylmethylacrylamide (1a, 0.3 mmol), 2-bromo-5-fluoropyridine (2d, 4 equiv.), Cs₂CO₃ (2 equiv.), and BTO-700 (200 mg) were added to a stainless steel ball mill jar. Then, DMSO (0.2 μL / mg) was added to the jar using a pipette. After the addition was complete, the jar was sealed, evacuated, and purged with argon gas. This evacuation and purging process was repeated three times until the stainless steel jar was filled with argon gas. The jar was then placed in a planetary ball mill at 500 rpm and reacted at room temperature for 24 h. After the reaction, 20 mL of ethyl acetate was added to the stainless steel jar for extraction. The material was then filtered using a vacuum funnel and washed with ethyl acetate until the supernatant showed no fluorescence. The solvent was evaporated to dryness, and the sample was purified by silica gel column chromatography. Elution was performed using a petroleum ether / dichloromethane / ethyl acetate system to obtain 3-(5-fluoropyridine-2-yl)- N 2-Dimethyl- N -Phenylacetamide (4d).

[0083] The reaction process described above is shown in the following formula:

[0084] The characterization data of the product on day 4 are as follows: Yellow brown liquid (Yield 67%, 54.6 mg). 1 H-NMR (400 MHz, CDCl3): δ 8.29 (d, J = 3.2 Hz, 1H), 7.34 – 7.24 (m, 4H), 7.09 (dd, J = 8.8, 4.4 Hz, 1H), 6.82 (d, J = 7.2 Hz, 2H), 3.18 – 3.14 (m, 1H), 3.12 (s, 3H), 2.97 – 2.88 (m, 1H), 2.64 (dd, J = 13.6, 5.2 Hz, 1H), 1.07 (d, J = 6.8 Hz, 3H). 13C-NMR (101 MHz, CDCl3): δ 175.8, 158.3 (d, J C-F = 254.5 Hz), 156.2 (d, J C-F = 4.0 Hz), 143.8, 137.0 (d, J C-F = 22.2 Hz), 129.7, 127.8, 127.2, 124.5 (d, J C-F = 4.0 Hz), 123.0 (d, J C-F = 17.2 Hz), 41.8, 37.5, 37.4, 18.5. 19 F-NMR(376 MHz, CDCl3): δ -131.1. HRMS (ESI) m / z Calcd. for C 16 H 17 FN2ONa [M+Na] + 295.1223, Found295.1227. Example 41 Add 15 stainless steel balls with a diameter of 10 mm and 45 stainless steel balls with a diameter of 5 mm to a 100 mL stainless steel ball mill jar, and weigh them sequentially. N -methyl- N 1-Phenylenemethylacrylamide (1a, 0.3 mmol), 2-bromo-3-methylpyridine (2e, 4 equiv.), Cs₂CO₃ (2 equiv.), and BTO-700 (200 mg) were added to a stainless steel ball mill jar. Then, DMSO (0.2 μL / mg) was added to the jar using a pipette. After the addition was complete, the jar was sealed, evacuated, and purged with argon. This evacuation and purging process was repeated three times until the stainless steel jar was filled with argon. The jar was then placed in a planetary ball mill at 500 rpm and reacted at room temperature for 24 h. After the reaction, 20 mL of ethyl acetate was added to the stainless steel jar for complete extraction. The material was then filtered using a vacuum funnel and washed with ethyl acetate until the supernatant showed no fluorescence. The solvent was evaporated to dryness, and the sample was purified by silica gel column chromatography. The sample was eluted with a petroleum ether / dichloromethane / ethyl acetate system, yielding the desired product in 70% yield. N 2-Dimethyl-3-(3-methylpyridin-2-yl)- N -Phenylacetamide (4e).

[0085] The reaction process described above is shown in the following formula:

[0086] The characterization data of product 4e are as follows: Yellow brown solid (Yield 70%, 56.2 mg). 1 H-NMR (400 MHz, CDCl3): δ 8.28 (d, J = 4.8 Hz, 1H), 7.33 – 7.24 (m, 4H), 7.00 – 6.96 (m, 3H), 3.25 (dd, J = 14.4, 9.6 Hz, 1H), 3.15 (s, 3H), 3.11 – 3.06 (m, 1H), 2.59 (dd, J = 14.4, 4.4 Hz, 1H), 2.20 (s, 3H), 1.10 (d, J = 6.8 Hz, 3H). 13 C-NMR (101 MHz, CDCl3): δ 176.4, 158.3, 146.2, 144.1, 137.4, 131.5, 129.5, 127.6,127.5, 121.1, 39.2, 37.5, 35.8, 18.8, 18.5. Melting point = 48.6–50.8 o C.HRMS(ESI) m / z Calcd. for C 17 H 21 N2O [M+H] + 269.1654, Found 269.1659. Example 42 Add 15 stainless steel balls with a diameter of 10 mm and 45 stainless steel balls with a diameter of 5 mm to a 100 mL stainless steel ball mill jar, and weigh them sequentially. N -methyl- N1-Phenylenemethylacrylamide (1a, 0.3 mmol), 2-bromo-6-methylpyridine (2f, 4 equiv.), Cs₂CO₃ (2 equiv.), and BTO-700 (200 mg) were added to a stainless steel ball mill jar. Then, DMSO (0.2 μL / mg) was added to the jar using a pipette. After the addition was complete, the jar was sealed, evacuated, and purged with argon gas. This evacuation and purging process was repeated three times until the stainless steel jar was filled with argon gas. The jar was then placed in a planetary ball mill at 500 rpm and reacted at room temperature for 24 h. After the reaction, 20 mL of ethyl acetate was added to the stainless steel jar for extraction. The material was then filtered using a vacuum funnel and washed with ethyl acetate until the supernatant showed no fluorescence. The solvent was evaporated to dryness, and the sample was purified by silica gel column chromatography. The sample was eluted with a petroleum ether / dichloromethane / ethyl acetate system, yielding the desired product in 70% yield. N 2-Dimethyl-3-(6-methylpyridin-2-yl)- N -Phenylacetamide (4f).

[0087] The reaction process described above is shown in the following formula:

[0088] The characterization data of product 4f are as follows: Pale yellow liquid (Yield 70%, 56.7 mg). 1 H-NMR (400 MHz, CDCl3): δ 7.42 (t, J = 7.6 Hz, 1H), 7.25-7.22 (m, 3H), 6.95 (d, J =8.0 Hz, 1H), 6.89 (d, J = 7.6 Hz, 1H), 6.68-6.61 (m, 2H), 3.11 – 3.05 (m, 4H), 2.96-2.88 (m, 1H), 2.62 – 2.54 (m, 1H), 2.43 (s, 3H), 1.09 (d, J = 6.8 Hz, 3H). 13 C-NMR (101 MHz, CDCl3): δ 175.9, 159.3, 157.5, 143.7, 136.5, 129.4,127.6, 127.2, 120.8, 120.6, 42.9, 37.7, 37.2, 24.4, 18.6. HRMS (ESI) m / zCalcd. for C 17 H 21 N2O [M+H] +269.1654, Found 269.1657. Example 43 Add 15 stainless steel balls with a diameter of 10 mm and 45 stainless steel balls with a diameter of 5 mm to a 100 mL stainless steel ball mill jar, and weigh them sequentially. N -methyl- N 1-Phenylenemethylacrylamide (1a, 0.3 mmol), 2-bromo-4-trifluoromethylpyridine (2g, 4 equiv.), Cs₂CO₃ (2 equiv.), and BTO-700 (200 mg) were added to a stainless steel ball mill jar. Then, DMSO (0.2 μL / mg) was added to the jar using a pipette. After the addition was complete, the jar was sealed, evacuated, and purged with argon gas. This evacuation and purging process was repeated three times until the stainless steel jar was filled with argon gas. The jar was then placed in a planetary ball mill at 500 rpm and reacted at room temperature for 24 h. After the reaction, 20 mL of ethyl acetate was added to the stainless steel jar for extraction. The material was then filtered using a vacuum funnel and washed with ethyl acetate until the supernatant showed no fluorescence. The solvent was evaporated to dryness, and the sample was purified by silica gel column chromatography. The sample was eluted with a petroleum ether / dichloromethane / ethyl acetate system, yielding the desired product in 77% yield. N 2-Dimethyl- N -Phenylacetyl-3-(4-(trifluoromethyl)pyridin-2-yl)propionamide (4g).

[0089] The reaction process described above is shown in the following formula:

[0090] The characterization data for 4g of the product are as follows: Yellow brown liquid (Yield 77%, 77.1 mg). 1 H-NMR (400 MHz, CDCl3): δ 8.60 (d, J = 5.2 Hz, 1H), 7.30 – 7.22 (m, 5H), 6.81 (d, J =7.2 Hz, 2H), 3.25 (dd, J = 14.0, 10.0 Hz, 1H), 3.10 (s, 3H), 2.96 – 2.89 (m,1H), 2.71 (dd, J = 13.6, 4.4 Hz, 1H), 1.08 (d, J = 6.8 Hz, 3H). 13C-NMR (101 MHz, CDCl3): δ 175.5, 161.9, 150.1, 143.8, 138.4 (q, J C-F = 33.3 Hz), 129.7, 127.9,127.2, 122.9 (q, J C-F = 273.7 Hz), 119.1 (q, J C-F = 4.0 Hz), 116.9 (q, J C-F = 4.0Hz), 42.6, 37.4, 37.1, 18.4. 19 F-NMR(376 MHz, CDCl3): δ -64.8. HRMS (ESI) m / zCalcd. for C 17 H 18 F3N2O [M+H] + 323.1371, Found 323.1374. Example 44 Add 15 stainless steel balls with a diameter of 10 mm and 45 stainless steel balls with a diameter of 5 mm to a 100 mL stainless steel ball mill jar, and weigh them sequentially. N -methyl- N 1-Phenylenemethylacrylamide (1a, 0.3 mmol), 2-bromo-6-trifluoromethylpyridine (2h, 4 equiv.), Cs₂CO₃ (2 equiv.), and BTO-700 (200 mg) were added to a stainless steel ball mill jar. Then, DMSO (0.2 μL / mg) was added to the jar using a pipette. After the addition was complete, the jar was sealed, evacuated, and purged with argon gas. This evacuation and purging process was repeated three times until the stainless steel jar was filled with argon gas. The jar was then placed in a planetary ball mill at 500 rpm and reacted at room temperature for 24 h. After the reaction, 20 mL of ethyl acetate was added to the stainless steel jar for complete extraction. The material was then filtered using a vacuum funnel and washed with ethyl acetate until the supernatant showed no fluorescence. The solvent was evaporated to dryness, and the sample was purified by silica gel column chromatography. The sample was eluted with a petroleum ether / dichloromethane / ethyl acetate system, yielding a product with a yield of 36%. N 2-Dimethyl- N -Phenylacetyl-3-(6-(trifluoromethyl)pyridin-2-yl)propionamide (4h).

[0091] The reaction process described above is shown in the following formula:

[0092] The characterization data of the product at 4 h are as follows: Yellow liquid (Yield 36%, 34.8 mg). 1 H-NMR (400MHz, CDCl3): δ 7.74 (t, J = 8.0 Hz, 1H), 7.51 (d, J = 7.6 Hz, 1H), 7.37 – 7.26(m, 4H), 6.89 (d, J = 7.2 Hz, 2H), 3.28 (dd, J = 14.0, 10.8 Hz, 1H), 3.16 –3.06 (m, 4H), 2.73 (dd, J = 13.6, 4.0 Hz, 1H), 1.10 (dd, J = 6.8 Hz, 3H). 13 C-NMR (101 MHz, CDCl3): δ 175.6, 161.4, 147.6 (q, J C-F =33.3 Hz), 143.7, 137.5,129.8, 127.9, 127.4, 126.8, 121.8 (q, J C-F = 274.7 Hz), 118.0 (q, J C-F = 3.0 Hz),42.1, 37.4, 36.9, 18.7. 19 F-NMR(376 MHz, CDCl3): δ -67.7. HRMS (ESI) m / z Calcd.for C 17 H 17 F3N2ONa [M+Na] + 345.1191, Found 345.1195. Example 45 Add 15 stainless steel balls with a diameter of 10 mm and 45 stainless steel balls with a diameter of 5 mm to a 100 mL stainless steel ball mill jar, and weigh them sequentially. N -methyl- N1-Phenylenemethylacrylamide (1a, 0.3 mmol), 2-bromopyridine (2i, 4 equiv.), Cs₂CO₃ (2 equiv.), and BTO-700 (200 mg) were added to a stainless steel ball mill jar. Then, DMSO (0.2 μL / mg) was added to the jar using a pipette. After the addition was complete, the jar was sealed, evacuated, and purged with argon. This evacuation and purging process was repeated three times until the stainless steel jar was filled with argon. The jar was then placed in a planetary ball mill at 500 rpm and reacted at room temperature for 24 h. After the reaction, 20 mL of ethyl acetate was added to the stainless steel jar for extraction. The material was then filtered using a vacuum funnel and washed with ethyl acetate until the supernatant showed no fluorescence. The solvent was evaporated to dryness, and the sample was purified by silica gel column chromatography. The sample was eluted with a petroleum ether / dichloromethane / ethyl acetate system, yielding DMSO in 86% yield. N 2-Dimethyl- N -Phenylacetyl-3-(pyridin-2-yl)propionamide (4i).

[0093] The reaction process described above is shown in the following formula:

[0094] The characterization data of product 4i are as follows: Yellow brown solid (Yield 86%, 65.3 mg). 1 H-NMR (400 MHz, CDCl3): δ 8.45 (d, J = 4.8 Hz, 1H), 7.56 (td, J = 7.6, 2.0 Hz, 1H),7.32 – 7.28 (m, 3H), 7.13 – 7.09 (m, 2H), 6.76 (d, J = 7.2 Hz, 2H), 3.20 –3.16 (m, 1H), 3.13 (s, 3H), 2.99 – 2.90 (m, 1H), 2.68 (dd, J = 12.8, 4.8 Hz, 1H), 1.10 (d, J = 6.8 Hz, 3H). 13 C-NMR (101 MHz, CDCl3): δ 175.9, 160.1, 149.1,143.8, 136.3, 129.6, 127.7, 127.2, 123.7, 121.3, 42.8, 37.6, 37.4, 18.5.Melting point = 65.6–66.7 oC. HRMS (ESI) m / z Calcd. for C 16 H 19 N2O [M+H] + 255.1497, Found 255.1501. Example 46 Add 15 stainless steel balls with a diameter of 10 mm and 45 stainless steel balls with a diameter of 5 mm to a 100 mL stainless steel ball mill jar, and weigh them sequentially. N -methyl- N 1,2-phenylmethylacrylamide (1a, 0.3 mmol), iodobenzene (2j, 4 equiv.), Cs₂CO₃ (2 equiv.), and BTO-700 (200 mg) were added to a stainless steel ball mill jar. Then, DMSO (0.2 μL / mg) was added to the jar using a pipette. After the addition was complete, the jar was sealed, evacuated, and purged with argon gas. This evacuation and purging process was repeated three times until the stainless steel jar was filled with argon gas. The jar was then placed in a planetary ball mill at 500 rpm and reacted at room temperature for 24 h. After the reaction, 20 mL of ethyl acetate was added to the stainless steel jar for extraction. The material was then filtered using a vacuum funnel and washed with ethyl acetate until the supernatant showed no fluorescence. The solvent was evaporated to dryness, and the sample was purified by silica gel column chromatography. The sample was eluted with a petroleum ether / dichloromethane / ethyl acetate system, yielding a product with a yield of 36%. N 2-Dimethyl- N ,3-Diphenylpropionamide (4j).

[0095] The reaction process described above is shown in the following formula:

[0096] The characterization data of product 4j are as follows: Yellow liquid (Yield 19%, 14.3 mg). 1 H-NMR (400MHz, CDCl3): δ 7.30 – 7.26 (m, 3H), 7.23 – 7.20 (m, 3H), 6.98 (dd, J = 7.6,2.0 Hz, 2H), 6.67 (s, 2H), 3.15 (s, 3H), 2.96 (dd, J = 12.8, 8.4 Hz, 1H), 2.66– 2.57 (m, 1H), 2.49 (dd, J = 12.8, 6.0 Hz, 1H), 1.08 (d, J = 6.8 Hz, 3H). 13C-NMR (101 MHz, CDCl3): δ 176.0, 144.0, 140.3, 129.7, 129.2, 128.3, 127.8,127.4, 126.3, 40.9, 39.3, 37.4, 18.1. HRMS (ESI) m / z Calcd. for C 11 H 14 F3N2O [M+H] + 247.1058, Found 247.1063. Example 47 Fifteen stainless steel balls with a diameter of 10 mm and forty-five stainless steel balls with a diameter of 5 mm were added to a 100 mL stainless steel ball mill jar. 3-Methyl-1-(aniline)-3-buten-2-one (1 oz, 0.3 mmol), 2-bromoquinoline (2 kJ, 4 equiv.), Cs₂CO₃ (2 equiv.), and BTO-700 (200 mg) were then weighed and added to the jar. DMSO (0.2 μL / mg) was then added to the jar using a pipette. After the addition was complete, the jar was sealed, evacuated, and filled with argon gas. This evacuation and gas exchange was repeated three times until the stainless steel jar was filled with argon gas. The jar was then placed in a planetary ball mill, and the reaction was carried out at 500 rpm for 24 h at room temperature. After the reaction was completed, 20 mL of ethyl acetate was added to the stainless steel container for extraction. The material was then filtered using a vacuum funnel and washed with ethyl acetate until the supernatant showed no fluorescence. The solvent was evaporated to dryness, and the sample was purified by silica gel column chromatography. The sample was eluted with a petroleum ether / dichloromethane / ethyl acetate system to give 3-methyl-1-(phenylamino)-4-(quinolin-2-yl)butane-2-one (4k) in 46% yield.

[0097] The reaction process described above is shown in the following formula:

[0098] The characterization data of product 4k are as follows: Yellow brown solid (Yield 46%, 42.3 mg). 1 H-NMR (400 MHz, CDCl3): δ 8.02 (d, J = 8.4 Hz, 1H), 7.80 (dd, J = 22.0, 8.4 Hz, 2H), 7.63 (t, J = 7.6 Hz, 1H), 7.49 (t, J = 7.2 Hz, 1H), 7.26 (d, J= 8.4 Hz, 1H),7.16 – 7.07 (m, 3H), 6.96 (d, J = 7.2 Hz, 2H), 6.77 (t, J = 5.6 Hz, 1H), 4.39(dd, J = 14.8, 5.6 Hz, 1H), 4.24 (dd, J = 14.8, 5.2 Hz, 1H), 3.35 – 3.28 (m,1H), 3.11 – 3.05 (m, 2H), 1.29 (d, J = 6.4 Hz, 3H). 13 C-NMR (101 MHz, CDCl3): δ175.8, 160.4, 147.6, 138.3, 136.6, 129.6, 128.6, 128.5, 127.7, 127.6, 127.2,126.9, 126.1, 122.6, 43.5, 42.8, 40.9, 18.1. Melting point = 95.0–96.5 o C.HRMS (ESI) m / z Calcd. for C 20 H 21 N2O [M+H] + 305.1654, Found 305.1659. The above descriptions are merely embodiments of the present invention, and common knowledge regarding specific structures and characteristics is not elaborated upon here. It should be noted that those skilled in the art can make various modifications and improvements without departing from the structure of the present invention, and these should also be considered within the scope of protection of the present invention. These modifications and improvements will not affect the effectiveness of the present invention or the practicality of the patent. The scope of protection claimed in this application should be determined by the content of its claims, and the specific embodiments described in the specification can be used to interpret the content of the claims.

Claims

1. A mechanically driven synthesis method for a hydrogenated aryl product, characterized in that: Includes the following steps: Using aryl or alkyl acrylamides of Formula 1a and aryl halides of Formula 2a as substrates, and piezoelectric materials as catalysts, the hydroarylated products of Formula 3 were synthesized via a mechanically driven approach under conditions of liquid-assisted abrasives and alkaline substances. The synthetic route is shown in the figure below: ； R1 is independently selected from methyl, phenyl, 2-methylphenyl, 2-isopropylphenyl, 2-chlorophenyl, 2-bromophenyl, 2-iodophenyl, 2-pyrrolephenyl, 3-methylphenyl, 4-methylphenyl, 4-methoxyphenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 2,6-dimethylphenyl, 2-naphthyl, 2-phenylprophiazolyl; R2 is independently selected from hydrogen, methyl, ethyl, and phenyl; R3 is independently selected from hydrogen and methyl; R4 is independently selected from hydrogen, 5-methyl, 5-methoxy, 5-fluoro, 5-trifluoromethyl, 3-methyl, 6-methyl, 4-trifluoromethyl, and 6-trifluoromethyl. n is the number of carbon atoms, either 0 or 1; X is a halogen; A represents either carbon or nitrogen.

2. The mechanically driven synthesis method for a hydrogenated aryl product according to claim 1, characterized in that: The piezoelectric material is one of barium titanate, zinc oxide, copper borate, and titanium dioxide.

3. The mechanically driven synthesis method for a hydrogenated aryl product according to claim 2, characterized in that: The piezoelectric material is barium titanate, which is prepared by hydrothermal synthesis combined with heat treatment at a temperature of 0~1000°C. o C, heat treatment time is 1 to 6 hours.

4. The mechanically driven synthesis method for a hydrogenated aryl product according to claim 3, characterized in that: The amounts of the aryl or alkyl acrylamide 1a, aryl halide 2a, piezoelectric material, liquid auxiliary abrasive and alkaline substance added are 0.1~1.5 mmol, 2~5 equiv, 0~250 mg, 0~0.3 μL / mg, and 0~3 equiv, respectively.

5. The mechanically driven synthesis method for a hydrogenated aryl product according to claim 4, characterized in that: The alkaline substance is at least one of the following: cesium carbonate, potassium carbonate, potassium bicarbonate, sodium carbonate, sodium bicarbonate, sodium hydroxide, potassium hydroxide, potassium tert-butoxide, triethylamine, and diethylamine.

6. The mechanically driven synthesis method for a hydrogenated aryl product according to claim 5, characterized in that: The liquid auxiliary abrasive is at least one of DMSO, DMF, DCM, THF, MeCN, Acetone, 1,4-Dioxane, H2O, MeOH, n-hexane, and Toluene, or is solvent-free.

7. The mechanically driven synthesis method for a hydrogenated aryl product according to claim 6, characterized in that: The dosage of LAG is 0~0.3 μL / mg.

8. The mechanically driven synthesis method for a hydroarylized product according to claim 7, characterized in that: The ball-to-material ratio of the mechanically driven mill is 35:1 to 245:1; the ball mill speed of the mechanically driven mill is 400 to 600 rpm; and the reaction time of the mechanically driven mill is 3 to 36 h.

9. The mechanically driven synthesis method for a hydroarylized product according to claim 8, characterized in that: The reaction atmosphere is at least one of argon, vacuum, air, or oxygen.

10. The mechanically driven synthesis method for a hydrogenated aryl product according to claim 9, characterized in that: The mechanically driven milling media is at least one of stainless steel balls, tungsten carbide balls, alumina balls, and agate balls.

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