Photoinduction-based catalyst-free aryl cyano compound synthesis method
Through a photo-induced catalyst-free method, alkyl trifluoroborate and cyanoaromatic hydrocarbons generate EDA complexes under ultraviolet light excitation to directly synthesize aromatic cyano compounds, solving the problems of high cost of precious metal catalysts, many toxic byproducts and harsh reaction conditions in the existing technology, and realizing green and efficient synthesis of aromatic cyano compounds.
Patent Information
- Application Number
- CN202510621592.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-05-14
- Publication Date
- 2025-09-26
AI Technical Summary
Existing technologies for synthesizing aromatic cyano compounds suffer from the problems of high cost of precious metal catalysts, numerous toxic byproducts, harsh reaction conditions, and poor selectivity, making it difficult to achieve green, economical, and efficient synthesis.
A photoinduced catalyst-free method is used to form a homogeneous reaction system by reacting alkyl trifluoroborate with cyanoaromatic hydrocarbon in a polar solvent. Ultraviolet light is used to excite the alkyl trifluoroborate to generate an alkyl free radical intermediate, which forms an EDA complex with a boron tetrafluoride anion. The alkyl free radical intermediate directly reacts with an electron-deficient aromatic nitrile to form an aromatic cyano compound.
No precious metal catalysts and toxic additives are required, the reaction conditions are mild, the operation is simple, the substrate applicability is wide, the yield and selectivity are high, it is environmentally friendly, and it is suitable for a variety of synthesis needs.
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Figure CN120698903A_ABST
Abstract
Description
Technical Field
[0001] The present application belongs to the technical field of organic synthesis, and specifically relates to a method for synthesizing aromatic cyano compounds based on light induction and without catalyst. Background Art
[0002] As the core structural unit of cyanoaromatic hydrocarbon compounds, the aryl cyano structure has irreplaceable industrial value in the fields of pharmaceuticals, agricultural chemicals, and optoelectronic materials. The cyanoaromatic amine pharmacophore of the EGFR inhibitor osimertinib, the cyanopyridine skeleton of neonicotinoid insecticides, and the cyano receptor unit of thermally activated delayed fluorescence materials (Nature Communications, 2023, 14(1): 4561) all confirm the key role of this structure in the design of bioactive and functional materials. The green process of the synthesis technology of cyanoaromatic hydrocarbon intermediates is directly related to the sustainable development of downstream industries such as pharmaceuticals and agricultural chemicals.
[0003] Existing synthesis technologies face multiple bottlenecks: In the field of photocatalysis, traditional [Ru(bpy)3] 2+ Although the system can achieve cyanide insertion through CH activation, it has defects such as low precious metal photosensitizer cycle efficiency, high energy consumption of ultraviolet light source, and poor catalytic activity (Nature Reviews Chemistry, 2022, 6(11): 823-838). The recently proposed electron donor-acceptor (EDA) complex strategy reduces the carbon footprint, but still produces by-products (J.Am.Chem.Soc., 2018, 140, 1122). In terms of electrochemical synthesis, although the transition metal-free direct electrosynthesis method developed by Wu Shuhua's team has a yield of 90%, the activity of the platinum electrode decays sharply after 5 cycles. The biocatalytic principle is limited by the poor universality of the substrate and the low reaction efficiency. Although the hydrogen bond induced proximity effect system designed by Yang Gang's team improves the activity, it has not yet broken through the limitations of small molecule synthesis.
[0004] Recently, some researchers have proposed improvement measures. For example, the biphasic water-organic solvent system developed by the University of Washington solved the solubility problem of K4[Fe(CN)6] by coordinating Ni(II) precatalyst with commercial ligands, achieving electrode cycle stability while maintaining high yield. In addition, the dynamic covalent chemical strategy uses potassium cyanotrifluoroborate (Ar-C≡N-BF3K) to stabilize the intermediate through BN coordination, with a conversion rate of 98% in supercritical CO2. However, the unsustainable nature of the above-mentioned catalytic system, poor reaction selectivity and insufficient economy are still the core problems restricting industrial application. Therefore, the development of green, non-toxic, cost-effective and efficient synthesis technology can achieve sustainable development. Summary of the Invention
[0005] In order to overcome the deficiencies of the prior art, the present application provides a method for synthesizing aryl cyano compounds based on light induction and without catalyst. By illuminating and exciting a system of alkyl trifluoroborate and cyanoarene, the alkyl trifluoroborate undergoes single electron transfer (SET) deboronation to generate a highly active alkyl radical intermediate. The departing boron tetrafluoride anion combines with the cyanoarene to form an EDA complex; the alkyl radical intermediate then selectively attacks the electron-deficient aromatic ring site of the electron-deficient aromatic nitrile of the EDA complex to directly generate an aryl cyano compound. This method does not require metal catalysts, oxidants, or chemical additives, and the reaction conditions are mild. It is a green and efficient solution for the synthesis of aryl cyano compounds.
[0006] In order to achieve the above objectives, this application adopts the following technical solutions:
[0007] A method for synthesizing an aryl cyano compound based on light induction and without catalyst, comprising:
[0008] dissolving an alkyl trifluoroborate and a cyanoarene in a polar solvent to form a homogeneous reaction system;
[0009] performing an anaerobic treatment on the homogeneous reaction system to obtain an anaerobic reaction environment;
[0010] Irradiating the homogeneous reaction system with a light source containing ultraviolet light of a wavelength of 200 nm to 780 nm to stimulate the cleavage of the alkyl trifluoroborate to generate an alkyl radical intermediate and a boron tetrafluoride anion; the boron tetrafluoride anion forms an EDA complex with the cyanoarene; and
[0011] The alkyl radical intermediate and the EDA complex are directly used to synthesize an aryl cyano compound.
[0012] Furthermore, the alkyl trifluoroborate includes potassium benzyl trifluoroborate, potassium p-fluorobenzyl trifluoroborate, potassium p-methoxybenzyl trifluoroborate, potassium isobenzofuran trifluoroborate, potassium tert-butoxymethyl trifluoroborate, potassium 2,4-difluorobenzyl trifluoroborate, potassium cyclohexylmethyl trifluoroborate, potassium [1,1′-biphenyl]-4-methyl trifluoroborate or potassium naphthylmethyl trifluoroborate.
[0013] Furthermore, the cyanoaromatic hydrocarbon includes terephthalonitrile, isonicotinonitrile, 4-acetylbenzonitrile, methyl 4-cyanobenzoate or 2,5-dimethylterephthalonitrile.
[0014] Furthermore, the polar solvent is selected from at least one of acetonitrile, dimethyl sulfoxide, N,N-dimethylformamide or acetone.
[0015] Furthermore, the light source includes at least one of a blue LED lamp, an ultraviolet LED lamp, a xenon lamp and natural light.
[0016] Furthermore, the wavelength of the ultraviolet light is 420 nm.
[0017] Furthermore, the temperature of the synthesis process is controlled at 25-40° C., the synthesis time is 6-8 hours, and the molar ratio of the alkyl trifluoroborate to the cyanoaromatic hydrocarbon is 1:1-1:2.
[0018] Furthermore, the anaerobic treatment includes introducing an inert gas into the homogeneous reaction system at a flow rate of 50 mL / min to replace the oxygen in the homogeneous reaction system and then sealing the system to obtain an anaerobic reaction environment.
[0019] Furthermore, it also includes:
[0020] Monitor the progress of the synthesis by thin layer chromatography until the starting material spots disappear; and
[0021] The synthesized product was transferred to a rotary evaporator and concentrated under reduced pressure at 40° C. to remove the polar solvent. The residue was purified by silica gel column chromatography to obtain an aryl cyano compound.
[0022] Furthermore, the molar ratio of petroleum ether to ethyl acetate in the thin layer chromatography is 5:1;
[0023] The molar ratio of petroleum ether to ethyl acetate in the silica gel column chromatography is 20:1.
[0024] Compared with the prior art, this application has the following advantages:
[0025] 1. No precious metal catalysts required: Traditional technologies require precious metal catalysts such as palladium and rhodium, which are costly and carry the risk of metal residue. This application eliminates the need for metal catalysts and toxic additives, effectively reducing costs and pollution risks.
[0026] 2. Environmentally friendly: It avoids the use of strong oxidants in traditional processes, reduces the production of toxic by-products and high-salt wastewater, and is more environmentally friendly.
[0027] 3. Mild reaction conditions: The reaction can be carried out at room temperature and pressure, without the need for harsh conditions such as high temperature and high pressure, which reduces energy consumption and operational difficulty.
[0028] 4. Easy to operate: The experimental operation process is relatively simple, without the need for complex equipment and tedious steps, and is easy to apply in laboratories and industrial production.
[0029] 5. Broad substrate applicability and high reactivity: A rich variety of alkyl trifluoroborates and cyanoarene substrates are available, meeting diverse synthetic needs. Furthermore, this method exhibits excellent reactivity, with yields exceeding 85% for multiple target products and selectivity exceeding 90%.
[0030] In summary, the present application provides a green, efficient and economical synthesis of aromatic cyano compounds, which is expected to be widely used in the field of organic synthesis and promote the sustainable development of related industries. BRIEF DESCRIPTION OF THE DRAWINGS
[0031] The drawings described herein are used to provide a further understanding of the present application and constitute a part of the present application. The illustrative embodiments of the present application and their descriptions are used to explain the present application but do not constitute an improper limitation on the present application. In the drawings:
[0032] Figure 1 A flow chart of the method of this application;
[0033] Figure 2 This is the H NMR spectrum of the reaction of potassium cyclopentylmethyl trifluoroborate and terephthalonitrile;
[0034] Figure 3 This is the NMR carbon spectrum of the reaction result of cyclopentylmethyl potassium trifluoroborate and terephthalonitrile;
[0035] Figure 4 This is the H NMR spectrum of the reaction of potassium benzyl trifluoroborate and terephthalonitrile;
[0036] Figure 5 This is the NMR carbon spectrum of the reaction result of potassium benzyl trifluoroborate and terephthalonitrile;
[0037] Figure 6 This is the H NMR spectrum of the reaction of potassium p-fluorobenzyl trifluoroborate and terephthalonitrile;
[0038] Figure 7 This is the NMR carbon spectrum of the reaction result of potassium p-fluorobenzyl trifluoroborate and terephthalonitrile;
[0039] Figure 8 This is the H NMR spectrum of the reaction of potassium p-methoxybenzyl trifluoroborate and terephthalonitrile;
[0040] Figure 9 This is the NMR carbon spectrum of the reaction result of potassium p-methoxybenzyl trifluoroborate and terephthalonitrile;
[0041] Figure 10 This is the H NMR spectrum of the reaction of potassium isobenzofuran trifluoroborate and terephthalonitrile;
[0042] Figure 11 This is the NMR carbon spectrum of the reaction of potassium isobenzofuran trifluoroborate and terephthalonitrile;
[0043] Figure 12 This is the H NMR spectrum of the reaction of potassium benzyl trifluoroborate and isonicotinonitrile;
[0044] Figure 13This is the NMR carbon spectrum of the reaction result of potassium benzyl trifluoroborate and isonicotinonitrile;
[0045] Figure 14 This is the H NMR spectrum of the reaction of potassium benzyl trifluoroborate and methyl 4-cyanobenzoate;
[0046] Figure 15 This is the C NMR spectrum of the reaction result of potassium benzyltrifluoroborate and methyl 4-cyanobenzoate. DETAILED DESCRIPTION
[0047] In order to enable those skilled in the art to better understand the solution of the present application, the technical solution in the embodiments of the present application will be clearly and completely described below in conjunction with the drawings in the embodiments of the present application.
[0048] In the description of this application, it should be understood that the relationship between the method steps can be in sequence or not, as long as it does not affect the overall technical effect, and therefore cannot be understood as a limitation on this application. The following description of this application is only to be understood as a description of individual embodiments of the technical solution of this application. Other embodiments are not reflected in the following description, but it does not mean that this application excludes these other embodiments, and the technical solution of this application is not limited to the specific implementation methods described below, and the scope of protection of this application is not limited to only the specific implementation methods described below. Based on the embodiments in this application, all other embodiments obtained by ordinary technicians in this field without making creative work should fall within the scope of protection of this application.
[0049] It should be noted that, if the terms "first", "second", etc. appear in the specification and claims of the present application and the above-mentioned drawings, the description is only used to distinguish similar objects and is not necessarily used to describe a specific order or sequential order. It should be understood that the terms used in this way can be interchangeable where appropriate, so that the embodiments of the present application described herein can be implemented in a sequence other than those illustrated or described herein. In addition, the terms "including" and "having" and any of their variations are intended to cover non-exclusive inclusions, for example, a process, method, system, product or device comprising a series of steps or units is not necessarily limited to those steps or units clearly listed, but may include other steps or units that are not clearly listed or inherent to these processes, methods, products or devices.
[0050] In some embodiments, as Figure 1 As shown, the present application provides a method for synthesizing an aromatic cyano compound based on light induction and without catalyst, comprising:
[0051] S1: dissolving alkyl trifluoroborate and cyanoarene in a polar solvent to form a homogeneous reaction system;
[0052] Specifically, the molar ratio of the alkyl trifluoroborate to the cyanoarene is 1:1-1:2.
[0053] The alkyl trifluoroborate includes potassium benzyl trifluoroborate, potassium p-fluorobenzyl trifluoroborate, potassium p-methoxybenzyl trifluoroborate, potassium isobenzofuran trifluoroborate, potassium tert-butoxymethyl trifluoroborate, potassium 2,4-difluorobenzyl trifluoroborate, potassium cyclohexylmethyl trifluoroborate, potassium [1,1′-biphenyl]-4-methyl trifluoroborate or potassium naphthylmethyl trifluoroborate.
[0054] The cyanoaromatic hydrocarbons include terephthalonitrile, isonicotinonitrile, 4-acetylbenzonitrile, methyl 4-cyanobenzoate or 2,5-dimethylterephthalonitrile.
[0055] The polar solvent is selected from at least one of acetonitrile, dimethyl sulfoxide, N,N-dimethylformamide or acetone.
[0056] S2: performing an anaerobic treatment on the homogeneous reaction system to obtain an anaerobic reaction environment;
[0057] Specifically, the anaerobic treatment includes introducing an inert gas into the homogeneous reaction system at a flow rate of 50 mL / min to replace the oxygen in the homogeneous reaction system, and then sealing the system to obtain an anaerobic reaction environment.
[0058] S3: irradiating the homogeneous reaction system with a light source containing ultraviolet light with a wavelength of 200 nm to 780 nm to stimulate the cleavage of the alkyl trifluoroborate to generate an alkyl radical intermediate and a boron tetrafluoride anion; the boron tetrafluoride anion forms an EDA complex with the cyanoarene;
[0059] Specifically, the light source includes at least one of a blue LED lamp, an ultraviolet LED lamp, a xenon lamp, and natural light. Furthermore, the wavelength of the ultraviolet light is preferably 420 nm. The synthesis process temperature is controlled at 25-40° C., and the synthesis time is 6-8 hours.
[0060] S4: The alkyl radical intermediate and the EDA complex are directly used to synthesize an aryl cyano compound.
[0061] Specifically, the alkyl radical selectively attacks the electron-deficient site in the EDA complex to directly synthesize the target product, an aryl cyano compound.
[0062] In some embodiments, the method further comprises: monitoring the synthesis progress by thin layer chromatography until the raw material spots disappear; and transferring the synthesized product to a rotary evaporator and concentrating under reduced pressure at 40° C. to remove the polar solvent, and purifying the residue by silica gel column chromatography to obtain an aromatic cyano compound.
[0063] Specifically, the molar ratio of petroleum ether to ethyl acetate in the thin layer chromatography is 5:1; the molar ratio of petroleum ether to ethyl acetate in the silica gel column chromatography is 20:1.
[0064] The following is the experimental operation process of the method of this application, including reaction system construction, reaction condition setting, reaction monitoring and product analysis.
[0065] Specific examples 1-6 are as follows:
[0066] Example 1: Potassium cyclopentylmethyl trifluoroborate and terephthalonitrile
[0067] Cyclopentylmethyl trifluoroborate potassium (1.0 mmol, 188.4 mg) and terephthalonitrile (1.2 mmol, 153.8 mg) were accurately weighed in a 25 mL quartz reaction tube, 5 mL of acetonitrile was added as a solvent, and magnetic stirring was performed until the solution was completely dissolved to form a homogeneous solution. Subsequently, nitrogen was introduced into the reaction system at a flow rate of 50 mL / min for 10 minutes, and the oxygen in the system was completely replaced and the reaction tube was sealed to ensure an oxygen-free environment. Next, the reaction tube was placed directly below a 420 nm blue LED array (light intensity 50 mW / cm 2 , the light source is 10 cm away), the circulating water cooling system is turned on to keep the temperature constant at 25±1°C, and the light reaction is continued for 8 hours. During this period, the temperature fluctuation is monitored in real time and does not exceed ±1°C. After the reaction is completed, the mixture is transferred to a rotary evaporator and concentrated under reduced pressure at 40°C to remove acetonitrile. The residue is purified by silica gel column chromatography (petroleum ether / ethyl acetate = 20:1) to obtain a solid product 4-cyclopentylbenzonitrile, such as Figure 2-3 As shown. 1 H NMR (400 MHz, CDCI3): δ = 1.52-1.61 (m, 2H), 1.67-7.1.75 (m, 2H), 1.79-1.86 (m, 2H), 2.05-2.12 (m, 2H), 2.99-3.08 (m, 1H), 7.32 (d, J = 8.4 Hz, 2H), 7.56 (d, J = 8.4 Hz, 2H) ppm. C NMR (100 MHz, CDCI3): δ = 25.6, 34.6, 46.1, 109.5, 119.4, 128.0, 132.2, 152.5 ppm, confirming the product structure. The final isolated yield reached 92%, and the HPLC analysis purity was >99.5%, verifying the high efficiency and selectivity of the reaction.
[0068] Example 2: Potassium benzyl trifluoroborate and terephthalonitrile
[0069] In a 25 mL quartz reaction tube, potassium benzyl trifluoroborate (1.0 mmol, 196.1 mg) and terephthalonitrile (1.2 mmol, 153.8 mg) were accurately weighed, 5 mL DMSO was added as a solvent, and magnetic stirring was performed until the mixture was completely dissolved to form a homogeneous solution. Subsequently, nitrogen was introduced into the reaction system at a flow rate of 50 mL / min for 10 minutes, and the reaction tube was sealed after completely replacing the oxygen in the system to ensure an oxygen-free environment. Next, the reaction tube was placed directly below a 420 nm blue light LED array (light intensity 50 mW / cm 2 , the light source is 10 cm away), the circulating water cooling system is turned on to keep the temperature constant at 20±1°C, and the light reaction is continued for 8 hours. During this period, the temperature fluctuation is monitored in real time and does not exceed ±1°C. After the reaction is completed, the mixture is transferred to a rotary evaporator and concentrated under reduced pressure at 40°C to remove DMSO. The residue is purified by silica gel column chromatography (petroleum ether / ethyl acetate = 20:1) to obtain a solid product 4-benzylbenzonitrile, such as Figure 4-5 As shown. 1 H NMR (400 MHz, CDCI3): δ = 4.02 (s, 2H), 7.14-7.16 (m, 2H), 7.21-7.36 (overlap, 6H), 7.55 (d, J = 8.4 Hz, 2H) ppm. C NMR (100 MHz, CDCI3): δ = 42.3, 110.1, 119.1, 126.7, 128.8, 129.0, 129.7, 132.4, 139.4, 146.8 ppm, confirming the product structure. The final isolated yield reached 90%, and the HPLC purity was >97.5%, verifying the high efficiency and selectivity of the reaction.
[0070] Example 3: Potassium p-fluorobenzyl trifluoroborate and terephthalonitrile
[0071] In a 25 mL quartz reaction tube, potassium p-fluorobenzyl trifluoroborate (1.0 mmol, 214.1 mg) and terephthalonitrile (1.2 mmol, 153.8 mg) were accurately weighed, 5 mL DMSO was added as a solvent, and magnetic stirring was performed until the mixture was completely dissolved to form a homogeneous solution. Subsequently, nitrogen was introduced into the reaction system at a flow rate of 50 mL / min for 10 minutes, and the reaction tube was sealed after completely replacing the oxygen in the system to ensure an oxygen-free environment. Next, the reaction tube was placed under a UV LED (spectral range 200-400 nm) (light intensity 50 mW / cm 2, the light source is 10 cm away), the circulating water cooling system is turned on to keep the temperature constant at 20±1°C, and the light reaction is continued for 8 hours. During this period, the temperature fluctuation is monitored in real time and does not exceed ±1°C. After the reaction is completed, the mixture is transferred to a rotary evaporator and concentrated under reduced pressure at 40°C to remove DMSO. The residue is purified by silica gel column chromatography (petroleum ether / ethyl acetate = 20:1) to obtain a solid product 4-(4-fluorobenzyl)benzonitrile, such as Figure 6-7 As shown. 1 H NMR (400 MHz, CDCI3): δ = 4.00 (s, 2H), 6.97-7.02 (m, 2H), 7.10-7.13 (m, 2H), 7.25-7.27 (overlap, 2H), 7.57 (d, J = 8.4 Hz, 2H) ppm. 13C NMR (100 MHz, CDCI3): δ = 41.2, 110.4, 115.5, 115.8, 119.0, 129.6, 130.5, 130.6, 132.5, 135.1, 146.6, 160.6, 163.0 ppm, confirming the product structure. The final isolated yield reached 88%, and the HPLC purity was >90.5%, verifying the high efficiency and selectivity of the reaction.
[0072] Example 4: Potassium p-methoxybenzyl trifluoroborate and terephthalonitrile
[0073] In a 25 mL quartz reaction tube, potassium p-methoxybenzyl trifluoroborate (1.0 mmol, 226.2 mg) and terephthalonitrile (1.2 mmol, 153.8 mg) were accurately weighed, 5 mL DMSO was added as a solvent, and magnetic stirring was performed until the mixture was completely dissolved to form a homogeneous solution. Subsequently, nitrogen was introduced into the reaction system at a flow rate of 50 mL / min for 10 minutes, and the reaction tube was sealed after completely replacing the oxygen in the system to ensure an oxygen-free environment. Next, the reaction tube was placed under a xenon lamp (spectral range 380-780 nm) (light intensity 150 mW / cm 2 , the light source is 20 cm away), the circulating water cooling system is turned on to keep the temperature constant at 20±1°C, and the light reaction is continued for 8 hours. During this period, the temperature fluctuation is monitored in real time and does not exceed ±1°C. After the reaction is completed, the mixture is transferred to a rotary evaporator and concentrated under reduced pressure at 40°C to remove DMSO. The residue is purified by silica gel column chromatography (petroleum ether / ethyl acetate = 20:1) to obtain a solid product 4-(4-methoxybenzyl)benzonitrile, such as Figure 8-9 As shown. 1H NMR (400 MHz, CDCI3): δ = 3.79 (s, 3H), 3.97 (s, 2H), 6.84-6.87 (m, 2H), 7.07 (d, J = 8.8 Hz, 2H), 7.26-7.28 (overlap, 2H), 7.56 (d, J = 8.4 Hz, 2H) ppm. C NMR (100 MHz, CDCI3): δ = 41.2, 55.4, 110.0, 114.3, 119.2, 129.7, 130.1, 131.5, 132.4, 147.4, 158.4 ppm, confirming the product structure. The final isolated yield reached 91%, and the HPLC analysis purity was >99.5%, verifying the high efficiency and selectivity of the reaction.
[0074] Example 5: Potassium Isobenzofuran Trifluoroborate and Terephthalonitrile
[0075] In a 25 mL quartz reaction tube, potassium isobenzofuran trifluoroborate (1.0 mmol, 252.2 mg) and terephthalonitrile (1.2 mmol, 153.8 mg) were accurately weighed, 5 mL DMSO was added as a solvent, and magnetic stirring was performed until the mixture was completely dissolved to form a homogeneous solution. Subsequently, nitrogen was introduced into the reaction system at a flow rate of 50 mL / min for 10 minutes to completely replace the oxygen in the system and then the reaction tube was sealed to ensure an oxygen-free environment. Next, the reaction tube was placed in a natural light environment (sunny, 30-37° C.) and the light reaction was continued for 12 hours for 3 days. After the reaction was completed, the mixture was transferred to a rotary evaporator and concentrated under reduced pressure at 40° C. to remove DMSO. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 20:1) to obtain a solid product 5-benzylisobenzofuran-1(3H)-one, as shown in FIG. Figure 10-11 As shown. 1 H NMR (400 MHz, CDCI3): δ = 4.12 (s, 2H), 5.26 (s, 2H), 7.19 (d, J = 6.8 Hz, 2H), 7.23-7.27 (overlap, 2H), 7.31-7.34 (m, 2H), 7.38 (d, J = 8.4 Hz, 1H), 7.84 (d, J = 6.2 Hz, 1H) ppm. 13C NMR (100 MHz, CDCI3): δ = 42.3, 69.6, 122.4, 123.9, 125.9, 126.8, 128.9, 129.1, 130.2, 139.7, 147.4, 148.5, 171.2 ppm, confirming the structure of the product. The final isolated yield reached 47% and the HPLC analysis purity was >90%, verifying the high efficiency and selectivity of the reaction.
[0076] Example 6: Potassium benzyl trifluoroborate and isonicotinonitrile
[0077] In a 25 mL quartz reaction tube, potassium benzyl trifluoroborate (1.0 mmol, 184.1 mg) and isonicotinonitrile (1.2 mmol, 129.8 mg) were accurately weighed, 5 mL DMSO was added as a solvent, and magnetic stirring was performed until completely dissolved to form a homogeneous solution. Subsequently, nitrogen was introduced into the reaction system at a flow rate of 50 mL / min for 10 minutes, and the reaction tube was sealed after completely replacing the oxygen in the system to ensure an oxygen-free environment. Next, the reaction tube was placed directly below a 420 nm blue LED array (light intensity 50 mW / cm 2 , the light source is 10 cm away), the circulating water cooling system is turned on to keep the temperature constant at 25±1°C, and the light reaction is continued for 8 hours. During this period, the temperature fluctuation is monitored in real time and does not exceed ±1°C. After the reaction is completed, the mixture is transferred to a rotary evaporator and concentrated under reduced pressure at 40°C to remove DMSO. The residue is purified by silica gel column chromatography (petroleum ether / ethyl acetate = 20:1) to obtain a solid product 4-benzylpyridine, such as Figure 12-13 As shown. 1 H NMR (400 MHz, CDCI3): δ = 3.97 (s, 2H), 7.10 (d, J = 4.8 Hz, 2H), 7.16-7.19 (m, 2H), 7.22-7.27 (overlap, 1H), 7.30-7.34 (m, 2H), 8.49-8.50 (m, 2H) ppm. C NMR (100 MHz, CDCI3): δ = 41.4, 124.4, 126.8, 128.7, 129.2, 139.0, 149.9, 150.2 ppm, confirming the product structure. The final isolated yield reached 87%, and the HPLC analysis purity was >92%, verifying the high efficiency and selectivity of the reaction.
[0078] Example 7: Potassium benzyl trifluoroborate and methyl 4-cyanobenzoate
[0079] Benzyl trifluoroborate potassium (1.0 mmol, 196.1 mg) and methyl 4-cyanobenzoate (1.2 mmol, 193.0 mg) were accurately weighed in a 25 mL quartz reaction tube, 5 mL DMSO was added as a solvent, and the mixture was stirred until completely dissolved. Subsequently, nitrogen was introduced into the reaction system at a flow rate of 50 mL / min for 10 minutes, and the reaction tube was sealed after the oxygen in the system was completely replaced to ensure an oxygen-free environment. Next, the reaction tube was placed directly below a 420 nm blue light LED array (light intensity 50 mW / cm 2, the light source is 10 cm away), the circulating water cooling system is turned on to keep the temperature constant at 25±1°C, and the light reaction is continued for 8 hours. After the reaction is completed, the mixture is transferred to a rotary evaporator and concentrated under reduced pressure at 40°C to remove DMSO. The residue is purified by silica gel column chromatography (petroleum ether / ethyl acetate = 20:1) to obtain a solid product, methyl 4-benzylbenzoate, as shown Figure 14-15 As shown. 1 H NMR (400 MHz, CDCI3): δ = 3.89 (s, 3H), 4.03 (s, 2H), 7.17 (d, J = 6.4 Hz, 2H), 7.20-7.31 (overlap, 5H), 7.96 (d, J = 8.0 Hz, 2H) ppm. C NMR (100 MHz, CDCI3): δ = 42.0, 52.2, 126.5, 128.2, 128.7, 129.1, 129.9, 140.3, 146.7, 167.2 ppm, confirming the product structure. The final isolated yield reached 57%, and the HPLC analysis purity was >90%, verifying the high efficiency and selectivity of the reaction.
[0080] The above-described embodiments only express several implementation methods of the present application, and their descriptions are relatively specific and detailed, but they should not be understood as limiting the scope of the invention patent. It should be pointed out that for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present application, and these all fall within the scope of protection of the present application. Therefore, the scope of protection of the patent in this application should be based on the attached claims, and the selection and description of the implementation methods are to best illustrate the principles of the present application and its practical application, so as to enable other technicians in this field to best use the present application with various modifications suitable for the specific purpose envisioned and the various described implementation methods.
Claims
1. A method for synthesizing an aromatic cyano compound based on light induction and without catalyst, characterized in that: include: dissolving an alkyl trifluoroborate and a cyanoarene in a polar solvent to form a homogeneous reaction system; performing an anaerobic treatment on the homogeneous reaction system to obtain an anaerobic reaction environment; Irradiating the homogeneous reaction system with a light source containing ultraviolet light of a wavelength of 200 nm to 780 nm to stimulate the cleavage of the alkyl trifluoroborate to generate an alkyl radical intermediate and a boron tetrafluoride anion; the boron tetrafluoride anion forms an EDA complex with the cyanoarene; and The alkyl radical intermediate and the EDA complex are directly used to synthesize an aryl cyano compound.
2. The method for synthesizing an aromatic cyano compound based on light induction and without catalyst according to claim 1, characterized in that: The alkyl trifluoroborate includes potassium benzyl trifluoroborate, potassium p-fluorobenzyl trifluoroborate, potassium p-methoxybenzyl trifluoroborate, potassium isobenzofuran trifluoroborate, potassium tert-butoxymethyl trifluoroborate, potassium 2,4-difluorobenzyl trifluoroborate, potassium cyclohexylmethyl trifluoroborate, potassium [1,1′-biphenyl]-4-methyl trifluoroborate or potassium naphthylmethyl trifluoroborate.
3. The method for synthesizing an aromatic cyano compound based on light induction and without catalyst according to claim 1, characterized in that: The cyanoaromatic hydrocarbons include terephthalonitrile, isonicotinonitrile, 4-acetylbenzonitrile, methyl 4-cyanobenzoate or 2,5-dimethylterephthalonitrile.
4. The method for synthesizing an aromatic cyano compound based on light induction and without catalyst according to claim 3, characterized in that: The polar solvent is selected from at least one of acetonitrile, dimethyl sulfoxide, N,N-dimethylformamide or acetone.
5. The method for synthesizing an aromatic cyano compound based on light induction and without catalyst according to claim 1, characterized in that: The light source includes at least one of a blue LED lamp, an ultraviolet LED lamp, a xenon lamp and natural light.
6. The method for synthesizing an aromatic cyano compound based on light induction and without catalyst according to claim 5, characterized in that: The wavelength of the ultraviolet light is 420 nm.
7. The method for synthesizing an aromatic cyano compound based on light induction and without catalyst according to claim 1, characterized in that: The temperature of the synthesis process is controlled at 25-40° C., and the synthesis time is 6-8 hours. The molar ratio of the alkyl trifluoroborate to the cyano aromatic hydrocarbon is 1:1-1:
2.
8. The method for synthesizing an aromatic cyano compound based on light induction and without catalyst according to claim 1, characterized in that: The anaerobic treatment includes introducing an inert gas into the homogeneous reaction system at a flow rate of 50 mL / min to replace the oxygen in the homogeneous reaction system and then sealing the system to obtain an anaerobic reaction environment.
9. The method for synthesizing an aromatic cyano compound based on light induction and without catalyst according to claim 1, characterized in that: Also includes: The synthesis progress was monitored by thin-layer chromatography until the starting material spots disappeared; as well as The synthesized product was transferred to a rotary evaporator and concentrated under reduced pressure at 40° C. to remove the polar solvent. The residue was purified by silica gel column chromatography to obtain an aryl cyano compound.
10. The method for synthesizing an aromatic cyano compound based on light induction and without catalyst according to claim 9, characterized in that: The molar ratio of petroleum ether to ethyl acetate in the thin layer chromatography was 5:1; The molar ratio of petroleum ether to ethyl acetate in the silica gel column chromatography is 20:1.