Pyridine derivative compound as well as preparation method and application thereof

Abstract

The invention discloses a pyridine derivative compound as well as a preparation method and application thereof, and belongs to the technical field of chemical synthesis, the chemical formula of the pyridine derivative compound is shown as follows: in the formula, R1 is any one of hydrogen, 4-methyl, 2-methyl, 4-fluorine and 2-fluorine; r2 is any one of a 4-phenyl group and a 4-trifluoromethyl group; r3 is hydrogen or fluorine; the invention provides a pyridine derivative compound with a novel structure, and the pyridine derivative compound has excellent antibacterial performance, and is particularly applied to industrial application of staphylococcus aureus, escherichia coli and the like as an antibacterial agent.

Description

Technical Field

[0001] The present application relates to a pyridine derivative compound and a preparation method and application thereof, belonging to the technical field of chemical synthesis. Background Art

[0002] Nitrogen-containing compounds, including nitramines, imines, and secondary amines, are widely used in research laboratories and the chemical industry as important intermediates for the synthesis of fine chemicals, pharmaceuticals, and agrochemicals. Both aromatic and cyclic amines occupy a special place in medicinal chemistry. α-Aminopyridines, in particular, are not only ubiquitous in chemical synthesis plants as dyes and important industrial materials, but are also important components of various pharmaceutical formulations.

[0003] In 2020, Smith.J. reported in Journal of Organic Chemistry, 85(5), 1234-1240 that 2-aminopyridine was generated by heating pyridine with ammonia at high temperature (200°C); in Nature Chemistry volume 13, 1207-1213 (2021), a direct olefination reaction of pyridine was reported: by introducing a functionalized carbene ligand-coordinated nickel-aluminum (Ni(0)-Al(III)) bimetallic catalytic strategy, a direct olefination reaction of one equivalent of pyridine was achieved, providing an economical and efficient approach for the late modification of widely existing biologically active pyridine structure molecules; in ACS Catal. 2022, 12, 16, 10499-10505, a visible light-catalyzed C-H arylation reaction of pyridine was reported. They used Ir(ppy) as a photocatalyst and aryl diazonium salts as arylation reagents to achieve C-H arylation of pyridine and its derivatives under mild reaction conditions. With the development of visible light in organic synthesis, photoredox-catalyzed reductive coupling of imines with electron-deficient aromatic hydrocarbons has become an important method. The synthesis of such compounds inevitably involves an α-amino radical process. However, both traditional metal-catalyzed and visible light-catalyzed imine reductions suffer from drawbacks such as high catalyst usage, high cost, and difficulty in recycling.

[0004] Therefore, there is an urgent need to find a new method that is simple, efficient, and has mild reaction conditions to construct pyridine derivatives. Summary of the Invention

[0005] In view of the problems in the prior art, the first aspect of the present invention is to provide a pyridine derivative compound.

[0006] The technical solution adopted by the present invention is as follows:

[0007] A pyridine derivative compound, the chemical formula of which is as follows:

[0008]

[0009] Where:

[0010] R1 is any one of hydrogen, 4-methyl, 2-methyl, 4-fluoro, and 2-fluoro;

[0011] R2 is any one of 4-phenyl and 4-trifluoromethyl;

[0012] R3 is hydrogen or fluorine.

[0013] The second aspect of the present invention is to provide a simple and efficient method for preparing pyridine compounds, comprising the following steps: using benzaldehyde, aniline and 4-cyanopyridine as raw materials, using CdSeS / CdZnSe / ZnSe / ZnS core-shell quantum dots as photocatalysts, and preparing pyridine derivative compounds under the induction of visible light.

[0014] The reaction equation of the present invention is as follows

[0015]

[0016] Where:

[0017] R1 is any one of hydrogen, 4-methyl, 2-methyl, 4-fluoro, and 2-fluoro;

[0018] R2 is any one of 4-phenyl and 4-trifluoromethyl;

[0019] R3 is hydrogen or fluorine.

[0020] Further settings are:

[0021] The molar ratio of the reaction is benzaldehyde:aniline:4-cyanopyridine=1-3:1-2:1-2, preferably benzaldehyde:aniline:4-cyanopyridine=2:1.5:1.

[0022] The reaction is preferably carried out in an organic solvent, and the organic solvent is selected from any one of toluene, toluene+isopropanol, toluene+DMSO, toluene+DMF, and toluene+acetonitrile.

[0023] The reaction is preferably carried out in the presence of an additive, wherein the additive is selected from any one of 1-hexylthiol, 4-methylthiophenol, and 4-fluorothiophenol.

[0024] The reaction is preferably carried out in the presence of a base, and the base is selected from any one of sodium acetate, DIPEA, DBU, and tBuONa.

[0025] The product is purified by using petroleum ether and ethyl acetate as developing agents to separate the product by column chromatography after the reaction is completed, and then drying the product after concentration.

[0026] In the reaction, the amount of the catalyst CdSeS / CdZnSe / ZnSe / ZnS core-shell quantum dots used is 1 to 2, calculated based on the molar amount of cyanopyridine.

[0027] The third aspect of the present invention is to provide a use of the aforementioned pyridine derivative compound in the preparation of antibacterial drugs.

[0028] The present invention has the following beneficial effects:

[0029] 1. The present invention provides a pyridine derivative compound with a novel structure. The pyridine derivative compound has excellent antibacterial properties, specifically targeting Staphylococcus aureus, Escherichia coli, etc., and has industrial application as an antibacterial drug.

[0030] 2. The present invention also provides a method for synthesizing pyridine derivatives, utilizing visible light-mediated quantum dots to prepare pyridine derivatives. The present invention utilizes CdSeS / CdZnSe / ZnSe / ZnS core-shell quantum dots as photocatalysts, providing a new approach for preparing pyridine derivatives. These quantum dots have the advantages of high stability, high light utilization, broad absorption in the visible light region, and reusability. They can replace organic dyes and transition metal catalysts for the visible light preparation of pyridine derivatives.

[0031] 3. The present invention utilizes visible light at room temperature, and the reaction conditions are mild, thus avoiding the potential safety hazards caused by high-temperature reactions and making it easy to control the reaction. At the same time, the reaction operation process and post-processing are simple; while reducing the preparation cost, a high-yield, high-purity product is obtained, showing better reaction and economic advantages.

[0032] The present invention will be further described below with reference to the accompanying drawings and specific embodiments. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 Absorption and fluorescence spectra of CdSeS / CdZnSe / ZnSe / ZnS core-shell quantum dots prepared in an embodiment of the present invention.

[0034] Figure 2 This is a transmission electron microscopy image of CdSeS / CdZnSe / ZnSe / ZnS core-shell quantum dots prepared in an embodiment of the present invention.

[0035] Figure 3 This is the H NMR spectrum of the pyridine derivative compound prepared in Example 1 of the present invention.

[0036] Figure 4This is the NMR carbon spectrum of the pyridine derivative compound prepared in Example 1 of the present invention.

[0037] Figure 5 This is a comparison of the antibacterial effect of the product prepared in Example 7 on Staphylococcus aureus. DETAILED DESCRIPTION

[0038] The catalyst CdSeS / CdZnSe / ZnSe / ZnS core-shell quantum dots used in the embodiment of the present invention are prepared by the following method:

[0039] (1) Synthesis of reaction precursors:

[0040] Preparation of Se-S-ODE suspension: 1 mmol of selenium powder (Se) and 1 mmol of sulfur powder (S) were mixed with 10 mL of 1-octadecene (ODE) by ultrasonication and ultrasonicated for 10 minutes to prepare Se-S-ODE suspension.

[0041] Preparation of S-TBP suspension: Sulfur powder (0.640 g, 0.002 mol) was dissolved in tributyl phosphate (TBP) (10 mL) by ultrasonication and ultrasonicated for 10 minutes to prepare S-TBP suspension.

[0042] Preparation of Se-TBP suspension: Se powder (1.58 g, 0.01 mol) was dissolved in TBP (10 mL) by ultrasonication and ultrasonicated for 10 minutes to prepare Se-TBP suspension.

[0043] Preparation of zinc oleic acid-ODE suspension: Zinc acetate (5.49 g, 0.03 mol) and oleic acid (42 g, 0.15 mol) were charged into a 250 mL three-necked flask with 50 mL of ODE. After stirring with argon bubbling for 10 min, the mixture was heated to 200 °C to obtain a zinc oleic acid-ODE suspension.

[0044] Preparation of cadmium oleic acid-ODE suspension: Cadmium acetate (0.53 g, 0.002 mol) and oleic acid (1.4 g, 0.005 mol) were charged into a 100 mL three-necked flask containing 40 mL of ODE. After stirring with argon bubbling for 10 min, the mixture was heated to 200 °C to obtain a cadmium oleic acid-ODE suspension.

[0045] Preparation of CdSeS core quantum dots: The cadmium oleate-ODE suspension prepared above was heated to 250°C under an argon atmosphere. 5 mL of Se-S-ODE suspension was quickly injected into the hot solution. The reaction temperature was maintained at 250°C for further growth for 10 minutes to obtain CdSeS core quantum dots.

[0046] (2) Synthesis of CdSeS / CdZnSe / ZnSe / ZnS core-shell quantum dots:

[0047] The prepared zinc oleate-ODE suspension was heated to 200°C under an argon atmosphere, and CdSeS core quantum dots dissolved in 0.5 mL of ODE were injected. The temperature was then raised to 300°C, and 2 mL of Se-TBP suspension and 1.5 mL of cadmium oleate-ODE suspension were injected and allowed to react for 10 minutes. 10 mL of Se-TBP suspension and 3 mL of S-TBP suspension were then injected and the reaction continued for 5 minutes. Finally, to precipitate the core quantum dots from the reaction solution, a mixture of acetone and methanol (volume ratio 3:1) was prepared as the precipitation solution. The crude reaction solution was placed in a 500 mL sample vial. The precipitation solution (100 mL) was added to the sample vial, and the sample vial was quickly placed in a centrifuge at 4000 rpm for 3 minutes. The supernatant was quickly removed, and the nanocrystal precipitate was dissolved in 5 mL of toluene to obtain CdSeS / CdZnSe / ZnSe / ZnS core-shell quantum dots.

[0048] (3) Product confirmation:

[0049] After the reaction, the CdSeS / CdZnSe / ZnSe / ZnS core-shell quantum dots were characterized by UV, fluorescence, and transmission electron microscopy. Figure 1 、 Figure 2 As shown. Figure 1 As shown: CdSeS / CdZnS core-shell quantum dots have an ultraviolet absorption peak at 500-565nm and a maximum emission peak at 532nm, and have strong fluorescence; in addition, Figure 2 It can be seen that the quantum dots are uniform in size and similar in morphology, and are evenly distributed in the range of 13-15nm.

[0050] Example 1:

[0051] A method for preparing a pyridine derivative compound comprises the following steps:

[0052] Toluene (2.0 mL) and isopropanol (0.5 mL) were added to a 4 mL glass vial. 4-Cyanopyridine (0.2 mmol, 0.0208 g), aniline (0.3 mmol, 0.0279 g), CH3COONa (0.4 mmol, 0.0328 g), 1-hexanethiol (0.4 mmol, 0.0417 g), and benzaldehyde (0.4 mmol, 0.0425 g) were then added sequentially. After mixing, 50 μL (250 μL / mmol, 0.2 mmol) of CdSeS / CdZnSe / ZnSe / ZnS quantum dots were added. The mixed solution was purged with argon for 10 minutes and then reacted under irradiation with a 3 W blue LED (420 nm) for 24 hours. After completion of the reaction, 8 mL of acetonitrile was added for precipitation, and the quantum dots were removed by centrifugation. The organic layer was concentrated. The crude mixture was separated by silica gel column chromatography (ethyl acetate / petroleum ether 1:5), the eluent was dried over anhydrous sodium sulfate, and concentrated in vacuo to obtain N-(phenyl(pyridin-4-yl)methyl)aniline in a yield of 90%.

[0053] The reaction equations involved are as follows:

[0054]

[0055] Product Confirmation:

[0056] like Figure 3 As shown: 1 H NMR(400MHz,Chloroform-d)δ8.52(d,J=5.1Hz,2H),7.31(dd,J=7.5,4.4Hz,7H),7.12( t,J=7.7Hz,2H),6.72(t,J=7.4Hz,1H),6.51(d,J=8.0Hz,2H),5.44(s,1H),4.29(s,1H).

[0057] like Figure 4 As shown: 13 C NMR (101MHz, CDCl3) δ151.9,150.2,146.9,141.6,129.3,129.2,128.2,127.8,122.4,118.4,113.6,62.4.

[0058] Alternative Example: Effect of Different Reaction Conditions on Yield

[0059] The preparation method is the same as that of Example 1, except that the types of catalyst, solvent, additive and base used in the reaction are adjusted, as shown in Table 1.

[0060] Table 1

[0061]

[0062]

[0063] Note: Replacement Example 1-17 is a reaction carried out without light.

[0064] As shown in Table 1, in the synthesis process of pyridine derivatives, the process conditions shown in Example 1 were adopted to obtain the highest product yield, which was 90%.

[0065] Example 2

[0066] Benzaldehyde (0.4 mmol) was replaced by 4-methylbenzaldehyde (0.4 mmol). Other conditions and operation procedures were the same as those in Example 1 to obtain N-(pyridin-4-yl(p-tolyl)methyl)aniline with a yield of 85% (45.6 mg).

[0067] The reaction equations involved are as follows:

[0068]

[0069] Product Confirmation:

[0070] 1 H NMR(400MHz,Chloroform-d)δ8.55-8.50(m,2H),7.33-7.29(m,2H),7.18-7.08(m,6 H),6.71(t,J=7.3Hz,1H),6.52-6.47(m,2H),5.41(s,1H),4.24(s,1H),2.32(s,3H).

[0071] 13 C NMR (101MHz, CDCl3) δ152.1,150.1,146.9,138.8,138.0,129.8,129.3,127.7,122.4,118.3,113.6,62.1,21.2.

[0072] Example 3

[0073] Benzaldehyde (0.4 mmol) was replaced by 2-methylbenzaldehyde (0.4 mmol). Other conditions and operation procedures were the same as those in Example 1 to obtain N-(pyridin-4-yl(o-tolyl)methyl)aniline with a yield of 84% (45.6 mg).

[0074] The reaction equations involved are as follows:

[0075]

[0076] Product Confirmation:

[0077] 1 H NMR(400MHz,Chloroform-d)δ8.58-8.47(m,2H),7.28(d,J=5.2Hz,2H),7.21(td,J=4.5,3.8,2.6Hz,2H),7.16-7.08( m,3H),7.02(d,J=7.6Hz,1H),6.71(td,J=7.4,1.1Hz,1H),6.51-6.46(m,2H),5.66(s,1H),4.17(s,1H),2.37(s,3H).

[0078] 13 C NMR (101MHz, CDCl3) δ151.6,150.0,147.0,139.5,136.3,131.0,129.4,128.1,127.8,126.7,123.0,118.2,113.2,58.5,19.5.

[0079] Example 4

[0080] Benzaldehyde (0.4 mmol) was replaced by 4-fluorobenzaldehyde (0.4 mmol). Other conditions and procedures were the same as in Example 1 to obtain N-((4-fluorophenyl)(pyridin-4-yl)methyl)aniline with a yield of 81% (46.0 mg).

[0081] The reaction equations involved are as follows:

[0082]

[0083] Product Confirmation:

[0084] 1 H NMR(400MHz,Chloroform-d)δ8.57(d,J=6.2Hz,2H),7.32(d,J=6.1Hz,2H),7.25(dd,J=8.7,5.5Hz,2H),7.12(t,J=7.9 Hz,2H),7.01(t,J=8.6Hz,2H),6.73(t,J=7.3Hz,1H),6.50(d,J=8.1Hz,2H),5.44(d,J=2.5Hz,1H),4.29-4.18(d,1H).

[0085] 13C NMR (101MHz, CDCl3) δ163.7,161.2,152.3,149.7,146.6,137.2,137.2,133.7 ,129.6,129.5,129.4,129.4,127.6,122.6,118.6,116.2,116.0,113.7,61.6.

[0086] 19 F NMR (376MHz,CDCl3)δ-113.56.

[0087] Example 5

[0088] Benzaldehyde (0.4 mmol) was replaced with 2-fluorobenzaldehyde (0.4 mmol). Other conditions and procedures were the same as in Example 1 to give N-((2-fluorophenyl)(pyridin-4-yl)methyl)aniline with a yield of 85% (45.9 mg).

[0089] The reaction equations involved are as follows:

[0090]

[0091] Product Confirmation:

[0092] 1 H NMR(400MHz,Chloroform-d)δ8.53(d,J=5.5Hz,2H),7.34-7.23(m,4H),7.10(ddt,J=17.6,10. 6,8.3Hz,4H),6.74(t,J=7.3Hz,1H),6.56(d,J=8.2Hz,2H),5.81(d,J=3.5Hz,1H),4.32(s,1H).

[0093] 13 C NMR (101MHz, CDCl3) δ161.5,159.1,151.0,150.2,146.6,129.8,129.8,12 9.4,128.8,128.7,124.9,124.8,122.4,118.6,116.1,115.9,113.6,55.5.

[0094] 19 F NMR (376MHz,CDCl3)δ-117.51.

[0095] Example 6

[0096] 4-Aminobiphenyl (0.3 mmol) was used instead of aniline (0.3 mmol). Other conditions and operation procedures were the same as those in Example 1 to obtain N-(phenyl(pyridin-4-yl)methyl)-[1,1'-biphenyl]-4-amine with a yield of 84% (55.3 mg).

[0097] The reaction equations involved are as follows;

[0098]

[0099] Product Confirmation:

[0100] 1 H NMR(400MHz,Chloroform-d)δ8.53(d,J=5.0Hz,2H),7.48(d,J=7.7Hz,2H),7.34(dt,J=2 2.0,8.1Hz,11H),7.23(t,J=7.8Hz,1H),6.57(d,J=7.9Hz,2H),5.48(s,1H),4.39(s,1H).

[0101] 13 C NMR (101MHz, CDCl3) δ151.8,150.2,146.3,141.5,141.1,131.3,129.2,128.8,1 28.3,128.0,127.8,126.4,126.4,122.5,113.9,62.4.HRMS(ESI-TOF)m / z:[M+H] + Calcdfor C 24 H 21 N2 + 337.1700; Found 337.1691.

[0102] Example 7

[0103] 4-Trifluoromethylaniline (0.3 mmol) was substituted for aniline (0.3 mmol). Other conditions and operation procedures were the same as those in Example 1 to obtain 4-(1,1-difluoroethyl)-N-(phenyl(pyridin-4-yl)methyl)aniline with a yield of 69% (44.3 mg).

[0104] The reaction equations involved are as follows:

[0105]

[0106] Product Confirmation:

[0107] 1H NMR(400MHz,Chloroform-d)δ8.55(d,J=5.1Hz,2H),7.35(dt,J=6.4,4.0Hz,5H),7.29 (t,J=5.7Hz,4H),6.54(d,J=8.4Hz,2H),5.51(d,J=4.3Hz,1H),4.66(d,J=4.4Hz,1H).

[0108] 13 C NMR (101MHz, CDCl3) δ150.9,150.2,149.2,140.7,129.3,128.5,127.7,126.7,126.7,126.7,126.6,122.3,112.9,61.9.

[0109] 19 F NMR(376MHz, CDCl3)δ-61.04.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 19 H 16 F3N2 + 329.1261; Found 329.1260.

[0110] Example 8

[0111] 3-Chloropyridine (0.2 mmol) was used instead of pyridine (0.2 mmol). Other conditions and procedures were the same as in Example 1 to obtain N-((3-fluoropyridin-4-yl)(phenyl)methyl)aniline with a yield of 88% (47.9 mg).

[0112] The reaction equations involved are as follows:

[0113]

[0114] Product Confirmation:

[0115] 1 H NMR(400MHz,Chloroform-d)δ8.39(d,J=1.8Hz,1H),8.36(d,J=4.9Hz,1H),7.52(d,J=5.6Hz,1H),7.33(s,5H) ,7.13(t,J=7.8Hz,2H),6.74(t,J=7.4Hz,1H),6.52(d,J=7.9Hz,2H),5.78(d,J=2.6Hz,1H),4.32-4.16(m,1H).

[0116] 13C NMR (101MHz, CDCl3) δ158.8,156.3,146.5,146.3,146.3,140.2,138.4,138.2,129.4,129.2,128.4,127.6,122.5,118.6,113.5,56.3,56.3.

[0117] 19 F NMR(376MHz,CDCl3)δ-131.83.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 18 H 16 FN2 + 279.1293; Found 279.1302.

[0118] Example 9: Recycling of quantum dots

[0119] This example mainly tests the reusability of quantum dots, and the method is as follows:

[0120] Following the method of Example 1, after the reaction was complete, 10 mL of acetonitrile was added to the reaction solution to precipitate the quantum dots. The quantum dots were then separated by centrifugation, washed with ethanol, and dried. 2 mL of toluene was added to the treated quantum dots, and the solution was heated to uniformly disperse the quantum dots in the toluene solution until the solution became clear. This solution was then reapplied to prepare a pyridine derivative compound, following the above steps, for five cycles. The yields were measured, as shown in Table 2.

[0121] Table 2. Recovery times and yield of quantum dots

[0122] Recycling times Yield (%) 1 time 90 2 times 86 3 times 85 4 times 82 5 times 83

[0123] As shown in Table 2, the quantum dot catalyst prepared by the present invention still has good catalytic performance after being recycled and reused multiple times, and has broad industrial application prospects.

[0124] Application Example: Antibacterial Performance Evaluation

[0125] The products prepared in Examples 3-8 were tested for antibacterial properties by the following methods:

[0126] 1. Antibacterial performance test of Examples 3, 5, and 6

[0127] 1.1 Weigh 60 mg of the products obtained in Examples 3, 5, and 6, respectively, dissolve them in DMSO, and dilute them with water to a concentration of 60 mg / ml. Use the inhibition zone method to test the inhibitory effects of the reagent solutions on Staphylococcus aureus.

[0128] 1.2 Experimental method: Activate Staphylococcus aureus in advance to make its OD 600 =0.6-0.8, then dilute the bacterial solution to OD 600 =0.08. Use a cotton swab to evenly apply the bacterial solution to the broth. Next, soak blank drug-susceptibility paper strips in varying concentrations of reagent solution and solvent for one hour to fully submerge the strips. Finally, place sections of the paper strips soaked with reagent solution onto the broth-saturated culture medium. Incubate the strips upside down in a 37°C constant temperature and humidity chamber overnight. After incubation, remove the strips and observe the results, recording the inhibition rate, as shown in Table 3.

[0129] Table 3

[0130] Serial number Test method Diameter of inhibition zone (mm) Example 3 Inhibition zone 5.0 Example 5 Inhibition zone 8.0 Example 6 Inhibition zone 4.5

[0131] 2. Antibacterial performance test of Example 7

[0132] 2.1 Preparation of antibacterial material samples

[0133] The product of Example 7 was accurately weighed, dissolved in DMSO and diluted to 10 mg / mL, and its inhibitory effect on Staphylococcus aureus was tested.

[0134] 2.2 Preparation of bacterial suspension

[0135] Take each test strain, inoculate fresh slant culture medium, and culture at 35℃ for 16-20 hours. Elute the bacterial moss with nutrient broth medium in appropriate amount, compare the turbidity with a 0.5 McFarland turbidimeter tube, and dilute appropriately to a concentration of about 5×10 6 CFU / mL is reserved.

[0136] 2.3 Determination of antibacterial rate

[0137] 2.3.1 Vaccination

[0138] After turning on the clean bench fan for 30 minutes, perform sterile operation. Pipette 100uL (5×10 6 CFU / mL) were added into sterile test tubes, and 0.5 mL of 10 mg / mL dilution of antibacterial material was added separately, and the counts were made after 4 hours.

[0139] 2.3.2 Counting culture

[0140] Aseptically pipette 1 mL of each dilution level of bacterial solution into a sterile plate. Melt nutrient agar, then heat to 46°C, and add 15 mL to each plate. Mix thoroughly, cover, and allow to solidify. Once solidified, invert the plate and incubate overnight at 37°C (Staphylococcus aureus at 36 ± 1°C). Count the number of bacterial colonies in each dilution level plate. Dip a sterile cotton swab into the bacterial solution and swirl it against the tube wall to remove excess. DMSO solvent serves as a blank control.

[0141] Use a cotton swab to evenly smear 1 mL of each dilution of the bacterial solution three times onto the surface of 15 mL of solid nutrient agar in a plate. Rotate the plate 60° each time to ensure that the bacterial solution evenly covers the entire agar surface. Finally, smear the solution around the edge of the plate to remove any residual bacterial solution. Leave the plate coated with the drug at room temperature for 5 minutes to allow the bacterial solution to fully absorb onto the agar surface. Then, apply the filter paper soaked in the drug to the agar surface inoculated with the test bacteria. Evenly apply the filter paper to the agar surface, with the distance between the filter paper pieces being no less than 24 mm and the distance between the paper pieces and the edge of the plate being no less than 15 mm. After smearing, incubate in a 37°C constant temperature incubator for 18 hours and observe the size of the inhibition zone.

[0142] 2.4 Data Processing

[0143] Inhibition rate = ((D1 (mm) - D0 (mm)) / D1 (mm)) * 100% (wherein: D1 blank group inhibition zone diameter = 3.5 mm, D0 sample inhibition zone diameter).

[0144] The antibacterial performance test is shown in Table 4

[0145] Table 4

[0146]

[0147]

[0148] 3. Antibacterial performance test of Examples 4 and 8

[0149] The products of Examples 4 and 8 were weighed, dissolved in DMSO and diluted to 5 mg / mL, and their inhibitory effects on Escherichia coli were tested.

[0150] 3.1OD value test

[0151] The OD value is positively correlated with the number of bacteria. During bacterial culture, as the bacteria grow and multiply, the number of bacteria in the culture solution increases, the absorption and scattering of light increases, and the OD value also increases accordingly.

[0152] 3.2 Experimental method: Escherichia coli was inoculated into liquid culture medium, and samples with a concentration of 5 mg / mL were added respectively. After culturing at 37°C for 12 hours, the OD600 value of the bacterial solution was measured using a spectrophotometer.

[0153] The antibacterial performance test results are shown in Table 5:

[0154] Table 5

[0155] Serial number Test method Test data Test results Example 4 OD value test Control group OD600 = 1.62 Sample OD600 = 0.426 Significant decline Example 8 OD value test Control group OD600 = 1.62 Sample OD600 = 0.123 Significant decline

[0156] Compared with the control group: In the absence of the sample, E. coli grew and multiplied normally in the control group. The OD600 values ​​of the other experimental groups were all lower than those of the control group, indicating that the differences between the experimental groups and the control group were significant, that is, the samples of Example 4 and Example 8 had a real inhibitory effect on the growth of E. coli.

[0157] analyze:

[0158] Combined with Table 3-5 and Figure 5 As shown in the figure: using different antibacterial performance test methods, it is shown that the prepared pyridine derivative compounds have a certain antibacterial effect on Staphylococcus aureus and Escherichia coli, among which the antibacterial effect of the product of Example 7 can reach 100.0%.

[0159] Summarize:

[0160] The present invention realizes a three-component pyridine derivatization reaction with a cyanopyridine core as the core, aniline, and benzaldehyde under the action of a base through visible light induction. The reaction conditions are mild, the raw materials are cheap and readily available, the operation process is simple, the reaction is widely applicable, and it can effectively replace the synthesis of traditional complex pyridine derivatives without the need for complex substrate design. At the same time, since the compound with pyridine as the core has high pharmacological activity, it has strong practicality.

[0161] It is understood that the above specific description of the present invention is only used to illustrate the present invention and is not limited to the technical solutions described in the embodiments of the present invention. Those skilled in the art should understand that the present invention can still be modified or replaced with equivalents to achieve the same technical effects; as long as the use requirements are met, they are all within the scope of protection of the present invention.

Claims

1. A pyridine derivative compound, the structural formula of which is shown below: Where: R1 is any one of hydrogen, 4-methyl, 2-methyl, 4-fluoro, and 2-fluoro; R2 is any one of 4-phenyl and 4-trifluoromethyl; R3 is hydrogen or fluorine.

2. A method for preparing the pyridine derivative compound according to claim 1, characterized in that: Pyridine derivatives were prepared using benzaldehyde, aniline and 4-cyanopyridine as raw materials and CdSeS / CdZnSe / ZnSe / ZnS core-shell quantum dots as photocatalysts under the induction of visible light. Where: R1 is any one of hydrogen, 4-methyl, 2-methyl, 4-fluoro, and 2-fluoro; R2 is any one of 4-phenyl and 4-trifluoromethyl; R3 is hydrogen or fluorine.

3. The method for preparing a pyridine derivative compound according to claim 2, wherein: The molar ratio of the reaction is benzaldehyde:aniline:4-cyanopyridine=1-3:1-2:1-2.

4. The method for preparing a pyridine derivative compound according to claim 2, wherein: The molar ratio of the reaction is benzaldehyde:aniline:4-cyanopyridine=2:1.5:

1.

5. The method for preparing a pyridine derivative compound according to claim 2, wherein: The reaction is carried out in an organic solvent, and the organic solvent is selected from any one of toluene, toluene+isopropanol, toluene+DMSO, toluene+DMF, and toluene+acetonitrile.

6. The method for preparing a pyridine derivative compound according to claim 2, wherein: The reaction is carried out in the presence of an additive, and the additive is selected from any one of 1-hexanethiol, 4-methylthiophenol, and 4-fluorothiophenol.

7. The method for preparing a pyridine derivative compound according to claim 2, wherein: The reaction is carried out in the presence of a base, and the base is selected from any one of sodium acetate, DIPEA, DBU, and tBuONa.

8. The method for preparing a pyridine derivative compound according to claim 2, wherein: In the reaction, the amount of the catalyst CdSeS / CdZnSe / ZnSe / ZnS core-shell quantum dots used is 1 to 2, calculated based on the molar amount of cyanopyridine.

9. The method for preparing a pyridine derivative compound according to claim 2, wherein: The product is purified by using petroleum ether and ethyl acetate as developing agents to separate the product by column chromatography after the reaction is completed, and then drying the product after concentration.

10. Use of the pyridine derivative compound according to claim 1 in the preparation of antibacterial drugs.

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