3-cyanopyridine compound as well as preparation method and application thereof

Abstract

The invention provides a 3-cyanopyridine compound as well as a preparation method and application thereof. The 3-cyanopyridine compound disclosed by the invention can be used as a fluorescent probe to show stable aggregation-induced emission (AIE) performance in an aggregation state. The 3-cyanopyridine compound has the advantages of high response speed, high selectivity and high sensitivity in the aspect of fluorescence detection of trace iron ions and nitro aromatic explosives, and can realize fluorescence detection of trace iron ions and nitro aromatic explosives in an aggregation state. The 3-cyanopyridine compound also has certain antibacterial activity, and has application potential in preparation of antibacterial drugs. The invention provides the preparation method of the 3-cyanopyridine compound, and the benzopyran nitrile compound which is easy to prepare is used as a raw material, inorganic base is selected, and a series of 3-cyanopyridine compounds are obtained through a series of cascade reactions. The synthesis method has the advantages of no need of metal catalysis, simplicity, feasibility, wide substrate application range, high yield and the like.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis, and particularly relates to a 3-cyanopyridine compound, a preparation method thereof and an application thereof. Background Art

[0002] The tandem reaction is an effective synthetic strategy. This strategy involves adding reactants in a single reaction flask and continuously performing two or more steps of transformation to form products without separating the intermediates. The tandem reaction not only reduces the reaction time, reaction steps and the use of consumables during the reaction process, but also easily converts reactants into complex molecules with high regioselectivity or stereoselectivity through simple steps. Obviously, the tandem reaction avoids the separation of intermediates, greatly reduces the reaction operation cost, and contributes to the development of sustainable chemistry. Therefore, the tandem reaction has attracted extensive attention from researchers in organic synthesis.

[0003] 3-Cyanopyridine, also known as nicotinonitrile, is an important class of nitrogen-containing heterocyclic compounds. Compounds containing a 3-cyanopyridine unit are multifunctional molecules and also have certain biological activities. Therefore, the synthesis of 3-cyanopyridine compounds has begun to attract attention in recent years, but the progress of its green synthesis is relatively slow. By-products may be formed in the tandem reaction for various reasons, resulting in too low a yield and difficult separation of the target product. Or, from the perspective of green chemistry, some tandem reactions cannot achieve a 100% atom economy synthetic transformation. Therefore, it is still challenging to achieve a tandem reaction with 100% atom economy under mild conditions. In addition, there are relatively few relevant literatures reported on the efficient synthesis of 3-cyanopyridine compounds. Summary of the Invention

[0004] In order to overcome the problems existing in the above-mentioned prior art, one of the purposes of the present invention is to provide a 3-cyanopyridine compound. The second purpose of the present invention is to provide a preparation method of the above 3-cyanopyridine compound. The third purpose of the present invention is to provide the application of the above 3-cyanopyridine compound in detecting iron ions. The fourth purpose of the present invention is to provide a method for detecting iron ions. The fifth purpose of the present invention is to provide the application of the above 3-cyanopyridine compound in detecting nitroaromatic explosives. The sixth purpose of the present invention is to provide a method for detecting nitroaromatic explosives. The seventh purpose of the present invention is to provide the application of the above 3-cyanopyridine compound in preparing antibacterial drugs.

[0005] In order to achieve the above purposes, the technical solutions adopted by the present invention are as follows:

[0006] The first aspect of the present invention provides a 3-cyanopyridine compound, and the chemical structure formula of the 3-cyanopyridine compound is as shown in Formula 3:

[0007]

[0008] Among them, R1 is a halogen group, a C1-C3 alkoxy group, a C1-C3 alkyl group or absent; R2 is a C1-C3 alkyl group or a phenyl group.

[0009] Preferably, the compound structural formula of the 3-cyanopyridine compound is shown as any one of Formula 3a-Formula 3f:

[0010]

[0011] The second aspect of the present invention provides a preparation method of the 3-cyanopyridine compound described in the first aspect, including the following steps: using the benzopyran carbonitrile compound shown in Formula 1, pyrrolidine, and an inorganic base as raw materials, reacting in an organic solvent to obtain the 3-cyanopyridine compound;

[0012] The compound structural formula of the benzopyran carbonitrile compound is shown as Formula 1:

[0013] Among them, R1 is a halogen group, a C1-C3 alkoxy group, a C1-C3 alkyl group or absent.

[0014] Preferably, the benzopyran carbonitrile compound is selected from 2-methyl-6-fluorobenzopyran carbonitrile, 2-methyl-6-chlorobenzopyran carbonitrile, 2-methyl-6-bromobenzopyran carbonitrile, 2,6-dimethylbenzopyran carbonitrile, 2-phenylbenzopyran carbonitrile, 2-methyl-6-methoxybenzopyran carbonitrile.

[0015] Preferably, the reaction temperature of the reaction is 70-90 °C.

[0016] More preferably, the reaction temperature of the reaction is 75-85 °C.

[0017] Preferably, the reaction time of the reaction is 1.5-3 h.

[0018] More preferably, the reaction time of the reaction is 2-2.5 h.

[0019] Preferably, the molar ratio of the benzopyran carbonitrile compound to pyrrolidine is 1:(8-12).

[0020] More preferably, the molar ratio of the benzopyran carbonitrile compound to pyrrolidine is 1:(9-11).

[0021] Preferably, the organic solvent is acetonitrile or ethanol.

[0022] Preferably, the dosage ratio of the benzopyran carbonitrile compound to the solvent is 1 mmol:(30-60) mL.

[0023] More preferably, the dosage ratio of the benzopyran nitrile compound to acetonitrile is 1 mmol:(35 - 50) mL.

[0024] Preferably, the inorganic base is sodium hydroxide.

[0025] Preferably, the molar ratio of the benzopyran nitrile compound to the inorganic base is 1:(8 - 12).

[0026] More preferably, the molar ratio of the benzopyran nitrile compound to sodium hydroxide is 1:(9 - 11).

[0027] Preferably, it specifically includes the following steps: adding the benzopyran nitrile compound, pyrrolidine, and sodium hydroxide into an organic solvent, reacting in the organic solvent, removing the organic solvent after the reaction, adding water to dissolve, adjusting the pH of the solution to neutral with an inorganic acid solution, and finally extracting the organic phase to enrich the target product to obtain the 3-cyanopyridine compound.

[0028] More preferably, the inorganic acid is hydrochloric acid.

[0029] The third aspect of the present invention provides the application of the 3-cyanopyridine compound described in the first aspect in any one of the following A) or B):

[0030] A) Detecting iron ions;

[0031] B) Preparing a product for detecting iron ions.

[0032] Preferably, the application of the 3-cyanopyridine compound as a fluorescent probe in the detection of iron ions.

[0033] Preferably, the application of the 3-cyanopyridine compound in the preparation of a fluorescent sensor for detecting iron ions.

[0034] Preferably, the application of the 3-cyanopyridine compound in the preparation of a test strip for detecting iron ions.

[0035] The fourth aspect of the present invention provides a method for detecting iron ions, including the following steps: preparing a fluorescent probe solution with the 3-cyanopyridine compound described in the first aspect, adding the solution to be detected, and if the fluorescent probe solution undergoes fluorescence quenching, it is detected that the solution to be detected contains iron ions.

[0036] Preferably, the detection system of the fluorescent probe solution is a DMSO-H2O solution.

[0037] More preferably, the volume percentage of water in the DMSO-H2O solution is 40% - 90%.

[0038] Further preferably, the volume percentage of water in the DMSO-H2O solution is 60% - 90%.

[0039] Preferably, a fluorescence spectroscopy detection method is adopted. During detection, 405 nm fluorescence is used as the excitation light, and the fluorescence change range with a monitoring and detection wavelength of 300 - 800 nm is used to obtain fluorescence data. If the fluorescence intensity of the fluorescence emission peak of the fluorescent probe solution at 440 - 460 nm decreases to 50% of the original intensity, the presence of iron ions is detected.

[0040] The fifth aspect of the present invention provides the application of the 3 - cyanopyridine compound described in the first aspect in any one of the following C) or D):

[0041] C) Detecting nitroaromatic explosives;

[0042] D) Preparing a product for detecting nitroaromatic explosives.

[0043] Preferably, the application of the 3 - cyanopyridine compound as a fluorescent probe in the detection of nitroaromatic explosives.

[0044] Preferably, the application of the 3 - cyanopyridine compound in the preparation of a fluorescent sensor for detecting nitroaromatic explosives.

[0045] Preferably, the application of the 3 - cyanopyridine compound in the preparation of a test paper for detecting nitroaromatic explosives.

[0046] Preferably, the nitroaromatic explosives are selected from 2 - nitrobenzoic acid (NBAc), 2,4 - dinitrophenol (DNP), 2 - nitroaniline (NA), 2,4,6 - trinitrophenol (PA), 2 - nitrobenzaldehyde (NBA).

[0047] The sixth aspect of the present invention provides a method for detecting nitroaromatic explosives, including the following steps: preparing a fluorescent probe solution with the 3 - cyanopyridine compound described in the first aspect, adding the solution to be detected. If the fluorescent probe solution undergoes fluorescence quenching, it is detected that the solution to be detected contains nitroaromatic explosives.

[0048] Preferably, the detection system of the fluorescent probe solution is a DMSO - H2O solution.

[0049] More preferably, the volume percentage of water in the DMSO - H2O solution is 40% - 90%.

[0050] Even more preferably, the volume percentage of water in the DMSO - H2O solution is 50% - 70%.

[0051] Preferably, a fluorescence spectrum detection method is adopted, 405nm fluorescence is used as the excitation light during detection, and the fluorescence change range of 300-800nm ​​wavelength is monitored and detected to obtain fluorescence data. If the fluorescence emission peak fluorescence intensity of the fluorescent probe solution at 440-460nm is reduced to 50% of the original intensity, the presence of nitroaromatic explosives is detected.

[0052] The seventh aspect of the present invention provides use of the 3-cyanopyridine compound described in the first aspect in the preparation of antibacterial drugs.

[0053] Preferably, the 3-cyanopyridine compound is used in the preparation of anti-staphylococcal drugs.

[0054] Preferably, the 3-cyanopyridine compound is used in the preparation of anti-Escherichia coli drugs.

[0055] The beneficial effects of the present invention are:

[0056] (1) The present invention provides a 3-cyanopyridine compound, which can be used as a fluorescent probe to exhibit stable aggregation-induced emission (AIE) performance in an aggregated state. The 3-cyanopyridine compound has the advantages of fast response speed, high selectivity and high sensitivity in the fluorescent detection of trace iron ions; the detection process of iron ions using AIE fluorescent probe is fast, no large-scale detection equipment is required, and it belongs to a "Turn-off" type probe, which has important application value in the field of biochemistry. The 3-cyanopyridine compound also has the advantages of fast response speed, high selectivity and high sensitivity in the fluorescent detection of nitroaromatic explosives; it can realize the fluorescent detection of nitroaromatic explosives (such as NBAc, DNP, NA, PA and NBA) in an aggregated state, and is expected to have potential applications in the field of public safety. The 3-cyanopyridine compound also has certain antibacterial activity and has application potential in the preparation of antibacterial drugs.

[0057] (2) The present invention provides a method for preparing the above-mentioned 3-cyanopyridine compound. The present invention uses an easily prepared benzopyran nitrile compound as a raw material, selects a suitable inorganic base (sodium hydroxide has the best yield), and obtains a series of 3-cyanopyridine compounds through a series of tandem reactions such as ring opening, isomerization, and ring closing between benzopyran nitrile and pyrrolidine. The synthesis method has the advantages of not requiring metal catalysis, being simple and easy to operate, having a wide range of substrate applications, and having a high yield. Using the method provided by the present invention, dozens of 3-cyanopyridine fluorescent small molecules containing different substituents at the 1 and 4 positions can be synthesized, namely, a series of new 3-cyanopyridine derivatives. BRIEF DESCRIPTION OF THE DRAWINGS

[0058] Figure 1 is the fluorescence intensity change curve of the probe solution of compound 3b in Example 2;

[0059] Figure 2 Fluorescence intensity change curve of the probe solution of Compound 3b in Example 2;

[0060] Figure 3 Fluorescence intensity change curve of the probe solution of Compound 3c in Example 3;

[0061] Figure 4 Fluorescence intensity change curve of the probe solution of Compound 3c in Example 3;

[0062] Figure 5 Fluorescence intensity change curve of the probe solution of Compound 3d in Example 4;

[0063] Figure 6 Fluorescence intensity change curve of the probe solution of Compound 3d in Example 4;

[0064] Figure 7 Fluorescence intensity change curve of the probe solution of Compound 3e in Example 5;

[0065] Figure 8 Fluorescence intensity change curve of the probe solution of Compound 3e in Example 5;

[0066] Figure 9 Fluorescence intensity change curve of the probe solution of Compound 3f in Example 6;

[0067] Figure 10 Fluorescence intensity change curve of the probe solution of Compound 3f in Example 6;

[0068] Figure 11 Ultraviolet absorption spectrum of the probe solution of Compound 3f in Example 6;

[0069] Figure 12 Dynamic light scattering test chart of the probe solution of Compound 3f in Example 6;

[0070] Figure 13 Fluorescence intensity change results of the probe solution of Compound 3f for detecting different metal ions;

[0071] Figure 14 Fluorescence intensity change results of the probe solution of Compound 3f for detecting different concentrations of iron ions;

[0072] Figure 15 Fluorescence intensity change results of the probe solution of Compound 3f for detecting different aromatic nitro explosives;

[0073] Figure 16 Fluorescence intensity change results of the probe solution of Compound 3f for detecting different concentrations of the aromatic nitro explosive NBAc;

[0074] Figure 17 Results of detecting fluorescence intensity changes of aromatic nitro explosive DNP at different concentrations with the probe solution of compound 3f;

[0075] Figure 18 Results of detecting fluorescence intensity changes of aromatic nitro explosive NA at different concentrations with the probe solution of compound 3f;

[0076] Figure 19 Results of detecting fluorescence intensity changes of aromatic nitro explosive PA at different concentrations with the probe solution of compound 3f;

[0077] Figure 20 Results of detecting fluorescence intensity changes of aromatic nitro explosive NBA at different concentrations with the probe solution of compound 3f. Specific implementation manners

[0078] The content of the present invention will be further described in detail through specific embodiments below. The raw materials used in the following embodiments, unless otherwise specified, can be obtained from conventional commercial channels or prepared and separated by simple synthesis; the processes adopted, unless otherwise specified, are all conventional processes in the art.

[0079] In the embodiments of the present invention, the 3-cyanopyridine compounds are synthesized by benzopyran carbonitrile and pyrrolidine under the promotion of inorganic base, and the synthesis reaction formula is as follows:

[0080]

[0081] In Formula 1 and Formula 3, R1 is selected from methoxy, fluorine, chlorine, bromine, methyl or absent; R2 is methyl.

[0082] Example 1

[0083] Example 1 provides a 3-cyanopyridine compound 3a and its synthesis method, and the synthesis method is as follows:

[0084] Add 2-methyl-6-fluorobenzopyran carbonitrile (0.1 mmol, 0.023 g), pyrrolidine (1 mmol, 0.071 g) and NaOH (1 mmol, 0.040 g) into a 25 mL round-bottom flask, dissolve in 4 mL of MeCN, and stir at 80 °C for 2 h. After the reaction is completed, spin-dry the reaction solvent, add 15 mL of water to dissolve, adjust the pH of the solution to neutral (pH = 7) with HCl (6 M) solution, then extract with dichloromethane (15 mL × 3), collect the organic phase, dry the organic phase with anhydrous sodium sulfate, concentrate under reduced pressure, and separate by column chromatography (petroleum ether / ethyl acetate = 10 / 1, v / v) to obtain the product 3a, a yellow solid (26.4 mg, 88.7%), with a melting point of 171.8 - 173.2 °C.

[0085] The structural formula of compound 3a and related characterization data are as follows:

[0086]

[0087] 1 H NMR(600MHz,CDCl3),δ,ppm:1.97(t,J=6.6Hz,4H,CH2-6,7),2.42(s,3H,CH3-3),3.80(t,J=6.6Hz,4H,CH2-5,8),5.91(b,1H,OH),6.42(s,1H,ArH-1),6.81-6.85(m,1H,ArH-14),6.90-6.93(m,1H,ArH-15),6.95-6.99(m,1H,ArH-17);

[0088] 13 C NMR(150MHz,CDCl3),δ,ppm:25.1(C-3),25.7(C-6,7),49.4(C-5,8),87.1(C-9),112.7(C-1),116.5(d,J=23.9Hz,C-17),117.1(d,J=22.8Hz,C-15),117.6(d,J=8.0Hz,C-14),118.9(C-10),125.9(d,J=7.7Hz,C-12),148.9(d,J=2.3Hz,C-13),152.4(C-11),156.7(d,J=238.2Hz,C-16),157.8(C-2),162.3(C-4);

[0089] 19 F NMR(564MHz,CDCl3),δ,ppm:-123.8;

[0090] ESI-HRMS,m / z:Calcd for C 17 H 17 N3OF[M+H] + :298.1350,Found:298.1345。

[0091] Example 2

[0092] Example 2 provides a 3-cyanopyridine compound 3b and its synthesis method. The specific synthesis method is as follows:

[0093] To a 25 mL round-bottom flask, add 2-methyl-6-chlorobenzopyran carbonitrile (0.1 mmol, 0.024 g), pyrrolidine (1 mmol, 0.071 g) and NaOH (1 mmol, 0.040 g). Dissolve them in 4 mL of MeCN and stir at 80 °C for 2 h. After the reaction is completed, rotary evaporate the reaction solvent, add 15 mL of water to dissolve, adjust the pH of the solution to neutral (pH = 7) with HCl (6 M) solution, then extract with dichloromethane (15 mL × 3). Collect the organic phase, dry the organic phase with anhydrous sodium sulfate, concentrate under reduced pressure, and separate by column chromatography (petroleum ether / ethyl acetate = 10 / 1, v / v) to obtain product 3b, a pale yellow solid (25.8 mg, 82.3%), melting point 188.9 - 190.4 °C.

[0094] The structural formula of compound 3b and related characterization data are as follows:

[0095]

[0096] 1 H NMR (600 MHz, CDCl3), δ, ppm: 1.97 (t, J = 6.6 Hz, 4H, CH2-6,7), 2.42 (s, 3H, CH3-3), 3.79 (t, J = 6.6 Hz, 4H, CH2-5,8), 6.40 (s, 1H, ArH-1), 6.78 (d, J = 8.4 Hz, 1H, ArH-15), 7.16 (s, 1H, ArH-17), 7.18 (d, J = 8.4 Hz, 1H, ArH-14);

[0097] 13 C NMR (150 MHz, CDCl3), δ, ppm: 25.1 (C-3), 25.7 (C-6,7), 49.4 (C-5,8), 87.1 (C-9), 112.8 (C-1), 117.9 (C-10), 119.0 (C-14), 125.4 (C-16), 126.5 (C-17), 129.7 (C-12), 130.5 (C-15), 151.7 (C-13), 152.4 (C-11), 157.7 (C-2), 162.4 (C-4);

[0098] ESI-HRMS, m / z: Calcd for C 17 H 17 N3OCl [M+H] + : 314.1055, Found: 314.1048.

[0099] Example 3

[0100] Example 3 provides a 3-cyanopyridine compound 3c and its synthesis method, and the synthesis method is as follows:

[0101] Add 2-methyl-6-bromobenzopyran carbonitrile (0.1 mmol, 0.029 g), pyrrolidine (1 mmol, 0.071 g) and NaOH (1 mmol, 0.040 g) into a 25 mL round-bottom flask, dissolve them in 4 mL of MeCN, and stir at 80 °C for 2 h. After the reaction is completed, spin-dry the reaction solvent, add 15 mL of water to dissolve it, adjust the pH of the solution to neutral (pH = 7) with HCl (6 M) solution, then extract with dichloromethane (15 mL × 3), collect the organic phase, dry the organic phase with anhydrous sodium sulfate, concentrate under reduced pressure, and separate by column chromatography (petroleum ether / ethyl acetate = 10 / 1, v / v) to obtain the product 3c, a pale yellow solid (26.8 mg, 74.9%), melting point 209.3 - 210.1 °C.

[0102] The structural formula and related characterization data of compound 3c are as follows:

[0103]

[0104] 1 H NMR (600 MHz, CDCl3), δ, ppm: 1.96 (t, J = 6.6 Hz, 4H, CH2-6,7), 2.41 (s, 1H, CH3-3), 3.78 (t, J = 6.6 Hz, 4H, CH2-5,8), 6.40 (s, 1H, ArH-1), 6.68 (d, J = 9.0 Hz, 1H, ArH-15), 6.85 (b, 1H, OH), 7.26 - 7.33 (m, 2H, ArH-14,17);

[0105] 13 C NMR (150 MHz, CDCl3), δ, ppm: 25.1 (C-3), 25.7 (C-6,7), 49.4 (C-5,8), 87.0 (C-9), 112.2 (C-1), 112.9 (C-10), 118.3 (C-14), 119.1 (C-16), 127.0 (C-12), 132.5 (C-15), 133.3 (C-17), 152.5 (C-13), 152.6 (C-11), 157.6 (C-2), 162.3 (C-4);

[0106] ESI-HRMS, m / z: Calcd for C 17 H 17 N3OBr [M + H] + : 358.0550, Found: 358.0542.

[0107] Example 4

[0108] Example 4 provides a 3-cyanopyridine compound 3d and its synthesis method, and the synthesis method is as follows:

[0109] Add 2,6-dimethylbenzopyran carbonitrile (0.1 mmol, 0.022 g), pyrrolidine (1 mmol, 0.071 g) and NaOH (1 mmol, 0.040 g) to a 25 mL round-bottom flask, dissolve in 4 mL of MeCN, and stir at 80 °C for 2 h. After the reaction is completed, spin-dry the reaction solvent, add 15 mL of water to dissolve, adjust the pH of the solution to neutral (pH = 7) with HCl (6 M) solution, then extract with dichloromethane (15 mL × 3), collect the organic phase, dry the organic phase with anhydrous sodium sulfate, concentrate under reduced pressure, and separate by column chromatography (petroleum ether / ethyl acetate = 10 / 1, v / v) to obtain the product 3d, a pale yellow solid (27.90 mg, 95.1%), melting point 142.9 - 143.7 °C.

[0110] The structural formula and related characterization data of compound 3d are as follows:

[0111]

[0112] 1 H NMR (600 MHz, CDCl3), δ, ppm: 1.91 (t, J = 6.6 Hz, 4H, CH2-6,7), 2.38 (s, 3H, CH3-17), 2.48 (s, 3H, CH3-3), 3.55 (t, J = 6.6 Hz, 4H, CH2-5,8), 6.95 (s, 1H, ArH-1), 7.12 (d, J = 8.4 Hz, 1H, ArH-14), 7.23 (d, J = 8.4 Hz, 1H, ArH-15), 7.64 (s, 1H, ArH-18);

[0113] 13 C NMR (150 MHz, CDCl3), δ, ppm: 21.0 (C-3), 25.2 (C-6,7), 25.5 (C-17), 50.5 (C-5,8), 96.3 (C-9), 103.4 (C-1), 116.8 (C-10), 123.7 (C-14), 132.3 (C-16,18), 133.4 (C-12), 144.7 (C-15), 150.7 (C-13), 158.1 (C-11), 158.2 (C-2), 161.8 (C-4);

[0114] ESI-HRMS, m / z: Calcd for C18 H 18 N3O[M-H] + ,294.1601,found:294.1596。

[0115] Example 5

[0116] Example 5 provides a 3-cyanopyridine compound 3e and its synthesis method. The synthesis method is as follows:

[0117] Add 2-phenylbenzopyran carbonitrile (0.1 mmol, 0.027 g), pyrrolidine (1 mmol, 0.071), and NaOH (1 mmol, 0.040 g) to a 25 mL round-bottom flask, dissolve in 4 mL of MeCN, and stir at 80 °C for 2 h. After the reaction is completed, rotary evaporate the reaction solvent, add 15 mL of water to dissolve, adjust the pH of the solution to neutral (pH = 7) with HCl (6 M) solution, then extract with dichloromethane (15 mL × 3), collect the organic phase, dry the organic phase with anhydrous sodium sulfate, concentrate under reduced pressure, and separate by column chromatography (petroleum ether / ethyl acetate = 10 / 1, v / v) to obtain product 3e, a white solid (24.31 mg, 95.1%), melting point 221.4 - 223.4 °C.

[0118] The structural formula of compound 3e and related characterization data are as follows:

[0119]

[0120] 1 H NMR(600MHz,CDCl3),δ,ppm:2.05(t,J=6.6Hz,4H,CH2-11,12),3.96(t,J=6.6Hz,4H,CH2-10,13),5.37(s,1H,OH),6.98(d,J=8.4Hz,1H,ArH-22),7.04-7.10(m,1H,ArH-20),7.12(s,1H,ArH-1),7.30-7.37(m,2H,ArH-19,21),7.45-7.50(m,3H,ArH-5,6,7),8.06-8.10(m,2H,ArH-4,8);

[0121] 1313C NMR (150 MHz, CDCl3), δ, ppm: 20.5 (C-11), 21.3 (C-12), 61.5 (C-10, 13), 84.7 (C-14), 105.3 (C-1), 115.7 (C-19), 116.8 (C-6), 117.2 (C-15), 118.4 (C-17, C-21), 125.0 (C-4, 8, 5, 7), 135.9 (C-20, 22), 136.2 (C-3), 151.1 (C-18), 153.1 (C-2), 161.7 (C-9, 16);

[0122] ESI-HRMS, m / z: Calcd for C 22 H 20 N3O [M+H] + : 342.1601, Found: 342.1596.

[0123] Example 6

[0124] Example 6 provides a 3-cyanopyridine compound 3f and its synthesis method, and the synthesis method is as follows:

[0125] 2-Methyl-6-methoxybenzopyran carbonitrile (0.1 mmol, 0.024 g), pyrrolidine (1 mmol, 0.071 g) and NaOH (1 mmol, 0.040 g) were added to a 25 mL round-bottom flask, dissolved in 4 mL of MeCN, and stirred at 80 °C for 2 h. After the reaction was completed, the reaction solvent was evaporated to dryness, 15 mL of water was added to dissolve it, and the pH of the solution was adjusted to neutral (pH = 7) with HCl (6 M) solution, and then extracted with dichloromethane (15 mL × 3). The organic phase was collected, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography (petroleum ether / ethyl acetate = 10 / 1, v / v) to obtain the product 3f, a white solid (29.42 mg, 95.1%), with a melting point of 165.8 - 168.2 °C.

[0126] The structural formula and related characterization data of compound 3f are as follows:

[0127]

[0128] 11H NMR (600 MHz, CDCl3), δ, ppm: 1.95 (t, J = 6.6 Hz, 4H, CH2-6,7), 2.41 (s, 3H, CH3-3), 3.78 (s, 3H, OCH3-17), 3.79 - 3.80 (t, J = 6.6 Hz, 4H, CH2-5,8), 5.96 (b, 1H, OH), 6.45 (s, 1H, ArH-1), 6.74 (s, 1H, ArH-18), 6.81 - 6.84 (m, 2H, ArH-14,15);

[0129] 13 13C NMR (150 MHz, CDCl3), δ, ppm: 25.0 (C-3), 25.7 (C-6,7), 49.5 (C-17), 55.9 (C-5,8), 87.5 (C-9), 113.0 (C-1), 115.0 (C-18), 116.5 (C-15), 117.7 (C-14), 119.0 (C-10), 125.5 (C-12), 146.8 (C-13), 153.4 (C-16), 153.7 (C-11), 157.8 (C-2), 161.8 (C-4);

[0130] ESI-HRMS, m / z: Calcd for C 18 H 20 N3O2 [M+H] + : 310.1550, Found: 310.1545.

[0131] Detection Experiment Analysis

[0132] 1. Aggregation-Induced Emission (AIE) Performance Experiment

[0133] (1) Dissolve compound 3b in DMSO and add a certain amount of water. Prepare a series of DMSO / H2O solutions of compound 3b with a total volume of 5 mL and a concentration of 10 μM according to the water content rate (0%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 99%). Then, test the fluorescence of this series of DMSO / aqueous solutions of compound 3b by a fluorescence spectrometer (fluorescence test conditions: excitation wavelength 280 nm, scanning wavelength range 300 - 800 nm, slit 10.0 nm, photomultiplier tube voltage 450 V), draw a fluorescence intensity change curve with the excitation wavelength as the abscissa and the fluorescence intensity as the ordinate (as Figure 1 shown), and then draw a fluorescence intensity change curve with the water content rate (f w ) as the abscissa and the peak value of the fluorescence intensity as the ordinate (as Figure 2 shown). FromFigure 1 and 2 It can be seen that compound 3b has obvious aggregation-induced emission (AIE) characteristics, and the fluorescence characteristic peak of compound 3b as a fluorescent probe is located at 450 nm.

[0134] (2) Dissolve compound 3c in DMSO, add a certain amount of water, and prepare a series of DMSO / water (DMSO / H2O) solutions of compound 3c with a total volume of 5 mL and a concentration of 10 μM according to the water content rates (0%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 99%). Then, test the fluorescence of this series of DMSO / aqueous solutions of compound 3c by a fluorescence spectrometer (fluorescence test conditions: excitation wavelength 280 nm, scanning wavelength range 300 - 800 nm, slit 10.0 nm, photomultiplier tube voltage 450 V), plot a fluorescence intensity change curve with the excitation wavelength as the abscissa and the fluorescence intensity as the ordinate (as Figure 3 shown), and then plot a fluorescence intensity change curve with the water content rate (f w ) as the abscissa and the peak value of the fluorescence intensity as the ordinate (as Figure 4 shown). It can be seen from Figure 3 and 4 that compound 3c has obvious aggregation-induced emission (AIE) characteristics, and the fluorescence characteristic peak of compound 3c as a fluorescent probe is located at 450 nm.

[0135] (3) Dissolve compound 3d in DMSO, add a certain amount of water, and prepare a series of DMSO / water (DMSO / H2O) solutions of compound 3d with a total volume of 5 mL and a concentration of 10 μM according to the water content rates (0%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 99%). Then, test the fluorescence of this series of DMSO / aqueous solutions of compound 3d by a fluorescence spectrometer (fluorescence test conditions: excitation wavelength 280 nm, scanning wavelength range 300 - 800 nm, slit 10.0 nm, photomultiplier tube voltage 450 V), plot a fluorescence intensity change curve with the excitation wavelength as the abscissa and the fluorescence intensity as the ordinate (as Figure 5 shown), and then plot a fluorescence intensity change curve with the water content rate (f w ) as the abscissa and the peak value of the fluorescence intensity as the ordinate (as Figure 6 shown). It can be seen from Figure 5 and 6 that compound 3d has obvious aggregation-induced emission (AIE) characteristics, and the fluorescence characteristic peak of compound 3d as a fluorescent probe is located at 450 nm.

[0136] (4) Dissolve compound 3e in DMSO and add a certain amount of water. Prepare a series of DMSO / water (DMSO / H2O) solutions of compound 3e with a total volume of 5 mL and a concentration of 10 μM according to the water content rates (0%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 99%). Then, use a fluorescence spectrometer to measure the fluorescence of this series of DMSO / aqueous solutions of compound 3e (fluorescence measurement conditions: excitation wavelength 280 nm, scanning wavelength range 300 - 800 nm, slit 10.0 nm, photomultiplier tube voltage 450 V). Plot a fluorescence intensity change curve with the excitation wavelength as the abscissa and the fluorescence intensity as the ordinate (as shown in Figure 7 ). Then, plot a fluorescence intensity change curve with the water content rate (f w ) as the abscissa and the peak value of the fluorescence intensity as the ordinate (as shown in Figure 8 ). It can be seen from Figure 7 and 8 that compound 3e has obvious aggregation-induced emission (AIE) characteristics, and the fluorescence characteristic peak of compound 3e as a fluorescence probe is located at 450 nm.

[0137] (5) Dissolve compound 3f in DMSO and add a certain amount of water. Prepare a series of DMSO / water (DMSO / H2O) solutions of compound 3f with a total volume of 5 mL and a concentration of 10 μM according to the water content rates (0%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 99%). Then, use a fluorescence spectrometer, an ultraviolet absorption spectrometer, and a nanoparticle size and zeta potential analyzer to measure the fluorescence, ultraviolet, etc. of this series of DMSO / aqueous solutions of compound 3f (fluorescence measurement conditions: excitation wavelength 280 nm, scanning wavelength range 300 - 800 nm, slit 10.0 nm, photomultiplier tube voltage 450 V). The results are as shown in Figures 9 - 12 . It can be seen from Figure 9 and 10 that as the water content rate increases from 0% to 60%, the fluorescence intensity of compound 3f increases significantly; and in Figure 11 , due to the light scattering effect, when the water content rate is greater than 60%, compound 3f shows a flat tail in the long-wavelength region of ultraviolet absorption. Therefore, compound 3f has obvious aggregation-induced emission (AIE) characteristics. In addition, through the dynamic light scattering test study shown in Figure 12 , it is further confirmed that compound 3f has obvious AIE characteristics. The fluorescence characteristic peak of compound 3f as a fluorescence probe is located at 450 nm.

[0138] 2. Application of compound 3f as a fluorescence probe in the detection of Fe 3+

[0139] (1) Compound 3f as a fluorescent probe for the specific detection of Fe 3+ Specific detection

[0140] Prepare a 1 μM fluorescent probe 3f solution with a solvent system of DMSO / H2O solution (water content 60%);

[0141] Prepare a metal ion stock solution with a concentration of 20 equiv. (Na + , K + , Ag + , Mg 2+ , Ca 2+ , Ba 2+ , Mn 2+ , Cu 2+ , Cd 2+ , Hg 2+ , Fe 2+ , Pb 2+ , Zn 2+ , Cd 2+ , Ni 2+ , Al 3+ , Cr 3+ , and Fe 3+ ).

[0142] Add the metal ion stock solution to the above fluorescent probe 3f solution respectively. Select a fluorescence spectrometer and perform fluorescence tests under the conditions of an excitation wavelength of 280 nm, a scanning wavelength range of 300 - 800 nm, a slit of 10.0 nm, and a photomultiplier tube voltage of 450 V. Shake for a few seconds before the test and measure the fluorescence emission spectra of the probe solution after adding different metal ion stock solutions respectively. The test shows that only after adding Fe 3+ , the fluorescence of 3f is quenched, and the results are as Figure 13 shown.

[0143] (2) Compound 3f as a fluorescent probe for the quantitative detection of Fe 3+ Quantitative detection

[0144] In a DMSO / H2O (80%) solution with a water content, gradually add Fe 3+ solution from 0 to 20 equiv. Use the scanning wavelength range as the abscissa and the fluorescence intensity as the ordinate to plot a fluorescence titration curve for Fe 3+ . The results are as Figure 14 shown. The fluorescence intensity shows a linear relationship with the sample concentration, indicating that compound 3f can be used as a fluorescent probe for the quantitative detection of Fe 3+ .

[0145] 3. Application of compound 3f as a fluorescent probe in the detection of nitroaromatic explosives

[0146] (1) Compound 3f as a fluorescent probe for the detection of nitroaromatic explosives

[0147] Prepare a fluorescent probe 3f solution with a solvent system of DMSO / H2O solution (water content 60%) at a concentration of 1 μM.

[0148] Prepare stock solutions of nitroaromatic explosives at a concentration of 20 equiv., including 2,4,6-trinitrophenol (PA), 2,4-dinitrophenol (DNP), 4-nitrophenol (NP), 2,4,6-trinitrotoluene (TNT), 2,4-dinitrotoluene (DNT), 4-nitrotoluene (NT), nitrobenzene (NB), 2-nitrobenzaldehyde (NBA), 2-nitrobenzoic acid (NBAc), o-hydroxybenzoic acid (HBAc), phenol (Phenol), 2-nitroaniline (NA), and nitromethane (NM).

[0149] Add the stock solutions of nitroaromatic explosives to the above fluorescent probe 3f solution respectively. Using a fluorescence spectrometer, perform fluorescence tests under the conditions of an excitation wavelength of 280 nm, a scanning wavelength range of 300 - 800 nm, a slit of 10.0 nm, and a photomultiplier tube voltage of 450 V. Oscillate for a few seconds before the test and measure the fluorescence emission spectra of the probe solution after adding different stock solutions of nitroaromatic explosives. The results are as Figure 15 shown, where curve ① is for PA, curve ② is for DNP, curve ③ is for NP, curve ④ is for TNT, curve ⑤ is for DNT, curve ⑥ is for NT, curve ⑦ is for NB, curve ⑧ is for NBA, curve ⑨ is for NBAc, curve ⑩ is for HBAc, curve is for Phenol, curve is for NA, curve is for NM. The tests show that the fluorescence of 3f is quenched after adding NBAc, DNP, NA, PA, and NBA.

[0150] (2) Quantitative detection of NBAc using compound 3f as a fluorescent probe

[0151] In one embodiment, in a DMSO / H2O (60%) solution with a water content, gradually add a 2-nitrobenzoic acid (NBAc) solution from 0 to 20 equiv. Using the scanning wavelength range as the abscissa and the fluorescence intensity as the ordinate, plot the fluorescence titration curve for NBAc. The results are as Figure 16 shown. The fluorescence intensity shows a linear relationship with the sample concentration, indicating that compound 3f can be used as a fluorescent probe for the quantitative detection of NBAc.

[0152] (3) Quantitative detection of DNP using compound 3f as a fluorescent probe

[0153] In one embodiment, in a DMSO / H2O (60%) solution with a certain water content, a 2,4-dinitrophenol (DNP) solution is gradually added in an amount of 0 to 20 equiv. Using the scanning wavelength range as the abscissa and the fluorescence intensity as the ordinate, a fluorescence titration curve for DNP is plotted. The results are as follows Figure 17 shown. The fluorescence intensity shows a linear relationship with the sample concentration, indicating that compound 3f can be used as a fluorescence probe for the quantitative detection of DNP.

[0154] (4) Quantitative detection of NA using compound 3f as a fluorescence probe

[0155] In one embodiment, in a DMSO / H2O (60%) solution with a certain water content, a 2-nitroaniline (NA) solution is gradually added in an amount of 0 to 20 equiv. Using the scanning wavelength range as the abscissa and the fluorescence intensity as the ordinate, a fluorescence titration curve for NA is plotted. The results are as follows Figure 18 shown. The fluorescence intensity shows a linear relationship with the sample concentration, indicating that compound 3f can be used as a fluorescence probe for the quantitative detection of NA.

[0156] (5) Quantitative detection of PA using compound 3f as a fluorescence probe

[0157] In one embodiment, in a DMSO / H2O (60%) solution with a certain water content, a 2,4,6-trinitrophenol (PA) solution is gradually added in an amount of 0 to 20 equiv. Using the scanning wavelength range as the abscissa and the fluorescence intensity as the ordinate, a fluorescence titration curve for PA is plotted. The results are as follows Figure 19 shown. The fluorescence intensity shows a linear relationship with the sample concentration, indicating that compound 3f can be used as a fluorescence probe for the quantitative detection of PA.

[0158] (6) Quantitative detection of NBA using compound 3f as a fluorescence probe

[0159] In one embodiment, in a DMSO / H2O (60%) solution with a certain water content, a 2-nitrobenzaldehyde (NBA) solution is gradually added in an amount of 0 to 20 equiv. Using the scanning wavelength range as the abscissa and the fluorescence intensity as the ordinate, a fluorescence titration curve for NBA is plotted. The results are as follows Figure 20 shown. The fluorescence intensity shows a linear relationship with the sample concentration, indicating that compound 3f can be used as a fluorescence probe for the quantitative detection of NBA.

[0160] Bioactivity experimental analysis

[0161] 1. Experimental procedure

[0162] (1) The strains used in the experiment were Escherichia coli ATCC 43894 and Staphylococcus aureus ATCC 25923.

[0163] The compounds to be detected were compounds 3a - 3f.

[0164] (2) Activation of bacterial strains and preparation of bacterial solutions

[0165] Escherichia coli ATCC 43894 and Staphylococcus aureus ATCC 25923 stored at -80°C were dispersed on LB agar medium by the streaking method and cultured in a 37°C biochemical incubator for 24 h. A single colony on the medium was picked with an inoculation loop and inoculated into 2 mL of liquid broth culture and cultured for 12 h. Then, 50 μL of the bacterial solution was diluted 1:100 and expanded to the logarithmic growth phase.

[0166] (3) Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) tests

[0167] The bacterial solution cultured to the logarithmic growth phase was diluted with LB culture medium to OD 600 = 0.1 for standby. Weigh 8 mg of the compound to prepare a stock solution with a concentration of 4 mg / mL, and continuously dilute it with LB broth culture medium in a 96-well plate to prepare solutions with different concentrations (180 μL). An equal volume of the diluted bacterial solution (20 μL) was added to the 96-well plate, and the final concentration of the polymer was controlled to be 2000, 1000, 500, 250, 125, 62.5, 31.25, 15.625, 7.8125 μg / mL. Then it was cultured in a 37°C constant temperature incubator (Escherichia coli was cultured for 18 h, and Staphylococcus aureus was cultured for 18 - 20 h). If there was no obvious increase in bacteria at the minimum concentration, it was the MIC of the compound. The bacterial suspension without the compound was used as the negative control, and the LB broth without the compound and bacteria was used as the positive control. Each concentration was set with three parallel controls and three technical replicates were carried out to confirm the MIC value of each bacterium.

[0168] MBC refers to the lowest concentration required for the compound to completely kill bacteria. 100 μL of the non-turbid group in the above MIC test was spread on an agar plate. After culturing at 37°C for 24 h, the lowest concentration group without colony growth was the MBC.

[0169] 2. Results and discussion

[0170] As can be seen from Table 1, the selected compounds all have certain biological activities. Compared with similar tests, the representative compounds in this application can achieve antibacterial effects at lower concentrations as drugs, and the results are better than those reported in the literature (such as Wang Y L; Liu Z H, Liu T, et al. Chemistryselect, 2024, 9, e202401299).

[0171] Minimum antibacterial activities of some compounds in Table 1

[0172]

[0173] The synthesized 3-cyanopyridine has certain antibacterial activities against bacteria. Among them, the chloro-substituted product 3b and the bromo-substituted product 3c have higher antibacterial activities against Gram-positive bacteria. This is because the surface of bacteria carries negative charges, and structures carrying positive charges are easily adsorbed to the surface of bacteria through electrostatic interactions. The hydrophobic and hydrophilic structures of compounds also affect their bactericidal activities. The lipophilic hydrophobic structure is easily to damage the cell membrane, causing the leakage of cell contents and achieving the bactericidal effect.

[0174] The above are the preferred embodiments of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and refinements can be made, and these improvements and refinements are also regarded as the protection scope of the present invention.

Claims

1. A 3-cyanopyridine compound, characterized in that, The chemical structural formula of the 3-cyanopyridine compound is shown in Formula 3: wherein, R1 is a halogen group, a C1-C3 alkoxy group, a C1-C3 alkyl group or absent; R2 is a C1-C3 alkyl group or a phenyl group.

2. The 3-cyanopyridine compound according to claim 1, wherein The chemical structural formula of the 3-cyanopyridine compound is shown in any one of Formula 3a - Formula 3f:

3. A method for preparing the 3-cyanopyridine compound according to claim 1 or 2, characterized in that, comprising the following steps: using a benzopyran carbonitrile compound, pyrrolidine, and an inorganic base as raw materials, reacting in an organic solvent to obtain the 3-cyanopyridine compound; The chemical structure formula of the benzopyran nitrile compound is shown in Formula 1 as follows: wherein R1 is as described in claim 1.

4. The preparation method of the 3-cyanopyridine compound according to claim 3, wherein, The process conditions of the preparation method are selected from at least one of the following: 1) The reaction temperature of the reaction is 70 - 90 °C; 2) The reaction time of the reaction is 1.5 - 3 h; 3) The molar ratio of the benzopyran carbonitrile compound to pyrrolidine is 1:(8 - 12); 4) The organic solvent is acetonitrile or ethanol; 5) The dosage ratio of the benzopyran carbonitrile compound to the solvent is 1 mmol:(30 - 60) mL.

5. The method for preparing a 3-cyanopyridine compound according to claim 3, characterized in that, The inorganic base is sodium hydroxide; and / or, the molar ratio of the benzopyran carbonitrile compound to the inorganic base is 1:(8 - 12).

6. Use of the 3-cyanopyridine compound according to claim 1 or 2 in any one of the following A) or B): A) Detecting iron ions; B) Preparing a product for detecting iron ions.

7. A method for detecting iron ions, characterized in that, Comprising the following steps: preparing a fluorescent probe solution with the 3-cyanopyridine compound according to claim 1 or 2, adding the solution to be detected, if the fluorescent probe solution undergoes fluorescence quenching, it is detected that the solution to be detected contains iron ions.

8. Use of the 3-cyanopyridine compound according to claim 1 or 2 in any one of the following C) or D): C) Detecting nitroaromatic explosives; D) Preparing a product for detecting nitroaromatic explosives.

9. A method for detecting nitroaromatic explosives, characterized in that, Comprising the following steps: preparing a fluorescent probe solution with the 3-cyanopyridine compound according to claim 1 or 2, adding the solution to be detected, if the fluorescent probe solution undergoes fluorescence quenching, it is detected that the solution to be detected contains nitroaromatic explosives.

10. Use of the 3-cyanopyridine compound according to claim 1 or 2 in the preparation of antibacterial drugs.

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