Polysubstituted pyridine compound as well as preparation method and application thereof

Abstract

The invention discloses a polysubstituted pyridine compound as well as a preparation method and application thereof. The polysubstituted pyridine compound is a compound shown in a formula 3. The polysubstituted pyridine compound of the compound shown in the formula 3 has a double-state emission fluorescence sensing characteristic, shows high brightness and stable fluorescence emission characteristic in a solid state and a liquid state, and can be effectively applied to rapid visual detection of various nitro aromatic explosives in an actual water sample.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of materials, in particular to a polysubstituted pyridine compound and a preparation method and application thereof. BACKGROUND

[0002] Dual-state emissive fluorophore (DSEphore) combines the advantages of high emission in the aggregated state of aggregation-induced emission (AIE) and high emission in the solution state of aggregation-induced quenching (ACQ) molecules, so developing novel DSEphore with excellent fluorescence performance has gradually become a new hotspot in the field of fluorescence research.

[0003] At present, the main strategies for designing DSEphore can be divided into three types: (1) regulating the balance between twisted structure and conjugated structure; (2) constructing push-pull structure molecules; (3) introducing long-chain alkyl or large steric groups into planar molecules. Among them, strategy (3) avoids the π-π stacking of planar molecules by introducing groups to achieve strong emission in the solid state.

[0004] For example, the related art reports that two freely rotatable aromatic rings are introduced into a planar nitrogen heteroaromatic fused ring, which effectively inhibits the planar stacking in the aggregated state, thereby realizing efficient dual-state emission. Similarly, the related art also introduces a large steric long alkyl chain fluorene ring into a planar benzotriazole, so that the planarity of the whole molecule presents a special twist, realizing high emission in solid and liquid states. The design of DSE molecules using strategy (3) often relies on large and complex planar molecules. In contrast, the modification of planar small molecules is rarely reported. Although so far, the related art has designed and synthesized a new type of non-fused aromatic fluorescent molecule with bright and adjustable dual-state emission performance, which shows that single-ring aromatic small molecules also have the potential to be developed as DSEphore. However, it is still difficult to obtain DSEphore with excellent performance through the modification of single-ring aromatic molecules, so it is worth further studying to develop new methods for preparing non-fused aromatic DSEphore. SUMMARY

[0005] The present application aims at at least solving one of the above-mentioned technical problems in the prior art. To this end, the object of the present application is to provide a polysubstituted pyridine compound and a preparation method and application thereof.

[0006] In order to achieve the above-mentioned object, the technical solution adopted by the present application is as follows: In a first aspect of the present application, a compound of formula 3 is provided: ; wherein X is selected from C, O, NH, S; R 1 is selected from H, halogen, C1-C6 alkyl; R 2 is selected from halogen, C1-C6 alkoxy.

[0007] In some embodiments, R 1 is selected from H, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, butyl, pentyl, hexyl.

[0008] In some embodiments, R 2 is selected from F, Cl, Br, I, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexyloxy.

[0009] In some embodiments, the compound of formula 3 is selected from the following compounds: , , .

[0010] In a second aspect of the present application, a preparation method of the compound of formula 3 is provided, comprising the following steps: reacting the compound of formula 2 with a compound of formula 4, a compound of formula 5 to obtain the compound of formula 3; ; ; ; wherein, X, R 1 , R 2 are defined as above.

[0011] In some embodiments, the reaction temperature of the reaction is 90-130 ℃, such as 100-120 ℃; the reaction time of the reaction is 2-6 h; such as 3-5 h.

[0012] In some embodiments, the reaction solvent of the reaction comprises at least one of tetrahydrofuran, dimethyl sulfoxide, benzene, toluene, xylene, acetone.

[0013] In some embodiments, the preparation method of the compound of formula 2 comprises the following steps: performing Knoevenagel reaction on the compound of formula 1 with malononitrile to obtain the compound of formula 2; ; wherein, R 1 are defined as above.

[0014] In some embodiments, the reaction temperature of the Knoevenagel reaction is 90-130 ℃, such as 100-120 ℃; the reaction time is 4-8 h, such as 5-7 h.

[0015] In some embodiments, the preparation method of the compound of formula 1 comprises the following steps: reacting the compound of formula 1-1 with sodium p-toluenesulfinate to obtain the compound of formula 1; ; wherein, R 1 are defined as above; the reaction is performed under the action of boron trifluoride etherate.

[0016] In some embodiments, the compound of Formula 3 is selected from the following compounds: 、 、 、 .

[0017] In a third aspect, the present application provides a detection device for nitroaromatic explosives, comprising the compound of Formula 3.

[0018] In some embodiments, the detection device comprises a detection test paper, wherein the compound of Formula 3 is loaded on the detection test paper.

[0019] In some embodiments, the compound of Formula 3 is loaded on the detection test paper in an amount of 0.01-0.1 mg / cm 2 , such as 0.02-0.08 mg / cm 2 , 0.03-0.08 mg / cm 2 , 0.035-0.075 mg / cm 2 .

[0020] In some embodiments, the detection device comprises a detection reagent, wherein the detection reagent comprises the compound of Formula 3.

[0021] In some embodiments, the compound of Formula 3 is loaded on the detection test paper in an amount of 0.01-0.1 mg / cm µ , such as 0.02-0.08 mg / cm µ , 0.03-0.08 mg / cm , 0.035-0.075 mg / cm

[0022] . 、 、 、 .

[0023] In a fourth aspect, the present application provides a detection method for nitroaromatic explosives, comprising the following steps: using the compound of Formula 3 for detection.

[0024] In some embodiments, the detection method for nitroaromatic explosives comprises the following steps: using the compound of Formula 3 to detect a solution containing nitroaromatic explosives.

[0025] In some embodiments, the solution containing nitroaromatic explosives has a concentration of nitroaromatic explosives of 0.1-100 µ mol / L, such as 1-50 µ mol / L.

[0026] In some embodiments, the nitroaromatic explosive includes a nitrophenol and / or a nitroaniline.

[0027] In some embodiments, the nitrophenol includes at least one of 2,4-dinitrophenol (DNP), 4-nitrophenol (NP), 2,4,6-trinitrophenol (PA).

[0028] In some embodiments, the nitroaniline includes 2-nitroaniline (NA).

[0029] In some embodiments, the compound of Formula 3 is selected from the following compounds: 、 、 、 .

[0030] The present application has the following advantages: The polysubstituted pyridine compound of the present application exhibits high brightness and stable fluorescence emission characteristics in solid and liquid states, i.e., has DSE characteristics.

[0031] The preparation method of the polysubstituted pyridine compound in the present application uses inexpensive and readily available raw materials, does not require expensive catalysts or special raw materials or equipment, the reaction conditions are easy to control, and the product purification is simple; avoids the high cost, complex steps or harsh conditions of traditional synthesis.

[0032] The polysubstituted pyridine compound of Formula 3 of the present application has a dual-state emission fluorescence sensing property, and can be effectively applied to rapid visual detection of various nitroaromatic explosives in actual water samples. In addition, the material can be made into a portable test strip through a simple process, and can exhibit rapid, high sensitivity, and visual detection of aromatic explosives. BRIEF DESCRIPTION OF DRAWINGS

[0033] Figure 1 FIG. 2 is a fluorescence emission spectrum of a sensing material for identifying a nitroaromatic explosive in Example 2 of the present application.

[0034] Figure 2 FIG. 3 is a relationship between fluorescence intensity and time of a sensing material for identifying a nitroaromatic explosive in Example 3 of the present application.

[0035] Figure 3 FIG. 4 is a result of a test strip for detecting a nitroaromatic explosive in Example 4 of the present application. DETAILED DESCRIPTION

[0036] The present invention will be further described in detail below through specific embodiments. Unless otherwise specified, the raw materials, reagents, or apparatus used in the embodiments and comparative examples are all available from conventional commercial sources or can be obtained by existing technical methods. Unless otherwise specified, the test or experimental methods are conventional methods in the art.

[0037] Example 1 This embodiment prepares a sensing material, and the specific process is as follows:

[0038]

[0039] In a 100 mL round-bottom flask, phenylacetylene (or 4-chlorophenylacetylene) (3.0 mmol, 1.0 eq.), sodium p-toluenesulfinate (7.2 mmol, 2.4 eq.), and BF3·OEt2 (1.5 mmol, 0.5 eq.) were added separately, followed by dichloroethane (15 mL) as a solvent. The mixture was magnetically stirred at room temperature for 4 h. After the reaction was completed as monitored by thin-layer chromatography (TCL), the mixture was concentrated under reduced pressure, extracted with ethyl acetate (3 × 25 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the crude product. Separation by column chromatography (petroleum ether / ethyl acetate = 6 / 1, v / v) yielded a white solid ketone sulfone compound. 1a - 1b .

[0040] Add ketone sulfone compounds to 50 mL round-bottom flasks. 1a (or 1b The reaction mixture was prepared with 1 mmol (1.0 eq.) of malononitrile (1.5 mmol, 2.0 eq.), 1.7 mmol (1.7 eq.) of ammonium acetate (1.7 mmol, 1.7 eq.), and an appropriate volume of a mixed solvent of Toluene / CH3COOH = 10:1 (v / v), and reacted at 110 °C for 6 h. After the reaction was complete as monitored by TCL, the mixture was cooled, concentrated under reduced pressure, neutralized with saturated sodium bicarbonate solution, and then extracted with dichloromethane (3 × 25 mL). The organic layer was dried with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the crude product. The crude product was then separated by column chromatography (petroleum ether / ethyl acetate = 3 / 1, v / v) to obtain the malononitrile alkenyl sulfone intermediate. 2a - 2b .

[0041] Add the intermediate to each 50 mL round-bottom flask. 2a (or 2bThe reaction mixture was prepared with 0.3 mmol (1.0 eq.) of 4-methoxybenzaldehyde (or 4-bromobenzaldehyde), 0.36 mmol (1.2 eq.) of hexahydropyridine (or morpholine) (0.6 mmol, 2.0 eq.) and an appropriate volume of Toluene as solvent, and reacted at 110 °C for 4 h. After the reaction was complete as monitored by TCL, the mixture was cooled and concentrated under reduced pressure, and extracted with dichloromethane (3 × 15 mL). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the crude product. Column chromatography (petroleum ether / ethyl acetate = 20 / 1, v / v) was used to obtain the pure product. 3a - 3d This allows for the acquisition of fluorescent sensing materials for detecting various aromatic explosives.

[0042] The sensing material 3a is a white solid with a melting point of mp = 144.1-145.4 ℃.

[0043] The structural formula and related characterization data of sensing material 3a are shown below:

[0044] 1 H NMR (600 MHz, CDCl3), δ ppm: 1.70-1.74 m , 2H, CH2-21), 1.77-1.81( m , 4H, ArH-20,22), 3.76 ( t , J = 5.4 Hz, 4H, CH2-19,23), 3.87 ( s , 3H, OCH3-1), 6.99 ( d , J = 9.0 Hz, 2H, ArH-3,5), 7.18 ( s , 1H, ArH-9), 7.47-7.53 ( m , 3H, ArH-15,16, 17), 7.60 ( d , J = 8.4 Hz, 2H, ArH-14,18), 8.05 ( d , J = 9.0 Hz, 2H, ArH-4,6); 13 C NMR (150 MHz, CDCl3), δ, ppm: 24.8 (C-21), 26.1 (C-20,22), 50.4 (C-19,23), 55.5 (C-1), 91.7 (C-11), 110.7 (C-24), 114.2 (C-3,5), 118.5 (C-9),128.8 (C-14,18), 128.85 (C-4,6), 128.9 (C-15,17), 129.6 (C-16), 130.8 (C 7),137.9 (C-13), 157.2 (C-10), 157.6 (C-8),161.5 (C-2), 163.2 (C-12). ESI-HRMS, m / z Calcd for C 24 H 24 N3O [M+H] + 370.1914, found: 370.1918. The sensing material 3b is a white solid with a melting point of mp = 156.7-158.1 ℃.

[0045] The structural formula and related characterization data of sensing material 3b are shown below:

[0046] 1 H NMR (600 MHz, CDCl3), δ ppm: 1.71-1.74 m , 2H, CH2-20), 1.76-1.80 ( m , 4H, CH2-19,21), 3.76 ( t , J = 5.4 Hz, 4H, CH2-18,22), 7.20 ( s , 1H, ArH-8), 7.48-7.53 ( m , 3H, ArH-14,15,16), 7.59-7.61 ( m , 4H, ArH-2,4,13,17), 7.94 ( d , J =8.4 Hz, 2H, ArH-3,5); 13 C NMR (150 MHz, CDCl3), δ, ppm: 24.7 (C-20), 26.1 (C-19,21), 50.4 (C-18,22), 92.8(C-10), 111.1 (C-23), 118.2 (C-8), 124.8 (C-1), 128.8 (C-3,5),128.9 (C-14,15,16), 129.8 (C-13,17), 132.1 (C-2,4), 137.2 (C-6), 137.6 (C-12), 156.8 (C-9), 157.6 (C-7), 163.1 (C-11). ESI-HRMS, m / z Calcd for C 23 H 20 BrN3[M+H] + : 418.0913, found: 418.0915. The sensing material 3c is a white solid with a melting point of mp = 146.3-147.5 ℃.

[0047] The structural formula and related characterization data of the sensing material 3c are shown below:

[0048] 1 H NMR (600 MHz, CDCl3), δ ppm: 3.79 t , J = 4.8 Hz, 4H, CH2-20,21),3.88 ( s , 3H, OCH3-1), 3.92 ( t , J = 4.8 Hz, 4H, CH2-19,22), 6.99 ( d , J = 9.0 Hz, 2H, ArH-3,5), 7.28 ( s , 1H, ArH-9), 7.50-7.54 ( m , 3H, CH2-14,18,16), 7.58-7.61( m , 2H, CH2-15,17), 8.04( d , J = 9.0 Hz, 2H, ArH-4,6); 13 C NMR (150 MHz, CDCl3),δ , ppm: 49.5 (C-19,22), 55.6 (C-1), 67.0 (C-20,21), 92.5 (C-11), 111.8 (C-23), 114.3 (C-3,5), 118.1 (C-9), 128.7 (C-14,18), 128.9 (C-4,6), 129.0 (C-15,17), 129.8 (C-16), 130.4 (C-7), 137.5 (C-13), 157.3 (C-10), 157.8(C-8), 161.7 (C-1), 162.8 (C-12). ESI-HRMS, m / z : C 23 H 21 N3O2[M+H] + : 372.1707, found:372.1709. The sensing material 3d is a white solid with a melting point of mp = 111.2-112.5 ℃.

[0049] The 3D structural formula and related characterization data of the sensing material are shown below:

[0050] 1 H NMR (600 MHz, CDCl3), δ ppm: 1.70-1.74 m , 2H, CH2-21), 1.76-1.80 ( m , 4H, 2CH2-20,22), 3.76 ( t , J = 5.4 Hz, 4H, CH2-19,23), 3.88 ( s , 3H, OCH3-1), 6.99 ( d , J = 9.0 Hz, 2H, ArH-3,5), 7.13 ( s , 1H, ArH-9), 7.48 ( d , J = 8.4 Hz, 2H,ArH-15,17), 7.53 ( d , J = 8.4 Hz, 2H, ArH-14,18), 8.03 ( d , J= 9.0 Hz, 2H, ArH-4,6); 13 C NMR (150 MHz, CDCl3), δ , ppm: 24.6 (C-21), 26.0 (C-20,22), 50.2 (C-19,23), 55.4 (C-1), 91.0 (C-11), 110.1 (C-24), 114.1 (C-3,5), 118.2 (C-9),128.8 (C-14,18), 129.0 (C-4,6), 130.0 (C-15,17), 130.5 (C-16), 135.8 (C-7), 136.2 (C-13), 155.8 (C-10), 157.7 (C-8), 161.5 (C-2), 162.9 (C-12). ESI-HRMS, m / z : C 24 H 22 ClN3O [M+H] + : 404.1524, found: 404.1515. Example 2 This embodiment uses sensing materials to identify nitro aromatic explosives. The specific process is as follows: Configure 8 groups of 10 μ An aqueous solution of sensing material 3a of M was prepared; 20 equiv. of different aromatic explosives and their contrast agents were added to 7 of these solutions for later use; a fluorescence spectrometer was used, with appropriate parameters set, to test the fluorescence emission spectra of 8 solutions. The results are as follows: Figure 1 As shown.

[0051] from Figure 1 It was observed that the aqueous solution of sensing material 3a exhibited strong fluorescence. However, the addition of DNP (2,4-dinitrophenol), NA (2-nitroaniline), NP (4-nitrophenol), and PA (2,4,6-trinitrophenol, i.e., picric acid) led to a significant decrease in the fluorescence intensity of the solution. Conversely, the addition of NM (nitromethane), HBAc (4-hydroxybenzoic acid), and Phenol (phenol) did not result in a significant change in the fluorescence intensity. This indicates that the fluorescent material can effectively identify various aromatic explosives such as DNP, NA, NP, and PA in the liquid state.

[0052] Example 3 This embodiment uses sensing materials to identify nitro aromatic explosives. The specific process is as follows: Configure 4 groups of 10 μAn aqueous solution of sensing material 3a of M was used. One set of solutions was added to a quartz cuvette, placed in a fluorescence spectrometer, and 20 equiv. NACs solution was rapidly added. The relationship between maximum intensity and time was recorded. Without any external force, the fluorescence intensity decreased strongly and rapidly, and within 10 s, the fluorescence weakened to a minimum and no longer changed significantly.

[0053] from Figure 2 It was observed that when 20 equiv. of NACs solution was added to the aqueous solution of sensing material 3a, the fluorescence intensity of 3a decreased rapidly within 10 s. This indicates that 3a can rapidly detect four aromatic explosives: NP, DNP, NA, and PA.

[0054] Example 4 This embodiment describes the preparation of a portable test strip loaded with sensing material and the use of this test strip for the detection of nitro aromatic explosives. The specific process is as follows: Cut 5 blank filter paper strips of the same size and set aside; prepare 10 mL of fluorescent material 3a (THF, 10 -3 M) solution; immersed in fluorescent material 3a (THF, 10) -3 Immerse the test strip in solution M for 1 minute, then remove and air dry to complete the preparation of the portable test strip.

[0055] Three drops of aromatic explosive (10) were added to the filter paper strips of the four groups of fluorescent material 3a respectively. -6 M), under a 365 nm ultraviolet lamp, can be observed as Figure 3 The results are shown.

[0056] Example 5 This embodiment uses sensing materials to detect NACs in actual water samples. The specific process is as follows: A solution of compound 3a was prepared using tap water as the actual water sample and THF. (10) μ M, H2O / THF, 6 / 4, v / v); then, NACs solutions of known concentrations were added, and their fluorescence intensity was tested; the experiment was repeated three times by comparing the calculated NACs concentration with the titration fitting line, and the recovery rate and relative standard deviation (RSD) were calculated to characterize the detection effect of fluorescent material 3a. The results of relevant tests and calculations are summarized in Table 1.

[0057] Table 1

[0058] As can be seen from the table, the recovery rate of fluorescent material 3a for the simulated detection of NACs ranges from 97.0% to 102.3%, with a relative standard deviation of less than 2%. Compared with the actual water sample detection of previously reported probes, it has excellent performance. This indicates that fluorescent material 3a, as an NACs probe, can accurately test NP, DNP, PA and NA in actual water samples and has the potential to be applied to practical detection.

[0059] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. Compound of Formula 3: ； in, X is selected from C, O, NH, S; R 1 Selected from H, halogens, C1-C6 alkyl groups; R 2 Selected from halogens and C1-C6 alkoxy groups.

2. The compound of formula 3 according to claim 1, characterized in that: R 1 Selected from H, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, butyl, pentyl, and hexyl.

3. The compound of formula 3 according to claim 1, characterized in that: R 2 Selected from F, Cl, Br, I, methoxy, ethoxy, propoxy, butoxy, pentoxy, and hexoxy.

4. The compound of formula 3 according to claim 1, characterized in that: Compound 3 is selected from the following compounds: 、 、 。 5. A method for preparing the compound of formula 3 according to any one of claims 1-4, characterized in that: Includes the following steps: Compound 2 was reacted with compounds 4 and 5 to prepare compound 3; ; ; Among them, X and R 1 R 2 The definition is as described in any one of claims 1-4.

6. The preparation method according to claim 5, characterized in that: The preparation method of the compound of formula 2 includes the following steps: reacting the compound of formula 1 with malononitrile using a Knoevenagel reaction to obtain the compound of formula 2; Among them, R 1 The definition is as described in any one of claims 1-4.

7. A detection device for nitroaromatic explosives, characterized in that: Includes the compound of formula 3 as described in any one of claims 1-4.

8. The detection device for nitroaromatic explosives according to claim 7, characterized in that: The detection device includes a test strip loaded with the compound of formula 3; or, the detection device includes a detection reagent comprising the compound of formula 3.

9. A method for detecting nitroaromatic explosives, characterized in that: Includes the following steps: The compound of formula 3 as described in any one of claims 1-4 was used for detection.

10. The method for detecting nitroaromatic explosives according to claim 9, characterized in that: The concentration of the nitro aromatic explosive in the solution is 0.1-100%. µ mol / L; and / or, the nitro aromatic explosive includes nitrophenol and / or nitroaniline.

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