Method for preparing ionic enamine compound from pyridinium-alkyne monomer and application of ionic enamine compound

Abstract

The invention discloses a method for preparing an ionic enamine compound from a pyridinium-alkyne monomer and application of the ionic enamine compound, belongs to the technical field of organic synthesis, and particularly relates to a method for preparing the ionic enamine compound by taking the pyridinium-alkyne monomer and an amine monomer as raw materials and carrying out alkyne-amine hydroamination reaction. The method can be carried out at room temperature without the action of a catalyst, the reaction efficiency is high, excellent regioselectivity and stereoselectivity are achieved, no by-product is generated in the reaction process, the atom economy is high, and the prepared ionic enamine compound contains ionic groups, is good in water solubility, contains heteroatoms and benzene rings in the structure, and can be used for preparing the ionic enamine compound. The compound has rich electrons, has a good application prospect in preparation of photodynamic drugs, photosensitizers, photodynamic antibacterial agents or biological imaging reagents, and can also be used as an effective synthon, that is, a nucleophilic reaction is further carried out, and compounds with more diversified structures are synthesized.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis, and particularly relates to a method for preparing ionic enamine compounds through pyridinium salt-alkyne monomers and its application. Background Art

[0002] Developing synthetic methods with mild reaction conditions has important scientific significance and practical value for the preparation and application of organic small molecules. Alkyne monomers are simple to synthesize, easy to obtain, and have high reaction activity. They are widely used in the field of chemical synthesis and are one of the important chemical synthons. Alkyne monomers play a crucial role in the design and synthesis of functional molecules. They can not only enrich organic synthesis methodologies, construct complex molecular skeletons, but also promote the development of interdisciplinary fields.

[0003] The molecular structure of enamine contains a double bond, and the carbon atom of this double bond is directly connected to a nitrogen atom. As an important structural unit and key intermediate in nitrogen-containing organic compounds, enamine compounds can be used to synthesize important bioactive molecules, drug molecules, chiral amine compounds, etc. Enamines can be formed by the dehydration condensation of aldehydes or ketones with secondary amines, but this reaction is reversible and requires the action of a strong dehydrating agent.

[0004] The hydroamination reaction of alkyne-amine is a new organic synthesis strategy. It stands out among many synthetic methods due to its significant advantages such as mild reaction conditions, fast reaction rate, high product yield, and excellent atom economy. The efficient and precise characteristics of this reaction highly conform to the core principles of click chemistry and are considered a new type of click reaction, especially suitable for the synthesis of enamine compounds. However, the existing reports on hydroamination reactions mainly use metal catalysis (NiH-Catalyzed Hydroamination / Cyclization Cascade: Rapid Access to Quinolines, ACS Catal., 2021, 11, 7772-7779) or organic base catalysis (Research Progress on the Hydroamination Reactions of Alkenes and Alkynes Catalyzed by Non-Noble Metals, Chinese Journal of Organic Chemistry, 2016, 36, 1163-1183). Due to the possible presence of organic bases or metal catalysts in the products, and the poor water solubility of some products, the above catalytic methods limit the application of their products in the fields of biology and luminescence.

[0005] In order to efficiently construct ionic enamine compounds and promote their application in the fields of biotherapy and imaging, it is of great research significance and application value to develop a synthetic method of ionic enamine compounds based on the click chemistry strategy, without the participation of catalysts and with mild reaction conditions. This method is expected to simplify the synthesis process of ionic enamine compounds, improve the synthesis efficiency, reduce energy consumption, increase atom economy, and thus promote the synthesis process and application development of related bioactive molecules. SUMMARY OF THE INVENTION

[0006] Aiming at the deficiencies existing in the above-mentioned prior art, the present invention provides a method for preparing ionic enamine compounds through pyridinium-alkyne monomers. This method does not require the action of a catalyst, can be carried out at room temperature, has high reaction efficiency, excellent regioselectivity and stereoselectivity, does not produce by-products during the reaction, and has high atom economy.

[0007] The specific technical solution adopted is as follows:

[0008] A method for preparing ionic enamine compounds through pyridinium-alkyne monomers, comprising:

[0009] Using pyridinium-alkyne monomers and amine monomers as raw materials, carrying out hydroamination of alkyne-amine to prepare ionic enamine compounds;

[0010] The structural formula of the pyridinium-alkyne monomer is shown in formula (Ⅰ) or (Ⅱ):

[0011]

[0012] wherein, A - is a halogen ion, an acid root ion or a base ion, R 1 is a hydrocarbon group with 1-200 carbon atoms, an oxygen-containing hydrocarbon group, a heteroaryl group or a hydrocarbon group substituted by an aryl group, R 2 is hydrogen, ethynyl, or a hydrocarbon group with 1-200 carbon atoms, an oxygen-containing hydrocarbon group, a heteroaryl group or a hydrocarbon group substituted by an aryl group;

[0013] The structural formula of the amine monomer is shown in formula (Ⅲ) or (Ⅳ):

[0014]

[0015] wherein, X is an alkylene group, an arylene group, a heteroarylene group or a tertiary amine arylene group with 1-200 carbon atoms; Y is an alkyl group, an aryl group, a heteroaryl group or an alkoxy group with 1-200 carbon atoms; R3 and R4 are each independently selected from hydrogen, a hydrocarbon group with 1-200 carbon atoms, an oxygen-containing hydrocarbon group, a heteroaryl group or a hydrocarbon group substituted by an aryl group.

[0016] Preferably, R 1 is an alkyl group with 1-10 carbon atoms.

[0017] Preferably, R 2 is hydrogen, ethynyl or an alkyl group with 1-10 carbon atoms.

[0018] Preferably, A - is an iodide ion, a bromide ion, a hydroxide ion, a trifluoromethanesulfonate ion, a tetrafluoroborate ion, a nitrate ion, a sulfate ion or a hexafluorophosphate ion.

[0019] The reaction mechanism of this reaction focuses on the activation of the α and γ positions of the pyridine ring after the nitrogen of pyridine is quaternized, making it easier to undergo nucleophilic reactions, thereby achieving the activation purpose and enabling the reaction to perform anti-Markovnikov addition at room temperature to synthesize ionic enamine compounds.

[0020] Furthermore, the hydroamination reaction is carried out in an organic solvent system, and the organic solvent is at least one of tetrahydrofuran, dichloromethane, methanol, acetonitrile, dimethyl sulfoxide, N,N-dimethylformamide, and N,N-dimethylacetamide.

[0021] Furthermore, the concentration of the pyridinium salt-alkyne monomer in the organic solvent is 0.2 - 1 mol / L, preferably 0.1 - 0.5 mol / L.

[0022] Furthermore, the conditions of the hydroamination reaction are preferably a temperature of 25 - 40 °C and a reaction time of 0.3 - 24 h, preferably 2 - 12 h.

[0023] Furthermore, when the pyridinium salt-alkyne monomer contains diethynyl, the pyridinium salt-alkyne monomer and the amine monomer shown in formula (Ⅳ) undergo a hydroamination reaction of alkyne-amine in a molar ratio of 1:2.0 - 2.5; when the pyridinium salt-alkyne monomer contains monoethynyl, the pyridinium salt-alkyne monomer and the amine monomer shown in formula (Ⅲ) undergo a hydroamination reaction of alkyne-amine in a molar ratio of 2.0 - 2.5:1; when the pyridinium salt-alkyne monomer contains monoethynyl, the pyridinium salt-alkyne monomer and the amine monomer shown in formula (Ⅳ) undergo a hydroamination reaction of alkyne-amine in a molar ratio of 1:1.0 - 2.0.

[0024] Furthermore, after the hydroamination reaction of alkyne-amine is completed, the obtained reaction solution is recrystallized with ether or purified by column chromatography, and dried to a constant weight to prepare an ionic enamine compound.

[0025] The present invention also provides an ionic enamine compound prepared by the above method.

[0026] The ionic enamine compound obtained by the present invention contains ionic groups, has good water solubility, and contains heteroatoms and benzene rings in its structure, having rich electrons. And this ionic enamine compound has strong fluorescence, and some have the ability to produce reactive oxygen species. The corresponding characteristics also provide certain possibilities for the application of this compound in the fields of bioimaging and photodynamic therapy. And due to the presence of its double bond structure, it can be used as an effective synthon, that is, further undergo nucleophilic reactions to synthesize more diverse compounds.

[0027] The present invention also provides the application of the described ionic enamine compound in the preparation of photodynamic drugs, photosensitizers, photodynamic antibacterial agents, or bioimaging reagents.

[0028] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0029] (1) The method of the present invention realizes the efficient spontaneous reaction of pyridinium-alkyne monomers and amino monomers, and successfully synthesizes n-π conjugated organic small molecules - ionic enamine compounds under mild conditions.

[0030] (2) The raw materials used in the method of the present invention are easy to obtain, can be directly purchased or synthesized through simple reactions, and the reaction conditions are mild. The reaction can be carried out at room temperature, with simple operation and high reaction efficiency. High-purity ionic enamine compounds can be obtained in a short time with high yields.

[0031] (3) The method of the present invention has good regioselectivity and stereoselectivity, does not produce by-products during the reaction, and has extremely high atom economy.

[0032] (4) The method of the present invention does not require any catalyst and can react at room temperature, avoiding the potential impact of catalyst residues on the optoelectronic and biological properties of the product.

[0033] (5) The ionic enamine compounds synthesized by the present invention have good water solubility and reactive oxygen generation ability, and can be used to prepare photodynamic drugs, photosensitizers, photodynamic antibacterial agents or bioimaging reagents, etc. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 1H NMR spectrum of ionic enamine compound 3a prepared in Example 1 in DMSO-d6.

[0035] Figure 2 13C NMR spectrum of amido enamine compound 3a prepared in Example 1 in DMSO-d6.

[0036] Figure 3 1H NMR spectrum of ionic enamine compound 3b prepared in Example 2 in DMSO-d6.

[0037] Figure 4 1H NMR spectrum of ionic enamine compound 3c prepared in Example 3 in DMSO-d6.

[0038] Figure 5 1H NMR spectrum of ionic enamine compound 3d prepared in Example 4 in DMSO-d6.

[0039] Figure 6 Characterization result diagram of ionic enamine compound 3b prepared in Example 2 in dimethyl sulfoxide solution, where (A) is the ultraviolet absorption spectrum diagram and (B) is the fluorescence emission spectrum diagram.

[0040] Figure 7 Characterization results of the ionic enamine compound 3c prepared in Example 3 in a dimethyl sulfoxide solution, where (A) is the ultraviolet absorption spectrum and (B) is the fluorescence emission spectrum.

[0041] Figure 8 Characterization diagram of the reactive oxygen species generation ability of the ionic enamine compound 3b prepared in Example 2 and the control photodynamic therapy reagent. Detailed implementation manners

[0042] To make the objectives, features, and advantages of the present invention more apparent and understandable, the following provides a detailed description through specific implementation manners. Many specific details are set forth in the following description to fully understand the present invention. However, the present invention can be implemented in many other ways different from those described herein, and those skilled in the art can make similar improvements without departing from the connotation of the present invention. Therefore, the present invention is not limited by the specific embodiments disclosed below. The technical features in each embodiment of the present invention can be combined correspondingly without conflict.

[0043] For the operation methods without specific conditions noted in the following examples, they are generally carried out under conventional conditions or according to the conditions recommended by the manufacturer. The content not described in detail in this specification belongs to the prior art well-known to those skilled in the art. The experimental materials used in the following examples can be obtained from conventional biochemical reagent companies without special instructions.

[0044] Example 1

[0045] The structural formula of the ionic enamine compound synthesized in this example is shown as 3a:

[0046]

[0047] The pyridinium salt-alkyne monomer 1a can be prepared according to the synthesis method in the published literature (The intersection of allenylidenes and mesomeric betaines. 1-Methylpyridinium-2-acetylide and its palladium complexes, Tetrahedron, 2016, 72, 7906-7911.); the amine monomer 2a is 9,9-dioctyl-9H-fluorene-2,7-diamine, which can be purchased from the market; the solvent is ultradry MeOH.

[0048] The preparation steps of the ionic enamine compound 3a are as follows:

[0049] In a 10 mL polymerization tube, 293.9 mg (1.1 mmol) of pyridinium-alkyne monomer 1a was added, dissolved in 2.5 mL of ultra-dry methanol, and then 210.4 mg (0.5 mmol) of amine monomer 2a was added using a microsyringe. After the amine monomer was completely dissolved, the reaction was carried out at 25 °C for 8 h, and a solid precipitated. After the reaction was completed, ether was added, filtered, washed, and dried to obtain ionic enamine compound 3a with a yield of 78%.

[0050] The 1H NMR spectrum and 13C NMR spectrum of the ionic enamine compound 3a obtained in this example are shown in Figure 1 and Figure 2 respectively; the structure characterization data are as follows:

[0051] 1 H NMR (400 MHz, DMSO-d6) δ 10.68 (d, J = 12.7 Hz, 2H), 8.62 (t, J = 12.7 Hz, 2H), 8.43 (d, J = 6.4 Hz, 2H), 8.38 (d, J = 8.8 Hz, 2H), 8.04 (t, J = 8.0 Hz, 2H), 7.72 (d, J = 8.1 Hz, 2H), 7.46 (s, 2H), 7.34–7.19 (m, 4H), 5.93 (d, J = 12.5 Hz, 2H), 3.98 (s, 6H), 2.12–1.92 (m, 4H), 1.41–0.85 (s, 24H), 0.74 (t, J = 7.0 Hz, 6H).

[0052] 13 C NMR (126 MHz, DMSO) δ 150.7, 146.9, 131.0, 118.8, 113.0, 108.9, 54.1, 41.0, 31.6, 30.0, 29.4, 29.2, 24.0, 22.5, 14.4.

[0053] HRMS (ESI): m / z [M] 2+ calculated for C 45 H 60 N4 2+ : 328.2404; found 328.2421.

[0054] This ionic enamine compound 3a is readily soluble in common large-polarity organic solvents such as methanol, ethanol, N,N-dimethylformamide, dimethyl sulfoxide, N,N-dimethylacetamide, and water at room temperature, and has excellent solubility.

[0055] Example 2

[0056] The structural formula of the ionic enamine compound synthesized in this example is shown as 3b:

[0057]

[0058] The specific reaction equation is as follows:

[0059]

[0060] The amine monomer 2b can be prepared according to the synthesis method in the published literature (Preparation of new enforcement polyamide nanocomposite filled by ternary layer double hydroxide and investigation of electrochemical activity, optical and thermal properties, Polymer Bulletin, 2021, 78, 6723-6741.); the solvent is ultra-dry MeOH.

[0061] The preparation steps of the ionic enamine compound 3b are as follows:

[0062] Add 293.9 mg (1.1 mmol) of pyridinium salt-alkyne monomer 1a into a 10 mL polymerization tube, dissolve it with 2.5 mL of ultra-dry methanol, then add 137.7 mg (0.5 mmol) of amine monomer 2b with a microsyringe. After the amine monomer is completely dissolved, react at 25 °C for 8 h, and a solid precipitates. After the reaction is completed, add ether, filter, wash, and dry to obtain the ionic enamine compound 3b with a yield of 82%.

[0063] The 1H NMR spectrum of the ionic enamine compound 3b obtained in this example is as Figure 3 shown; the structural characterization data are as follows:

[0064] 1 H NMR (400 MHz, DMSO-d6) δ 10.60 (d, J = 12.7 Hz, 2H), 8.51 (t, J = 12.6 Hz, 2H), 8.40 (d, J = 6.2 Hz, 2H), 8.32 (d, J = 8.7 Hz, 2H), 7.97 (t, J = 7.8 Hz, 2H), 7.34–7.18 (m, 8H), 7.06–6.92 (m, 7H), 5.88 (d, J = 12.5 Hz, 8H), 3.96 (s, 3H).

[0065] Dissolve the obtained ionic enamine compound 3b in dimethyl sulfoxide (1×10 -5mol / L), the absorption spectrum and fluorescence emission spectrum of this solution were tested, and the results are shown as A and B in Figure 6 respectively. It can be seen that the absorption spectrum of this molecule is: 447 nm, and the emission spectrum is: 546 nm, indicating that this ionic enamine compound has fluorescence emission ability and is suitable for fields such as fluorescence labeling, bioimaging, or optoelectronic materials.

[0066] This ionic enamine compound 3b is easily soluble in common large-polarity organic solvents such as methanol, ethanol, N,N-dimethylformamide, dimethyl sulfoxide, N,N-dimethylacetamide, and water at room temperature, and has excellent solubility.

[0067] Example 3

[0068] The structural formula of the ionic enamine compound synthesized in this example is shown as 3c:

[0069]

[0070] The specific reaction equation is shown as follows:

[0071]

[0072] The synthesis method of pyridinium salt-alkyne monomer 1b is described below; amine monomer 2c is 4-aminotriphenylamine, which can be purchased on the market; the solvent is ultra-dry MeOH.

[0073] The synthesis steps of pyridinium salt-alkyne monomer 1b are as follows: Add 2,6-diethynylpyridine (1.27 g, 10.0 mmol) to a 50 mL flame-dried two-necked round-bottom flask equipped with a magnetic stirrer. After evacuating and filling with nitrogen three times, under ice bath conditions, inject 15 mL of anhydrous dichloromethane into the flask through a syringe, and then slowly add methyl trifluoromethanesulfonate (1.64 g, 10.0 mmol). Then remove the ice bath and wait for the reaction temperature to slowly rise to room temperature. After detecting by TLC plate and the reaction is completed, add cold ether, filter, and wash repeatedly three times with cold ether and dichloromethane to obtain pyridinium salt-alkyne monomer 1b in the form of a beige solid (2.85 g, yield 98%). The structure characterization data are as follows: FT-IR (KBr disk), v(cm -1 ): 3200, 2107, 1596, 1569, 1478, 1263, 1157, 1026, 818, 637, 517. 1 1H NMR (500 MHz, DMSO-d6) δ 8.55 (t, J = 8.1 Hz, 1H), 8.34 (d, J = 8.1 Hz, 2H), 5.90 (s, 2H), 4.41 (s, 3H). 13¹³C NMR (126 MHz, DMSO-d₆) δ 145.1, 138.3, 132.4, 125.0, 122.4, 119.8, 117.3, 98.9, 75.0, 46.1.

[0074] The preparation steps of the ionic enamine compound 3c are as follows:

[0075] Add 145.6 mg (0.5 mmol) of pyridinium salt-alkyne monomer 1b to a 10 mL polymerization tube, dissolve it with 2.5 mL of ultradry methanol, and then add 286.4 mg (1.1 mmol) of amine monomer 2c with a microsyringe. After the amine monomer is completely dissolved, react at 25 °C for 8 h. A solid precipitates. After the reaction is completed, add diethyl ether, filter, wash, and dry to obtain the ionic enamine compound 3c with a yield of 81%.

[0076] The proton nuclear magnetic resonance spectrum of the ionic enamine compound 3c obtained in this example is as Figure 4 shown; the structural characterization data are as follows:

[0077] 1 ¹H NMR (400 MHz, DMSO-d₆) δ 10.09 (d, J = 12.2 Hz, 2H), 8.14 (t, J = 12.5 Hz, 2H), 7.82–7.62 (m, 3H), 7.35–7.14 (m, 12H), 7.11–6.86 (m, 16H), 5.91 (d, J = 12.7 Hz, 2H), 3.81 (s, 3H).

[0078] Dissolve the obtained ionic enamine compound 3c in dimethyl sulfoxide (1×10 -5 mol / L), and measure the absorption spectrum and fluorescence emission spectrum of this solution. The results are shown in Figure 7 A and B respectively. It can be seen that the absorption spectrum of this molecule is: 491 nm, and the emission spectrum is: 576 nm, indicating that this ionic enamine compound has fluorescence emission ability and is applicable to fields such as fluorescence labeling, bioimaging, or optoelectronic materials.

[0079] This ionic enamine compound 3c is easily soluble in common large-polarity organic solvents such as methanol, ethanol, N,N-dimethylformamide, dimethyl sulfoxide, and N,N-dimethylacetamide at room temperature, and has excellent solubility.

[0080] Example 4

[0081] The structural formula of the ionic enamine compound synthesized in this example is as shown in 3d:

[0082]

[0083] The specific reaction equation is as follows:

[0084]

[0085] The synthesis method of pyridinium salt-alkyne monomer 1b is the same as that in Example 3; the amine monomer 2d is aniline, which can be purchased from the market; the solvent is ultra-dry MeOH.

[0086] The preparation steps of the ionic enamine compound 3d are as follows:

[0087] Add 145.6 mg (0.5 mmol) of pyridinium salt-alkyne monomer 1b into a 10 mL polymerization tube, dissolve it with 2.5 mL of ultra-dry methanol, then add 100 μL (1.1 mmol) of amine monomer 2d with a microsyringe. After mixing evenly, react at 25 °C for 8 h, and a solid precipitates. After the reaction is completed, add ether, filter, wash, and dry to obtain the ionic enamine compound 3d with a yield of 90%.

[0088] The 1H NMR spectrum of the ionic enamine compound 3d obtained in this example is as Figure 5 shown; the structure characterization data are as follows:

[0089] 1 H NMR (500 MHz, DMSO-d6) δ 10.04 (d, J = 12.4 Hz, 2H), 8.19 (t, J = 12.6 Hz, 2H), 7.83 - 7.71 (m, 3H), 7.33 (t, J = 7.9 Hz, 4H), 7.24 (d, J = 7.8 Hz, 4H), 6.98 (t, J = 7.3 Hz, 2H), 5.94 (d, J = 12.7 Hz, 2H), 3.82 (s, 1H).

[0090] This ionic enamine compound 3d is easily soluble in common large-polarity organic solvents such as methanol, ethanol, N,N-dimethylformamide, dimethyl sulfoxide, and N,N-dimethylacetamide at room temperature, and has excellent solubility.

[0091] Example 5

[0092] The structural formula of the ionic enamine compound synthesized in this example is as shown in 3e:

[0093]

[0094] The specific reaction equation is as follows:

[0095]

[0096] The synthesis method of pyridinium salt-alkyne monomer 1a is the same as that in Example 1; the amine monomer 2d is aniline, which can be purchased from the market; the solvent is ultra-dry MeOH.

[0097] The preparation steps of the ionic enamine compound 3e are as follows:

[0098] Add 267.2 mg (1.0 mmol) of pyridinium salt-alkyne monomer 1a into a 10 mL polymerization tube, dissolve it with 2.5 mL of ultra-dry methanol, and then add 100 μL (1.2 mmol) of amine monomer 2d with a micro syringe. After mixing evenly, react at 25 °C for 2 h, and a solid precipitates. After the reaction is completed, add ether, filter, wash, and dry to obtain the ionic enamine compound 3e with a yield of 90%.

[0099] The ionic enamine compound 3e is readily soluble in common large-polarity organic solvents such as methanol, ethanol, N,N-dimethylformamide, dimethyl sulfoxide, and N,N-dimethylacetamide at room temperature, showing excellent solubility.

[0100] The characterization data of the 1H NMR spectrum of the ionic enamine compound 3e obtained in this example are as follows:

[0101] 1 H NMR(500MHz,Chloroform-d)δ10.22(s,1H),8.88(d,J=6.1Hz,1H),8.16(t,J=12.5Hz,2H),7.91–7.59(m,7H),6.41(d,J=12.5Hz,1H),3.90(s,3H).

[0102] Example 6

[0103] The structural formula of the ionic enamine compound synthesized in this example is shown as 3f:

[0104]

[0105] The specific reaction equation is shown as follows:

[0106]

[0107] The synthesis method of pyridinium salt-alkyne monomer 1b is the same as that in Example 3; amine monomer 2e is diethylamine, which can be purchased from the market; the solvent is ultra-dry MeOH.

[0108] The preparation steps of the ionic enamine compound 3f are as follows:

[0109] In a 10 mL polymerization tube, 145.6 mg (0.5 mmol) of pyridinium salt-alkyne monomer 1b was added, dissolved in 2.5 mL of ultradry methanol, and then 113 μL (1.1 mmol) of amine monomer 2e was added using a microsyringe. After mixing evenly, the reaction was carried out at 25 °C for 2 h. After the reaction, no treatment was required. After column chromatography separation with DCM:MeOH = 50:1, the ionic enamine compound 3e was obtained with a yield of 85%.

[0110] The ionic enamine compound 3f is readily soluble in common large-polarity organic solvents such as methanol, ethanol, N,N-dimethylformamide, dimethyl sulfoxide, and N,N-dimethylacetamide at room temperature, showing excellent solubility.

[0111] The characterization data of the 1H NMR spectrum of the ionic enamine compound 3f obtained in this example are as follows:

[0112] 1 H NMR (400 MHz, DMSO-d6) δ 7.63 (d, J = 12.9 Hz, 2H), 7.50 (t, J = 8.2 Hz, 1H), 7.20 (d, J = 8.2 Hz, 2H), 5.18 (d, J = 12.9 Hz, 2H), 3.71 (s, 3H), 3.38 (q, J = 7.2 Hz, 8H), 1.16 (t, J = 7.1 Hz, 12H).

[0113] Example 7

[0114] The structural formula of the ionic enamine compound synthesized in this example is as shown in 3g:

[0115]

[0116] The specific reaction equation is as shown below:

[0117]

[0118] The synthesis method of pyridinium salt-alkyne monomer 1b is the same as that in Example 3; amine monomer 2f is N-ethylaniline, which can be purchased from the market; the solvent is ultradry MeOH.

[0119] The preparation steps of the ionic enamine compound 3g are as follows:

[0120] 145.6 mg (0.5 mmol) of pyridinium salt-alkyne monomer 1b was added to a 10 mL polymerization tube, dissolved in 2.5 mL of ultradry methanol, and then 138 μL (1.1 mmol) of amine monomer 2f was added using a microsyringe. After mixing evenly, the reaction was carried out at 25 °C for 2 h. After the reaction was completed, no treatment was required. After column chromatography separation with DCM:MeOH = 50:1, the ionic enamine compound 3g was obtained with a yield of 85%.

[0121] The ionic enamine compound 3g is readily soluble in common large-polarity organic solvents such as methanol, ethanol, N,N-dimethylformamide, dimethyl sulfoxide, and N,N-dimethylacetamide at room temperature, and has excellent solubility.

[0122] The characterization data of the proton nuclear magnetic resonance spectrum of the ionic enamine compound 3g obtained in this example are as follows:

[0123] 1 H NMR (400 MHz, DMSO-d6) δ 7.85 (d, J = 13.2 Hz, 2H), 7.78–7.70 (m, 1H), 7.66 (d, J = 8.0 Hz, 2H), 7.52–7.31 (m, 8H), 7.21 (t, J = 7.1 Hz, 2H), 5.77 (d, J = 13.2 Hz, 2H), 3.98 (q, J = 7.1 Hz, 4H), 3.90 (s, 3H), 1.25 (t, J = 7.0 Hz, 6H).

[0124] Sample analysis

[0125] The ionic enamine compound 3b prepared in Example 2 was dissolved in dimethyl sulfoxide (1×10 -5 mol / L), and under a white light lamp power of 10 mw / cm 2 , its fluorescence intensity was measured every 30 s of irradiation, and its ability to generate reactive oxygen species was tested using the reactive oxygen indicator DCFH. As Figure 8 shown, it can be seen that the ability of the ionic enamine compound 3b to generate reactive oxygen species is much stronger than that of the commercial photodynamic therapy reagent Ce 6, indicating that it has good ability to generate reactive oxygen species and potential for photodynamic therapy.

[0126] The above-described embodiments have described the technical solutions of the present invention in detail. It should be understood that the above are only specific embodiments of the present invention and are not used to limit the present invention. Any modification, supplement, or substitution in a similar manner within the principle scope of the present invention shall be included within the protection scope of the present invention.

Claims

1. A method for preparing ionic enamine compounds from pyridinium-alkyne monomers, characterized in that, Comprising: Using pyridinium-alkyne monomers and amine monomers as raw materials, through the hydroamination reaction of alkyne-amine, an ionic enamine compound is prepared; The structural formula of the pyridinium-alkyne monomer is shown in Formula (Ⅰ) or (Ⅱ): Among them, A - is a halogen ion, an acid radical ion or a base ion, R 1 is a hydrocarbon group having 1 to 200 carbon atoms, an oxygen-containing hydrocarbon group, a heteroaryl group or a hydrocarbon group substituted by an aryl group, R 2 is hydrogen, an ethynyl group, or a hydrocarbon group having 1 to 200 carbon atoms, an oxygen-containing hydrocarbon group, a heteroaryl group or a hydrocarbon group substituted by an aryl group; The structural formula of the amine monomer is shown in Formula (Ⅲ) or (Ⅳ): Wherein, X is an alkylene group, an arylene group, a heteroarylene group or a tertiary amine arylene group with 1-200 carbon atoms; Y is an alkyl group, an aryl group, a heteroaryl group or an alkoxy group with 1-200 carbon atoms; R3 and R4 are each independently selected from hydrogen, a hydrocarbon group with 1-200 carbon atoms, an oxygen-containing hydrocarbon group, a heteroaryl group or a hydrocarbon group substituted by an aryl group.

2. The method for preparing an ionic enamine compound through a pyridinium salt-alkyne monomer according to claim 1, characterized in that, R 1 is an alkyl group having 1 to 10 carbon atoms, R 2 is hydrogen, ethynyl or an alkyl group having 1 to 10 carbon atoms.

3. The method for preparing an ionic enamine compound through a pyridinium-alkyne monomer according to claim 1, wherein A - is an iodide ion, a bromide ion, a hydroxide ion, a trifluoromethanesulfonate ion, a tetrafluoroborate ion, a nitrate ion, a sulfate ion or a hexafluorophosphate ion.

4. The method for preparing an ionic enamine compound through a pyridinium-alkyne monomer according to claim 1, characterized in that, The hydroamination reaction is carried out in an organic solvent system, and the organic solvent is at least one of tetrahydrofuran, dichloromethane, methanol, acetonitrile, dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide.

5. The method for preparing an ionic enamine compound through a pyridinium-alkyne monomer according to claim 1, characterized in that, The concentration of the pyridinium-alkyne monomer in the organic solvent is 0.2-1 mol / L.

6. The method for preparing an ionic enamine compound through a pyridinium salt-alkyne monomer according to claim 1, characterized in that, The conditions of the hydroamination reaction are a temperature of 25-40 °C and a reaction time of 0.3-24 h.

7. The method for preparing an ionic enamine compound through pyridinium-alkyne monomers according to claim 1, characterized in that When the pyridinium-alkyne monomer contains diethynyl, the pyridinium-alkyne monomer and the amine monomer shown in Formula (Ⅳ) carry out the hydroamination reaction of alkyne-amine at a molar ratio of 1:2.0-2.5; And / or, when the pyridinium-alkyne monomer contains monoethynyl, the pyridinium-alkyne monomer and the amine monomer shown in Formula (Ⅲ) carry out the hydroamination reaction of alkyne-amine at a molar ratio of 2.0-2.5:1; And / or, when the pyridinium-alkyne monomer contains monoethynyl, the pyridinium-alkyne monomer and the amine monomer shown in Formula (Ⅳ) carry out the hydroamination reaction of alkyne-amine at a molar ratio of 1:1.0-2.

0.

8. The method for preparing an ionic enamine compound through a pyridinium-alkyne monomer according to claim 1, wherein After the hydroamination reaction of alkyne-amine is completed, the obtained reaction solution is recrystallized with ether or purified by column chromatography, and dried to a constant weight to prepare an ionic enamine compound.

9. An ionic enamine compound, characterized in that, Prepared by the method according to any one of claims 1-8.

10. The application of the ionic enamine compound according to claim 9 in the preparation of a photodynamic drug, a photosensitizer, a photodynamic antibacterial agent or a bioimaging reagent.

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