Thiazole Orange Phosphonium Salt Compounds, Their Preparation Methods and Applications

Abstract

The present invention relates to the technical field of antibacterial dyes for textiles, and relates to a thiazole orange bis-quaternary phosphonium salt compound, a preparation method thereof and an application thereof. The structure of the thiazole orange bis-quaternary phosphonium salt compound is shown in Formula I. The present invention has a broad antibacterial spectrum and has antibacterial activity against Staphylococcus aureus, Escherichia coli, Candida albicans and Aspergillus niger at the same time.

Description

Technical Field

[0001] The present invention relates to the technical field of antibacterial dyes for textiles, and relates to a thiazole orange bisquaternary phosphonium salt compound, a preparation method thereof, and an application thereof. Background Art

[0002] Antibacterial dyes are a class of multifunctional compounds that simultaneously have dyeing and antibacterial functions, and have great application prospects in industries such as medicine, clothing, and food. For example, the dyeing and antibacterial finishing of fabrics are usually two independent processes traditionally. However, such a treatment method has the following problems: on the one hand, certain antibacterial finishing may affect the dyeing performance or other functional finishing; on the other hand, antibacterial finishing often requires a separate post-treatment process. Performing dyeing and finishing step by step will lead to an increase in cost and waste of resources, and will also cause greater environmental damage, which does not meet the requirements of sustainable development. Using antibacterial dyes can simultaneously perform the dyeing and antibacterial finishing of fabrics in the same step, and endow the fabrics with antibacterial properties while dyeing the fabrics. Compared with the traditional process, the use of antibacterial dyes reduces one wet treatment process, well reduces energy consumption, and reduces water consumption and wastewater discharge, which is undoubtedly more environmentally friendly.

[0003] Thiazole orange is a class of cationic dyes that contain both thiazole rings and quinoline rings in their molecular structures. It has many characteristics such as bright color, high fluorescence quantum yield, and large molar extinction coefficient. Thiazole orange is often used as a fluorescent probe for nucleic acids and is widely used in fields such as electrophoresis separation and quantitative determination of DNA. The cationic structural characteristics of thiazole orange endow it with the potential to be used in combination with other cationic antibacterial agents. Designing a series of antibacterial dye compounds with thiazole orange as the parent nucleus will be a very meaningful work. Summary of the Invention

[0004] In view of the problems existing in the above-mentioned prior art, the present invention has developed a thiazole orange bisquaternary phosphonium salt compound, a preparation method thereof, and the application of this thiazole orange bisquaternary phosphonium salt compound in the antibacterial field.

[0005] One technical solution of the present invention is to provide a thiazole orange bisquaternary phosphonium salt compound, and the compound structure is shown in Formula I,

[0006]

[0007] Wherein, X 1 and X 2 are selected from chlorine, bromine, iodine, p-toluenesulfonyloxy, benzenesulfonyloxy, methanesulfonyloxy, R 1 , R 2 , R 3 , R 4 , R 5 , and R6 Selected from methyl, ethyl, C3-C8 alkyl, phenyl, 4-chlorophenyl, 4-bromophenyl, 4-fluorophenyl, 4-iodophenyl, 4-trifluoromethoxyphenyl, 4-methoxyphenyl, 4-ethoxyphenyl, 4-methylphenyl, 4-trifluoromethylphenyl, R 7 Selected from methyl, ethyl, C3-C8 alkyl, phenyl, R 8 Selected from methyl, ethyl, C3-C8 alkyl, phenyl, nitro, nitroso, sulfonyl, methanesulfonyl, fluorine, chlorine, bromine, iodine, trifluoromethyl, difluoromethyl, R 9 Selected from methyl, ethyl, C3-C8 alkyl, phenyl, nitro, nitroso, sulfonyl, methanesulfonyl, fluorine, chlorine, bromine, iodine, trifluoromethyl, difluoromethyl, m = 0 - 30, n = 0 - 30.

[0008] In a preferred embodiment of the present invention, the above structure is as follows:

[0009] .

[0010] The second technical solution of the present invention is to provide a preparation method of the thiazole orange bisquaternary phosphonium salt compound as described in claim 1, comprising the following steps:

[0011]

[0012]

[0013] (a) Under the condition of air isolation, a first reaction solvent, a compound of formula 1, and a compound of formula 2 are added to a reaction kettle, the reaction temperature is 60 - 200 °C, and the reaction time is 6 - 72 hours to obtain a compound of formula 3, wherein the molar ratio of the compound of formula 1 to the compound of formula 2 is 1:1 - 10;

[0014] (b) Under the condition of air isolation, a second reaction solvent, the compound of formula 3, and a compound of formula 4 are added to a reaction kettle, the reaction temperature is 80 - 200 °C, and the reaction time is 12 - 102 hours to obtain a compound of formula 5, wherein the molar ratio of the compound of formula 3 to the compound of formula 4 is 1:1 - 10;

[0015] (c) Under the condition of air isolation, a third reaction solvent is added to a reaction kettle, and then a compound of formula 6 and a compound of formula 7 are added, the reaction temperature is 60 - 200 °C, and the reaction time is 3 - 72 hours to obtain a compound of formula 8, wherein the molar ratio of the compound of formula 6 to the compound of formula 7 is 1:1 - 10;

[0016] (d) Under the condition of isolating air, a fourth reaction solvent, a compound of formula 5 and a compound of formula 8 are added into a reaction kettle, and the reaction is carried out at a reaction temperature of 25 - 60 °C for 1 - 5 hours of heat preservation reaction to obtain a compound of formula 9, wherein the molar ratio of the compound of formula 5 to the compound of formula 8 is 1:1 - 10;

[0017] (e) Under the condition of isolating air, a fifth reaction solvent, a compound of formula 9 and a compound of formula 10 are added into a reaction kettle, and the reaction is carried out at a reaction temperature of 80 - 200 °C for 12 - 102 hours of heat preservation reaction to obtain a compound of formula I, wherein the molar ratio of the compound of formula 9 to the compound of formula 10 is 1:1 - 10;

[0018] Wherein, X 1 and X 2 are selected from chlorine, bromine, iodine, p-toluenesulfonyloxy, benzenesulfonyloxy, methanesulfonyloxy, R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are respectively selected from methyl, ethyl, C3 - C8 alkyl, phenyl, 4-chlorophenyl, 4-bromophenyl, 4-fluorophenyl, 4-iodophenyl, 4-trifluoromethoxyphenyl, 4-methoxyphenyl, 4-ethoxyphenyl, 4-methylphenyl, 4-trifluoromethylphenyl, R 7 is selected from methyl, ethyl, C3 - C8 alkyl, phenyl, R 8 is selected from methyl, ethyl, C3 - C8 alkyl, phenyl, nitro, nitroso, sulfonyl, methanesulfonyl, fluorine, chlorine, bromine, iodine, trifluoromethyl, difluoromethyl, R 9 is selected from methyl, ethyl, C3 - C8 alkyl, phenyl, nitro, nitroso, sulfonyl, methanesulfonyl, fluorine, chlorine, bromine, iodine, trifluoromethyl, difluoromethyl, m = 0 - 30, n = 0 - 30.

[0019] In a preferred embodiment of the present invention, in step (a), the above-mentioned first reaction solvent is at least one of acetonitrile, p-xylene, toluene, ethylene glycol diethyl ether, ethylene glycol dimethyl ether, DMF, DMSO, acetonitrile, ethyl acetate, tetrahydrofuran, 2-methyltetrahydrofuran or dioxane;

[0020] In a preferred embodiment of the present invention, in step (b), the above-mentioned second reaction solvent is at least one of o-xylene, p-xylene, o-xylene, m-xylene, toluene, ethylene glycol diethyl ether, DMF, DMSO, acetonitrile, acetone.

[0021] In a preferred embodiment of the present invention, in step (c), the third reaction solvent is at least one of acetonitrile, p-xylene, o-xylene, m-xylene, toluene, ethylene glycol diethyl ether, ethylene glycol dimethyl ether, DMF, DMSO, ethyl acetate, tetrahydrofuran, 2-methyltetrahydrofuran or dioxane.

[0022] In a preferred embodiment of the present invention, in step (d), the fourth reaction solvent is at least one of ethanol, methanol, isopropanol, n-butanol, p-xylene, o-xylene, m-xylene, toluene, ethylene glycol diethyl ether, ethylene glycol dimethyl ether, DMF, DMSO, acetonitrile, tetrahydrofuran, 2-methyltetrahydrofuran, dioxane.

[0023] In a preferred embodiment of the present invention, in step (e), the fifth reaction solvent is at least one of o-xylene, p-xylene, m-xylene, toluene, ethylene glycol diethyl ether, DMF, DMSO, acetonitrile or acetone.

[0024] In a preferred embodiment of the present invention, in step (d), it is also necessary to continue to add a basic reagent, and the basic reagent is at least one of triethylamine and N,N-diisopropylethylamine.

[0025] The third technical solution of the present invention is to provide the application of the above-mentioned thiazole orange bisquaternary phosphonium salt compound and the thiazole orange bisquaternary phosphonium salt compound prepared by the preparation method using the above-mentioned thiazole orange bisquaternary phosphonium salt compound in antibacterial materials.

[0026] Beneficial effects

[0027] The thiazole orange bisquaternary phosphonium salt compound of the present invention has three structures of thiazole ring, quinoline ring and quaternary phosphonium salt at the same time, has a broad antibacterial spectrum, and has antibacterial activity against Staphylococcus aureus, Escherichia coli, Candida albicans and Aspergillus niger at the same time. Specific embodiments

[0028] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative efforts fall within the protection scope of the present invention.

[0029] Example 1:

[0030]

[0031] Step (a): Preparation of compound 3-(3-bromopropyl)-2-methylbenzo[d]thiazole-3-bromide of formula 3-1

[0032] Maintain a slightly positive pressure of nitrogen. Add 2 L of acetonitrile, 149.21 g (1.0 mol) of the compound of Formula 1-1, 2-methylbenzothiazole, and 201.89 g (1.0 mol) of the compound of Formula 2-1, 1,3-dibromopropane, successively into a 5 L reaction flask. After adding, stir well, and heat the reaction solution to 82 °C for reaction. Keep the temperature for reaction for 24 hours until the reaction is complete.

[0033] Cool the reaction solution to room temperature, add 1000 ml of petroleum ether thereto, cool to 0 °C, keep the temperature overnight, a large amount of solid precipitates, filter, and collect the filter cake to obtain 254.55 g (0.725 mol) of the yellow solid product of Formula 3-1.

[0034] The yield is 72.5%.

[0035] Product purity: 98.53% (HPLC); NMR data: 1H NMR (400 MHz, DMSO-d6): δ 8.49 (d, 1H), 8.36 (d, 1H), 7.90 (t, 1H), 7.82 (t, 1H), 4.77 - 4.89 (m, 2H), 3.73 (t, 2H), 3.24 (s, 3H), 2.39 - 2.49 (m, 2H).

[0036] Step (b): Preparation of the compound of Formula 5-1

[0037] Maintain a slightly positive pressure of nitrogen. Add 1.8 L of p-xylene, 254.55 g (0.725 mol) of the compound of Formula 3-1, and 228.19 g (0.87 mol) of the compound of Formula 4-1, triphenylphosphine, successively into a 5 L reaction flask. After adding, stir well; heat the reaction solution to 138 °C for reaction. Keep the temperature for reaction for 12 hours until the reaction is complete.

[0038] Let the reaction solution cool naturally to room temperature, then continue to cool to 0 °C, keep the temperature for crystallization for 3 hours, a large amount of solid precipitates, filter, and collect the filter cake to obtain 417.14 g (0.680 mol) of the pink solid product of Formula 5-1.

[0039] The yield is 93.8%, product purity: 99.26% (HPLC); 1H NMR (400 MHz, DMSO-d6): δ 8.50 (d, 1H), 8.37 (d, 1H), 7.90 (t, 1H), 7.73 - 7.83 (m, 16H), 4.79 - 4.92 (m, 2H), 3.79 (t, 2H), 3.25 (s, 3H), 2.43 - 2.52 (m, 2H).

[0040] Step (c): Preparation of the compound of Formula 8-1

[0041] Maintain a slightly positive pressure of nitrogen. Sequentially add 2 L of acetonitrile, 163.60 g (1.0 mol) of the compound of Formula 6-1, 4-chloroquinoline, and 201.89 g (1.0 mol) of the compound of Formula 7-1, 1,3-dibromopropane into a 5 L reaction flask. After adding, stir well, and heat the reaction solution to 82 °C for reaction. Keep the reaction at this temperature for 18 hours until the reaction is complete.

[0042] Cool the reaction solution to room temperature, add an appropriate amount of petroleum ether thereto, cool to 0 °C, keep warm overnight, a large amount of solid precipitates, filter, and collect the filter cake to obtain 249.26 g (0.682 mol) of a yellow solid product.

[0043] The yield is 68.2%.

[0044] Product purity: 99.35% (HPLC); NMR data: 1H NMR (400 MHz, DMSO-d6): δ 8.49 - 8.74 (m, 2H), 8.31 - 8.41 (m, 2H), 8.06 - 8.21 (m, 2H), 5.29 - 5.36 (m, 2H), 3.78 (t, 2H), 2.49–2.57 (m, 2H).

[0045] Step (d): Preparation of the compound of Formula 9-1

[0046] Maintain a slightly positive pressure of nitrogen. Sequentially add 1.2 L of ethanol, 417.14 g (0.680 mol) of the compound of Formula 5-1, and 248.55 g (0.680 mol) of the compound of Formula 8-1 into a 5 L reaction flask, and stir well. Then add 6.88 g (0.068 mol) of triethylamine thereto. After adding, stir well, and heat the reaction solution to 40 °C for reaction. Keep the reaction at this temperature for 3 hours until the reaction is complete.

[0047] Cool the reaction solution to room temperature, add an appropriate amount of ethyl acetate and an appropriate amount of petroleum ether thereto, cool to 0 °C, keep warm overnight, a large amount of solid precipitates, filter, and collect the filter cake to obtain 540.13 g (0.627 mol) of a red solid product.

[0048] The yield is 92.2%.

[0049] Product purity: 98.75% (HPLC); NMR data: 1H NMR (400 MHz, DMSO-d6): δ 8.50 (d, 1H), 8.37 (d, 1H), 8.25 - 8.30 (m, 3H), 7.74 - 7.93 (m, 20H), 6.93 (s, 1H), 4.79 - 4.92 (m, 2H), 4.03 (t, 2H), 3.79 (t, 2H), 3.05 - 3.21 (m, 2H), 2.43 - 2.52 (m, 2H), 2.02 - 2.08 (m, 2H).

[0050] Step (e): Preparation of the compound of formula I-1

[0051] Maintain a slightly positive nitrogen pressure. Add 1.8 L of o-xylene, 540.13 g (0.627 mol) of the compound of formula 9-1, and 164.45 g (0.752 mol) of triphenylphosphine (the compound of formula 10-1) to a 5 L reaction flask in sequence. After addition, stir well; heat the reaction solution to 140 °C for reaction. Keep the temperature for 22 hours until the reaction is complete.

[0052] Let the reaction solution cool naturally to room temperature, then continue to cool to 0 °C, keep the temperature for crystallization for 3 hours, a large amount of solid will precipitate, filter, and collect the filter cake to obtain 650.32 g (0.579 mol) of a red solid product.

[0053] Yield 92.3%, total yield of 5-step reaction 39.47%, product purity: 99.16% (HPLC); NMR data: 1H NMR (400 MHz, DMSO-d6): δ 8.50 (d, 1H), 8.37 (d, 1H), 8.25 - 8.30 (m, 3H), 7.74 - 7.93 (m, 35H), 6.93 (s, 1H), 4.79 - 4.92 (m, 2H), 4.42 (t, 2H), 3.79 (t, 2H), 3.72 (t, 2H), 2.43 - 2.52 (m, 2H), 2.22 - 2.31 (m, 2H).

[0054] Example 2:

[0055]

[0056] Step (a): Preparation of the compound of formula 3-2

[0057] Maintain a slightly positive pressure of nitrogen. Sequentially add 3 L of 2-methyltetrahydrofuran, 149.21 g (1.0 mol) of the compound of Formula 1-2, 2-methylbenzothiazole, and 282.08 g (2.0 mol) of the compound of Formula 2-2, 1,5-dichloropentane into a 20 L reaction flask. After adding, stir well, and heat the reaction solution to 80 °C for reaction. Keep the temperature for reaction for 28 hours until the reaction is completed.

[0058] Cool the reaction solution to room temperature, add 3000 mL of petroleum ether thereto, cool to 0 °C, keep the temperature overnight, a large amount of solid precipitates, filter, and collect the filter cake to obtain 251.39 g (0.716 mol) of a yellow solid product.

[0059] The yield is 71.6%.

[0060] Product purity: 98.21% (HPLC); NMR data: 1H NMR (400 MHz, DMSO-d6): δ 8.51 (d, 1H), 8.37 (d, 1H), 7.91 (t, 1H), 7.82 (t, 1H), 4.75 - 4.85 (m, 2H), 3.58 (t, 2H), 3.25 (s, 3H), 2.01 - 2.03 (m, 2H), 1.75 - 1.79 (m, 2H), 1.27 - 1.30 (m, 2H).

[0061] Step (b): Preparation of the compound of Formula 5-2

[0062] Maintain a slightly positive pressure of nitrogen. Sequentially add 2 L of toluene, 251.39 g (0.716 mol) of the compound of Formula 3-1, and 281.70 g (1.074 mol) of the compound of Formula 4-2, tri-n-butylphosphine into a 5 L reaction flask. After adding, stir well; heat the reaction solution to 110 °C for reaction. Keep the temperature for reaction for 36 hours until the reaction is completed.

[0063] Let the reaction solution cool naturally to room temperature, then continue to cool to 0 °C, keep the temperature for crystallization for 8 hours, a large amount of solid precipitates, filter, and collect the filter cake to obtain 318.82 (0.647 mol) of a pink solid product.

[0064] The yield is 93.8%, product purity: 98.86% (HPLC); NMR data:

[0065] 1H NMR (400 MHz, DMSO-d6): δ 8.50 (d, 1H), 8.37 (d, 1H), 7.91 (t, 1H), 7.82 (t, 1H), 4.75 - 4.83 (m, 2H), 3.24 (s, 3H), 2.27 (t, 8H), 2.01 - 2.03 (m, 2H), 1.42 - 1.47 (m, 14H), 1.27 - 1.30 (m, 2H), 0.92 (t, 9H).

[0066] Step (c): Preparation of the compound of Formula 8-2

[0067] Maintain a slightly positive pressure of nitrogen. Add 2 L of ethylene glycol diethyl ether, 177.63 g (1.0 mol) of the compound of Formula 6-2, 2-methyl-4-chloroquinoline, and 371.90 g (1.2 mol) of the compound of Formula 7-2, 1,4-diiodobutane, successively into a 5 L reaction flask. After adding, stir well and heat the reaction solution to 120 °C for reaction. Keep the temperature for 12 hours until the reaction is complete.

[0068] Cool the reaction solution to room temperature, add 1000 mL of petroleum ether thereto, cool to 0 °C, keep the temperature overnight, a large amount of solid precipitates, filter, and collect the filter cake to obtain 325.20 (0.667 mol) of a yellow solid product.

[0069] Yield: 66.7%.

[0070] Product purity: 99.45% (HPLC); NMR data: 1H NMR (400 MHz, DMSO-d6): δ 8.56 (d, 1H), 8.46 (d, 1H), 8.22 (t, 1H), 8.01 (t, 1H), 7.55 (s, 1H), 5.18 - 5.25 (m, 2H), 2.93 (t, 2H), 2.67 (s, 3H), 2.00 - 2.03 (m, 2H), 1.82 - 1.85 (m, 2H).

[0071] Step (d): Preparation of the compound of Formula 9-2

[0072] Maintain a slightly positive pressure of nitrogen. Add 2 L of p-xylene, 318.82 (0.647 mol) of the compound of Formula 5-2, and 325.20 (0.667 mol) of the compound of Formula 8-2, successively into a 5 L reaction flask, and stir well. Then add 16.72 g (0.129 mol) of N,N-diisopropylethylamine thereto. After adding, stir well and heat the reaction solution to 50 °C for reaction. Keep the temperature for 2 hours until the reaction is complete.

[0073] The reaction solution was cooled to room temperature, 2000 mL of ethyl acetate and 2000 mL of petroleum ether were added thereto, cooled to 0 °C, kept warm overnight, a large amount of solid was precipitated, filtered, and the filter cake was collected to obtain 470.78 g (0.577 mol) of a red solid product.

[0074] The yield was 89.2%.

[0075] Product purity: 99.35% (HPLC); NMR data: 1H NMR (400 MHz, DMSO-d6): δ 8.50 (d, 1H), 8.37 (d, 1H), 8.25 - 8.30 (m, 3H), 7.90 - 7.93 (m, 2H), 7.82 (t, 1H), 7.28 (s, 1H), 6.90 (s, 1H), 4.75 - 4.83 (m, 2H), 3.03 - 3.17 (m, 2H), 2.93 (t, 2H), 2.54 (s, 3H), 2.27 (t, 8H), 2.01 - 2.03 (m, 2H), 1.82 - 1.87 (m, 4H), 1.42 - 1.47 (m, 14H), 1.27 - 1.30 (m, 2H), 0.92 (t, 9H).

[0076] Step (e): Preparation of the compound of formula I-2

[0077] Maintaining a slightly positive pressure of nitrogen, 2 L of toluene, 470.78 g (0.577 mol) of the compound of formula 9-2 and 302.75 g (1.154 mol) of triphenylphosphine of the compound of formula 10-2 were successively added to a 5 L reaction flask. After addition, it was stirred evenly; the reaction solution was heated to 110 °C for reaction. The reaction was kept warm for 60 hours and the reaction was completed.

[0078] The reaction solution was naturally cooled to room temperature, then further cooled to 0 °C, kept warm for crystallization for 3 hours, a large amount of solid was precipitated, filtered, and the filter cake was collected to obtain 569.479 g (0.528 mol) of a red solid product.

[0079] Yield: 91.5%, overall yield of the 5-step reaction: 35.2%, product purity: 99.25% (HPLC); NMR data: 1H NMR (400 MHz, DMSO-d6): δ 8.52 (d, 1H), 8.39 (d, 1H), 8.25 - 8.30 (m, 3H), 7.90 - 7.93 (m, 2H), 7.73 - 7.83 (m, 16H), 7.27 (s, 1H), 6.91 (s, 1H), 4.75 - 4.83 (m, 2H), 3.76 (t, 2H), 3.03 - 3.14 (m, 2H), 2.54 (s, 3H), 2.27 (t, 8H), 2.01 - 2.03 (m, 2H), 1.89 - 1.95 (m, 2H), 1.42 - 1.47 (m, 16H), 1.27 - 1.30 (m, 2H), 0.92 (t, 9H).

[0080] Example 3:

[0081]

[0082] Step (a): Preparation of the compound of Formula 3-3

[0083] Maintaining a slightly positive nitrogen pressure, successively add 4 L of ethylene glycol diethyl ether, 149.21 g (1.0 mol) of the compound of Formula 1-1, 2-methyl-6-nitrobenzothiazole, and 1279.62 g (3.0 mol) of the compound of Formula 2-3, 1,6-dimesylhexane, into a 20 L reaction flask. After addition, stir well and heat the reaction solution to 120 °C for reaction. Keep the temperature for reaction for 16 hours until the reaction is complete.

[0084] Cool the reaction solution to room temperature, add 3000 mL of petroleum ether thereto, cool to 0 °C, keep the temperature overnight, a large amount of solid precipitates, filter, and collect the filter cake to obtain 440.11 g (0.709 mol) of a green solid product.

[0085] Yield: 70.9%. Product purity: 98.87% (HPLC); NMR data: 1H NMR (400 MHz, DMSO-d6): δ 9.45 (s, 1H), 8.67 (d, 1H), 8.52 (d, 1H), 7.79 (d, 2H), 7.47 (d, 2H), 7.34 (d, 2H), 7.10 (d, 2H), 4.80 - 4.93 (m, 2H), 4.02 (t, 2H), 3.28 (s, 3H), 2.45 (s, 3H), 2.28 (s, 3H), 2.02 - 2.04 (m, 2H), 1.62 - 1.66 (m, 2H), 1.42 - 1.45 (m, 2H), 1.22 - 1.27 (m, 2H).

[0086] Step (b): Preparation of Compound of Formula 5-3

[0087] While maintaining a slightly positive pressure of nitrogen, 4 L of o-xylene, 440.11 g (0.709 mol) of the compound of Formula 3-3, and 371.93 g (1.418 mol) of triphenylphosphine of the compound of Formula 4-3 were successively added to a 10 L reaction flask. After addition, the mixture was stirred evenly; the reaction solution was heated to 140 °C for reaction. The reaction was carried out under insulation for 12 hours until completion.

[0088] The reaction solution was naturally cooled to room temperature, then further cooled to 0 °C, and crystallized under insulation for 3 hours. A large amount of solid was precipitated, filtered, and the filter cake was collected to obtain 573.95 g (0.649 mol) of a green solid product.

[0089] The yield was 91.6%, and the product purity was 99.36% (HPLC); NMR data:

[0090] 1H NMR (400 MHz, DMSO-d6): δ 9.44 (s, 1H), 8.66 (d, 1H), 8.52 (d, 1H), 7.73 - 7.83 (m, 15H), 7.47 (d, 4H), 7.10 (d, 4H), 4.80 - 4.93 (m, 2H), 3.78 (t, 2H), 3.28 (s, 3H), 2.28 (s, 6H), 2.02 - 2.04 (m, 2H), 1.55 - 1.59 (m, 2H), 1.40 - 1.42 (m, 2H), 1.22 - 1.27 (m, 2H).

[0091] Step (c): Preparation of Compound of Formula 8-3

[0092] While maintaining a slightly positive pressure of nitrogen, 3 L of DMF, 163.60 g (1.0 mol) of 4-chloroquinoline of the compound of Formula 6-3, and 201.89 g (1.5 mol) of 1,6-dichlorohexane of the compound of Formula 7-3 were successively added to a 10 L reaction flask. After addition, the mixture was stirred evenly, and the reaction solution was heated to 150 °C for reaction. The reaction was carried out under insulation for 6 hours until completion.

[0093] The reaction solution was cooled to room temperature, 2000 mL of petroleum ether was added thereto, cooled to 0 °C, and left overnight under insulation. A large amount of solid was precipitated, filtered, and the filter cake was collected to obtain 221.48 g (0.695 mol) of a yellow solid product.

[0094] Yield: 69.5%. Product purity: 99.27% (HPLC); NMR data: 1H NMR (400 MHz, DMSO-d6): δ 8.49 - 8.74 (m, 2H), 8.31 - 8.41 (m, 2H), δ 8.06 - 8.21 (m, 2H), 5.29 - 5.36 (m, 2H), 3.56 (t, 2H), 2.49–2.57 (m, 2H), 2.01 - 2.03 (m, 2H), 1.75 - 1.79 (m, 2H), 1.45 - 1.48 (m, 2H), 1.27 - 1.30 (m, 2H).

[0095] Step (d): Preparation of the compound of Formula 9-3

[0096] While maintaining a slightly positive pressure of nitrogen, sequentially add 1.2 L of ethylene glycol diethyl ether, 573.95 g (0.649 mol) of the compound of Formula 5-3, and 221.48 g (0.695 mol) of the compound of Formula 8-3 to a 5 L reaction flask, and stir well. Then add 19.7 g (0.195 mol) of triethylamine thereto. After addition, stir well, and heat the reaction solution to 60 °C for reaction. Keep the temperature for 1 hour, and the reaction is completed.

[0097] Cool the reaction solution to room temperature, add 2000 mL of ethyl acetate and 2000 mL of petroleum ether thereto, cool to 0 °C, keep the temperature overnight, a large amount of solid precipitates, filter, and collect the filter cake to obtain 654.20 g (0.580 mol) of an orange solid product.

[0098] Yield: 89.3%. Product purity: 98.66% (HPLC); NMR data: 1H NMR (400 MHz, DMSO-d6): δ 9.43 (s, 1H), 8.66 (d, 1H), 8.52 (d, 1H), 7.68 - 7.83 (m, 17H), 7.47 (d, 4H), 7.31 (d, 1H), 7.15 (s, 1H), 7.10 (d, 4H), 4.80 - 4.93 (m, 2H), 3.78 (t, 2H), 3.57 (t, 2H), 3.25 - 3.38 (m, 2H), 2.28 (s, 6H), 2.01 - 2.04 (m, 4H), 1.75 - 1.79 (m, 2H), 1.55 - 1.59 (m, 2H), 1.40 - 1.42 (m, 2H), 1.22 - 1.30 (m, 6H).

[0099] Step (e): Preparation of the compound of Formula I-3

[0100] Maintain a slightly positive pressure of nitrogen. Sequentially add 4 L of ethylene glycol diethyl ether, 654.20 g (0.580 mol) of the compound of Formula 9-3, and 456.04 g (1.739 mol) of triphenylphosphine, the compound of Formula 10-3, to a 10-L reaction flask. After adding, stir well; heat the reaction solution to 120 °C for reaction. Keep the temperature for 20 hours, and the reaction is completed.

[0101] Let the reaction solution cool naturally to room temperature, then continue to cool to 0 °C, keep the temperature for crystal precipitation for 3 hours, a large amount of solid precipitates, filter, and collect the filter cake to obtain 728.81 g (0.524 mol) of an orange solid product.

[0102] The yield is 90.4%, the total yield of the 5-step reaction is 36.4%, and the product purity is 99.36% (HPLC); NMR data: 1H NMR (400 MHz, DMSO-d6): δ 9.46 (s, 1H), 8.65 (d, 1H), 8.51 (d, 1H), 7.68 - 7.83 (m, 32H), 7.47 (d, 4H), 7.31 (d, 1H), 7.15 (s, 1H), 7.10 (d, 4H), 4.80 - 4.93 (m, 2H), 3.78 (t, 4H), 3.25 - 3.38 (m, 2H), 2.28 (s, 6H), 2.01 - 2.04 (m, 4H), 1.87 - 1.92 (m, 2H), 1.55 - 1.59 (m, 2H), 1.40 - 1.42 (m, 2H), 1.22 - 1.30 (m, 6H).

[0103] Example 4:

[0104]

[0105] Step (a): Preparation of the compound of Formula 3-4

[0106] Maintain a slightly positive pressure of nitrogen. Sequentially add 4 L of DMF, 149.21 g (1.0 mol) of 2-methylbenzothiazole, the compound of Formula 1-4, and 564.9 g (5.0 mol) of 1,3-dichloropropane, the compound of Formula 2-4, to a 20-L reaction flask. After adding, stir well, and heat the reaction solution to 150 °C for reaction. Keep the temperature for 5 hours, and the reaction is completed.

[0107] Cool the reaction solution to room temperature, add 3000 mL of petroleum ether to it, cool to 0 °C, keep the temperature overnight, a large amount of solid precipitates, filter, and collect the filter cake to obtain 262.19 (0.687 mol) of a yellow solid product.

[0108] The yield is 68.7%.

[0109] Product purity: 99.28% (HPLC); NMR data: 1H NMR (400 MHz, DMSO-d6): δ 8.51 (d, 1H), 8.38 (d, 1H), 7.90 (t, 1H), 7.82 (t, 1H), 4.81 - 4.89 (m, 2H), 3.85 (t, 2H), 3.26 (s, 3H), 2.45 - 2.56 (m, 2H).

[0110] Step (b): Preparation of the compound of Formula 5-4

[0111] Maintain a slightly positive nitrogen pressure. Add 4 L of ethylene glycol diethyl ether, 262.19 (0.687 mol) and 900.96 g (3.435 mol) of triphenylphosphine of the compound of Formula 4-4 to a 10 L reaction flask in sequence. After addition, stir well; heat the reaction solution to 120 °C for reaction. Keep the temperature for 15 hours and the reaction is completed.

[0112] Let the reaction solution cool naturally to room temperature, then continue to cool to 0 °C, keep the temperature for crystallization for 3 hours, a large amount of solid precipitates, filter, and collect the filter cake to obtain 310.39 g (0.635 mol) of pink solid product.

[0113] Yield: 92.5%, product purity: 98.66% (HPLC); NMR data: 1H NMR (400 MHz, DMSO-d6): δ 8.50 (d, 1H), 8.36 (d, 1H), 7.90 (t, 1H), 7.73 - 7.83 (m, 16H), 4.79 - 4.90 (m, 2H), 3.77 (t, 2H), 3.25 (s, 3H), 2.43 - 2.52 (m, 2H).

[0114] Step (c): Preparation of the compound of Formula 8-4

[0115] Maintain a slightly positive nitrogen pressure. Add 3 L of tetrahydrofuran, 163.60 g (1.0 mol) of 4-chloroquinoline of the compound of Formula 6-4, and 201.89 g (2.0 mol) of 1,3-dichloropropane of the compound of Formula 7-4 to a 10 L reaction flask in sequence. After addition, stir well, and heat the reaction solution to 66 °C for reaction. Keep the temperature for 72 hours and the reaction is completed.

[0116] Cool the reaction solution to room temperature, add 3000 mL of petroleum ether to it, cool to 0 °C, keep the temperature overnight, a large amount of solid precipitates, filter, and collect the filter cake to obtain 183.10 g (0.662 mol) of yellow solid product.

[0117] Yield: 66.2%.

[0118] Product purity: 98.17% (HPLC); NMR data: 1H NMR (400 MHz, DMSO-d6): δ 8.49 - 8.74 (m, 2H), 8.31 - 8.41 (m, 2H), δ 8.51 - 8.72 (m, 2H), 8.31 - 8.41 (m, 2H), 8.06 - 8.21 (m, 2H), 5.29 - 5.38 (m, 2H), 3.84 (t, 2H), 2.50–2.58 (m, 2H).

[0119] Step (d): Preparation of the compound of Formula 9-4

[0120] Maintain a slightly positive pressure of nitrogen. Add 1.2 L of DMF, 310.39 g (0.635 mol) of the compound of Formula 5-4 and 183.10 g (0.662 mol) of the compound of Formula 8-4 to a 5 L reaction flask in sequence, and stir well. Then add 6.88 g (0.068 mol) of triethylamine thereto. After adding, stir well, and heat the reaction solution to 60 °C for reaction. Keep the temperature for 1 hour, and the reaction is completed.

[0121] Cool the reaction solution to room temperature, add 2000 mL of ethyl acetate and 2000 mL of petroleum ether thereto, cool to 0 °C, keep the temperature overnight, a large amount of solid precipitates, filter, and collect the filter cake to obtain 413.83 g (0.568 mol) of a red solid product.

[0122] Yield: 89.5%.

[0123] Product purity: 98.76% (HPLC); NMR data: 1H NMR (400 MHz, DMSO-d6): δ 8.52 (d, 1H), 8.38 (d, 1H), 8.26 - 8.31 (m, 3H), 7.76 - 7.95 (m, 20H), 6.94 (s, 1H), 4.79 - 4.92 (m, 2H), 4.03 (t, 2H), 3.83 (t, 2H), 3.07 - 3.22 (m, 2H), 2.43 - 2.52 (m, 2H), 2.02 - 2.07 (m, 2H).

[0124] Step (e): Preparation of the compound of Formula I-4

[0125] Maintain a slightly positive pressure of nitrogen. Add 4 L of DMF, 413.83 g (0.568 mol) of the compound of Formula 9-4 and 596.26 g (2.27 mol) of tributylphosphine of the compound of Formula 10-4 to a 10 L reaction flask in sequence. After adding, stir well; heat the reaction solution to 150 °C for reaction. Keep the temperature for 16 hours, and the reaction is completed.

[0126] The reaction solution was naturally cooled to room temperature, then further cooled to 0 °C, and crystallized for 3 hours. A large amount of solid was precipitated, filtered, and the filter cake was collected to obtain 468.53 g (0.503 mol) of a red solid product.

[0127] The yield was 88.6%, the total yield of the 5-step reaction was 33.4%, and the product purity was 99.26% (HPLC); NMR data: 1H NMR (400 MHz, DMSO-d6): δ 8.53 (d, 1H), 8.39 (d, 1H), 8.26 - 8.34 (m, 3H), 7.73 - 7.92 (m, 20H), 6.92 (s, 1H), 4.79 - 4.90 (m, 2H), 4.02 (t, 2H), 3.07 - 3.22 (m, 2H), 2.43 - 2.52 (m, 2H), 2.35 (t, 2H), 2.27 (t, 6H), 1.72 - 1.78 (m, 2H), 1.42 - 1.47 (m, 12H), 0.92 (t, 9H).

[0128] Example 5:

[0129]

[0130] Step (a): Preparation of Compound of Formula 3-5

[0131] Maintaining a slightly positive nitrogen pressure, 4 L of ethyl acetate, 149.21 g (1.0 mol) of Compound of Formula 1-5 2-methylbenzothiazole, and 807.56 (4.0 mol) of Compound of Formula 2-5 1,3-dibromopropane were successively added to a 10 L reaction flask. After addition, it was stirred evenly, and the reaction solution was heated to 76 °C for reaction. The reaction was maintained for 40 hours until completion.

[0132] The reaction solution was cooled to room temperature, 3000 mL of petroleum ether was added thereto, cooled to 0 °C, and crystallized overnight. A large amount of solid was precipitated, filtered, and the filter cake was collected to obtain 247.17 g (0.704 mol) of a yellow solid product.

[0133] The yield was 70.4%. The product purity was 98.57% (HPLC); NMR data: 1H NMR (400 MHz, DMSO-d6): δ 8.49 (d, 1H), 8.36 (d, 1H), 7.90 (t, 1H), 7.82 (t, 1H), 4.77 - 4.89 (m, 2H), 3.73 (t, 2H), 3.24 (s, 3H), 2.39 - 2.49 (m, 2H).

[0134] Step (b): Preparation of Compound of Formula 5-5

[0135] Maintain a slightly positive nitrogen pressure, and successively add 4 L of DMF, 247.17 g (0.704 mol) of the compound of Formula 3-5, and 712.17 g (3.52 mol) of tributylphosphine (the compound of Formula 4-5) to a 10 L reaction flask. After adding, stir well; heat the reaction solution to 150 °C for reaction. Keep the temperature for reaction for 12 hours until the reaction is complete.

[0136] Let the reaction solution cool naturally to room temperature, then continue to cool to 0 °C, keep the temperature for crystal precipitation for 3 hours, a large amount of solid will precipitate, filter, and collect the filter cake to obtain 355.32 g (0.642 mol) of pink solid product.

[0137] The yield is 91.2%, and the product purity is 99.52% (HPLC); NMR data:

[0138] 1H NMR (400 MHz, DMSO-d6): δ 8.48 (d, 1H), 8.36 (d, 1H), 7.88 (t, 1H), 7.80 (t, 1H), 4.76 - 4.83 (m, 2H), 3.22 (s, 3H), 2.35 (t, 2H), 2.27 (t, 6H), 1.85 - 1.92 (m, 2H), 1.42 - 1.49 (m, 12H), 0.93 (t, 9H).

[0139] Step (c): Preparation of the compound of Formula 8-5

[0140] Maintain a slightly positive nitrogen pressure, and successively add 6 L of dioxane, 163.60 g (1.0 mol) of 4-chloroquinoline (the compound of Formula 6-5), and 1009.45 g (5.0 mol) of 1,3-dibromopropane (the compound of Formula 7-5) to a 20 L reaction flask. After adding, stir well, and heat the reaction solution to 101 °C for reaction. Keep the temperature for reaction for 25 hours until the reaction is complete.

[0141] Cool the reaction solution to room temperature, add 3000 mL of petroleum ether to it, cool to 0 °C, keep the temperature overnight, a large amount of solid will precipitate, filter, and collect the filter cake to obtain 254.38 g (0.696 mol) of yellow solid product.

[0142] The yield is 69.6%.

[0143] The product purity is 99.25% (HPLC); NMR data: 1H NMR (400 MHz, DMSO-d6): δ 8.49 - 8.74 (m, 2H), 8.31 - 8.41 (m, 2H), 8.06 - 8.21 (m, 2H), 5.29 - 5.36 (m, 2H), 3.78 (t, 2H), 2.49–2.57 (m, 2H).

[0144] Step (d): Preparation of the compound of Formula 9-5

[0145] Maintain a slightly positive pressure of nitrogen. Add 1.2 L of dioxane, 355.32 g (0.642 mol) of the compound of Formula 5-5, and 254.38 g (0.696 mol) of the compound of Formula 8-5 to a 5 L reaction flask in sequence, and stir well. Then add 25.99 g (0.257 mol) of triethylamine thereto. After adding, stir well, and heat the reaction solution to 40 °C for reaction. Keep the temperature for reaction for 3 hours until the reaction is completed.

[0146] Cool the reaction solution to room temperature, add 2000 mL of ethyl acetate and 2000 mL of petroleum ether thereto, cool to 0 °C, keep the temperature overnight, a large amount of solid precipitates, filter, and collect the filter cake to obtain 467.25 g (0.583 mol) of a red solid product.

[0147] The yield is 90.8%.

[0148] Product purity: 98.86% (HPLC); NMR data: 1H NMR (400 MHz, DMSO-d6): δ 8.49 (d, 1H), 8.38 (d, 1H), 8.25 - 8.31 (m, 3H), 7.89 (t, 1H), 7.81 (t, 1H), 7.66 - 7.75 (m, 3H), 6.92 (s, 1H), 4.76 - 4.83 (m, 2H), 3.45 (t, 2H), 3.07 - 3.20 (m, 2H), 2.35 (t, 2H), 2.27 (t, 6H), 2.00 - 2.03 (m, 2H), 1.85 - 1.92 (m, 2H), 1.42 - 1.47 (m, 12H), 0.93 (t, 9H).

[0149] Step (e): Preparation of the compound of Formula I-5

[0150] Maintain a slightly positive pressure of nitrogen. Add 6 L of acetonitrile, 467.25 g (0.583 mol) of the compound of Formula 9-5, and 589.70 g (2.915 mol) of tributylphosphine of the compound of Formula 10-5 to a 10 L reaction flask in sequence. After adding, stir well; heat the reaction solution to 80 °C for reaction. Keep the temperature for reaction for 102 hours until the reaction is completed.

[0151] Let the reaction solution cool naturally to room temperature, then continue to cool to 0 °C, keep the temperature for crystallization for 3 hours, a large amount of solid precipitates, filter, and collect the filter cake to obtain 510.86 g (0.509 mol) of a red solid product.

[0152] The yield was 87.3%, and the overall yield of the five-step reaction was 35.4%. The product purity was 99.16% (HPLC); NMR data: 1H NMR (400 MHz, DMSO-d6): δ 8.52 (d, 1H), 8.37 (d, 1H), 8.25 - 8.32 (m, 3H), 7.89 (t, 1H), 7.81 (t, 1H), 7.66 - 7.75 (m, 3H), 6.92 (s, 1H), 4.76 - 4.83 (m, 2H), 3.07 - 3.20 (m, 2H), 2.35 - 2.39 (m, 4H), 2.27 (t, 12H), 1.85 - 1.92 (m, 2H), 1.71 - 1.76 (m, 2H), 1.42 - 1.52 (m, 24H), 0.93 (t, 18H).

[0153] Antibacterial performance test of the compound:

[0154] Determination of MIC (minimum inhibitory concentration): The compounds (9-1, 9-2, 9-3, 9-4, 9-5, I-1, I-2, I-3, I-4, I-5) prepared in Examples 1-5 were mixed in LB nutrient broth and serially diluted two-fold by the microbroth dilution method. After adding a fixed amount of the test bacteria and culturing for a certain period of time, the lowest compound concentration at which no bacterial growth was observed was the MIC (minimum inhibitory concentration) of the compound against this bacterium.

[0155] The specific determination steps are as follows:

[0156] (1) Preparation of the bacterial suspension: On a sterile workbench, an appropriate amount of bacterial culture was picked up with a sterilized inoculation loop and transferred to 10 mL of LB broth culture medium, and cultured in a shaker at 37 °C for 6 - 8 h until the bacterial suspension reached a slight or moderate turbidity. To ensure the accuracy and precision of the drug sensitivity test, the concentration of the inoculated bacterial suspension must be controlled accordingly. Therefore, a small amount of the bacterial suspension was taken and diluted to 0.5 MacFarland standard concentration and then diluted 1000 times, and the bacterial suspension content was about 1×10 5 cfu / mL.

[0157] (2) Preparation of the antibacterial compound stock solution: The compound was dissolved in sterile water to prepare an antibacterial compound stock solution with a specific concentration, and a sterile filter head was used to remove any bacteria that might be contained in the solution.

[0158] (3) Preparation of MIC plates: Add 100 μL of LB broth to each well from the 2nd to the 7th row in columns 2 to 10 of a 96-well plate. Add 100 μL of the antibacterial compound stock solution to column 2. After pipetting and mixing well, aspirate 100 μL and transfer it to column 3, and so on, for a total of 8 concentration gradients. Discard 100 μL of the mixed solution from column 9. Do not add the drug solution to column 10 as a positive control. Then add 100 μL of the bacterial suspension to each well and pipette the mixed solution evenly. Add 200 μL of LB broth to column 11 without adding the bacterial solution as a negative control. After pipetting and mixing the compound and the bacterial solution, cover the 96-well plate and incubate it in a biochemical incubator at 37 °C for 20 - 24 h (for Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 6538) or at 28 °C for 40 - 48 h (for Candida albicans ATCC 10231 and Aspergillus niger ATCC 16404). Measure the OD570 value (optical density) of the bacterial solution using a microplate reader.

[0159] (4) Result determination: The MIC (minimum inhibitory concentration) is the concentration that completely inhibits bacterial growth in the 96-well plate. The specific results are shown in Table 1.

[0160]

[0161] From the above experimental results, it can be seen that thiazole orange bisquaternary phosphonium salt antibacterial dyes (Compound I-1, Compound I-2, Compound I-3, Compound I-4, Compound I-5) have excellent antibacterial effects against common strains (Staphylococcus aureus ATCC 6538, Escherichia coli ATCC 25922, Candida albicans ATCC 10231, Aspergillus niger ATCC 16404), and the minimum inhibitory concentrations are all below 30 mg / L.

[0162] Among them, Compound I-5 has particularly excellent antibacterial effects. The minimum inhibitory concentrations against common strains are all below 5 mg / L, and the minimum inhibitory concentrations against the three strains of Staphylococcus aureus ATCC 6538, Escherichia coli ATCC 25922, and Candida albicans ATCC 10231 are even as low as below 0.3 mg / L.

[0163] At the same time, thiazole orange monophosphonium salt antibacterial dyes (Compound 9-1, Compound 9-2, Compound 9-3, Compound 9-4, Compound 9-5) also have good antibacterial effects, but compared with thiazole orange bisquaternary phosphonium salt antibacterial dyes, the effects are significantly worse.

[0164] Those of ordinary skill in the art can also make many forms under the inspiration of this specification and without departing from the scope protected by the claims of the present invention, and all of these fall within the scope of protection of the present invention.

Claims

1. A thiazole orange bisquaternary phosphonium salt compound, characterized in that, The structure of the described compound is shown in Formula I, , wherein X 1 and X 2 are each independently selected from chlorine, bromine, iodine, p-toluenesulfonyloxy, benzenesulfonyloxy, methanesulfonyloxy, R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are each independently selected from methyl, ethyl, C3-C8 alkyl, phenyl, 4-chlorophenyl, 4-bromophenyl, 4-fluorophenyl, 4-iodophenyl, 4-trifluoromethoxyphenyl, 4-methoxyphenyl, 4-ethoxyphenyl, 4-methylphenyl, 4-trifluoromethylphenyl, R 7 is selected from methyl, ethyl, C3-C8 alkyl, phenyl, R 8 is selected from methyl, ethyl, C3-C8 alkyl, phenyl, nitro, nitroso, sulfonyl, methanesulfonyl, fluorine, chlorine, bromine, iodine, trifluoromethyl, difluoromethyl, R 9 is selected from methyl, ethyl, C3-C8 alkyl, phenyl, nitro, nitroso, sulfonyl, methanesulfonyl, fluorine, chlorine, bromine, iodine, trifluoromethyl, difluoromethyl, m = 0 - 30, n = 0 - 30.

2. A thiazole orange bisquaternary phosphonium salt compound, characterized in that, The structure is as follows: , , , , .

3. A method for preparing the thiazole orange bisquaternary phosphonium salt compound according to claim 1, characterized in that, It includes the following steps: , (a) Under the condition of air isolation, add a first reaction solvent, a compound of formula 1, and a compound of formula 2 into a reaction kettle, the reaction temperature is 60 - 200 °C, and the reaction time is 6 - 72 hours to obtain a compound of formula 3, wherein the molar ratio of the compound of formula 1 to the compound of formula 2 is 1:1 - 10; (b) Under the condition of air isolation, a second reaction solvent, a compound of formula 3 and a compound of formula 4 are added into a reaction kettle, the reaction temperature is 80 - 200 °C, and the reaction time is 12 - 102 hours to obtain a compound of formula 5, wherein the molar ratio of the compound of formula 3 to the compound of formula 4 is 1:1 - 10; (c) Under the condition of air isolation, a third reaction solvent is added into a reaction kettle, and then a compound of formula 6 and a compound of formula 7 are added, the reaction temperature is 60 - 200 °C, and the reaction time is 3 - 72 hours to obtain a compound of formula 8, wherein the molar ratio of the compound of formula 6 to the compound of formula 7 is 1:1 - 10; (d) Under the condition of air isolation, a fourth reaction solvent, the compound of formula 5 and the compound of formula 8 are added into a reaction kettle, the reaction is carried out at a reaction temperature of 25 - 60 °C, and the heat preservation reaction is carried out for 1 - 5 hours to obtain a compound of formula 9, wherein the molar ratio of the compound of formula 5 to the compound of formula 8 is 1:1 - 10; (e) Under the condition of air isolation, a fifth reaction solvent, the compound of formula 9 and the compound of formula 10 are added into a reaction kettle, the reaction is carried out at a reaction temperature of 80 - 200 °C, and the heat preservation reaction is carried out for 12 - 102 hours to obtain a compound of formula I, wherein the molar ratio of the compound of formula 9 to the compound of formula 10 is 1:1 - 10; Among them, X 1 and X 2 are selected from chlorine, bromine, iodine, p-toluenesulfonyloxy, benzenesulfonyloxy, methanesulfonyloxy, R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are respectively selected from methyl, ethyl, C3-C8 alkyl, phenyl, 4-chlorophenyl, 4-bromophenyl, 4-fluorophenyl, 4-iodophenyl, 4-trifluoromethoxyphenyl, 4-methoxyphenyl, 4-ethoxyphenyl, 4-methylphenyl, 4-trifluoromethylphenyl, R 7 is selected from methyl, ethyl, C3-C8 alkyl, phenyl, R 8 is selected from methyl, ethyl, C3-C8 alkyl, phenyl, nitro, nitroso, sulfonyl, methanesulfonyl, fluorine, chlorine, bromine, iodine, trifluoromethyl, difluoromethyl, R 9 is selected from methyl, ethyl, C3-C8 alkyl, phenyl, nitro, nitroso, sulfonyl, methanesulfonyl, fluorine, chlorine, bromine, iodine, trifluoromethyl, difluoromethyl, m = 0 - 30, n = 0 - 30.

4. A method for preparing the thiazole orange bisquaternary phosphonium salt compound according to claim 3, characterized in that, In step (a), the first reaction solvent is at least one of acetonitrile, p-xylene, o-xylene, m-xylene, toluene, ethylene glycol diethyl ether, ethylene glycol dimethyl ether, DMF, DMSO, acetonitrile, ethyl acetate, tetrahydrofuran, 2-methyltetrahydrofuran or dioxane.

5. A method for preparing the thiazole orange bisquaternary phosphonium salt compound according to claim 3, characterized in that, In step (b), the second reaction solvent is at least one of o-xylene, p-xylene, o-xylene, m-xylene, toluene, ethylene glycol diethyl ether, DMF, DMSO, acetonitrile, acetone.

6. A method for preparing the thiazole orange bisquaternary phosphonium salt compound according to claim 3, characterized in that, In step (c), the third reaction solvent is at least one of acetonitrile, p-xylene, o-xylene, m-xylene, toluene, ethylene glycol diethyl ether, ethylene glycol dimethyl ether, DMF, DMSO, ethyl acetate, tetrahydrofuran, 2-methyltetrahydrofuran or dioxane.

7. A method for preparing the thiazole orange bisquaternary phosphonium salt compound according to claim 3, characterized in that, In step (d), the fourth reaction solvent is at least one of ethanol, methanol, isopropanol, n-butanol, p-xylene, o-xylene, m-xylene, toluene, ethylene glycol diethyl ether, ethylene glycol dimethyl ether, DMF, DMSO, acetonitrile, tetrahydrofuran, 2-methyltetrahydrofuran, dioxane.

8. A method for preparing the thiazole orange bisquaternary phosphonium salt compound according to claim 3, characterized in that, In step (e), the fifth reaction solvent is at least one of o-xylene, p-xylene, m-xylene, toluene, ethylene glycol diethyl ether, DMF, DMSO, acetonitrile or acetone.

9. A method for preparing the thiazole orange bisquaternary phosphonium salt compound as claimed in claim 3, characterized in that in step (d), it is further necessary to continue adding a basic reagent, and the basic reagent is at least one of triethylamine and N,N-diisopropylethylamine.

10. The application of the thiazole orange bisquaternary phosphonium salt compound as claimed in any one of claims 1-2 or the thiazole orange bisquaternary phosphonium salt compound prepared by the preparation method of the thiazole orange bisquaternary phosphonium salt compound as claimed in any one of claims 3-9 in the preparation of materials against Staphylococcus aureus, Escherichia coli, Candida albicans and Aspergillus niger.

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