4-chloro-3, 5-dimethylphenol quaternary phosphonium salt derivative as well as preparation method and application thereof
By using 4-chloro-3,5-dimethylphenol quaternary phosphine salt derivatives that synergize with triphenyl quaternary phosphine salts, the problems of poor water solubility and drug resistance of 4-chloro-3,5-dimethylphenol were solved, achieving a highly efficient and broad-spectrum bactericidal effect.
Patent Information
- Application Number
- CN202511876137.8
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-12-12
- Publication Date
- 2026-03-20
AI Technical Summary
4-Chloro-3,5-dimethylphenol, as a bactericide, has poor solubility in water, is prone to precipitation, and poses a risk of inducing drug resistance in microorganisms, making it difficult to cope with complex microbial environments.
A 4-chloro-3,5-dimethylphenol quaternary phosphine salt derivative was developed to enhance antibacterial properties and broaden the antibacterial spectrum through synergistic effects with triphenyl quaternary phosphonium salt, and a simple preparation method was adopted to overcome the above-mentioned shortcomings.
It improves the water solubility of 4-chloro-3,5-dimethylphenol, enhances its antibacterial properties, broadens its antibacterial spectrum, reduces the risk of drug resistance, and improves its bactericidal efficiency.
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Figure CN121698906A_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the technical field of organic synthesis, and relates to a 4-chloro-3,5-dimethylphenol quaternary phosphonium salt derivative, a preparation method and application thereof. BACKGROUND
[0002] 4-chloro-3,5-dimethylphenol (i.e., p-chloro-m-cresol, referred to as PCMX) is a high-efficiency, broad-spectrum and safe bactericide recognized by the public, and is certified by the FDA in the United States as a preferred bactericide, and can be widely used as an antifungal and antibacterial agent in medical disinfection or personal care products, and can also be used as a preservative and antifungal agent in the industrial fields of glue, paint, paint, textile, leather, papermaking and the like. Its antibacterial effect is mainly achieved by destroying the cell wall of microorganisms, attacking the cell membrane and inactivating the key enzymes. With the increase of the public's awareness of microbial contamination and hygiene, the demand for disinfectant products has been greatly stimulated. In China, in recent years, the improvement of the people's education level and manufacturing standards has changed the consumers' concept, so that they seek high-quality and long-shelf-life products. Manufacturers try their best to meet the public's demand by processing and formulating, and constantly increase the use of microbial control products.
[0003] P-chloro-m-cresol has good killing effect on various gram-positive bacteria and gram-negative bacteria, fungi (such as molds and yeasts). It is durable, stable in nature, and has good compatibility; at the same time, it has poor water solubility, is easy to precipitate, or needs organic solvents or surfactants to assist dissolution. And there is a risk of inducing microorganisms to produce tolerance or drug resistance.
[0004] Single drug is difficult to cope with complex microbial environment. The future trend is to be compounded with bactericides with different mechanisms of action to achieve synergistic effect, expand the antibacterial spectrum, and delay drug resistance. Triphenyl quaternary phosphonium is a kind of cationic bactericide, and quaternary phosphonium salt is a new type of cationic antibacterial agent. Since phosphorus is a third period element, the ionic radius is large, the polarization effect is strong, and the positive charge is strong, so the quaternary phosphonium salt has good antibacterial property, wide spectrum, low toxicity, high temperature resistance and high stability, and has low foam, strong mud stripping capacity and wide pH application range. At the same time, triphenyl quaternary phosphonium salt can increase the cell membrane permeability of the molecule, increase the penetration force and mitochondrial enrichment capacity of the molecule, has synergistic effect with 4-chloro-3,5-dimethylphenol, can make up for the blank in the antibacterial spectrum of 4-chloro-3,5-dimethylphenol, reduce the occurrence of drug resistance, and make the product have a wider antibacterial spectrum and the ability of rapid sterilization. SUMMARY
[0005] In view of the problems existing in the prior art, the present application develops a 4-chloro-3, 5-dimethyl phenol quaternary phosphonium salt derivative, which has the characteristics of easy raw material, simple preparation method and low cost. At the same time, the target compound prepared by the method has the characteristics of good antibacterial property, wide antibacterial spectrum, low toxicity, high temperature resistance and high stability, which can overcome the shortcomings of weak antibacterial ability and narrow antibacterial spectrum of 4-chloro-3, 5-dimethyl phenol.
[0006] The present application discloses a 4-chloro-3, 5-dimethyl phenol quaternary phosphonium salt derivative, the structure general formula is as shown in formula P, In the formula, R is selected from substituted C1-C10 straight chain or branched alkyl or aryl, wherein the substituent group of the substituted C1-C10 straight chain or branched alkyl or aryl is at least one hydrogen, halogen, trifluoromethyl or C1-C6 alkyl; X is selected from chlorine or bromine; and n=0-10.
[0007] In a preferred embodiment of the present application, the structure general formula is as shown in formula P II, In the formula, R1 is selected from hydrogen, halogen, trifluoromethyl or C1-C6 alkyl; X is selected from chlorine or bromine; and n=1-6.
[0008] In a preferred embodiment of the present application, the representative compound structure is as follows: .
[0009] The present application discloses a preparation method of a 4-chloro-3, 5-dimethyl phenol quaternary phosphonium salt derivative, which comprises the following steps, The chemical reaction equation is as follows: .
[0010] In the reaction container, compound S01 and compound S02 are added in sequence, and a condensation reaction occurs under the action of a condensing agent, the reaction temperature is 0-50 DEG C, the reaction time is 3h-24h, after the reaction is completed, cooling, concentration and recrystallization are carried out to obtain the compound 4-chloro-3, 5-dimethyl phenol ester derivative, the first reaction solvent is selected from one or more mixtures of dichloromethane, tetrahydrofuran, DMF, DMSO, 1, 4-dioxane, ethyl acetate and 1, 2-dichloroethane; and the condensing agent is selected from one or more mixtures of DCC, DIC, EDC, EDCI, HATU, HBTU, TBTU, CDI, T3P and EEDQ; In the formula, R is selected from substituted C1-C10 straight chain or branched alkyl or aryl, wherein the substituent group of the substituted C1-C10 straight chain or branched alkyl or aryl is at least one hydrogen, halogen, trifluoromethyl or C1-C6 alkyl; X is selected from chlorine or bromine; and n=0-10.
[0011] In a preferred embodiment of the present application, in step (2), the molar ratio of compound S01 to compound S02 is 1:1-3.
[0012] In a preferred embodiment of the present application, in step (1), the compound S01 is triphenylphosphine, and in step (2), the compound prepared is a 4-chloro-3,5-dimethylphenol quaternary phosphonium salt derivative, wherein X is selected from chlorine or bromine; and n = 1-6.
[0013] The present application discloses the use of the above-mentioned 4-chloro-3,5-dimethylphenol quaternary phosphonium salt derivative or the 4-chloro-3,5-dimethylphenol quaternary phosphonium salt derivative prepared by the above-mentioned preparation method as an antibacterial agent or an antibacterial drug.
[0014] In a preferred embodiment of the present application, the use of the above-mentioned antibacterial agent or antibacterial drug includes the use against Escherichia coli, Pseudomonas aeruginosa, Candida albicans, yeast, Staphylococcus aureus, Salmonella, Bacillus subtilis, Listeria, sulfate-reducing bacteria, or Aspergillus niger.
[0015] The present application discloses an antibacterial solution, wherein the above-mentioned 4-chloro-3,5-dimethylphenol quaternary phosphonium salt derivative or the 4-chloro-3,5-dimethylphenol quaternary phosphonium salt derivative prepared by the above-mentioned preparation method is added.
[0016] The present application discloses an antibacterial resin, wherein the above-mentioned 4-chloro-3,5-dimethylphenol quaternary phosphonium salt derivative or the 4-chloro-3,5-dimethylphenol quaternary phosphonium salt derivative prepared by the above-mentioned preparation method is added. Advantages
[0017] The present application contains two functional groups of 4-chloro-3,5-dimethylphenol and quaternary phosphonium salt, which synergistically kill bacteria, improve the solubility of 4-chloro-3,5-dimethylphenol in water, enhance the antibacterial performance, expand the antibacterial spectrum, overcome drug resistance, and improve the bactericidal efficiency, thereby having high-efficiency and broad-spectrum bactericidal effect. BRIEF DESCRIPTION OF DRAWINGS
[0018] Figure 1 The figure is the nuclear magnetic resonance hydrogen spectrum of compound P1.
[0019] Figure 2 The figure is the high-performance liquid chromatogram of compound P1 at different wavelengths. DETAILED DESCRIPTION
[0020] The technical solutions in the embodiments of the present application will be clearly and completely described below. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative work fall within the scope of protection of the present application.
[0021] The raw materials used in the present application are all purchased from the market.
[0022] I. Synthesis of compounds P1-P9 Example 1
[0023] Synthesis of compound P1: .
[0024] First step: Under magnetic stirring, in a 1 L four-necked flask, ω-bromocarboxylic acid (64 g, 383 mmol, 1.0 eq) and triphenylphosphine (100 g, 381 mmol, 1.0 eq) were dissolved in 500 mL of ethyl acetate, and the reaction was refluxed under nitrogen protection for 24 hours. After the mixture was cooled to room temperature, it was concentrated under vacuum. The residue was crystallized with ethyl acetate, washed, and dried to obtain the corresponding 3- (carboxypropyl) triphenylphosphonium bromide, white solid 150 g, yield 92%, purity 98%.
[0025] ESI-HRMS (m / z): 349.2 [M-Br] + ; Second step: Under magnetic stirring, in a 1 L four-necked flask, 4-chloro-3,5-dimethylphenol (32 g, 200 mmol, 1.0 eq) and 3- (propionyl) triphenylphosphonium bromide (85 g, 200 mmol, 1.0 eq, CAS: 17857-14-6) were dissolved in CH2Cl2(300 mL), and N, N'-diisopropylcarbodiimide (DIC, 32 g, 260 mmol, 1.3 eq) was slowly added at room temperature. After the reaction was carried out at room temperature for 12 h, the reaction was monitored by TLC and HPLC, and then the solvent was directly evaporated by rotary evaporation after the reaction was completed. A yellow viscous semisolid was obtained, ethanol (200 mL) was added, mechanical stirring was carried out, and the mixture was cooled in an ice bath for 1 h, then filtered, the filter cake was washed with ethanol (100 mL), and the filter cake was dried to obtain a white solid 72 g, yield: 63%, purity: 95%. δ 1 H NMR (400 MHz, DMSO- d6) δ 7.96 - 7.74 (m, 16H), 7.01 (s, 2H), 3.73 - 3.61 (m, 2H), 2.82 (t, J = 6.9 Hz, 2H), 2.32 (s, 6H), 1.87 (q, J = 7.8, 7.4 Hz, 2H) ppm.
[0026] ESI-HRMS (m / z): 487.2 [M-Br] + Calcd. 487.16 [M-Br] + . Example 2
[0027] Synthesis of compound P2: .
[0028] First step: In a 1 L four necked flask, 5-bromovaleric acid (50 g, 276 mmol, 1.0 eq) and triphenylphosphine (72.4 g, 276 mmol, 1.0 eq) were dissolved in 500 mL of ethyl acetate under nitrogen protection and refluxed for 24 h under magnetic stirring. After the mixture was cooled to room temperature, it was concentrated under vacuum. The residue was crystallized with ethyl acetate, washed, dried to give the corresponding 4-(butyryl)triphenylphosphonium bromide as a white solid 98 g, yield 80%, purity 96%.
[0029] ESI-HRMS (m / z): 363.2 [M-Br] + Calcd. 363.15 [M-Br] + ; Second step: In a 1 L four necked flask, 4-chloro-3,5-dimethylphenol (10 g, 63.9 mmol, 1.0 eq) and 4-(butyryl)triphenylphosphonium bromide (28.3 g, 63.9 mmol, 1.0 eq) were dissolved in CH2Cl2(200 mL) under magnetic stirring, N,N'-diisopropylcarbodiimide (DIC, 9.7 g, 76.7 mmol, 1.2 eq) was added slowly at room temperature, the reaction was carried out for 16 h at room temperature, after the reaction was monitored by TLC and HPLC, the solvent was directly evaporated by rotary evaporation, concentrated to give a yellow sticky semi-solid, ethanol (80 mL) was added, mechanically stirred, cooled in ice bath for 2 h, suction filtered, the filter cake was washed with ethanol (100 mL), the filter cake was dried to give a white solid 20 g, yield: 62%, purity: 95%.
[0030] ESI-HRMS (m / z): 501.2 [M-Br] +, calculated 501.17 [M-Br] + . Example 3
[0031] Synthesis of compound P3: .
[0032] First step: In a 1 L four necked flask, 6-bromohexanoic acid (50 g, 256 mmol, 1.0 eq) and triphenylphosphine (67.2 g, 256 mmol, 1.0 eq) were dissolved in 500 mL of ethyl acetate under nitrogen protection and refluxed for 16 h with magnetic stirring. After the mixture was cooled to room temperature, it was concentrated under vacuum. The residue was crystallized with ethyl acetate, washed, dried to obtain the corresponding 5-(pentanoyl)triphenylphosphonium bromide, white solid 100 g, yield 85%, purity 97%.
[0033] ESI-HRMS (m / z): 377.2 [M-Br] + , calculated 377.17 [M-Br] + ; Second step: In a 1 L four necked flask, 4-chloro-3,5-dimethylphenol (12 g, 76.6 mmol, 1.0 eq) and 5-(pentanoyl)triphenylphosphonium bromide (35 g, 76.6 mmol, 1.0 eq) were dissolved in CH2Cl2(200 mL) with magnetic stirring, N,N'-diisopropylcarbodiimide (DIC, 11.6 g, 92 mmol, 1.2 eq) was added slowly at room temperature, and the reaction was carried out for 24 h at room temperature. After the reaction was completed by TLC and HPLC monitoring, the solvent was directly evaporated by rotary evaporation, concentrated to obtain a yellow viscous semi-solid, ethanol (100 mL) was added, mechanically stirred, and the slurry was cooled in an ice bath for 2 h, then suction filtered, the filter cake was washed with ethanol (100 mL), and the filter cake was dried to obtain a white solid 33 g, yield: 72%, purity: 96%.
[0034] ESI-HRMS (m / z): 515.2 [M-Br] + , calculated 515.19 [M-Br] + . Example 4
[0035] Synthesis of compound P4: .
[0036] First step: In a 1 L four necked flask, under magnetic stirring, the ω-chlorocarboxylic acid (50 g, 408 mmol, 1.0 eq) was dissolved in 500 mL of ethyl acetate with triphenylphosphine (107 g, 408 mmol, 1.0 eq) under nitrogen protection and refluxed for 36 h. After the mixture was cooled to room temperature, it was concentrated under vacuum. The residue was crystallized with ethyl acetate, slurried, washed, and dried to give the corresponding 3-(carboxypropyl)triphenylphosphonium chloride as a white solid 88 g, yield 62%, purity 96%.
[0037] ESI-HRMS (m / z): 349.2 [M-Cl] + Calcd. 349.14 [M-Cl] + ; Second step: In a 1 L four necked flask, under magnetic stirring, 4-chloro-3,5-dimethylphenol (20 g, 128 mmol, 1.0 eq), 3-(carboxypropyl)triphenylphosphonium bromide (49.3 g, 128 mmol, 1.0 eq) were dissolved in CH2Cl2(200 mL) and N,N'-diisopropylcarbodiimide (DIC, 20 g, 160 mmol, 1.25 eq) was added slowly at room temperature. After 24 h of reaction at room temperature, the reaction was monitored by TLC and HPLC and after completion of the reaction, the solvent was directly evaporated under vacuum to give a yellow sticky semi-solid. Ethanol (150 mL) was added, mechanically stirred, and slurry was cooled in an ice bath for 1 h. It was then filtered under suction, the filter cake was washed with ethanol (60 mL), and the filter cake was dried to give a white solid 43 g, yield: 69%, purity: 95%.
[0038] ESI-HRMS (m / z): 487.2 [M-Cl] + Calcd. 487.16 [M-Cl] + . Example 5
[0039] Synthesis of compound P5: .
[0040] First step: In a 1 L four necked flask, under magnetic stirring, the ω-bromocarboxylic acid (64 g, 383 mmol, 1.0 eq) was dissolved in 500 mL of ethyl acetate with tributylphosphine (60.6 g, 299 mmol, 1.0 eq) under nitrogen protection and refluxed for 24 h. After the mixture was cooled to room temperature, it was concentrated under vacuum. The residue was crystallized with ethyl acetate, slurried, washed, and dried to give the corresponding 3-(carboxypropyl)tributylphosphonium bromide as a white solid 100 g, yield 90%, purity 96%.
[0041] ESI-HRMS (m / z): 289.2 [M-Br] + Calculated value: 289.2 [M-Br] + .
[0042] Step Two: Under magnetic stirring, 4-chloro-3,5-dimethylphenol (15 g, 96 mmol, 1.0 eq) and 3-(carboxypropyl)tributylphosphine bromide (15 g, 95.8 mmol, 1.0 eq) were dissolved in CH2Cl2 (100 mL) in a 1 L four-necked flask. N,N'-diisopropylcarbodiimide (DIC, 15 g, 120 mmol, 1.2 eq) was slowly added at room temperature. After reacting for 12 h at room temperature, the reaction was monitored by TLC and HPLC. The solvent was directly evaporated by rotary evaporation and concentrated to obtain a yellow viscous semi-solid. Ethanol (100 mL) was added, and the mixture was mechanically stirred, cooled in an ice bath, and slurried for 1 h. The mixture was then filtered, and the filter cake was washed with ethanol (60 mL). The filter cake was dried to obtain 32 g of white solid. Yield: 66%, Purity: 95%.
[0043] ESI-HRMS (m / z): 427.3 [M-Br] + The calculated value is 427.25 [M-Br]. + . Example 6
[0044] Synthesis of compound P6: .
[0045] first step: ω-bromocarboxylic acid (64 g, 383 mmol, 1.0 eq) and diphenyl tert-butylphosphine (60.6 g, 299 mmol, 1.0 eq) were dissolved in 500 mL of ethyl acetate in a 1 L four-necked flask under stirring at room temperature. The mixture was refluxed for 24 hours under nitrogen protection. After cooling to room temperature, the mixture was concentrated under vacuum. The residue was crystallized from ethyl acetate, slurried, washed, and dried to give 100 g of the corresponding 3-(carboxypropyl)diphenyl tert-butylphosphine bromide, a white solid, with a yield of 90% and a purity of 96%.
[0046] ESI-HRMS (m / z): 329.2 [M-Br] + Calculated value: 329.17 [M-Br] + .
[0047] Step Two: Under magnetic stirring, 4-chloro-3,5-dimethylphenol (12 g, 76.6 mmol, 1.0 eq) and 3-(propylcarboxy)diphenyl-tert-butylphosphine bromide (25.2 g, 76.6 mmol, 1.0 eq) were dissolved in CH2Cl2 (200 mL) in a 1 L four-necked flask. N,N'-diisopropylcarbodiimide (DIC, 12 g, 95 mmol, 1.2 eq) was slowly added at room temperature. After reacting for 16 h at room temperature, the reaction was monitored by TLC and HPLC. The solvent was directly evaporated by rotary evaporation and concentrated to obtain a yellow viscous semi-solid. Ethanol (100 mL) was added, and the mixture was mechanically stirred, cooled in an ice bath, and slurried for 1 h. The mixture was then filtered, and the filter cake was washed with ethanol (100 mL). The filter cake was dried to obtain 26 g of white solid. Yield: 62%, Purity: 95%.
[0048] ESI-HRMS (m / z): 467.2 [M-Br] + The calculated value is 467.19 [M-Br]. + . Example 7
[0049] Synthesis of compound P7: .
[0050] first step: In a 1 L four-necked flask with stirring, ω-bromocarboxylic acid (20 g, 120 mmol, 1.0 eq) and tris(4-fluoro-phenyl)phosphine (38.6 g, 122 mmol, 1.0 eq) were dissolved in 500 mL of ethyl acetate and reacted under nitrogen protection by reflux for 24 hours. After the mixture cooled to room temperature, it was concentrated under vacuum. The residue was crystallized from ethyl acetate, slurried, washed, and dried to give 36 g of the corresponding 3-(propylcarboxy)tris(4-fluoro-phenyl)phosphine bromide, a white solid, with a yield of 62% and a purity of 95%.
[0051] ESI-HRMS (m / z): 403.2 [M-Br] + Calculated value: 403.11 [M-Br] + .
[0052] Step Two: Under magnetic stirring, 4-chloro-3,5-dimethylphenol (10 g, 63.9 mmol, 1.0 eq) and 3-(propylcarboxy)tris(4-fluoro-phenyl)phosphine bromide (25.8 g, 63.9 mmol, 1.0 eq) were dissolved in CH2Cl2 (200 mL) in a 1 L four-necked flask. N,N'-diisopropylcarbodiimide (DIC, 10.1 g, 80 mmol, 1.25 eq) was slowly added at room temperature. After reacting for 16 h at room temperature, the reaction was monitored by TLC and HPLC. The solvent was directly evaporated by rotary evaporation and concentrated to obtain a yellow viscous semi-solid. Ethanol (120 mL) was added, and the mixture was mechanically stirred, cooled in an ice bath, and slurried for 1 h. The mixture was then filtered, and the filter cake was washed with ethanol (50 mL). The filter cake was dried to obtain 28 g of white solid. Yield: 71%, Purity: 97%.
[0053] ESI-HRMS (m / z): 541.2 [M-Br] + The calculated value is 541.13 [M-Br]. + . Example 8
[0054] Synthesis of compound P8: .
[0055] first step: In a 1 L four-necked flask with stirring, ω-bromocarboxylic acid (20 g, 120 mmol, 1.0 eq) and tris(4-methylphenyl)phosphine (38.3 g, 126 mmol, 1.0 eq) were dissolved in 500 mL of ethyl acetate and reacted under nitrogen protection by reflux for 24 hours. After the mixture cooled to room temperature, it was concentrated under vacuum. The residue was crystallized from ethyl acetate, slurried, washed, and dried to give 44 g of the corresponding 3-(propylcarboxy)tris(4-methylphenyl)phosphine bromide, white solid, yield 78%, purity 96%.
[0056] Step Two: Under magnetic stirring, 4-chloro-3,5-dimethylphenol (13 g, 83 mmol, 1.0 eq) and 3-(propylcarboxy)tris(4-methyl-phenyl)phosphine bromide (39 g, 83 mmol, 1.0 eq) were dissolved in CH2Cl2 (200 mL) in a 1 L four-necked flask. N,N'-diisopropylcarbodiimide (DIC, 13 g, 104 mmol, 1.25 eq) was slowly added at room temperature. After reacting for 24 h at room temperature, the reaction was monitored by TLC and HPLC. The solvent was directly evaporated by rotary evaporation and concentrated to obtain a yellow viscous semi-solid. Ethanol (200 mL) was added, and the mixture was mechanically stirred, cooled in an ice bath, and slurried for 1 h. The mixture was then filtered, and the filter cake was washed with ethanol (100 mL). The filter cake was dried to obtain 41 g of white solid. Yield: 81%, Purity: 96%.
[0057] ESI-HRMS (m / z): 529.2 [M-Br] + The calculated value is 529.21 [M-Br]. + . Example 9
[0058] Synthesis of compound P9: .
[0059] first step: In a 1 L four-necked flask with stirring at room temperature, ω-bromocarboxylic acid (18.3 g, 109 mmol, 1.0 eq) and tris(4-trifluoromethylphenyl)phosphine (51 g, 109 mmol, 1.0 eq) were dissolved in 200 mL of ethyl acetate and refluxed under nitrogen protection for 16 hours. After the mixture cooled to room temperature, it was concentrated under vacuum. The residue was crystallized from ethyl acetate, slurried, washed, and dried to give 52 g of the corresponding 3-(propylcarboxy)tris(4-methyl-phenyl)phosphine bromide, white solid, yield 75%, purity 95%.
[0060] ESI-HRMS (m / z): 553.2 [M-Br] + Calculated value: 553.10 [M-Br] + .
[0061] Step Two: Under magnetic stirring, 4-chloro-3,5-dimethylphenol (10 g, 63.9 mmol, 1.0 eq) and (2-carboxypropyl)tris-(4-trifluoromethyl-phenyl)phosphine bromide (40.4 g, 55.5 mmol, 1.0 eq) were dissolved in CH2Cl2 (200 mL) in a 1 L four-necked flask. N,N'-diisopropylcarbodiimide (DIC, 10.1 g, 80 mmol, 1.25 eq) was slowly added at room temperature. After reacting for 16 h at room temperature, the reaction was monitored by TLC and HPLC. The solvent was then directly rotary evaporated and concentrated to obtain a yellow viscous liquid. Rapid silica gel column chromatography was performed with MeOH:CH2Cl2 as eluent at a ratio of 1:50 to 1:20, yielding 31 g of a white solid. Yield: 63%, Purity: 97%.
[0062] ESI-HRMS (m / z): 691.2 [M-Br] + The calculated value is 691.12 [M-Br]. + .
[0063] II. Microbial sterilization rate test: 1. Preparation of antibacterial plastic test samples and testing of their antibacterial properties: Take 100 parts of polystyrene, polyethylene, or polypropylene powder, and in each example, 1, 2, or 3 parts of the product powder, and mix thoroughly. Add the mixture to a micro twin-screw extruder at a processing temperature of 170℃-230℃ for melt blending and granulation; then, prepare 50mm*50mm test samples at an injection molding temperature of 190℃-210℃. The test method follows the People's Republic of China National Standard GB / T 31402-2015 / ISO 22916:2007, using the film-coating method to test the samples. The test bacteria are Escherichia coli and Staphylococcus aureus.
[0064] The results of the antibacterial activity tests of the compounds are as follows (Table 2):
[0065] illustrate: 1. No colony growth was observed in the negative control group.
[0066] In conclusion, the quaternary phosphonium salt derivatives P1-P9 of 4-chloro-3,5-dimethylphenol exhibit excellent bactericidal effects against Escherichia coli, Candida albicans, Staphylococcus aureus, and Pseudomonas aeruginosa. In particular, they also demonstrate strong bactericidal activity against Pseudomonas aeruginosa, which has relatively weak inhibitory activity against 4-chloro-3,5-dimethylphenol. This enhances the antibacterial activity of 4-chloro-3,5-dimethylphenol and expands its antibacterial spectrum and application range.
[0067] 2. The results of the antibacterial activity test of the compound's aqueous solution are as follows (Table 1):
[0068] 3. Antimicrobial performance durability test of antimicrobial plastic test samples:
[0069] In conclusion, the quaternary phosphonium salt derivative P1 of 4-chloro-3,5-dimethylphenol exhibits good durability in water, demonstrating that it is not easily precipitated in resin and possesses long-term antibacterial capabilities.
[0070] The above examples are only for illustrating the technical concept and features of the present invention, and are intended to enable those skilled in the art to understand the content of the present invention and implement it accordingly. They should not be used to limit the scope of protection of the present invention. All equivalent transformations or modifications made in accordance with the spirit and essence of the present invention should be covered within the scope of protection of the present invention.
Claims
1. A 4-chloro-3,5-dimethylphenol quaternary phosphine salt derivative, characterized in that, Its general structural formula is shown in equation P. In the formula, R is selected from C1-C10 straight-chain or branched alkyl groups with substituents, aryl groups with substituents, wherein the substituents in the C1-C10 straight-chain or branched alkyl groups with substituents are at least one hydrogen, halogen, trifluoromethyl, C1-C6 alkyl; X is selected from chlorine or bromine; n=0-10.
2. The 4-chloro-3,5-dimethylphenol quaternary phosphine salt derivative according to claim 1, characterized in that, Its general structural formula is shown in formula PⅡ. In the formula, R1 is arbitrarily selected from hydrogen, halogen, trifluoromethyl, C1-C6 alkyl; X is selected from chlorine or bromine; n=1-6.
3. The 4-chloro-3,5-dimethylphenol quaternary phosphine salt derivative according to claim 1 or 2, characterized in that, The structures of its representative compounds are as follows: .
4. A method for preparing a 4-chloro-3,5-dimethylphenol quaternary phosphine salt derivative, characterized in that, Includes the following steps, The chemical reaction equation is as follows: 。 In a reaction vessel, compounds SO1 and SO2 are added sequentially, and a condensation reaction occurs under the action of a condensing agent. The reaction temperature is 0-50℃, and the reaction time is 3-24 h. After the reaction is complete, the mixture is cooled, concentrated, and recrystallized to obtain a 4-chloro-3,5-dimethylphenol ester derivative. The first reaction solvent is selected from one or more of dichloromethane, tetrahydrofuran, DMF, DMSO, 1,4-dioxane, ethyl acetate, and 1,2-dichloroethane; the condensing agent is selected from one or more of DCC, DIC, EDC, EDCI, HATU, HBTU, TBTU, CDI, T3P, and EEDQ; in the formula, R is selected from a C1-C10 straight-chain or branched alkyl or aryl group with a substituent, wherein the substituent in the C1-C10 straight-chain or branched alkyl or aryl group is at least one hydrogen, halogen, trifluoromethyl, or C1-C6 alkyl; X is selected from chlorine or bromine; n=0-10.
5. The method for preparing the 4-chloro-3,5-dimethylphenol quaternary phosphine salt derivative according to claim 4, characterized in that, In step (2), the molar ratio of compound SO1 to compound SO2 is 1:1-3.
6. The method for preparing the 4-chloro-3,5-dimethylphenol quaternary phosphine salt derivative according to claim 4, characterized in that, In step (1), the compound SO1 is triphenylphosphine, and in step (2), the compound obtained is a 4-chloro-3,5-dimethylphenol quaternary phosphine salt derivative, where X is selected from chlorine or bromine; n=1-6.
7. The use of the 4-chloro-3,5-dimethylphenol quaternary phosphine salt derivative prepared by the method according to any one of claims 1-3 or any one of claims 4-6 as an antibacterial agent or antimicrobial drug.
8. The application as an antibacterial agent according to claim 7, characterized in that, The applications as antibacterial agents or antimicrobial drugs include those against Escherichia coli, Pseudomonas aeruginosa, Candida albicans, yeast, Staphylococcus aureus, Salmonella, Bacillus subtilis, Listeria, sulfate-reducing bacteria, or Aspergillus niger.
9. An antibacterial solution, characterized in that, The antibacterial solution contains the 4-chloro-3,5-dimethylphenol quaternary phosphine salt derivative as described in any one of claims 1-3, or the 4-chloro-3,5-dimethylphenol quaternary phosphine salt derivative prepared by the method described in any one of claims 4-6.
10. An antibacterial resin, characterized in that, The antibacterial resin is supplemented with the 4-chloro-3,5-dimethylphenol quaternary phosphine salt derivative as described in any one of claims 1-3, or the 4-chloro-3,5-dimethylphenol quaternary phosphine salt derivative prepared by the method described in any one of claims 4-6.