Butyl paraben cation salt derivative as well as preparation method and application thereof

Abstract

The invention discloses a butylparaben cation salt derivative, the structural general formula of which is shown as a formula P. In the formula, R is selected from C1-C12 straight chain or branched chain alkyl with substituent groups, five-membered or six-membered cycloalkyl or aryl with substituent groups, and the C1-C12 straight chain or branched chain alkyl with substituent groups, the five-membered or six-membered cycloalkyl or aryl with substituent groups, the C1-C12 straight chain or branched chain alkyl with substituent groups, the five-membered or six-membered cycloalkyl or aryl with substituent groups, the five-membered or six-membered cycloalkyl or aryl with substituent the substituent group in the five-membered or six-membered naphthenic base or aryl with the substituent group is at least one of hydrogen, halogen and C1-C6 alkyl; a is selected from-CO <-> or-CH2 <->; q is selected from nitrogen or phosphine; x is selected from chlorine or bromine; n is equal to 0-10. According to the invention, the antibacterial property and antibacterial spectrum of the butylparaben are improved, and the butylparaben has the advantages of rapid sterilization and long-acting sterilization, and also has efficient and broad-spectrum sterilization effects.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and specifically to a butylparaben cationic salt derivative, its preparation method, and its applications. Background Technology

[0002] Butyl paraben is a highly effective, broad-spectrum preservative, particularly effective against molds and yeasts, and is widely used in cosmetics and personal care products. Its core mechanism of action lies in the interference of its lipophilic molecules with microbial cell membranes and enzyme systems. Butyl parabens, in its lipophilic molecular form, penetrates cell membranes, inhibiting microbial growth or causing death through a dual action of physically disrupting membrane structure and chemically inhibiting key metabolic enzymes. Within the paraben family (methylparaben, ethylparaben, propylparaben, butylparaben), antibacterial activity generally increases with increasing ester chain length. Therefore, butyl parabens exhibits stronger antibacterial efficacy than methylparaben and ethylparaben, especially against molds and yeasts.

[0003]

[0004] The application of butyl parabens is limited by several factors, including poor water solubility, insufficient antibacterial spectrum, health controversies (estrogen-like activity), pH dependence, and formulation compatibility. Therefore, in modern product formulations, butyl parabens is primarily used as a component of preservative systems, scientifically compounded with other preservatives and bactericides with different mechanisms of action to achieve synergistic effects, broaden the antibacterial spectrum, and delay drug resistance. Cationic antibacterial agents possess excellent antibacterial properties, broad spectrum, high efficiency, low risk of inducing biological resistance, excellent surface affinity and durability, good chemical stability and safety, low toxicity, and environmental friendliness. They also exhibit low foaming, strong slime-removing ability, and a wide pH range. Furthermore, cationic antibacterial agents can increase cell membrane permeability, enhance molecular penetration and mitochondrial accumulation, synergistically complementing the cell membrane bactericidal mechanism of butyl parabens, thus expanding its antibacterial spectrum and application range. Quaternary phosphonium salt antibacterial agents, in particular, represent a new generation of development direction for organic cationic bactericides. It is not simply a replacement for quaternary ammonium salts, but plays an irreplaceable role in fields with higher performance requirements, more complex environments, and the need for long-lasting antibacterial effects. Its core advantages can be summarized as follows: it exhibits stronger, more stable, and more durable comprehensive performance in combating stubborn microorganisms (drug-resistant bacteria, fungi, tuberculosis bacilli) under complex environments (high temperature, organic pollution, extreme pH) and in critical areas. Despite its higher cost, its value is increasingly evident in key fields such as healthcare, high-end materials, and public safety. Summary of the Invention

[0005] In view of the problems existing in the prior art, the present invention develops a butyl paraben cationic salt derivative, which uses butyl paraben as a raw material with low cost and a direct and simple preparation method, featuring low cost and easy process scale-up. Furthermore, the target compound obtained by this method exhibits good antibacterial properties, a broad antibacterial spectrum, low toxicity, and high-temperature resistance, overcoming the shortcomings of butyl paraben, such as poor solubility, weak antibacterial ability, and narrow antibacterial spectrum.

[0006] This invention discloses a butylparaben cationic salt derivative with the general structural formula shown in Formula P. In the formula, R is selected from C1-C12 straight-chain or branched alkyl groups with substituents, five- or six-membered cycloalkyl groups with substituents, or aryl groups, wherein the substituent in the C1-C12 straight-chain or branched alkyl groups with substituents, or five- or six-membered cycloalkyl groups with substituents, is at least one hydrogen, halogen, or C1-C6 alkyl; A is selected from -CO- or -CH2-; Q is selected from nitrogen or phosphine; X is selected from chlorine or bromine; n = 0-10.

[0007] This invention also discloses butylparaben cationic salt derivatives, with the general structural formula shown in formula P-01. In the formula, R is selected from C1-C12 straight-chain or branched alkyl groups with substituents, five- or six-membered cycloalkyl groups with substituents, or aryl groups, wherein the substituent in the C1-C12 straight-chain or branched alkyl groups with substituents, or five- or six-membered cycloalkyl groups with substituents, is at least one hydrogen, halogen, or C1-C6 alkyl; A is selected from -CO- or -CH2-; X is selected from chlorine or bromine; n=0-10.

[0008] This invention also discloses butylparaben quaternary phosphine salt derivatives, with the general structural formula shown in formula P-02. In the formula, A is selected from -CO- or -CH2-; X is selected from chlorine or bromine; n = 1-6.

[0009] This invention also discloses butylparaben cationic salt derivatives, with the general structural formula shown in formula P-03. In the formula, R is selected from substituent C1-C12 straight-chain or branched alkyl groups, or substituent cycloalkyl groups, wherein the substituent C1-C12 straight-chain or branched alkyl groups are selected; A is selected from -CO- or -CH2-; X is selected from chlorine or bromine; n=0-10.

[0010] This invention also discloses butylparaben cationic salt derivatives, with representative compound structures as follows: .

[0011] This invention also discloses a method for preparing a butylparaben cationic salt derivative, comprising the following steps: The chemical reaction equation is as follows: , (1) Compound SO1 and compound SO2 are added to a reaction vessel in sequence. The reaction is carried out in a first reaction solvent at a temperature of 25℃-120℃ for 3h-36h. After the reaction is complete, the mixture is cooled, concentrated, and recrystallized from acetonitrile or ethyl acetate to obtain compound M1. The first reaction solvent is ethyl acetate, acetonitrile, or toluene. (2) In the reaction vessel, compound M1 and compound SO3 undergo a condensation reaction in the second reaction solvent under the action of a condensing agent. The reaction temperature is 0-100℃ and the reaction time is 3h-36h. After the reaction is complete, the mixture is cooled, concentrated, and recrystallized to obtain the butylparaben ester derivative. The second reaction solvent is selected from one or more of acetonitrile, dichloromethane, tetrahydrofuran, DMF, DMSO, 1,4-dioxane, ethyl acetate, and 1,2-dichloroethane. The condensing agent is selected from one or more of DCC, N,N'-diisopropylcarbodiimide, EDC, EDCI, HATU, HBTU, and TBTU. In the formula, R is selected from C1-C12 straight-chain or branched alkyl groups with substituents, five- or six-membered cycloalkyl groups with substituents, or aryl groups, wherein the substituent in the C1-C12 straight-chain or branched alkyl groups with substituents, or five- or six-membered cycloalkyl groups with substituents, is at least one hydrogen, halogen, or C1-C6 alkyl; Q is selected from nitrogen or phosphine; A is selected from -CO- or -CH2-; X is selected from chlorine or bromine; n = 0-10.

[0012] This invention also discloses a method for preparing a butylparaben cationic salt derivative, comprising the following steps: The chemical reaction equation is as follows: , (1) Compound SO3 and compound SO4 were added to the first reaction solvent in a reaction vessel. The reaction temperature was 0℃-120℃ and the reaction time was 3h-36h. After the reaction was complete, the mixture was cooled, concentrated, recrystallized or subjected to column chromatography to obtain compound M2. (2) In a reaction vessel, compound M2 and compound SO1 are reacted in the first reaction solvent acetonitrile or toluene at a temperature of 0℃-150℃ for 3h-36h. After the reaction is complete, the mixture is cooled, concentrated, and recrystallized to obtain compound P. In the formula, R is selected from C1-C12 straight-chain or branched alkyl groups with substituents, five- or six-membered cycloalkyl groups with substituents, or aryl groups, wherein the substituents in the C1-C8 straight-chain or branched alkyl groups with substituents, the five- or six-membered cycloalkyl groups with substituents, or aryl groups are at least one hydrogen atom, halogens, or C1-C6 alkyl groups; Q is selected from nitrogen or phosphine; A is selected from -CO- or -CH2-; X is selected from chlorine or bromine; n = 0-10.

[0013] The present invention also discloses a resin, wherein the above-mentioned butylparaben cationic salt derivative is added or the butylparaben cationic salt derivative is prepared by the above-mentioned method for preparing butylparaben cationic salt derivative.

[0014] The present invention also discloses the above-mentioned butylparaben cationic salt derivative or the butylparaben cationic salt derivative prepared by the above-mentioned preparation method, or the above-mentioned resin as an antibacterial agent or antibacterial drug.

[0015] In a preferred embodiment of the present invention, the above-mentioned application as an antibacterial agent or antimicrobial drug includes the application of antimicrobial drugs against Escherichia coli, Candida albicans, Pseudomonas aeruginosa, Aspergillus niger, or Staphylococcus aureus and Bacillus subtilis.

[0016] Maleimide compounds possess a wide range of biological activities, including antifungal, antibacterial, herbicidal, and insecticidal properties. They exhibit excellent antibacterial activity and low cytotoxicity, and their structural characteristics make them an important direction for future antibacterial drug development. This invention utilizes butylparaben and a cationic salt as functional groups for synergistic bactericidal action, enhancing antibacterial performance, expanding the antibacterial spectrum, and possessing the advantages of long-acting bactericides, thus showing broad application prospects and development potential. Attached Figure Description

[0017] Figure 1 This is the hydrogen NMR spectrum of compound P1.

[0018] Figure 2 The images show high-performance liquid chromatograms of compound P1 at different wavelengths. Detailed Implementation

[0019] 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, and not all of them. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0020] All raw materials used in this invention are purchased from the market.

[0021] I. Synthesis of compounds P1-P12

[0022] Synthesis of compound P1

[0023]

[0024] (1) Synthesis of P1-M1 Under magnetic stirring, 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 in a 1 L four-necked flask, and the mixture was refluxed under nitrogen protection 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 150 g of the corresponding 3-(carboxypropyl)triphenylphosphine bromide as a white solid, with a yield of 92% and a purity of 98%.

[0025] ESI-HRMS(m / z): 349.2 [M-Br]+; (2) Synthesis of P1 At room temperature, under magnetic stirring, butylparaben (30 g, 154 mmol, 1.1 eq, CAS No.: 94-26-8), 500 mL of dichloromethane, and P1-M1 (55 g, 128 mmol, 1 eq, CAS: 17857-14-6) were added to a 2 L reaction flask, followed by N,N'-diisopropylcarbodiimide (19 g, 150 mmol, 1.2 eq). The reaction was carried out at room temperature for 24 h, followed by reflux at 50 °C for 3 h. After the reaction was completed under TLC and HPLC monitoring, the solvent was directly rotary evaporated and concentrated to obtain a yellow viscous semi-solid. A small amount of ethanol was added to dissolve the semi-solid, followed by water addition and stirring. The mixture was filtered, and the filter cake was washed with methyl ether. Ethyl acetate (200 mL) was added, and the mixture was mechanically stirred and cooled in an ice bath for 1 h. The mixture was then filtered, and the filter cake was washed with ethyl acetate (100 mL). The filter cake was dried to obtain 36 g of white solid, yield: 60%, purity: 99%.

[0026] 1H NMR (400 MHz, DMSO-d6) δ 8.02 (d, J = 8.5 Hz, 2H), 7.96 – 7.74 (m,15H), 7.33 (d, J = 8.5 Hz, 2H), 4.28 (t, J = 6.4 Hz, 2H), 3.71 (td, J = 13.3,7.5 Hz, 2H), 2.89 (t, J = 6.9 Hz, 2H), 1.92 - 1.87 (m, 2H), 1.74 - 1.65 (m,2H), 1.47 - 1.38 (m, 2H), 0.93 (t, J = 7.4 Hz, 3H) ppm. ESI-HRMS (m / z): 525.2 [M-Br]+, calculated value 525.22 [M-Br]+.

[0027] Synthesis of compound P2

[0028] (1) Synthesis of P2-M1 Under magnetic stirring, 5-bromopentanoic 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 in a 1 L four-necked flask, and the mixture was refluxed under nitrogen protection 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 98 g of the corresponding 4-(butanocarboxy)triphenylphosphine bromide as a white solid, with a yield of 80% and a purity of 96%.

[0029] ESI-HRMS (m / z): 363.2 [M-Br]+, calculated value 363.15 [M-Br]+; (2) Synthesis of P2 At room temperature, under magnetic stirring, butylparaben (22 g, 113 mmol, 1.1 eq) was added to a 2 L reaction flask, followed by 600 mL of dichloromethane, P2-M1 (45.6 g, 103 mmol, 1 eq, CAS: 17814-85-6), and then N,N'-diisopropylcarbodiimide (15.6 g, 124 mmol, 1.2 eq). The reaction was carried out at room temperature for 16 h. After the reaction was completed under TLC and HPLC monitoring, the solvent was directly evaporated by rotary evaporation and concentrated to obtain a yellow viscous semi-solid. Ethyl acetate (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 ethyl acetate (50 mL). The filter cake was dried to obtain 41 g of white solid. Yield: 64%, Purity: 95%.

[0030] 1H NMR (400 MHz, DMSO-d6) δ 8.04 (d, J = 8.6 Hz, 2H), 7.98 – 7.75 (m,15H), 7.32 (d, J = 8.6 Hz, 2H), 4.28 (t, J = 6.4 Hz, 2H), 3.72 (td, J = 13.3,7.5 Hz, 2H), 2.91 (t, J = 6.9 Hz, 2H), 1.95 - 1.90 (m, 2H), 1.70 - 1.58 (m,2H), 1.43 - 1.28 (m, 4H), 0.93 (t, J = 7.4 Hz, 3H) ppm. ESI-HRMS (m / z): 539.2 [M-Br]+, calculated value 539.23 [M-Br]+.

[0031] Synthesis of compound P3

[0032] (1) Synthesis of P3-M2 Under magnetic stirring at room temperature, butylparaben (100 g, 0.51 mol, 1 eq.), acetonitrile (1 L), 1,6-dibromohexane (150 g, 0.62 mol, 1.2 eq.), and potassium carbonate (105 g, 0.765 mol, 1.5 eq.) were added to a 3 L reaction flask. After reacting for 2 h at room temperature, benzyltrimethylammonium chloride (6.94 g, 0.051 mol, 0.1 eq.) was added, and the mixture was heated to 50 °C and reacted for another 5 h. After the reaction was completed under TLC and HPLC monitoring, the solvent was directly rotary evaporated and concentrated to obtain a yellow viscous semi-solid. The concentrated reaction solution was filtered, and the filtrate was mixed with silica gel and DCM and subjected to column chromatography. The product spot appeared at DCM:MeOH = 40:1. After concentration, 100 g of colorless liquid P3-M1 was obtained, yield: 53%.

[0033] 1H NMR (400 MHz, DMSO-d6) δ 7.94 (J = 8.9 Hz, 2H), 7.02 (d, J = 8.9Hz, 2H), 4.24 (t, J = 6.4 Hz, 2H), 4.06 (t, J = 6.4 Hz, 2H), 3.55 – 3.42 (m,2H), 1.71 – 1.62 (m, 4H), 1.58 – 1.46 (m, 4H), 1.38 – 1.29 (m, 4H), 0.92 (t,J = 7.4 Hz, 3H) ppm. ESI-HRMS (m / z): 277.2 [M-Br]+, calculated value 277.18 [M-Br]+.

[0034] (2) Synthesis of P3 Under magnetic stirring at room temperature, P3-M2 (40 g, 0.11 mol, 1 eq.), acetonitrile (400 ml), and triphenylphosphine (57 g, 0.22 mol, 2 eq.) were added to a 1 L reaction flask. The mixture was heated to reflux and reacted for 36 h. After the reaction was completed under TLC and HPLC monitoring, the reaction solution was concentrated and stirred with silica gel. DCM column chromatography was used to remove triphenylphosphine and a small amount of starting material. The polarity was increased to DCM:MeOH = 20:1 to elute the product. The product was concentrated to obtain 29.5 g of a viscous oily substance with a purity of 99% and a yield of 43%. 1H NMR (400 MHz, DMSO-d6) δ 7.95 – 7.73 (m, 17H), 7.00 (d, J = 8.9Hz, 2H), 4.21 (t, J = 6.5 Hz, 2H), 4.00 (t, J = 6.4 Hz, 2H), 3.72 – 3.58 (m,2H), 1.73 – 1.61 (m, 4H), 1.60 – 1.50 (m, 4H), 1.49 – 1.33 (m, 4H), 0.91 (t,J = 7.4 Hz, 3H)ppm. ESI-HRMS (m / z): 539.3 [M-Br]+, calculated value 539.27 [M-Br]+.

[0035] Synthesis of compound P4

[0036] (1) Synthesis of P4-M2 Under magnetic stirring at room temperature, butylparaben (50 g, 0.25 mol, 1 eq.), acetonitrile (200 mL), 1-bromo-6-chlorohexane (61.6 g, 0.308 mol, 1.2 eq.), potassium carbonate (53.4 g, 0.386 mol, 1.5 eq.), and benzyltrimethylammonium chloride (3.5 g, 0.025 mol, 0.1 eq.) were added to a 3 L reaction flask. The mixture was heated to 80 °C and reacted for 6 h. After the reaction was completed under TLC and HPLC monitoring, the solvent was directly rotary evaporated and concentrated to obtain a yellow viscous semi-solid. The concentrated reaction solution was filtered, and the filtrate was mixed with silica gel and DCM and subjected to column chromatography. The product spot appeared at DCM:MeOH = 50:1. After concentration, 60 g of colorless liquid P4-M1 was obtained, yield: 75%.

[0037] 1H NMR (400 MHz, DMSO-d6) δ 7.88 (J = 8.9 Hz, 2H), 7.01 (d, J = 8.9Hz, 2H), 4.22 (t, J = 6.4 Hz, 2H), 4.02 (t, J = 6.4 Hz, 2H), 3.23 – 3.10 (m,2H), 1.73 – 1.61 (m, 4H), 1.56 – 1.42 (m, 4H), 1.33 – 1.25 (m, 4H), 0.92 (t,J = 7.4 Hz, 3H) ppm. ESI-HRMS (m / z): 277.2 [M-Br]+, calculated value 277.18 [M-Br]+.

[0038] (2) Synthesis of P4 Under room temperature and magnetic stirring, P4-M2 (40 g, 0.11 mol, 1 eq.), acetonitrile (400 ml), and triphenylphosphine (57 g, 0.22 mol, 2 eq.) were added to a 1 L reaction flask. The mixture was heated to reflux and reacted for 36 h. After the reaction was completed under TLC and HPLC monitoring, the reaction solution was concentrated and stirred with silica gel. DCM column chromatography was used to remove triphenylphosphine and a small amount of starting material. The polarity was increased to DCM:MeOH = 20:1 to elute the product. The product was concentrated to obtain 29.5 g of viscous oily substance with a purity of 99% and a yield of 43%.

[0039] 1H NMR (400 MHz, DMSO-d6) δ 8.05 – 7.78 (m, 17H), 7.02 (d, J = 8.9Hz, 2H), 4.28 (t, J = 6.5 Hz, 2H), 4.06 (t, J = 6.4 Hz, 2H), 3.86 – 3.68 (m,2H), 1.75 – 1.60 (m, 4H), 1.58 – 1.48 (m, 4H), 1.45 – 1.31 (m, 4H), 0.93 (t,J = 7.5 Hz, 3H) ppm. ESI-HRMS (m / z): 539.3 [M-Cl]+, calculated value 539.27 [M-Cl]+.

[0040] Synthesis of compound P5

[0041] Under magnetic stirring at room temperature, P3-M2 (50 g, 0.14 mol, 1 eq.), acetonitrile (400 ml), and tributylphosphine (56.6 g, 0.28 mol, 2 eq., CAS: 998-40-3) were added to a 1 L reaction flask. The mixture was heated to reflux and reacted for 36 h. After the reaction was completed under TLC and HPLC monitoring, the reaction solution was concentrated and stirred with silica gel. Tributylphosphine was removed by DCM column chromatography (DCM:MeOH = 50:1). The solution was concentrated to obtain 29.5 g of viscous oily substance with a purity of 99% and a yield of 43%.

[0042] ESI-HRMS (m / z): 479.3 [M-Br]+, calculated value 479.36 [M-Br]+.

[0043] Synthesis of compound P6

[0044] Under magnetic stirring at room temperature, P3-M2 (50 g, 0.14 mol, 1 eq.), acetonitrile (400 ml), and tert-butyldiphenylphosphine (67.8 g, 0.28 mol, 2 eq., CAS: 6002-34-2) were added to a 1 L reaction flask. The mixture was heated to reflux and reacted for 24 h. After the reaction was completed under TLC and HPLC monitoring, the reaction solution was concentrated and stirred with silica gel. DCM column chromatography was used to remove tert-butyldiphenylphosphine by elution. The DCM:MeOH = 50:1 column chromatography was performed, and the solution was concentrated to obtain 48 g of a viscous oily substance with a purity of 95% and a yield of 57%. ESI-HRMS (m / z): 519.3 [M-Br]+, calculated value 519.30 [M-Br]+.

[0045] Synthesis of compound P7

[0046] Under magnetic stirring at room temperature, P3-M2 (50 g, 0.14 mol, 1 eq.), acetonitrile (500 ml), and tris(4-fluorophenyl)phosphine (88 g, 0.28 mol, 2 eq., CAS: 18437-78-0) were added to a 1 L reaction flask. The mixture was heated to reflux and reacted for 24 h. After the reaction was completed under TLC and HPLC monitoring, the reaction solution was concentrated and stirred with silica gel. DCM column chromatography was used to remove tert-butyldiphenylphosphine by elution. The DCM:MeOH = 50:1 column chromatography was performed, and the solution was concentrated to obtain 58 g of a viscous oily substance with a purity of 95% and a yield of 61%. ESI-HRMS (m / z): 593.3 [M-Br]+, calculated value 593.24 [M-Br]+.

[0047] Synthesis of compound P8

[0048] Under magnetic stirring at room temperature, P3-M2 (50 g, 0.14 mol, 1 eq.), acetonitrile (500 ml), and triphenylmethylphosphine (85 g, 0.28 mol, 2 eq., CAS: 1038-95-5) were added to a 1 L reaction flask. The mixture was heated to reflux and reacted for 24 h. After the reaction was completed under TLC and HPLC monitoring, the reaction solution was concentrated and stirred with silica gel. Triphenylmethylphosphine was removed by DCM column chromatography (DCM:MeOH = 50:1). The solution was concentrated to obtain 66 g of a viscous oily substance with a purity of 95% and a yield of 71%. ESI-HRMS (m / z): 581.3 [M-Br]+, calculated value 581.32 [M-Br]+.

[0049] Synthesis of compound P9

[0050] (1) Synthesis of P9-M2 Under magnetic stirring at room temperature, P3SO3 (50 g, 0.26 mol, 1 eq.), acetonitrile (500 mL), 1,4-dibromobutane (112 g, 0.52 mol, 2 eq., CAS: 110-52-1), and potassium carbonate (53.5 g, 0.386 mol, 1.5 eq.) were added to a 3 L reaction flask. Benzyltrimethylammonium chloride (7 g, 0.052 mol, 0.2 eq.) was added, and the mixture was heated to 50 °C and reacted for 16 h. After the reaction was completed under TLC and HPLC monitoring, the solvent was directly rotary evaporated and concentrated to obtain a yellow, viscous semi-solid. The concentrated reaction solution was filtered, and the filtrate was mixed with silica gel and DCM for column chromatography. The product spot appeared at a DCM:MeOH ratio of 30:1. After concentration, 52 g of colorless liquid P9-M1 was obtained, yield: 61%.

[0051] 1H NMR (400 MHz, DMSO-d6) δ 7.97 (J = 8.9 Hz, 2H), 7.06 (d, J = 8.9Hz, 2H), 4.28 (t, J = 6.4 Hz, 2H), 4.07 (t, J = 6.4 Hz, 2H), 3.65 – 3.53 (m,2H), 1.90 – 1.82 (m, 2H), 1.72– 1.58 (m, 2H), 0.94 (t, J = 7.4 Hz, 3H) ppm. ESI-HRMS (m / z): 249.2 [M-Br]+, calculated value 249.15 [M-Br]+.

[0052] (2) Synthesis of P9 Under magnetic stirring at room temperature, P3-M2 (40 g, 0.12 mol, 1 eq.), acetonitrile (500 ml), and triphenylphosphine (64 g, 0.25 mol, 2 eq.) were added to a 1 L reaction flask. The mixture was heated to reflux and reacted for 20 h. After the reaction was completed under TLC and HPLC monitoring, the reaction solution was concentrated and stirred with silica gel. The product was then eluted using DCM column chromatography to remove triphenylphosphine. The polarity was increased to DCM:MeOH = 50:1, and the product was eluted and concentrated to obtain 60 g of viscous oily substance with a purity of 96% and a yield of 83%.

[0053] 1H NMR (400 MHz, DMSO-d6) δ 8.02 (J = 8.9 Hz, 2H), 7.12 (d, J = 8.9Hz, 2H), 4.36 (t, J = 6.4 Hz, 2H), 4.12 (t, J = 6.4 Hz, 2H), 3.76 – 3.62 (m,2H), 1.98 – 1.87 (m, 2H), 1.76– 1.62 (m, 2H), 0.93 (t, J = 7.4 Hz, 3H) ppm. ESI-HRMS (m / z): 511.2 [M-Br]+, calculated value 511.24 [M-Br]+.

[0054] Synthesis of compound P10

[0055] Under magnetic stirring at room temperature, P4-M2 (20 g, 63.9 mmol, 1 eq.), acetonitrile (200 ml), and N,N-dimethyl-n-octylamine (10 g, 63.9 mmol, 1 eq., CAS: 7378-99-6) were added to a 1 L reaction flask. The mixture was heated to reflux and reacted for 36 h. After the reaction was completed under TLC and HPLC monitoring, the reaction solution was concentrated, stirred with silica gel, and purified by DCM:MeOH = 20:1 column chromatography. The solution was then concentrated to obtain 15 g of a viscous oily substance with a purity of 96% and a yield of 50%. ESI-HRMS (m / z): 434.3 [M-Cl]+, calculated value 434.36 [M-Cl]+.

[0056] Synthesis of compound P11

[0057] Under magnetic stirring at room temperature, P4-M2 (20 g, 63.9 mmol, 1 eq.), acetonitrile (200 ml), and N,N-dimethylbenzylamine (8.64 g, 63.9 mmol, 1 eq., CAS: 103-83-3) were added to a 1 L reaction flask. The mixture was heated to reflux and reacted for 24 h. After the reaction was completed under TLC and HPLC monitoring, the reaction solution was concentrated and stirred with silica gel. The mixture was then subjected to DCM:MeOH = 20:1 column chromatography and concentrated to obtain 12 g of viscous oily substance with a purity of 94% and a yield of 42%.

[0058] ESI-HRMS (m / z): 412.3 [M-Cl]+, calculated value 412.28 [M-Cl]+.

[0059] Synthesis of compound P12

[0060] Under room temperature and magnetic stirring, P4-M2 (20 g, 63.9 mmol, 1 eq.), acetonitrile (200 ml), and N,N-dimethylcyclohexylamine (8.13 g, 63.9 mmol, 1 eq., CAS: 98-94-2) were added to a 1 L reaction flask. The mixture was heated to reflux and reacted for 24 h. After the reaction was completed under TLC and HPLC monitoring, the reaction solution was concentrated and stirred with silica gel. The solution was then purified by DCM:MeOH = 20:1 column chromatography and concentrated to obtain 15 g of viscous oily substance with a purity of 92% and a yield of 53%.

[0061] ESI-HRMS (m / z): 404.3 [M-Cl]+, calculated value 404.32 [M-Cl]+. II. Microbial sterilization rate test

[0062] Preparation of antibacterial plastic test samples and testing of their antibacterial properties: Take 100 parts of polystyrene powder, and in each example, 1.5 parts, 2 parts, or 3 parts of the product powder, and mix them evenly. Add the mixture to a micro twin-screw extruder, process at a temperature of 150℃-250℃, and melt-blend and granulate. Then, prepare 50mm*50mm test samples at an injection molding temperature of 190℃-210℃. The test method is in accordance with 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.

[0063] The results of the antibacterial activity tests of the compounds are as follows (Table 1):

[0064] Note: No bacterial colonies grew in the negative control group.

[0065] In conclusion, the cationic antibacterial derivatives of butylparaben exhibit excellent bactericidal effects against *Escherichia coli*, *Candida albicans*, *Staphylococcus aureus*, *Pseudomonas aeruginosa*, and *Aspergillus niger*. They are particularly effective against *Pseudomonas aeruginosa*, against which butylparaben has relatively weak inhibitory activity, thus expanding the antibacterial spectrum and application range of butylparaben. Specifically, P3 shows excellent bactericidal activity against *Escherichia coli*, *Candida albicans*, *Staphylococcus aureus*, *Pseudomonas aeruginosa*, and *Aspergillus niger*, while P1-P12 all show excellent bactericidal activity against *Pseudomonas aeruginosa*.

[0066] 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 butylparaben cationic salt derivative, characterized in that, The general structural formula is shown in equation P. In the formula, R is selected from C1-C12 straight-chain or branched alkyl groups with substituents, five- or six-membered cycloalkyl groups with substituents, or aryl groups, wherein the substituent in the C1-C12 straight-chain or branched alkyl groups with substituents, or five- or six-membered cycloalkyl groups with substituents, is at least one hydrogen, halogen, or C1-C6 alkyl; A is selected from -CO- or -CH2-; Q is selected from nitrogen or phosphine; X is selected from chlorine or bromine; n = 0-10.

2. The butylparaben cationic salt derivative according to claim 1, characterized in that, The general structural formula is shown in equation P-01. In the formula, R is selected from C1-C12 straight-chain or branched alkyl groups with substituents, five- or six-membered cycloalkyl groups with substituents, or aryl groups, wherein the substituent in the C1-C12 straight-chain or branched alkyl groups with substituents, or five- or six-membered cycloalkyl groups with substituents, is at least one hydrogen, halogen, or C1-C6 alkyl; A is selected from -CO- or -CH2-; X is selected from chlorine or bromine; n=0-10.

3. The butylparaben quaternary phosphine salt derivative according to claim 2, characterized in that, The general structural formula is shown in formula P-02. In the formula, A is selected from -CO- or -CH2-; X is selected from chlorine or bromine; n = 1-6.

4. The butylparaben cationic salt derivative according to claim 1, characterized in that, The general structural formula is shown in equation P-03. In the formula, R is selected from substituent C1-C12 straight-chain or branched alkyl groups, or substituent cycloalkyl groups, wherein the substituent C1-C12 straight-chain or branched alkyl groups are selected; A is selected from -CO- or -CH2-; X is selected from chlorine or bromine; n=0-10.

5. The butylparaben cationic salt derivative according to any one of claims 1-4, characterized in that, The structures of representative compounds are as follows: .

6. A method for preparing a butylparaben cationic salt derivative, characterized in that, Includes the following steps, The chemical reaction equation is as follows: , (1) Compound SO1 and compound SO2 are added to a reaction vessel in sequence. The reaction is carried out in a first reaction solvent at a temperature of 25℃-120℃ for 3h-36h. After the reaction is complete, the mixture is cooled, concentrated, and recrystallized from acetonitrile or ethyl acetate to obtain compound M1. The first reaction solvent is ethyl acetate, acetonitrile, or toluene. (2) In the reaction vessel, compound M1 and compound SO3 undergo a condensation reaction in the second reaction solvent under the action of a condensing agent. The reaction temperature is 0-100℃ and the reaction time is 3h-36h. After the reaction is complete, the mixture is cooled, concentrated, and recrystallized to obtain the butylparaben ester derivative. The second reaction solvent is selected from one or more of acetonitrile, dichloromethane, tetrahydrofuran, DMF, DMSO, 1,4-dioxane, ethyl acetate, and 1,2-dichloroethane. The condensing agent is selected from one or more of DCC, N,N'-diisopropylcarbodiimide, EDC, EDCI, HATU, HBTU, and TBTU. In the formula, R is selected from C1-C12 straight-chain or branched alkyl groups with substituents, five- or six-membered cycloalkyl groups with substituents, or aryl groups, wherein the substituent in the C1-C12 straight-chain or branched alkyl groups with substituents, or five- or six-membered cycloalkyl groups with substituents, is at least one hydrogen, halogen, or C1-C6 alkyl; Q is selected from nitrogen or phosphine; A is selected from -CO- or -CH2-; X is selected from chlorine or bromine; n = 0-10.

7. A method for preparing a butylparaben cationic salt derivative, characterized in that, Includes the following steps, The chemical reaction equation is as follows: , (1) Compound SO3 and compound SO4 were added to the first reaction solvent in a reaction vessel. The reaction temperature was 0℃-120℃ and the reaction time was 3h-36h. After the reaction was complete, the mixture was cooled, concentrated, recrystallized or subjected to column chromatography to obtain compound M2. (2) In a reaction vessel, compound M2 and compound SO1 are reacted in the first reaction solvent acetonitrile or toluene at a temperature of 0℃-150℃ for 3h-36h. After the reaction is complete, the mixture is cooled, concentrated, and recrystallized to obtain compound P. In the formula, R is selected from C1-C12 straight-chain or branched alkyl groups with substituents, five- or six-membered cycloalkyl groups with substituents, or aryl groups, wherein the substituent in the C1-C12 straight-chain or branched alkyl groups with substituents, or five- or six-membered cycloalkyl groups with substituents, is at least one hydrogen, halogen, or C1-C6 alkyl; Q is selected from nitrogen or phosphine; A is selected from -CO- or -CH2-; X is selected from chlorine or bromine; n = 0-10.

8. A resin, characterized in that, Add the butylparaben cationic salt derivative as claimed in any one of claims 1-5 or the butylparaben cationic salt derivative prepared by the method of any one of claims 6-7.

9. The butylparaben cationic salt derivative according to any one of claims 1-5 or the butylparaben cationic salt derivative according to any one of claims 6-7, or the resin according to claim 8, as an antibacterial agent or antimicrobial drug.

10. The application of the butyl paraben cationic salt derivative according to claim 9 as an antibacterial agent, characterized in that, The aforementioned applications as antibacterial agents or antimicrobial drugs include applications against Escherichia coli, Candida albicans, Pseudomonas aeruginosa, Aspergillus niger, Staphylococcus aureus, and Bacillus subtilis.

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