Quaternary ammonium salt composite bactericide capable of efficiently killing fungi and preparation method of quaternary ammonium salt composite bactericide

Abstract

The invention discloses a quaternary ammonium salt composite bactericide capable of efficiently killing fungi and a preparation method of the quaternary ammonium salt composite bactericide. The preparation method comprises the following steps: S1, preparing zinc oxide nanoparticles; s2, adding the prepared zinc oxide nanoparticles into a buffer solution, adding dopamine hydrochloride, and preparing modified zinc oxide after the reaction is finished; s3, adding the modified zinc oxide and 1-vinyl imidazole into N, N-dimethylformamide, and carrying out a reaction for 2 to 2.5 h so as to obtain modified zinc oxide; s4, under the nitrogen atmosphere, adding the modified zinc oxide and 1-bromopentane into cyclohexane, and heating to 50 DEG C to prepare the quaternary ammonium salt composite bactericide; the sterilizing effect of the sterilizing agent is remarkably improved through cooperation of quaternary ammonium salt and zinc oxide nanoparticles, the sterilizing effect of the composite sterilizing agent is remarkably improved through the synergistic sterilizing performance of quaternary ammonium salt and zinc oxide by inoculating imidazole quaternary ammonium salt to the surface of zinc oxide, and the heat stability of the composite sterilizing agent can be remarkably improved through introduced imidazole groups.

Description

Technical Field

[0001] The invention relates to the technical field of fungicides, and in particular to a quaternary ammonium salt composite fungicide and a preparation method thereof. Background Art

[0002] In daily life, various surfaces are vulnerable to invasion by microorganisms (bacteria, viruses, etc.) in the air and solutions, which may endanger human health. Potentially harmful bacteria are everywhere around us. For example, talking, coughing, sneezing, and even breathing can produce water vapor droplets containing bacteria. Similarly, bacteria present in liquids (for example, drinking water and catheter fluids in hospitals) can attach to the inner surfaces of blood vessels and pipes and grow and multiply. When the number of cells increases on the surface, microbial cells usually begin to form biofilms, which are composed of a polysaccharide matrix in which the cells are embedded. This biofilm allows microbial cells to survive in harsh conditions, and the embedded cells can be up to 1,000 times less sensitive to most antibiotics and other biocides, which can become a source of stubborn infections.

[0003] Quaternary ammonium salt fungicide is a broad-spectrum fungicide that can effectively kill bacteria, molds, yeasts and other microorganisms. It also has a good inhibitory effect on intestinal pathogens and bacteria contaminated in food. It is highly efficient and can kill or inhibit microorganisms in a short period of time, effectively preventing food spoilage, bacterial infection and other problems. However, quaternary ammonium salts have poor thermal stability, so how to improve the heat resistance of quaternary ammonium salt fungicides and further improve the bactericidal effect is a technical problem that needs to be solved urgently. Summary of the invention

[0004] In order to solve the above technical problems, the present invention provides a quaternary ammonium salt composite fungicide and a preparation method thereof.

[0005] The purpose of the present invention can be achieved through the following technical solutions:

[0006] A method for preparing a highly effective quaternary ammonium salt composite fungicide for killing fungi comprises the following steps:

[0007] Step S1, adding zinc acetate dihydrate and tetrabutylammonium bromide to anhydrous ethanol, heating and refluxing for reaction for 1 hour, adding 10% by mass potassium hydroxide ethanol solution after the reaction, continuing stirring and reacting for 12 hours, centrifuging and precipitating after the reaction, washing three times with methanol to obtain zinc oxide nanoparticles, and controlling the dosage ratio of zinc acetate dihydrate, tetrabutylammonium bromide, potassium hydroxide and anhydrous ethanol to be 4.10-4.20g:6.0-6.05g:0.8-1g:20-30mL.

[0008] Step S2, adding the prepared zinc oxide nanoparticles to a Tris-buffer buffer solution of pH=8.5, stirring at a uniform speed and adding dopamine hydrochloride, stirring at a uniform speed and reacting for 2 hours at room temperature, centrifuging after the reaction is completed, washing the filter cake three times with deionized water to obtain modified zinc oxide, and controlling the dosage ratio of zinc oxide nanoparticles, Tris-buffer buffer solution and dopamine hydrochloride to be 2-5g:100-150mL:0.2-0.5g;

[0009] In step S2, dopamine hydrochloride is polymerized on the surface of zinc oxide nanoparticles to form polydopamine to obtain modified zinc oxide.

[0010] Step S3, adding modified zinc oxide and 1-vinylimidazole to N,N-dimethylformamide, stirring at a uniform speed and adding 1,8-diazabicycloundec-7-ene, continuing stirring and reacting for 2-2.5h to obtain modified zinc oxide, wherein the amount ratio of modified zinc oxide, 1-vinylimidazole and N,N-dimethylformamide is controlled to be 2-2.5g:1-1.2g:100mL, and the amount of 1,8-diazabicycloundec-7-ene is 3-5% of the total weight of modified zinc oxide and 1-vinylimidazole;

[0011] In step S3, the amino group on the modified zinc oxide and the carbon-carbon double bond on 1-vinylimidazole undergo Michael addition reaction, thereby grafting 1-vinylimidazole onto the surface of zinc oxide.

[0012] Step S4, under a nitrogen atmosphere, adding modified zinc oxide and 1-bromopentane to cyclohexane, heating to 50° C., stirring at a uniform speed and reacting for 24 hours, filtering and washing to obtain a quaternary ammonium salt composite fungicide, wherein the dosage ratio of modified zinc oxide, 1-bromopentane and cyclohexane is controlled to be 1-1.8 g: 2.25-2.45 g: 10-20 mL.

[0013] In step S4, the imidazole group on the modified zinc oxide undergoes a quaternization reaction with 1-bromopentane, and imidazole quaternary ammonium salt is connected to the surface of zinc oxide. The synergistic bactericidal property of the quaternary ammonium salt and zinc oxide significantly improves the bactericidal effect of the composite bactericide, and the introduced imidazole group can significantly improve the thermal stability of the composite bactericide.

[0014] A quaternary ammonium salt composite fungicide is prepared by the above preparation method.

[0015] The invention has the beneficial effects as follows: a quaternary ammonium salt composite bactericide is prepared by the invention, and the bactericidal effect of the bactericide is significantly improved by the quaternary ammonium salt and zinc oxide nanoparticles. In the preparation process of the bactericide, dopamine hydrochloride is firstly polymerized on the surface of zinc oxide nanoparticles to form polydopamine to prepare modified zinc oxide, and then the amino group on the modified zinc oxide and the carbon-carbon double bond on 1-vinyl imidazole are subjected to Michael addition reaction, and then 1-vinyl imidazole is grafted on the surface of zinc oxide, and finally the imidazole group on the modified zinc oxide is subjected to quaternization reaction with 1-bromopentane, and the imidazole quaternary ammonium salt is connected to the surface of zinc oxide, and the bactericidal effect of the composite bactericide is significantly improved by the synergistic bactericidal property of the quaternary ammonium salt and zinc oxide, and the introduced imidazole group can significantly improve the thermal stability of the composite bactericide. DETAILED DESCRIPTION

[0016] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0017] Embodiment 1: A method for preparing a highly effective fungicidal quaternary ammonium salt composite fungicide, comprising the following steps:

[0018] Step S1, adding zinc acetate dihydrate and tetrabutylammonium bromide to anhydrous ethanol, heating and reflux reaction for 1h, adding 10% by mass potassium hydroxide ethanol solution after the reaction, continuing stirring and reacting for 12h, centrifuging and precipitating after the reaction, washing three times with methanol to obtain zinc oxide nanoparticles, and controlling the dosage ratio of zinc acetate dihydrate, tetrabutylammonium bromide, potassium hydroxide and anhydrous ethanol to be 4.10g:6.0g:0.8g:20mL.

[0019] Step S2, adding the prepared zinc oxide nanoparticles to a Tris-buffer buffer solution of pH=8.5, stirring at a uniform speed and adding dopamine hydrochloride, stirring at a uniform speed and reacting for 2 hours at room temperature, centrifuging after the reaction, washing the filter cake three times with deionized water to obtain modified zinc oxide, and controlling the dosage ratio of zinc oxide nanoparticles, Tris-buffer buffer solution and dopamine hydrochloride to be 2g:100mL:0.2g;

[0020] Step S3, adding modified zinc oxide and 1-vinylimidazole to N,N-dimethylformamide, stirring at a uniform speed and adding 1,8-diazabicycloundec-7-ene, continuing stirring and reacting for 2-2.5 hours to obtain modified zinc oxide, wherein the amount ratio of modified zinc oxide, 1-vinylimidazole and N,N-dimethylformamide is controlled to be 2g:1g:100mL, and the amount of 1,8-diazabicycloundec-7-ene is 3% of the total weight of modified zinc oxide and 1-vinylimidazole;

[0021] Step S4, under a nitrogen atmosphere, adding modified zinc oxide and 1-bromopentane to cyclohexane, heating to 50°C, stirring at a uniform speed and reacting for 24 hours, filtering and washing to obtain a quaternary ammonium salt composite fungicide, wherein the dosage ratio of modified zinc oxide, 1-bromopentane and cyclohexane is controlled to be 1 g:2.25 g:10 mL.

[0022] After 14 days of high temperature testing at 54°C, the effective content decreased by less than 5%.

[0023] After 90 days of high temperature testing at 37°C, the effective content decreased by less than 10%.

[0024] Embodiment 2: A method for preparing a highly effective fungicidal quaternary ammonium salt composite fungicide, comprising the following steps:

[0025] Step S1, adding zinc acetate dihydrate and tetrabutylammonium bromide to anhydrous ethanol, heating and reflux for reaction for 1 hour, adding 10% by mass potassium hydroxide ethanol solution after the reaction, continuing stirring and reacting for 12 hours, centrifuging and precipitating after the reaction, washing three times with methanol to obtain zinc oxide nanoparticles, and controlling the dosage ratio of zinc acetate dihydrate, tetrabutylammonium bromide, potassium hydroxide and anhydrous ethanol to be 4.12g:6.02g:0.8g:25mL.

[0026] Step S2, adding the prepared zinc oxide nanoparticles to a Tris-buffer buffer solution of pH=8.5, stirring at a uniform speed and adding dopamine hydrochloride, stirring at a uniform speed and reacting for 2 hours at room temperature, centrifuging after the reaction is completed, washing the filter cake three times with deionized water to obtain modified zinc oxide, and controlling the dosage ratio of zinc oxide nanoparticles, Tris-buffer buffer solution and dopamine hydrochloride to be 3g:120mL:0.3g;

[0027] Step S3, adding modified zinc oxide and 1-vinylimidazole to N, N-dimethylformamide, stirring at a uniform speed and adding 1,8-diazabicycloundec-7-ene, continuing stirring and reacting for 2.2 hours to obtain modified zinc oxide, wherein the amount ratio of modified zinc oxide, 1-vinylimidazole and N, N-dimethylformamide is controlled to be 2.2 g:1.1 g:100 mL, and the amount of 1,8-diazabicycloundec-7-ene is 4% of the total weight of modified zinc oxide and 1-vinylimidazole;

[0028] Step S4, under a nitrogen atmosphere, adding modified zinc oxide and 1-bromopentane to cyclohexane, heating to 50°C, stirring at a uniform speed and reacting for 24 hours, filtering and washing to obtain a quaternary ammonium salt composite fungicide, wherein the amount ratio of modified zinc oxide, 1-bromopentane and cyclohexane is controlled to be 1.7 g:2.30 g:15 mL.

[0029] After 14 days of high temperature testing at 54°C, the effective content decreased by less than 5%.

[0030] After 90 days of high temperature testing at 37°C, the effective content decreased by less than 10%.

[0031] Embodiment 3: A method for preparing a highly effective fungicidal quaternary ammonium salt composite fungicide, comprising the following steps:

[0032] Step S1, adding zinc acetate dihydrate and tetrabutylammonium bromide to anhydrous ethanol, heating and reflux for reaction for 1 hour, adding 10% by mass potassium hydroxide ethanol solution after the reaction, continuing stirring and reacting for 12 hours, centrifuging and precipitating after the reaction, washing three times with methanol to obtain zinc oxide nanoparticles, and controlling the dosage ratio of zinc acetate dihydrate, tetrabutylammonium bromide, potassium hydroxide and anhydrous ethanol to be 4.18g:6.04g:1g:30mL.

[0033] Step S2, adding the prepared zinc oxide nanoparticles to a Tris-buffer buffer solution of pH=8.5, stirring at a uniform speed and adding dopamine hydrochloride, stirring at a uniform speed and reacting for 2 hours at room temperature, centrifuging after the reaction is completed, washing the filter cake three times with deionized water to obtain modified zinc oxide, and controlling the dosage ratio of zinc oxide nanoparticles, Tris-buffer buffer solution and dopamine hydrochloride to be 4g:150mL:0.4g;

[0034] Step S3, adding modified zinc oxide and 1-vinylimidazole to N, N-dimethylformamide, stirring at a uniform speed and adding 1,8-diazabicycloundec-7-ene, continuing stirring and reacting for 2.4 hours to obtain modified zinc oxide, wherein the amount ratio of modified zinc oxide, 1-vinylimidazole and N, N-dimethylformamide is controlled to be 2.4 g:1.2 g:100 mL, and the amount of 1,8-diazabicycloundec-7-ene is 5% of the total weight of modified zinc oxide and 1-vinylimidazole;

[0035] Step S4, under a nitrogen atmosphere, adding modified zinc oxide and 1-bromopentane to cyclohexane, heating to 50°C, stirring at a uniform speed and reacting for 24 hours, filtering and washing to obtain a quaternary ammonium salt composite fungicide, wherein the dosage ratio of modified zinc oxide, 1-bromopentane and cyclohexane is controlled to be 1.6 g:2.45 g:20 mL.

[0036] After 14 days of high temperature testing at 54°C, the effective content decreased by less than 5%.

[0037] After 90 days of high temperature testing at 37°C, the effective content decreased by less than 10%.

[0038] Embodiment 4: A method for preparing a highly effective quaternary ammonium salt composite fungicide for killing fungi, comprising the following steps:

[0039] Step S1, adding zinc acetate dihydrate and tetrabutylammonium bromide to anhydrous ethanol, heating and reflux for reaction for 1 hour, adding 10% by mass potassium hydroxide ethanol solution after the reaction, continuing stirring and reacting for 12 hours, centrifuging and precipitating after the reaction, washing three times with methanol to obtain zinc oxide nanoparticles, and controlling the dosage ratio of zinc acetate dihydrate, tetrabutylammonium bromide, potassium hydroxide and anhydrous ethanol to be 4.20g:6.05g:1g:30mL.

[0040] Step S2, adding the prepared zinc oxide nanoparticles to a Tris-buffer buffer solution of pH=8.5, stirring at a uniform speed and adding dopamine hydrochloride, stirring at a uniform speed and reacting for 2 hours at room temperature, centrifuging after the reaction, washing the filter cake three times with deionized water to obtain modified zinc oxide, and controlling the dosage ratio of zinc oxide nanoparticles, Tris-buffer buffer solution and dopamine hydrochloride to be 5g:150mL:0.5g;

[0041] Step S3, adding modified zinc oxide and 1-vinylimidazole to N,N-dimethylformamide, stirring at a uniform speed and adding 1,8-diazabicycloundec-7-ene, continuing stirring and reacting for 2.5 hours to obtain modified zinc oxide, wherein the amount ratio of modified zinc oxide, 1-vinylimidazole and N,N-dimethylformamide is controlled to be 2.5g:1.2g:100mL, and the amount of 1,8-diazabicycloundec-7-ene is 5% of the total weight of modified zinc oxide and 1-vinylimidazole;

[0042] Step S4, under a nitrogen atmosphere, adding modified zinc oxide and 1-bromopentane to cyclohexane, heating to 50°C, stirring at a uniform speed and reacting for 24 hours, filtering and washing to obtain a quaternary ammonium salt composite fungicide, wherein the amount ratio of modified zinc oxide, 1-bromopentane and cyclohexane is controlled to be 1.8 g:2.45 g:20 mL.

[0043] After 14 days of high temperature testing at 54°C, the effective content decreased by less than 5%.

[0044] After 90 days of high temperature testing at 37°C, the effective content decreased by less than 10%.

[0045] Comparative Example 1: Compared with Example 1, this comparative example uses nano zinc oxide instead of the composite fungicide, and the rest is the same as Example 1.

[0046] Comparative Example 2: Compared with Example 1, this comparative example uses a commercially available quaternary ammonium salt instead of the composite fungicide, and the rest is the same as Example 1.

[0047] The bactericidal properties of the bactericides prepared in Examples 1-4 and Comparative Examples 1-2 were tested, and the results are shown in Table 1 below:

[0048] According to the Technical Specifications for Disinfection (2002 Edition), "2.1 Technical Specifications for Inspection of Disinfection Effect of Disinfection Products", the bacteria and fungi killing rates of the prepared fungicides were tested at a concentration of 0.1% for 30 seconds; the virus killing rates of the prepared fungicides were tested at a concentration of 0.1% for 5 minutes.

[0049] Inspection basis:

[0050] "Technical Specifications for Disinfection" (2002 Edition) 2.1.1.5 Neutralizer Identification Test

[0051] "Technical Specifications for Disinfection" (2002 Edition) 2.1.1.7 Quantitative Bacterial Killing Test

[0052] Evaluation basis:

[0053] "Technical Specifications for Disinfection" (2002 Edition) 2.1.1.5 Neutralizer Identification Test

[0054] "Technical Specifications for Disinfection" (2002 Edition) 2.1.1.7 Quantitative Bacterial Killing Test

[0055] Table 1 Escherichia coli killing rate (%) Staphylococcus aureus killing rate (%) Candida albicans killing rate (%) Varicella-zoster killing rate (%) Example 1 ＞99.9999 ＞99.9999 ＞99.999 ＞99.99 Example 2 ＞99.9999 ＞99.9999 ＞99.999 ＞99.99 Example 3 ＞99.9999 ＞99.9999 ＞99.999 ＞99.99 Example 4 ＞99.9999 ＞99.9999 ＞99.999 ＞99.99 Comparative Example 1 99.8 98.5 96.6 90.1 Comparative Example 2 99.93 99.92 99.81 95.5

[0056] It can be seen from Table 1 above that the composite fungicides prepared in Examples 1-4 of the present invention have excellent fungicidal properties.

[0057] The above contents are merely examples and explanations of the concept of the present invention. The technicians in this technical field may make various modifications or additions to the specific embodiments described or replace them in a similar manner. As long as they do not deviate from the concept of the invention or exceed the scope defined by the claims, they should all fall within the protection scope of the present invention.

Claims

1. A method for preparing a quaternary ammonium salt composite fungicide with high efficiency in killing fungi, characterized in that: The steps include: Step S1, adding zinc acetate dihydrate and tetrabutylammonium bromide to anhydrous ethanol, heating and reflux for reaction for 1 hour, adding 10% by mass potassium hydroxide ethanol solution after the reaction, continuing stirring and reacting for 12 hours, centrifuging and precipitating after the reaction, and washing with methanol three times to obtain zinc oxide nanoparticles; Step S2, adding the prepared zinc oxide nanoparticles into a Tris-buffer buffer at pH=8.5, stirring at a uniform speed and adding dopamine hydrochloride, stirring at a uniform speed and reacting at room temperature for 2 hours, centrifuging after the reaction is completed, and washing the filter cake three times with deionized water to obtain modified zinc oxide; Step S3, adding modified zinc oxide and 1-vinylimidazole to N,N-dimethylformamide, stirring at a uniform speed and adding 1,8-diazabicycloundec-7-ene, continuing stirring and reacting for 2-2.5 hours to obtain modified zinc oxide; Step S4, under a nitrogen atmosphere, adding modified zinc oxide and 1-bromopentane into cyclohexane, heating to 50° C., stirring at a uniform speed and reacting for 24 hours, filtering and washing to obtain a quaternary ammonium salt composite fungicide.

2. The method for preparing a highly effective fungicidal quaternary ammonium salt composite bactericide according to claim 1, characterized in that: In step S1, the dosage ratio of zinc acetate dihydrate, tetrabutylammonium bromide, potassium hydroxide and anhydrous ethanol is controlled to be 4.10-4.20 g: 6.0-6.05 g: 0.8-1 g: 20-30 mL.

3. The method for preparing a highly effective fungicidal quaternary ammonium salt composite bactericide according to claim 1, characterized in that: In step S2, the dosage ratio of zinc oxide nanoparticles, Tris-buffer buffer and dopamine hydrochloride is controlled to be 2-5 g: 100-150 mL: 0.2-0.5 g.

4. The method for preparing a highly effective fungicidal quaternary ammonium salt composite bactericide according to claim 1, characterized in that: In step S3, the dosage ratio of modified zinc oxide, 1-vinylimidazole and N,N-dimethylformamide is controlled to be 2-2.5 g: 1-1.2 g: 100 mL, and the dosage of 1,8-diazabicycloundec-7-ene is 3-5% of the total weight of modified zinc oxide and 1-vinylimidazole.

5. The method for preparing a highly effective fungicidal quaternary ammonium salt composite bactericide according to claim 1, characterized in that: In step S4, the dosage ratio of modified zinc oxide, 1-bromopentane and cyclohexane is controlled to be 1-1.8 g: 2.25-2.45 g: 10-20 mL.

6. A quaternary ammonium salt composite fungicide, characterized in that: Prepared by the preparation method according to any one of claims 1 to 5.