Isothiazolinone compound with high antibacterial activity and low ecological toxicity as well as preparation method and application of isothiazolinone compound

Abstract

The invention discloses an isothiazolinone compound with high antibacterial activity and low ecological toxicity, and relates to the field of marine antifouling paints, and the chemical name of the isothiazolinone compound is 2-butyl-4, 5-dichloroisothiazolin-3 (2H)-ketone or 4, 5-dichloro-2-(2-(2-methoxyethoxy) ethyl) isothiazolin-3 (2H)-ketone. The preparation method comprises the following steps: S1, reacting a compound 1 with oxalyl chloride in a solvent environment by taking DMF as a catalyst to obtain an intermediate product 2; s2, reacting the intermediate product 2 with an amine compound and N, N-diisopropylethylamine in a solvent environment to obtain an intermediate product 3; s3, reacting the intermediate product 3 with sulfonyl chloride in a solvent environment to obtain a target compound. The isothiazolinone bacteriostatic agent which is high in activity, low in toxicity and environmentally friendly is synthesized and is applied to marine pollution resistance, and the ecological safety is greatly improved.

Description

Technical Field

[0001] The invention relates to the field of marine antifouling coatings, and in particular to an isothiazolinone compound with high antibacterial activity and low ecotoxicity, and a preparation method and application thereof. Background Art

[0002] Isothiazolinone compounds have a broad spectrum of inhibitory effects on microbial growth and are widely added as preservatives and fungicides to personal care products, household products, coatings, adhesives and other products. At present, the largest production and use of isothiazolinones are methylisothiazolinone (MIT), methylchloroisothiazolinone (MCI), octylisothiazolinone (OIT), benzisothiazolinone (BIT) and 4,5-dichloro-n-octyl-4-isothiazolin-3-one (DCOIT). Among them, DCOIT is used in the commercial antifouling promoter SeaNine 211 due to its high efficiency and broad-spectrum antibacterial activity. It is an active ingredient in a variety of antifouling coatings to inhibit the attachment of fouling organisms (such as barnacles, mussels, tubeworms and seaweed) in the marine environment to the surfaces of artificial buildings and ships, reduce the increase in ship weight and navigation resistance caused by biological fouling, and reduce the huge economic losses and ecological disturbances caused by it. However, in addition to having efficient antibacterial activity, an excellent fungicide must also be harmless or low-toxic to non-target organisms and environmentally friendly.

[0003] Current research has found that these commercial isothiazolinone compounds are gradually released into the environment during large-scale production, use and processing, inducing a variety of toxic effects, including sensitization and contact dermatitis, neurotoxicity, reproductive endocrine toxicity and transgenerational toxicity, posing a potential threat to the health of humans and other organisms. For example, DCOIT has high lipophilicity and bioaccumulation; in oyster samples from Awaji Island, Japan, the cumulative concentration of DCOIT was detected to reach 0.3μg / kg (wet weight). At the same time, many studies have shown that DCOIT has significant acute toxicity to a variety of non-target organisms in the water body (such as bacteria, phytoplankton, zooplankton and bony fish) when used as an antifouling agent.

[0004] There have been related studies on the synthesis and sterilization application of isothiazolinone compounds in the prior art, but most of the synthesis steps are complicated, the raw materials are expensive, or the yield purity is not high, which is not conducive to further promotion and application as a bactericide. Therefore, it is necessary to develop an isothiazolinone compound with high antibacterial activity, low ecotoxicity, and environmental friendliness, as well as a preparation method and application in sterilization, marine antifouling, etc. Summary of the invention

[0005] The purpose of the present invention is to solve the shortcomings of the above-mentioned background technology and provide an isothiazolinone compound with high antibacterial activity, low ecotoxicity and environmental friendliness, as well as a preparation method thereof and its application in sterilization and marine antifouling. The preparation method is simple, without special requirements such as high temperature, high pressure or sensitive reagents, and the sterilization effect is not only more prominent than the existing commercial "star product" - DCOIT, but also has lower toxicity to non-target organisms.

[0006] The technical solution of the present invention is: an isothiazolinone compound with high antibacterial activity and low ecotoxicity, the structure of which isothiazolinone compound is shown as follows (I):

[0007]

[0008] Wherein, the substituent R is R1 or R2,

[0009] The R1 is -CH2CH2CH2CH3, and the R2 is -CH2CH2OCH2CH2OCH3.

[0010] When R is R1, the structure of the isothiazolinone compound is shown in I-1 below, and the chemical name is 2-butyl-4,5-dichloroisothiazol-3(2H)-one;

[0011] When R is R2, the structure of the isothiazolinone compound is shown in the following I-2, and the chemical name is 4,5-dichloro-2-(2-(2-methoxyethoxy)ethyl)isothiazol-3(2H)-one.

[0012]

[0013] The present invention also provides a method for preparing the above-mentioned isothiazolinone compounds with high antibacterial activity and low ecotoxicity. The synthetic route is as follows:

[0014]

[0015] The preparation method comprises the following steps:

[0016] S1, reacting compound 1 with oxalyl chloride (COCl) 2 in a solvent environment with N,N-dimethylformamide DMF as a catalyst to obtain an intermediate product 2;

[0017] S2, reacting the intermediate product 2 with an amine compound R-NH2 and N,N-diisopropylethylamine DIEA in a solvent environment to obtain an intermediate product 3;

[0018] S3. React the intermediate product 3 with sulfonyl chloride SO2Cl2 in a solvent environment to obtain the target compound I.

[0019] Preferably, in step S1, compound 1 is reacted with oxalyl chloride (COCl) 2 in a solvent environment with N,N-dimethylformamide DMF as a catalyst, specifically comprising:

[0020] Compound 1 is placed in a solvent and DMF is added. The reaction system is cooled to 0°C and oxalyl chloride (COCl) 2 is added dropwise. After the addition is complete, the entire reaction system is stirred at room temperature for 5 to 8 hours. After the reaction is complete, a solid intermediate product 2 is obtained through separation and purification.

[0021] Preferably, in step S2, the intermediate product 2 is reacted with an amine compound R-NH2 and N,N-diisopropylethylamine DIEA in a solvent environment, specifically comprising:

[0022] The amine compound R-NH2 is placed in a solvent and DIEA is added. The reaction system is cooled to 0°C and then the intermediate product 2 is slowly added. After the addition is completed, the entire reaction system is stirred at room temperature for 5 to 8 hours. After the reaction is completed, the solid intermediate product 3 is obtained by separation and purification.

[0023] Preferably, in step S3, the intermediate product 3 is reacted with sulfonyl chloride SO2Cl2 in a solvent environment, specifically comprising:

[0024] The intermediate product 3 is placed in a solvent, the reaction system is cooled to 0°C and then sulfonyl chloride SO2Cl2 is slowly added dropwise. After the addition is completed, the entire reaction system is stirred at room temperature for 4 to 6 hours. After the reaction is completed, the solid target compound I is obtained by separation and purification.

[0025] Preferably, the molar ratio of the compound 1, oxalyl chloride (COCl) 2, and the catalyst DMF is 1:3-3.5:0.1-0.3.

[0026] The molar ratio of the intermediate product 2, the amine compound R-NH2 and DIEA is 1:2-2.5:4-4.5.

[0027] The molar ratio of the intermediate product 3 and sulfonyl chloride SO2Cl2 is 1:20-25.

[0028] Furthermore, the molar ratio of the compound 1, oxalyl chloride (COCl) 2, and the catalyst DMF is 1:3:0.1.

[0029] The molar ratio of the intermediate product 2, the amine compound R-NH2 and DIEA is 1:2:4.

[0030] The molar ratio of the intermediate product 3, sulfonyl chloride and SO2Cl2 is 1:20.

[0031] Furthermore, R in the amine compound R-NH2 is consistent with R in the target compound I, specifically including:

[0032] When R in the target compound I is R1, the amine compound is n-butylamine R1-NH2;

[0033] When R in the target compound I is R2, the amine compound is 2-(2-methoxyethoxy)ethane-1-amine R2-NH2.

[0034] In the above steps S1-S3, the solvent is dichloromethane DCM or ethyl acetate.

[0035] The chemical name of compound 1 is 3,3'-disulfanyldipropionic acid.

[0036] The present invention also provides the use of the above isothiazolinone compounds with high antibacterial activity and low ecotoxicity as antibacterial agents for use in marine antifouling coatings.

[0037] The beneficial effects of the present invention are:

[0038] 1. The present invention synthesizes an isothiazolinone antibacterial agent with high activity, low toxicity and environmental friendliness, and applies it to marine antifouling.

[0039] 2. The synthesis process is relatively mild, the steps are simple, the raw material cost is low, and the purity of the obtained product is as high as over 97.8%.

[0040] 3. Compared with existing commercial isothiazolinone antibacterial agents, the present invention focuses on isothiazolinone compounds with shorter side chains and develops their advantages such as high activity and low toxicity. The median lethal dose of compounds I-1 and I-2 for zebrafish embryos is approximately 1.48 times and 7.27 times that of DCOIT. Therefore, the lethality of compounds I-1 and I-2 for zebrafish embryos is significantly lower than that of DCOIT, and the ecological safety is greatly improved. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] The drawings herein are incorporated into the specification and constitute a part of the specification, illustrate embodiments consistent with the present application, and are used together with the specification to explain the principles of the present application. In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the drawings required for use in the embodiments or the prior art description will be briefly introduced below. Obviously, for ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative labor.

[0042] Figure 1 LC-MS detection spectrum of compound I-1

[0043] Figure 2 For compound I-1 1 H NMR spectrum

[0044] Figure 3LC-MS detection spectrum of compound I-2

[0045] Figure 4 For compound I-2 1 H NMR spectrum

[0046] Figure 5 The inhibitory effect of compound I-1 and DCOIT on two different pathogenic bacteria

[0047] Figure 6 Surface biofouling of PVC panels coated with different antifouling agents after being immersed in seawater for 6 months

[0048] Figure 7 is the 96h lethality of zebrafish embryos. DETAILED DESCRIPTION

[0049] To make the purpose, technical scheme and advantages of the embodiments of the present application clearer, the technical scheme in the embodiments of the present application will be clearly and completely described below in conjunction with the drawings in the embodiments of the present application. Obviously, the described embodiments are part of the embodiments of the present application, rather than all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in the field without making creative work belong to the scope of protection of the present application. Unless otherwise specified, various raw materials and equipment used in the present application can be purchased from the market or can be prepared by existing methods. The following specific embodiments further describe the present invention in detail.

[0050] In view of the defects that commercial isothiazolinone compounds are gradually released into the environment during large-scale production, use and treatment, inducing various toxic effects, and having complex synthesis steps, expensive raw materials, or low yield purity, the present invention provides an isothiazolinone compound with higher antibacterial activity, lower toxicity, and more environmentally friendly, as well as a preparation method and application in sterilization and marine antifouling. The preparation method is simple, without special requirements such as high temperature, high pressure or sensitive reagents, and the sterilization effect is more prominent than DCOIT, and the toxicity to non-target organisms is lower.

[0051] The present invention provides an isothiazolinone compound with high antibacterial activity and low ecotoxicity. The structure of the isothiazolinone compound is shown in (I) below:

[0052]

[0053] Wherein, the substituent R is R1 or R2,

[0054] The R1 is -CH2CH2CH2CH3, and the R2 is -CH2CH2OCH2CH2OCH3.

[0055] When R is R1, the structure of the isothiazolinone compound is shown in I-1 below:

[0056] When R is R2, the structure of the isothiazolinone compound is shown in I-2 below.

[0057]

[0058] The chemical name of compound I-1 is 2-butyl-4,5-dichloroisothiazol-3(2H)-one;

[0059] The chemical name of compound I-2 is 4,5-dichloro-2-(2-(2-methoxyethoxy)ethyl)isothiazol-3(2H)-one.

[0060] The synthetic route of the above isothiazolinone compound I is as follows:

[0061]

[0062] The preparation method is as follows:

[0063] S1. Compound 1 (3,3'-disulfanyldipropionic acid) was placed in a solvent of dichloromethane (DCM) and N,N-dimethylformamide (DMF) was added as a catalyst. The reaction system was cooled to 0°C and oxalyl chloride (COCl) 2 was added dropwise. After the addition was completed, the entire reaction system was stirred at room temperature for 5 hours. After the reaction was completed, the solid intermediate product 2 was obtained by separation and purification (i.e., rotary evaporation under reduced pressure).

[0064] S2, placing an amine compound R-NH2 (when the target compound is I-1, the amine compound is n-butylamine; when the target compound is I-2, the amine compound is 2-(2-methoxyethoxy)ethane-1-amine) in a solvent DCM dichloromethane and adding N,N-diisopropylethylamine DIEA, cooling the reaction system to 0°C and slowly adding the intermediate product 2, after the addition is completed, stirring the entire reaction system at room temperature for 5 hours, after the reaction is completed, separating and purifying to obtain a solid intermediate product 3,

[0065] The specific operation of separation and purification includes: pouring the reaction solution into water, then extracting with the same volume of dichloromethane DCM twice, combining the organic phases and concentrating to dryness; adding methyl tert-butyl ether to the crude product for slurrying for 1 hour, filtering and vacuum drying to obtain a solid intermediate product 3;

[0066] S3, placing the intermediate product 3 in a solvent, cooling the reaction system to 0°C, and then slowly dropping sulfonyl chloride SO2Cl2, stirring the entire reaction system at room temperature for 4 hours, and after the reaction is completed, separating and purifying to obtain the solid target compound I;

[0067] When the target compound is I-1, the specific operations of separation and purification include: concentrating the crude product to dryness under reduced pressure, and purifying it by column chromatography (SiO2, volume ratio of petroleum ether / ethyl acetate = 20 / 1 to 1 / 1) to obtain the target compound.

[0068] When the target compound is I-2, the specific operation of separation and purification includes: rotary evaporation of the crude product under reduced pressure, and then purification by preparative liquid chromatography to obtain the target compound.

[0069] The room temperature in the above preparation method is 25° C., which is a conventional room temperature in the art.

[0070] Example 1

[0071] This embodiment provides a method for preparing an isothiazolinone compound 2-butyl-4,5-dichloroisothiazol-3(2H)-one (target compound I-1), which is as follows:

[0072] S1. In a 100mL three-necked flask equipped with a stirring device, a condenser and a thermometer, compound 1 3,3'-disulfanyldipropionic acid (5.00g, 23.8mmoL), 35mL dichloromethane (DCM), and N,N-dimethylformamide (DMF) (174mg, 183.0μL, 2.38mmoL) as a catalyst were added in sequence. After the reaction system was cooled to 0°C, oxalyl chloride (9.05g, 71.4mmoL, 6.24mL) was added dropwise to the above reaction solution, and the reaction was stirred at 25°C for 5 hours. The white solid intermediate product 2 (5.2g) was obtained by rotary evaporation under reduced pressure. The reaction formula of step S1 is as follows.

[0073]

[0074] S2. In a 100mL three-necked flask equipped with a stirring device, a condenser and a thermometer, add n-butylamine (4.43g, 40.4mmol, 5.99mL), then add 35mL of dichloromethane, N,N-diisopropylethylamine DIEA (10.4g, 80.8mmoL, 14.1mL), wait for the reaction solution to cool to 0°C, and slowly add intermediate product 2 (5.00g, 20.2mmoL). Then, the reaction solution was stirred at 25°C for 5 hours. After the reaction was completed, the reaction solution was poured into 100mL of water, and then extracted twice with the same volume of dichloromethane, and the organic phases were combined and concentrated to dryness; the crude product was added with 50mL of methyl tert-butyl ether and pulped for 1 hour, and filtered and dried to obtain 4.50g of white solid intermediate product 3. The reaction formula of step S2 is as follows.

[0075]

[0076] S3, in a 100mL three-necked flask equipped with a stirring device, a condenser and a thermometer, add the intermediate product 3 (2.60g, 8.11mmoL) and 20mL of dichloromethane, wait for the reaction solution to cool to 0°C, slowly add sulfonyl chloride (SO2Cl2) (21.9g, 162.2mmoL, 16.2mL), and then stir the reaction solution at 25°C for 4 hours. After the reaction is completed, the crude product is concentrated to dryness under reduced pressure, and purified by column chromatography (SiO2, petroleum ether / ethyl acetate = 20 / 1 to 1 / 1) to obtain 1.22g of white solid, namely compound I-1 (purity 97.8%).

[0077]

[0078] LC-MS and NMR of compound I-1 ( 1 H NMR) detection data are as follows Figure 1 and Figure 2 shown.

[0079] Example 2

[0080] This embodiment provides a method for preparing an isothiazolinone compound 4,5-dichloro-2-(2-(2-methoxyethoxy)ethyl)isothiazol-3(2H)-one (target compound I-2), which is as follows:

[0081] S1. In a 250mL three-necked flask equipped with a stirring device, a condenser and a thermometer, compound 1 3,3'-disulfanyldipropionic acid (10.0g, 47.6mmoL), 70mL dichloromethane (DCM), and N,N-dimethylformamide (DMF) (366μL, 4.76mmoL) as a catalyst were added in sequence. After the reaction system was cooled to 0°C, oxalyl chloride (18.1g, 142.8mmoL) was added dropwise to the above reaction solution, and the reaction was stirred at 25°C for 5 hours. The white solid intermediate product 1 (10g) was obtained by rotary evaporation under reduced pressure. The reaction formula of step S1 is as follows.

[0082]

[0083] S2, in a 250mL three-necked flask equipped with a stirring device, a condenser and a thermometer, add 2-(2-methoxyethoxy)ethane-1-amine (8.1g, 68.0mmoL), then add 56mL of dichloromethane, N,N-diisopropylethylamine DIEA (17.6g, 136mmoL, 23.7mL), wait for the reaction solution to cool to 0°C, and slowly add the intermediate product 2 (8.4g, 34.0mmoL). Then, the reaction solution was stirred at 25°C for 5 hours. After the reaction was completed, the reaction solution was poured into 100mL of water, and then extracted twice with the same volume of dichloromethane, and the organic phases were combined and concentrated to dryness; the crude product was added with 50mL of methyl tert-butyl ether and slurried for 1 hour, and filtered to obtain 6g of white solid intermediate product 3. The reaction formula of step S2 is as follows.

[0084]

[0085] S3. In a 100mL three-necked flask equipped with a stirring device, a condenser and a thermometer, 3g of intermediate product 3 ((3.00g, 7.27mmoL) and 30mL of dichloromethane were added. After the reaction solution was cooled to 0°C, sulfonyl chloride (SO2Cl2) (19.6g, 145.4mmoL, 14.5mL) was slowly added dropwise, and then the reaction solution was stirred at 25°C for 4 hours. After the reaction was completed, the crude product was concentrated to dryness under reduced pressure and then purified by preparative liquid chromatography (chromatographic column: Phenomenex Luna C18 80*30mm*3um; mobile phase: [H2O (0.1% trifluoroacetic acid)-acetonitrile]; gradient: 20%-50% acetonitrile) to obtain 1.06g of compound I-2 (purity 100%). The reaction formula of step S3 is as follows.

[0086]

[0087] LC-MS and NMR of compound I-2 ( 1 H NMR) detection data are as follows Figure 3 and Figure 4 shown.

[0088] Performance Testing

[0089] from Figure 1-2 It can be seen that there is only one main substance in the liquid chromatogram, indicating that the reaction for synthesizing compound I-1 is very thorough and the purity of the obtained substance I-1 is very high. 1 HNMR (400mHz, CDCl3) spectrum is δ3.81 (t, J=7.27Hz, 2H), 1.34-1.44 (m, 2H), 0.96 (t, J=7.39Hz, 3H).

[0090] from Figure 3-4It can be seen that there is only one substance in the liquid chromatogram, indicating that the reaction for synthesizing compound I-2 is very thorough and the purity of the obtained substance I-2 is 100%. 1 HNMR (400mHz, CDCl3) spectrum is δ4.01-4.07 (m, 2H), 3.70-3.74 (m, 2H), 3.62-3.67 (m, 2H), 3.54-3.59 (m, 2H), 3.39 (s, 3H).

[0091] Antibacterial test

[0092] Six paper pieces with a diameter of 5 mm were soaked in a solution of compound I-1 and DCOIT at a concentration of 5000 μmol / L, and then placed on a culture medium inoculated with Aeromonas hydrophila and Escherichia coli. After culturing in a constant temperature incubator at 28°C for 18 hours, the radius of the inhibition zone was recorded with a ruler (sample repetition number n=18). The results are shown in Figure 5 As shown, compound I-1 exhibited significant inhibitory effects on these two different pathogens, and the inhibitory effects were better than those of the commercially used DCOIT.

[0093] Antifouling performance test

[0094] The compounds I-1 and I-2 of the present invention can be used as antifouling agents to prepare marine antifouling coatings for inhibiting the attachment of marine fouling organisms, etc. The specific preparation method is: all raw materials, including adhesives (15g acrylic copolymers and 20g resins), antifouling agents (8g I-1, I-2 or DCOIT), pigments (5g cuprous oxide), fillers (10g calcium carbonate) and additives (2g bentonite), are first uniformly dispersed in 100mL xylene at a speed of 1500 rpm for 30 minutes, and then ball milled twice to achieve a particle size of about 20mm. The coating configured with each compound is applied to a polyvinyl chloride plate (200 mm * 150 mm) 3 times using a brush and dried for 24h between each application. Each coating formulation contains three repetitions (n=3), and the total dry film thickness is measured to be 80-100mm.

[0095] The dried boards were then placed in the seawater of Yung Shue O, Hong Kong (water depth 50 cm) for 6 months (November 2023-April 2024) to observe the biofouling. The control group was prepared in the same way except that it did not contain the antifouling agent. The results are as follows Figure 6 As shown, after 6 months, the control group had serious biofouling, while the coating containing compound I-1 almost completely inhibited the biofouling on the board surface. Compound I-2 and DCOIT coating groups had a certain amount of biofouling on the surface, but it was significantly weaker than the control group.

[0096] Ecological safety assessment test

[0097] Zebrafish embryos 2 hours after fertilization (2hpf) were used as model organisms to study the toxicity of compounds I-1 and I-2 to non-target organisms and compare them with commercial DCOIT. The specific steps are as follows: Prepare different concentrations of compound I-1, I-2 and DCOIT exposure solution, take 5mL and put it into the wells of a 6-well plate, and put 25 zebrafish embryos (n=6) in each well. The 6-well plate was placed in a constant temperature room at 28±0.5℃, with a light-dark cycle of 14h light / 10h dark. New exposure solution was replaced every 24h, and exposure was continued until 96hpf. The mortality rate of zebrafish embryos was recorded. The results are as follows: Figure 7 shown.

[0098] from Figure 7 It can be seen that the median lethal dose (LC50) of compounds I-1, I-2, and DCOIT was fitted. 50 ) were 0.4613μM, 2.043μM, and 0.2812μM, respectively. The lethality of compounds I-1 and I-2 to zebrafish embryos was significantly lower than that of DCOIT, showing a higher median lethal dose (LC 50 ), the median lethal doses of compounds I-1 and I-2 were approximately 1.48 times and 7.27 times that of DCOIT.

[0099] As can be seen from the above, the present invention designs and synthesizes isothiazolinone antibacterial agents with better activity, lower toxicity and more environmental friendliness, and applies them to marine antifouling. The synthesis process is relatively mild, the steps are simple, the cost of raw materials is low, and the purity and yield of the obtained products are relatively high. Compared with existing commercial isothiazolinone antibacterial agents, the present invention focuses on isothiazolinone compounds with shorter side chains, and develops their advantages such as high activity and low toxicity.

Claims

1. An isothiazolinone compound with high antibacterial activity and low ecotoxicity, characterized in that: The structure of isothiazolinone compounds is shown below (I): Wherein, the substituent R is R1 or R2, The R1 is -CH2CH2CH2CH3, and the R2 is -CH2CH2OCH2CH2OCH3.

2. A method for preparing an isothiazolinone compound with high antibacterial activity and low ecotoxicity as claimed in claim 1, characterized in that: The synthetic route is as follows: The preparation method comprises the following steps: S1, reacting compound 1 with oxalyl chloride (COCl) 2 in a solvent environment with N,N-dimethylformamide DMF as a catalyst to obtain an intermediate product 2; S2, reacting the intermediate product 2 with an amine compound R-NH2 and N,N-diisopropylethylamine DIEA in a solvent environment to obtain an intermediate product 3; S3. React the intermediate product 3 with sulfonyl chloride SO2Cl2 in a solvent environment to obtain the target compound I.

3. The method for preparing the isothiazolinone compounds with high antibacterial activity and low ecotoxicity as claimed in claim 2, characterized in that: In step S1, compound 1 is reacted with oxalyl chloride (COCl) 2 in a solvent environment with N,N-dimethylformamide DMF as a catalyst, specifically comprising: Compound 1 is placed in a solvent and DMF is added. The reaction system is cooled to 0°C and oxalyl chloride (COCl) 2 is added dropwise. After the addition is complete, the entire reaction system is stirred at room temperature for 5 to 8 hours. After the reaction is complete, a solid intermediate product 2 is obtained through separation and purification.

4. The method for preparing the isothiazolinone compounds with high antibacterial activity and low ecotoxicity as claimed in claim 2, characterized in that: In step S2, the intermediate product 2 is reacted with an amine compound R-NH2 and N,N-diisopropylethylamine DIEA in a solvent environment, specifically comprising: The amine compound R-NH2 is placed in a solvent and DIEA is added. The reaction system is cooled to 0°C and then the intermediate product 2 is slowly added. After the addition is completed, the entire reaction system is stirred at room temperature for 5 to 8 hours. After the reaction is completed, the solid intermediate product 3 is obtained by separation and purification.

5. The method for preparing the isothiazolinone compounds with high antibacterial activity and low ecotoxicity as claimed in claim 2, characterized in that: In step S3, the intermediate product 3 is reacted with sulfonyl chloride SO2Cl2 in a solvent environment, specifically comprising: The intermediate product 3 is placed in a solvent, the reaction system is cooled to 0°C and then sulfonyl chloride SO2Cl2 is slowly added dropwise. After the addition is completed, the entire reaction system is stirred at room temperature for 4 to 6 hours. After the reaction is completed, the solid target compound I is obtained by separation and purification.

6. The method for preparing the isothiazolinone compounds with high antibacterial activity and low ecotoxicity as claimed in claim 2, characterized in that: The molar ratio of the compound 1, oxalyl chloride (COCl) 2 and the catalyst DMF is 1:3-3.5:0.1-0.

3. The molar ratio of the intermediate product 2, the amine compound R-NH2 and DIEA is 1:2-2.5:4-4.

5. The molar ratio of the intermediate product 3 and sulfonyl chloride SO2Cl2 is 1:20-25.

7. The method for preparing the isothiazolinone compounds with high antibacterial activity and low ecotoxicity as claimed in claim 6, characterized in that: The molar ratio of the compound 1, oxalyl chloride (COCl) 2 and the catalyst DMF is 1:3:0.

1. The molar ratio of the intermediate product 2, the amine compound R-NH2 and DIEA is 1:2:

4. The molar ratio of the intermediate product 3 and sulfonyl chloride SO2Cl2 is 1:

20.

8. The method for preparing the isothiazolinone compounds with high antibacterial activity and low ecotoxicity as claimed in claim 2, characterized in that: The R in the amine compound R-NH2 is consistent with the R in the target compound I, specifically including: When R in the target compound I is R1, the amine compound is n-butylamine; When R in the target compound I is R2, the amine compound is 2-(2-methoxyethoxy)ethane-1-amine.

9. An application of the isothiazolinone compound with high antibacterial activity and low ecotoxicity as claimed in claim 1, characterized in that: Used as an antibacterial agent in marine antifouling coatings.

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