WO2017095051A2 - Composition containing naphthoquinone derivative for controlling harmful algae and method for controlling harmful algae using same - Google Patents

Abstract

The present invention relates to a composition containing a naphthoquinone derivative for controlling harmful algae and a method for controlling harmful algae using the same. The composition for controlling harmful algae according to the present invention can selectively control only harmful algae that abnormally proliferate in a pond, a reservoir, a lake, a marsh, a stream, a river, or the like, and thus, the composition according to the present invention is very useful in preventing the formation of a large amount of harmful algae in freshwater or saltwater and preventing the contamination of water.

Description

Harmful algae control composition comprising naphthoquinone derivatives and harmful algae control method using the same

The present invention relates to a harmful algae control composition comprising a naphthoquitone derivative and a method for controlling the harmful algae using the same.

In Korea, the eutrophic aquatic ecosystem in temperate regions has abundant nutrients, creating a favorable environment for the growth of primary producers such as phytoplankton, and the generation of harmful algal blooms (HAB) is repeated every year. Ministry of Environment 2012).

Harmful algal blooms (HABs) are causing various industrial problems, depending on their habitat. The outbreaks of harmful algae in lakes, streams, reservoirs, fish farms, etc., include: 1) aquatic deaths (Duke et al., Weed Sci. 50: 138-151, 2002); 2) It produces off-flavor substances and degrades the quality of drinking water and farmed fish. For example, in the habitats of harmful algae Oscillatoria perornata, the fish smell off- flavors) (Duke et al., Weed Sci. 50: 138-151, 2002); 3) Toxins that are harmful to humans and animals are produced, for example, some birds, such as the genus Microcystis, Nodularia, Anabaena, and Aphanizomenon. Are known to produce toxins that are harmful to humans and animals, respectively, microcystins, nodularin, anatoxin and saxitoxin (Haider et al., Chemosphere 52: 1-21, 2003); 4) causing discomfort and impeding leisure and industrial activity due to the coloring of water and the formation of scum; 5) Over-treatment of chlorine is necessary due to filter paper closure and inhibition of flocculation sedimentation during water treatment, causing economic loss.

Therefore, techniques have been developed to remove or mitigate the phenomena caused by harmful algae-causing organisms. Techniques known to date include chemical spraying, ultrasonic and ozone treatment, sponge recovery and sedimentation, and yellow soil spraying.

Controlling waterborne contaminants (self-producing organics: green algae) caused by the outbreak of harmful algae in eutrophic lakes and streams is an essential part of solving water resource problems, and the technology to be applied is also economical and has the least amount of ecosystem disruption. Eco-friendly technology

However, the chemical spraying method has been used since the past as a method of spraying copper sulfate (CuSO4), chlorine dioxide (ClO2), simazine (Simazine), etc. Among them, copper sulfate, which is widely used because it is the lowest cost, It can affect other marine organisms, cause problems in terms of toxicity and corrosion to other organisms in the water, and because it only shows temporary effects, it must be used repeatedly, and copper sulfate becomes unstable under the high alkaline environmental conditions accompanying red tide. Because of the large amount of processing has to be disadvantageous.

Ultrasonic treatment is the method of destroying cells of red tide causative organisms by ultrasonic waves (160 ~ 400kHz), and ozone treatment is a method to neutralize the toxic effects of red tide by putting high pressure ozone in the water where red tide is generated. It is not yet reached.

Sponge recovery and sedimentation is a method of generating bubbles by using a pressure flotation device consisting of a centrifuge, agglomeration main tank, a mixing tank, and a pressure flotation tank to adsorb, float, and recover red tide organisms from the sea surface. Is adsorbed and precipitated red tide organisms in seawater, and aluminum ions in loess destroy the cells of living organisms. However, when the yellow soil is sprayed in seawater, suspended solids are increased, and there is a problem that fish gill closure may affect living organisms such as respiratory failure in fish farms and fish farms where settlement organisms live in the lower layers.

In addition to the algae, physiological and chemical methods such as in-depth aeration / forced circulation, pressure injury / physical collection, and ultrasonic / ozone treatment and biological agents using bacteria, viruses, fungi, protozoa, and zooplankton that can control green algae And other physical and chemical methods are widely used for improving and maintaining water quality in medium and small scale water systems. However, this method has many cases where it is difficult to apply and the effect is insignificant depending on the size and environmental characteristics of the applied water system. In addition, there is a problem that additional costs such as power, labor, equipment, operating costs. In the case of biological methods, the effects have not been recognized in the actual field to date, and problems such as disturbance of ecosystems due to the administration of exogenous species and incurring necessary culture facilities and maintenance costs before administration to the site have arisen.

For example, the government has invested KRW 193 billion as a part of the comprehensive water management system for the four major rivers. River purification facilities, pressurized flotation facilities, aquatic planting islands, lake water quality survey vessels, water purification wetlands, ecological treasures (Edo) Although green algae prevention projects were carried out from 1999 to 2005 using existing green algae control technologies such as treatment facilities (stormfilter, etc.), the four major river algae prevention programs were found to be ineffective.

Therefore, there is an urgent need to develop a new harmful algae control technique that can solve the problems of the above-described conventional techniques and effectively control the harmful algae.

The present invention has been made to solve the above problems, the present invention is to provide a harmful algae control composition comprising a naphthoquinone derivative that can selectively control the growth of harmful algae.

In addition, the present invention is to provide a method for controlling or preventing abnormal growth of harmful algae using the harmful algae control composition.

In order to solve the above problems, the present invention provides a composition for controlling harmful algae comprising a compound selected from the group consisting of compounds represented by the following [Formula 1] to [Formula 5] or a salt thereof as an active ingredient:

In [Formula 1] to [Formula 5],

X is O, S or NR ₂ ,

R ₁ is hydrogen, halogen, CF ₃ , a substituted or unsubstituted alkyl group having 1 to 12 carbon atoms, or a substituted or unsubstituted alkoxy group having 1 to 12 carbon atoms,

R ₂ is hydrogen, acetyl (Ac) or t-butoxycarbonyl (Boc),

R ₃ is any one selected from the following [Formula 1],

[Formula 1]

In [Formula 1],

* Indicates the position of binding to the above [Formula 5].

In addition, the present invention provides a method for controlling harmful algae comprising treating the harmful algae control composition in a region in which harmful algae is busy or in a region in which developmental symptoms are observed.

The harmful algae control composition according to the present invention can selectively control only harmful algae in which abnormal proliferation occurs in ponds, reservoirs, lakes, lakes, rivers, or rivers, thereby preventing the occurrence of harmful algae in fresh or seawater and preventing water pollution. It can be very useful to prevent this. In addition, it can be utilized as an important antifouling agent or paint for green algae and red tide has the advantage that the possibility of commercialization is very large.

1 is a view showing the results of testing the green algae control effect on the freshwater microalgae of the harmful algae control composition according to an embodiment of the present invention.

2 is a view showing the results of testing the green algae control effect on the seawater microalgae of the harmful algae control composition according to an embodiment of the present invention.

Figure 3 of the harmful algae control composition according to the present invention for Selenastrum capricornutum, Daphnia magna, Zebrafish (Danio rerio) as indicator organisms for the US EPA standard ecotoxicity assessment A diagram showing the results of the ecotoxicity assessment.

Figure 4 is a graph measuring the amount of change in phytoplankton in the microcosm during the treatment of harmful algae control composition according to the present invention for the field water of the Nakdong river dominated by Stephanodiscus (Stephanodiscus).

Figure 5 is a graph measuring the change in phytoplankton except for stephanodiscus in the microcosm when the composition for controlling harmful alga according to the present invention with respect to the site number of the Nakdong river dominated by Stephanodiscus (Stephanodiscus).

Figure 6 is a graph showing the change in species diversity index of phytoplankton in microcosm when the composition for controlling harmful alga according to the present invention with respect to the field water of the Nakdong River dominated by Stephanodiscus (Stephanodiscus).

Hereinafter, the present invention will be described in more detail.

Copper sulfate or copper organic compounds, which have been conventionally used as algae killing agents for harmful algae, have excellent control effects on harmful algae, but are costly, toxic to other organisms, and secondary environmental pollution by chemicals. There was a problem causing. In addition, there was a problem that the selective algae control is not possible to cause a wide range of damage to harmless bird species. There was a problem of causing secondary disturbance in the ecosystem.

The present invention is a solution to the conventional harmful algae control technology described above, which has a selective control effect only on harmful algae to prevent a wide range of damage to aquatic organisms and ecosystem secondary disturbances and harmful algae using the same It relates to a method of controlling.

Specifically, the present invention provides a harmful algae control composition comprising a compound selected from the group consisting of compounds represented by the following [Formula 1] to [Formula 5] or a salt thereof as an active ingredient:

In [Formula 1] to [Formula 5],

X is O, S or NR ₂ ,

R ₁ is hydrogen, halogen, CF ₃ , a substituted or unsubstituted alkyl group having 1 to 12 carbon atoms, or a substituted or unsubstituted alkoxy group having 1 to 12 carbon atoms,

R ₂ is hydrogen, acetyl (Ac) or t-butoxycarbonyl (Boc),

R ₃ is any one selected from the following [Formula 1],

[Formula 1]

In [Formula 1],

* Indicates the position of binding to the above [Formula 5].

In this case, the compound represented by the above [Formula 1] to [Formula 5] comprises a compound selected from the compound represented by the following [Formula 6] to [Formula 56] or homologue compounds thereof, or salts thereof as an active ingredient. :

In addition, the salts of the compounds can be prepared in situ or separately reacted with an inorganic base or an organic base during the final separation, purification and synthesis of the compounds of the present invention.

The salt may form a salt with a base when the compound of the present invention contains an acidic group. Examples of the salt include, but are not limited to, alkali metals such as lithium salts, sodium salts or potassium salts. Salts of; Salts with alkaline earth metals such as barium or calcium; Salts with other metals such as magnesium salts; Organic base salts such as salts with dicyclohexylamine; Salts with basic amino acids such as lysine or arginine.

In addition, when the compound of the present invention contains a basic group in the molecule, an acid addition salt may be formed. Examples of such acid addition salt include, but are not limited to, inorganic acids, especially hydrofluoric acid (eg, hydrofluoric acid, hydrobromic acid, Hydroiodic acid or hydrochloric acid), salts with nitric acid, carbonate, sulfuric acid or phosphoric acid; Salts with lower alkyl sulfonic acids such as methanesulfonic acid, trifluoromethanesulfonic acid or ethanesulfonic acid; Salts with benzenesulfonic acid or p-toluenesulfonic acid; Salts with organic carboxylic acids such as acetic acid, fumaric acid, tartaric acid, oxalic acid, maleic acid, malic acid, succinic acid or citric acid; And salts with amino acids such as glutamic acid or aspartic acid.

Unless otherwise specified below, "Compound 1" to [Formula 5] or "Compound 6-56" according to the present invention is the compound itself, salts, hydrates, and solvates thereof. Can be used as a concept including all isomers.

The term "hydrate" includes a compound of the present invention comprising a stoichiometric or non-stoichiometric amount of water bound by a non-covalent intermolecular force. Or salts thereof.

The term "solvate" refers to a compound of the present invention or a salt thereof comprising a stoichiometric or nonstoichiometric amount of solvent bound by noncovalent intermolecular forces.

The term "isomer" means a compound of the present invention or a salt thereof that has the same chemical formula or molecular formula, but which is optically or stereoscopically different.

The compounds according to the invention can be prepared and used by methods known in the art, by their modified methods or by the method according to the invention, or can be purchased and used commercially.

The reaction solvent that can be used in the production process is not particularly limited as long as it is not involved in the reaction, for example, ethers such as diethyl ether, tetrahydrofuran, dioxane; Halogenated hydrocarbons such as dichloromethane and chloroform; Amines such as pyridine, piperidine and triethylamine, acetone; Alkyl ketones such as methyl ethyl ketone and methyl isobutyl; Alcohols such as methanol, ethanol and propanol; Aprotic polar solvents such as N, N-dimethylformamide, N, N-dimethylacetamide, acetonitrile, dimethyl sulfoxide, hexamethyl phosphate triamide, and the like, and especially non-reactive used in organic synthesis. Among the organic solvents, a solvent capable of separating the water generated during the reaction by the Dean-Stark trap is preferred. Examples of such a solvent include, but are not limited to, benzene, toluene, xylene, and the like. Separation and purification of the reaction product is carried out through a process such as concentration, extraction, and the like, which is commonly performed in organic synthesis, and separation and purification may be performed through purification by column chromatography on silica gel, if necessary.

The invention also includes any modification to the methods for the preparation of the compounds, wherein the intermediate product obtainable in any of its steps can be used as starting material for the remaining steps, the starting material being reacted under reaction conditions. Formed within, or the reaction components can be used in the form of its salts or optically enantiomers.

Therefore, the present invention relates to a method for preparing the compound of the above [Formula 1] to [Formula 5] from another viewpoint. The preparation method is merely an exemplary method thereof, and may be suitably modified by various methods based on the art. For example, the separation and purification of non-exemplified compounds according to the present invention Modifications apparent to those skilled in the art can be successfully carried out, for example, by appropriately protecting the interferer, replacing it with another suitable reagent known in the art, or by customarily changing the reaction conditions.

Those skilled in the art to which the present invention pertains, the specific reaction conditions for the preparation of the compounds of [Formula 1] to [Formula 5] according to the present invention will be confirmed through the preparation examples and examples to be described later As such, detailed description thereof will be omitted.

On the other hand, algae (algae) inhabit the sea or fresh water and affect the ecosystem a lot, the term "harmful algae" used in the present invention, causing the algae or red tide phenomena that adversely affects the following A bird that adversely affects the environment and economic activities.

i) causing visual discomfort and inhibition of recreational activity such as pigmentation or scum formation, dead fish, etc.

ii) causing unpleasant feelings due to toxins and health damage to humans and livestock

iii) killing native animals or moving habitats, changing populations, and losing food due to the destruction of ecosystems;

iv) local economic losses due to reduced recreational activities and travel, and economic losses due to lack of drinking water, agricultural water and industrial water.

v) Death of livestock and wildlife by toxins, and death of fish and aquatic organisms due to reduced dissolved oxygen in water during decomposition of mass-proliferated algae.

vi) odors in species of value (salmon and trout)

Red tide is a phenomenon in which the color of the sea turns red, reddish brown, tan, green, yellow green and yellow due to abnormal growth of plankton due to the influx of organic pollutants, nitrogen and phosphorus from the land to the sea. The causes of such red tide are mainly flagella algae and diatoms, and in addition, ciliated insects, cyanobacteria and red bacteria are known to cause red tide.

In recent years, the trend of red tide has increased globally due to the increase of marine pollutants with the development of industrialization.In Korea, 104 red tide peaks in the 1970s have been observed since red tide was observed in the vibrating bay near Jinhae Bay in 1961. In 1995, red tide has occurred in the south and southeast coasts since 1995.

On the other hand, when red tide occurs, the dissolved oxygen in the water is depleted, and the ocean is in a state in which oxygen is scarcely rapidly, resulting in the mass death of fish and fish and fish, and the mass propagation of plankton is also attached to the fish's gills, which also chokes the fish. In particular, flagella algae, Cocollidinium, generates harmful toxins, causing fish to die. In addition, about 50% of the animal protein consumed by more than 2 billion people in the world is supplied from the sea, and the destruction of marine ecosystems due to red tides can seriously affect these food resources, further degrading the value of water use, Beyond economic value, it causes a large environmental problem.

The present invention has an algicidal effect against the flagella algae and diatoms, cyanobacteria, etc. which cause the red tide.

In addition, the present invention is very effective in suppressing the growth of red algae as well as the above-described red algae.

Green algae refers to a phenomenon in which floating algae, or phytoplankton, multiply and accumulate on the surface of water in eutrophic lakes or slow-flowing streams, thereby turning the color of the green color significantly green. Green algae is a symbolic phenomenon of water eutrophication, causing severe taste and toxic substances and destroying the balance and order of the entire aquatic ecosystem as well as its value as a water resource.

These green algae generally occur only in fresh water. Plant wastewater, domestic sewage, fertilizers, pesticides, livestock and human manure, and other land pollutants enter rivers or lakes, are sedimented in the lower part of the body of water, decomposed by bacteria and decomposed. Organics produce nitrogen and phosphorus, which feed plankton, causing green algae in sea and fresh water. These green algae reduce dissolved oxygen in the water, produce toxic green algae and various green alga planktons, killing fish and aquatic organisms, and depositing heavy metals in the bottom of the water where organic matters from the land are deposited. It can pollute and poison fish, and cause many problems such as environmental damage and damage to natural beauty.

In particular, in the aquatic ecosystems of temperate regions like Korea, the generation of algae has exploded every year, creating an environment favorable for the growth of primary producers such as phytoplankton based on rich nutrients. In particular, algae blooming in rivers and lakes are mainly cyanobacteria in summer and diatoms in spring and winter, but various species of algae, such as wa- chyloid and small silver flanking seedlings, vary depending on the region. It is caused by.

Table 1-Major freshwater algae species and their characteristics that cause green algae

The green algae is a symbolic phenomenon of water eutrophication, causing severe odors and generating toxic substances, which destroys the balance and order of the entire aquatic ecosystem as well as its value as a water resource.

The composition for controlling harmful algae containing the compound of [Formula 1] to [Formula 6] according to the present invention is a microalgae (namzo, diatoms, green algae, in freshwater or seawater such as ponds, reservoirs, lakes, lakes, rivers or rivers) It is possible to more effectively control the occurrence of green algae caused by abnormal proliferation of euglejo steel, whiskey imitation steel and yellow wool imitation steel, brown schist imitation steel and redness steel).

Among the harmful algae exhibiting the green algae and red tide phenomena, the harmful algae that may exhibit the algae effect of the present invention include Namjo River, Diatom Steel, Green Algae River, Waco-Modulated Steel, Needle-Shaped Hair Steel, Euglenazo Steel, Yellow Knitted Steel, Brown Knitted Steel and Contains red algae algae.

In particular, the Cyanophyceae algae is a microcystis, Anabena, Aphanizomenon, Oscillatoria, and Waronichinia genus algae. It may be selected, and preferably may be algae of the genus Microcystis or Anabaena.

The diatom steel (Bacillariophyceae) algae are Stefanodiscus, Cyclotella, Cyclostaphanos, Aulacoseira, Mellosira, Thalassiosira, Ketose Chatoceros Skeletonema, Achnanthes, Asterionella, Acanthoceras, Navicula, Nitzschia, Diploloneis ), Cymbella, Gomphonema, Surirella, Synedra, Frazilaria, Cylindrotheca, Eucampia, Kosmarium ( Cosmarium, and a group consisting of birds of the genus Tabellaria, and may preferably be a bird of the genus Stepanoodiscus, Cyclolotella, or Aulacoseira. .

The algae (Chlorophyceae) algae are Closteriopsis (Closteriopsis), Closterium (Closterium), Hydrotheca (Hydrotheca), Spirogyra (Spirogyra), Gonatozygon (Aconastrum), Micractinium, Lagerheimia, Westella, Eudorina, Pandorina, Volvox, Dictiospaerium, Clarococum (Chlorococcum), Botryococcus, Staurastrum, Closterium, Monoraphidium, Ankistrodesmus, Kirchneriella , Pediastrum, Senedesmus, Coelastrium, Clamydomonas and Chlorella genus.

The Euglenophyceae algae may be selected from a crowd consisting of Trachelomonas, Phacus, and Euglena.

The algae (Dinophyceae) algae (Alecandrium), Coclodinium (Cochlodinium), heterocapsa (Heterocapsa), Prorocentrum (Prorocentrum), Peridinium (Ceratium), the crowd consisting of algae Can be selected from.

The needle-like imitation steel (IRaphidophyceae) algae may be a genus Chattonella (Chattonella).

The Chrysophyceae algae may be selected from the group consisting of Dinobryon, Euroglena, Synura, and Malolomonas algae.

The brown flagella steel (Cryptophyceae) algae may be Cryptomonas algae.

The red blood (Phodophyceae) algae may be algae of the genus Rhodomonas.

With respect to the algae described above, as can be seen from the results of the following examples, it was confirmed that the compounds of the present invention represented by the above [Formula 1] to [Formula 5] have an effect of killing harmful algae, green algae and It was confirmed that the red tide phenomenon can be effectively controlled.

In one embodiment, the present invention provides a composition for controlling harmful algae containing a compound selected from the group consisting of compounds represented by the above [Formula 1] to [Formula 5] or a salt thereof as an active ingredient.

The harmful algae control composition of the present invention can be prepared in a variety of forms according to known methods, formulations for the stable expression of the effect within the range that does not inhibit the effect, enhanced adhesion to the organism to be applied, simplicity of transport and treatment It may further comprise a surfactant such as an academically acceptable solid carrier, liquid carrier, liquid diluent, liquefied gas diluent, solid diluent, or other suitable adjuvant such as emulsifiers, dispersants or foaming agents.

The harmful algae control composition of the present invention may preferably be formulated into an emulsion, an hydrating agent, a granule, a powder, a capsule and a gel, and is preferably provided as a contact agent for buoyancy of the preparation.

Furthermore, as another embodiment, the present invention is harmful including the treatment of a compound selected from the group consisting of the compounds represented by the above [Formula 1] to [Formula 5] or salts thereof to the area where the harmful algae occurred or to the area of development Provides a method for controlling algae.

For example, long-term storage and commercialization of the composition in the form of a powder or a high concentration of liquid form, by spraying locally on the area where the green algae occurred or visible signs using a simple green alga within a few days to a week Can be controlled and prevented.

At this time, it is preferable to block the mass growth in advance by treating the composition in the early stage of the generation of harmful algae.

As such, the present invention. It is a technology (green control or prevention) that can be applied to the restoration and preservation management of small-scale water systems, and applied to artificial farms, golf courses, parks, amusement parks, ponds in recreational facilities, reservoirs, lakes, rivers, and agricultural reservoirs scattered throughout the country. Preventing damage and controlling harmful algae does not cause other environmental pollution. In addition, it can be used as a major component of antifouling paint used in ships, wharf facilities, swimming pools, buildings, etc., and replaces toxic conventional paints. It can also be prevented.

In addition, it is applied as a pretreatment technology for water treatment facilities (water and sewage treatment) to secure drinking water, agricultural water, and industrial water, thereby preventing filter blockage and overexposure of toxic substances, thereby reducing economic burden and ensuring safety of drinking water. have.

In addition, it can be applied to the improvement of water quality of the water system such as lakes (dams), water sources and sewage which are relatively large water systems, and the development of environmental technology. Therefore, it is possible to produce excellent agricultural products due to the improvement of agricultural water, and to improve national health through stabilization of drinking water. In addition, it can contribute to the creation of high value-added products through the export of technology and transfer of technology to countries with high green algae problems such as China or high demand for antifouling paints from attached algae such as Thailand. have. Lastly, due to the development of technology, it can be actively used for red tide control occurring on the coast.

Hereinafter, the present invention will be described in more detail with reference to preferred embodiments. However, these examples and the like are intended to explain the present invention in more detail, and it will be apparent to those skilled in the art that the scope of the present invention is not limited thereto.

Production Example  : According to the present invention Naphthoquinone  Preparation of Derivatives

Naphthoquinone derivatives according to the present invention were prepared by the following method.

[Formula 6]: 2-(((6- Bromo -1H- benzo [d] imidazol -2- yl ) amino) methyl) -5,8-dimethoxy-naphthalene-1,4-dione

Under room temperature and nitrogen atmosphere, 2.1 g of (1,4,5,8-tetramethoxynaphthalen-2-yl) methanol, 0.4 g of 6-bromo-1H-benzo [d] imidazol-2-amine, in an oven-dried Schlenk tube, 25 mg K ₂ CO ₃ , ₃ mg of [Cp * IrCl ₂ ] ₂ and 5 mL of toluene were added and mixed. The mixture was then heated at 130 ° C. for 12 hours and then cooled to ambient temperature. Next, the mixture was concentrated in vacuo and purified by flash column chromatography (hexane: EtOAc = 4: 1 to 1: 1) to give a compound.

Yield: 65%

¹ H NMR (CDCl ₃ , 400 MHz) d 7.38 (s, 1H), 7.09 (s, 2H), 6.91-6.83 (m, 3H), 6.08 (bs, 1H), 4.63 (s, 2H), 3.96 ( s, 3H), 3.90 (s, 3H), 3.88 (s, 3H), 3.83 (s, 3H).

[Formula 7]: N-((1,4,5,8- Tetramethoxynaphthalen -2- yl ) methyl) -1H-benzo [d] imidazol-2-amine

In an oven at room temperature and nitrogen, 2.1 g of (1,4,5,8-tetramethoxynaphthalen-2-yl) methanol, 25 mg K ₂ CO ₃ , ₃ mg [Cp * IrCl ₂ ] ₂ and toluene in an oven-dried Schlenk tube Using 5 mL to prepare the compound of [Formula 7]. Specifically, the mixture was heated at 130 ° C. for 12 hours and then cooled to ambient temperature. Next, the mixture was concentrated in vacuo and purified by flash column chromatography (hexane: EtOAc = 4: 1 to 1: 1) to give a compound.

Yield: 57%

¹ H NMR (CDCl ₃ , 400 MHz) d 7.26 (s, 1H & CDCl _{3 ,} overlapped), 7.24 (d, 2H & CDCl _{3 ,} overlapped), 7.01 (d, J = 8.8 Hz, 2H), 6.86-6.83 (m, 2H), 4,66 (s, 3H), 3.96 (s, 3H), 3.88 (s, 3H), 3.87 (s, 3H), 3.79 (s, 3H).

[Formula 8]: 5-Methyl-N-((1,4,5,8- tetramethoxynaphthalen -2- yl ) methyl) -1H-benzo [d] imidazol-2-amine

In an oven at room temperature and nitrogen, 2.1 g of (1,4,5,8-tetramethoxynaphthalen-2-yl) methanol, 25 mg K ₂ CO ₃ , ₃ mg [Cp * IrCl ₂ ] ₂ and toluene in an oven-dried Schlenk tube 5 mL was used to prepare the compound of [Formula 8]. Specifically, the mixture was heated at 130 ° C. for 12 hours and then cooled to ambient temperature. Next, the mixture was concentrated in vacuo and purified by flash column chromatography (hexane: EtOAc = 4: 1 to 1: 1) to give a compound.

Yield: 60%

¹ H NMR (CDCl ₃ , 400 MHz) d 7.21-7.05 (m, 2H), 6.90-6.82 (m, 4H), 6.08 (bs, 1H), 4.65 (s, 2H), 3.96 (s, 3H), 3.88 (s, 3H), 3.87 (s, 3H), 3.84 (s, 3H), 2.37 (s, 3H).

[Formula 9]: 5- Chloro -N-((1,4,5,8- tetramethoxynaphthalen -2- yl ) methyl) -1H-benzo [d] imidazol-2-amine

In an oven at room temperature and nitrogen, 2.1 g of (1,4,5,8-tetramethoxynaphthalen-2-yl) methanol, 25 mg K ₂ CO ₃ , ₃ mg [Cp * IrCl ₂ ] ₂ and toluene in an oven-dried Schlenk tube Using 5 mL to prepare the compound of [Formula 9]. Specifically, the mixture was heated at 130 ° C. for 12 hours and then cooled to ambient temperature. Next, the mixture was concentrated in vacuo and purified by flash column chromatography (hexane: EtOAc = 4: 1 to 1: 1) to give a compound.

Yield: 50%

¹ H NMR (CDCl ₃ , 400 MHz) d 7.22 (d, J = 6.0 Hz, 1H), 7.12 (d, J = 8.0 Hz, 1H), 7.67 (d, J = 8.0 Hz, 1H), 6.91-6.84 (m, 3H), 4.62 (s, 2H), 3.96 (s, 3H), 3.92 (s, 3H), 3.90 (s, 3H), 3.87 (s, 3H).

[Formula 10]: 5- Methoxy -N-((1,4,5,8- tetramethoxynaphthalen -2-yl) methyl) -1H-benzo [d] imidazol-2-amine

In an oven at room temperature and nitrogen, 2.1 g of (1,4,5,8-tetramethoxynaphthalen-2-yl) methanol, 25 mg K ₂ CO ₃ , ₃ mg [Cp * IrCl ₂ ] ₂ and toluene in an oven-dried Schlenk tube 5 mL was used to prepare the compound of [Formula 10]. Specifically, the mixture was heated at 130 ° C. for 12 hours and then cooled to ambient temperature. Next, the mixture was concentrated in vacuo and purified by flash column chromatography (hexane: EtOAc = 4: 1 to 1: 1) to give a compound.

Yield: 70%

¹ H NMR (CDCl ₃ , 400 MHz) d 7.07 (d, J = 8.6 Hz, 1H), 6.87-6.79 (m, 3H), 6.71 6.67 (m, 1H), 4.63 (s, 2H), 3.93 3.70 ( m, 15H).

[Formula 11]: 5- Fluoro -N-((1,4,5,8- tetramethoxynaphthalen -2- yl ) methyl) -1H-benzo [d] imidazol-2-amine

In an oven at room temperature and nitrogen, 2.1 g of (1,4,5,8-tetramethoxynaphthalen-2-yl) methanol, 25 mg K ₂ CO ₃ , ₃ mg [Cp * IrCl ₂ ] ₂ and toluene in an oven-dried Schlenk tube Using 5 mL to prepare the compound of [Formula 11]. Specifically, the mixture was heated at 130 ° C. for 12 hours and then cooled to ambient temperature. Next, the mixture was concentrated in vacuo and purified by flash column chromatography (hexane: EtOAc = 4: 1 to 1: 1) to give a compound.

Yield: 45%

¹ H NMR (CDCl ₃ , 400 MHz) d 7.21 (s, 1H), 6.98 (s, 1H), 6.90 6.84 (m, 2H), 6.75 6.71 (m, 1H), 6.25 (bs, 1H), 4.64 ( s, 2H), 3.96 (s, 3H), 3.89 (s, 3H), 3.87 (s, 3H), 3.82 (s, 3H).

[Formula 12], [Formula 13]: 1- (6-bromo-2-((((1,4,5,8-tetramethoxynaphthalen-2-yl) methyl) amino) -1H-benzo [d] imidazol-1 -yl) ethan-1-one, 1- (5- bromo -2-((((1,4,5,8-tetramethoxynaphthalen-2-yl) methyl) a mino) -1H-benzo [d] imidazol-1-yl) ethan-1-one

CH ₂ Cl ₂ for 1 hour at room temperature 54 mg of Ac ₂ O was added to 100 mg of the compound of Formula 6 and 13 mg of NaH in 5 mL at room temperature. After 4 hours, the reaction mixture was concentrated and dried in vacuo. The residue was mixed with water and extracted with CH ₂ Cl ₂ , then the extract was washed with water, dried over Na ₂ SO ₄ and evaporated under vacuum. Finally, purification was performed by flash column chromatography (hexane: EtOAc = 4: 1 to 1: 1) to obtain a compound having a solid content of [Formula 12] and [Formula 13] in a ratio of 1: 1. Yield: 84%

Formula 14: 1- (2-(((1,4,5,8- Tetramethoxynaphthalen -2- yl ) methyl) amino) -1H-benzo [d] imidazol-1-yl) ethan-1-one

CH ₂ Cl ₂ for 1 hour at room temperature 54 mg of Ac ₂ O was added to 100 mg of the compound of Formula 7 and 13 mg of NaH in 5 mL at room temperature. After 4 hours, the reaction mixture was concentrated and dried in vacuo. The residue was mixed with water and extracted with CH ₂ Cl ₂ , then the extract was washed with water, dried over Na ₂ SO ₄ and evaporated under vacuum. Finally, the compound was purified by flash column chromatography (hexane: EtOAc = 4: 1 to 1: 1) to obtain a solid compound of Chemical Formula 14. Yield: 91%

¹ H NMR (CDCl ₃ , 400 MHz) d 8.16 8.12 (m, 1H), 7.47 (d, J = 8.2 Hz, 1H), 7.45 (d, J = 8.2 Hz, 1H), 7.10 7.06 (m, 2H) , 6.84 (d, J = 2.0 Hz, 2H), 4.96 (d, J = 2.0 Hz, 2H), 3.95 (s, 3H), 3.91 (s, 3H), 3.85 (s, 3H), 3.83 (s, 3H), 2.76 (s, 3H).

[Formula 15], [Formula 16]: 1- (6-Methyl-2-(((1,4,5,8-tetramethoxynaphthalen-2-yl) methyl) amino) -1H-benzo [d] imidazol-1 -yl) ethan-1-one, 1- (5-methyl-2-(((1,4,5,8- tetramethoxynaphth alen -2- yl ) methyl) amino) -1H-benzo [d] imidazol-1-yl) ethan-1-one

CH ₂ Cl ₂ for 1 hour at room temperature 54 mg of Ac ₂ O was added to 100 mg of the compound of Formula 8 and 13 mg of NaH in 5 mL at room temperature. After 4 hours, the reaction mixture was concentrated and dried in vacuo. The residue was mixed with water and extracted with CH ₂ Cl ₂ , then the extract was washed with water, dried over Na ₂ SO ₄ and evaporated under vacuum. Finally, purification was performed by flash column chromatography (hexane: EtOAc = 4: 1 to 1: 1) to obtain a compound having a solid content of [Formula 15] and [Formula 16] in a ratio of 1: 1. Yield: 86%

[Formula 17], [Formula 18]: 1- (6-Chloro-2-((((1,4,5,8-tetramethoxynaphthalen-2-yl) methyl) amino) -1H-benzo [d] imidazol-1 -yl) ethan-1-one, 1- (5- chloro -2-(((1,4,5,8- tetramethoxynaphth alen -2- yl ) methyl) amino) -1H-benzo [d] imidazol-1-yl) ethan-1-one

CH ₂ Cl ₂ for 1 hour at room temperature 54 mg of Ac ₂ O was added to 100 mg of stirred compound of Formula 9 and 13 mg of NaH in 5 mL at room temperature. After 4 hours, the reaction mixture was concentrated and dried in vacuo. The residue was mixed with water and extracted with CH ₂ Cl ₂ , then the extract was washed with water, dried over Na ₂ SO ₄ and evaporated under vacuum. Finally, purification was performed by flash column chromatography (hexane: EtOAc = 4: 1 to 1: 1) to obtain a compound having a solid content of Formula 17 and Formula 18 at a ratio of 1: 1. Yield: 80%

Formula 19], Formula 20: 1- (6-Methoxy-2-(((1,4,5,8-tetramethoxynaphthalen-2-yl) methyl) -amino) -1H-benzo [d] imidazol- 1-yl) ethan-1-one, 1- (5- methoxy -2-(((1,4,5,8- tetramethoxynaphthalen -2- yl ) methyl) amino) -1H-benzo [d] imidazol-1-yl) ethan-1-one

CH ₂ Cl ₂ for 1 hour at room temperature 54 mg of Ac ₂ O was added to 100 mg of stirred compound of Formula 10 and 13 mg of NaH in 5 mL at room temperature. After 4 hours, the reaction mixture was concentrated and dried in vacuo. The residue was mixed with water and extracted with CH ₂ Cl ₂ , then the extract was washed with water, dried over Na ₂ SO ₄ and evaporated under vacuum. Finally, purification was performed by flash column chromatography (hexane: EtOAc = 4: 1 to 1: 1) to obtain a compound having a solid content of [Formula 19] and [Formula 20] in a ratio of 1: 1. Yield: 91%

[Formula 21], [Formula 22]: 1- (6-Fluoro-2-((((1,4,5,8-tetramethoxynaphthalen-2-yl) methyl) amino) -1H-benzo [d] imidazol-1 -yl) ethan-1-one, 1- (5- fluoro -2-(((1,4,5,8- tetramethoxynaphth alen -2- yl ) methyl) amino) -1H-benzo [d] imidazol-1-yl) ethan-1-one

CH ₂ Cl ₂ for 1 hour at room temperature 54 mg of Ac ₂ O was added to 100 mg of the compound of Formula 11 and 13 mg of NaH in 5 mL at room temperature. After 4 hours, the reaction mixture was concentrated and dried in vacuo. The residue was mixed with water and extracted with CH ₂ Cl ₂ , then the extract was washed with water, Na ₂ SO ₄ Dried over and evaporated under vacuum. Finally, purification was performed by flash column chromatography (hexane: EtOAc = 4: 1 to 1: 1) to obtain a compound having a solid content of [Formula 19] and [Formula 20] in a ratio of 1: 1. Yield: 78%

[Formula 23]: 2-(((6- bromo -1H- benzo [d] imidazol -2- yl ) amino) methyl) -5,8-dimethoxy-naphthalene-1,4-dione

At 0 ° C., 206 mg of ammonium cerium (IV) nitrate dissolved in water (0.5 mL) was added to a mixture of Formula 12 and Formula 13 in 1 mL of acetonitrile at 0 ° C. Stir for 1 hour. After the reaction was completed, water was added and the resulting aqueous phase was extracted with CH ₃ Cl ₃ . The organic layer was washed with water and brine, dried over Na ₂ S0 ₄ and concentrated under reduced pressure. Finally, purification was performed by flash column chromatography (hexane: EtOAc = 1: 1) to obtain a compound of a solid content of [Formula 23]. Yield: 21%

¹ H NMR (CDCl ₃ , 400 MHz) d 7.50 (s, 1H), 7.36 (s, 1H), 7.12 (d, J = 8.2 Hz, 1H), 7.08 (d, J = 8.2 Hz, 1H), 6.78 (d, J = 5.7 Hz, 2H), 4.86 (bs, 1H), 3.88 (s, 6H).

Formula 24: 2-(((1H- Benzo [d] imidazol -2- yl ) amino) methyl) -5,8- dimethoxy -naphthalene-1,4-dione

At 0 ° C., 206 mg of ammonium cerium (IV) nitrate dissolved in water (0.5 mL) was added to the stirred compound of [Formula 14] in 2 mL of acetonitrile, followed by stirring for 1 hour. After the reaction was completed, water was added and the resulting aqueous phase was extracted with CH ₃ Cl ₃ . The organic layer was washed with water and brine, dried over Na ₂ S0 ₄ and concentrated under reduced pressure. Finally, purification was performed by flash column chromatography (hexane: EtOAc = 1: 1) to obtain a compound of a solid content of [Formula 24]. Yield: 21%

Formula 25: 2-(((1-acetyl-6- bromo -1H- benzo [d] imidazol -2-yl) amino) methyl) -5,8-dimethoxy-naphthalene-1,4-dione

At -40 ° C., 206 mg of ammonium cerium (IV) nitrate dissolved in water (0.5 mL) in 80 mg (1: 1) of a mixture of Formula 12 and Formula 13 in 2 mL of acetonitrile. Stir for 1 hour after addition. After the reaction was completed, water was added and the resulting aqueous phase was extracted with CH ₃ Cl ₃ . The organic layer was washed with water and brine, dried over Na ₂ S0 ₄ and concentrated under reduced pressure. Finally, purification was performed by flash column chromatography (hexane: EtOAc = 5: 1) to obtain a compound of solid content of [Formula 25]. Yield: 36%

¹ H NMR (CDCl ₃ , 400 MHz) d 8.33-8.29 (m, 0.5 H), 8.26 8.24 (m, 0.5 H), 7.56 (d, J = 4.0 Hz, 1H), 7.52 (d, J = 6.4 Hz , 1H), 7.38 (d, J = 8.4 Hz, 0.5 H), 7.21 7.17 (m, 1.5 H), 6.78 (s, 1H), 4.86 (d, J = 6.0 Hz, 2H), 3.95 (d, J = 3.6 Hz, 3H), 3.92 (s, 3H), 2.76 (d, J = 6.0 Hz, 3H).

Formula 26: 2-(((1-Acetyl-1H- benzo [d] imidazol -2- yl ) amino) methyl) -5,8-dimethoxy-naphthalene-1,4-dione

At -40 ° C, 206 mg of ammonium cerium (IV) nitrate dissolved in water (0.5 mL) was added to 80 mg of the compound of [Formula 14] in 2 mL of acetonitrile, followed by stirring for 1 hour. After the reaction was completed, water was added and the resulting aqueous phase was extracted with CH ₃ Cl ₃ . The organic layer was washed with water and brine, dried over Na ₂ S0 ₄ and concentrated under reduced pressure. Finally, purification was performed by flash column chromatography (hexane: EtOAc = 5: 1) to obtain a compound of solid content of [Formula 26]. Yield: 40%

¹ H NMR (CDCl ₃ , 400 MHz) d 8.35 8.33 (m, 1H), 7.59 (s, 1H), 7.42 7.40 (m, 2H), 7.09 (t, J = 8.0 Hz, 1H), 6.78 (s, 2H), 4.90 (d, J = 6.4 Hz, 2H), 3.95 (s, 3H), 3.93 (s, 3H), 2.78 (s, 3H).

[Formula 27], [Formula 28]: tert -butyl 6- bromo -2-((((1,4,5,8-tetramethoxynaphthalen-2-yl) methyl) amino) -1H-benzo [d] imidazole-1-carboxylate, tert-butyl 5- bromo -2-(((1,4,5,8- tetramethoxyna phthalen -2- yl ) methyl) amino) -1H-benzo [d] imidazole-1-carboxylate

At room temperature, 195 mg of Boc ₂ O was added to 100 mg of the stirred compound of Chemical Formula 6 in 5 mL of MeOH, and reacted for 12 hours. The reaction mixture was diluted with water and extracted with DCM. The extract was washed with water, dried over Na ₂ SO ₄ , concentrated in vacuo and purified by flash column chromatography (hexane: EtOAc = 6: 1) to obtain a solid compound [Formula 27] and [Formula 28]. Obtained. Yield: 39% (Formula 27), 45% (Formula 28)

¹ H NMR (CDCl ₃ , 400 MHz) d 7.74 (s, 1H), 7.52 (d, J = 9.6 Hz, 1H), 7.32 7,25 (m, 1H), 7.03 (s, 1H) , 6.84 (s, 2H), 4.91 (d, J = 6.4 Hz, 2H), 3.95 (s, 3H), 3.91 (s, 3H), 3.89 (s, 3H), 3.82 (s, 3H), 1.67 ( s, 9H).

¹ H NMR (CDCl ₃ , 400 MHz) d 7.53 (s, 1H), 7.43 (d, J = 9.6 Hz, 1H), 7.14 (d, J = 9.6 Hz, 1H), 7.03 (s, 1H), 6.87 (d, J = 9.8 Hz, 2H), 4.92 (d, J = 5.5 Hz, 2H), 3.95 (s, 3H), 3.91 (s, 3H), 3.89 (s, 3H), 3.82 ( s, 3 H), 1.65 (s, 9 H).

Formula 29: tert -butyl 5- bromo -2-(((5,8- dimethoxy -1,4- dioxo -1,4-dihydronaphthalen-2-yl) methyl) amino) -1H-benzo [d] imidazole-1-carboxylate

At 0 ° C., 64 mg of ammonium cerium (IV) nitrate dissolved in water (0.5 mL) was added to 36 mg of agitated compound in 2 mL of acetonitrile, followed by stirring for 1 hour. After the reaction was completed, water was slowly added, and the resulting aqueous solution was extracted with CHCl ₃ . The organic layer was washed with water and brine, dried over Na ₂ S0 ₄ and concentrated under reduced pressure. Finally, purification was performed by flash column chromatography (hexane: EtOAc = 5: 1) to obtain a compound of solid content of [Formula 29]. Yield: 59%

¹ H NMR (CDCl ₃ , 400 MHz) d 7.74 (s, 1H), 7.57 (br s, 1H), 7.31 (s, 2H), 7.20 (d, J = 7.2 Hz, 1H), 6.78 (s, 1H ), 4.68 (d, J = 6.4 Hz, 1H), 3.97 (s, 3H), 3.94 (s, 3H), 1.75 (s, 9H).

Formula 30: N-((1,4-dimethoxynaphthalen-2-yl) methyl) benzo [d] thiazol-2-amine

At room temperature, 550 mg of alcohol, 280 mg of benzo [d] thiazol-2-amine, 85 mg of sodium hydroxide and 2 mL of toluene were added and mixed in a round bottom flask. The reaction mixture was heated at 120 ° C. for 15 hours, then cooled to room temperature and concentrated in vacuo. Finally, the compound was purified by flash column chromatography (hexane: EtOAc = 2: 1) to obtain a compound having a solid content of [Formula 30]. Yield: 69%

¹ H NMR (CDCl ₃ , 400 MHz) d 8.24 (d, J = 8.2 Hz, 1H), 8.07 (d, J = 8.2 Hz, 1H), 7.60-7.48 (m, 4H), 7.35 7.31 (m, 1H ), 7.14 7.10 (m, 1H), 6.82 (s, 1H), 5.71 (s, 1H), 4.85 (s, 2H), 3.96 (s, 3H), 3.95 (s, 3H).

Formula 31]: N-((1,4-Dimethoxynaphthalen-2-yl) methyl) benzo [d] oxazol-2-amine

At room temperature, the compound of [Formula 31] was prepared using 550 mg of alcohol, 85 mg of sodium hydroxide and 2 mL of toluene in a round bottom flask. Specifically, these reaction mixtures were heated at 120 ° C. for 15 hours, then cooled to room temperature and concentrated under vacuum. Finally, the residue was purified by flash column chromatography (hexane: EtOAc = 2: 1) to obtain a compound having a solid content of [Formula 31]. Yield: 70%

¹ H NMR (CDCl ₃ , 400 MHz) d 8.21 (d, J = 8.0, 1H), 8.02 (d, J = 8.0 Hz, 1H), 7.53 7.44 (m, 2H), 7.28 (d, J = 7.6 Hz , 1H), 7.23 (d, J = 7.6 Hz, 1H), 7.10 7.06 (m, 1H), 7.01 6.97 (m, 1H), 6.78 (s, 1H), 6.31 (s, 1H), 4.83 (s, 2H), 3.88 (s, 3H), 3.86 (s, 3H).

Formula 32: N-((1,4- Dimethoxynaphthalen -2- yl ) methyl) -5-fluorobenzo [d] oxazol-2-amine

At room temperature, a compound of [Formula 32] was prepared using 550 mg of alcohol, 85 mg of sodium hydroxide, and 2 mL of toluene in a round bottom flask. Specifically, these reaction mixtures were heated at 120 ° C. for 15 hours, then cooled to room temperature and concentrated under vacuum. Finally, purification was performed by flash column chromatography (hexane: EtOAc = 2: 1) to obtain a compound of solid content of [Formula 32]. Yield: 63%

¹ H NMR (CDCl ₃ , 400 MHz) d 8.22 (d, J = 8.2 Hz, 1H), 8.02 (d, J = 8.2 Hz, 1H), 7.55-7.36 (m, 2H), 7.14 7.10 (m, 1H ), 7.02-6.96 (m, 1H), 6.77 (s, 1H), 6.70-6.78 (m, 1H), 6.14 (s, 1H), 4.82 (s, 2H), 3.90 (s, 3H), 3.88 ( s, 3H).

Formula 33: 5- Chloro -N-((1,4-dimethoxynaphthalen-2-yl) methyl) benzo [d] oxazol-2-amine

At room temperature, the compound of [Formula 33] was prepared using 550 mg of alcohol, 85 mg of sodium hydroxide and 2 mL of toluene in a round bottom flask. Specifically, these reaction mixtures were heated at 120 ° C. for 15 hours, then cooled to room temperature and concentrated under vacuum. Finally, the residue was purified by flash column chromatography (hexane: EtOAc = 2: 1) to obtain a compound having a solid content of Chemical Formula 33. Yield: 64%

¹ H NMR (CDCl ₃ , 400 MHz) d 8.25 (d, J = 8.2 Hz, 1H), 8.06 (d, J = 8.2 Hz, 1H), 7.60 7.56 (m, 1H), 7.54 7.50 (m, 1H) , 7.35 (s, 1H), 7.16 (s, 1H), 7.03 6.99 (m, 1H), 6.80 (s, 1H), 5.23 (s, 1H), 4.85 (s, 2H), 3.96 (s, 6H) .

Formula 34: 6- Chloro -N-((1,4-dimethoxynaphthalen-2-yl) methyl) benzo [d] oxazol-2-amine

At room temperature, the compound of [Formula 34] was prepared using 550 mg of alcohol, 85 mg of sodium hydroxide, and 2 mL of toluene in a round bottom flask. Specifically, these reaction mixtures were heated at 120 ° C. for 15 hours, then cooled to room temperature and concentrated under vacuum. Finally, the residue was purified by flash column chromatography (hexane: EtOAc = 2: 1) to obtain a compound of solid content of [Formula 34]. Yield: 66%

¹ H NMR (CDCl ₃ , 400 MHz) d 8.24 (d, J = 8.8 Hz, 1H), 8.05 (d, J = 8.8 Hz, 1H), 7.58 7.54 (m, 1H), 7.52 7.48 (m, 1H) , 7.25 (d, 1H & CDCl _{3 ,} overlapped), 7.15 7.11 (m, 1H), 6.79 (s, 1H), 5.65 (s, 1H), 4.83 (s, 2H), 3.98 (s, 1H).

Formula 35: 5- Chloro -N-((1,4-dimethoxynaphthalen-2-yl) methyl) benzo [d] thiazol-2-amine

At room temperature, the compound of [Formula 35] was prepared using 550 mg of alcohol, 85 mg of sodium hydroxide and 2 mL of toluene in a round bottom flask. Specifically, these reaction mixtures were heated at 120 ° C. for 15 hours, then cooled to room temperature and concentrated under vacuum. Finally, purification was performed by flash column chromatography (hexane: EtOAc = 2: 1) to obtain a compound of solid content of [Formula 35]. Yield: 66%

¹ H NMR (CDCl ₃ , 400 MHz) d 8.23 (d, J = 8.2 Hz, 1H), 8.06 (d, J = 8.2 Hz, 1H), 7.58-7.44 (m, 4H), 7.08 7.04 (m, 1H ), 6.78 (s, 1H), 4.82 (s, 2H), 3.95 (s, 3H), 3.92 (s, 3H).

Formula 36: N-((1,4- Dimethoxynaphthalen -2- yl ) methyl) -5- (trifluoromethyl) benzo [d] thiazol-2-amine

At room temperature, the compound of [Formula 36] was prepared using 550 mg of alcohol, 85 mg of sodium hydroxide and 2 mL of toluene in a round bottom flask. Specifically, these reaction mixtures were heated at 120 ° C. for 15 hours, then cooled to room temperature and concentrated under vacuum. Finally, the residue was purified by flash column chromatography (hexane: EtOAc = 2: 1) to obtain a compound having a solid content of [Formula 36]. Yield: 51%

¹ H NMR (CDCl ₃ , 400 MHz) d 8.24 (d, J = 8.2 Hz, 1H), 8.06 (d, J = 8.2 Hz, 1H), 7.81 (s, 1H), 7.67 (d, J = 8.2 Hz , 1H), 7.59 7.55 (m, 1H), 7.52 7.48 (m, 1H), 7.36 7.32 (m, 1H), 6.79 (s, 1H), 5.93 (s, 1H), 4.85 (s, 2H), 3.96 (s, 3 H), 3.85 (s 3 H).

Formula 37] 2-((benzo [d] thiazol-2-ylamino) methyl) naphthalene-1,4-dione

At 0 ° C., 163 mg of ammonium cerium (IV) nitrate dissolved in water (0.5 mL) was added to 40 mg of the stirred compound of Formula 30 in 1 mL of acetonitrile, followed by stirring for 1 hour. After the reaction was completed, water was slowly added, and the resulting aqueous solution was extracted with CHCl ₃ . The organic layer was washed with water and brine, dried over Na ₂ S0 ₄ and concentrated under reduced pressure. Finally, the residue was purified by flash column chromatography (hexane: EtOAc = 3: 1) to obtain a compound having a solid content of [Formula 37]. Yield: 61%

¹ H NMR (CDCl ₃ , 400 MHz) d 8.12 (d, J = 3.5 Hz, 1H), 8.11 (d, J = 3.5 Hz, 1H), 7.76 (d, J = 3.2 Hz, 2H), 7.34 7.27 ( m, 1H), 7.15 7.09 (m, 1H), 7.05 (s, 1H), 5.76 (s, 1H), 4.86 (s, 2H).

Formula 38: 2-((Benzo [d] oxazol-2-ylamino) methyl) naphthalene-1,4-dione

At 0 ° C., 163 mg of ammonium cerium (IV) nitrate dissolved in water (0.5 mL) was added to 40 mg of the stirred compound of Formula 31 in 1 mL of acetonitrile, followed by stirring for 1 hour. After the reaction was completed, water was slowly added, and the resulting aqueous solution was extracted with CHCl ₃ . The organic layer was washed with water and brine, dried over Na ₂ S0 ₄ and concentrated under reduced pressure. Finally, purification was performed by flash column chromatography (hexane: EtOAc = 3: 1) to obtain a compound of solid content of [Formula 38]. Yield: 65%

¹ H NMR (CDCl ₃ , 400 MHz) d 8.12 (d, J = 3.5 Hz, 1H), 8.11 (d, J = 3.5 Hz, 1H), 7.76 (d, J = 3.2 Hz, 2H), 7.34 7.27 ( m, 1H), 7.15 7.09 (m, 1H), 7.05 (s, 1H), 5.76 (s, 1H), 4.86 (s, 2H).

Formula 39: 2-(((5- Fluorobenzo [d] oxazol -2- yl ) amino) methyl) naphthalene-1,4-dione

At 0 ° C., 163 mg of ammonium cerium (IV) nitrate dissolved in water (0.5 mL) was added to 40 mg of the stirred compound of Formula 32 in 1 mL of acetonitrile, followed by stirring for 1 hour. After the reaction was completed, water was slowly added, and the resulting aqueous solution was extracted with CHCl ₃ . The organic layer was washed with water and brine, dried over Na ₂ S0 ₄ and concentrated under reduced pressure. Finally, the residue was purified by flash column chromatography (hexane: EtOAc = 3: 1) to obtain a compound having a solid content of [Formula 39]. Yield: 54%

¹ H NMR (CDCl ₃ , 400 MHz) d 8.12 (d, J = 8.9, 1H), 8.08 (d, J = 8.9, 1H), 7.79 7.77 (m, 2H), 7.18 7.14 (m, 1H), 7.08 7.05 (m, 1 H), 7.03 (s, 1 H), 6.78 6.73 (m, 1 H), 5.82 (s, 1 H), 4.61 (s, 2H).

Formula 40: 2-(((5- Chlorobenzo [d] oxazol -2- yl ) amino) methyl) naphthalene-1,4-dione

At 0 ° C., 163 mg of ammonium cerium (IV) nitrate dissolved in water (0.5 mL) was added to 40 mg of the stirred compound of Formula 33 in 1 mL of acetonitrile, followed by stirring for 1 hour. After the reaction was completed, water was slowly added, and the resulting aqueous solution was extracted with CHCl ₃ . The organic layer was washed with water and brine, dried over Na ₂ S0 ₄ and concentrated under reduced pressure. Finally, the residue was purified by flash column chromatography (hexane: EtOAc = 3: 1) to obtain a compound having a solid content of [Formula 40]. Yield: 59%

¹ H NMR (CDCl ₃ , 400 MHz) d 8.12 (d, J = 8.6 Hz, 1H), 8.08 (d, J = 8.6 Hz, 1H), 7.75 (s, 2H), 7.17 (d, J = 8.0 Hz , 1H), 7.15 (d, J = 8.0 Hz, 2H), 7.02 (s, 1H), 7.00 (d, J = 8.0 Hz, 1H), 5.82 (s, 1H), 4.62 (s, 2H).

Formula 41: 2-(((6- Chlorobenzo [d] oxazol -2- yl ) amino) methyl) naphthalene-1,4-dione

At 0 ° C., 163 mg of ammonium cerium (IV) nitrate dissolved in water (0.5 mL) was added to 40 mg of the stirred compound of formula 34 in 1 mL of acetonitrile, followed by stirring for 1 hour. After the reaction was completed, water was slowly added, and the resulting aqueous solution was extracted with CHCl ₃ . The organic layer was washed with water and brine, dried over Na ₂ S0 ₄ and concentrated under reduced pressure. Finally, the residue was purified by flash column chromatography (hexane: EtOAc = 3: 1) to obtain a compound of a solid content of [Formula 41]. Yield: 61%

¹ H NMR (CDCl ₃ , 400 MHz) d 8.12 (d, J = 8.6 Hz, 1H), 8.07 (d, J = 8.6 Hz, 1H), 7.77 (d, J = 8.6 Hz, 2H), 7.26 (s , 1H & CDCl _{3 ,} overlapped), 7.25 (d, 1H & CDCl _{3 ,} overlapped), 7.24 (d, J = 8.0 Hz, 1H), 7.03 (s, 1H), 5.79 (s, 1H), 4.62 (s , 2H).

Formula 42: 2-(((5- Chlorobenzo [d] thiazol -2-yl) amino) methyl) naphthalene-1,4-dione

At 0 ° C., 163 mg of ammonium cerium (IV) nitrate dissolved in water (0.5 mL) was added to 40 mg of the stirred compound of Formula 35 in 1 mL of acetonitrile, followed by stirring for 1 hour. After the reaction was completed, water was slowly added, and the resulting aqueous solution was extracted with CHCl ₃ . The organic layer was washed with water and brine, dried over Na ₂ S0 ₄ and concentrated under reduced pressure. Finally, the residue was purified by flash column chromatography (hexane: EtOAc = 3: 1) to obtain a compound having a solid content of [Formula 42]. Yield: 57%

¹ H NMR (CDCl ₃ , 400 MHz) d 8.14 8.10 (m, 1H), 8.09 8.05 (m, 1H), 7.79 7.75 (m, 2H), 7.52 (s, 1H), 7.47 (d, J = 8.4 Hz , 1H), 7.09 (d, J = 8.4, 1H), 7.04 (s, 1H), 5.74 (s, 1H), 4.64 (s, 2H).

Formula 43: 2-(((5- (Trifluoromethyl) benzo [d] thiazol -2-yl) amino) methyl) naphthalene-1,4-dione

At 0 ° C., 163 mg of ammonium cerium (IV) nitrate dissolved in water (0.5 mL) was added to 40 mg of the stirred compound of Formula 36 in 1 mL of acetonitrile, followed by stirring for 1 hour. After the reaction was completed, water was slowly added, and the resulting aqueous solution was extracted with CHCl ₃ . The organic layer was washed with water and brine, dried over Na ₂ S0 ₄ and concentrated under reduced pressure. Finally, purification was performed by flash column chromatography (hexane: EtOAc = 3: 1) to obtain a compound of solid content of [Formula 43]. Yield: 51%

¹ H NMR (CDCl ₃ , 400 MHz) d 8.15 8.11 (m, 1H), 8.10 8.06 (m, 1H), 7.77 (s, 1H), 7.78 (d, J = 7.2 Hz, 2H), 7.33 7.05 (m , 3H), 5.79 (s, 1H), 4.68 (s, 2H).

Formula 44: N-((1,4- dimethoxynaphthalen -2- yl ) methyl) -1H-benzo [d] imidazol-2-amine

Under ambient temperature and nitrogen atmosphere, 94 mg of (1,4-dimethoxynaphthalen-2-yl) methanol, 50 mg of 1H-benzo [d] imidazol-2-amine, 3 mg of K ₂ CO ₃ , in a Schlenk tube dried in an oven [ 0.9 mg of Cp * IrCl ₂ ] ₂ and 1.5 mL of toluene were added and mixed. The mixture was then heated at 120 ° C. for 12 hours and then cooled to ambient temperature. Next, the mixture was concentrated in vacuo and purified by flash column chromatography (hexane: EtOAc = 4: 1 to 1: 1) to give a compound.

Yield: 61%

¹ H NMR (CDCl ₃ , 400 MHz) d 8.13 (d, J = 8.4 Hz, 1H), 8.04 (d, J = 8.5 Hz, 1H), 7.59 7.55 (m, 1H), 7.51 7.47 (m, 1H) , 7.25 (d, J = 8.8 Hz, 2H), 7.01 (d, J = 8.8 Hz, 2H), 6.58 (s, 1H), 4.60 (s, 2H), 4.03 (s, 3H), 3.54 (s, 3H).

[Formula 45]: 1- (2-(((1,4- dimethoxynaphthalen -2- yl ) methyl) amino) -1H-benzo [d] imidazol-1-yl) ethan-1-one

CH ₂ Cl ₂ for 1 hour at room temperature To 140 mg of the compound of Formula 44 and 25 mg of NaH in 5 mL were added 107 mg of Ac ₂ O at room temperature and stirred for 4 hours. The reaction mixture was washed with water and extracted with CH ₂ Cl ₂ . The separated organic solution was washed with water, dried over Na ₂ SO ₄ and concentrated in vacuo. Finally, purification by flash column chromatography (hexane: EtOAc = 4: 1) afforded the compound of [Formula 45]. Yield: 89%

¹ H NMR (CDCl ₃ , 400 MHz) d 8.22 (d, J = 8.2 Hz, 1H), 8.08 (d, J = 8.2 Hz, 1H), 7.61-7.42 (m, 3H), 7.39 (d, J = 8.8 Hz, 1H), 7.27 (t, 1H & CDCl _{3 ,} overlapped), 7.13 7.09 (m, 1H), 6.88 (s, 1H), 4.98 (d, J = 6.4 Hz, 2H), 3.98 (s, 3H ), 3.97 (s, 3 H), 2.77 (s, 3 H).

Formula 46: 1- (2-(((1,4- dimethoxynaphthalen -2- yl ) methyl) amino) -1H-benzo [d] imidazol-1-yl) ethan-1-one

At -40 ° C, 32 mg of ammonium cerium (IV) nitrate dissolved in water (0.5 mL) was added to 15 mg of the stirred compound of formula 45 in 1 mL of acetonitrile, followed by stirring for 1 hour. . After the reaction was completed, water was slowly added and extracted with CHCl ₃ . The organic layer was washed with water and brine, dried over Na ₂ S0 ₄ and concentrated under reduced pressure. Finally, purification by flash column chromatography (hexane: EtOAc = 5: 1) afforded the compound of [Formula 46]. Yield: 56%

¹ H NMR (CDCl ₃ , 400 MHz) d 8.23 8.19 (m, 1H), 8.15 8.11 (m, 1H), 8.08 8.04 (m, 1H), 7.77 7.73 (m, 2H), 7.41 (d, J = 3.1 Hz, 1H), 7.39 (d, J = 3.1 Hz, 1H), 7.23 7.21 (m, 1H & CDCl _{3 ,} overlapped), 7.11 7.07 (m, 1H), 6.95 (s, 1H), 4.78 (d, J = 5.1 Hz, 1H), 2.81 (s, 3H).

Formula 47: 3-((1,4- dioxo -1,4- dihydronaphthalen -2- yl ) amino) propanoic  acid

At room temperature, 158 mg of stirred naphthalen-1,4-dione in 5 mL of methanol was added to 107 mg of stirred 3-aminopropanoic acid in 5 mL of methanol. After 24 hours of reaction at room temperature, the reaction mixture was concentrated in vacuo and purified by flash column chromatography (100% EtOAc) to give the compound of [Formula 47]. Yield: 51%

¹ H NMR (DMSO, 400 MHz) d 7.98 (d, J = 7.6 Hz, 1H), 7.97 (d, J = 7.6 Hz, 1H), 7.85 7.81 (m, 1H), 7.75 7.71 (m, 1H), 7.50 (s, 1 H), 3.21 (t, J = 6.4 Hz, 2H), 2.59 (t, J = 6.4 Hz, 2H).

Formula 48: 4-((1,4- Dioxo -1,4- dihydronaphthalen -2- yl ) amino) butanoic  acid

At room temperature, 158 mg of stirred naphthalen-1,4-dione in 5 mL of methanol was prepared using 5 mL of methanol to prepare a compound of Formula 48. Specifically, after 24 hours of reaction at room temperature, the reaction mixture was concentrated in vacuo and purified by flash column chromatography (100% EtOAc) to obtain the compound of [Formula 48]. Yield: 53%

¹ H NMR (DMSO, 400 MHz) d 7.98 (d, J = 7.6 Hz, 1H), 7.94 (d, J = 7.6 Hz, 1H), 7.84 7.81 (m, 1H), 7.74 7.71 (m, 1H), 7.66 (s, 1 H), 4.10 (bs, 1 H), 3.22 -3.17 (m, 2 H), 2.30 (t, J = 7.2 Hz, 2H), 1.79 (q, J = 7.2 Hz, 2H).

Formula 49: N ^6- (1,4-Dioxo-1,4-dihydronaphthalen-2-yl) lysine

At room temperature, the compound of [Formula 49] was prepared using 5 mL of methanol in 158 mg of stirred naphthalen-1,4-dione in 5 mL of methanol. Specifically, after 24 hours of reaction at room temperature, the reaction mixture was concentrated in vacuo and purified by flash column chromatography (100% EtOAc) to obtain the compound of [Formula 49]. Yield: 68%

¹ H NMR (DMSO, 400 MHz) d 7.79 (d, J = 7.8 Hz, 1H), 7.95 (d, J = 7.8 Hz, 1H), 7.84 7.80 (m, 1H), 7.73 7.72 (m, 1H), 7.45 (d, J = 5.2 Hz, 1H), 5.58 (s, 1H), 3.40 (1H & H ₂ O _, overlapped), 2.70 (s, 2H), 1.77 1.76 (m, 2H), 1.53 (bs, 2H ), 1.33 1.24 (2H).

[Formula 50]: 1- (4- ( Diethylamino ) phenyl) -2- (1,4- dioxo -1,4-dihydronaphthalen-2-yl) hydrazine-1-carboxylate

At room temperature, the compound of [Formula 50] was prepared using 5 mL of methanol in 158 mg of stirred naphthalen-1,4-dione in 5 mL of methanol. Specifically, after 24 hours of reaction at room temperature, the reaction mixture was concentrated in vacuo and purified by flash column chromatography (100% EtOAc) to obtain a compound of [Formula 50]. Yield: 57%

¹ H NMR (CDCl ₃ , 400 MHz) d 8.08 (d, J = 7.2 Hz, 1H), 8.04 (d, J = 7.2 Hz, 1H), 7.74 7.70 (m, 2H), 7.65 7.62 (m, 1H) , 7.21 (d, J = 8.8 Hz, 2H), 6.59 (d, J = 8.8 Hz, 2H), 6.08 (s, 1H), 3.36 (q, J = 6.8 Hz, 4H), 1.46 (s, 9H) , 1.14 (t, J = 6.8 Hz, 6H).

Formula 51: 2-((2- (Diethylamino) ethyl) amino) naphthalene-1,4-dione

At room temperature, the compound of [Formula 51] was prepared using 5 mL of methanol in 158 mg of naphthalen-1,4-dione, which was stirred in 5 mL of methanol. Specifically, after 24 hours of reaction at room temperature, the reaction mixture was concentrated in vacuo and purified by flash column chromatography (100% EtOAc) to obtain the compound of [Formula 51]. Yield: 62%

¹ H NMR (CDCl ₃ , 400 MHz) d 8.11 (d, J = 7.2 Hz, 1H), 8.04 (d, J = 7.2 Hz, 1H), 7.97 (s, 1H), 7.74 7.70 (m, 1H), 7.63 7.59 (m, 1H), 5.68 (s, 1H), 3.21 3.17 (m, 2H), 2.79 2.76 (m, 2H), 2.61 (q, J = 6.8 Hz, 4H), 1.07 (t, J = 6.8 Hz, 6H).

Formula 52] 2-((3- (Diethylamino) propyl) amino) naphthalene-1,4-dione

At room temperature, the compound of [Formula 52] was prepared by using 5 mL of methanol in 158 mg of naphthalen-1,4-dione, which was stirred in 5 mL of methanol. Specifically, after 24 hours of reaction at room temperature, the reaction mixture was concentrated in vacuo and purified by flash column chromatography (100% EtOAc) to obtain the compound of [Formula 52]. Yield: 60%

¹ H NMR (CDCl ₃ , 400 MHz) d 8.11 (d, J = 7.2 Hz, 1H), 8.04 (d, J = 7.2 Hz, 1H), 7.97 (s, 1H), 7.74 7.70 (m, 1H), 7.63 7.59 (m, 1H), 5.68 (s, 1H), 3.22 3.18 (m, 2H), 2.62-2.53 (m, 6H), 1.85-1.80 (m, 2H), 1.08 (t, J = 7.2 Hz, 6H).

Formula 53] 2-((4- (Diethylamino) butyl) amino) naphthalene-1,4-dione

At room temperature, the compound of [Formula 53] was prepared by using 5 mL of methanol in 158 mg of naphthalen-1,4-dione, which was stirred in 5 mL of methanol. Specifically, after 24 hours of reaction at room temperature, the reaction mixture was concentrated in vacuo and purified by flash column chromatography (100% EtOAc) to obtain the compound of [Formula 53]. Yield: 60%

¹ H NMR (CDCl ₃ , 400 MHz) d 8.11 (d, J = 7.4 HzHH, 1H), 8.05 (d, J = 7.4 Hz, 1H), 7.76 7.72 (m, 1H), 7.65 7.61 (m, 1H) , 6.41 (bs, 1H), 5.72 (s, 1H), 3.24 3.20 (m, 2H), 2.63 (q, J = 7.2 Hz, 4H), 7.53 (t, J = 7.2 Hz, 2H), 1.77 1.70 ( m, 2H), 1.65 1.60 (m, 2H), 1.07 ( J = 7.2 Hz, 6H).

Formula 54: 2-((1,4- Dioxo -1,4- dihydronaphthalen -2- yl ) amino) ethane-1-sulfonic acid

At room temperature, the compound of [Formula 54] was prepared using 5 mL of methanol in 158 mg of stirred naphthalen-1,4-dione in 5 mL of methanol. Specifically, after 24 hours of reaction at room temperature, the reaction mixture was concentrated in vacuo and purified by flash column chromatography (100% EtOAc) to obtain the compound of [Formula 54]. Yield: 29%

¹ H NMR (DMSO, 400 MHz) d 7.99 (d, J = 8.0 Hz, 1H), 7.95 (d, J = 8.0 Hz, 1H), 7.85-7.79 (m, 2H), 7.75 7.71 (m, 1H) , 5.64 (s, 1 H), 3.32 (2H & H ₂ O _, overlapped), 2.75 (t, J = 7.2 Hz, 2H).

Formula 55: 3-((1,4- Dioxo -1,4- dihydronaphthalen -2- yl ) amino) propane-1-sulfonic acid

At room temperature, the compound of [Formula 55] was prepared using 5 mL of methanol in 158 mg of naphthalen-1,4-dione, which was stirred in 5 mL of methanol. Specifically, after 24 hours of reaction at room temperature, the reaction mixture was concentrated in vacuo and purified by flash column chromatography (100% EtOAc) to obtain the compound of [Formula 55]. Yield: 25%

¹ H NMR (DMSO, 400 MHz) d 7.98 (d, J = 7.6 Hz, 1H), 7.94 (d, J = 7.6 Hz, 1H), 7.84 7.82 (m, 1H), 7.74 7.70 (m, 2H), 5.71 (s, 1 H), 3.27 3.25 (m, 2 H), 2.54-2.48 (m, 2H), 1.86 (t, J = 6.8 Hz, 2H).

Formula 56: 4-((1,4- Dioxo -1,4- dihydronaphthalen -2- yl ) amino) butane-1-sulfonic acid

At room temperature, the compound of [Formula 56] was prepared using 5 mL of methanol in 158 mg of naphthalen-1,4-dione, which was stirred in 5 mL of methanol. Specifically, after 24 hours of reaction at room temperature, the reaction mixture was concentrated in vacuo and purified by flash column chromatography (100% EtOAc) to obtain the compound of [Formula 56]. Yield: 21%

¹ H NMR (DMSO, 400 MHz) d 7.99 (d, J = 7.6 Hz, 1H), 7.94 (d, J = 7.6 Hz, 1H), 7.84 7.81 (m, 1H), 7.74 7.72 (m, 1H), 7.63 7.60 (m, 1 H), 5.68 (s, 1 H), 3.18 3.16 (m, 2 H), 2.46 2.44 (m, 2H), 1.63 1.62 (m, 4H).

Example 1 Measurement of Harmful Algae Effect

The effects of harmful algae killing at various inoculation concentrations of the compounds according to the present invention were measured.

To this end, as a treatment group (experimental group), fresh algae harmful algae, Microcystis aeruginosa ( Microcystis aeruginosa ) , Anabaena flos -aqua ( Anavena floss -Aqua), diatom Stephanodiscus hantzschii (Stephanoscus Hantzchi ) , Cyclotella meneginia ( Cyclotelena menegenia ), Aulacoseira ( Aulaco Seira), Synedra acus ( Sinedra acus ), Scenedesmus actus ( Cinedesmus Actus ), seaweed harmful algae Alexandrium tamarens (Alexandrarium Tamarens ), Cochlodinium polykrikoides (kokeulrodinium poly Corey Koh des), Heterocapsa triquetra (hetero kapsa tree Quebec Tra), Prorocentrum micans , Protocentrum Mycans , Chattonella marina , Heterosigma akashiwo ( heterosigma acacio ), diatom Pseudo- nitzschia pungens (Sudonishician pungens ) were used. Culture conditions are shown in Table 2 below.

The experiment was first conducted with 10 mL of Microcystis each. aeruginosa (microsistis aeruginosa), Anabaena flos -aqua ( Avenena Flos -Aqua), Stephanodiscus hantzschii ( Stephanodiscus Hantzchi ), Scenedesmus actus ( Cinedesmus Actus ), Aulacoseira ( Aulaco Seira) 5 × 10 ⁵ cells / mL were prepared, and in the case of Cyclotella meneginia ( cyclotelella menegenia ), 1 10 ⁵ cells / mL was prepared, and then the compounds represented by [Formula 6] to [Formula 56] were variously prepared. Inoculation was carried out to the final concentration was 0.1, 0.2, 0.5, 1, 2, 5, 10, 20, 50 M was treated. Seawater Algae Alexandrium tamarens (Alexandrarium Tamarens ), Cochlodinium polykrikoides ( Coclodinium polycoricoides ), Heterocapsa triquetra (Heterocapsa Triquetra), Prorocentrum micans ( Procentrum Mycans ), Chattonella marina ( Chattonella Marina), Heterosigma In the case of akashiwo ( heterosigma acacio ) and Pseudo-nitzschia pungens (pseudo -nichsia pungens ), 1 × 10 ³ cells / mL prepared after inoculating the compounds represented by the above [Formula 6] to [Formula 56] at various concentrations The final concentration was treated to 0.1, 0.2, 0.5, 1, 2, 5, 10, 20, 50 M, respectively. Treatment conditions were directly counted visually by SR-chamber or heamocytometer under incubation or inverted microscope while incubating for 7 days or 10 days under incubation conditions of algae. After 7 or 10 days after treatment, the reduction ratio of the cells, ie, the algal activity (%), was calculated using the following formula.

Algal activity (%) = (1- Tt / Ct ) x 100

In the above formula, T represents the density of cells after compound treatment, C represents the density of cells not treated with compound, and t represents culture time.

The algae effect was derived by inoculating the substances developed for various phytoplankton including harmful algae at concentrations of 1, 5, 10, and 20M, respectively. Algal activity of each compound obtained on the basis of the above formula was expressed as <60, 70, 80, 90%.

In addition, the algicidal effects of the compounds were screened using a Microplate assay. After culture of the algae of interest in the log growth phase in 48 well plates, the synthesized derivatives were inoculated into each algal species in each log growth period at a concentration of 1 to 20 uM and cultured and counted for 7 days. On day 0, 1, 2, 4, and 7, take 10-50 ul of sample from each well, place on a Neubauer hemocytometer or SR chamber, count the intact algae cells under an IX71 microscope (Olympus, Japan). The killing ability (%) of the substance was determined by measuring the cell number decreased compared to the control. The cell counts of the 7th day of the experiment showed the killing ability of the corresponding algae according to the concentration of each algae. However, after 7 days from the start of the experiment, it was determined that the killing ability of the control group was lower than 60, and the special killing effect was less than 60, and the results are shown in FIGS. 1 to 2.

1 is a view showing the results of testing the green algae control effect on the freshwater microalgae of the harmful algae control composition according to an embodiment of the present invention, Figure 2 is a composition of the harmful algae control composition according to an embodiment of the present invention A diagram showing the results of testing the green algae control effect on seawater microalgae.

As a result, the compounds of [Formula 6] to [Formula 56] according to the present invention showed more than 90% of the killing ability at 1, 5, 10, 20 uM concentrations of cyanobacteria Anabaena sp. And Microcystis sp. Especially, even at very low concentration of 1 uM, more than 90% of the effects could be observed, and only harmful cyanobacteria could be specifically controlled. Especially, Anabaena sp. Showed more than 90% algae effect at low concentration of 1 uM, and it was the main causative species of algae in winter and the diatoms Stephanodiscus sp. At 1, 5, 10, 20 uM showed more than 80% of the killing effect. In addition, diatoms Synedra , Aulacoseira and cyanobacteria Cosmarium, Scnedesmus were not affected except the main causative species in summer and winter. In addition, Alexandrium , a marine red tide species tamarens , Cochlodinium polykrikoides, Heterocapsa triquetra, Prorocentrum micans , Chattonella marina , Heterosigma Most of akashiwo and Pseudo-nitzschia pungens showed more than 90% algae effect at 5 uM concentration. In addition, most of the experiments showed that the algae effect was insignificant for the other groups other than the green algae and the red tide problem organisms.

Therefore, according to the above results, a composition containing the compounds of the present invention as an active ingredient is Aulacoseira. granulata , Synedra While it has little effect on species that are relatively less problematic in freshwater and brackish waters such as acus , it has been found that there is an excellent algae effect against harmful algae that cause green algae and red tide phenomena at home and abroad.

Example 2: Ecotoxicity Test

Selenastrium , an indicator organism for evaluating ecotoxicity of OECD, EPA, to investigate the effects of compounds according to the present invention on ecosystem capricornutum (selenastrium capricornium ) , Daphnia magna , Danio Ecotoxicity assessment was performed using rerio (zebrafish ) .

In the case of surface algae, Selenastrum capricornutum (selenastrum capricornium ) was prepared and inoculated with a new compound to prepare a starting density and inoculation concentration of the indicator organism at 1 × 10 ⁴ cells / mL, 2, 1, 0.5, 0.2, and 0.1 μM, respectively. . Mixed cultures were incubated under the optimal growth conditions of indicator organisms (20 ° C., 50 mol / m ² s, EG: JM medium, 12hr light: 12hr dark cycle). The change in the number of indicator organisms was directly observed under an optical microscope for 72 hours at 12 hours.

Next, in the case of surface zooplankton, 10 adult animals of zooplankton Daphnia magna (Daffnia magna ), which have not been born for 24 hours, were prepared in three repeats, and the starting concentration was 2, 1 Prepared to be 0.5, 0.2, 0.1 μM. Culture conditions were 25 ℃, 50 mol / m ² s, 12hr light: 12hr dark cycle culture conditions were observed for 48 hours in 24 hours increments. As a culture water of Daphnia Magna, 3 L of sterile water (DW) containing 0.024 g of KCl, 0.738 g of MgSO ₄ 7H ₂ O, 0.360 g of CaSO ₄ 7H ₂ O, and 0.576 g of NaHCO ₃ were prepared. Observation of the species was performed by naked eye and recorded.

Finally, surface fish Danio For rerio (zebrafish ) organisms, randomly selected Danio rerios of 2-3 cm were exposed to 7 animals. Inoculation with the new compound was prepared to have a starting concentration of 2, 1, 0.5, 0.2, 0.1 μM. Culture conditions were 25 ℃, 50 mol / m ² s, 12hr light: 12hr dark cycle culture conditions were observed for 96 hours population in 24 hours increments.

Figure 3 of the composition for controlling harmful algae according to the present invention for Selenastrium capricornutum, Daphnia magna, Zebrafish (Danio rerio) as indicator organisms for the EPA standard ecotoxicity assessment A diagram showing the results of the ecotoxicity assessment.

As a result, the compounds according to the present invention are Selenastrum capricortrum, Daphnia magna, Danio according to the inoculation concentration There was no tendency to observe the change in cell number of rerio , and it was confirmed that there was almost no decrease in the host population compared to the control even in 2 μM with relatively high inoculation concentration in all the experimental groups.

Example 3: 10 L scale Microcosm test for species diversity enhancing effect

Stephanodiscus sp. To determine whether the algae control technology using the composition for controlling harmful algae containing the compounds according to the present invention affects aquatic ecosystem restoration and species diversity. Microcosm experiments were performed using the predominant Nakdong River field water.

Figure 4 is a graph measuring the amount of change in phytoplankton in microcosm when the harmful algae control composition according to the present invention with respect to the field number of the Nakdong River dominant stephanodiscus, Figure 5 except for stephanodiscus in microcosm It is a graph measuring the change in phytoplankton, Figure 6 is a graph showing the change in species diversity index of phytoplankton in the microcosm.

Stephanodiscus sp., A target bird, increased from 3.9 × 10 ³ cells / mL to 9.1 × 10 ⁴ cells / mL in the control group during the experimental period, but in the treatment group inoculated with the compound according to the present invention from day 2 to 10 after inoculation continue to decrease until the 10th day, the target species Stephanodiscus While the sp. species decreased to 6.4 × 10 ² cells / ml, the algae effect was observed to be 99%, whereas for phytoplankton other than the target species Stephanodiscus sp., in the control group, the Stephanodiscus sp. On the 10th day, phytoplankton did not grow at all, but the phytoplankton did not grow at all, but in the treatment group treated with the present invention, Stephanodiscus sp. It was confirmed that the conditions were satisfied. As a result of the change in the dominant species, it was confirmed that a variety of useful algae grow in the treatment group treated with the compound according to the present invention, and the species diversity index was measured based on these results, and the compound according to the present invention was treated with the control group. We found that the diversity index improved significantly.

According to the present invention can be very useful for preventing harmful algae generation and fresh water pollution occurring in fresh or sea water. In addition, it can be utilized as an important antifouling agent or paint for green algae and red tide has the advantage that the possibility of commercialization is very large.

Claims (3)

1. Toxic algae control composition comprising a compound selected from the group consisting of compounds represented by the following [Formula 1] to [Formula 5] or salts thereof as an active ingredient:

   

   In [Formula 1] to [Formula 5],

   X is O, S or NR ₂ ,

   R ₁ is hydrogen, halogen, CF ₃ , a substituted or unsubstituted alkyl group having 1 to 12 carbon atoms, or a substituted or unsubstituted alkoxy group having 1 to 12 carbon atoms,

   R ₂ is hydrogen, acetyl (Ac) or t-butoxycarbonyl (Boc),

   R ₃ is any one selected from the following [Formula 1],

   [Formula 1]

   

   In [Formula 1],

   * Indicates the position of binding to the above [Formula 5].
2. A method for controlling harmful algae comprising treating the harmful algae control composition containing the compound of claim 1 or a salt thereof in an area in which the harmful algae is busy or in an area in which developmental symptoms are observed.
3. The method according to claim 2, wherein the treatment is performed in the form of spraying locally using a vessel.

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