Agents for controlling underwater fouling organisms

Abstract: The present invention provides the use as undersea anti-fouling reagent of an indole compound of Formula (1): (wherein Y represents hydrogen, lower alkyl, or phenyl; X¹, X², X³, X⁴, X⁵ and X⁶ independently represent hydrogen, halogen, lower alkyl, lower alkoxy, nitro, cyano, cyano lower alkyl, halogenated lower alkyl, di-lower-alkylamino-lower alkyl, etc.) The compounds of formula (1) are safe and effective underwater anti-fouling reagents.

Description: 1. Introduction The present invention relates to agents that prevent unwanted fouling organisms from attaching and growing on ship hulls, culturing nets, set-nets, sea equipments such as buoys, the cooling water tubes of atomic power plants or thermal electric power plants, and the inlet channels of heat exchangers in the petrochemical industry. 2. Background of the Invention In ship hulls, underwater structures, the inlet channels of a cooling water tubes and other structures that are always exposed to water, there are various shellfish and algae such as Balanus , Mytilus , Hydrozoa , Ulva , Enteromorpha as well as others that attach and grow, or even overgrow. The attachment of these organisms to these structures causes economic damage in various forms: increased attachment to ship hulls slows down the cruising speed of these vessels, increases fuel consumption and also causes serious economical loss due to the cancellation of service in order to clean the ship hulls. Their attachment to cooling water equipment decreases heat conductivity which eventually reduces the cooling power of the equipment. A variety of agents useful for controlling fouling organisms in fresh water or sea water have been used to prevent the attachment and overgrowth of these organisms. Copper compounds and organolin compounds are known active anti-fouling agents, and are still extensively used today. Anti-fouling agents in the form of a paint can contain 10-50% by weight of the active ingredient and can be used to paint surfaces such as ship hulls. The paint prevents attachment and growth of fouling organisms by continuously releasing anti-fouling agents underwater. 3. Summary of the Invention The reagents of the present invention have excellent anti-fouling properlies against underwater fouling organisms. The reagents are more effective than conventional anti-fouling agents containing heavy metals and more importantly, are safe for our health and the environment. 4. Detailed Description of the Invention Environmental problems such as polluted rivers and sea with heavy metals and toxic compounds have been caused by the industrial use of such materials. For example, stern warnings have been issued regarding the effects of heavy metal compounds, especially organotin compounds which are widely used and known to be effective anti-fouling reagents because of their effect on the natural environment and on health when accumulated in the body via food such as fish and shellfish. Therefore, there is a need for the development of safe and effective anti-fouling compounds. WO90/06975 describes marine anti-fouling compositions containing an agent comprising a herbicide or pesticide. Agents disclosed include 3-indolacetic acid. Eur. J. Med. Chem. - Chim. Ther., 1983- 18 ; 261-267 describes the preparation of bromoderivatives of gramines. The present inventors have attempted to develop highly-safe, and effective anti-fouling compounds. It has been found that particular indole compounds have an excellent repellent effect against fouling organisms. The present invention provides the use of an indole compound of formula (I): wherein Y represents hydrogen, C₁-C₅ alkyl, or phenyl; X¹, X², X³, X⁴, X⁵ and X⁶ independently represent hydrogen, halogen, C₁-C₅ alkyl, C₁-C₅ alkoxy, nitro, cyano, cyano C₁-C₅ alkyl, halogenated C₁-C₅ alkyl, substituted or unsubstituted phenyl, aralkyl, aralkyloxy, C₂-C₆ alkoxycarbonyl, aliphatic C₂-C₆ acyl, aliphatic C₂-C₆ acyloxy, aromatic acyl, C₃-C₇ cycloalkylamino-C₁-C₅ alkyl, nitrovinyl, pyridyl C₁-C₅ alkyl, carbamoyl C₁-C₅ alkyl, carbamoyl, diallylamino C₁-C₅ alkyl or di-C₁-C₅ alkylamino-C₁-C₅ alkyl, as an underwater anti-fouling reagent. In the formula (1), alkyl represented by X¹, X², X³, X⁴, X⁵, X⁶ or Y refers to a straight or branched alkyl group having 1-5 carbon atoms and includes methyl, ethyl, propyl, isopropyl, sec-butyl, pentyl and hexyl. Examples of halogen represented by X¹, X², X³, X⁴, X⁵ or X⁶ includes a fluorine, chlorine, bromine or iodine atom. C₁₋₅ alkoxy includes methoxy, ethoxy, propoxy and butoxy. Cyano C₁₋₅ alkyl refers to said C₁₋₅ alkyl substituted by a cyano group. Examples include cyanomethyl, cyanoethyl and cyanopropyl. Halogenated C₁₋₅ alkyl refers to said C₁₋₅ alkyl substituted by said halogen. Examples of halogenated C₁₋₅ alkyl include chloromethyl, trifluoromethyl and 2-bromoethyl. Examples of substituted phenyl includes a phenyl group substituted by amino, halogen, C₁₋₅ alkyl or C₁₋₅ alkoxy. Examples of aralkyl include a benzyl group. Examples of aralkyloxy include a benzyloxy group. C₂₋₅ alkoxycarbonyl includes methoxycarbonyl, ethoxycarbonyl, propoxcarbonyl, butoxycarbonyl. Aliphatic C₂₋₆ acyl includes acetoxy and propionyloxy. Examples of an aromatic acyl include unsubstituted benzoyl or a benzoyl group substituted by amino, halogen, C₁₋₅ alkyl, or C₁₋₅ alkoxy; C₃₋₇ cycloalkylamino C₁₋₅ alkyl includes cyclohexylaminomethyl, cyclohexylaminoethyl, cyclopentylaminomethyl and cyclopentylaminoethyl. Examples of pyridyl C₁₋₅ alkyl include pyridylmethyl, pyridylethyl, and pyridylpropyl. Examples of carbamoyl C₁₋₅ alkyl include carbamoylmethyl, carbamoylethy and carbamoylpropyl. Diallylamino C₁₋₅ alkyl includes diallylaminomethyl, diallylaminoethyl and diallylaminopropyl. Examples of di C₁₋₅ alkylamino C₁₋₅ alkyl include dimethylaminomethyl, dimethylaminoethyl and dimethylaminopropyl. Examples of indole compounds represented by the formula (I) include but not limited to those listed in Table 1. The indole compounds shown in Table 1 are all known compounds and can be chemically synthesized by conventional methods known in the art. Most of the indole compounds described above are found in animals, plants, and bacteria and can be obtained by extraction and purification from these organisms. For example, 2,5,6-Tribromo-1-methylgramine (Compound No.91), an indole compound represented by the formula(1) wherein X¹,X⁴ and X⁵ are bromine; X³ and X⁶ are hydrogen; X² is dimethylaminomethyl; and Y is methyl, is known to be found in Zoobotryon verticillatum , a species of Bryozoa [Aiya Sato et al ., Tetrahedron Lett ., 2 4 , 481. (1983)]. In addition, Compound No.91 can also be extracted and purified from Zoobotryon pellucidum , as is disclosed by the present inventors. Solvents used for extracting these compounds include typical organic solvents, preferably acetone or ethanol. Purification methods include those known in the art such as partition chromatography, preferably silica gel chromatography using a mixture of hexane and ethyl acetate as an eluent. The indole compounds used as the active ingredient in the present invention may be used alone or in combination with other anti-fouling agents. Active ingredients extracted from organisms may be used as a crude extract or purified. if necessary. The anti-fouling compounds of the present invention may be used by formulating the agents in numerous forms including as a paint, a solution and as an emulsion. Formulation is carried out as usual without any difficulties. For example, when the reagents of the present invention are used as a paint, an anti-fouling paint is prepared by formulating one of the active ingredients described above with other components as described below. The anti-fouling paint can then be applied to ship hulls, underwater structures and inlet channels of water coolong systems. The anti-fouling paint comprises the active ingredient of the present invention and film-forming ingredients, including solvents which are selected according to use. extender pigments, coloring pigments and additives. Film-forming ingredients includes chlorinated rubber resin, vinyl acetate resin, acrylic resin and natural resin. The active ingredient is typically formulated 1-45% by weight based on the weight of the anti-fouling point, preferably 5-20%. When the reagents of the present invention are used as a solution, an anti-fouling solution is prepared by formulating the active ingredients with film-forming ingredients as described above and by dissolving the mixture in solvents. The anti-fouling solution is then applied to farming nets and set-nets in order to prevent overgrowth of the fouling organisms. Film-forming ingredients used in the anti-fouling solution include chlorinated rubber resin, vinyl acetate resin, acrylic resin and natural resin. Solvents include toluene, xylene, cumene, methylisobutylketon, ethyl acetate and methanol. Additives such as a plasticizer can be added to the anti-fouling solution, if necessary. The active ingredient is typically formulated 2-70% by weight based on the weight of an anti-fouling solution, preferably 5-30%. When the agent is employed as an emulsion, an anti-fouling solution is prepared according to the conventional method in the art, by dissolving active ingredients described above in solvents and by adding surfactants to the mixture. Surfactants include those typically used in the art. When the agents of the present invention are used as emulsion, the active ingredient is typically formulated 5-50% by weight based on the weight of anti-fouling emulsion, preferably 10-40%. The anti-fouling reagents of the present invention may be used by kneading the agents into polymer resin materials of fishing nets and the materials of underwater structure such as concrete. 5. Examples The present invention will be more readily understood with reference to the following examples. However, these examples are intended to illustrate the present invention and are not to be construed to limit the scope of the invention. Example 1 Effect of indole compounds in Table 1' on Balanus and Artemia Various indole compounds were tested for their affect on attachment of the larvae of Balanus amphitrite , an infamous fouling organism, as well as their attect on other beneficial organisms such as Artemia salina , a zooplankton used as feed for juvenile fish. Selected compounds in Table 1, 0.05mg each, were dissolved in 0.1ml methanol. Round plates (4cm in diameter) were then uniformly coated with the solution and air-dried to evaporate methanol. 5ml of filtrated sea water, 10 larvae of B . amphitrite in the attachment stage of the development, and 5 larvae of A. salina were placed in the each plate. The plate was incubated in the darkroom at 23 °C for 24 hours. After 24-hour incubation, the number of molted B. amphitrite attached to the bottom of the plate was counted to evaluate the effect of the test compound and the number of dead A. salina was also counted to evaluate the safety of the compound for beneficial organism. As comparison, a similar test was carried out using 0.05 mg of Bis(tributyltin)oxide (hereafter referred to as "TBTO") instead of the compound in Table 1. The above test was repeated three times and the resulting numbers were averaged. Table 2 shows the results. The compound number in Table 2 corresponds the one in Table 1. (%) Compound No. Attachment rate of larvae Mortality of Artemia 2 0 0 4 0 0 6 0 0 8 0 0 10 5 0 12 5 0 14 10 0 16 10 0 18 15 0 20 0 0 22 0 0 24 0 0 26 0 0 28 0 0 30 0 0 32 0 0 34 0 0 36 0 0 38 0 0 40 0 0 42 0 0 44 5 0 46 10 0 48 10 0 50 0 0 52 15 0 54 0 0 56 0 0 60 0 0 64 0 0 66 0 0 68 10 0 TBTO 0 100 non-agent 85 0 Example 2 Comparison of the anti-fouling reagents of the invention with Copper Sulfate and TBTO Various indole compounds of formula(1) wherein X² is the di-lower-alkylamino-lower alkyl, were tested for effect on the attachment of larvae of B. amphitrite . Selected compounds in Table 1, 0.05 mg and 0.005 mg each, were dissolved in 0.1 ml methanol. Round plates (4 cm in diameter) were then uniformly coated with the solution and air-dried for removing methanol. 5 ml of filtrated sea water, 10 larvae of B. amphitrite in the attachment stage of the development were placed in each plate. The plate was incubated in the darkroom at 23 °C for 24 hours. After 24-hour incubation, the number of molted B. amphitrite attached to the bottom of the plate was counted to evaluated the effect of the test compound. As a comparison, a similar test was carried out using Copper Sulfate and TBTO instead of the compound in Table 1. The above test was repeated three times and the resulting numbers were averaged. Table 3 shows the results. The compound number in Table 3 corresponds the number used of Table 1. Compound No. Dosage(mg/5ml) and attachment rate of larvae (%) Condition of non-attached larvae 0.05mg-dosage 0.05mg 0.005mg 70 0 35 vigorously swim 71 0 15 vigorously swim 72 0 0 vigorously swim 73 0 5 vigorously swim 74 0 5 vigorously swim 75 0 0 vigorously swim 76 0 0 vigorously swim 77 0 0 vigorously swim 78 0 0 vigorously swim 79 0 0 vigorously swim 80 0 5 vigorously swim 81 0 0 vigorously swim 82 0 0 vigorously swim 83 0 0 vigorously swim 84 0 10 vigorously swim 85 0 0 vigorously swim 86 0 0 vigorously swim 87 0 0 vigorously swim 88 0 0 vigorously swim 89 0 0 vigorously swim 90 0 0 vigorously swim 92 0 5 vigorously swim 93 0 35 vigorously swim Copper Sulfate 0 30 all larvae died TBTO 0 0 all larvae died Non-agent 85 As is evident from Table 3, Copper Sulfate and TBTO prevent Balanus from attachment based on their toxicities, otherwise, the reagents of the present invention prevent the organisms from attaching without killing them. Example 3 Compound No.91 obtained from Zoobotryon pellucidum 2.1Kg of Zoobotryon pellucidum (phylum Tentaculata, class Bryozoan) were extracted with 3 Kg of acetone. After extraction, acetone was removed under reduced pressure and the residue was partitioned with 800 ml ethyl acetate and 1200 ml water. The ethyl acetate layer was separated and evaporated under reduced pressure. The resulting residue was purified by silica gel chromatography using an eluent of 30 % ethyl acetate in hexane (v/v) to give 610 mg of Compound No.91. In the analyses, ¹H-NMR spectrum, visible light absorption spectrometry, and mass spectrometry, the compound thus obtained was found to be equivalent to the compound in the art. Example 4 Comparison of the anti-fouling effect of Compound No.91 with Copper Sulfate and TBTO Compound No.91 obtained in Example 3 was tested for effect on attachment using the larvae of B. amphitrite . 0.05 mg of Compound No.91 was dissolved in 0.1 ml methanol. Round plates (4 cm in diameter) were then uniformly coated with the solution and air-dried to remove methanol. 5 ml of filtrated sea water, 10 larvae of B. amphitrite in the attachment stage of the development were placed in each plate. The plate was incubated in the darkroom at 23 °C for 24 hours. After 24-hour incubation, the number of molted B. amphitrite attached to the bottom of the plate was counted to evaluate the effect of the test compound. As a comparison, a similar test was carried out using 0.1 mg of Copper Sulfate, 0.05 mg of TBTO and the absence of any agent instead of Compound No.91. Table 4 shows the results. Test plot Active ingredient Dosage (mg) Attachment rate (%) Condition of non-attached larvae Example 4 Compound No.91 0.05 0 Vigorously swim (50%) Comparison4 Copper Sulfate 0.1 0 All larvae died Comparison 5 TBTO 0.05 0 All larvae died Comparison 6 Non-agent 0 70 Vigorously swim (100%) Example 5 Formulation of the anti-fouling reagents of the invention When the anti-fouling reagents of the present invention is used as a preventive paint for the attachment of fouling organisms, the formulation is as follows. Formulation 1 Composition Weight (%) Invention compound 15 Rosin WW 6 VYHH(synthetic vinyl resin) 6 Tricresyl phosphate 2 Talc 15 Barium sulfate 15 Red iron oxide 10 Xylene 26 Methylisobutylketon 5 Total 100 Formulation 2 Composition Weight (%) Invention compound 10 Rosin WW 6 VYHH(synthetic vinyl resin) 6 Tricresyl phosphate 2 Talc 20 Barium sulfate 15 Red iron oxide 10 Xylene 20 Methylisobutylketon 11 Total 100

Claims: Use of an indole compound of formula (I): wherein Y represents hydrogen, C₁-C₅ alkyl, or phenyl; X¹, X², X³, X⁴, X⁵ and X⁶ independently represent hydrogen, halogen, C₁-C₅ alkyl, C₁-C₅ alkoxy, nitro, cyano, cyano C₁-C₅ alkyl, halogenated C₁-C₅ alkyl, substituted or unsubstituted phenyl, aralkyl, aralkyloxy, C₂-C₆ alkoxycarbonyl, aliphatic C₂-C₆ acyl, aliphatic C₂-C₆ acyloxy, aromatic acyl, C₃-C₇ cycloalkylamino-C₁-C₅ alkyl, nitrovinyl, pyridyl C₁-C₅ alkyl, carbamoyl C₁-C₅ alkyl, carbamoyl, diallylamino C₁-C₅ alkyl or di-C₁-C₅ alkylamino-C₁-C₅ alkyl, as an underwater anti-fouling reagent. Use according to claim 1, wherein X² represents hydrogen, C₁-C₅ alkyl, cyano, cyano C₁-C₅ alkyl, halogenated C₁-C₅ alkyl, substituted or unsubstituted phenyl, aromatic acyl, C₃-C₇ cycloalkylamino-C₁-C₅ alkyl, nitrovinyl, pyridyl C₁-C₅ alkyl, carbamoyl C₁-C₅ alkyl, diallylamino C₁-C₅ alkyl or di-C₁-C₅ alkylamino-C₁-C₅ alkyl. Use according to claim 1, wherein X² represents di-C₁-C₅ alkylamino-C₁-C₅ alkyl. Use according to claim 1, wherein X² represent dimethylaminomethyl. A paint in which an indole compound of formula (I) as defined in any one of claims 1 to 4 is present as an underwater anti-fouling reagent. A paint according to claim 5 which contains 1 to 45% by weight of the indole compound of formula (I). A emulsion in which an indole compound of formula (I) as defined in any one of claims 1 to 4 is present as an underwater anti-fouling reagent. A emulsion according to claim 7 which contains 5 to 50% by weight of the indole compound of formula (I).

Inventors: KONYA KAZUMI, MIKI WATARU, SHIMIZU NOBUYOSHI, KONYA, KAZUMI, MIKI, WATARU, SHIMIZU, NOBUYOSHI, Konya, Kazumi, c/o Shimizu Lab., Marine, Miki, Wataru, c/o Shimizu Lab., Marine, Shimizu, Nobuyoshi, c/o Shimizu Lab., Marine
Applicants: MARINE BIOTECH INST CO LTD, MARINE BIOTECHNOLOGY INSTITUTE CO., LTD.
Application year: 1993
Main classification: A01N43
IPC codes: C12P17, A01N43, C12R1, C09D5, C07D209, A01N63