WO2006035891A1

WO2006035891A1 - Isonitriles and antifouling agents against the adhesion of aquatics

Info

Publication number: WO2006035891A1
Application number: PCT/JP2005/017988
Authority: WO
Inventors: Yoshikazu Kitano; Yasuyuki Nogata; Isamu Sakaguchi; Manzo Shiono
Original assignee: National University Corporation Tokyo University Of Agriculture And Technology; Central Research Institute Of Electric Power Industry
Priority date: 2004-09-30
Filing date: 2005-09-29
Publication date: 2006-04-06
Also published as: JPWO2006035891A1; JP4933261B2

Abstract

Isonitriles represented by the general formula (1) and antifouling agents against the adhesion of aquatics containing the same: (1) wherein R1 is CH2X (wherein X is hydroxy, halogeno, isocyano, amino, substituted amino, or optionally substituted, alkoxy, alkenyloxy, acyloxy, organosulfonyloxy, organosulfenyl, organosulfinyl, organosulfonyl, amido, or imido) or COOR4 (wherein R4 is optionally substituted, alkyl, alkenyl, or aralkyl); and R2 and R3 are each independently alkyl.

Description

Specification

Isonitrile compound and underwater biofouling agent

Technical field

TECHNICAL FIELD [0001] The present invention relates to an isonitrile compound having a repellent effect on aquatic organisms and an aquatic organism antifouling agent containing the iso-torrui compound as an active ingredient.

Background art

[0002] Among marine organisms, marine organisms known as fouling organisms such as barnacles, mussels, hydroworms and bryozoans are fishery-related facilities such as ship bottoms, aquaculture nets, stationary nets and buoys; Undersea structures such as undersea oil field rigs; cooling water intakes of coastal factories such as thermal power plants, heat exchange cooling water piping, seawater intake facilities such as aquariums and cultivation fisheries centers, etc. Deterioration of workability due to clogging of meshes, especially in the case of clogging of aquaculture fishing nets, suppression of cultured fish growth due to poor circulation of seawater, subsidence of buoys, reduction of seabed oil field rig strength due to increased seawater resistance, seaside factory Due to the blockage of the cooling water channels, there is a great deal of damage such as insufficient cooling water and reduced power plant output.

Conventionally, the control of these underwater organisms includes heavy metals such as organotin compounds such as tributyltinoxide and copper compounds such as cuprous oxide and copper sulfide (for example, see Non-Patent Document 1). An antifouling agent is used. Powerful organic tin compounds have been widely used as ship bottom paints because they have an excellent antifouling effect, but as the amount of use increases, it has been shown to have a negative impact on marine organisms such as infertile shells of snails. I've been strong. Therefore, in Japan, antifouling agents containing organotin compounds have been banned from production and use, and discussions are proceeding in the direction of banning use worldwide. Also, in places such as yacht harbor where copper compounds, especially cuprous oxide, have been used in large quantities, the concentration of cuprous oxide on the sea floor has reached a certain level that could adversely affect marine life. An example is reported.

[0004] Therefore, the development of technology that is economical and harmless and non-polluting is now an urgent issue, and among these, natural biological substances (such as pheromones and allerochemicals) are urgent issues. A method of suppressing adhesion using a biological substance that affects an individual (for example, Non-patent document 2) and methods for suppressing adhesion using synthetic derivatives having higher performance using them as leads (for example, see patent document 1) have been proposed.

[0005] Patent Document 1: Japanese Patent Application Laid-Open No. 2002-370907

Non-Patent Document l: Chem. Rev. 2003, No. 103, p. 3431-3448

Non-Patent Document 2: "Report of the Central Research Institute of Electric Power Research on literature on naturally-occurring anti-substance active substances Survey Report: U99024", December 1999, Central Research Institute of Electric Power Industry

Disclosure of the invention

Problems to be solved by the invention

[0006] However, the method described in Non-Patent Document 2 still has a problem in terms of cost for practical use. Further, the method described in Patent Document 1 has a problem in terms of cost, such as using an expensive organometallic compound in the production process of the synthetic derivative, and there is room for further improvement.

[0007] Therefore, an object of the present invention is to solve the above-mentioned problems, and to provide an underwater biofouling agent that is highly safe for fish and shellfish and the human body and that can be easily manufactured at low cost. Means for solving the problem

[0008] The present invention provides:

[1] General formula (1):

[0009] [Chemical 1]

[Wherein R ¹ represents a CH X group (X represents a hydroxyl group, a halogen atom, an isocyano group, an amino group, a substituted amino group,

2

An alkoxy group, a alkoxy group, an acyloxy group, an organic sulfo-oxy group, an organic sulfur group, an organic sulfur group, Each represents a sulfo group, an amide group or an imide group) or a COOR ⁴ group (R ⁴ represents an optionally substituted alkyl group, alkenyl group or aralkyl group), and R ³ independently represents an alkyl group.

An iso-torrui compound (hereinafter referred to as “iso-tolyl compound (1)”), and

[2] An underwater biofouling agent containing the iso-tolyl compound (1) (hereinafter referred to as “antifouling agent (2)

")

About.

The invention's effect

[0011] The antifouling agent (2) of the present invention has a very high value from the viewpoint of environmental conservation because it has an excellent repellent effect on organisms attached to the water and at the same time is highly safe against marine organisms. Since it can be easily manufactured, it can be provided at low cost.

[0012] [Fig. 1] Concentration of iso-trirui compound (1) (CT—1 to CT—3) obtained in Synthesis Examples 2 to 4, barnacle larvae attachment rate, and barnacle larvae mortality It is a figure which shows the relationship.

[Figure 2] Relationship between the concentration of iso-trirui compound (1) (CT—4 to CT—7) obtained in Synthesis Examples 5-8 and the attachment rate of barnacle larvae and the death rate of barnacle larvae FIG.

[Fig. 3] The relationship between the concentration of iso-trirui compound (1) (CT—8 to CT—10) obtained in Synthesis Examples 9-11 and the attachment rate of barnacle larvae and the death rate of barnacle larvae is shown. FIG.

[Fig. 4] The relationship between the concentration of iso-trirui compound (1) (CT—11 to CT—14) obtained in Synthesis Examples 12-14 and the attachment rate of barnacle larvae and the death rate of barnacle larvae are shown. FIG.

[Fig.5] Shows the relationship between the concentration of iso-trirui compound (1) (CT—15-CT-18) obtained in Synthesis Examples 15-18 and the attachment rate of barnacle larvae and the death rate of barnacle larvae FIG.

[FIG. 6] The relationship between the concentration of iso-trirui compound (1) (CT—19 to CT—22) obtained in Synthesis Examples 19 to 22 and the attachment rate of barnacle larvae and the death rate of barnacle larvae is shown. FIG.

FIG. 7 is a graph showing the relationship between the concentration of iso-triruy compound (1) (CT-23) obtained in Synthesis Example 23, the rate of attachment of barnacle larvae, and the rate of death of barnacle larvae.

[Fig. 8] Concentration of copper sulfate, barnacle larvae adhesion rate and barnacle larvae in comparative examples It is a figure which shows the relationship with a mortality rate.

BEST MODE FOR CARRYING OUT THE INVENTION

In the general formula (1), R ¹ represents a CH X group (X represents a hydroxyl group, a halogen atom, an isocyano group, an amino group)

2

An alkoxy group, an alkenyloxy group, an acyloxyl group, an organic sulfooxyl group, an organic sulfuryl group, an organic sulfuryl group, an organic sulfonyl group, an amide group. Or an imide group) or a COOR ⁴ group (R ⁴ represents an alkyl group, a alkenyl group or an aralkyl group, which may have a substituent).

[0014] Examples of the halogen atom represented by X include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.

[0015] Examples of the substituted amino group represented by X include a methylamino group, an ethylamino group, a phenylamino group, a dimethylamino group, a jetylamino group, a phenylmethylamino group, a pyrrolidyl group, a piperidyl group, a morpholino group, and a piperazinyl group. Etc.

As the alkoxy group represented by X, for example, a methoxy group, an ethoxy group, a propoxy group, a butoxy group, a hexyloxy group, an octyloxy group, a dodecyloxy group, an octadecyloxy group, and the like, preferably having 1 to 18 carbon atoms. An alkoxy group is mentioned.

[0017] Examples of the alkoxy group represented by X include an alkoxy group having preferably 2 to 8 carbon atoms, such as an aralkyl group, a butyroxy group, and an otaturoxy group.

[0018] Examples of the acyloxy group represented by X include, for example, an acetoxy group, a propanoyloxy group, an octenoyloxy group, a benzoyloxy group, an allyloyloxy group, a methacryloyloxy group, and the like. Examples include 1 to 8 acyloxyl groups.

[0019] Examples of the organic sulfo-oxy group represented by X include a methane sulfo-oxy group, a benzene sulfo-oxy group, a p-toluene sulfo-oxy group, and the like.

[0020] Examples of the organic sulfur group represented by X include a methanesulfuric group, an ethanesulfuryl group, an octanesulfuric group, and a benzenesulfuric group.

[0021] Examples of the organic sulfier group represented by X include a methane sulfiel group, an octanes sulfiel group, a benzene sulfiel group, and a p-toluene sulfiel group. [0022] Examples of the organic sulfole group represented by X include a methanesulfonyl group, an octanesulfonyl group, a benzenesulfonyl group, a p-toluenesulfonyl group, and the like.

[0023] Examples of the amide group represented by X include a formamide group, a acetoamide group, and a benzamide group.

[0024] Examples of the imide group represented by X include a phthalimide group.

[0025] The alkoxy group, alkoxyl group, acyloxyl group, organic sulfoloxy group, organic sulfur group, organic sulfur group, organic sulfol group, amide group and imide group represented by X are each a substituent. You may have. Examples of the substituent include a hydroxyl group; a methyl group, an ethyl group, a propyl group, a butyl group and the like, preferably an alkyl group having 1 to 4 carbon atoms; a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, and the like. Halogen atom; isocyanano group and the like.

[0026] Further, as the alkyl group represented by R ^{4 in} addition to the COOR ⁴ group, for example, methyl group, ethyl group, propyl group, butyl group, pentyl group, hexyl group, heptyl group, octyl group Preferably, an alkyl group having 1 to 8 carbon atoms is used.

Examples of the alkenyl group represented by R ⁴ include an alkenyl group having 2 to 8 carbon atoms, such as an aryl group, a prenyl group, and an otaenyl group.

[0028] Examples of the aralkyl group represented by R ⁴ include a benzyl group, a phenethyl group, a naphthylmethyl group, and the like.

[0029] Examples of the substituent that R ⁴ may have include, for example, a hydroxyl group; an alkyl group having preferably 1 to 4 carbon atoms such as a methyl group, an ethyl group, a propyl group, and a butyl group; a fluorine atom, chlorine A halogen atom such as an atom, a bromine atom or an iodine atom; an isocyano group;

[0030] In the general formula (1), each of R ² and R ³ independently represents an alkyl group. Examples of the alkyl group include a methyl group, an ethyl group, a propyl group, an isopropyl group, an n butyl group, an isobutyl group, and a t butyl group, preferably an alkyl group having 1 to 4 carbon atoms.

[0031] A representative example of the iso-tolyl compound (1) of the present invention is 7-isocyanano 3, 7 dimethyl.

1-octanol, acetic acid 7 isocyano 3, 7 dimethyloctyl, benzoic acid 7 isocyano 3, 7 dimethyloctyl, 1 chloro-7 isocyano 3, 7 dimethylocta , P Toluenesulfonic acid 7-Isocyano-3,7-dimethyloctyl, 8 -— (7-Isocyano 3,7 dimethyloctyloxy) 1-Otaten, 7 Isocyanan 3,7 Dimethyloctanoic acid 7-Octenyl, 7— Otathenic acid 7-Isocyano 3,7-Dimethyloctyl, 1-Bromo 7-Isocyano 3,7 Dimethyloctane, 1-Lodo 7-Isocyano 3,7 Dimethyloctane, 1-Fluoro-7-Isocyano 3,7 Dimethyloctane, 7-Isocyano 1-methoxy-1,3,7-dimethyloctane, di (7-isocyano-3,7-dimethyloctyl) ether, (7-isocyanano-3,7-dimethyloctyl) (3,7-dimethyl-6-octatur) ether, di (7- Isocyanan 3,7-dimethyloctyl) sulfide, di (7-isocyano 3,7-dimethyloctyl) sulfoxide, di (7-i Sosanol 3,7-dimethyloctyl) sulfone, N- (7-isocyanan 3,7-dimethyloctyl) phthalimide, N- (7 isocyano 3,7 dimethyloctyl) formamide, 1,7 diisocyanan 3,7-dimethyloctane, 7-isocyanan 3,7-dimethyloctylamine, N— (7-isocyanano 3,7 dimethyloctyl) acetamide, 1,7 diisocyanano 3,7-dimethyloctane, 7-isocyanano 3,7-dimethyloctylamine, N— ( 7-Sosocyano 3,7-dimethyloctyl) acetamide, 7-isocyano 3,7-dimethyloctyl acrylate, 7-isocyano 3,7-dimethyloctyl methacrylate, and the like.

[0032] There are no particular restrictions on the method for producing the iso-torrui compound (1). The compound in which X in the iso-tolyl compound (1) is a hydroxyl group is, for example, citronellol (or a compound obtained by hydrating citronellol with an acid catalyst such as sulfuric acid) in the presence of a Lewis acid and trimethylsilyl cyanide. It can be obtained by reacting with an isocyanating agent such as sodium chloride at normal temperature and pressure. Examples of strong Lewis acids include zinc bromide, zinc chloride, zinc iodide, silver trifluoromethanesulfonate, silver perchlorate, and silver tetrafluoroborate. Citronellol can be easily and inexpensively hand-manufactured by rectification of natural extracts or hydrogenation of citral or geraol.

[0033] In addition, the other iso-tolyl compound (1) is obtained by converting the hydroxyl group of 7isocyano 3,7-dimethyloctanol obtained by the above method to various functional groups as required. By doing so, it can be easily manufactured. More specifically, (i) 7-isocyanano For example, by reacting 3,7-dimethyloctanol with an acylating agent such as an acid halide or acid anhydride, the hydroxyl group of 7-isocyanano 3,7-dimethyloctanol is converted to an acyloxyl group. (Ii) The hydroxyl group of 7-isocyano 3,7-dimethyloctanol is converted to an organic sulfo-loxy group by reacting with an organic sulfonating agent such as organic sulfonyl chloride. And (iii) the ability to react with a halogenating agent such as chlorothionyl, phosphorus oxychloride, phosphorus tribromide, or 7-isocyanano-3,7-dimethyloctyl organic sulfonate, By using a halogenating agent such as potassium halide, the hydroxyl group of 7-isocyano 3,7-dimethyloctanol can be converted to a nitrogen atom.

[0034] The antifouling agent (2) of the present invention may contain a single iso-trirui compound (1), or two or more iso-trilui compounds (1). It may contain. Further, other antifouling agents may be contained within the range without impairing the effects of the present invention.

[0035] There are no particular restrictions on the form of use of the antifouling agent (2). For example, [A] iso-triruly compound (1) is contained in a paint (specifically, a mixture of a film-forming agent, a plasticizer, a desiccant, a flow preventer, a regulator, a pigment, a solvent, etc.). [B] Iso-Torrui compound (1) is dissolved in a solvent to make a solution, [C] Iso-Torrui compound (1) is emulsified with an emulsifier to make an emulsion, or [D] The iso-tolyl compound (1) can be encapsulated and used, and the iso-tolyl compound (1) can be used as it is.

[0036] [A] In the case where the iso-tolyl compound (1) is used in a paint, for example, an anti-fouling paint is prepared by containing the iso-tolyl compound (1) in the paint, By applying the paint to the ship bottom, underwater structures, cooling intakes, etc., harmful organisms can be avoided.

[0037] Examples of the film-forming agent that is one component of the paint include synthetic resins such as phthalate resin, vinyl resin, acrylic resin, epoxy resin, and polyurethane; natural resins such as pine chaper and copal gum Examples thereof include vegetable oils such as flaxseed oil and soybean oil; animal oils such as sardine oil. Examples of the plasticizer include chlorinated paraffin and dioctyl phthalate. Examples of the desiccant include cobalt naphthenate and manganese naphthenate. Examples of the flow preventive agent include organic bentonite, zinc stearate, and EG wax. Examples of regulators include anti-skinning agents and color separation prevention. Agents, antifoaming agents and the like. Examples of the pigment include coloring pigments; extender pigments such as calcium carbonate, talc, and silica powder; special pigments such as cuprous oxide and organic antifouling agents. Examples of the solvent include aromatic hydrocarbons such as toluene, xylene and cumene; esters such as ethyl acetate and butyl acetate; ketones such as methyl isobutyl ketone and diisopropyl ketone; methanol, ethanol, n-propanol, isopropanol, n- Examples include alcohols such as butanol; water and the like.

[0038] When the paint is used by incorporating the iso-trirui compound (1) in the paint, the amount of the iso-trilui compound (1) used is preferably 0.1 to 50 mass with respect to the whole paint. %, More preferably 0.5 to 30% by mass. The amount of other components in the paint is not particularly limited and may be determined as appropriate according to the intended use.

[0039] [B] When the iso-triruly compound (1) is used in the form of a solution by dissolving it in a solvent, for example, it is obtained after dissolving in a solvent together with a film forming agent and, if necessary, an additive. By applying or penetrating the obtained solution to fish nets such as aquaculture fishing nets and stationary fishing nets, and underwater earth and lumber, harmful adherent organisms can be avoided. As the powerful solvent, the same solvents as those described above can be used. Examples of the coating film forming agent include the same coating film forming agents. Examples of the additive include the same plasticizers, desiccants and regulators.

[0040] When iso-triruly compound (1) is used as a solution by dissolving it in a solvent, the amount of iso-tolyl-louly compound (1) of the present invention used is usually based on the whole solution. Preferably it is 0.00001-9 0 mass%, More preferably, it is 0.00001-30 mass%. The amount of other components in the solution may be determined as appropriate according to the intended use.

[0041] [C] When the isonitrile compound (1) is emulsified with an emulsifier and used as an emulsion, a surfactant is further added to the solution of the iso-tolyl compound (1). By preparing the emulsion by the method and applying or penetrating the solution to fish nets such as aquaculture fishing nets and stationary fishing nets, submerged soil wood, etc., harmful adherent organisms can be avoided. As the surfactant, commonly used ones can be used. For example, anionic surfactants such as alkylbenzene sulfonates and fatty acid salts, cationic surfactants such as organic ammonium salts, polyoxyethylene alkyl ethers, and the like. Nonionic surfactants such as The Examples of a conventional method for preparing an emulsion include a method in which an iso-triruly compound (1) and a surfactant are mixed and stirred in water.

[0042] When iso-torrui compound (1) is used as an emulsion, the amount of iso-tolyl compound (1) used is usually preferably from 0.0001 to 80 mass based on the total amount of the emulsion. %, More preferably 0.00001 to 30% by mass. The ratio of ingredients in other emulsions should be determined according to the intended use!

[0043] [D] When encapsulating the iso-torrui compound (1) in a capsule, attach the capsule with the iso-tolyl compound (1) encapsulated in a fishing net. By eluting the iso-trirui compound (1) little by little from the capsule, it is possible to avoid the organisms attached to the water.

[0044] The amount of the iso-trirui compound (1) used in the capsule is usually preferably 0.001 to 5 mmol / mL, more preferably 0.1 to 1 volume with respect to the volume inside the capsule. Te with 5 mmol Z mL.

Example

[0045] Hereinafter, the present invention will be described in more detail by way of examples. However, the present invention is not limited to these examples.

Citronellol (460 mg) was dissolved in methylene chloride (3 mL), trimethylsilyl cyanide (580 μL) and silver perchlorate (9 lO mg) were added, and the mixture was stirred at room temperature for 15 hours. After adding 5 mL of saturated aqueous sodium hydrogen carbonate solution to the reaction mixture and stirring for another 5 minutes, 15 mL of saturated brine was added, filtered through Celite, and washed with 200 mL of ethyl acetate. The organic layer was washed with water and saturated Japanese brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane Z ethyl acetate = 1/2 (volume ratio)), 7-isocyanano 3,7 dimethyl 1-octanol having the following properties [CT-1] Called. 490 mg was obtained.

[0047] (NMR measurement result of CT 1)

— NMR (600MHz, CDC1, TMS) δ: 0.93 (3Η, d, J = 6.6Hz

3), 1. 15—

1.22 (1H, m), 1.30 (1H, br), 1.32—1.67 (14H, m), 1.40 (6H, br), 3. 63-3.74 (2H, m)

1 ³ C-NMR (150.8 MHz, CDC1, TMS) δ: 19.49, 21.53, 28.94, 29.0

Three

2, 29. 34, 36. 86, 39. 84, 42. 61, 57. 39 (t, J = 5. OHz), 61. 02, 152. 90 (t, J = 5.0 Hz)

[0048] <Synthesis example 2>

Citronellol (10 g) was charged with 60 mL of 35% sulfuric acid and stirred at room temperature for 18 hours under an argon atmosphere. The reaction mixture was neutralized with 10% aqueous KOH solution, and extracted with 300 mL of ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 7-hydroxycitronellol llg.

[0049] 1. Hydroxycitronellol 1.47 g was dissolved in -tromethane 30 mL, trimethylsilyl cyanide 1.4 mL and silver perchlorate 2. lg were added, and the mixture was stirred at room temperature for 1 hour. To the reaction mixture was added 10 mL of a saturated aqueous sodium hydrogen carbonate solution, and the mixture was further stirred for 5 minutes. Then, 30 mL of saturated saline was added to the mixture, filtered through Celite, and washed with 200 mL of ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane Z ethyl acetate = 1/2 (volume ratio)) to obtain 1.3 g of “CT-1”.

[0050] <Synthesis Example 3>

220 mg of “CT-1” was dissolved in 1.5 mL of pyridine, 1.5 mL of acetic anhydride was added, and the mixture was stirred at room temperature for 14 hours. To the reaction mixture was added 30 mL of saturated brine, and the mixture was further stirred for 5 minutes, and then extracted with 150 mL of ethyl acetate. The organic layer was washed with 3M hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane Z ethyl acetate = 4Z 1 (volume ratio)) and acetic acid 7 isocyano 3,7 dimethyloctyl [hereinafter referred to as “CT-2”] having the following physical properties. ] 240 mg was obtained.

[0051] (NMR measurement result of CT 2)

— NMR (600MHz, CDC1, TMS) δ: 0.93 (3Η, d, J = 6.6Hz), 1. 15—

Three

1.23 (1H, m), 1.31—1.71 (14H, m), 1.40 (6H, t, J = l. 8Hz), 2.05 (3 H, s), 4.06 —4. 15 (2H, m) ¹³ C-NMR (150.8 MHz, CDC1, TMS) δ: 19.34, 21.00, 21.48, 28.9

Three

9, 29.73, 35.43, 36.64, 42.60, 57.34 (t, J = 5.0 Hz), 62.82, 153.02 (t, J = 5.0 Hz), 171. 16

[0052] <Synthesis Example 4>

[CT-l] 220 mg was dissolved in 1.5 mL of pyridine, 0.2 mL of benzoyl chloride was added, and the mixture was stirred at room temperature for 24 hours. To the reaction mixture was added 30 mL of saturated brine, and the mixture was further stirred for 5 minutes, and then extracted with 150 mL of ethyl acetate. The organic layer was washed with 3M hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane Z ethyl acetate = 10 Zl (volume ratio)) and benzoic acid 7-isocyanano-3,7 dimethyloctyl [hereinafter referred to as “CT-3”] Called. 200mg was obtained.

[0053] (NMR measurement result of CT 3)

— NMR (600MHz, CDC1, TMS) δ: 0.99 (3Η, d, J = 6.6Hz), 1. 20—

Three

1.27 (1H, m), 1.35—1.63 (12H, m), 1.64—1.73 (1H, m), 1.79—1.86 (1H, m), 4 32-4. 41 (2H, m), 7. 42— 7. 46 (2H, m), 7. 54— 7. 57 (1H, m), 8. 02-8. 05 (2H, m)

1 ³ C-NMR (150.8 MHz, CDC1, TMS) δ: 19. 47, 21. 52, 28. 98, 28.9

Three

9, 29. 89, 35. 54, 36. 68, 42. 61, 57. 34 (t, J = 5.0 Hz), 63. 33, 128. 34, 129. 52, 130. 45, 132. 83 , 153. 04 (t, J = 5.0 Hz), 166. 65

550 mg of “CT-1” was dissolved in 3 mL of pyridine, 860 mg of p-toluenesulfuryl chloride was added, and the mixture was stirred at room temperature for 2 days. To the reaction mixture was added 30 mL of saturated brine, and the mixture was further stirred for 5 minutes, and then extracted with 150 mL of ethyl acetate. The organic layer was washed with 3M hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane Z ethyl acetate = 10 Zl (volume ratio)) and 1 chloro-7-isocyano 3, 7 dimethyloctane (hereinafter referred to as “CT-4”) with the following physical properties: Called. 260mg was obtained.

[0055] (NMR measurement result of CT 4) H—NMR (600 MHz, CDC1, TMS) δ: 0.93 (3H, d, J = 6.6 Hz), 1. 15—

Three

1.23 (1H, m), 1.31— 1.63 (12H, m), 1.40 (6H, t, J = l. 8Hz), 1.66—1.74 (1H, m), 1. 77- 1. 84 (1H, m), 3.51—3.62 (2H, m)

1 ³ C-NMR (150.8 MHz, CDC1, TMS) δ: 18. 90, 21. 45, 28. 98, 29.0

Three

3, 30. 14, 36. 36, 39. 64, 42. 55, 43. 14, 57. 35 (t, J = 5.0 Hz), 153. 05 (t, J = 5.0 Hz)

[0056] <Synthesis Example 6>

“CT-1” lg was dissolved in 5 mL of pyridine, and 1.6 g of p-toluenesulfuryl chloride was added under ice cooling, and the mixture was further stirred for 12 hours under the same conditions. To the reaction mixture was added 30 mL of saturated brine, and the mixture was further stirred for 5 minutes, and then extracted with 200 mL of ethyl acetate. The organic layer was washed with 3M hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane Z ethyl acetate = 3Zl (volume ratio)) and p-toluenesulfonic acid 7-isocyanano 3, 7 dimethyloctyl [hereinafter referred to as “CT-5”] Called. ] 1.8 g was obtained.

[0057] (NMR measurement result of CT 5)

— NMR (600MHz, CDC1, TMS) δ: 0.84 (3Η, d, J = 6. 6Hz), 1. 09—

Three

1.16 (1H, m), 1.22- 1.29 (1H, m), 1.39 (6H, t, J = l. 8Hz), 1.32—1.52 (11H, m), 1. 53— 1. 61 (1H, m), 1. 65— 1. 72 (1H, m), 2. 46 (3H, s),

4.02-4.12 (2H, m), 7.36 (2H, d, J = 8. lHz), 7. 79 (2H, d, J = 8.1 Hz) 1 ³ C-NMR (150. 8MHz, CDC1, TMS) δ: 18. 96, 21. 35, 21. 61, 28.9

Three

4, 28. 98, 29. 05, 35. 66, 36. 35, 42. 45, 57. 31 (t, J = 5.0 Hz), 68. 80, 127. 85, 129. 82, 133. 19 144.68, 153.01 (t, J = 5.0 Hz)

155 mg of “CT-1” was dissolved in 6 mL of dimethylformamide (DMF), and 170 mg of 8 bromo 1 otaten and 60 mg of sodium hydride were added and stirred at room temperature for 15 hours. To the reaction mixture was added 30 mL of saturated aqueous ammonium chloride solution, and the mixture was extracted with 150 mL of ethyl acetate. The organic layer was washed with water and saturated brine, and then anhydrous magnesium sulfate was used. Dry and concentrate under reduced pressure. The residue was purified by silica gel column chromatography (hexane z ethyl acetate = 40Zl ~: LOZ1 (volume ratio)) and had the following properties: 8- (7 isocyanan 3, 7 dimethyloctyloxy) 1-otaten [ Hereinafter referred to as “CT-6”. l lOmg was obtained.

[0059] (NMR measurement result of CT 6)

— NMR (600MHz, CDC1, TMS) δ: 0.91 (3Η, d, J = 6.6Hz), 1. 13—

Three

1.20 (1H, m), 1.25- 1.65 (22H, m), 1.40 (6H, br), 2.01—2.07 (2H, m), 3.35- 3. 48 (4H, m), 4. 89- 5. 02 (2H, m), 5. 76- 5. 85 (1H, m) 1 3 C-NMR (150 8MHz, CDC1, TMS.) δ: 19. 53, 21. 54, 26. 06, 28. 8

Three

6, 28. 95, 28. 97, 29. 01, 29. 72, 29. 81, 33. 71, 36. 74, 36. 93, 42. 70, 57. 38 (t, J = 5. OHz) , 69. 03, 70. 98, 114. 16, 139. 10, 152. 94 (t, J = 5. OHz)

[Synthesis Example 8]

Hydroxycitronellol 500 mg was dissolved in 5 mL of acetone, and 1 mL of Diones reagent (CrO 2 / H 2 SO aq) was added under ice cooling, and the mixture was further stirred for 1 hour. 2-Propano to the reaction mixture

3 2 4

After adding 1 mL of the solution to inactivate the excess diones reagent, 30 mL of saturated saline was added and extracted with 150 mL of ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give 480 mg of 7-hydroxy-1,3,7-dimethyloctanoic acid.

[0061] 150 mg of 7-hydroxy-3,7-dimethyloctanoic acid was dissolved in DMFlOmL, and 175 mg of 8-bromo-1-otaten and 400 mg of potassium carbonate were added thereto and stirred at room temperature for 12 hours. 30 mL of water was added to the reaction mixture, followed by extraction with 150 mL of ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane Z ethyl acetate = 5/1 (volume ratio)) to obtain 220 mg of 7-hydroxy-1,3,7-dimethyloctanoic acid 7-otate-nore.

[0062] 7 Hydroxy 1,3,7 Dimethyloctanoic acid 7-Otatur 210 mg was dissolved in -tromethane 2 mL, and trimethylsilyl cyanide 110 L and silver perchlorate 175 mg were added. Stir for hours. To the reaction mixture was added 2 mL of a saturated aqueous sodium hydrogen carbonate solution, and the mixture was further stirred for 5 minutes. Then, 10 mL of saturated saline was added, filtered through Celite, and washed with 150 mL of ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane Z ethyl acetate = 10 Zl (volume ratio)) and 7-isociano 3, 7 dimethyloctanoic acid 7-octatur [CT-7] having the following properties: Called. ] 170 mg¾ ^ For defense.

[0063] (NMR measurement result of CT 7)

— NMR (600MHz, CDC1, TMS) δ: 0.96 (3Η, d, J = 6.6Hz), 1. 19—

Three

1.26 (1H, m), 1.29— 1.66 (18H, m), 1.40 (6H, t, J = l. 8Hz), 1.94—2.08 (4H, m), 2.14 (1H, dd, J = 14. 7, 8. 1Hz), 2.29 (1H, dd, J = 14. 7, 6.2 Hz), 4.07 (2H, t, J = 6. 6Hz), 4.91—5.02 (2H, m), 5.75—5.84 (1H, m)

¹³ C-NMR (150. 8 MHz, CDC1, TMS) δ: 19.61, 21.51, 25.78, 28.5

Three

9, 28. 66, 28. 75, 28. 95, 29. 01, 30. 15, 33. 64, 36. 37, 41. 82, 42. 43, 57. 30 (t, J = 5. OHz) , 64. 34, 114. 30, 138. 92, 153. 10 (t, J = 5. OHz), 173. 16

7-Otatenol (5 g) was dissolved in acetone (50 mL), and Dione's reagent (20 mL) was added under ice cooling, followed by further stirring for 2 hours. To the reaction mixture, 5 mL of 2 propanol was added to inactivate excess Jones reagent, and then 30 mL of saturated saline was added and extracted with 300 mL of ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 5.3 g of 7-otatenic acid.

[0065] 7 Otatenic acid (1.3 g) was mixed with 1 mL of sodium chloride and heated to reflux for 2 hours, and then the reaction mixture was concentrated under reduced pressure to obtain 1.6 g of 7-otatenic acid chloride. It was.

[0066] 170 mg of "CT-1" was dissolved in 2 mL of pyridine, and 250 mg of 7-otatenic acid chloride was added and stirred at room temperature for 24 hours. To the reaction mixture was added saturated saline (10 mL), and the mixture was further stirred for 5 minutes, followed by extraction with 150 mL of ethyl acetate. 3M hydrochloric acid, saturated sodium bicarbonate The extract was washed with an aqueous solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane z ethyl acetate = 20 Zl ~: LOZ1 (volume ratio)) and had the following properties: 7-Otathenic acid 7-isocyanano 3, 7 dimethyloctyl [hereinafter “CT — 8 ”. ] 256mg was obtained.

[0067] (NMR measurement result of CT 8)

— NMR (600MHz, CDC1, TMS) δ: 0.93 (3Η, d, J = 6.6Hz), 1. 15—

Three

1.23 (1H, m), 1.29— 1.66 (22H, m), 1.40 (6H, t, J = l. 8Hz), 2.02—2.07 (2H, m), 2.30 (2H, t, J = 7.3Hz), 4.06—4.15 (2H, m), 4.90—5.02 (2H, m), 5.75-5.83 ( 1H, m)

1 ³ C-NMR (150.8 MHz, CDC1, TMS) δ: 19. 35, 21. 50, 24. 82, 28.4

Three

9, 28. 58, 28. 99, 29. 77, 33. 52, 34. 31, 35. 50, 36. 66, 42. 61, 57. 34 (t, J = 5.0 Hz), 62. 61 , 114. 38, 138. 78, 153. 05 (t, J = 5.0 Hz), 173. 8 6

[Synthesis Example 10]

“CT-5” 720 mg was dissolved in 30 mL of acetonitrinore, 400 mg of odorous sodium was added and heated to reflux for 6 hours. After adding 150 mL of ethyl acetate to the reaction mixture, the organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane Z ethyl acetate = 20Z 1 (volume ratio)), and 1-bromo 7-isocyano 3,7 dimethyloctane [hereinafter referred to as “CT-9”. 530 mg was obtained.

[0069] (NMR measurement result of CT 9)

— NMR (600MHz, CDC1, TMS) δ: 0.92 (3Η, d, J = 6.6Hz), 1. 23—

Three

1.15 (1H, m), 1.63- 1.31 (11H, m), 1.40 (6H, t, J = l. 8Hz), 1.73—1.64 (2H, m), 1. 93— 1. 85 (1H, m), 3. 50— 3. 37 (2H, m)

1 ³ C-NMR (150.8 MHz, CDC1, TMS) δ: 18. 78, 21. 43, 28. 98, 29.0

Three

3, 31. 40, 31. 91, 36. 24, 39. 88, 42. 55, 57. 34 (t, J = 5.0 Hz), 153. 10 (t, J = 5.0 Hz)

[0070] Synthesis Example 11> “CT-5” (2.2 g) was dissolved in acetonitrile (50 mL), sodium iodide (1.6 g) was added, and the mixture was heated to reflux for 1 hour. 50 mL of water was added to the reaction mixture, followed by extraction with 200 mL of hexane. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane Z ethyl acetate = 40Zl (volume ratio)) and 1-yodo-7-isocyanato-1,7 dimethyloctane [hereinafter referred to as “CT-” 10 ". ] 1. 52 g was obtained.

[0071] (NMR measurement result of CT 10)

— NMR (600MHz, CDC1, TMS) δ: 0.91 (3Η, d, J = 6.6Hz), 1. 14—

Three

1.22 (1H, m), 1.30— 1.69 (2H, m), 1.31— 1.63 (11H, m), 1.41 (6H, t, J = l. 8Hz), 1. 84- 1. 92 (1H, m), 3.14—3.20 (1H, m), 3.23—3.28 (1H, m)

¹³ C-NMR (150.8 MHz, CDC1, TMS) δ: 4.96, 18.56, 21.41, 28.98

Three

, 29. 03, 33. 63, 36. 01, 40. 73, 42. 56, 57. 33 (t, J = 5.0 Hz), 153. 10 (t, J = 5.0 Hz)

227 mg of “CT-5” was dissolved in 10 mL of methanol, and 770 mg of potassium potato was added and heated to reflux for 20 hours. 20 mL of water was added to the reaction mixture, followed by extraction with 150 mL of hexane. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane Z ethyl acetate = 15 Zl to 5 Zl (volume ratio)) and 1-fluorinated 7-isocyano 3, 7 dimethyloctane [hereinafter referred to as “CT— 11 ". ] 29 mg and 7 isocyano 1-methoxy 3, 7 dimethyloctane [hereinafter referred to as “CT-12”. ] Got 68mg o

[0073] (NMR measurement result of CT 11)

— NMR (600MHz, CDC1, TMS) δ: 0.95 (3Η, d, J = 6.6Hz), 1. 17—

Three

1.25 (1H, m), 1.31— 1.63 (12H, m), 1.40 (6H, t, J = l. 8Hz), 1.62—1.80 (2H, m), 4. 43—4. 57 (2H, m)

1 ³ C-NMR (150.8MHz, CDC1, TMS) δ: 19.37, 21.52, 28.99, 29.0 4, 29.21 (d, J = 5.0Hz), 36.72, 37.30 (d, J = 18.6Hz), 42.60, 57.38 (t, J = 5.0Hz), 82 53 (d, J = 163. 8Hz), 153. 07 (t, J = 5.0 Hz)

[0074] (CT 12 NMR measurement results)

— NMR (600MHz, CDC1, TMS) δ: 0.91 (3H, d, J = 6.6Hz), 1. 14—

Three

1.21 (1H, m), 1.30- 1.66 (15H, m), 1.40 (6H, t, J = l. 8Hz), 3.33 (3 H, s), 3.38 -3.44 (1H, m)

1 ³ C-NMR (150. 8 MHz, CDC1, TMS) δ: 19.51, 21. 56, 28. 99, 29.0

Three

3, 29. 74, 36. 67, 36. 94, 42. 69, 57. 40 (t, J = 5.0 Hz), 58. 59, 71. 02, 152. 97 (t, J = 5.0 Hz )

[0075] <Synthesis Example 13>

Citronellol 6.5 g was dissolved in 20 mL of pyridine, and 10.3 g of p-toluenesulfonic acid chloride was added under ice cooling, and the mixture was further stirred for 24 hours under the same conditions. To the reaction mixture was added 40 mL of saturated brine, and the mixture was further stirred for 5 minutes, and then extracted with 250 mL of ethyl acetate. The organic layer was washed with 3M hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give p-toluenesulfonic acid 3,7-dimethyl-6-otatur 13. 3g was obtained.

[0076] p Toluenesulfonic acid 3,7 dimethyl-6-octatur 2.2 g was dissolved in acetonitrile 30 ml, sodium iodide 1.6 g was added, and the mixture was heated to reflux for 1 hour. 30 mL of water was added to the reaction mixture, followed by extraction with 200 mL of hexane. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane Z ethyl acetate = 40 Zl (volume ratio)) to obtain 1.52 g of 8-iodo-2,6-dimethyl-2-otaten having the following physical properties.

[0077] Dissolve 528 mg of citronellol in 5 mL of DMF, add 40 mg of sodium hydride 1 in an argon atmosphere, stir at room temperature for 15 minutes, and then add 600 mg of 2,3,6-dimethyl-2-octene to the reaction mixture. The mixture was stirred at 110 ° C. for 18 hours under an argon atmosphere. To the reaction mixture, 20 mL of a saturated aqueous ammonium chloride solution was added, followed by extraction with 150 mL of ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (hexa Z (ethyl acetate = 30 Zl˜: LOZl (volume ratio)) to obtain 200 mg of di (3,7 dimethyl-6-octatur) ether.

[0078] 200 mg of di (3,7 dimethyl-6-octatur) ether was dissolved in 2 mL of methylene chloride, 450 μL of trimethylsilyl cyanide and 700 mg of silver perchlorate were added, and the mixture was stirred at room temperature for 24 hours. To the reaction mixture was added 20 mL of a saturated aqueous sodium hydrogen carbonate solution, and the mixture was further stirred for 5 minutes. Then, 30 mL of saturated brine was added, and the mixture was filtered through Celite, and washed with 200 mL of ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane Zethyl acetate = 10 Zl (volume ratio)), and di (7-sosocyano 3, 7 dimethyloctyl) ether having the following physical properties [hereinafter referred to as “CT 13”. Called. I got 150mg.

[0079] (NMR measurement result of CT 13)

— NMR (600MHz, CDC1, TMS) δ: 0.91 (6Η, d, J = 6.6Hz), 1. 13—

Three

1.21 (2H, m), 1.29— 1.66 (28H, m), 1.40 (12H, t, J = l. 8Hz), 3.38—3.48 (4H, m)

¹³ C—NMR (150. 8 MHz, CDC1, TMS) δ: 19. 56, 19. 57, 21. 57, 29.0

Three

1, 29. 03, 29. 84, 29. 86, 36. 76, 36. 96, 36. 98, 42. 73, 57. 41 (t, J = 5.0 Hz), 69. 12, 69. 16 152.98 (t, J = 5.0 Hz)

[0080] <Synthesis Example 14>

[CT-4] 640 mg was dissolved in 20 mL of methanol, 760 mg of sodium sulfide nonahydrate was added, and the mixture was heated to reflux for 20 hours. To the reaction mixture was added 50 mL of saturated brine, and the mixture was extracted with 200 mL of ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane Z ethyl acetate = 200Z1 (volume ratio)) and di (7 isocyanate 3,7 dimethyloctyl) sulfide having the following physical properties [hereinafter referred to as “CT-14”. ] 300 mg was obtained.

[0081] (NMR measurement result of CT 14)

— NMR (600MHz, CDC1, TMS) δ: 0.91 (6Η, d, J = 6.6Hz), 1. 21— 1.13 (2H, m), 1.40 (12H, t, J = l. 8Hz), 1.64—1.28 (28H, m), 2.60—2.45 (4H, m)

¹³ C-NMR (150. 8 MHz, CDC1, TMS) δ: 19. 21, 21. 53, 28. 97, 29.0

Three

0, 29. 89, 29. 91, 32. 04, 32. 07, 36. 55, 36. 79, 36. 80, 42. 63, 57. 35 (t, J = 5.0 Hz), 153. 02 (t, J = 5.0 Hz)

[CT-14] 76 mg was dissolved in 10 mL of methanol, and 53 mg of sodium periodate was prepared and stirred at room temperature for 20 hours. After adding 20 mL of saturated brine to the reaction mixture, extraction was performed with 150 mL of ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography 1 (hexane Z ethyl acetate = 1Z3 (volume ratio)) and di (7-isocyanano-3,7-dimethyloctyl) sulfoxide [hereinafter referred to as “CT-15”] having the following physical properties: Called. 30mg was obtained.

[0083] (CT-15 NMR measurement results)

— NMR (600MHz, CDC1, TMS) δ: 0.96 (3Η, d, J = 6.6Hz), 0.97 (3

Three

H, d, J = 6.6 Hz), 1.28- 1.17 (2H, m), 1.40 (12H, br), 1.66— 1.34 (2 6H, m), 1.87 -1.74 (2H, m), 2.75— 2.60 (4H, m)

1 ³ C-NMR (150.8 MHz, CDC1, TMS) δ: 19. 07, 19. 24, 21. 48, 28.9

Three

0, 28. 94, 28. 95, 28. 99, 29. 25, 29. 31, 29. 44, 29. 49, 32. 17, 32. 40, 36. 34, 36. 48, 42. 49, 50. 10, 50. 18, 57. 30 (t, J = 5. OHz), 153. 06 (t, J = 5. OHz)

Citronellol (10 g) was dissolved in pyridine (20 mL), p-toluenesulfuryl chloride (14.6 g) was added, and the mixture was stirred at room temperature for 3 days. To the reaction mixture was added 30 mL of saturated brine, and the mixture was further stirred for 5 minutes, and then extracted with 200 mL of hexane. The organic layer was washed with 3M hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 8.5 g of citronellyl chloride.

[0085] Citronellyl chloride 7.8g was dissolved in methanol lOOmL, and sodium sulfide 'nanohydrate 8 g was added and heated to reflux for 20 hours. After adding 10 mL of saturated saline to the reaction mixture, extraction was performed with 300 mL of ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 7 g of di (3,7-dimethyl-6-octyl) sulfide.

[0086] 2.lg of di (3,7 dimethyl-6-octatur) sulfide was dissolved in 30mL of methanol, 433mg of sodium periodate was added, and the mixture was heated to reflux at room temperature for 15 hours. After adding 30 mL of saturated Japanese salt water to the reaction mixture, it was extracted with 150 mL of ethyl acetate. The organic layer was washed with water and saturated Japanese brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane Z ethyl acetate = 40 Zl to 5/1 (volume ratio)) to obtain 210 mg of di (3,7 dimethyl-6-octatur) sulfone.

[0087] 210 mg of di (3,7 dimethyl-6-octatur) sulfone was dissolved in 2 mL of methylene chloride, 330 μL of trimethylsilyl cyanide and 500 mg of silver perchlorate were added, and the mixture was stirred at room temperature for 24 hours. To the reaction mixture, 20 mL of a saturated aqueous sodium hydrogen carbonate solution was added, and the mixture was further stirred for 5 minutes. Then, 20 mL of saturated saline was added to the mixture, filtered through Celite, and washed with 150 mL of ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane Z ethyl acetate = 2Zl (volume ratio)), and di (7-isocyanano-3,7dimethyloctyl) sulfone [hereinafter referred to as “CT-16”] having the following physical properties. Called. I got lOOmg

[0088] (NMR measurement result of CT 16)

— NMR (600MHz, CDC1, TMS) δ: 0.96 (3Η, d, J = 6.6Hz), 1. 18—

Three

1.26 (2H, m), 1.32—1.71 (26H, m), 1.40 (12H, br), 1.84—1.92 (2H, m), 2.88—3. 03 (4H, m)

1 ³ C—NMR (150. 8 MHz, CDC1, TMS) δ: 19. 09, 21. 54, 28. 56, 28.9

Three

9, 29. 04, 32. 03, 36. 33, 42. 52, 50. 84, 57. 35 (t, J = 5. OHz), 153. 27 (t, J = 5. OHz)

[0089] <Synthesis Example 17> [CT—l] Dissolve 250 mg in 5 mL of DMF, add 100 mg of sodium hydride in an argon atmosphere, stir at room temperature for 15 minutes, add 500 mg of citronellyozide to the reaction mixture, and then at room temperature for 8 hours. Stir. To the reaction mixture was added 20 mL of a saturated aqueous solution of ammonium chloride, followed by extraction with 150 mL of ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 30/1 ~: LO / 1 (volume ratio)) and (7-isocyanano 3, 7-dimethyloctyl) (3, 7-dimethyl). 1-Otate) Ether [Hereafter referred to as “CT-17”. ] 25 mg was obtained.

[0090] (NMR measurement result of CT-17)

— NMR (600MHz, CDC1, TMS) δ: 0.89 (3Η, d, J = 6.6Hz), 0.91 (3

Three

H, d, J = 6.6 Hz), 1.11-1.22 (2H, m), 1.40 (6H, t, J = l.8Hz), 1.60 (3H, br), 1. 30- 1. 66 (22H, m), 1. 68 (3H, br), 1. 91— 2. 05 (2H, m), 3. 38- 3. 48 (4H, m), 5. 05— 5. 12 (1H, m)

1 ³ C-NMR (150. 8 MHz, CDC1, TMS) δ: 17. 64, 19. 55, 19. 60, 21.5

Three

6, 25. 50, 25. 72, 28. 99, 29. 03, 29. 68, 29. 69, 29. 82, 29. 84, 36. 74, 36. 78, 36. 95, 36. 97, 37. 25, 37. 27, 42. 73, 57. 40 (t, J = 5.0 Hz), 6 9. 08, 69. 10, 69. 27, 69. 30, 124. 87, 131. 12, 152. 98 (t, J = 5.0 Hz)

[0091] <Synthesis Example 18>

Dissolve 3.4 g of citronellol in 30 mL of tetrahydrofuran, add 5.9 g of triphenylphosphine, 3.6 g of phthalimide, and 5.4 mL of azodicarboxylic acid isopropyl ester under argon and ice cooling. Stir for 1 hour. To the reaction mixture, 20 mL of a saturated aqueous solution of ammonium chloride was added, followed by extraction with 150 mL of ethyl acetate. The organic layer was washed with 5% aqueous potassium hydroxide solution, water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane Z ethyl acetate = 10 Zl (volume ratio)) to obtain 4.9 g of Ν— (3,7-dimethyl 6-otatur) phthalimide.

[0092] N— (3,7 Dimethyl-6-Otatur) phthalimide 1.5 g was dissolved in 20 mL of methylene chloride and trimethylsilyl cyanide 1. 1 mL and 1.6 g of silver perchlorate were added at room temperature. Stir for hours. To the reaction mixture was added 30 mL of saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with 200 mL of ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane Z ethyl acetate = 1Z1 (volume ratio)), and N— (7-isocyanano-3,7-dimethyloctyl) phthalimide [hereinafter referred to as “CT-18” Called. 192 mg was obtained.

N— (3,7-dimethyl-6-octatur) phthalimide (3.6 g) was dissolved in methanol (30 mL), and hydrazine monohydrate (880 L) was added and heated to reflux for 1 hour. 50 mL of saturated saline was added to the reaction mixture, followed by extraction with 150 mL of ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure to obtain 1.36 g of 3,7-dimethyl-6-otaturamine.

[0094] 3,7-Dimethyl-6-otathuramine 1. 36 g was dissolved in 40 mL of ethyl formate, and 50 mg of p-toluenesulfonic acid was added and heated to reflux for 14 hours. To the reaction mixture was added 1 OOmL of ethyl acetate, and the organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane Z ethyl acetate = 5 Zl to OZl (volume ratio)) to obtain 850 mg of Ν- (3,7-dimethyl-6-otatur) formamide.

[0095] 300 mg of N- (3,7-dimethyl-6-octatur) formamide was dissolved in 5 mL of methylene chloride, 460 L of trimethylsilyl cyanide and 680 mg of silver perchlorate were added, and the mixture was stirred at room temperature for 24 hours. To the reaction mixture was added 20 mL of saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with 150 mL of ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Hexane Z ethyl acetate = 1Z1 (volume ratio)), N- (7-Isocyano-3,7-dimethyloctyl) formamide [hereinafter referred to as “CT-19” . ] 192 mg was obtained.

[0096] <Synthesis Example 20>

“CT-19” 170 mg dissolved in 2 mL of pyridine, p-toluenesulfuryl chloride 312 m g was added and stirred at room temperature for 16 hours. After adding 20 mL of saturated saline to the reaction mixture, extraction was performed with 150 mL of ethyl acetate. The organic layer was washed with 3M hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane Z ethyl acetate = 10/1 (volume ratio)) and 1,7 diisocyanano 3,7 dimethyloctane [hereinafter referred to as “CT 20”. ] 86 mg was obtained.

[Synthesis Example 21]

“CT-18” lg was dissolved in 30 mL of methanol, and 200 μL of hydrazine 'monohydrate was added and heated under reflux for 2 hours. To the reaction mixture was added 50 mL of saturated brine, and the mixture was extracted with 150 mL of ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by aminosilica gel column chromatography (ethyl acetate Zmethanol = 10/1 (volume ratio)) to give 7-isocyanano 3, 7-dimethyloctylamine [hereinafter referred to as “CT-21”. Called. ] 300 mg was obtained.

[Synthesis Example 22]

“CT-21” lOOmg was dissolved in 500 μL of pyridine, 500 μL of acetic anhydride was added, and the mixture was stirred at room temperature for 10 hours. To the reaction mixture, 20 mL of saturated saline was added, and then extracted with 100 mL of ethyl acetate. The organic layer was washed with 3M hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane Z ethyl acetate = 1/9 (volume ratio)), and N- (7-isocyano 3,7 dimethyloctyl) acetamide [hereinafter referred to as “CT-2 2”. ^] Was obtained 104mg.

[0099] <Synthesis Example 23>

18.7 g of “CT-1” was dissolved in 70 mL of methylene chloride, 17 mL of triethylamine and 12 mL of methacrylic acid chloride were added under ice cooling, and the mixture was further stirred for 4 hours under the same conditions. The reaction mixture was concentrated, ethyl acetate (lOOmL) was added, the mixture was filtered, and then concentrated under reduced pressure. By subjecting the residue to single evaporation under reduced pressure [105 ° CZl33Pa (lmmHg)], the following physical properties were obtained: 7 isocyanomethacrylate 7, 7dimethyloctyl methacrylate (hereinafter referred to as “CT-23” o) 2.96 g Obtained. [0100] (NMR measurement result of CT 23)

— NMR (600MHz, CDC1, TMS) δ: 0.95 (3H, d, J = 6.6Hz), 1. 16—

Three

1.76 (15H, m), 1.93— 1.95 (3H, m), 4.13—4. 24 (2H, m), 5.52—5.5 6 (1H, m), 6 07-6. 10 (1H, m)

[0101] <Synthesis Example 24>

16.8 g of “CT-1” was dissolved in 70 mL of methylene chloride, 20 mL of triethylamine and 10 mL of acrylic acid chloride were added under ice-cooling, and the mixture was further stirred for 4 hours under the same conditions. After concentrating the reaction mixture, lOOmL of ethyl acetate was added and the solid was filtered, and then concentrated under reduced pressure, and crude 7-isocyanano 3, 7 dimethyloctyl acrylate [hereinafter referred to as “CT-24”]. 21.8 g was obtained.

[0102] (NMR measurement result of CT 24)

— NMR (600MHz, CDC1, TMS) δ: 0.95 (3Η, d, J = 6.6Hz), 1. 16—

Three

1.24 (2H, m), 1.30—1.76 (13H, m), 6.40 (1H, dd, J = 10, 1.5 Hz), 6.13 (1H, dd, J = 18 , 10Hz), 6.40 (1H, dd, J = 18, 1.5 Hz)

[0103] <Example 1>

The test method in Example 1 was devised by Rittschofe using a multiwell plate (see Rittschof et.al, J. Exp. Mar. Bio. Eel., 82, p. 131-146 (1984)). Based on this. As the sample, “CT1” to “CT23” produced in Synthesis Examples 1 to 23 were used as the iso-trirui compound (1).

[0104] The repellent effects of "CT1" to "CT23" were tested using Cypris larvae of vertebrate gibbons fed with diatoms in an incubator at 25 ° C. For the test, a 24-well polystyrene multiwell plate (capacity: 3.2 mL, diameter: 15.5 mm, height: 17.6 mm) manufactured by Corning was used, and each compound of “CT1” to “CT23” was about 0.3 mL of methanol. The mixed solution dissolved in was poured into a well, dried to remove methanol, and then 2 mL of filtered seawater was injected. The concentration of the compound to be tested (μg / mL) was adjusted to 0.01, 0.03, 0.1, 0.3, 1, 3, and 10 for each compound. 1 Uenoreki 6 6 barnacle larvae were housed, and 4 uels were in 1 concentration zone. After 5 days, the number of individuals attached and the number of dead individuals were counted under a stereoscopic microscope. And mortality were calculated.

[0105] The test was repeated three times, and the average value was calculated. The concentration of iso-tolyl compound (1) was plotted on the horizontal axis, and the adhesion rate of barnacle larvae was plotted on the vertical axis. At the same time, the mortality of barnacle larvae at each concentration was plotted. The results are shown in graphs 1 to 23 in Figs. However, the plot of adhesion rate of barnacle larvae is indicated by black squares (country), and the death rate of barnacle larvae is indicated by black diamonds (♦).

[0106] <Comparative Example>

The test was conducted in the same manner as in Example 1 except that copper sulfate was used in place of the iso-trirui compound (1). The result is shown in graph 24 in FIG.

[0107] From graphs 1 to 23 in Figs. 1 to 7, it can be seen that the iso-tolyl compound (1) of the present invention has an excellent effect of preventing the adhesion of barnacle larvae. Further, from the graph 24 in FIG. 8, it can be seen that the copper compound (copper sulfate) also has an effect of preventing adhesion of barnacle larvae.

[0108] However, the antifouling agent (2) containing the iso-triruly compound (1) of the present invention is different from the graph 24 of FIG. The mortality rate of barnacle larvae has hardly increased even at concentrations of 0.3 μgZmL or higher. Therefore, the antifouling agent (2) containing the iso-trirui compound (1) has a repellent effect that prevents adhesion of marine organisms due to toxicity. Recognize. Therefore, it can be seen that the iso-trirui compound (1) and the antifouling agent (2) of the present invention are very gentle compounds for marine organisms.

[0109] Further, in addition to the above features, the iso-trirui compound (1) and the antifouling agent (2) of the present invention have an advantage that they can be easily produced at low cost. It can be said that it is very useful in industry.

Industrial applicability

[0110] The iso-trirui compound (1) of the present invention has a repellent effect in spite of its low toxicity to underwater organisms, and is therefore preferably used, for example, as an underwater organism antifouling agent. be able to.

Claims

Claim [1] General formula (1)

[Chemical 1]

2

An alkoxy group, alkoxy group, acyloxyl group, organic sulfoloxy group, organic sulfol group, organic sulfur group, organic sulfol group, amide group or an optionally substituted group or substituent. Represents an imide group) or COOR ⁴ group (R ⁴ represents an optionally substituted alkyl group, alkenyl group or aralkyl group), and each R ³ independently represents an alkyl group.

Iso-Torrui compound represented by

General formula (1):

[Chemical 2]

2

An alkoxy group, alkoxy group, acyloxyl group, organic sulfoloxy group, organic sulfol group, organic sulfur group, organic sulfol group, amide group or an optionally substituted group or substituent. Imide group) or COOR ⁴ group (R ⁴ has a substituent) Each represents an alkyl group, an alkenyl group or an aralkyl group, and each and R ³ independently represents an alkyl group.

An underwater biofouling agent containing an isonitrile compound represented by