JPWO2006035891A1 - Isonitrile compounds and underwater biofouling agents - Google Patents

Abstract

General formula (1): [wherein R1 is a CH2X group (X is a hydroxyl group, a halogen atom, an isocyano group, an amino group, a substituted amino group, or an optionally substituted alkoxy group, an alkenyloxy group, an acyloxy group. Group, organic sulfonyloxy group, organic sulfenyl group, organic sulfinyl group, organic sulfonyl group, amide group or imide group) or COOR4 group (R4 may have a substituent, alkyl group, alkenyl group) Or an aralkyl group, and each R2 and R3 independently represents an alkyl group], and an underwater-fouling biofouling agent containing the isonitrile compound.

Description

  The present invention relates to an isonitrile compound having a repelling effect on aquatic organisms and an aquatic organism antifouling agent containing the isonitrile compound as an active ingredient.

  Among marine life, underwater organisms such as barnacles, mussels, hydro-insects, bryozoans, etc., known as fouling organisms, are fishery-related facilities such as ship bottoms, aquaculture nets, stationary nets, and buoys; subsea oil field rigs, etc. Underwater structures; cooling water intake channels and heat exchanger cooling water pipes of coastal factories such as thermal power plants; adhering to seawater intake facilities such as aquariums and cultivation fisheries centers, increasing ship running resistance, mesh Deterioration of workability due to clogging, especially in the case of clogging of aquaculture fishing nets, suppression of growth of cultured fish due to deterioration of seawater circulation, buoy subsidence, decrease in seabed oil field rig strength due to increased seawater resistance, blockage of cooling water channels in coastal factories As a result, the cooling water is insufficient and the output of the power plant is reduced.

  Conventionally, antifouling agents containing heavy metals such as organotin compounds such as tributyltin oxide and copper compounds such as cuprous oxide and copper sulfide (for example, see Non-Patent Document 1) have been used for the control of these underwater organisms. It has been. Such organotin compounds have been widely used as ship bottom paints because they have an excellent antifouling effect, but have been found to have adverse effects on marine organisms such as sterilization of snails as the amount used increases. For this reason, in Japan, antifouling agents containing organotin compounds have been banned from production and use, and discussions are ongoing in the direction of banning use worldwide. Also, in places such as yacht harbor where copper compounds, particularly cuprous oxide, have been used in large quantities, there is an example where the concentration of cuprous oxide on the sea floor has reached a certain level that could adversely affect marine life. It has been reported.

  Therefore, the development of technology that is economical, harmless and non-polluting organisms is currently an urgent issue. Among them, natural biological substances (such as pheromones and allelochemicals) A method of suppressing adhesion using a biological substance that has an effect (for example, see Non-Patent Document 2), or a method of suppressing adhesion using a synthetic derivative with better performance using them as a lead (for example, a patent) Document 1) has been proposed.

JP 2002-370907 A Chem. Rev. 2003, No. 103, p. 3431-3448 "Report of the Central Research Institute of Electric Power Research literature on natural repellent active substances: Research report: U99024", December 1999, Central Research Institute of Electric Power

  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 cost such as using an expensive organometallic compound in the production process of the synthetic derivative, and there is room for further improvement.

  Accordingly, an object of the present invention is to solve the above-mentioned problems and to provide an underwater biofouling antifouling agent that is highly safe for fish and shellfish and the human body and can be easily manufactured at low cost.

The present invention
[1] General formula (1):

[Wherein, R ¹ represents a CH ₂ X group (X represents a hydroxyl group, a halogen atom, an isocyano group, an amino group, a substituted amino group, or an optionally substituted alkoxy group, alkenyloxy group, acyloxyl group, An organic sulfonyloxy group, an organic sulfenyl group, an organic sulfinyl group, an organic sulfonyl group, an amide group or an imide group) or a COOR ⁴ group (R ⁴ may have an substituent, an alkyl group, an alkenyl group, or Each of R ² and R ³ independently represents an alkyl group]
And an underwater antifouling agent (hereinafter referred to as “antifouling agent (2)”) containing the isonitrile compound (1). )
About.

  The antifouling agent (2) of the present invention has an excellent repellent effect on organisms attached to the water and at the same time has a high safety against marine organisms, so it has extremely high value from the viewpoint of environmental conservation and can be easily obtained from inexpensive raw materials. Therefore, it can be provided at low cost.

It is a figure which shows the relationship between the density | concentration of the isonitrile compound (1) (CT-1 to CT-3) obtained by the synthesis examples 2-4, the adhesion rate of a barnacle larva, and the mortality of a barnacle larva. It is a figure which shows the relationship between the density | concentration of the isonitrile compound (1) (CT-4-CT-7) obtained by the synthesis examples 5-8, the adhesion rate of a barnacle larva, and the mortality of a barnacle larva. It is a figure which shows the relationship between the density | concentration of the isonitrile compound (1) (CT-8-CT-10) obtained by the synthesis examples 9-11, the adhesion rate of a barnacle larva, and the mortality of a barnacle larva. It is a figure which shows the relationship between the density | concentration of the isonitrile compound (1) (CT-11-CT-14) obtained by the synthesis examples 12-14, the adhesion rate of a barnacle larva, and the mortality of a barnacle larva. It is a figure which shows the relationship between the density | concentration of the isonitrile compound (1) (CT-15-CT-18) obtained by the synthesis examples 15-18, the adhesion rate of a barnacle larva, and the mortality of a barnacle larva. It is a figure which shows the relationship between the density | concentration of the isonitrile compound (1) (CT-19-CT-22) obtained by the synthesis examples 19-22, the adhesion rate of a barnacle larva, and the mortality of a barnacle larva. It is a figure which shows the relationship between the density | concentration of the isonitrile compound (1) (CT-23) obtained by the synthesis example 23, the adhesion rate of a barnacle larva, and the mortality of a barnacle larva. It is a figure which shows the relationship between the density | concentration of the copper sulfate in a comparative example, the adhesion rate of a barnacle larva, and the mortality of a barnacle larva.

In the general formula (1), R ¹ is a CH ₂ X group (X is a hydroxyl group, a halogen atom, an isocyano group, an amino group, a substituted amino group, or an optionally substituted alkoxy group, alkenyloxy group, acyloxy group. Group, an organic sulfonyloxy group, an organic sulfenyl group, an organic sulfinyl group, an organic sulfonyl group, an amide group or an imide group) or a COOR ⁴ group (R ⁴ is an alkyl group which may have a substituent, An alkenyl group or an aralkyl group).

  Examples of the halogen atom represented by X include a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.

  Examples of the substituted amino group represented by X include a methylamino group, an ethylamino group, a phenylamino group, a dimethylamino group, a diethylamino group, a phenylmethylamino group, a pyrrolidinyl group, a piperidinyl group, a morpholino group, and a piperazinyl group. .

  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 an alkoxy group having 1 to 18 carbon atoms Is mentioned.

  Examples of the alkenyloxy group represented by X include alkenyloxy groups having preferably 2 to 8 carbon atoms, such as allyloxy group, butenyloxy group, octenyloxy group and the like.

  Examples of the acyloxyl group represented by X include an acetoxy group, a propanoyloxy group, an octenoyloxy group, a benzoyloxy group, an acryloyloxy group, and a methacryloyloxy group, preferably an acyloxyl group having 1 to 8 carbon atoms. Can be mentioned.

  Examples of the organic sulfonyloxy group represented by X include a methanesulfonyloxy group, a benzenesulfonyloxy group, and a p-toluenesulfonyloxy group.

  Examples of the organic sulfenyl group represented by X include a methanesulfenyl group, an ethanesulfenyl group, an octanesulphenyl group, and a benzenesulfenyl group.

  Examples of the organic sulfinyl group represented by X include a methanesulfinyl group, an octanesulphinyl group, a benzenesulfinyl group, and a p-toluenesulfinyl group.

  Examples of the organic sulfonyl group represented by X include a methanesulfonyl group, an octanesulfonyl group, a benzenesulfonyl group, and a p-toluenesulfonyl group.

  Examples of the amide group represented by X include a formamide group, an acetamide group, a benzamide group, and the like.

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

  The alkoxy group, alkenyloxy group, acyloxyl group, organic sulfonyloxy group, organic sulfenyl group, organic sulfinyl group, organic sulfonyl group, amide group, and imide group represented by X may each have a substituent. . Examples of the substituent 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 halogen atom such as a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom; An isocyano group etc. are mentioned.

In the COOR ⁴ group, as the alkyl group represented by R ⁴ , for example, a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group, a hexyl group, a heptyl group, an octyl group, etc. Of the alkyl group.

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

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

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, a chlorine atom, and bromine A halogen atom such as an atom or iodine atom; an isocyano group;

In General formula (1), each R < ² > and R < ³ > shows an alkyl group each independently. 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.

  Representative examples of the isonitrile compound (1) of the present invention include 7-isocyano-3,7-dimethyl-1-octanol, 7-isocyano-3,7-dimethyloctyl acetate, and 7-isocyano-3,7-benzoic acid. Dimethyloctyl, 1-chloro-7-isocyano-3,7-dimethyloctane, p-toluenesulfonic acid 7-isocyano-3,7-dimethyloctyl, 8- (7-isocyano-3,7-dimethyloctyloxy)- 1-octene, 7-isocyano-3,7-dimethyloctanoic acid 7-octenyl, 7-octenoic acid 7-isocyano-3,7-dimethyloctyl, 1-bromo-7-isocyano-3,7-dimethyloctane, 1 -Iodo-7-isocyano-3,7-dimethyloctane, 1-fluoro-7-isocyano-3,7-dimethyloctane, 7 Isocyano-1-methoxy-3,7-dimethyloctane, di (7-isocyano-3,7-dimethyloctyl) ether, (7-isocyano-3,7-dimethyloctyl) (3,7-dimethyl-6-octenyl) ) Ether, di (7-isocyano-3,7-dimethyloctyl) sulfide, di (7-isocyano-3,7-dimethyloctyl) sulfoxide, di (7-isocyano-3,7-dimethyloctyl) sulfone, N-- (7-isocyano-3,7-dimethyloctyl) phthalimide, N- (7-isocyano-3,7-dimethyloctyl) formamide, 1,7-diisocyano-3,7-dimethyloctane, 7-isocyano-3,7 -Dimethyloctylamine, N- (7-isocyano-3,7-dimethyloctyl) acetamide, 1,7-di Socyano-3,7-dimethyloctane, 7-isocyano-3,7-dimethyloctylamine, N- (7-isocyano-3,7-dimethyloctyl) acetamide, 7-isocyano-3,7-dimethyloctyl acrylate, Examples include 7-isocyano-3,7-dimethyloctyl methacrylate.

  There is no restriction | limiting in particular in the manufacturing method of an isonitrile compound (1). In the isonitrile compound (1), a compound in which X is a hydroxyl group is obtained by, for example, reacting citronellol (or a compound obtained by hydrating citronellol with an acid catalyst such as sulfuric acid) in the presence of a Lewis acid and an isocyanating agent such as trimethylsilyl cyanide at room temperature. It can be obtained by reacting under pressure. Examples of the Lewis acid include zinc bromide, zinc chloride, zinc iodide, silver trifluoromethanesulfonate, silver perchlorate, and silver tetrafluoroborate. Citronellol can be easily obtained at low cost by rectification of a natural extract or hydrogenation of citral or geraniol.

  Further, the other isonitrile compound (1) is easily produced by converting the hydroxyl group of 7-isocyano-3,7-dimethyloctanol obtained by the above method into various functional groups by a conventional method as necessary. be able to. More specifically, (i) 7-isocyano-3,7-dimethyloctanol is reacted with an acylating agent such as an acid halide or acid anhydride, for example. The hydroxyl group of octanol can be converted to an acyloxyl group, and (ii) the hydroxyl group of 7-isocyano-3,7-dimethyloctanol is converted to an organic sulfonyloxy group by reacting with an organic sulfonylating agent such as an organic sulfonyl halide. And (iii) reacting with a halogenating agent such as thionyl chloride, phosphorus oxychloride, phosphorus tribromide or the like to obtain 7-isocyano-3,7-dimethyloctyl organic sulfonate, 7-isocyano-3,7-dimethyloctano by using a halogenating agent such as potassium halide Le hydroxyl groups can be converted into a halogen atom.

  The antifouling agent (2) of the present invention may contain a single isonitrile compound (1) or may contain two or more isonitrile compounds (1). Moreover, if it is in the range which does not impair the effect of this invention, you may contain another antifouling agent.

  There is no restriction | limiting in particular in the usage form of antifouling agent (2). For example, [A] isonitrile compound (1) is contained in a paint (specifically, a mixture of a film-forming agent, a plasticizer, a desiccant, a flow inhibitor, a regulator, a pigment, a solvent, etc.) The isonitrile compound (1) is dissolved in a solvent to form a solution, the [C] isonitrile compound (1) is emulsified with an emulsifier to form an emulsion, or the [D] isonitrile compound (1) is encapsulated in a capsule. In addition to being usable, the isonitrile compound (1) can be used as it is.

  [A] When the isonitrile compound (1) is used in a paint, for example, the isonitrile compound (1) is contained in the paint to prepare an antifouling paint, and the antifouling paint is used for the ship bottom, underwater structure, and cooling. By applying to intake channels, harmful organisms can be avoided.

  Examples of the film forming agent that is one component of the paint include synthetic resins such as phthalic acid resin, vinyl resin, acrylic resin, epoxy resin and polyurethane; natural resins such as pine ani, copal gum; flaxseed oil and soybean oil. Vegetable oils; 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 the adjusting agent include an anti-skinning agent, a color separation preventing agent, and an antifoaming agent. 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 and n-butanol. Alcohols such as; water etc.

  When the isonitrile compound (1) is used in a paint, the amount of the isonitrile compound (1) is preferably 0.1 to 50% by weight, more preferably 0.5 to 30% by weight based on the whole paint. %. There is no restriction | limiting in particular in the amount of components in other coating materials, What is necessary is just to determine suitably according to the use.

  [B] When the isonitrile compound (1) is dissolved in a solvent and used as a solution, for example, after being dissolved in a solvent together with a film-forming agent and, if necessary, an additive, By attaching or penetrating fish nets such as stationary fishing nets and underwater earth and lumber, harmful adherent organisms can be avoided. As such a 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.

  When the isonitrile compound (1) is dissolved in a solvent and used as a solution, the use amount of the isonitrile compound (1) of the present invention is usually preferably from 0.00001 to 90% by mass relative to the whole solution. Preferably it is 0.00001-30 mass%. There is no restriction | limiting in particular in the amount of components in other solutions, What is necessary is just to determine suitably according to the use.

  [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 isonitrile compound (1) to prepare an emulsion by a conventional method. By applying or penetrating fish nets such as aquaculture fishing nets and stationary fishing nets and underwater earth and lumber, 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, and polyoxyethylene alkyl ethers. Nonionic surfactants such as Examples of the conventional method for preparing an emulsion include a method of mixing an isonitrile compound (1) and a surfactant and stirring in water.

  When the isonitrile compound (1) is used as an emulsion, the amount of the isonitrile compound (1) used is usually preferably 0.00001 to 80% by mass, more preferably 0.00001 to 30% by mass with respect to the entire emulsion. %. There is no restriction | limiting in particular in the ratio of the component in another emulsion, What is necessary is just to determine suitably according to a use.

  [D] When the isonitrile compound (1) is encapsulated and used, the capsule in which the isonitrile compound (1) is encapsulated is attached to a fishing net and the isonitrile compound (1) little by little from the capsule. It is possible to avoid the organisms attached to the water by eluting.

  The amount of the isonitrile compound (1) used in the capsule is usually preferably 0.001 to 5 mmol / mL, more preferably 0.1 to 5 mmol / mL with respect to the volume inside the capsule.

  EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this invention is not limited at all by these Examples.

<Synthesis Example 1>
Citronellol (460 mg) was dissolved in methylene chloride (3 mL), trimethylsilylcyanide (580 μL) and silver perchlorate (910 mg) were added, and the mixture was stirred at room temperature for 15 hours. To the reaction mixture was added 5 mL of saturated aqueous sodium hydrogen carbonate solution, and the mixture was further stirred for 5 minutes. Then, 15 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 / ethyl acetate = 1/2 (volume ratio)), and 7-isocyano-3,7-dimethyl-1-octanol [hereinafter referred to as “CT-1” having the following physical properties. ". 490 mg was obtained.

(CT-1 NMR measurement results)
¹ H-NMR (600 MHz, CDCl ₃ , TMS) δ: 0.93 (3H, d, J = 6.6 Hz), 1.15 to 1.22 (1H, m), 1.30 (1H, br) 1.32-1.67 (14H, m), 1.40 (6H, br), 3.63-3.74 (2H, m)
¹³ C-NMR (150.8 MHz, CDCl ₃ , TMS) δ: 19.49, 21.53, 28.94, 29.02, 29.34, 36.86, 39.84, 42.61, 57. 39 (t, J = 5.0 Hz), 61.02, 152.90 (t, J = 5.0 Hz)

<Synthesis Example 2>
60 g of 35% sulfuric acid was added to 10 g of citronellol, and the mixture was 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 11 g of 7-hydroxycitronellol.

  1.47 g of 7-hydroxycitronellol was dissolved in 30 mL of nitromethane, 1.4 mL of trimethylsilyl cyanide and 2.1 g of silver perchlorate were added, and the mixture was stirred at room temperature for 1 hour. 10 mL of saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture, and the mixture was further stirred for 5 minutes. Then, 30 mL of saturated brine was added, 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 / ethyl acetate = 1/2 (volume ratio)) to obtain 1.3 g of “CT-1”.

<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 / ethyl acetate = 4/1 (volume ratio)), and 7-isocyano-3,7-dimethyloctyl acetate [hereinafter referred to as “CT-2”] having the following physical properties. Called. ] 240 mg was obtained.

(NMR measurement result of CT-2)
¹ H-NMR (600 MHz, CDCl ₃ , TMS) δ: 0.93 (3H, d, J = 6.6 Hz), 1.15-1.23 (1H, m), 1.31-1.71 ( 14H, m), 1.40 (6H, t, J = 1.8 Hz), 2.05 (3H, s), 4.06 to 4.15 (2H, m)
¹³ C-NMR (150.8 MHz, CDCl ₃ , TMS) δ: 19.34, 21.00, 21.48, 28.99, 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

<Synthesis Example 4>
[CT-1] 220 mg was dissolved in pyridine 1.5 mL, benzoyl chloride 0.2 mL 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 / ethyl acetate = 10/1 (volume ratio)) and benzoic acid 7-isocyano-3,7-dimethyloctyl [hereinafter referred to as “CT-3”] having the following physical properties. Called. 200 mg was obtained.

(NMR measurement result of CT-3)
¹ H-NMR (600 MHz, CDCl ₃ , TMS) δ: 0.99 (3H, d, J = 6.6 Hz), 1.20-1.27 (1H, m), 1.35 to 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)
¹³ C-NMR (150.8 MHz, CDCl ₃ , TMS) δ: 19.47, 21.52, 28.98, 28.99, 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

<Synthesis Example 5>
550 mg of “CT-1” was dissolved in 3 mL of pyridine, 860 mg of p-toluenesulfonyl 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 / ethyl acetate = 10/1 (volume ratio)), and 1-chloro-7-isocyano-3,7-dimethyloctane [hereinafter referred to as “CT- 4 ". ] 260 mg was obtained.

(NMR measurement result of CT-4)
¹ H-NMR (600 MHz, CDCl ₃ , TMS) δ: 0.93 (3H, d, J = 6.6 Hz), 1.15-1.23 (1H, m), 1.31-1.63 ( 12H, m), 1.40 (6H, t, J = 1.8 Hz), 1.66-1.74 (1H, m), 1.77-1.84 (1H, m), 3.51- 3.62 (2H, m)
¹³ C-NMR (150.8 MHz, CDCl ₃ , TMS) δ: 18.90, 21.45, 28.98, 29.03, 30.14, 36.36, 39.64, 42.55, 43. 14, 57.35 (t, J = 5.0 Hz), 153.05 (t, J = 5.0 Hz)

<Synthesis Example 6>
1 g of “CT-1” was dissolved in 5 mL of pyridine, 1.6 g of p-toluenesulfonyl 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 / ethyl acetate = 3/1 (volume ratio)), and p-toluenesulfonic acid 7-isocyano-3,7-dimethyloctyl [hereinafter referred to as “CT” -5 ". 1.8 g was obtained.

(NMR measurement result of CT-5)
¹ H-NMR (600 MHz, CDCl ₃ , TMS) δ: 0.84 (3H, d, J = 6.6 Hz), 1.09-1.16 (1H, m), 1.22-1.29 ( 1H, m), 1.39 (6H, t, J = 1.8 Hz), 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 = 8.1 Hz), 7.79 ( 2H, d, J = 8.1Hz)
¹³ C-NMR (150.8 MHz, CDCl ₃ , TMS) δ: 18.96, 21.35, 21.61, 28.94, 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)

<Synthesis Example 7>
155 mg of “CT-1” was dissolved in 6 mL of dimethylformamide (DMF), 170 mg of 8-bromo-1-octene and 60 mg of sodium hydride were added, and the mixture was stirred at room temperature for 15 hours. After adding 30 mL of saturated aqueous ammonium chloride solution 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 (hexane / ethyl acetate = 40/1 to 10/1 (volume ratio)), and 8- (7-isocyano-3,7-dimethyloctyloxy)-having the following physical properties: 1-octene [hereinafter referred to as “CT-6”. 110 mg was obtained.

(CT-6 NMR measurement results)
¹ H-NMR (600 MHz, CDCl ₃ , TMS) δ: 0.91 (3H, d, J = 6.6 Hz), 1.13 to 1.20 (1H, m), 1.25 to 1.65 ( 22H, m), 1.40 (6H, br), 2.01-1.07 (2H, m), 3.35-3.48 (4H, m), 4.89-5.02 (2H, m) 5.76-5.85 (1H, m)
¹³ C-NMR (150.8 MHz, CDCl ₃ , TMS) δ: 19.53, 21.54, 26.06, 28.86, 28.95, 28.97, 29.01, 29.72, 29. 81, 33.71, 36.74, 36.93, 42.70, 57.38 (t, J = 5.0 Hz), 69.03, 70.98, 114.16, 139.10, 152.94 (T, J = 5.0Hz)

<Synthesis Example 8>
Hydroxycitronellol (500 mg) was dissolved in acetone (5 mL), Jones reagent (CrO ₃ / H ₂ SO ₄ aq) (1 mL) was added under ice cooling, and the mixture was further stirred for 1 hour. To the reaction mixture, 1 mL of 2-propanol was added to deactivate the excess Jones reagent, 30 mL of saturated brine was added, and the mixture was 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 obtain 480 mg of 7-hydroxy-3,7-dimethyloctanoic acid.

  150 mg of 7-hydroxy-3,7-dimethyloctanoic acid was dissolved in 10 mL of DMF, 175 mg of 8-bromo-1-octene and 400 mg of potassium carbonate were added, and the mixture was 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 / ethyl acetate = 5/1 (volume ratio)) to obtain 220 mg of 7-hydroxy-3,7-dimethyloctanoic acid 7-octenyl.

  210 mg of 7-hydroxy-3,7-dimethyloctanoic acid 7-octenyl was dissolved in 2 mL of nitromethane, 110 μL of trimethylsilyl cyanide and 175 mg of silver perchlorate were added, and the mixture was stirred at room temperature for 1 hour. To the reaction mixture was added 2 mL of saturated aqueous sodium hydrogen carbonate solution, and the mixture was further stirred for 5 minutes. Then, 10 mL of saturated brine was added, and the mixture was 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 / ethyl acetate = 10/1 (volume ratio)), and 7-isocyano-3,7-dimethyloctanoic acid having the following physical properties [hereinafter referred to as “CT- 7 ". 170 mg was obtained.

(NMR measurement result of CT-7)
¹ H-NMR (600 MHz, CDCl ₃ , TMS) δ: 0.96 (3H, d, J = 6.6 Hz), 1.19-1.26 (1H, m), 1.29-1.66 ( 18H, m), 1.40 (6H, t, J = 1.8 Hz), 1.94-2.08 (4H, m), 2.14 (1H, dd, J = 14.7, 8.1 Hz) ), 2.29 (1H, dd, J = 14.7, 6.2 Hz), 4.07 (2H, t, J = 6.6 Hz), 4.91-5.02 (2H, m), 5 .75-5.84 (1H, m)
¹³ C-NMR (150.8 MHz, CDCl ₃ , TMS) δ: 19.61, 21.51, 25.78, 28.59, 28.66, 28.75, 28.95, 29.01, 30. 15, 33.64, 36.37, 41.82, 42.43, 57.30 (t, J = 5.0 Hz), 64.34, 114.30, 138.92, 153.10 (t, J = 5.0 Hz), 173.16

<Synthesis Example 9>
7-octenol (5 g) was dissolved in 50 mL of acetone, and 20 mL of Jones reagent was added under ice cooling, and the mixture was further stirred for 2 hours. To the reaction mixture, 5 mL of 2-propanol was added to deactivate the excess Jones reagent, 30 mL of saturated brine was added, and the mixture was 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-octenoic acid.

  After adding 1 mL of thionyl chloride to 1.3 g of 7-octenoic acid and heating to reflux for 2 hours, the reaction mixture was concentrated under reduced pressure to obtain 1.6 g of 7-octenoic acid chloride.

  170 mg of “CT-1” was dissolved in 2 mL of pyridine, 250 mg of 7-octenoic acid chloride was added, and the mixture was stirred at room temperature for 24 hours. 10 mL of saturated brine was added to the reaction mixture, 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 / ethyl acetate = 20/1 to 10/1 (volume ratio)), and 7-octenoic acid 7-isocyano-3,7-dimethyloctyl [below] having the following physical properties. , Referred to as “CT-8”. ] 256 mg was obtained.

(NMR measurement result of CT-8)
¹ H-NMR (600 MHz, CDCl ₃ , TMS) δ: 0.93 (3H, d, J = 6.6 Hz), 1.15 to 1.23 (1H, m), 1.29 to 1.66 ( 22H, m), 1.40 (6H, t, J = 1.8 Hz), 2.02-2.07 (2H, m), 2.30 (2H, t, J = 7.3 Hz), 4. 06-4.15 (2H, m), 4.90-5.02 (2H, m), 5.75-5.83 (1H, m)
¹³ C-NMR (150.8 MHz, CDCl ₃ , TMS) δ: 19.35, 21.50, 24.82, 28.49, 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) ), 173.86

<Synthesis Example 10>
720 mg of “CT-5” was dissolved in 30 mL of acetonitrile, 400 mg of sodium bromide was added, and the mixture was 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 / ethyl acetate = 20/1 (volume ratio)) and 1-bromo-7-isocyano-3,7-dimethyloctane [hereinafter referred to as “CT-9”. 530 mg was obtained.

(NMR measurement result of CT-9)
¹ H-NMR (600 MHz, CDCl ₃ , TMS) δ: 0.92 (3H, d, J = 6.6 Hz), 1.23-1.15 (1H, m), 1.63-1.31 ( 11H, m), 1.40 (6H, t, J = 1.8 Hz), 1.73-1.64 (2H, m), 1.93-1.85 (1H, m), 3.50- 3.37 (2H, m)
¹³ C-NMR (150.8 MHz, CDCl ₃ , TMS) δ: 18.78, 21.43, 28.98, 29.03, 31.40, 31.91, 36.24, 39.88, 42. 55, 57.34 (t, J = 5.0 Hz), 153.10 (t, J = 5.0 Hz)

<Synthesis Example 11>
2.2 g of “CT-5” was dissolved in 50 mL of acetonitrile, 1.6 g of sodium iodide 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 / ethyl acetate = 40/1 (volume ratio)), and 1-iodo-7-isocyano-3,7-dimethyloctane [hereinafter referred to as “CT- 10 ". ] 1.52 g was obtained.

(NMR measurement result of CT-10)
¹ H-NMR (600 MHz, CDCl ₃ , TMS) δ: 0.91 (3H, d, J = 6.6 Hz), 1.14-1.22 (1H, m), 1.30-1.69 ( 2H, m), 1.31-1.63 (11H, m), 1.41 (6H, t, J = 1.8 Hz), 1.84-1.92 (1H, m), 3.14- 3.20 (1H, m), 3.23-3.28 (1H, m)
¹³ C-NMR (150.8 MHz, CDCl ₃ , TMS) δ: 4.96, 18.56, 21.41, 28.98, 29.03, 33.63, 36.01, 40.73, 42. 56, 57.33 (t, J = 5.0 Hz), 153.10 (t, J = 5.0 Hz)

<Synthesis Example 12>
227 mg of “CT-5” was dissolved in 10 mL of methanol, 770 mg of potassium fluoride was added, and the mixture was 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 / ethyl acetate = 15/1 to 5/1 (volume ratio)), and 1-fluoro-7-isocyano-3,7-dimethyloctane [hereinafter referred to as the following physical properties] , Referred to as “CT-11”. ] 29 mg and 7-isocyano-1-methoxy-3,7-dimethyloctane [hereinafter referred to as “CT-12”. ] 68 mg was obtained.

(NMR measurement result of CT-11)
¹ H-NMR (600 MHz, CDCl ₃ , TMS) δ: 0.95 (3H, d, J = 6.6 Hz), 1.17-1.25 (1H, m), 1.31-1.63 ( 12H, m), 1.40 (6H, t, J = 1.8 Hz), 1.62-1.80 (2H, m), 4.43-4.57 (2H, m)
¹³ C-NMR (150.8 MHz, CDCl ₃ , TMS) δ: 19.37, 21.52, 28.99, 29.04, 29.21 (d, J = 5.0 Hz), 36.72, 37 .30 (d, J = 18.6 Hz), 42.60, 57.38 (t, J = 5.0 Hz), 82.53 (d, J = 163.8 Hz), 153.07 (t, J = 5.0Hz)

(NMR measurement result of CT-12)
¹ H-NMR (600 MHz, CDCl ₃ , TMS) δ: 0.91 (3H, d, J = 6.6 Hz), 1.14 to 1.21 (1H, m), 1.30 to 1.66 ( 15H, m), 1.40 (6H, t, J = 1.8 Hz), 3.33 (3H, s), 3.38-3.44 (1H, m)
¹³ C-NMR (150.8 MHz, CDCl ₃ , TMS) δ: 19.51, 21.56, 28.99, 29.03, 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)

<Synthesis Example 13>
Citronellol 6.5g was melt | dissolved in pyridine 20mL, p-toluenesulfonic acid chloride 10.3g was added under ice-cooling, and also it stirred under the same conditions for 24 hours. 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, concentrated under reduced pressure, and p-toluenesulfonic acid 3,7-dimethyl-6-octenyl 13 .3 g was obtained.

  2.2 g of 3,7-dimethyl-6-octenyl p-toluenesulfonate was dissolved in 30 mL of acetonitrile, 1.6 g of sodium iodide 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 / ethyl acetate = 40/1 (volume ratio)) to obtain 1.52 g of 8-iodo-2,6-dimethyl-2-octene having the following physical properties.

  Citronellol (528 mg) was dissolved in DMF (5 mL), sodium hydride (140 mg) was added in an argon atmosphere, and the mixture was stirred at room temperature for 15 minutes, and then 8-iodo-2,6-dimethyl-2-octene (600 mg) was added to the reaction mixture. , And stirred at 110 ° C. for 18 hours. After adding 20 mL of saturated aqueous ammonium chloride solution to the reaction mixture, 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 / ethyl acetate = 30/1 to 10/1 (volume ratio)) to obtain 200 mg of di (3,7-dimethyl-6-octenyl) ether.

  200 mg of di (3,7-dimethyl-6-octenyl) 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, 20 mL of saturated aqueous sodium hydrogen carbonate solution was added and stirred for another 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 / ethyl acetate = 10/1 (volume ratio)), and di (7-isocyano-3,7-dimethyloctyl) ether having the following physical properties [hereinafter referred to as “CT- 13 ". 150 mg was obtained.

(NMR measurement result of CT-13)
¹ H-NMR (600 MHz, CDCl ₃ , TMS) δ: 0.91 (6H, d, J = 6.6 Hz), 1.13 to 1.21 (2H, m), 1.29 to 1.66 ( 28H, m), 1.40 (12H, t, J = 1.8 Hz), 3.38-3.48 (4H, m)
¹³ C-NMR (150.8 MHz, CDCl ₃ , TMS) δ: 19.56, 19.57, 21.57, 29.01, 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)

<Synthesis Example 14>
[CT-4] 640 mg was dissolved in methanol 20 mL, sodium sulfide nonahydrate 760 mg 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 / ethyl acetate = 200/1 (volume ratio)) to obtain di (7-isocyano-3,7-dimethyloctyl) sulfide [hereinafter referred to as “CT- 14 ". ] 300 mg was obtained.

(NMR measurement result of CT-14)
¹ H-NMR (600 MHz, CDCl ₃ , TMS) δ: 0.91 (6H, d, J = 6.6 Hz), 1.21-1.13 (2H, m), 1.40 (12H, t, J = 1.8 Hz), 1.64-1.28 (28H, m), 2.60-2.45 (4H, m)
¹³ C-NMR (150.8 MHz, CDCl ₃ , TMS) δ: 19.21, 21.53, 28.97, 29.00, 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)

<Synthesis Example 15>
76 mg of [CT-14] was dissolved in 10 mL of methanol, 53 mg of sodium periodate was added, and the mixture was stirred at room temperature for 20 hours. To the reaction mixture was added 20 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 silica gel column chromatography (hexane / ethyl acetate = 1/3 (volume ratio)), and di (7-isocyano-3,7-dimethyloctyl) sulfoxide having the following physical properties [hereinafter referred to as “CT- 15 ”. ] 30 mg was obtained.

(NMR measurement result of CT-15)
¹ H-NMR (600 MHz, CDCl ₃ , TMS) δ: 0.96 (3H, d, J = 6.6 Hz), 0.97 (3H, d, J = 6.6 Hz), 1.28-1. 17 (2H, m), 1.40 (12H, br), 1.66-1.34 (26H, m), 1.87-1.74 (2H, m), 2.75-2.60 ( 4H, m)
¹³ C-NMR (150.8 MHz, CDCl ₃ , TMS) δ: 19.07, 19.24, 21.48, 28.90, 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 = 5.0 Hz) 153.06 (t, J = 5.0 Hz)

<Synthesis Example 16>
Citronellol (10 g) was dissolved in pyridine (20 mL), p-toluenesulfonyl 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.

  7.8 g of citronellyl chloride was dissolved in 100 mL of methanol, 8 g of sodium sulfide nonahydrate was added, and the mixture was heated to reflux for 20 hours. 100 mL of saturated brine was added to the reaction mixture, followed by extraction 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-octenyl) sulfide.

  Di (3,7-dimethyl-6-octenyl) sulfide (2.1 g) was dissolved in methanol (30 mL), sodium periodate (433 mg) was added, and the mixture was heated to reflux for 15 hours at room temperature. To the reaction mixture was added 30 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 silica gel column chromatography (hexane / ethyl acetate-40 / 1-5 / 1 (volume ratio)) to obtain 210 mg of di (3,7-dimethyl-6-octenyl) sulfone.

  210 mg of di (3,7-dimethyl-6-octenyl) 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 saturated aqueous sodium hydrogen carbonate solution was added and stirred for another 5 minutes. Then, 20 mL of saturated brine was added, and the mixture was 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 / ethyl acetate = 2/1 (volume ratio)) and di (7-isocyano-3,7-dimethyloctyl) sulfone [hereinafter referred to as “CT- 16 ". 100 mg was obtained.

(NMR measurement result of CT-16)
¹ H-NMR (600 MHz, CDCl ₃ , TMS) δ: 0.96 (3H, d, J = 6.6 Hz), 1.18-1.26 (2H, m), 1.32-1.71 ( 26H, m), 1.40 (12H, br), 1.84-1.92 (2H, m), 2.88-3.03 (4H, m)
¹³ C-NMR (150.8 MHz, CDCl ₃ , TMS) δ: 19.09, 21.54, 28.56, 28.99, 29.04, 32.03, 36.33, 42.52, 50. 84, 57.35 (t, J = 5.0 Hz), 153.27 (t, J = 5.0 Hz)

<Synthesis Example 17>
[CT-1] 250 mg was dissolved in 5 mL of DMF. Under argon atmosphere, 100 mg of sodium hydride was added and stirred at room temperature for 15 minutes, and then 500 mg of citronellyl iodide was added to the reaction mixture, followed by stirring at room temperature for 8 hours. After adding 20 mL of saturated aqueous ammonium chloride solution to the reaction mixture, 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 / ethyl acetate = 30/1 to 10/1 (volume ratio)) to give (7-isocyano-3,7-dimethyloctyl) (3,7-dimethyl-6- Octenyl) ether [hereinafter referred to as “CT-17”. ] 25 mg was obtained.

(NMR measurement result of CT-17)
¹ H-NMR (600 MHz, CDCl ₃ , TMS) δ: 0.89 (3H, d, J = 6.6 Hz), 0.91 (3H, d, J = 6.6 Hz), 1.11-1. 22 (2H, m), 1.40 (6H, t, J = 1.8 Hz), 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)
¹³ C-NMR (150.8 MHz, CDCl ₃ , TMS) δ: 17.64, 19.55, 19.60, 21.56, 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), 69.08, 69.10, 69.27, 69.30, 124.87, 131.12, 152.98 (t, J = 5.0 Hz)

<Synthesis Example 18>
Citronellol 3.4 g was dissolved in 30 mL of tetrahydrofuran, and 5.9 g of triphenylphosphine, 3.6 g of phthalimide and 5.4 mL of azodicarboxylic acid isopropyl ester were added under an argon atmosphere and ice cooling, and the mixture was cooled for 1 hour under ice cooling. Stir. After adding 20 mL of saturated aqueous ammonium chloride solution to the reaction mixture, the mixture was extracted 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 / ethyl acetate = 10/1 (volume ratio)) to obtain 4.9 g of N- (3,7-dimethyl-6-octenyl) phthalimide.

  N- (3,7-dimethyl-6-octenyl) phthalimide (1.5 g) was dissolved in methylene chloride (20 mL), trimethylsilyl cyanide (1.1 mL) and silver perchlorate (1.6 g) were added, and the mixture was stirred at room temperature for 14 hours. After adding 30 mL of saturated aqueous sodium hydrogen carbonate solution to the reaction mixture, extraction was performed 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 / ethyl acetate = 1/1 (volume ratio)), and N- (7-isocyano-3,7-dimethyloctyl) phthalimide [hereinafter referred to as “CT-18”. . 192 mg was obtained.

<Synthesis Example 19>
3.6 g of N- (3,7-dimethyl-6-octenyl) phthalimide was dissolved in 30 mL of methanol, 880 μL of hydrazine monohydrate was added, and the mixture was heated to reflux for 1 hour. After adding 50 mL of saturated brine to the reaction mixture, 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 then concentrated under reduced pressure to obtain 1.36 g of 3,7-dimethyl-6-octenylamine.

  1.36 g of 3,7-dimethyl-6-octenylamine was dissolved in 40 mL of ethyl formate, 50 mg of p-toluenesulfonic acid was added, and the mixture was heated to reflux for 14 hours. Ethyl acetate (100 mL) was added to the reaction mixture, 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 / ethyl acetate = 5/1 to 0/1 (volume ratio)) to obtain 850 mg of N- (3,7-dimethyl-6-octenyl) formamide.

  300 mg of N- (3,7-dimethyl-6-octenyl) formamide was dissolved in 5 mL of methylene chloride, 460 μL of trimethylsilylcyanide and 680 mg of silver perchlorate were added, and the mixture was stirred at room temperature for 24 hours. After adding 20 mL of saturated aqueous sodium hydrogen carbonate solution to the reaction mixture, 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 / ethyl acetate = 1/1 (volume ratio)), and N- (7-isocyano-3,7-dimethyloctyl) formamide [hereinafter referred to as “CT-19”. . 192 mg was obtained.

<Synthesis Example 20>
170 mg of “CT-19” was dissolved in 2 mL of pyridine, 312 mg of p-toluenesulfonyl chloride was added, and the mixture was stirred at room temperature for 16 hours. To the reaction mixture was added 20 mL of saturated brine, and the mixture was 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 / ethyl acetate = 10/1 (volume ratio)), and 1,7-diisocyano-3,7-dimethyloctane [hereinafter referred to as “CT-20”. ] 86 mg was obtained.

<Synthesis Example 21>
1 g of “CT-18” was dissolved in 30 mL of methanol, 200 μL of hydrazine monohydrate was added, and the mixture was heated to reflux for 2 hours. After adding 50 mL of saturated brine to the reaction mixture, 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 amino silica gel column chromatography (ethyl acetate / methanol = 10/1 (volume ratio)), and 7-isocyano-3,7-dimethyloctylamine [hereinafter referred to as “CT-21”. ] 300 mg was obtained.

<Synthesis Example 22>
100 mg of “CT-21” 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. After adding 20 mL of saturated saline to the reaction mixture, extraction was performed 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 / ethyl acetate = 1/9 (volume ratio)), and N- (7-isocyano-3,7-dimethyloctyl) acetamide [hereinafter referred to as “CT-22”. . 104 mg was obtained.

<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, 100 mL of ethyl acetate was added, filtered, and concentrated under reduced pressure. By subjecting the residue to single evaporation [105 ° C./133 Pa (1 mmHg)] under reduced pressure, 7-isocyano-3,7-dimethyloctyl methacrylate having the following physical properties [hereinafter referred to as “CT-23”]. ] 2.96 g was obtained.

(NMR measurement result of CT-23)
¹ H-NMR (600 MHz, CDCl ₃ , TMS) δ: 0.95 (3H, d, J = 6.6 Hz), 1.16-1.76 (15H, m), 1.93-1.95 ( 3H, m), 4.13-4.24 (2H, m), 5.52-5.56 (1H, m), 6.07-6.10 (1H, m)

<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, 100 mL of ethyl acetate was added and the solid was filtered, then concentrated under reduced pressure, and crude 7-isocyano-3,7-dimethyloctyl acrylate [hereinafter referred to as “CT-24”. ] 21.8 g was obtained.

(NMR measurement result of CT-24)
¹ H-NMR (600 MHz, CDCl ₃ , TMS) δ: 0.95 (3H, d, J = 6.6 Hz), 1.16 to 1.24 (2H, m), 1.30 to 1.76 ( 13H, m), 6.40 (1H, dd, J = 10, 1.5 Hz), 6.13 (1H, dd, J = 18, 10 Hz), 6.40 (1H, dd, J = 18, 1 .5Hz)

<Example 1>
The test method in Example 1 was devised by Rittschof et al. Using a multi-well plate (see Rittschof et.al, J. Exp. Mar. Bio. Ecl., 82, p. 131-146 (1984)). Based on. As the sample, “CT1” to “CT23” produced in Synthesis Examples 1 to 23 were used as the isonitrile compound (1).

  The repellent effect of “CT1” to “CT23” was tested using cypris larvae of the vertical barnacles fed with diatoms in an incubator at 25 ° C. For the test, a 24-well polystyrene multiwell plate (volume: 3.2 mL, diameter: 15.5 mm, height: 17.6 mm) made 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 wells, 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, 10 for each compound. Six barnacle larvae were accommodated per well, and 4 wells were defined as one concentration group. After 5 days, the number of adhered individuals and the number of dead individuals were counted under a stereoscopic microscope, and the adhesion rate and mortality rate of barnacle larvae for each concentration were calculated.

  In addition, the test was repeated 3 times, the average value was calculated | required, the density | concentration of the isonitrile compound (1) was plotted on the horizontal axis, and the adhesion rate of the barnacle larvae was plotted on the vertical axis. At the same time, barnacle larvae mortality at each concentration was plotted. The results are shown in graphs 1 to 23 in FIGS. The barnacle larvae adherence rate plot is indicated by a black square (■), and the barnacle larvae mortality rate is indicated by a black diamond (♦).

<Comparative example>
The test was performed in the same manner as in Example 1 except that copper sulfate was used instead of the isonitrile compound (1). The result is shown in the graph 24 of FIG.

  1 to 7 show that the isonitrile compound (1) of the present invention has an excellent effect of preventing adhesion of barnacle larvae. Moreover, it can be seen from the graph 24 in FIG. 8 that the copper compound (copper sulfate) also has the effect of preventing the adhesion of barnacle larvae.

  However, the antifouling agent (2) containing the isonitrile compound (1) of the present invention has a barnacle larvae even if the concentration of the isonitrile compound (1) is 0.3 μg / mL or more as compared with the graph 24 (comparative example) in FIG. There has been little increase in mortality. From this, it can be seen that the antifouling agent (2) containing the isonitrile compound (1) does not prevent adhesion of marine organisms due to toxicity but prevents adhesion due to a repellent effect. Therefore, it can be seen that the isonitrile compound (1) and the antifouling agent (2) of the present invention are very gentle compounds for marine organisms.

  Further, the isonitrile compound (1) and the antifouling agent (2) of the present invention have the advantage that they can be easily produced at a lower cost in addition to the above characteristics, and can be said to be very useful industrially.

  The isonitrile compound (1) of the present invention has a repellent effect in spite of its low toxicity to underwater organisms, and therefore can be suitably used for, for example, underwater organism antifouling agents.

Claims (2)

General formula (1):

[Wherein, R ¹ represents a CH ₂ X group (X represents a hydroxyl group, a halogen atom, an isocyano group, an amino group, a substituted amino group, or an optionally substituted alkoxy group, alkenyloxy group, acyloxyl group, An organic sulfonyloxy group, an organic sulfenyl group, an organic sulfinyl group, an organic sulfonyl group, an amide group or an imide group) or a COOR ⁴ group (R ⁴ is an optionally substituted alkyl group, alkenyl group or aralkyl group). Each of R ² and R ³ independently represents an alkyl group.
An isonitrile compound represented by General formula (1):

[Wherein, R ¹ represents a CH ₂ X group (X represents a hydroxyl group, a halogen atom, an isocyano group, an amino group, a substituted amino group, or an optionally substituted alkoxy group, alkenyloxy group, acyloxyl group, An organic sulfonyloxy group, an organic sulfenyl group, an organic sulfinyl group, an organic sulfonyl group, an amide group or an imide group) or a COOR ⁴ group (R ⁴ may have an substituent, an alkyl group, an alkenyl group, or Each of R ² and R ³ independently represents an alkyl group]
A biofouling agent attached to water containing an isonitrile compound represented by the formula:

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