Method for producing 17-methylalkane compounds

Abstract

To provide: a novel compound as a synthetic intermediate for efficiently preparing 17-methylalkane compounds; a process for preparing the same; and a process for preparing 17-methylalkane compounds.SOLUTION: A preparation process includes the step of a coupling reaction of a compound represented by the formula 5 (5: M2=MgCl) in the figure with 1-bromo-5-chloropentane to obtain a 17-methylalkane compound represented by the formula 1 (1: X1=Cl) in the figure.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a method for producing 17-methylalkane compounds. More specifically, the present invention relates to a method for producing 17-methylalkane compounds, specifically for the Argentine ant, which is one of the world's 100 worst invasive alien species. Linepithema humile This invention relates to a method for producing 17-methylpentatriacontane and 17-methylheptatriacontane, which are nesting partner recognition pheromones of staghorn larvae. [Background technology]

[0002] Argentine ants ( Linepithema humile Argentine ants have invaded countries around the world, forming supercolonies and displacing native ants, thus having a significant impact on ecosystems. Furthermore, Argentine ants form a symbiotic relationship with agricultural pests such as aphids and scale insects, obtaining their honeydew in exchange for protecting these pests from natural enemies. As a result, biological control methods using natural enemies are often ineffective in areas with high ant densities. In addition, they can invade homes through even the smallest gaps, making them a sanitary pest. Until now, Argentine ants have been controlled by spraying insecticides, but this conventional method is not only ineffective against Argentine ants but is also undesirable from an environmental perspective. Therefore, biological control methods that minimize the use of insecticides are being investigated, and among these, control using nestmate recognition pheromones is expected to be one promising method (see Non-Patent Documents 1 and 2 below).

[0003] Argentine ants ( Linepithema humileVarious compounds are known as nesting partner recognition pheromones for staghorn worms, including 15-methylpentatriacontane, 17-methylpentatriacontane, 5,13,17-trimethyltritriacontane, 5,13,17-trimethylpentatriacontane, and 5,13,17-trimethylheptatriacontane. Among these, 5,13,17-trimethylalkane compounds such as 5,13,17-trimethyltritriacontane, 5,13,17-trimethylpentatriacontane, and 5,13,17-trimethylheptatriacontane, as well as 17-methylalkane compounds such as 17-methylpentatriacontane and 17-methylheptatriacontane, have been shown to have particularly high activity (see Non-Patent Literature 1, 2, and 3 below). In the following explanation, we will focus on 17-methylalkane compounds.

[0004] A method for synthesizing 17-methylpentatriacontane, a 17-methylalkane compound, has been reported to be produced in a total of three steps with a yield of 37.32%, as described below (Non-Patent Literature 2 below). For example, 17-methyl-17-pentatriacontanol is synthesized by reacting 2-octadecanone with octadecylmagnesium bromide (first step), and the obtained 17-methyl-17-pentatriacontanol is reacted with an acid catalyst. p - In the presence of toluenesulfonic acid, 17-methylenepentatriacontane is synthesized by dehydration in benzene (second step). Subsequently, the obtained 17-methylenepentatriacontane is subjected to hydrogenation in diethyl ether in the presence of palladium carbon (Pd / C) (third step) to produce the above-mentioned 17-methylpentatriacontane (Non-Patent Literature 2).

[0005] Furthermore, a method for synthesizing 17-methylheptatriacontan, a 17-methylalkane compound, has been reported, as described below, in a total of three steps with a yield of 73.63% (Non-Patent Literature 2). For example, 17-methyl-17-heptatriacontanol is synthesized by reacting 2-octadecanone with eicosylmagnesium bromide (first step), and the obtained 17-methyl-17-heptatriacontanol is then reacted with an acid catalyst. p - In the presence of toluenesulfonic acid, 17-methyleneheptatriacontane is synthesized by dehydration in benzene (second step). Subsequently, the obtained 17-methyleneheptatriacontane is subjected to hydrogenation in diethyl ether in the presence of palladium carbon (Pd / C) (third step) to produce the above-mentioned 17-methylheptatriacontane. [Prior art documents] [Non-patent literature]

[0006] [Non-Patent Document 1] Neil D Tsutsui et al.,BMC Biology,2009,7,71. [Non-Patent Document 2] Neil D Tsutsui et al.,J.Chem.Ecol.,2010,36,751-758. [Non-Patent Document 3] E. Sunamura et al., Insectes Sociaux, 2009, 56, 143-147. [Non-Patent Document 4] Dennis H. Burns et al.,J. Am. Chem. Soc.,1997,119,2125-2133. [Overview of the project] [Problems that the invention aims to solve]

[0007] However, both methods for producing 17-methylpentatriacontane and 17-methylheptatriacontane in Non-Patent Literature 2 are unsuitable for industrial use because they utilize large quantities of benzene as a solvent, which is highly toxic to humans. Furthermore, the use of flammable palladium carbon in diethyl ether, a special flammable solvent, makes industrialization difficult. Moreover, as the authors of Non-Patent Literature 2 also state, hydrocarbons that are homocoupling products of Grignard reagents are produced as by-products in the first step. Specifically, the reaction of 2-octadecanone with octadecylmagnesium bromide produces hexatriacontane, and the reaction of 2-octadecanone with eicosylmagnesium bromide produces tetracontane. At this time, hexatriacontane (molecular weight: 506.99) has a molecular weight and boiling point close to that of the target compound 17-methyl-17-pentatriacontanol (molecular weight: 522.97), making purification by distillation difficult. Furthermore, tetracontane (molecular weight: 563.08) has a molecular weight and boiling point close to that of the target compound, 17-methyl-17-heptatriacontanol (molecular weight: 551.03), making purification by distillation difficult. Therefore, in the first step, the authors perform purification by column chromatography instead of distillation, indicating that purification by column chromatography is essential in this manufacturing method. However, purification by column chromatography is difficult to implement on an industrial scale (over 100 kg), making it unsuitable for industrial production.

[0008] In addition, 2-octadecanone, used as a raw material, is difficult to obtain industrially (over 100 kg), requiring separate synthesis. Furthermore, since it is a solid at room temperature (25°C), it is cumbersome to charge it into the reactor as a solid, while charging it as a solution requires the addition of a large amount of solvent or heating, resulting in low productivity and the need for specialized equipment, making it unsuitable for industrial production. Moreover, the Grignard reagent used in the first step is thought to be prepared from the corresponding bromoalkane and magnesium, but the corresponding bromoalkanes, 1-bromooctadecane and 1-bromoicosan, are both solids. However, these bromoalkanes, 1-bromooctadecane and 1-bromoicosan, need to be reacted with magnesium as a solution when preparing the Grignard reagent, requiring a large amount of solvent, thus resulting in low productivity and unsuitability for industrial production. Furthermore, the method for producing 17-methylpentatriacontane is also insufficient. Hepta Although similar to the method for producing triacontane, the yield of 17-methylpentatriacontane is remarkably low at 37.32% across all three steps. Therefore, it is difficult to produce 17-methylalkane compounds in good industrial yield using the method described in Non-Patent Literature 2.

[0009] The present invention has been made in view of the above circumstances and aims to provide a novel compound that is a synthetic intermediate for efficiently producing 17-methylalkane compounds, including 17-methylpentatriacontane and 17-methylheptatriacontane. The present invention also aims to provide a method for producing the novel compound, and a method for producing 17-methylalkane compounds, including 17-methylpentatriacontane and 17-methylheptatriacontane, from the novel compound. [Means for solving the problem]

[0010] The inventors, through diligent research to solve the above problems, have found that the 1-halo-7-methyltricosanate compound according to the present invention is a novel compound. This 1-halo-7-methyltricosanate compound can be produced inexpensively and in large quantities, and can be purified by distillation alone. Furthermore, the inventors have found that this 1-halo-7-methyltricosanate compound efficiently produces 17-methylalkane compounds, including 17-methylpentatriacontane and 17-methylheptatriacontane. This production method can be performed in high yield by a coupling reaction between a 7-methyltricosyl nucleophile, which can be easily prepared from the above 1-halo-7-methyltricosanate compound, and an inexpensive and industrially available alkyl electrophile. Moreover, this production method has been found to be economical and industrially viable for producing 17-methylpentatriacontane and 17-methylheptatriacontane.

[0011] According to a first aspect of the present invention, the following general formula (1): [ka] (In the formula, X 1 (This represents a halogen atom.) A 1-halo-7-methyltricosene compound represented by [formula] is provided.

[0012] According to a second aspect of the present invention, the above 1-halo-7-methyltricosan compound (1) is given the following general formula (2): [ka] (In the formula, M 1 Li, MgZ 1 , CuZ 1 Or CuLiZ 1 Represents Z 1 is halogen (Represents an atom or a 7-methyltricosyl group.) It is converted to a 7-methyltricosyl nucleophile represented by the following formula (2), and then the 7-methyltricosyl nucleophile (2) is mixed with the following general formula (3): [ka] (wherein X 2 represents a halogen atom or p -toluenesulfonyloxy group, and n represents 11 to 13.) By a coupling reaction with an alkyl electrophilic reagent represented by the following general formula (4):

Chemical formula

[0013] According to the third aspect of the present invention, the following general formula (5):

Chemical formula

Chemical formula

[0014] According to a fourth aspect of the present invention, The following general formula (7): [ka] (In the formula, M 3 Li, MgZ 3 , CuZ 3 Or CuLiZ 3 Represents Z 3 (This represents a halogen atom or a pentadecyl group.) A pentadecyl nucleophile represented by the following general formula (8): [ka] (In the formula, X 5 and X 6 (These represent halogen atoms that may be the same or different from each other.) Through a coupling reaction with a 1,3-dihalo-2-methylpropane compound represented by the following formula (9): [ka] (In the formula, X 7 (This represents a halogen atom.) A step to obtain a 1-halo-2-methyloctadecane compound represented by, The process involves preparing the 2-methyloctadecyl nucleophile (5) from the above 1-halo-2-methyloctadecane compound (9), and 17-methylalkane compounds (4) further containing A method for manufacturing this is provided.

[0015] According to a fifth aspect of the present invention, The following general formula (5): [ka] (In the formula, M 2 Li, MgZ 2 , CuZ 2 Or CuLiZ 2 Represents Z 2 (This represents a halogen atom or a 2-methyloctadecyl group.) A 2-methyloctadecyl nucleophile represented by the following general formula (6): [ka] (In the formula, X 3 and X 4 (These represent halogen atoms that may be the same or different from each other.) Coupling reactions with 1,5-dihalopentane compounds represented by the following general formula (1): [ka] (In the formula, X 1 (This represents a halogen atom.) Step to obtain a 1-halo-7-methyltricosene compound (1) represented by A method for producing the above-mentioned 1-halo-7-methyltricosan compound (1) is provided, which includes the above-mentioned 1-halo-7-methyltricosan compound (1). The production method may further include a purification step of purifying the 1-halo-7-methyltricosan compound (1) after the step of obtaining the above-mentioned 1-halo-7-methyltricosan compound (1), and the purification step may be carried out by distillation alone. [Effects of the Invention]

[0016] According to the present invention, 17-methylalkane compounds, including 17-methylpentatriacontane and 17-methylheptatriacontane, can be produced in high yield in an economical and efficient manner with minimal environmental impact. Furthermore, according to the present invention, a sufficient boiling point difference can be obtained between the by-products generated in each step and the target compound, making purification by distillation, which is suitable for scale-up, possible. Moreover, according to the present invention, since all raw materials and intermediates are liquids, handling is easy, enabling a reduction in environmental impact and a significant improvement in productivity. In addition, according to the present invention, a novel synthetic intermediate useful for producing the above 17-methylalkane compounds can be provided. [Modes for carrying out the invention]

[0017] A 1-halo-7-methyltricosene compound (1) represented by the following general formula (1) and a method for producing the same. (i) The above 1-halo-7-methyltricosene compound (1) is described below. [ka]

[0018] X in the above general formula (1) 1 X represents a halogen atom. Halogen atom X 1 Specifically, examples include chlorine atoms, bromine atoms, and iodine atoms, with chlorine atoms and bromine atoms being preferred from the viewpoint of melting point or solvent solubility, and chlorine atoms being particularly preferred.

[0019] Specific examples of 1-halo-7-methyltricosan compounds (1) include 1-chloro-7-methyltricosan, 1-bromo-7-methyltricosan, and 1-iodo-7-methyltricosan. As the 1-halo-7-methyltricosane compound (1), 1-chloro-7-methyltricosane and 1-bromo-7-methyltricosane are preferred from the viewpoint of melting point or solvent solubility, and 1-chloro-7-methyltricosane is particularly preferred.

[0020] (ii) The method for producing the above 1-halo-7-methyltricosene compound (1) will be described below. 1-Halo-7-methyltricosane compound (1) can be prepared, for example, by a coupling reaction between a 2-methyloctadecyl nucleophile represented by the following general formula (5) and a 1,5-dihalopentane compound represented by the following general formula (6), as shown in the following chemical reaction equation.

[0021] [ka]

[0022] (iii) The 2-methyloctadecyl nucleophile (5) described above will be explained below. M in the above general formula (5) 2 Li, MgZ 2 , CuZ 2 Represents Z 2 represents a halogen atom or a 2-methyloctadecyl group. Halogen atom Z 2 Specifically, examples include chlorine atoms, bromine atoms, and iodine atoms.

[0023] Specific examples of 2-methyloctadecyl nucleophile reagents (5) include 2-methyloctadecyllithium; 2-methyloctadecylmagnesium halide reagents (Grignard reagents) such as 2-methyloctadecylmagnesium chloride, 2-methyloctadecylmagnesium bromide, and 2-methyloctadecylmagnesium iodide; bis[2-methyloctadecyl] cuplate; and Gilman reagents such as lithium=bis[2-methyloctadecyl] cuplate. From the viewpoint of ease of preparation (versatility), 2-methyloctadecylmagnesium halide reagents are preferred. One type of 2-methyloctadecyl nucleophile (5) may be used, or two or more types as needed. Furthermore, the 2-methyloctadecyl nucleophile (5) can be prepared, for example, by the manufacturing method described later.

[0024] (iv) Next, the above 1,5-dihalopentane compound (6) will be described below. X in the above general formula (6) 3 and X 4 X represents halogen atoms that may be the same or different from each other. 3 and X 4 Specifically, examples include chlorine atoms, bromine atoms, and iodine atoms. X 3 and X 4 Examples of such combinations include chlorine atom and chlorine atom, bromine atom and chlorine atom, chlorine atom and iodine atom, bromine atom and bromine atom, bromine atom and iodine atom, and iodine atom and iodine atom. Specific examples of the 1,5-dihalopentane compound (6) include 1,5-dichloropentane, 1,5-dibromopentane, 1,5-diiodopenane, 1-bromo-5-chloropentane, 1-chloro-5-iodopenane, and 1-bromo-5-iodopenane. From the viewpoint of yield, 1-bromo-5-chloropentane, 1-chloro-5-iodopenane, and 1-bromo-5-iodopenane are preferred. One or more types of 1,5-dihalopentane compounds (6) may be used as needed. Furthermore, 1,5-dihalopentane compounds (6) may be commercially available or synthesized in-house.

[0025] The 1,5-dihalopentane compound (6) can be synthesized, for example, by halogenation of 1,5-pentanediol.

[0026] (v) Next, the coupling reaction between the 2-methyloctadecyl nucleophile (5) and the 1,5-dihalopentane compound (6) will be described below. In this coupling reaction, the amount of 2-methyloctadecyl nucleophile (5) used is preferably 0.8 to 1.4 moles per mole of 1,5-dihalopentane compound (6), from an economic standpoint.

[0027] A solvent may be used in the coupling reaction as needed. Examples of solvents include common solvents such as ether-based solvents like tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), diethyl ether, dibutyl ether, 4-methyltetrahydropyran (MTHP), cyclopentyl methyl ether, and 1,4-dioxane; and hydrocarbon-based solvents such as hexane, heptane, benzene, toluene, xylene, and cumene. N , N -Dimethylformamide (DMF), N , N -Dimethylacetamide (DMAC), N -Methylpyrrolidone (NMP), dimethyl sulfoxide (DMSO), γ-butyrolactone (GBL), acetonitrile, N , N Examples of polar solvents include dimethylpropylene urea (DMPU), hexamethylphosphoric triamide (HMPA), dichloromethane, and chloroform. However, from the viewpoint of reactivity, hydrocarbon solvents such as toluene and xylene; ether solvents such as tetrahydrofuran, 2-methyltetrahydrofuran, and 4-methyltetrahydropyran; and acetonitrile are preferred, with tetrahydrofuran, 2-methyltetrahydrofuran, toluene, and xylene being more preferred. The solvent may be one type or, if necessary, two or more types. Furthermore, commercially available solvents can be used. The amount of solvent used is preferably 30 to 5000 g, more preferably 50 to 3000 g, per mole of 1,5-dihalopentane compound (6), from the viewpoint of reactivity.

[0028] A catalyst may be used in the coupling reaction as needed. Examples of catalysts include copper compounds of monovalent copper halides such as cuprous chloride, cuprous bromide, and cuprous iodide, and divalent copper halides such as cupric chloride, cupric bromide, and cupric iodide. From the viewpoint of reactivity, monovalent copper halides are preferred, and cuprous iodide is more preferred. The catalyst may be of one type or, if necessary, two or more types. Furthermore, commercially available catalysts can be used. The amount of catalyst used is preferably 0.0003 to 0.3 moles, more preferably 0.001 to 0.1 moles, per mole of 1,5-dihalopentane compound (6), from the viewpoint of reaction rate and / or post-treatment.

[0029] When a catalyst is used in the coupling reaction, a co-catalyst may be used as needed. Examples of such co-catalysts include trialkyl phosphite compounds having 3 to 9 carbon atoms, such as triethyl phosphite; phosphorus compounds such as triarylphosphine compounds having 18 to 21 carbon atoms, such as triphenylphosphine and tritlylphosphine; and arylphosphine compounds having 22 to 44 carbon atoms, such as 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP). However, from the viewpoint of reactivity, trialkyl phosphite compounds are preferred. The co-catalyst may be of one type or, if necessary, two or more types. Furthermore, commercially available co-catalysts can be used. The amount of the co-catalyst used is preferably 0.001 to 0.500 moles, more preferably 0.005 to 0.200 moles, per mole of 1,5-dihalopentane compound (6), from the viewpoint of reactivity.

[0030] When a catalyst is used in the coupling reaction, lithium halides may be added as needed. Examples of lithium halides include lithium chloride, lithium bromide, and lithium iodide, with lithium chloride being preferred from the viewpoint of reactivity. From the viewpoint of reactivity, the amount of lithium halide used in the coupling reaction is preferably 0.005 to 0.250 moles per mole of 1,5-dihalopentane compound (6).

[0031] The reaction temperature in this coupling reaction varies depending on the 2-methyloctadecyl nucleophile (5) used, but from the viewpoint of reactivity, it is preferably -78 to 70°C, more preferably -20 to 50°C, and even more preferably 5 to 35°C. The reaction time in this coupling reaction varies depending on the solvent and / or reaction scale used, but from the viewpoint of reactivity, it is preferably 0.5 to 100 hours.

[0032] X in the above general formula (6) 3 and X 4 If the X atoms are different from each other, the coupling reaction can be carried out while preferentially reacting with the more reactive halogen atom by appropriately selecting the catalyst or reaction temperature. For example, if the X atoms are different from each other... 3 and X 4 If a 1,5-dihalopentane compound (6) is used in which the combination is a chlorine atom and a bromine atom or a chlorine atom and an iodine atom, then X in the 1-halo-7-methyltricosan compound (1) 1 This can be a chlorine atom. Also, different X 3 and X 4 If we use a 1,5-dihalopentane compound (6) in which the combination is a bromine atom and an iodine atom, then X in the 1-halo-7-methyltricosan compound (1) 1 This can be represented as a bromine atom.

[0033] In the main step of the coupling reaction to produce 1-halo-7-methyltricosan compound (1), 17,20-dimethylhexatriacontane, which has 38 carbon atoms, is produced as a by-product impurity. However, a sufficient boiling point difference can be ensured between this impurity and the target compound, 1-halo-7-methyltricosan compound (1), which has 24 carbon atoms. Therefore, the target compound can be easily separated and purified from the impurity by distillation, and as a result, high-purity 1-halo-7-methyltricosan compound (1) can be produced.

[0034] Furthermore, the melting point of haloalkane compounds increases with increasing carbon number. For example, 1-chlorohexadecane has a melting point of 8-14°C, 1-chlorooctadecane has a melting point of 20°C, 1-chloroeicosane has a melting point of 37°C, and 1-chlorodocosane has a melting point of 41°C. Therefore, at room temperature of 20-25°C, compounds up to 16 carbon atoms, such as 1-chlorohexadecane, can be used as liquids without the need for heating or dissolution in a solvent. On the other hand, among the above 1-halo-7-methyltricosane compounds (1), 1-chloro-7-methyltricosane (1:X) has 24 carbon atoms. 1 Contrary to expectations, 1-(Cl) remained in a liquid state even at 15°C. This is thought to be because, unlike linear haloalkanes, the presence of methyl branching at an appropriate position lowers the melting point, allowing it to maintain a liquid state. Furthermore, although we initially considered a synthesis method via 1-chloro-2-methyleicosane as an intermediate for synthesizing 17-methylalkane compounds, we found that 1-chloro-7-methyltricosan (1:X) remained in a liquid state even at 15°C. 1 Despite having the same methyl branching as =Cl, and also having 21 carbon atoms, 1-chloro-7-methyltricosan (1:X 1 Despite having a lower concentration than Cl, it remained solid at 15°C. Thus, the 1-halo-7-methyltricosane compound (1) successfully reduced its melting point significantly due to the introduction of methyl branching at appropriate positions, and since it can be used as a liquid at room temperature, it can be easily utilized as an intermediate for the production of 17-methylalkane compounds.

[0035] (vi) Next, the method for producing the 2-methyloctadecyl nucleophile reagent (5) described above will be explained below. The 2-methyloctadecyl nucleophile (5) can be prepared by conventional methods or by the method described below.

[0036] As the 2-methyloctadecyl nucleophile (5), for example, 2-methyloctadecylmagnesium halide reagent (5:M 2 =MgZ 2 ;Z 2 The manufacturing method for the above-mentioned halogen atom is described below. 2-Methyloctadecylmagnesium halide reagent (5:M) 2 =MgZ 2 ;Z 2 The above halogen atom is a Grignard reagent.

[0037] 2-Methyloctadecylmagnesium halide reagent (5:M) 2 =MgZ 2 ;Z 2 The above-mentioned halogen atom can be prepared, for example, by reacting a 1-halo-2-methyloctadecane compound represented by the following general formula (9) with magnesium in a solvent, as shown in the following chemical reaction equation.

[0038] [ka]

[0039] (vii) First, the above 1-halo-2-methyloctadecane compound (9) will be explained below. X in the general formula (9) above 7 X represents a halogen atom. Halogen atom X 7 Specifically, examples include chlorine atoms, bromine atoms, and iodine atoms. Specific examples of 1-halo-2-methyloctadecane compounds (9) include 1-chloro-2-methyloctadecane, 1-bromo-2-methyloctadecane, and 1-iodo-2-methyloctadecane.

[0040] One or more types of 1-halo-2-methyloctadecane compounds (9) may be used as needed. Furthermore, 1-halo-2-methyloctadecane compounds (9) may be commercially available or independently synthesized.

[0041] The amount of magnesium used is preferably 1.0 to 2.0 grams per mole of 1-halo-2-methyloctadecane compound (9), from the viewpoint of completing the reaction. Examples of the above solvents include common solvents such as ether-based solvents like tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), diethyl ether, dibutyl ether, 4-methyltetrahydropyran (MTHP), cyclopentyl methyl ether, and 1,4-dioxane; and hydrocarbon-based solvents such as hexane, heptane, benzene, toluene, xylene, and cumene. However, from the viewpoint of the reaction rate for the production of the Grignard reagent, hydrocarbon-based solvents such as toluene and xylene, and ether-based solvents such as tetrahydrofuran, 2-methyltetrahydrofuran, and 4-methyltetrahydropyran are preferred, and tetrahydrofuran, 2-methyltetrahydrofuran, and 4-methyltetrahydropyran are more preferred. The solvent may be one type or, if necessary, two or more types. Furthermore, commercially available solvents can be used. The amount of solvent used is preferably 30 to 5000 g, more preferably 50 to 3000 g, per mole of 1-halo-2-methyloctadecane compound (9), from the viewpoint of reactivity.

[0042] The reaction temperature in the above reaction with magnesium varies depending on the solvent used, but from the viewpoint of reactivity, it is preferably 30 to 120°C. The reaction time in the above reaction with magnesium varies depending on the solvent and / or reaction scale used, but from the viewpoint of reactivity, it is preferably 0.5 to 100 hours.

[0043] (viii) Next, the method for producing the above 1-halo-2-methyloctadecane compound (9) will be described below. 1-Halo-2-methyloctadecane compound (9) can be prepared by conventional methods or by the methods described below.

[0044] The 1-halo-2-methyloctadecane compound (9) can be prepared, for example, by a coupling reaction between a pentadecyl nucleophile represented by the following general formula (7) and a 1,3-dihalo-2-methylpropane compound represented by the following general formula (8), as shown in the following chemical reaction equation.

[0045] [ka]

[0046] (ix) The pentadecyl nucleophile (7) described above is explained below. M in the above general formula (7) 3 Li, MgZ 3 , CuZ 3 Or CuLiZ 3 Represents Z 3 represents a halogen atom or a pentadecyl group. Halogen atom Z 3 Specifically, these include chlorine atoms, bromine atoms, and iodine. etc. These include bromine atoms and chlorine atoms, which are particularly preferred.

[0047] Specific examples of pentadecyl nucleophiles (7) include pentadecyl lithium; pentadecyl magnesium halide reagents (Grignard reagents) such as pentadecyl magnesium chloride, pentadecyl magnesium bromide, and pentadecyl magnesium iodide; bis[pentadecyl] cue plates; and Gilman reagents such as lithium=bis[pentadecyl] cue plates. Pentadecyl magnesium halide reagents are preferred from the viewpoint of ease of preparation (versatility). One type of pentadecyl nucleophile (7) may be used, or two or more types as needed. The pentadecyl nucleophile (7) may be commercially available, or it may be prepared, for example, by the manufacturing method described later.

[0048] (x) Next, the above 1,3-dihalo-2-methylpropane compound (8) will be described below. X in the above general formula (8) 5 and X 6 X represents halogen atoms that may be the same or different from each other. 5 and X 6 Specifically, examples include chlorine atoms, bromine atoms, and iodine atoms. X 5 and X 6 Examples of such combinations include chlorine atom and chlorine atom, bromine atom and chlorine atom, chlorine atom and iodine atom, bromine atom and bromine atom, bromine atom and iodine atom, and iodine atom and iodine atom. Specific examples of the 1,3-dihalo-2-methylpropane compound (8) include 1,3-dichloro-2-methylpropane, 1,3-dibromo-2-methylpropane, 1,3-diiodo-2-methylpropane, 1-bromo-3-chloro-2-methylpropane, 1-chloro-3-iodo-2-methylpropane, and 1-bromo-3-iodo-2-methylpropane. From the viewpoint of yield, 1-bromo-3-chloro-2-methylpropane, 1-chloro-3-iodo-2-methylpropane, and 1-bromo-3-iodo-2-methylpropane are particularly preferred. One or more types of 1,3-dihalo-2-methylpropane compound (8) may be used as needed. Furthermore, 1,3-dihalo-2-methylpropane compound (8) may be commercially available or independently synthesized.

[0049] 1,3-Dihalo-2-methylpropane compounds (8) can be synthesized, for example, by halogenation of 2-methyl-1,3-propanediol.

[0050] (xi) Next, the coupling reaction between the pentadecyl nucleophile (7) and the 1,3-dihalo-2-methylpropane compound (8) will be described below. In this coupling reaction, the amount of pentadecyl nucleophile (7) used is preferably 0.8 to 1.4 moles per mole of 1,3-dihalo-2-methylpropane compound (8), from an economic standpoint.

[0051] A solvent may be used in the coupling reaction as needed. Examples of solvents include common solvents such as ether-based solvents like tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), diethyl ether, dibutyl ether, 4-methyltetrahydropyran (MTHP), cyclopentyl methyl ether, and 1,4-dioxane; and hydrocarbon-based solvents such as hexane, heptane, benzene, toluene, xylene, and cumene. N , N -Dimethylformamide (DMF), N , N -Dimethylacetamide (DMAC), N -Methylpyrrolidone (NMP), dimethyl sulfoxide (DMSO), γ-butyrolactone (GBL), acetonitrile, N , N Examples of polar solvents include dimethylpropylene urea (DMPU), hexamethylphosphoric triamide (HMPA), dichloromethane, and chloroform. However, from the viewpoint of reactivity, hydrocarbon solvents such as toluene and xylene, ether solvents such as tetrahydrofuran, 2-methyltetrahydrofuran, and 4-methyltetrahydropyran, and acetonitrile are preferred, with tetrahydrofuran, 2-methyltetrahydrofuran, toluene, and xylene being more preferred. The solvent may be one type or, if necessary, two or more types. Furthermore, commercially available solvents can be used. The amount of solvent used is preferably 30 to 5000 g, more preferably 50 to 3000 g, per mole of 1,3-dihalo-2-methylpropane compound (8), from the viewpoint of reactivity.

[0052] A catalyst may be used in the coupling reaction as needed. Examples of catalysts include copper compounds of monovalent copper halides such as cuprous chloride, cuprous bromide, and cuprous iodide, and divalent copper halides such as cupric chloride, cupric bromide, and cupric iodide. From the viewpoint of reactivity, monovalent copper halides are preferred, and cuprous iodide is more preferred. The catalyst may be of one type or, if necessary, two or more types. Furthermore, commercially available catalysts can be used. The amount of catalyst used is preferably 0.0003 to 0.3 moles, more preferably 0.001 to 0.1 moles, per mole of 1,3-dihalo-2-methylpropane compound (8), from the viewpoint of reaction rate and / or post-treatment.

[0053] When a catalyst is used in the coupling reaction, a co-catalyst may be used as needed. Examples of such co-catalysts include trialkyl phosphite compounds having 3 to 9 carbon atoms, such as triethyl phosphite; triarylphosphine compounds having 18 to 21 carbon atoms, such as triphenylphosphine and tritlylphosphine; and phosphorus compounds such as arylphosphine compounds having 22 to 44 carbon atoms, such as 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP). However, from the viewpoint of reactivity, trialkyl phosphite compounds are preferred. The co-catalyst may be of one type or, if necessary, two or more types. Furthermore, commercially available co-catalysts can be used. The amount of the co-catalyst used is preferably 0.001 to 0.500 moles, more preferably 0.005 to 0.200 moles, per mole of 1,3-dihalo-2-methylpropane compound (8), from the viewpoint of reactivity.

[0054] When a catalyst is used in the coupling reaction, lithium halides may be added as needed. Examples of lithium halides include lithium chloride, lithium bromide, and lithium iodide, with lithium chloride being preferred from the viewpoint of reactivity. From the viewpoint of reactivity, the amount of lithium halide used in the coupling reaction is preferably 0.005 to 0.250 moles per mole of 1,3-dihalo-2-methylpropane compound (8).

[0055] The reaction temperature in this coupling reaction varies depending on the pentadecyl nucleophile (7) used, but from the viewpoint of reactivity, it is preferably -78 to 70°C, more preferably -20 to 50°C, and even more preferably 5 to 35°C. The reaction time in this coupling reaction varies depending on the solvent and / or reaction scale used, but from the viewpoint of reactivity, it is preferably 0.5 to 100 hours.

[0056] X in the above general formula (8) 5 and X 6 If the X atoms are different from each other, the coupling reaction can be carried out while preferentially reacting with the more reactive halogen atom by appropriately selecting the catalyst or reaction temperature. For example, if the X atoms are different from each other... 5 and X 6 If we use a 1,3-dihalo-2-methylpropane compound (8) in which the combination is a chlorine atom and a bromine atom or a chlorine atom and an iodine atom, then X in the 1-halo-2-methyloctadecane compound (9) 7 This can be a chlorine atom. Also, different X 5 and X 6 If we use the 1,3-dihalo-2-methylpropane compound (8), in which the combination is a bromine atom and an iodine atom, then the X in the 1-halo-2-methyloctadecane compound (9) 7 This can be represented as a bromine atom.

[0057] In the main step of the coupling reaction to produce the 1-halo-2-methyloctadecane compound (9), triacontane with 30 carbon atoms is produced as a by-product impurity. However, a sufficient boiling point difference can be ensured between this impurity and the target compound, the 1-halo-2-methyloctadecane compound (9) with 19 carbon atoms. Therefore, the target compound can be easily separated and purified from the impurity by distillation, and as a result, a high-purity 1-halo-2-methyloctadecane compound (9) can be produced.

[0058] Also, as described above, the melting point of the haloalkane compound increases as the number of carbon atoms increases. For example, at room temperature of 20 to 25 °C, up to 1-chlorohexadecane with 16 carbon atoms can be used as a liquid without the need for heating and dissolution in a solvent. On the other hand, 1-chloro-2-methyleicosane with 21 carbon atoms synthesized separately was a solid at 15 °C, while the 1-halo-2-methyloctadecane compound (9) and 1-chloro-2-methyloctadecane, which also have a methyl branch, were in a liquid state even at 15 °C.

[0059] (xii) Next, the method for producing the above-mentioned pentadecyl nucleophilic reagent (7) will be described below. The pentadecyl nucleophilic reagent (7) can be prepared according to a conventional method or according to the method described below.

[0060] For example, as the pentadecyl nucleophilic reagent (7), the method for producing the pentadecyl magnesium - halide reagent (7:M 3 =MgZ 3 , Z 3 being a halogen atom) will be described below. The pentadecyl magnesium - halide reagent (7:M 3 =MgZ 3 ) is a Grignard reagent.

[0061] The pentadecyl magnesium - halide reagent (7:M 3 =MgZ 3 ) can be prepared, for example, by reacting a 1 - halopentadecane compound represented by the following general formula (10) with magnesium in a solvent as shown by the following chemical reaction formula.

[0062]

Chemical formula

[0063] First, the above 1 - halopentadecane compound (10) will be described below. In the above general formula (10), X 8 represents a halogen atom. The halogen atom X 8 Specifically, examples include chlorine atoms, bromine atoms, and iodine atoms. Specific examples of 1-halopentadecane compounds (10) include 1-chloropentadecane, 1-bromopentadecane, and 1-iodopentadecane.

[0064] One type of 1-halopentadecane compound (10) or two or more types may be used as needed. Furthermore, the 1-halopentadecane compound (10) may be commercially available or it may be independently synthesized.

[0065] The amount of magnesium used is preferably 1.0 to 2.0 grams per mole of 1-halopentadecane compound (10), from the viewpoint of completing the reaction. Examples of the above solvents include common solvents such as ether-based solvents like tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), diethyl ether, dibutyl ether, 4-methyltetrahydropyran (MTHP), cyclopentyl methyl ether, and 1,4-dioxane; and hydrocarbon-based solvents such as hexane, heptane, benzene, toluene, xylene, and cumene. However, from the viewpoint of the reaction rate for the production of the Grignard reagent, hydrocarbon-based solvents such as toluene and xylene, and ether-based solvents such as tetrahydrofuran, 2-methyltetrahydrofuran, and 4-methyltetrahydropyran are preferred, and tetrahydrofuran, 2-methyltetrahydrofuran, and 4-methyltetrahydropyran are more preferred. The solvent may be one type or, if necessary, two or more types. Furthermore, commercially available solvents can be used. The amount of solvent used is preferably 30 to 5000 g, more preferably 50 to 3000 g, per mole of 1-halopentadecane compound (10), from the viewpoint of reactivity.

[0066] The reaction temperature in the above reaction with magnesium varies depending on the solvent used, but from the viewpoint of reactivity, it is preferably 30 to 120°C. The reaction time in the above reaction with magnesium varies depending on the solvent and / or reaction scale used, but from the viewpoint of reactivity, it is preferably 0.5 to 100 hours.

[0067] <ii>Regarding the method for producing a 17-methylalkane compound represented by the following general formula (4) One of the target compounds of the present invention, a 17-methylalkane compound represented by the following general formula (4), is prepared according to the production method shown by the following chemical reaction formula.

Chemical formula

[0068] (i) First, the above 7-methyltricosyl nucleophilic reagent (2) will be described below. M in the above general formula (2) 1 represents Li, MgZ 1 , CuZ 1 or CuLiZ 1 , and Z 1 represents a halogen atom or a 7-methyltricosyl group. Specific examples of the halogen atom Z 1 include a chlorine atom, a bromine atom, an iodine atom, and the like. The 7-methyltricosylmagnesium = halide reagent (2: M 1 = MgZ 1 ) is a Grignard reagent.

[0069] Specific examples of the 7-methyltricosyl nucleophilic reagent (2) include lithium 7-methyltricosyl; 7-methyltricosylmagnesium = chloride, 7-methyltricosylmagnesium = bromide, and 7-methyltricosylmagnesium = iodide, etc., 7-methyltricosylmagnesium = halide reagents (Grignard reagents); bis[7-methyltricosyl]cuprate; and Gilman reagents such as lithium = bis[7-methyltricosyl]cuprate, etc. From the viewpoint of ease of preparation (versatility), 7-methyltricosylmagnesium = halide reagents are preferred.

[0070] (ii) The method for producing the above 7-methyltricosyl nucleophilic reagent (2) will be described below. The manufacturing method includes at least a step of obtaining a 7-methyltricosyl nucleophile (2) using the above-mentioned 1-halo-7-methyltricosane compound (1).

[0071] As the 7-methyltricosyl nucleophile (2), for example, 7-methyltricosylmagnesium = halide reagent (2:M 1 =MgZ 1 , Z 1 The manufacturing method for the above-mentioned halogen atom is described below. 7-Methyltricosylmagnesium halide reagent (2:M) 1 =MgZ 1 , Z 1 The above-mentioned halogen atom can be prepared, for example, by reacting the above-mentioned 1-halo-7-methyltricosane compound (1) with magnesium in a solvent, as shown in the following chemical reaction equation.

[0072] [ka]

[0073] One type of 1-halo-7-methyltricosene compound (1) may be used, or two or more types as needed.

[0074] The amount of magnesium used is preferably 1.0 to 2.0 grams per mole of 1-halo-7-methyltricosane compound (1), from the viewpoint of completing the reaction. Examples of the above solvents include common solvents such as ether-based solvents like tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), diethyl ether, dibutyl ether, 4-methyltetrahydropyran (MTHP), cyclopentyl methyl ether, and 1,4-dioxane; and hydrocarbon-based solvents such as hexane, heptane, benzene, toluene, xylene, and cumene. However, from the viewpoint of the reaction rate for the production of the Grignard reagent, hydrocarbon-based solvents such as toluene and xylene, and ether-based solvents such as tetrahydrofuran, 2-methyltetrahydrofuran, and 4-methyltetrahydropyran are preferred, and tetrahydrofuran, 2-methyltetrahydrofuran, and 4-methyltetrahydropyran are more preferred. The solvent may be one type or, if necessary, two or more types. Furthermore, commercially available solvents can be used. The amount of solvent used is preferably 30 to 5000 g, more preferably 50 to 3000 g, per mole of 1-halo-7-methyltricosane compound (1), from the viewpoint of reactivity.

[0075] The reaction temperature in the above reaction with magnesium varies depending on the solvent used, but from the viewpoint of reactivity, it is preferably 30 to 120°C. The reaction time in the above reaction with magnesium varies depending on the solvent and / or reaction scale used, but from the viewpoint of reactivity, it is preferably 0.5 to 100 hours.

[0076] (iii) Next, a method for producing the 17-methylalkane compound (4) using the 7-methyltricosyl nucleophile (2) described above will be explained. The manufacturing method includes at least a step of obtaining a 17-methylalkane compound (4) by a coupling reaction between the above-mentioned 7-methyltricosyl nucleophile (2) and an alkyl electrophile represented by the following general formula (3).

[0077] [ka] One type of 7-methyltricosyl nucleophile (2) or two or more types may be used as needed. Furthermore, the 7-methyltricosyl nucleophile (2) may be commercially available or synthesized in-house.

[0078] (iv) Next, the alkyl electrophile reagent (3) described above will be explained below. X in the general formula (3) above 2 is a halogen atom or p - Represents a toluenesulfonyloxy group (CH3-C6H6-SO2-O(TsO) group). Halogen atom X 2 Specifically, examples include chlorine atoms, bromine atoms, and iodine atoms, with bromine atoms and iodine atoms being particularly preferred. In the general formula (3) above, n represents 11 to 13. Specific examples of alkyl electrophiles (3) include 1-halododecane compounds such as 1-chlorododecane, 1-bromodododecane, and 1-iodododecane (n=11); dodecyl = p -Toluene sulfonate (n=11); 1-halotridecane compounds such as 1-chlorotridecane, 1-bromotridecane and 1-iodotridecane (n=12); tridecyl = p -toluene sulfonate (n=12); and 1-halotetradecane compounds such as 1-chlorotetradecane, 1-bromotetradecane and 1-iodotetradecane (n=13); tetradecyl = p -Toluene sulfonate (n=13) is one example, and from the viewpoint of ease of preparation (versatility), 1-halododecane compounds (n=11), 1-halotridecane compounds (n=12), and 1-halotetradecane compounds (n=13) are preferred. When n is 11, the 17-methylalkane compound (4) produced by the coupling reaction of the above-mentioned 7-methyltricosyl nucleophile (2) and the alkyl electrophile (3:n=11) with n=11 is 17-methylpentatriacontane (4:n=11), which is one of the target compounds of the present invention. When n is 13, the 17-methylalkane compound (4) produced by the coupling reaction of the above-mentioned 7-methyltricosyl nucleophile (2) and the alkyl electrophile (3:n=13) with n=13 is 17-methylheptatriacontane (4:n=13), which is one of the target compounds of the present invention. Alkyl electrophile reagent (3) may be used as one type or, if necessary, as two or more types. Furthermore, alkyl electrophile reagent (3) may be commercially available or may be synthesized independently.

[0079] Alkyl electrophile reagent (3) is, for example, halogenation of 1-alkanol or 1-alkanol in the presence of a base. p It can be synthesized by tosylation with -toluenesulfonyl chloride.

[0080] (v) Next, the coupling reaction between the 7-methyltricosyl nucleophile (2) and the alkyl electrophile (3) will be described below. X 2 but p -The alkyl electrophile (3), which is a toluenesulfonyloxy group, is X 2 It can be used in the above coupling reaction, similar to alkyl electrophiles (3) in which the halogen atom is. p - This is because the toluenesulfonyloxy group is a good leaving group, similar to halogen atoms such as bromine atoms (see, for example, page 2127 of Non-Patent Document 4 mentioned above, "Table 1" and related descriptions).

[0081] In this coupling reaction, the amount of 7-methyltricosyl nucleophile (2) used is preferably 0.8 to 1.2 moles per mole of alkyl electrophile (3), from an economic standpoint.

[0082] A solvent may be used in the coupling reaction as needed. Examples of solvents include common solvents such as ether-based solvents like tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), diethyl ether, dibutyl ether, 4-methyltetrahydropyran (MTHP), cyclopentyl methyl ether, and 1,4-dioxane; and hydrocarbon-based solvents such as hexane, heptane, benzene, toluene, xylene, and cumene. N , N -Dimethylformamide (DMF), N , N -Dimethylacetamide (DMAC), N -Methylpyrrolidone (NMP), dimethyl sulfoxide (DMSO), γ-butyrolactone (GBL), acetonitrile, N , N Examples of polar solvents include dimethylpropylene urea (DMPU), hexamethylphosphoric triamide (HMPA), dichloromethane, and chloroform. However, from the viewpoint of reactivity, hydrocarbon solvents such as toluene and xylene; ether solvents such as tetrahydrofuran, 2-methyltetrahydrofuran, and 4-methyltetrahydropyran; and acetonitrile are preferred, with tetrahydrofuran, 2-methyltetrahydrofuran, toluene, and xylene being more preferred. The solvent may be one type or, if necessary, two or more types. Furthermore, commercially available solvents can be used. The amount of solvent used is preferably 30 to 5000 g, more preferably 50 to 3000 g, per mole of 7-methyltricosyl nucleophile (2), from the viewpoint of reactivity.

[0083] A catalyst may be used in the coupling reaction as needed. Examples of catalysts include copper compounds of monovalent copper halides such as cuprous chloride, cuprous bromide, and cuprous iodide, and divalent copper halides such as cupric chloride, cupric bromide, and cupric iodide. From the viewpoint of reactivity, monovalent copper halides are preferred, and cuprous chloride is more preferred. The catalyst may be of one type or, if necessary, two or more types. Furthermore, commercially available catalysts can be used. The amount of catalyst used is preferably 0.0003 to 0.300 moles, more preferably 0.001 to 0.100 moles, per mole of 7-methyltricosyl nucleophile (2), from the viewpoint of reaction rate and / or post-treatment.

[0084] When a catalyst is used in the coupling reaction, a co-catalyst may be used as needed. Examples of such co-catalysts include trialkyl phosphite compounds having 3 to 9 carbon atoms, such as triethyl phosphite; triarylphosphine compounds having 18 to 21 carbon atoms, such as triphenylphosphine and tritlylphosphine; and phosphorus compounds such as arylphosphine compounds having 22 to 44 carbon atoms, such as 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP). However, from the viewpoint of reactivity, trialkyl phosphite compounds are preferred. The co-catalyst may be of one type or, if necessary, two or more types. Furthermore, commercially available co-catalysts can be used. The amount of the co-catalyst used is preferably 0.001 to 0.500 moles, more preferably 0.005 to 0.200 moles, per mole of 7-methyltricosyl nucleophile (2), from the viewpoint of reactivity.

[0085] When a catalyst is used in the coupling reaction, lithium halides may be added as needed. Examples of lithium halides include lithium chloride, lithium bromide, and lithium iodide, with lithium chloride being preferred from the viewpoint of reactivity. From the viewpoint of reactivity, the amount of lithium halide used in the coupling reaction is preferably 0.005 to 0.250 moles per mole of 7-methyltricosyl nucleophile (2).

[0086] The reaction temperature in this coupling reaction varies depending on the 7-methyltricosyl nucleophile (2) used, but from the viewpoint of reactivity, it is preferably -78 to 70°C, more preferably -20 to 50°C, and even more preferably 5 to 35°C. The reaction time in this coupling reaction varies depending on the solvent and / or reaction scale used, but from the viewpoint of reactivity, it is preferably 0.5 to 100 hours.

[0087] (vi) Next, the above 17-methylalkane compound (4) will be described below. In the above general formula (4), n is defined as in the above general formula (3). Specific examples of 17-methylalkane compounds (4) include 17-methylpentatriacontane (4:n=11), 17-methylhexatriacontane (4:n=12), and 17-methylheptatriacontane (4:n=13). In the main step of the coupling reaction to produce 17-methylpentatriacontane (4:n=11), one of the target compounds of the present invention, tetracosane with 24 carbon atoms and 17,30-dimethylhexatetracontane with 48 carbon atoms are produced as by-products. However, a sufficient boiling point difference can be ensured between these impurities and the target compound, 17-methylpentatriacontane (4:n=11) with 36 carbon atoms. Furthermore, since the impurity 17,30-dimethylhexatetracontane with 48 carbon atoms has a very high melting point, it can be easily separated during post-treatment of the coupling reaction because it precipitates as a solid on the reactor wall and does not dissolve and mix into the organic layer. Therefore, the target compound can be easily separated and purified from the impurities by distillation, column chromatography, recrystallization, or a combination thereof, and as a result, high-purity 17-methylpentatriacontane (4:n=11) can be produced. Similarly, in the main step of the coupling reaction to produce 17-methylheptatriacontane (4:n=13), one of the target compounds of the present invention, octacosane (28 carbon atoms) and 17,30-dimethylhexatetracontane (48 carbon atoms) are produced as by-products. However, a sufficient boiling point difference can be ensured between these impurities and the target compound, 17-methylheptatriacontane (4:n=13), which has 38 carbon atoms. Furthermore, since the impurity 17,30-dimethylhexatetracontane (48 carbon atoms) has a very high melting point, it can be easily separated during post-treatment of the coupling reaction because it precipitates as a solid on the reactor wall and does not dissolve and mix into the organic layer. Therefore, the target compound can be easily separated and purified from the impurities by distillation, column chromatography, recrystallization, or a combination thereof, and as a result, high-purity 17-methylheptatriacontane (4:n=13) can be produced.

[0088] As described above, the 17-methylalkane compound (4), which is a nestmate recognition pheromone for Argentine ants, can be produced in a short number of steps, with high productivity and efficiency, from the synthetic intermediate, 1-halo-7-methyltricosan compound (1).

[0089] [Examples] The present invention will be specifically described below with reference to examples, but the present invention is not limited to the following examples. In the following, "purity" refers to the area percentage obtained by gas chromatography (GC) analysis unless otherwise specified, and "production ratio" refers to the relative ratio of the area percentages obtained by GC analysis. Furthermore, "yield" was calculated based on the area percentages obtained by GC analysis. In each example, reaction monitoring and yield calculation were performed according to the following GC conditions. GC conditions: GC: Shimadzu Corporation capillary gas chromatograph GC-2014, column: DB-5, 0.25 μm x 0.25 mmφ x 30 m, carrier gas: He (1.55 mL / min), detector: FID, column temperature: 150℃, heating at 5℃ / min to 230℃; UA-5, 0.25 μm x 0.25 mmφ x 10 m, carrier gas: He (1.55 mL / min), detector: FID, column temperature: 230℃, heating at 10℃ / min to 300℃.

[0090] The yield was calculated according to the following formula, taking into account the purity (%GC) of the raw materials and products. Yield (%) = {[(Weight of product obtained by reaction × %GC) / Molecular weight of product]} ÷[(Weight of starting material in reaction × %GC) / Molecular weight of starting material]}×100 Note that THF is tetrahydrofuran, and NMP is N -methyl-2-pyrrolidone and Et represent the ethyl group.

[0091] [Example 1] 1-Chloro-2-methyloctadecane (9:X 7 Production of 1-chloropentadecane, a raw material for (Cl)

[0092] [ka]

[0093] At room temperature, magnesium (160.74 g, 6.61 gram atoms) and tetrahydrofuran (1890.00 g) were added to a reactor and stirred at 60-65°C for 25 minutes. Next, 1-chlorododecane (1290.12 g, 6.30 moles, 100% purity) was added dropwise to the reactor at 60-75°C. After the addition was complete, the mixture was stirred at 75-80°C for 2 hours to prepare dodecylmagnesium chloride. Next, cuprous iodide (12.00 g, 0.063 mol), triethyl phosphite (25.12 g, 0.15 mol), tetrahydrofuran (630.00 g), and 1-bromo-3-chloropropane (922.44 g, 5.86 mol) were added to another reactor, and the prepared dodecyl magnesium chloride was added dropwise at 5-15°C. After the dropwise addition was complete, the mixture was stirred at 10-20°C for 1 hour. Next, aqueous ammonium chloride solution (ammonium chloride (63.00 g) and water (1735.66 g)), 20% hydrochloric acid (63.00 g), and 25% sodium hydroxide aqueous solution (32.04 g) were added to the reaction mixture and separated. The resulting organic layer was concentrated under reduced pressure, and the residue was distilled under reduced pressure to obtain 1-chloropentadecane (1311.04 g, 5.26 mol, purity 99.08%, bp = 150.3~152.3°C / 0.37 kPa (2.8 mmHg)) in liquid form with a yield of 89.81%. The obtained 1-chloropentadecane did not contain tetracosan, a homocoupling product of dodecylmagnesium chloride (below the GC detection limit).

[0094] The spectral data of 1-chloropentadecane obtained above is shown below. [Nuclear Magnetic Resonance Spectrum] 1 H-NMR (500MHz, CDCl3): δ=0.88(3H,t,J=6.9Hz),1.21-1.34(22H,m),1.38-1.46(2H,m),1.77(2H,tt,J=6.9Hz,6.9Hz),3.53(2H,t,J=6.9Hz); 13 C-NMR (125MHz, CDCl3): δ=14.1,22.7,26.9,28.9,29.4,29.47,29.55,29.62,29.65,29.69,31.9,32.7,45.2 [Mass Spectrum] EI-Mass Spectrum (70eV): m / z 246(M + ),217,203,189,175,161,147,133,119,105,71,57,43,29 [Infrared absorption spectrum] (D-ATR): ν = 2955, 2924, 2854, 1466, 1377, 1308, 723, 655

[0095] [Example 2] 1-Chloro-2-methyloctadecane (9:X 7 Manufacturing of =Cl)

[0096] [ka]

[0097] At room temperature, magnesium (120.90 g, 4.98 gram atoms) and tetrahydrofuran (1421.40 g) were added to the reactor and stirred at 60-65°C for 37 minutes. Next, 1-chloropentadecane (1180.48 g, 4.74 mol, 99.08% purity) prepared in Example 1 was added dropwise to the reactor at 60-75°C. After the addition was complete, the mixture was stirred at 75-80°C for 2 hours to produce pentadecylmagnesium chloride (7:M 3 A solution (=MgCl) was prepared. Next, in another reactor, cuprous iodide (CuI) (9.02 g, 0.047 mol), triethyl phosphite (P(OEt)3) (18.90 g, 0.11 mol), tetrahydrofuran (947.60 g), and 1-bromo-3-chloro-2-methylpropane (8:X 5 =Br,X 6 755.52 g, 4.41 mol, 100% purity =Cl) was added, and the prepared pentadecylmagnesium chloride was added dropwise at 10-20°C. After the addition was complete, the mixture was stirred at 10-20°C for 1.5 hours. Next, aqueous ammonium chloride solution (ammonium chloride (47.38 g) and water (1305.32 g)), 20% by mass hydrochloric acid (90.72 g), and 25% by mass aqueous sodium hydroxide solution (45.36 g) were added to the reaction mixture and separated. The resulting organic layer was concentrated under reduced pressure, and the residue was distilled under reduced pressure to obtain 1-chloro-2-methyloctadecane (9:X 7 =Cl)(1190.20g, 3.89 mol, purity 98.92%, bp=161.1~167.0℃ / 0.044kPa(0.33mmHg)) was obtained as a liquid in a yield of 88.20%. The obtained 1-chloro-2-methyloctadecane(9:X 7 The compound (=Cl) did not contain triacontane, a homocoupling product of pentadecylmagnesium chloride (below the GC detection limit).

[0098] The 1-chloro-2-methyloctadecane (9:X) obtained above 7 The spectral data for (=Cl) is shown below. [Nuclear Magnetic Resonance Spectrum] 1 H-NMR (500MHz, CDCl3): δ=0.88(3H,t,J=6.9Hz),1.00(3H,d,J=6.9Hz),1.20-1.50(30H ,m),1.76-1.84(1H,m),3.48(1H,dd,J=10.5Hz,5.4Hz),3.40(1H,dd,J=10.5Hz,6.5Hz); 13 C-NMR (125MHz, CDCl3): δ=14.11,17.77,22.69,26.84,29.37,29.59,29.63,29.66,29.70,29.75,31.93,33.97,35.52,51.28 [Mass Spectrum] EI-Mass Spectrum (70eV): m / z 302(M + ),253,197,188,169,153,141,127,113,105,99,85,71,57,41 [Infrared absorption spectrum] (D-ATR): ν = 2924, 2853, 1465, 1378, 722, 688

[0099] [Example 3] 1-Chloro-7-methyltricosan (1:X 1 Manufacturing of =Cl)

[0100] [ka]

[0101] At room temperature, magnesium (59.35 g, 2.44 gram atoms) and tetrahydrofuran (930.40 g) were added to the reactor and stirred at 60-65°C for 35 minutes. Next, 1-chloro-2-methyloctadecane (9:X) prepared in Example 2 was added to the reactor. 7 2-methyloctadecylmagnesium chloride (5:M) (712.40g, 2.33 mol, purity 98.92%) was added dropwise at 60-75°C. After the addition was complete, the mixture was stirred at 75-80°C for 2 hours to obtain 2-methyloctadecylmagnesium chloride (5:M) 2 A solution (=MgCl) was prepared. Next, in another reactor, cuprous iodide (4.43 g, 0.023 mol), triethyl phosphite (9.28 g, 0.056 mol), tetrahydrofuran (465.20 g), and 1-bromo-5-chloropentane (6:X 4 =Br,X 3 1-chloro-7-methyltricosan (1:X) was obtained by adding 1-chloro-7-methyltricosan (1:X) (409.88 g, 2.21 mol, 100% purity) and then adding the prepared pentadecylmagnesium chloride dropwise at 15-25°C. After the dropwise addition was complete, the mixture was stirred at 20-30°C for 1.5 hours. Next, aqueous ammonium chloride solution (ammonium chloride (23.26 g) and water (640.81 g)), 20% by mass hydrochloric acid (22.27 g), and 25% by mass aqueous sodium hydroxide solution (11.83 g) to the reaction mixture and separating the liquids. The resulting organic layer was concentrated under reduced pressure, and the residue was distilled under reduced pressure to obtain 1-chloro-7-methyltricosan (1:X) 1 =Cl)(708.34g, 1.85 mol, purity 97.18%, bp=183.1~196.2℃ / 0.044kPa(0.33mmHg)) was obtained as a liquid in a yield of 83.50%. The obtained 1-chloro-7-methyltricosan (1:X 1 =Cl) contains 2-methyloctadecylmagnesium chloride (5:M 2 The homocoupling compound 17,20-dimethylhexatriacontane (=MgCl) was not present (below the GC detection limit).

[0102] The 1-chloro-7-methyltricosan (1:X) obtained above 1 The spectral data for (=Cl) is shown below. [Nuclear Magnetic Resonance Spectrum] 1 H-NMR (500MHz, CDCl3): δ=0.84(3H,d,J=6.5Hz),0.88(3H,t,J=6.9Hz),1.04-1.12(2H,m),1 .20-1.33(35H,m),1.38-1.47(2H,m),1.77(2H,tt,J=6.9Hz,6.9Hz),3.53(2H,t,J=6.9Hz); 13 C-NMR(125MHz,CDCl3):δ=14.11,19.68,22.70,26.90,26.93,27.09,29.25, 29.37,29.66,29.71,29.74,30.02,31.93,32.68,32.71,36.95,37.06,45.17 [Mass Spectrum] EI-Mass Spectrum (70eV): m / z 357(M + -14), 253, 224, 197, 169, 147, 111, 99, 85, 71, 57, 43, 29 [Infrared absorption spectrum] (D-ATR): ν = 2924, 2853, 1465, 1377, 1304, 723, 656

[0103] [Example 4] Production of 17-methylpentatriacontane (4:n=11)

[0104] [ka]

[0105] At room temperature, magnesium (3.31 g, 0.14 gram atoms) and tetrahydrofuran (86.5 g) were added to the reactor and stirred at 60-65°C for 28 minutes. Next, 1-chloro-7-methyltricosan (1:X) prepared in Example 3 was added to the reactor. 1 7-methyltricosylmagnesium chloride (2:M) was added dropwise at 60-75°C. After the addition was complete, the mixture was stirred at 75-80°C for 3.5 hours to obtain 7-methyltricosylmagnesium chloride (2:M). 1 A solution (=MgCl) was prepared. Next, in another reactor, cuprous chloride (0.15 g, 0.0015 mol), triethyl phosphite (1.46 g, 0.0088 mol), lithium chloride (0.10 g, 0.0024 mol), tetrahydrofuran (100.00 g), and 1-bromododecane (3:X) were added. 2 Add Br (n=11) (32.38g, 0.13 mol) and at 15-25°C, the above-prepared 7-methyltricosylmagnesium chloride (2:M 1 7-methylpentatriacontane (4:n=11) (56.51g, 0.10 mol, purity 93.48%) was obtained as a solid in 80.23% yield. The obtained 17-methylpentatriacontane (4:n=11) was then purified by silica gel column chromatography (hexane:ethyl acetate = 100:0) to obtain 7-methyltricosylmagnesium chloride (2:M) in 2:30% sodium hydroxide aqueous solution (2:30%). The obtained 17-methylpentatriacontane (4:n=11) was then purified by 7-methyltricosylmagnesium chloride (2:M) in 80.23% yield. 1 The homocoupling product of 17,30-dimethylhexatetracontane (=MgCl) was not present (below the GC detection limit). In this example, purification was performed by column chromatography, but since there are no impurities to be separated, purification by distillation and / or recrystallization is also possible.

[0106] The spectral data for 17-methylpentatriacontane (4:n=11) obtained above is shown below. [Nuclear Magnetic Resonance Spectrum] 1 H-NMR (500MHz, CDCl3): δ=0.84(3H,d,J=6.9Hz),0.88(6H,t-like,J=6.9Hz),1.18-1.33(65H,m); 13 C-NMR (125MHz, CDCl3): δ=14.13,19.73,22.67,22.71,27.11,29.38,29.68,29.73,29.76,30.05,31.95,32.76,37.11 [Mass Spectrum] EI-Mass Spectrum (70eV): m / z 492(M + -14), 280, 252, 224, 197, 183, 169, 155, 141, 127, 113, 99, 85, 71, 57, 43, 29 [Infrared absorption spectrum] (D-ATR): ν = 2956, 2917, 2850, 1470, 1377, 720

[0107] [Example 5] Production of 17-methylheptatriacontane (4:n=13)

[0108] [ka]

[0109] At room temperature, magnesium (3.31 g, 0.14 gram atoms) and tetrahydrofuran (86.5 g) were added to the reactor and stirred at 60-65°C for 19 minutes. Next, 1-chloro-7-methyltricosan (1:X) prepared in Example 3 was added to the reactor. 1 7-methyltricosylmagnesium chloride (2:M) (49.87g, 0.13 mol, purity 97.18%) was added dropwise at 60-75°C. After the addition was complete, the mixture was stirred at 75-80°C for 5 hours to obtain 7-methyltricosylmagnesium chloride (2:M) 1 A solution (=MgCl) was prepared. Next, in another reactor, cuprous chloride (0.15 g, 0.0015 mol), triethyl phosphite (1.46 g, 0.0088 mol), lithium chloride (0.10 g, 0.0024 mol), tetrahydrofuran (100.00 g), and 1-bromotetradecane (3:X) were added. 2 Add Br (n=13) (36.02g, 0.13 mol) and at 15-25°C, the above-prepared 7-methyltricosylmagnesium chloride (2:M 1 7-methylheptatriacontane (4:n=13) (54.82 g, 0.094 mol, purity 91.51%) was obtained as a solid in 72.18% yield. The obtained 17-methylheptatriacontane (4:n=13) was then purified by silica gel column chromatography (hexane:ethyl acetate = 100:0) to obtain 7-methyltricosylmagnesium chloride (2:M) in 20-30°C for 2 hours. Next, aqueous acetic acid solution (acetic acid (1.30 g) and water (35.79 g)) was added to the reaction mixture and separated. The resulting organic layer was then subjected to vacuum distillation to separate octacosane. The residue was then purified by silica gel column chromatography (hexane:ethyl acetate = 100:0) to obtain 17-methylheptatriacontane (4:n=13) (54.82 g, 0.094 mol, purity 91.51%). 1 The homocoupling product of 17,30-dimethylhexatetracontane (=MgCl) was not present (below the GC detection limit). In this example, purification was performed by column chromatography, but since there are no impurities to be separated, purification by distillation and recrystallization is also possible.

[0110] The spectral data for 17-methylheptatriacontane (4:n=13) obtained above is shown below. [Nuclear Magnetic Resonance Spectrum] 1 H-NMR (500MHz, CDCl3): δ=0.84(3H,d,J=6.5Hz),0.88(6H,t,J=6.9Hz),1.03-1.12(2H,m),1.20-1.33(67H,m); 13 C-NMR (125MHz, CDCl3): δ=14.12,19.73,22.71,27.10,29.38,29.68,29.72,29.75,30.05,31.94,32.75,37.11 [Mass Spectrum] EI-Mass Spectrum (70eV): m / z 519(M + -1), 463, 393, 351, 308, 252, 183, 169, 155, 141, 71, 57 [Infrared absorption spectrum] (D-ATR): ν = 2958, 2918, 2850, 1473, 1464, 1377, 729, 719

[0111] [Example 6] 1-Bromo-7-methyltricosan(1:X 1 Manufacturing of =Br)

[0112] [ka]

[0113] At room temperature, add 1-chloro-7-methyltricosan (1:X) to the reactor. 1 =Cl)(10.00g, 0.26 mol, purity 97.18%), 1-bromopropane (CH3CH2CH2Br)(19.02g, 0.15 mol), sodium bromide (NaBr)(0.53g, 0.0052 mol), N -Methyl-2-pyrrolidone (NMP) (19.00 g) was added and the mixture was heated to 110-120°C. 1-chloropropane produced during the reaction was distilled off the reaction system, and after confirming a reaction rate >99% by GC, the mixture was cooled to 25°C. Next, water (35.16 g) and hexane (10.31 g) were added to the reaction mixture and separated. The resulting organic layer was concentrated, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate = 50:1) to obtain 1-bromo-7-methyltricosan (1:X 1 =Br)(10.93g, 0.26 mol, 100% purity) was obtained as a liquid in 100% yield.

[0114] The 1-bromo-7-methyltricosene (1:X) obtained above 1 The spectral data for Br (=Br) is shown below. [Nuclear Magnetic Resonance Spectrum] 1 H-NMR (500MHz, CDCl3): δ=0.84(3H,d,J=6.5Hz),0.88(3H,t,J=6.9Hz),1.03-1.14(2H,m),1 .18-1.36(35H,m),1.39-1.47(2H,m),1.86(2H,tt,J=6.9Hz,6.9Hz),3.41(2H,t,J=6.9Hz); 13 C-NMR(125MHz,CDCl3):δ=14.11,19.68,22.70,26.87,27.09,28.23,29.13, 29.37,29.66,29.71,29.74,30.02,31.93,32.71,32.86,34.02,36.94,37.06 [Mass Spectrum] EI-Mass Spectrum (70eV): m / z 403(M + -13), 337, 253, 191, 169, 155, 127, 111, 99, 85, 71, 57, 43, 29 [Infrared absorption spectrum] (D-ATR): ν = 2923, 2853, 1465, 1377, 1259, 722, 648, 566< / ii>

Claims

1. The following general formula (1): 【Chemistry 1】 (In the formula, X １ (This represents a halogen atom.) A 1-halo-7-methyltricosene compound represented by [the formula shown].

2. The following general formula (1): 【Chemistry 2】 (In the formula, X １ (This represents a halogen atom.) The 1-halo-7-methyltricosene compound (1) represented by the following general formula (2): 【Transformation 3】 (In the formula, M １ Li, MgZ １ CuZ １ Or CuLiZ １ Represents Z １ (This represents a halogen atom or a 7-methyltricosyl group.) It is converted to a 7-methyltricosyl nucleophile represented by the following formula (2), and then the 7-methyltricosyl nucleophile (2) is mixed with the following general formula (3): 【Chemistry 4】 (In the formula, X ２ (where n represents a halogen atom or a p-toluenesulfonyloxy group, and n represents 11 to 13.) Through a coupling reaction with an alkyl electrophile represented by the following general formula (4): 【Transformation 5】 (In the formula, n is as defined above.) Steps to obtain a 17-methylalkane compound represented by A method for producing the 17-methylalkane compound (4), comprising at least the following:

3. The following general formula (5): 【Transformation 6】 (wherein, M ２ represents Li, MgZ ２ , CuZ ２ or CuLiZ ２ , and Z ２ represents a halogen atom or a 2-methyloctadecyl group.) A 2-methyloctadecyl nucleophile represented by the following general formula (6): 【Transformation 7】 (In the formula, X ３ and X ４ (These represent halogen atoms that may be the same or different from each other.) A step to obtain the 1-halo-7-methyltricosan compound (1) by a coupling reaction with a 1,5-dihalopentane compound represented by . A method for producing a 17-methylalkane compound (4) according to claim 2, further comprising:

4. The following general formula (7): 【Transformation 8】 (In the formula, M ３ Li, MgZ ３ CuZ ３ Or CuLiZ ３ Represents Z ３ (This represents a halogen atom or a pentadecyl group.) A pentadecyl nucleophile represented by the following general formula (8): 【Chemistry 9】 (In the formula, X ５ and X ６ (These represent halogen atoms that may be the same or different from each other.) Through a coupling reaction with a 1,3-dihalo-2-methylpropane compound represented by the following formula (9): 【Chemistry 10】 (In the formula, X ７ (This represents a halogen atom.) A step to obtain a 1-halo-2-methyloctadecane compound represented by, A step of preparing the 2-methyloctadecyl nucleophile (5) from the 1-halo-2-methyloctadecane compound (9) and A method for producing the 17-methylalkane compound (4) according to claim 3, further comprising:

5. The following general formula (5): 【Chemistry 11】 (In the formula, M ２ Li, MgZ ２ CuZ ２ Or CuLiZ ２ Represents Z ２ (This represents a halogen atom or a 2-methyloctadecyl group.) A 2-methyloctadecyl nucleophile represented by the following general formula (6): 【Chemistry 12】 (In the formula, X ３ and X ４ (These represent halogen atoms that may be the same or different from each other.) Coupling reactions with 1,5-dihalopentane compounds represented by the following general formula (1): 【Chemistry 13】 (In the formula, X １ (This represents a halogen atom.) Steps to obtain a 1-halo-7-methyltricosene compound (1) represented by A method for producing the 1-halo-7-methyltricosan compound (1), which includes the above-mentioned compound.

6. The following general formula (7): 【Chemistry 14】 (In the formula, M ３ Li, MgZ ３ CuZ ３ Or CuLiZ ３ Represents Z ３ (This represents a halogen atom or a pentadecyl group.) A pentadecyl nucleophile represented by the following general formula (8): 【Chemistry 15】 (In the formula, X ５ and X ６ (These represent halogen atoms that may be the same or different from each other.) Through a coupling reaction with a 1,3-dihalo-2-methylpropane compound represented by the following formula (9): 【Chemistry 16】 (In the formula, X ７ (This represents a halogen atom.) A step to obtain a 1-halo-2-methyloctadecane compound represented by, A step of preparing the 2-methyloctadecyl nucleophile (5) from the 1-halo-2-methyloctadecane compound (9) and A method for producing a 1-halo-7-methyltricosan compound (1) according to claim 5, further comprising:

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