Patent Application
20240400484
The present invention relates to a haloalkyl alkoxymethyl ether compound, and also relates to a process for preparing 13,15-dimethylheptacosane from the haloalkyl alkoxymethyl ether compound and for preparing synthetic intermediate for preparing the haloalkyl alkoxymethyl ether compound.
The Red imported fire ant (scientific name: Solenopsis invicta) is a sanitary pest originating in South America, and inflicts many pet and human bites each year in the United States and Taiwan. Bites of the Red imported fire ant are reported to be extremely painful (see Non-Patent Literature 1 below), and sometimes trigger allergic reactions, such as anaphylactic shock, which may cause death. Therefore, many countries are highly concerned about the invasion and establishment of the Red imported fire ant. In countries where the Red imported fire ant is already established, such as the United States, China, Taiwan, and Australia, efforts to employ pest control methods other than pesticides have been focused on the use of microsporidian protozoans (Kneallhazia solenopsae) or the entomopathogenic fungus Beauveria bassiana, as well as the use of cuticular hydrocarbons (see Non-Patent Literature 2 below).
Known cuticular hydrocarbons of the Red imported fire ant include heptacosane, 13-methylheptacosane, 13,15-dimethylheptacosane, 3-methylheptacosane, and 3,9-dimethylheptacosane (see Non-Patent Literature 1 below).
As mentioned above, known cuticular hydrocarbons of the Red imported fire ant include heptacosane, 13-methylheptacosane, 13,15-dimethylheptacosane, 3-methylheptacosane, and 3,9-dimethylheptacosane. Although the disclosure focuses on 13,15-dimethylheptacosane among such cuticular hydrocarbons, the present invention is not limited thereto. While 13,15-dimethylheptacosane itself is a known compound, its preparation process is unknown.
The present invention has been made in view of the aforementioned circumstances, and aims to provide a novel synthetic intermediate useful for preparing 13,15-dimethylheptacosane, and a process for preparing the synthetic intermediate. The present invention also aims to provide an efficient, and preferably economic, process for preparing 13,15-dimethylheptacosane from the aforesaid synthetic intermediate.
As a result of intensive research to overcome the aforesaid problems of the prior art, the present inventors found that a haloalkyl alkoxymethyl ether compound is a key intermediate that can comprehensively synthesize various compounds having a 1,3-dimethyl skeleton. The present inventors further found an inexpensive and efficient process for preparing the haloalkyl alkoxymethyl ether compound, and an efficient process for preparing 13,15-dimethylheptacosane, which is a cuticular hydrocarbon compound of the Red imported fire ant, from the haloalkyl alkoxymethyl ether compound, and thus have completed the present invention. The aforesaid preparation process also was found to be suited to industrial application.
According to a first aspect of the present invention, there is provided a process for preparing a haloalkyl alkoxymethyl ether compound of the following general formula (1B):
According to a second aspect of the present invention, there is provided a process for preparing 4,6-dimethyloctadecanol of the following formula (7):
the process comprising the steps of
wherein M2B represents Li, MgZ2B, CuZ2B, or CuLiZ2B, Z2B represents a halogen atom or a 6-alkoxymethoxy-1,3-dimethylhexyl group, and R1 is as defined above;
X2(CH2)11CH3 (5)
wherein R1 is as defined above,
According to a third aspect of the present invention, there is provided a process for preparing 13,15-dimethylheptacosane of the following general formula (11):
the process comprising the steps of
wherein X3 represents a halogen atom,
X4(CH2)8CH3 (10)
According to a fourth aspect of the present invention, there is provided a haloalkyl alkoxymethyl ether compound of the following general formula (1):
wherein X1 represents a halogen atom, R1 represents a hydrogen atom, an n-alkyl group having 1 to 9 carbon atoms, or a phenyl group, and n represents 1 or 2.
According to the present invention, it is possible to prepare a haloalkyl alkoxymethyl ether compound that is a building block for comprehensively synthesizing compounds having a 1,3-dimethyl skeleton. The haloalkyl alkoxymethyl ether compound can be used as a key intermediate to efficiently prepare 13,15-dimethylheptacosane, a compound having a 1,3-dimethyl skeleton, with less environmental impact and fewer steps. The preparation process is also economic.
First, the haloalkyl alkoxymethyl ether compound (1) will be explained in detail below.
In the general formula (1) above, X1 represents a halogen atom. Examples of the halogen atom X1 include a chlorine atom, a bromine atom, and an iodine atom. A chlorine atom and a bromine atom are preferred. By using said chlorine atom and bromine atom, a preferred reactivity may be ensured. A chlorine atom is particularly preferred. By using said chlorine atom, a particularly preferred reactivity may be ensured.
In the general formula (1) above, R1 represents a hydrogen atom, an n-alkyl group having 1 to 9 carbon atoms, or a phenyl group.
Examples of the n-alkyl group R1 include a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group, a hexyl group, a heptyl group, an octyl group, and a nonyl group.
n represents an integer of 1 or 2.
Specific examples of the haloalkyl alkoxymethyl ether compound (1) include the following compounds:
One target compound of the present invention, 6-halo-4-methylheptyl alkoxymethyl ether compound (1B), is prepared from the 4-halopentyl alkoxymethyl ether compound (1A) according to the preparation process of the following chemical reaction formula:
Namely, the 6-halo-4-methylheptyl alkoxymethyl ether compound (1B) may be prepared by converting the 4-halopentyl alkoxymethyl ether compound (1A) into the nucleophilic reagent, 4-alkoxymethoxy-1-methylbutyl (2A), then subjecting the nucleophilic reagent, 4-alkoxymethoxy-1-methylbutyl (2A), to a nucleophilic addition reaction with propylene oxide (3) to form the 6-hydroxy-4-methylheptyl alkoxymethyl ether compound (4), and then subjecting the 6-hydroxy-4-methylheptyl alkoxymethyl ether compound (4) to a halogenation reaction.
The nucleophilic reagent, 4-alkoxymethoxy-1-methylbutyl (2A), is represented by the following general formula (2A):
In the general formula (2A) above, M1A represents Li, MgZ1A, CuZ1A, or CuLiZ1A, and Z1A represents a halogen atom or a 4-alkoxymethoxy-1-methylbutyl group. Examples of the halogen atom Z1A include a chlorine atom, a bromine atom, and an iodine atom. A chlorine atom and a bromine atom are preferred. By using said chlorine atom and bromine atom, a preferred reactivity may be ensured. A chlorine atom is particularly preferred. By using said chlorine atom, a particularly preferred reactivity may be ensured.
In the general formula (2A) above, R1 is as defined for the general formula (1), X1 represents a halogen atom, and R1 represents a hydrogen atom, an n-alkyl group having 1 to 9 carbon atoms, or a phenyl group.
When M1A is MgZ1A in the general formula (2A) above, the nucleophilic reagent, 4-alkoxymethoxy-1-methylbutyl (2A:M1A=MgZ1A), is a Grignard reagent.
Specific examples of the nucleophilic reagent, 4-alkoxymethoxy-1-methylbutyl (2A), include the following examples:
Grignard reagents such as 4-alkoxymethoxy-1-methylbutylmagnesium halide compounds are preferred. By using said 4-alkoxymethoxy-1-methylbutylmagnesium halide compounds, a preferred reactivity may be ensured.
The nucleophilic reagent, 4-alkoxymethoxy-1-methylbutyl (2A), may be prepared from the aforesaid 4-halopentyl alkoxymethyl ether compound (1A). The process for preparing the 4-halopentyl alkoxymethyl ether compound (1A) is elaborated in Section III below.
A process for preparing the nucleophilic reagent, 4-alkoxymethoxy-1-methylbutyl (2A), when M1A is MgZ1A, that is, the 4-alkoxymethoxy-1-methylbutylmagnesium halide reagent (2A:M1A=MgZ1A) (which is a Grignard reagent), will be described in detail as an example.
The 4-alkoxymethoxy-1-methylbutylmagnesium halide reagent (2A: when M1A=MgZ1A and Z1A=halogen atom) may be prepared, for example, by reacting the aforesaid 4-halopentyl alkoxymethyl ether compound (1A) with magnesium in a solvent, as shown in the following chemical reaction formula:
The amount of magnesium used, per mol of the 4-halopentyl alkoxymethyl ether compound (1A), is preferably 1.0 to 2.0 gram atoms. By using said preferred amount, a preferred completion of the reaction may be ensured.
Examples of the solvent include general solvents such as, for example, ether solvents such as tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), diethyl ether, dibutyl ether, 4-methyltetrahydropyran (MTHP), cyclopentylmethylether, and 1,4-dioxane; and hydrocarbon solvents such as hexane, heptane, benzene, toluene, xylene, and cumene. Hydrocarbon solvents such as toluene and xylene; and ether solvents such as tetrahydrofuran, 2-methyltetrahydrofuran, and 4-methyltetrahydropyran are preferred. By using said hydrocarbon solvents such as toluene and xylene; and ether solvents such as tetrahydrofuran, 2-methyltetrahydrofuran, and 4-methyltetrahydropyran, a preferred reaction rate of forming of the aforesaid Grignard reagent may be ensured. Tetrahydrofuran, 2-methyltetrahydrofuran, and 4-methyltetrahydropyran are more preferred. By using said tetrahydrofuran, 2-methyltetrahydrofuran, and 4-methyltetrahydropyran, a more preferred reaction rate of forming of the aforesaid Grignard reagent may be ensured.
The solvent may be used alone or in combination thereof, if necessary. The solvent may be a commercially available one.
The amount of the solvent used, per mol of the 4-halopentyl alkoxymethyl ether compound (1A), is preferably 30 to 5,000 g, and more preferably 50 to 3,000 g. By using said preferred amount and said more preferred amount, a preferred reactivity and a more preferred reactivity may be ensured.
The reaction temperature varies, depending on the solvent used, and is preferably 30 to 120° C. By using said preferred reaction temperature, a preferred reactivity may be ensured.
The reaction time varies, depending on the solvent used and/or production scale, and 0.5 to 100 hours is preferred. By using said reaction time, a preferred reactivity may be ensured.
The 6-hydroxy-4-methylheptyl alkoxymethyl ether compound (4) is represented by the following general formula (4):
In the general formula (4) above, R1 is as defined for the general formula (1).
Specific examples of the 6-hydroxy-4-methylheptyl alkoxymethyl ether compound (4) include 6-hydroxy-4-methylheptyl methoxymethyl ether, 6-hydroxy-4-methylheptyl ethoxymethyl ether, 6-hydroxy-4-methylheptyl propyloxymethyl ether, 6-hydroxy-4-methylheptyl butyloxymethyl ether, 6-hydroxy-4-methylheptyl pentyloxymethyl ether, 6-hydroxy-4-methylheptyl hexyloxymethyl ether, 6-hydroxy-4-methylheptyl heptyloxymethyl ether, 6-hydroxy-4-methylheptyl octyloxymethyl ether, 6-hydroxy-4-methylheptyl nonyloxymethyl ether, 6-hydroxy-4-methylheptyl decyloxymethyl ether, and 6-hydroxy-4-methylheptyl benzyloxymethyl ether.
The 6-hydroxy-4-methylheptyl alkoxymethyl ether compound (4) may be prepared from the aforesaid nucleophilic reagent, 4-alkoxymethoxy-1-methylbutyl (2A), as shown in the following chemical reaction formula:
The preparation process includes at least a step of subjecting the nucleophilic reagent, 4-alkoxymethoxy-1-methylbutyl (2A), to a nucleophilic addition reaction with propylene oxide of the following general formula (3) to form the 6-hydroxy-4-methylheptyl alkoxymethyl ether compound (4).
In the aforesaid nucleophilic addition reaction, the nucleophilic reagent, 4-alkoxymethoxy-1-methylbutyl (2A), may be used alone or in combination thereof, if necessary.
Propylene oxide (3) may be a commercially available one, or may be synthesized in house.
The amount of the nucleophilic reagent, 4-alkoxymethoxy-1-methylbutyl (2A), per mol of propylene oxide (3), used in the nucleophilic addition reaction is preferably 0.6 to 1.3 mol. By using said preferred amount, preferred economy may be ensured.
A solvent may be incorporated in the nucleophilic addition reaction, if necessary.
Examples of the solvent include general solvents such as, for example, ether solvents such as tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), diethyl ether, dibutyl ether, 4-methyltetrahydropyran (MTHP), cyclopentylmethylether, and 1,4-dioxane; hydrocarbon solvents such as hexane, heptane, benzene, toluene, xylene, and cumene; and polar solvents such as N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), dimethyl sulfoxide (DMSO), γ-butyrolactone (GBL), acetonitrile, N,N′-dimethylpropylene urea (DMPU), hexamethylphosphoric triamide (HMPA), dichloromethane, and chloroform. Hydrocarbon solvents such as toluene and xylene; ether solvents such as tetrahydrofuran, 2-methyltetrahydrofuran, and 4-methyltetrahydropyran; and acetonitrile are preferred. By using said hydrocarbon solvents such as toluene and xylene; ether solvents such as tetrahydrofuran, 2-methyltetrahydrofuran, and 4-methyltetrahydropyran; and acetonitrile, a preferred reactivity may be ensured. Tetrahydrofuran, 2-methyltetrahydrofuran, toluene, and xylene are more preferred. By using said tetrahydrofuran, 2-methyltetrahydrofuran, toluene, and xylene, a more preferred reactivity may be ensured.
The solvent may be used alone or in combination thereof, if necessary. The solvent may be a commercially available one.
The amount of the solvent used, per mol of the nucleophilic reagent, 4-alkoxymethoxy-1-methylbutyl (2A), is preferably 30 to 5,000 g, and more preferably 50 to 3,000 g. By using said preferred amount and said more preferred amount, a preferred reactivity and a more preferred reactivity may be ensured.
The nucleophilic addition reaction may be carried out in the presence of a catalyst, if necessary. Examples of the catalyst include cuprous halides such as cuprous chloride, cuprous bromide, and cuprous iodide; and cupric halides such as cupric chloride, cupric bromide, and cupric iodide. Cuprous halides are preferred, and cuprous chloride is more preferred. By using said cuprous halides, a preferred reactivity may be ensured. By using said cuprous chloride, a more preferred reactivity may be ensured.
The catalyst may be used alone or in combination thereof, if necessary. The catalyst may be a commercially available one.
The amount of the catalyst used, per mol of the nucleophilic reagent, 4-alkoxymethoxy-1-methylbutyl (2A), is preferably 0.0001 to 0.300 mol, and more preferably 0.0003 to 0.100 mol. By using said preferred amount and said more preferred amount, a preferred reaction rate and/or post-treatment and a more preferred reaction rate and/or post-treatment may be ensured.
When the nucleophilic addition reaction is carried out in the presence of the catalyst, a co-catalyst may be used, if necessary. Examples of the co-catalyst include phosphorus compounds such as trialkyl phosphite compounds having 3 to 9 carbon atoms such as triethyl phosphite; and such as triarylphosphine compounds having 18 to 21 carbon atoms such as triphenylphosphine. A trialkyl phosphite compound having 3 to 9 carbon atoms, which is a liquid at a room temperature, is preferred. By using said trialkyl phosphite compound having 3 to 9 carbon atoms, a preferred handling may be ensured.
The co-catalyst may be used alone or in combination thereof, if necessary. The co-catalyst may be a commercially available one.
When the co-catalyst is used, the amount of the co-catalyst used, per mol of the nucleophilic reagent, 4-alkoxymethoxy-1-methylbutyl (2A), is preferably more than 0 up to 0.500 mol, and more preferably more than 0 up to 0.200 mol. By using said preferred amount and said more preferred amount, a preferred reactivity and a more preferred reactivity may be ensured.
When the nucleophilic addition reaction is carried out in the presence of the catalyst, a lithium halide may be added, if necessary.
Examples of the lithium halide include lithium chloride, lithium bromide, and lithium iodide. Lithium chloride is preferred. By using said lithium chloride, a preferred reactivity may be ensured.
The lithium halide may be used alone or in combination thereof, if necessary. The lithium halide may be a commercially available one.
When the lithium halide is used, the amount of the lithium halide used, per mol of the nucleophilic reagent, 4-alkoxymethoxy-1-methylbutyl (2A), is preferably more than 0 up to 0.250 mol. By using said preferred amount, a preferred reactivity may be ensured.
The reaction temperature of the nucleophilic addition reaction varies, depending on the nucleophilic reagent, 4-alkoxymethoxy-1-methylbutyl (2A), used, and is preferably-78 to 70° C., more preferably-20 to 50° C., and most preferably 5 to 35° C. By using said preferred reaction temperature, said more preferred reaction temperature, and said most preferred reaction temperature, a preferred reactivity, a more preferred reactivity, and a most preferred reactivity may be ensured.
The reaction time of the nucleophilic addition reaction varies, depending on the solvent used and/or production scale, and is preferably 0.5 to 100 hours. By using said preferred reaction time, a preferred reactivity may be ensured.
(iii) 6-Halo-4-Methylheptyl Alkoxymethyl Ether Compound (1B) and Process for Preparing 6-Halo-4-Methylheptyl Alkoxymethyl Ether Compound (1B)
The 6-halo-4-methylheptyl alkoxymethyl ether compound (1B) may be prepared from the aforesaid 6-hydroxy-4-methylheptyl alkoxymethyl ether compound (4).
The preparation process includes a step of subjecting the 6-hydroxy-4-methylheptyl alkoxymethyl ether compound (4) to a halogenation reaction.
The halogenation reaction may be carried out by, for example, a process of tosylating a hydroxy group with a p-toluenesulfonyl halide compound and then halogenating with the metal salt, lithium halide compound; or a process of directly halogenating a hydroxy group with a halogenating agent.
Examples of the halogenating agent include halogens such as chlorine, bromine, and iodine; hydrogen halide compounds such as hydrogen chloride, hydrogen bromide, and hydrogen iodide; methanesulfonyl halide compounds such as methanesulfonyl chloride, methanesulfonyl bromide, and methanesulfonyl iodide; benzenesulfonyl halide compounds such as benzenesulfonyl chloride, benzenesulfonyl bromide, and benzenesulfonyl iodide; p-toluenesulfonyl halide compounds such as p-toluenesulfonyl chloride, p-toluenesulfonyl bromide, and p-toluenesulfonyl iodide; thionyl halide compounds such as thionyl chloride, thionyl bromide, and thionyl iodide; phosphorus halide compounds such as phosphorus trichloride, phosphorus pentachloride, and phosphorus tribromide; carbon tetrahalide compounds such as carbon tetrachloride, carbon tetrabromide, and carbon tetraiodide; alkylsilyl halide compounds such as trimethylsilyl chloride, trimethylsilyl bromide, trimethylsilyl iodide, triethylsilyl chloride, triethylsilyl bromide, triethylsilyl iodide, triisopropylsilyl chloride, triisopropylsilyl bromide, triisopropylsilyl iodide, tert-butyldimethylsilyl chloride, tert-butyldimethylsilyl bromide, and tert-butyldimethylsilyl iodide; oxalyl halide compounds such as oxalyl chloride, oxalyl bromide, and oxalyl iodide; and N-halosuccinimide compounds such as N-chlorosuccinimide, N-bromosuccinimide, and N-iodosuccinimide. Methanesulfonyl halide compounds, benzenesulfonyl compounds, p-toluenesulfonyl halide compounds, and thionyl halide compounds are preferred. By using said methanesulfonyl halide compounds, benzenesulfonyl halide compounds, p-toluenesulfonyl halide compounds, and thionyl halide compounds, a preferred suppression of side reactions may be ensured. Methanesulfonyl halide compounds, benzenesulfonyl halide compounds, and thionyl halide compounds are particularly preferred. By using said methanesulfonyl halide compounds, benzenesulfonyl halide compounds, and thionyl halide compounds, a particularly preferred suppression of side reactions may be ensured.
The halogenating agent may be used alone or in combination thereof, if necessary. The halogenating agent may be a commercially available one.
The amount of the halogenating agent used, per mol of the 6-hydroxy-4-methylheptyl alkoxymethyl ether compound (4), is preferably 0.8 to 5.0 mol, and more preferably 1.0 to 2.5 mol. By using said preferred amount and said more preferred amount, a preferred reactivity and a more preferred reactivity may be ensured.
A base may be incorporated in the halogenation reaction, if necessary.
Examples of the base include hydroxides such as sodium hydroxide, potassium hydroxide, calcium hydroxide, and magnesium hydroxide; carbonates such as sodium carbonate, potassium carbonate, calcium carbonate, and magnesium carbonate; and amines such as triethylamine, N,N-diisopropylethylamine, piperidine, pyrrolidine, pyridine, lutidine, 4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline, and 1,8-diazabicyclo [5.4.0]-7-undecene (DBU).
When a methanesulfonyl halide compound, a benzenesulfonyl halide compound, a p-toluenesulfonyl halide compound, or the like is used as the aforesaid halogenating agent, the base is preferably amines, and more preferably pyridines such as pyridine, lutidine, and 4-dimethylaminopyridine.
When a thionyl halide compound is used as the halogenating agent, the base is preferably amines, and more preferably trialkylamines such as triethylamine.
The base may be used alone or in combination thereof, if necessary. The base may be a commercially available one.
When the base is used, the amount of the base used, per mol of the 6-hydroxy-4-methylheptyl alkoxymethyl ether compound (4), is preferably more than 0 up to 8.0 mol, and more preferably more than 0 up to 3.0 mol. By using said preferred amount and said more preferred amount, preferred yield and/or economy and a more preferred yield and/or economy may be ensured.
A metal salt may be added in the halogenation reaction, if necessary.
Examples of the metal salt include lithium salts such as lithium chloride, lithium bromide, and lithium iodide; sodium salts such as sodium chloride, sodium bromide, and sodium iodide; potassium salts such as potassium chloride, potassium bromide, and potassium iodide; calcium salts such as calcium chloride, calcium bromide, and calcium iodide; and magnesium salts such as magnesium chloride, magnesium bromide, and magnesium iodide.
When the halogenation with the metal salt, lithium halide compound, is carried out after the tosylation, the reaction is carried out with, for example, lithium salts such as lithium chloride, lithium bromide, and lithium iodide.
The metal salt may be used alone or in combination thereof, if necessary. The metal salt may be a commercially available one.
When the metal salt is used, the amount of the metal salt used, per mol of the 6-hydroxy-4-methylheptyl alkoxymethyl ether compound (4), is preferably more than 0 up to 30.0 mol, and more preferably more than 0 up to 5.0 mol. By using said preferred amount and said more preferred amount, a preferred reactivity and a more preferred reactivity may be ensured.
Although the metal salt increases the concentration of halide ions in the reaction system to thereby enhance the reactivity, it is preferred not to incorporate the metal salt in the reaction. By not incorporating the metal salt, preferred economy and/or environmental protection may be ensured.
A solvent may be incorporated in the halogenation reaction, if necessary.
Examples of the solvent include general solvents such as, for example, ether solvents such as tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), diethyl ether, dibutyl ether, 4-methyltetrahydropyran (MTHP), cyclopentylmethylether, and 1,4-dioxane; hydrocarbon solvents such as hexane, heptane, benzene, toluene, xylene, and cumene; polar solvents such as N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), dimethyl sulfoxide (DMSO), γ-butyrolactone (GBL), acetonitrile, acetone, N,N′-dimethylpropylene urea (DMPU), hexamethylphosphoric triamide (HMPA), dichloromethane, and chloroform; and ester solvents such as methyl acetate, ethyl acetate, n-propyl acetate, and n-butyl acetate. 2-Methyltetrahydrofuran, 4-methyltetrahydropyran, dichloromethane, chloroform, γ-butyrolactone, N-methylpyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide, and acetonitrile are preferred. By using said 2-methyltetrahydrofuran, 4-methyltetrahydropyran, dichloromethane, chloroform, γ-butyrolactone, N-methylpyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide, and acetonitrile, a preferred reactivity may be ensured. 2-Methyltetrahydrofuran, γ-butyrolactone, and acetonitrile are particularly preferred. By using said 2-methyltetrahydrofuran, γ-butyrolactone, and acetonitrile, particularly preferred safety may be ensured.
The solvent may be used alone or in combination thereof, if necessary. The solvent may be a commercially available one.
When a solvent is incorporated in the halogenation reaction, the amount of the solvent used, per mol of the 6-hydroxy-4-methylheptyl alkoxymethyl ether compound (4), is preferably more than 0 up to 3,000 g, and more preferably more than 0 up to 800 g.
The solvent may occupy part of the reactor space, which reduces the space for the starting materials, and reduces productivity. Therefore, the reaction may be carried out without a solvent, or with the base as the solvent.
The reaction temperature of the halogenation reaction varies, depending on the halogenating agent used, and is preferably 5 to 180° C., and more preferably 20 to 120° C. By using said preferred reaction temperature and said more preferred reaction temperature, a preferred reactivity and a more preferred reactivity may be ensured.
The reaction time of the halogenation reaction varies, depending on the halogenating agent used and/or production scale, and is preferably 0.5 to 100 hours. By using said preferred reaction time, a preferred reactivity may be ensured.
Thus, the 6-halo-4-methylheptyl alkoxymethyl ether compound (1B:n=2 for compound (1)) may be prepared by three-carbon homologation from the haloalkyl alkoxymethyl ether compound, 4-halopentyl alkoxymethyl ether compound (1A:n=1 for compound (1)). Then, the 6-halo-4-methylheptyl alkoxymethyl ether compound (1B) thus prepared may be used to prepare compounds such as 3,5-dimethyldodecanoic acid, 4,6-dimethyl-1-nonanamine, 4,6-dimethyl-1-undecanol, and 13,15-dimethylheptacosane having 1,3-dimethyl skeletons as in the following reaction formula:
III. Process for Preparing the Aforesaid Haloalkyl Alkoxymethyl Ether Compound (1A:n=1 for Compound (1))
One target compound of the present invention, 4-halopentyl alkoxymethyl ether compound (1A), may be prepared according to, for example, the preparation process of the following chemical reaction formula:
Namely, the 4-halopentyl alkoxymethyl ether compound (1A) may be prepared by opening the tetrahydrofuran ring of 2-methyltetrahydrofuran with an acid halide, followed by elimination of the acyl group, and then alkoxymethylation of the hydroxy group.
The 4-halopentyl acylate compound (13) is represented by the following general formula (13):
In the general formula (13) above, R2 represents an alkyl group having 1 to 9 carbon atoms or a phenyl group, and X1 is as defined for the general formula (1A).
Examples of the alkyl group R2 include a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group, a hexyl group, a heptyl group, an octyl group, a nonyl group, and a tert-butyl group.
Examples of the halogen atom X1 include a chlorine atom, a bromine atom, and an iodine atom. A chlorine atom and a bromine atom are preferred. By using said chlorine atom and bromine atom, a preferred reactivity may be ensured. A chlorine atom is particularly preferred. By using said chlorine atom, a particularly preferred reactivity may be ensured.
Specific examples of the 4-halopentyl acylate compound (13) include 4-chloropentyl acetate, 4-bromopentyl acetate, 4-iodopentyl acetate, 4-chloropentyl propionate, 4-bromopentyl propionate, 4-iodopentyl propionate, 4-chloropentyl butyrate, 4-bromopentyl butyrate, 4-iodopentyl butyrate, 4-chloropentyl valerate, 4-bromopentyl valerate, 4-iodopentyl valerate, 4-chloropentyl pivaloate, 4-bromopentyl pivaloate, 4-iodopentyl pivaloate, 4-chloropentyl benzoate, 4-bromopentyl benzoate, and 4-iodopentyl benzoate.
The 4-halopentyl acylate compound (13) may be prepared using 2-methyltetrahydrofuran and the acid halide (12), as shown in the following chemical reaction formula:
The preparation process includes a step of opening the tetrahydrofuran ring of 2-methyltetrahydrofuran with the acid halide (12).
The acid halide (12) will be described in detail below.
The acid halide (12) is represented by the following general formula (12):
In the general formula (12), R2 and X1 are as defined for the general formula (13).
Specific examples of the acid halide (12) include acetyl halide compounds such as acetyl chloride, acetyl bromide, and acetyl iodide; propionyl halide compounds such as propionyl chloride, propionyl bromide, and propionyl iodide; butyryl halide compounds such as butyryl chloride, butyryl bromide, and butyryl iodide; valeryl halide compounds such as valeryl chloride, valeryl bromide, and valeryl iodide; pivaloyl halide compounds such as pivaloyl chloride, pivaloyl bromide, and pivaloyl iodide; and benzoyl halide compounds such as benzoyl chloride, benzoyl bromide, and benzoyl iodide.
The amount of the acid halide (12) used, per mol of 2-methyltetrahydrofuran, is preferably 0.7 to 1.5 mol, and more preferably 0.8 to 1.1 mol. By using said preferred amount and said more preferred amount, a preferred completion of the reaction and a more preferred completion of the reaction may be ensured.
The ring-opening reaction may be carried out in the presence of a catalyst, if necessary. Examples of the catalyst include zinc halide compounds such as zinc chloride, zinc bromide, and zinc iodide; titanium compounds such as titanium tetrachloride, titanium tetrabromide, titanium (IV) methoxide, titanium (IV) ethoxide, titanium (IV) isopropoxide, and titanium (IV) oxide; and zirconium compounds such as zirconium oxide. Zinc halide compounds are preferred. By using said zinc halide compounds, a preferred reactivity may be ensured.
The catalyst may be used alone or in combination thereof, if necessary. The catalyst may be a commercially available one.
The amount of the catalyst used, per mol of 2-methyltetrahydrofuran, is preferably 0.0001 to 0.3 mol, and more preferably 0.001 to 0.1 mol. By using said preferred amount and said more preferred amount, a preferred completion of the reaction and a more preferred completion of the reaction may be ensured.
A solvent may be incorporated in the ring-opening reaction, if necessary.
Examples of the solvent include those that do not affect the reaction such as, for example, hydrocarbon solvents such as hexane, heptane, benzene, toluene, xylene, and cumene. In view of easy preparation, 2-methyltetrahydrofuran may be used as both a solvent and a substrate without using another solvent.
The solvent may be used alone or in combination thereof, if necessary. The solvent may be a commercially available one.
When the solvent is used, the amount of the solvent used, per mol of 2-methyltetrahydrofuran, is preferably more than 0 up to 3,000 g, and more preferably more than 0 up to 500 g. By using said preferred amount and said more preferred amount, a preferred reactivity and a more preferred reactivity may be ensured.
The reaction temperature varies, depending on the production scale, and is preferably-15 to 85° C., and more preferably-10 to 45° C. By using said preferred reaction temperature and said more preferred reaction temperature, a preferred reactivity and a more preferred reactivity may be ensured.
The reaction time varies, depending on the solvent used and/or production scale, and is preferably 0.5 to 100 hours. By using said preferred reaction time, a preferred reactivity may be ensured.
The 4-halo-1-pentanol compound (15) is represented by the following general formula (15):
In the general formula (15) above, X1 is as defined for the general formula (12).
Specific examples of the 4-halo-1-pentanol compound (15) include 4-chloro-1-pentanol, 4-bromo-1-pentanol, and 4-iodo-1-pentanol.
The 4-halo-1-pentanol compound (15) may be prepared by deacylating the acyl group of the aforesaid 4-halopentyl acylate compound (13) with the organometallic reagent R3M3 (14).
In the general formula (14) above, R3 represents an alkyl group having 1 to 14 carbon atoms, and preferably 1 to 8 carbon atoms, or an ethynyl group.
Examples of the alkyl group R3 include a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group, a hexyl group, a heptyl group, an octyl group, a nonyl group, a decyl group, an undecyl group, a dodecyl group, a tridecyl group, and a tetradecyl group.
In the general formula (14) above, M3 represents Li, Na, K, Ag, MgZ4, or CaZ4, and Z4 represents a halogen atom or R3. Examples of the halogen atom Z4 include a chlorine atom, a bromine atom, and an iodine atom.
Specific examples of the organometallic reagent R3M3 (14) include Grignard reagents such as alkyllithiums such as methyllithium, ethyllithium, propyllithium, n-butyllithium, sec-butyllithium, tert-butyllithium, pentyllithium, hexyllithium, heptyllithium, octyllithium, nonyllithium, and decyllithium; methylmagnesium halide compounds such as methylmagnesium chloride, methylmagnesium bromide, and methylmagnesium iodide; ethylmagnesium halide compounds such as ethylmagnesium chloride, ethylmagnesium bromide, and ethylmagnesium iodide; propylmagnesium halide compounds such as propylmagnesium chloride, propylmagnesium bromide, and propylmagnesium iodide; butylmagnesium halide compounds such as butylmagnesium chloride, butylmagnesium bromide, and butylmagnesium iodide; pentylmagnesium halide compounds such as pentylmagnesium chloride, pentylmagnesium bromide, and pentylmagnesium iodide; hexylmagnesium halide compounds such as hexylmagnesium chloride, hexylmagnesium bromide, and hexylmagnesium iodide; heptylmagnesium halide compounds such as heptylmagnesium chloride, heptylmagnesium bromide, and heptylmagnesium iodide; octylmagnesium halide compounds such as octylmagnesium chloride, octylmagnesium bromide, and octylmagnesium iodide; nonylmagnesium halide compounds such as nonylmagnesium chloride, nonylmagnesium bromide, and nonylmagnesium iodide; decylmagnesium halide compounds such as decylmagnesium chloride, decylmagnesium bromide, and decylmagnesium iodide; and metal acetylides such as lithium acetylide, sodium acetylide, potassium acetylide, calcium acetylide, and silver acetylide. Grignard reagents are preferred. By using said Grignard reagents, a preferred reactivity may be ensured.
The amount of the organometallic reagent R3M3 (14) used, per mol of the 4-halopentyl acylate compound (13), is preferably 1.5 to 5.0 mol, and more preferably 2.0 to 3.5 mol. By using said preferred amount and said more preferred amount, a preferred completion of the reaction and a more preferred completion of the reaction may be ensured.
A solvent may be incorporated in the deacylation, if necessary.
Examples of the solvent include general solvents such as, for example, ether solvents such as tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), diethyl ether, dibutyl ether, 4-methyltetrahydropyran (MTHP), cyclopentylmethylether, and 1,4-dioxane; hydrocarbon solvents such as hexane, heptane, benzene, toluene, xylene, and cumene; and polar solvents such as N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), dimethyl sulfoxide (DMSO), γ-butyrolactone (GBL), acetonitrile, N,N′-dimethylpropylene urea (DMPU), hexamethylphosphoric triamide (HMPA), dichloromethane, and chloroform. Hydrocarbon solvents such as toluene and xylene; ether solvents such as tetrahydrofuran, 2-methyltetrahydrofuran, and 4-methyltetrahydropyran; and acetonitrile are preferred. By using said hydrocarbon solvents such as toluene and xylene; ether solvents such as tetrahydrofuran, 2-methyltetrahydrofuran, and 4-methyltetrahydropyran; and acetonitrile, a preferred reactivity may be ensured. Tetrahydrofuran, 2-methyltetrahydrofuran, toluene, and xylene are more preferred. By using said tetrahydrofuran, 2-methyltetrahydrofuran, toluene, and xylene, a more preferred reactivity may be ensured.
The solvent may be used alone or in combination thereof, if necessary. The solvent may be a commercially available one.
When the solvent is incorporated in the deacylation, the amount of the solvent used, per mol of the 4-halopentyl acylate compound (13), is preferably more than 0 up to 5,000 g, and more preferably more than 0 up to 3,000 g. By using said preferred amount and said more preferred amount, a preferred reactivity and a more preferred reactivity may be ensured.
The reaction temperature of the deacylation varies, depending on the production scale, and is preferably-15 to 90° C., and more preferably 10 to 50° C. By using said preferred reaction temperature and said more preferred reaction temperature, a preferred reactivity and a more preferred reactivity may be ensured.
The reaction time of the deacylation varies, depending on the solvent used and/or production scale, and is preferably 0.5 to 100 hours. By using said preferred reaction time, a preferred reactivity may be ensured.
(iii) 4-Halopentyl Alkoxymethyl Ether Compound (1A) and Process for Preparing 4-Halopentyl Alkoxymethyl Ether Compound (1A)
The 4-halopentyl alkoxymethyl ether compound (1A) may be prepared from the aforesaid 4-halo-1-pentanol compound (15).
The preparation process includes a step of alkoxymethylating the 4-halo-1-pentanol compound (15) with the halomethyl alkyl ether compound (16).
The halomethyl alkyl ether compound (16) will be described in detail below.
The halomethyl alkyl ether compound (16) is represented by the following general formula (16):
In the general formula (16) above, X5 represents a halogen atom. Examples of the halogen atom X5 include a chlorine atom, a bromine atom, and an iodine atom. A chlorine atom and a bromine atom are preferred. By using said chlorine atom and bromine atom, a preferred reactivity may be ensured. A chlorine atom is particularly preferred. By using said chlorine atom, a particularly preferred reactivity may be ensured.
In the general formula (16) above, R1 is as defined for the general formula (1A) above.
Specific examples of the halomethyl alkyl ether compound (16) include the following compounds:
Chloromethyl methyl ether, chloromethyl ethyl ether, chloromethyl propyl ether, chloromethyl butyl ether, and chloromethyl benzyl ether are preferred. By using said chloromethyl methyl ether, chloromethyl ethyl ether, chloromethyl propyl ether, chloromethyl butyl ether, and chloromethyl benzyl ether, a preferred availability may be ensured. Chloromethyl methyl ether and chloromethyl ethyl ether are more preferred. By using said chloromethyl methyl ether and chloromethyl ethyl ether, a more preferred availability may be ensured.
The halomethyl alkyl ether compound (16) may be a commercially available one, or may be synthesized in house (see, for example, Example 3 below).
The amount of the halomethyl alkyl ether compound (16) used, per mol of the 4-halo-1-pentanol compound (15), is preferably 1.0 to 3.0 mol, and more preferably 1.0 to 1.8 mol. By using said preferred amount and said more preferred amount, a preferred completion of the reaction and a more preferred completion of the reaction may be ensured.
A base may be incorporated in the alkoxymethylation reaction, if necessary.
Examples of the base include amines such as triethylamine, N,N-diisopropylethylamine, piperidine, pyrrolidine, pyridine, lutidine, 4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline, N,N-dipropylaniline, N,N-dibutylaniline, and 1,8-diazabicyclo [5.4.0]-7-undecene (DBU).
The base may be used alone or in combination thereof, if necessary. The base may be a commercially available one.
The amount of the base used, per mol of the 4-halo-1-pentanol compound (15), is preferably 0.1 to 4.0 mol, and more preferably 1.0 to 2.5 mol. By using said preferred amount and said more preferred amount, a preferred yield and economy and a more preferred yield and economy may be ensured.
A solvent may be incorporated in the alkoxymethylation, if necessary.
Examples of the solvent include general solvents such as, for example, ether solvents such as tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), diethyl ether, dibutyl ether, 4-methyltetrahydropyran (MTHP), cyclopentylmethylether, and 1,4-dioxane; hydrocarbon solvents such as hexane, heptane, benzene, toluene, xylene, and cumene; polar solvents such as N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), dimethyl sulfoxide (DMSO), γ-butyrolactone (GBL), acetonitrile, N,N′-dimethylpropylene urea (DMPU), hexamethylphosphoric triamide (HMPA), dichloromethane, and chloroform; and ester solvents such as methyl acetate, ethyl acetate, n-propyl acetate, and n-butyl acetate. Hydrocarbon solvents such as toluene and xylene; and ester solvents such as methyl acetate and ethyl acetate are preferred. By using said hydrocarbon solvents such as toluene and xylene; and ester solvents such as methyl acetate and ethyl acetate, a preferred reactivity may be ensured. The aforesaid alkoxymethylation may be carried out without a solvent to avoid reduced ease of preparation.
The solvent may be used alone or in combination thereof, if necessary. The solvent may be a commercially available one.
When a solvent is incorporated in the alkoxymethylation, the amount of the solvent used, per mol of the 4-halo-1-pentanol compound (15), is preferably more than 0 up to 1,500 g.
The reaction temperature of the alkoxymethylation varies, depending on the production scale, and is preferably-15 to 60° C., and more preferably 10 to 40° C. By using said preferred reaction temperature and said more preferred reaction temperature, a preferred reactivity and a more preferred reactivity may be ensured.
The reaction time of the alkoxymethylation varies, depending on the solvent used and/or production scale, and is preferably 0.5 to 100 hours. By using said preferred reaction time, a preferred reactivity may be ensured.
One target compound of the present invention, 13,15-dimethylheptacosane of the following formula (11), is prepared from the nucleophilic reagent, 6-alkoxymethoxy-1,3-dimethylhexyl, of the following general formula (2B) according to the preparation process of the following chemical reaction formula:
Namely, 13,15-dimethylheptacosane (11) may be prepared by subjecting the nucleophilic reagent, 6-alkoxymethoxy-1,3-dimethylhexyl (2B), to a coupling reaction with the 1-halododecane compound (5) to prepare the 4,6-dimethyloctadecyl alkoxymethyl ether compound (6), and then subjecting the 4,6-dimethyloctadecyl alkoxymethyl ether compound (6) to a dealkoxymethylation reaction to form 4,6-dimethyloctadecanol (7). The 4,6-dimethyloctadecanol (7) is then subjected to a halogenation reaction to form the 1-halo-4,6-dimethyloctadecane compound (8). The 1-halo-4,6-dimethyloctadecane compound (8) is then converted into the nucleophilic reagent, 4,6-dimethyloctadecyl (9), followed by subjecting the nucleophilic reagent, 4,6-dimethyloctadecyl (9), to a coupling reaction with the 1-halononane compound (10) to prepare 13,15-dimethylheptacosane (11).
The 4,6-dimethyloctadecyl alkoxymethyl ether compound (6) is represented by the following general formula (6):
In the general formula (6) above, R1 is as defined for the general formula (1A) above.
Specific examples of the 4,6-dimethyloctadecyl alkoxymethyl ether compound (6) include 4,6-dimethyloctadecyl methoxymethyl ether, 4,6-dimethyloctadecyl ethoxymethyl ether, 4,6-dimethyloctadecyl propyloxymethyl ether, 4,6-dimethyloctadecyl butyloxymethyl ether, 4,6-dimethyloctadecyl pentyloxymethyl ether, 4,6-dimethyloctadecyl hexyloxymethyl ether, 4,6-dimethyloctadecyl heptyloxymethyl ether, 4,6-dimethyloctadecyl octyloxymethyl ether, 4,6-dimethyloctadecyl nonyloxymethyl ether, 4,6-dimethyloctadecyl decyloxymethyl ether, and 4,6-dimethyloctadecyl benzyloxymethyl ether.
The 4,6-dimethyloctadecyl alkoxymethyl ether compound (6) may be prepared from, for example, the nucleophilic reagent, 6-alkoxymethoxy-1,3-dimethylhexyl, of the following general formula (2B) and the 1-halododecane compound of the following general formula (5), as shown in the following chemical reaction formula:
The preparation process includes a step of subjecting the nucleophilic reagent, 6-alkoxymethoxy-1,3-dimethylhexyl (2B), to a coupling reaction with the 1-halododecane compound (5).
The aforesaid nucleophilic reagent, 6-alkoxymethoxy-1,3-dimethylhexyl (2B), will be described in detail below.
The nucleophilic reagent, 6-alkoxymethoxy-1,3-dimethylhexyl (2B), is represented by the following general formula (2B):
In the general formula (2B) above, M2B represents Li, MgZ2B, CuZ2B, or CuLiZ2B, and Z2B represents a halogen atom or a 6-alkoxymethoxy-1,3-dimethylhexyl group. Examples of the halogen atom Z2B include a chlorine atom, a bromine atom, and an iodine atom. A chlorine atom and a bromine atom are preferred. By using said chlorine atom and bromine atom, a preferred reactivity may be ensured. A chlorine atom is particularly preferred. By using said chlorine atom, a particularly preferred reactivity may be ensured.
When M2B is MgZ2B in the general formula (2B) above, the nucleophilic reagent, 6-alkoxymethoxy-1,3-dimethylhexyl (2B: M2B=MgZ2B), is a Grignard reagent.
Specific examples of the nucleophilic reagent, 6-alkoxymethoxy-1,3-dimethylhexyl (2B), include the following:
The aforesaid 1-halododecane compound (5) will be described in detail below.
The 1-halododecane compound (5) is represented by the following general formula (5):
X2(CH2)11CH3 (5)
In the general formula (5) above, X2 represents a halogen atom. Examples of the halogen atom X2 include a chlorine atom, a bromine atom, and an iodine atom. A bromine atom and an iodine atom are preferred. By using said bromine atom and iodine atom, a preferred reactivity may be ensured. A bromine atom is particularly preferred. By using said bromine atom, a particularly preferred reactivity may be ensured.
Specific examples of the 1-halododecane compound (5) include 1-chlorododecane, 1-bromododecane, and 1-iodododecane. 1-Bromododecane and 1-iodododecane are preferred. By using said 1-bromododecane and 1-iodododecane, a preferred yield may be ensured.
The 1-halododecane compound (5) may be used alone or in combination thereof, if necessary. The 1-halododecane compound (5) may be a commercially available one, or may be synthesized in house.
The 1-halododecane compound (5) may be prepared by, for example, subjecting 1-dodecanol to a halogenation reaction.
The coupling reaction of the nucleophilic reagent, 6-alkoxymethoxy-1,3-dimethylhexyl (2B), with the 1-halododecane compound (5) will be described in detail below.
The amount of the nucleophilic reagent, 6-alkoxymethoxy-1,3-dimethylhexyl (2B), per mol of the 1-halododecane compound (5), used in the coupling reaction is preferably 0.8 to 1.4 mol. By using said preferred amount, preferred economy may be ensured.
A solvent may be incorporated in the coupling reaction, if necessary.
Examples of the solvent include general solvents such as, for example, ether solvents such as tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), diethyl ether, dibutyl ether, 4-methyltetrahydropyran (MTHP), cyclopentylmethylether, and 1,4-dioxane; hydrocarbon solvents such as hexane, heptane, benzene, toluene, xylene, and cumene; and polar solvents such as N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), dimethyl sulfoxide (DMSO), γ-butyrolactone (GBL), acetonitrile, N,N′-dimethylpropylene urea (DMPU), hexamethylphosphoric triamide (HMPA), dichloromethane, and chloroform.
Hydrocarbon solvents such as toluene and xylene; ether solvents such as tetrahydrofuran, 2-methyltetrahydrofuran, and 4-methyltetrahydropyran; and acetonitrile are preferred. By using said hydrocarbon solvents such as toluene and xylene; ether solvents such as tetrahydrofuran, 2-methyltetrahydrofuran, and 4-methyltetrahydropyran; and acetonitrile, a preferred reactivity may be ensured. Tetrahydrofuran, 2-methyltetrahydrofuran, toluene, and xylene are more preferred. By using said tetrahydrofuran, 2-methyltetrahydrofuran, toluene, and xylene, a more preferred reactivity may be ensured.
The solvent may be used alone or in combination thereof, if necessary. The solvent may be a commercially available one.
The amount of the solvent used, per mol of the 1-halododecane compound (5), is preferably 30 to 5,000 g, and more preferably 50 to 3,000 g. By using said preferred amount and said more preferred amount, a preferred reactivity and a more preferred reactivity may be ensured.
The coupling reaction may be carried out in the presence of a catalyst, if necessary. Examples of the catalyst include cuprous halides such as cuprous chloride, cuprous bromide, and cuprous iodide; and cupric halides such as cupric chloride, cupric bromide, and cupric iodide. Cuprous halides are preferred. By using said cuprous halides, a preferred reactivity may be ensured. Cuprous chloride is more preferred. By using said cuprous chloride, a more preferred reactivity may be ensured.
The catalyst may be used alone or in combination thereof, if necessary. The catalyst may be a commercially available one.
The amount of the catalyst used, per mol of the 1-halododecane compound (5), is preferably 0.0003 to 0.3 mol, and more preferably 0.001 to 0.1 mol. By using said preferred amount and said more preferred amount, a preferred reaction rate and/or post-treatment and a more preferred reaction rate and/or post-treatment may be ensured.
When the coupling reaction is carried out in the presence of a catalyst, a co-catalyst may be used, if necessary. Examples of the co-catalyst include phosphorus compounds such as trialkyl phosphite compounds having 3 to 9 carbon atoms such as triethyl phosphite; and triarylphosphine compounds having 18 to 21 carbon atoms such as triphenylphosphine. Trialkyl phosphite compounds are preferred. By using said trialkyl phosphite compounds, a preferred reactivity may be ensured.
The co-catalyst may be used alone or in combination thereof, if necessary. The co-catalyst may be a commercially available one.
The amount of the co-catalyst used, per mol of the 1-halododecane compound (5), is preferably 0.001 to 0.500 mol, and more preferably 0.005 to 0.200 mol. By using said preferred amount and said more preferred amount, a preferred reactivity and a more preferred reactivity may be ensured.
When the coupling reaction is carried out in the presence of a catalyst, a lithium halide may be added, if necessary.
Examples of the lithium halide include lithium chloride, lithium bromide, and lithium iodide. Lithium chloride is preferred. By using said lithium chloride, a preferred reactivity may be ensured.
The lithium halide may be used alone or in combination thereof, if necessary. The lithium halide may be a commercially available one.
The amount of the lithium halide used in the coupling reaction, per mol of the 1-halododecane compound (5), is preferably 0.005 to 0.250 mol. By using said preferred amount, a preferred reactivity may be ensured.
The reaction temperature of the coupling reaction varies, depending on the nucleophilic reagent, 6-alkoxymethoxy-1,3-dimethylhexyl (2B), used, and is preferably-78 to 70° C., more preferably-20 to 50° C., and most preferably 5 to 35° C. By using said preferred reaction temperature, said more preferred reaction temperature, and said most preferred reaction temperature, a preferred reactivity, a more preferred reactivity, and a most preferred reactivity may be ensured.
The reaction time of the coupling reaction varies, depending on the solvent used and/or production scale, and is preferably 0.5 to 100 hours. By using said preferred reaction time, a preferred reactivity may be ensured.
A process for preparing 4,6-dimethyloctadecanol (7) will be explained in detail below.
4,6-Dimethyloctadecanol (7) may be prepared, for example, from the aforesaid 4,6-dimethyloctadecyl alkoxymethyl ether compound (6), as shown in the following chemical reaction formula:
The preparation process includes a step of subjecting the 4,6-dimethyloctadecyl alkoxymethyl ether compound (6) to a dealkoxymethylation reaction.
Optimal conditions of the dealkoxymethylation reaction vary, depending on R1. When R1 is a phenyl group, the dealkoxymethylation can be carried out, for example, under Birch reduction conditions in which sodium is used in liquid ammonia. When R1 is a methyl group, the dealkoxymethylation may be carried out using an acid, water, or an alcohol compound (17).
Examples of acid include inorganic acids such as hydrochloric acid and hydrobromic acid; sulfonic acids such as p-toluenesulfonic acid and benzenesulfonic acid; organic acids such as trifluoroacetic acid, acetic acid, formic acid, and oxalic acid; and Lewis acids such as iodotrimethylsilane and titanium tetrachloride. P-toluenesulfonic acid, benzenesulfonic acid, hydrochloric acid, and hydrobromic acid are preferred. By using said p-toluenesulfonic acid, benzenesulfonic acid, hydrochloric acid, and hydrobromic acid, a preferred suppression of side reactions may be ensured. P-toluenesulfonic acid, hydrochloric acid, and hydrobromic acid are particularly preferred. By using said p-toluenesulfonic acid, hydrochloric acid, and hydrobromic acid, a particularly preferred suppression of side reactions may be ensured.
The acid may be used alone or in combination thereof, if necessary. The acid may be a commercially available one.
The amount of the acid used, per mol of the 4,6-dimethyloctadecyl alkoxymethyl ether compound (6), is preferably 0.0001 to 10.0 mol, and more preferably 0.001 to 1.0 mol.
The alcohol compound (17) is represented by the following general formula:
R4OH (17)
In the general formula (17) above, R4 represents a monovalent hydrocarbon group having 1 to 15 carbon atoms, and preferably 1 to 6 carbon atoms. A monovalent hydrocarbon group having 1 to 6 carbon atoms is preferred. By using said monovalent hydrocarbon group having 1 to 6 carbon atoms, a preferred price or availability may be ensured. Examples of the monovalent hydrocarbon group include linear saturated hydrocarbon groups such as a methyl group, an ethyl group, an n-propyl group, an n-butyl group, an n-pentyl group, an n-hexyl group, an n-heptyl group, an n-octyl group, an n-nonyl group, an n-decyl group, an n-undecyl group, and an n-dodecyl group; branched saturated hydrocarbon groups such as an isopropyl group, a sec-butyl group, and a 2-methylbutyl group; linear unsaturated hydrocarbon groups such as a 2-propenyl group; branched unsaturated hydrocarbon groups such as a 2-methyl-2-propenyl group; cyclic saturated hydrocarbon groups such as a cyclopropyl group; and isomers thereof. A part of the hydrogen atoms in the hydrocarbon groups may be substituted with a methyl group, an ethyl group, or a hydroxy group.
The monovalent hydrocarbon group is preferably a methyl group, an ethyl group, an n-propyl group, and an n-butyl group. By using said methyl group, ethyl group, n-propyl group, and n-butyl group, a preferred ease of handling of the alcohol compound (17) (encompassing, for example, the price and ease of removability due to the low boiling point) and/or quantity of starting materials due to the alcohol compound use may be ensured.
Examples of the alcohol compound (17) include linear alcohols such as methanol, ethanol, n-propanol, n-butanol, n-pentanol, n-hexanol, n-heptanol, n-octanol, n-nonanol, n-decanol, n-undecanol, n-dodecanol, n-tridecanol, n-tetradecanol, and n-pentadecanol; branched alcohols such as isopropanol and 2-butanol; and diols such as ethylene glycol, propylene glycol, 2-methyl-1,3-propanediol, 2,2-dimethyl-1,3-propanediol, 1,2-dimethyl-1,3-propanediol, 1,3-dimethyl-1,3-propanediol, and 2-methyl-1,4-butanediol. Methanol and ethanol are preferred. By using said methanol and ethanol, a preferred reactivity may be ensured. Methanol is particularly preferred. By using said methanol, a particularly preferred reactivity may be ensured.
The alcohol compound (17) may be used alone or in combination thereof, if necessary. The alcohol compound (17) may be a commercially available one.
The amount of the alcohol compound (17) used, per mol of the 4,6-dimethyloctadecyl alkoxymethyl ether compound (6), is preferably 1 to 1,000 mol, and more preferably 1 to 100 mol. By using said preferred amount and said more preferred amount, a preferred reactivity and a more preferred reactivity may be ensured.
When water is used, the amount of the water used, per mol of the 4,6-dimethyloctadecyl alkoxymethyl ether compound (6), is preferably more than 0 up to 1,000 mol, and more preferably more than 0 up to 100 mol. By using said preferred amount and said more preferred amount, a preferred reactivity and a more preferred reactivity may be ensured.
A solvent other than the alcohol compound (17) may be incorporated in the dealkoxymethylation reaction, if necessary.
Examples of the solvent include general solvents such as, for example, ether solvents such as tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), diethyl ether, dibutyl ether, 4-methyltetrahydropyran (MTHP), cyclopentylmethylether, and 1,4-dioxane; hydrocarbon solvents such as hexane, heptane, benzene, toluene, xylene, and cumene; polar solvents such as N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), dimethyl sulfoxide (DMSO), γ-butyrolactone (GBL), acetonitrile, N,N′-dimethylpropylene urea (DMPU), hexamethylphosphoric triamide (HMPA), dichloromethane, and chloroform; and ester solvents such as methyl acetate, ethyl acetate, n-propyl acetate, and n-butyl acetate.
The solvent may be used alone or in combination thereof, if necessary. The solvent may be a commercially available one.
When a solvent is incorporated in the dealkoxymethylation reaction, the amount of the solvent used, per mol of the 4,6-dimethyloctadecyl alkoxymethyl ether compound (6), is preferably more than 0 up to 2,000 g, and more preferably more than 0 up to 500 g.
The solvent may occupy part of the reactor space, which reduces the space for the starting materials, and reduces productivity. Therefore, the dealkoxymethylation may be carried out without a solvent.
The reaction temperature of the dealkoxymethylation varies, depending on the 4,6-dimethyloctadecyl alkoxymethyl ether compound (6) used, and is preferably-5 to 180° C., and more preferably 10 to 130° C. By using said preferred reaction temperature and said more preferred reaction temperature, a preferred reactivity and a more preferred reactivity may be ensured.
The reaction time of the dealkoxymethylation varies, depending on the 4,6-dimethyloctadecyl alkoxymethyl ether compound (6) used or production scale, and is preferably 0.5 to 100 hours. By using said preferred reaction time, a preferred reactivity may be ensured.
In the dealkoxymethylation, by-produced alkoxymethoxymethane may be distilled off from the reaction system, if necessary, whereby the equilibrium is shifted to the product side to reduce the reaction time.
(iii) 1-Halo-4,6-Dimethyloctadecane Compound (8) and Process for Preparing 1-Halo-4,6-Dimethyloctadecane Compound (8)
The 1-halo-4,6-dimethyloctadecane compound (8) is represented by the following general formula (8):
In the general formula (8) above, X3 represents a halogen atom. Examples of the halogen atom X3 include a chlorine atom, a bromine atom, and an iodine atom. A chlorine atom and a bromine atom are preferred. By using said chlorine atom and bromine atom, a preferred reactivity may be ensured. A chlorine atom is particularly preferred. By using said chlorine atom, a particularly preferred reactivity may be ensured.
The 1-halo-4,6-dimethyloctadecane compound (8) may be prepared, for example, from 4,6-dimethyloctadecanol of the following general formula (7), as shown in the following chemical reaction formula:
The preparation process includes a step of subjecting 4,6-dimethyloctadecanol (7) to a halogenation reaction.
The halogenation reaction may be carried out by, for example, a process of tosylating the hydroxy group with a p-toluenesulfonyl halide compound and then halogenating with the metal salt, lithium halide compound; or a process of directly halogenating the hydroxy group with a halogenating agent.
Examples of the halogenating agent include halogens such as chlorine, bromine, and iodine; hydrogen halide compounds such as hydrogen chloride, hydrogen bromide, and hydrogen iodide; methanesulfonyl halide compounds such as methanesulfonyl chloride, methanesulfonyl bromide, and methanesulfonyl iodide; benzenesulfonyl halide compounds such as benzenesulfonyl chloride, benzenesulfonyl bromide, and benzenesulfonyl iodide; p-toluenesulfonyl halide compounds such as p-toluenesulfonyl chloride, p-toluenesulfonyl bromide, and p-toluenesulfonyl iodide; thionyl halide compounds such as thionyl chloride, thionyl bromide, and thionyl iodide; phosphorus halide compounds such as phosphorus trichloride, phosphorus pentachloride, and phosphorus tribromide; carbon tetrahalide compounds such as carbon tetrachloride, carbon tetrabromide, and carbon tetraiodide; alkylsilyl halide compounds such as trimethylsilyl chloride, trimethylsilyl bromide, trimethylsilyl iodide, triethylsilyl chloride, triethylsilyl bromide, triethylsilyl iodide, triisopropylsilyl chloride, triisopropylsilyl bromide, triisopropylsilyl iodide, tert-butyldimethylsilyl chloride, tert-butyldimethylsilyl bromide, and tert-butyldimethylsilyl iodide; oxalyl halide compounds such as oxalyl chloride, oxalyl bromide, and oxalyl iodide; and N-halosuccinimide compounds such as N-chlorosuccinimide, N-bromosuccinimide, and N-iodosuccinimide. Methanesulfonyl halide compounds, benzenesulfonyl halide compounds, p-toluenesulfonyl halide compounds, and thionyl halide compounds are preferred. By using said methanesulfonyl halide compounds, benzenesulfonyl halide compounds, p-toluenesulfonyl halide compounds, and thionyl halide compounds, a preferred suppression of side reactions may be ensured. Methanesulfonyl halide compounds, benzenesulfonyl halide compounds, and thionyl halide compounds are particularly preferred. By using said methanesulfonyl halide compounds, benzenesulfonyl halide compounds, and thionyl halide compounds, a particularly preferred suppression of side reactions may be ensured.
The halogenating agent may be used alone or in combination thereof, if necessary. The halogenating agent may be a commercially available one.
The amount of the halogenating agent used, per mol of 4,6-dimethyloctadecanol (7), is preferably 0.8 to 5.0 mol, and more preferably 1.0 to 2.5 mol. By using said preferred amount and said more preferred amount, a preferred reactivity and a more preferred reactivity may be ensured.
A base may be incorporated in the halogenation reaction, if necessary.
Examples of the base include hydroxides such as sodium hydroxide, potassium hydroxide, calcium hydroxide, and magnesium hydroxide; carbonates such as sodium carbonate, potassium carbonate, calcium carbonate, and magnesium carbonate; and amines such as triethylamine, N,N-diisopropylethylamine, piperidine, pyrrolidine, pyridine, lutidine, 4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline, and 1,8-diazabicyclo [5.4.0]-7-undecene (DBU).
When a methanesulfonyl halide compound, a benzenesulfonyl halide compound, a p-toluenesulfonyl halide compound, or the like is used as the halogenating agent, the base is preferably amines, and more preferably pyridines such as pyridine, lutidine, and 4-dimethylaminopyridine.
When a thionyl halide compound is used as the halogenating agent, the base is preferably amines, and more preferably trialkylamines such as triethylamine.
The base may be used alone or in combination thereof, if necessary. The base may be a commercially available one.
When the base is used, the amount of the base used, per mol of 4,6-dimethyloctadecanol (7), is preferably more than 0 up to 8.0 mol, and more preferably more than 0 up to 3.0 mol. By using said preferred amount and said more preferred amount, a preferred yield and/or economy and a more preferred yield and/or economy may be ensured.
A metal salt may be incorporated in the halogenation reaction, if necessary.
Examples of the metal salt include lithium salts such as lithium chloride, lithium bromide, and lithium iodide; sodium salts such as sodium chloride, sodium bromide, and sodium iodide; potassium salts such as potassium chloride, potassium bromide, and potassium iodide; calcium salts such as calcium chloride, calcium bromide, and calcium iodide; and magnesium salts such as magnesium chloride, magnesium bromide, and magnesium iodide.
When the halogenation with the metal salt, lithium halide compound, is carried out after the tosylation, the reaction is carried out with, for example, lithium salts such as lithium chloride, lithium bromide, and lithium iodide.
The metal salt may be used alone or in combination thereof, if necessary. The metal salt may be a commercially available one.
When the metal salt is used, the amount of the metal salt used, per mol of 4,6-dimethyloctadecanol (7), is preferably more than 0 up to 30.0 mol, and more preferably more than 0 up to 5.0 mol. By using said preferred amount and said more preferred amount, a preferred reactivity and a more preferred reactivity may be ensured.
Although the metal salt increases the concentration of halide ions in the reaction system to thereby enhance the reactivity, it is preferred not to incorporate the metal salt in the reaction. By not incorporating the metal salt, preferred economy and/or environmental protection may be ensured.
A solvent may be incorporated in the halogenation reaction, if necessary.
Examples of the solvent include general solvents such as, for example, ether solvents such as tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), diethyl ether, dibutyl ether, 4-methyltetrahydropyran (MTHP), cyclopentylmethylether, and 1,4-dioxane; hydrocarbon solvents such as hexane, heptane, benzene, toluene, xylene, and cumene; polar solvents such as N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), dimethyl sulfoxide (DMSO), γ-butyrolactone (GBL), acetonitrile, acetone, N,N′-dimethylpropylene urea (DMPU), hexamethylphosphoric triamide (HMPA), dichloromethane, and chloroform; and ester solvents such as methyl acetate, ethyl acetate, n-propyl acetate, and n-butyl acetate. 2-Methyltetrahydrofuran, 4-methyltetrahydropyran, dichloromethane, chloroform, γ-butyrolactone, N-methylpyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide, and acetonitrile are preferred. By using said 2-methyltetrahydrofuran, 4-methyltetrahydropyran, dichloromethane, chloroform, γ-butyrolactone, N-methylpyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide, and acetonitrile, a preferred reactivity may be ensured. 2-Methyltetrahydrofuran, γ-butyrolactone, and acetonitrile are particularly preferred. By using said 2-methyltetrahydrofuran, γ-butyrolactone, and acetonitrile, a particularly preferred safety may be ensured.
The solvent may be used alone or in combination thereof, if necessary. The solvent may be a commercially available one.
When a solvent is incorporated in the halogenation reaction, the amount of the solvent used, per mol of 4,6-dimethyloctadecanol (7), is preferably more than 0 up to 3,000 g, and more preferably more than 0 up to 800 g.
The solvent may occupy part of the reactor space, which reduces the space for the starting materials, and reduces productivity. Therefore, the reaction may be carried out without a solvent, or with the base as the solvent.
The reaction temperature of the halogenation reaction varies, depending on the halogenating agent used, and is preferably 5 to 180° C., and more preferably 20 to 120° C. By using said preferred reaction temperature and said more preferred reaction temperature, a preferred reactivity and a more preferred reactivity may be ensured.
The reaction time of the halogenation reaction varies, depending on the halogenating agent used and/or production scale, and is preferably 0.5 to 100 hours. By using said preferred reaction time, a preferred reactivity may be ensured.
The nucleophilic reagent, 4,6-dimethyloctadecyl (9), is represented by the following general formula (9):
In the general formula (9) above, M2 represents Li, MgZ2, CuZ2, or CuLiZ2, and Z2 represents a halogen atom or a 4,6-dimethyloctadecyl group. Examples of the halogen atom Z2 include a chlorine atom, a bromine atom, and an iodine atom.
Specific examples of the nucleophilic reagent, 4,6-dimethyloctadecyl (9), include 4,6-dimethyloctadecyllithium (when M2=Li); 4,6-dimethyloctadecylmagnesium halide compounds (when M2=MgZ2) such as 4,6-dimethyloctadecylmagnesium chloride, 4,6-dimethyloctadecylmagnesium bromide, and 4,6-dimethyloctadecylmagnesium iodide (i.e., Grignard reagents); bis [4,6-dimethyloctadecyl]cuprate (when M2=CuZ2); and lithium bis [4,6-dimethyloctadecyl]cuprate (when M2=CuLiZ2) (i.e., Gilman reagents).
The nucleophilic reagent, 4,6-dimethyloctadecyl (9), may be prepared in a conventional process or a process described below.
A process for preparing the nucleophilic reagent, 4,6-dimethyloctadecyl (9), in which M2 is MgZ2, that is, a 4,6-dimethyloctadecylmagnesium halide reagent (9: M2=MgZ2) (i.e., a Grignard reagent), will be described in detail below as an example.
The 4,6-dimethyloctadecylmagnesium halide reagent (9: M2=MgZ2, Z2=halogen atom) may be prepared by, for example, reacting the aforesaid 1-halo-4,6-dimethyloctadecane compound (8) with magnesium in a solvent, as shown in the following chemical reaction formula:
The amount of magnesium used, per mol of the 1-halo-4,6-dimethyloctadecane compound (8), is preferably 1.0 to 2.0 gram atoms. By using said preferred amount, a preferred completion of the reaction may be ensured.
Examples of the solvent include general solvents such as, for example, ether solvents such as tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), diethyl ether, dibutyl ether, 4-methyltetrahydropyran (MTHP), cyclopentylmethylether, and 1,4-dioxane; and hydrocarbon solvents such as hexane, heptane, benzene, toluene, xylene, and cumene. Hydrocarbon solvents such as toluene and xylene; and ether solvents such as tetrahydrofuran, 2-methyltetrahydrofuran, and 4-methyltetrahydropyran are preferred. By using said hydrocarbon solvents such as toluene and xylene; and ether solvents such as tetrahydrofuran, 2-methyltetrahydrofuran, and 4-methyltetrahydropyran, a preferred reaction rate of forming of the aforesaid Grignard reagent may be ensured. Tetrahydrofuran, 2-methyltetrahydrofuran, and 4-methyltetrahydropyran are more preferred. By using said tetrahydrofuran, 2-methyltetrahydrofuran, and 4-methyltetrahydropyran, a more preferred reaction rate of forming of the aforesaid Grignard reagent may be ensured.
The solvent may be used alone or in combination thereof, if necessary. The solvent may be a commercially available one.
The amount of the solvent used, per mol of the 1-halo-4,6-dimethyloctadecane compound (8), is preferably 30 to 5,000 g, and more preferably 50 to 3,000 g. By using said preferred amount and said more preferred amount, a preferred reactivity and a more preferred reactivity may be ensured.
The reaction temperature varies, depending on the solvent used, and is preferably 30 to 120° C. By using said preferred reaction temperature, a preferred reactivity may be ensured.
The reaction time varies, depending on the solvent used and/or production scale, and is preferably 0.5 to 100 hours. By using said preferred reaction time, a preferred reactivity may be ensured.
13,15-Dimethylheptacosane (11) is represented by the following general formula (11):
13,15-Dimethylheptacosane (11) may be prepared from, for example, the aforesaid nucleophilic reagent, 4,6-dimethyloctadecyl (9), and the 1-halononane compound of the following general formula (10), as shown in the following chemical reaction formula:
The preparation process includes a step of subjecting the nucleophilic reagent, 4,6-dimethyloctadecyl (9), to a coupling reaction with the 1-halononane compound (10).
The aforesaid 1-halononane compound (10) will be described in detail below.
The 1-halononane compound (10) is represented by the following general formula (10):
X4(CH2)8CH3 (10)
In the general formula (10) above, X4 represents a halogen atom. Examples of the halogen atom X4 include a chlorine atom, a bromine atom, and an iodine atom. A bromine atom and an iodine atom are preferred. By using said bromine atom and iodine atom, a preferred reactivity may be ensured. A bromine atom is particularly preferred. By using said a bromine atom, a particularly preferred reactivity may be ensured.
Specific examples of the 1-halononane compound (10) include 1-chlorononane, 1-bromononane, and 1-iodononane. 1-Bromononane and 1-iodononane are preferred. By using said 1-bromononane and 1-iodononane, a preferred yield may be ensured.
The 1-halononane compound (10) may be used alone or in combination thereof, if necessary. The 1-halononane compound (10) may be a commercially available one, or may be synthesized in house.
The 1-halononane compound (10) may be prepared by, for example, subjecting nonanol to a halogenation reaction.
The coupling reaction of the nucleophilic reagent, 4,6-dimethyloctadecyl (9), with the 1-halononane compound (10) will be described in detail below.
The amount of the nucleophilic reagent, 4,6-dimethyloctadecyl (9), per mol of 1-halononane compound (10), used in the coupling reaction is preferably 0.8 to 1.4 mol. By using said preferred amount, preferred economy may be ensured.
A solvent may be incorporated in the coupling reaction, if necessary.
Examples of the solvent include general solvents such as, for example, ether solvents such as tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), diethyl ether, dibutyl ether, 4-methyltetrahydropyran (MTHP), cyclopentylmethylether, and 1,4-dioxane; hydrocarbon solvents such as hexane, heptane, benzene, toluene, xylene, and cumene; and polar solvents such as N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), dimethyl sulfoxide (DMSO), γ-butyrolactone (GBL), acetonitrile, N,N′-dimethylpropylene urea (DMPU), hexamethylphosphoric triamide (HMPA), dichloromethane, and chloroform. Hydrocarbon solvents such as toluene and xylene; ether solvents such as tetrahydrofuran, 2-methyltetrahydrofuran, and 4-methyltetrahydropyran; and acetonitrile are preferred. By using said hydrocarbon solvents such as toluene and xylene; ether solvents such as tetrahydrofuran, 2-methyltetrahydrofuran, and 4-methyltetrahydropyran; and acetonitrile, a preferred reactivity may be ensured. Tetrahydrofuran, 2-methyltetrahydrofuran, toluene, and xylene are more preferred. By using said tetrahydrofuran, 2-methyltetrahydrofuran, toluene, and xylene, a more preferred reactivity may be ensured.
The solvent may be used alone or in combination thereof, if necessary. The solvent may be a commercially available one.
The amount of the solvent used, per mol of 1-halononane compound (10), is preferably 30 to 5,000 g, and more preferably 50 to 3,000 g. By using said preferred amount and said more preferred amount, a preferred reactivity and a more preferred reactivity may be ensured.
The coupling reaction may be carried out in the presence of a catalyst, if necessary. Examples of the catalyst include cuprous halides such as cuprous chloride, cuprous bromide, and cuprous iodide; and cupric halides such as cupric chloride, cupric bromide, and cupric iodide. Cuprous halides are preferred. By using said cuprous halides, a preferred reactivity may be ensured. Cuprous chloride is more preferred. By using said cuprous chloride, a more preferred reactivity may be ensured.
The catalyst may be used alone or in combination thereof, if necessary. The catalyst may be a commercially available one.
The amount of the catalyst used, per mol of 1-halononane compound (10), is preferably 0.0003 to 0.3 mol, and more preferably 0.001 to 0.1 mol. By using said preferred amount and said more preferred amount, a preferred reaction rate and/or post-treatment and a more preferred reaction rate and/or post-treatment may be ensured.
When the coupling reaction is carried out in the presence of a catalyst, a co-catalyst may be used, if necessary. Examples of the co-catalyst include phosphorus compounds such as trialkyl phosphite compounds having 3 to 9 carbon atoms such as triethyl phosphite; and triarylphosphine compounds having 18 to 21 carbon atoms such as triphenylphosphine. Trialkyl phosphite compounds are preferred. By using said trialkyl phosphite compounds, a preferred reactivity may be ensured.
The co-catalyst may be used alone or in combination thereof, if necessary. The co-catalyst may be a commercially available one.
The amount of the co-catalyst used, per mol of 1-halononane compound (10), is preferably 0.001 to 0.500 mol, and more preferably 0.005 to 0.200 mol. By using said preferred amount and said more preferred amount, a preferred reactivity and a more preferred reactivity may be ensured.
When the coupling reaction is carried out in the presence of a catalyst, a lithium halide may be added, if necessary.
Examples of the lithium halide include lithium chloride, lithium bromide, and lithium iodide. Lithium chloride is preferred. By using said lithium chloride, a preferred reactivity may be ensured.
The lithium halide may be used alone or in combination thereof, if necessary. The lithium halide may be a commercially available one.
The amount of lithium halide used in the coupling reaction, per mol of 1-halononane compound (10), is preferably 0.005 to 0.250 mol. By using said preferred amount, a preferred reactivity may be ensured.
The reaction temperature of the coupling reaction varies, depending on the nucleophilic reagent, 4,6-dimethyloctadecyl (9), used, and is preferably-78 to 70° C., more preferably-20 to 50° C., and most preferably 5 to 35° C. By using said preferred reaction temperature, said more preferred reaction temperature, and said most preferred reaction temperature, a preferred reactivity, a more preferred reactivity, and a most preferred reactivity may be ensured.
The reaction time of the coupling reaction varies, depending on the solvent used and/or production scale, and is preferably 0.5 to 100 hours. By using said preferred reaction time, a preferred reactivity may be ensured.
Thus, according to the present invention, the haloalkyl alkoxymethyl ether compound (1B) and the haloalkyl alkoxymethyl ether compound (1A), which are synthetic intermediates, can be easily and efficiently prepared. According to the present invention, the cuticular hydrocarbon of the Red imported fire ant (scientific name: Solenopsis invicta), 13,15-dimethylheptacosane (11), can be efficiently prepared with easy preparation and fewer steps, from the haloalkyl alkoxymethyl ether compound (1B) or from the haloalkyl alkoxymethyl ether compound (1A) via the haloalkyl alkoxymethyl ether compound (1B).
The present invention will be described with reference to the following Examples. It should be noted that the present invention is not limited to or by the Examples.
The term “purity” as used herein means an area percentage in gas chromatography (GC), unless otherwise specified. The term “product ratio” means a ratio of area percentages in GC. The term “yield” is calculated from the area percentages determined by GC.
In the Examples, monitoring of the reactions and calculation of the yields were carried out in the following GC conditions.
GC conditions: GC: Capillary gas chromatograph GC-2014 (Shimadzu Corporation); column: DB-5, 0.25 μm×0.25 mmϕ×30 m; carrier gas: He (1.55 mL/min), detector: FID; column temperature: 150° C., elevated in a rate of 5° C./min, and up to 230° C.; column: DB-WAX, 0.25 μm×0.25 mmϕ×30 m; carrier gas: He (1.55 mL/min), detector: FID; column temperature: 150° C., elevated in a rate of 5° C./min, and up to 230° C.
The yield was calculated according to the following equation in consideration of purities (% GC) of a starting material and a product.
Yield (%)={[(weight of a product obtained by a reaction×% GC)/molecular weight of a product]+[(weight of a starting material in a reaction×% GC)/molecular weight of a starting material]×100
THF represents tetrahydrofuran, GBL represents γ-butyrolactone, PO represents propylene oxide, Ph represents a phenyl group, Bu represents a butyl group, and Et represents an ethyl group.
Zinc chloride (95.40 g, 0.70 mol) and 2-methyltetrahydrofuran (1,326.40 g, 15.40 mol) were placed in a reactor at a room temperature and stirred for 32 minutes at −5 to 5° C. Acetyl chloride (12: R2=CH3, X1=Cl) (1,099.00 g, 14.00 mol) was then added dropwise to the reactor at −5 to 5° C. After the completion of the dropwise addition, the reaction mixture was stirred for 2 hours at −5 to 5° C. Water (1,000 g) was then added to the reaction mixture, followed by phase separation. The organic layer thus obtained was subjected to distillation at a reduced pressure to obtain 4-chloropentyl acetate (13: R2=CH3, X1=Cl) (2,051.43 g, 12.34 mol, purity 99.03%, b.p.=71.0 to 78.9° C./0.40 kPa (3.0 mmHg)) with a yield of 88.11%.
The following is the spectrum data of 4-chloropentyl acetate (13: R2=CH3, X1=Cl) thus obtained.
Nuclear magnetic resonance spectrum: 1H-NMR (500 MHZ, CDCl3): δ=1.51 (3H, J=6.9 Hz), 1.67-1.91 (4H, m), 2.04 (3H, s), 3.99-4.12 (3H, m); 13C-NMR (500 MHz, CDCl3): δ=20.90, 25.32, 25.85, 36.65, 58.07, 63.77, 171.03.
Mass spectrum: EI-mass spectrum (70 eV): m/z 165 (M++1), 121, 101, 86, 68, 43.
Infrared absorption spectrum: (D-ATR): ν=2971, 1739, 1446, 1365, 1240, 1036, 977, 875, 607.
A THF solution (2,324.32 g) of methylmagnesium chloride (6.01 mol) was placed in a reactor at a room temperature and stirred for 12 minutes at 10 to 20° C. 4-Chloropentyl acetate (13: R2=CH3, X1=Cl) (453.84 g, 2.73 mol, purity 99.03%) obtained in Example 1 was then added dropwise to the reactor at 15 to 40° C. After the completion of the dropwise addition, the reaction mixture was stirred for 6 hours at 25 to 35° C. 20% by mass hydrochloric acid (1,343.73 g with 7.37 mol of hydrogen chloride) was then added to the reaction mixture, followed by phase separation. 4-Chloro-1-pentanol (15: X1=Cl) (376.05 g, 2.43 mol, purity 79.16%) was obtained with a crude yield of 80.11% by concentrating the organic layer thus obtained at a reduced pressure.
The following is the spectrum data of 4-chloro-1-pentanol (15: X1=Cl) thus obtained.
Nuclear magnetic resonance spectrum: 1H-NMR (500 MHZ, CDCl3): δ=1.51 (3H, J=6.5 Hz), 1.61-1.87 (4H, m), 2.58 (1H, br.s), 3.66 (2H, t, J=6.1 Hz), 4.02-4.09 (1H, m); 13C-NMR (500 MHZ, CDCl3): δ=25.36, 29.63, 36.54, 58.58, 62.15.
Mass spectrum: EI-mass spectrum (70 eV): m/z 104 (M+−18), 89, 76, 68, 56, 41.
Infrared absorption spectrum: (D-ATR): ν=3331, 2971, 2947, 2873, 1446, 1380, 1258, 1193, 1127, 1060, 1029, 1011, 982, 899, 671, 611.
Dimethoxymethane (271.58 g, 3.57 mol) and zinc chloride (3.31 g, 0.024 mol) were placed in a reactor at a room temperature and stirred for 3 minutes at 15 to 25° C. Acetyl chloride (247.78 g, 3.16 mol) was then added dropwise to the reactor at 30 to 40° C. After the completion of the dropwise addition, chloromethyl methyl ether (16: R1=H, X5=Cl) was formed by stirring for 2 hours at 35 to 45° C.
Then, N,N-diethylaniline (615.96 g, 4.13 mol) and 4-chloro-1-pentanol (15: X1=Cl) (376.05 g, 2.43 mol, purity 79.16%) obtained in Example 2 were added dropwise to the aforesaid reactor at 20 to 30° C. After the completion of the dropwise addition, the reaction mixture was stirred for 4 hours at 20 to 30° C. An aqueous solution of 25% by mass sodium hydroxide (842.47 g with 5.27 mol of sodium hydroxide) and water (535.04 g) were then added to the reaction mixture, followed by phase separation. The organic layer thus obtained was washed three times with 20% by mass hydrochloric acid (336.23 g, 1.84 mol). Continuing, washing with an aqueous solution of 25% by mass sodium hydroxide (152.60 g with 0.97 mol of sodium hydroxide) and then with methanol (40.97 g, 1.28 mol) were sequentially carried out, followed by phase separation. The organic layer thus obtained was subjected to distillation at a reduced pressure to obtain 4-chloropentyl methoxymethyl ether (1:n=1, R1=H, X1=Cl) (387.39 g, 2.27 mol, purity 97.61%, b.p.=68.1 to 77.9° C./0.67 kPa (5.0 mmHg)) with a yield of 83.11%.
The following is the spectrum data of 4-chloropentyl methoxymethyl ether (1A: R=H, X1=Cl) thus obtained.
Nuclear magnetic resonance spectrum: 1H-NMR (500 MHZ, CDCl3): δ=1.52 (3H, J=6.5 Hz), 1.61-1.88 (4H, m), 3.35 (3H, s), 3.51-3.58 (2H, m), 4.01-4.09 (1H, m), 4.60 (2H, s); 13C-NMR (500 MHZ, CDCl3): δ=25.36, 26.90, 37.04, 55.13, 58.50, 67.02, 96.37.
Mass spectrum: EI-mass spectrum (70 eV): m/z 165 (M+−1), 151, 136, 120, 104, 85, 69, 45.
Infrared absorption spectrum: (D-ATR): ν=2930, 2883, 1446, 1381, 1261, 1215, 1152, 1110, 1080, 1044, 919, 610.
Magnesium (89.30 g, 3.68 gram atoms) and tetrahydrofuran (1,050.00 g) were placed in a reactor at a room temperature and stirred for 21 minutes at 60 to 65° C. 4-Chloropentyl methoxymethyl ether (1A: R1=H, X1=Cl) (583.28 g, 3.50 mol, purity 100%) prepared according to Example 3 was then added dropwise to the reactor at 60 to 75° C. After the completion of the dropwise addition, 4-methoxymethoxy-1-methylbutylmagnesium chloride (2A: R1=H, M1A=MgCl) was formed by stirring for 4 hours at 75 to 80° C.
Then, the internal temperature of the aforesaid reactor was cooled to 0 to 10° C. Continuing, cuprous chloride (0.73 g, 0.0070 mol) was added to the reactor, and then propylene oxide (233.77 g, 4.02 mol) was added dropwise at 5 to 30° C. After the completion of the dropwise addition, the reaction mixture was stirred for 1.5 hours at 15 to 25° C. An aqueous solution of acetic acid (prepared from acetic acid (477.65 g) and water (1,433.19 g)) and hexane (339.68 g) were then added to the reaction mixture, followed by phase separation. The organic layer thus obtained was concentrated at a reduced pressure. The resulting concentrate was then subjected to distillation at a reduced pressure to obtain 6-hydroxy-4-methylheptyl methoxymethyl ether (4: R1=H) (579.26 g, 2.99 mol, purity 98.25%, b.p.=107.0 to 111.5° C./0.049 kPa (0.37 mmHg)) with a yield of 85.45%.
The following is the spectrum data of 6-hydroxy-4-methylheptyl methoxymethyl ether (4: R1=H) thus obtained.
Nuclear magnetic resonance spectrum: 1H-NMR (500 MHZ, CDCl3): δ=0.89 (3H, dd, J=6.7 Hz, 3.4 Hz), 1.10-1.70 (8H, m), 1.16 (3H, dd, J=6.9 Hz, 6.1 Hz), 3.33 (3H, J=1.2 Hz), 3.46-3.52 (2H, m), 3.83-3.91 (1H, m), 4.59 (2H, J=1.2 Hz); 13C-NMR (500 MHz, CDCl3): δ=19.30, 20.01, 23.69, 24.32, 27.01, 27.06, 29.22, 29.55, 33.11, 34.00, 46.69, 46.86, 55.05, 65.66, 65.97, 68.05, 68.09, 96.32, 96.34.
Mass spectrum: EI-mass spectrum (70 eV): m/z 190 (M+), 176, 159, 127, 109, 95, 85, 69, 55, 45.
Infrared absorption spectrum: (D-ATR): ν=3422, 2928, 1460, 1377, 1305, 1215, 1153, 1110, 1046, 920, 626.
6-Hydroxy-4-methylheptyl methoxymethyl ether (4: R1=H) (555.14 g, 2.87 mol, purity 98.25%) obtained in Example 4, pyridine (340.05 g, 4.30 mol), and GBL (429.90 g) were placed in a reactor and stirred for 21 minutes at 35 to 45° C.
Methanesulfonyl chloride (CH3SO2Cl) (393.96 g, 3.44 mol) was then added dropwise at 35 to 55° C. After the completion of the dropwise addition, the reaction mixture was heated to 60 to 65° C. and stirred for 9 hours. After the completion of the stirring, water (716.50 g) and hexane (429.90 g) were added, followed by phase separation. The aqueous layer was removed to obtain the organic layer. The organic layer thus obtained was washed with an aqueous solution of acetic acid (prepared from acetic acid (30.16 g) and water (377.10 g)), followed by washing with an aqueous solution of sodium bicarbonate (prepared from sodium bicarbonate (15.08 g) and water (377.10 g)). The organic layer thus obtained was concentrated at a reduced pressure. The resulting concentrate was then subjected to distillation at a reduced pressure to obtain 6-chloro-4-methylheptyl methoxymethyl ether (1B: R1=H, X1=Cl) (486.24 g, 2.07 mol, purity 88.86%, b.p.=86.0 to 95.4° C./0.29 kPa (2.2 mmHg)) with a yield of 72.23%.
The following is the spectrum data of 6-chloro-4-methylheptyl methoxymethyl ether (1B: R1=H, X1=Cl) thus obtained.
Nuclear magnetic resonance spectrum: 1H-NMR (500 MHz, CDCl3): δ=0.90 (3H, dd, J=6.7 Hz, 3.9 Hz), 1.10-1.45 (2H, m), 1.45-1.53 (3H, m), 1.53-1.80 (5H, m), 3.35 (3H, J=0.75 Hz), 3.50 (2H, t, J=6.9 Hz), 4.05-4.14 (1H, m), 4.61 (2H, s); 13C-NMR (500 MHZ, CDCl3): δ=18.68, 19.59, 25.37, 26.08, 26.90, 27.06, 30.10, 30.20, 32.43, 33.69, 47.60, 47.90, 55.09, 56.65, 56.87, 67.93, 67.99, 96.38, 96.41.
Mass spectrum: EI-mass spectrum (70 eV): m/z 207 (M+−1), 193, 177, 163, 147, 127, 111, 95, 82, 69, 45.
Infrared absorption spectrum: (D-ATR): ν=2929, 2879, 1455, 1380, 1214, 1152, 1111, 1047, 919, 675, 615.
Dibutoxymethane (3.75 g, 0.023 mol) and zinc chloride (0.02 g, 0.00018 mol) were placed in a reactor at a room temperature and stirred for 18 minutes at 15 to 25° C. Acetyl chloride (1.62 g, 0.021 mol) was then added dropwise to the reactor at 30 to 40° C. After the completion of the dropwise addition, the reaction mixture was stirred for 6 hours at 38 to 42° C. to obtain chloromethyl butyl ether.
A mixed solution of N,N-diethylaniline (3.09 g, 0.021 mol) and 6-chloro-4-methylheptanol (3.00 g, 0.018 mol) was then added dropwise to the reactor at 20 to 30° C. After the completion of the dropwise addition, the reaction mixture was stirred for 17 hours at 20 to 30° C. An aqueous solution of 25% by mass sodium hydroxide (3.12 g) and water (1.98 g) were then added to the reaction mixture, followed by phase separation. The organic layer thus obtained was concentrated at a reduced pressure. The resulting concentrate was then subjected to distillation at a reduced pressure to obtain 6-chloro-4-methylheptyl butyloxymethyl ether (1B: R1=CH2CH2CH3, X1=Cl) (3.30 g, 0.012 mol, purity 92.84%, b.p.=95.0 to 97.1° C./0.085 kPa (0.64 mmHg)) with a yield of 67.99%.
The following is the spectrum data of 6-chloro-4-methylheptyl butyloxymethyl ether (1B: R1=CH2CH2CH3, X1=Cl) thus obtained.
Nuclear magnetic resonance spectrum: 1H-NMR (500 MHZ, CDCl3): δ=0.88-0.94 (6H, m), 1.10-1.80 (14H, m), 3.51 (2H, t, J=6.9 Hz), 3.52 (2H, t, J=6.9 Hz), 4.05-4.14 (1H, m), 4.66 (2H, s); 13C-NMR (500 MHZ, CDCl3): δ=13.86, 18.68, 19.36, 19.60, 25.36, 26.09, 26.91, 27.08, 30.11, 30.21, 31.79, 32.47, 33.72, 47.58, 47.90, 56.65, 56.88, 67.53, 67.55, 67.91, 67.98, 95.26, 95.29.
Mass spectrum: EI-mass spectrum (70 eV): m/z 249 (M+−1), 177, 141, 111, 87, 57.
Infrared absorption spectrum: (D-ATR): ν=2958, 2931, 2873, 1458, 1380, 1115, 1072, 1048, 826, 739, 676, 617.
Benzyl chloromethyl ether (3.60 g, 0.021 mol, purity 90.00%), and toluene (4.00 g) were placed a reactor at a room temperature and stirred for 11 minutes at 15 to 25° C. A mixed solution of N,N-diethylaniline (3.09 g, 0.021 mol) and 6-chloro-4-methylheptanol (3.00 g, 0.018 mol) was then added dropwise to the reactor at 20 to 30° C. After the completion of the dropwise addition, the reaction mixture was stirred for 24 hours at 20 to 30° C. An aqueous solution of 25% by mass sodium hydroxide (4.07 g) and water (2.58 g) were then added to the reaction mixture, followed by phase separation. The organic layer thus obtained was concentrated at a reduced pressure. The resulting concentrate was then subjected to distillation at a reduced pressure to obtain 6-chloro-4-methylheptyl benzyloxymethyl ether (1B: R1=Ph, X1=Cl) (4.38 g, 0.014 mol, purity 89.72%, b.p.=131.1 to 134.8° C./0.043 kPa (0.32 mmHg)) with a yield of 76.68%.
The following is the spectrum data of 6-chloro-4-methylheptyl benzyloxymethyl ether (1B: R1=Ph, X1=Cl) thus obtained.
Nuclear magnetic resonance spectrum: 1H-NMR (500 MHz, CDCl3): δ=0.92 (3H, q, J=3.4 Hz), 1.54-1.82 (10H, m), 3.59 (2H, t, J=6.9 Hz), 4.07-4.16 (1H, m), 4.61 (2H, J=1.2 Hz), 4.76 (2H, s), 7.27-7.33 (1H, m), 7.33-7.38 (4H, m); 13C-NMR (500 MHz, CDCl3): δ=18.69, 19.61, 25.37, 26.09, 26.89, 27.05, 30.12, 30.21, 32.42, 33.70, 47.56, 47.87, 56.66, 56.89, 68.20, 68.23, 69.26, 69.28, 94.62, 94.65, 127.63, 127.81, 127.84, 128.38, 137.94.
Mass spectrum: EI-mass spectrum (70 e V): m/z 284 (M+), 193, 147, 120, 91, 69.
Infrared absorption spectrum: (D-ATR): ν=3031, 2929, 2872, 1454, 1379, 1207, 1168, 1113, 1049, 1028, 736, 698, 614.
Magnesium (8.69 g, 0.36 gram atoms) and tetrahydrofuran (102.18 g) were placed in a reactor at a room temperature and stirred for 12 minutes at 60 to 65° C. 6-Chloro-4-methylheptyl methoxymethyl ether (1B: R1=H, X1=Cl) (80.01 g, 0.34 mol, purity 88.86%) obtained in Example 5 was then added dropwise to the reactor at 60 to 75° C. After the completion of the dropwise addition, the reaction mixture was stirred for 3 hours at 75 to 80° C. to obtain 6-methoxymethoxy-1,3-dimethylhexylmagnesium chloride (2B: R1=H, M2B=MgCl).
Then, cuprous chloride (0.38 g, 0.0038 mol), triethyl phosphite (3.82 g, 0.023 mol), tetrahydrofuran (100.00 g), and 1-bromododecane (5: X2=Br) (84.89 g, 0.34 mol) were placed in another reactor, to which the aforesaid 6-methoxymethoxy-1,3-dimethylhexylmagnesium chloride (2B: R1=H, M2B=MgCl) prepared above was added dropwise at 5 to 20° C. After the completion of the dropwise addition, the reaction mixture was stirred for 2 hours at 15 to 25° C. An aqueous solution of acetic acid (prepared from acetic acid (5.41 g) and water (93.84 g)) and an aqueous solution of 25% by mass sodium hydroxide (7.13 g) were then added to the reaction mixture, followed by phase separation. The organic layer thus obtained was concentrated at a reduced pressure. The resulting concentrate was then subjected to distillation at a reduced pressure to obtain 4,6-dimethyloctadecyl methoxymethyl ether (6: R1=H) (92.93 g, 0.24 mol, purity 90.10%, b.p.=149.0 to 161.1° C./0.061 kPa (0.46 mmHg)) with a yield of 71.74%.
The following is the spectrum data of 4,6-dimethyloctadecyl methoxymethyl ether (6: R1=H) thus obtained.
Nuclear magnetic resonance spectrum: 1H-NMR (500 MHZ, CDCl3): δ=0.79-0.86 (6H, m), 0.88 (3H, t, J=6.9 Hz), 1.00-1.70 (30H, m), 3.36 (3H, s), 3.50 (2H, t, J=6.9 Hz), 4.62 (2H, s); 13C-NMR (500 MHz, CDCl3): δ=14.10, 19.40, 19.48, 20.17, 20.28, 22.69, 26.91, 27.06, 27.15, 27.30, 29.36, 29.65, 29.70, 29.73, 29.90, 29.97, 30.00, 30.01, 30.05, 31.92, 33.22, 34.31, 36.83, 37.99, 44.78, 45.11, 55.06, 68.24, 68.30, 96.39.
Mass spectrum: EI-mass spectrum (70 eV): m/z 341 (M+−1), 297, 237, 196, 167, 139, 111, 85, 69, 45.
Infrared absorption spectrum: (D-ATR): ν=2924, 2853, 1465, 1378, 1153, 1112, 1047, 921, 722.
4,6-Dimethyloctadecyl methoxymethyl ether (6: R1=H) (75.13 g, 0.20 mol, purity 90.10%) obtained in Example 8, methanol (98.80 g, 3.08 mol), and 20% by mass hydrochloric acid (9.88 g with 0.054 mol of hydrogen chloride) were placed in a reactor equipped with a distillation tower. The reaction mixture was heated to 60° C. and stirred for 19 minutes. After the completion of the stirring, the internal temperature of the reactor was heated to 65 to 70° C. to distill off a mixture of by-produced dimethoxymethane and methanol from the distillation tower. The reaction mixture was sampled during the reaction. After the conversion was confirmed to be 100%, water (59.28 g) was added to the reaction mixture, followed by phase separation. The aqueous layer was removed to obtain the organic layer. The organic layer thus obtained was concentrated at a reduced pressure. The resulting concentrate was then subjected to distillation at a reduced pressure to obtain 4,6-dimethyloctadecanol (7) (63.44 g, 0.19 mol, purity 91.15%, b.p.=141.2 to 163.1° C./0.037 kPa (0.28 mmHg)) with a yield of 98.00%.
The following is the spectrum data of 4,6-dimethyloctadecanol (7) thus obtained.
Nuclear magnetic resonance spectrum: 1H-NMR (500 MHz, CDCl3): δ=0.79-0.86 (6H, m), 0.88 (3H, t, J=6.9 Hz), 1.00-1.66 (31H, m), 3.62 (2H, t, J=6.9 Hz); 13C-NMR (500 MHZ, CDCl3): δ=14.09, 19.44, 19.47, 20.20, 20.24, 22.68, 26.92, 27.05, 29.35, 29.65, 29.69, 29.72, 29.89, 29.97, 30.00, 30.04, 30.19, 30.33, 31.91, 32.72, 33.83, 36.85, 37.97, 44.75, 45.08, 63.43, 63.47.
Mass spectrum: EI-mass spectrum (70 eV): m/z 297 (M+−1) 280, 266, 252, 237, 210, 196, 182, 168, 154, 125, 111, 97, 83, 69, 55, 41.
Infrared absorption spectrum: (D-ATR): νmax=3321, 2955, 2924, 2853, 1465, 1378, 1057, 721.
4,6-Dimethyloctadecanol (7) (63.23 g, 0.19 mol, purity 91.15%) obtained in Example 9, pyridine (22.90 g, 0.29 mol), and GBL (63.23 g) were placed in a reactor and stirred for 22 minutes at 40° C.
Methanesulfonyl chloride (CH3SO2Cl) (26.53 g, 0.23 mol) was then added dropwise at 40 to 60° C. After the completion of the dropwise addition, the reaction mixture was heated to 60 to 65° C. and stirred for 9 hours. After the completion of the stirring, water (60.00 g) and hexane (60.00 g) were added to the reaction mixture, followed by phase separation. The aqueous layer was removed to obtain the organic layer. The organic layer thus obtained was washed with an aqueous solution of acetic acid (prepared from acetic acid (2.03 g) and water (60.00 g)), followed by washing with an aqueous solution of sodium bicarbonate (prepared from sodium bicarbonate (1.02 g) and water (60.00 g)). The organic layer thus obtained was concentrated at a reduced pressure. The resulting concentrate was then subjected to distillation at a reduced pressure to obtain 1-chloro-4,6-dimethyloctadecane (8: X3=Cl) (61.12 g, 0.18 mol, purity 91.65%, b.p.=166.1 to 172.5° C./0.40 kPa (3.0 mmHg)) with a yield of 91.55%.
The following is the spectrum data of 1-chloro-4,6-dimethyloctadecane (8: X3=Cl) thus obtained.
Nuclear magnetic resonance spectrum: 1H-NMR (500 MHZ, CDCl3): δ=0.80-0.91 (9H, m), 1.00-1.60 (28H, m), 1.68-1.86 (2H, m), 3.52 (2H, t, J=6.9 Hz); 13C-NMR (500 MHz, CDCl3): δ=14.11, 19.39, 19.49, 20.15, 20.22, 22.70, 26.91, 27.04, 29.37, 29.58, 29.66, 29.70, 29.73, 29.99, 30.01, 30.04, 30.18, 30.33, 31.93, 33.96, 35.06, 36.84, 37.90, 44.67, 44.97, 45.51, 45.53.
Mass spectrum: EI-mass spectrum (70 e V): m/z 301 (M+−15), 239, 197, 147, 111, 85, 57.
Infrared absorption spectrum: (D-ATR): νmax=2956, 2924, 2853, 1464, 1378, 723, 656.
Magnesium (2.21 g, 0.091 gram atoms) and tetrahydrofuran (90.00 g) were placed in a reactor at a room temperature and stirred for 28 minutes at 60 to 65° C. 1-Chloro-4,6-dimethyloctadecane (8: X3=Cl) (30.00 g, 0.087 mol, purity 91.65%) obtained in Example 10 was then added dropwise to the reactor at 60 to 75° C. After the completion of the dropwise addition, the reaction mixture was stirred for 4 hours at 75 to 80° C. to obtain 4,6-dimethyloctadecylmagnesium chloride (9: M2=MgCl).
Then, cuprous chloride (0.10 g, 0.00098 mol), triethyl phosphite (0.97 g, 0.0059 mol), lithium chloride (0.07 g, 0.0016 mol), tetrahydrofuran (100.00 g), and 1-bromononane (10: X4=Br) (17.97 g, 0.087 mol) were placed in another reactor, to which the aforesaid 4,6-dimethyloctadecylmagnesium chloride (9: M2=MgCl) prepared above was added dropwise at 15 to 25° C. After the completion of the dropwise addition, the reaction mixture was stirred for 2 hours at 20 to 30° C. An aqueous solution of acetic acid (prepared from acetic acid (0.87 g) and water (23.90 g)), 20% by mass hydrochloric acid (1.82 g), and an aqueous solution of 25% by mass sodium hydroxide (1.82 g) were then added to the reaction mixture, followed by phase separation. The organic layer thus obtained was concentrated at a reduced pressure. The resulting concentrate was then subjected to distillation at a reduced pressure to distill off low-boiling impurities. The resulting concentrate was then purified by silica gel column chromatography (hexane=100) to obtain 13,15-dimethylheptacosane (11) (27.13 g, 0.058 mol, purity 87.87%) with a yield of 67.24%.
The following is the spectrum data of 13,15-dimethylheptacosane (11) thus obtained.
Nuclear magnetic resonance spectrum: 1H-NMR (500 MHZ, CDCl3): δ=0.88 (6H, t, J=6.9 Hz), 0.82 (6H, dd, J=10.9 Hz, 6.9 Hz), 1.01-1.07 (2H, m), 1.16-1.34 (46H, m); 13C-NMR (500 MHZ, CDCl3): δ=14.12, 19.57, 20.32, 22.71, 26.92, 27.09, 29.38, 29.68, 29.73, 29.76, 30.01, 30.03, 30.07, 31.95, 36.90, 37.99.
Mass spectrum: EI-mass spectrum (70 e V): m/z 393 (M+−15), 365, 295, 267, 239, 196, 169, 141, 113, 85, 57, 29.
Infrared absorption spectrum: (D-ATR): ν=2956, 2923, 2853, 1466, 1377, 721.
Triphenylphosphine (PPh3) (5.51 g, 0.021 mol) and acetonitrile (CH3CN) (15.45 g) were placed in a reactor at a room temperature and stirred for 26 minutes at 0 to 10° C. Bromine (Br2) (3.21 g, 0.020 mol) was then added dropwise to the reactor at 0 to 10° C. After the completion of the dropwise addition, the reaction mixture was stirred for 3 hours. A mixed solution of 6-hydroxy-4-methylheptyl methoxymethyl ether (4: R1=H) (2.93 g, 0.015 mol, purity 98.25%) obtained in Example 4 and triethylamine (2.14 g, 0.021 mol) was then added dropwise at 0 to 10° C. After the completion of the dropwise addition, the reaction mixture was stirred for 13 hours at 15 to 25° C. An aqueous solution of acetic acid (4.33 g) and hexane (6.60 g) were then added to the reaction mixture, followed by phase separation. The organic layer thus obtained was concentrated at a reduced pressure. The resulting concentrate was then purified by silica gel column chromatography (hexane:ethyl acetate=70:1 to 5:1) to obtain 6-bromo-4-methylheptyl methoxymethyl ether (1B: R1=H, X1=Br) (0.38 g, 0.00080 mol, purity 53.50%) with a yield of 5.31%.
The following is the spectrum data of 6-bromo-4-methylheptyl methoxymethyl ether (1B: R1=H, X1=Br) thus obtained.
Nuclear magnetic resonance spectrum: 1H-NMR (500 MHZ, CDCl3): δ=0.87-0.94 (3H, m), 1.10-1.96 (10H, m), 3.36 (3H, s), 3.47-3.54 (2H, m), 4.14-4.25 (1H, m), 4.61 (2H, s); 13C-NMR (500 MHZ, CDCl3): δ=18.61, 18.63, 19.43, 19.45, 26.40, 26.88, 27.06, 27.18, 30.03, 30.83, 31.20, 31.31, 32.32, 33.57, 33.97, 48.36, 48.53, 48.73, 49.29, 49.53, 50.18, 67.93, 96.39, 96.43.
Mass spectrum: EI-mass spectrum (70 eV): m/z 253 (M++1), 221, 191, 164, 141, 111, 69, 45.
Infrared absorption spectrum: (D-ATR): ν=2955, 2925, 2872, 1454, 1380, 1243, 1210, 11444, 1111, 1046, 919, 622, 540.
| Number | Date | Country | Kind |
|---|---|---|---|
| 2023-090372 | May 2023 | JP | national |
