8-(acyloxy) alkanal compound, method for preparing same, and method for preparing 2, 9-diacetoxyundecane from 8-(acyloxy) alkanal compound

Abstract

The present invention provides an 8-(acyloxy) alkanal compound (1) wherein n represents 0 or 1, and R1 represents a linear or branched alkyl group having 1 to 10 carbon atoms, a phenyl group, or a phenyl group in which one or more hydrogen atoms are substituted by halogen atoms, and a method for preparing the same. The present invention relates to a process for the preparation of 2, 9-undecane diol (3), comprising the steps of subjecting the above 8-(acyloxy) alkanal compound (1) to a nucleophilic addition reaction with a nucleophilic reagent alkyl compound (2), where M1 represents Li, MgZ1, CuZ1 or CuLiZ1, n represents 0 or 1, and Z1 represents a halogen atom, methyl or ethyl, to form 2, 9-undecane diol (3), and subjecting the 2, 9-undecane diol (3) to an acetylation reaction to form 2, 9-undecane diol (3). And 3, 9-diacetoxyundecane (4) is obtained. # imgabs0 #

Description

Technical Field

[0001] The present invention relates to 8-(acyloxy)alkanal compounds and methods for preparing the same. The present invention also relates to methods for preparing 2,9-diacetoxyundecane from the above-mentioned 8-(acyloxy)alkanal compounds. The present invention also relates to methods for preparing 8-(acyloxy)nonanal compounds, 8-(acyloxy)decanal compounds and 2,9-diacetoxyundecane from the above-mentioned 8-(acyloxy)alkanal compounds. Background Art

[0002] The Swedish midge (scientific name: Contarinia nasturtii) is a vegetable pest native to Europe that feeds on Brassica plants such as broccoli and cauliflower. The Swedish midge larvae feed on the leaves and flowers of the plant by secreting digestive juices that break down the cuticle, causing the leaves to twist, round and wrinkle, the leaves to be damaged in clumps, and the petioles to be eaten, which significantly reduces the value of the product. Because the larvae are protected by the leaves, typical pesticides are often ineffective due to poor contact, making control difficult. Due to concerns about residual pesticides, biological control methods have attracted attention, and one promising method is the use of sex pheromones (hereinafter referred to as Non-Patent Document 1).

[0003] It is reported that the sex pheromone composition of the Swedish midge is a mixture of (2S,9S)-2,9-diacetoxyundecane, (2S,10S)-2,10-diacetoxyundecane and (2S)-2-acetoxyundecane in a ratio of 1:2:0.02 (hereinafter referred to as Non-Patent Document 2).

[0004] For example, the following method has been reported as a method for preparing the above-mentioned (2S, 9S)-2,9-diacetoxyundecane, which includes a total of seven steps and a yield of 21.39% (hereinafter non-patent document 2). The method includes reacting the starting material 7-bromo-1-heptene with magnesium in tetrahydrofuran (THF) to form 6-heptenyl magnesium bromide, and then reacting 6-heptenyl magnesium bromide with propylene oxide in the presence of a copper catalyst to form (2S)-9-decene-2-ol. The (2S)-9-decene-2-ol thus obtained is then reacted with sodium hydride in tetrahydrofuran in the presence of tetrabutylammonium iodide, and then reacted with benzyl bromide to form (2S)-2-benzyloxy-9-decene. The (2S)-2-benzyloxy-9-decene thus obtained is then reacted with AD-mixed-β in aqueous tert-butyl alcohol to form (2R, 9S)-9-(benzyloxy)-1,2-decanediol. The (2R,9S)-9-(benzyloxy)-1,2-decanediol thus obtained is then reacted with p-toluenesulfonyl chloride in pyridine to form (2R,9S)-1-(4-methylbenzenesulfonic acid)-9-(benzyloxy)-1,2-decanediol ester. The (2R,9S)-1-(4-methylbenzenesulfonic acid)-9-(benzyloxy)-1,2-decanediol thus obtained is then reacted with methylmagnesium chloride in tetrahydrofuran to form (3S,10S)-10-(benzyloxy)-3-undecanol, and then the (3S,10S)-10-(benzyloxy)-3-undecanol thus obtained is reacted with hydrogen in ethanol in the presence of a palladium-carbon catalyst to form (2S,9S)-2,9-undecanediol. The (2S,9S)-2,9-undecanediol thus obtained was acetylated with acetic anhydride in the presence of pyridine and 4-dimethylaminopyridine (DMAP) to obtain the target compound (2S,9S)-2,9-diacetoxyundecane.

[0005] Prior art literature

[0006] [Patent Document]

[0007] [Patent Document 1] Japanese Patent Application No. 2019-189535.

[0008] [Non-patent literature]

[0009] [Non-patent document 1] Elisabeth A. Hodgdon et al., The Canadian Entomologist, 2022, 154, e37, 1-17.

[0010] [Non-patent document 2] Ylva Hillbur et al., J. Chem. Ecol., 2005, 31(8), 1807-1828.

[0011] Purpose of the Invention

[0012] However, the preparation method of non-patent document 2 uses highly toxic and expensive AD-mixed-β, which is used five times as much as the starting material, making the method unsuitable for industrial application. AD-mixed-β here is a mixture of expensive hydroquinidine-1,4-phthalazine diyl diether, potassium carbonate and potassium ferrocyanide, and highly toxic potassium osmate dihydrate. The preparation method of non-patent document 2 also uses flammable palladium carbon, making the method unsuitable for industrial application. Due to the large number of steps and low yield, the industrialization of the preparation method of non-patent document 2 is also difficult.

[0013] In view of the above situation, the present invention aims to provide a novel synthetic intermediate that can be used to prepare 2,9-diacetoxyundecane and a method for preparing the synthetic intermediate. The present invention also aims to provide an effective method for preparing 2,9-diacetoxyundecane from the synthetic intermediate, preferably an effective and economical method for preparing 2,9-diacetoxyundecane from the synthetic intermediate, and particularly preferably a method for preparing 2,9-diacetoxyundecane from the synthetic intermediate suitable for industrial application. Summary of the invention

[0014] As a result of in-depth research to overcome the above-mentioned problems of the prior art, the inventors have found that the key intermediate that can synthesize 2,9-diacetoxy undecane is a new compound 8-(acyloxy) alkanal compound. The inventors have also found a method for preparing the new compound 8-(acyloxy) alkanal compound, particularly a cheap and effective method, and found a method for preparing the sex pheromone 2,9-diacetoxy undecane of Swedish midge from the 8-(acyloxy) alkanal compound, particularly an effective method, thereby completing the present invention. It has also been found that the above-mentioned method for preparing the above-mentioned 8-(acyloxy) alkanal compound and the above-mentioned method for preparing the above-mentioned 2,9-diacetoxy undecane are suitable for industrial applications.

[0015] According to a first aspect of the present invention, there is provided an 8-(acyloxy)alkanal compound having the following general formula (1):

[0016]

[0017] Where n represents 0 or 1, R 1 It represents a straight-chain or branched alkyl group having 1 to 10 carbon atoms, a phenyl group, or a phenyl group in which one or more hydrogen atoms are substituted by a halogen atom.

[0018] According to a second aspect of the present invention, there is provided a method for preparing 2,9-diacetoxyundecane of the following formula (4):

[0019]

[0020] The method comprises the following steps:

[0021] The following 8-(acyloxy)alkanal compound of general formula (1) is prepared:

[0022]

[0023] Where n represents 0 or 1, and R 1 represents a straight-chain or branched alkyl group having 1 to 10 carbon atoms, a phenyl group, or a phenyl group in which one or more hydrogen atoms are substituted by a halogen atom,

[0024] With the following nucleophilic alkyl compound of general formula (2)

[0025] CH3(CH2) (1-n) M 1 (2)

[0026] Among them, M 1 Indicates Li, MgZ 1 ,CuZ 1 or CuLiZ 1 , n represents 0 or 1, and Z 1 represents a halogen atom, a methyl group or an ethyl group,

[0027] A nucleophilic addition reaction is carried out to form 2,9-undecanediol of the following formula (3):

[0028]

[0029] and subjecting the 2,9-undecanediol (3) to an acetylation reaction to form the 2,9-diacetoxyundecane (4).

[0030] According to a third aspect of the present invention, there is provided a method for preparing an 8-(acyloxy)alkanal compound of the following general formula (1):

[0031]

[0032] Where n represents 0 or 1, R 1 represents a straight-chain or branched alkyl group having 1 to 10 carbon atoms, a phenyl group, or a phenyl group in which one or more hydrogen atoms are substituted by a halogen atom,

[0033] The method comprises the following steps:

[0034] The following dialkoxy acyloxy alkane compound of the general formula (5) is used:

[0035]

[0036] Where n represents 0 or 1, R 1As defined above, and R 3 and R 4 independently represent a monovalent hydrocarbon group having 1 to 15 carbon atoms; or R 3 and R 4 Together they form a divalent hydrocarbon radical R having 2 to 10 carbon atoms 3 -R 4 , and undergo a hydrolysis reaction to form the above-mentioned 8-(acyloxy)alkanal compound (1).

[0037] According to a fourth aspect of the present invention, there is provided a method for preparing an 8-(acyloxy)alkanal compound (1) as defined in the third aspect, wherein n is 0 (also referred to in this specification as "8-(acyloxy)nonanal compound (1: n=0)" or "8-(acyloxy)nonanal compound (1), wherein n=0"),

[0038] The method comprises the following steps:

[0039] The following 6-halogeno-1,1-dialkoxyhexane compound of general formula (6):

[0040]

[0041] Where X represents a halogen atom, and R 3 and R 4 independently represent a monovalent hydrocarbon group having 1 to 15 carbon atoms; or R 3 and R 4 Together they form a divalent hydrocarbon radical R having 2 to 10 carbon atoms 3 -R 4 , converted into a nucleophile 6,6-dialkoxyhexyl compound of the following general formula (7):

[0042]

[0043] Among them, M 2 Indicates Li, MgZ 2 ,CuZ 2 or CuLiZ 2 , Z 2 represents a halogen atom or a 6,6-dialkoxyhexyl group, and R 3 and R 4 As defined above,

[0044] The nucleophilic 6,6-dialkoxyhexyl compound (7) is then subjected to a nucleophilic addition reaction with propylene oxide of the following formula (8):

[0045]

[0046] To form the following 9,9-dialkoxy-2-nonanol compound of general formula (9A):

[0047]

[0048] Where R 3 and R 4 As defined above,

[0049] The 9,9-dialkoxy-2-nonanol compound (9A) is acylated to form a 9,9-dialkoxy-2-acyloxynonane compound of the following general formula (5A), which is the above general formula (5) wherein n is 0:

[0050]

[0051] Where R 1 , R 3 and R 4 As defined above,

[0052] And the preparation method according to the third aspect comprises subjecting the 9,9-dialkoxy-2-acyloxynonane compound (5A) to a hydrolysis reaction to form the 8-(acyloxy)nonanal compound (1) wherein n is 0.

[0053] According to a fifth aspect of the present invention, there is provided a method for preparing an 8-(acyloxy)alkanal compound (1) as defined in the third aspect, wherein n is 1 (also referred to in the present specification as "8-(acyloxy)decanal compound (1: n=1)" or "8-(acyloxy)decanal compound (1), wherein n=1"),

[0054] The method comprises the following steps:

[0055] The following 6-halogeno-1,1-dialkoxyhexane compound of the general formula (6):

[0056]

[0057] Where X represents a halogen atom, and R 3 and R 4 independently represent a monovalent hydrocarbon group having 1 to 15 carbon atoms; or R 3 and R 4 Together they form a divalent hydrocarbon radical R having 2 to 10 carbon atoms 3 -R 4 , converted into a nucleophile 6,6-dialkoxyhexyl compound of the following general formula (7):

[0058]

[0059] Among them, M 2 Indicates Li, MgZ 2 ,CuZ2 or CuLiZ 2 , Z 2 represents a halogen atom or a 6,6-dialkoxyhexyl group, and R 3 and R 4 As defined above,

[0060] The nucleophilic 6,6-dialkoxyhexyl compound (7) is then subjected to a nucleophilic addition reaction with 1,2-butylene oxide of the following formula (10):

[0061]

[0062] To form the following 10,10-dialkoxy-3-decanol compound of general formula (9B):

[0063]

[0064] Where R 3 and R 4 As defined above,

[0065] The 10,10-dialkoxy-3-decanol (9B) is acylated to form a 10,10-dialkoxy-3-acyloxydecane compound of the following general formula (5B), which is the above general formula (5) wherein n is 1:

[0066]

[0067] Where R 1 , R 3 and R 4 As defined above,

[0068] And the preparation method according to the third aspect comprises subjecting the 10,10-dialkoxy-3-acyloxydecane compound (5B) to a hydrolysis reaction to form the 8-(acyloxy)decanal compound (1) wherein n is 1.

[0069] According to a sixth aspect of the present invention, there is provided a method for preparing 2,9-diacetoxyundecane (4) as defined in the second aspect,

[0070] The method comprises the following steps:

[0071] According to the third aspect, the preparation method comprises preparing the 8-(acyloxy)alkanal compound (1) from the dialkoxyacyloxyalkane compound (5), and

[0072] And the preparation method according to the second aspect comprises preparing the 2,9-diacetoxyundecane (4) from the 8-(acyloxy)alkanal compound (1).

[0073] According to a seventh aspect of the present invention, there is provided a method for preparing 2,9-diacetoxyundecane (4) as defined in the second aspect,

[0074] The method comprises the following steps:

[0075] The following 6-halogeno-1,1-dialkoxyhexane compound of the general formula (6):

[0076]

[0077] Where X represents a halogen atom, and R 3 and R 4 independently represent a monovalent hydrocarbon group having 1 to 15 carbon atoms; or R 3 and R 4 Together they form a divalent hydrocarbon radical R having 2 to 10 carbon atoms 3 -R 4 , converted into a nucleophile 6,6-dialkoxyhexyl compound of the following general formula (7):

[0078]

[0079] Among them, M 2 Indicates Li, MgZ 2 ,CuZ 2 or CuLiZ 2 , Z 2 represents a halogen atom or a 6,6-dialkoxyhexyl group, and R 3 and R 4 As mentioned above,

[0080] The nucleophilic 6,6-dialkoxyhexyl compound (7) is then subjected to a nucleophilic addition reaction with propylene oxide of the following formula (8):

[0081]

[0082] To form the following 9,9-dialkoxy-2-nonanol compound of general formula (9A):

[0083]

[0084] Where R 3 and R 4 As defined above,

[0085] The 9,9-dialkoxy-2-nonanol compound (9A) is acylated to form a 9,9-dialkoxy-2-acyloxynonane compound of the following general formula (5A):

[0086]

[0087] Where R1 , R 3 and R 4 As defined above,

[0088] The 9,9-dialkoxy-2-acyloxynonane compound (5A) is subjected to a hydrolysis reaction to form an 8-(acyloxy)alkanal compound (1) wherein n is 0, which is the above-mentioned general formula (1) wherein n is 0,

[0089] And the above-mentioned preparation method according to the second aspect comprises preparing the 2,9-diacetoxyundecane (4) from an 8-(acyloxy)alkanal compound (1) in which n is 0.

[0090] According to an eighth aspect of the present invention, there is provided a method for preparing 2,9-diacetoxyundecane (4) as defined in the second aspect,

[0091] The method comprises the following steps:

[0092] The following 6-halogeno-1,1-dialkoxyhexane compound of the general formula (6):

[0093]

[0094] Where X represents a halogen atom, and R 3 and R 4 independently represent a monovalent hydrocarbon group having 1 to 15 carbon atoms; or R 3 and R 4 Together they form a divalent hydrocarbon radical R having 2 to 10 carbon atoms 3 -R 4 , converted into a nucleophile 6,6-dialkoxyhexyl compound of the following general formula (7):

[0095]

[0096] Among them, M 2 Indicates Li, MgZ 2 ,CuZ 2 or CuLiZ 2 , Z 2 represents a halogen atom or a 6,6-dialkoxyhexyl group, and R 3 and R 4 As defined above,

[0097] The nucleophilic 6,6-dialkoxyhexyl compound (7) is then subjected to a nucleophilic addition reaction with 1,2-butylene oxide of the following formula (10):

[0098]

[0099] To form the following 10,10-dialkoxy-3-decanol compound of general formula (9B):

[0100]

[0101] Where R 3 and R 4 As defined above,

[0102] The 10,10-dialkoxy-3-decanol compound (9B) is acylated to form a 10,10-dialkoxy-3-acyloxydecane compound of the following general formula (5B), which is the above general formula (5) wherein n is 1:

[0103]

[0104] Where R 1 , R 3 and R 4 As defined above,

[0105] The 10,10-dialkoxy-3-acyloxydecane compound (5B) is subjected to a hydrolysis reaction to form an 8-(acyloxy)alkanal compound (1) wherein n is 1, which is the above-mentioned general formula (1) wherein n is 1,

[0106] And the above-mentioned preparation method according to the second aspect comprises preparing the 2,9-diacetoxyundecane (4) from an 8-(acyloxy)alkanal compound (1) in which n is 1.

[0107] According to the present invention, an 8-(acyloxy)alkanal compound can be prepared, which is a synthetic intermediate that allows efficient synthesis of 2,9-diacetoxy undecane. In addition, by using an 8-(acyloxy)alkanal compound as a key intermediate, 2,9-diacetoxy undecane can be efficiently prepared with fewer steps and low environmental impact. The preparation method is also economical. DETAILED DESCRIPTION

[0108] I. 8-(Acyloxy)alkanal compounds of the following general formula (1)

[0109] First, the 8-(acyloxy)alkanal compound (1) will be explained in detail below.

[0110]

[0111] In the above general formula (1), n ​​represents 0 or 1.

[0112] In this specification, when n is 0, the symbol "8-(acyloxy)alkanal compound (1:n=0)" or "8-(acyloxy)alkanal compound (1A)" is used, and when n is 1, the symbol "8-(acyloxy)alkanal compound (1:n=1)" or "8-(acyloxy)alkanal compound (1B)" is used.

[0113] In the above general formula (1), R 1 It represents a straight-chain or branched alkyl group having 1 to 10, preferably 1 to 6, more preferably 1, 2, 3 or 4 carbon atoms, a phenyl group or a phenyl group in which one or more hydrogen atoms are substituted by a halogen atom.

[0114] A straight chain or branched alkyl group having 1 to 10 carbon atoms 1 Examples of include methyl, ethyl, n-propyl, n-butyl, isopropyl, sec-butyl and tert-butyl.

[0115] Examples of the halogen atoms of the phenyl group in which one or more hydrogen atoms are replaced by halogen atoms include fluorine atoms, chlorine atoms, bromine atoms and iodine atoms. Any hydrogen atom of the phenyl group may be replaced by a halogen atom. The number of halogen atoms in the phenyl group is 1, 2, 3, 4 or 5. When a plurality of hydrogen atoms of the phenyl group are replaced by halogen atoms, the halogen atoms are independent of each other.

[0116] As specific examples of the 8-(acyloxy)alkanal compound (1), 8-(acyloxy)alkanal compound (1A) and 8-(acyloxy)alkanal compound (1B) will be described below.

[0117] Examples of the 8-(acyloxy)alkanal compound (1A) include the following compounds:

[0118] 8-(Acyloxy)nonanal compounds, such as 8-(acetyloxy)nonanal, 8-(propionyloxy)nonanal, 8-(butyryloxy)nonanal, 8-(isobutyryloxy)nonanal, 8-(2-methylbutyryloxy)nonanal, 8-(pivaloyloxy)nonanal, and 8-(benzoyloxy)nonanal.

[0119] Examples of the 8-(acyloxy)alkanal compound (1B) include the following compounds:

[0120] 8-(Acyloxy)decanal compounds, such as 8-(acetyloxy)decanal, 8-(propionyloxy)decanal, 8-(butyryloxy)decanal, 8-(isobutyryloxy)decanal, 8-(2-methylbutyryloxy)decanal, 8-(pivaloyloxy)decanal and 8-(benzoyloxy)decanal.

[0121] II. A method for preparing the above-mentioned 8-(acyloxy)alkanal compound (1).

[0122] The target compound 8-(acyloxy)alkanal compound (1) of the present invention can be prepared from a 6-halogeno-1,1-dialkoxyhexane compound of the following general formula (6) according to the preparation method of the following chemical reaction formula, for example.

[0123]

[0124] Specifically, the 8-(acyloxy)alkanal compound (1) can be prepared by the following steps: (i) converting a 6-halogeno-1,1-dialkoxyhexane compound (6) into a nucleophile 6,6-dialkoxyhexyl compound (7), then (ii) subjecting the nucleophile 6,6-dialkoxyhexyl compound (7) to a nucleophilic addition reaction with propylene oxide (8) or 1,2-butylene oxide (10) to form a dialkoxyalkanol compound (9), then (iii) acylating the dialkoxyalkanol compound (9) to form a dialkoxyacyloxyalkane compound (5), and then (iv) hydrolyzing the dialkoxyacyloxyalkane compound (5).

[0125] (i) The above-mentioned nucleophilic reagent 6,6-dialkoxyhexyl compound (7) and a method for preparing the above-mentioned nucleophilic reagent 6,6-dialkoxyhexyl compound (7)

[0126] (a) The nucleophilic agent 6,6-dialkoxyhexyl compound (7) will be described in detail below.

[0127] The nucleophilic agent 6,6-dialkoxyhexyl compound (7) is represented by the following general formula (7):

[0128]

[0129] In the above general formula (7), M 2 Indicates Li, MgZ 2 ,CuZ 2 or CuLiZ 2 , and Z 2 represents a halogen atom or a 6,6-dialkoxyhexyl group. Halogen atom Z 2 Examples of include chlorine atoms, bromine atoms, and iodine atoms. Chlorine atoms and bromine atoms are preferred. By using the chlorine atoms and bromine atoms, preferred reactivity can be ensured. Chlorine atoms are particularly preferred. By using the chlorine atoms, particularly preferred reactivity can be ensured.

[0130] In the above general formula (7), R 3 and R 4 each independently represents a monovalent hydrocarbon group having 1 to 15 carbon atoms, preferably 1 to 10 carbon atoms, more preferably 1 to 5 carbon atoms, even more preferably 1 to 4 carbon atoms; or R 3 and R 4Together they form a divalent hydrocarbon radical R having 2 to 10 carbon atoms, preferably 2 to 5 carbon atoms 3 -R 4 .

[0131] Examples of monovalent hydrocarbon groups having 1 to 15 carbon atoms include straight-chain saturated hydrocarbon groups such as methyl groups, ethyl groups, n-propyl groups, n-butyl groups, n-pentyl groups, n-hexyl groups, n-heptyl groups, n-octyl groups, n-nonyl groups, n-decyl groups, n-undecyl groups, and n-dodecyl groups; branched saturated hydrocarbon groups such as isopropyl groups, 2-methylpropyl groups, and 2-methylbutyl groups; straight-chain unsaturated hydrocarbon groups such as 2-propenyl groups; branched unsaturated hydrocarbon groups such as 2-methyl-2-propenyl groups; cyclic saturated hydrocarbon groups such as cyclopropyl groups; and isomers thereof. A portion of hydrogen atoms in the hydrocarbon group may be substituted by a methyl group or an ethyl group.

[0132] The monovalent hydrocarbon group is preferably a methyl group, an ethyl group, an n-propyl group, and an n-butyl group. By using the methyl group, the ethyl group, the n-propyl group, and the n-butyl group, preferable handling properties can be ensured.

[0133] When R 3 and R 4 Together they form a divalent hydrocarbon radical R having 2 to 10 carbon atoms 3 -R 4 When the divalent hydrocarbon group is substituted, examples of the divalent hydrocarbon group include a straight-chain saturated hydrocarbon group such as an ethylene group, a 1,3-propylene group, and a 1,4-butylene group; a branched saturated hydrocarbon group such as a 1,2-propylene group, a 2,2-dimethyl-1,3-propylene group, a 1,2-butylene group, a 1,3-butylene group, a 2,3-butylene group, and a 2,3-dimethyl-2,3-butylene group; a straight-chain unsaturated hydrocarbon group such as a 1-vinylvinyl group; a branched unsaturated hydrocarbon group such as a 2-methylene-1,3-propylene group; a cyclic hydrocarbon group such as a 1,2-cyclopropenyl group and a 1,2-cyclobutenyl group; and isomers thereof. A part of the hydrogen atoms in the hydrocarbon group may be substituted with a methyl group or an ethyl group.

[0134] In view of preferred deprotection reactivity, ease of purification and / or availability, the divalent hydrocarbon group is preferably a lower hydrocarbon group of 2 to 4 carbon atoms, which has high reactivity and is easy to remove deprotection by-products by washing or concentration.

[0135] Therefore, the divalent hydrocarbon group is particularly preferably an ethylene group, a 1,2-propylene group, a 1,3-propylene group, a 1,2-butylene group, a 1,3-butylene group and a 2,3-dimethyl-2,3-butylene group. By using the ethylene group, the 1,2-propylene group, the 1,3-propylene group, the 1,2-butylene group, the 1,3-butylene group and the 2,3-dimethyl-2,3-butylene group, particularly preferred deprotection reactivity, easy purification and / or availability can be ensured.

[0136] When M 2 is MgZ in the above general formula (7) 2 When the nucleophile 6,6-dialkoxyhexyl compound (7:M 2 =MgZ 2 ) is a Grignard reagent.

[0137] Specific examples of the nucleophilic 6,6-dialkoxyhexyl compound (7) include the following compounds:

[0138] 6,6-Dialkoxyhexyl lithium compound (when M 2 =Li), such as 6,6-dimethoxyhexyllithium, 6,6-diethoxyhexyllithium, 6,6-dipropoxyhexyllithium, 6,6-dibutoxyhexyllithium, 6,6-dipentyloxyhexyllithium, 6,6-dihexyloxyhexyllithium, 6,6-diheptyloxyhexyllithium, 6,6-dioctyloxyhexyllithium, 6,6-dinonyloxyhexyllithium, 6,6-didecyloxyhexyllithium, [5-(1,3-dioxolan-2-yl)pentyl]lithium, and [5-(1,3-dioxolan-2-yl)pentyl]lithium;

[0139] 6,6-Dialkoxyhexylmagnesium halide compound (when M 2 =MgZ 2), such as 6,6-dimethoxyhexylmagnesium chloride, 6,6-diethoxyhexylmagnesium chloride, 6,6-dipropoxyhexylmagnesium chloride, 6,6-dibutoxyhexylmagnesium chloride, 6,6-dipentoxyhexylmagnesium chloride, 6,6-dihexyloxyhexylmagnesium chloride, 6,6-diheptyloxyhexylmagnesium chloride, 6,6-dioctyloxyhexylmagnesium chloride, 6,6-dinonyloxyhexylmagnesium chloride, 6,6-didecyloxyhexylmagnesium chloride, [5-(1,3-dioxolan-2-yl)pentyl]magnesium chloride, [5-(1,3-dioxolan-2-yl)pentyl]magnesium chloride, 6,6-dimethoxyhexylmagnesium bromide, 6,6-diethoxyhexylmagnesium bromide, 6,6-dipropoxyhexylmagnesium bromide, 6,6-dibutoxyhexylmagnesium bromide, 6,6-dipentoxyhexylmagnesium bromide, 6,6-dihexyloxyhexylmagnesium bromide, 6,6-diheptyloxyhexylmagnesium bromide Magnesium, 6,6-dioctyloxyhexylmagnesium bromide, 6,6-dinonyloxyhexylmagnesium bromide, 6,6-didecyloxyhexylmagnesium bromide, [5-(1,3-dioxolan-2-yl)pentyl]magnesium bromide, [5-(1,3-dioxolan-2-yl)pentyl]magnesium bromide, 6,6-dimethoxyhexylmagnesium iodide, 6,6-diethoxyhexylmagnesium iodide, 6,6-dipropoxyhexylmagnesium iodide, 6,6-dibutoxyhexyl Magnesium iodide, 6,6-dipentyloxyhexylmagnesium iodide, 6,6-dihexyloxyhexylmagnesium iodide, 6,6-diheptyloxyhexylmagnesium iodide, 6,6-dioctyloxyhexylmagnesium iodide, 6,6-dinonyloxyhexylmagnesium iodide, 6,6-didecyloxyhexylmagnesium iodide, [5-(1,3-dioxolan-2-yl)pentyl]magnesium iodide, and [5-(1,3-dioxolan-2-yl)pentyl]magnesium iodide (i.e., Grignard reagents);

[0140] Bis[6,6-dialkoxyhexyl] cuprate compound (when M 2 =CuZ 2 ), such as bis[6,6-dimethoxyhexyl]cuprate, bis[6,6-diethoxyhexyl]cuprate, bis[6,6-dipropoxyhexyl]cuprate, bis[6,6-dibutoxyhexyl]cuprate, bis[6,6-dipentoxyhexyl]cuprate, bis[6,6-dihexyloxyhexyl]cuprate, bis[6,6-diheptyloxyhexyl]cuprate, bis[6,6-dioctyloxyhexyl]cuprate, bis[6,6-dinonyloxyhexyl]cuprate, and bis[6,6-didecyloxyhexyl]cuprate; and

[0141] Gilman reagent (when M 2 =CuLiZ 2), such as bis[6,6-dialkoxyhexyl]copperate lithium compounds, such as bis[6,6-dimethoxyhexyl]copperate lithium, bis[6,6-diethoxyhexyl]copperate lithium, bis[6,6-dipropoxyhexyl]copperate lithium, bis[6,6-dibutoxyhexyl]copperate lithium, bis[6,6-dipentyloxyhexyl]copperate lithium, bis[6,6-dihexyloxyhexyl]copperate lithium, bis[6,6-diheptyloxyhexyl]copperate lithium, bis[6,6-dioctyloxyhexyl]copperate lithium, bis[6,6-dinonyloxyhexyl]copperate lithium, and bis[6,6-didecyloxyhexyl]copperate lithium (i.e., Gilman reagent).

[0142] A Grignard reagent such as 6,6-dimethoxyhexylmagnesium halide compound is preferred. By using the Grignard reagent such as 6,6-dimethoxyhexylmagnesium halide compound, preferred reactivity can be ensured.

[0143] (b) The method for preparing the above-mentioned nucleophilic 6,6-dialkoxyhexyl compound (7) will be described in detail below.

[0144] The nucleophilic 6,6-dialkoxyhexyl compound (7) can be prepared from the above-mentioned 6-halogenated-1,1-dialkoxyhexane compound (6). The 6-halogenated-1,1-dialkoxyhexane compound (6) can be prepared according to the preparation method described in, for example, Japanese Patent Application Publication No. 2019-189535.

[0145] The preparation of M will be described in detail as an example. 2 MgZ 2 The nucleophilic reagent 6,6-dialkoxyhexyl compound (7), that is, 6,6-dialkoxyhexyl magnesium halide reagent (7: M 2 =MgZ 2 ) (i.e., Grignard reagent) method.

[0146] 6,6-Dialkoxyhexylmagnesium halide reagent (7: when M 2 =MgZ 2 ) can be prepared by, for example, reacting the above-mentioned 6-halogeno-1,1-dialkoxyhexane compound (6) with magnesium in a solvent, as shown in the following chemical reaction formula:

[0147]

[0148] The amount of magnesium used is preferably 1.0 to 2.0 gram atoms per mol of the 6-halogeno-1,1-dialkoxyhexane compound (6). By using the preferred amount, it is possible to ensure that the preferred reaction is completed.

[0149] Examples of solvents include general solvents, such as ether solvents such as tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), diethyl ether, butyl ether, 4-methyltetrahydropyran (MTHP), cyclopentyl methyl ether and 1,4-dioxane; and hydrocarbon solvents such as hexane, heptane, benzene, toluene, xylene and isopropylbenzene. Preferred hydrocarbon solvents are toluene and xylene; and ether solvents are tetrahydrofuran, 2-methyltetrahydrofuran, and 4-methyltetrahydropyran. By using the hydrocarbon solvents such as toluene and xylene; and ether solvents such as tetrahydrofuran, 2-methyltetrahydrofuran and 4-methyltetrahydropyran, the preferred reaction rate for forming the above-mentioned Grignard reagent can be ensured. More preferred are tetrahydrofuran, 2-methyltetrahydrofuran and 4-methyltetrahydropyran. By using the tetrahydrofuran, 2-methyltetrahydrofuran and 4-methyltetrahydropyran, the preferred reaction rate for forming the above-mentioned Grignard reagent can be ensured.

[0150] If necessary, solvents may be used alone or in combination. The solvent may be a commercially available solvent.

[0151] The amount of the solvent used is preferably 30 to 5000 g, more preferably 50 to 3000 g per mol of the 6-halogeno-1,1-dialkoxyhexane compound (6). By using the preferred amount and the more preferred amount, preferred reactivity and more preferred reactivity can be ensured.

[0152] The reaction temperature varies depending on the solvent used, but is preferably 30 to 120° C. By using the preferred reaction temperature, preferred reactivity can be ensured.

[0153] The reaction time varies depending on the solvent used and / or the production scale, and is preferably 0.5 to 100 hours. By using the preferred reaction time, preferred reactivity can be ensured.

[0154] (ii) The above-mentioned dialkoxyalkanol compound (9) and a method for preparing the above-mentioned dialkoxyalkanol compound (9)

[0155] (a) The dialkoxyalkanol compound (9) will be described in detail below.

[0156] The dialkoxyalkanol compound (9) is represented by the following general formula (9):

[0157]

[0158] In the above general formula (9), R 3 and R 4 As defined in general formula (7), and n is as defined in general formula (1) above.

[0159] In this specification, when n is 0, the symbol dialkoxyalkanol compound (9:n=0), dialkoxyalkanol compound (9A) or 9,9-dialkoxy-2-nonanol compound (9A) is used, and when n is 1, the symbol dialkoxyalkanol compound (9:n=1), dialkoxyalkanol compound (9B) or 10,10-dialkoxy-3-decanol compound (9B) is used.

[0160] As specific examples of the dialkoxyalkanol compound (9), a dialkoxyalkanol compound (9A) and a dialkoxyalkanol compound (9B) will be described below.

[0161] Examples of the dialkoxyalkanol compound (9A) include the following compounds:

[0162] 9,9-dialkoxy-2-nonanol compounds, such as 9,9-dimethoxy-2-nonanol, 9,9-diethoxy-2-nonanol, 9,9-dipropoxy-2-nonanol, 9,9-dibutoxy-2-nonanol, 9,9-dipentyloxy-2-nonanol, 9,9-dihexyloxy-2-nonanol, 9,9-diheptyloxy-2-nonanol, 9,9-dioctyloxy-2-nonanol, 9,9-dinonyloxy-2-nonanol, 9,9-didecyloxy-2-nonanol, α-methyl-1,3-dioxolane-2-heptanol, and α-methyl-1,3-dioxane-2-heptanol.

[0163] Examples of the dialkoxyalkanol compound (9B) include the following compounds:

[0164] 10,10-Dialkoxy-3-decanol compounds, such as 10,10-dimethoxy-3-decanol, 10,10-diethoxy-3-decanol, 10,10-dipropoxy-3-decanol, 10,10-dibutoxy-3-decanol, 10,10-dipentyloxy-3-decanol, 10,10-dihexyloxy-3-decanol, 10,10-diheptyloxy-3-decanol, 10,10-dioctyloxy-3-decanol, 10,10-dinonyloxy-3-decanol, 10,10-didecyloxy-3-decanol, α-ethyl-1,3-dioxolane-2-heptanol, and α-ethyl-1,3-dioxane-2-heptanol.

[0165] (b) The process for preparing the above-mentioned dialkoxyalkanol compound (9) will be described in detail below.

[0166] The dialkoxyalkanol compound (9) can be prepared from the above-mentioned nucleophilic reagent 6,6-dialkoxyhexyl compound (7), as shown in the following chemical reaction formula:

[0167]

[0168] The preparation method comprises at least the step of subjecting a nucleophilic 6,6-dialkoxyhexyl compound (7) to a nucleophilic addition reaction with propylene oxide of the above general formula (8) or 1,2-butylene oxide of the above general formula (10) to form a dialkoxyalkanol compound (9A) or (9B), respectively.

[0169] In the above nucleophilic addition reaction, the nucleophilic agent 6,6-dialkoxyhexyl compound (7) may be used alone or in combination, if necessary.

[0170] Propylene oxide (8) and 1,2-butylene oxide (10) are both commercially available or can be synthesized by oneself.

[0171] In the nucleophilic addition reaction, the amount of the nucleophilic 6,6-dialkoxyhexyl compound (7) used is preferably 0.6 to 1.3 mol per mol of propylene oxide (8) or 1,2-butylene oxide (10). By using the preferred amount, preferred economy can be ensured.

[0172] If desired, a solvent may be incorporated into the nucleophilic addition reaction.

[0173] Examples of the solvent include general solvents, such as ether solvents such as tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), diethyl ether, butyl ether, 4-methyltetrahydropyran (MTHP), cyclopentyl methyl ether 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 acid triamide (HMPA), dichloromethane and chloroform. Preferred hydrocarbon solvents include toluene and xylene; ether solvents such as tetrahydrofuran, 2-methyltetrahydrofuran and 4-methyltetrahydropyran; and acetonitrile. By using the hydrocarbon solvents such as toluene and xylene; ether solvents such as tetrahydrofuran, 2-methyltetrahydrofuran and 4-methyltetrahydropyran; and acetonitrile, preferred reactivity can be ensured. Tetrahydrofuran, 2-methyltetrahydrofuran, toluene and xylene are more preferred. By using the tetrahydrofuran, 2-methyltetrahydrofuran, toluene and xylene, more preferred reactivity can be ensured.

[0174] If necessary, solvents may be used alone or in combination. The solvent may be a commercially available solvent.

[0175] The amount of the solvent used is preferably 30 to 5000 g, more preferably 50 to 3000 g, per mol of the nucleophilic 6,6-dialkoxyhexyl compound (7). By using the preferred amount and the more preferred amount, preferred reactivity and more preferred reactivity can be ensured.

[0176] If necessary, the nucleophilic addition reaction can be carried out in the presence of a catalyst. Examples of catalysts 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 the cuprous halides, preferred reactivity can be ensured. More preferred is cuprous chloride. By using the cuprous chloride, more preferred reactivity can be ensured.

[0177] If necessary, a catalyst may be used alone or in combination. The catalyst may be a commercially available catalyst.

[0178] The amount of the catalyst used is preferably 0.0001 to 0.300 mol, more preferably 0.0003 to 0.100 mol, per mol of the nucleophilic 6,6-dialkoxyhexyl compound (7). By using the preferred amount and the more preferred amount, a preferred reaction rate and / or post-treatment and a more preferred reaction rate and / or post-treatment can be ensured.

[0179] When the nucleophilic addition reaction is carried out in the presence of a catalyst, a cocatalyst may be used if necessary. Examples of cocatalysts include phosphorus compounds, such as trialkyl phosphites having 3 to 9 carbon atoms, such as triethyl phosphite; and triaryl phosphine compounds having 18 to 21 carbon atoms, such as triphenylphosphine. Trialkyl phosphites having 3 to 9 carbon atoms that are preferably liquid at room temperature are used. By using the trialkyl phosphites having 3 to 9 carbon atoms, preferred treatment can be ensured.

[0180] If necessary, a co-catalyst may be used alone or in combination. The co-catalyst may be a commercially available co-catalyst.

[0181] When a co-catalyst is used, the amount of the co-catalyst used is preferably greater than 0 to 0.500 mol, more preferably greater than 0 to 0.200 mol, per mol of the nucleophilic 6,6-dialkoxyhexyl compound (7). By using the preferred amount and the more preferred amount, preferred reactivity and more preferred reactivity can be ensured.

[0182] When the nucleophilic addition reaction is carried out in the presence of a catalyst, a lithium halide may be added, if necessary.

[0183] Examples of lithium halides include lithium chloride, lithium bromide, and lithium iodide. Lithium chloride is preferred. By using the lithium chloride, preferred reactivity can be ensured.

[0184] If necessary, lithium halides may be used alone or in combination. The lithium halide may be a commercially available lithium halide.

[0185] When lithium halide is used, the amount of lithium halide used is preferably greater than 0 to 0.250 mol per mol of the nucleophilic 6,6-dialkoxyhexyl compound (7). By using the preferred amount, preferred reactivity can be ensured.

[0186] The reaction temperature of the nucleophilic addition reaction varies depending on the nucleophilic 6,6-dialkoxyhexyl compound (7) used, and is preferably -78 to 70° C., more preferably -20 to 50° C., and even more preferably 5 to 35° C. By using the preferred reaction temperature, the more preferred reaction temperature, and the even more preferred reaction temperature, preferred reactivity, more preferred reactivity, and even more preferred reactivity can be ensured.

[0187] The reaction time of the nucleophilic addition reaction varies depending on the solvent used and / or the production scale, and is preferably 0.5 to 100 hours. By using the preferred reaction time, preferred reactivity can be ensured.

[0188] (iii) The above-mentioned dialkoxyacyloxyalkane compound (5) and a method for preparing the above-mentioned dialkoxyacyloxyalkane compound (5)

[0189] (a) The dialkoxyacyloxyalkane compound (5) is represented by the following general formula (5):

[0190]

[0191] In the above general formula (5), R 3 and R 4 As defined in general formula (7), and n and R 1 As defined by general formula (1).

[0192] In the present specification, when n is 0, the symbol 9,9-dialkoxy-2-acyloxynonane compound (5: n = 0) or 9,9-dialkoxy-2-acyloxynonane compound (5A) is used, and when n is 1, the symbol 10,10-dialkoxy-3-acyloxydecane compound (5: n = 1) or 10,10-dialkoxy-3-acyloxydecane compound (5B) is used.

[0193] As specific examples of the dialkoxyacyloxyalkane compound (5), a 9,9-dialkoxy-2-acyloxynonane compound (5A) and a 10,10-dialkoxy-3-acyloxydecane compound (5B) will be described below.

[0194] Examples of the 9,9-dialkoxy-2-acyloxynonane compound (5A) include the following compounds:

[0195] 9,9-dialkoxy-2-acetoxynonane compounds such as 9,9-dimethoxy-2-acetoxynonane, 9,9-diethoxy-2-acetoxynonane, 9,9-dipropoxy-2-acetoxynonane, 9,9-dibutoxy-2-acetoxynonane, 9,9-dipentyloxy-2-acetoxynonane, 9,9-dihexyloxy-2-acetoxynonane, 9,9-diheptyloxy-2-acetyloxynonane, 9,9-dioctyloxy-2-acetyloxynonane, 9,9-dinonyloxy-2-acetyloxynonane, 9,9-didecyloxy-2-acetyloxynonane, α-methyl-1,3-dioxolane-2-heptyl acetate, and α-methyl-1,3-dioxolane-2-heptyl acetate;

[0196] 9,9-dialkoxy-2-pivaloyloxynonane compounds, such as 9,9-dimethoxy-2-pivaloyloxynonane, 9,9-diethoxy-2-pivaloyloxynonane, 9,9-dipropoxy-2-pivaloyloxynonane, 9,9-dibutoxy-2-pivaloyloxynonane, 9,9-dipentyloxy-2-pivaloyloxynonane, 9,9-dihexyloxy-2-pivaloyloxynonane, 9,9-diheptyloxy-2-pivaloyloxynonane, 9,9-dioctyloxy-2-pivaloyloxynonane, 9,9-dinonyloxy-2-pivaloyloxynonane, and 9,9-didecyloxy-2-pivaloyloxynonane; and

[0197] 9,9-Dialkoxy-2-benzyloxynonane compounds, such as 9,9-dimethoxy-2-benzyloxynonane, 9,9-diethoxy-2-benzyloxynonane, 9,9-dipropoxy-2-benzyloxynonane, 9,9-dibutoxy-2-benzyloxynonane, 9,9-dipentyloxy-2-benzyloxynonane, 9,9-dihexyloxy-2-benzyloxynonane, 9,9-diheptyloxy-2-benzyloxynonane, 9,9-dioctyloxy-2-benzyloxynonane, 9,9-dinonyloxy-2-benzyloxynonane, and 9,9-didecyloxy-2-benzyloxynonane.

[0198] Examples of the 10,10-dialkoxy-3-acyloxydecane compound (5B) include the following compounds:

[0199] 10,10-dialkoxy-3-acetoxydecane compounds, such as 10,10-dimethoxy-3-acetoxydecane, 10,10-diethoxy-3-acetoxydecane, 10,10-dipropoxy-3-acetoxydecane, 10,10-dibutoxy-3-acetoxydecane, 10,10-dipentyloxy-3-acetoxydecane, 10,10-dihexyloxy-3-acetoxydecane, 10,10-diheptyloxy-3-acetyloxydecane, 10,10-dioctyloxy-3-acetyloxydecane, 10,10-dinonyloxy-3-acetyloxydecane, 10,10-didecyloxy-3-acetyloxydecane, α-ethyl-1,3-dioxolane-2-heptyl acetate, and α-ethyl-1,3-dioxolane-2-heptyl acetate;

[0200] 10,10-dialkoxy-3-pivaloyloxydecane compounds, such as 10,10-dimethoxy-3-pivaloyloxydecane, 10,10-diethoxy-3-pivaloyloxydecane, 10,10-dipropoxy-3-pivaloyloxydecane, 10,10-dibutoxy-3-pivaloyloxydecane, 10,10-dipentyloxy-3-pivaloyloxydecane, 10,10-dihexyloxy-3-pivaloyloxydecane, 10,10-diheptyloxy-3-pivaloyloxydecane, 10,10-dioctyloxy-3-pivaloyloxydecane, 10,10-dinonyloxy-3-pivaloyloxydecane, and 10,10-didecyloxy-3-pivaloyloxydecane; and

[0201] 10,10-Dialkoxy-3-benzyloxydecane compounds, such as 10,10-dimethoxy-3-benzyloxydecane, 10,10-diethoxy-3-benzyloxydecane, 10,10-dipropoxy-3-benzyloxydecane, 10,10-dibutoxy-3-benzyloxydecane, 10,10-dipentyloxy-3-benzyloxydecane, 10,10-dihexyloxy-3-benzyloxydecane, 10,10-diheptyloxy-3-benzyloxydecane, 10,10-dioctyloxy-3-benzyloxydecane, 10,10-dinonyloxy-3-benzyloxydecane, and 10,10-didecyloxy-3-benzyloxydecane.

[0202] (b) The process for preparing the above-mentioned dialkoxyacyloxyalkane compound (5) will be described in detail below.

[0203] For example, the dialkoxy acyloxy alkane compound (5) can be prepared from the dialkoxy alkanol compound (9) as shown in the following chemical reaction formula:

[0204]

[0205] In the above general formula (5), R 3 and R4 As defined in general formula (7), and n and R 1 As defined by general formula (1).

[0206] The production method comprises the step of subjecting a dialkoxyalkanol compound (9) to acylation.

[0207] Acylation can be performed, for example, by acylating the hydroxyl group of the dialkoxyalkanol compound (9) with an acylating agent.

[0208] Examples of the acylating agent include the following compounds:

[0209] Carboxylic acids, such as acetic acid, propionic acid, butyric acid, pivalic acid, and benzoic acid;

[0210] anhydrides, such as acetic anhydride, pivalic anhydride, and benzoic anhydride;

[0211] Acyl halide compounds such as acetyl chloride, acetyl bromide, acetyl iodide, propionyl chloride, propionyl bromide, propionyl iodide, butyryl chloride, butyryl bromide, butyryl iodide, pivaloyl chloride, pivaloyl bromide, pivaloyl iodide, benzoyl chloride, benzoyl bromide and benzoyl iodide;

[0212] Alkanoate compounds such as methyl acetate, ethyl acetate, methyl propionate, ethyl propionate, methyl butyrate, ethyl butyrate, methyl pivalate, and ethyl pivalate; and

[0213] Paraben compounds, such as methyl paraben and ethyl paraben.

[0214] The acylating agent is preferably an acid anhydride and an acid halide. By using the acid anhydride and the acid halide, a preferred reactivity can be ensured. An acid anhydride is more preferred. By using the acid anhydride, a more preferred reactivity can be ensured.

[0215] The amount of the acylating agent used is preferably 1.0 to 10.0 mol, more preferably 1.0 to 5.0 mol, per mol of the dialkoxyalkanol compound (9). By using the preferred amount and the more preferred amount, preferred reactivity and / or economy and more preferred reactivity and / or economy can be ensured.

[0216] If necessary, an acid or a base may be added in the acylation.

[0217] Examples of the acid include inorganic acids such as hydrochloric acid, sulfuric acid and nitric acid; aromatic sulfonic acids such as benzenesulfonic acid and p-toluenesulfonic acid; and Lewis acids such as aluminum trichloride, aluminum ethoxide, aluminum isopropoxide, aluminum oxide, boron trifluoride, boron trichloride, boron tribromide, magnesium chloride, magnesium bromide, magnesium iodide, zinc chloride, zinc bromide, zinc iodide, tin tetrachloride, tin tetrabromide, dibutyltin dichloride, dibutyltin dimethoxide, dibutyltin oxide, titanium tetrachloride, titanium tetrabromide, titanium (IV) methoxide, titanium (IV) ethoxide, titanium (IV) isopropoxide and titanium (IV) oxide.

[0218] If desired, the acids may be used alone or in combination.

[0219] When an acid is used, the amount of the acid used is preferably greater than 0 to 3.00 mol, more preferably greater than 0 to 1.50 mol, per mol of the dialkoxyalkanol compound (9). By using the preferred amount and the more preferred amount, preferred reactivity and / or economy and more preferred reactivity and / or economy can be ensured.

[0220] Examples of the base include the following compounds:

[0221] trialkylamine compounds, such as trimethylamine, triethylamine and N,N-diisopropylethylamine;

[0222] Cyclic amine compounds, such as piperidine, pyrrolidine, and 1,8-diazabicyclo[5.4.0]-7-undecene (DBU);

[0223] Aromatic amine compounds, such as pyridine, lutidine, N,N-dimethylaniline, N,N-diethylaniline, N,N-dibutylaniline and 4-dimethylaminopyridine;

[0224] Metal alkoxides, such as sodium methoxide, sodium ethoxide, sodium tert-butoxide, sodium tert-amylate, lithium methoxide, lithium ethoxide, lithium tert-butoxide, lithium tert-amylate, potassium methoxide, potassium ethoxide, potassium tert-butoxide, and potassium tert-amylate;

[0225] Alkyl lithiums, such as methyl lithium, ethyl lithium, propyl lithium, n-butyl lithium, sec-butyl lithium, tert-butyl lithium, pentyl lithium, hexyl lithium, heptyl lithium, octyl lithium, nonyl lithium and decyl lithium;

[0226] Grignard reagents such as methylmagnesium chloride, methylmagnesium bromide, methylmagnesium iodide, ethylmagnesium chloride, ethylmagnesium bromide, ethylmagnesium iodide, propylmagnesium chloride, propylmagnesium bromide, propylmagnesium iodide, butylmagnesium chloride, butylmagnesium bromide, butylmagnesium iodide, pentylmagnesium chloride, pentylmagnesium bromide, pentylmagnesium iodide, hexylmagnesium chloride, hexylmagnesium bromide, hexylmagnesium iodide, heptylmagnesium chloride, heptylmagnesium bromide, heptylmagnesium iodide, octylmagnesium chloride, octylmagnesium bromide, octylmagnesium iodide, nonylmagnesium chloride, nonylmagnesium bromide, nonylmagnesium iodide, decylmagnesium chloride, decylmagnesium bromide, and decylmagnesium iodide; and

[0227] Metal acetylides, such as lithium acetylide, sodium acetylide, potassium acetylide, calcium acetylide, and silver acetylide.

[0228] If necessary, a base may be used alone or in combination.

[0229] When a base is used, the amount of the base used is preferably greater than 0 to 10.0 mol, more preferably greater than 0 to 5.0 mol, per mol of the dialkoxyalkanol compound (9). By using the preferred amount and the more preferred amount, preferred reactivity and / or economy and more preferred reactivity and / or economy can be ensured.

[0230] If necessary, a solvent may be incorporated in the acylation.

[0231] Examples of solvents include general solvents, such as ether solvents such as tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), ether, butyl ether, 4-methyltetrahydropyran (MTHP), cyclopentyl methyl ether 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, dichloromethane, chloroform and hexamethylphosphoric acid triamide (HMPA). Preferred ether solvents include tetrahydrofuran, 2-methyltetrahydrofuran and 4-methyltetrahydropyran; and hydrocarbon solvents such as toluene and xylene. Preferable reactivity can be ensured by using the ether solvents such as tetrahydrofuran, 2-methyltetrahydrofuran and 4-methyltetrahydropyran; and hydrocarbon solvents such as toluene and xylene.

[0232] If necessary, solvents may be used alone or in combination. The solvent may be a commercially available solvent.

[0233] If desired, a solvent may be incorporated in the acylation, or the acylation may be carried out in the absence of a solvent.

[0234] The amount of the solvent used in the acylation is preferably more than 0 to 5000 g, more preferably more than 0 to 2000 g, per mol of the dialkoxyalkanol compound (9). By using the preferred amount and the more preferred amount, preferred reactivity and more preferred reactivity can be ensured.

[0235] The reaction temperature of acylation varies depending on the acylating agent and / or solvent used, and is preferably -40 to 120° C., more preferably -20 to 100° C., and even more preferably 0 to 80° C. By using the preferred reaction temperature, the more preferred reaction temperature, and the even more preferred reaction temperature, preferred reactivity, more preferred reactivity, and even more preferred reactivity can be ensured.

[0236] The reaction time of the acylation is preferably 0.5 to 100 hours. By using the preferred reaction time, preferred reactivity can be ensured.

[0237] In the preparation of the dialkoxyalkanol compound (9) and the dialkoxyacyloxyalkane compound (5), the nucleophilic substitution reaction and the acylation may be carried out separately, or the acylation may be carried out continuously after the nucleophilic substitution reaction (see Examples 3 and 4 below). The continuous reaction is more preferred. By carrying out the continuous reaction, more preferred solvent saving and / or reaction time reduction can be ensured.

[0238] (iv) The above-mentioned 8-(acyloxy)alkanal compound (1) and a method for preparing the above-mentioned 8-(acyloxy)alkanal compound (1)

[0239] (a) The 8-(Acyloxy)alkanal compound (1) is as mentioned above.

[0240] (b) The process for preparing the 8-(acyloxy)alkanal compound (1) will be described in detail below.

[0241] The 8-(acyloxy)alkanal compound (1) can be prepared from the above-mentioned dialkoxyacyloxyalkane compound (5) as shown in the following chemical reaction formula:

[0242]

[0243] The method for preparing the 8-(acyloxy)alkanal compound (1) comprises the step of subjecting a dialkoxyacyloxyalkane compound (5) to a hydrolysis reaction.

[0244] In the above hydrolysis reaction, dialkoxyacyloxyalkane compounds (5) may be used alone or in combination, if necessary.

[0245] For example, the hydrolysis reaction can be carried out using an acid and water.

[0246] Examples of the acid include inorganic acids such as hydrochloric acid and hydrobromic acid; and p-toluenesulfonic acid, benzenesulfonic acid, trifluoroacetic acid, acetic acid, formic acid, oxalic acid, iodotrimethylsilane and titanium tetrachloride. Preferred are acetic acid, formic acid, oxalic acid, p-toluenesulfonic acid and benzenesulfonic acid. By using the acetic acid, formic acid, oxalic acid, p-toluenesulfonic acid and benzenesulfonic acid, preferred reactivity can be ensured. More preferred are p-toluenesulfonic acid and benzenesulfonic acid. By using the p-toluenesulfonic acid and benzenesulfonic acid, more preferred reaction yield can be ensured.

[0247] If necessary, an acid may be used alone or in combination. The acid may be a commercially available acid.

[0248] The amount of the acid to be used is preferably 0.01 to 10.0 mol per mol of the dialkoxyacyloxyalkane compound (5).

[0249] The amount of water used is preferably 18 to 7000 g, and more preferably 18 to 3000 g, per mol of the dialkoxyacyloxyalkane compound (5). By using the preferred amount and the more preferred amount, preferred reactivity and more preferred reactivity can be ensured.

[0250] If desired, a solvent other than acid or water may be incorporated into the hydrolysis reaction.

[0251] Examples of the solvent include general solvents, for example, ether solvents such as tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), diethyl ether, butyl ether, 4-methyltetrahydropyran (MTHP), cyclopentyl methyl ether 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 acid triamide (HMPA), dichloromethane and chloroform; ester solvents such as methyl acetate, ethyl acetate, n-propyl acetate and n-butyl acetate; and alcohol solvents such as methanol and ethanol.

[0252] If necessary, solvents may be used alone or in combination. The solvent may be a commercially available solvent.

[0253] The optimal solvent varies depending on the acid used. For example, when oxalic acid is used as the acid, tetrahydrofuran, 2-methyltetrahydrofuran, acetone and γ-butyrolactone are preferred. By using the tetrahydrofuran, 2-methyltetrahydrofuran, acetone and γ-butyrolactone, preferred reactivity can be ensured. When p-toluenesulfonic acid or benzenesulfonic acid is used as the acid, hydrocarbon solvents such as toluene and xylene; and alcohol solvents such as methanol and ethanol are preferred. By using the hydrocarbon solvents such as toluene and xylene; and alcohol solvents such as methanol and ethanol, preferred reactivity can be ensured.

[0254] The amount of the solvent used is preferably greater than 0 to 7000 g, more preferably greater than 0 to 3000 g, per mol of the dialkoxyacyloxyalkane compound (5). By using the preferred amount and the more preferred amount, preferred reactivity and more preferred reactivity can be ensured.

[0255] The reaction temperature of the hydrolysis reaction varies depending on the acid and / or solvent used, and is preferably -15 to 180° C., more preferably 5 to 120° C. By using the preferred reaction temperature and the more preferred reaction temperature, preferred reactivity and more preferred reactivity can be ensured.

[0256] The reaction time of the hydrolysis reaction varies depending on the acid and solvent used and / or the production scale, and is preferably 0.5 to 100 hours. By using the preferred reaction time, preferred reactivity can be ensured.

[0257] Thus, a synthetic intermediate 8-(acyloxy)alkanal compound (1) useful in the preparation of 2,9-diacetoxyundecane of the following general formula (4) can be prepared.

[0258]

[0259] However, initially, efforts have been made to use an 8-hydroxyalkanal compound, i.e., an 8-(acyloxy)alkanal compound (1) in which the hydroxyl group is not protected by an acyl group, as an intermediate for preparing 2,9-diacetoxyundecane (4) (see formula (11) of Comparative Example 1 below), rather than the above-mentioned 8-(acyloxy)alkanal compound (1), because it is considered meaningless to protect the hydroxyl group only once with an acyl group and then eliminate the acyl group to release the hydroxyl group. However, it is clear that the reaction of the hydroxyl group and the formyl group greatly reduces the yield when synthesizing the 8-hydroxyalkanal compound (11) (see Comparative Example 1 below). Therefore, although this seems to be a roundabout technique, it has been shown that obtaining an aldehyde by hydrolyzing the acetal in a hydroxyl-protected state is extremely important from the perspective of yield.

[0260] III. Method for preparing 2,9-diacetoxyundecane

[0261] The target compound 2,9-diacetoxyundecane (4) of the present invention can be prepared, for example, from the above-mentioned 8-(acyloxy)alkanal compound (1), as shown in the following chemical reaction formula:

[0262]

[0263] Specifically, 2,9-diacetoxyundecane (4) can be prepared by (i) subjecting an 8-(acyloxy)alkanal compound (1) to a nucleophilic addition reaction with a nucleophilic alkyl compound (2), undergoing nucleophilic addition with a formyl group and eliminating the acyl group to form 2,9-undecanediol (3), followed by (ii) acetylation of the 2,9-undecanediol (3).

[0264] (i) Method for preparing the above-mentioned 2,9-undecanediol (3)

[0265] (a) The preparation method of 2,9-undecanediol (3) will be described in detail below.

[0266] 2,9-Undecanediol (3) can be prepared from the above 8-(acyloxy)alkanal compound (1) as shown in the following chemical reaction formula:

[0267]

[0268] The preparation method comprises the step of subjecting the 8-(acyloxy)alkanal compound (1) to a nucleophilic addition reaction with a nucleophilic alkyl compound of the above general formula (2).

[0269] The nucleophilic alkyl compound (2) will be described in detail below.

[0270] In the general formula (2), M 1 Indicates Li, MgZ 1 ,CuZ 1 or CuLiZ 1 , Z 1 represents a halogen atom, a methyl group or an ethyl group, and n is as defined in the above general formula (1).

[0271] Specific examples of the nucleophilic alkyl compound (2) include the following compounds:

[0272] Alkyl lithium compounds (when M 1 =Li), such as methyllithium and ethyllithium;

[0273] Alkyl magnesium halide compound (when M 1 =MgZ 1 ), such as methylmagnesium chloride, methylmagnesium bromide, methylmagnesium iodide, ethylmagnesium chloride, ethylmagnesium bromide, and ethylmagnesium iodide (i.e., Grignard reagents);

[0274] Dialkyl cuprate compound (when M 1 =CuZ 1 ), such as dimethyl cuprate and diethyl cuprate; and

[0275] Gilman reagent (when M 1 =CuLiZ 1 ), such as lithium dialkyl cuprate compounds, such as lithium dimethyl cuprate and lithium diethyl cuprate (i.e., Gilman reagent)

[0276] In the above nucleophilic addition reaction, a nucleophilic agent alkyl compound (2) may be used alone or in combination, if necessary.

[0277] In the nucleophilic addition reaction, the amount of the nucleophilic agent alkyl compound (2) used is preferably 3.0 to 15.0 mol, more preferably 3.0 to 10.0 mol, and even more preferably 3.1 to 6.0 mol per mol of the 8-(acyloxy)alkanal compound (1). By using the preferred amount, the more preferred amount, and the even more preferred amount, preferred reactivity, more preferred reactivity, and even more preferred reactivity can be ensured.

[0278] If desired, a solvent may be incorporated into the nucleophilic addition reaction.

[0279] Examples of the solvent include general solvents, such as ether solvents such as tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), diethyl ether, butyl ether, 4-methyltetrahydropyran (MTHP), cyclopentyl methyl ether 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 acid triamide (HMPA), dichloromethane and chloroform. Preferred hydrocarbon solvents include toluene and xylene; ether solvents such as tetrahydrofuran, 2-methyltetrahydrofuran and 4-methyltetrahydropyran; and acetonitrile. By using the hydrocarbon solvents such as toluene and xylene; ether solvents such as tetrahydrofuran, 2-methyltetrahydrofuran and 4-methyltetrahydropyran; and acetonitrile, preferred reactivity can be ensured. Tetrahydrofuran, 2-methyltetrahydrofuran, toluene and xylene are more preferred. By using the tetrahydrofuran, 2-methyltetrahydrofuran, toluene and xylene, more preferred reactivity can be ensured.

[0280] If necessary, solvents may be used alone or in combination. The solvent may be a commercially available solvent.

[0281] The amount of the solvent used is preferably 30 to 5000 g, more preferably 50 to 3000 g, per mol of the above 8-(acyloxy)alkanal compound (1). By using the preferred amount and the more preferred amount, preferred reactivity and more preferred reactivity can be ensured.

[0282] The reaction temperature of the nucleophilic addition reaction varies depending on the 8-(acyloxy)alkanal compound (1) used, and is preferably -78 to 150° C., more preferably -20 to 100° C., and even more preferably 20 to 70° C. By using the preferred reaction temperature, the more preferred reaction temperature, and the even more preferred reaction temperature, preferred reactivity, more preferred reactivity, and even more preferred reactivity can be ensured.

[0283] The reaction time of the nucleophilic addition reaction varies depending on the solvent used and / or the production scale, and is preferably 0.5 to 100 hours. By using the preferred reaction time, preferred reactivity can be ensured.

[0284] (ii) Method for preparing the above-mentioned 2,9-diacetoxyundecane (4)

[0285] (a) A method for preparing 2,9-diacetoxyundecane (4) will be described in detail below. 2,9-diacetoxyundecane (4) can be prepared from the above-mentioned 2,9-undecanediol (3).

[0286]

[0287] The preparation method comprises the step of subjecting 2,9-undecanediol (3) to an acetylation reaction.

[0288] For example, the acetylation reaction can be performed by acetylation of the hydroxyl group of 2,9-undecanediol (3) with an acetylating agent.

[0289] Examples of acetylating agents include the following compounds:

[0290] acetic acid;

[0291] Acid anhydrides, such as acetic anhydride;

[0292] Acetyl halide compounds such as acetyl chloride, acetyl bromide and acetyl iodide; and

[0293] Acetate compounds such as methyl acetate, ethyl acetate, propyl acetate, butyl acetate, pentyl acetate and hexyl acetate.

[0294] The acetylating agent is preferably an acid anhydride and an acetyl halide compound. By using the acid anhydride and the acetyl halide compound, preferred reactivity can be ensured. The acetylating agent is more preferably an acid anhydride. By using the acid anhydride, preferred reactivity can be ensured.

[0295] The amount of the acetylating agent used is preferably 2.0 to 15.0 mol, more preferably 2.0 to 10.0 mol, and even more preferably 2.1 to 8.0 mol per mol of 2,9-undecanediol (3). By using the preferred amount, the more preferred amount, and the even more preferred amount, preferred reactivity and / or economy, more preferred reactivity and / or economy, and even more preferred reactivity and / or economy can be ensured.

[0296] If desired, an acid or a base may be added during the acetylation.

[0297] Examples of the acid include inorganic acids such as hydrochloric acid, sulfuric acid and nitric acid; aromatic sulfonic acids such as benzenesulfonic acid and p-toluenesulfonic acid; and Lewis acids such as aluminum trichloride, aluminum ethoxide, aluminum isopropoxide, aluminum oxide, boron trifluoride, boron trichloride, boron tribromide, magnesium chloride, magnesium bromide, magnesium iodide, zinc chloride, zinc bromide, zinc iodide, tin tetrachloride, tin tetrabromide, dibutyltin dichloride, dibutyltin dimethoxide, dibutyltin oxide, titanium tetrachloride, titanium tetrabromide, titanium (IV) methoxide, titanium (IV) ethoxide, titanium (IV) isopropoxide and titanium (IV) oxide.

[0298] If desired, the acids may be used alone or in combination.

[0299] When an acid is used, the amount of the acid used is preferably greater than 0 to 3.00 mol, more preferably greater than 0 to 1.50 mol, per mol of 2,9-undecanediol (3). By using the preferred amount and the more preferred amount, preferred reactivity and / or economy and more preferred reactivity and / or economy can be ensured.

[0300] Examples of the base include the following compounds:

[0301] trialkylamine compounds, such as trimethylamine, triethylamine and N,N-diisopropylethylamine;

[0302] Cyclic amine compounds, such as piperidine, pyrrolidine, and 1,8-diazabicyclo[5.4.0]-7-undecene (DBU);

[0303] Aromatic amine compounds, such as pyridine, lutidine, N,N-dimethylaniline, N,N-diethylaniline, N,N-dibutylaniline and 4-dimethylaminopyridine;

[0304] Metal alkoxides, such as sodium methoxide, sodium ethoxide, sodium tert-butoxide, sodium tert-amylate, lithium methoxide, lithium ethoxide, lithium tert-butoxide, lithium tert-amylate, potassium methoxide, potassium ethoxide, potassium tert-butoxide, and potassium tert-amylate;

[0305] Alkyl lithiums, such as methyl lithium, ethyl lithium, propyl lithium, n-butyl lithium, sec-butyl lithium, tert-butyl lithium, pentyl lithium, hexyl lithium, heptyl lithium, octyl lithium, nonyl lithium and decyl lithium;

[0306] Grignard reagents such as methylmagnesium chloride, methylmagnesium bromide, methylmagnesium iodide, ethylmagnesium chloride, ethylmagnesium bromide, ethylmagnesium iodide, propylmagnesium chloride, propylmagnesium bromide, propylmagnesium iodide, butylmagnesium chloride, butylmagnesium bromide, butylmagnesium iodide, pentylmagnesium chloride, pentylmagnesium bromide, pentylmagnesium iodide, hexylmagnesium chloride, hexylmagnesium bromide, hexylmagnesium iodide, heptylmagnesium chloride, heptylmagnesium bromide, heptylmagnesium iodide, octylmagnesium chloride, octylmagnesium bromide, octylmagnesium iodide, nonylmagnesium chloride, nonylmagnesium bromide, nonylmagnesium iodide, decylmagnesium chloride, decylmagnesium bromide and decylmagnesium iodide;

[0307] Metal acetylides, such as lithium acetylide, sodium acetylide, potassium acetylide, calcium acetylide, and silver acetylide; and

[0308] Inorganic metal salts, such as potassium carbonate, sodium carbonate and calcium carbonate.

[0309] If necessary, a base may be used alone or in combination.

[0310] When a base is used, the amount of the base used is preferably greater than 0 to 10.0 mol, more preferably greater than 0 to 5.0 mol, per mol of the dialkoxyalkanol compound (9). By using the preferred amount and the more preferred amount, preferred reactivity and / or economy and more preferred reactivity and / or economy can be ensured.

[0311] If desired, a common solvent may be incorporated into the acetylation.

[0312] Examples of solvents include ether solvents such as tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), ether, butyl ether, 4-methyltetrahydropyran (MTHP), cyclopentyl methyl ether 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, acetonitrile, dichloromethane, chloroform and hexamethylphosphoric acid triamide (HMPA). Preferred ether solvents are tetrahydrofuran, 2-methyltetrahydrofuran and 4-methyltetrahydropyran; and hydrocarbon solvents such as toluene and xylene. By using the ether solvents such as tetrahydrofuran, 2-methyltetrahydrofuran and 4-methyltetrahydropyran; and hydrocarbon solvents such as toluene and xylene, preferred reactivity can be ensured.

[0313] If necessary, solvents may be used alone or in combination. The solvent may be a commercially available solvent.

[0314] If desired, a solvent may be incorporated into the acetylation, or the acetylation may be carried out in the absence of a solvent.

[0315] The amount of the solvent used in the acetylation is preferably greater than 0 to 5000 g, more preferably greater than 0 to 2000 g, per mol of the above 2,9-undecanediol (3). By using the preferred amount and the more preferred amount, preferred reactivity and more preferred reactivity can be ensured.

[0316] The reaction temperature of acetylation varies depending on the acetylating agent and / or solvent used, and is preferably -40 to 100° C., more preferably -20 to 80° C., and even more preferably 0 to 80° C. By using the preferred reaction temperature, the more preferred reaction temperature, and the even more preferred reaction temperature, preferred reactivity, more preferred reactivity, and even more preferred reactivity can be ensured.

[0317] The reaction time of acetylation is preferably 0.5 to 100 hours. By using the preferred reaction time, preferred reactivity can be ensured.

[0318] In the preparation of 2,9-undecanediol (3) and the preparation of 2,9-diacetoxyundecane (4), the nucleophilic substitution reaction and the acetylation reaction may be carried out separately, or the acetylation reaction may be carried out continuously after the nucleophilic substitution reaction (see Examples 7 and 8 below). By carrying out the continuous reaction, solvent saving and / or shortening of the reaction time can be ensured, and since contact with water of the water-soluble 2,9-undecanediol (3) can be avoided, the yield of 2,9-diacetoxyundecane (4) in the two-step process is improved.

[0319] Therefore, according to the present invention, the synthetic intermediate 8-(acyloxy)alkanal compound (1) can be prepared simply and efficiently. According to the present invention, the sex pheromone 2,9-diacetoxyundecane (4) of Swedish midge (scientific name: Contarinianasturtii) can be prepared efficiently, with ease of preparation and fewer steps. Specifically, by continuously performing acylation and acetylation steps, 2,9-diacetoxyundecane (4) can be prepared from a 6-halogeno-1,1-dialkoxyhexane compound (6) in high yield in four steps.

[0320] Example

[0321] The present invention is described with reference to the following examples. It should be construed that the present invention is not limited to or by these examples.

[0322] Unless otherwise indicated, the term "purity" as used herein refers to the area percentage of gas chromatography (GC). The term "product ratio" refers to the ratio of the area percentages of GC. The term "yield" is calculated from the area percentage determined by GC.

[0323] In the embodiment, monitoring reaction and calculating yield are carried out under the following GC conditions:

[0324] 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, increasing at a rate of 5 °C / min, reaching a maximum of 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, increasing at a rate of 5 °C / min, reaching a maximum of 230 °C.

[0325] Taking into account the purity (%GC) of the starting material and the product, the yield was calculated by the following equation.

[0326] Yield (%) = {[(weight of product obtained by reaction×%GC) / molecular weight of product]÷[(weight of starting material in reaction×%GC) / molecular weight of starting material]}×100.

[0327] THF represents tetrahydrofuran, Ph represents a phenyl group, Ts represents a toluenesulfonyl group, Ac represents an acetyl group, Bu represents an n-butyl group, t Bu represents a tert-butyl group, and Et represents an ethyl group.

[0328] Example 1: Preparation of 9,9-diethoxy-2-nonanol (9A:R 3 =R 4 =Et)

[0329]

[0330] Magnesium (89.30 g, 3.68 gram atoms) and tetrahydrofuran (1050.00 g) were placed in a reactor at room temperature and stirred at 60 to 65° C. for 42 minutes. Then 6-chloro-1,1-diethoxyhexane (6:R 3 =R 4 =Et, X = Cl) (744.93 g, 3.50 mol, purity 98.08%) was added dropwise to the reactor at 60 to 75°C. After the addition was completed, the reaction mixture was stirred at 75 to 80°C for 3 hours to form 6,6-diethoxyhexylmagnesium chloride (7:R 3 =R 4 =Et,M 2 =MgCl).

[0331] The internal temperature of the above reactor was then cooled to 0 to 10°C, cuprous chloride (0.73 g, 0.0070 mol) was added to the reactor, and propylene oxide (233.77 g, 4.02 mol) was then added dropwise to the reactor at 5 to 30°C. After the addition was completed, the reaction mixture was stirred at 15 to 25°C for 2.5 hours. An acetic acid aqueous solution (prepared from acetic acid (477.65 g) and water (964.31 g)) was then added to the reaction mixture, followed by phase separation. The organic layer thus obtained was concentrated under reduced pressure, and the resulting concentrate was distilled under reduced pressure to obtain 9,9-diethoxy-2-nonanol (9A:R 3 =R 4 =Et) (727.52 g, 3.06 mol, purity 97.70%, bp = 132.0 to 141.0 ° C / 0.041 kPa (0.31 mmHg)), the yield was 87.39%.

[0332] The following is the 9,9-diethoxy-2-nonanol (9A:R 3 =R 4=Et) spectral data.

[0333] NMR Spectrum: 1 H-NMR (500MHz, CDCl3): δ=1.12-1.23(9H,m),1.23-1.62(13H,m),3.43-3.52(2 H,m),3.56-3.65(2H,m).3.54(1H,dt,J=7.2Hz,7.2Hz),4.45(1H,t,J=5.8Hz); 13 C-NMR (125MHz, CDCl3): δ=15.30,18.36,23.43,24.63,25.63,29.38,33.52,39.27,60.78,68.03,102.89.

[0334] Mass spectrum: EI-mass spectrum (70eV): m / z 231 (M + -1),215,187,169,141,123,103,75,47,29.

[0335] Infrared absorption spectrum: (D-ATR): ν = 3421, 2974, 2930, 2858, 1457, 1374, 1345, 1126, 1062, 996, 944 cm -1

[0336] Example 2: Preparation of 10,10-diethoxy-3-decanol (9B:R 3 =R 4 =Et)

[0337]

[0338] Magnesium (89.30 g, 3.68 gram atoms) and tetrahydrofuran (1050.00 g) were placed in a reactor at room temperature and stirred at 60 to 65° C. for 42 minutes. Then 6-chloro-1,1-diethoxyhexane (6:R 3 =R 4 =Et, X = Cl) (744.93 g, 3.50 mol, purity 98.08%) was added dropwise to the reactor at 60 to 75°C. After the addition was completed, the reaction mixture was stirred at 75 to 80°C for 3 hours to form 6,6-diethoxyhexylmagnesium chloride (7:R 3 =R 4 =Et,M 2 =MgCl).

[0339] The internal temperature of the above reactor was then cooled to 0 to 10°C, cuprous chloride (0.73 g, 0.0070 mol) was added to the reactor, and then 1,2-butylene oxide (290.24 g, 4.02 mol) was added dropwise to the reactor at 5 to 30°C. After the addition was completed, the reaction mixture was stirred at 15 to 25°C for 2.5 hours. An acetic acid aqueous solution (prepared from acetic acid (477.65 g) and water (964.31 g)) was then added to the reaction mixture, followed by phase separation. The organic layer thus obtained was concentrated under reduced pressure, and the resulting concentrate was distilled under reduced pressure to obtain 10,10-diethoxy-3-decanol (9B:R 3 =R 4 =Et) (767.62 g, 3.06 mol, purity 98.21%, bp = 140.0 to 145.6°C / 0.17 kPa (1.3 mmHg)), with a yield of 87.42%.

[0340] The following is the 10,10-diethoxy-3-decanol (9B:R 3 =R 4 =Et) spectral data.

[0341] NMR Spectrum: 1 H-NMR (500MHz, CDCl3): δ = 0.92 (3H, t, J = 7.2Hz), 1.18 (6H, t, J = 7.2Hz), 1.22 (1H, t, J = 7.2Hz), 1.25-1. 62(14H,m),3.42-3.53(2H,m),3.58-3.65(2H,m),3.69(1H,dt,J=6.9Hz,6.9Hz),4.45(1H,t,J=5.8Hz); 13 C-NMR (125MHz, CDCl3): δ=9.09,9.82,15.31,24.65,25.52,29.40,29.58,30.10,33.53,36.86,60.78,102.89.

[0342] Mass spectrum: EI-mass spectrum (70eV): m / z 245 (M + -1),229,201,183,171,155,137,103,75,47,29.

[0343] Infrared absorption spectrum: (D-ATR): ν=3430,2974,2930,2858,1462,1374,1344,1126,1061,999cm -1 .

[0344] Example 3: Preparation of 9,9-diethoxy-2-acetoxynonane (5A:R 3 =R 4 =Et,R 1 =CH3)

[0345]

[0346] Magnesium (89.30 g, 3.68 gram atoms) and tetrahydrofuran (1050.00 g) were placed in a reactor at room temperature and stirred at 60 to 65° C. for 20 minutes. Then 6-chloro-1,1-diethoxyhexane (6:R 3 =R 4 =Et, X = Cl) (744.93 g, 3.50 mol, purity 98.08%) was added dropwise to the reactor at 60 to 75°C. After the addition was completed, the reaction mixture was stirred at 75 to 80°C for 3 hours to form 6,6-diethoxyhexylmagnesium chloride (7:R 3 =R 4 =Et,M 2 =MgCl).

[0347] The internal temperature of the above reactor was then cooled to 0 to 10°C, cuprous chloride (0.73 g, 0.0070 mol) was added to the reactor, and propylene oxide (233.77 g, 4.02 mol) was then added dropwise to the reactor at 5 to 30°C. After the addition was completed, the reaction mixture was stirred at 15 to 25°C for 2 hours. Acetic anhydride (410.91 g, 4.02 mol) was then added dropwise to the reaction mixture at 20 to 60°C and stirred at 30 to 40°C for 1.5 hours. Water (964.31 g) was then added to the reaction mixture, and then phase separation was performed. The organic layer thus obtained was concentrated under reduced pressure, and the resulting concentrate was distilled under reduced pressure to obtain 9,9-diethoxy-2-acetoxynonane (5A:R 3 =R 4 =Et,R 1 =CH3) (874.02 g, 3.11 mol, purity 97.67%, bp = 140.0 to 147.9°C / 0.44 kPa (3.3 mmHg)), with a yield of 88.89%.

[0348] The following is the 9,9-diethoxy-2-acetoxynonane (5A:R 3 =R 4 =Et,R 1 =CH3) spectral data.

[0349] NMR Spectrum: 1H-NMR (500MHz, CDCl3): δ=1.16-1.20(9H,m),1.22-1.36(8H,m),1.39-1.61(4H,m),2.00(3H,s ),3.43-3.50(2H,m),3.58-3.65(2H,m),4.45(1H,t,J=5.7Hz),4.86(1H,tq,J=6.1Hz,6.1Hz); 13 C-NMR (125MHz, CDCl3): δ=15.31,19.90,21.33,24.61,25.26,29.31,33.51,35.84,60.78,70.96,102.87,170.72.

[0350] Mass spectrum: EI-mass spectrum (70eV): m / z 273 (M + -1),229,215,185,169,123,103,75,57,43,29.

[0351] Infrared absorption spectrum: (D-ATR): ν = 2975, 2933, 1860, 1738, 1445, 1373, 1347, 1244, 1127, 1062, 953 cm -1 .

[0352] Example 4: Preparation of 10,10-diethoxy-3-acetoxydecane (5B:R 3 =R 4 =Et,R 1 =CH3)

[0353]

[0354] Magnesium (89.30 g, 3.68 gram atoms) and tetrahydrofuran (1050.00 g) were placed in a reactor at room temperature and stirred at 60 to 65° C. for 20 minutes. Then 6-chloro-1,1-diethoxyhexane (6:R 3 =R 4 =Et, X = Cl) (744.93 g, 3.50 mol, purity 98.08%) was added dropwise to the reactor at 60 to 75°C. After the addition was completed, the reaction mixture was stirred at 75 to 80°C for 3 hours to form 6,6-diethoxyhexylmagnesium chloride (7:R 3 =R 4 =Et,M 2 =MgCl).

[0355] The internal temperature of the above reactor was then cooled to 0 to 10°C, cuprous chloride (0.73 g, 0.0070 mol) was added to the reactor, and 1,2-butylene oxide (290.24 g, 4.02 mol) was then added dropwise to the reactor at 5 to 30°C. After the addition was completed, the reaction mixture was stirred at 15 to 25°C for 2 hours. Acetic anhydride (410.91 g, 4.02 mol) was then added dropwise to the reaction mixture at 20 to 60°C and stirred at 30 to 40°C for 1.5 hours. Water (964.31 g) was then added to the reaction mixture, and then phase separation was performed. The organic layer thus obtained was concentrated under reduced pressure, and the resulting concentrate was distilled under reduced pressure to obtain 10,10-diethoxy-3-acetoxydecane (5B:R 3 =R 4 =Et,R 1 =CH3) (897.83, 3.03 mol, purity 97.24%, bp = 143.0 to 148.1°C / 0.059 kPa (0.44 mmHg)), with a yield of 86.50%.

[0356] The following is the 10,10-diethoxy-3-acetoxydecane (5B:R 3 =R 4 =Et,R 1 =CH3) spectral data.

[0357] NMR Spectrum: 1 H-NMR (500MHz, CDCl3): δ = 0.86 (3H, t, J = 7.3Hz), 1.18 (6H, t, J = 7.3Hz), 1.21-1.37 (8H, m), 1.45-1.62 (6H, m ),2.02(3H,s),3.43-3.51(2H,m),3.58-3.66(2H,m),4.45(1H,t,J=5.7Hz),4.78(1H,tt,J=6.3Hz,6.3Hz); 13 C-NMR (125MHz, CDCl3): δ=9.53,15.31,21.20,24.62,25.19,26.89,29.32,29.41,33.51,60.78,75.45,102.88,170.91.

[0358] Mass spectrum: EI-mass spectrum (70eV): m / z 287 (M + -1),243,229,199,183,137,103,75,57,43,29.

[0359] Infrared absorption spectrum: (D-ATR): ν = 2973, 2933, 2860, 1738, 1461, 1373, 1243, 1127, 1063, 1019, 955 cm -1 .

[0360] Example 5: Preparation of 8-(acetoxy)nonanal (1:R 1 =CH3, n=0)

[0361]

[0362] The 9,9-diethoxy-2-acetoxynonane (5A:R 3 =R 4 =Et,R 1 =CH3) (103.58, 0.37 mol, purity 97.67%), p-toluenesulfonic acid hydrate (0.50 g, 0.0026 mol), water (66.40 g, 3.69 mol) and toluene (40.00 g) were placed in a reactor at room temperature, and ethanol was distilled off at 60 to 70°C. After confirming that the conversion was 99% by GC, the reaction mixture was cooled to 20 to 30°C, and the water layer was removed to obtain an organic layer. The organic layer thus obtained was distilled under reduced pressure to obtain 8-(acetoxy)nonanal (1:R 1 =CH3, n = 0) (67.51 g, 0.33 mol, purity 98.85%, bp = 110.0 to 118.1 ° C / 0.19 kPa (1.4 mmHg)), the yield is 90.38%.

[0363] The following is the 8-(acetoxy)nonanal (1:R 1 =CH3, n=0) spectral data.

[0364] NMR Spectrum: 1 H-NMR (500MHz, CDCl3): δ = 1.17 (3H, d, J = 6.5Hz), 1.22-1.35 (6H, m), 1.40-1.49 (1H, m), 1.50-1.65 (3H ,m),2.01(3H,s),2.40(2H,dt,J=1.9Hz,7.3Hz),4.86(1H,tq,J=6.5Hz,6.5Hz),9.74(1H,t,J=1.9Hz); 13 C-NMR (125MHz, CDCl3): δ = 19.89, 21.32, 21.90, 25.11, 28.96, 29.09, 35.75, 43.79, 70.84, 170.72, 202.70.

[0365] Mass spectrum: EI-mass spectrum (70eV): m / z 201 (M + +1),157,140,122,112,97,81,67,55,43,29.

[0366] Infrared absorption spectrum: (D-ATR): ν = 2977, 2934, 2859, 2719, 1732, 1462, 1373, 1245, 1137, 1022, 952 cm -1 .

[0367] Example 6: Preparation of 8-(acetoxy)decanal (1:R 1 =CH3, n = 1)

[0368]

[0369] The 10,10-diethoxy-3-acetoxydecane (5B:R 3 =R 4 =Et,R 1 =CH3) (109.36 g, 0.37 mol, purity 97.24%), p-toluenesulfonic acid hydrate (0.50 g, 0.0026 mol), water (66.40 g, 3.69 mol) and toluene (40.00 g) were placed in a reactor at room temperature, and ethanol was distilled off at 60 to 70°C. After confirming that the conversion was 99% by GC, the reaction mixture was cooled to 20 to 30°C, and the water layer was removed to obtain an organic layer. The organic layer thus obtained was distilled under reduced pressure to obtain 8-(acetoxy)decanal (1:R 1 =CH3, n = 1) (67.45 g, 0.31 mol, purity 98.11%, bp = 110.0 to 119.1 ° C / 0.19 kPa (1.4 mmHg)), the yield is 83.75%.

[0370] The following is the 8-(acetoxy)decanal (1:R 1 =CH3, n=1) spectrum data.

[0371] NMR Spectrum: 1 H-NMR (500MHz, CDCl3): δ = 0.85 (3H, t, J = 7.3Hz), 1.20-1.35 (6H, m), 1.45-1.66 (6H, m), 2.02 ( 3H, s), 2.40 (2H, dt, J = 1.9Hz, 7.3Hz), 4.77 (1H, quint-like, J = 6.1Hz), 9.74 (1H, t, J = 1.9Hz); 13C-NMR (125MHz, CDCl3): δ = 9.52, 21.18, 21.90, 25.04, 26.89, 28.97, 29.16, 33.44, 43.78, 75.31, 170.91, 202.70.

[0372] Mass spectrum: EI-mass spectrum (70eV): m / z 215 (M + +1),185,171,156,143,125,113,101,81,69,55,43,29.

[0373] Infrared absorption spectrum: (D-ATR): ν = 2968, 2935, 2859, 2719, 1732, 1463, 1373, 1245, 1113, 1020, 956 cm -1 .

[0374] Example 7: Preparation of 2,9-diacetoxyundecane (4)

[0375]

[0376] A tetrahydrofuran solution of methylmagnesium chloride (399.35 g) (containing 1.03 mol of methylmagnesium chloride) was placed in a reactor at 15 to 25° C., and then 8-(acetoxy)decanal (1:R 1 =CH3, n = 1) (67.45g, 0.31mol, purity 98.11%) and stirred at 30 to 40°C for 4 hours. Then, acetic anhydride (111.73g, 1.09mol) was added dropwise at 40 to 60°C and stirred at 30 to 40°C for 2 hours. Then, water (500.00g) was added to the reaction mixture, and then phase separation was performed. The aqueous layer was removed to obtain an organic layer. The organic layer thus obtained was concentrated under reduced pressure, and the resulting concentrate was distilled under reduced pressure to obtain 2,9-diacetoxyundecane (4) (80.73g, 0.28mol, purity 95.01%, bp = 115.6 to 122.1°C / 0.080kPa (0.60mmHg)), and the yield of the two-step method was 90.04%.

[0377] The following are the spectrum data of 2,9-diacetoxyundecane (4) prepared in this way.

[0378] NMR Spectrum: 1H-NMR (500MHz, CDCl3): δ = 0.86 (3H, t, J = 7.3Hz), 1.18 (3H, d, J = 6.5Hz), 1.20-1.33 (8H, m), 1.37-1.6 0(6H,m),2.00(3H,s),2.02(3H,s),4.78(1H,quint-like,J=6.6Hz),4.86(1H,tq,J=6.5Hz,6.5Hz); 13 C-NMR (125MHz, CDCl3): δ=9.53,19.91,21.20,21.33,25.18,25.25,26.90,29.26,29.34,33.50,35.82,70.93,75.40,170.72,170.92.

[0379] Mass spectrum: EI-mass spectrum (70eV): m / z 273 (M + +1),229,215,201,183,169,155,141,123,96,81,67,43,29.

[0380] Infrared absorption spectrum: (D-ATR): νmax = 2971, 2935, 2859, 1737, 1463, 1372, 1244, 1128, 1021, 953 cm -1 .

[0381] Example 8: Preparation of 2,9-diacetoxyundecane (4)

[0382]

[0383] A tetrahydrofuran solution of ethyl magnesium chloride (816.59 g) (containing 1.67 mol of methyl magnesium chloride) was placed in a reactor at 15 to 25° C., and then 8-(acetoxy)nonanal (1:R 1 =CH3, n = 0) (103.32 g, 0.51 mol, purity 98.08%) and stirred at 30 to 40 ° C for 5 hours. Then acetic anhydride (180.80 g, 1.77 mol) was added dropwise at 40 to 60 ° C and stirred at 30 to 40 ° C for 3.5 hours. Water (809.14 g) was then added to the reaction mixture, and then phase separation was performed. The aqueous layer was removed to obtain an organic layer. The organic layer thus obtained was concentrated under reduced pressure, and the resulting concentrate was distilled under reduced pressure to obtain 2,9-diacetoxyundecane (4) (122.60 g, 0.42 mol, purity 92.38%, bp = 115.6 to 122.1 ° C / 0.080 kPa (0.60 mmHg)), and the yield of the two-step method was 82.18%.

[0384] The spectrum data of 2,9-diacetoxyundecane (4) obtained in this way were the same as those obtained in Example 7.

[0385] Example 9: Preparation of 8-(trimethylacetoxy)decanal (1:R 1 =C(CH3)3, n=1)

[0386]

[0387] 8-Hydroxydecanal (11) (4.0 g, 0.023 mol, purity 98.59%), pyridine (2.90 g, 0.037 mol) and acetonitrile (10.00 g) prepared as in Comparative Example 1 below were placed in a reactor at room temperature and stirred at 15 to 25° C. for 14 minutes. Pivaloyl chloride (2.76 g, 0.023 mol) was then added dropwise at 20 to 30° C. and stirred at 20 to 30° C. for 8 hours. Water (15.00 g) was then added to the reaction mixture, followed by phase separation. The aqueous layer was removed to obtain an organic layer. The organic layer thus obtained was concentrated under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography (hexane: ethyl acetate = 30: 1 to 5: 1) to obtain 8-(trimethylacetoxy)decanal (1: R 1 =C(CH3)3, n=1)(2.08 g, 0.0080 mol, purity 98.24%), yield 34.89%.

[0388] The following is the 8-(trimethylacetoxy)decanal (1:R 1 =C(CH3)3, n=1).

[0389] NMR Spectrum: 1 H-NMR (500MHz, CDCl3): δ = 0.85 (3H, t, J = 7.3Hz), 1.18 (9H, s), 1.21-1.34 (6H, m), 1.43-1.64 (6H,m),2.40(2H,dt,J=1.9Hz,7.3Hz),4.76(1H,tt,J=7.3Hz,5.3Hz),9.74(1H,t,J=1.9Hz); 13 C-NMR (125MHz, CDCl3): δ = 9.48, 21.92, 25.01, 26.93, 27.18, 28.99, 29.17, 33.50, 38.82, 43.80, 74.75, 178.26, 202.72.

[0390] Mass spectrum: EI-mass spectrum (70eV): m / z 257 (M + +1),227,213,199,171,155,137,95,81,57,41.

[0391] Infrared absorption spectrum: (D-ATR): νmax = 2970, 2935, 2860, 2716, 1724, 1480, 1462, 1396, 1367, 1284, 1166, 1113, 1032, 936 cm -1 .

[0392] Example 10: Preparation of 8-(Benzoyloxy)decanal (1:R 1 =Ph,n=1)

[0393]

[0394] 8-Hydroxydecanal (11) (4.0 g, 0.023 mol, purity 98.59%), pyridine (2.90 g, 0.037 mol) and acetonitrile (10.00 g) prepared as in Comparative Example 1 below were placed in a reactor at room temperature and stirred at 15 to 25° C. for 10 minutes. Benzoyl chloride (3.22 g, 0.023 mol) was then added dropwise at 20 to 30° C. and stirred at 20 to 30° C. for 7 hours. Water (15.00 g) was then added to the reaction mixture, which was then phase separated. The aqueous layer was removed to obtain an organic layer. The organic layer thus obtained was concentrated under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography (hexane: ethyl acetate = 10: 1 to 5: 1) to obtain 8-(benzoyloxy)decanal (1: R 1 =Ph, n=1) (1.13 g, 0.0041 mol, purity 100%), the yield was 17.80%.

[0395] The following is the 8-(benzoyloxy)decanal (1:R 1 =Ph, n=1) spectrum data.

[0396] NMR Spectrum: 1 H-NMR (500MHz, CDCl3): δ = 0.94 (3H, t, J = 7.3Hz), 1.26-1.44 (6H, m), 1,54-1.76 (6H, m), 2.39 (2H, dt, J = 1.9Hz, 7.3 Hz),5.03-5.10(1H,m),7.43(2H,t-like,J=8.1Hz),7.52-7.57(1H,m),8.02-8.06(2H,m),9.73(1H,t,J=1.9Hz); 13C-NMR (125MHz, CDCl3): δ = 9.61, 21.92, 25.10, 27.06, 29.97, 29.19, 33.56, 43.78, 75.98, 128.27, 129.48, 130.76, 132.68, 166.36, 202.72.

[0397] Mass spectrum: EI-mass spectrum (70eV): m / z 275 (M + -1),248,233,218,200,154,123,105,77,55,41.

[0398] Infrared absorption spectrum: (D-ATR): ν = 2968, 2935, 2858, 2718, 1716, 1602, 1585, 1451, 1275, 1176, 1107, 1070, 1026 cm -1 .

[0399] Comparative Example 1: Preparation of 8-hydroxynonanal (11)

[0400]

[0401] The 9,9-diethoxy-2-nonanol (9A:R 3 =R 4 =Et, n = 0) (200.00 g, 0.84 mol, purity 97.70%), oxalic acid dihydrate (318.04 g, 2.52 mol), tetrahydrofuran (840.90 g) and water (840.90 g) were placed in a reactor at room temperature and stirred at 60 to 65°C for 2.5 hours. Hexane (494.62 g) was then added and stirred for 30 minutes. After the stirring was completed, the reaction mixture was allowed to stand for phase separation, and then the aqueous layer was removed to obtain an organic layer. The organic layer thus obtained was concentrated under reduced pressure, and the concentrate obtained was distilled under reduced pressure to obtain 8-hydroxynonanal (11) (18.29 g, 0.10 mol, purity 88.26%) with a yield of 12.12%. The yield was extremely low compared to the method for preparing 8-(acyloxy)alkanal compound (1).

[0402] The following are the spectrum data of 8-hydroxynonanal (11) thus prepared.

[0403] NMR Spectrum: 1H-NMR (500MHz, CDCl3): δ = 1.15 (3H, d, J = 6.1Hz), 1.20-1.49 (8H, m), 1.56-1.65 (2H, m), 1 .71(1H,br.s),2.40(2H,dt,J=1.9Hz,7.3Hz),3.71-3.80(1H,m),9.73(1H,t,J=1.9Hz); 13 C-NMR (125MHz, CDCl3): δ = 21.90, 23.42, 25.45, 29.02, 29.26, 39.11, 43.78, 67.93, 202.83.

[0404] Mass spectrum: EI-mass spectrum (70eV): m / z 157 (M + -1),143,125,114,96,81,68,57,45,29.

[0405] Infrared absorption spectrum: (D-ATR): ν = 3406, 2930, 2857, 1724, 1463, 1373, 1112, 1062, 943 cm -1 .

Claims

1. An 8-(acyloxy)alkanal compound having the following general formula (1): Where n represents 0 or 1, R 1 It represents a straight-chain or branched alkyl group having 1 to 10 carbon atoms, a phenyl group, or a phenyl group in which one or more hydrogen atoms are substituted by a halogen atom.

2. A method for preparing 2,9-diacetoxyundecane of the following formula (4): The method comprises the following steps: The following 8-(acyloxy)alkanal compound of general formula (1) is prepared: Where n represents 0 or 1, and R 1 represents a straight-chain or branched alkyl group having 1 to 10 carbon atoms, a phenyl group, or a phenyl group in which one or more hydrogen atoms are substituted by a halogen atom, With the following nucleophilic alkyl compound of general formula (2) CH3(CH2) (1-n) M 1 (2) Among them, M 1 Indicates Li, MgZ 1 ,CuZ 1 or CuLiZ 1 , n represents 0 or 1, and Z 1 represents a halogen atom, a methyl group or an ethyl group, A nucleophilic addition reaction is carried out to form 2,9-undecanediol of the following formula (3): and subjecting the 2,9-undecanediol (3) to an acetylation reaction to form the 2,9-diacetoxyundecane (4).

3. A method for preparing an 8-(acyloxy)alkanal compound of the following general formula (1): Where n represents 0 or 1, and R 1 represents a straight-chain or branched alkyl group having 1 to 10 carbon atoms, a phenyl group, or a phenyl group in which one or more hydrogen atoms are substituted by a halogen atom, The method comprises the following steps: The following dialkoxy acyloxy alkane compound of the general formula (5) is used: Where n represents 0 or 1, R 1 As defined above, and R 3 and R 4 independently represent a monovalent hydrocarbon group having 1 to 15 carbon atoms; or R 3 and R 4 Together they form a divalent hydrocarbon radical R having 2 to 10 carbon atoms 3 -R 4 , The hydrolysis reaction is carried out to form the above-mentioned 8-(acyloxy)alkanal compound (1).

4. A method for preparing an 8-(acyloxy)alkanal compound (1) as defined in claim 3, wherein n is 0, The method comprises the following steps: The following 6-halogeno-1,1-dialkoxyhexane compound of the general formula (6): Where X represents a halogen atom, and R 3 and R 4 independently represent a monovalent hydrocarbon group having 1 to 15 carbon atoms; or R 3 and R 4 Together they form a divalent hydrocarbon radical R having 2 to 10 carbon atoms 3 -R 4 , Converted into a nucleophile 6,6-dialkoxyhexyl compound of the following general formula (7): Among them, M 2 Indicates Li, MgZ 2 ,CuZ 2 or CuLiZ 2 , Z 2 represents a halogen atom or a 6,6-dialkoxyhexyl group, and R 3 and R 4 As defined above, The nucleophilic 6,6-dialkoxyhexyl compound (7) is then subjected to a nucleophilic addition reaction with propylene oxide of the following formula (8): To form the following 9,9-dialkoxy-2-nonanol compound of general formula (9A): Where R 3 and R 4 As defined above, Acylating the 9,9-dialkoxy-2-nonanol compound (9A) to form a dialkoxyacyloxyalkane compound (5) as defined in claim 3 when n is 0; And the method according to claim 3, preparing the 8-(acyloxy)alkanal compound (1) when n is 0 as defined in claim 3 by subjecting the dialkoxyacyloxyalkane compound (5) when n is 0 as defined in claim 3 to a hydrolysis reaction.

5. A method for preparing an 8-(acyloxy)alkanal compound (1) as defined in claim 3, wherein n is 1, The method comprises the following steps: The following 6-halogeno-1,1-dialkoxyhexane compound of the general formula (6): Where X represents a halogen atom, and R 3 and R 4 independently represent a monovalent hydrocarbon group having 1 to 15 carbon atoms; or R 3 and R 4 Together they form a divalent hydrocarbon radical R having 2 to 10 carbon atoms 3 -R 4 , Converted into a nucleophile 6,6-dialkoxyhexyl compound of the following general formula (7): Among them, M 2 Indicates Li, MgZ 2 ,CuZ 2 or CuLiZ 2 , Z 2 represents a halogen atom or a 6,6-dialkoxyhexyl group, and R 3 and R 4 As defined above, The nucleophilic 6,6-dialkoxyhexyl compound (7) is then subjected to a nucleophilic addition reaction with 1,2-butylene oxide of the following formula (10): To form the following 10,10-dialkoxy-3-decanol compound of general formula (9B): Where R 3 and R 4 As defined above, Acylating the 10,10-dialkoxy-3-decanol (9B) to form a dialkoxyacyloxyalkane compound (5) as defined in claim 3, provided that n is 1; And the method according to claim 3, preparing the 8-(acyloxy)alkanal compound (1) when n is 1 as defined in claim 3 by subjecting the dialkoxyacyloxyalkane compound (5) when n is 1 as defined in claim 3 to a hydrolysis reaction.

6. A process for preparing 2,9-diacetoxyundecane (4) as defined in claim 2, The method comprises the following steps: The method according to claim 3, wherein the 8-(acyloxy)alkanal compound (1) is prepared from the dialkoxyacyloxyalkane compound (5), and The method according to claim 2, wherein the 2,9-diacetoxyundecane (4) is prepared from the 8-(acyloxy)alkanal compound (1).

7. A process for preparing 2,9-diacetoxyundecane (4) as defined in claim 2, The method comprises the following steps: The following 6-halogeno-1,1-dialkoxyhexane compound of the general formula (6): Where X represents a halogen atom, and R 3 and R 4 independently represent a monovalent hydrocarbon group having 1 to 15 carbon atoms; or R 3 and R 4 Together they form a divalent hydrocarbon radical R having 2 to 10 carbon atoms 3 -R 4 , Converted into a nucleophile 6,6-dialkoxyhexyl compound of the following general formula (7): Among them, M 2 Indicates Li, MgZ 2 ,CuZ 2 or CuLiZ 2 , Z 2 represents a halogen atom or a 6,6-dialkoxyhexyl group, and R 3 and R 4 As mentioned above, The nucleophilic 6,6-dialkoxyhexyl compound (7) is then subjected to a nucleophilic addition reaction with propylene oxide of the following formula (8): To form the following 9,9-dialkoxy-2-nonanol compound of general formula (9A): Where R 3 and R 4 As defined above, The 9,9-dialkoxy-2-nonanol compound (9A) is acylated to form a 9,9-dialkoxy-2-acyloxynonane compound of the following general formula (5A): Where R 1 , R 3 and R 4 As defined above, The 9,9-dialkoxy-2-acyloxynonane compound (5A) is subjected to a hydrolysis reaction to form an 8-(acyloxy)alkanal compound (1) as defined in claim 2, wherein n is 0, And the method according to claim 2, preparing 2,9-diacetoxyundecane (4) from the 8-(acyloxy)alkanal compound (1) as defined in claim 3 when n is 0.

8. A process for preparing 2,9-diacetoxyundecane (4) as defined in claim 2, The method comprises the following steps: The following 6-halogeno-1,1-dialkoxyhexane compound of the general formula (6): Where X represents a halogen atom, and R 3 and R 4 independently represent a monovalent hydrocarbon group having 1 to 15 carbon atoms; or R 3 and R 4 Together they form a divalent hydrocarbon radical R having 2 to 10 carbon atoms 3 -R 4 , Converted into a nucleophile 6,6-dialkoxyhexyl compound of the following general formula (7): Among them, M 2 Indicates Li, MgZ 2 ,CuZ 2 or CuLiZ 2 , Z 2 represents a halogen atom or a 6,6-dialkoxyhexyl group, and R 3 and R 4 As defined above, The nucleophilic 6,6-dialkoxyhexyl compound (7) is then subjected to a nucleophilic addition reaction with 1,2-butylene oxide of the following formula (10): To form the following 10,10-dialkoxy-3-decanol compound of general formula (9B): Where R 3 and R 4 As defined above, The 10,10-dialkoxy-3-decanol compound (9B) is acylated to form a 10,10-dialkoxy-3-acyloxydecane compound of the following general formula (5B): Where R 1 , R 3 and R 4 As defined above, The 10,10-dialkoxy-3-acyloxydecane compound (5B) is subjected to a hydrolysis reaction to form an 8-(acyloxy)alkanal compound (1) as defined in claim 2, wherein n is 1, And the method according to claim 2, preparing 2,9-diacetoxyundecane (4) from the 8-(acyloxy)alkanal compound (1) as defined in claim 3 when n is 1.

Images