阅读说明：本技术 制备(e2,z6)-2,6-壬二烯醛的方法 (Process for preparing (E2, Z6) -2, 6-nonadienal ) 是由 山下美与志 三宅裕树 金生刚 于 2019-08-22 设计创作，主要内容包括：本发明的目的是提供一种制备下式(4)的(E2,Z6)-2,6-壬二烯醛的工业化并经济的方法：<Image he="182" wi="523" file="DDA0002176055150000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>本发明提供一种制备(E2,Z6)-2,6-壬二烯醛(4)的方法,该方法至少包括以下步骤：在三氧化硫络合物和下式(3)的胺化合物存在下,用下式(2)的亚砜化合物使下式(1)的(Z3,Z6)-3,6-壬二烯-1-醇氧化,以形成上述(E2,Z6)-2,6-壬二烯醛(4)：<Image he="87" wi="700" file="DDA0002176055150000012.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>其中R<Sup>1</Sup>代表具有1至12个碳原子的一价烃基,其中R<Sup>2</Sup>、R<Sup>3</Sup>和R<Sup>4</Sup>各自独立地代表具有1至12个碳原子的一价烃基,或者R<Sup>3</Sup>和R<Sup>4</Sup>可彼此键合以形成具有3至12个碳原子的二价烃基R<Sup>3</Sup>-R<Sup>4</Sup>。(The object of the present invention is to provide an industrial and economical process for preparing (E2, Z6) -2, 6-nonadienal of the following formula (4): the present invention provides a process for preparing (E2, Z6) -2, 6-nonadienal (4), which comprises at least the following steps: oxidizing (Z3, Z6) -3, 6-nonadien-1-ol of the following formula (1) with a sulfoxide compound of the following formula (2) in the presence of a sulfur trioxide complex and an amine compound of the following formula (3) to form the above-mentioned (E2, Z6) -2, 6-nonadienal (4): wherein R is 1 Represents a monovalent hydrocarbon group having 1 to 12 carbon atoms, wherein R 2 、R 3 And R 4 Each independently represents a monovalent hydrocarbon group having 1 to 12 carbon atoms, or R 3 And R 4 Can be bonded to each other to form a divalent hydrocarbon radical R having 3 to 12 carbon atoms 3 ‑R 4 。)

1. A process for preparing (E2, Z6) -2, 6-nonadienal of the following formula (4):

the method at least comprises the following steps:

oxidizing (Z3, Z6) -3, 6-nonadien-1-ol of the following formula (1) with a sulfoxide compound of the following formula (2) in the presence of a sulfur trioxide complex and an amine compound of the following formula (3) to form the above-mentioned (E2, Z6) -2, 6-nonadienal (4):

wherein R is¹Represents a monovalent hydrocarbon group having 1 to 12 carbon atoms,

wherein R is²、R³And R⁴Each independently represents a monovalent hydrocarbon group having 1 to 12 carbon atoms, or R³And R⁴Can be bonded to each other to form a divalent hydrocarbon radical R having 3 to 12 carbon atoms³-R⁴。

2. The method according to claim 1, wherein the sulfur trioxide complex is selected from the group consisting of sulfur trioxide pyridine complex, sulfur trioxide trimethylamine complex, sulfur trioxide triethylamine complex, sulfur trioxide ethyldiisopropylamine complex, and sulfur trioxide N, N-dimethylformamide complex.

3. The method according to claim 1 or 2, wherein the amine compound (3) is selected from the group consisting of trialkylamine compounds and cyclic tertiary amine compounds.

Technical Field

The invention relates to a method for producing (E2, Z6) -2, 6-nonadienal.

Background

(E2, Z6) -2, 6-nonadienal is a known useful intermediate for the preparation of (E2) -cis-6, 7-epoxy-2-nonenal, (E2) -cis-6, 7-epoxy-2-nonenal is an aggregation pheromone of red-necked longicorn (scientific name: Aromia bungi), and red-necked longicorn is a known pest of Japanese trees such as cherry, Japanese apricot, peach, and plum (non-patent document 1 mentioned below). It is required to establish an industrial and economical process for preparing the above intermediate (E2, Z6) -2, 6-nonadienal to develop a new technology for controlling red-necked longicorn using aggregation pheromone of red-necked longicorn.

The following methods are reported for the preparation of (E2, Z6) -2, 6-nonadienal: one method includes ethylating and diethoxymethylating both alkynyl ends of 1, 5-hexadiyne as a starting material, respectively, and then carrying out partial hydrogenation (non-patent document 1, described below); one method starts with 4-pyranoxybutyraldehyde in which the Wittig reaction is carried out twice (non-patent document 2, described below); a method in which (1, 3-dioxolan-2-ylmethyl) triphenylphosphonium bromide is reacted with a base and then subjected to wittig reaction with Z-4-heptanal (non-patent document 3, described below); a method of ozonolysis (ozonolysis) of Z, Z, Z-1,4, 7-cyclononane triene (non-patent document 4, described below).

Disclosure of Invention

However, the method reported in non-patent document 1 has a problem that the method requires many production steps and the selectivity in the ethylation step is low. The method reported in non-patent document 2 has a problem that the yield of the wittig reaction is extremely low.

The method reported in non-patent document 3 has a problem that 1-methyl-1, 5, 7-triazabicyclo [4.4.0] decene is required as a base in the step of preparing a reagent for wittig reaction, but such a base is difficult to obtain industrially in large quantities. The method reported in non-patent document 4 has a problem that ozonolysis is difficult to industrially perform.

As described above, the conventional methods have many problems and cannot be mass-produced in an industrial and economical manner.

The present invention has been made under these circumstances, and has an object to overcome the problems of the prior art and to provide an industrial and economical process for preparing (E2, Z6) -2, 6-nonadienal.

As a result of intensive studies, the present inventors have found that (E2, Z6) -2, 6-nonadienal can be produced with high selectivity and high yield by oxidizing (Z3, Z6) -3, 6-nonadien-1-ol, which is known as a commercially available fragrance, with a sulfoxide compound in the presence of a sulfur trioxide complex and an amine compound, thereby completing the present invention.

According to one aspect of the present invention, there is provided a process for producing (E2, Z6) -2, 6-nonadienal of the following formula (4):

the method at least comprises the following steps:

oxidizing (Z3, Z6) -3, 6-nonadien-1-ol of the following formula (1) with a sulfoxide compound of the following formula (2) in the presence of a sulfur trioxide complex and an amine compound of the following formula (3) to form the above-mentioned (E2, Z6) -2, 6-nonadienal (4) of the above-mentioned formula (4):

wherein R is¹Represents a monovalent hydrocarbon group having 1 to 12 carbon atoms,

wherein R is²、R³And R⁴Each independently represents a monovalent hydrocarbon group having 1 to 12 carbon atoms, or R³And R⁴Can be bonded to each other to form a divalent hydrocarbon radical R having 3 to 12 carbon atoms³-R⁴。

The present invention can efficiently, industrially and economically produce (E2, Z6) -2, 6-nonadienal, which is a useful intermediate for producing (E2) -cis-6, 7-epoxy-2-nonenal as an aggregation pheromone of red-necked longicorn.

Detailed Description

The process for producing (E2, Z6) -2, 6-nonadienal of the following formula (4) according to the present invention is described below.

As shown in the above reaction formula, the process at least comprises oxidizing (Z3, Z6) -3, 6-nonadien-1-ol (hereinafter referred to as "(Z3, Z6) -3, 6-nonadien-1-ol (1)") of the above formula (1) in the presence of a sulfur trioxide complex as an activator and an amine compound of the above formula (3) (hereinafter referred to as "amine compound (3)") using a sulfoxide compound of the above formula (2) (hereinafter referred to as "sulfoxide compound (2)") as an oxidizing agent to produce (E2, Z6) -2, 6-nonadienal (hereinafter referred to as "(E2, Z6) -2, 6-nonadienal (4)") of the above formula (4).

(Z3, Z6) -3, 6-nonadien-1-ol (1) as starting material

(Z3, Z6) -3, 6-nonadien-1-ol (1) is commercially available or can be synthesized indoors.

2. Sulfoxide Compound (2)

The sulfoxide compound (2) is used as an oxidizing agent for the above oxidation. R in the formula (2)¹Represents a monovalent hydrocarbon group having 1 to 12, preferably 1 to 6, carbon atoms.

R¹Examples of (B) include straight-chain saturated hydrocarbon groups such as methyl, ethyl, 1-propyl, 1-butyl, 1-pentyl, 1-hexyl, 1-heptyl, 1-octyl, 1-nonyl, 1-decyl, 1-undecyl, and 1-dodecylClustering; branched saturated hydrocarbon groups such as 1, 1-dimethylethyl, 1-methylethyl, 2-methylpropyl, and 2-methylbutyl groups; straight chain unsaturated hydrocarbon groups such as 2-propenyl group; branched unsaturated hydrocarbon groups such as 2-methyl-2-propenyl group; cyclic saturated hydrocarbon groups such as cyclopropyl groups; aryl, such as phenyl groups; and aralkyl groups, such as benzyl groups. Also included are isomers thereof. The hydrogen atom of the hydrocarbon group may be substituted with a group such as a methyl group or an ethyl group.

In view of reactivity or operability, R¹Preferably a methyl, ethyl, 1-propyl or 1-dodecyl group.

Examples of the sulfoxide compound (2) include dimethyl sulfoxide, methyl ethyl sulfoxide, methyl propyl sulfoxide, methyl butyl sulfoxide, methyl pentyl sulfoxide, methyl dodecyl sulfoxide, methyl 1-methylethyl sulfoxide, methyl 2-methylpropyl sulfoxide, methyl 1, 1-dimethylethyl sulfoxide, methylphenyl sulfoxide and methylbenzyl sulfoxide. The sulfoxide compound (2) is preferably dimethyl sulfoxide and methyl dodecyl sulfoxide in view of price, availability, reactivity or odor of a by-product. The sulfoxide compounds (2) can be used alone or in combination, if necessary. The sulfoxide compound (2) may be commercially available.

The amount of the sulfoxide compound (2) used is preferably 1.0 to 70.0mol, more preferably 1.5 to 50.0mol, per mol of (Z3, Z6) -3, 6-nonadien-1-ol (1) in view of reactivity or yield.

3. Sulfur trioxide complexes

The sulfur trioxide complex acts as an activator for the above mentioned oxidation. Examples of the sulfur trioxide complex include sulfur trioxide pyridine complex, sulfur trioxide trimethylamine complex, sulfur trioxide triethylamine complex, sulfur trioxide ethyldiisopropylamine complex, and sulfur trioxide N, N-dimethylformamide complex. The sulfur trioxide complex is preferably a sulfur trioxide pyridine complex in view of reactivity. The sulfur trioxide complexes can be used alone or in combination, if desired. The sulfur trioxide complex may be commercially available.

In view of reactivity or yield, the amount of the sulfur trioxide complex to be used is preferably 1.0mol to 10.0mol, more preferably 2.0mol to 5.0mol, further more preferably 2.5mol to 3.5mol per mol of (Z3, Z6) -3, 6-nonadien-1-ol (1).

The molar ratio of the sulfoxide compound (2) to the sulfur trioxide complex is preferably 10.0 to 15.0 in view of reactivity or yield.

The sulfur trioxide complex can be added after dilution with a suitable solvent, such as dimethyl sulfoxide, dichloromethane, chloroform, ethyl acetate or toluene.

4. Amine Compound (3)

The amine compound (3) is used as an aid to the above-mentioned oxidation. R in the formula (3)²、R³And R⁴Each independently represents a monovalent hydrocarbon group having 1 to 12, preferably 1 to 6, carbon atoms, or R³And R⁴Can be bonded to each other to form a divalent hydrocarbon radical R having 3 to 12, preferably 3 to 6, carbon atoms³-R⁴。

R²、R³And R⁴R which may be defined for the sulfoxide compound (2)¹The same or different.

Divalent hydrocarbon radical R³-R⁴Examples of (b) include straight-chain saturated hydrocarbon groups such as 1, 3-propene, 1, 4-butene, 1, 5-pentene, 1, 6-hexene, 1, 7-heptene, 1, 8-octene, 1, 9-nonene, 1, 10-decene, 1, 11-undecene, and 1, 12-dodecene groups; branched saturated hydrocarbon groups such as 2, 2-dimethyl-1, 3-propene, 1, 3-butene and 2, 3-dimethyl-1, 3-butene groups; straight chain unsaturated hydrocarbon groups such as 1, 3-propylene and 1, 4-butylene groups; branched unsaturated hydrocarbon groups such as 2-methylene-1, 3-propylene groups; and cyclic hydrocarbon groups such as 1, 2-cyclopropene and 1, 2-cyclobutene groups. Also included are isomers thereof. The hydrogen atom of the hydrocarbon group may be substituted with a group such as a methyl group or an ethyl group.

Examples of the amine compound (3) include: trialkylamine compounds such as trimethylamine, triethylamine, tripropylamine, tributylamine, trioctylamine, tridodecylamine, diisopropylethylamine, dimethyloctylamine, and didodecylethylamine; and cyclic tertiary amine compounds such as N-methylpiperidine, N-ethylpiperidine, N-butylpiperidine, N-methylpyrrolidine, N-ethylpyrrolidine and N-butylpyrrolidine. The amine compound (3) is preferably trimethylamine, triethylamine and tripropylamine in view of price, availability or reactivity. The amine compound (3) may be used alone or in combination, if necessary. The amine compound (3) may be commercially available.

The amount of the amine compound (3) used is preferably 1.0mol to 10.0mol, more preferably 3.0mol to 6.0mol, per mol of (Z3, Z6) -3, 6-nonadien-1-ol (1) in view of reactivity or yield.

In view of reactivity or yield, the molar ratio of the amine compound (3) to the sulfur trioxide complex is preferably 1.0 to 2.0, more preferably 1.5 to 1.8.

5. Oxidation by oxygen

If desired, the oxidation can be carried out in a solvent.

The solvent used in the oxidation is not particularly limited as long as it does not adversely affect the oxidation. Examples of the solvent include halogen-based solvents such as dichloromethane, chloroform, carbon tetrachloride, trichloroethane and tetrachloroethane, and hydrocarbon-based solvents such as pentane, hexane, heptane and cyclohexane. The solvent is preferably dichloromethane in view of reactivity or yield. The solvents used in the oxidation may be used alone or in combination, if necessary. The solvent may be commercially available.

The sulfoxide compound (2) or amine compound (3) used for oxidation may also be used as a solvent.

The amount of the solvent to be used is preferably 1000.0g to 10000.0g, more preferably 3000.0g to 8000.0g, per mol of (Z3, Z6) -3, 6-nonadien-1-ol (1) in view of economy or reactivity.

The reaction temperature is preferably-50 ℃ to 80 ℃, more preferably 0 ℃ to 50 ℃ in view of the reaction rate or yield.

The duration of the oxidation may vary depending on, for example, the solvent and the scale of production. In view of productivity, the range is preferably 1 hour to 30 hours, more preferably 1 hour to 12 hours.

The present inventors found that, when oxidation is carried out with the sulfoxide compound (2) in the presence of a sulfur trioxide complex and an amine compound (3), the hydroxyl group of (Z3, Z6) -3, 6-nonadien-1-ol (1) is oxidized to an aldehyde group, and at the same time, the double bond at the 3-position is rearranged to the 2-position, and then isomerization is sufficiently carried out.

(E2, Z6) -2, 6-nonadienal (4) can be produced with high purity, high yield and high selectivity under the above-mentioned oxidation conditions, i.e., with the sulfoxide compound (2) in the presence of a sulfur trioxide complex and an amine compound (3).

6. Synthesis of (E2) -cis-6, 7-epoxy-2-nonenal from (E2, Z6) -2, 6-nonenal (4)

(E2, Z6) -2, 6-nonadienal (4) which can be prepared according to the invention is a useful intermediate for the preparation of (E2) -cis-6, 7-epoxy-2-nonenal of the following formula (5), (E2) -cis-6, 7-epoxy-2-nonenal being the aggregation pheromone of the red-necked longicorn (scientific name: Aromiangii) which is considered to be a pest such as cherry, Japanese apricot, peach and plum.

The preparation method comprises the step of epoxidizing (E2, Z6) -2, 6-nonadienal (4) to form the (E2) -cis-6, 7-epoxy-2-nonenal (5).

Epoxidation can be carried out, for example, by reacting (E2, Z6) -2, 6-nonadienal (4) with an epoxidizing agent in a solvent.

Examples of the epoxidizing agent include organic percarboxylic acid compounds having 1 to 7 carbon atoms, such as performic acid, peracetic acid, perpropionic acid, pertrifluoroacetic acid, perbenzoic acid, m-chloroperbenzoic acid and 4-nitroperbenzoic acid, and dioxirane compounds, such as 3, 3-dimethyl-1, 2-dioxirane, 3-ethyl-3-methyl-1, 2-dioxirane, 3-methyl-3-trifluoromethyl-1, 2-dioxirane, 3-difluoro-1, 2-dioxirane and 1, 2-dioxaspiro [2,5] octane. In view of reactivity, yield or ease of handling, the epoxidizing agent is preferably performic acid, peracetic acid or m-chloroperbenzoic acid, more preferably m-chloroperbenzoic acid. If desired, epoxidizing agents may be used alone or in combination. Epoxidizing agents may be commercially available.

In view of economy or reactivity, the epoxide is preferably used in an amount of 1.0 to 3.0mol, more preferably 1.0 to 1.5mol, per mol of (E2, Z6) -2, 6-nonadienal (4).

The epoxidation may be an asymmetric epoxidation under Jacobsen-Katsuki epoxidation conditions or under Shi asymmetric epoxidation conditions.

When an organic percarboxylic acid compound is used as the epoxidizing agent, an alkali metal bicarbonate such as sodium bicarbonate may be added to the reaction system, if necessary, to prevent the reaction system from becoming acidic due to the carboxylic acid compound derived from the organic percarboxylic acid compound.

Examples of the solvent used for the epoxidation include: halogen-based solvents such as dichloromethane, chloroform, carbon tetrachloride, trichloroethane and tetrachloroethane; hydrocarbon solvents such as pentane, hexane, heptane and cyclohexane; aromatic solvents such as benzene and toluene; ether solvents such as diethyl ether, tetrahydrofuran, 1, 4-dioxane, t-butyl methyl ether and methyl tetrahydropyran; ester solvents such as methyl acetate, ethyl acetate and butyl acetate; and nitrile solvents such as acetonitrile. In view of reactivity or yield, the solvent used for epoxidation is preferably dichloromethane, chloroform, tetrahydrofuran or ethyl acetate. These solvents may be used alone or in combination, if necessary. The solvent may be commercially available.

The amount of the solvent to be used is preferably 1000.0g to 5000.0g, more preferably 2000.0g to 4000.0g, per mol of (E2, Z6) -2, 6-nonadienal (4) in view of economy or reactivity.

The reaction temperature is preferably-30 ℃ to 50 ℃, more preferably-10 ℃ to 30 ℃ in view of the reaction rate or yield.

The duration of the epoxidation may vary depending on, for example, the solvent and the scale of production. In view of productivity, the range is preferably 1 hour to 30 hours, more preferably 1 hour to 15 hours.

(E2) -cis-6, 7-epoxy-2-nonenal (5)

(E2) Examples of the cis-6, 7-epoxy-2-nonenal (5) include (E2, R6, S7) -6, 7-epoxy-2-nonenal of the following formula (5-1):

and (E2, S6, R7) -6, 7-epoxy-2-nonenal of the following formula (5-2):

and mixtures thereof.