阅读说明：本技术 制备(e2)-顺-6,7-环氧-2-壬烯醛的方法 (Process for preparing (E2) -cis-6, 7-epoxy-2-nonenal ) 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(3)的(E2)-顺-6,7-环氧-2-壬烯醛的工业化并经济的方法：<Image he="261" wi="577" file="DDA0002176052760000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>本发明提供了一种制备(E2)-顺-6,7-环氧-2-壬烯醛(3)的方法,包括至少以下步骤：使下式(1)的(Z3,Z6)-3,6-壬二烯-1-醇进行氧化：<Image he="187" wi="585" file="DDA0002176052760000012.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>以形成下式(2)的(E2,Z6)-2,6-壬二烯醛；和<Image he="202" wi="590" file="DDA0002176052760000013.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>环氧化所得(E2,Z6)-2,6-壬二烯醛,以形成前述(E2)-顺-6,7-环氧-2-壬烯醛(3)。(The object of the present invention is to provide an industrial and economical process for preparing (E2) -cis-6, 7-epoxy-2-nonenal of the following formula (3): the invention provides a method for preparing (E2) -cis-6, 7-epoxy-2-nonenal (3), which comprises at least the following steps: (Z3, Z6) -3, 6-nonadien-1-ol of the following formula (1): to form (E2, Z6) -2, 6-nonadienal of the following formula (2); and the resulting (E2, Z6) -2, 6-nonadienal is epoxidized to form the aforementioned (E2) -cis-6, 7-epoxy-2-nonenal (3).)

1. A process for preparing (E2) -cis-6, 7-epoxy-2-nonenal of the formula (3):

the method comprises at least the following steps:

(Z3, Z6) -3, 6-nonadien-1-ol of the following formula (1):

to form (E2, Z6) -2, 6-nonadienal of the following formula (2); and

the resulting (E2, Z6) -2, 6-nonadienal is epoxidized to form the aforementioned (E2) -cis-6, 7-epoxy-2-nonenal (3).

2. The method according to claim 1, wherein the oxidation is performed using an oxidizing agent selected from the group consisting of a higher valent iodine compound, a chromic acid compound, a sulfoxide compound of the following formula (4), a manganese compound, a nitroxyl radical compound, and a perruthenate compound:

CH₃(R¹)S＝O

(4)

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

3. The method of claim 2, wherein the oxidizing agent is a sulfoxide compound of the following formula (4):

CH₃(R¹)S＝O

(4)

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

the oxidation is carried out with a sulfoxide compound in the presence of a sulfur trioxide complex and an amine compound of the following formula (5):

N(R²)(R³)(R⁴)

(5)

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 from 3 to 12 carbon atoms³-R⁴。

4. The method according to claim 3, 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.

5. The method of claim 3, wherein the amine compound is selected from the group consisting of trialkylamine compounds and cyclic tertiary amine compounds.

6. The process according to claim 1, wherein the oxidation is carried out with a sulfoxide compound of the following formula (4) in the presence of a sulfur trioxide complex and an amine compound of the following formula (5):

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 from 3 to 12 carbon atoms³-R⁴。

Technical Field

The present invention relates to a process for the preparation of (E2) -cis-6, 7-epoxy-2-nonenal, which is known as the aggregation pheromone of red-neck longicorn (scientific name: Aromia bungi).

Background

The larvae of red-neck longicorn eat or eat dry rosaceous trees such as cherry, japanese apricot, peach, and plum, thereby damaging these trees. Weakening or wilting of these trees due to damage has become a serious problem. They were first found to invade japan in 2012 and were designated as "quarantine pests".

To control red-necked longicorn, trapping adult insects, piercing larvae emerging from the trunk with needles, and injecting insecticides into their invasive pores have been performed, but these methods are not effective enough. Therefore, it is necessary to develop a new efficient control method.

Mating disruption or mass trapping using insect pheromones is expected to be one of the new control methods. Tian Xu et al reported that the aggregation pheromone of red-necked longicorn is (E2) -cis-6, 7-epoxy-2-nonenal (non-patent document 1 mentioned below).

Xu et al reported a method for producing (E2) -cis-6, 7-epoxy-2-nonenal by epoxidizing the 6-position olefin moiety of (E2, Z6) -2, 6-nonenal with m-chloroperbenzoic acid (non-patent document 1).

Disclosure of Invention

However, the method for producing (E2) -cis-6, 7-epoxy-2-nonenal reported in non-patent document 1 has problems that it is difficult and costly to obtain the starting material (E2, Z6) -2, 6-nonenal on a large scale.

The present invention has been made under these circumstances, and has an object to overcome the above-mentioned problems of the prior art and to provide an industrial and economical process for preparing (E2) -cis-6, 7-epoxy-2-nonenal.

As a result of intensive studies, the present inventors have found that (E2, Z6) -2, 6-nonadienal can be industrially and economically produced by oxidizing (Z3, Z6) -3, 6-nonadien-1-ol, which is a known flavoring agent and is available in large quantities in the industry, and (E2) -cis-6, 7-epoxy-2-nonadienal can be industrially produced from (E2, Z6) -2, 6-nonadienal at low cost, thereby completing the present invention.

According to one aspect of the present invention, there is provided a process for preparing (E2) -cis-6, 7-epoxy-2-nonenal of the following formula (3):

the method at least comprises the following steps:

(Z3, Z6) -3, 6-nonadien-1-ol of the following formula (1):

to form (E2, Z6) -2, 6-nonadienal of the following formula (2): and

the resulting (E2, Z6) -2, 6-nonadienal is epoxidized to form the aforementioned (E2) -cis-6, 7-epoxy-2-nonenal (3).

One embodiment of the present invention makes it possible to efficiently, industrially and economically produce (E2) -cis-6, 7-epoxy-2-nonenal known as Reynonella erythropolis gathering pheromone.

Detailed Description

The process for preparing (E2) -cis-6, 7-epoxy-2-nonenal according to the present invention will be described below.

A. Step of oxidation

The oxidizing step includes a step of oxidizing (Z3, Z6) -3, 6-nonadien-1-ol of the following formula (1) to form (E2, Z6) -2, 6-nonadienal of the following formula (2).

(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. Oxidation by oxygen

The oxidation can be carried out, for example, by reacting (Z3, Z6) -3, 6-nonadien-1-ol (1) with an oxidizing agent in a solvent.

Examples of the oxidizing agent include (a) a higher iodine compound, (b) a chromic acid compound, (c) a sulfoxide compound, (d) a manganese compound, (e) a nitroxyl compound, and (f) a perrhenate compound. In view of the yield or selectivity of regioisomers (regioisomers), (a) higher iodine compounds, (b) chromic acid compounds, and (c) sulfoxide compounds are preferable, and (c) sulfoxide compounds are more preferable. The oxidizing agents may be used alone or in combination, if necessary. The oxidizing agent may be commercially available.

(a) High-valent iodine compound

Examples of the higher iodine compounds include 2-iodoxybenzoic acid (2-iodoxybenzoic acid), 1,1,1-triacetoxy-1,1-dihydro-1, 2-benziodoxy-3 (1H) -one (1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H) -one), and 2-iodoxy-5-methylbenzenesulfonic acid. 2-iodoacyl-5-methylbenzenesulfonic acid can be prepared, for example, by reacting potassium 2-iodo-5-methylbenzenesulfonate with a hydrogen monopersulfate (monopersulfate), such as potassium monopersulfate.

(b) Chromic acid compound

Examples of chromic acid compounds include chromic oxide pyridinium complex, pyridinium chlorochromate, and pyridinium dichromate.

(c) Sulfoxide compounds

The sulfoxide compound is represented by the following formula (4):

CH₃(R¹)S＝O

(4)

(hereinafter referred to as "sulfoxide compound (4)").

R in the formula (4)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-hexyl-nonyl, 1-decyl, 1-undecyl and 1-dodecyl groups; 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, R¹Preference is given to methyl, ethyl, 1-propyl or 1-dodecyl radicals.

Examples of the sulfoxide compound (4) 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 (4) is preferably dimethyl sulfoxide and methyl dodecyl sulfoxide in view of price, availability, reactivity or odor of a by-product. The sulfoxide compounds (4) can be used alone or in combination, if necessary.

(d) Manganese compound

Examples of the manganese compound include manganese dioxide and barium manganate.

(e) Nitroxyl radical compounds

Examples of nitroxyl radical compounds include 2,2,6, 6-tetramethylpiperidine 1-oxyl, 4-hydroxy-2, 2,6, 6-tetramethylpiperidine 1-oxyl, 2-azaadamantane N-oxyl, 1-methyl-2-azaadamantane N-oxyl and 9-azaadamantane N-oxyl.

(f) Perruthenate compounds (Perruthenate compounds)

Examples of perruthenate compounds include ammonium perruthenate compounds, such as tetrapropylammonium perruthenate.

In view of reactivity or yield, it is preferable to add the oxidizing agent such as the above-mentioned (a) to (f) in an amount of 1.0mol to 70.0mol, more preferably 1.5mol to 50.0mol, per mol of (Z3, Z6) -3, 6-nonadien-1-ol (1).

When the sulfoxide compound (c) is used as the oxidizing agent, it is preferable to use an activating agent together.

Examples of the activating agent include sulfur trioxide complex, acid anhydride, carbodiimide compound, oxalyl chloride and phosphorus pentoxide. The activator may be commercially available.

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.

Examples of the acid anhydride include acetic anhydride and trifluoroacetic anhydride.

Examples of the carbodiimide compound include dicyclohexylcarbodiimide, diisopropylcarbodiimide and 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride.

The amount of the activator used is preferably 1.0mol to 10.0mol, more preferably 2.0mol to 5.0mol, still more preferably 2.5mol to 3.5mol per mol of (Z3, Z6) -3, 6-nonadien-1-ol (1) in view of reactivity or yield.

The mol ratio of the oxidizing agent (sulfoxide compound) to the activating agent is preferably 10.0 to 15.0 in view of reactivity or yield.

The activating agent may be added after dilution with a suitable solvent, such as dimethyl sulfoxide, dichloromethane, chloroform, ethyl acetate or toluene.

When a sulfur trioxide complex, an acid anhydride, a carbodiimide compound, oxalyl chloride or phosphorus pentoxide is used as the activator, a base is preferably used as an auxiliary for the aforementioned oxidation.

Examples of the base include amine compounds of the following formula (5):

N(R²)(R³)(R⁴)

(5)

(hereinafter referred to as "amine compound (5)") and a heterocyclic aromatic amine compound.

R in the formula (5)²、R³And R⁴Each independently of the other represents a compound having 1 to 12, preferably 1 to 12A monovalent hydrocarbon group of 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 with the sulfoxide compound (4)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-nonyl, 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 (5) include trialkylamine compounds such as trimethylamine, triethylamine, tripropylamine, tributylamine, trioctylamine, tridecylamine, 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 (5) is preferably trimethylamine, triethylamine and tripropylamine in view of price, availability or reactivity. The amine compound (5) may be used alone or in combination, if necessary. The amine compound (5) may be commercially available.

Examples of the heterocyclic aromatic amine compound include pyridine and quinoline. The heterocyclic aromatic amine compounds may be used alone or in combination, if necessary. The heterocyclic aromatic amine compound may be commercially available.

The amount of the base to be used is preferably 1.0 to 10.0mol, more preferably 3.0 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 base to the activator is preferably 1.0 to 2.0, more preferably 1.5 to 1.8.

When a carbodiimide compound is used as an activating agent, acids may be used together.

Examples of acids include trifluoroacetic acid, difluoroacetic acid, trichloroacetic acid, dichloroacetic acid, monochloroacetic acid, cyanoacetic acid, orthophosphoric anhydride, and phosphorous acid. In view of reactivity, the acid is preferably trifluoroacetic acid, dichloroacetic acid or orthophosphoric anhydride. These acids may be used alone or in combination, if necessary. The acid may be commercially available.

The amount of the acid is preferably 0.3 to 2.0mol, more preferably 0.3 to 0.5mol per mol of (Z3, Z6) -3, 6-nonadien-1-ol (1) in view of the reactivity or the amount of by-products of impurities.

When the nitroxyl radical compound (e) is used as the oxidizing agent, hypochlorite or iodobenzene diacetate may be used as the reoxidant agent, if necessary.

When the perruthenate compound (f) is used as the oxidizing agent, an amine oxide compound such as N-methylmorpholine oxide may be used as the reoxidant agent, if necessary.

If desired, a solvent may be used in the oxidation.

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 type solvents such as dichloromethane, chloroform, carbon tetrachloride, trichloroethane and tetrachloroethane, and hydrocarbon type 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 a commercially available solvent.

The sulfoxide compound (4) or base used in the 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 have found that, when the oxidation is carried out with the sulfoxide compound (4) particularly preferably in the presence of a sulfur trioxide complex and an amine compound (5), the hydroxyl group of (Z3, Z6) -3, 6-nonadien-1-ol (1) can be oxidized into an aldehyde group, and at the same time, the double bond at the 3-position is rearranged to the 2-position, and then the isomerization is sufficiently carried out.

Examples of the combination of the sulfoxide compound (4) with sulfur trioxide complex and the amine compound (5) include a combination of dimethyl sulfoxide, sulfur trioxide pyridine complex and triethylamine, a combination of methyl dodecyl sulfoxide, sulfur trioxide pyridine complex and triethylamine, and a combination of dimethyl sulfoxide, sulfur trioxide pyridine complex and tripropylamine.

(E2, Z6) -2, 6-nonadienal (2) can be produced with high purity, high yield and high selectivity using the sulfoxide compound (4) under the above-mentioned oxidation conditions, i.e., in the presence of a sulfur trioxide complex and an amine compound (5).

In one embodiment of the present invention, the oxidation may be carried out with a sulfoxide compound of the following formula (4) in the presence of a sulfur trioxide complex and an amine compound of the following formula (5):

CH₃(R¹)S＝O N(R²)(R³)(R⁴)

(4) (5)

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 from 3 to 12 carbon atoms³-R⁴。

B. Step of epoxidation

The epoxidation step comprises the step of epoxidizing (E2, Z6) -2, 6-nonadienal (2) to form (E2) -cis-6, 7-epoxy-2-nonenal of the following formula (3).

Epoxidation can be carried out, for example, by reacting (E2, Z6) -2, 6-nonadienal (2) 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 (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 (1, 2-dioxaaspiro [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.

The amount of the epoxidizing agent to be used is preferably 1.0mol to 3.0mol, more preferably 1.0mol to 1.5mol, per mol of (E2, Z6) -2, 6-nonadienal (2) in view of economy or reactivity.

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 in the epoxidation reaction 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. The solvent used in the epoxidation reaction is preferably dichloromethane, chloroform, tetrahydrofuran or ethyl acetate in view of reactivity or yield. 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 (2) 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.

C. End product (E2) -cis-6, 7-epoxy-2-nonenal (3)

(E2) Examples of the cis-6, 7-epoxy-2-nonenal (3) include (E2, R6, S7) -6, 7-epoxy-2-nonenal of the following formula (3-1):

and (E2, S6, R7) -6, 7-epoxy-2-nonenal of the following formula (3-2):

and mixtures thereof.