JP2006182741A - Method of isomerizing 2-alkenyl cyclic ether compound - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an efficient method of isomerizing a cyclic ether having a 2-alkenyl group. <P>SOLUTION: The method of isomerizing a 2-alkenyl cyclic ether compound comprises allowing an acid to act on the cyclic ether compound having a 2-alkenyl group represented by formula (1) (wherein ring Z is a ≥3-membered saturated ring containing oxygen; C<SP>1</SP>and C<SP>2</SP>are each carbon constituting ring Z; R<SP>1</SP>is an organic group; R<SP>2</SP>, R<SP>3</SP>, and R<SP>4</SP>are the same or different and each hydrogen or an organic group; and two or more of R<SP>2</SP>, R<SP>3</SP>, and R<SP>4</SP>may be linked with one another to form a ring with the adjacent carbon or the carbon-carbon double bond) to isomerize the steric configuration with the R<SP>1</SP>linked with carbon C<SP>1</SP>and the alkenyl group linked with carbon C<SP>2</SP>from the trans configuration to the cis configuration or from the cis configuration to the trans configuration. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a method for isomerizing a cyclic ether compound having an alkenyl group at the 2-position.

  Cyclic ether compounds having an alkenyl group at the 2-position are useful as fine chemicals such as fragrances, pharmaceuticals and agricultural chemicals, and intermediates thereof. When the cyclic ether compound having an alkenyl group at the 2-position has another substituent in the ring, the cis isomer and the trans isomer are in a steric positional relationship between the alkenyl group and the substituent. Geometric isomers exist. Since such geometric isomers have different physical properties, only one of the isomers may be useful. In addition, since the characteristics (for example, aroma characteristics, etc.) change depending on the abundance ratio of the two isomers, an isomer mixture having a ratio in a specific range may be useful.

  As a typical example of a cyclic ether compound having an alkenyl group at the 2-position, 4-methyl-2- (2-methyl-1-propenyl) tetrahydro-2H-pyran (also referred to as “rose oxide”) is known. ing. Rose oxide has four isomers, geometric isomers and optical isomers [cis- (2S, 4R) isomer, cis- (2R, 4S) isomer, trans- (2R, 4R) isomer, trans- (2S, 4S) body] exists. Rose oxide is used as a fragrance to emit a refreshing flower-like fragrance, but there are subtle differences in the fragrance depending on its isomer, cis-rose oxide has a geranium-like, mint-like green note, trans -Rose oxide is said to have a slightly strong fragrance compared to the cis form (see Patent Document 1).

  As a production method for obtaining a specific isomer of rose oxide, (S) -citronellol or (R) -citronellol is used as a raw material, bromide is reacted with bromide in the presence of soda ash, and an aliquot is present in an acetonitrile solvent. A method is known in which dehydrobromination is performed to obtain dehydrocitronellol, cyclized with dilute sulfuric acid to obtain rose oxide, and purified by precision distillation to obtain each isomer (see Patent Document 1). . In addition, a method is known in which dehydrocitronellol is cyclized with dilute sulfuric acid to obtain rose oxide, and then purified by silica gel column chromatography to obtain a cis isomer (see Non-Patent Document 1). However, these methods are not only costly because the isomers are separated by precision distillation or column chromatography, but also the disadvantage that the undesired isomer produced by the reaction is unnecessary, and the utilization efficiency of raw materials is low. Have

Japanese Patent Laid-Open No. 9-169993 Journal of Organic Chemistry (JOC), 47, 1982, p. 47

Accordingly, an object of the present invention is to provide an efficient isomerization method for a cyclic ether compound having an alkenyl group at the 2-position.
Another object of the present invention is to provide a method for efficiently obtaining cis-form rose oxide.
Still another object of the present invention is to provide a method for efficiently converting a trans isomer of a cyclic ether compound having an alkenyl group at the 2-position to a cis isomer.
Another object of the present invention is to provide one of the geometrical isomers of a trans ether and a cis isomer of a cyclic ether compound having an alkenyl group at the 2-position, or an isomer mixture containing either one of the geometrical isomers as a main component. It is in providing the method of manufacturing efficiently.

（式中、環Ｚは酸素原子を含有する３員以上の飽和環であり、Ｃ¹、Ｃ²はそれぞれ環Ｚを構成している炭素原子である。Ｒ¹は有機基を示し、Ｒ²、Ｒ³、Ｒ⁴は、同一又は異なって、水素原子又は有機基を示す。Ｒ²、Ｒ³、Ｒ⁴は、２以上が結合して、隣接する炭素原子又は炭素−炭素二重結合とともに環を形成していてもよい）
で表される２位にアルケニル基を有する環状エーテル化合物に酸を作用させて、炭素原子Ｃ¹に結合しているＲ¹と炭素原子Ｃ²に結合しているアルケニル基についての立体配置をトランス配置からシス配置へ、又はシス配置からトランス配置へ異性化することを特徴とする２−アルケニル環状エーテル化合物の異性化方法を提供する。 As a result of intensive studies on a method for preferentially obtaining one of the geometric isomers of a cyclic ether compound having an alkenyl group at the 2-position, the present inventors have found that the cyclic ether compound having an alkenyl group at the 2-position has an acid. As a result of the treatment, it was found that the isomerization reaction proceeds smoothly, and the present invention was completed.
That is, the present invention provides the following formula (1):

(In the formula, ring Z is a 3 or more member saturated ring containing an oxygen atom, and C ¹ and C ² are each a carbon atom constituting ring Z. R ¹ represents an organic group, R ² , R ³ and R ⁴ are the same or different and each represents a hydrogen atom or an organic group, and R ² , R ³ and R ⁴ are bonded together to form an adjacent carbon atom or carbon-carbon double bond. A ring may be formed)
An acid is allowed to act on the cyclic ether compound having an alkenyl group at the 2-position represented by formula ( ¹⁾ to convert the configuration of R ¹ bonded to the carbon atom C ¹ and the alkenyl group bonded to the carbon atom C ² to trans. There is provided a method of isomerizing a 2-alkenyl cyclic ether compound characterized by isomerizing from a configuration to a cis configuration or from a cis configuration to a trans configuration.

で表される４−メチル−２−（２−メチル−１−プロペニル）テトラヒドロ−２Ｈ−ピランに酸を作用させて、トランス体をシス体に異性化する方法が挙げられる。 As a preferred embodiment of the isomerization method, the following formula (2)

And a method in which an acid is allowed to act on 4-methyl-2- (2-methyl-1-propenyl) tetrahydro-2H-pyran represented by the following formula:

Examples another preferred embodiment of the isomerization process, the formula by the action of an acid to a compound represented by (1), alkenyl bonded to R ¹ and the carbon atom C ² bonded to the carbon atom C ¹ A method of isomerizing the configuration of the group from the trans configuration to the cis configuration is exemplified.

（式中、環Ｚは酸素原子を含有する３員以上の飽和環であり、Ｃ¹、Ｃ²はそれぞれ環Ｚを構成している炭素原子である。Ｒ¹は有機基を示し、Ｒ²、Ｒ³、Ｒ⁴は、同一又は異なって、水素原子又は有機基を示す。Ｒ²、Ｒ³、Ｒ⁴は、２以上が結合して、隣接する炭素原子又は炭素−炭素二重結合とともに環を形成していてもよい）
で表される２位にアルケニル基を有する環状エーテル化合物に酸を作用させて、炭素原子Ｃ¹に結合しているＲ¹と炭素原子Ｃ²に結合しているアルケニル基についての立体配置をトランス配置からシス配置へ、又はシス配置からトランス配置へ異性化することにより、該化合物のシス体又はトランス体を得ることを特徴とするシス又はトランス−２−アルケニル環状エーテル化合物の製造方法を提供する。 The present invention also provides the following formula (1):

(In the formula, ring Z is a 3 or more member saturated ring containing an oxygen atom, and C ¹ and C ² are each a carbon atom constituting ring Z. R ¹ represents an organic group, R ² , R ³ and R ⁴ are the same or different and each represents a hydrogen atom or an organic group, and R ² , R ³ and R ⁴ are bonded together to form an adjacent carbon atom or carbon-carbon double bond. A ring may be formed)
An acid is allowed to act on the cyclic ether compound having an alkenyl group at the 2-position represented by formula ( ¹⁾ to convert the configuration of R ¹ bonded to the carbon atom C ¹ and the alkenyl group bonded to the carbon atom C ² to trans. Provided is a method for producing a cis or trans-2-alkenyl cyclic ether compound, wherein a cis isomer or a trans isomer of the compound is obtained by isomerization from a configuration to a cis configuration or from a cis configuration to a trans configuration. .

  According to the present invention, a cyclic ether compound having an alkenyl group at the 2-position can be efficiently isomerized. Further, cis-form rose oxide or rose oxide containing cis-form as a main component can be obtained efficiently. Furthermore, a trans isomer of a cyclic ether compound having an alkenyl group at the 2-position can be efficiently converted to a cis isomer. Further, according to the present invention, any one of the trans isomer and cis isomer of a cyclic ether compound having an alkenyl group at the 2-position, or an isomer mixture having one of the geometric isomers as a main component can be efficiently obtained. Can be manufactured.

[Cyclic ether compound having an alkenyl group at the 2-position]
In the present invention, a cyclic ether compound having an alkenyl group at the 2-position represented by the formula (1) is used as a raw material. In the formula (1), the ring Z is a 3 or more member saturated ring containing an oxygen atom, and C ¹ and C ² are each a carbon atom constituting the ring Z. R ¹ represents an organic group, and R ² , R ³ and R ⁴ are the same or different and represent a hydrogen atom or an organic group. Two or more of R ² , R ³ and R ⁴ may be bonded to form a ring together with the adjacent carbon atom or carbon-carbon double bond. The compound represented by the formula (1), the configurations for the alkenyl group bonded to R ¹ and the carbon atom C ² bonded to the carbon atom ^{C 1 (-CR 4 = CR 2} R 3) There are trans isomers in a trans configuration and cis isomers in which the steric configuration is a cis configuration.

Ring Z includes, for example, a 3 to 10-membered oxygen-containing saturated ring composed of carbon atoms except for oxygen atoms shown in the formulas such as oxirane ring, oxetane ring, oxirane ring, oxane ring, oxepane ring, oxocan ring, etc. Is mentioned. Of these, a 3- to 8-membered oxygen-containing saturated ring, particularly a 5-membered or 6-membered oxygen-containing saturated ring (oxolane ring or oxane ring) is preferable. Ring Z usually has no substituent other than R ¹ and alkenyl group (—CR ⁴ ═CR ² R ³ ) shown in the formula, but may have ^one . Examples of the substituent include an alkyl group (C _1-4 alkyl group such as a methyl group) and an alkoxy group.

Examples of the organic group in R ¹ , R ² , R ³ , and R ⁴ include a hydrocarbon group, a heterocyclic group, and a hydroxyl group protected with a protecting group (alkoxy group, aryloxy group, aralkyloxy group, acyloxy group). Etc.), mercapto groups protected with protecting groups (including alkylthio groups, arylthio groups, aralkylthio groups, acylthio groups, etc.), amino groups protected with protecting groups (mono- or dialkyl-substituted amino groups, acylamino groups, etc.) ), Carboxyl groups protected with protecting groups (substituted oxycarbonyl groups such as alkoxycarbonyl groups, aryloxycarbonyl groups, aralkyloxycarbonyl groups; amide groups such as carbamoyl groups, mono- or dialkylcarbamoyl groups), acyl Group (C _1-10 acyl group and the like), cyano group and the like. As the protecting group, a protecting group commonly used in the field of organic synthesis can be used.

  Examples of the hydrocarbon group include an aliphatic hydrocarbon group, an alicyclic hydrocarbon group, an aromatic hydrocarbon group, and a group in which two or more of these are bonded. Examples of the aliphatic hydrocarbon group include 1 to 20 carbon atoms such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, pentyl, hexyl, octyl, decyl, and allyl groups (preferably 1-10, and more preferably 1-6) linear or branched aliphatic hydrocarbon groups (alkyl groups, alkenyl groups, and alkynyl groups). Examples of the alicyclic hydrocarbon group include alicyclic hydrocarbon groups having about 3 to 15 carbon atoms (preferably 3 to 8 carbon atoms) such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, and cyclooctyl groups. (Cycloalkyl group, cycloalkenyl group, bridged carbocyclic group and the like). Examples of the aromatic hydrocarbon group include aromatic hydrocarbon groups having about 6 to 14 carbon atoms such as phenyl and naphthyl groups.

These hydrocarbon groups have various substituents such as halogen atoms (fluorine, chlorine, bromine, iodine atoms), oxo groups, hydroxyl groups protected with protecting groups (alkoxy groups, aryloxy groups, aralkyloxy groups, Mercapto groups protected with protecting groups (including alkylthio groups, arylthio groups, aralkylthio groups, acylthio groups, etc.), amino groups protected with protecting groups (mono- or dialkyl-substituted amino groups, acylamino) Carboxyl groups protected with protecting groups (substituted oxycarbonyl groups such as alkoxycarbonyl groups, aryloxycarbonyl groups, aralkyloxycarbonyl groups; amide groups such as carbamoyl groups, mono- or dialkylcarbamoyl groups) Nitro group, acyl group, cyano group, alkyl group (for example, Methyl, such as C _1-4 alkyl group such as ethyl group), a cycloalkyl group, an aryl group (e.g., phenyl and naphthyl groups), may have and heterocyclic groups. As the protecting group, a protecting group commonly used in the field of organic synthesis can be used.

  The heterocyclic ring constituting the heterocyclic group as an example of the organic group includes an aromatic heterocyclic ring and a non-aromatic heterocyclic ring. As such a heterocyclic ring, for example, a heterocyclic ring containing an oxygen atom as a hetero atom (for example, 5-membered ring such as furan, tetrahydrofuran, oxazole, isoxazole, 4-oxo-4H-pyran, tetrahydropyran, morpholine, etc. 6-membered ring, condensed ring such as benzofuran, isobenzofuran, 4-oxo-4H-chromene, chroman, isochroman, etc.), heterocycle containing a sulfur atom as a hetero atom (for example, 5 such as thiophene, thiazole, isothiazole, thiadiazole, etc.) 5-membered rings, 6-membered rings such as 4-oxo-4H-thiopyran, condensed rings such as benzothiophene, etc.) and heterocycles containing nitrogen atoms as heteroatoms (eg, pyrrole, pyrrolidine, pyrazole, imidazole, triazole, etc.) Ring, pyridine, pyridazine, pyrimi Emissions, pyrazine, piperidine, 6-membered ring such as piperazine, indole, indoline, quinoline, acridine, naphthyridine, quinazoline, other condensed rings purine) and the like. These heterocyclic groups may have a substituent (for example, a group similar to the substituent that the hydrocarbon group may have).

Examples of the ring formed by combining two or more of R ² , R ³ , and R ⁴ together with the adjacent carbon atom or carbon-carbon double bond include cyclopropane, cyclobutane, cyclopentane, cyclopentene, cyclohexane, and cyclohexene. , Cyclooctane, cyclodecane, cyclododecane ring, decalin ring, adamantane ring and the like non-aromatic carbon of about 3 to 20 members (preferably 3 to 15 members, more preferably 5 to 15 members, especially 5 to 8 members) Ring (cycloalkane ring, cycloalkene ring, bridged carbocycle) and the like. These rings may have a substituent (for example, the same group as the substituent which the hydrocarbon group may have), and other rings (non-aromatic ring or aromaticity). Ring) may be condensed.

Preferred R ¹ is a C _1-10 aliphatic hydrocarbon group (methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, pentyl, hexyl, octyl, decyl group, etc .; especially C _{1- 6} alkyl group), an alicyclic hydrocarbon group (for example, C _3-15 cycloalkyl group or cycloalkenyl group such as cyclopentyl, cyclohexyl, cyclohexenyl group, etc.), C _6-14 aryl group and the like. Preferable R ² , R ³ and R ⁴ include a hydrogen atom in addition to the groups listed as the preferable R ¹ . In addition, two or more of R ² , R ³ and R ⁴ are bonded to each other, and together with the adjacent carbon atom or carbon-carbon double bond, the non-aromatic carbocycle having about 3 to 15 members (particularly 5 to 8 members). It is also preferable to form

  The most typical example of the 2-alkenyl cyclic ether compound represented by the formula (1) is 4-methyl-2- (2-methyl-1-propenyl) tetrahydro-2H— represented by the formula (2). It is pyran (rose oxide). Other examples of the compound represented by the formula (1) include 2-methyl-2-vinyl-5- (2-hydroxy-2-propyl) tetrahydrofuran, tetrahydro-2,2,6-trimethyl-6-vinylpyran- Examples include 3-ol, 5-isopropenyl-2-methyl-2-vinyltetrahydrofuran, 1-oxaspiro [4.5] -2,6,10,10-tetramethyl-6-decene.

[Production of cyclic ether compound having alkenyl group at 2-position]
As the 2-alkenyl cyclic ether compound represented by the formula (1), those obtained by any production method can be used. For example, as a method for obtaining rose oxide, in addition to the methods described in Patent Document 1 and Non-Patent Document 1, dl-citronellol (3,7-dimethyl-6-octen-1-ol) is photooxidized and then sulfite. A method obtained by reduction with sodium to give 3,7-dimethyl-5-octene-1,7-diol and reacting with dilute sulfuric acid (Precision Organic Synthesis [Experimental Manual], page 458, 1987, Nanedo ), 3,7-dimethyl-5-octene-1,5-diol treated with p-toluenesulfonic acid (Helv. Chim. Acta 70, 1987, 1879), 3,7-dimethyl-5 There is a method obtained by treating octene-1,5-diol with palladium acetate and 1,4-diphenylphosphinobutane (JP-A-9-67361).

（式中、Ｃ¹、Ｃ²はそれぞれ炭素原子である。Ｒ¹は有機基を示し、Ｒ²、Ｒ³、Ｒ⁴は、同一又は異なって、水素原子又は有機基を示す。Ｒ²、Ｒ³、Ｒ⁴は、２以上が結合して、隣接する炭素原子又は炭素−炭素二重結合とともに環を形成していてもよい）
で表されるアルケニル基を有するアルコールを酸素と反応させることにより得ることもできる。 The 2-alkenyl cyclic ether compound represented by the formula (1) has a corresponding formula (3)

(In the formula, C ¹ and C ² are each a carbon atom. R ¹ represents an organic group, and R ² , R ³ and R ⁴ are the same or different and represent a hydrogen atom or an organic group. R ² , R ³ and R ⁴ may be bonded together to form a ring together with adjacent carbon atoms or carbon-carbon double bonds.
It can also obtain by making the alcohol which has an alkenyl group represented by oxygen react with oxygen.

  As oxygen, molecular oxygen can be used. The molecular oxygen is not particularly limited, and pure oxygen may be used, or oxygen or air diluted with an inert gas such as nitrogen, helium, argon, or carbon dioxide may be used. Oxygen may be generated in the system. The amount of oxygen used varies depending on the type of substrate [alcohol having an alkenyl group represented by formula (3)], but is usually 0.5 mol or more (for example, 1 mol or more) with respect to 1 mol of the substrate. , Preferably it is 1-100 mol, More preferably, it is about 2-50 mol. Often an excess of oxygen is used relative to the substrate.

  The reaction with oxygen may be carried out in the presence of a catalyst. As the catalyst, for example, transition metal compounds such as cobalt compounds and manganese compounds can be used. Examples of the cobalt compound include organic acid salts such as cobalt formate, cobalt acetate, cobalt propionate, cobalt naphthenate, cobalt stearate, and cobalt lactate; cobalt hydroxide, cobalt oxide, cobalt chloride, cobalt bromide, cobalt nitrate, Examples thereof include inorganic compounds such as cobalt sulfate and cobalt phosphate; divalent or trivalent cobalt compounds such as complexes such as cobalt acetylacetonate. Examples of manganese compounds include organic acid salts such as manganese formate, manganese acetate, manganese propionate, manganese naphthenate, manganese stearate, and manganese lactate; manganese hydroxide, manganese oxide, manganese chloride, manganese bromide, and nitric acid. Inorganic compounds such as manganese, manganese sulfate, and manganese phosphate; divalent or trivalent manganese compounds such as a complex such as manganese acetylacetonate; These transition metal compounds can be used alone or in combination of two or more. Among these, a cobalt compound, a manganese compound, or a mixture thereof is preferable.

  When using a transition metal compound etc. as a catalyst, the usage-amount is 0.01-30 mol% with respect to a substrate, Preferably it is about 0.1-20 mol%.

［式中、Ｘは酸素原子又は−ＯＲ基（Ｒは水素原子又はヒドロキシル基の保護基を示す）を示す。２つの炭素原子から左方に伸びる線はそれぞれ結合手を示す］
で表される骨格を環の構成要素として含む窒素原子含有環状化合物を用いることもできる。この窒素原子含有環状化合物は前記遷移金属化合物（例えば、コバルト化合物及び／又はマンガン化合物）と組み合わせて用いてもよい。触媒として、イミド系化合物と遷移金属化合物とを組み合わせて用いると、反応速度や反応選択性が大幅に向上することがある。 Moreover, as a catalyst, following formula (i)

[Wherein, X represents an oxygen atom or an —OR group (R represents a hydrogen atom or a protecting group for a hydroxyl group). Lines extending to the left from two carbon atoms each represent a bond]
It is also possible to use a nitrogen atom-containing cyclic compound containing a skeleton represented by The nitrogen atom-containing cyclic compound may be used in combination with the transition metal compound (for example, a cobalt compound and / or a manganese compound). When a combination of an imide compound and a transition metal compound is used as a catalyst, the reaction rate and reaction selectivity may be greatly improved.

  In the formula (i), the bond between the nitrogen atom and X is a single bond or a double bond. The nitrogen atom-containing cyclic compound may have a plurality of skeletons represented by formula (i) in the molecule. In the nitrogen atom-containing cyclic compound, when X is an —OR group and R is a protecting group for a hydroxyl group, a plurality of portions excluding R in the skeleton represented by formula (i) It may be connected via. In the formula (i), as the hydroxyl-protecting group represented by R, a hydroxyl-protecting group commonly used in the field of organic synthesis can be used.

  In the case where X is an —OR group, when a plurality of moieties other than R (N-oxycyclic imide skeleton) in the skeleton represented by formula (i) are bonded via R, For example, polycarboxylic acid acyl groups such as oxalyl, malonyl, succinyl, glutaryl, adipoyl, phthaloyl, isophthaloyl, terephthaloyl group; carbonyl group; methylene, ethylidene, isopropylidene, cyclopentylidene, cyclohexylidene, benzylidene group, etc. And a valent hydrocarbon group (particularly a group that forms an acetal bond with two hydroxyl groups).

  Preferred R is, for example, a hydrogen atom; a group capable of forming an acetal or hemiacetal group with a hydroxyl group such as methoxymethyl; an acid such as carboxylic acid, sulfonic acid, carbonic acid, carbamic acid, sulfuric acid, phosphoric acid or boric acid. Examples include hydrolyzable protecting groups that can be removed by hydrolysis, such as groups (acyl group, sulfonyl group, alkoxycarbonyl group, carbamoyl group, etc.) excluding OH group.

［式中、ｎは０又は１を示す。Ｘは酸素原子又は−ＯＲ基（Ｒは水素原子又はヒドロキシル基の保護基を示す）を示す］
で表されるＮ−置換環状イミド骨格を有する環状イミド系化合物が含まれる。前記環状イミド系化合物は、分子中に、式（Ｉ）で表されるＮ−置換環状イミド骨格を複数個有していてもよい。また、この環状イミド系化合物は、前記Ｘが−ＯＲ基であり且つＲがヒドロキシル基の保護基である場合、Ｎ−置換環状イミド骨格のうちＲを除く部分（Ｎ−オキシ環状イミド骨格）が複数個、Ｒを介して結合していてもよい。 Examples of the nitrogen atom-containing cyclic compound include the following formula (I):

[Wherein n represents 0 or 1; X represents an oxygen atom or —OR group (R represents a hydrogen atom or a hydroxyl protecting group)]
And a cyclic imide compound having an N-substituted cyclic imide skeleton represented by the formula: The cyclic imide compound may have a plurality of N-substituted cyclic imide skeletons represented by the formula (I) in the molecule. In the cyclic imide compound, when X is an —OR group and R is a protecting group for a hydroxyl group, a portion excluding R (N-oxycyclic imide skeleton) in the N-substituted cyclic imide skeleton A plurality of them may be bonded via R.

  In the formula (I), n represents 0 or 1. That is, Formula (I) represents a 5-membered N-substituted cyclic imide skeleton when n is 0, and represents a 6-membered N-substituted cyclic imide skeleton when n is 1.

  Representative examples of compounds having a 5-membered N-substituted cyclic imide skeleton among preferable imide compounds include, for example, N-hydroxysuccinimide, N-hydroxy-α-methylsuccinimide, N-hydroxymaleimide, N-hydroxyhexahydrophthalimide, N, N'-dihydroxycyclohexanetetracarboxylic diimide, N-hydroxyphthalimide, N-hydroxytetrabromophthalimide, N-hydroxytetrachlorophthalimide, N-hydroxyhet Acid imide, N-hydroxyhymic acid imide, N-hydroxy trimellitic acid imide, N, N'-dihydroxypyromellitic acid diimide, N, N'-dihydroxynaphthalene tetracarboxylic acid diimide, α, β-diacetoxy-N- Hydroxysuccinic acid , N-hydroxy-α, β-bis (propionyloxy) succinimide and the like, wherein X is an —OR group and R is a hydrogen atom; corresponding to these compounds, R is acetyl A compound which is an acyl group such as a group, propionyl group, benzoyl group; formulas such as N-methoxymethyloxyphthalimide, N- (2-methoxyethoxymethyloxy) phthalimide, N-tetrahydropyranyloxyphthalimide A compound in which X in (I) is an —OR group and R is a group capable of forming an acetal or hemiacetal bond with a hydroxyl group; N-methanesulfonyloxyphthalimide, N- (p-toluenesulfonyloxy) phthalic acid A compound in which X in the formula (I) such as an imide is an —OR group and R is a sulfonyl group; Sulfuric esters of tall acid imide, nitrate, X in formula (I), such as phosphoric acid ester or boric acid ester and R is like compound is a group obtained by dividing the OH group from an inorganic acid by -OR groups.

  Representative examples of compounds having a 6-membered N-substituted cyclic imide skeleton among preferable imide compounds include, for example, N-hydroxyglutarimide, N-hydroxy-α, α-dimethylglutarimide, N-hydroxy-β, β-dimethylglutarimide, N-hydroxy-1,8-decalin dicarboxylic imide, N, N′-dihydroxy-1,8; 4,5-decalin tetracarboxylic diimide, N-hydroxy-1,8-naphthalenedicarboxylic X in formula (I) such as acid imide (N-hydroxynaphthalic acid imide), N, N′-dihydroxy-1,8; 4,5-naphthalenetetracarboxylic acid diimide and the like, and R is a hydrogen atom Compounds corresponding to these compounds, wherein R is an acyl group such as an acetyl group, a propionyl group or a benzoyl group X in formula (I) such as N-methoxymethyloxy-1,8-naphthalenedicarboxylic acid imide, N, N′-bis (methoxymethyloxy) -1,8; 4,5-naphthalenetetracarboxylic acid diimide, -OR group and R is a group capable of forming an acetal or hemiacetal bond with a hydroxyl group; N-methanesulfonyloxy-1,8-naphthalenedicarboxylic imide, N, N'-bis (methanesulfonyloxy) -1,8; 4,5-naphthalenetetracarboxylic acid diimide or the like compound in which X in the formula (I) is an -OR group and R is a sulfonyl group; N-hydroxy-1,8-naphthalenedicarboxylic acid imide or N , N′-dihydroxy-1,8; 4,5-naphthalene tetracarboxylic acid diimide sulfate, nitrate, Examples include compounds in which X in the formula (I) such as an acid ester or borate ester is an —OR group and R is a group obtained by removing an OH group from an inorganic acid.

［式中、ｍは１又は２を示す。Ｇは炭素原子又は窒素原子を示し、ｍが２のとき、２つのＧは同一でもよく異なっていてもよい。Ｒは前記に同じ］
で表される環状アシルウレア骨格を有する環状アシルウレア系化合物が含まれる。前記環状アシルウレア系化合物は、分子中に、式（II）で表される環状アシルウレア骨格を複数個有していてもよい。また、この環状アシルウレア系化合物は、式（II）で表される環状アシルウレア骨格のうちＲを除く部分（Ｎ−オキシ環状アシルウレア骨格）が複数個、Ｒを介して結合していてもよい。前記環状アシルウレア骨格を構成する原子Ｇ、及び該Ｇに結合している窒素原子は各種置換基を有していてもよく、また、前記環状アシルウレア骨格には非芳香族性又は芳香族性環が縮合していてもよい。さらに、前記環状アシルウレア骨格は環に二重結合を有していてもよい。 The nitrogen atom-containing cyclic compound includes the following formula (II) in addition to the cyclic imide compound.

[Wherein m represents 1 or 2. G represents a carbon atom or a nitrogen atom, and when m is 2, two Gs may be the same or different. R is the same as above]
And a cyclic acylurea compound having a cyclic acylurea skeleton represented by the formula: The cyclic acylurea compound may have a plurality of cyclic acylurea skeletons represented by the formula (II) in the molecule. In the cyclic acylurea compound, a plurality of portions (N-oxy cyclic acylurea skeleton) excluding R in the cyclic acylurea skeleton represented by the formula (II) may be bonded via R. The atom G constituting the cyclic acylurea skeleton and the nitrogen atom bonded to the G may have various substituents, and the cyclic acylurea skeleton has a non-aromatic or aromatic ring. It may be condensed. Furthermore, the cyclic acylurea skeleton may have a double bond in the ring.

  Representative examples of preferred cyclic acylurea compounds include, for example, 3-hydroxyhydantoin, 1,3-dihydroxyhydantoin, 4-hydroxy-1,2,4-triazolidine-3,5-dione, 4-hydroxy-1, 2,4-triazoline-3,5-dione, hexahydro-3-hydroxy-1,3-diazine-2,4-dione, hexahydro-1,3-dihydroxy-1,3-diazine-2,4-dione, Hexahydro-1,3-dihydroxy-1,3-diazine-2,4,6-trione, 3-hydroxyuracil, hexahydro-4-hydroxy-1,2,4-triazine-3,5-dione, hexahydro-1 , 3,5-trihydroxy-1,3,5-triazine-2,4,6-trione, 1,3,5-triacetoxy-hexa Dro-1,3,5-triazine-2,4,6-trione, 1,3,5-tris (benzoyloxy) -hexahydro-1,3,5-triazine-2,4,6-trione, hexahydro- 1,3,5-tris (methoxymethyloxy) -1,3,5-triazine-2,4,6-trione, hexahydro-1-hydroxy-1,3,5-triazine-2,6-dione, hexahydro -1-hydroxy-3,5-dimethyl-1,3,5-triazine-2,6-dione, 1-acetoxy-hexahydro-1,3,5-triazine-2,6-dione, 1-acetoxy-hexahydro 3,5-dimethyl-1,3,5-triazine-2,6-dione, 1-benzoyloxy-hexahydro-1,3,5-triazine-2,6-dione, 1-benzoylo Sheet - hexahydro-3,5-dimethyl-1,3,5-triazine-2,6-dione, hexahydro-5-hydroxy-1,2,3,5-tetrazine-4,6-dione, and the like.

  Among the nitrogen atom-containing cyclic compounds, a compound in which X is an —OR group and R is a hydrogen atom (N-hydroxy cyclic compound) can be produced according to a known method or by a combination of known methods. it can. Among the nitrogen atom-containing cyclic compounds, a compound in which X is an —OR group and R is a protecting group for a hydroxyl group is a conventional compound (N-hydroxy cyclic compound) in which R is a hydrogen atom. It can be prepared by introducing a desired protecting group using a protecting group introduction reaction.

  Specifically, among the cyclic imide compounds, a compound in which X is an —OR group and R is a hydrogen atom (N-hydroxy cyclic imide compound) is a conventional imidization reaction, for example, a corresponding acid anhydride. Can be obtained by a method of reacting with hydroxylamine and imidizing via ring opening and ring closing of an acid anhydride group. For example, N-acetoxyphthalimide can be obtained by reacting N-hydroxyphthalimide with acetic anhydride or reacting acetyl halide in the presence of a base. It is also possible to manufacture by other methods.

  Particularly preferred imide compounds are N-hydroxyimide compounds derived from aliphatic polycarboxylic anhydrides (cyclic anhydrides) or aromatic polycarboxylic anhydrides (cyclic anhydrides) (for example, N-hydroxysuccinic acid). Imide, N-hydroxyphthalimide, N, N'-dihydroxypyromellitic diimide, N-hydroxyglutarimide, N-hydroxy-1,8-naphthalenedicarboxylic imide, N, N'-dihydroxy-1,8; 4,5-naphthalenetetracarboxylic acid diimide and the like); and compounds obtained by introducing a protecting group into the hydroxyl group of the N-hydroxyimide compound.

  Among the cyclic acylurea compounds, for example, 1,3,5-triacetoxy-hexahydro-1,3,5-triazine-2,4,6-trione (= 1,3,5-triacetoxyisocyanuric acid) is , Hexahydro-1,3,5-trihydroxy-1,3,5-triazine-2,4,6-trione (= 1,3,5-trihydroxyisocyanuric acid) and acetic anhydride, It can be obtained by reacting acetyl halide in the presence.

  The nitrogen atom-containing cyclic compound containing the skeleton represented by formula (i) as a ring component can be used alone or in combination of two or more in the reaction. For example, a cyclic imide compound having a cyclic imide skeleton represented by formula (I) and a cyclic acylurea compound having a cyclic acylurea skeleton represented by formula (II) can be used in combination. The nitrogen atom-containing cyclic compound may be generated in the reaction system. The nitrogen atom-containing cyclic compound may be used in a form supported on a support such as activated carbon or silica.

  The amount of the nitrogen atom-containing cyclic compound used can be selected within a wide range, for example, 0.0000001 to 1 mol, preferably 0.000001 to 0.5 mol, more preferably 0.00001, relative to 1 mol of the substrate. It is about -0.4 mol, and is often about 0.0001-0.35 mol.

  In the reaction, a promoter can be used. By using the catalyst and the cocatalyst together, the reaction rate and the selectivity of the reaction can be improved. Examples of the co-catalyst include an organic salt composed of a polyatomic cation or polyatomic anion containing a group 15 or 16 element of the periodic table to which at least one organic group is bonded, and a counter ion. Preferred organic salts include, for example, quaternary ammonium salts, quaternary phosphonium salts, methanesulfonate, p-toluenesulfonate, and the like. The amount of the organic salt used is, for example, about 0.001 to 0.1 mol, preferably about 0.005 to 0.08 mol, with respect to 1 mol of the catalyst.

  A strong acid (for example, a compound having a pKa2 (25 ° C.) or lower) may be used as a cocatalyst. Preferred strong acids include, for example, hydrogen halides, hydrohalic acids, sulfuric acids, heteropoly acids and the like. The amount of the strong acid used is, for example, about 0.001 to 3 mol with respect to 1 mol of the catalyst.

  Furthermore, a compound having a carbonyl group to which an electron withdrawing group is bonded may be used as a cocatalyst. Typical examples of the compound having a carbonyl group to which an electron withdrawing group is bonded include hexafluoroacetone, trifluoroacetic acid, pentafluorophenyl ketone, pentafluorophenyl ketone, and benzoic acid. The amount of the compound used is, for example, about 0.0001 to 3 mol with respect to 1 mol of the cycloalkane (substrate).

  In addition, a radical generator or a radical reaction accelerator may be present in the reaction system. Examples of such components include hydrous such as halogen (chlorine, bromine, etc.), peracid (peracetic acid, m-chloroperbenzoic acid, etc.), peroxide (hydrogen peroxide, t-butyl hydroperoxide (TBHP), etc. Peroxide), nitric acid or nitrous acid or salts thereof, nitrogen dioxide, aldehydes such as benzaldehyde, and the like. When these components are present in the system, the reaction may be accelerated. The usage-amount of these components is about 0.001-3 mol with respect to 1 mol of said catalysts.

  The oxidation reaction is usually performed in the presence of a solvent. Examples of the solvent include aromatic hydrocarbons such as benzene; halogenated hydrocarbons such as dichloromethane, chloroform, 1,2-dichloroethane and dichlorobenzene; alcohols such as t-butanol and t-amyl alcohol; acetonitrile, Examples include nitriles such as benzonitrile; carboxylic acids such as acetic acid and propionic acid; amides such as formamide, acetamide, dimethylformamide (DMF), and dimethylacetamide. These solvents may be used as a mixture.

  The reaction temperature is, for example, 0 to 200 ° C, preferably 10 to 150 ° C, more preferably 15 to 120 ° C. If the reaction temperature is less than 0 ° C., the reaction rate is slow, and if the reaction temperature is too high, the selectivity of the target product tends to decrease. The reaction pressure may be normal pressure or under pressure. Further, the reaction can be carried out by any method such as batch, semi-batch and continuous methods.

By the above reaction, the cyclic ether compound in which the oxygen atom of the alcohol having an alkenyl group represented by the formula (3) used as a raw material is bonded to the carbon atom C ² to which the alkenyl group is bonded [cyclized ether compound ) Is produced.

  The reaction product can be separated and purified by separation means such as filtration, concentration, distillation, extraction, crystallization, recrystallization, column chromatography and the like. The reaction mixture obtained by the reaction may be subjected to the next isomerization reaction as it is or after simple treatment such as dilution or concentration without separating the reaction product.

[Isomerization]
In the present invention, the formula is reacted with an acid to cyclic ether compound having a 2-position alkenyl group represented by (1), bonded to R ¹ and the carbon atom C ² bonded to the carbon atom C ¹ The configuration of the alkenyl group is isomerized from the trans configuration to the cis configuration or from the cis configuration to the trans configuration.

  Examples of the acid include inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, and boric acid; methanesulfonic acid, trifluoromethanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, naphthalenesulfonic acid, and the like. Sulfonic acids; strong acid cation exchange resins. Of these, sulfuric acid, sulfonic acids, strong acid cation exchange resins and the like are preferable, and sulfonic acids are particularly preferable.

  The amount of acid used varies depending on the type of acid and the like, but is usually in the range of about 0.5 to 100 mol% with respect to the cyclic ether compound having an alkenyl group at the 2-position represented by formula (1). is there. When sulfonic acids are used as the acid, the amount used is preferably 1 to 20 mol%, more preferably based on the cyclic ether compound having an alkenyl group at the 2-position represented by the formula (1). 1.5 to 15 mol%.

  The reaction proceeds smoothly even without solvent, but may be performed in a solvent inert to the reaction. Examples of the solvent include aromatic hydrocarbons such as benzene and toluene; aliphatic hydrocarbons such as hexane and octane; alicyclic hydrocarbons such as cyclohexane; dichloromethane, chloroform, 1,2-dichloroethane, dichlorobenzene, and the like. Examples include halogenated hydrocarbons; nitriles such as acetonitrile and benzonitrile; carboxylic acids such as acetic acid and propionic acid; amides such as formamide, acetamide, dimethylformamide (DMF), and dimethylacetamide; water and the like. May be used as a mixture.

  The reaction temperature of the isomerization varies depending on the kind of the cyclic ether compound having an alkenyl group at the 2-position represented by the formula (1), the kind of the acid catalyst, etc., but is generally −40 ° C. to 150 ° C., preferably 0 It is the range of -100 degreeC.

  The isomerization reaction proceeds in the direction in which the ratio of thermodynamically stable isomers increases. Therefore, depending on the type of cyclic ether compound having an alkenyl group at the 2-position represented by the formula (1), there are cases where a cis isomer is advantageously formed and trans isomers are advantageously formed. In many cases, the cyclic ether compound having an alkenyl group at the 2-position represented by the formula (1) is 4-methyl-2- (2-methyl-1-propenyl) tetrahydro-2H-pyran (rose oxide). The reaction proceeds in the direction of increasing the ratio of cis isomers.

  The reaction can be stopped by neutralizing the acid. Therefore, a 2-alkenyl cyclic ether compound having a desired isomer ratio can be obtained by selecting the timing of neutralizing the acid by adding an alkali or the like. Examples of the alkali include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; alkali metal carbonates such as sodium carbonate and potassium carbonate; alkali metal hydrogen carbonates such as sodium hydrogen carbonate; calcium hydroxide and hydroxide Examples include alkaline earth metal hydroxides such as magnesium; alkaline earth metal carbonates such as calcium carbonate and magnesium carbonate. Alkalis are often added in the form of aqueous solutions or suspensions.

  Since the present invention can easily stop the reaction as described above, it is suitable for obtaining an isomer mixture having a desired isomer ratio (trans-cis isomer ratio). It is useful to obtain a desired isomer or an isomer mixture having a high ratio of desired isomers from an isomer mixture having a relatively small ratio of the desired isomer or a desired isomer. For example, the ratio (Ia / Ib) between the desired (or higher ratio) geometric isomer Ia and the undesired (or lower ratio) geometric isomer Ib (Ia / Ib) is 0/100 or more and less than 80/20 (particularly 0 / 100 to 75/25) is obtained from a single isomer or isomer mixture having a isomer ratio of 100/0 to 80/20 (particularly 100/0 to 85/15). be able to.

  The reaction product can be separated and purified by separation means such as liquidity adjustment, filtration, concentration, distillation, extraction, crystallization, recrystallization, column chromatography and the like. The undesired geometric isomer separated in the separation / purification step can be recycled to the reaction step. Therefore, the desired geometric isomer can be produced very efficiently.

  Hereinafter, the present invention will be described in more detail based on examples, but the present invention is not limited to these examples.

Production Example 1
In a 2 L glass flask equipped with a condenser and a stirrer, 198.27 g (1.27 mol) of 3,7-dimethyl-6-octen-1-ol and 62.45 g of N-hydroxyphthalimide (0.38 mol) ), Cobalt nitrate (II) hexahydrate 7.37 g (25.3 mmol), manganese acetate (II) tetrahydrate 6.30 g (25.7 mmol), and acetonitrile 806 g were added under an oxygen atmosphere (0. 3). 1 MPa) and stirred at 75 ° C. for 7 hours. When the composition in the obtained reaction mixture was analyzed by gas chromatography, it was found that rose oxide was 68.11 g (0.44 mol, yield 34.8%), the raw material 3,7-dimethyl-6-octene- 1-ol was contained in 65.23 g (0.42 mol, recovery rate 32.9%). The ratio of the cis-isomer of rose oxide was 65.1% (analyzed value by gas chromatography).
The solid matter in the reaction mixture obtained above was filtered off, acetonitrile in the filtrate was distilled off by a rotary evaporator, and the residue was distilled to obtain a fraction [distillation temperature 48 to 118 ° C./25 mmHg ( = 3.3 kPa) 64.9 g] contains 45.6 g of rose oxide (purity 70.4%), and the cis-isomer ratio was 65.5% (analyzed by gas chromatography). It was.

Example 1
0.83 g (8.53 mmol, 5 mol%) of methanesulfonic acid was added to 37.1 g of rose oxide obtained in Production Example 1 (pure content 26.1 g, 0.17 mol), and the reaction was conducted under a nitrogen atmosphere. Stir at 4 ° C. for 4 hours. The reaction mixture was cooled to room temperature and then neutralized by adding a 0.5N aqueous sodium hydrogen carbonate solution. When the upper layer (35.8 g) was separated and analyzed by gas chromatography, it contained 73.0% (26.1 g, 0.17 mol) of rose oxide. The ratio of cis-isomer of rose oxide was 90.2% (analyzed value by gas chromatography).

Example 2
To 2.00 g of rose oxide obtained in Production Example 1 (pure content: 1.41 g, 9.1 mmol), 0.085 g (0.88 mmol, 10 mol%) of methanesulfonic acid was added. Stir for 2 hours at ° C. The reaction mixture was cooled to room temperature and then neutralized by adding a 0.5N aqueous sodium hydrogen carbonate solution. When the upper layer (1.89 g) was separated and analyzed by gas chromatography, it contained 74.1% (1.40 g, 9.1 mmol) of rose oxide. The ratio of the cis-isomer of rose oxide was 90.7% (analyzed value by gas chromatography).

Example 3
1.00 g of rose oxide obtained in Production Example 1 (pure content: 0.70 g, 4.5 mmol), 0.25 g (2.5 mmol, 5.6 mol%) of 98 wt% sulfuric acid, and 4.75 g of water And stirred at 20 ° C. for 4 hours under a nitrogen atmosphere. The reaction mixture was neutralized with 0.5N aqueous sodium hydrogen carbonate solution. When the upper layer (0.95 g) was separated and analyzed by gas chromatography, it contained 70.8% (0.67 g, 4.4 mmol) of rose oxide. The ratio of the cis-isomer of rose oxide was 86.8% (analyzed value by gas chromatography).

Example 4
To 1.00 g of rose oxide obtained in Production Example 1 (pure content 0.70 g, 4.5 mmol), 0.022 g of p-toluenesulfonic acid monohydrate (0.11 mmol, 2.5 mol%) And stirred at 40 ° C. for 4 hours under a nitrogen atmosphere. The reaction mixture was cooled to room temperature and then neutralized by adding a 0.5N aqueous sodium hydrogen carbonate solution. The upper layer (0.96 g) was separated and analyzed by gas chromatography. As a result, 71.9% (0.69 g, 4.5 mmol) of rose oxide was contained. The ratio of the cis-isomer of rose oxide was 87.0% (analyzed value by gas chromatography).

Example 5
In a 20 ml glass flask equipped with a condenser and a stirrer, 1.98 g (12.7 mmol) of 3,7-dimethyl-6-octen-1-ol, 207 mg (1.27 mmol) of N-hydroxyphthalimide, Cobalt (III) acetylacetonate (181 mg, 0.51 mmol), cobalt acetate (II) tetrahydrate (32 mg, 0.127 mmol), and acetonitrile (8.1 g) were placed in an oxygen atmosphere (0.1 MPa) at 30 ° C. For 4 hours. To the obtained reaction mixture, 61 mg (0.64 mmol, 5 mol%) of methanesulfonic acid was added, and the mixture was stirred at 40 ° C. for 4 hours under a nitrogen atmosphere. The composition of the obtained reaction mixture was analyzed by gas chromatography. As a result, 0.55 g of rose oxide (3.6 mmol, yield 28%), the raw material 3,7-dimethyl-6-octene-1- All contained 0.86 g (5.5 mmol, recovery 43.3%). The ratio of the cis-isomer of rose oxide was 90.3% (analyzed value by gas chromatography).

Claims (4)

Following formula (1)

(In the formula, ring Z is a 3 or more member saturated ring containing an oxygen atom, and C ¹ and C ² are each a carbon atom constituting ring Z. R ¹ represents an organic group, R ² , R ³ and R ⁴ are the same or different and each represents a hydrogen atom or an organic group, and R ² , R ³ and R ⁴ are bonded together to form an adjacent carbon atom or carbon-carbon double bond. A ring may be formed)
An acid is allowed to act on the cyclic ether compound having an alkenyl group at the 2-position represented by formula ( ¹⁾ to convert the configuration of R ¹ bonded to the carbon atom C ¹ and the alkenyl group bonded to the carbon atom C ² to trans. A method for isomerizing a 2-alkenyl cyclic ether compound, characterized by isomerization from a configuration to a cis configuration or from a cis configuration to a trans configuration. Following formula (2)

The 2-alkenyl cyclic ether according to claim 1, wherein an acid is allowed to act on 4-methyl-2- (2-methyl-1-propenyl) tetrahydro-2H-pyran represented by formula (I) to isomerize the trans isomer to the cis isomer. Compound isomerization method. By the action of an acid to the compound of formula (1), the cis configuration the configuration of the alkenyl groups bonded to R ¹ and the carbon atom C ² bonded to the carbon atom C ¹ from trans-configuration The method for isomerizing a 2-alkenyl cyclic ether compound according to claim 1, wherein the isomerization is performed. Following formula (1)

(In the formula, ring Z is a 3 or more member saturated ring containing an oxygen atom, and C ¹ and C ² are each a carbon atom constituting ring Z. R ¹ represents an organic group, R ² , R ³ and R ⁴ are the same or different and each represents a hydrogen atom or an organic group, and R ² , R ³ and R ⁴ are bonded together to form an adjacent carbon atom or carbon-carbon double bond. A ring may be formed)
An acid is allowed to act on the cyclic ether compound having an alkenyl group at the 2-position represented by formula ( ¹⁾ to convert the configuration of R ¹ bonded to the carbon atom C ¹ and the alkenyl group bonded to the carbon atom C ² to trans. A process for producing a cis or trans-2-alkenyl cyclic ether compound, wherein a cis isomer or a trans isomer of the compound is obtained by isomerization from a configuration to a cis configuration or from a cis configuration to a trans configuration.