WO2020130080A1 - Method for producing p-quinones - Google Patents

Abstract

The purpose of the present invention is to provide a method for synthesizing a p-quinone using one of alkoxy-substituted benzenes as a starting material.　The present invention relates to a method for producing a compound of formula (II) (wherein R², R³, R⁴ and R⁵ are as defined below) from a compound of formula (I) (wherein R¹ represents an alkyl group; R², R³, R⁴ and R⁵ may be the same or different, and each represents a hydrogen atom or an organic functional group; R² and R³, and R⁴ and R⁵ may respectively combine with each other to form a ring, and the ring may have a substituent thereon; and R⁶ represents a hydrogen atom or the like) or the like. This method comprises a step for oxidizing a compound of formula (I) or the like in the presence of: a solvent that is selected from among water and a mixed solvent of water and an organic solvent; a persulfuric acid salt; and at least one compound that is selected from among 2-iodoxybenzoic acid, 2-iodosobenzoic acid, 2-iodobenzoic acid and the like.

Description

Process for producing p-quinones

The present invention relates to a method for producing p-quinones.

For the synthesis of quinones, it is known to use a heavy metal such as silver oxide (AgO) or ammonium cerium (IV) nitrate ((NH ₄ ) ₂ Ce(NO ₃ ) ₆ ) as an oxidizing agent. Development of a non-metal type oxidation method is required because it gives an environmental load from the viewpoint of treatment. Under these circumstances, a non-metal type hypervalent iodine oxidizing agent has been developed in recent years and is currently used in the synthesis of p-quinone. For example, in the p-quinone synthesis method using [bis(trifluoroacetoxy)iodo]benzene (PIFA), a method of synthesizing from phenols (Non-Patent Document 1) and a method of synthesizing from 1,4-dimethoxybenzenes (Non-Patent Document 2) is known, and particularly the latter gives a high yield result (FIG. 1 of Non-Patent Document 2). This is because two methoxys have been previously introduced into the 1,4-dimethoxybenzenes at the para-position, and by-products such as o-quinone are unlikely to occur. However, 1,4-dimethoxybenzenes are disubstituted products in which methoxy is introduced at the para-position in advance, and therefore their synthesis is not as simple as that of phenols. The former method using phenols is mainly used.

On the other hand, a method for synthesizing p-quinone using anisole as a raw material is known (Non-patent documents 3 and 4). However, in the method of Non-Patent Document 3, since o-quinone is by-produced, it is not easy to purify p-quinone, and the yield is low. Further, the yield of the method of Non-Patent Document 4 is low, and a by-product in which the benzene ring is opened becomes a main product. Therefore, these methods are rarely used.

It is an object to provide a method for synthesizing p-quinone even when methoxymono-substituted benzenes, which are easily available, are used as a raw material.

MEANS TO SOLVE THE PROBLEM As a result of earnestly studying in order to solve the said subject, the present inventors used benzenes having alkoxy by using monopotassium peroxomonosulfate and/or oxone and a specific organic iodine compound in the presence of water. It was found that the ether bond site and the para-position of p-quinone were selectively oxolated, and the method for producing p-quinone was completed. The representative present invention is as follows.

Item 1.
Formula (I)

[In the formula,
R ¹ represents alkyl or 1-(3,4-dimethoxyphenyl)-1,3-dihydroxy-2-propyl,
R ² and R ³ are the same or different and each represents a hydrogen atom or an organic functional group, and R ² and R ³ may be bonded to each other to form a ring, and the ring has a substituent on the ring. You may have.
R ⁴ and R ⁵ are the same or different and each represents a hydrogen atom or an organic functional group, and R ⁴ and R ⁵ may be bonded to each other to form a ring, and the ring has a substituent on the ring. You may have.
R ⁶ represents a hydrogen atom, hydroxy, amino, alkoxy, thiol or halogen. ] From the compound or lignin represented by
Formula (II)

[Wherein R ² , R ³ , R ⁴ and R ⁵ are the same as defined above. ]
A method for producing a compound represented by:
A compound represented by the formula (I) or lignins,
In a solvent selected from water and a mixed solvent of water and an organic solvent,
At least one persulfate selected from monopotassium peroxomonosulfate and oxone, and 2-iodoxybenzoic acid (IBX), 2-iodosobenzoic acid (IBA), 2-iodobenzoic acid (2-IB), 2- Alkali metal salt of IB (2-IBM), 2-iodoxybenzenesulfonic acid (IBS), 2-iodosobenzenesulfonic acid (IBSA), 2-iodobenzenesulfonic acid (2-IS), 2-IS alkali Metal salt (2-ISM), iodooxybenzene (PhIO ₂ ), iodobenzene (PhI), 2-iodobenzeneacetic acid (IPAA), IPAA alkali metal salt (IPAAM), 2-iodobenzenepropanoic acid (IPPA), Alkali metal salt of IPPA (IPPAM), and at least one organic compound selected from the group consisting of substituents in which these benzene rings are substituted with halogen, alkoxy, hydroxy, amino, nitro, cyano, carboxy, acyloxy or lower alkyl. Iodine compounds,
A method comprising the step of oxidizing in the presence of
Item 2.
Item 2. The method according to Item 1, wherein the oxidizing step is performed under conditions in which hydrogen peroxide or hydrogen peroxide and a metal catalyst are further present.
Item 3.
Item 3. The method according to Item 1 or 2, wherein R ⁶ is a hydrogen atom.
Item 4.
Item 4. The method according to any one of Items 1 to 3, wherein R ¹ is lower alkyl.
Item 5.
R ² and R ³ are the same or different and are a hydrogen atom, halogen, alkyl or alkoxy, or R ² and R ³ are bonded to each other to form a benzene ring,
R ⁴ and R ⁵ are the same or different and are a hydrogen atom, halogen, alkyl or alkoxy, or R ⁴ and R ⁵ are bonded to each other to form a benzene ring,
Item 5. The method according to any one of Items 1 to 4.

According to the present invention, p-quinones can be produced from the compound of the above formula (I). Further, according to the present invention, p-quinones can be produced from the compound of the above formula (I) even if the reaction temperature is in the normal temperature range (for example, 10°C to 30°C). Furthermore, according to the present invention, the production of by-products, o-quinones, is suppressed. Further, according to the present invention, lignins can be converted into useful low molecular weight compounds such as the compound of the above formula (II).

FIG. 1 is a graph showing the yield (%) of 2-methoxy-1,4-benzoquinone when the solvent is acetonitrile, a mixed solution of acetonitrile and water mixed at various volume ratios, or water. (Test Example 2). The horizontal axis represents the water content of the solvent, and the vertical axis represents the yield.

The above summary of the present invention is not intended to describe each disclosed embodiment or every implementation of the present invention.
The following description of the invention more specifically illustrates example embodiments.
In some places of the invention, guidance is provided through examples, which examples can be used in various combinations.
In each case, the exemplary groups can serve as non-exclusive and representative groups.
All publications, patents and patent applications cited herein are hereby incorporated by reference in their entirety.

Terms Unless otherwise specified, the symbols and abbreviations used in the present specification are understood to have meanings commonly used in the technical field to which the present invention belongs, in the context of the present specification.
The term “comprising” is used herein to be inclusive of the terms “consisting essentially of” and “consisting of”.
Any process, treatment, or operation described herein may be performed at room temperature unless otherwise stated. In the present specification, room temperature can mean a temperature within the range of 10°C to 40°C.
In the present specification, the notation “Cn-Cm” (where n and m are each numbers) means that the number of carbon atoms is n or more and m or less, as is usually understood by those skilled in the art. Represents.

One embodiment of the present invention is the formula (I)

[In the formula,
R ¹ represents alkyl or 1-(3,4-dimethoxyphenyl)-1,3-dihydroxy-2-propyl,
R ² and R ³ are the same or different and each represents a hydrogen atom or an organic functional group, and R ² and R ³ may be bonded to each other to form a ring, and the ring has a substituent on the ring. You may have.
R ⁴ and R ⁵ are the same or different and each represents a hydrogen atom or an organic functional group, and R ⁴ and R ⁵ may be bonded to each other to form a ring, and the ring has a substituent on the ring. You may have.
R ⁶ represents a hydrogen atom, hydroxy, amino, alkoxy, thiol or halogen. ] From the compound or lignin represented by
Formula (II)

[Wherein R ² , R ³ , R ⁴ and R ⁵ are the same as defined above. ]
A method for producing a compound represented by:
A compound represented by the formula (I) or lignins,
In a solvent selected from water and a mixed solvent of water and an organic solvent,
At least one persulfate selected from monopotassium peroxomonosulfate and oxone, and 2-iodoxybenzoic acid (IBX), 2-iodosobenzoic acid (IBA), 2-iodobenzoic acid (2-IB), 2- Alkali metal salt of IB (2-IBM), 2-iodoxybenzenesulfonic acid (IBS), 2-iodosobenzenesulfonic acid (IBSA), 2-iodobenzenesulfonic acid (2-IS), 2-IS alkali Metal salt (2-ISM), iodooxybenzene (PhIO ₂ ), iodobenzene (PhI), 2-iodobenzeneacetic acid (IPAA), IPAA alkali metal salt (IPAAM), 2-iodobenzenepropanoic acid (IPPA), Alkali metal salt of IPPA (IPPAM), and at least one organic compound selected from the group consisting of substituents in which these benzene rings are substituted with halogen, alkoxy, hydroxy, amino, nitro, cyano, carboxy, acyloxy or lower alkyl. Iodine compounds,
A method comprising the step of oxidizing in the presence of

In the present invention, “alkyl” includes, for example, C1-C12 alkyl having a linear, branched or cyclic structure, preferably C1-C6 alkyl, more preferably C1-C4 alkyl, particularly preferably Is C1-C3 alkyl. Specifically, linear or branched alkyl includes methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 2-butyl, isobutyl, t-butyl, n-pentyl, neopentyl, n. -Hexyl, isohexyl, 3-methylpentyl and the like, and examples of the alkyl having a cyclic structure include cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclobutylmethyl, cyclopentyl, cyclopentylmethyl, cyclohexyl, cyclohexylmethyl, cyclohexylethyl and the like. To be It is preferably lower alkyl, more preferably linear C1-C6 alkyl (methyl, ethyl, 1-propyl, 1-butyl, n-pentyl, n-hexyl), 2-propyl, 2-butyl or t-. Butyl, more preferably linear C1-C4 alkyl, particularly preferably methyl or ethyl.

In the present invention, examples of the “lower alkyl” include C1-C6 alkyl having a linear, branched or cyclic structure, preferably C1-C4 alkyl, more preferably C1-C3 alkyl. To be Specifically, linear or branched lower alkyl includes methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 2-butyl, isobutyl, t-butyl, n-pentyl, neopentyl, Examples thereof include n-hexyl and isohexyl, and examples of the lower alkyl having a cyclic structure include cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclobutylmethyl, cyclopentyl, cyclopentylmethyl, cyclohexyl and the like. Preferred are methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, t-butyl, cyclopropyl and the like.

In the present invention, examples of the “organic functional group” include alkyl, hydroxyalkyl, halogenoalkyl, hydroxycycloalkyl, cycloalkyl, aralkyl, alkenyl, alkynyl, alkoxy, halogenoalkoxy, alkylthio, mono- or dialkylamino, acyl, carbamoyl, Examples thereof include phenyl and naphthyl. Preferred are alkyl, hydroxyalkyl, hydroxycycloalkyl, cycloalkyl, alkoxy, phenyl, etc., and more preferred are methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 2-butyl, isobutyl, t-butyl. , Methoxy, ethoxy, 1-propoxy, 2-propoxy, 1-butoxy, 2-butoxy, isobutoxy, t-butoxy and the like.

In the present invention, examples of the “halogen” include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, and preferably a bromine atom and an iodine atom.

In the present invention, examples of “hydroxyalkyl” include the above-mentioned alkyl having at least one (eg, one or two) hydroxy. Specifically, hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2-hydroxypropyl, 1-methyl-2-hydroxyethyl, 4-hydroxybutyl, 2,2-dimethyl-2- Hydroxyethyl, 5-hydroxypentyl, 3,3-dimethyl-3-hydroxypropyl, 6-hydroxyhexyl, dihydroxymethyl, 1,2-dihydroxyethyl, 2,3-dihydroxypropyl, 3,4-dihydroxybutyl, 4, Examples thereof include 5-dihydroxypentyl, 5,6-dihydroxyhexyl, etc., preferably an alkyl having one hydroxy, and more preferably a lower alkyl having one hydroxy.

In the present invention, the “halogenoalkyl” is, for example, a C1-C6 linear or branched alkyl having 1 to 13 halogens (halogeno C1-C6 alkyl), and specifically, fluoromethyl, difluoro Examples include halogeno C1-C6 alkyl such as methyl, trifluoromethyl, trichloromethyl, fluoroethyl, 1,1,1-trifluoroethyl, monofluoro-n-propyl, perfluoro-n-propyl and perfluoroisopropyl. It is preferably halogeno C1-C4 alkyl, more preferably halogeno C1-C4 alkyl having 1 to 7 halogen atoms, and further preferably halogeno C1-C4 alkyl having 1 to 3 halogen atoms.

In the present invention, examples of “hydroxycycloalkyl” include the above C3-C7 cyclic alkyl having at least one (eg, one or two) hydroxy. Specifically, 1-hydroxycyclopropyl, 2-hydroxycyclopropyl, 1-hydroxycyclobutyl, 3-hydroxycyclobutyl, 1-hydroxycyclopentyl, 3,4-dihydroxycyclopentyl, 1-hydroxycyclohexyl, 4-hydroxycyclohexyl , 1-hydroxycycloheptyl and the like, and preferably hydroxycycloalkyl having one hydroxy.

In the present invention, examples of “cycloalkyl-alkyl” include C1-C4 alkyl substituted with C3-C7 cycloalkyl such as cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl and cycloheptylmethyl. In cycloalkyl-alkyl, the number of cycloalkyl contained in alkyl is 1 or more, preferably 1 or 2, and more preferably 1.

In the present invention, examples of “aralkyl” include C7-C13 aralkyl such as benzyl, phenethyl, naphthylmethyl and fluorenylmethyl.

In the present invention, “alkenyl” means an unsaturated hydrocarbon group which may be linear, branched or cyclic and has at least one double bond (eg, 1 or 2), and examples thereof include Vinyl, allyl, 1-propenyl, 2-methyl-2-propenyl, isopropenyl, 1-butenyl, 2-butenyl, 3-butenyl, isobutenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-methyl-2 And C2-C6 alkenyl such as -butenyl, 3-methyl-2-butenyl, 5-hexenyl, 1-cyclopentenyl, 1-cyclohexenyl, 3-methyl-3-butenyl and the like.

In the present invention, “alkynyl” means an unsaturated hydrocarbon group which may be linear, branched or cyclic and has at least one triple bond (eg, 1 or 2), for example, ethynyl. C2-C6 alkynyl such as 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl and 1-methyl-2-propynyl.

In the present invention, “alkoxy” includes, for example, C1-C12 alkoxy having a straight chain, branched or cyclic structure, preferably C1-C8 alkoxy, more preferably C1-C6 alkoxy, and further Preferred is C1-C4 alkoxy, and particularly preferred is C1-C3 alkoxy. Specifically, linear or branched alkoxy includes methoxy, ethoxy, 1-propoxy, 2-propoxy, 1-butoxy, 2-butoxy, isobutoxy, t-butoxy, n-pentyloxy, neopentyl. Oxy, n-hexyloxy, isohexyloxy, 3-methylpentyloxy and the like can be mentioned. Examples of alkoxy having a cyclic structure include cyclopropoxy, cyclopropylmethoxy, cyclobutyroxy, cyclobutylmethoxy, cyclopentyloxy, cyclopentylmethoxy, cyclohexyloxy, cyclohexylmethoxy, cyclohexylethoxy and the like. Preferred are methoxy, ethoxy, 2-propoxy, t-butoxy, cyclopropoxy and the like.

In the present invention, the “halogenoalkoxy” is a C1-C6 linear or branched alkoxy having 1 to 13 halogen atoms (halogenoC1-C6 alkoxy), for example, fluoromethoxy, difluoromethoxy, trifluoro. Halogeno C1-C6 alkoxy such as methoxy, trichloromethoxy, fluoroethoxy, 1,1,1-trifluoroethoxy, monofluoro-n-propoxy, perfluoro-n-propoxy, perfluoro-isopropoxy, preferably halogeno C1- C4 alkoxy is mentioned, more preferably halogeno C1-C4 alkoxy having 1 to 7 halogen atoms.

In the present invention, the “alkylthio” may be linear, branched or cyclic and is, for example, methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, tert-butylthio, n-pentylthio. C1-C6 alkylthio such as isopentylthio, hexylthio, cyclopentylthio and cyclohexylthio.

In the present invention, “monoalkylamino” includes, for example, methylamino, ethylamino, n-propylamino, isopropylamino, n-butylamino, isobutylamino, tert-butylamino, n-pentylamino, isopentylamino, hexyl. Mention may be made of amino mono-substituted with straight chain or branched C1-C6 alkyl such as amino.

In the present invention, “dialkylamino” includes, for example, dimethylamino, diethylamino, di(n-propyl)amino, diisopropylamino, di(n-butyl)amino, diisobutylamino, di(tert-butyl)amino, di(n-butyl)amino. -Pentyl)amino, diisopentylamino, dihexylamino, methylethylamino, methylisopropylamino and the like, which may be the same or different linear, branched or cyclic C1-C6 alkyl disubstituted amino.

In the present invention, “acyl” means alkylcarbonyl or arylcarbonyl.

In the present invention, “alkylcarbonyl” includes, for example, methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, isopropylcarbonyl, n-butylcarbonyl, isobutylcarbonyl, tert-butylcarbonyl, n-pentylcarbonyl, isopentylcarbonyl, hexylcarbonyl. And straight-chain, branched or cyclic (C1-C8 alkyl)carbonyl such as cyclopentylcarbonyl and cyclohexylcarbonyl.

Examples of the “arylcarbonyl” in the present invention include phenylcarbonyl, naphthylcarbonyl, fluorenylcarbonyl, anthrylcarbonyl, biphenylylcarbonyl, tetrahydronaphthylcarbonyl, chromanylcarbonyl, indanylcarbonyl, phenanthrylcarbonyl and the like ( C6-C13 aryl)carbonyl.

In the present invention, “acyloxy” means alkylcarbonyloxy or arylcarbonyloxy.

In the present invention, “alkylcarbonyloxy” includes, for example, methylcarbonyloxy, ethylcarbonyloxy, n-propylcarbonyloxy, isopropylcarbonyloxy, n-butylcarbonyloxy, isobutylcarbonyloxy, tert-butylcarbonyloxy, n-pentyl. Examples thereof include linear or branched (C1-C6 alkyl)carbonyloxy groups such as carbonyloxy, isopentylcarbonyloxy and hexylcarbonyloxy.

Examples of the “arylcarbonyloxy” in the present invention include phenylcarbonyloxy, naphthylcarbonyloxy, fluorenylcarbonyloxy, anthrylcarbonyloxy, biphenylylcarbonyloxy, tetrahydronaphthylcarbonyloxy, chromanylcarbonyloxy, 2,3. (C6-C13 aryl)carbonyloxy groups such as -dihydro-1,4-dioxanaphthalenylcarbonyloxy, indanylcarbonyloxy and phenanthrylcarbonyloxy.

<raw material>
The compound represented by the formula (I) is a raw material of the compound represented by the formula (II) together with lignins. In the present invention, OR ¹ and R ⁶ in the formula (I) are converted into oxo by oxidation to produce a compound represented by the formula (II).

In the formula (I), R ¹ is alkyl or 1-(3,4-dimethoxyphenyl)-1,3-dihydroxy-2-propyl. Here, the alkyl may be linear or branched lower alkyl, more preferably methyl, ethyl, 1-propyl, 2-propyl, 1-butyl or t-butyl, even more preferably It is methyl or ethyl.

When R ¹ is “1-(3,4-dimethoxyphenyl)-1,3-dihydroxy-2-propyl”, —OR ¹ means a group represented by the following formula (in the formula, * Indicates a bond that bonds to the carbon atom of the benzene ring in formula (I)).

In formula (I), R ² and R ³ are the same or different and each is a hydrogen atom or an organic functional group. Here, the organic functional group is as described above, preferably a hydrogen atom, lower alkyl or C1-C6 alkoxy. R ² and R ³ may be bonded to each other to form a ring, and the ring may have a substituent on the ring. Examples of the ring include a 3- to 10-membered monocyclic or bicyclic saturated or unsaturated carbocycle and a 3- to 10-membered monocyclic or bicyclic saturated or unsaturated heterocycle.

The monocyclic saturated or unsaturated carbocycle is, for example, a 3- to 6-membered carbocycle, and specifically, benzene, cyclopropane, cyclobutane, cyclopentane, cyclopentene, cyclopentadiene, cyclohexane, cyclohexene, cyclo Hexadiene and the like can be mentioned, with preference given to benzene, cyclopentane and cyclohexane.

The bicyclic saturated or unsaturated carbocyclic ring is, for example, an 8- to 10-membered carbocyclic ring, and specifically includes naphthalene, dihydronaphthalene, tetrahydronaphthalene, perhydronaphthalene, pentalene, perhydropentalene, azulene, perylene. Examples include hydroazulene, indene, perhydroindene, indane and the like. Preferably, it is a bicyclic carbon ring having a benzene ring, and examples thereof include naphthalene, dihydronaphthalene, indene, and indane.

The saturated or unsaturated heterocycle contains 1 to 5 heteroatoms (preferably 1 or 2 nitrogen atoms) selected from oxygen atom, nitrogen atom and sulfur atom as ring-constituting atoms.

The monocyclic saturated or unsaturated heterocycle is, for example, a 3- to 8-membered heterocycle, and specifically, pyrrole, imidazole, triazole, tetrazole, pyrazole, furan, thiophene, oxazole, isoxazole, thiazole, Unsaturated heterocycles such as isothiazole, furazan, oxadiazole, thiadiazole, pyridine, pyrazine, pyrimidine, pyridazine, azepine, pyran, thiopyran, oxepin, thiepine, oxazine, oxadiazine, oxazepine, oxadiazepine, thiazine, thiazinane, thiazepine, thiadiazepine Aziridine, azetidine, thiirane, oxetane, azetidine, thietane, pyrrolidine, tetrohydrofuran, humanlahydrothiophene, piperidine, tetrahydropyran, tetrahydrothiopyran, piperazine, pyrazolidine, imidazolidine, isoxazolidine, isothiazolidine, morpholine, thiomorpholine, etc. And saturated heterocycles. Preferred are pyrrole, imidazole, pyridine, pyrimidine and pyrazine.

The bicyclic saturated or unsaturated heterocycle is, for example, an 8- to 10-membered heterocycle, and specifically, indole, isoindole, indolizine, benzofuran, isobenzofuran, benzothiophene, isobenzothiophene, indazole. , Quinoline, isoquinoline, quinolidine, purine, phthalazine, pteridine, naphthyridine, quinoxaline, quinazoline, cinnoline, benzoxazole, benzothiazole, benzimidazole, benzodioxole, benzooxathiol, chromene, benzofurazan, benzothiadiazole, benzotriazole, dihydrobenzofuran , Dihydrobenzothiophene, dihydroisobenzothiophene, dihydroisobenzofuran, dihydroindazole, dihydroquinoline, tetrahydroquinoline, dihydroisoquinoline, tetrahydroisoquinoline, dihydrophthalazine, tetrahydrophthalazine, dihydronaphthyridine, tetrahydronaphthyridine, dihydroquinoxaline, tetrahydroquinoxaline, dihydro Examples thereof include quinazoline, tetrahydroquinazoline, dihydrocinnoline, tetrahydrocinnoline, benzooxathiane, dihydrobenzoxazine, dihydrobenzothiazine, pyrazinomorpholine, dihydrobenzoxazole, dihydrobenzothiazole, and dihydrobenzimidazole.

The ring to which R ² and R ³ are bonded may have a substituent on the ring. The substituents include halogen, cyano, nitro, alkyl, hydroxyalkyl, halogenoalkyl, hydroxycycloalkyl, cycloalkyl, aralkyl, alkenyl, alkynyl, alkoxy, halogenoalkoxy, alkylthio, mono- or dialkylamino, acyl, carboxy, carbamoyl. , Phenyl, naphthyl and the like. Preferred are alkyl, hydroxyalkyl, hydroxycycloalkyl, cycloalkyl, alkoxy, phenyl, etc., and more preferred are methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 2-butyl, isobutyl, t-butyl. , Methoxy, ethoxy, 1-propoxy, 2-propoxy, 1-butoxy, 2-butoxy, isobutoxy, t-butoxy and the like.
The number of substituents on the ring is, for example, 1 to 5, preferably 1 to 3, and more preferably 1 or 2.

In formula (I), R ⁴ and R ⁵ are the same or different and each is a hydrogen atom or an organic functional group. Here, the organic functional group is as described above. R ⁴ and R ⁵ may be bonded to each other to form a ring, and the ring may have a substituent on the ring. Examples of the ring include a 3- to 10-membered monocyclic or bicyclic saturated or unsaturated carbocycle, and a 3- to 10-membered monocyclic or bicyclic saturated or unsaturated heterocycle. The substituents are the same as those described for R ² and R ³ .

In formula (I), R ⁶ is a hydrogen atom, hydroxy, amino, alkoxy, thiol or halogen, preferably a hydrogen atom and hydroxy.

Preferred compounds represented by formula (I) are
R ¹ is lower alkyl or 1-(3,4-dimethoxyphenyl)-1,3-dihydroxy-2-propyl, R ⁶ is a hydrogen atom, R ² and R ³ are bonded to each other and are unsubstituted. A compound which is a benzene ring and R ⁴ and R ⁵ are the same or different and is a hydrogen atom, lower alkyl or lower alkoxy; or R ¹ is lower alkyl or 1-(3,4-dimethoxyphenyl)-1,3- Dihydroxy-2-propyl, R ⁶ is a hydrogen atom, at least one of R ² , R ³ , R ⁴ and R ⁵ is a hydrogen atom, and the remaining groups are lower alkyl or lower alkoxy. , A compound which may be the same or different when the remaining groups are plural;
Is.

More preferred compounds of formula (I) are
R ¹ is methyl, ethyl or 1-(3,4-dimethoxyphenyl)-1,3-dihydroxy-2-propyl, R ⁶ is a hydrogen atom, and R ² and R ³ are substituted with one another A compound having no benzene ring and R ⁴ and R ⁵ both being hydrogen atoms; or R ¹ is methyl, ethyl or 1-(3,4-dimethoxyphenyl)-1,3-dihydroxy-2-propyl, R ⁶ is a hydrogen atom, at least one of R ² , R ³ , R ⁴ and R ⁵ is a hydrogen atom, the remaining group is methyl, ethyl, methoxy or ethoxy, and the remaining group is When there are plural compounds, they may be the same or different;
Is.

Specific examples of the compound represented by the formula (I) are shown below.

The raw material in the present invention may be lignins. Lignin is a major constituent of the cell wall of plants, and a large amount of it is generated as a by-product in the papermaking process, so it is desired to effectively utilize it. Although the exact chemical structure of lignin has not been elucidated, it is known to be a polymer obtained by polymerizing a lignin monomer called monolignol. Monolignol is a p-hydroxycinnamic alcohol whose basic skeleton is a phenylpropane unit (C6-C3 unit), and coniferyl alcohol, sinapyl alcohol and p-coumaryl alcohol are typical. In lignin, the monomers are bound to each other by an ether bond and a carbon-carbon bond, of which β-O-4 bonds account for about 50%.

In the present invention, the lignins have a structure unique to lignin. For example, it refers to a structure having a structure unique to lignin such as a structure in which the above-mentioned monomers are bonded or a structure mainly having a β-O-4 bond as an inter-monomer bond. It may be a lignin derivative that has been modified, modified, or reduced in molecular weight. Examples of lignins are those partially having the structures shown below.

Examples of lignins include lignosulfonic acid and craft lignin. Lignosulfonic acid is preferred.

In the present invention, it has been confirmed in a test using a lignin model substrate that the β-O-4 bond can be cleaved to produce p-quinone, so lignins can also be used as a raw material.

<Products>
In the present invention, the compound represented by the formula (I) or lignin is converted into the compound represented by the formula (II) by oxidizing the compound by a predetermined method. ^{R 2,} R 3 in formula (II), ^{R 4} and ^{R 5} are the same as ^{R 2,} R 3, ^{R 4} and ^{R 5} in the formula (I).

<Oxidation process>
In the present invention, the compound represented by formula (I) or lignin is oxidized in the presence of a persulfate and an organic iodine compound in a suitable solvent.

The organic iodine compound may be a hypervalent iodine catalyst or its precursor. The raw material is converted to p-quinone by treating the raw material with a hypervalent iodine catalyst having an oxidizing action or a precursor thereof and a persulfate in a solvent. At this time, the hypervalent iodine catalyst is reduced and converted into a precursor. The precursor is oxidized by persulfate and converted to a hypervalent iodine catalyst. For example, the reaction process formula of one embodiment of the present invention is as follows: 2-iodoxobenzoic acid (IBA), which is a hypervalent iodine catalyst, oxidizes methoxybenzene, which is a raw material, and is itself reduced to give a precursor. It is converted to 2-iodobenzoic acid (2-IB), which is the body, and 2-IB is oxidized by oxone and converted to IBA.

The present inventor tested the organic iodine compound in the absence of persulfate, and as a result, the yield of p-quinones was low. Therefore, persulfate oxidizes the precursor and converts it into a hypervalent iodine catalyst. It is possible that p-quinones are produced not only by the action but also by some action in the oxidation of the raw material.

<Solvent>
In the present invention, a solvent selected from water and a mixed solvent of water and an organic solvent is used in the oxidation step. In the present invention, water (water or water in a mixed solvent) is important in terms of dissolving oxone and introducing an oxygen atom at the p-position.

As the solvent, a mixed solvent of water and an organic solvent is preferable. The mixing ratio (volume ratio) is not particularly limited as long as the target product can be produced, but for example, the organic solvent/water is 85/15 to 0/100, preferably 70/30 to 50/50.

Examples of the organic solvent in the mixed solvent include tetrahydrofuran (THF), ether solvents such as dioxane and dimethoxymethane, hydrocarbon solvents such as benzene, N,N-dimethylformamide (DMF), N-methylpyrrolidone (NMP) and acetonitrile. Aprotic solvent such as methanol, ethanol, tert-butyl alcohol, 2,2,2-trifluoroethanol (TFE), 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) And the like. Two or more kinds of these solvents may be mixed and used at an appropriate ratio. Preferred are aprotic solvents and protic solvents, and more preferred are acetonitrile and methanol.

<Persulfate>
The oxidation step uses at least one persulfate salt selected from monopotassium peroxomonosulfate and oxone. Monopotassium peroxomonosulfate is a monopotassium salt of peroxomonosulfate (H ₂ SO ₅ ) and is represented by the chemical formula of KHSO ₅ . Oxone is a registered trademark and is represented by the chemical formula of 2KHSO ₅ ·KHSO ₄ ·K ₂ SO ₄ . In the present invention, both may be mixed and used at an appropriate ratio. The mixing ratio is, for example, monopotassium peroxomonosulfate:oxone 1:95 to 99:1 (molar ratio). A preferred persulfate is oxone.

The amount of the persulfate used is not particularly limited as long as it can produce the desired product, but is usually 2 mol or more, preferably 2 mol to 10 mol, and more preferably 3 mol to 10 mol with respect to 1 mol of the raw material.

<Organic iodine compound>
The organic iodine compound used in the oxidation step has a compound in which an iodine atom is bonded to a benzene ring and an acidic group, carboxy or sulfo, is bonded to the ortho position (the carboxy or sulfo is bonded to the iodine atom to form (Including the case of forming a member ring) and an alkali metal salt thereof; a compound in which an iodine atom is bonded to a benzene ring and an alkyl having carboxy or sulfo is bonded to the ortho position thereof and an alkali metal salt thereof; iodobenzene; and iodooxy Contains benzene. Examples of the organic iodine compound include 2-iodoxybenzoic acid (IBX), 2-iodosobenzoic acid (IBA), 2-iodobenzoic acid (2-IB), 2-IB alkali metal salt (2-IBM), 2- Iodooxybenzenesulfonic acid (IBS), 2-iodosobenzenesulfonic acid (IBSA), 2-iodobenzenesulfonic acid (2-IS), 2-IS alkali metal salt (2-ISM), iodooxybenzene (PhIO) ₂ ), iodobenzene (PhI), 2-iodobenzeneacetic acid (IPAA), IPAA alkali metal salt (IPAAM), 2-iodobenzenepropanoic acid (IPPA), IPPA alkali metal salt (IPPAM), these benzene rings May be a substituent substituted with halogen, alkoxy, hydroxy, amino, nitro, cyano, carboxy, acyloxy, or lower alkyl, and these may be used alone or in combination of two or more.

2-iodoxybenzoic acid (IBX), 2-iodosobenzoic acid (IBA), 2-iodobenzoic acid (2-IB), 2-IB alkali metal salt (2-IBM), 2-iodoxybenzenesulfonic acid ( IBS), 2-iodosobenzenesulfonic acid (IBSA), 2-iodobenzenesulfonic acid (2-IS), 2-IS alkali metal salt (2-ISM), iodooxybenzene (PhIO ₂ ), iodobenzene ( PhI), 2-iodobenzeneacetic acid (IPAA), IPAA alkali metal salt (IPAAM), 2-iodobenzenepropanoic acid (IPPA), IPPA alkali metal salt (IPPAM) are compounds represented by the following chemical structural formulas. Is. In the chemical structural formula, M represents an alkali metal atom.

2-IBM, 2-ISM, IPAAM and IPPAM are, for example, sodium salt, potassium salt and lithium salt, preferably sodium salt and potassium salt.

In the present invention, 2-IB or 2-IBM is oxidized under persulfate or other oxidizing agent to be converted into IBA, and IBA oxidizes the raw material under persulfate to oxidize and Is converted to 2-IB or 2-IBM, and 2-IB or 2-IBM is converted to IBA under persulfate. IBX also oxidizes and oxidizes the raw material under persulfate and converts itself to 2-IB or 2-IBM, but 2-IB or 2-IBM converts to IBA under persulfate. Then, the cycle is started. Similarly, 2-IS or 2-ISM is oxidized under persulfate or other oxidant to be converted to IBSA, and IBSA oxidizes and oxidizes the raw material under persulfate as well as 2-IS. Or, it is converted to 2-ISM, and 2-IS or 2-ISM is converted to IBSA under persulfate, resulting in a cycle. IBS also oxidizes and oxidizes the raw material under persulfate and is converted to 2-IS or 2-ISM, but 2-IS or 2-ISM is converted to IBSA under persulfate. Enter the catalyst cycle. Therefore, it can be said that 2-IB and 2-IBM are precursors of IBX and IBA, and 2-IS and 2-ISM are precursors of IBS and IBSA. Similarly, PhI can be said to be a precursor of PhIO ₂ .

IBX, IBA, 2-IB, 2-IBM, IBS, IBSA, 2-IS, 2-ISM, PhIO ₂ , PhI, IPAA, IPAAM, IPPA, and IPPAM are known compounds, and commercially available ones are also known. Those manufactured by a known method can also be used.

In the present invention, IBX, IBA, 2-IB, 2-IBM, IBS, IBSA, 2-IS, 2-ISM, PhIO ₂ , PhI, IPAA, IPAAM, IPPA, or IPPAM benzene ring is halogen, alkoxy, Substituted products substituted with hydroxy, amino, nitro, cyano, carboxy, acyloxy, or lower alkyl can also be used as the organic iodine compound. The halogen is preferably a bromine atom or an iodine atom, more preferably an iodine atom. As acyloxy, acetoxy or tert-butylcarbonyloxy is preferable, and acetoxy is more preferable. The lower alkyl is preferably methyl, ethyl, 1-propyl, 2-propyl or t-butyl, more preferably methyl.

The number of these substituents in the above-mentioned substitution product is 1 to 4, preferably 1 or 2, and more preferably 1.

From the viewpoint of yield, it is preferable that these substituents in the above-mentioned substituted product are present at the para position of the iodine atom bonded to the benzene ring.

In one embodiment, the organic iodine compound is IBX, IBA, 2-IB, 2-IBM, IBS, IBSA, 2-IS, 2-ISM, and compounds in which a methyl group is bonded to the para position of the iodine atom in these compounds. It is at least 1 sort(s) selected from the group which consists of. When these organic iodine compounds are used, the yield of the compound represented by the formula (II) is high.

In another embodiment, the organic iodine compound is at least 1 selected from the group consisting of IBS, IBSA, 2-IS, 2-ISM, and a compound having a methyl group bonded to the para position of the iodine atom in these compounds. It is a seed. When these organic iodine compounds are used, the compound represented by the formula (II) can be produced in a low amount (for example, a catalytic amount).

Further, it is known that the organic iodine compound is used by supporting it on a carrier such as a resin such as silica gel and polystyrene, and in the present invention, the organic iodine compound supported on the carrier may be used.

The amount of the organic iodine compound used is not particularly limited as long as the intended product can be produced, but relative to 1 mol of the raw material, for example, 0.001 mol or more, 0.005 mol or more, 0.01 mol or more, 0.05 mol or more , 0.1 mol or more, 10 mol or less, 5 mol or less, 2 mol or less, 1 mol or less, 0.5 mol or less, 0.1 mol or less, etc., preferably 0.001 mol to 10 mol, more preferably Is 0.005 mol to 10 mol, more preferably 0.05 mol to 10 mol, and still more preferably 0.05 mol to 1 mol.

<Oxidizing agent>
An oxidizing agent may be used in the oxidation step. The use of the oxidizing agent facilitates the oxo oxidation of the raw material. It is considered that this is because radical active species that contribute to the reaction are likely to be generated.

As the oxidant, for example, peroxides such as oxone, hydrogen peroxide, metachloroperbenzoic acid (mCPBA), peracetic acid, sodium periodate, sodium hypochlorite, ozone and dimethyldioxirane (DDO) can be used. They may be used alone or in combination of two or more. Preferred oxidants are oxone, peracetic acid, or metachloroperbenzoic acid (mCPBA).

The amount of the oxidizing agent used is not particularly limited as long as the target product can be produced, but is usually 1 mol or more, preferably 1 to 10 mol, and more preferably 5 to 10 mol per 1 mol of the raw material.

<Metal catalyst>
A metal catalyst may be used in the oxidation step. The use of the metal catalyst facilitates the oxo oxidation of the raw material. It is considered that this is because radical active species that contribute to the reaction are likely to be generated.

Examples of the metal catalyst include vanadium oxide (V) (V ₂ O ₅ ), vanadium (III) oxide, ruthenium (IV) oxide (RuO ₂ ), ruthenium oxide (VIII), titanium oxide (IV) (TiO ₂ ), and the like. Metal oxides can be used.

The amount of the metal catalyst used is not particularly limited as long as the intended product can be produced, but is usually 0.05 mol or more, preferably 0.05 to 0.5 mol, and more preferably 0 mol, relative to 1 mol of the raw material. 0.05 to 0.1 mol.

From the viewpoint of improving yield, it is preferable to use the metal catalyst in combination with an oxidant.

<Oxidation reaction>
In the oxidation step, the target product can be produced without heating the reaction system, but it may be heated. The reaction temperature is generally 4°C-40°C, preferably 10°C-40°C, more preferably 30°C-35°C. The reaction time is not particularly limited as long as the desired product can be produced, but it is usually 30 minutes or more, preferably 1.5 hours to 3 hours.

In the oxidation step, the raw material, persulfate and organic iodine compound may be present in the solvent, and in addition to these, an oxidizing agent and/or a metal catalyst may be present. If necessary, the reaction system may be heated. The order of adding the solvent, the raw material, the persulfate, and the organic iodine compound is not particularly limited. For example, the raw material and the organic iodine compound are added to an organic solvent, and the persulfate, water, and optionally an oxidizing agent and/or a metal catalyst are added. Should be added.

The target product obtained in the above oxidation step can be isolated and purified. For example, isolation procedures such as filtration, concentration, and extraction are performed to separate the crude reaction product from the reaction mixture, and then the crude reaction product is subjected to general purification procedures such as column chromatography and recrystallization. By providing, the desired product can be isolated and purified from the reaction mixture. In the oxidation step, the target substance is often dissolved in a solvent, and in that case, the target substance can be extracted with an appropriate solvent such as deuterated chloroform or dichloromethane. In the present invention, the production of isomers such as o-quinone is suppressed, so that the desired product can be easily purified.

Hereinafter, the present invention will be specifically described with reference to test examples and the like, but the present invention is not limited to the embodiments shown in these.

The abbreviations of the compounds used in the following examples are as follows.
MeCN: Acetonitrile
NaIO ₄ : Sodium periodate
PIDA: Iodobenzene diacetate
PIFA: [bis(trifluoroacetoxy)iodo]benzene
PhI(OCO-tBu) ₂ : Bis(pivaloyloxy)iodo(III)benzene
MesI(OAc) ₂ : Iodume Citirange Acetate
IBA: 2-Iodosobenzoic acid
IBX: 2-iodoxybenzoic acid
2-IB:2-iodobenzoic acid
IBS: 2-iodoxybenzenesulfonic acid
2-IS: 2-iodobenzenesulfonic acid
2-ISM-Na: Sodium 2-iodobenzenesulfonate
2-ISM-K: Potassium 2-iodobenzenesulfonate
PhI: Iodobenzene
IPAA: 2-iodobenzeneacetic acid
IPPA: 2-iodobenzenepropanoic acid

<Test Example 1> Examination of Organic Iodine Compound According to the following reaction process formula, synthesis was performed using the organic iodine compound, persulfate and oxidizing agent shown in Tables 1 and 2.

1-Methoxynaphthalene (0.2 mmol, 31.6 mg) and the organic iodine compounds shown in Tables 1 and 2 were placed in a 10 mL eggplant flask, dissolved in acetonitrile (2.5 mL), and then added to Tables 1 and 2 A component (Oxone, V ₂ O ₅ ) which is not soluble in the organic solvent shown in 1 above was added, and further water (2.5 mL) and hydrogen peroxide shown in Tables 1 and 2 were added. After stirring at room temperature for the time shown in Table 1 and Table 2 using a magnetic stirrer, the reaction mixture was transferred to a separatory funnel using dichloromethane (40 mL), and the lower organic layer was dehydrated by natural filtration. I went. After concentration with an evaporator, silica gel chromatography was performed to obtain 1,4-naphthoquinone.
¹ H NMR (400 MHz, CDCl ₃ ): δ 6.98 (2H, s), 7.76 (2H, dd, J = 5.9, 3.4 Hz), 8.08 (2H, dd, J = 5.4, 3.4 Hz) ppm.

When NaIO ₄ , PIDA, PIFA, PhI(OCO-tBu) ₂ or MesI(OAc) ₂ was used as the organic iodine compound, the yield of the target compound was as low as 3% at maximum (entry 1-entry Five).
In the presence of IBA, IBX or 2-IB and oxone, the yield of the desired product was 30 to 60%, the conversion yield was 65 to 99%, which was higher than when other iodine compounds were used. Although not shown in Tables 1 and 2, the by-product 1,2-naphthoquinone was not detected (entry 13 to entry 22).
When IBX and IBA in an amount of 1 equivalent or less were used together with Oxone, the yield of the target substance was 6% at maximum (entry 6 to entry 9), and no catalytic action was observed.

<Test Example 2> Examination of mixing ratio of organic solvent and water Mixing ratio of organic solvent and water in the synthesis of 2-methoxy-1,4-benzoquinone from 1,3-dimethoxybenzene using oxone and 2-IB Examination of (acetonitrile/water; volume ratio)

According to the above reaction process formula, 1,3-dimethoxybenzene (4a) (0.1 mmol, 13.8 mg), 2-IB (0.1 mmol, 24.8 mg) and 1,4-dinitrobenzene as a standard substance were added to a 5 mL sample tube. (0.05 mmol, 8.4 mg) was added, and oxone (0.3 mmol, 184 mg) and a predetermined volume ratio of acetonitrile/water mixed solvent (1.0 mL) were added thereto and stirred with a magnetic stir bar. After stirring at room temperature for 1.5 hours, deuterated chloroform (1 mL) was added and shaken vigorously, and the obtained organic layer was subjected to quantitative NMR. Under the measurement conditions of observation center (6 ppm), observation range (6 ppm) and relaxation delay time (40 seconds), the NMR yield of 2-methoxy-1,4-benzoquinone (4b) was determined. The results are shown in Figure 1.
The volume ratio (acetonitrile/water) of the mixed solvent is as follows.
100/0, 80/20, 60/40, 50/50, 40/60, 30/70, 20/80, 0/100

From FIG. 1, it was confirmed that the solvent cannot be produced only by acetonitrile, and the synthetic reaction of 2-methoxy-1,4-benzoquinone proceeds in the presence of water or a mixed solvent of water and an organic solvent. Further, when a solvent containing water (including a case where the solvent is only water) was used, almost no by-products were formed.

<Test Example 3> Examination of Substrate Synthesis of 1,4-benzoquinone of Formula (II) from Compound of Formula (I) Using Oxone and 2-IB

[In the above reaction scheme, R ¹ to R ⁶ are the same as above. ]

Synthesis was performed according to the above reaction scheme.
A compound (1.0 mmol) of formula (I) shown in Table 3 and 2-IB (1.0 mmol, 248 mg) were placed in a 10 mL eggplant-shaped flask, and these were dissolved in acetonitrile (4 mL), followed by oxone ( 3.0 mmol, 1.844 g) and water (6 mL) were added, and the mixture was stirred with a magnetic stir bar. After stirring at room temperature for 1 hour, the solid matter was removed by suction filtration, and the product was extracted with dichloromethane (50 mL×2). The organic layer was washed with saturated aqueous sodium hydrogen carbonate solution (100 mL), and then dehydrated by natural filtration. After concentration by an evaporator, the compound of 5b was subjected to suction filtration using methanol, the compounds of 6b, 9b and 10b were subjected to silica gel chromatography using dichloromethane, and the compounds of 7b and 8b were mixed solvent (dichloromethane-pentane= Silica gel chromatography using 1:1) gave the compound of formula (II). The yield is shown in Table 3.

<Test Example 4> Investigation of organic iodine compound 2-methoxy-[1,4]benzoquinone (4b) and 2 in the oxidation reaction of 1-isopropoxy-2-methoxybenzene (11a) using oxone and an organic iodine compound Of isopropoxy-[1,4]benzoquinone (11b) formation ratio and conversion efficiency

According to the above reaction scheme, the following organic iodine compound (cat.) was used for the synthesis.

Put compound 11a (0.1 mmol, 16.6 mg) shown in the above reaction scheme, organic iodine compound (0.1 mmol) and 1,4-dinitrobenzene (0.05 mmol, 8.4 mg) as a standard substance into a 5 mL sample tube. , These were dissolved in acetonitrile (0.4 mL), oxone (0.3 mmol, 184 mg) and water (0.6 mL) were added, and the mixture was stirred with a magnetic stir bar. After stirring at room temperature for the time (1.5 hours or 3.0 hours) shown in Table 4, deuterated chloroform (1 mL) was added, and the mixture was vigorously shaken, and the obtained organic layer was subjected to quantitative NMR. The measurement conditions were the observation center (6 ppm), the observation range (6 ppm), and the relaxation delay time (40 seconds). Table 4 shows the NMR yields and conversion rates of compound 4b and compound 11b. 2-Isopropoxy-[1,4]benzoquinone (11b) could be easily purified by silica gel chromatography using dichloromethane.
¹ H NMR (400 MHz, CDCl ₃ ): δ 1.38 (6H, d, J = 6.0 Hz), 4.46 (1H, sep, J= 6.0 Hz), 5.89 (1H, d, J = 1.4 Hz), 6.66- 6.69 (2H, m) ppm.

In this test example, a mixture of the secondary ether oxidation product 4b and the primary ether oxidation product 11b was obtained, and since the primary ether oxidation product 11b was the main product, the primary ether group was more easily oxidized. It was confirmed. In addition, in this test example, it was confirmed that IPAA, IPPA and PhI also convert the raw material compounds into the p-quinone form.

Regarding 2-IB, the yield and 11b selectivity were improved by using 5-Me2-IB with a methyl group introduced at the 5-position. For 2-ISM, 11b selectivity was improved by using 5-Me2-ISM with a methyl group introduced at the 5-position. From these facts, it was confirmed that the selectivity was improved by introducing an alkyl into the para-position of the iodine atom of the organic iodine compound.

It was found that almost no by-products were generated from those that showed a value close to the total yield of p-quinone (Total yield) and the conversion efficiency (Conversions) of 11a. In this case, compound 11b could be purified by a simple method using silica gel chromatography.

<Test Example 5> Examination of p-quinone conversion from lignin model substrate A lignin model substrate having a β-O-4 structure using oxone and an organic iodine compound, namely 1-(3,4-dimethoxyphenyl)-2 Synthesis of 2-methoxy-[1,4]benzoquinone (4b) from -(2-methoxyphenoxy)-1,3-propanediol (12a)

According to the above reaction scheme, the following organic iodine compound (cat.) was used for the synthesis.

Put 12a (0.1 mmol, 33.4 mg), organic iodine compound (0.1 mmol or 0.005 mmol) and 1,4-dinitrobenzene (0.05 mmol, 8.4 mg) as a standard substance into a 5 mL sample tube, and add them to acetonitrile (0.4 mg). After solubilizing with Oxone (0.3 mL, 184 mg) and water (0.6 mL), the mixture was stirred with a magnetic stir bar. After stirring at room temperature for 3 hours, deuterated chloroform (1 mL) was added and shaken vigorously, and the obtained organic layer was subjected to quantitative NMR. The measurement conditions were the observation center (6 ppm), the observation range (6 ppm), and the relaxation delay time (40 seconds). The NMR yield of 4b was 45% for 2-IB, 50% for 5-Me2-IB, 35% for 2-ISM-Na, and 41% for 5-Me2-ISM-K.

In this test example, it was confirmed that the lignin residue bonded to the benzene ring was more likely to be p-quinoneized than the methoxy group. In this test example, the lignin model substrate 12a was converted into a useful low molecular weight compound 4b. The lignin model substrate 12a has a β-O-4 structure. The β-O-4 structure is an ether bond that accounts for about 50% of the total bond mode in lignin. In the present test example, the β-O-4 structure of this substrate was cleaved to cleave 2-methoxy-[1,4]benzoquinone. Therefore, the production method of the present invention uses lignin as a raw material to produce useful p-quinone. It was confirmed that it can be converted into a low molecular weight compound of the system.

<Test Example 6> Examination of Reaction Using Catalytic Amount of Organic Iodine Compound 2,6-Dimethoxy-[1, from 1,3,5-trimethoxybenzene (5a) using oxone and a catalytic amount of organic iodine compound Synthesis of 4]benzoquinone (5b) and synthesis of 2-methoxy-6-methyl-[1,4]benzoquinone (10b) from 3,5-dimethoxytoluene (10a)

According to the above reaction scheme, synthesis was performed using a catalytic amount of 2-iodobenzoic acid (2-IB).

Put compound 5a (0.1 mmol, 16.8 mg) and 2-IB (0.005 mmol, 12.4 mg) in a 5 mL sample tube, dissolve them with acetonitrile (0.4 mL), and then oxone (0.3 mmol, 184 mg). And water (0.6 mL) were added and stirred with a magnetic stir bar. After stirring at room temperature for 3 hours, the solid matter was removed by suction filtration, and the product was extracted with dichloromethane (50 mL twice). The organic layer was washed with saturated aqueous sodium hydrogen carbonate solution (100 mL) and then dehydrated by natural filtration. After concentration by an evaporator, compound 5b was obtained by suction filtration using methanol. The isolated yield of 5b was 62%.

Compound 5b was obtained in the same manner except that the amount of 2-IB was changed to 0.02 mmol and 49.6 mg and the stirring time was changed to 1 hour. The isolated yield of 5b was 80%.

Compound 5a (0.1 mmol, 16.8 mg) was replaced with compound 10a (0.1 mmol, 15.2 mg), stirring time was changed to 2 hours, suction filtration using methanol was replaced with silica gel chromatography using dichloromethane. In the same manner, Compound 10b was obtained. The isolated yield of 10b was 86%.

It was confirmed by this test example that the compounds 5b and 10b could be obtained in good yield even when a catalytic amount of 2-IB (0.005 mmol) was used. In addition, compound 5b was obtained in a high yield of 80% even when a small amount (0.02 mmol) of 2-IB was used.

Also, in all the syntheses of this test example, the conversion efficiencies (Conversions) of the raw material compounds 5a and 10a were close to the yields (Yield) of the p-quinone compounds 5b and 10b. From this, it was confirmed that even when a catalytic amount of the organic iodine compound was used, almost no by-products were generated. Therefore, the compounds 5b and 10b could be purified by a simple method such as suction filtration and silica gel chromatography.

INDUSTRIAL APPLICABILITY The present invention is suitable for decomposing lignin, which is highly water-soluble among lignins, because the reaction proceeds in the presence of water. In addition, sulfonic acid-based organic iodine compounds (2-ISM-Na and 5-Me 2-ISM-K) were able to decompose lignin with a small amount (catalytic amount).
As a method for converting a lignin model substrate into p-quinone, it is known that the maximum yield is 30% by using a porphyrin-oxone reaction system (New J. Chem., 1989, 13, 801). ). The present invention is superior to this method in terms of activity and ease of catalyst synthesis.

Claims (5)

1. Formula (I)
   

   

   [In the formula,
   R ¹ represents alkyl or 1-(3,4-dimethoxyphenyl)-1,3-dihydroxy-2-propyl,
   R ² and R ³ are the same or different and each represents a hydrogen atom or an organic functional group, and R ² and R ³ may be bonded to each other to form a ring, and the ring has a substituent on the ring. You may have.
   R ⁴ and R ⁵ are the same or different and each represents a hydrogen atom or an organic functional group, and R ⁴ and R ⁵ may be bonded to each other to form a ring, and the ring has a substituent on the ring. You may have.
   R ⁶ represents a hydrogen atom, hydroxy, amino, alkoxy, thiol or halogen. ] From the compound or lignin represented by
   Formula (II)
   

   

   [Wherein R ² , R ³ , R ⁴ and R ⁵ are the same as defined above. ]
   A method for producing a compound represented by:
   A compound represented by the formula (I) or lignins,
   In a solvent selected from water and a mixed solvent of water and an organic solvent,
   At least one persulfate selected from monopotassium peroxomonosulfate and oxone, and 2-iodoxybenzoic acid (IBX), 2-iodosobenzoic acid (IBA), 2-iodobenzoic acid (2-IB), 2- Alkali metal salt of IB (2-IBM), 2-iodoxybenzenesulfonic acid (IBS), 2-iodosobenzenesulfonic acid (IBSA), 2-iodobenzenesulfonic acid (2-IS), 2-IS alkali Metal salt (2-ISM), iodooxybenzene (PhIO ₂ ), iodobenzene (PhI), 2-iodobenzeneacetic acid (IPAA), IPAA alkali metal salt (IPAAM), 2-iodobenzenepropanoic acid (IPPA), Alkali metal salt of IPPA (IPPAM), and at least one organic compound selected from the group consisting of substituents in which these benzene rings are substituted with halogen, alkoxy, hydroxy, amino, nitro, cyano, carboxy, acyloxy or lower alkyl. Iodine compounds,
   A method comprising the step of oxidizing in the presence of
2. The method according to claim 1, wherein the oxidizing step is performed under conditions in which hydrogen peroxide or hydrogen peroxide and a metal catalyst are further present.
3. The method according to claim 1, wherein R ⁶ is a hydrogen atom.
4. The method according to any one of claims 1 to 3, wherein R ¹ is lower alkyl.
5. R ² and R ³ are the same or different and are a hydrogen atom, alkyl or alkoxy, or R ² and R ³ are bonded to each other to form a benzene ring,
   R ⁴ and R ⁵ are the same or different and are a hydrogen atom, alkyl or alkoxy, or R ⁴ and R ⁵ are bonded to each other to form a benzene ring,
   The method according to any one of claims 1 to 4.

Images