Method for producing azulene compound

Abstract

To provide a method for producing an azulene compound with higher safety and efficiency.SOLUTION: A method for producing a compound having an azulene skeleton includes the step of subjecting a composition containing a compound having a hydrogenated azulene skeleton to a flow-based dehydrogenation, the dehydrogenation to be conducted in the presence of a transition metal catalyst, and a porous catalyst and / or acid catalyst.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a method for producing a compound having an azulene skeleton (azulene compound). [Background technology]

[0002] Guaiazulene has long been used as an anti-inflammatory drug for stomatitis, dermatitis, and the like, and its derivative, sodium guaiazulene sulfonate, is widely used in pharmaceuticals such as anti-inflammatory drugs and anti-peptic ulcer drugs, quasi-drugs, and cosmetics.

[0003] Known methods for producing guaiazulene include dehydrating natural essential oils and then subjecting them to a thermal dehydrogenation reaction with sulfur at 200°C or higher (Patent Document 1). Also known is a method in which Eucalyptus globulus oil is dehydrated with boric acid and then dehydrogenated at 260°C using palladium carbon (Patent Document 2). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] CN 108863707 A [Patent Document 2] CN 111943802 A Summary of the Invention [Problem to be solved by the invention]

[0005] According to the conventional production methods such as those disclosed in Patent Documents 1 and 2, a high reaction temperature is required for the dehydrogenation reaction, and harmful hydrogen sulfide is generated by the reaction with sulfur, resulting in safety and efficiency issues in industrial production.

[0006] The main object of the present invention is to provide a safer and more efficient method for producing an azulene compound. [Means for solving the problem]

[0007] The present inventors conducted extensive research to solve the above-mentioned problems and found that a compound having an azulene skeleton can be produced more safely and efficiently by subjecting a composition containing a compound having a hydrogenated azulene skeleton to a flow dehydrogenation reaction in the presence of a transition metal catalyst and a porous catalyst and / or an acid catalyst. The present invention was completed based on this finding and through further research.

[0008] The present invention includes the following aspects. Section 1. A method for producing a compound having an azulene skeleton, comprising: A method comprising the step of subjecting a composition containing a compound having a hydrogenated azulene skeleton to a flow dehydrogenation reaction, wherein the dehydrogenation reaction is carried out in the presence of a transition metal catalyst, a porous catalyst, and / or an acid catalyst. Section 2. Item 1. The method according to Item 1, wherein the dehydrogenation reaction is carried out in the presence of a transition metal catalyst, a porous catalyst, and an acid catalyst. Section 3. Item 3. The method according to Item 1 or 2, wherein the transition metal catalyst contains at least one selected from the group consisting of transition metals of Groups 8 to 10 of the periodic table. Section 4. 4. The method according to any one of Items 1 to 3, wherein the porous catalyst is at least one selected from the group consisting of activated carbon, zeolite, and celite. Section 5. 5. The method according to any one of items 1 to 4, wherein the acid catalyst comprises at least one selected from the group consisting of a cation exchange resin, acidic silica, and an inorganic acid. Section 6. 6. The method according to any one of Items 1 to 5, wherein the compound having a hydrogenated azulene skeleton is at least one selected from the group consisting of compounds having a decahydroazulene skeleton, compounds having an octahydroazulene skeleton, compounds having a decahydro-1H-cyclopropa[e]azulene skeleton, and compounds having an octahydro-1H-cyclopropa[e]azulene skeleton. Section 7. Item 7. The method according to any one of Items 1 to 6, wherein the composition contains a plant essential oil containing the compound having the hydrogenated azulene skeleton. [Effects of the Invention]

[0009] According to the present invention, an azulene compound can be produced more safely and efficiently than by conventional batch-type production methods. [Brief explanation of the drawings]

[0010] [Figure 1] Figure 1 shows a schematic diagram of a typical flow reactor. DETAILED DESCRIPTION OF THE INVENTION

[0011] In one embodiment of the present invention, a method for producing a compound having an azulene skeleton includes a step (hereinafter, sometimes referred to as “step (1)”) of subjecting a composition containing a hydrogenated compound having an azulene skeleton (hereinafter, sometimes referred to as “composition X”) to a flow-type dehydrogenation reaction, and the dehydrogenation reaction is carried out in the presence of a transition metal catalyst and a porous catalyst and / or an acid catalyst.

[0012] (Compounds with hydrogenated azulene skeleton) In this specification, the term "hydrogenated azulene skeleton" is used to encompass skeleton A, which is composed of a ring in which at least some of the carbon-carbon double bonds of an azulene ring have been replaced with carbon-carbon single bonds, and skeleton B, which is composed of two substituents that are substituted on skeleton A at any position (for example, at the ortho position) and are bonded to each other to form a ring.

[0013] Examples of the skeleton A include a decahydroazulene skeleton, an octahydroazulene skeleton, a hexahydroazulene skeleton, and a tetrahydroazulene skeleton. The skeleton A is preferably a decahydroazulene skeleton or an octahydroazulene skeleton.

[0014] Examples of the skeleton B include a decahydro-1H-cyclopropa[e]azulene skeleton, an octahydro-1H-cyclopropa[e]azulene skeleton, a hexahydro-1H-cyclopropa[e]azulene skeleton, a tetrahydro-1H-cyclopropa[e]azulene skeleton, and a 1,2,3,4,5,6,7,8-octahydro-4,7-methanoazulene skeleton. Preferably, the skeleton B is a decahydro-1H-cyclopropa[e]azulene skeleton or an octahydro-1H-cyclopropa[e]azulene skeleton.

[0015] A compound (raw material compound) having a hydrogenated azulene skeleton usually has one or more substituents on the hydrogenated azulene skeleton, such as a hydroxyl group and an aliphatic hydrocarbon group which may have one or more substituents.

[0016] Examples of the aliphatic hydrocarbon group include an alkyl group, an alkenyl group, a cycloalkyl group, and a cycloalkenyl group.

[0017] Examples of the alkyl group include linear or branched C alkyl groups such as methyl, ethyl, propyl (n-propyl, isopropyl), butyl (n-butyl, isobutyl, sec-butyl, tert-butyl), pentyl, and hexyl groups. 1-12 Examples include alkyl groups.

[0018] Examples of the alkenyl group include linear or branched C alkyl groups such as vinyl, 1-propen-1-yl, 2-propen-1-yl, isopropenyl, 2-buten-1-yl, 4-penten-1-yl, and 5-hexen-1-yl. 2-12 Examples include alkenyl groups.

[0019] Examples of the cycloalkyl group include a C cycloalkyl group such as a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, and a cycloheptyl group. 3-20 Examples include a cycloalkyl group.

[0020] Examples of the cycloalkenyl group include a C cycloalkenyl group such as a cyclopropenyl group, a cyclobutenyl group, a cyclopentenyl group, a cyclohexenyl group, and a cycloheptenyl group. 3-20 Examples include a cycloalkenyl group.

[0021] The aliphatic hydrocarbon group may have, for example, a hydroxyl group as a substituent. Examples of the aliphatic hydrocarbon group having a hydroxyl group as one or more substituents include the above-mentioned alkyl groups substituted with one or more hydroxyl groups (hydroxyalkyl groups), and the above-mentioned alkenyl groups, cycloalkyl groups, or cycloalkenyl groups substituted with one or more hydroxyl groups.

[0022] The substituent optionally substituted on the hydrogenated azulene skeleton is preferably at least one selected from the group consisting of a hydroxyl group, an alkyl group, an alkenyl group, and a hydroxyalkyl group.

[0023] Examples of compounds having a hydrogenated azulene skeleton include guaiol, gurjunene, aromadendrene, guaienes, ledol, ledene, and patchulenes.

[0024] Composition X (raw material) may contain only one compound having a hydrogenated azulene skeleton, or may contain two or more compounds.

[0025] Plant essential oils usually contain a compound having a hydrogenated azulene skeleton. Therefore, the compound having a hydrogenated azulene skeleton may be contained in composition X in the form of a plant essential oil. That is, composition X may be a composition containing a plant essential oil. The plant essential oil is not particularly limited, but examples thereof include camphor oil, eucalyptus oil, celery oil, patchouli oil, geranium oil, peppermint oil, Gurjun Balasam oil, Guaiac wood oil, Eucalyptus globulus oil, and mixed oils of two or more of these.

[0026] (solvent) In one embodiment, composition X preferably does not contain a solvent (is solvent-free). In another embodiment, composition X preferably further contains a solvent. The solvent may be, for example, a nonpolar solvent, a protic polar solvent, or an aprotic polar solvent. Specific examples of the solvent include the following solvents. Aliphatic hydrocarbon solvents such as cyclohexane, methylcyclohexane, decahydronaphthalene, 1,2,3,4-tetrahydronaphthalene, and n-dodecane; Aromatic hydrocarbon solvents such as mesitylene, pseudocumene, xylene, and toluene; Halogenated hydrocarbon solvents such as chlorobenzene, dichlorobenzene, and bromobenzene; · Alcoholic solvents such as n-butanol, n-pentanol, n-hexanol, n-heptanol, n-octanol; Ether solvents such as dioxane, tetrahydrofuran, and cyclopentyl methyl ether; Carboxylic acid solvents such as acetic acid and formic acid; Sulfoxide solvents such as dimethyl sulfoxide and sulfolane; Amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; Urea solvents such as 1,3-dimethyl-2-imidazolidinone; and · Ionic liquids such as tetrahexylammonium bromide, 1-methyl-3-propylimidazolium bromide, and triethylsulfonium bis(trifluoromethanesulfonyl)imide. The solvent may be used alone or in the form of a mixture of two or more solvents in any ratio.

[0027] The content of the solvent in Composition X is not particularly limited. For example, the concentration of the compound having a hydrogenated azulene skeleton is preferably 0.01 mol / L or more or 0.05 mol / L or more, and preferably 3.5 mol / L or less or 3 mol / L or less. In one embodiment, the concentration of the compound having a hydrogenated azulene skeleton is preferably 2 mol / L or less or 1 mol / L or less. Furthermore, when the compound having a hydrogenated azulene skeleton is used in the form of a plant essential oil, the content of the solvent per 1 g of plant essential oil is preferably 0 mL or more, 0.5 mL or more, 1 mL or more, 1.5 mL or more, or 2 mL or more, and preferably 300 mL or less, 250 mL or less, 200 mL or less, 150 mL or less, 100 mL or less, or 50 mL or less.

[0028] Composition X may also be, for example, an unreacted residue that may be contained in the reaction product of step (1).

[0029] (transition metal catalyst) Examples of transition metals contained in the transition metal catalyst include, but are not limited to, transition metals of Group 8 of the periodic table such as ruthenium; transition metals of Group 9 of the periodic table such as cobalt and rhodium; and transition metals of Group 10 of the periodic table such as nickel, palladium, and platinum. The transition metal catalyst may contain only one type of transition metal, or may contain two or more types. The transition metal is preferably ruthenium, rhodium, palladium, or platinum, and more preferably palladium.

[0030] The transition metal catalyst is preferably used in the form of a solid-phase catalyst in which the transition metal is supported on a solid-phase support. Examples of solid-phase supports include activated carbon, alumina, silica, barium sulfate, and calcium carbonate. The amount of the transition metal supported on the solid-phase support may be, for example, 0.5% by mass or more, or 1% by mass or more, or 20% by mass or less, 15% by mass or less, 10% by mass or less, or 7% by mass or less.

[0031] (porous catalyst) Examples of porous catalysts include activated carbon, celite, activated clay, acid clay, and zeolite. Of these, the zeolite may be any of synthetic zeolite, artificial zeolite, and natural zeolite. Examples of the crystal structure of zeolite include A-type, X-type, beta, ZSM-5, ferrierite, mordenite, L-type, and Y-type. One type of porous catalyst may be used alone, or two or more types may be used in combination. The porous catalyst is preferably at least one selected from the group consisting of activated carbon, zeolite, and celite (for example, activated carbon alone, zeolite alone, celite alone, or a combination of zeolite and celite).

[0032] The particle size of the porous catalyst may be, for example, 10 mesh or more or 15 mesh or more, or 250 mesh or less or 200 mesh or less. The particle size can be expressed as the range of the sieve opening size by sieving, for example, using a standard sieve specified in JIS Z 88019.

[0033] The pore size of the porous catalyst may be, for example, 0.1 nm or more, 0.2 nm or more, 0.3 nm or more, 0.4 nm or more, or 0.5 nm or more, or 200 nm or less, 150 nm or less, or 100 nm or less. The pore size can be measured, for example, by a gas adsorption method and can be determined based on the adsorption isotherm of nitrogen gas at 77 K.

[0034] The specific surface area of ​​the porous catalyst is, for example, 20 m 2 / g or more, 50m 2 / g or more, 100m 2 / g or more, 300m 2 / g or more, 500m 2 / g or more, 700m 2 / g or more, or 1000m 2 / g or more, and 2 The specific surface area can be measured, for example, by a gas adsorption method, and can be determined based on the adsorption isotherm of nitrogen gas at 77K.

[0035] The amount of the porous catalyst is preferably 50 parts by mass or more, or 100 parts by mass or more, per 100 parts by mass of the transition metal catalyst. In one embodiment, the amount of the porous catalyst is preferably 200 parts by mass or more, 300 parts by mass or more, 400 parts by mass or more, or 500 parts by mass or more, per 100 parts by mass of the transition metal catalyst. The amount of the porous catalyst is preferably 5,000 parts by mass or less, 4,000 parts by mass or less, 3,000 parts by mass or less, 2,000 parts by mass or less, or 1,000 parts by mass or less, per 100 parts by mass of the transition metal in the transition metal catalyst. The amount of the porous catalyst is preferably 30,000 parts by mass or less, 25,000 parts by mass or less, or 20,000 parts by mass or less, per 100 parts by mass of the transition metal in the transition metal catalyst.

[0036] (acid catalyst) Examples of acid catalysts include solid acid catalysts such as cation exchange resins, acidic silica, and inorganic acids. Examples of cation exchange resins include sulfonic acid-type cation exchange resins such as Amberlite™ and Amberlyst™, and carboxylic acid-type cation exchange resins. Examples of acidic silicas include silica having sulfonic acid groups such as Chromatorex™ SO3H, and silica having carboxylic acid groups such as Chromatorex™ COOH. Examples of inorganic acids include boric acid. One acid catalyst may be used alone or in combination of two or more. These acid catalysts may also be combined with amines. The amines may be linear or cyclic amines. Examples of linear amines include trialkylamines such as triethylamine. Examples of cyclic amines include nitrogen-containing aromatic heterocycles such as pyridine. One amine may be used alone or in combination of two or more. In a preferred embodiment, the acid catalyst includes at least one selected from the group consisting of a cation exchange resin, acidic silica, and an inorganic acid, and may further include an amine. In this embodiment, the acid catalyst is preferably silica having sulfonic acid groups, such as Chromatorex™ SO3H, or a combination of such silica and a trialkylamine, such as triethylamine.

[0037] The amount of the acid catalyst is preferably 0.1 parts by mass or more, 0.5 parts by mass or more, or 1 part by mass or more, and preferably 100 parts by mass or less, 95 parts by mass or less, or 90 parts by mass or less, per 100 parts by mass of the transition metal catalyst. In one embodiment, the amount of the acid catalyst is preferably 80 parts by mass or less, 50 parts by mass or less, or 30 parts by mass or less, per 100 parts by mass of the transition metal catalyst. In another embodiment, the amount of the acid catalyst is preferably 10 parts by mass or less, per 100 parts by mass of the transition metal in the transition metal catalyst. The amount of the acid catalyst is preferably 2500 parts by mass or less or 2000 parts by mass or less, per 100 parts by mass of the transition metal in the transition metal catalyst. Furthermore, when the acid catalyst is combined with a porous catalyst, the amount of the acid catalyst is preferably 0.1 parts by mass or more, 0.5 parts by mass or more, or 1 part by mass or more, and preferably 100 parts by mass or less, 90 parts by mass or less, or 80 parts by mass or less, per 100 parts by mass of the porous catalyst. In one embodiment, the amount of the acid catalyst is preferably 50 parts by mass or less, 40 parts by mass or less, 30 parts by mass or less, 20 parts by mass or less, or 10 parts by mass or less, relative to 100 parts by mass of the porous catalyst.

[0038] (Other ingredients) Step (1) may be carried out in the presence of other components, such as a base catalyst and a scavenger.

[0039] Examples of the base catalyst include alkaline earth metal oxides such as magnesium oxide, calcium oxide, and barium oxide; alkaline earth metal hydroxides such as magnesium hydroxide and barium hydroxide; and zeolites exchanged with alkali metal ions.

[0040] The scavenger is not particularly limited as long as it is a compound that can act as a hydrogen acceptor. For example, olefins such as ethylene, propylene, butadiene, styrene, α-methylstyrene, p-methylstyrene, and d-limonene; ketones such as cyclohexanone and acetophenone; unsaturated fatty acids such as oleic acid, linoleic acid, and linolenic acid; oxygen, sulfur dioxide, and the like can be used.

[0041] The other components may be used alone or in combination of two or more.

[0042] (Flow dehydrogenation reaction) Compared with conventional batch-type dehydrogenation reactions, flow-type dehydrogenation reactions are advantageous in that, for example, they have good heat transfer efficiency because temperature control of only the reaction field is sufficient, and the reaction field conditions are maintained even when the reaction scale is large. Furthermore, when a solid-phase catalyst is used, it is advantageous in that operations such as filtration to remove the catalyst after the reaction are not required. These are significant advantages for industrial-scale production.

[0043] The dehydrogenation reaction is preferably carried out in a flow reactor equipped with a column containing a transition metal catalyst and a porous catalyst and / or an acid catalyst as a solid-phase catalyst. Figure 1 shows a schematic diagram of a typical flow reactor. The flow reactor includes: column 1 packed with the solid-phase catalyst; supply section 2 for supplying composition X to the top of column 1; supply section 3 for supplying a scavenger to the top of column 1; supply section 4 for supplying an inert gas to the top of column 1; and recovery section 5 for recovering the reaction product from the bottom of column 1.

[0044] The flow rate of composition X is, for example, 0.01 mL / min or more, preferably 0.05 mL / min or more, and more preferably 0.1 mL / min or more, and is, for example, 10,000 mL / min or less, preferably 5,000 mL / min or less, and more preferably 1,000 mL / min or less.

[0045] The atmosphere for the dehydrogenation reaction may be, for example, an inert gas such as nitrogen or argon, or air. Nitrogen or argon is preferred. The flow rate of the atmosphere is not particularly limited, but may be, for example, 0.01 mL / min or more and 10 mL / min or less.

[0046] The reaction temperature for the dehydrogenation reaction is not particularly limited, but is, for example, −70° C. or higher, preferably −20° C. or higher, more preferably 0° C. or higher, even more preferably 20° C. or higher, still more preferably 50° C. or higher, particularly preferably 100° C. or higher, and especially preferably 120° C. or higher. The reaction temperature is, for example, 500° C. or lower, preferably 400° C. or lower, more preferably 250° C. or lower, and even more preferably 200° C. or lower.

[0047] The dehydrogenation reaction can be carried out under normal pressure, elevated pressure, or reduced pressure. Specific pressures may be, for example, -3 MPa or higher or 0 MPa or higher, or 3 MPa or lower or 1 MPa or lower.

[0048] In one embodiment of the present invention, the method for producing a compound having an azulene skeleton may include, in addition to step (1), step (2) of performing one or more treatments of washing, drying, separation, and purification. When the method includes a step of separating the reaction product of step (1) into a high-concentration layer and a low-concentration layer, the method may further include step (3) of using the low-concentration layer as composition X and subjecting it to a dehydrogenation reaction.

[0049] (product) A compound (product) having an azulene skeleton usually has one or more substituents on the azulene skeleton. Examples of the substituent include a hydroxyl group and an aliphatic hydrocarbon group which may have one or more substituents. Examples of the aliphatic hydrocarbon group which may have one or more substituents include the same groups as those described in the section "Compound having a hydrogenated azulene skeleton." [Example]

[0050] Examples of the present invention will be described below, but the present invention is not limited to these examples.

[0051] [Method for measuring the conversion rate and production rate of guaiazulene] The conversion rate and production rate (%) of guaiazulene are values ​​calculated from the molar amounts of guaiazulene and substrate (gurjunene, guaiol, etc.) using the following formula. The molar amounts were determined by the internal standard method from gas chromatographic analysis of the reaction solution. Conversion rate (%) = (1 - [substrate after reaction] / [substrate before reaction]) x 100 Production rate (%) = [guaiazulene in reaction solution] / [substrate before reaction] × 100

[0052] The conditions for gas chromatographic analysis are as follows: Equipment: Gas chromatograph Agilent Technologies 7820A (Agilent Technologies) Column: Inertcap5 0.53 mm x 30 m, 2.0 μm (GL Sciences) Detector: FID Injection temperature: 250℃ Detector temperature: 250℃ Column temperature: 50°C to 250°C at 10°C / min

[0053] [Example 1] A stainless steel column tube (10 mm x 300 mm, with a stainless steel filter) for flow reactors was packed with a mixture of 0.4 g of 5% Pd / C (Type STD, N.E. Chemcat) as a transition metal catalyst, 4 g of activated carbon (Nacalai Tesque, product code 07912-05) as a porous catalyst, and 0.1 g of Chromatorex™ SO3H MB100-75 / 200 (Fuji Silysia Chemical) as an acid catalyst, and attached to the flow reactor shown in Figure 1. A solution of 78.6 g of Gurjun Balasam oil dissolved in 500 mL of decalin was prepared as the raw material solution. Nitrogen was flowed at 1 mL / min, and the solvent decalin was pumped at a rate of 1 mL / min to replace the atmosphere in the column. The column thermostat was then heated to 200 °C, and the flow path was switched to the raw material solution, which was then pumped into the column at a flow rate of 0.5 mL / min. The distilled reaction liquid was analyzed using a gas chromatograph (FID-GC). Three hours after the start of the reaction, the production rate of guaiazulene was 15.6%.

[0054] [Example 2] Except for changing the amount of the acid catalyst to 0.04 g, the same procedure as in Example 1 was carried out. As a result of gas chromatographic analysis, the production rate of guaiazulene was 13.8% 3 hours after the start of the reaction.

[0055] [Example 3] Except for changing the porous catalyst to celite, the same operation as in Example 1 was carried out. As a result of gas chromatographic analysis, the production rate of guaiazulene was 10.7% 3 hours after the start of the reaction.

[0056] [Example 4] Except for not using an acid catalyst, the procedure was the same as in Example 1. As a result of gas chromatographic analysis, the production rate of guaiazulene was 8.6% 3 hours after the start of the reaction.

[0057] [Example 5] Except for changing the transition metal catalyst to 3% Pt / C, the procedure was the same as in Example 1. As a result of gas chromatographic analysis, the production rate of guaiazulene was 5.5% 3 hours after the start of the reaction.

[0058] [Example 6] Except for changing the transition metal catalyst to 5% Rh / C, the procedure was the same as in Example 1. As a result of gas chromatographic analysis, the production rate of guaiazulene was 5.1% 3 hours after the start of the reaction.

[0059] [Example 7] Except for changing the transition metal catalyst to 5% Ru / C, the procedure was the same as in Example 1. As a result of gas chromatographic analysis, the production rate of guaiazulene was 5.2% 3 hours after the start of the reaction.

[0060] [Example 8] The same procedure as in Example 1 was repeated, except that the raw material was changed to a solution of 13.1 g of guaiac wood oil dissolved in 500 ml of decalin, and the column thermostatic bath was heated to 180° C. Gas chromatographic analysis showed that the production rate of guaiazulene was 10.5% 3 hours after the start of the reaction.

[0061] [Example 9] The procedure was the same as in Example 1, except that the raw material was changed to a solution of 78.6 g of Gurjun Balasam oil dissolved in 250 ml of decalin, the amount of transition metal catalyst was changed to 0.8 g, the porous catalyst was changed to 2 g of Zeolum A-4 LPH (manufactured by Tosoh Corporation) and 4 g of Celite, and the acid catalyst was changed to 0.7 g of Chromatorex (trademark) SO3H-TEA (triethylamine-attached). Gas chromatographic analysis showed that the production rate of guaiazulene was 15.0% 3 hours after the start of the reaction.

[0062] [Comparative Example 1] Except for not using a transition metal catalyst or an acid catalyst, the procedure was the same as in Example 1. As a result of gas chromatographic analysis, the production rate of guaiazulene was 2.5% 3 hours after the start of the reaction.

[0063] Comparative Example 2 Except for using neither a porous catalyst nor an acid catalyst, the procedure was the same as in Example 1. The column became clogged during the reaction, making it impossible to obtain a reaction liquid.

[0064] The results are shown in Table 1. [Table 1] [Explanation of symbols]

[0065] 1 column 2. Supply section that supplies composition X 3. Supply Department that supplies scavengers 4. Inert gas supply section 5. Recovery section for recovering reaction products

Claims

1. A method for producing a compound having an azulene skeleton, comprising the step of subjecting a composition containing a compound having a hydroazulene skeleton to a flow-type dehydrogenation reaction, wherein the dehydrogenation reaction is carried out in the presence of a transition metal catalyst and a porous catalyst and / or an acid catalyst.

2. The method according to claim 1, wherein the dehydrogenation reaction is carried out in the presence of a transition metal catalyst, a porous catalyst, and an acid catalyst.

3. The method according to claim 1 or 2, wherein the transition metal catalyst contains at least one selected from the group consisting of transition metals of Groups 8 to 10 of the periodic table.

4. The method according to claim 1 or 2, wherein the porous catalyst is at least one selected from the group consisting of activated carbon, zeolite, and celite.

5. The method according to claim 1 or 2, wherein the acid catalyst includes at least one selected from the group consisting of a cation exchange resin, acidic silica, and an inorganic acid.

6. The method according to claim 1 or 2, wherein the compound having a hydroazulene skeleton is at least one selected from the group consisting of a compound having a decahydroazulene skeleton, a compound having an octahydroazulene skeleton, a compound having a decahydro-1H-cyclopropa[e]azulene skeleton, and a compound having an octahydro-1H-cyclopropa[e]azulene skeleton.

7. The method according to claim 1 or 2, wherein the composition contains an essential oil of a plant containing the compound having a hydroazulene skeleton. ​

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