Methods for producing azulenes

Abstract

To provide a simple and efficient method for producing azulenes. [Solution] A method for producing azulenes comprising the step of heating a mixture containing a compound having a hydride azulene skeleton or a composition containing such a compound, and at least one disulfide selected from the group consisting of substituted aromatic disulfides and long-chain alkyl disulfides, thereby causing a dehydrogenation reaction of the compound.

Description

Technical Field

[0001] The present invention relates to a method for producing azulenes.

Background Art

[0002] Azulene is a structural isomer of naphthalene, and is a deep blue non-benzenoid aromatic compound having a basic skeleton of 10 carbon atoms. Guaiazulene, which is one of compounds having an azulene skeleton, is a compound having an anti-inflammatory effect, and is used as an anti-inflammatory drug for stomatitis, dermatitis and the like. Further, azulene exhibits unique optical properties and redox behavior due to the structure of the azulene skeleton in which a five-membered ring and a seven-membered ring are fused. Therefore, azulene is also attracting attention as an electronic material for semiconductors and the like.

[0003] In the following description, "a compound having an azulene skeleton" may be referred to as "azulenes".

[0004] As a method for producing azulenes, a method for producing azulenes by subjecting hydrogenated azulenes to dehydrogenation reaction at high temperature using sulfur, selenium or diphenyl disulfide has been known for a long time. Further, a method for producing azulenes by subjecting hydrogenated azulenes to dehydrogenation reaction using a transition metal catalyst is known (see, for example, Patent Document 1).

Prior Art Literature

Patent Literature

[0005]

Patent Document 1

Summary of the Invention

Problem to be Solved by the Invention

[0006] However, the production method of compounds containing a hydrogenated azulene skeleton (hydrogenated azulenes) by dehydrogenating them with sulfur or selenium produces toxic and foul-smelling compounds such as hydrogen sulfide as byproducts. Similarly, the production method of dehydrogenating hydrogenated azulenes with diphenyl disulfide also produces thiophenol, a toxic and foul-smelling substance, as a byproduct. Therefore, when these reactions are adopted industrially, sufficient odor control measures are necessary, and improvements have been sought.

[0007] On the other hand, the dehydrogenation reaction of hydrogenated azulenes using a transition metal catalyst does not produce any foul-smelling compounds, thus eliminating the need for odor control measures. However, this reaction has a low yield, making it difficult to adopt industrially.

[0008] Therefore, there was a need for a novel method for producing azulenes that would minimize the generation of foul-smelling by-products, be easy to perform, and allow for efficient production with high yields.

[0009] This invention has been made in view of these circumstances, and aims to provide a simple and efficient method for producing azulenes. [Means for solving the problem]

[0010] To solve the above problems, one aspect of the present invention includes the following aspects.

[0011] [1] A method for producing azulenes, comprising the step of heating a mixture containing a compound having a hydrogenated azulene skeleton or a composition containing the compound and at least one disulfide selected from the group consisting of substituted aromatic disulfides and long-chain alkyl disulfides, thereby dehydrogenating the compound.

[0012] [2] The method for producing azulenes according to [1], wherein the compound having a hydrogenated azulene skeleton is at least one selected from the group consisting of a compound having a hexahydroazulene 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.

[0013] [3] A method for producing azulenes according to [1] or [2], wherein the composition is a plant-derived component.

[0014] [4] The method for producing azulenes according to any one of the claims [1] to [3], wherein the disulfide is at least one selected from the group consisting of 2,2'-dithiobis(methyl benzoate), di-p-isopropylphenyl disulfide, di-2-naphthyl disulfide, 2,2'-dithiodianiline, bis(2-benzamidophenyl) disulfide, bis(4-methoxyphenyl) disulfide, and didodecyl disulfide.

[0015] [5] A method for producing azulenes according to any one of the items [1] to [4], wherein the dehydrogenation reaction step is carried out in a batch reactor.

[0016] [6] A method for producing azulenes according to any one of the items [1] to [4], wherein the dehydrogenation reaction step is carried out in a flow reactor. [Effects of the Invention]

[0017] According to the present invention, a simple and efficient method for producing azulenes can be provided. [Brief explanation of the drawing]

[0018] [Figure 1] Figure 1 is an explanatory diagram of a flow-type reactor used in the production of azulenes. [Figure 2] Figure 2 is an explanatory diagram of a flow-type reactor used in the production of azulenes. MODE FOR CARRYING OUT THE INVENTION

[0019] The method for producing azulene compounds according to the present embodiment comprises a step of heating a mixture containing a compound having a hydrogenated azulene skeleton or a composition containing said compound, and at least one disulfide selected from the group consisting of substituted aromatic disulfides and long-chain alkyl disulfides, to cause dehydrogenation reaction of said compound. In the following description, the combination of substituted aromatic disulfide and long-chain alkyl disulfide may be simply referred to as "disulfide".

[0020] <Compound having hydrogenated azulene skeleton> The "compound having a hydrogenated azulene skeleton" refers to a compound in which the double bonds of the azulene ring of an azulene compound are replaced with single bonds (hydrogenated). A skeleton in which the double bonds of the azulene ring are replaced with single bonds is referred to as a "hydrogenated azulene skeleton".

[0021] In the present embodiment, examples of the compound having a hydrogenated azulene skeleton include at least one selected from the group consisting of compounds having a hexahydroazulene 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.

[0022] These compounds may have one or more substituents on the hydrogenated azulene skeleton. Examples of the substituents include a hydroxy group and an aliphatic hydrocarbon group. The aliphatic hydrocarbon group may be substituted with one or more hydroxy groups. Further, the aliphatic hydrocarbon group may form a condensed ring with the hydrogenated azulene skeleton.

[0023] Examples of the "compound having a hexahydroazulene skeleton" include, for example, • 3,8-dimethyl-5-propan-2-yl-1,2,6,7,8,8a-hexahydroazulene (common name: isogujazulene) 3,8-dimethyl-5-propa-1-en-2-yl-1,2,3,4,5,6,7,8-octahydroazulene-1-ol 3,8-dimethyl-5-propa-1-en-2-yl-1,2,3,3α,4,5,6,7-octahydroazulene (common name: δ-guayene) · 1,4-dimethyl-7-propan-2-yl-1,2,3,4,5,6-hexahydroazulene 1-Methyl-4-methylidene-7-propan-2-yl-2,3,3a,5,6,8a-hexahydroazulene-1-ol (common name: alismol) • 1,4-dimethyl-7-propane-2-ylidene-2,3,4,5,6,8-hexahydro-1H-azulene (common name: β-guayene) 3,8-dimethyl-5-propane-2-ylidene-2,4,6,7,8,8a-hexahydro-1H-azulene One could list these:

[0024] Examples of "compounds having an octahydroazulene skeleton" include: (3S,3αS,5R)-3,8-dimethyl-5-propan-2-yl-1,2,3,3a,4,5,6,7-octahydroazulene (common name: brunesene) 3,8-dimethyl-5-propan-2-yl-1,2,3,3a,4,5,6,7-octahydroazulene (common name: apitonene-1) (3R,3αS,5S)-3,8-dimethyl-5-propan-2-yl-1,2,3,3a,4,5,6,7-octahydroazulene 1,4-Dimethyl-7-propan-2-yl-1,2,3,4,5,6,7,8-octahydroazulene 3,8-Dimethyl-5-propan-2-yl-1,2,3,4,5,6,7,8,8a-Octahydroazulene ·2-[(3R,5S,8R)-3,8-dimethyl-1,2,3,4,5,6,7,8-octahydroazulene-5-yl]]propan-2-ol (common name: α-guaiol) ·2-[(3S,3αR,5S)-3,8-dimethyl-1,2,3,3a,4,5,6,7-octahydroazulene-5-yl]propan-2-ol (common name: brunesol) ·2-[(5R,8S,8αS)-3,8-dimethyl-1,2,3,4,5,6,7,8,8a-octahydroazulene-5-yl]propane-2-ol 1,4-dimethyl-7-propane-2-ylidene-1,2,3,3a,5,6,8,8a-octahydroazulene-4-ol We can list some examples.

[0025] Examples of compounds having a decahydro-1H-cyclopropa[e]azulene skeleton include: · 1,1,4,7-Tetramethyl-1a,2,3,4,4a,5,6,7,7a,7b-Decahydrocyclopropa[e]azulene (common name: aromadendrene) 1,1,4,7-Tetramethyl-2,3,4,5,6,7,7a,7b-Octahydro-1aH-Cyclopropa[h]azulene-4a-ol (common name: Palstrol) (1aR,4R,4aS,7R,7aS,7bS)-1,1,4,7-tetramethyl-2,3,4a,5,6,7,7a,7b-octahydro-1aH-cyclopropa[e]azulene-4-ol (common name: Redor) (1aR,4S,4aS,7R,7aS,7bR)-1,1,4,7-tetramethyl-1a,2,3,4a,5,6,7a,7b-octahydrocyclopropa[h]azulene-4,7-diol • 1,1,4,7-Tetramethyl-1a,2,3,5,6,7,7a,7b-Octahydrocyclopropa[h]azulene-4,4a-diol 1,1,4,7-Tetramethyl-2,3,4,4a,5,6,7,7b-Octahydro-1aH-cyclopropa[e]azulene-7a-ol (common name: 5-aromadendranol) (4S,4aS,7S,7aS)-1,1,4,7-tetramethyl-1a,2,3,4,5,6,7a,7b-octahydrocyclopropa[h]azulene-4a,7-diol We can list some examples.

[0026] Examples of "compounds having an octahydro-1H-cyclopropa[e]azulene skeleton" include: · 1,1,4,7-Tetramethyl-1a,2,3,4,4a,5,6,7b-Octahydrocyclopropa[e]azulene (common name: α-gluchenene) 1,1,4,7-Tetramethyl-1a,2,3,5,6,7,7a,7b-Octahydrocyclopropa[e]azulene (common name: 1(10)-aromadendrene) 1,1,4,7-Tetramethyl-1a,2,3,4,5,6,7,7b-Octahydrocyclopropa[e]azulene (common name: isoledene) · 1,1,7-trimethyl-4-methylidene-2,3,4a,5,6,7,7a,7b-octahydro-1aH-cyclopropa[e]azulene (common name: aromadendren) · 1,1,4,7-Tetramethyl-2,3,6,7,7a,7b-Hexahydro-1aH-cyclopropa[e]azulene-4-ol (common name: 1-aromadendrene-10-ol) · 1,1,4,7-Tetramethyl-3,4,5,6,7,7b-Hexahydro-2H-cyclopropa[e]azulene-1a-ol (common name: 1(5)-aromadendren-7-ol) · 1,1,4,7-Tetramethyl-1a,2,3,4,4a,5,6,7b-Octahydrocyclopropa[e]azulene-2-ol (common name: 8α-hydroxy-α-gluchenene) (1,4,7-trimethyl-1a,2,3,4,4a,5,6,7b-octahydrocyclopropa[e]azulene-1-yl)methanol (common name: 4-aromadendrene-12-ol) 1,1,4,7-Tetramethyl-1a,2,3,4,4a,5,6,7b-Octahydrocyclopropa[e]azulene-3-ol We can list some examples.

[0027] The compounds described above are illustrative examples, and the compounds that can be used in the method for producing azulenes are not limited to those described above. As will be described in more detail later, any compound having a hydrogenated azulene skeleton that undergoes a dehydrogenation reaction and generates an azulene skeleton when heated together with at least one disulfide selected from the group consisting of substituted aromatic disulfides and long-chain alkyl disulfides is applicable as a starting material for the method for producing azulenes in this embodiment.

[0028] In the method for producing azulenes, the above-mentioned compounds may be used individually or as part of a composition containing the above-mentioned compounds.

[0029] When using the above-mentioned compound composition as a raw material for azulene production methods, the composition is preferably composed of plant-derived components. Examples of plant-derived components include essential oils such as camphor oil, eucalyptus oil, patchouli oil, geranium oil, peppermint oil, Gurjun balsam oil, Guaiac wood oil, Eucalyptus globulus oil, and Wintera colorata oil.

[0030] These plant-derived components are known to contain compounds having a hydride azulene skeleton and can be used as raw materials for azulene production methods. The aforementioned plant-derived components may be used individually or in combination of two or more.

[0031] Disulfide In the method for producing azulenes according to this embodiment, the disulfide used in the dehydrogenation reaction is a disulfide that has a less odor in the reaction mixture than the reaction mixture after dehydrogenation using the known diphenyl disulfide.

[0032] Odor evaluation is performed by sensory evaluation using the sense of smell. After dehydrogenating a compound having a hydrogenated azulene skeleton using each disulfide, the odor of the reaction mixture is checked. The odor of the reaction mixture in a reaction system using known diphenyl disulfides is used as a standard, and the following criteria are used for judgment. The evaluation result when using diphenyl disulfide is a C according to the following criteria. An A or B rating in the odor evaluation result is considered a pass, and a C rating is considered a fail. A: There is an odor, but it does not interfere with the work. B: There is an odor, but if odor control measures are taken, it will not interfere with the work. C: It has a strong odor and cannot be used.

[0033] The aromatic ring of the "substituted aromatic disulfide" used may be an aromatic ring having 6 to 10 carbon atoms, or a six-membered heterocycle. The substituents attached to the aromatic ring may include alkyl groups, ester groups, alkoxy groups, amino groups, and amide groups.

[0034] Examples of such compounds include: · Di-p-isopropylphenyl disulfide • 2,2'-Dithiobis(methyl benzoate) • Bis(4-methoxyphenyl) disulfide · di-2-naphthyl disulfide ·2,2'-Dithiodianiline • Bis(2-benzamidephenyl) disulfide We can list some examples.

[0035] Furthermore, in the "long-chain alkyl disulfide," the number of carbon atoms in the alkyl group bonded to the sulfur atom may be 8 to 20, 8 to 16, or 8 to 14. Also, the alkyl group bonded to the sulfur atom may be linear or branched.

[0036] Examples of such compounds include: • Dinonyl disulfide Didecyl disulfide • Diundecyl disulfide • Zidodecyl disulfide We can list some examples.

[0037] In the method for producing azulenes, only one type of disulfide may be used, or two or more types may be used in combination.

[0038] <solvent> The compound having a hydride azulene skeleton or a composition containing said compound and the disulfide should be mutually soluble and form a homogeneous mixture. The mixture may also contain a solvent in addition to the compound having a hydride azulene skeleton and the disulfide. The fact that the mixture is a solvent-containing solution makes it easier to dissolve the disulfide, which is solid at room temperature, in the solvent and apply it to the flow reactor described later.

[0039] In this embodiment, various solvents can be used as long as they dissolve the compound having a hydride azulene skeleton, the disulfide, and the resulting compound having an azulene skeleton. Examples of usable solvents include triglycerides, tetraethylene glycol, and mesitylene.

[0040] The method for producing azulenes in this embodiment may be carried out in a batch reactor or a flow reactor for the dehydrogenation reaction. The method of production in this embodiment is easy to apply to a flow reactor because the dehydrogenation reaction can be carried out by a homogeneous system reaction using a mixture in which the compounds used are dissolved in each other.

[0041] Figures 1 and 2 are explanatory diagrams of a flow-type reactor used in the production of azulenes. The reactor 100A shown in Figure 1 comprises a storage tank 1 for storing a mixture of raw materials, a heating unit 2 for heating the mixture, a cooling unit 3 for cooling the heated mixture (reaction mixture), and a recovery tank 4 for recovering and storing the reaction mixture. The storage tank 1, heating unit 2, cooling unit 3, and recovery tank 4 are connected in this order by piping 5. A liquid transfer pump 6 and a back pressure regulating device 7 are located within the path of piping 5. The liquid transfer pump 6 transfers the mixture and reaction mixture towards the downstream recovery tank 4. The back pressure regulating device 7 applies back pressure towards the upstream storage tank 1.

[0042] In reactor 100A, the reaction mixture recovered in recovery tank 4 may be stored again in storage tank 1 and passed through heating section 2 multiple times.

[0043] In reactor 100B shown in Figure 2, the storage tank 1, heating section 2, cooling section 3, and recovery tank 4 are connected in this order by piping 5. In reactor 100B, the piping following the back pressure adjustment device 7 located within the path of piping 5 is connected to the storage tank 1, forming a circulation system.

[0044] Furthermore, a switching valve 51 is provided in the path of the piping 5 between the storage tank 1 and the liquid transfer pump 6 (between the storage tank 1 and the heating unit 2), and the recovery tank 4 is connected via a bypass 52 connected to the switching valve 51.

[0045] Reactor 100B can form a closed-system reaction section 50 connected to a back pressure adjustment device 7 by a switching valve 51, which includes a heating section 2 and a cooling section 3, and a piping 5. The reaction section 50 functions as a circulating flow reactor by supplying liquid with a liquid supply pump 6 installed in the path of the piping 5. In the reaction section 50, the yield of the target product can be improved by repeating the dehydrogenation reaction while circulating the mixture.

[0046] Each component of reactors 100A and 100B can employ a known configuration.

[0047] The reaction rate of the dehydrogenation reaction of compounds having a hydride azulene skeleton can be controlled by adjusting various conditions such as the starting material concentration, the ratio of the compound having a hydride azulene skeleton to the disulfide, the reaction temperature (temperature of heating section 2), and the liquid delivery rate.

[0048] Furthermore, when using reactor 100A, the reaction rate of the dehydrogenation reaction can be controlled by the number of times the mixture (reaction mixture) is passed through the heating section 2.

[0049] Furthermore, when reactor 100B is used, the reaction rate of the dehydrogenation reaction can be controlled by the circulation time in the reaction section 50.

[0050] The desired azulenes can be obtained by separating the azulenes contained in the reaction mixture using a known separation method.

[0051] In the method for producing azulenes, the above-mentioned compound having a hydrogenated azulene skeleton is heated together with at least one disulfide selected from the group consisting of substituted aromatic disulfides and long-chain alkyl disulfides to induce a dehydrogenation reaction in the compound having a hydrogenated azulene skeleton, thereby obtaining the desired compound having an azulene skeleton.

[0052] For example, as a compound having the hydride azulene skeleton described above, α-glujunene, which has the octahydro-1H-cyclopropa[e]azulene skeleton, is used. When heated together with the above disulfide, the hydride azulene skeleton undergoes a dehydrogenation reaction as shown in formula (A) below, yielding guaiazulene, an azulene.

[0053] [ka]

[0054] In this case, by heating α-glujunene together with one or more disulfides selected from the group consisting of aromatic disulfides and long-chain alkyl disulfides having the above-mentioned substituents, the odor of the reaction mixture is suppressed compared to the conventional system using diphenyl disulfide. From the viewpoint of suppressing odor, • 2,2'-Dithiobis(methyl benzoate) · Di-p-isopropylphenyl disulfide · di-2-naphthyl disulfide • Bis(4-methoxyphenyl) disulfide ·2,2'-Dithiodianiline • Bis(2-benzamidephenyl) disulfide • Zidodecyl disulfide These are preferred. Furthermore, di-p-isopropylphenyl disulfide, 2,2'-dithiobis(methyl benzoate), bis(4-methoxyphenyl) disulfide, and di-2-naphthyl disulfide are more preferred due to their high reaction yield.

[0055] Furthermore, the manufacturing method of this embodiment yields the target product in a higher yield compared to known reactions that use transition metal catalysts for dehydrogenation.

[0056] Furthermore, the desired azulenes can be easily isolated from the reaction mixture obtained by the manufacturing method of this embodiment using known methods.

[0057] Therefore, the method for producing azulenes with the above configuration can provide a simple and efficient manufacturing method.

[0058] Preferred embodiments of the present invention have been described above with reference to the attached drawings, but the present invention is not limited to these examples. The shapes and combinations of the constituent members shown in the above examples are merely examples, and can be modified in various ways based on design, specifications, etc., without departing from the spirit of the present invention. [Examples]

[0059] The present invention will be described below with reference to examples, but the present invention is not limited to these examples.

[0060] In the following examples, a mixture of an α-glujunene composition (α-glujunene content: 83%) and each compound was heated and reacted to obtain guaiazulene (formula (A) below). α-glujunene corresponds to the "compound having a hydrogenated azulene skeleton" in the present invention.

[0061] [ka]

[0062] The reaction was evaluated by determining the yield of guaiazulene obtained relative to the amount of α-glujunene used as the starting material. In the yield calculation, the molecular weight of α-glujunene was assumed to be 204 and the molecular weight of guaiazulene was assumed to be 198.

[0063] The above reaction was carried out in both a batch reactor and a flow reactor.

[0064] Furthermore, the odor of the reaction mixture after the reaction was evaluated using the following method. Odor evaluation was performed by sensory evaluation using the sense of smell. After carrying out the reaction of formula (A) above using each disulfide, the odor of the reaction mixture was checked. The odor of the reaction mixture in a reaction system using known diphenyl disulfide was used as a standard, and the following criteria were used for judgment. The evaluation result when using diphenyl disulfide was a C rating according to the following criteria. An A or B rating in the odor evaluation result was considered a pass, and a C rating was considered a fail. A: There is an odor, but it does not interfere with the work. B: There is an odor, but if odor control measures are taken, it will not interfere with the work. C: It has a strong odor and cannot be used.

[0065] [Batch reactor] (Example 1) 98.2 g of 2,2'-dithiobis(methyl benzoate) (formula (1) below) was added to a flask and heated to 250°C while stirring until melted. 20.0 g of α-glujunen composition (81.37 mmol of α-glujunen) was added dropwise to the resulting molten solution using a dropping funnel, and the mixture was reacted at 250°C for 10 minutes after addition.

[0066] [ka]

[0067] After the reaction, the mixture was separated and isolated to obtain 9.57 g (48.34 mmol) of guaiazulene in a yield of 59.4 mol%.

[0068] (Example 2) 73.9 g of di-p-isopropylphenyl disulfide (formula (2) below) was added to a flask and heated to 250°C while stirring. 10 g of α-glujunen composition (40.69 mmol of α-glujunen) was added dropwise to the heated solution using a dropping funnel, and the mixture was reacted at 250°C for 10 minutes after addition.

[0069] [ka]

[0070] Isolation was performed by liquid-liquid separation, yielding 4.6 g (23.23 mmol) of guaiazulene in a yield of 57.2 mol%.

[0071] (Example 3) 4.7 g of di-2-naphthyl disulfide (formula (3) below) was added to a flask and heated to 260°C while stirring until melted. 1.0 g of α-glujunen composition (4.07 mmol of α-glujunen) was added dropwise to the resulting molten solution using a dropping funnel, and the mixture was reacted at 260°C for 10 minutes after addition.

[0072] [ka]

[0073] After the reaction, quantification was performed by liquid chromatography to obtain 0.46 g (2.30 mmol) of guaiazulene in a yield of 56.6 mol%.

[0074] (Example 4) 3.6 g of 2,2'-dithiodianiline (formula (4) below) was added to a flask and heated to 200°C while stirring until melted. 1.0 g of α-glujunen composition (4.07 mmol of α-glujunen) was added dropwise to the resulting molten solution using a dropping funnel, and the mixture was reacted at 206°C for 10 minutes after addition.

[0075] [ka]

[0076] After the reaction, quantification was performed by liquid chromatography to obtain 0.25 g (1.26 mmol) of guaiazulene in a yield of 31.0 mol%.

[0077] (Example 5) 6.7 g of bis(2-benzamidophenyl) disulfide (formula (5) below) was added to a flask and heated to 175°C while stirring until melted. 1.0 g of α-glujunen composition (4.07 mmol of α-glujunen) was added dropwise to the resulting molten solution using a dropping funnel, and the mixture was reacted at 175°C for 10 minutes after addition.

[0078] [ka]

[0079] Workup and isolation were performed by liquid-liquid separation to obtain 0.29 g (1.46 mmol) of guaiazulene in a yield of 36.0 mol%.

[0080] (Example 6) 6.8 g of bis(4-methoxyphenyl) disulfide (formula (6) below) was added to a flask and heated to 240°C while stirring. 1.0 g of α-glujunen composition (4.07 mmol of α-glujunen) was added dropwise to the heated solution using a dropping funnel, and the mixture was reacted at 245°C for 10 minutes after addition.

[0081] [ka]

[0082] After the reaction, the solution was quantified by liquid chromatography, yielding 0.51 g (2.59 mmol) of guaiazulene at 63.7 mol%.

[0083] (Example 7) 9.8 g of didodecyl disulfide (formula (7) below) was added to a flask and heated to 250°C while stirring until melted. 1.0 g of α-glujunen composition (4.07 mmol of α-glujunen) was added dropwise to the resulting molten solution using a dropping funnel, and the mixture was reacted at 250°C for 10 minutes after addition.

[0084] [ka]

[0085] After the reaction, quantification was performed by gas chromatography, yielding 0.18 g (0.91 mmol) of guaiazulene in a yield of 22.0 mol%.

[0086] (Comparative Example 1) 3.6 g of di-p-tolyl disulfide (formula (C1) below) was added to a flask and heated to 250°C while stirring until melted. 1.0 g of α-glujunen composition (4.07 mmol of α-glujunen) was added dropwise to the resulting molten solution using a dropping funnel, and the mixture was reacted at 250°C for 10 minutes after addition.

[0087] [ka]

[0088] After the reaction, the solution was quantified by gas chromatography, yielding 0.42 g (2.11 mmol) of guaiazulene at 52.0 mol%.

[0089] (Comparative Example 2) 4.9 g of bis(p-tert-butylphenyl) disulfide (formula (C2) below) was added to a flask and heated to 250°C while stirring until melted. 1.0 g of α-glujunen composition (4.07 mmol of α-glujunen) was added dropwise to the resulting molten solution using a dropping funnel, and the mixture was reacted at 250°C for 10 minutes after addition.

[0090] [ka]

[0091] After the reaction, quantification was performed by liquid chromatography to obtain 0.412 g (2.08 mmol) of guaiazulene in a yield of 51.1 mol%.

[0092] (Comparative Example 3) 6.8 g of bis(2,4-dimethylphenyl) disulfide (formula (C3) below) was added to a flask and heated to 250°C while stirring. 1.0 g of α-glujunen composition (4.07 mmol of α-glujunen) was added dropwise to the heated solution using a dropping funnel, and the mixture was reacted at 250°C for 10 minutes after addition.

[0093] [ka]

[0094] After the reaction, quantification was performed by liquid chromatography to obtain 0.51 g (2.55 mmol) of guaiazulene in a yield of 62.7 mol%.

[0095] (Comparative Example 4) 3.2 g of 2,2'-dipyridyl disulfide (formula (C4) below) and 1.0 g of α-glujunen composition (4.07 mmol of α-glujunen) were added to a flask. The contents of the flask were heated to 230°C while stirring to dissolve and react the contents.

[0096] [ka]

[0097] After the reaction, quantification was performed by liquid chromatography to obtain 0.06 g (0.31 mmol) of guaiazulene in a yield of 7.5 mol%.

[0098] (Comparative Example 5) 2.2 g of 1,2-benzothiazolin-3-one (formula (C5) below) and 1.0 g of α-glujunen composition (4.07 mmol of α-glujunen) were added to a flask. The contents of the flask were heated to 250°C while stirring to melt the contents, and the mixture was reacted at 250°C for 3 minutes.

[0099] [ka]

[0100] After the reaction, the solution was diluted with 5 mL of toluene and quantified by gas chromatography to obtain 0.099 g (0.5 mmol) of guaiazulene in a yield of 11.3%.

[0101] [Flow reactor] (Example 8) A flow reactor with a configuration similar to reactor 100A shown in Figure 1 was used. 22.2 g of di-p-isopropylphenyl disulfide (formula (2) above) and 5.0 g of α-glujunen composition (α-glujunen 20.34 mmol) were mixed, and the heating section 2 was heated to 280°C. The mixture was then passed through the heating section 2 at a flow rate of 2 mL / min without applying back pressure.

[0102] After collecting the resulting reaction solution, it was passed through reactor 100A again under the same conditions. After a total of 15 passes, the reaction was terminated.

[0103] The reaction mixture was quantified by liquid chromatography, yielding 2.3 g (11.86 mmol) of guaiazulene in a yield of 58.3 mol%.

[0104] (Example 9) A flow reactor with a configuration similar to reactor 100B shown in Figure 2 was used. 33.3 g of di-p-isopropylphenyl disulfide (formula (2) above) and 7.5 g of α-glujunen composition (30.51 mmol of α-glujunen) were mixed, the heating section 2 was heated to 280°C, and the mixture was passed through the heating section 2 at a flow rate of 2 mL / min without back pressure. The mixture was circulated for 250 minutes to complete the reaction.

[0105] The reaction mixture was quantified by liquid chromatography, yielding 3.5 g (17.52 mmol) of guaiazulene in a yield of 57.4 mol%.

[0106] (Example 10) A flow reactor with a configuration similar to reactor 100B shown in Figure 2 was used. α-glucunene was reacted in the same manner as in Example 8, except that a back pressure of 0.2 to 0.4 MPa was applied using the back pressure adjustment device 7, and the reaction time (circulation time) was set to 150 minutes.

[0107] The reaction mixture was quantified by liquid chromatography, yielding 3.0 g (15.25 mmol) of guaiazulene in a yield of 50.0 mol%.

[0108] (Reference example) A tube-type flow reactor with a configuration similar to reactor 100A shown in Figure 1 was used. 6 g of di-p-tolyl disulfide (formula (C1) above) and 1.0 g of α-glujunen composition (4.07 mmol of α-glujunen) were heated to 65°C and melted. 2 mL of triglyceride was added to the resulting molten mixture, and the mixture was passed through a flow reactor heated to 350°C in heating section 2 at a flow rate of 0.2 mL / min.

[0109] The resulting reaction solution was quantified by gas chromatography, yielding 0.084 g (0.42 mmol) of guaiazulene in a yield of 10.3 mol%.

[0110] The evaluation results are shown in Tables 1 and 2 below. Table 1 shows the results using a batch reactor, and Table 2 shows the results using a flow reactor.

[0111] [Table 1]

[0112] [Table 2]

[0113] The evaluation results showed that for Examples 1-7, which used a batch reactor, the yield was high at over 20 mol%, and the odor of the reaction mixture was not significant enough to interfere with the work. Furthermore, for Examples 1-6, the yield was over 30 mol%, indicating that the target product could be obtained in an even higher yield.

[0114] On the other hand, while Comparative Examples 1-3 showed high reaction yields, the reaction mixtures had an unpleasant odor that interfered with the work. In Comparative Example 4, odor was not a problem, but the yield was low. In addition, in Comparative Example 5, since no disulfide compound was used, the odor of the reaction mixture was not a problem, but the yield was low.

[0115] In Examples 8-10, which used a flow reactor, it was confirmed that by repeatedly reacting the reaction mixture, results equivalent to those obtained with a batch reactor (Example 2) could be obtained.

[0116] Furthermore, by comparing the reference example with Example 2, it was confirmed that in a flow reactor, the target product can be obtained through the dehydrogenation reaction even with just one pass of the liquid, but the yield is lower than that of a batch reactor.

[0117] Based on the above results, it has been confirmed that the present invention is useful. [Explanation of Symbols]

[0118] 1...Storage tank, 2...Heating section, 3...Cooling section, 4...Recovery tank, 5...Piping, 6...Liquid transfer pump, 7...Back pressure adjustment device, 50...Reaction section, 51...Switching valve, 52...Bypass, 100A, 100B...Reactor

Claims

1. A method for producing azulenes, comprising the step of heating a mixture containing a compound having a hydride azulene skeleton or a composition containing said compound, and at least one disulfide selected from the group consisting of substituted aromatic disulfides and long-chain alkyl disulfides, thereby causing a dehydrogenation reaction of said compound.

2. The method for producing azulenes according to claim 1, wherein the compound having a hydrogenated azulene skeleton is at least one selected from the group consisting of a compound having a hexahydroazulene 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.

3. A method for producing azulenes according to claim 1 or 2, wherein the composition is derived from plant materials.

4. The method for producing azulenes according to claim 1 or 2, wherein the disulfide is at least one selected from the group consisting of 2,2'-dithiobis(methyl benzoate), di-p-isopropylphenyl disulfide, di-2-naphthyl disulfide, 2,2'-dithiodianiline, bis(2-benzamidophenyl) disulfide, bis(4-methoxyphenyl) disulfide, and didodecyl disulfide.

5. The method for producing azulenes according to claim 1 or 2, wherein the dehydrogenation reaction step is carried out in a batch reactor.

6. The method for producing azulenes according to claim 1 or 2, wherein the dehydrogenation reaction step is carried out in a flow reactor.

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