Production method of 2-methyl-5,6-dihydro-2h-pyran

Abstract

The purpose of the present invention is to provide a production method of 2-methyl-5,6-dihydro-2H-pyran, by which a high yield can be achieved even in the case of reacting at a relatively low temperature and in which the adhesion of precipitates to a reactor, piping and measurement instruments is suppressed. The production method of 2-methyl-5,6-dihydro-2H-pyran of the present invention comprises reacting 1,3-pentadiene and a formaldehyde-generating substance in a solvent in the presence of a Lewis acid catalyst at a temperature within a preset range in a single reactor to thereby synthesize 2-methyl-5,6-dihydro-2H-pyran.

Description

Method for producing 2-methyl-5,6-dihydro-2H-pyran

[0001] The present invention relates to a method for producing 2-methyl-5,6-dihydro-2H-pyran.

[0002] 2-Methyl-5,6-dihydro-2H-pyran is an industrially useful compound as a precursor for producing cis-3-hexenol, which can be used as a raw material for fragrances and flavors that impart a fresh, green leaf-like aroma. A synthesis method for 2-methyl-5,6-dihydro-2H-pyran via the Diels-Alder reaction of 1,3-pentadiene with formaldehyde has been reported. Because 1,3-pentadiene is readily available as a petrochemical product, this production method is expected to be applicable to industrial production.

[0003] For example, Patent Document 1 describes the production of 2-methyl-5,6-dihydropyran by reacting 1,3-pentadiene with paraformaldehyde at 240° C. Furthermore, Patent Document 2 describes the production of 2-methyl-5,6-dihydropyran by supplying anhydrous formaldehyde gas vaporized in a high-pressure reactor to a high-pressure reactor containing a conjugated diene hydrocarbon, a Lewis acid catalyst, and a solvent, and reacting the two together.

[0004] Japanese Patent Publication No. 55-102531 Chinese Patent Application Publication No. 101143860

[0005] However, reactions at high temperatures such as 240°C can result in a decrease in the yield of the target compound due to factors such as excessive reaction progress, resulting in the production of large amounts of polymers, and in some cases, deposits such as carbides, which are thought to be derived from such polymers, can adhere to the reactor and become impossible to clean. Furthermore, the method of supplying vaporized formaldehyde gas to a high-pressure reactor requires at least two reactors, which increases the equipment size and safety risks associated with high pressure. Furthermore, paraformaldehyde deposits can adhere to piping and instruments, such as pressure gauges, through which the vaporized formaldehyde gas flows, increasing the risk of pipe blockage and instrument failure. Therefore, there is room for improvement in the industrial production of 2-methyl-5,6-dihydro-2H-pyran, in terms of achieving an excellent yield even when the reaction is carried out at a relatively low temperature and suppressing the adhesion of deposits to the reactor, piping, and instruments.

[0006] Therefore, an object of the present invention is to provide a method for producing 2-methyl-5,6-dihydro-2H-pyran, which can achieve an excellent yield even when the reaction is carried out at a relatively low temperature, and which suppresses adhesion of deposits to the reactor, piping, and instruments.

[0007] The present inventors have conducted extensive research to achieve the above object. As a result, the present inventors have found that, under conditions for synthesizing 2-methyl-5,6-dihydro-2H-pyran by reacting 1,3-pentadiene with a formaldehyde-generating substance in a solvent in the presence of a Lewis acid catalyst, the reaction can be carried out at a relatively low temperature, that it is possible to suppress adhesion of precipitates such as carbides to the reactor, which are thought to be derived from high molecular weight substances that are generated when the reaction proceeds excessively at high temperatures, and that it is possible to achieve an excellent yield. They have also found that, by carrying out the synthesis reaction in a single reactor, it is not necessary to supply formaldehyde gas from an external source, it is possible to suppress adhesion of precipitates derived from formaldehyde gas to piping and instruments, and it is possible to reduce safety risks due to high pressure, and have completed the present invention.

[0008] That is, the present invention has an object to advantageously solve the above-mentioned problems, and the method for producing 2-methyl-5,6-dihydro-2H-pyran of the present invention (hereinafter referred to as the "production method of the present invention") is characterized by comprising reacting 1,3-pentadiene with a formaldehyde-generating substance in a solvent in the presence of a Lewis acid catalyst at a temperature of 60°C or higher but lower than 100°C in a single reactor to synthesize 2-methyl-5,6-dihydro-2H-pyran. By carrying out the synthesis reaction according to the above configuration, it is possible to achieve an excellent yield even at such a relatively low temperature. Furthermore, by carrying out the synthesis reaction at such a relatively low temperature, it is possible to suppress the problem that, when the synthesis reaction is carried out at a high temperature, excessive reaction progress can lead to the production of large amounts of polymers, reducing the yield of the target compound, and in some cases, the problem of deposits such as carbides that are thought to be derived from such polymers adhering to the reactor and becoming impossible to clean, thereby improving industrial applicability. Furthermore, by performing the synthesis reaction in one reactor, there is no need to use a separate reactor such as a reactor for generating formaldehyde gas. This prevents deposits from forming on piping and instruments due to the formaldehyde gas, and the reactor does not become overpressurized due to the supply of formaldehyde gas. This reduces safety risks such as damage to the reaction system (reactor, piping, instruments), and ejection or leakage of contents from the reaction system.

[0009] In the production method of the present invention, the solvent preferably has a dielectric constant greater than 2.0 and equal to or less than 8.0. If the dielectric constant of the solvent is greater than the lower limit, the catalytic activity of the Lewis acid catalyst is enhanced, promoting the Diels-Alder reaction even at relatively low temperatures. As a result, it contributes to achieving an excellent yield even at relatively low temperatures. If the dielectric constant of the solvent is equal to or less than the upper limit, the activity of the Lewis acid catalyst is slightly suppressed, but the Diels-Alder reaction proceeds sufficiently even at relatively low temperatures. As a result, it contributes to achieving a good yield even at relatively low temperatures. The dielectric constant of the solvent can be determined by referring to publicly available information, as described below. When the solvent is a mixed solvent, it can be determined as the average of the dielectric constants corresponding to the weight ratios of the solvents contained in the mixed solvent, as described below.

[0010] In the production method of the present invention, the solvent preferably contains a compound having an ether bond in its chemical structure. When the solvent contains a compound having an ether bond in its chemical structure, the compound coordinates to the Lewis acid catalyst via the lone electron pair contained in the oxygen atom in the ether bond, enhancing the catalytic activity of the Lewis acid catalyst and promoting the Diels-Alder reaction even under relatively low temperature conditions. As a result, it is possible to achieve an excellent yield even when the reaction is carried out at a relatively low temperature.

[0011] In the production method of the present invention, the Lewis acid catalyst preferably contains a metal triflate. Use of a metal triflate as the Lewis acid catalyst provides high catalytic activity, an excellent yield, and high stability against moisture contamination.

[0012] In the production method of the present invention, the Lewis acid catalyst preferably contains a metal species having an electronegativity of 1.3 or more as a simple metal. The higher the electronegativity of the metal species, the higher the acidity of the Lewis acid catalyst and the higher the catalytic activity. As a result, an excellent yield can be achieved even when the reaction is carried out at a relatively low temperature.

[0013] In the production method of the present invention, the Lewis acid catalyst preferably contains a metal species whose metal ion valence is at least 3. As the metal ion valence increases, such as at least 3, the catalytic activity of the Lewis acid catalyst containing the metal species increases, and as a result, an excellent yield can be achieved even when the reaction is carried out at a relatively low temperature.

[0014] The method for producing cis-3-hexenol of the present invention is characterized by comprising the steps of producing 2-methyl-5,6-dihydro-2H-pyran using the above-described production method, and reducing the resulting 2-methyl-5,6-dihydro-2H-pyran to obtain cis-3-hexenol. Because the above-described production method is used in the step of producing 2-methyl-5,6-dihydro-2H-pyran, an excellent yield can be achieved, and the problem of deposits such as carbides adhering to the reactor and becoming impossible to clean can be suppressed. Furthermore, because a separate reactor such as a reactor for generating formaldehyde gas is not used, the adhesion of deposits derived from formaldehyde gas to piping and instruments can be suppressed, and safety risks such as damage to the reaction system (reactor, piping, instruments) due to high pressure caused by formaldehyde gas, and ejection or leakage of contents from the reaction system, can be reduced.

[0015] According to the present invention, it is possible to provide a method for producing 2-methyl-5,6-dihydro-2H-pyran, which can achieve an excellent yield even when the reaction is carried out at a relatively low temperature, and which suppresses adhesion of deposits to the reactor, piping, and instruments.

[0016] Hereinafter, embodiments of the present invention will be described in detail.

[0017] (Method for Producing 2-methyl-5,6-dihydro-2H-pyran) The method for producing 2-methyl-5,6-dihydro-2H-pyran of the present invention (hereinafter referred to as "the production method of the present invention") comprises reacting 1,3-pentadiene with a formaldehyde-generating substance in a solvent in the presence of a Lewis acid catalyst at a temperature within a predetermined range in a single reactor to synthesize 2-methyl-5,6-dihydro-2H-pyran. In the production method of the present invention, other substances may be optionally added to the reaction system. Furthermore, the production method of the present invention may optionally further include other steps. The temperature within the predetermined range is a relatively low temperature, as described below.

[0018] By configuring the production method of the present invention as described above, the synthesis reaction can be carried out at a relatively low temperature, and 2-methyl-5,6-dihydro-2H-pyran can be obtained in excellent yield even under relatively low-temperature conditions. Furthermore, because the synthesis reaction can be carried out at a relatively low temperature, problems that occur when the synthesis reaction is carried out at a high temperature, such as excessive reaction progress, resulting in the production of a large amount of polymers and a decrease in the yield of the target compound, and in some cases, deposits such as carbides thought to be derived from such polymers, can be prevented from adhering to the reactor and becoming impossible to clean, thereby improving industrial applicability. Furthermore, by carrying out the synthesis reaction in a single reactor, a separate reactor, such as a reactor for generating formaldehyde gas, is not required. This prevents the adhesion of deposits derived from formaldehyde gas to piping and instruments, and prevents the reactor from becoming overpressurized due to the supply of formaldehyde gas, thereby reducing safety risks such as damage to the reaction system (reactor, piping, instruments), and the ejection or leakage of contents from the reaction system.

[0019] The production method of the present invention utilizes a reaction in which 2-methyl-5,6-dihydro-2H-pyran is synthesized by a Diels-Alder reaction (addition reaction) between 1,3-pentadiene and formaldehyde generated from a formaldehyde-generating substance. When the reaction system is heated to the reaction temperature, formaldehyde is generated by, for example, decomposition of the formaldehyde-generating substance or release of formaldehyde adsorbed on the formaldehyde-generating substance, and the generated formaldehyde is then used in the reaction. In this reaction, there are two structurally possible directions of addition of formaldehyde to 1,3-pentadiene. However, in practice, almost only 2-methyl-5,6-dihydro-2H-pyran is generated as the addition reaction product, and by-products due to the reverse addition reaction (i.e., compounds having the structure of 5-methyl-5,6-dihydro-2H-pyran) are rarely generated. Therefore, the appearance of such by-products need not be considered.

[0020] The materials and conditions used in the production method of the present invention will be explained below.

[0021] <1,3-Pentadiene> 1,3-pentadiene exists as cis-1,3-pentadiene and trans-1,3-pentadiene isomers, but almost exclusively trans-1,3-pentadiene undergoes the synthesis reaction of the present invention. Therefore, the 1,3-pentadiene used in the production method of the present invention may contain trans-1,3-pentadiene, i.e., it may be trans-1,3-pentadiene or a mixture of cis-1,3-pentadiene and trans-1,3-pentadiene. Furthermore, the cis / trans ratio of the 1,3-pentadiene used in the production method of the present invention is not particularly limited, and may be, for example, 60 / 40 or less, preferably 50 / 50 or less, and more preferably 40 / 60 or less.

[0022] <Formaldehyde-generating substance> The "formaldehyde-generating substance" used in the production method of the present invention refers to a substance that generates formaldehyde upon decomposition, a substance that releases formaldehyde adsorbed on an adsorbent (e.g., activated carbon, silica gel, etc.), or a substance that releases formaldehyde dissolved in a liquid (e.g., water, methanol, ethanol, THF, etc.). Furthermore, the term "formaldehyde-generating substance" does not include formaldehyde itself. Examples of substances that generate formaldehyde upon decomposition include paraformaldehyde, low-polymerization polyoxymethylene, and cyclic polyoxymethylenes such as 1,3,5-trioxane. Examples of substances that release adsorbed formaldehyde include adsorbents (e.g., activated carbon, silica gel, etc.) that have adsorbed formaldehyde. Examples of substances that release dissolved formaldehyde include aqueous formaldehyde solutions (formalin). During the synthesis reaction of 2-methyl-5,6-dihydro-2H-pyran, when the formaldehyde-generating substance is heated to the reaction temperature in the reaction mixture, it releases formaldehyde that has been decomposed, adsorbed, or dissolved to generate formaldehyde, and the generated formaldehyde is then supplied to the synthesis reaction. Note that, from the viewpoints that using a gas as the formaldehyde-generating substance may require two or more reactors and that the reaction pressure may become high, resulting in a risk of reduced safety and a decrease in the durability of the equipment, the formaldehyde-generating substance is preferably a solid or liquid at room temperature and atmospheric pressure, and among these, paraformaldehyde is preferred. In this specification, "room temperature" refers to 23°C, and "atmospheric pressure" refers to 1 atm (absolute pressure).

[0023] <Ratio of Formaldehyde-Generating Substance to 1,3-Pentadiene Used Amounts> In the production method of the present invention, the ratio of the amount of formaldehyde-generating substance used (in terms of formaldehyde molar equivalents) to the amount of 1,3-pentadiene used (in terms of moles) (formaldehyde-generating substance / 1,3-pentadiene ratio) is not particularly limited, and may be, for example, 0.5 or more, preferably 0.7 or more, more preferably 0.9 or more, and for example, 2 or less, preferably 1.7 or less, and more preferably 1.3 or less. From the viewpoint that a larger amount of formaldehyde promotes the reaction, it is preferable that the ratio be equal to or greater than the lower limit. On the other hand, from the viewpoint that an excessive amount of formaldehyde can easily cause deposition of formaldehyde-derived deposits to adhere to piping and instruments such as pressure gauges, thereby increasing the risk of failure, it is preferable that the ratio be equal to or less than the upper limit.

[0024] <Solvent> The solvent used in the production method of the present invention is not particularly limited as long as it is a solvent suitable for the purpose of the present invention. Furthermore, the solvent may or may not be soluble in the formaldehyde-generating substance and / or the Lewis acid catalyst. The solvent may be a single solvent or a mixed solvent. Furthermore, when the formaldehyde-generating substance is a substance that releases dissolved formaldehyde, the solvent that dissolved formaldehyde in the dissolved formaldehyde-releasing substance may constitute the solvent used in the production method of the present invention. Examples of compounds that constitute the solvent include organic solvent compounds and water. Examples of organic solvent compounds include compounds having an ether bond in their chemical structure (ether-based organic solvent compounds), such as tetrahydrofuran (THF), ethylene glycol dimethyl ether, 2-methyltetrahydrofuran, diethylene glycol dimethyl ether, tetrahydropyran, cyclopentyl methyl ether, 1,4-dioxane, 12-crown-4, 15-crown-5, and polyethylene glycol; alcohol-based organic solvent compounds, such as ethylene glycol, methanol, ethanol, 2-propanol, 2-butanol, and benzyl alcohol; chlorocarbon-based organic solvent compounds, such as 1,2-dichloroethane, dichloromethane, 1,1,2,2-tetrachloroethane, and tetrachloromethane; and hydrocarbon-based organic solvent compounds, such as toluene and hexane.

[0025] The solvent preferably has a dielectric constant greater than 2.0 and equal to or less than 8.0. The dielectric constant of the solvent may be more preferably equal to or greater than 2.05, even more preferably equal to or greater than 2.1, even more preferably equal to or less than 7.6, and even more preferably equal to or less than 7.2. Here, "dielectric constant" refers to the dielectric constant measured at a temperature between 20°C and 30°C. Furthermore, "dielectric constant within the above range" refers to the dielectric constant at at least one temperature between 20°C and 30°C being within the above range. If the dielectric constant of the solvent is greater than or equal to the above lower limit, the catalytic activity of the Lewis acid catalyst is enhanced, and the Diels-Alder reaction is promoted even under relatively low temperature conditions, thereby contributing to achieving an excellent yield even when the reaction is carried out at a relatively low temperature. If the dielectric constant of the solvent is equal to or less than the above upper limit, the activity of the Lewis acid catalyst is slightly suppressed, but the Diels-Alder reaction proceeds sufficiently even under relatively low temperature conditions, thereby contributing to achieving an excellent yield even when the reaction is carried out at a relatively low temperature.

[0026] When the solvent is a single solvent, the dielectric constant can be determined by referring to publicly available information about each solvent, for example, the following Table 1. Then, a solvent having a dielectric constant within the above range can be appropriately selected based on the referred information.

[0027]

[0028] (Table notes) *1) Handbook of Chemistry and Physics 87th Edition, 6, pp. 135-156, 2006-2007 *2) CPME relative permittivity and its measurement temperature: from the Zeon Corporation website

[0029] When the solvent is a mixed solvent, the relative dielectric constant of the mixed solvent can be calculated as follows. For example, in the case of a mixed solvent of two solvents, the relative dielectric constant D of the mixed solvent of solvent A and solvent B is ａｂ is calculated by the following formula according to the literature (Lange's Handbook of Chemistry, 12th Ed. (1979), McGraw-Hill, Inc.): ａｂ = (D ａ ×x+Dｂ × y) / (x + y) Solvent A: relative dielectric constant D ａ , weight ratio x Solvent B: relative dielectric constant D ｂ , weight ratio y In the case of a mixed solvent of three or more solvents, the relative dielectric constant can be similarly determined as the average of the relative dielectric constants according to the weight ratio of each solvent.

[0030] From the viewpoint of dissolving 1,3-pentadiene, the solvent preferably contains an organic solvent compound. Furthermore, the solvent more preferably contains a compound having an ether bond in its chemical structure (an ether-based organic solvent compound) as the organic solvent compound. Furthermore, the solvent still more preferably contains 1,4-dioxane, tetrahydropyran, or ethylene glycol dimethyl ether as the compound having an ether bond in its chemical structure. The content of the compound having an ether bond in the solvent is preferably 30% by mass or more, more preferably 50% by mass or more, and even more preferably 70% by mass or more. When the solvent contains a compound having an ether bond in its chemical structure, the compound coordinates to the Lewis acid catalyst via the lone electron pair contained in the oxygen atom in the ether bond, enhancing the catalytic activity of the Lewis acid catalyst and promoting the Diels-Alder reaction even under relatively low-temperature conditions. As a result, it becomes possible to achieve an excellent yield even when the reaction is carried out at a relatively low temperature.

[0031] <<Amount of Solvent Used>> The amount of solvent used is not particularly limited, but may be, for example, 0.5 mL or more, preferably 1 mL or more, more preferably 2 mL or more, and for example, 20 mL or less, preferably 10 mL or less, and more preferably 5 mL or less, per gram of 1,3-pentadiene. If the amount of solvent used is equal to or greater than the above-mentioned lower limit, for example, in the case where a compound having an ether bond is included in the chemical structure, the catalytic activity of the Lewis acid catalyst is enhanced due to the effect of the lone electron pair contained in the oxygen atom in the ether bond, promoting the Diels-Alder reaction. As a result, it is possible to achieve an excellent yield even when the reaction is carried out at a relatively low temperature. Furthermore, if the amount of solvent used is equal to or less than the above-mentioned upper limit, the concentration of the raw material compounds is not diluted, and the reaction proceeds appropriately.

[0032] <Lewis Acid Catalyst> The Lewis acid catalyst used in the production method of the present invention is not particularly limited, but Lewis acids suitable for Diels-Alder reactions can be particularly used. Examples of Lewis acid catalysts include metal halides, metal triflates, alkylated metals, alkylated metal halides, metal alkoxides, boron halides, and boron triflates.

[0033] Examples of halogens that can be contained in the Lewis acid catalyst include fluorine, chlorine, bromine, iodine, etc. Examples of alkyls that can be contained in the Lewis acid catalyst include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, cyclohexyl, etc. Examples of alkoxys that can be contained in the Lewis acid catalyst include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, s-butoxy, t-butoxy, cyclohexyloxy, etc.

[0034] Examples of metal species that can be contained in the Lewis acid catalyst include beryllium, magnesium, aluminum, calcium, scandium, titanium, vanadium, chromium, manganese, iron, cobalt, nickel, copper, zinc, gallium, selenium, strontium, yttrium, zirconium, niobium, molybdenum, ruthenium, rhodium, palladium, silver, indium, tin, tellurium, barium, lanthanum, cerium, praseodymium, neodymium, samarium, europium, gadolinium, terbium, dysprosium, holmium, erbium, thulium, ytterbium, lutetium, hafnium, tantalum, tungsten, rhenium, osmium, iridium, platinum, gold, thallium, lead, bismuth, etc. Among these, examples of metal species in which the valence of the metal ion is monovalent include silver and thallium. Examples of metal species having a valence of 2 include beryllium, magnesium, calcium, manganese, iron, cobalt, nickel, copper, zinc, strontium, palladium, and barium. Examples of metal species having a valence of 3 include aluminum, scandium, vanadium, chromium, iron, gallium, yttrium, ruthenium, rhodium, indium, lanthanum, cerium, praseodymium, neodymium, samarium, europium, gadolinium, terbium, dysprosium, holmium, erbium, thulium, ytterbium, lutetium, gold, and bismuth. Examples of metal species having a valence of 4 include titanium, selenium, zirconium, tin, hafnium, tantalum, osmium, iridium, platinum, and lead. Examples of metal species having a valence of 5 include niobium, molybdenum, and rhenium. Examples of metal species having a metal ion valence of 6 include tungsten. Examples of metal species having a metal ion valence of 7 include manganese and rhenium. Note that for metal species having multiple possible metal ion valences, each metal species is not limited to the above-mentioned valence classifications and can be classified into all possible metal ion valences. The Lewis acid catalyst preferably contains a metal species having a metal ion valence of 3 or more (e.g., 3, 4, 5, 6, 7).The higher the valence of the metal ion, such as 3 or more, the higher the catalytic activity of the Lewis acid catalyst containing that metal species, and as a result, it is possible to achieve an excellent yield even when the reaction is carried out at a relatively low temperature. Furthermore, it is preferable that the Lewis acid catalyst contains a metal species whose electronegativity of the single metal is 1.3 or more. The higher the electronegativity of the metal species, the higher the acidity of the Lewis acid catalyst and the higher the catalytic activity, and as a result, it is possible to achieve an excellent yield even when the reaction is carried out at a relatively low temperature. Examples of metal species having an electronegativity of 1.3 or more include beryllium, magnesium, aluminum, scandium, selenium, titanium, vanadium, chromium, manganese, iron, cobalt, nickel, copper, zinc, gallium, zirconium, niobium, molybdenum, ruthenium, rhodium, palladium, silver, indium, tin, tellurium, hafnium, tantalum, tungsten, rhenium, osmium, iridium, platinum, gold, thallium, lead, and bismuth.

[0035] Examples of metal halides include silver(I) chloride, zinc chloride, aluminum chloride, scandium chloride, indium chloride, bismuth chloride, gold(III) chloride, rhodium chloride, ruthenium chloride, titanium tetrachloride, tin tetrachloride, hafnium tetrachloride, zirconium tetrachloride, iridium tetrachloride, osmium tetrachloride, lead tetrachloride, platinum tetrachloride, selenium tetrachloride, molybdenum pentachloride, rhenium pentachloride, and tungsten hexachloride. Examples of metal triflates include silver(I) triflate, zinc triflate, aluminum triflate, scandium triflate, indium triflate, bismuth triflate, gold(III) triflate, rhodium triflate, ruthenium triflate, titanium triflate, tin triflate, hafnium triflate, zirconium triflate, iridium triflate, osmium triflate, lead(IV) triflate, platinum(IV) triflate, celene triflate, molybdenum(V) triflate, rhenium(V) triflate, and tungsten(VI) triflate. Examples of alkylated metals include trimethylaluminum, triethylaluminum, and triisobutylaluminum. Examples of alkylated metal halides include diethylchloroaluminum, dichloroethylaluminum, dichloromethylaluminum, dimethylchloroaluminum, dichloroethylaluminum, and diethylchloroaluminum. Examples of metal alkoxides include aluminum isopropoxide, titanium butoxide, etc. Examples of boron halides include boron trifluoride, boron trichloride, etc.

[0036] The Lewis acid catalyst preferably contains a metal triflate, from the viewpoints of high catalytic activity, excellent yield, and high resistance to moisture contamination. Among these, bismuth triflate, hafnium triflate, molybdenum (V) triflate, and tungsten (VI) triflate are more preferred. The Lewis acid catalyst may be introduced into the reaction system itself, or a precursor of the Lewis acid catalyst may be introduced into the reaction system and formed in the reaction system. For example, when a metal triflate is used as the Lewis acid catalyst, it may be added to the reaction system in the form of a metal triflate compound, or a metal species-containing substance (e.g., metal halide, metal salt, etc.) and a triflate-containing substance (e.g., trifluoromethanesulfonic acid, trifluoromethanesulfonate, etc.) may be added to the reaction system in the form of separate substances to form the metal triflate in the reaction system.

[0037] <<Amount of Lewis Acid Catalyst Used>> The amount of Lewis acid catalyst used is not particularly limited, but may be, for example, 0.1 mol % or more, preferably 0.5 mol % or more, more preferably 0.8 mol % or more, and for example, 5 mol % or less, preferably 4 mol % or less, and more preferably 2 mol % or less, based on 1,3-pentadiene being 100 mol %. When the amount of Lewis acid catalyst used is equal to or greater than the above-mentioned lower limit, the reaction is promoted, and as a result, an excellent yield can be achieved even when the reaction is carried out at a relatively low temperature. Furthermore, when the amount of Lewis acid catalyst used is equal to or less than the above-mentioned upper limit, excessive reaction is suppressed, and it is possible to prevent deposits such as carbides resulting from high molecular weight products that are the product of excessive reaction from adhering to the reactor.

[0038] <Other substances that may be added to the reaction system> In the production method of the present invention, other substances may be optionally added to the reaction system. Examples of other substances include an antioxidant and a polymerization inhibitor.

[0039] <Reactor> The reactor may be a heatable reactor that contains a mixture of 1,3-pentadiene, a formaldehyde-generating substance, a solvent, a Lewis acid catalyst (including a precursor of the Lewis acid catalyst), and optionally other substances. That is, in the present invention, 2-methyl-5,6-dihydro-2H-pyran is synthesized in a single reactor. Note that, when producing 2-methyl-5,6-dihydro-2H-pyran, multiple reactors may be connected. Performing the synthesis reaction in a single reactor contributes to reducing the space required for the production equipment, reducing the chance of equipment breakdowns, and improving the efficiency of operation and maintenance of the production equipment, thereby improving industrial applicability. Furthermore, if the synthesis reaction is carried out in one reactor, there is no need to use a separate reactor, such as a reactor for generating formaldehyde gas, and therefore the reactor will not become highly pressurized due to the supply of formaldehyde gas, thereby reducing safety risks such as damage to the reaction system (reactor, piping, instruments), ejection or leakage of contents from the reaction system, and suppressing the adhesion of deposits derived from formaldehyde gas to the piping and instruments. The type of reactor is not particularly limited as long as the object of the present invention can be achieved, but one having a stirring device and made of a material having excellent corrosion resistance and mechanical strength (e.g., stainless steel) is preferred.

[0040] <Reaction Temperature> The temperature at which the synthesis reaction is carried out in the production method of the present invention is 60°C or higher but lower than 100°C. The reaction temperature is preferably 65°C or higher, more preferably 70°C or higher, and preferably 95°C or lower, more preferably 90°C or lower. In the production method of the present invention, even when the synthesis reaction is carried out at such a relatively low temperature range, an excellent yield of the target compound can be achieved. If the reaction temperature is higher than the above upper limit, excessive reaction progress occurs, resulting in the production of a large amount of polymers, thereby reducing the yield of the target compound. In addition, in some cases, particularly when the synthesis reaction is carried out at a higher reaction temperature (e.g., about 240°C) as in conventional technology, deposits such as carbides, which are thought to be derived from such polymers, may adhere to the reactor and become impossible to clean. On the other hand, since the production method of the present invention is carried out at a relatively low temperature, such a decrease in yield and adhesion of deposits to the reactor can be suppressed, thereby improving industrial applicability. If the reaction temperature is lower than the above lower limit, the temperature will not be sufficient for decomposing the formaldehyde-generating substance or for releasing adsorbed formaldehyde from the formaldehyde-generating substance, resulting in insufficient generation of formaldehyde and a decrease in the yield of the target compound.

[0041] <Reaction Pressure> The pressure under which the synthesis reaction is carried out in the production method of the present invention is not particularly limited, but in the case of high pressure or negative pressure, it is preferably a pressure equivalent to atmospheric pressure (about 0.1 MPa) from the viewpoint of increasing safety risks, such as damage to the reaction system (reactor, piping, instruments) and ejection or leakage of contents from the reaction system. In other words, it is preferable not to perform pressurization or negative pressure operations on the reaction system. The pressure (absolute pressure) under which the synthesis reaction is carried out may be, for example, 0.07 MPa or more, preferably 0.08 MPa or more, more preferably 0.09 MPa or more, for example, 0.26 MPa or less, preferably 0.24 MPa or less, more preferably 0.22 MPa or less.

[0042] <Reaction Procedure> In the production method of the present invention, the synthesis reaction is carried out by heating a mixture of 1,3-pentadiene, a formaldehyde-generating substance, a solvent, a Lewis acid catalyst, and optionally other substances described above in a reactor to the reaction temperature described above. The synthesis reaction is preferably carried out with stirring. The components used in the synthesis reaction may be mixed in the reactor or may be mixed in advance before being charged into the reactor. Furthermore, the components used in the synthesis reaction may be charged in their entirety at the beginning, or may be charged in divided amounts successively. In the mixture, 1,3-pentadiene is preferably dissolved in the solvent, but the formaldehyde-generating substance and Lewis acid catalyst may or may not be dissolved in the solvent.

[0043] <Other Steps> The production method of the present invention may optionally further include other steps. Examples of such other steps include a cooling step, a step of removing remaining components, a washing step, and a distillation step. The cooling step is a step of cooling the reaction solution after the synthesis reaction to, for example, 50°C or less, preferably 40°C or less, and more preferably 30°C or less. The step of removing remaining components is a step of removing remaining components (e.g., Lewis acid catalyst, remaining paraformaldehyde) from the reaction solution, and can be carried out by, for example, filtration, decantation, or the like. The washing step is a step of washing the reaction solution with water or an aqueous solution. Examples of aqueous solutions include aqueous sodium carbonate, saturated saline, and aqueous sodium bicarbonate. The distillation step is a step of distilling the reaction solution to separate the target compound, 2-methyl-5,6-dihydro-2H-pyran, as a colorless liquid having a boiling point of approximately 105 to 106°C.

[0044] <Uses of 2-methyl-5,6-dihydro-2H-pyran> 2-methyl-5,6-dihydro-2H-pyran obtained by the production method of the present invention can be used as a precursor for producing cis-3-hexenol, which can be used as a raw material for fragrances and flavors that impart a fresh, green leaf-like aroma. cis-3-hexenol can be produced, for example, according to the following production method for cis-3-hexenol.

[0045] (Production Method of cis-3-hexenol) The production method of cis-3-hexenol of the present invention includes a step of producing 2-methyl-5,6-dihydro-2H-pyran using the above-mentioned production method of 2-methyl-5,6-dihydro-2H-pyran, and a step of reducing the obtained 2-methyl-5,6-dihydro-2H-pyran to obtain cis-3-hexenol. In the production method of cis-3-hexenol of the present invention, "reduction" refers to a reaction in which the bond between the oxygen atom and the carbon atom at the 2-position in 2-methyl-5,6-dihydro-2H-pyran is cleaved and a hydrogen atom is added, without modifying other moieties (e.g., double bonds) at all.

[0046] The method for producing cis-3-hexenol of the present invention uses the above-mentioned production method in the step of producing 2-methyl-5,6-dihydro-2H-pyran, and therefore can achieve an excellent yield and can suppress the problem of deposits such as carbides adhering to the reactor and becoming impossible to clean. Furthermore, since a separate reactor such as a reactor for generating formaldehyde gas is not used, it is possible to suppress the adhesion of deposits derived from formaldehyde gas to piping and instruments, and to reduce safety risks such as damage to the reaction system (reactor, piping, instruments) due to high pressure caused by formaldehyde gas, and spraying or leakage of contents from the reaction system.

[0047] <Reduction Conditions> The conditions for the reduction are not particularly limited, as long as they allow selective reduction of the above-mentioned sites. For example, the reduction may be carried out in an amine in the presence of an alkali metal. Examples of amines include ammonia, lower alkylamines such as methylamine, dimethylamine, ethylamine, and diethylamine, and ethylenediamine, with ethylamine being preferred. The amount of amine used is not particularly limited, but may be, for example, 1 part by mass or more, preferably 2 parts by mass or more, more preferably 5 parts by mass or more, and for example, 50 parts by mass or less, preferably 20 parts by mass or less, and more preferably 10 parts by mass or less, per part by mass of 2-methyl-5,6-dihydro-2H-pyran. Examples of alkali metals include lithium, sodium, and potassium, with potassium being preferred. The amount of alkali metal used is not particularly limited, but may be, for example, 0.5 mol or more, preferably 1 mol or more, more preferably 1.5 mol or more, and for example, 3.5 mol or less, preferably 3 mol or less, and more preferably 2.5 mol or less, per 1 mole of 2-methyl-5,6-dihydro-2H-pyran. The reduction temperature may be, for example, −100° C. or higher, preferably −80° C. or higher, more preferably −60° C. or higher, and may be, for example, 50° C. or lower, preferably 0° C. or lower, more preferably −50° C. or lower. The reduction time is not particularly limited, but it is preferable to carry out the reduction at least until the alkali metal has disappeared, and more preferably to carry out the reduction for a similar period of time after the alkali metal has disappeared. For example, it is thought that it takes about 2 to 3 hours for the alkali metal to disappear.

[0048] <Other Steps> The method for producing cis-3-hexenol of the present invention may further include other steps as desired. Examples of the other steps include a reduction reaction termination step and a purification step.

[0049] <<Reduction Reaction Termination Step>> The method for producing cis-3-hexenol of the present invention may optionally further include a step of terminating the reduction reaction. The reduction reaction can be terminated, for example, by adding ammonium halide to the reduction reaction system. Examples of ammonium halides include ammonium chloride, ammonium bromide, and ammonium iodide. The amount of ammonium halide used is not particularly limited, but may be, for example, 0.5 parts by mass or more, preferably 0.7 parts by mass or more, and more preferably 1 part by mass or more, and for example, 10 parts by mass or less, preferably 5 parts by mass or less, and more preferably 2 parts by mass or less, relative to 1 part by mass of 2-methyl-5,6-dihydro-2H-pyran.

[0050] <<Purification Step>> The method for producing cis-3-hexenol of the present invention may optionally further include a step of purifying the cis-3-hexenol obtained by reduction. Purification of cis-3-hexenol may include, for example, at least one or all of the following operations: recovery of the amine, extraction of cis-3-hexenol, washing, drying, and distillation. Recovery of the amine can be achieved, for example, by heating the reaction system to distill off the amine. Extraction of cis-3-hexenol can be achieved, for example, using a hydrophobic solvent such as ether. Washing of cis-3-hexenol can be achieved, for example, with water. Drying of cis-3-hexenol can be achieved, for example, using anhydrous sodium sulfate. Distillation of cis-3-hexenol can be achieved, for example, by obtaining a fraction having a boiling point of approximately 154 to 159°C as cis-3-hexenol under atmospheric pressure.

[0051] <<Uses of cis-3-hexenol>> Cis-3-hexenol obtained by the method for producing cis-3-hexenol of the present invention can be used as a raw material for fragrances and flavors that impart a fresh, green leaf-like aroma.

[0052] The present invention will be described in detail below based on examples, but the present invention is not limited to these examples. In the examples and comparative examples, the yield of 2-methyl-5,6-dihydro-2H-pyran (MDHP), the internal pressure of the reactor, the presence or absence of adhesion of charcoal to the reactor, and the presence or absence of adhesion of paraformaldehyde (PFA) precipitates to piping and a pressure gauge were measured or evaluated according to the following methods.

[0053] (Methods for measurement or evaluation) <Yield of 2-methyl-5,6-dihydro-2H-pyran (MDHP)> The final reaction solution was weighed, and the mass of the reaction solution was regarded as the yield of MDHP. The yield of MDHP was calculated based on the total amount of 1,3-pentadiene as the raw material and the amount of trans-1,3-pentadiene (t-PPL) in the raw material.

[0054] <Internal Pressure of Reactor> The internal pressure (absolute pressure) was determined from the indication of the pressure gauge of the autoclave (autoclave A in Comparative Example 10).

[0055] <Presence or Absence of Adhesion of Carbonized Matter to Reactor> After the reaction liquid was recovered, the inside of the autoclave (autoclave A in Comparative Example 10) was visually inspected for the presence or absence of adhering matter.

[0056] <Presence or Absence of Paraformaldehyde (PFA) Precipitates on Piping and Pressure Gauge> After the reaction, the presence or absence of deposits on the piping and pressure gauge was visually observed.

[0057] Example 1 To a stainless steel autoclave reactor were added 81.7 g of 1,3-pentadiene (manufactured by Zeon Corporation: cis-trans mixture, cis / trans ratio = 31 / 69), 40.0 g of paraformaldehyde, and 196 mL of 1,4-dioxane (1,4-DO) as a solvent (organic solvent). Bismuth triflate as a Lewis acid catalyst was then added in an amount of 1.0 mol % based on 100 mol % of 1,3-pentadiene, and the mixture was heated and stirred for 12 hours at a predetermined temperature listed in Table 1. The reaction mixture was then cooled and washed with 482 mL of a 1 mol / L aqueous sodium carbonate solution to remove residual components (such as the Lewis acid catalyst and residual paraformaldehyde). The resulting organic layer was distilled under atmospheric pressure to obtain a colorless liquid with a boiling point of 105 to 106°C in a yield of 49% based on the total 1,3-pentadiene (71% based on trans-1,3-pentadiene). １ The H-NMR peaks coincided with those of 2-methyl-5,6-dihydro-2H-pyran, confirming that this liquid was 2-methyl-5,6-dihydro-2H-pyran. １ H-NMR (CDCl3) δ [ppm]: 1.2 (d, 3H), 1.9 (m, 1H), 3.7 (m, 1H), 4.0 (m, 1H), 4.2 (m, 1H), 5.6 (m, 1H), 5.8 (m, 1H)

[0058] (Examples 2 to 4: Change of Solvent) The same procedure as in Example 1 was carried out except that the solvents used were the respective predetermined solvents (organic solvents) shown in Table 2.

[0059] Example 5, Comparative Examples 1 and 2: Change in Reaction Temperature The same operations as in Example 4 were carried out except that the temperature during heating and stirring (reaction temperature) was changed to each of the predetermined temperatures shown in Table 2.

[0060] Examples 6 to 11: Change of Lewis acid catalyst The same procedure as in Example 4 was carried out except that each of the Lewis acid catalysts shown in Table 2 was used as the catalyst.

[0061] Example 12: Formation of a Metal Triflate Lewis Acid Catalyst by Mixing a Metal Halide and Trifluoromethanesulfonic Acid. 81.7 g of 1,3-pentadiene (manufactured by Zeon Corporation: cis-trans mixture, cis / trans ratio = 31 / 69), 40.0 g of paraformaldehyde, and 196 mL of tetrahydrofuran (organic solvent) were added to a stainless steel autoclave. 3.3 g of molybdenum pentachloride (1.0 mol % relative to 1,3-pentadiene) and 18.1 g of trifluoromethanesulfonic acid were then added, and the mixture was heated and stirred at 80°C for 12 hours. It was believed that molybdenum triflate, acting as a Lewis acid catalyst, was formed from molybdenum pentachloride and trifluoromethanesulfonic acid in the reaction mixture. The reaction mixture was then cooled and washed with 482 mL of a 1 mol / L aqueous sodium carbonate solution to remove remaining components (such as the Lewis acid catalyst and residual paraformaldehyde). The resulting organic layer was distilled under atmospheric pressure to obtain a colorless liquid having a boiling point of 105 to 106°C in a yield of 47% based on total 1,3-pentadiene (68% based on trans 1,3-pentadiene).

[0062] Example 13: Formation of a Metal Triflate Lewis Acid Catalyst by Mixing a Metal Halide and Trifluoromethanesulfonic Acid. 81.7 g of 1,3-pentadiene (manufactured by Zeon Corporation: cis-trans mixture, cis / trans ratio = 31 / 69), 40.0 g of paraformaldehyde, and 196 mL of tetrahydrofuran (organic solvent) were added to a stainless steel autoclave. 4.7 g of tungsten hexachloride (1.0 mol % relative to 1,3-pentadiene) and 18.1 g of trifluoromethanesulfonic acid were then added, and the mixture was heated and stirred at 80°C for 12 hours. It was believed that tungsten triflate, acting as a Lewis acid catalyst, was formed from tungsten hexachloride and trifluoromethanesulfonic acid in the reaction mixture. The reaction mixture was then cooled and washed with 482 mL of a 1 mol / L aqueous sodium carbonate solution to remove remaining components (such as the Lewis acid catalyst and residual paraformaldehyde). The resulting organic layer was distilled under atmospheric pressure to obtain a colorless liquid having a boiling point of 105 to 106°C in a yield of 48% based on total 1,3-pentadiene (70% based on trans 1,3-pentadiene).

[0063] Comparative Examples 3 to 5: Synthesis without Solvent: 81.7 g of 1,3-pentadiene (manufactured by Zeon Corporation: cis-trans mixture, cis / trans ratio = 31 / 69), 40.0 g of paraformaldehyde, and 1.0 mol % of aluminum chloride serving as a Lewis acid catalyst relative to the 1,3-pentadiene were placed in a stainless steel autoclave as a reactor, and the mixture was heated and stirred for 12 hours at each of the predetermined temperatures listed in Table 1. Thereafter, the reaction solution was cooled and washed with 482 mL of a 1 mol / L aqueous solution of sodium bicarbonate to remove remaining components (such as the Lewis acid catalyst and residual paraformaldehyde). Thereafter, the same operations as in Example 1 were carried out.

[0064] Comparative Example 6: Synthesis without Lewis Acid Catalyst The same operations as in Example 4 were carried out, except that no Lewis acid catalyst was used during the synthesis reaction and the temperature during heating and stirring (reaction temperature) was changed to a predetermined temperature shown in Table 2.

[0065] Comparative Examples 7 to 9: Synthesis without Lewis Acid Catalyst or Solvent To a stainless steel autoclave serving as a reactor, 81.7 g of 1,3-pentadiene (manufactured by Zeon Corporation: cis-trans mixture, cis / trans ratio = 31 / 69) and 40.0 g of paraformaldehyde were added, and the mixture was heated and stirred for 12 hours at the respective predetermined temperatures shown in Table 1. Thereafter, the reaction solution was cooled, and the reaction solution was washed with 482 mL of a 1 mol / L aqueous sodium hydrogen carbonate solution to remove remaining components (Lewis acid catalyst, remaining paraformaldehyde, etc.). Thereafter, the same operations as in Example 1 were carried out.

[0066] Comparative Example 10: Synthesis Using Two Reactors To a stainless steel autoclave A, 81.7 g of 1,3-pentadiene (manufactured by Zeon Corporation: cis-trans mixture, cis / trans ratio = 31 / 69), 196 mL of a predetermined solvent (organic solvent) described in Table 1, and 1.0 mol % of zinc chloride as a Lewis acid catalyst relative to the 1,3-pentadiene were added. Meanwhile, 40.0 g of paraformaldehyde and 360 g of liquid paraffin were added to a stainless steel autoclave B. After connecting autoclaves A and B via piping, autoclave A was heated and stirred at 80°C, and autoclave B was gradually heated from 80°C to 140°C for 6 hours with heating and stirring to generate formaldehyde gas. The generated formaldehyde gas was supplied to autoclave A via piping, and the 1,3-pentadiene and formaldehyde gas were reacted in autoclave A. Thereafter, the reaction solution in autoclave A was cooled, and the reaction solution was washed with 482 mL of a 1 mol / L aqueous solution of sodium hydrogen carbonate to remove remaining components (Lewis acid catalyst, remaining paraformaldehyde, etc.), after which the same operations as in Example 1 were carried out.

[0067] (Results) In each example and comparative example, the yield of 2-methyl-5,6-dihydro-2H-pyran (MDHP), the internal pressure (absolute pressure) of the autoclave (autoclave A in Comparative Example 10) reactor during the synthesis reaction, the presence or absence of adhesion of char to the reactor, and the presence or absence of adhesion of paraformaldehyde (PFA) precipitates to the piping and pressure gauge were measured or evaluated. The yield of MDHP is based on the total amount of 1,3-pentadiene as the raw material and the amount of trans-1,3-pentadiene (t-PPL) in the raw material. The results are shown in Table 2.

[0068]

[0069] (Meanings and notes of abbreviations and other names in the table) t-PPL: trans-1,3-pentadiene PFA: paraformaldehyde MDHP: 2-methyl-5,6-dihydropyran 1,4-DO: 1,4-dioxane Monoglyme: ethylene glycol dimethyl ether THP: tetrahydropyran THF: tetrahydrofuran TfOH: trifluoromethanesulfonic acid *The temperature outside the parentheses is the temperature of the synthesis reactor (autoclave A), and the temperature inside the parentheses is the temperature of the PFA decomposition vessel (autoclave B)

[0070] Comparison of Examples 1 to 13 according to the production method of the present invention with Comparative Examples 1 to 10 showed that, according to the production method of the present invention, an excellent yield of 2-methyl-5,6-dihydro-2H-pyran was achieved and adhesion of precipitates to the reactor, piping, and instruments was suppressed. Furthermore, Comparative Example 3, in which a solvent was not used, had a low yield. However, Comparative Examples 4 and 5, in which the reaction temperature was increased under the same conditions, also did not increase the yield, and instead, the problem of precipitates adhering to the reactor occurred. Furthermore, Comparative Example 7, in which a Lewis acid catalyst and a solvent were not used, also had a low yield. However, Comparative Example 8, in which the reaction temperature was increased under the same conditions, also did not increase the yield. Comparative Example 9 had an increased yield, but both Comparative Examples 8 and 9 experienced the problem of precipitates adhering to the reactor.

[0071] According to the present invention, it is possible to provide a method for producing 2-methyl-5,6-dihydro-2H-pyran, which can achieve an excellent yield even when the reaction is carried out at a relatively low temperature, and which suppresses adhesion of deposits to the reactor, piping, and instruments.

Claims

1. A method for producing 2-methyl-5,6-dihydro-2H-pyran, comprising reacting 1,3-pentadiene with a formaldehyde-generating substance in a solvent in the presence of a Lewis acid catalyst at a temperature of 60°C or higher and lower than 100°C in a single reactor to synthesize 2-methyl-5,6-dihydro-2H-pyran.

2. The method according to claim 1 , wherein the solvent has a relative dielectric constant of more than 2.0 and not more than 8.

0.

3. The method according to claim 1 , wherein the solvent contains a compound having an ether bond in its chemical structure.

4. The method of claim 1 , wherein the Lewis acid catalyst comprises a metal triflate.

5. The method according to claim 1 , wherein the Lewis acid catalyst contains a metal species whose elemental metal has an electronegativity of 1.3 or more.

6. The method according to claim 1 , wherein the Lewis acid catalyst contains a metal species having a metal ion valence of three or more.

7. A step of producing 2-methyl-5,6-dihydro-2H-pyran using the production method according to any one of claims 1 to 6; a step of reducing the obtained 2-methyl-5,6-dihydro-2H-pyran to obtain cis-3-hexenol. A method for producing cis-3-hexenol, comprising: