Method for producing 2,4-dialkylbenzaldehyde

Abstract

The purpose of the present invention is to provide a method for producing 2,4-dialkylbenzaldehyde having an excellent conversion rate, an excellent yield, and excellent regioselectivity of formylation, the method comprising causing carbon monoxide to act on a reaction raw material containing specific m-dialkylbenzene in the presence of hydrogen fluoride and boron trifluoride.　A method for producing 2,4-dialkylbenzaldehyde according to the present invention comprises a step for formylating at least a position (a) by causing carbon monoxide to act on a reaction raw material containing m-dialkylbenzene represented by formula (1) in the presence of hydrogen fluoride and boron trifluoride, wherein the reaction raw material is dialkylbenzene containing greater than 90 mol% of the m-dialkylbenzene represented by formula (1), and the number of moles of boron trifluoride with respect to 1 mole of the m-dialkylbenzene represented by formula (1) is 0.7-0.3. (In the formula, R1 represents a C1-C3 alkyl group, and R2 represents a C2-C7 chain or cyclic alkyl group having secondary or tertiary carbon at a benzylic position. Here, the number of carbon atoms in R2 is larger than the number of carbon atoms in R1.)

Description

[Technical field]

[0001] The present invention relates to a process for producing a 2,4-dialkylbenzaldehyde. [Background technology]

[0002] Conventionally, alkylbenzaldehydes have attracted attention for their use in fragrances and as fragrance raw materials. In these applications, not only fragrance but also low skin sensitization and biodegradability are important, and for these properties, the substitution position of the substituent and the abundance ratio of isomers are important. Patent Document 1 describes a method in which 1-isobutyl-3-methylbenzene is reacted with carbon monoxide under pressure in the presence of triflic acid to directly introduce a formyl group into the 4-position. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] JP 2017-533926 A Summary of the Invention [Problem to be solved by the invention]

[0004] Patent Document 1 describes a method for producing 4-isobutyl-2-methylbenzaldehyde by reacting 1-isobutyl-3-methylbenzene with carbon monoxide under pressure in the presence of triflic acid. However, in the examples, it only describes a method for obtaining 2-methyl-4-isobutylbenzaldehyde by reacting 1-isobutyl-3-methyl-4-bromobenzene with dimethylformamide. An object of the present invention is to provide a method for producing 2,4-dialkylbenzaldehyde which is excellent in conversion and yield and in site selectivity of formylation, by reacting a reaction raw material containing a specific m-dialkylbenzene with carbon monoxide in the presence of hydrogen fluoride and boron trifluoride. [Means for solving the problem]

[0005] As a result of intensive research, the inventors have found that when a reaction raw material containing m-dialkylbenzene is reacted with carbon monoxide in the presence of hydrogen fluoride and boron trifluoride, by using a specific m-dialkylbenzene as the reaction raw material and further by setting the amount of boron trifluoride added to the m-dialkylbenzene within a specific range, a high conversion and yield can be obtained and the formylation reaction proceeds with extremely regioselectivity, thereby completing the present invention. That is, the present invention is as follows.

[0006] <1> A method for producing 2,4-dialkylbenzaldehyde, comprising the steps of reacting a reaction raw material containing a m-dialkylbenzene represented by formula (1) with carbon monoxide in the presence of hydrogen fluoride and boron trifluoride to formylate at least position (a), wherein the reaction raw material is a dialkylbenzene containing more than 90 mol% of the m-dialkylbenzene represented by formula (1), and the number of moles of boron trifluoride per mole of the m-dialkylbenzene represented by formula (1) is 0.7 mol or more and 3.0 mol or less.

[0007] [ka] (In the formula, R 1 represents an alkyl group having 1 to 3 carbon atoms, and R 2 represents a linear or cyclic alkyl group having 2 to 7 carbon atoms and a secondary or tertiary carbon at the benzyl position. 2 The number of carbon atoms in R 1 )

[0008] <2> The reaction temperature is between -40°C and 10°C. <1> 2. A method for producing 2,4-dialkylbenzaldehyde according to claim 1. <3> The number of moles of hydrogen fluoride per mole of m-dialkylbenzene represented by formula (1) is 2.5 moles or more and 20 moles or less. <1> or <2> 2. A method for producing 2,4-dialkylbenzaldehyde according to claim 1. <4> R 1 is a methyl group or an ethyl group, and R 2 is an ethyl group, an n-propyl group, an isopropyl group, an isobutyl group, or a neopentyl group; <1> ~ <3> 2. A method for producing a 2,4-dialkylbenzaldehyde according to any one of claims 1 to 11. <5> R 1 is a methyl group; <1> ~ <4> 2. A method for producing a 2,4-dialkylbenzaldehyde according to any one of claims 1 to 11. <6> R 1 is a methyl group, and R 2 is an isopropyl group or R 1 is a methyl group, and R 2 is an isobutyl group, or R 1 is a methyl group, and R 2 is a neopentyl group; <1> ~ <5> 2. A method for producing a 2,4-dialkylbenzaldehyde according to any one of claims 1 to 11. <7> In the obtained 2,4-dialkylbenzaldehyde, the content of 2,4-dialkylbenzaldehyde in which the position (a) is formylated is 80 mol % or more. <1> ~ <6> 2. A method for producing a 2,4-dialkylbenzaldehyde according to any one of claims 1 to 11. Effect of the Invention

[0009] According to the present invention, it is possible to provide a method for producing 2,4-dialkylbenzaldehyde which is excellent in conversion and yield and in site selectivity for formylation, by reacting a reaction raw material containing a specific m-dialkylbenzene with carbon monoxide in the presence of hydrogen fluoride and boron trifluoride. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] [Method for producing 2,4-dialkylbenzaldehyde] The production method of 2,4-dialkylbenzaldehyde of the present invention (hereinafter also simply referred to as the "production method of the present invention") comprises a step of reacting a reaction raw material containing m-dialkylbenzene represented by formula (1) with carbon monoxide in the presence of hydrogen fluoride and boron trifluoride to formylate at least position (a), wherein the reaction raw material is a dialkylbenzene containing more than 90 mol% of m-dialkylbenzene represented by formula (1), and the number of moles of boron trifluoride per mole of m-dialkylbenzene represented by formula (1) is 0.7 mol or more and 3.0 mol or less.

[0011] [ka] (In the formula, R 1 represents an alkyl group having 1 to 3 carbon atoms, and R 2 represents a linear or cyclic alkyl group having 2 to 7 carbon atoms and a secondary or tertiary carbon at the benzyl position. 2 The number of carbon atoms in R 1 )

[0012] The reaction scheme of the present invention is shown below.

[0013] [ka] (In the formula, R 1 represents an alkyl group having 1 to 3 carbon atoms, and R 2 represents a linear or cyclic alkyl group having 2 to 7 carbon atoms and a secondary or tertiary carbon at the benzyl position. 2 The number of carbon atoms in R 1 )

[0014] In general, when m-dialkylbenzene is subjected to a formylation reaction, the para-position (p-position) of each alkyl group is formylated, resulting in a mixture of two isomers. Specifically, for example, when a compound such as the above formula (1) is formylated, a mixture of a compound represented by formula (2) and a compound represented by formula (3) is generally obtained as a reaction product. Since these compounds have similar physical properties and are difficult to separate and purify, a production method in which formylation proceeds regioselectively and a compound represented by formula (2) can be obtained in a high isomer ratio has been desired. In addition, in the formylation of a compound represented by formula (1), side reactions such as disproportionation reactions may occur. According to the present invention, a 2,4-dialkylbenzaldehyde (a compound represented by formula (2)) in which at least the (a) position is formylated can be obtained, and a 2,4-dialkylbenzaldehyde (a compound represented by formula (2)) in which the (a) position is formylated can be obtained with high regioselectivity. Conventionally, as described in Patent Document 1, a method of functionalizing the (a) position by bromination and a method of reacting with carbon monoxide in the presence of triflic acid (trifluoromethanesulfonic acid) have been known. However, there has been a demand for a production method that can be produced more inexpensively and efficiently, has excellent conversion and yield, and is excellent in the positional selectivity of formylation, resulting in a high isomer ratio. The present inventors have found that when a reaction raw material containing a specific amount or more of m-dialkylbenzene having a specific structure is used and carbon monoxide is reacted with it in the presence of hydrogen fluoride and boron trifluoride to perform formylation, by setting the molar ratio of boron trifluoride to m-dialkylbenzene represented by formula (1) within a specific range, regioselectivity is extremely improved and 2,4-dialkylbenzaldehyde formylated at position (a) can be obtained with good conversion and yield. The detailed reason why the above reaction occurs is unclear, but in formula (1), R 2 R 1 It is believed that the formylation at the (a) position was promoted by making the substituent bulkier than R. 1 and R 2It is very important that R is a specific substituent. For example, R 2 It has been reported that when R is tert-butyl, the yield decreases. 2 does not necessarily have to be a bulky substituent, but it is important that the benzyl position is a specific substituent that is a secondary or tertiary carbon. In addition, it has been found that the position selectivity of formylation is improved by controlling the molar ratio of boron trifluoride to m-dialkylbenzene represented by formula (1) within a specific range. The present invention will be described in detail below.

[0015] <Reaction materials> In the present invention, the reaction raw material contains m-dialkylbenzene represented by the following formula (1), and the reaction raw material is a dialkylbenzene containing m-dialkylbenzene represented by the following formula (1) in more than 90 mol % of the reaction raw material. The reaction raw materials include m-dialkylbenzene represented by formula (1) and R 1 and R 2 p-Dialkylbenzenes, which have R 1 and R 2 R such as o-dialkylbenzene, which has 1 and R 2 As a substituent, the alkylbenzene may contain a dialkylbenzene having the following formula (I) or (II) as a substituent in an amount of 10 mol % or less. The content of the m-dialkylbenzene represented by formula (1) in the reaction raw material is more than 90 mol%, preferably 93 mol% or more, more preferably 96 mol% or more, and may be 100 mol%, from the viewpoint of obtaining 2,4-dialkylbenzaldehyde having few impurities and by-products and excellent position selectivity of formylation.

[0016] [ka] (In the formula, R 1 represents an alkyl group having 1 to 3 carbon atoms, and R 2represents a linear or cyclic alkyl group having 2 to 7 carbon atoms and a secondary or tertiary carbon at the benzyl position. 2 The number of carbon atoms in R 1 )

[0017] [Compound represented by formula (1)] In the above formula (1), R 1 represents an alkyl group having 1 to 3 carbon atoms, and R 2 represents a linear or cyclic alkyl group having 2 to 7 carbon atoms and a secondary or tertiary carbon at the benzyl position. 2 The number of carbon atoms in R 1 In the present invention, the reaction raw material R 1 and R 2 By containing more than 90 mol % of the compound represented by formula (1) in which R is a specific substituent, the formylation reaction proceeds with high regioselectivity and excellent conversion and yield. 2 is a tert-butyl group, i.e., R 2 When a compound having a quaternary carbon atom at the benzylic position is used, the yield decreases. R 1 From the viewpoint of reactivity, is preferably a methyl group or an ethyl group, and more preferably a methyl group. R 2 R is a linear or cyclic alkyl group having 2 to 7 carbon atoms, with the benzyl position being a secondary or tertiary carbon, and from the viewpoint of reactivity and position selectivity, the number of carbon atoms is preferably 2 to 6, and more preferably 3 to 5. 2 Specific examples of R include an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, a sec-butyl group, an isobutyl group, an n-pentyl group, a sec-pentyl group, a 3-pentyl group, an isopentyl group, a neopentyl group, a cyclopentyl group, and a cyclohexyl group. 2From the viewpoints of reactivity and regioselectivity, is preferably an ethyl group, an n-propyl group, an isopropyl group, an isobutyl group, or a neopentyl group, more preferably an n-propyl group, an isopropyl group, an isobutyl group, or a neopentyl group, even more preferably an isopropyl group, an isobutyl group, or a neopentyl group, still more preferably an isopropyl group or a neopentyl group, and still more preferably a neopentyl group. The compound represented by formula (1) is R 1 is a methyl group, and R 2 is an isopropyl group or R 1 is a methyl group, and R 2 is an isobutyl group, or R 1 is a methyl group, and R 2 is preferably a neopentyl group, and R 1 is a methyl group, and R 2 is an isopropyl group, or R 1 is a methyl group, and R 2 is more preferably a neopentyl group, and R 1 is a methyl group, and R 2 More preferably, is a neopentyl group.

[0018] <Method for producing the compound represented by formula (1)> The compound represented by formula (1) may be a commercially available product. 1 Compounds in which is a methyl group can also be synthesized as follows.

[0019] [ka]

[0020] Benzene with R 2 The compound substituted with R is reacted with carbon monoxide in the presence of hydrogen fluoride and boron trifluoride to give R 2 The p-position of is formylated to give a p-alkylbenzaldehyde. Next, the resulting p-alkylbenzaldehyde is reduced in the presence of a palladium catalyst to reduce the formyl group to a methyl group. Furthermore, the obtained p-dialkylbenzene is subjected to an isomerization reaction in the presence of hydrogen fluoride and boron trifluoride to isolate m-dialkylbenzene.

[0021] <Boron trifluoride> In the present invention, the reaction raw material is reacted with carbon monoxide in the presence of hydrogen fluoride and boron trifluoride. In this case, the number of moles of boron trifluoride per mole of m-dialkylbenzene represented by formula (1) is 0.7 moles or more, preferably 0.8 moles or more, more preferably 1.2 moles or more, and even more preferably 1.4 moles or more from the viewpoint of reactivity, and is 3.0 moles or less, preferably 2.8 moles or less, more preferably 2.4 moles or less, and even more preferably 2.0 moles or less from the viewpoint of improving the isomer ratio and economical viewpoint.

[0022] <Hydrogen fluoride> Hydrogen fluoride (HF) also functions as a solvent for the reaction. From the viewpoint of reactivity, hydrogen fluoride is preferably substantially anhydrous. Here, "substantially anhydrous" means that the water content is 5% by mass or less, preferably 1% by mass or less, and more preferably 0.1% by mass or less.

[0023] The molar ratio of hydrogen fluoride to the m-dialkylbenzene represented by formula (1), which is the reaction raw material (hydrogen fluoride / m-dialkylbenzene represented by formula (1)) is preferably 2.5 or more, more preferably 5.0 or more, and even more preferably 7.0 or more, from the viewpoints of suppressing reactivity with carbon monoxide and side reactions, and is preferably 20.0 or less, more preferably 15.0 or less, and even more preferably 10.0 or less, from the viewpoints of economic efficiency and production efficiency.

[0024] <Reaction conditions> [Reaction temperature] In the present invention, a reaction raw material containing a m-dialkylbenzene represented by formula (1) is reacted with carbon monoxide in the presence of hydrogen fluoride and boron trifluoride. The temperature at which carbon monoxide is reacted during the reaction is, from the viewpoints of improving reactivity, suppressing side reactions, and improving the position selectivity at which a formyl group is introduced, preferably −40° C. or higher, more preferably −35° C. or higher, even more preferably −30° C. or higher, and is preferably 10° C. or lower, more preferably 5° C. or lower. Here, when the compound represented by formula (1) is m-isobutyltoluene, from the viewpoint of increasing the shielding effect and improving the position selectivity at which the formyl group is introduced, the reaction temperature is preferably −40° C. or higher, more preferably −30° C. or higher, even more preferably −5° C. or higher, and is preferably 10° C. or lower, more preferably 5° C. or lower. In addition, when the compound represented by formula (1) is m-neopentyltoluene, the neopentyl group is bulky, so the difference in shielding effect due to temperature increase is small. Therefore, the reaction temperature is preferably -30°C or higher, more preferably -15°C or higher, even more preferably -5°C or higher, and preferably 10°C or lower, more preferably 5°C or lower.

[0025] [Reaction pressure] The reaction between the reaction raw materials and carbon monoxide is preferably carried out under pressure. From the viewpoint of improving reactivity and suppressing side reactions, the pressure during the reaction is, in terms of carbon monoxide partial pressure, preferably 1.0 MPaG or more, more preferably 1.5 MPaG or more, even more preferably 1.8 MPaG or more, and is preferably 3.0 MPaG or less, more preferably 2.5 MPaG or less, even more preferably 2.2 MPaG or less.

[0026] [Reaction time] In the present invention, the reaction time is not particularly limited, but from the viewpoint of allowing the reaction to proceed sufficiently, suppressing side reactions and decomposition of the product, and producing efficiently, the reaction time is preferably 10 minutes or more, more preferably 20 minutes or more, even more preferably 30 minutes or more, and is preferably 24 hours or less, more preferably 12 hours or less, even more preferably 5 hours or less.

[0027] 〔solvent〕 The production method of the present invention may be carried out in the presence of a solvent. The solvent to be used is not particularly limited as long as it has good solubility for the reaction raw materials and is inactive against hydrogen fluoride and boron trifluoride. Examples of the solvent include saturated aliphatic hydrocarbons such as hexane, heptane, and decane, aromatic hydrocarbons such as benzene and toluene, and halogenated aliphatic hydrocarbons such as chloroform, methylene chloride, and dichloroethane. These solvents may be used alone or in combination of two or more. The amount of the solvent used is not particularly limited, and may be appropriately selected from the viewpoints of reaction uniformity, reaction rate, and solvent removal. In the present invention, since hydrogen fluoride present during the reaction also functions as a solvent, it is not necessary to use a solvent.

[0028] [Reaction format] The type of the production method of the present invention is not particularly limited, and any type of method such as a batch type, semi-batch type, or continuous type may be used. However, a continuous type is preferred from the viewpoint of the recovery and reuse of the catalyst and production efficiency. The apparatus used in the production method is a reaction apparatus capable of sufficiently mixing the liquid phase and the gas phase under pressure while controlling the temperature. For example, in a batch system, a reactor equipped with a stirrer is charged with the reaction raw materials, hydrogen fluoride, boron trifluoride, and, if necessary, a solvent, and the contents are stirred while maintaining the liquid temperature preferably between -30°C and 10°C. The pressure is then increased with carbon monoxide, preferably between 1.0 MPaG and 3.0 MPaG, and the pressure and liquid temperature are then maintained for 10 minutes to 5 hours until carbon monoxide is no longer absorbed, after which the reaction product liquid can be withdrawn and 2,4-dialkylbenzaldehyde can be obtained.

[0029] In the semi-batch system, hydrogen fluoride and boron trifluoride are charged into a reactor equipped with a stirrer, the contents are stirred, and the liquid temperature is set to preferably between -30°C and 10°C so as to keep the temperature constant, and then the pressure is increased by preferably between 1.0 MPaG and 3.0 MPaG using carbon monoxide to keep the pressure constant so that carbon monoxide can be supplied. Thereafter, reaction raw materials dissolved in a solvent are supplied as necessary, and after the end of the supply, the system is maintained for 10 minutes to 5 hours until the absorption of carbon monoxide stops, and then the reaction product liquid is withdrawn to obtain 2,4-dialkylbenzaldehyde.

[0030] In the continuous process, hydrogen fluoride and boron trifluoride are first charged into a reactor equipped with a stirrer, the contents are stirred, and the liquid temperature is set to preferably between -30°C and 10°C, and the temperature is kept constant. Then, the pressure is increased by carbon monoxide, preferably between 1.0 MPaG and 3.0 MPaG, so that carbon monoxide can be supplied to keep the pressure constant. Then, a semi-batch reaction is carried out in which the reaction raw materials dissolved in a solvent are supplied as necessary. Then, hydrogen fluoride, boron trifluoride, and the reaction raw materials dissolved in a solvent as necessary are supplied, and the reaction product liquid is continuously extracted. The residence time of the reaction liquid in the reactor is preferably between 10 minutes and 5 hours. By setting the residence time to between 10 minutes and 5 hours, 2,4-dialkylbenzaldehyde can be efficiently produced.

[0031] After removing hydrogen fluoride and boron trifluoride from the resulting reaction solution containing 2,4-dialkylbenzaldehyde, the reaction solution can be purified by a conventional method such as distillation, extraction, etc. In order to remove hydrogen fluoride from the reaction solution, the reaction solution may be neutralized and washed with water using an aqueous sodium hydroxide solution.

[0032] In the present invention, the conversion rate indicates the extent to which the m-dialkylbenzene represented by formula (1) contained in the reaction raw material has been consumed, and is represented by the following formula. Conversion rate (mol%) = {1 - (amount (moles) of m-dialkylbenzene represented by formula (1) remaining after reaction) / (amount (moles) of m-dialkylbenzene represented by formula (1) in the reaction raw material)} x 100 In the present invention, a high conversion rate can be obtained by using a specific reaction raw material and setting the molar number of boron trifluoride relative to the m-dialkylbenzene represented by formula (1) within a specific range. The conversion rate is preferably 70 mol% or more, more preferably 80 mol% or more, even more preferably 90 mol% or more, and even more preferably 95 mol% or more, and 100 mol% or less. In order to bring the conversion rate into the above range, it is preferable to appropriately adjust the reaction temperature, reaction time, carbon monoxide pressure, and the amounts of hydrogen fluoride and boron trifluoride.

[0033] [2,4-Dialkylbenzaldehyde] In the production method of the present invention, at least the (a) position in formula (1) is formylated. The following chemical formula is formula (1) with the substitution position specified for the sake of explanation. In general, when a reaction material containing m-dialkylbenzene is reacted with carbon monoxide in the presence of hydrogen fluoride and boron trifluoride, in addition to the position (a) in formula (1), R 1 The para-position (p-position) of (c) is easily formylated. 1 and R 2 The meta-position (m-position) of (b) and R 1 and R 2 Formylation at the ortho (o-) position (d) hardly proceeds at all.

[0034] [ka] (In the formula, R 1 represents an alkyl group having 1 to 3 carbon atoms, and R 2 represents a linear or cyclic alkyl group having 2 to 7 carbon atoms and a secondary or tertiary carbon at the benzyl position. 2 The number of carbon atoms in R 1 The number of carbon atoms is greater than that of the .

[0035] In the present invention, the yield (mol %) means the total amount (molar number) of dialkylbenzaldehyde obtained relative to the amount (molar number) of m-dialkylbenzene contained in the reaction raw material and represented by formula (1), and is represented by the following formula. Yield (mol %)={(total amount (moles) of dialkylbenzaldehyde obtained) / (amount (moles) of m-dialkylbenzene represented by formula (1) in the reaction raw material)}×100 Here, the total amount of dialkylbenzaldehyde obtained means the total amount of dialkylbenzaldehyde formylated at any of the above positions (a), (b), (c), and (d), and as described above, can be approximated to the total amount of 2,4-dialkylbenzaldehyde formylated at position (a) and 2,4-dialkylbenzaldehyde formylated at position (c). If a side reaction such as a disproportionation reaction (see JP-A-2005-120037) occurs, the yield decreases. In the present invention, a high yield can be obtained by using specific reaction raw materials and setting the molar number of boron trifluoride relative to the m-dialkylbenzene represented by formula (1) within a specific range. The yield is preferably 70 mol % or more, more preferably 80 mol % or more, even more preferably 90 mol % or more, and even more preferably 95 mol % or more, and 100 mol % or less. In order to achieve a yield within the above range, it is preferable to appropriately adjust the reaction temperature, reaction time, carbon monoxide pressure, and the amounts of hydrogen fluoride and boron trifluoride.

[0036] The isomer ratio (mol %) of 2,4-dialkylbenzaldehyde formylated at position (a) means the amount (mol number) of 2,4-dialkylbenzaldehyde formylated at position (a) relative to the total amount (mol number) of dialkylbenzaldehyde formylated at any of positions (a), (b), (c), and (d). As described above, the total amount (mol number) of dialkylbenzaldehyde can be approximated to the total amount (mol number) of 2,4-dialkylbenzaldehyde formylated at position (a) and 2,4-dialkylbenzaldehyde formylated at position (c). In the present invention, by using a specific reaction raw material and setting the number of moles of boron trifluoride relative to the m-dialkylbenzene represented by formula (1) within a specific range, the (a) position is formylated with high regioselectivity, and a high isomer ratio is obtained. The isomer ratio (mol %) of 2,4-dialkylbenzaldehyde formylated at the (a) position is preferably 60 mol % or more, more preferably 70 mol % or more, even more preferably 80 mol % or more, still more preferably 85 mol % or more, still more preferably 90 mol % or more, still more preferably 95 mol % or more, and 100 mol % or less. In order to set the isomer ratio within the above range, it is preferable to appropriately adjust the reaction temperature, reaction time, carbon monoxide pressure, and the amounts of hydrogen fluoride and boron trifluoride.

[0037] The yield of 2,4-dialkylbenzaldehyde in which the (a) position is formylated is calculated as follows from the above yield and the isomer ratio. Yield (mol%) of 2,4-dialkylbenzaldehyde in which the (a) position is formylated ≒ Yield (mol%) × Isomer ratio (mol%) / 100 In the present invention, by using specific reaction raw materials and setting the molar number of boron trifluoride relative to the m-dialkylbenzene represented by formula (1) within a specific range, it is possible to obtain 2,4-dialkylbenzaldehyde in which the (a) position is formylated in high yield. The yield (mol %) of the 2,4-dialkylbenzaldehyde in which the (a) position is formylated is preferably 40 mol % or more, more preferably 50 mol % or more, even more preferably 60 mol % or more, still more preferably 65 mol % or more, still more preferably 70 mol % or more, still more preferably 80 mol % or more, still more preferably 90 mol % or more, still more preferably 95 mol % or more, and is 100 mol % or less. The yield of the 2,4-dialkylbenzaldehyde in which the (a) position is formylated can be improved by improving the yield and the isomer ratio, and it is preferable to appropriately adjust the reaction temperature, reaction time, carbon monoxide pressure, the amounts of hydrogen fluoride and boron trifluoride, and the like. EXAMPLES

[0038] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

[0039] The reaction results were evaluated according to the following formula. Conversion rate (mol%) = {1-(amount of reactant remaining after reaction (moles)) / (amount of reactant charged (moles))} x 100 Yield (mol%)=(amount of 2,4-dialkylbenzaldehyde obtained (number of moles)) / (amount of reactant (number of moles))×100 In calculating the yield, the term "obtained 2,4-dialkylbenzaldehyde" refers to the mixture of 2,4-dialkylbenzaldehyde in which the position (a) in formula (1) is formylated and the R 1 The total amount of the compound (molar number) includes the 2,4-dialkylbenzaldehyde in which the p-position is formylated. Isomer ratio (mol %)=(amount (moles) of 2,4-dialkylbenzaldehyde in which the (a) position in formula (1) is formylated) / (total amount (moles) of 2,4-dialkylbenzaldehyde obtained)×100 The amount (molar number) of each substance was calculated by dividing the peak area by the molecular weight in GC analysis and taking the ratio. In addition, by multiplying the yield by the isomer ratio, the amount of substance (number of moles) of 2,4-dialkylbenzaldehyde in which the position (a) is formylated with respect to the charged amount of substance (number of moles) of the reaction raw material was determined (mol%). Yield × isomer ratio (mol%) = yield (mol%) × isomer ratio (mol%) ÷ 100

[0040] <Gas chromatography analysis (GC analysis)> Apparatus: GC-2010 Plus (manufactured by Shimadzu Corporation) Detector: FID Column: DB-1 (capillary column manufactured by Agilent) (0.32 mm φ × 30 m × 0.50 μm) Temperature rising condition: The temperature is raised from 100 °C to 310 °C at a rate of 5 °C / min and held at 310 °C for 20 minutes

[0041] <NMR spectrum analysis> Apparatus 1: Bruker Avance2 600MHz-NMR (5 mm Cryo-CPDUL Probe) (manufactured by BRUKER) Apparatus 2: JEOL JNM-AL-400 400MHz (manufactured by JEOL Ltd.) Solvent: deuterated chloroform (CDCl3) Measurement mode: 1 H, 13 C, Internal standard substance: tetramethylsilane (TMS) For the measurement of 4-isopropyl-2-methylbenzaldehyde, apparatus 1 was used, and for the measurement of 4-isobutyl-2-methylbenzaldehyde and 4-neopentyl-2-methylbenzaldehyde, apparatus 2 was used.

[0042] <Mass spectrometry (GC-MS)> Apparatus: GCMS-QP2010 Ultra (manufactured by Shimadzu Corporation) Ionization method: EI

[0043] <Example 1> A 500 mL autoclave equipped with a nack-drive stirrer, three inlet nozzles at the top and one outlet nozzle at the bottom, and with an internal temperature controllable by a jacket, was used as the formylation reactor. A coolant was passed through the jacket of the autoclave and cooled to −25° C., and 120.5 g (6.02 mol) of hydrogen fluoride was charged into the autoclave. Thereafter, while stirring and adjusting the temperature so that it did not exceed -25°C, 92.0 g (1.36 mol) of boron trifluoride was added. After adding boron trifluoride, the pressure in the autoclave was increased to 2.0 MPaG with carbon monoxide while keeping the temperature inside the autoclave at -25°C, and a mixed solution of 101.2 g (0.75 mol) of m-normal propyl toluene and 10.1 g of n-hexane was added. Note that, as the m-normal propyl toluene, normal propyl toluene having a m-normal propyl toluene content of 96.5 mass% was used, and 104.9 g of normal propyl toluene was added so that the amount of m-normal propyl toluene added was 101.2 g. After stirring for 50 minutes while maintaining a temperature of -25°C and a pressure of 2.0MPaG, the reaction mixture in the autoclave was drained into ice water. The drained liquid was shaken well and the oil layer was separated. The oil layer obtained was neutralized and washed with water, and then analyzed by gas chromatography (GC). The conversion rate of m-normal propyl toluene was 97.4 mol%, and the total yield (yield) of the two isomers, 4-normal propyl-2-methylbenzaldehyde and 2-normal propyl-4-methylbenzaldehyde, was 95.6 mol%. In addition, the amount of 4-normal propyl-2-methylbenzaldehyde (isomer ratio) relative to the total amount of 4-normal propyl-2-methylbenzaldehyde and 2-normal propyl-4-methylbenzaldehyde was 72.5 mol%.

[0044] <Examples 2 to 9 and Comparative Examples 1 to 3> 2,4-Dialkylbenzaldehyde was produced in the same manner as in Example 1, except that the reaction conditions, the types and amounts of various raw materials, catalysts, solvents, etc. used in the reaction were changed as shown in Table 1. The results are shown in Table 1.

[0045] The assignment of GC peaks was performed by GC-MS analysis (molecular weight) and NMR spectrum analysis. The structures, NMR spectra, and GC-MS analysis results of 4-isopropyl-2-methylbenzaldehyde obtained as the main product in Example 2, 4-isobutyl-2-methylbenzaldehyde obtained as the main product in Examples 3 to 6, and 4-neopentyl-2-methylbenzaldehyde obtained as the main product in Examples 7 and 8 are shown below.

[0046] [4-Isopropyl-2-methylbenzaldehyde] 1 H NMR (600 MHz, CDCl3) δ 1.26-1.27 (6H, d, J = 6.6Hz), 2.65 (3H, s), 2.89-2.96 (1H, sep, J = 6.6Hz), 7.11 (1H, s), 7.21-7.22 (1H, d, J = 7.8Hz), 7.72-7.73 (1H, d, J = 7.8Hz), 10.2 (1H, s) 13 C NMR (150 MHz, CDCl3) δ 19.8, 23.6, 34.3, 124.4, 130.0, 132.3, 132.6, 140.8, 155.3, 192.4 MS(EI):m / z (%) 51(8), 65(13), 77(15), 91(49), 105(27), 119(65), 133(37), 147(100), 162(M +· , 95)

[0047] [ka]

[0048] [4-isobutyl-2-methylbenzaldehyde] 1H NMR (400 MHz, CDCl3) δ 0.91-0.92 (6H, d, J = 6.8Hz), 1.85-1.96 (1H, m), 2.49-2.51 (2H, d, J = 7.2Hz), 2.65 (3H, s), 7.03 (1H, s), 7.12-7.14 (1H, d, J = 7.6Hz), 7.70-7.72 (1H, d, J = 7.6Hz), 10.21 (1H, s) 13 C NMR (100 MHz, CDCl3) δ 19.7, 22.4, 30.1, 45.4, 127.1, 132.2, 132.3, 132.6, 140.4, 148.3, 192.4 MS(EI):m / z (%) 43(23), 77(13), 91(37), 105(58), 134(100), 176(M +· , 77)

[0049]

change

[0050] 〔4-ネオペンチル-2-メチルベンズアルデヒド〕 1 H NMR (400 MHz, CDCl3) δ 0.92 (9H, s), 2.52 (2H, s), 2.65 (3H, s), 7.01 (1H, s), 7.11-7.13 (1H, d, J = 7.6Hz), 7.69-7.71 (1H, d, J = 7.6Hz), 10.23 (1H, s) 13 C NMR (100 MHz, CDCl3) δ 19.7, 29.5, 32.1, 50.3, 128.5, 131.8, 132.3, 133.9, 139.9, 146.4, 192.5 MS(EI):m / z (%) 57(65), 77(8), 91(26), 105(40), 134(100), 175(11), 190(M +· , 29)

[0051] [ka]

[0052] [Table 1]

[0053] According to the results in Table 1, by the production method of the present invention, m-dialkylbenzene represented by formula (1) was formylated to 2,4-dialkylbenzaldehyde in which position (a) in formula (1) was formylated with high conversion, yield, and isomer ratio. On the other hand, in Comparative Examples 1 and 2 in which the molar ratio of boron trifluoride to m-dialkylbenzene represented by formula (1) was less than 0.7, sufficient conversion and yield were not obtained, and the yield of 2,4-dialkylbenzaldehyde in which the (a) position in formula (1) was formylated was low. 2 In Comparative Example 3, in which a raw material in which is a tert-butyl group was used, the yield was low, and the yield of 2,4-dialkylbenzaldehyde in which the position (a) in formula (1) was formylated was low. [Industrial Applicability]

[0054] According to the present invention, a method for producing 2,4-dialkylbenzaldehyde excellent in conversion rate, yield, and position selectivity can be provided using a reaction raw material containing m-dialkylbenzene. The obtained 2,4-dialkylbenzaldehyde is considered to be useful as a synthetic raw material compound for fragrances and the like.

Claims

1. The method includes a step of reacting a reaction raw material containing an m-dialkylbenzene represented by formula (1) with carbon monoxide in the presence of hydrogen fluoride and boron trifluoride to formylate at least the position (a), The reaction raw material is a dialkylbenzene containing more than 90 mol% of m-dialkylbenzene represented by formula (1), the number of moles of boron trifluoride per mole of m-dialkylbenzene represented by formula (1) is 1.5 moles or more and 3.0 moles or less, The number of moles of hydrogen fluoride per mole of m-dialkylbenzene represented by formula (1) is 2.5 moles or more and 8.0 moles or less. A method for producing 2,4-dialkylbenzaldehyde. 【Chemistry 1】 (In the formula, R １ represents an alkyl group having 1 to 3 carbon atoms; R ２ represents a linear or cyclic alkyl group having 2 to 7 carbon atoms and a secondary or tertiary carbon at the benzyl position. ２ The number of carbon atoms in R １ (The number of carbon atoms is greater than that of

2. The method for producing 2,4-dialkylbenzaldehyde according to claim 1, wherein the reaction temperature is from -40°C to 10°C.

3. R １ is a methyl group or an ethyl group, and R ２ The method for producing a 2,4-dialkylbenzaldehyde according to claim 1 or 2, wherein is an ethyl group, an n-propyl group, an isopropyl group, an isobutyl group, or a neopentyl group.

4. R １ The method for producing a 2,4-dialkylbenzaldehyde according to any one of claims 1 to 3, wherein is a methyl group.

5. R １ is a methyl group, and R ２ is an isopropyl group, or R １ is a methyl group, and R ２ is an isobutyl group, or R １ is a methyl group, and R ２ The method for producing a 2,4-dialkylbenzaldehyde according to any one of claims 1 to 4, wherein is a neopentyl group.

6. The method for producing a 2,4-dialkylbenzaldehyde according to claim 1, wherein R 1 is a methyl group and R 2 is an isopropyl group, or R 1 is a methyl group and R 2 is a neopentyl group.

7. The method for producing a 2,4-dialkylbenzaldehyde according to any one of claims 1 to 6, wherein the content of 2,4-dialkylbenzaldehyde formylated at position (a) in the obtained 2,4-dialkylbenzaldehyde is 80 mol % or more.

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