JP7707811B2 - Method for producing alkylfuran carboxylate ester - Google Patents

Description

The present invention aims to provide a method for producing alkyl furane carboxylate esters. In particular, the present invention relates to a method for producing alkyl furane carboxylate esters using alkyl furane aldehyde as a starting material.

Methods for producing alkylfuran carboxylates have been investigated. For example, Non-Patent Document 1 describes the production of 5-methyl-2-furoate from 5-(chloromethyl)-2-furaldehyde (chloromethylfurfural).

ACS Sustainable Chemistry &Engineering, 7(6), 5588-5601; 2019

However, in the method described in Non-Patent Document 1, even if a sufficient amount of catalyst or base is used, the reaction may not proceed properly. That is, a new method for producing an alkylfuran carboxylate is required. In particular, a method for producing an alkylfuran carboxylate in which the reaction proceeds sufficiently even with a small amount of base is required.
The present invention aims to solve the above problems and to provide a novel method for producing alkylfuran carboxylates.

In light of the above-mentioned problems, the present inventors have conducted research and found that it is possible to sufficiently proceed with the nucleophilic reaction to produce the alkyl furane carboxylate by using an alkyl furane aldehyde, instead of chloromethyl furfural, as a starting material, reacting a nucleophilic agent (alcohol) in the presence of a catalyst, a base, and a solvent, and adjusting the amount of the catalyst to a predetermined effective amount and a predetermined molar ratio of the base/catalyst, thereby completing the present invention. Specifically, the above-mentioned problems have been solved by the following means.
<1> A method for producing an alkylfuran carboxylate, which comprises carrying out an oxidation-reduction reaction between an alkylfuranaldehyde and a compound represented by A-OH (wherein A is an organic group having 1 to 10 carbon atoms) using a base and a solvent in the presence of an N-heterocyclic carbene catalyst, wherein the amount of effective catalyst is 0.005 mol or more per mol of alkylfuranaldehyde, and the molar ratio of base/catalyst is 0.08 or more.
<2> The method for producing an alkylfuran carboxylate according to <1>, wherein the molar ratio of the base to the catalyst is 0.08 or more and 20.0 or less.
<3> The method for producing an alkyl furan carboxylate according to <1> or <2>, wherein the base includes at least one of diazabicycloundecene, sodium carbonate, sodium hydroxide, triethylamine, sodium methoxide, and potassium carbonate.
<4> The method for producing an alkylfuran carboxylate according to any one of <1> to <3>, wherein the effective amount of the catalyst is 0.01 moles or more per mole of the alkylfuran aldehyde.
<5> The method for producing an alkylfuran carboxylate according to any one of <1> to <4>, wherein the molar ratio of the base to the catalyst is 0.5 or more.
<6> The method for producing an alkylfuran carboxylate according to any one of <1> to <5>, wherein the N-heterocyclic carbene catalyst has a pKa of 33.0 or less, as calculated from the free energy of a stable structure of the catalyst molecule in methanol determined by an SMD method using Gaussian 16.
<7> The method for producing an alkylfuran carboxylate according to <6>, wherein the pKa of the N-heterocyclic carbene catalyst is 20.0 or more.
<8> The method for producing an alkylfuran carboxylate according to any one of <1> to <7>, wherein the N-heterocyclic carbene catalyst comprises at least one selected from the group consisting of triazolium, imidazolinium, imidazolium, and thiazolium.
<9> The method for producing an alkylfuran carboxylate according to any one of <1> to <8>, wherein the N-heterocyclic carbene catalyst comprises at least one catalyst represented by the following formula (C):
(In formula (C), ^R and ^R each independently represent a hydrogen atom, an alkyl group having 1 to 12 carbon atoms, an alkoxy group having 1 to 12 carbon atoms, an aryl group having 6 to 18 carbon atoms, a heteroaryl group having 4 to 16 carbon atoms, a halogenated alkyl group having 1 to 12 carbon atoms, a halogenated aryl group having 6 to 18 carbon atoms, an alkylaryl group having 7 to 20 carbon atoms, or an arylalkyl group having 7 to 20 carbon atoms. Z represents -S- or ^-NR -. X represents a methine group (= ^CR -), a nitrogen atom (=N-), or a methylene group (-CR ^- ). When X represents a methine group or a nitrogen atom _, the dashed line in the formula represents a double bond, and when X represents a methylene group, the dashed line in the formula represents a single bond. In the formula, ^R , ^R and R ^C6 is independently a hydrogen atom, an alkyl group having 1 to 12 carbon atoms, an alkenyl group having 2 to 12 carbon atoms, an alkynyl group having 2 to 12 carbon atoms, an aryl group having 6 to 18 carbon atoms, an alkoxy group having 1 to 12 carbon atoms, an acyl group having 2 to 12 carbon atoms, a hydroxyl group, a carboxyl group, or a halogen atom. Y ^- represents a counter anion. R ^C2 and R ^C3 , R ^C2 and R ^C5 , and R ^C2 and R ^C6 may be bonded to each other or condensed to form a ring.
<10> The method for producing an alkylfuran carboxylate according to <9>, wherein the catalyst represented by formula (C) includes at least one catalyst represented by formula (C4).
(In formula (C4), R ¹³ represents a group having the same meaning as R ^C1 . R ²³ represents a group having the same meaning as R ^C2 . R ³³ represents a group having the same meaning as R ^C3 . Y ⁻ represents a counter anion . R ²³ and R ³³ may be bonded to each other or condensed to form a ring . )
<11> The method for producing an alkylfuran carboxylate according to any one of <1> to <10>, wherein the alkylfuran aldehyde is a compound represented by formula (F1).
(In formula (F1), R is an alkyl group having 1 to 10 carbon atoms.)
<12> The method for producing an alkylfuran carboxylate according to any one of <1> to <11>, wherein the alkylfuran carboxylate is a compound represented by formula (F2):
(In formula (F2), R is an alkyl group having 1 to 10 carbon atoms, and A is an organic group having 1 to 10 carbon atoms.)
<13> The method for producing an alkyl furan carboxylate according to any one of <1> to <12>, wherein in the compound represented by A-OH, A is an alkyl group having 1 to 5 carbon atoms.

This invention makes it possible to provide a new method for producing alkylfuran carboxylate esters.

Hereinafter, an embodiment of the present invention (hereinafter, simply referred to as the present embodiment) will be described in detail. Note that the present embodiment is an example for explaining the present invention, and the present invention is not limited to the present embodiment.
In this specification, the word "to" is used to mean that the numerical values before and after it are included as the lower limit and upper limit.
In this specification, various physical properties and characteristic values are those at 23° C. unless otherwise specified.
In the description of groups (atomic groups) in this specification, the notation that does not indicate whether it is substituted or unsubstituted includes both groups (atomic groups) that have no substituents and groups (atomic groups) that have substituents. For example, "alkyl group" includes not only alkyl groups that have no substituents (unsubstituted alkyl groups), but also alkyl groups that have substituents (substituted alkyl groups). In this specification, the notation that does not indicate whether it is substituted or unsubstituted is preferably unsubstituted.
In cases where the standards shown in this specification differ depending on the year and the measurement methods, etc., they will be based on the standards as of January 1, 2021, unless otherwise specified.

The method for producing an alkylfuran carboxylate of the present embodiment involves carrying out an oxidation-reduction reaction between an alkylfuranaldehyde and a compound represented by A-OH (wherein A is an organic group having 1 to 10 carbon atoms) using a base and a solvent in the presence of an N-heterocyclic carbene catalyst, and is characterized in that the effective amount of the catalyst is 0.005 mol or more relative to the alkylfuranaldehyde, and the molar ratio of base/catalyst is 0.08 or more.
By adopting such a configuration, an oxidation-reduction reaction between the alkylfuran aldehyde and the compound represented by A-OH (wherein A is an organic group having 1 to 10 carbon atoms) can be effectively promoted, and an alkylfuran carboxylate can be produced in high yield.

In the production method of this embodiment, the alkyl furan aldehyde is a substrate for the oxidation-reduction reaction, and the alkyl furan aldehyde is usually added to the reaction system. However, the alkyl furan aldehyde may also be an intermediate for producing an alkyl furan carboxylate ester.

The number of carbon atoms in the alkyl group having 1 to 10 carbon atoms in the alkyl furan aldehyde is preferably 8 or less, more preferably 6 or less, even more preferably 5 or less, even more preferably 4 or less, even more preferably 3 or less, may be 2 or less, or may even be 1.

The molecular weight of the alkylfuran aldehyde is preferably 111 to 500, and more preferably 111 to 300.

The alkylfuran aldehyde is preferably a compound represented by formula (F1).
(In formula (F1), R is an alkyl group having 1 to 10 carbon atoms.)

The number of carbon atoms in the alkyl group of R is preferably 8 or less, more preferably 6 or less, even more preferably 5 or less, still more preferably 4 or less, and even more preferably 3 or less, and may be 2 or less, or may be 1.
Specific examples of R include a methyl group, an ethyl group, an isopropyl group, an n-propyl group, an isobutyl group, an n-butyl group, and a tert-butyl group. Of these, a methyl group, an ethyl group, and an isopropyl group are preferred, and a methyl group is more preferred.

In this embodiment, only one type of alkyl furan aldehyde may be used, or two or more types may be used.

The target product of the manufacturing method of this embodiment is an alkyl furan carboxylate. Usually, the alkyl furan carboxylate (product mixture) produced from the reaction system is taken out and, if necessary, separated from the catalyst and impurities (by-products) are removed. However, the alkyl furan carboxylate may be an intermediate for producing another compound. That is, further reactions may be allowed to proceed in the same reaction system.

The alkyl group of the alkylfuran carboxylate (the alkyl group corresponding to R in formula (F2)) is the same as the alkyl group of the alkylfuran aldehyde (the alkyl group corresponding to R in formula (F1)).
The alkyl furan carboxylate is preferably a compound represented by formula (F2).
(In formula (F2), R is an alkyl group having 1 to 10 carbon atoms, and A is an organic group having 1 to 10 carbon atoms.)
R has the same meaning as R in formula (F1), and A has the same meaning as A in the compound represented by A-OH.

In the production method of this embodiment, an oxidation-reduction reaction is carried out between an alkylfuranaldehyde and a compound represented by A-OH (wherein A is an organic group having 1 to 10 carbon atoms). That is, the compound represented by A-OH acts as a nucleophile that nucleophiles the formyl group of the alkylfuranaldehyde.
The organic group having 1 to 10 carbon atoms, which is A in A-OH, is preferably a hydrocarbon group having 1 to 10 carbon atoms, or a group formed by a combination of a hydrocarbon group having 1 to 10 carbon atoms and -O- and/or -C(=O)-, more preferably an alkyl group having 1 to 10 carbon atoms, or a group formed by a combination of an alkyl group having 1 to 10 carbon atoms and -O- and/or -C(=O)-, and is preferably an alkyl group having 1 to 10 carbon atoms.
The number of carbon atoms in A is preferably 8 or less, more preferably 6 or less, even more preferably 5 or less, still more preferably 4 or less, and even more preferably 3 or less, and may be 2 or less, or may be 1.
The hydrocarbon group represented by A is preferably a linear, branched or cyclic alkyl group or an aryl group, and more preferably a linear alkyl group (primary alcohol). By using a primary alcohol, the reactivity is improved and the yield tends to be higher.
The molecular weight of the compound represented by A-OH is preferably 32 or more, and is preferably 500 or less, more preferably 300 or less, even more preferably 200 or less, and even more preferably 100 or less.

Examples of the compound represented by A-OH include methanol, ethanol, isopropanol, isobutanol, n-propanol, n-butanol, and the compounds shown below.

In this embodiment, the compound represented by A-OH may be the same substance as the solvent, the details of which will be described later. For example, there is a case in which both the compound represented by A-OH and the solvent are methanol.

In the oxidation-reduction reaction, the amount of the compound represented by A-OH (nucleophile) relative to 1 mole of the substrate is preferably 1 mole or more, more preferably more than 1 mole, even more preferably 1.5 moles or more, and even more preferably 2.5 moles or more. The amount of the compound represented by A-OH (nucleophile) relative to 1 mole of the substrate is preferably 20 moles or less, more preferably 10 moles or less, even more preferably 8 moles or less, even more preferably 5 moles or less, and even more preferably 4 moles or less.
In the oxidation-reduction reaction of the present embodiment, the compound represented by A-OH may be used alone or in combination of two or more. When two or more types are used, it is preferable that the total amount is in the above range.
When the compound represented by A-OH is used as a solvent, the amount of the compound to be added is in the same preferred range as the amount of the solvent to be added.

In the production method of this embodiment, the oxidation-reduction reaction is carried out in the presence of an N-heterocyclic carbene catalyst. By using an N-heterocyclic carbene catalyst, the reaction proceeds more effectively.
The N-heterocyclic carbene catalyst is not particularly limited as long as it is partially or completely soluble in a solvent (reaction solvent), and it is preferable that 90% by mass or more, further 95% by mass or more, particularly 99% by mass or more, and more particularly 100% by mass of the N-heterocyclic carbene catalyst is soluble in the solvent at the reaction temperature.
The N-heterocyclic carbene catalyst preferably has a pKa of 33.0 or less, calculated from the free energy by determining a stable structure of the catalyst molecule in methanol using a solvation model density (SMD) with Gaussian 16 (hereinafter, sometimes simply referred to as the "pKa of the N-heterocyclic carbene catalyst").
More specifically, the pKa of the N-heterocyclic carbene catalyst was calculated by using the software Gaussian16 and performing structural optimization calculations of the gas-state molecule under the conditions of B3LYP/6-31+G(d). Vibration calculations were performed on the obtained structure, and it was confirmed that it was a stable structure without imaginary vibrations. When determining the stable structure, the conformation before and after acid dissociation was made the same except for the presence or absence of hydrogen. The free energy at 298.15 K of the molecule in the gas state and in the solvent was calculated by one-point calculation using M06-2X/6-311++G(d,p). At this time, SMD was adopted as the solvation model to take into account the solvent effect. Methanol was used as the solvent. The dissolution free energy of protons was adopted as "-255.6 kcal/mol". From the free energy of each state calculated using this method, the free energy difference ΔGsoln before and after acid dissociation was calculated, and the pKa was calculated.
By using the N-heterocyclic carbene catalyst obtained by the above method, the conversion rate of the alkylfuran aldehyde can be increased, and the reaction rate (reaction cycle) of the reaction system can be increased.

The pKa of the N-heterocyclic carbene catalyst is preferably 32.0 or less, more preferably 31.5 or less, and further preferably 31.0 or less, 30.5 or less, 30.0 or less, 29.5 or less, 29.0 or less, 28.5 or less, 28.0 or less, 27.5 or less, 27.0 or less, 26.5 or less, 26.0 or less, 25.5 or less, and 25.0 or less in this order. By making it equal to or less than the upper limit, the yield of the obtained alkyl furan carboxylate is further improved. Furthermore, the pKa of the N-heterocyclic carbene catalyst is preferably 15.0 or more, more preferably 16.0 or more, and further preferably 17.0 or more, 17.5 or more, 18.0 or more, 18.5 or more, 19.0 or more, 19.5 or more, 20.0 or more, 20.5 or more, 21.0 or more, 21.5 or more, 22.0 or more, 22.5 or more, and 23.0 or more in this order.
In the oxidation-reduction reaction of the present embodiment, only one type of N-heterocyclic carbene catalyst may be used, or two or more types may be used. When two or more types are used, each of the N-heterocyclic carbene catalysts satisfies the above-mentioned preferred range.

The N-heterocyclic carbene catalyst causes the reaction to proceed in the presence of a base.
The N-heterocyclic carbene catalyst preferably comprises at least one selected from the group consisting of triazolium, imidazolinium, imidazolium and thiazolium, more preferably comprises at least one selected from the group consisting of triazolium, imidazolinium and imidazolium, even more preferably comprises at least one selected from the group consisting of triazolium and imidazolinium, and even more preferably comprises at least one triazolium.

More specifically, the N-heterocyclic carbene catalyst preferably contains at least one catalyst represented by the following formula (C):
(In formula (C), ^R and ^R each independently represent a hydrogen atom, an alkyl group having 1 to 12 carbon atoms, an alkoxy group having 1 to 12 carbon atoms, an aryl group having 6 to 18 carbon atoms, a heteroaryl group having 4 to 16 carbon atoms, a halogenated alkyl group having 1 to 12 carbon atoms, a halogenated aryl group having 6 to 18 carbon atoms, an alkylaryl group having 7 to 20 carbon atoms, or an arylalkyl group having 7 to 20 carbon atoms. Z represents -S- or ^-NR -. X represents a methine group (= ^CR -), a nitrogen atom (=N-), or a methylene group (-CR ^- ). When X represents a methine group or a nitrogen atom _, the dashed line in the formula represents a double bond, and when X represents a methylene group, the dashed line in the formula represents a single bond. In the formula, ^R , ^R and R ^C6 is each independently a hydrogen atom, an alkyl group having 1 to 12 carbon atoms, an alkenyl group having 2 to 12 carbon atoms, an alkynyl group having 2 to 12 carbon atoms, an aryl group having 6 to 18 carbon atoms, an alkoxy group having 1 to 12 carbon atoms, an acyl group having 2 to 12 carbon atoms, a hydroxyl ^group , a carboxyl ^group , or a halogen atom. Y ^- represents a counter anion. R and ^R , ^{R and R} , R and ^R , ^R and ^R , R and ^R may be bonded to each other or condensed to form a ring.
The two R ^C6s contained in the methylene group (-CR ^C6 ₂ -) may be the same or different. Hereinafter, when two or more groups with the same symbol are present in one compound, the two or more groups with the same symbol may be the same or different.

In this embodiment, the alkyl group is intended to include cycloalkyl groups in addition to linear and branched alkyl groups. Additionally, the alkylaryl group and arylalkyl group are intended to include groups in which a cyclic alkyl and an aryl (e.g., a benzene ring) are condensed.

R ^C1 and R ^C2 each independently represent a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 12 carbon atoms, an aryl group having 6 to 12 carbon atoms, a halogenated alkyl group having 1 to 6 carbon atoms, a halogenated aryl group having 6 to 12 carbon atoms, an alkylaryl group having 7 to 13 carbon atoms, or an arylalkyl group having 7 to 13 carbon atoms. The halogen atom contained in the halogenated alkyl group and the halogenated aryl group is preferably a fluorine atom or a chlorine atom.

R ^C3 , R ^C5 and R ^C6 are each independently preferably a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 6 carbon atoms, an alkynyl group having 2 to 6 carbon atoms, an aryl group having 6 to 12 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, an acyl group having 2 to 7 carbon atoms, a hydroxy group, a carboxy group, or a halogen atom, more preferably a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, or an aryl group having 6 to 12 carbon atoms, even more preferably a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, and still more preferably a hydrogen atom.

There are no particular limitations on the monovalent anion, but Y ⁻ is preferably an anion containing a halogen, and more preferably F ⁻ , Cl ⁻ , Br ⁻ , I ⁻ or BF ₄ ⁻ .

When the catalyst represented by the above formula (C) has a methine group at X, it is preferably represented by the following formula (C2).
(In formula (C2), R ¹¹ represents a group having the same meaning as R ^C1 . R ²¹ represents a group having the same meaning as R ^C2 . R ³¹ represents a group having the same meaning as R ^C3 . R ⁵¹ represents a group having the same meaning as R ^C5 . Y ⁻ represents a counter anion. R ²¹ and R ³¹ , R ²¹ and R ⁵¹ , and R ¹¹ and R ⁵¹ may be bonded to each other or condensed to form a ring.)

R ¹¹ and R ³¹ each independently preferably represent an alkyl group having 1 to 12 carbon atoms, and more preferably an alkyl group having 1 to 6 carbon atoms.
R ²¹ and R ⁵¹ are preferably hydrogen atoms.

When the catalyst represented by the above formula (C) has a methylene group at X, it is preferably represented by the following formula (C3).
(In formula (C3), R ¹² represents a group having the same meaning as R ^C1 . R ²² represents a group having the same meaning as R ^C2 . R ³² represents a group having the same meaning as R ^C3 . R ⁶² represents a group having the same meaning as R ^C6 . Y ⁻ represents a counter anion. R ²² and R ³² , R ²² and R ⁶² , and R ¹² and R ⁶² may be bonded to each other or condensed to form a ring.)

R ¹² and R ³² are each preferably an alkyl group having 1 to 12 carbon atoms, an aryl group having 6 to 18 carbon atoms, or an arylalkyl group having 7 to 20 carbon atoms.
R ²² and R ⁶² are preferably hydrogen atoms.

When the catalyst represented by the above formula (C) has a nitrogen atom in X, it is preferably represented by the following formula (C4).
(In formula (C4), R ¹³ represents a group having the same meaning as R ^C1 . R ²³ represents a group having the same meaning as R ^C2 . R ³³ represents a group having the same meaning as R ^C3 . Y ⁻ represents a counter anion . R ²³ and R ³³ may be bonded to each other or condensed to form a ring . )

R ¹³ and R ³³ each independently represent preferably an alkyl group having 1 to 12 carbon atoms, more preferably an alkyl group having 1 to 5 carbon atoms, even more preferably an alkyl group having 1 to 3 carbon atoms, and still more preferably a methyl group.
^R23 is preferably a hydrogen atom.

When the catalyst represented by the above formula (C4) forms a ring together with R ²³ and R ³³ , it is preferably represented by the following formula (C5).
(In formula (C5), R ¹⁴ represents a group having the same meaning as R ^C1 . R ⁷⁴ , R ⁸⁴ , and R ⁹⁴ each independently represent a group having the same meaning as R ^C2 . ^{Y −} represents a counter anion.)

R ¹⁴ is preferably a halogenated aryl group having 6 to 18 carbon atoms or an alkylaryl group having 7 to 20 carbon atoms.
R ⁷⁴ , R ⁸⁴ and R ⁹⁴ are preferably hydrogen atoms.

When the catalyst represented by the above formula (C) has a sulfur atom in Z, it is preferably represented by the following formula (C4).
(In formula (C6), R ¹⁵ represents a group having the same meaning as R ^C1 . R ²⁵ represents a group having the same meaning as R ^C2 . R ⁵⁵ represents a group having the same meaning as R ^C5 . Y ⁻ represents a counter anion. R ¹⁵ and R ⁵⁵ , and R ⁵⁵ and R ²⁵ may be bonded to each other or condensed to form a ring.)

In this embodiment, the catalyst represented by formula (C4) is particularly preferred.

Examples of the catalyst include the following compounds. It is needless to say that the present embodiment is not limited to these.

In the redox reaction, the amount of the N-heterocyclic carbene catalyst relative to 1 mole of the substrate is preferably 0.0001 moles or more, more preferably 0.001 moles or more, even more preferably 0.01 moles or more, even more preferably 0.05 moles or more, even more preferably 0.1 moles or more, and even more preferably 0.2 moles or more. By setting the amount to be equal to or more than the lower limit, the redox reaction tends to proceed more effectively. The amount of the catalyst relative to 1 mole of the substrate is preferably 5.0 moles or less, more preferably 3.0 moles or less, even more preferably 1.0 moles or less, even more preferably 0.5 moles or less, and even more preferably 0.4 moles or less.
In the oxidation-reduction reaction of the present embodiment, the N-heterocyclic carbene catalyst may be used alone or in combination of two or more. When two or more types are used, the total amount is preferably within the above range.

In the production method of this embodiment, the oxidation-reduction reaction is carried out in the presence of a base, which increases the yield of the alkyl furan carboxylate.
The base may be an organic base or an inorganic base. Examples of the base include alkylamines, alkanolamines, polyamines, hydroxylamine, cyclic amines, quaternary ammonium, alkali metal-containing compounds, and alkaline earth metal-containing compounds. Of these, alkylamines, polyamines, cyclic amines, and alkali metal-containing compounds are preferred, diazabicycloundecene, sodium carbonate, sodium hydroxide, triethylamine, sodium methoxide, and potassium carbonate are more preferred, and the base preferably contains at least one of diazabicycloundecene, sodium carbonate, and potassium carbonate, more preferably contains diazabicycloundecene and/or sodium carbonate, and even more preferably contains diazabicycloundecene.

In this embodiment, the effective catalyst amount is 0.005 moles or more. The effective catalyst amount means the smaller number of moles of the amount of catalyst and the amount of base added per mole of substrate. It is presumed that the base and catalyst actually contribute to the redox reaction within this range of amounts. The effective catalyst amount is preferably 0.01 moles or more, more preferably 0.02 moles or more, even more preferably 0.04 moles or more, even more preferably 0.1 moles or more, and even more preferably 0.2 moles or more per mole of alkylfuran aldehyde. By setting the amount to the lower limit or more, the yield of alkylfuran carboxylate tends to be improved. The upper limit of the effective catalyst amount is not particularly determined, but from the viewpoint of saving the amount of base and catalyst, it is more preferably 1.0 moles or less, more preferably 0.8 moles or less, and even more preferably 0.5 moles or less.

In this embodiment, the molar ratio of base/catalyst is 0.08 or more. By setting such a mass ratio, the yield of the alkyl furan carboxylate can be increased. The molar ratio of base/catalyst is preferably 0.1 or more, more preferably 0.3 or more, even more preferably 0.5 or more, and even more preferably 0.8 or more. The molar ratio of base/catalyst is also preferably 20.0 or less, more preferably 10.0 or less, even more preferably 8.0 or less, even more preferably 4.0 or less, even more preferably 3.0 or less, and even more preferably 2.0 or less. In this embodiment, even if the molar ratio of base/catalyst is 4.0 or less, further 3.0 or less, and particularly 2.0 or less, a high yield can be achieved and the amount of base used can be reduced.

In the production method of this embodiment, it is preferable to further carry out the oxidation-reduction reaction in the presence of an oxidizing agent. By using an oxidizing agent, the progress of side reactions can be more effectively suppressed.
The type of the oxidizing agent is not particularly limited, and may be an organic compound or an inorganic compound.
The amount of the oxidizing agent can be appropriately determined depending on the type of the oxidizing agent, but for example, the amount of the oxidizing agent per mole of the substrate is preferably 0.01 mole or more and 20.0 moles or less.
In the oxidation-reduction reaction of the present embodiment, only one oxidizing agent may be used, or two or more oxidizing agents may be used. When two or more oxidizing agents are used, the total amount is preferably within the above range.

In the present embodiment, when the oxidizing agent is an organic compound, examples of the oxidizing agent include hypervalent organic iodine compounds such as quinone, nitrobenzene, and 2-iodobenzoic acid, nitroxy radical compounds such as 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), and organic peroxides such as m-chlorobenzoic acid, and quinone is preferable. Here, quinone refers to a compound in which two hydrogen atoms bonded to the benzene ring of an aromatic hydrocarbon are each replaced with an oxygen atom.
In addition, oxidizing agents described in Oxidizing Agents for Organic Synthesis, Third Edition, published by Fujifilm Wako Pure Chemical Industries, Ltd., the contents of which are incorporated herein by reference, may also be used.

The molecular weight of the quinone as an oxidizing agent is preferably 108 or more, and is preferably 1000 or less, more preferably 800 or less, and may be 600 or less.

The oxidizing agent preferably contains at least one oxidizing agent represented by formula (O).
(In formula (O), R ¹ to R ⁸ each independently represent a hydrogen atom, an alkyl group having 1 to 12 carbon atoms, an alkenyl group having 2 to 12 carbon atoms, an alkynyl group having 2 to 12 carbon atoms, an alkoxy group having 1 to 12 carbon atoms, an aryl group having 6 to 18 carbon atoms, an acyl group having 2 to 12 carbon atoms, or a hydroxy group. When ^{R 1} to R ⁸ are an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, an aryl group, or an acyl group, each of R ¹ to R ⁸ may have, as a substituent bonded to a carbon atom in the formula, an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, a hydroxy group, a halogen atom, a cyano group, or a nitro group. m is 1 or 0. R ¹ and R ² , R ³ and R ⁴ , R ⁵ and R ⁶ , and R ⁷ and R ⁸ may each be bonded to each other or condensed to form a ring.)

It is preferable that R ¹ to R ⁸ are each independently a hydrogen atom, an alkyl group having 1 to 12 carbon atoms, or an alkoxy group having 1 to 12 carbon atoms, more preferably each independently a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, or an alkoxy group having 1 to 8 carbon atoms, and further preferably each independently a hydrogen atom or an alkyl group having 1 to 6 carbon atoms.

An example of the formula (O) in which m is 0 and R ¹ and R ² , and R ³ and R ⁴ are condensed with each other to form a 6-membered ring is the following formula (O-1).
(In formula (O-1), R ¹⁰¹ to R ¹⁰⁸ each independently represent a group having the same meaning as R ¹ in formula (O).)

R ¹⁰¹ to R ¹⁰⁸ each independently represent a group having the same meaning as R ¹ above, and are preferably a hydrogen atom or an alkyl group having 1 to 6 carbon atoms.

An example of the formula (O) in which m is 1 and ^R1 and ^R2 , ^R3 and ^R4 , ^R5 and ^R6 , and ^R7 and ^R8 are each condensed with each other to form a 6-membered ring is the following formula (O-2).
(In formula (O-2), R ²⁰¹ to R ²⁰⁴ each independently represent a group having the same meaning as R ¹ in formula (O).)

R ²⁰¹ to R ²⁰⁴ each independently represent a group having the same meaning as R ¹ above, and are preferably a hydrogen atom. n1, n2, n3, and n4 each independently represent an integer of 1 to 4.

An example of formula (O) in which m is 1 and ^R1 and ^R2 , ^R3 and ^R4 , ^R5 and ^R6 , and ^R7 and ^R8 are not condensed with each other to form a ring is formula (O-3) below.
(In formula (O-3), R ³⁰¹ to R ³⁰⁸ each independently represent a group having the same meaning as R ¹ in formula (O).)

R ³⁰¹ to R ³⁰⁸ each independently represent a group having the same meaning as R ¹ above, preferably a hydrogen atom or an alkyl group having 1 to 12 carbon atoms, more preferably a hydrogen atom or an alkyl group having 1 to 8 carbon atoms.

An example of the formula (O) in which m is 0 and R ¹ and R ² , and R ³ and R ⁴ are not condensed with each other to form a ring is the following formula (O-4).
(In formula (O-4), R ⁴⁰¹ to R ⁴⁰⁴ each independently represent a group having the same meaning as R ¹ in formula (O).)
R ⁴⁰¹ to R ⁴⁰⁴ each independently represent a group having the same meaning as R ¹ above, and are preferably a hydrogen atom, an alkyl group having 1 to 12 carbon atoms, or an alkoxy group having 1 to 12 carbon atoms, more preferably a hydrogen atom or an alkyl group having 1 to 12 carbon atoms, and even more preferably a hydrogen atom or an alkyl group having 1 to 8 carbon atoms. When R ⁴⁰¹ to R ⁴⁰⁴ are an alkyl group or an alkoxy group, the alkyl group or alkoxy group may have a halogen atom as a substituent bonded to a carbon atom in the formula.

In this embodiment, formula (O-1), formula (O-3) and formula (O-4) are preferred, formula (O-3) and (O-4) are more preferred, and formula (O-3) is even more preferred.

Examples of the oxidizing agent include the following compounds. It goes without saying that the present embodiment is not limited to these. Here, tBu is a tert-butyl group.

In the oxidation-reduction reaction, the amount of quinone relative to 1 mole of substrate is preferably 0.01 moles or more, more preferably 0.05 moles or more, even more preferably 0.1 moles or more, even more preferably 0.5 moles or more, and even more preferably 0.8 moles or more. By making it equal to or more than the lower limit, the yield of alkylfuran carboxylate tends to be improved. In addition, the amount of oxidizing agent relative to 1 mole of substrate may be 3.0 moles or less, 2.5 moles or less, 2.0 moles or less, 1.5 moles or less, or 1.2 moles or less.
In the oxidation-reduction reaction of the present embodiment, only one quinone may be used, or two or more quinones may be used. When two or more quinones are used, the total amount is preferably within the above range.

In this embodiment, when the oxidizing agent is an inorganic compound, examples include permanganates such as potassium permanganate; chromates such as potassium dichromate and chromium oxide; nitric acids such as nitric acid and potassium nitrate; halogens such as fluorine, chlorine, bromine, and iodine; peroxides such as hydrogen peroxide and sodium peroxide; oxides such as copper (II) oxide, lead (IV) oxide, and manganese (IV) oxide; and metal salts such as iron chloride and copper sulfate. Oxides are preferred, and manganese oxide is more preferred.

In the oxidation-reduction reaction, the amount of the inorganic compound as an oxidizing agent relative to 1 mole of the substrate is preferably 1.00 moles or more, more preferably 3.00 moles or more, and even more preferably 5.00 moles or more, and is preferably 20.0 moles or less, more preferably 15.0 moles or less, and even more preferably 10.0 moles or less.
In the oxidation-reduction reaction of the present embodiment, only one type of inorganic compound may be used as the oxidizing agent, or two or more types may be used. When two or more types are used, the total amount is preferably within the above range.

In the production method of this embodiment, the oxidation-reduction reaction is preferably carried out in the presence of a solvent.
The solvent is not particularly limited as long as it can dissolve a part or all of the alkylfuranaldehyde and does not interfere with the oxidation-reduction reaction.
Examples of the solvent used in the production method of the present embodiment include aromatic hydrocarbon solvents, aliphatic hydrocarbon solvents, amide solvents, ether solvents, alcohol solvents, halogen solvents, and ester solvents. Of these, aromatic hydrocarbon solvents, ether solvents, and alcohol solvents are preferred, and ether solvents and sulfoxide solvents are more preferred.

Specific examples of aromatic hydrocarbon solvents include benzene and toluene.
Specific examples of the amide solvent include acetonitrile, N,N-dimethylacetamide, and N,N-dimethylformamide.
Specific examples of the ether solvent include tetrahydrofuran (hereinafter also referred to as THF) and diethyl ether.
Specific examples of the alcohol solvent include methanol, ethanol, isopropanol, etc. The alcohol solvent can also be a nucleophile.
Specific examples of halogen solvents include dichloromethane, dichloroethane, and chloroform.
A specific example of the ester solvent is ethyl acetate.
Specific examples of sulfoxide solvents include dimethyl sulfoxide and the like.

In the oxidation-reduction reaction, the amount of the solvent used is not particularly limited, but from the viewpoints of productivity and energy efficiency, it is preferably 0.5 times by mass or more, more preferably 0.8 times by mass or more, and even more preferably 1.0 times by mass or more relative to the substrate (alkylfuranaldehyde). In addition, the amount of the solvent used is preferably 200 times by mass or less, more preferably 100 times by mass or less, even more preferably 50 times by mass or less, and even more preferably 30 times by mass or less relative to the substrate.
In the oxidation-reduction reaction, the solvent may be used alone or in combination of two or more. When two or more solvents are used, the total amount is preferably within the above range.

The reaction temperature of the oxidation-reduction reaction in the production method of this embodiment is not particularly limited, but is preferably −80° C. or higher, more preferably 0° C. or higher, even more preferably 15° C. or higher, still more preferably 20° C. or higher, and even more preferably 25° C. or higher. In addition, the reaction temperature of the oxidation-reduction reaction is preferably 200° C. or lower, more preferably 150° C. or lower, even more preferably 100° C. or lower, still more preferably 50° C. or lower, and even more preferably 40° C. or lower.
In the manufacturing method of this embodiment, the reaction temperature may be the same except for the initial temperature rise and the final temperature fall (however, a variation of ±5°C is considered to be an error), or the reaction may be carried out in two or more stages. In this embodiment, it is preferable that the reaction temperature is the same except for the initial temperature rise and the final temperature fall (however, a variation of ±5°C is considered to be an error).

The reaction time of the oxidation-reduction reaction in the manufacturing method of this embodiment is preferably 1 minute or more, may be 30 minutes or more, may be 1 hour or more, or may be 1.5 hours or more. The reaction time of the oxidation-reduction reaction is preferably 50 hours or less, may be 30 hours or less, or may be 25 hours or less.

After the reaction, the reaction mixture and the catalyst can be separated by a general method such as settling, centrifugation, or filtration. Depending on the catalyst used, the catalyst is preferably separated under an inert gas atmosphere such as nitrogen or argon to prevent ignition. The reaction mixture may be purified by appropriately post-treating the reaction mixture after concentrating the resulting reaction solution as necessary and using the residue as it is as a raw material or intermediate. Specific methods for post-treatment include known purification methods such as extraction, distillation, and chromatography. Two or more of these purification methods may be combined.

In the manufacturing method of this embodiment, the higher the conversion rate of the raw material, the better, and it is preferably 50 mol% or more, and more preferably 80 mol% or more. The upper limit is ideally 100 mol%.

In the manufacturing method of this embodiment, the higher the yield of alkylfuran carboxylate, the better; it is preferably 3% or more, more preferably 10% or more, and even more preferably 30% or more. The upper limit is ideally 100 mol%.

In the manufacturing method of this embodiment, salts are not usually produced as by-products. Therefore, the resulting alkyl furoate esters are preferably used for various applications. In particular, the alkyl furoate esters obtained by the manufacturing method of this embodiment are preferably used as various industrial materials or raw materials thereof.

The present invention will be described in more detail below with reference to examples. The materials, amounts, ratios, processing contents, processing procedures, etc. shown in the following examples can be appropriately changed without departing from the spirit of the present invention. Therefore, the scope of the present invention is not limited to the specific examples shown below.
If the measuring instruments used in the examples are difficult to obtain due to discontinuation or the like, measurements can be made using other instruments with equivalent performance.

Raw material <substrate>
MFF: Methylfurfural, Fujifilm Wako Pure Chemical Industries, 133-11771
CMF: chloromethylfurfural, Toronto Research Chemicals Inc., product number C369220
PrFF: Isopropylfurfural, manufactured by Matrix Scientific, 14497-27-9
<Solvent>
Methanol: Fujifilm Wako Pure Chemical Industries, 137-01823
Toluene: Fujifilm Wako Pure Chemical Industries, 204-01866
THF: Tetrahydrofuran, Fujifilm Wako Pure Chemical Industries, 206-00483
<Base>
_Na2CO3 : Fujifilm Wako Pure Chemical Industries, _199-01585
DBU: Diazabicycloundecene, manufactured by Tokyo Chemical Industry Co., Ltd., D1270
TEA: Fujifilm Wako Pure Chemical Industries, 208-02643
NaOH: Fujifilm Wako Pure Chemical Industries, 194-18865
NaOMe: Tokyo Chemical Industry Co., Ltd., S0485
_K2CO3 : Fujifilm Wako Pure Chemical Industries, _162-03495
<Nucleophiles>
Methanol: Fujifilm Wako Pure Chemical Industries, 137-01823
PrOH: normal propyl alcohol, manufactured by Tokyo Chemical Industry Co., Ltd., P0491

<Catalyst>
Cat-1: Sigma-Aldrich, 708607-1G, Tokyo Chemical Industry Co., Ltd., D3962
The stable structure of the catalyst molecule in methanol was determined by the SMD method using Gaussian 16, and the pKa calculated from the free energy was 24.1.

Example 1
<Production of methyl furoate>
0.11 g (1 mmol) of MFF, 1 g of methanol, 0.07 g (0.3 eq, 0.3 mmol) of Cat-1, and 0.031 g (0.3 eq, 0.3 mmol) of sodium carbonate were added to a 25 mL flask in this order. The mixture was stirred at 30°C for 20 hours. After the reaction was completed, the mixture was analyzed by GC and quantified by the absolute calibration curve method. The GC analysis was performed under the following conditions.
Equipment: Shimadzu GC-2014
Column HP-5 (60m x 0.25mm, film thickness: 0.25μm)
Carrier gas: Helium, 1 mL/min constant flow
Oven 50°C (5min hold) - at 20°C/min - 320°C (15min hold)
Injection port: 320°C, Split (20:1), septum purge flow rate: 3 mL/min
Injection volume 1μL
The amount of the nucleophile indicates the total amount of methanol as the nucleophile when methanol is used as the solvent.

Examples 2 to 14, Comparative Examples 1 to 7
The procedure of Example 1 was repeated except for the changes shown in Tables 1 to 3. The results are shown in Tables 1 to 3.

In the above Tables 1 to 3, base/cat indicates the molar ratio of base/catalyst.
In the production method of the present invention, alkylfuran carboxylates were obtained in high yields (Examples 1 to 10). In contrast, when the effective catalyst amount was less than 0.005 moles (Comparative Examples 1, 2, 4, and 7), the yields were low. Also, when the base/catalyst molar ratio was less than 0.08 (Comparative Examples 1 to 4 and 7), the yields were low. Furthermore, when the substrate was CMF (Comparative Examples 5 and 6), the yields were low.
Furthermore, as is clear from a comparison of Examples 1 to 3 and a comparison of Examples 4 to 7, by setting the base/catalyst molar ratio to 5.0 or less, or even 3.0 or less, a higher yield could be achieved and the amount of base used could be reduced.

Claims (13)

A method for producing an alkylfuran carboxylate, comprising carrying out an oxidation-reduction reaction between an alkylfuran aldehyde and a compound represented by A-OH (wherein A is an organic group having 1 to 10 carbon atoms) in the presence of an N-heterocyclic carbene catalyst, using a base and a solvent, the method comprising the steps of:
The effective amount of catalyst is 0.005 moles or more per mole of alkylfuran aldehyde;
A process for producing an alkylfuran carboxylate, wherein the molar ratio of base to catalyst is 0.08 or more. The method for producing an alkylfuran carboxylate according to claim 1, wherein the molar ratio of the base to the catalyst is 0.08 or more and 20.0 or less. The method for producing an alkyl furoate ester according to claim 1 or 2, wherein the base comprises at least one of diazabicycloundecene, sodium carbonate, sodium hydroxide, triethylamine, sodium methoxide, and potassium carbonate. The method for producing an alkylfuran carboxylate according to any one of claims 1 to 3, wherein the effective amount of catalyst is 0.01 moles or more per mole of alkylfuran aldehyde. The method for producing an alkylfuran carboxylate according to any one of claims 1 to 4, wherein the base/catalyst molar ratio is 0.5 or more. The method for producing an alkylfuran carboxylate according to any one of claims 1 to 5, wherein the N-heterocyclic carbene catalyst has a pKa of 33.0 or less, calculated from the free energy of the stable structure of the catalyst molecule in methanol by the SMD method using Gaussian 16. The method for producing alkylfuran carboxylate esters according to claim 6, wherein the pKa of the N-heterocyclic carbene catalyst is 20.0 or more. The method for producing an alkylfuran carboxylate according to any one of claims 1 to 7, wherein the N-heterocyclic carbene catalyst comprises at least one selected from the group consisting of triazolium, imidazolinium, imidazolium and thiazolium. The method for producing an alkylfuran carboxylate according to any one of claims 1 to 8, wherein the N-heterocyclic carbene catalyst comprises at least one catalyst represented by the following formula (C):
(In formula (C), ^R and ^R each independently represent a hydrogen atom, an alkyl group having 1 to 12 carbon atoms, an alkoxy group having 1 to 12 carbon atoms, an aryl group having 6 to 18 carbon atoms, a heteroaryl group having 4 to 16 carbon atoms, a halogenated alkyl group having 1 to 12 carbon atoms, a halogenated aryl group having 6 to 18 carbon atoms, an alkylaryl group having 7 to 20 carbon atoms, or an arylalkyl group having 7 to 20 carbon atoms. Z represents -S- or ^-NR -. X represents a methine group (= ^CR -), a nitrogen atom (=N-), or a methylene group (-CR ^- ). When X represents a methine group or a nitrogen atom _, the dashed line in the formula represents a double bond, and when X represents a methylene group, the dashed line in the formula represents a single bond. In the formula, ^R , ^R and R ^C6 is independently a hydrogen atom, an alkyl group having 1 to 12 carbon atoms, an alkenyl group having 2 to 12 carbon atoms, an alkynyl group having 2 to 12 carbon atoms, an aryl group having 6 to 18 carbon atoms, an alkoxy group having 1 to 12 carbon atoms, an acyl group having 2 to 12 carbon atoms, a hydroxyl group, a carboxyl group, or a halogen atom. Y ^- represents a counter anion. R ^C2 and R ^C3 , R ^C2 and R ^C5 , and R ^C2 and R ^C6 may be bonded to each other or condensed to form a ring. The method for producing an alkyl furan carboxylate according to claim 9, wherein the catalyst represented by formula (C) comprises at least one catalyst represented by formula (C4).
(In formula (C4), R ¹³ represents a group having the same meaning as R ^C1 . R ²³ represents a group having the same meaning as R ^C2 . R ³³ represents a group having the same meaning as R ^C3 . Y ⁻ represents a counter anion . R ²³ and R ³³ may be bonded to each other or condensed to form a ring . ) The method for producing an alkylfuran carboxylate according to any one of claims 1 to 10, wherein the alkylfuran aldehyde is a compound represented by formula (F1).
(In formula (F1), R is an alkyl group having 1 to 10 carbon atoms.) The method for producing an alkylfuran carboxylate according to any one of claims 1 to 11, wherein the alkylfuran carboxylate is a compound represented by formula (F2).
(In formula (F2), R is an alkyl group having 1 to 10 carbon atoms, and A is an organic group having 1 to 10 carbon atoms.) The method for producing an alkylfuran carboxylate according to any one of claims 1 to 12, wherein in the compound represented by A-OH, A is an alkyl group having 1 to 5 carbon atoms.