JP2010209002A - Method for producing 3-furaldehyde derivative - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for industrially efficiently producing 3-furaldehyde derivative from an easily available raw material. <P>SOLUTION: The method for producing the 3-furaldehyde derivative represented by formula (4) (wherein, R<SP>1</SP>is hydrogen or an organic group; and R<SP>2</SP>is hydrogen or an organic group) includes reacting an aldehyde with a carbonyl compound represented by formula (3) (wherein, R<SP>2</SP>is the same as the above; and R<SP>3</SP>and R<SP>4</SP>are the same or different, and each hydrogen or hydrocarbon) or an equivalent thereof. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a method for producing 3-furaldehyde derivatives, and more particularly to a method for producing a 3-furaldehyde derivative by reacting an aldehyde or its equivalent with a carbonyl compound or its equivalent. The 3-furaldehyde derivatives are useful as fine chemicals such as dyes, pharmaceuticals, physiologically active substances, polymer raw materials, synthetic intermediates of high-functional materials, and intermediate raw materials of other organic chemicals.

  Conventionally, as a method for producing a furan compound, a method in which a 1,4-dicarbonyl compound is used as a starting material and cyclized and dehydrated in the presence of an acid catalyst is known (see Non-Patent Document 1). However, this method is difficult to obtain raw materials, is not a versatile technique, and is not an industrially efficient method for producing furan compounds. In particular, there are few known methods for industrially efficiently producing 3-furaldehyde derivatives from readily available raw materials.

Chem, Lett. , 1983, 1007

  An object of the present invention is to provide a method capable of industrially efficiently producing a 3-furaldehyde derivative from readily available raw materials.

  As a result of intensive studies to achieve the above object, the present inventors have reacted aldehyde or an equivalent thereof with a carbonyl compound or an equivalent thereof, whereby the cyclization reaction by the coupling proceeds smoothly, and this is dealt with. The inventors have found that a 3-furaldehyde derivative can be obtained in a good yield and completed the present invention.

（式中、Ｒ¹は水素原子又は有機基を示す）
で表されるアルデヒド又はその等価体と、下記式（２）

（式中、Ｒ²は水素原子又は有機基を示す）
で表されるアルデヒド若しくはその等価体又は下記式（３）

（式中、Ｒ²は水素原子又は有機基を示し、Ｒ³、Ｒ⁴は、同一又は異なって水素原子又は炭化水素基を示す。Ｒ³、Ｒ⁴は、互いに結合して、隣接する２つの酸素原子及び炭素原子とともに環を形成していてもよい）
で表されるカルボニル化合物若しくはその等価体とを反応させて、下記式（４）

（式中、Ｒ¹、Ｒ²は前記に同じ）
で表される３−フラアルデヒド誘導体を得ることを特徴とする３−フラアルデヒド誘導体の製造法を提供する。 That is, the present invention provides the following formula (1):

(Wherein R ¹ represents a hydrogen atom or an organic group)
Or an equivalent thereof, and the following formula (2)

(Wherein R ² represents a hydrogen atom or an organic group)
Or an equivalent thereof, or the following formula (3)

(In the formula, R ² represents a hydrogen atom or an organic group, and R ³ and R ⁴ are the same or different and represent a hydrogen atom or a hydrocarbon group. R ³ and R ⁴ are bonded to each other and adjacent to each other. May form a ring with two oxygen and carbon atoms)
Is reacted with a carbonyl compound represented by the following formula (4):

(Wherein R ¹ and R ² are the same as above)
The 3-furaldehyde derivative represented by these is obtained, The manufacturing method of the 3-furaldehyde derivative characterized by the above-mentioned is provided.

（式中、Ｒ²は水素原子又は有機基を示す）
で表される３−フラアルデヒド誘導体を得てもよい。 In this production method, an aldehyde represented by the formula (2) or an equivalent thereof is used as the aldehyde represented by the formula (1) or an equivalent thereof, and the following formula (4a)

(Wherein, R ² represents a hydrogen atom or an organic group)
You may obtain 3-furaldehyde derivative represented by these.

The reaction may be performed in the presence of a palladium compound catalyst (A). Further, in addition to the palladium compound catalyst (A), an oxo further containing a heteropolyacid or a salt thereof (B1) or, as a whole, an element of P or Si and at least one element selected from V, Mo and W The reaction can also be carried out in the presence of a promoter (B) comprising a mixture of acids or salts (B2). As the heteropolyacid or its salt (B1), those containing P or Si element and at least one element selected from V, Mo and W as constituent elements can be preferably used. In addition, as the heteropolyacid or a salt thereof (B1), the following formula
A _{3 + n} [PMo _12-n V _n O ₄₀ ]
(In the formula, A represents at least one selected from a hydrogen atom, NH ₄ , an alkali metal and an alkaline earth metal, and n is an integer of 0 to 10)
Or phosphomolybdic acid or a salt thereof represented by

  In the above production method, it is also preferable to carry out the reaction in the presence of a Lewis acid (C) in addition to the palladium compound catalyst (A).

  According to the method of the present invention, a 3-furaldehyde derivative can be industrially efficiently produced from a readily available raw material under mild conditions.

[Reaction components]
In the present invention, the aldehyde represented by the formula (1) or an equivalent thereof, the aldehyde represented by the formula (2) or an equivalent thereof, or the carbonyl compound represented by the formula (3) or an equivalent thereof. And react. When the aldehyde represented by the formula (2) or an equivalent thereof is used as the reaction partner of the aldehyde represented by the formula (1) or an equivalent thereof, the carbonyl compound represented by the formula (3) or an equivalent thereof The same product is obtained when the isomer is used, because the aldehyde represented by the formula (2) or its equivalent is equivalent to the carbonyl compound represented by the formula (3) in the course of the reaction. This is thought to be through the body. The aldehyde represented by formula (1) or its equivalent and the carbonyl compound represented by formula (3) or its equivalent form a furan ring by cyclization by coupling.

In formula (1), R ¹ represents a hydrogen atom or an organic group. In formula (2), R ² represents a hydrogen atom or an organic group. In Formula (3), R ² represents a hydrogen atom or an organic group as described above, and R ³ and R ⁴ are the same or different and represent a hydrogen atom or a hydrocarbon group. R ^3, R ⁴ are bonded to each other, may form a ring with the adjacent two oxygen atoms and carbon atoms.

The organic group in R ¹ and R ² may be any group that does not impair the reaction. For example, a hydrocarbon group, a heterocyclic group, a substituted oxy group, an N-substituted amino group, an acyl group, and this carbonyl group Examples include a protector, a substituted oxycarbonyl group, a carboxyl group, a substituted or unsubstituted carbamoyl group, a cyano group, a substituted or unsubstituted iminoalkyl group, a sulfur acid ester group, and a group in which a plurality of these are bonded. The carboxyl group and the like may be protected with a conventional protecting group. Although carbon number of an organic group is not specifically limited, For example, it is 1-20, Preferably it is about 1-10.

  The hydrocarbon group includes an aliphatic hydrocarbon group, an alicyclic hydrocarbon group, and an aromatic hydrocarbon group. Examples of the aliphatic hydrocarbon group include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, pentyl, hexyl, octyl, decyl, tetradecyl, hexadecyl, octadecyl, vinyl, allyl, 1- A linear or branched aliphatic hydrocarbon group (alkyl group, alkenyl group, and alkynyl group) having about 1 to 20 carbon atoms (preferably 1 to 10, more preferably 1 to 6) such as propenyl and ethynyl groups. Etc.

  Examples of the alicyclic hydrocarbon group include 3 to 20 carbon atoms (preferably 3 to 15 carbon atoms) such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, cyclooctyl, cyclodecyl, cyclododecyl, adamantyl and norbornyl groups. ) Alicyclic hydrocarbon groups (cycloalkyl groups, cycloalkenyl groups, bridged cyclic hydrocarbon groups, etc.).

  Examples of the aromatic hydrocarbon group include aromatic hydrocarbon groups having about 6 to 20 carbon atoms such as phenyl and naphthyl groups.

  These hydrocarbon groups may be protected by various substituents such as halogen atoms (fluorine, chlorine, bromine, iodine atoms), oxo groups, hydroxyl groups which may be protected with protecting groups, and protecting groups. A good hydroxymethyl group, an amino group which may be protected with a protecting group, a carboxyl group which may be protected with a protecting group, a substituted oxycarbonyl group, a substituted or unsubstituted carbamoyl group, a nitro group, an acyl group, a cyano group, It may have a heterocyclic group or the like. As the protecting group, a protecting group commonly used in the field of organic synthesis can be used.

Among the organic groups, the heterocyclic ring constituting the heterocyclic group includes an aromatic heterocyclic ring and a non-aromatic heterocyclic ring. As such a heterocyclic ring, for example, a heterocyclic ring containing an oxygen atom as a hetero atom (for example, 5-membered ring such as furan, tetrahydrofuran, oxazole, isoxazole, 4-oxo-4H-pyran, tetrahydropyran, morpholine, etc. 6-membered ring, condensed ring such as benzofuran, isobenzofuran, 4-oxo-4H-chromene, chromane, isochroman, etc.), heterocycle containing a sulfur atom as a hetero atom (for example, 5 such as thiophene, thiazole, isothiazole, thiadiazole, etc.) 5-membered rings, 6-membered rings such as 4-oxo-4H-thiopyran, condensed rings such as benzothiophene, etc.) and heterocycles containing nitrogen atoms as heteroatoms (eg, pyrrole, pyrrolidine, pyrazole, imidazole, triazole, etc.) Ring, pyridine, pyridazine, pyrimi Emissions, pyrazine, piperidine, 6-membered ring such as piperazine, indole, indoline, quinoline, acridine, naphthyridine, quinazoline, other condensed rings purine) and the like. These heterocyclic groups include substituents [for example, the same groups as the substituents that the hydrocarbon group may have, alkyl groups (for example, C _1-4 alkyl groups such as methyl and ethyl groups, etc.) , A cycloalkyl group, an aryl group (eg, phenyl, naphthyl group, etc.)].

  Among the organic groups, examples of the substituted oxy group include alkoxy groups such as methoxy, ethoxy, propoxy, and butoxy groups (such as alkoxy groups having about 1 to 10 carbon atoms); aryloxy groups such as phenoxy and naphthyloxy groups; benzyl Aralkyloxy groups such as oxy groups; Cycloalkyloxy groups such as cyclohexyloxy groups; Acyloxy groups such as acetoxy, propionyloxy, butyryloxy, (meth) acryloyloxy, cyclohexanecarbonyloxy, benzoyloxy groups (having about 1 to 10 carbon atoms) Acyloxy group, etc.). N-substituted amino groups include, for example, N, N-dimethylamino, N, N-diethylamino, piperidino groups and the like.

  Examples of the acyl group include aliphatic, alicyclic, aromatic or heterocyclic acyl such as formyl, acetyl, propionyl, butyryl, (meth) acryloyl, cyclopentanecarbonyl, cyclohexanecarbonyl, benzoyl, naphthoyl, and pyridylcarbonyl groups. Group (acyl group having about 1 to 10 carbon atoms). Examples of the carbonyl protected form of the acyl group include acetal forms such as dimethyl acetal, diethyl acetal, 1,3-dioxane and 1,3-dioxolane; and dithioacetal forms such as S, S′-dimethyldithioacetal.

  Examples of the substituted oxycarbonyl group include alkoxycarbonyl groups such as methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, and butoxycarbonyl groups; alkenyloxycarbonyl groups such as vinyloxycarbonyl groups; cyclopentyloxycarbonyl, cyclohexyloxycarbonyl groups and the like. Alkyloxycarbonyl; aryloxycarbonyl group such as phenoxycarbonyl group; aralkyloxycarbonyl group such as benzyloxycarbonyl group; heterocyclic-oxycarbonyl group such as pyridyloxycarbonyl group; acyloxycarbonyl group (acid anhydride group) and the like It is done.

  Examples of the substituted or unsubstituted carbamoyl group include carbamoyl, N-methylcarbamoyl, N-phenylcarbamoyl, N, N-dimethylcarbamoyl, 1-pyrrolidinylcarbonyl, piperidinocarbonyl group and the like. Sulfuric acid ester groups include sulfonic acid ester groups such as methyl sulfonate and ethyl sulfonate groups, and sulfinic acid ester groups such as methyl sulfinate and ethyl sulfinate groups.

Preferred R ^1, R ^2, a hydrogen atom, a hydrocarbon may have a substituent hydrogen group [for example, (particularly C _1-10 aliphatic hydrocarbon group) C _1-20 aliphatic hydrocarbon group, C _6-20 aromatic hydrocarbon group (phenyl group, naphthyl group, etc.), C _3-20 alicyclic hydrocarbon group (about 3-8 membered cycloalkyl group, bridged cyclic hydrocarbon group, etc.), haloalkyl A group (for example, a C _1-6 haloalkyl group such as a trifluoromethyl group, particularly a C _1-4 haloalkyl group), a heterocyclic group, a substituted oxy group (C _1-10 alkoxy group, aryloxy group, aralkyloxy group) Group, cycloalkyloxy group, C _1-10 acyloxy group, etc.), acyl group, carbonyl protector of acyl group, substituted oxycarbonyl group (for example, C _1-6 alkoxy-carbonyl group, aryloxycarbonyl group, aralkyloxycarbonyl) Base Such cycloalkyloxy group), a carboxyl group, a substituted or unsubstituted carbamoyl group, a cyano group, and the like sulfur acid ester groups.

Examples of the hydrocarbon group in R ³ and R ⁴ include an aliphatic hydrocarbon group, an alicyclic hydrocarbon group, an aromatic hydrocarbon group, and a group in which two or more of these are bonded. Examples of the aliphatic hydrocarbon group include 1 to C carbon atoms such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, pentyl, hexyl, vinyl, allyl, 1-propenyl, and ethynyl group. Examples include about 20 (preferably 1 to 10, more preferably 1 to 6) linear or branched aliphatic hydrocarbon groups (alkyl group, alkenyl group, and alkynyl group). Examples of the alicyclic hydrocarbon group include alicyclic hydrocarbon groups having about 3 to 20 carbon atoms (preferably 3 to 15 carbon atoms) such as cyclopentyl and cyclohexyl groups (cycloalkyl groups, cycloalkenyl groups, bridges). Cyclic hydrocarbon groups, etc.). Examples of the aromatic hydrocarbon group include aromatic hydrocarbon groups having about 6 to 20 carbon atoms such as phenyl and naphthyl groups. Examples of the group in which an aliphatic hydrocarbon group and an aromatic hydrocarbon group are bonded include an aralkyl group such as a benzyl group. These hydrocarbon groups may be protected by various substituents such as halogen atoms (fluorine, chlorine, bromine, iodine atoms), oxo groups, hydroxyl groups which may be protected with protecting groups, and protecting groups. A good hydroxymethyl group, an amino group which may be protected with a protecting group, a carboxyl group which may be protected with a protecting group, a substituted oxycarbonyl group, a substituted or unsubstituted carbamoyl group, a nitro group, an acyl group, a cyano group, It may have a heterocyclic group or the like. As the protecting group, a protecting group commonly used in the field of organic synthesis can be used.

Examples of the ring formed by combining R ³ and R ⁴ together with two adjacent oxygen and carbon atoms include a 1,3-dioxolane ring and a 1,3-dioxane ring.

  Representative examples of the aldehyde represented by the formula (1) include, for example, acetaldehyde, propionaldehyde, butyraldehyde, isobutyraldehyde, amyl aldehyde (valeraldehyde), isoamyl aldehyde, hexanal, heptanal, octanal, nonanal, decanal, and dodecanal. And phenylacetaldehyde. The equivalent of the aldehyde represented by the formula (1) includes a compound that gives the same reaction product as the aldehyde represented by the formula (1), for example, a multimer such as paraaldehyde (acetaldehyde trimer), formyl Derivatives (eg, acetal, hemiacetal, etc.) whose group is protected with a protecting group (eg, a protective group that forms acetal or hemiacetal), etc.

  Typical examples of the aldehyde represented by the formula (2) include propionaldehyde, butyraldehyde, amylaldehyde (valeraldehyde), hexanal, heptanal, octanal, nonanal, decanal, dodecanal and the like. An equivalent of the aldehyde represented by the formula (2) is a compound that gives the same reaction product as the aldehyde represented by the formula (2), for example, a formyl group is a protecting group (a protecting group that forms an acetal or a hemiacetal). Etc.) and the like (acetal, hemiacetal, etc.) and the like.

  As typical examples of the carbonyl compound represented by the formula (3), for example, 3,3-dimethoxypropionaldehyde; 3,4-dimethoxy-2-butanone, 3,4-diethoxy-2-butanone and the like Compounds in which formyl group of oxobutyraldehyde is acetal protected; compounds in which formyl group of 3-oxoamylaldehyde such as 5,5-dimethoxy-3-pentanone, 5,5-diethoxy-3-pentanone is acetal protected; 6 1,6-dimethoxy-4-hexanone, 6,6-diethoxy-4-hexanone and the like, a compound in which the formyl group of 3-oxohexanol is acetal protected; 1-oxo-1-phenyl-3,3-dimethoxypropane, 1 3-oxo-3-phenylpropionates such as oxo-1-phenyl-3,3-diethoxypropane Formyl group dehydrogenase is like acetal protected compound. An equivalent of the carbonyl compound represented by the formula (3) is a compound that gives the same reaction product as the carbonyl compound represented by the formula (3), for example, a carbonyl group is a protecting group (a protecting group that forms an acetal, etc. ) -Protected derivatives.

[catalyst]
The method of the present invention does not necessarily require a catalyst, but it is preferable to use a catalyst to accelerate the reaction. As the catalyst, for example, a catalyst (such as a platinum group metal compound catalyst) used in an oxidation reaction can be used, and among them, a palladium compound catalyst (A) is preferable.

  Examples of the palladium compound catalyst (A) include metal palladium (single), zero-valent palladium compounds such as zero-valent palladium complexes; and organic divalent palladium such as palladium acetate (II) and palladium (II) cyanide. Acid salts, organic complexes of divalent palladium such as dichlorobis (benzonitrile) palladium (II), palladium fluoride (II), palladium chloride (II), palladium bromide (II), palladium iodide (II), etc. Divalent palladium halides, divalent palladium oxyacid salts such as palladium (II) nitrate, palladium (II) sulfate, palladium (II) oxide, palladium (II) sulfide, palladium (II) selenide, water Divalent palladium compounds such as inorganic complexes of divalent palladium such as palladium oxide (II) and tetraammine palladium (II) chloride Can be illustrated.

  Among these palladium compounds, divalent palladium organic acid salts or organic complexes such as palladium (II) acetate and palladium (II) acetylacetonate, divalent palladium halides such as palladium (II) chloride, Divalent palladium compounds such as divalent palladium oxyacid salts such as palladium (II) sulfate are preferred.

  The palladium compound may be used in a form supported on a support such as activated carbon, silica, alumina, zeolite. Moreover, as a palladium compound, it can also be used with the form which incorporated palladium as a structural element of natural minerals, such as a hydrotalcite and a hydroxyapatite. A palladium compound can be used individually or in combination of 2 or more types.

  The amount of the palladium compound used is, for example, 0.00001 to 0.6 mol, preferably 0.001 to 0.5 mol, more preferably 0.05 to 1 mol of the compound used in a small amount among the raw material components. About 0.3 mol.

[Cocatalyst]
In the present invention, a cocatalyst can be used together with the catalyst. For example, when a palladium compound catalyst (A) is used as a catalyst, together with the palladium compound catalyst (A), a heteropolyacid or a salt thereof (B1), or, as a whole, an element of P or Si, and V, Mo and W A promoter (B) comprising a mixture (B2) of an oxo acid or a salt thereof containing at least one element selected from the above may be used. By using the cocatalyst (B), the reaction rate and the yield of the target compound are increased.

  In the heteropolyacid or its salt (B1), the heteropolyacid is a condensate of oxygen acids containing two or more different types of central ions, and is also referred to as a heteronuclear condensed acid. Heteropolyacids include, for example, oxygen acid ions of elements such as P, As, Sn, Si, Ti, and Zr (for example, phosphoric acid and silicic acid) and oxygen acid ions of elements such as V, Mo, and W (for example, , Vanadic acid, molybdic acid, tungstic acid, etc.), and various heteropolyacids are possible by combinations thereof.

  The heteroatom of the oxygen acid that constitutes the heteropolyacid is not particularly limited. For example, Cu, Be, B, Al, C, Si, Ge, Sn, Ti, Zr, Ce, Th, N, P, As, Sb, Examples thereof include V, Nb, Ta, Cr, Mo, W, U, Se, Te, Mn, I, Fe, Co, Ni, Rh, Os, Ir, and Pt. A preferred heteropolyacid contains at least one element of P, Si, V, Mo, and W, more preferably P or Si, and at least one element of V, Mo, and W (particularly, V and Mo). Containing.

The heteropoly acid or heteropoly acid anion constituting the salt can be used those of various compositions, but the composition of the preferred heteropolyacid anion can be expressed by XM ₁₂ O _40. In this composition formula, X is an element such as Si or P, and M is an element such as Mo, W, or V. Examples of the heteropolyacid anion having such a composition include anions of phosphomolybdic acid, phosphotungstic acid, silicomolybdic acid, silicotungstic acid, and phosphovanadomolybdic acid.

The heteropolyacid may be a free heteropolyacid, and may be used as a salt of the heteropolyacid by substituting at least a part of hydrogen atoms corresponding to the cation of the heteropolyacid with another cation. Examples of the cation capable of substituting for the hydrogen atom include ammonium (such as NH ₄ ), alkali metal (such as Cs, Rb, K, Na, and Li), alkaline earth metal (such as Ba, Sr, Ca, and Mg), and the like. Can be illustrated.

Among the heteropolyacids or salts thereof, phosphovanadomolybdic acid or phosphomolybdic acid represented by the following formula or a salt thereof is preferably used.
A _{3 + n} [PMo _12-n V _n O ₄₀ ]
[Wherein, A represents a heteropolyacid cation, and n is an integer of 0 to 10 (preferably 1 to 10)]

Examples of the cation represented by A include the above-mentioned cation in addition to a hydrogen atom. Of these, complete proton type phosphovanadomolybdic acid or phosphomolybdic acid, and phosphovanadomolybdate or ammonium phosphomolybdate in which some or all of the protons are substituted with NH ₄ are particularly preferable. In this case, n is usually 0 to 4 (preferably 1 to 4). Examples of the complete proton type phosphovanadmolybdic acid include H ₄ PMo ₁₁ VO ₄₀ , H ₅ PMo ₁₀ V ₂ O ₄₀ , H ₆ PMo ₉ V ₃ O ₄₀ , and H ₇ PMo ₈ V ₄ O ₄₀ .

  The heteropolyacid or salt thereof may be an anhydride or a crystal water-containing material. Moreover, you may use heteropoly acid or its salt with the form carry | supported to support | carriers, such as activated carbon. In this case, the heteropolyacid or salt thereof and the palladium compound may be dispersed and supported on the same carrier. Heteropolyacid and its salt can be used individually or in combination of 2 or more types.

  The mixture of oxoacids or salts thereof (B2) is particularly preferably a mixture of oxoacids or salts thereof containing P or Si element and at least one element selected from V, Mo and W as a whole. It is not limited. In the present specification, the term “oxo acid” is used to mean including a heteropoly acid, and the term “oxo acid” in the narrow sense is used to mean that the heteropoly acid is not included.

  Examples of the heteropolyacid containing P, Si, V, Mo, or W include phosphomolybdic acid, phosphotungstic acid, phosphovanadic acid, phosphovanadmolybdic acid, silicomolybdic acid, silicotungstic acid, and cayvanadic acid. Examples of the narrowly-defined oxo acid containing P, Si, V, Mo, or W include phosphoric acid, silicic acid, vanadic acid, molybdic acid, and tungstic acid. Examples of the heteropolyacid salt and the narrowly-defined oxoacid salt include ammonium salts, alkali metal salts, and alkaline earth metal salts.

  As an embodiment of the mixture of oxo acids or salts thereof (B2), (i) a mixture of two or more heteropolyacids or salts thereof (for example, a mixture of phosphomolybdic acid or a salt thereof and phosphobananadic acid or a salt thereof) (Ii) a mixture of a heteropolyacid or a salt thereof and a narrowly-defined oxo acid or a salt thereof (for example, a mixture of phosphomolybdic acid or a salt thereof and vanadic acid or a salt thereof, And (iii) a mixture of two or more narrowly defined oxo acids or salts thereof (for example, a mixture of phosphoric acid or a salt thereof and molybdic acid or a salt thereof and vanadic acid or a salt thereof). It is done. The oxo acid or salt thereof may be an anhydride or a crystal water-containing product.

In the case of a heteropolyacid or a salt thereof (B1), the ratio of each element can be adjusted to the above range by mixing two or more heteropolyacids or salts thereof having different compositions. For example, two or more kinds of phosphovanadomolybdic acid represented by the formula A _{3 + n} [PMo _12-n V _n O ₄₀ ] or a salt thereof (n = 1 to 10) having different compositions may be mixed, A phosphomolybdic acid represented by A _{3 + n} [PMo _{12 -n} V _n O ₄₀ ] or a salt thereof (n = 1 to 10), and a phosphomolybdic acid represented by the formula A ₃ PMo ₁₂ O ₄₀ or a salt thereof A catalyst in which the ratio of each element falls within the above range can be prepared by mixing with a salt.

  Although the usage-amount of a cocatalyst (B) is not specifically limited, For example, 0.00001-0.5 mol, Preferably it is 0.0001-0.1 with respect to 1 mol of the compound used in a small amount among raw material components. Mole, more preferably about 0.001 to 0.05 mole.

  When the palladium compound catalyst (A) is used, a Lewis acid (C) may be used together with the palladium compound catalyst (A) or together with the palladium compound catalyst (A) and the cocatalyst (B). By using the Lewis acid (C), the reaction rate and the yield of the target compound are increased.

  As Lewis acid (C), it does not specifically limit, For example, the compound containing a periodic table 3 group, 4 group, 12 group, 13 group, 14 group or 15 group element is mentioned. A Lewis acid can be used individually or in combination of 2 or more types. The Group 3 elements of the periodic table include scandium; yttrium; lanthanoids such as lanthanum, cerium, praseodymium, neodymium, samarium, gadolinium, ytterbium; and actinides such as actinium and thorium. The periodic table group 4 elements include titanium, zirconium, hafnium, and the like. The periodic table group 12 elements include zinc and cadmium. Periodic table group 13 elements include boron, aluminum, gallium, indium, and thallium. The group 14 element of the periodic table includes silicon, germanium, tin, lead and the like. The group 15 element of the periodic table includes antimony, bismuth and the like. Examples of compounds containing these elements include halides (fluorides, chlorides, bromides, iodides) and triflates (trifluoromethanesulfonate) of these elements.

Representative examples of Lewis acids include cerium chloride (CeCl ₃ ), gadolinium chloride (GdCl ₃ ), ytterbium triflate [Yb (OTf) ₃ ], samarium triflate [Sm (OTf) ₃ ], gadolinium triflate [Gd (OTf) ₃ ] halides or triflates of Group 3 elements of the periodic table; halides or triflates of Group 4 elements of the periodic table such as zirconium chloride (ZrCl ₂ ); halides of Group 8 elements of the periodic table such as iron chloride (FeCl ₃ ) Or a triflate; a halide or triflate of a Group 12 element such as zinc chloride (ZnCl ₂ ); a halide or triflate of a Group 13 element such as indium chloride (InCl ₃ ) or indium bromide (InBr ₃ ); tin (SnCl ₂₎ Ha of the periodic table group 14 elements such as Gen product or triflate; and halides or triflates of the periodic table group 15 elements such as bismuth chloride are exemplified. Among these, a halide or triflate of a group 3 element (particularly cerium) of the periodic table is particularly preferable. Also, iron chloride is preferable because it is inexpensive and easily available.

  The amount of the Lewis acid used is, for example, 0.00001 to 0.6 mol, preferably 0.001 to 0.5 mol, and more preferably 0. It is about 05-0.3 mol.

  In the method of the present invention, in addition to the above-described catalyst, a compound having a coordination property to palladium (coordinating compound) is added to the reaction system in order to increase the reaction rate or improve the selectivity of the reaction. May be.

[reaction]
The reaction is carried out in the presence or absence of a solvent, preferably in the presence of a solvent. The solvent can be appropriately selected depending on the type of raw material. Examples of the solvent include organic acids such as carboxylic acids such as acetic acid, propionic acid and trifluoroacetic acid; amides such as formamide, acetamide, dimethylformamide (DMF) and dimethylacetamide; nitro compounds such as nitromethane and nitroethane; ethyl acetate; Esters such as butyl acetate; Ketones such as acetone and methyl ethyl ketone; Chain or cyclic ethers such as diethyl ether, diisopropyl ether, dimethoxyethane, tetrahydrofuran, and dioxane; methanol, ethanol, propanol, butanol, t-butyl alcohol, etc. Alcohols; aliphatic hydrocarbons such as hexane and octane; alicyclic hydrocarbons such as cyclopentane, cyclohexane, and methylcyclohexane; chloroform, dichloromethane, di Water; Roroetan, halogenated hydrocarbons such as carbon tetrachloride and mixtures of these solvents. Among these solvents, a protic solvent containing an oxygen atom (for example, a solvent having a structure of —OH), more specifically, an alcohol such as methanol and ethanol; a carboxylic acid such as acetic acid and propionic acid, and the like An organic acid of; a mixed solution thereof is preferred.

  The ratio of the aldehyde represented by the formula (1) or its equivalent to the aldehyde represented by the formula (2) or its equivalent or the carbonyl compound represented by the formula (3) or its equivalent is Although it can select suitably according to the kind, combination, etc. of a compound, from the point of reactivity etc., usually the former [The aldehyde represented by Formula (1) or its equivalent] / The latter [Formula (2) Aldehyde or equivalent thereof, or carbonyl compound represented by formula (3) or equivalent thereof] (molar ratio) = about 0.8 to 50, preferably about 1.5 to 30, more preferably about 2 to 20. is there.

[oxygen]
The method of the present invention does not necessarily require oxygen, but it is preferable to use oxygen. As oxygen, molecular oxygen is preferably used. The molecular oxygen is not particularly limited, and pure oxygen may be used, or oxygen or air diluted with an inert gas such as nitrogen, helium, or argon may be used. Oxygen can function as a reoxidant for catalysts (such as palladium compounds).

The amount of oxygen used (as O ₂ ) is usually 0.5 mol or more (for example, 1 mol or more), preferably 1 to 100 mol, more preferably 1 mol of the compound to be used in a small amount among the raw material components. It is about 1-50 mol. A large excess of oxygen may be used.

  In the method of the present invention, the reaction proceeds smoothly even under relatively mild conditions. Although reaction temperature can be suitably selected according to the kind etc. of raw material compound, it is 0-200 degreeC normally, Preferably it is 10-150 degreeC, More preferably, it is about 20-120 degreeC. The reaction may be performed at normal pressure or under pressure. The reaction can be carried out by a conventional method such as batch, semi-batch or continuous, preferably in the presence or flow of oxygen. The order of addition of reaction components, catalysts, etc. is not particularly limited. For example, an aldehyde represented by the formula (1) or an equivalent thereof in a mixed solution containing a catalyst (including a cocatalyst and a Lewis acid if necessary) And an aldehyde represented by the formula (2) or an equivalent thereof, or a mixed solution containing a carbonyl compound represented by the formula (3) or an equivalent thereof, a catalyst and the formula (2) An aldehyde represented by the formula (1) in a mixed solution (including a cocatalyst and a Lewis acid as necessary) containing an aldehyde or an equivalent thereof or a carbonyl compound represented by the formula (3) or an equivalent thereof Alternatively, a method of dropping a solution containing an equivalent thereof is preferably used.

According to this method, an aldehyde represented by formula (1) or an equivalent thereof, an aldehyde represented by formula (2) or an equivalent thereof, or a carbonyl compound represented by formula (3) or an equivalent thereof In the meantime, a coupling reaction (a dehydrogenation reaction or an acetalization reaction may occur before that) proceeds to produce a 3-furaldehyde derivative represented by the above formula (4). In the formula (4), R ¹ and R ² are the same as described above.

In this production method, by using the aldehyde represented by the formula (2) or an equivalent thereof as the aldehyde represented by the formula (1) or an equivalent thereof, the compound represented by the formula (2) is represented by the formula (1 A 3-furaldehyde derivative represented by the above formula (4a) corresponding to a dimer of the aldehyde represented by the formula (2) or an equivalent thereof. it can. Wherein (4a), R ² is as defined above. For example, by using only the compound represented by the formula (2) as a reaction raw material, a compound represented by the formula (4a) in which the compound is dimerized is obtained.

  After completion of the reaction, the reaction product can be separated and purified by, for example, separation means such as filtration, concentration, distillation, extraction, crystallization, recrystallization, adsorption, column chromatography, or a combination thereof.

  The 3-furaldehyde derivative obtained by the method of the present invention can be used as fine chemicals such as dyes, pharmaceuticals and polymer raw materials, synthetic intermediates of high-functional materials, intermediate raw materials of other organic chemicals, and the like.

  Hereinafter, the present invention will be described in more detail based on examples, but the present invention is not limited to these examples.

Example 1
To the reactor, palladium (II) acetate [Pd (OAc) ₂ ] (0.2 mmol), H ₄ PMo ₁₁ V ₁ O ₄₀ (14 μmol), cerium chloride heptahydrate (CeCl ₃ .7H ₂ O) (0. 2 mmol), methanol (1.0 ml), acetic acid (2.0 ml) and valeraldehyde (2 mmol) were charged and reacted at 80 ° C. for 15 hours in an atmosphere of oxygen at 1 atmosphere (0.1 MPa). When the reaction solution was analyzed by gas chromatography after the reaction, 2-ethyl-5-propyl-3-furaldehyde was produced in a yield of 36%. In addition, 3-propionyl-5-propylfuran was produced in 8% yield. The conversion of valeraldehyde was 97%.

Example 2
The reaction was conducted in the same manner as in Example 1 except that iron chloride hexahydrate (FeCl ₃ .6H ₂ O) was used instead of cerium chloride heptahydrate (CeCl ₃ .7H ₂ O). When the reaction solution was analyzed by gas chromatography after the reaction, 2-ethyl-5-propyl-3-furaldehyde was produced in a yield of 7%. The conversion of valeraldehyde was 66%.

Example 3
The reaction was performed in the same manner as in Example 1 except that gadolinium chloride hexahydrate (GdCl ₃ .6H ₂ O) was used instead of cerium chloride heptahydrate (CeCl ₃ .7H ₂ O). When the reaction solution was analyzed by gas chromatography after the reaction, 2-ethyl-5-propyl-3-furaldehyde was produced in a yield of 6%. The conversion of valeraldehyde was 75%.

Example 4
The reaction was performed in the same manner as in Example 1 except that decanal (2 mmol) was used instead of valeraldehyde (2 mmol). When the reaction solution was analyzed by gas chromatography after the reaction, 2-heptyl-5-octyl-3-furaldehyde was produced in a yield of 34%. In addition, 4-octanoyl-2-octylfuran was produced in a yield of 6%, 2-nonenal 1%, and methyl decanoate 4%. The conversion of decanal was 96%.

Example 5
The reaction was conducted in the same manner as in Example 1 except that decanal (2 mmol) was used instead of valeraldehyde (2 mmol) and water (0.4 ml) was used instead of methanol (1.0 ml). When the reaction solution was analyzed by gas chromatography after the reaction, 2-heptyl-5-octyl-3-furaldehyde was produced in a yield of 23%. In addition, 4-octanoyl-2-octylfuran was produced in a yield of 2% and 2-nonenal in a yield of 17%. The conversion of decanal was 94%.

Example 6
The reaction was performed in the same manner as in Example 1 except that water (0.4 ml) was used instead of methanol (1.0 ml). When the reaction solution was analyzed by gas chromatography after the reaction, 2-ethyl-5-propyl-3-furaldehyde was produced in a yield of 22%. In addition, 2-propyl-2-heptenal was produced in a yield of 7%. The conversion of valeraldehyde was 99% or more.

Example 7
The reaction was conducted in the same manner as in Example 1 except that ethanol (1.4 ml) was used instead of methanol (1.0 ml). When the reaction solution was analyzed by gas chromatography after the reaction, 2-ethyl-5-propyl-3-furaldehyde was produced in a yield of 12%. In addition, 4-propionyl-2-propylfuran was produced in a yield of 2% and 2-propyl-2-heptenal in a yield of 6%. The conversion of valeraldehyde was 99% or more.

Example 8
To the reactor, palladium (II) acetate [Pd (OAc) ₂ ] (0.1 mmol), H ₄ PMo ₁₁ V ₁ O ₄₀ (7 μmol), cerium chloride heptahydrate (CeCl ₃ .7H ₂ O) (0. 1 mmol), methanol (1.0 ml), acetic acid (2.0 ml), 4,4-dimethoxy-2-butanone (1 mmol) and valeraldehyde (1 mmol) were charged under an atmosphere of oxygen at 1 atmosphere (0.1 MPa). The reaction was carried out at 50 ° C. for 4 hours. When the reaction solution was analyzed by gas chromatography after the reaction, 2-methyl-5-propyl-3-furaldehyde was produced in a yield of 34%. In addition, 4-acetyl-2-propylfuran was produced in a yield of 4%. The conversion of 4,4-dimethoxy-2-butanone was 83%.

Example 9
The reaction was performed in the same manner as in Example 8 except that 3 mmol of valeraldehyde was used. When the reaction solution was analyzed by gas chromatography after the reaction, 2-methyl-5-propyl-3-furaldehyde was produced in a yield of 72%. In addition, 4-acetyl-2-propylfuran was produced in a yield of 9%. The conversion of 4,4-dimethoxy-2-butanone was 93%.

Example 10
The reaction was performed in the same manner as in Example 8 except that 5 mmol of valeraldehyde was used. When the reaction solution was analyzed by gas chromatography after the reaction, 2-methyl-5-propyl-3-furaldehyde was produced in a yield of 83% (isolation yield 72%). In addition, 4-acetyl-2-propylfuran was produced in a yield of 11%. The conversion of 4,4-dimethoxy-2-butanone was 97%.

Example 11
The reaction was performed in the same manner as in Example 8 except that 10 mmol of valeraldehyde was used. When the reaction solution was analyzed by gas chromatography after the reaction, 2-methyl-5-propyl-3-furaldehyde was produced in a yield of 49%. In addition, 4-acetyl-2-propylfuran was produced in a yield of 11%. The conversion of 4,4-dimethoxy-2-butanone was 96%.

Example 12
The reaction was performed in the same manner as in Example 8 except that 5 mmol of propionaldehyde was used instead of valeraldehyde (1 mmol). When the reaction solution was analyzed by gas chromatography after the reaction, 2,5-dimethyl-3-furaldehyde was produced in a yield of 94% or more. In addition, 3-acetyl-2,5-dimethylfuran was produced in a yield of 6%.

Example 13
The reaction was conducted in the same manner as in Example 8 except that 5 mmol of butyraldehyde was used instead of valeraldehyde (1 mmol). When the reaction solution was analyzed by gas chromatography after the reaction, 5-ethyl-2-methyl-3-furaldehyde was produced in a yield of 73%. In addition, 3-acetyl-5-ethyl-2-methylfuran was produced in a yield of 7%.

Example 14
The reaction was conducted in the same manner as in Example 8 except that 5 mmol of isovaleraldehyde was used instead of valeraldehyde (1 mmol). After the reaction, the reaction solution was analyzed by gas chromatography. As a result, 5-isopropyl-2-methyl-3-furaldehyde was produced in a yield of 59%. In addition, 3-acetyl-5-isopropyl-2-methylfuran was produced in a yield of 6%.

Example 15
The reaction was performed in the same manner as in Example 8 except that 5 mmol of decanal was used instead of valeraldehyde (1 mmol). When the reaction solution was analyzed by gas chromatography after the reaction, 2-methyl-5-octyl-3-furaldehyde was produced in a yield of 82%. In addition, trace amounts of 3-acetyl-2-methyl-5-octylfuran were generated.

Example 16
To the reactor, palladium (II) acetate [Pd (OAc) ₂ ] (0.2 mmol), H ₄ PMo ₁₁ V ₁ O ₄₀ (14 μmol), cerium chloride heptahydrate (CeCl ₃ .7H ₂ O) (0. 2 mmol), methanol (1.0 ml), acetic acid (2.0 ml), acetaldehyde (1 mmol) and propionaldehyde (1 mmol) were charged and reacted at 80 ° C. for 15 hours in an atmosphere of oxygen 1 atm (0.1 MPa). . When the reaction solution was analyzed by gas chromatography after the reaction, 3-furaldehyde was similarly produced.

Claims (7)

Following formula (1)

(Wherein R ¹ represents a hydrogen atom or an organic group)
Or an equivalent thereof, and the following formula (2)

(Wherein R ² represents a hydrogen atom or an organic group)
Or an equivalent thereof, or the following formula (3)

(In the formula, R ² represents a hydrogen atom or an organic group, and R ³ and R ⁴ are the same or different and represent a hydrogen atom or a hydrocarbon group. R ³ and R ⁴ are bonded to each other and adjacent to each other. May form a ring with two oxygen and carbon atoms)
Is reacted with a carbonyl compound represented by the following formula (4):

(Wherein R ¹ and R ² are the same as above)
A method for producing a 3-furaldehyde derivative, characterized in that a 3-furaldehyde derivative represented by the formula: Using the aldehyde represented by the formula (2) or an equivalent thereof as the aldehyde represented by the formula (1) or an equivalent thereof, the following formula (4a)

(Wherein R ² represents a hydrogen atom or an organic group)
The method for producing a 3-furaldehyde derivative according to claim 1, wherein a 3-furaldehyde derivative represented by the formula:   The method for producing a 3-furaldehyde derivative according to claim 1 or 2, wherein the reaction is carried out in the presence of a palladium compound catalyst (A).   In addition to the palladium compound catalyst (A), a heteropolyacid or a salt thereof (B1), or an oxo acid containing P or Si as a whole and at least one element selected from V, Mo and W, or The method for producing a 3-furaldehyde derivative according to claim 3, wherein the reaction is carried out in the presence of a promoter (B) comprising the salt mixture (B2).   The method for producing a 3-furaldehyde derivative according to claim 4, wherein the heteropolyacid or a salt thereof (B1) contains P or Si as a constituent element and at least one element selected from V, Mo and W. . Heteropolyacid or its salt (B1) has the formula
A _{3 + n} [PMo _12-n V _n O ₄₀ ]
(In the formula, A is a hydrogen atom, NH _4, represents at least one selected from alkali metals and alkaline earth metals, n represents an integer of 0)
The method for producing a 3-furaldehyde derivative according to claim 4 or 5, which is phosphovanadomolybdic acid or phosphomolybdic acid represented by the formula:   The method for producing a 3-furaldehyde derivative according to any one of claims 3 to 6, wherein the reaction is further performed in the presence of a Lewis acid (C) in addition to the palladium compound catalyst (A).