JP5633067B2 - Furan derivative and method for producing the same - Google Patents

Description

  The present invention relates to an efficient method for producing a furan derivative and a novel furan derivative.

Furan derivatives having an aromatic substituent at the 2,5-position are functional chemicals used in fields such as medicine, agricultural chemicals, and electronic materials. For example, furans having an alkoxyaryl group at the 2,5-position, etc. are known to have growth-suppressing / inhibiting effects on breast cancer, renal cancer, malignant melanoma and other cancer cells, and are expected to be used as anticancer agents. (Non-Patent Documents 1 and 2). In addition, furans having an aryl group at the 2,5-position, etc. have been reported as application examples as hole transport materials in organic EL materials and basic skeletons in molecular wire materials, and can also be used as organic electronic materials. It is a compound (Non-Patent Documents 3 and 4).
As a conventional method for producing such 2,5-diarylfurans, 1,4-diketones having an aryl group at the 1,4-position in the presence of an acid catalyst such as polyphosphoric acid or p-toluenesulfonic acid are used. The Knorr method (Non-patent Documents 1, 5, and 6) for carrying out a cyclization reaction, and the method for carrying out a cross coupling (Still coupling reaction) between 2,5-distanylfuran and an aryl halide in the presence of a palladium catalyst (Non-Patent Document 1) Patent Document 2), a method of cross-coupling of 2,5-dibromofuran and an aryl Grignard reagent (heteroaryl Grignard reagent) in the presence of a palladium catalyst (Non-Patent Document 7), 1,4- Reduction and cyclization reaction by reacting 2-butene-1,4-dione (or 2-butyne-1,4-dione) having an aryl group at the position with formic acid and sulfuric acid Method (Non-patent Document 8), 1,4-diaryl-1-methoxy-1,3-diene obtained by reacting arylacetylene with methanol in the presence of a ruthenium catalyst, p-toluenesulfonic acid, cupric chloride And a method of hydrolyzing and cyclizing by treatment with water (Non-patent Document 9) and the like have been known.

  However, in these methods, (1) 1,4-diketones having an aryl group, 2,5-distanylfuran, 2,5-dibromofuran, 2-butene-1,4-dione, arylacetylene, etc. Raw material compounds are expensive and / or are not easily obtained and synthesized (Non-Patent Documents 1, 2, 5-9), (2) An expensive noble metal such as palladium or ruthenium is required as a catalyst (non-patent documents) Patent Documents 2, 7-9), (3) While using a tin compound that is problematic in safety, there are problems such as the generation of a large amount of tin compounds as waste (Non-Patent Document 2). It was not an industrially advantageous method.

On the other hand, anisole and methyl succinic anhydride were reacted in the presence of an H—Y type zeolite catalyst having a Si / Al ratio = 15.9 (silica / alumina ratio = 8.0), and 2,5-diarylfurans 2 , 5-bis (4-methoxyphenyl) -3-methylfuran was reported (Non-patent Document 10).
However, in this report, the main product in the reaction at 150 ° C. for 24 hours under normal heating is the 4-membered lactone 4,4-bis (4-methoxyphenyl) -2-methyl- The yield of 2,5-bis (4-methoxyphenyl) -3-methylfuran, which is 4-butenolide and obtained as a small amount of by-product, is only 4%. I couldn't.

J. et al. Med. Chem. , 44, 3838 (2001) Eur. J. et al. Med. Chem. , 41, 756 (2006) Chem. Commun. , 2336 (2002) Chem. Commun. , 2824 (2002) Synthesis, 593 (1984). J. et al. Org. Chem. , 60, 301 (1995) Tetrahedron, 41, 1919 (1985) J. et al. Org. Chem. 68, 5392 (2003) Angew. Chem. Int. Ed. , 48, 1681 (2009) Acta Chem. Scand. , 51, 1229 (1997)

  This invention is made | formed in view of the above situations, Comprising: It aims at manufacturing efficiently the furans which have an aromatic substituent in 2, 5-position.

  As a result of intensive studies to solve the above problems, the present inventors have (1) aromatic compounds and succinic acid derivatives (succinic anhydride, succinic acid or diesters thereof) which are inexpensive and readily available raw materials. The reaction using a hydrogen atom proceeds smoothly in the presence of an acid catalyst under microwave irradiation, and furans having an aromatic substituent at the 2,5-position can be obtained in good yield, and (2) Depending on the type, the inventors have found a novel fact that the reaction proceeds efficiently without microwave irradiation, and have completed the present invention.

（式中、カルボニル基の隣の２個の炭素原子上のそれぞれ２個の水素原子のうちの一つが反応に関与しない基で置換されていても差し支えない。）
で表されるコハク酸無水物又は
Ｒ’Ｏ_２Ｃ（ＣＨ_２）_２ＣＯ_２Ｒ’ （IIＢ）
（式中、Ｒ’は水素原子又はアルキル基であり、カルボニル基の隣の２個の炭素原子上のそれぞれ２個の水素原子のうちの一つが反応に関与しない基で置換されていても差し支えない。）
で表されるコハク酸又はそのジエステル化合物を、マイクロ波照射下、酸触媒存在下で反応させることを特徴とする下記一般式（III）

（式中、Ｒは前記と同じ意味である。また、炭素上の水素原子の一部又は全部が反応に関与しない基で置換されていても差し支えない。）
で表される２，５−ジアリールフラン類の製造方法。
〈２〉前記の酸触媒として固体酸触媒を用いることを特徴とする〈１〉に記載の製造方法。
〈３〉前記の固体酸触媒として、ゼオライト、モンモリロナイト又はヘテロポリ酸を用いることを特徴とする〈２〉に記載の製造方法。
〈４〉前記のゼオライトとして、ベータ型、Ｙ型、モルデナイト型又はＺＳＭ−５型のゼオライトを使用することを特徴とする〈３〉に記載の製造方法。
〈５〉前記のゼオライトとして、シリカ／アルミナ比が２〜６００のものを使用することを特徴とする〈３〉又は〈４〉に記載の製造方法。
〈６〉下記一般式（Ｉ）
ＲＨ （Ｉ）
（式中、Ｒは１価の炭化水素環又は複素環の芳香族有機基を示し、環上の水素原子の一部が反応に関与しない基で置換されていても差し支えない。）
で表される芳香族化合物と、下記一般式（IIＡ）

（式中、カルボニル基の隣の２個の炭素原子上のそれぞれ２個の水素原子のうちの一つが反応に関与しない基で置換されていても差し支えない。）
で表されるコハク酸無水物又は
Ｒ’Ｏ_２Ｃ（ＣＨ_２）_２ＣＯ_２Ｒ’ （IIＢ）
（式中、Ｒ’は水素原子又はアルキル基であり、カルボニル基の隣の２個の炭素原子上のそれぞれ２個の水素原子のうちの一つが反応に関与しない基で置換されていても差し支えない。）
で表されるコハク酸又はそのジエステル化合物を、酸触媒存在下で反応させて、下記一般式（III）

（式中、Ｒは前記と同じ意味である。また、炭素上の水素原子の一部が反応に関与しない基で置換されていても差し支えない。）
で表される２，５−ジアリールフラン類を製造方法であって、
前記の酸触媒として、ベータ型ゼオライト（シリカ／アルミナ比が２〜６００）を用いて、マイクロ波照射を行わずに反応を行うことを特徴とする２，５−ジアリールフラン類の製造方法。
〈７〉下記一般式（IＶ）で表されるフラン誘導体。

（式中、Ｒ”は、４−メトキシ−３−メチルフェニル基、２，３−ジヒドロベンゾフラン−５−イル基、又は１，４−ベンゾジオキサン−６−イル基である。） That is, this application provides the following inventions.
<1> The following general formula (I)
RH (I)
(In the formula, R represents a monovalent hydrocarbon ring or heterocyclic aromatic organic group, and a part of hydrogen atoms on the ring may be substituted with a group not participating in the reaction.)
An aromatic compound represented by the following general formula (IIA)

(In the formula, one of each two hydrogen atoms on the two carbon atoms adjacent to the carbonyl group may be substituted with a group not participating in the reaction.)
Or succinic anhydride represented by the formula: R′O ₂ C (CH ₂ ) ₂ CO ₂ R ′ (IIB)
(In the formula, R ′ is a hydrogen atom or an alkyl group, and one of two hydrogen atoms on the two carbon atoms adjacent to the carbonyl group may be substituted with a group which does not participate in the reaction. Absent.)
Wherein the succinic acid or its diester compound is reacted in the presence of an acid catalyst in the presence of microwave irradiation.

(In the formula, R has the same meaning as described above. In addition, some or all of the hydrogen atoms on the carbon may be substituted with a group that does not participate in the reaction.)
The manufacturing method of the 2, 5- diaryl furans represented by these.
<2> The production method according to <1>, wherein a solid acid catalyst is used as the acid catalyst.
<3> The production method according to <2>, wherein zeolite, montmorillonite, or heteropolyacid is used as the solid acid catalyst.
<4> The production method according to <3>, wherein a zeolite of a beta type, a Y type, a mordenite type, or a ZSM-5 type is used as the zeolite.
<5> The production method according to <3> or <4>, wherein the zeolite has a silica / alumina ratio of 2 to 600.
<6> The following general formula (I)
RH (I)
(In the formula, R represents a monovalent hydrocarbon ring or heterocyclic aromatic organic group, and a part of hydrogen atoms on the ring may be substituted with a group not participating in the reaction.)
An aromatic compound represented by the following general formula (IIA)

(In the formula, one of each two hydrogen atoms on the two carbon atoms adjacent to the carbonyl group may be substituted with a group not participating in the reaction.)
Or succinic anhydride represented by the formula: R′O ₂ C (CH ₂ ) ₂ CO ₂ R ′ (IIB)
(In the formula, R ′ is a hydrogen atom or an alkyl group, and one of two hydrogen atoms on the two carbon atoms adjacent to the carbonyl group may be substituted with a group which does not participate in the reaction. Absent.)
Is reacted with a succinic acid represented by the following formula (III):

(In the formula, R has the same meaning as described above. In addition, a part of hydrogen atoms on carbon may be substituted with a group not participating in the reaction.)
A process for producing 2,5-diarylfurans represented by:
As the acid catalyst, with a beta-type peptidase zeolite (silica / alumina ratio of 2 to 600), method for producing 2,5-diaryl furans, characterized in that the reaction is carried out without microwave irradiation.
<7> A furan derivative represented by the following general formula (IV).

(In the formula, R ″ represents a 4-methoxy-3-methylphenyl group, a 2,3-dihydrobenzofuran-5-yl group, or a 1,4-benzodioxan-6-yl group.)

  By using the manufacturing method of this invention, there exists an advantage that the furan derivative which has an aromatic substituent can be obtained more efficiently compared with the conventional method.

上記式に示すように、無水コハク酸又はコハク酸が原料である場合、共生成物は水のみであることから、本反応系は低環境負荷型のクリーンな反応系である。 Hereinafter, the present invention will be described in detail.
The production method of the present invention is characterized in that an aromatic compound and a succinic acid derivative are reacted in the presence of an acid catalyst.
This reaction proceeds with dehydration when the succinic acid derivative is succinic anhydride or succinic acid, and proceeds with dealcoholization and dehydration when it is a succinic acid diester. The reaction route estimated when succinic anhydride or succinic acid is used as a raw material is shown below.

As shown in the above formula, when succinic anhydride or succinic acid is a raw material, since the co-product is only water, this reaction system is a clean reaction system with a low environmental load.

In the present invention, the aromatic compound used as a raw material is represented by the following general formula (I):
RH (I)
(Wherein, R represents a monovalent hydrocarbon ring or aromatic organic group of heterocycles, no problem be substituted with a group in which some of the hydrogen atoms on the ring is not involved in the reaction.)
In hydrocarbon ring or represented are those heterocycles.

In the general formula (I), when R is a hydrocarbon ring, it is preferably endocyclic carbon number 6 to 22, more preferably 6 to 14.
Therefore, specific examples of the aromatic compound of the hydrocarbon ring include benzene, naphthalene, anthracene, phenanthrene, pyrene, perylene, pentacene and the like.

In the above R, a part of hydrogen atoms on the ring may be substituted with a group that does not participate in the reaction. Specific examples of these groups include alkyl groups such as a methyl group, an isopropyl group, and a hexyl group. In addition to alkoxy groups such as methoxy group, methoxy group, ethoxy group, isopropoxy group, butoxy group, hexyloxy group, oxyethylene group and oxyethyleneoxy which are divalent groups that bind two carbon atoms on the ring Groups and the like.
Therefore, specific examples of compounds having these groups include toluene, anisole, ethoxybenzene (phenetole), butoxybenzene, hexyloxybenzene, 2-methylanisole, 2,6-dimethylanisole, 1,2-dimethoxybenzene, 2,3-dihydrobenzofuran, 1,3-benzodioxole, 1,4-benzodioxan and the like can be mentioned.

Furthermore, when R is a heterocyclic ring , a hetero atom is a sulfur atom, an oxygen atom, a nitrogen atom or the like, and the number of carbon atoms in the ring is preferably 4 to 12, more preferably 4 to 8.
Accordingly, specific examples of the aromatic compound of the heterocyclic ring include thiophene, benzothiophene, dibenzothiophene, furan, benzofuran, dibenzofuran, N-methylpyrrole and the like.

で表されるコハク酸無水物又は
Ｒ’Ｏ_２Ｃ（ＣＨ_２）_２ＣＯ_２Ｒ’ （IIＢ）
（式中、Ｒ’は水素原子又はアルキル基であり、カルボニル基の隣の２個の炭素原子上のそれぞれ２個の水素原子のうちの一つが反応に関与しない基で置換されていても差し支えない。）
で表されるコハク酸又はそのジエステル化合物である。 On the other hand, the succinic acid derivative to be reacted with the aromatic compound has the following general formula (IIA)

Or succinic anhydride represented by the formula: R′O ₂ C (CH ₂ ) ₂ CO ₂ R ′ (IIB)
(In the formula, R ′ is a hydrogen atom or an alkyl group, and one of two hydrogen atoms on the two carbon atoms adjacent to the carbonyl group may be substituted with a group which does not participate in the reaction. Absent.)
Or a diester compound thereof.

R ′ in the general formula (IIB) is a hydrogen atom or an alkyl group, and when R ′ is an alkyl group, examples thereof include a methyl group and an ethyl group.
In the general formulas (IIA) and (IIB), one of two hydrogen atoms on the two carbon atoms adjacent to the carbonyl group may be substituted with a group that does not participate in the reaction. Specific examples of these groups include alkyl groups such as methyl group, isopropyl group, hexyl group, decyl group, tetradecyl group, etc., alkenyl groups such as hexenyl group, octenyl group, dodecenyl group, methoxy group, ethoxy group, In addition to an alkoxy group such as an isopropoxy group and a hexyloxy group, a tetramethylene group, an oxyethylene group, an oxyethyleneoxy group, and the like, which are divalent groups for bonding two carbon atoms, can be exemplified.
Therefore, specific examples of the compound having these groups include succinic anhydride, 2-methyl succinic anhydride, 2-ethyl succinic anhydride, 2,3-dimethyl as represented by the general formula (IIA). Succinic anhydride, 2- (1-dodecenyl) succinic anhydride, 1,2-cyclohexanedicarboxylic anhydride, 4-methylcyclohexane-1,2-dicarboxylic anhydride, 5-norbornene-2,3-dicarboxylic Examples of acid anhydrides include succinic acid, 2-methyl succinic acid, 2,3-dimethyl succinic acid, dimethyl succinate, and diethyl succinate.

  The molar ratio of the aromatic compound to the succinic acid derivative can be arbitrarily selected, but considering the yield of the furan derivative relative to the succinic acid derivative, it is usually 0.5 or more and 300 or less, preferably 1 or more and 200 or less. Yes, more preferably 2 or more and 150 or less.

In the present invention, various conventionally known acid catalysts which proceed efficiently under microwave irradiation and are used in Friedel-Crafts type electrophilic substitution reaction and the like can be used.
Specific examples thereof include various acidic compounds such as metal salts, metal oxides and other inorganic substances, organic substances, etc. If the inorganic substances are shown more specifically, metal salts (chlorides such as aluminum and iron, bromides, etc.) And inorganic solid acids such as zeolite, montmorillonite, silica, and heteropolyacid having protic hydrogen atoms or metal cations (aluminum, titanium, gallium, iron, cerium, scandium, etc.).
In more detail, organic substances are represented by Nafion having a sulfo group (Nafion, registered trademark, available from DuPont), Dowex (registered trademark, available from Dow Chemical), Amberlite (Amberlite). , Registered trademark, available from Rohm & Hass) and other organic solid acids. Furthermore, a catalyst in which an organic acidic compound such as Nafion is supported on silica or the like (for example, Nafion SAC-13) can also be used.

As the type of zeolite used as a catalyst, various types of zeolite having a basic skeleton such as beta type, Y type, ZSM-5 type, mordenite type, and SAPO type can be used. Among these, beta type, Y type, Mordenite type and ZSM-5 type are preferred, beta type and Y type are more preferred, and beta type is even more preferred.
In these zeolites, various types of zeolites such as Bronsted acid type having a protonic hydrogen atom and Lewis acid type having a metal cation can be used. Among these, the proton type having a protonic hydrogen atom is represented by H-beta type, HY type, H-mordenite type, H-ZSM-5 type and the like. Furthermore, those of ammonium type, NH ₄ - Use _mordenite, by firing the NH 4 -ZSM-5 type or the like of the zeolite, even those converted into a proton type - beta, _NH 4 -Y type, NH ₄ can do.
Furthermore, about the silica / alumina ratio of a zeolite, although various ratios can be selected according to reaction conditions, Preferably it is 2-600, More preferably, it is 3-500, More preferably, it is 3-400.

As these zeolites, various types including commercial products can be used. Specific examples of commercially available products include CP811C, CP811E, CP811Q, CP811TL, CP811E-75, CP811C-300, CP814E, CP814N, CP814Q, CP814T, and the like, which are commercially available from Zeolist. UOP-Beta etc. which are marketed from UOP, such as 930HOA and 940HOA which are marketed, are mentioned. Examples of the Y-type zeolite include CBV600, CBV712, CBV720, and CBV780 commercially available from Zeolis Corporation, and 360HOA and 320HOA commercially available from Tosoh Corporation. Furthermore, examples of the mordenite type zeolite include CBV90A commercially available from Zeolis Corporation, and 690HOA and 620HOA commercially available from Tosoh Corporation. Examples of ZSM-5 type zeolite include CBV5525 commercially available from Zeolis Corporation. Is mentioned.
The amount of catalyst relative to the raw material can be arbitrarily determined, but in terms of weight ratio, it is usually about 0.0001 to 100, preferably about 0.001 to 70, and more preferably about 0.001 to 50.

  In the microwave irradiation reaction of the present invention, various commercially available devices equipped with contact-type or non-contact-type temperature sensors can be used. The output of microwave irradiation, the type of cavity (multimode, single mode), the form of irradiation (continuous, intermittent), etc. can be arbitrarily determined according to the scale and type of reaction. The frequency of the microwave is usually 0.3 to 30 GHz.

  In the reaction under microwave irradiation, in order to heat the reaction system more efficiently, a heating material (susceptor) that absorbs microwaves and generates heat can be added to the reaction system. As the kind of the heating material, various conventionally known materials such as activated carbon, graphite, silicon carbide, titanium carbide and the like can be used. Further, a molded catalyst obtained by mixing the catalyst described above and the heating material powder and calcining using an appropriate binder such as sepiolite or holmite can also be used.

  In the present invention, depending on the type of catalyst, it is possible to carry out the reaction efficiently without performing microwave irradiation. Such catalysts include beta-type, mordenite-type, or ZSM-5-type zeolites (whose silica / alumina ratio is 2 to 600), Y-type zeolites (silica / alumina ratio is 10-600), montmorillonite, or Examples include heteropolyacids.

The reaction of the present invention can be carried out in a liquid phase or a gas phase depending on the reaction temperature and reaction pressure. Moreover, as a form of a reaction apparatus, it can carry out with various forms conventionally known, such as a batch type and a flow type.
The reaction temperature is 20 ° C. or higher, preferably 20 to 350 ° C., more preferably 20 to 300 ° C. Furthermore, the reaction pressure is usually 0.1 to 100 atm, preferably 0.1 to 80 atm, and more preferably 0.1 to 60 atm.
The reaction time depends on the reaction temperature, the amount of catalyst, the form of the reaction apparatus, etc., but is about 1 to 240 minutes, preferably about 1 to 180 minutes, and more preferably about 1 to 120 minutes.

When this reaction is carried out in a liquid phase system, it can be carried out with or without a solvent, but when a solvent is used, hydrocarbons such as decalin (decahydronaphthalene) and decane, chlorobenzene, 1,2- or 1,3 -React with raw materials such as dichlorobenzene, 2,4-dichlorotoluene, 1,2,4-trichlorobenzene, halogenated hydrocarbons such as 1,2- or 1,3-dibromobenzene, ethers such as dibutyl ether Various solvents except for can be used, and two or more kinds can be mixed and used.
An aromatic compound having a lower reactivity than the starting aromatic compound can also be used as a solvent. For example, when anisole is used as a raw material, toluene, xylene or the like can be used as a solvent.
On the other hand, when this reaction is carried out in the gas phase, the reaction can be carried out by mixing an inert gas such as nitrogen.

  Purification of the furan derivative produced by the method of the present invention can be easily achieved by means usually used in organic chemistry such as recrystallization, column chromatography and distillation.

（式中、Ｒ”は、４−メトキシ−３−メチルフェニル基、２，３−ジヒドロベンゾフラン−５−イル基、又は１，４−ベンゾジオキサン−６−イル基である。）
これらのアルコキシ構造を有するフラン誘導体は、制ガン作用を示すジアリールフランと類似した構造を有し、制ガン剤等としての利用を期待できる。 Moreover, the novel furan derivative represented with the following general formula (IV) is provided by the manufacturing method of this invention.

(In the formula, R ″ represents a 4-methoxy-3-methylphenyl group, a 2,3-dihydrobenzofuran-5-yl group, or a 1,4-benzodioxan-6-yl group.)
These furan derivatives having an alkoxy structure have a structure similar to that of a diarylfuran exhibiting an anticancer activity, and can be expected to be used as an anticancer agent or the like.

EXAMPLES Next, although an Example demonstrates this invention further more concretely, this invention is not limited to these Examples.
Example 1
Anisole (Ia) 20 mmol, succinic anhydride (IIAa) 0.2 mmol, H-beta type zeolite CP811C (manufactured by Zeolis) 100 mg, activated carbon 40 mg in a reaction tube, a microwave irradiation apparatus equipped with a radiation thermometer ( The reaction was carried out at 200 ° C. for 30 minutes with stirring using a Discover LabMate (single mode type) manufactured by CEM. As a result of analyzing the product with a gas chromatograph and a gas chromatograph mass spectrometer, it was found that 2,5-bis (4-methoxyphenyl) furan (IIIa) was produced in a yield of 74.8% (see Table 1). ).

(Examples 2-86)
The reaction conditions (type and amount of raw materials, catalyst, additive, solvent, reaction apparatus, temperature, time, etc.) were changed, and the reaction and analysis were conducted in the same manner as in Example 1, and the results of measuring the yield of the product were Table 1 shows.

(Example 87)
A mixture of anisole (Ia) 28 mmol, succinic anhydride (IIAa) 0.40 mmol, H-beta type zeolite CP811C (manufactured by Zeolis) 200 mg, 1,2-dichlorobenzene 1 mL was placed in a reaction tube and equipped with a radiation thermometer. Using a microwave irradiation apparatus (Initiator manufactured by Biotage, single mode type), the reaction was carried out at 200 ° C. for 30 minutes while stirring. The solid was separated from the supernatant with a centrifuge, and the solid was washed with acetone (2 mL, 1 time) and toluene (4 mL, 2 times). The supernatant and washings were combined and concentrated under reduced pressure, and the resulting solid was washed with hexane, resulting in 0.26 mmol (yield 65%) of 2,5-bis (4-methoxyphenyl) furan (IIIa). I was able to.

(Example 88)
Ethoxybenzene (Ib) 20 mmol, succinic anhydride (IIAa) 0.20 mmol, H-beta type zeolite CP811C (manufactured by Zeolis) 100 mg of a mixture was put into a reaction tube, and a microwave irradiation apparatus (CEM, equipped with a radiation thermometer) Using a Discover, single mode type), the reaction was carried out at 220 ° C. for 30 minutes while stirring. The solid was separated from the supernatant with a centrifuge, and the solid was washed with acetone and toluene (1.5 mL each). The same reaction and post-treatment were repeated four more times. All supernatants and washings were combined, concentrated under reduced pressure, and purified by column chromatography (silica gel, toluene / hexane = 2/1). 0.48 mmol (yield 48%) of -bis (4-ethoxyphenyl) furan (IIIb) could be obtained.

Example 89
Using a mixture of 2-methylanisole (Ic) 12.5 mmol, succinic anhydride (IIAa) 0.50 mmol, H-beta type zeolite CP811C (manufactured by Zeolis) 200 mg, 1,2-dichlorobenzene 2 mL, the reaction temperature was adjusted. The reaction and post-treatment were performed in the same manner as in Example 87 except that the temperature was 250 ° C., and purification by column chromatography (silica gel, toluene / hexane = 2/3) was performed. As a result, 2,5-bis (4-methoxy- 0.21 mmol (42% yield) of 3-methylphenyl) furan (IIIc) could be obtained.

(IIIc) is a compound not yet described in the literature, and its physical property values and spectral data are as follows.
Mp: 144-146 ° C.
¹ H-NMR (CDCl ₃ ): δ 2.27 (s, 6H, CH ₃ ), 3.85 (s, 6H, OCH ₃ ), 6.55 (s, 2H, furan ring H), 6.84 (d, J = 8.4 Hz, 2H, aromatic ring H), 7.49-7.52 (m, 2H, aromatic ring H), 7.52-7.55 (m, 2H, aromatic ring H).
¹³ C-NMR (CDCl ₃ ): δ 16.3, 55.4, 105.4, 110.1, 122.3, 123.7, 126.2, 126.9, 152.9, 157.2.
IR (KBr): ν 1610, 1493, 1463, 1440, 1277, 1249, 1173, 1136, 1029, 884, 819, 785 cm ^-1 .
GC-MS (EI, 70eV): m / z (relative intensity) 308 (M ⁺ , 88), 293 (100), 278 (17), 154 (18), 115 (16).

(Example 90)
Reaction was carried out using a mixture of 2,3-dihydrobenzofuran (Id) 7.5 mmol, succinic anhydride (IIAa) 0.50 mmol, H-beta type zeolite CP811C (manufactured by Zeolis) 200 mg, 1,2-dichlorobenzene 2 mL. The reaction and post-treatment were performed in the same manner as in Example 87 except that the temperature was 230 ° C., and purification by column chromatography (silica gel, toluene / hexane = 3/1) was performed. As a result, 2,5-bis (2, 0.23 mmol (yield 46%) of 3-dihydrobenzofuran-5-yl) furan (IIId) could be obtained.

(IIId) is a compound not yet described in the literature, and its physical property values and spectral data were as follows.
Mp: 177-179 ° C.
¹ H-NMR (CDCl ₃ ): δ 3.25 (t, J = 8.8 Hz, 4H, OCCH ₂ ), 4.60 (t, J = 8.8 Hz, 4H, OCH ₂ ), 6.52 (s, 2H, furan ring H) , 6.81 (d, J = 8.1 Hz, 2H, aromatic ring H), 7.49 (dd, J = 8.1, 1.8 Hz, 2H, aromatic ring H), 7.56 (d, J = 1.8 Hz, 2H, aromatic ring H) .
¹³ C-NMR (CDCl ₃ ): δ 29.7, 71.4, 105.2, 109.4, 120.5, 123.9, 124.1, 127.5, 153.0, 159.5.
IR (KBr): ν 1613, 1487, 1439, 1281, 1229, 1107, 980, 945, 891, 795, 680 cm ^-1 .
GC-MS (EI, 70eV): m / z (relative intensity) 304 (M ⁺ , 100), 157 (8), 152 (12), 147 (9), 128 (9), 91 (9).

(Example 91)
1,4-Benzodioxane (Ie) 10 mmol, Succinic anhydride (IIAa) 0.50 mmol, H-beta type zeolite CP811C (manufactured by Zeolis) 200 mg, 1,2-dichlorobenzene 2 mL, using a mixture of reaction temperature, The reaction and post-treatment were performed in the same manner as in Example 87 except that the temperature was 230 ° C., and purification by column chromatography (silica gel, toluene) was performed. As a result, 2,5-bis (1,4-benzodioxan-6-yl ) 0.21 mmol (42% yield) of furan (IIIe) could be obtained.

(IIIe) is a compound not yet described in the literature, and its physical property values and spectral data are as follows.
Mp: 105-106 ° C.
¹ H-NMR (CDCl ₃ ): δ 4.29 (s, 8H, OCH ₂ ), 6.55 (s, 2H, furan ring H), 6.88 (d, J = 8.4 Hz, 2H, aromatic ring H), 7.20 (dd , J = 8.4, 2.0 Hz, 2H, aromatic ring H), 7.23 (d, J = 2.0 Hz, 2H, aromatic ring H).
¹³ C-NMR (CDCl ₃ ): δ 64.4, 64.5, 106.0, 112.6, 117.2, 117.6, 124.8, 143.0, 143.7, 152.5.
IR (KBr): ν 1587, 1498, 1459, 1312, 1281, 1244, 1223, 1127, 1064, 892, 867, 852, 815, 790 cm ^-1 .
GC-MS (EI, 70eV): m / z (relative intensity) 336 (M ⁺ , 100), 280 (69), 226 (10), 224 (20), 168 (19), 140 (11), 139 (16), 63 (12).

In Example 1 and Example 6 described above, the reaction was performed using an oil bath heating device instead of the microwave irradiation device. As a result, the yield of (IIIa) was 53.7% and 31.6%, respectively. (Example 7 and Example 8 respectively).
Although these values are lower than 74.8% and 44.4% obtained in Example 1 and Example 6, it is shown that (IIIa) can also be obtained by a normal heating method without microwave irradiation. .

  According to the method of the present invention, furan derivatives useful as functional chemicals can be efficiently and safely produced using inexpensive and readily available raw materials. Therefore, the utility value of the present invention is high, and its industrial significance is great. is there.

Claims (7)

The following general formula (I)
RH (I)
(Wherein, R represents a monovalent represents an aromatic organic radical of a hydrocarbon ring or a heterocyclic ring, no problem even if some of the hydrogen atoms on the ring is optionally substituted with groups which do not participate in the reaction.)
An aromatic compound represented by the following general formula (IIA)

(In the formula, one of each two hydrogen atoms on the two carbon atoms adjacent to the carbonyl group may be substituted with a group not participating in the reaction.)
Or succinic anhydride represented by the formula: R′O ₂ C (CH ₂ ) ₂ CO ₂ R ′ (IIB)
(In the formula, R ′ is a hydrogen atom or an alkyl group, and one of two hydrogen atoms on the two carbon atoms adjacent to the carbonyl group may be substituted with a group which does not participate in the reaction. Absent.)
Wherein the succinic acid or its diester compound is reacted in the presence of an acid catalyst in the presence of microwave irradiation.

(In the formula, R has the same meaning as described above. In addition, a part of hydrogen atoms on carbon may be substituted with a group not participating in the reaction.)
The manufacturing method of the 2, 5- diaryl furans represented by these.   The production method according to claim 1, wherein a solid acid catalyst is used as the acid catalyst.   The production method according to claim 2, wherein zeolite, montmorillonite or heteropolyacid is used as the solid acid catalyst.   The production method according to claim 3, wherein a zeolite of a beta type, a Y type, a mordenite type or a ZSM-5 type is used as the zeolite.   The production method according to claim 3 or 4, wherein a zeolite having a silica / alumina ratio of 2 to 600 is used as the zeolite. The following general formula (I)
RH (I)
(In the formula, R represents a monovalent hydrocarbon ring or heterocyclic aromatic organic group, and a part of hydrogen atoms on the ring may be substituted with a group not participating in the reaction.)
An aromatic compound represented by the following general formula (IIA)

(In the formula, one of each two hydrogen atoms on the two carbon atoms adjacent to the carbonyl group may be substituted with a group not participating in the reaction.)
Or succinic anhydride represented by the formula: R′O ₂ C (CH ₂ ) ₂ CO ₂ R ′ (IIB)
(In the formula, R ′ is a hydrogen atom or an alkyl group, and one of two hydrogen atoms on the two carbon atoms adjacent to the carbonyl group may be substituted with a group which does not participate in the reaction. Absent.)
Is reacted with a succinic acid represented by the following formula (III):

(In the formula, R has the same meaning as described above. In addition, a part of hydrogen atoms on carbon may be substituted with a group not participating in the reaction.)
A process for producing 2,5-diarylfurans represented by:
As the acid catalyst, with a beta-type peptidase zeolite (silica / alumina ratio of 2 to 600), method for producing 2,5-diaryl furans, characterized in that the reaction is carried out without microwave irradiation. A furan derivative represented by the following general formula (IV).

(In the formula, R ″ represents a 4-methoxy-3-methylphenyl group, a 2,3-dihydrobenzofuran-5-yl group, or a 1,4-benzodioxan-6-yl group.)