JP2010202589A - METHOD FOR PRODUCING 2,3-DIHYDRO-THIENO[3,4-b]FURAN DERIVATIVE AND NEW COMPOUND USED THEREFOR - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new compound that permits acquisition of a 2,3-dihydro-thieno[3,4-b]furan derivative in a high yield under a mild condition, a method for producing the same and a method for producing the furan derivative using the same. <P>SOLUTION: A new compound represented by general formula (1) [wherein R<SP>1</SP>, R<SP>2</SP>, R<SP>3</SP>and R<SP>4</SP>are each independently a hydrogen atom or an optionally substituted 1-20C hydrocarbon group] is subjected to an intramolecular cyclization reaction to give the 2,3-dihydro-thieno[3,4-b]furan derivative. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a novel compound having a thiophene skeleton and a method for producing the same, and a method for producing a 2,3-dihydro-thieno [3,4-b] furan derivative using the same.

  Conventionally, as a method for producing 2,3-dihydro-thieno [3,4-b] furan, a method in which 2-methoxycarbonyl-3-hydroxy-4-hydroxyethylthiophene is subjected to a ring-closing reaction and then demethoxycarbonylated. Is known (Patent Document 1). However, the method described in Patent Document 1 has a problem in terms of safety and energy efficiency because it is necessary to heat at a high temperature of 350 ° C. Further, a method for obtaining 2,3-dihydro-thieno [3,4-b] furan in high yield is desired, since the yield from α-hydroxymethylenebutyrolactone as a starting material is 2% or less.

Japanese Patent Publication No. 48-14067

  The present invention has been made to solve the above problems, and a novel compound capable of obtaining a 2,3-dihydro-thieno [3,4-b] furan derivative in mild conditions and in a high yield, and its It is an object of the present invention to provide a production method and a production method of the furan derivative using the production method.

［式中、Ｒ^１、Ｒ^２、Ｒ^３及びＲ^４は、それぞれ独立して水素原子又は置換基を有してもよい炭素数１〜２０の炭化水素基である。］
で示される化合物を提供することによって解決される。 The above problem is solved by the following general formula (1):

[Wherein, R ¹ , R ² , R ³ and R ⁴ are each independently a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms which may have a substituent. ]
This is solved by providing a compound represented by:

［式中、Ｒ^１、Ｒ^２、Ｒ^３及びＲ^４は、それぞれ独立して水素原子又は置換基を有してもよい炭素数１〜２０の炭化水素基である。］
で示される化合物を提供することによって解決される。 Moreover, the said subject is the following general formula (2):

[Wherein, R ¹ , R ² , R ³ and R ⁴ are each independently a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms which may have a substituent. ]
This is solved by providing a compound represented by:

［式中、Ｒ^１、Ｒ^２、Ｒ^３及びＲ^４は、それぞれ独立して水素原子又は置換基を有してもよい炭素数１〜２０の炭化水素基である。］
で示される化合物を提供することによって解決される。 Further, the above problem is solved by the following general formula (3):

[Wherein, R ¹ , R ² , R ³ and R ⁴ are each independently a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms which may have a substituent. ]
This is solved by providing a compound represented by:

［式中、Ｒ^１、Ｒ^２、Ｒ^３及びＲ^４は、それぞれ独立して水素原子又は置換基を有してもよい炭素数１〜２０の炭化水素基である。］
で示される化合物を分子内環化反応させる、下記一般式（４）：

［式中、Ｒ^１、Ｒ^２、Ｒ^３及びＲ^４は、前記と同義である。］
で示される２，３−ジヒドロ−チエノ［３，４−ｂ］フラン誘導体の製造方法を提供することによって解決される。 Moreover, the said subject is the following general formula (1):

[Wherein, R ¹ , R ² , R ³ and R ⁴ are each independently a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms which may have a substituent. ]
The following general formula (4):

[Wherein, R ¹ , R ² , R ³ and R ⁴ have the same meanings as described above. ]
It is solved by providing a method for producing a 2,3-dihydro-thieno [3,4-b] furan derivative represented by the formula:

［式中、Ｒ^１、Ｒ^２、Ｒ^３及びＲ^４は、それぞれ独立して水素原子又は置換基を有してもよい炭素数１〜２０の炭化水素基である。］
で示される化合物をアルカリ加水分解させる、下記一般式（１）：

［式中、Ｒ^１、Ｒ^２、Ｒ^３及びＲ^４は、前記と同義である。］
で示される化合物の製造方法を提供することによって解決される。 Moreover, the said subject is the following general formula (2):

[Wherein, R ¹ , R ² , R ³ and R ⁴ are each independently a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms which may have a substituent. ]
The following general formula (1):

[Wherein, R ¹ , R ² , R ³ and R ⁴ have the same meanings as described above. ]
It is solved by providing the manufacturing method of the compound shown by these.

［式中、Ｒ^１、Ｒ^２、Ｒ^３及びＲ^４は、それぞれ独立して水素原子又は置換基を有してもよい炭素数１〜２０の炭化水素基である。］
で示される化合物を脱臭素化反応させる、下記一般式（２）：

［式中、Ｒ^１、Ｒ^２、Ｒ^３及びＲ^４は、前記と同義である。］
で示される化合物の製造方法を提供することによって解決される。 Moreover, the said subject is the following general formula (3):

[Wherein, R ¹ , R ² , R ³ and R ⁴ are each independently a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms which may have a substituent. ]
The following general formula (2):

^{Wherein, R 1, R 2, R} 3 and ^{R 4} have the same meanings as defined above. ]
It is solved by providing the manufacturing method of the compound shown by these.

［式中、Ｒ^１、Ｒ^２、Ｒ^３及びＲ^４は、それぞれ独立して水素原子又は置換基を有してもよい炭素数１〜２０の炭化水素基である。］
で示される化合物に対して臭素及び酢酸を反応させる、下記一般式（３）：

［式中、Ｒ^１、Ｒ^２、Ｒ^３及びＲ^４は、前記と同義である。］
で示される化合物の製造方法を提供することによっても解決される。 Moreover, the said subject is the following general formula (5):

[Wherein, R ¹ , R ² , R ³ and R ⁴ are each independently a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms which may have a substituent. ]
In the following general formula (3), bromine and acetic acid are reacted with the compound represented by:

[Wherein, R ¹ , R ² , R ³ and R ⁴ have the same meanings as described above. ]
It can also be solved by providing a method for producing the compound represented by the formula:

  By using the novel compound of the present invention, a 2,3-dihydro-thieno [3,4-b] furan derivative can be provided under mild conditions and in a high yield. The 2,3-dihydro-thieno [3,4-b] furan derivative thus obtained is not only used as an additive to intermediates and flavoring agents such as pharmaceuticals and agricultural chemicals, but also to conductive materials and electrochromic. It is suitably used as a raw material for polymers useful as materials.

  According to the present invention, the compounds represented by the general formulas (1), (2) and (3), and 2,3-dihydro-thieno [3, represented by the general formula (4) using these as intermediates 4-b] A method for producing a furan derivative is provided. The compounds represented by the general formulas (1), (2) and (3) are novel compounds. Details will be described below.

［式中、Ｒ^１、Ｒ^２、Ｒ^３及びＲ^４は、それぞれ独立して水素原子又は置換基を有してもよい炭素数１〜２０の炭化水素基である。］

[Wherein, R ¹ , R ² , R ³ and R ⁴ are each independently a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms which may have a substituent. ]

［式中、Ｒ^１、Ｒ^２、Ｒ^３及びＲ^４は、前記と同義である。］

[Wherein, R ¹ , R ² , R ³ and R ⁴ have the same meanings as described above. ]

［式中、Ｒ^１、Ｒ^２、Ｒ^３及びＲ^４は、前記と同義である。］

[Wherein, R ¹ , R ² , R ³ and R ⁴ have the same meanings as described above. ]

［式中、Ｒ^１、Ｒ^２、Ｒ^３及びＲ^４は、前記と同義である。］

[Wherein, R ¹ , R ² , R ³ and R ⁴ have the same meanings as described above. ]

In the compounds represented by the general formulas (1) to (4), R ¹ , R ² , R ³ and R ⁴ each independently have 1 to 20 carbon atoms which may have a hydrogen atom or a substituent. It is a hydrocarbon group.

  The hydrocarbon group having 1 to 20 carbon atoms which may have a substituent may have, for example, an alkyl group which may have a substituent, an alkenyl group which may have a substituent, or a substituent. Examples thereof include a good aryl group and an optionally substituted cycloalkyl group.

  The alkyl group which may have a substituent may be linear or branched. Examples of the alkyl group include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n-pentyl group, isopentyl group, neopentyl group, A tert-pentyl group, n-hexyl group, isohexyl group, 2-ethylhexyl group, n-heptyl group, n-octyl group, n-nonyl group, n-decyl group and the like can be mentioned.

  The alkenyl group which may have a substituent may be linear or branched. Examples of the alkenyl group include a vinyl group, an allyl group, a methylvinyl group, a propenyl group, a butenyl group, a pentenyl group, a hexenyl group, a cyclopropenyl group, a cyclobutenyl group, a cyclopentenyl group, and a cyclohexenyl group.

  Examples of the aryl group that may have a substituent include a phenyl group, a naphthyl group, an anthryl group, and a phenanthryl group.

  Examples of the cycloalkyl group which may have a substituent include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptanyl group, a cyclooctanyl group, a cyclononanyl group, a cyclodecanyl group, a cycloundecanyl group, and a cyclohexane group. A dodecanyl group etc. are mentioned.

The alkyl group, alkenyl group, aryl group and cycloalkyl group described above may have a substituent. Examples of the substituent include alkoxy groups such as methoxy group, ethoxy group, propoxy group and butoxy group; Group, alkylthio group such as ethylthio group; hydroxy group; thiol group and the like. In consideration of the reaction rate of intramolecular cyclization reaction in step 4 below, it is preferable that at least one of R ¹ or R ² is a hydrogen atom, Both R ¹ and R ² are hydrogen atoms Is more preferable. That is, the compound represented by the general formula (1) is preferably a primary alcohol or a secondary alcohol, and more preferably a primary alcohol.

  The novel compound represented by the general formula (3) is reacted with bromine and acetic acid using the compound represented by the general formula (5) as a starting compound as in Step 1 represented by the following chemical reaction formula (I). can get.

［式中、Ｒ^１、Ｒ^２、Ｒ^３及びＲ^４は、それぞれ独立して水素原子又は置換基を有してもよい炭素数１〜２０の炭化水素基である。］

[Wherein, R ¹ , R ² , R ³ and R ⁴ are each independently a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms which may have a substituent. ]

Step 1 represented by the chemical reaction formula (I) is a step of reacting the compound represented by the general formula (5) with bromine and acetic acid. By this reaction, the 2-position, 4-position and 5-position of the thiophene skeleton in the compound represented by the general formula (5) are substituted with bromine, and the hydroxy group is substituted with an acetyl group, which is represented by the general formula (3). A compound can be obtained. R ¹ , R ² , R ³ and R ⁴ in the compound represented by the general formula (5) are the same as those exemplified in the description of the compounds represented by the general formulas (1) to (4). Can be used.

  The usage-amount of bromine in the said process 1 is not specifically limited, It is preferable that it is 3-12 mol with respect to 1 mol of compounds shown by General formula (5). If the amount of bromine used is less than 3 moles, the bromine substitution reaction may be insufficient. On the other hand, when the amount of bromine used exceeds 12 moles, there is a possibility that a substitution reaction other than the 2nd, 4th and 5th positions of the thiophene skeleton may occur, and it is more preferably 6 moles or less. Moreover, the usage-amount of the acetic acid in the said process 1 is not specifically limited, It is preferable that it is 1-100 mass parts with respect to 1 mass part of compounds shown by General formula (5).

  It does not specifically limit as reaction temperature in the said process 1, It is preferable that it is 20-100 degreeC. When reaction temperature is less than 20 degreeC, there exists a possibility that reaction rate may become very slow, and it is more preferable that it is 40 degreeC or more. On the other hand, when reaction temperature exceeds 100 degreeC, there exists a possibility of accelerating | stimulating decomposition | disassembly of a product, and it is more preferable that it is 80 degrees C or less. The compound represented by the general formula (3) thus obtained can be preferably used as a starting compound for the debromination reaction in the next step 2 without isolation.

  The novel compound represented by the general formula (2) is subjected to a debromination reaction with the compound represented by the general formula (3) obtained by the above step 1 as in the step 2 represented by the following chemical reaction formula (II). Can be obtained.

［式中、Ｒ^１、Ｒ^２、Ｒ^３及びＲ^４は、それぞれ独立して水素原子又は置換基を有してもよい炭素数１〜２０の炭化水素基である。］

[Wherein, R ¹ , R ² , R ³ and R ⁴ are each independently a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms which may have a substituent. ]

  Step 2 represented by the chemical reaction formula (II) is a step of debromination reaction of the compound represented by the general formula (3). By this reaction, bromine at the 2-position and 5-position of the thiophene skeleton in the compound represented by the general formula (3) is debrominated to obtain a compound represented by the general formula (2).

  A preferred embodiment of the above step 2 is a method of debromination using zinc powder in the presence of acetic acid. It does not specifically limit as the usage-amount of the zinc powder in the said process 2, It is preferable that it is 2-20 mol with respect to 1 mol of compounds shown by General formula (3). When the usage-amount of zinc powder is less than 2 mol, there exists a possibility that debromination reaction may become inadequate, and it is more preferable that it is 3 mol or more. On the other hand, when the usage-amount of zinc powder exceeds 20 mol, there exists a possibility that the debromination reaction in 4-position may occur, It is more preferable that it is 10 mol or less, It is further more preferable that it is 6 mol or less. Moreover, the usage-amount of the acetic acid in the said process 2 is not specifically limited, It is preferable that it is 0.1-100 mass parts with respect to 1 mass part of compounds shown by General formula (3).

  It does not specifically limit as reaction temperature in the said process 2, It is preferable that it is 80-140 degreeC. When reaction temperature is less than 80 degreeC, there exists a possibility that reaction rate may become very slow, and it is more preferable that it is 90 degreeC or more. On the other hand, when reaction temperature exceeds 140 degreeC, there exists a possibility of promoting decomposition | disassembly of a product, and it is more preferable that it is 120 degrees C or less. The compound represented by the general formula (2) thus obtained can be used as a starting compound for the alkali hydrolysis reaction in the next step 3 without preferably being isolated.

  The novel compound represented by the general formula (1) is obtained by alkaline hydrolysis of the compound represented by the general formula (2) obtained by the above step 2 as in the step 3 represented by the following chemical reaction formula (III). Is obtained.

［式中、Ｒ^１、Ｒ^２、Ｒ^３及びＲ^４は、それぞれ独立して水素原子又は置換基を有してもよい炭素数１〜２０の炭化水素基である。］

[Wherein, R ¹ , R ² , R ³ and R ⁴ are each independently a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms which may have a substituent. ]

  Step 3 represented by the chemical reaction formula (III) is a step of subjecting the compound represented by the general formula (2) to alkali hydrolysis. Alkaline hydrolysis is suitably performed by a method of reacting with a base in the presence of a solvent. Examples of the base used in the alkaline hydrolysis include alkali metal hydroxides such as sodium hydroxide, potassium hydroxide and lithium hydroxide; alkaline earth metal hydroxides such as calcium hydroxide and barium hydroxide. Among these, alkali metal hydroxides are preferably used, and sodium hydroxide is particularly preferably used. The usage-amount of the base used is not specifically limited, It is preferable that it is 0.001-1 mol with respect to 1 mol of compounds shown by General formula (2).

  As the solvent used in Step 3, water, alcohol and the like are preferably used. Examples of the alcohol include methanol, ethanol, n-propanol, and 2-propanol. These solvents may be used alone or in combination. The usage-amount of this solvent is not specifically limited, It is preferable that it is 1-100 mass parts with respect to 1 mass part of compounds shown by General formula (2). Moreover, it does not specifically limit about the reaction temperature at the time of carrying out alkali hydrolysis, It is preferable that it is 0-60 degreeC. When reaction temperature is less than 0 degreeC, there exists a possibility that reaction rate may become very slow, and it is more preferable that it is 10 degreeC or more. On the other hand, when reaction temperature exceeds 60 degreeC, there exists a possibility of accelerating | stimulating decomposition | disassembly of a product, and it is more preferable that it is 40 degrees C or less.

  Further, the present invention provides an intramolecular cyclization reaction of the compound represented by the general formula (1) obtained by the above step 3 as in the step 4 represented by the following chemical reaction formula (IV). A 2,3-dihydro-thieno [3,4-b] furan derivative represented by (4) is obtained.

［式中、Ｒ^１、Ｒ^２、Ｒ^３及びＲ^４は、それぞれ独立して水素原子又は置換基を有してもよい炭素数１〜２０の炭化水素基である。］

[Wherein, R ¹ , R ² , R ³ and R ⁴ are each independently a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms which may have a substituent. ]

  A preferred embodiment of the above step 4 is a method of carrying out an intramolecular cyclization reaction using a metal hydride and a copper reagent. The metal hydride used in Step 4 is not particularly limited, and alkali metal hydrides such as sodium hydride, potassium hydride, and lithium hydride; alkaline earth metal hydrides such as calcium hydride and magnesium hydride, and the like Is mentioned. Among these, alkali metal hydrides are preferably used from the viewpoint of good reactivity. It does not specifically limit as the usage-amount of a metal hydride, It is preferable that it is 1-10 mol with respect to 1 mol of compounds shown by General formula (1).

  Moreover, it does not specifically limit as a copper reagent used at the said process 4, Copper halide; Copper halides, such as copper (I) chloride, copper (I) bromide, copper (I) iodide, etc. are mentioned. From the viewpoint of good reactivity, copper halide is preferably used, and copper (I) bromide is particularly preferably used. It does not specifically limit as the usage-amount of a copper reagent, It is preferable that it is 0.01-1 mol with respect to 1 mol of compounds shown by General formula (1).

  It does not specifically limit as a solvent used by the intramolecular cyclization reaction of the said process 4, An aprotic polar solvent is used suitably. Specific examples include N-methylformamide, N-ethylformamide, N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidinone, 1,3-dimethyl-2-imidazolidinone and other amide solvents. A sulfoxide solvent such as dimethyl sulfoxide, methyl ethyl sulfoxide, and diethyl sulfoxide; These solvents may be used alone or in combination. The usage-amount of this solvent is not specifically limited, It is preferable that it is 1-100 mass parts with respect to 1 mass part of compounds shown by General formula (1).

  The reaction temperature for the intramolecular cyclization reaction is not particularly limited, and is preferably 50 to 200 ° C. When reaction temperature is less than 50 degreeC, there exists a possibility that reaction rate may become very slow, it is more preferable that it is 70 degreeC or more, and it is still more preferable that it is 90 degreeC or more. On the other hand, when reaction temperature exceeds 200 degreeC, there exists a possibility of promoting decomposition | disassembly of a product, and it is more preferable that it is 180 degrees C or less. Moreover, you may isolate and refine | purify as needed after reaction. As a specific example, water and an organic solvent such as toluene, ethyl acetate and methylene chloride are added to the reaction mixture, and separated into an organic phase and an aqueous phase using a separatory funnel, and the organic phase is anhydrous sodium sulfate, etc. And then concentrating after drying, and the resulting crude product may be purified by recrystallization, distillation, silica gel column chromatography, or the like. Thereby, the 2,3-dihydro-thieno [3,4-b] furan derivative represented by the general formula (4) having high purity can be obtained.

  As explained above, 2,3-dihydro-thieno [3] represented by the general formula (4) obtained by using the novel compound of the present invention represented by the general formulas (1), (2) and (3) above. , 4-b] furan derivatives include, for example, intermediates such as pharmaceuticals and agricultural chemicals, foods, beverages, animal feeds, drugs and tobacco, or flavoring agents as described in Japanese Patent Publication No. 48-14067. In addition to being used as an additive to the composition, conductive materials, electrochromic materials, photoelectric conversion materials, electroluminescent materials, nonlinear optical materials, field effect transistor materials, RF-ID materials, memory materials, sensor materials, conductive materials The polymer is preferably used as a raw material monomer for a conductive polymer, particularly preferably for a conductive print paste and an ink jet paint.

  Hereinafter, the present invention will be described more specifically with reference to examples.

Example 1
[Synthesis of 1-acetyl-2- (2,4,5-tribromothiophen-3-yl) -ethane represented by the formula (3a)]
To a 200 ml three-necked flask equipped with a thermometer and a dropping funnel, 15.0 g (117 mmol) of 2- (thiophen-3-yl) -ethan-1-ol represented by the formula (5a) and 27 ml of acetic acid were added. The system was purged with nitrogen and heated to 50 ° C., and then 56.1 g (351 mmol) of bromine was added over 30 minutes. Thereafter, the reaction vessel was shielded from light and stirred at 50 ° C. for 15 hours. After completion of the reaction, 200 ml of hexane, 200 ml of saturated sodium thiosulfate aqueous solution and 200 ml of saturated sodium hydrogen carbonate aqueous solution were added. The organic and aqueous phases were separated and the aqueous phase was extracted with 200 ml of hexane. The combined organic phase was dried over anhydrous sodium sulfate and then concentrated under reduced pressure to give 1-acetyl-2- (2,4,5-tribromothiophen-3-yl)-represented by the formula (3a). A crude product of ethane was obtained. The chemical reaction formula is shown below.

The NMR data of 1-acetyl-2- (2,4,5-tribromothiophen-3-yl) -ethane represented by the formula (3a) was as follows.
¹ H-NMR (270 MHz, CDCl ₃ , TMS) δ: 4.22 (t, 2H, J = 6.8 Hz), 3.01 (t, 2H, J = 6.8 Hz), 2.05 (s, 3H)

Example 2
[Synthesis of 1-acetyl-2- (4-bromothiophen-3-yl) -ethane represented by the formula (2a)]
To a 300 ml three-necked flask equipped with a thermometer and a dropping funnel, 30 ml of acetic acid and 30.6 g (469 mmol) of zinc powder were added. 1-acetyl-2- (2,4,5-tribromothiophene-3 represented by the formula (3a) obtained in Example 1 diluted with 20 ml of acetic acid after replacing the system with nitrogen and heating to 70 ° C. The total amount of -yl) -ethane crude product was added over 1 hour. Thereafter, the system was heated to 100 ° C. and stirred for 3 hours. After completion of the reaction, the system was cooled to room temperature, and 200 ml of hexane and 200 ml of saturated brine were added. The organic and aqueous phases were separated and the aqueous phase was extracted with 200 ml of hexane. The combined organic phases were dried over anhydrous sodium sulfate and concentrated under reduced pressure to give a crude product of 1-acetyl-2- (4-bromothiophen-3-yl) -ethane represented by the formula (2a) Got. The chemical reaction formula is shown below.

The NMR data of 1-acetyl-2- (4-bromothiophen-3-yl) -ethane represented by the formula (2a) was as follows.
_{^{1 H-NMR (270MHz, CDCl}} 3, TMS) δ: 7.24 (d, 1H, J = 3.5Hz), 7.06 (d, 1H, J = 3.5Hz), 4.29 (t, 2H, J = 7.0 Hz), 2.94 (t, 2H, J = 7.0 Hz), 2.04 (s, 3H)

Example 3
[Synthesis of 2- (4-bromothiophen-3-yl) -ethan-1-ol represented by the formula (1a)]
To a 200 ml three-necked flask equipped with a thermometer, 50 ml of 35 wt% aqueous sodium hydroxide and 50 ml of ethanol were added. The whole amount of the crude product of 1-acetyl-2- (4-bromothiophen-3-yl) -ethane represented by the formula (2a) obtained in Example 2 was added to the system, and the mixture was added at room temperature (20 ° C.). Stir for 10 minutes. After completion of the reaction, 100 ml of toluene and 100 ml of saturated brine were added, the organic phase and the aqueous phase were separated, and the aqueous phase was extracted 3 times with 100 ml of toluene. The combined organic phases are dried over anhydrous sodium sulfate and then concentrated under reduced pressure to give a crude product of 2- (4-bromothiophen-3-yl) -ethan-1-ol represented by formula (1a) I got a thing. By purifying the crude product by silica gel column chromatography, 13.2 g (63. 2) of 2- (4-bromothiophen-3-yl) -ethan-1-ol represented by the formula (1a) having the following physical properties was obtained. 7 mmol, an isolated yield of 54.5% from the compound represented by the formula (5a)). The chemical reaction formula is shown below.

The NMR data of 2- (4-bromothiophen-3-yl) -ethan-1-ol represented by the formula (1a) was as follows.
¹ H-NMR (270 MHz, CDCl ₃ , TMS) δ: 7.25 (d, 1H, J = 3.5 Hz), 7.10 (d, 1H, J = 3.5 Hz), 3.85 (t, 2H, J = 6.5 Hz), 2.88 (t, 2H, J = 6.5 Hz), 1.70 (br, 1H)

Example 4
[Synthesis of 2,3-dihydro-thieno [3,4-b] furan represented by the formula (4a)]
In a three-necked flask with an internal volume of 50 ml equipped with a thermometer, 5.40 g (26.1 mmol) of 2- (4-bromothiophen-3-yl) -ethan-1-ol represented by the formula (1a) and N-methyl 10 ml of pyrrolidinone was added. After replacing the system with nitrogen, 1.25 g (31.3 mmol) of sodium hydride (60%) was added, and the mixture was stirred at room temperature for 20 minutes. After heating the system to 95 ° C., 0.47 g (3.3 mmol) of copper (I) bromide was added and stirred for 2 minutes. After completion of the reaction, the reaction vessel was ice-cooled, 10 ml of distilled water and 30 ml of toluene were added, the organic phase and the aqueous phase were separated, and the aqueous phase was extracted with 30 ml of toluene. The combined organic phases were dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain a crude product. By purifying the crude product by silica gel column chromatography, 250 mg (1.98 mmol, 2,98% of 2,3-dihydro-thieno [3,4-b] furan represented by the formula (4a) having the following physical properties was isolated. Rate 7.6%). The chemical reaction formula is shown below.

The NMR data of 2,3-dihydro-thieno [3,4-b] furan represented by the formula (4a) were as follows.
¹ H-NMR (270 MHz, CDCl ₃ , TMS) δ: 6.72 (dd, 1H, J = 2.4 Hz, 1.4 Hz), 6.01 (d, 1H, J = 2.4 Hz), 4.89 (t, 2H, J = 7.8), 2.99 (dt, 2H, J = 1.4 Hz, 7.8 Hz)

Claims (7)

The following general formula (1):

[Wherein, R ¹ , R ² , R ³ and R ⁴ are each independently a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms which may have a substituent. ]
A compound represented by The following general formula (2):

[Wherein, R ¹ , R ² , R ³ and R ⁴ are each independently a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms which may have a substituent. ]
A compound represented by The following general formula (3):

[Wherein, R ¹ , R ² , R ³ and R ⁴ are each independently a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms which may have a substituent. ]
A compound represented by The following general formula (1):

[Wherein, R ¹ , R ² , R ³ and R ⁴ are each independently a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms which may have a substituent. ]
The following general formula (4):

[Wherein, R ¹ , R ² , R ³ and R ⁴ have the same meanings as described above. ]
The manufacturing method of the 2,3-dihydro-thieno [3,4-b] furan derivative shown by these. The following general formula (2):

[Wherein, R ¹ , R ² , R ³ and R ⁴ are each independently a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms which may have a substituent. ]
The following general formula (1):

^{Wherein, R 1, R 2, R} 3 and ^{R 4} have the same meanings as defined above. ]
The manufacturing method of the compound shown by these. The following general formula (3):

[Wherein, R ¹ , R ² , R ³ and R ⁴ are each independently a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms which may have a substituent. ]
The following general formula (2):

[Wherein, R ¹ , R ² , R ³ and R ⁴ have the same meanings as described above. ]
The manufacturing method of the compound shown by these. The following general formula (5):

[Wherein, R ¹ , R ² , R ³ and R ⁴ are each independently a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms which may have a substituent. ]
In the following general formula (3), bromine and acetic acid are reacted with the compound represented by:

[Wherein, R ¹ , R ² , R ³ and R ⁴ have the same meanings as described above. ]
The manufacturing method of the compound shown by these.