JP2005200375A - Method for producing thiophene compound - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for simply producing a thiophene compound in high yield and high purity. <P>SOLUTION: The method for producing a thiophene compound represented by general formula (1) (wherein R<SB>11</SB>and R<SB>13</SB>are each independently a hydrogen atom or a substituent group; R<SB>12</SB>is a substituted or unsubstituted alkyl group, alkenyl group, alkynyl group, aryl group or heterocyclic group, with the proviso that R<SB>11</SB>and R<SB>12</SB>or R<SB>12</SB>and R<SB>13</SB>each together may form a 5- or 6-membered ring) comprises reacting a compound represented by general formula (2) (wherein R<SB>21</SB>and R<SB>23</SB>are each independently a hydrogen atom or a substituent group; R<SB>22</SB>is a substituted or unsubstituted alkyl group, alkenyl group, alkynyl group, alkyl group, aryl group or heterocyclic group, with the proviso that R<SB>21</SB>and R<SB>22</SB>or R<SB>22</SB>and R<SB>23</SB>each together may form 5- or 6-membered ring) with sulfur in the presence of an inorganic base. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a method for producing a thiophene compound. More specifically, the present invention relates to a method for producing a 2-aminothiophene compound in a simple, high yield and high purity.

  A thiophene compound is a useful compound as a synthetic intermediate for functional compounds such as photographic additives, sensitizing dyes, dyes, electronic materials, and pharmaceuticals. Non-Patent Document 1 describes a synthesis method for obtaining a 2-aminothiophene compound by reacting a compound represented by the general formula (2) with sulfur in the presence of an organic base. However, since the dimerization reaction of the compound represented by the general formula (2) always occurs as a side reaction, the yield and purity of the obtained 2-aminothiophene compound are both low, and the purification process is particularly complicated. The dimerization reaction is described in Non-Patent Document 2. On the other hand, Non-Patent Document 3 describes a synthesis method using a catalytic amount of an organic base in order to improve yield and purity. However, the yield and purity are still insufficient, and the substrate versatility is poor.

By K. Geward, Chem. Ber .; 3571 (1965) Yu. T. Abramenko, Journal of Organic Chemistry (US); 230-235 (1986) By MH Elnagdi, Liebigs Ann. Chem .; 1215-1219 (1990)

  As described above, as a method for producing a thiophene compound, when the compound represented by the general formula (2) is reacted with sulfur in the presence of an organic base, the yield is low and the purity is low. It is not a safe manufacturing method. Therefore, the objective of this invention is providing the manufacturing method of the 2-aminothiophene compound represented by General formula (1) with high yield, high purity, and simple.

As a result of investigations to overcome these conventional problems, the present inventors have reacted with sulfur in the presence of an inorganic base using the compound represented by the general formula (2) as a starting material. It has been found that the 2-aminothiophene compound represented by the general formula (1) can be synthesized with high yield and high purity. That is, the above object of the present invention has been achieved by the following method.
(1) A method for producing a thiophene compound represented by the following general formula (1), wherein the compound represented by the following general formula (2) is reacted with sulfur in the presence of an inorganic base.

(Wherein R ₁₁ and R ₁₃ each independently represent a hydrogen atom or a substituent, and R ₁₂ represents a substituted or unsubstituted alkyl group, alkenyl group, alkynyl group, aryl group or heterocyclic group, provided that R ₁₁ and R ₁₂ or R ₁₂ and R ₁₃ may be bonded to each other to form a 5- or 6-membered ring.)

(Wherein R ₂₁ and R ₂₃ each independently represent a hydrogen atom or a substituent, and R ₂₂ represents a substituted or unsubstituted alkyl group, alkenyl group, alkynyl group, aryl group or heterocyclic group, provided that R ₂₁ and R ₂₂ or R ₂₂ and R ₂₃ may be bonded to each other to form a 5- or 6-membered ring.
(2) R _{11 in the} general formula (1) is a hydrogen atom or an electron withdrawing group, and R ₁₃ is a hydrogen atom, a halogen atom, an alkyl group, an aryl group, an alkoxy group, an aryloxy group, or a heterocyclic oxy group. , Acyloxy group, carbamoyloxy group, alkoxycarbonyloxy group, aryloxycarbonyloxy group, amino group (including anilino group), acylamino group, aminocarbonylamino group, alkoxycarbonylamino group, aryloxycarbonylamino group, sulfamoyl The method for producing a thiophene compound according to (1), which is an amino group, an alkyl and arylsulfonylamino group, a mercapto group, an alkylthio group, an arylthio group, a heterocyclic thio group, an acyl group, or an imide group.
(3) 0.01 to 0.5 mol of the inorganic base is mixed with 1 mol of the compound represented by the general formula (2), described in (1) or (2) A method for producing a thiophene compound.
(4) The inorganic base is at least one selected from sodium hydrogen carbonate, potassium hydrogen carbonate, sodium carbonate, potassium carbonate, sodium acetate, potassium acetate, lithium hydroxide, sodium hydroxide and potassium hydroxide. The method for producing a thiophene compound according to any one of (1) to (3).
(5) The method for producing a thiophene compound according to any one of (1) to (4), wherein an alcohol is used as a reaction solvent.

  According to the method for producing a thiophene compound of the present invention, the 2-aminothiophene compound represented by the general formula (1) can be obtained by a simple method, high yield and high purity.

First, the thiophene compound produced by the production method of the present invention will be described in detail.
The thiophene compound obtained by the production method of the present invention is a compound represented by the following general formula (1).

In the general formula (1), R ₁₁ and R ₁₃ each independently represent a hydrogen atom or a substituent, and examples of the substituent include the following groups.
For example, halogen atom, alkyl group (including cycloalkyl group and bicycloalkyl group), alkenyl group (including cycloalkenyl group and bicycloalkenyl group), alkynyl group, aryl group, heterocyclic group, cyano group, hydroxyl group, nitro Group, carboxyl group, alkoxy group, aryloxy group, silyloxy group, heterocyclic oxy group, acyloxy group, carbamoyloxy group, alkoxycarbonyloxy group, aryloxycarbonyloxy group, amino group (including anilino group), acylamino group, Aminocarbonylamino group, alkoxycarbonylamino group, aryloxycarbonylamino group, sulfamoylamino group, alkyl and arylsulfonylamino group, mercapto group, alkylthio group, arylthio group, heterocyclic thio group, Famoyl group, sulfo group, alkyl and arylsulfinyl group, alkyl and arylsulfonyl group, acyl group, aryloxycarbonyl group, alkoxycarbonyl group, carbamoyl group, imide group, phosphino group, phosphinyl group, phosphinyloxy group, phosphini And a ruamino group.

  More specifically, examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.

  Examples of the alkyl group include linear, branched, and cyclic substituted or unsubstituted alkyl groups, and also include cycloalkyl groups, bicycloalkyl groups, and tricyclo structures having many ring structures. An alkyl group (for example, an alkyl group of an alkylthio group) in the substituents described below also represents such an alkyl group. Specifically, the alkyl group is preferably an alkyl group having 1 to 30 carbon atoms, such as a methyl group, ethyl group, n-propyl group, isopropyl group, t-butyl group, n-octyl group, eicosyl group, 2-chloroethyl group, 2-cyanoethyl group, 2-ethylhexyl group and the like can be mentioned, and the cycloalkyl group is preferably a substituted or unsubstituted cycloalkyl group having 3 to 30 carbon atoms, such as cyclohexyl group, cyclopentyl group. 4-n-dodecylcyclohexyl group and the like, and the bicycloalkyl group is preferably a substituted or unsubstituted bicycloalkyl group having 5 to 30 carbon atoms, that is, a bicyclic alkane having 5 to 30 carbon atoms to a hydrogen atom. A monovalent group such as a bicyclo [1,2,2] heptan-2-yl group, B [2,2,2] octan-3-yl group.

Examples of the alkenyl group include linear, branched, and cyclic substituted or unsubstituted alkenyl groups, and include cycloalkenyl groups and bicycloalkenyl groups. Specifically, the alkenyl group is preferably a substituted or unsubstituted alkenyl group having 2 to 30 carbon atoms, such as a vinyl group, an allyl group, a prenyl group, a geranyl group, an oleyl group, and the like. Is preferably a substituted or unsubstituted cycloalkenyl group having 3 to 30 carbon atoms, that is, a monovalent group obtained by removing one hydrogen atom of a cycloalkene having 3 to 30 carbon atoms, such as 2-cyclopentene-1 -Yl group, 2-cyclohexen-1-yl group and the like. As the bicycloalkenyl group, a substituted or unsubstituted bicycloalkenyl group, preferably a substituted or unsubstituted bicycloalkenyl group having 5 to 30 carbon atoms, That is, a monovalent group obtained by removing one hydrogen atom of a bicycloalkene having one double bond, for example, bicyclo [ , 2,1] hept-2-en-1-yl group, a bicyclo [2,2,2] oct-2-en-4-yl group and the like.
The alkynyl group is preferably a substituted or unsubstituted alkynyl group having 2 to 30 carbon atoms, such as an ethynyl group, a propargyl group, or a trimethylsilylethynyl group.

The aryl group is preferably a substituted or unsubstituted aryl group having 6 to 30 carbon atoms, such as a phenyl group, a p-tolyl group, a naphthyl group, an m-chlorophenyl group, an o-hexadecanoylaminophenyl group, and the like. Can be mentioned.
The heterocyclic group is preferably a monovalent group obtained by removing one hydrogen atom from a 5- or 6-membered substituted or unsubstituted aromatic or non-aromatic heterocyclic compound, more preferably 3 carbon atoms. To 30 5- or 6-membered aromatic heterocyclic group, for example, 2-furyl group, 2-thienyl group, 2-pyrimidinyl group, 2-benzothiazolyl group and the like.
The alkoxy group is preferably a substituted or unsubstituted alkoxy group having 1 to 30 carbon atoms, such as a methoxy group, an ethoxy group, an isopropoxy group, a t-butoxy group, an n-octyloxy group, or a 2-methoxyethoxy group. Etc.

The aryloxy group is preferably a substituted or unsubstituted aryloxy group having 6 to 30 carbon atoms, such as a phenoxy group, 2-methylphenoxy group, 4-t-butylphenoxy group, 3-nitrophenoxy group, 2 -Tetradecanoylaminophenoxy group etc. are mentioned.
Preferred examples of the heterocyclic oxy group include substituted or unsubstituted heterocyclic oxy groups having 2 to 30 carbon atoms, such as a 1-phenyltetrazole-5-oxy group and a 2-tetrahydropyranyloxy group.
The acyloxy group is preferably a formyloxy group, a substituted or unsubstituted alkylcarbonyloxy group having 2 to 30 carbon atoms, a substituted or unsubstituted arylcarbonyloxy group having 6 to 30 carbon atoms, such as a formyloxy group, Examples include acetyloxy group, pivaloyloxy group, stearoyloxy group, benzoyloxy group, p-methoxyphenylcarbonyloxy group and the like.
The carbamoyloxy group is preferably a substituted or unsubstituted carbamoyloxy group having 1 to 30 carbon atoms, such as N, N-dimethylcarbamoyloxy group, N, N-diethylcarbamoyloxy group, morpholinocarbonyloxy group, N , N-di-n-octylaminocarbonyloxy group, Nn-octylcarbamoyloxy group and the like.

The alkoxycarbonyloxy group is preferably a substituted or unsubstituted alkoxycarbonyloxy group having 2 to 30 carbon atoms, such as a methoxycarbonyloxy group, an ethoxycarbonyloxy group, a t-butoxycarbonyloxy group, or an n-octylcarbonyloxy group. Etc.
The aryloxycarbonyloxy group is preferably a substituted or unsubstituted aryloxycarbonyloxy group having 7 to 30 carbon atoms, such as phenoxycarbonyloxy group, p-methoxyphenoxycarbonyloxy group, pn-hexadecyloxy. Examples include phenoxycarbonyloxy group.
The amino group is preferably an amino group, a substituted or unsubstituted alkylamino group having 1 to 30 carbon atoms, a substituted or unsubstituted anilino group having 6 to 30 carbon atoms, such as an amino group, a methylamino group, or dimethyl group. An amino group, an anilino group, an N-methyl-anilino group, a diphenylamino group, etc. are mentioned.
The acylamino group is preferably a formylamino group, a substituted or unsubstituted alkylcarbonylamino group having 1 to 30 carbon atoms, a substituted or unsubstituted arylcarbonylamino group having 6 to 30 carbon atoms, such as a formylamino group, Examples include acetylamino group, pivaloylamino group, lauroylamino group, benzoylamino group, 3,4,5-tri-n-octyloxyphenylcarbonylamino group and the like.

The aminocarbonylamino group is preferably a substituted or unsubstituted aminocarbonylamino group having 1 to 30 carbon atoms, such as a carbamoylamino group, an N, N-dimethylaminocarbonylamino group, or an N, N-diethylaminocarbonylamino group. And a morpholinocarbonylamino group.
The alkoxycarbonylamino group is preferably a substituted or unsubstituted alkoxycarbonylamino group having 2 to 30 carbon atoms, such as a methoxycarbonylamino group, an ethoxycarbonylamino group, a t-butoxycarbonylamino group, or an n-octadecyloxycarbonylamino group. N-methyl-methoxycarbonylamino group and the like.
The aryloxycarbonylamino group is preferably a substituted or unsubstituted aryloxycarbonylamino group having 7 to 30 carbon atoms, such as phenoxycarbonylamino group, p-chlorophenoxycarbonylamino group, mn-octyloxyphenoxy. Examples thereof include a carbonylamino group.
The sulfamoylamino group is preferably a substituted or unsubstituted sulfamoylamino group having 0 to 30 carbon atoms, such as a sulfamoylamino group, N, N-dimethylaminosulfonylamino group, Nn- Examples include octylaminosulfonylamino group.

The alkyl and arylsulfonylamino group is preferably a substituted or unsubstituted alkylsulfonylamino group having 1 to 30 carbon atoms, a substituted or unsubstituted arylsulfonylamino group having 6 to 30 carbon atoms, such as a methylsulfonylamino group. Butylsulfonylamino group, phenylsulfonylamino group, 2,3,5-trichlorophenylsulfonylamino group, p-methylphenylsulfonylamino group, and the like.
The alkylthio group is preferably a substituted or unsubstituted alkylthio group having 1 to 30 carbon atoms, such as a methylthio group, an ethylthio group, and an n-hexadecylthio group.
Preferred examples of the arylthio group include substituted or unsubstituted arylthio groups having 6 to 30 carbon atoms such as a phenylthio group, a p-chlorophenylthio group, and an m-methoxyphenylthio group.
Preferred examples of the heterocyclic thio group include substituted or unsubstituted heterocyclic thio groups having 2 to 30 carbon atoms, such as a 2-benzothiazolylthio group and a 1-phenyltetrazol-5-ylthio group.
The sulfamoyl group is preferably a substituted or unsubstituted sulfamoyl group having 0 to 30 carbon atoms, such as N-ethylsulfamoyl group, N- (3-dodecyloxypropyl) sulfamoyl group, N, N-dimethylsulfuryl group. Examples include a famoyl group, an N-acetylsulfamoyl group, an N-benzoylsulfamoyl group, and an N- (N′-phenylcarbamoyl) sulfamoyl group.

As the alkyl and arylsulfinyl groups, a substituted or unsubstituted alkylsulfinyl group having 1 to 30 carbon atoms, a substituted or unsubstituted arylsulfinyl group having 6 to 30 carbon atoms such as a methylsulfinyl group, an ethylsulfinyl group, phenyl Examples thereof include a sulfinyl group and a p-methylphenylsulfinyl group.
As the alkyl and arylsulfonyl groups, a substituted or unsubstituted alkylsulfonyl group having 1 to 30 carbon atoms, a substituted or unsubstituted arylsulfonyl group having 6 to 30 carbon atoms such as a methylsulfonyl group, an ethylsulfonyl group, and a phenyl group are preferable. A sulfonyl group, p-methylphenylsulfonyl group, etc. are mentioned.
The acyl group is preferably a formyl group, a substituted or unsubstituted alkylcarbonyl group having 2 to 30 carbon atoms, a substituted or unsubstituted arylcarbonyl group having 7 to 30 carbon atoms, a substituted or unsubstituted group having 4 to 30 carbon atoms. Heterocyclic carbonyl groups bonded to carbonyl groups at substituted carbon atoms, such as acetyl, pivaloyl, 2-chloroacetyl, stearoyl, benzoyl, pn-octyloxyphenylcarbonyl, 2-pyridyl Examples thereof include a carbonyl group and a 2-furylcarbonyl group.
The aryloxycarbonyl group is preferably a substituted or unsubstituted aryloxycarbonyl group having 7 to 30 carbon atoms, such as phenoxycarbonyl group, o-chlorophenoxycarbonyl group, m-nitrophenoxycarbonyl group, pt- A butylphenoxycarbonyl group etc. are mentioned.

Preferred examples of the alkoxycarbonyl group include substituted or unsubstituted alkoxycarbonyl groups having 2 to 30 carbon atoms such as a methoxycarbonyl group, an ethoxycarbonyl group, a t-butoxycarbonyl group, and an n-octadecyloxycarbonyl group.
The carbamoyl group is preferably a substituted or unsubstituted carbamoyl group having 1 to 30 carbon atoms, such as a carbamoyl group, an N-methylcarbamoyl group, an N, N-dimethylcarbamoyl group, or an N, N-di-n-octyl group. Examples thereof include a carbamoyl group and an N- (methylsulfonyl) carbamoyl group.
Preferred examples of the imide group include an N-succinimide group and an N-phthalimide group.
Preferred examples of the phosphino group include substituted or unsubstituted phosphino groups having 2 to 30 carbon atoms, such as a dimethylphosphino group, a diphenylphosphino group, and a methylphenoxyphosphino group.
The phosphinyl group is preferably a substituted or unsubstituted phosphinyl group having 2 to 30 carbon atoms, such as a phosphinyl group, a dioctyloxyphosphinyl group, a diethoxyphosphinyl group, and the like.
Preferred examples of the phosphinyloxy group include substituted or unsubstituted phosphinyloxy groups having 2 to 30 carbon atoms such as a diphenoxyphosphinyloxy group and a dioctyloxyphosphinyloxy group.
The phosphinylamino group is preferably a substituted or unsubstituted phosphinylamino group having 2 to 30 carbon atoms, such as a dimethoxyphosphinylamino group or a dimethylaminophosphinylamino group.

  Among the above functional groups, those having a hydrogen atom may be substituted with the above functional group. Examples of such functional groups include an alkylcarbonylaminosulfonyl group, an arylcarbonylaminosulfonyl group, an alkylsulfonylaminocarbonyl group, and an arylsulfonylaminocarbonyl group. Examples thereof include a methylsulfonylaminocarbonyl group, a p-methylphenylsulfonylaminocarbonyl group, an acetylaminosulfonyl group, and a benzoylaminosulfonyl group.

R ₁₁ is preferably a hydrogen atom or an electron withdrawing group, more preferably a hydrogen atom, a halogen atom, an alkyl group, an aryl group, a cyano group, a nitro group, a carboxyl group, a carbamoyl group, an alkoxycarbonyl group, an acyl group. Groups, alkyl and arylsulfinyl groups, alkyl and arylsulfonyl groups, sulfamoyl groups or heterocyclic groups.
As used herein, an “electron-withdrawing group” is a substituent having an electron-withdrawing property due to an electronic effect, and Hammett's substituent constant, which is a measure of the electron-withdrawing and electron-donating properties of the substituent. If the σp value is used, it is a substituent having a large σp value. Examples include cyano group, nitro group, halogen atom, carbamoyl group, trifluoromethyl group, alkoxycarbonyl group, acyl group, alkyl and arylsulfonyl group. Hammett's substituent constant σp value will be described briefly. The Hammett rule is an empirical rule proposed by LP Hammett in 1935 to quantitatively discuss the influence of substituents on the reaction or equilibrium of benzene derivatives, but this is widely accepted today. ing. Substituent constants determined by Hammett's rule include a σp value and a σm value, and these values can be found in many general books. For example, JA Dean edition “Lange's Handbook of Chemistry” Edition, 1979 (McGraw-Hill) and “Chemicals” special edition, 122, 96-103, 1979 (Nankodo).
R ₁₁ is particularly preferably a cyano group, an alkoxycarbonyl group, an acyl group, an alkylsulfonyl group or a carbamoyl group.

R ₁₃ is preferably a hydrogen atom, halogen atom, alkyl group, aryl group, alkoxy group, aryloxy group, heterocyclic oxy group, acyloxy group, carbamoyloxy group, alkoxycarbonyloxy group, aryloxycarbonyloxy group, amino group. Group (including anilino group), acylamino group, aminocarbonylamino group, alkoxycarbonylamino group, aryloxycarbonylamino group, sulfamoylamino group, alkyl and arylsulfonylamino group, mercapto group, alkylthio group, arylthio group, hetero A ring thio group, an acyl group or an imide group, particularly preferably a hydrogen atom, an alkyl group or an aryl group.

In the general formula (1), R ₁₂ represents a substituted or unsubstituted alkyl group, alkenyl group, alkynyl group, aryl group or heterocyclic group. R ₁₂ is preferably a branched or cyclic alkyl group, alkenyl group, aryl group, thiophene ring group, pyridine ring group, thiazole ring group or benzothiazole ring group.

  Next, preferred examples of the general formula (1) are given as specific examples, but the present invention is not limited thereto.

  The thiophene compound may exist as a tautomer depending on the type of substituent. Any tautomer in pure form, any mixture of tautomers is encompassed by the compounds of the present invention.

  The thiophene compound includes those accompanied with a counter salt by the synthesis process or isolation method. Any salt may be used, but examples thereof include halogen ions, sulfate ions, nitrate ions, carbonate ions, sulfonate ions, phosphate ions, acetate ions, metal ions, and ammonium ions. Depending on the structure, an inner salt may be formed.

Next, a method for producing the compound represented by the above general formula (1) of the present invention (a method for producing a thiophene compound) will be described in detail.
The production method of the present invention includes a step of reacting a compound represented by the following general formula (2) with sulfur in the presence of an inorganic base.

(Wherein R ₂₁ and R ₂₃ each independently represent a hydrogen atom or a substituent, and R ₂₂ represents a substituted or unsubstituted alkyl group, alkenyl group, alkynyl group, aryl group or heterocyclic group, provided that R ₂₁ and R ₂₂ or R ₂₂ and R ₂₃ may be bonded to each other to form a 5- or 6-membered ring.)
In the general formula _(2), each of R 21 _{to R 23,} the same meaning as each of _R 11 _{to R 13} in the general formula (1). That is, R ₂₁ corresponds to R ₁₁ , R ₂₂ corresponds to R ₁₂ , and R ₂₃ corresponds to R ₁₃ .

The compound represented by the general formula (2) can be obtained by any technique . Org. Chem. , 2784-2789 (1966).
Moreover, as sulfur used in the present invention, it is commercially available in the form of colloidal, crystalline, powdery, sulfur, etc., and any form can be used, but it is preferable to use powdered sulfur. .
Although the usage-amount of sulfur can be selected suitably, about 0.5-10 mol is normally mixed and used with respect to 1 mol of compounds represented by General formula (2), More preferably, it is 0.7-5. In particular, 0.9 to 1.5 mol is used.

Examples of the inorganic base used in the present invention include sodium hydrogen carbonate, potassium hydrogen carbonate, sodium carbonate, potassium carbonate, sodium acetate, potassium acetate, lithium hydroxide, sodium hydroxide, and potassium hydroxide. Sodium hydrogen carbonate, potassium hydrogen carbonate, sodium acetate, and potassium acetate are preferable, and sodium hydrogen carbonate is particularly preferable.
Although the usage-amount of an inorganic base can be selected suitably, about 0.001-10 mol is normally mixed and used with respect to 1 mol of compounds represented by General formula (2), More preferably, it is 0.005-1. 0.5 mol, particularly preferably 0.01 to 0.5 mol.

  Even when there is no solvent in producing the compound represented by the general formula (1), the reaction proceeds by appropriately mixing the compound represented by the general formula (2), sulfur, and an inorganic base, but water or an organic solvent. The reaction proceeds in the same manner even if is used. For example, the compound represented by the general formula (2) and sulfur can be suspended in an organic solvent, an inorganic base can be added, and the reaction mixture can be reacted by heating and stirring. The type of the organic solvent can be appropriately selected depending on the reaction system. For example, acetonitrile, propionitrile, butyronitrile, alcohol (for example, methanol, ethanol, i-propyl alcohol, etc.), methylene chloride, chloroform, Carbon tetrachloride, dichloroethane, ethyl acetate, butyl acetate, toluene, benzene, hexane, diethyl ether, tetrahydrofuran, 1,4-dioxane, N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMAC), or Examples thereof include N, N-dimethylimidazolidinone (DMI) and sulfolane. These solvents may be appropriately combined and used as a mixture. In carrying out the reaction of the present invention, the organic solvent as a reaction solvent is preferably acetonitrile or alcohol, and particularly preferably ethanol. Further, the amount of the organic solvent to be used is not particularly limited and can be appropriately selected according to the type of reaction system. Usually, the organic solvent is generally 0 by mass with respect to the compound of the general formula (2). About 100 times is suitable, 0.5-50 times is preferable, Most preferably, it is 1-20 times.

The reaction temperature in the method of the present invention is not particularly limited and can be appropriately selected depending on the type of reaction system and the concentration of the compound of the reaction species, but is usually about −20 ° C. to 150 ° C., preferably 0 ° C. It is -120 degreeC, Most preferably, it is 20 degreeC-80 degreeC.
Although the reaction time is not particularly limited, it is usually about 1 minute to 24 hours, preferably 5 minutes to 12 hours, and more preferably 10 minutes to 5 hours.
Further, the order of adding the compound represented by the general formula (2), sulfur, and inorganic base into the reaction system is arbitrary, and is not particularly limited.

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

Example 1
A 2-aminothiophene compound (Exemplary Compound D-8) was synthesized according to the following synthesis scheme.

(1) Synthesis of Intermediate A Intermediate A was synthesized according to the synthesis method described in J. Org. Chem. , 2784-2789 (1966) using β-acetylnaphthalene as a starting material.
(2) Synthesis of Exemplary Compound (D-8) Intermediate A 2.18 g (10 mmol) and sulfur 321 mg (10 mmol) were suspended in ethanol 20 mL, and sodium bicarbonate 168 mg (2 mmol) was added at room temperature. When this reaction mixture was heated and stirred at an internal temperature of 50 ° C., the reaction mixture gradually became homogeneous. After stirring at an internal temperature of 50 ° C. for 3 hours and cooling with ice, crystals were deposited. Further, 20 mL of water was added to the reaction solution and stirred for 10 minutes, and then the crystals were collected by filtration, washed with water, dried and 2.33 g of the exemplified compound (D-8) (white crystals, 93% yield, HPLC) (Purity 98.5%).
¹ H-NMR (300 MHz, CDCl ₃ )
8.09 (s, 1H), 7.8-7.9 (m, 3H), 7.6-7.7 (m, 1H), 7.4-7.6 (m, 2H), 6. 47 (s, 1H), 4.90 (s, 2H)

Example 2
A 2-aminothiophene compound (Exemplary Compound D-2) was synthesized according to the following synthesis scheme.

(1) Synthesis of Intermediate B Intermediate B uses 4′-methylacetophenone as a starting material, J. Chem. Res. Miniprint , 2434-2452 (1990); J. Org. Chem. , 2784-2789 (1966) ); Synthesized according to the synthesis method described in J. Am. Chem. Soc. , 1050 (1945).
(2) Synthesis of Exemplary Compound (D-2) 1.82 g (10 mmol) of Intermediate B and 321 mg (10 mmol) of sulfur were suspended in 10 mL of ethanol, and 84 mg (1 mmol) of sodium bicarbonate was added at room temperature. When this reaction mixture was heated and stirred at an internal temperature of 50 ° C., the reaction mixture gradually became homogeneous. The reaction solution was stirred for 2.5 hours at an internal temperature of 50 ° C., and then ice-cooled, 1 mL of 1N hydrochloric acid and 20 mL of water were added and stirred to precipitate crystals. The crystals were collected by filtration, washed with water, and dried to obtain 2.07 g (white crystals, yield 97%, HPLC purity 99.0%) of the exemplified compound (D-2).
¹ H-NMR (300 MHz, CDCl ₃ )
7.47 (d, J = 8.1 Hz, 2H), 7.22 (d, J = 8.1 Hz, 2H), 6.32 (s, 1H), 4.86 (s, 2H), 2. 37 (s, 3H)

Test example
Chem. Ber .; 3571 (1965) and Liebigs Ann. Chem .; 1215-1219 (1990) were used as comparative examples, and the examples of the present invention using inorganic bases were compared with those prepared using organic bases (morpholine). The production rates of Intermediate A, (D-8) and YDye were compared by HPLC.

  10 mmol of sulfur was suspended in 20 mL of ethanol in 10 mmol of the following intermediate A, and the indicated amounts of the bases shown in Table 1 were added at room temperature. The reaction mixture was stirred at an internal temperature of 50 ° C. for the reaction times shown in the table below. And each reaction liquid was extract | collected, and each production rate of the intermediate body A, (D-8), and YDye was calculated | required by the area (%) in HPLC measurement. The results are shown in Table 1.

As shown in Table 1 above, it can be seen that when an inorganic base, particularly sodium hydrogen carbonate, is used as the base, the production rate of (D-8) is high. That is, by using a compound represented by the general formula (2) as a starting material and using sulfur and an inorganic base, particularly sodium hydrogen carbonate, a high yield of the 2-aminothiophene compound represented by the general formula (1) is obtained. And can be synthesized with high purity.

Claims (5)

A method for producing a thiophene compound represented by the following general formula (1), wherein the compound represented by the following general formula (2) is reacted with sulfur in the presence of an inorganic base.

(Wherein R ₁₁ and R ₁₃ each independently represent a hydrogen atom or a substituent, and R ₁₂ represents a substituted or unsubstituted alkyl group, alkenyl group, alkynyl group, aryl group or heterocyclic group, provided that R ₁₁ and R ₁₂ or R ₁₂ and R ₁₃ may be bonded to each other to form a 5- or 6-membered ring.)

(Wherein R ₂₁ and R ₂₃ each independently represent a hydrogen atom or a substituent, and R ₂₂ represents a substituted or unsubstituted alkyl group, alkenyl group, alkynyl group, aryl group or heterocyclic group, provided that R ₂₁ and R ₂₂ or R ₂₂ and R ₂₃ may be bonded to each other to form a 5- or 6-membered ring.) R _{11 in the} general formula (1) is a hydrogen atom or an electron withdrawing group, and R ₁₃ is a hydrogen atom, a halogen atom, an alkyl group, an aryl group, an alkoxy group, an aryloxy group, a heterocyclic oxy group, or an acyloxy group. Carbamoyloxy group, alkoxycarbonyloxy group, aryloxycarbonyloxy group, amino group (including anilino group), acylamino group, aminocarbonylamino group, alkoxycarbonylamino group, aryloxycarbonylamino group, sulfamoylamino group, The method for producing a thiophene compound according to claim 1, which is an alkyl or arylsulfonylamino group, a mercapto group, an alkylthio group, an arylthio group, a heterocyclic thio group, an acyl group or an imide group.   The method for producing a thiophene compound according to claim 1, wherein 0.01 to 0.5 mol of the inorganic base is mixed with 1 mol of the compound represented by the general formula (2).   The inorganic base is at least one selected from sodium hydrogen carbonate, potassium hydrogen carbonate, sodium carbonate, potassium carbonate, sodium acetate, potassium acetate, lithium hydroxide, sodium hydroxide and potassium hydroxide. The manufacturing method of the thiophene compound of any one of 1-3. The method for producing a thiophene compound according to any one of claims 1 to 4, wherein an alcohol is used as a reaction solvent.