Method for producing thiazole compounds

Abstract

To provide a production method for a thiazole compound capable of efficiently obtaining a compound having two thiazole rings by few processes.SOLUTION: There is provided a production method for a thiazole compound represented by a formula (2) [in the formula, the dotted line arcs represented by B1 and B2 indicate that the ring structures which may have a skeleton part represented by a full line and a substituent are formed, and the dotted line in the skeleton part represented by the full line indicates that a pair of atoms connected by the dotted line may be connected by a double bond]. The method includes a process of cyclizing a compound represented by formula (1) [in the formula, each of A1 and A2 represents 4-15C aromatic ring or heterocycle which is independent of each other and may have a substituent] under the existence of at least one oxidant, at least one oxidation auxiliary agent and at least one base.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a process for producing a thiazole compound. [Background technology]

[0002] Compounds having a thiazole ring are useful for applications such as medicines and electrical materials. As a method for synthesizing such compounds, Non-Patent Document 1 describes a synthesis method in which potassium ferricyanide is used in an ethanol solvent for a compound having one thiocarbonyl group. In addition, Non-Patent Document 2 describes a synthesis method in which iron chloride is used in a dimethyl sulfoxide (DMSO) solvent. [Prior art documents] [Non-patent literature]

[0003] [Non-Patent Document 1] Annerose Muller et al. “Darstellung von substituierten 2-Aryl(Hetaryl)-naphtho-[1,2-d]thiazolen”, Zeitschrift fuer Chemie, 1985, Volume 25, Issue 1, pp.23-24 [Non-Patent Document 2] Haibo Wang et al. “Fe-catalysed oxidative CH functionalization / CS bond formation”, Chemical Communications, 2012, Volume 48, pp.76-78 Summary of the Invention [Problem to be solved by the invention]

[0004] However, when the methods described in Non-Patent Documents 1 and 2 are applied to the synthesis of a compound having two thiazole rings, multiple steps may be required, and the methods are not sufficient for producing the compound.

[0005] Therefore, an object of the present invention is to provide a method for producing a thiazole compound, which can efficiently produce a compound having two thiazole rings through fewer steps. [Means for solving the problem]

[0006] As a result of detailed studies to solve the above problems, the present inventors have found that a compound having two thiazole rings can be efficiently obtained by using an oxidizing agent, an oxidation promoter, and a base in combination. That is, the present invention includes the following preferred embodiments. [1] In the presence of at least one oxidizing agent, at least one oxidation promoter and at least one base, a compound represented by the formula (1) is reacted with a fluorine-containing compound represented by the formula (1). [ka] [In the formula, A1 and A2 each independently represent an aromatic ring or heterocycle having 4 to 15 carbon atoms which may have a substituent] The method includes a step of cyclizing a compound represented by formula (2): [ka] [In the formula, the dotted arcs represented by B1 and B2 form a ring structure which may have a substituent together with the skeletal portion represented by the solid line; the dotted portion in the skeletal portion represented by the solid line indicates that a pair of atoms connected by the dotted line may be connected by a double bond] A method for producing a thiazole compound represented by the formula: [2] The method according to [1], wherein A1 and / or A2 in the formula (1) contain an aromatic ring having an electron-donating group. [3] The method according to [1] or [2], wherein the oxidizing agent comprises an iron halide compound. [4] The method according to any one of [1] to [3], wherein the oxidation promoter comprises a persulfate. [5] The method according to any one of [1] to [4], wherein the oxidizing agent is present in an amount of 0.01 molar equivalent or more and 4 molar equivalents or less relative to 1 molar equivalent of the compound represented by the formula (1). [6] The method according to any one of [1] to [5], wherein the base comprises a pyridine derivative. [7] The method according to any one of [1] to [6], wherein the base is present in an amount of 2 molar equivalents or more and 82.5 molar equivalents or less relative to 1 molar equivalent of the compound represented by the formula (1). [8] The method according to any one of [1] to [7], wherein the cyclization is carried out in the presence of a solvent. [9] The method according to [8], wherein the solvent comprises an aprotic polar solvent and / or an aromatic solvent. Effect of the Invention

[0007] According to the present invention, there can be provided a method for producing a thiazole compound, which can efficiently produce a compound having two thiazole rings through fewer steps. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0008] Hereinafter, the embodiments of the present invention will be described in detail. Note that the scope of the present invention is not limited to the embodiments described here, and various modifications can be made without departing from the spirit of the present invention.

[0009] The present invention relates to a method for producing a thiol compound represented by the formula (1) in the presence of at least one oxidizing agent, at least one co-oxidizing agent and at least one base. [ka] [In the formula, A1 and A2 each independently represent an aromatic ring or heterocycle having 4 to 15 carbon atoms which may have a substituent] The method includes a step of cyclizing a compound represented by formula (2): [ka] [In the formula, the dotted arcs represented by B1 and B2 form a ring structure which may have a substituent together with the skeletal portion represented by the solid line; the dotted portion in the skeletal portion represented by the solid line indicates that a pair of atoms connected by the dotted line may be connected by a double bond] The present invention relates to a method for producing a thiazole compound represented by the following formula:

[0010] In the present invention, the mechanism by which cyclization proceeds is not clear, but the following mechanism is presumed. Trivalent iron oxidizes the sulfur atom of the compound represented by formula (1) to form a sulfur radical. The sulfur radical bonds with the carbon atoms in A1 and A2, and cyclization proceeds to form a thiazole ring. Iron that has been reduced from trivalent to divalent to form the sulfur radical is oxidized back to trivalent by the oxidation promoter. However, even if the mechanism by which cyclization proceeds differs from the above presumption, it is still within the scope of the present invention.

[0011] In the present invention, A1 and A2 in the compound represented by the general formula (1) each independently represent an aromatic ring or heterocyclic ring having 4 to 15 carbon atoms, which may have a substituent. Examples of such aromatic rings include, but are not limited to, a benzene ring, a naphthalene ring, a phenanthrene ring, and an anthracene ring.

[0012] In the present invention, a heterocycle means a ring containing at least one atom other than carbon atom, such as an oxygen atom, a sulfur atom, or a nitrogen atom, as an atom constituting the ring. Examples of such heterocycles include, but are not limited to, a furan ring, a benzofuran ring, a pyran ring, a pyrrole ring, an indole ring, a thiophene ring, a benzothiophene ring, a pyridine ring, a pyrazine ring, a pyrimidine ring, a pyrroline ring, a pyrazole ring, a thiazole ring, a benzothiazole ring, a thienothiazole ring, an oxazole ring, a benzoxazole ring, a quinoline ring, and a phenanthroline ring.

[0013] Among the above aromatic rings and heterocyclic rings, a benzene ring and a naphthalene ring are preferred from the viewpoint of easiness in proceeding with the reaction, and a benzene ring is more preferred.

[0014] Examples of the substituent that A1 and A2 may have include, but are not limited to, a halogen atom, an alkyl group having 1 to 10 carbon atoms, an alkoxy group having 1 to 10 carbon atoms, an aryl group, an alkoxycarbonyl group having 1 to 8 carbon atoms, a hydroxyl group, a sulfonic acid group, a halogenated alkyl group having 1 to 10 carbon atoms, a cyano group, a nitro group, a nitroso group, an amino group, a carboxy group, an alkylsulfanyl group having 1 to 8 carbon atoms, an aryloxy group having 1 to 8 carbon atoms, a thiol group, and a sulfamoyl group.

[0015] The number of the substituents is not particularly limited, but when the group has a substituent, usually, 1 to 2 substituents are preferred.

[0016] From the viewpoint of facilitating the reaction, A1 and / or A2 preferably contain an aromatic ring having an electron-donating group, more preferably contain an aromatic ring having an alkyl group having 1 to 10 carbon atoms or an alkoxy group having 1 to 10 carbon atoms, and further preferably contain an aromatic ring having a methyl group or a methoxy group.

[0017] A1 and / or A2 are, for example, the following formulae (A-1) to (A-11): [ka] [In the formula, * represents a bond and Me represents a methyl group] Examples of the group include a group represented by the following formula:

[0018] In the present invention, the oxidizing agent preferably contains an iron halide compound. Examples of the iron halide compound include iron fluoride, iron chloride, iron bromide, and iron iodide, and iron chloride or iron bromide is preferred because it is easy to obtain the target substance having a thiazole ring in high yield and is easy to handle. The iron halide may be used alone or in combination of two or more.

[0019] Hydrates of iron halide compounds exist, but it is preferable to use anhydrous iron because there is no risk of the reaction efficiency decreasing due to the inclusion of hydrated water in the system. Furthermore, iron halide compounds include those containing divalent iron and those containing trivalent iron, but iron halide containing trivalent iron is preferred because it is easy to oxidize the sulfur element in the compound represented by formula (1) and form sulfur radicals in the above-mentioned cyclization mechanism. In this reaction, trivalent iron can be reduced to divalent iron.

[0020] The oxidizing agent is present in an amount of preferably 0.01 molar equivalent or more, more preferably 0.1 molar equivalent or more, and preferably 4 molar equivalents or less, more preferably 2 molar equivalents or less, relative to 1 molar equivalent of the compound represented by formula (1). When the amount of the oxidizing agent is equal to or more than the lower limit and equal to or less than the upper limit, it is easy to form sulfur radicals necessary for cyclization and to suppress side reactions. When an oxidizing agent other than an iron halide compound is used in combination, the proportion of the iron halide compound in the total oxidizing agent is preferably 80 mass% or more, more preferably 90 mass% or more, and even more preferably 95 mass% or more.

[0021] In the present invention, the oxidation assistant preferably contains a persulfate. Examples of persulfate include ammonium persulfate, sodium persulfate, and potassium persulfate, but ammonium persulfate is preferred because it is easy to reoxidize the oxidant and the cyclization is likely to proceed efficiently. One type of persulfate may be used alone, or two or more types may be used in combination. As described above, the trivalent iron contained in the iron halide, which is the oxidant, can oxidize the sulfur in the compound represented by formula (1) and reduce itself to divalent iron, but the oxidation assistant in the present invention mainly plays a role in oxidizing the reduced divalent iron back to trivalent iron. If the oxidation assistant does not exist, it is thought that a large amount of the oxidant is required to oxidize the compound represented by formula (1), but by using the oxidation assistant in combination, the oxidant can be reused, and the amount of the oxidant required can be reduced. In the present invention, depending on the reaction conditions, the compound acting as an oxidant can act as an oxidation assistant and / or the compound acting as an oxidation assistant can act as an oxidant. In a preferred embodiment of the present invention, the oxidizing agent includes one or more selected from the group consisting of iron chloride and iron bromide, and the oxidizing co-agent includes one or more selected from the group consisting of ammonium persulfate, sodium persulfate, and potassium persulfate.

[0022] The oxidation aid is present in an amount of preferably 2 molar equivalents or more, more preferably 4 molar equivalents or more, and preferably 10 molar equivalents or less, more preferably 8 molar equivalents or less, relative to 1 molar equivalent of the compound represented by formula (1). When the amount of the oxidation aid is equal to or more than the lower limit and equal to or less than the upper limit, the oxidizing agent is easily reoxidized sufficiently and excessive oxidation is easily suppressed. When an oxidation aid other than persulfate is used in combination, the proportion of persulfate in the total oxidation aid is preferably 85 mass% or more, more preferably 95 mass% or more, and even more preferably 98 mass% or more.

[0023] In the present invention, the base preferably contains a pyridine derivative. Examples of pyridine derivatives include pyridine, 2-methylpyridine (α-picoline), 3-methylpyridine (β-picoline), 4-methylpyridine (γ-picoline), 5-ethyl-2-picoline, and 2,6-lutidine, among which pyridine and 3-methylpyridine are preferred because cyclization proceeds selectively and side reactions are easily suppressed. The pyridine derivative may be used alone or in combination of two or more.

[0024] The base is preferably 2 molar equivalents or more, more preferably 10 molar equivalents or more, even more preferably 15 molar equivalents or more, and preferably 82.5 molar equivalents or less, more preferably 65 molar equivalents or less, and even more preferably 55 molar equivalents or less, relative to 1 molar equivalent of the compound represented by the formula (1). When the amount of the base is equal to or more than the lower limit and equal to or less than the upper limit, selective cyclization is likely to proceed, so that the desired thiazole ring derivative is likely to be obtained. In addition, in any purification step, the removal of the solvent may be facilitated. When a base other than a pyridine derivative is used in combination, the proportion of pyridine in the total base is preferably 70% by mass or more, more preferably 80% by mass or more, and even more preferably 90% by mass or more. When a pyridine derivative is used as a solvent to be described later, the pyridine derivative as the solvent may also serve as a base.

[0025] In the present invention, the step of cyclizing the compound of formula (1) in the presence of at least one oxidizing agent, at least one oxidation promoter, and at least one base to obtain the compound represented by formula (2) is preferably carried out in the presence of a solvent.

[0026] The solvent preferably contains an aprotic polar solvent and / or an aromatic solvent. Examples of such aprotic polar solvents include acetonitrile, dimethylsulfoxide, dimethylformamide, dimethylacetamide, dichloromethane, dichloroethane, tetrahydrofuran, ethyl acetate, acetone, dimethylimidazolidinone, hexamethylphosphoric triamide, and N-methylpyrrolidone. Examples of aromatic solvents include pyridine and its derivatives, benzene, chlorobenzene, dichlorobenzene, xylene, toluene, dimethoxybenzene, mesitylene, and dimethylaniline. These solvents may be used alone or in combination of two or more. As described above, when the solvent contains pyridine and / or its derivatives, it may also function as a base, so that the solvent preferably contains pyridine and / or its derivatives. When a solvent other than pyridine and / or its derivatives is used in combination, the ratio of each solvent is not particularly limited, but the amount of pyridine and / or its derivatives in the total solvent is within the range specified for the base.

[0027] The amount of the solvent used is not particularly limited, but is usually 2 parts by mass or more, preferably 5 parts by mass or more, and more preferably 10 parts by mass or more, relative to 1 part by mass of the compound represented by formula (1) so that each compound can be sufficiently dissolved and cyclization can proceed efficiently, and is usually 100 parts by mass or less, preferably 70 parts by mass or less, and more preferably 50 parts by mass or less, to avoid using an excessive amount of solvent.

[0028] In the present invention, the cyclization step may be carried out at a temperature of, for example, 0 to 50°C, preferably 5 to 40°C, more preferably 10 to 30°C, and further preferably room temperature (about 15 to 25°C). When the temperature of the cyclization step is within the above range, side reactions are easily suppressed. In addition, since the conditions are mild, the target compound can be obtained more safely. The method of adjusting the temperature is not particularly limited, and for example, an oil bath or a water bath can be used.

[0029] The time for the cyclization step is not particularly limited. Although the time required for the cyclization step tends to be shorter when the temperature is high, side reactions are more likely to occur, so the cyclization step may be carried out for any time depending on the type, ratio, and temperature of the compounds used. The time for the cyclization step may be, for example, 0.5 to 24 hours, preferably 1 to 18 hours, and more preferably 3 to 12 hours. In the present invention, the time for the cyclization step is set to the time when the compound represented by formula (1), the base, and one or more of the oxidizing agent and the oxidation promoter start to coexist, and is set to the time when the conversion of the raw materials and the reaction intermediates stops.

[0030] The cyclization step may be carried out in air or under an inert gas atmosphere (e.g., nitrogen, argon, etc.), and may be carried out under normal pressure, elevated pressure, or reduced pressure. In a preferred embodiment, it is carried out under normal pressure and an inert gas atmosphere.

[0031] In the present invention, the compound represented by formula (1), the oxidizing agent, the oxidizing agent, and the base are preferably dehydrated before the cyclization step. The method for dehydration is not particularly limited, but examples thereof include drying.

[0032] In the present invention, the method of cyclizing the compound represented by formula (1) in the presence of the oxidizing agent, the oxidizing assistant, and the base is not particularly limited, and any method may be selected depending on the type and amount of the compound to be used. For example, a method of dissolving the compound represented by formula (1), the oxidizing agent, the oxidizing assistant, and the base in a solvent and mixing them can be mentioned. In this case, the order in which the compound represented by formula (1), the oxidizing agent, the oxidizing assistant, and the base are dissolved in the solvent does not matter, and they may be dissolved in any order depending on the type or amount of the compound to be used. In addition, the method of mixing the compounds is also not particularly limited, and each compound may be added directly to the solvent, or each compound may be dissolved in a solvent in advance to form a solution, and the solutions may be mixed. Alternatively, a method of combining the above two methods, that is, some compounds may be added directly and some compounds may be added in a solution state. The mixing method is also not particularly limited, and each compound may be added to the system at the same time, or each compound may be added continuously one by one. When each compound is added continuously in a solution state, the solution may be added dropwise. In addition, the oxidizing agent or the oxidizing assistant may also be dissolved in a solvent, and then the solution may be added dropwise.

[0033] The reaction system may contain substances other than the above-mentioned compounds as long as they do not affect the cyclization, such as molecular sieves.

[0034] Through the cyclization step, the compound represented by formula (1) is converted into a compound represented by formula (2): [ka] [In the formula, the dotted arcs represented by B1 and B2 form a ring structure which may have a substituent together with the skeletal portion represented by the solid line; the dotted portion in the skeletal portion represented by the solid line indicates that a pair of atoms connected by the dotted line may be connected by a double bond] That is, the nitrogen atom and sulfur atom in the compound represented by formula (1) are bonded to the carbon atoms in A1 and A2 to form the ring structure represented by B1 and B2, thereby obtaining a compound represented by formula (2) having a thiazole ring.

[0035] The progress of cyclization from the compound represented by formula (1) to the compound represented by formula (2) can be monitored, for example, by in-situ FTIR (Fourier transform infrared spectroscopy).

[0036] After the cyclization has progressed completely as determined by the monitoring, the compound represented by formula (2) may be purified, if necessary, by removing the solvent used in the cyclization. The purification method is not particularly limited, and known methods such as distillation, separation, filtration, etc. may be used.

[0037] According to the manufacturing method of the present invention, the desired compound having two rings can be obtained efficiently with fewer steps even from starting compounds having substituents that have been considered difficult to obtain. Specifically, two thiazole rings can be formed in one step without repeated cyclization steps. Furthermore, the desired compound having two rings can be obtained in a relatively high yield. EXAMPLES

[0038] The present invention will be described in more detail with reference to the following examples and comparative examples, but the present invention is not limited thereto.

[0039] <Yield> The yield of the target compound was determined by high performance liquid chromatography (HPLC) under the following measurement conditions. (Measurement conditions) Measurement equipment: HPLC LC-10AT (Shimadzu Corporation) Column: L-Column ODS (inner diameter 3.0 mm, length 150 mm, particle size 3 μm) Temperature: 40℃ Mobile phase A: 0.1%(v / v)-TFA / water Mobile phase B: 0.1% (v / v)-TFA / acetonitrile Gradient: 0min 10%-B 30min 100%-B 45min 100%-B Flow rate: 0.5mL / min Injection volume: 5μL Detection wavelength: 254 nm

[0040] <Production of thiazole compounds> Example 1 The following formula: [ka] [In the formula, Me represents a methyl group] 0.40 g of a compound represented by the formula (hereinafter referred to as compound A) was added to a 20 mL four-neck flask equipped with a stirrer, a Dimroth condenser, and a thermometer, and 4.48 g (11.2 parts by mass relative to compound A) of pyridine (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) was added and stirred to dissolve. Next, 0.033 g (0.1 molar equivalent relative to compound A) of iron (III) bromide (manufactured by Sigma-Aldrich Japan Co., Ltd.) and 1.01 g (4.0 molar equivalent relative to compound A) of ammonium persulfate (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) were added and stirred, and the internal temperature was set to 25°C. After stirring for 12 hours at 25°C, 4.0 g of water was added and filtered, and 0.40 g of a crude product was obtained as a filtrate. Compound A was converted to the following formula: [ka] [In the formula, Me represents a methyl group] (hereinafter referred to as Compound B) was obtained in a yield of 96%.

[0041] Example 2 Cyclization was carried out in the same manner as in Example 1, except that pyridine was changed to 3-methylpyridine (manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd.) (11.2 parts by mass relative to compound A). The yield of compound B was 71%.

[0042] Example 3 Cyclization was carried out in the same manner as in Example 1, except that ammonium persulfate was replaced with sodium persulfate (manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd.) (4.0 molar equivalents relative to compound A). The yield of compound B was 89%.

[0043] Example 4 Dimethyl sulfoxide (DMSO) (manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd.) (7.0 parts by mass relative to compound A) and pyridine (4 molar equivalents relative to compound A) were added to a 20 mL four-neck flask equipped with a stirrer, a Dimroth condenser, and a thermometer, and iron (III) bromide (0.1 molar equivalent relative to compound A) and ammonium persulfate (2.0 molar equivalents relative to compound A) were added and mixed with stirring until the internal temperature was 25°C. To this, 0.40 g of compound A dissolved in DMSO (4.2 parts by mass relative to compound A) was gradually added over 2 hours, and the mixture was further stirred at 25° C. for 10 hours. Then, 4.0 g of water was added and filtered to obtain compound B. The yield of compound B was 91%.

[0044] Example 5 Cyclization was carried out in the same manner as in Example 1, except that iron (III) bromide was changed to iron (III) chloride (0.1 molar equivalent relative to compound A), ammonium persulfate (4.0 molar equivalent relative to compound A) was changed to sodium persulfate (8.0 molar equivalent relative to compound A), pyridine was changed from 50.1 molar equivalent relative to compound A to 4 molar equivalent, and acetonitrile (12.0 parts by mass relative to compound A) was used as the solvent. The yield of compound B was 69%.

[0045] Example 6 Cyclization was carried out in the same manner as in Example 1, except that iron (III) bromide was changed to iron (III) chloride (0.1 molar equivalent relative to compound A), ammonium persulfate was changed to sodium persulfate (4.0 molar equivalent relative to compound A), and pyridine was changed to a mixture of pyridine and monochlorobenzene (1:1 in mass ratio) (11.2 parts by mass relative to compound A). The yield of compound B was 69%.

[0046] Example 7 Cyclization was carried out in the same manner as in Example 6, except that the mixture of pyridine and monochlorobenzene (1:1 by mass ratio) was changed to a mixture of pyridine and dimethoxybenzene (1:1 by mass ratio) (11.2 parts by mass relative to compound A). The yield of compound B was 76%.

[0047] Example 8 Cyclization was carried out in the same manner as in Example 1, except that iron(III) bromide was changed to iron(III) chloride (0.1 molar equivalent relative to compound A) and ammonium persulfate was changed to sodium persulfate (4.0 molar equivalent relative to compound A). The yield of compound B was 80%.

[0048] Example 9 Cyclization was carried out in the same manner as in Example 1, except that iron(III) bromide was changed to iron(III) chloride (0.1 molar equivalent relative to compound A) and sodium persulfate was changed to potassium persulfate (4.0 molar equivalent relative to compound A). The yield of compound B was 66%.

[0049] Example 10 Cyclization was carried out in the same manner as in Example 1, except that iron(III) bromide was replaced with iron(III) chloride (0.1 molar equivalent relative to compound A). The yield of compound B was 86%.

[0050] Example 11 Cyclization was carried out in the same manner as in Example 8, except that the amount of iron(III) chloride was changed from 0.1 molar equivalent to 0.01 molar equivalent relative to compound A. The yield of compound B was 77%.

[0051] Example 12 In a 20mL four-neck flask equipped with a stirrer, a Dimroth condenser, and a thermometer, 0.40g of compound A, sodium persulfate (4.0 molar equivalents relative to compound A), and pyridine (11.2 parts by mass relative to compound A) were stirred and mixed, and the internal temperature was set to 25°C. Iron (III) chloride (2.0 molar equivalents relative to compound A) was gradually added thereto over 3 hours, and the mixture was further stirred at 25°C for 9 hours. Then, 4.0g of water was added and filtered to obtain compound B. The yield of compound B was 75%.

[0052] Example 13 Instead of compound A, [ka] [In the formula, Me represents a methyl group] The cyclization was carried out in the same manner as in Example 5, except that a compound represented by the following formula (hereinafter referred to as compound C) was used, the amount of iron(III) chloride was 0.1 molar equivalent relative to compound C, the amount of sodium persulfate was 8.0 molar equivalent relative to compound C, the amount of acetonitrile was 11.2 parts by mass relative to compound C, and the amount of pyridine was 4.0 molar equivalent relative to compound C. [ka] [In the formula, Me represents a methyl group] The yield of the compound represented by the formula (hereinafter referred to as compound D) was 35%.

[0053] Example 14 Cyclization was carried out in the same manner as in Example 13, except that iron(III) chloride was changed to iron(III) bromide (0.1 molar equivalent relative to compound C), and sodium persulfate (8.0 molar equivalent relative to compound C) was changed to ammonium persulfate (4.0 molar equivalent relative to compound C). The yield of compound D was 34%.

[0054] Example 15 Instead of compound C, [ka] The cyclization was carried out in the same manner as in Example 13, except that a compound represented by the following formula (hereinafter referred to as compound E) was used, the amount of iron (III) chloride was 0.1 molar equivalent relative to compound E, the solvent was changed from acetonitrile (11.2 parts by mass relative to compound C) to pyridine (12 parts by mass relative to compound E), and sodium persulfate (8.0 molar equivalent relative to compound C) was changed to ammonium persulfate (4.0 molar equivalent relative to compound E). [ka] The yield of the compound represented by the formula (hereinafter referred to as compound F) was 98%.

[0055] Comparative Example 1 The cyclization was carried out in the same manner as in Example 1, except that iron (III) bromide (0.1 molar equivalent relative to compound A) was changed to potassium ferricyanide (4.0 molar equivalent relative to compound A), pyridine (11.2 parts by mass relative to compound A) was changed to ethanol (12.0 parts by mass relative to compound A), sodium hydroxide (4.0 molar equivalent relative to compound A) was used as a base, and ammonium persulfate was not used. The yield of compound B was 0%.

[0056] Comparative Example 2 The cyclization was carried out in the same manner as in Example 1, except that iron(III) bromide (0.1 molar equivalent relative to compound A) was changed to thionyl chloride (10.0 molar equivalent relative to compound A), pyridine (11.2 parts by mass relative to compound A) was changed to water (10.0 parts by mass relative to compound A), and ammonium persulfate was not used. The yield of compound B was 0%.

[0057] Comparative Example 3 Cyclization was carried out in the same manner as in Example 1, except that iron(III) bromide (0.1 molar equivalent relative to compound A) was replaced with N-bromosuccinimide (1.2 molar equivalent relative to compound A), pyridine (11.2 parts by mass relative to compound A) was replaced with chloroform (10.0 parts by mass relative to compound A), and ammonium persulfate was not used. The yield of compound B was 0%.

[0058] Comparative Example 4 Cyclization was carried out in the same manner as in Example 1, except that iron (III) bromide (0.1 molar equivalent relative to compound A) was changed to cerium (IV) ammonium nitrate (4.2 molar equivalent relative to compound A), pyridine (11.2 parts by mass relative to compound A) was changed to a mixture of 100 parts by mass of acetonitrile and 10.0 parts by mass of water, sodium hydrogen carbonate (6.0 parts by mass relative to compound A) was used as a base, and ammonium persulfate was not used. The yield of compound B was 0%.

[0059] The above results are summarized in Table 1.

[0060] [Table 1]

[0061] It is clear that all of Examples 1 to 15 are production methods capable of obtaining a compound having two thiazole rings with fewer steps, whereas Comparative Examples 1 to 4 failed to obtain a compound having two thiazole rings. [Industrial Applicability]

[0062] The present invention provides a method for efficiently producing a thiazole compound having two thiazole rings through a small number of steps. Such a method is useful for efficiently producing a thiazole compound useful for applications such as medicines and electrical materials. Preferred aspects of the present specification include at least the following. [1] In the presence of at least one oxidizing agent, at least one oxidation promoter, and at least one base, a thiol group represented by the formula (1) is reacted with a thiol group represented by the formula (1). TIFF0007597525000014.tif3184 [In the formula, A 1 and A 2 each independently represents an aromatic ring or heterocycle having 4 to 15 carbon atoms which may have a substituent. The method includes a step of cyclizing a compound represented by formula (2): TIFF0007597525000015.tif30105 [In the formula, B 1 and B. 2 represents that the dotted arc, together with the skeletal portion represented by the solid line, forms a ring structure which may have a substituent; the dotted portion in the skeletal portion represented by the solid line represents that a pair of atoms connected by the dotted line may be connected by a double bond. A method for producing a thiazole compound represented by the formula: [2] A in the above formula (1) 1 and / or A 2 The method according to claim 1, wherein the aromatic ring has an electron-donating group. [3] The method according to [1] or [2], wherein the oxidizing agent comprises an iron halide compound. [4] The method according to any one of [1] to [3], wherein the oxidation promoter comprises a persulfate. [5] The method according to any one of [1] to [4], wherein the oxidizing agent is present in an amount of 0.01 molar equivalent to 4 molar equivalents relative to 1 molar equivalent of the compound represented by formula (1). [6] The method according to any one of [1] to [5], wherein the base comprises a pyridine derivative. [7] The method according to any one of [1] to [6], wherein the base is present in an amount of 2 molar equivalents or more and 82.5 molar equivalents or less relative to 1 molar equivalent of the compound represented by the formula (1). [8] The method according to any one of [1] to [7], wherein the cyclization is carried out in the presence of a solvent. [9] The method according to [8], wherein the solvent comprises an aprotic polar solvent and / or an aromatic solvent.

Claims

[Claim 1] In the presence of at least one oxidizing agent, at least one co-oxidizing agent, at least one base, and a solvent, a compound represented by the formula (1) is reacted with a fluorine-containing compound represented by the formula (1) 【Chemistry 1】 [In the formula, A １ and A ２ each independently represents an aromatic ring or heterocycle having 4 to 15 carbon atoms, which has an alkyl group having 1 to 10 carbon atoms or an alkoxy group having 1 to 10 carbon atoms. The method includes a step of cyclizing a compound represented by the formula: the oxidizing agent comprises an iron halide compound; The oxidation promoter includes a persulfate. The base comprises a pyridine derivative, The solvent includes an aprotic polar solvent and / or an aromatic solvent; the oxidizing agent is present in an amount of 0.01 molar equivalent to 4 molar equivalents relative to 1 molar equivalent of the compound represented by formula (1); the oxidation promoter is present in an amount of 2 to 10 molar equivalents relative to 1 molar equivalent of the compound represented by formula (1); The base is present in an amount of 2 molar equivalents or more and 82.5 molar equivalents or less relative to 1 molar equivalent of the compound represented by formula (1); The solvent is present in an amount of 2 parts by mass or more and 100 parts by mass or less relative to 1 part by mass of the compound represented by formula (1). Formula (2) 【Chemistry 2】 [In the formula, B １ and B ２ represents a ring structure which may have a substituent together with the skeletal portion represented by the solid line, and is formed by bonding a nitrogen atom and a sulfur atom in the compound represented by formula (1) to carbon atoms in A 1 and A 2 ; the dotted portion in the skeletal portion represented by the solid line represents that a pair of atoms connected by the dotted line may be connected by a double bond. A method for producing a thiazole compound represented by the formula:

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