METHOD FOR PRODUCING ARYL THIOL ESTER COMPOUND

Abstract

The present invention provides a production method capable of synthesizing an aryl thiol ester compound under mild conditions rapidly at a high yield. The present invention provides a method for producing an aryl thiol ester compound including producing an aryl thiol ester compound represented by the following general formula (1) from a diazonium compound represented by the following general formula (2) and a thioate compound represented by the following general formula (3) by a Sandmeyer-type coupling reaction using a catalyst, [wherein A.sup.1 and A.sup.2 are each independently an optionally substituted aryl group or an optionally substituted heteroaryl group; X.sup.1 is a monovalent anion; and M.sup.1 is a monovalent cation].

##STR00001##

Claims

1. method for producing an aryl thiol ester compound, comprising producing an aryl thiol ester compound represented by the following general formula (1) from a diazonium compound represented by the following general formula (2) and a thioate compound represented by the following general formula (3) by a Sandmeyer-type coupling reaction using a catalyst, ##STR00008## [in the formula, A.sup.1 is an optionally substituted aryl group or an optionally substituted heteroaryl group; X.sup.1 is a monovalent anion] ##STR00009## [in the formula, A.sup.2 is an optionally substituted aryl group or an optionally substituted heteroaryl group; M.sup.1 is a monovalent cation] ##STR00010## [in the formula, A.sup.1 and A.sup.2 are the same as described above].

2. The method for producing an aryl thiol ester compound according to claim 1, wherein the catalyst is a transition metal complex.

3. The method for producing an aryl thiol ester compound according to claim 2, wherein the transition metal complex is a copper complex.

4. The method for producing an aryl thiol ester compound according to claim 2, wherein the transition metal complex includes a bidentate nitrogen chelate ligand.

5. The method for producing an aryl thiol ester compound according to claim 2, wherein the transition metal complex is composed of a copper (I) ion and one or more ligands selected from the group consisting of 1,10-phenanthroline, 2,2-bipyridine and derivatives thereof.

6. The method for producing an aryl thiol ester compound according to claims 1, wherein prior to the Sandmeyer-type coupling reaction, an aminoaryl compound represented by the following general formula (4) is diazotized to produce the compound represented by the general formula (2)
Chemical Formula 4
A.sup.1-NH.sub.2 (4) [in the formula, A.sup.1 is the same as described above].

Description

EXAMPLES

[0054] The present invention will be described below with reference to Examples, but the present invention is not limited to these Examples.

[0055] The NMR equipment used for analysis of the Examples and the Comparative Examples was JNM-EC Z 400 S (400 MHz) manufactured by JEOL Ltd. Tetramethylsilane was set at 0 PPM for .sup.1H NMR, and C.sub.6F.sub.6 was set at 162 PPM for .sup.19F NMR.

Example 1

[0056] 4-Methoxyphenyl benzothioate was synthesized as follows.

(1) Diazotization of Aminoaryl

[0057] First, a benzenediazonium salt was synthesized by a general synthetic method.

##STR00006##

[0058] Boron trifluoride-diethyl ether complex (BF.sub.3.OEt.sub.2) (1.5 mmol, 1.5 eq.) was added to a solution of 4-methoxyaniline (1 mmol, 1 eq.) dissolved in 3 mL THF at ice-bath temperature. After stirring for 5 minutes, tert-butyl nitrite (1.2 mmol, 1.2 eq.) was added dropwise to the solution at 0 C. After stirring for an additional 15 minutes, the precipitate (benzenediazonium salt) was collected by filtration and washed with diethyl ether.

(2) Sandmeyer-Type Coupling Reaction

[0059] An aryl thiobenzoate was synthesized from benzenediazonium salt and thiobenzoate by a Sandmeyer-type coupling reaction using a copper complex catalyst. CuSCN, CuBr.SMe.sub.2or CuCN.LiCl (THF solution) was used as the copper (I) source, and 1,10-phenanthroline (Phen), bathophenanthroline (Bathophen) or BBBPY was used as the ligand.

##STR00007##

[0060] In an argon-filled drybox, a glass vial was charged with a copper (I) source (X mol %), a ligand (X mol %), potassium thiobenzoate (229 mg, 1.3 mmol) and a magnetic stir bar, followed by MeCN (1 mL), and stirred for approximately 2 minutes. The reaction mixture was a red suspension containing undissolved potassium thiobenzoate. 4-Methoxybenzenediazonium tetrafluoroborate (222 mg, 1.0 mmol) dissolved in MeCN (2 mL) was added dropwise to the reaction mixture at room temperature using a syringe. Visible nitrogen gas formation occurred during the addition. The syringe was previously washed using 1 mL of MeCN. After stirring the reaction mixture at room temperature or for 1 hour, the resulting reaction was transferred to a 50 mL flask. After adding silica to the flask, the solvent was evaporated in vacuo. Subsequently, column chromatography (hexane : DCM=2:1 to 1:1 (volume ratio)) was performed to obtain 4-methoxyphenyl benzothioate as a yellow solid. [0061] 1H NMR (400 MHz) 8.06-8.02 (m, 2H), 7.63-7.58 (m, 1H), 7.52-7.46 (m, 2H), 7.46-7.41 (m, 2H), 7.02-6.98 (m, 2H), 3.85 (s, 3H).

[0062] Table 1 shows the copper complex catalyst (copper (1) source and ligand), the amount of copper complex used (X mol % in the reaction formula), the reaction temperature, and the yield (%) of 4-methoxyphenylbenzothioate in each test group. In Table 1, / indicates no addition. For example, for test group 9, CuSCN (12 mg, 0.1 mmol) was used as the copper (I) source, 1,10-phenanthroline (18 mg, 0.1 mmol) was used as the ligand, and 4-methoxyphenylbenzothioate (195 mg) (80% yield) was obtained.

TABLE-US-00001 TABLE 1 Amount of Reaction Test Copper (I) Catalyst Added Temperature Yield Group Source Ligand (mol %) ( C.) (%) 1 / / / r.t. 64.8 2 CuSCN / 20 r.t. 62.9 3 CuBrSMe2 / 20 r.t. 65.3 4 CuCNLiCl / 20 r.t. 65.1 (in THF) 5 CuSCN Phen 20 r.t. 71.3 6 CuSCN Bathophen 20 r.t. 75.3 7 CuSCN bbbpy 20 r.t. 75.2 8 CuSCN Phen 10 r.t. 80.0 9 CuSCN Bathophen 10 r.t. 74.7 10 CuSCN Phen 10 30 C. 76.5 11 CuSCN Phen 10 0 C. 74.6

[0063] There was no or very little improvement in yield in test groups 2 to 4 using uncomplexed copper as a catalyst compared to test group 1 without catalyst. On the other hand, test groups 5 to 11 using a copper complex catalyst showed a clear improvement in yield regardless of the type of copper (I) source and ligand used. In particular, test group 8, in which 10 mol % of a copper complex catalyst composed of CuSCN and 1,10-phenanthroline was used with respect to benzenediazonium salt (4-methoxybenzenediazonium tetrafluoroborate), yielded an extremely high yield of 80%.

[0064] Comparing test groups 8, 10 and 11, test group 8 showed the highest yield, and test groups 10 and 11 also showed sufficient yield improvement, indicating that the effect of improving the yield by using a transition metal complex as a catalyst can be obtained even in a low-temperature environment with a reaction temperature of 30 C. to 0 C.

INDUSTRIAL APPLICABILITY

[0065] The present invention provides a method for producing an aryl thiol ester compound which can be rapidly synthesized at a high yield under relatively mild conditions. In addition, since the aryl thiol ester compound produced by the present invention is useful as an intermediate for producing various organic compounds, the present invention is useful for producing active ingredients of pharmaceuticals and agricultural chemicals, organic materials and the like.